Detection of VBNC Vibrio cholerae by RT-Real Time PCR based on differential gene expression analysis

Abstract

The recognition of the viable but non-culturable (VBNC) state of pathogenic bacteria has brought with it many questions to answer related to the need to detect and quantify viable bacteria in the environment in an accurate way. To assess viability of Vibrio cholerae, we developed a RT-Real Time PCR technique based on differential expression analysis from mRNA deep sequencing data. We compared two induction conditions to achieve the VBNC state: a bacterial suspension induced by artificial seawater at 4 °C, and the addition of c-di-GMP. The evaluation of the up-regulated genes in the induced bacterial samples was compared with a fresh culture in the mid-exponential phase. The data analysis was performed with the NOISeq R-package and revealed 17 up-regulated genes for induction condition I and 22 up-regulated genes for induction condition II. Only one region was found to be up-regulated for both induction conditions. The VCA0656 gene related to the aminoimidazole riboside kinase protein was detected as the most up-regulated region and used as a genetic marker to precisely detect the VBNC state in combination with the RT-Real Time PCR technique. This approach describes a novel method to differentiate the VBNC state of V. cholerae in water samples.

Gene circuit engineering to improve the performance of a whole-cell lead biosensor

Abstract

To improve the performance of a whole-cell biosensor for lead detection, we designed six gene circuits by re-configuring the regulatory elements and incorporating positive feedback loops to the circuits. The lead resistance operon pbr encodes six genes with pbrRT on one side of the promoter and pbrABCD on the other side. PbrR, the divergent promoter it regulates, and GFP were used to design the lead biosensors. One has pbrR and gfp on opposite sides of the promoter mimicking the native operon. We re-configured it by placing pbrR and gfp on the same side or under two separate promoters. The one with pbrR and gfp on the same side demonstrated lead sensitivity 10 times higher than the others. Positive feedback loop was introduced to these circuits. The strength of the output signal from the designs with positive feedback loop was 1.5–2 times stronger than those without positive feedback. This study demonstrates the importance of configuration and positive feedback as effective strategies to improve the performance of lead biosensors and they can be extended to the design of other whole-cell biosensors.

Molecular Diversity of Fungal Inhibitor Cystine Knot Peptides Evolved by Domain Repeat and Fusion

Abstract

Peptides with an inhibitor cystine knot (ICK) motif are extensively present in animals and plants where they exert a diversity of biological functions. However, few studies have been undertaken on this class of peptides in fungi. In this work, we identify a total of 386 fungal ICK peptides and proteins containing this motif by computational data mining of fungal genome databases, which exhibit 14 different exon-intron structures. According to their domain architectures, these proteins are classified into three distinct structural types, including single domains, tandem repeat domains and fusion domains, in which six families belonging to single and tandem repeat domains show remarkable sequence similarity to those from animals and plants, suggesting their orthologous relationship. Extremely high molecular diversity in fungal ICKs might be attributable to different genetic mechanisms, such as gene/domain duplication and fusion. This work not only enlarges the number of ICK peptides in multicellular organisms, but also uncovers their complex evolutionary history in a specific lineage.

Strange-but-true: a (quick) new argument for contextualism about ‘know’

Abstract

A powerful objection to subject-sensitive invariantism (SSI) concerns various 'strange-but-true' (or "embarrassing") conditionals. One popular response to this objection is to argue that strange-but-true conditionals pose a problem for non-sceptical epistemological theories in general. In the present paper, it is argued that strange-but-true conditionals are not a problem for contextualism about 'know'. This observation undercuts the proposed defence of SSI, and supplies a surprising new argument for contextualism.

A weak symmetry condition for probabilistic measures of confirmation

Abstract

This paper presents a symmetry condition for probabilistic measures of confirmation which is weaker than commutativity symmetry, disconfirmation commutativity symmetry but also antisymmetry. It is based on the idea that for any value a probabilistic measure of confirmation can assign there is a corresponding case where degrees of confirmation are symmetric. It is shown that a number of prominent confirmation measures such as Carnap's difference function, Rescher's measure of confirmation, Gaifman's confirmation rate and Mortimer's inverted difference function do not satisfy this condition and instead exhibit a previously unnoticed and rather puzzling behavior in certain cases of disconfirmation. This behavior also carries over to probabilistic measures of information change, causal strength, explanatory power and coherence.

Aboutness in imagination

Abstract

I present a formal theory of the logic and aboutness of imagination. Aboutness is understood as the relation between meaningful items and what they concern, as per Yablo and Fine's works on the notion. Imagination is understood as per Chalmers' positive conceivability: the intentional state of a subject who conceives that p by imagining a situation—a configuration of objects and properties—verifying p. So far aboutness theory has been developed mainly for linguistic representation, but it is natural to extend it to intentional states. The proposed framework combines a modal semantics with a mereology of contents: imagination operators are understood as variably strict quantifiers over worlds with a content-preservation constraint.

Preferences, reasoning errors, and resource egalitarianism

Abstract

In this paper I aim to examine some problematic implications of the fact that individuals are prone to making systematic reasoning errors, for resource egalitarianism. I begin by disentangling the concepts of preferences, choices and ambitions, which are sometimes used interchangeably by egalitarians. Subsequently, I claim that the most plausible interpretation of resource egalitarianism takes preferences, not choices, as the site of responsibility. This distinction is salient, since preference-sensitive resource egalitarianism is faced with an important objection when applied to situations in which the empirically reasonable assumption that individuals have different degrees of computational abilities is introduced. I first show that this objection can be raised in cases involving individuals who have incomplete information, but that it ultimately fails for such cases since we can appeal to higher order insurance markets in order to mitigate any initial concerns. I further claim, however, that the objection is much more powerful in cases involving individuals who have different reasoning skills, since the appeal to higher order insurance markets is no longer tenable. Consequently, the ideal principle of justice proposed by Dworkin is met with a new feasibility challenge. Finally, I claim that the problem of reasoning errors and various forms of cognitive biases also affect Dworkin's non-ideal principle of justice, skewing the outputs of the hypothetical insurance mechanism in an unjustifiable manner.

Appropriate emotions and the metaphysics of time

Abstract

Prior used our emotions to argue that tensed language cannot be translated by tenseless language. However, it is widely accepted that Mellor and MacBeath have shown that our emotions do not imply the existence of tensed facts. I criticise this orthodoxy. There is a natural and plausible view of the appropriateness of emotions which in combination with Prior's argument implies the existence of tensed facts. The Mellor/MacBeath position does nothing to upset this natural view and therefore is not sufficient to block one drawing conclusions for the metaphysics of time from the nature of our emotions.

In defence of single-premise closure

Abstract

It's often thought that the phenomenon of risk aggregation poses a problem for multi-premise closure but not for single-premise closure (either with respect to knowledge or with respect to justified belief). But recently, Lasonen-Aarnio and Schechter have challenged this thought. Lasonen-Aarnio argues that, insofar as risk aggregation poses a problem for multi-premise closure, it poses a similar problem for single-premise closure. For she thinks that, there being such a thing as deductive risk, risk may aggregate over a single premise and the deduction itself. Schechter argues that single-premise closure succumbs to risk aggregation outright. For he thinks that there could be a long sequence of competent single-premise deductions such that, even though we are justified in believing the initial premise of the sequence, intutively, we are not justified in believing the final conclusion. This intuition, Schechter thinks, vitiates single-premise closure. In this paper, I defend single-premise closure against the arguments offered by Lasonen-Aarnio and Schechter.

Prudence and past selves

Abstract

An important platitude about prudential rationality is that I should not refuse to sacrifice a smaller amount of present welfare for the sake of larger future benefits. I ought, in other words, to treat my present and future as of equal prudential significance. The demands of prudence are less clear, however, when it comes to one's past selves. In this paper, I argue that past benefits are possible in (at least) two ways, and that this fact cannot be easily accommodated by traditional approaches to prudential rationality. Against univocal accounts of prudential rationality, I hold that the possibility of past benefits suggests that a bias toward the present and future is defensible when it comes to some welfare goods, but that prudential reasons are temporally neutral between when it comes to the success or failure of one's long-term projects.

Effect of local application of transcutaneous carbon dioxide on survival of random pattern skin flaps

Publication date: Available online 28 June 2018
Source:Journal of Plastic, Reconstructive & Aesthetic Surgery
Author(s): Izumi Saito, Takumi Hasegawa, Takeshi Ueha, Daisuke Takeda, Eiji Iwata, Satomi Arimoto, Akiko Sakakibara, Masaya Akashi, Shunsuke Sakakibara, Yoshitada Sakai, Hiroto Terashi, Takahide Komori
IntroductionSkin flap procedures are widely used to reconstruct skin and soft tissue defects. Skin flap necrosis is a serious postoperative complication. Many researchers have introduced pharmacological agents to improve flap ischemia in experimental studies. However, these outcomes remain controversial. We previously demonstrated that transcutaneous CO2 application improves hypoxia in fracture repair. In this study, we hypothesized that improving hypoxia by transcutaneous CO2 application can improve the blood flow of skin flaps and increase angiogenesis. We investigated whether transcutaneous CO2 application can increase the survival of random pattern skin flaps.Materials and MethodsSix-week-old male Sprague–Dawley rats were divided into two equal groups: the control group (n=6) and CO2 group (n=6). A random pattern skin flap was performed. Topical CO2 was applied by means of a hydrogel every day for 5 days in the CO2 group. The flap survival area was measured on postoperative days 1, 3, and 5. The vessel density and expression of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and hypoxia-inducible factor-1α (HIF-1α) were evaluated on postoperative day 5.ResultsA statistically significant difference was found in the percentage of the flap survival area between the two groups on postoperative days 3 and 5 (p<0.05). Furthermore, the expression of VEGF and bFGF was significantly higher and that of HIF-1α was significantly lower in the CO2 than control group (p<0.05).ConclusionsTranscutaneous CO2 application can improve the blood flow of skin flaps and increase angiogenesis, thus increasing the survival of random pattern skin flaps.

A comparison of patient satisfaction (using the Breast-Q questionnaire) with bilateral breast reconstruction following risk-reducing or therapeutic mastectomy

Publication date: Available online 28 June 2018
Source:Journal of Plastic, Reconstructive & Aesthetic Surgery
Author(s): F. Kazzazi, R. Haggie, P. Forouhi, N. Kazzazi, L. Wyld, C.M. Malata
IntroductionPatients undergoing mastectomy and immediate breast reconstruction for cancer may be expected to have different perceptions of long term outcomes compared with those who have this operation prophylactically.MethodsPatients who underwent bilateral mastectomy and breast reconstruction from 2008-2014 at the Cambridge Breast Unit were identified from a prospective register and their notes audited. They were classified according to their indication for surgery: bilaterally therapeutic, bilaterally risk-reducing or combination. The Breast-Q™ questionnaire was posted to participants using the "total Dillman method". Q-SCORE software was utilized to analyze patient satisfaction scores.Results65 responses were received (58%) of which 8 were excluded leaving 57 usable for the study. The therapeutic group had higher patient satisfaction than the risk-reducing group across most domains; breast, outcome, psychosocial, sexual, physical, information. The combination group scored lower and BRCA gene mutation positive patients the lowest. Physical wellbeing was maintained across all groups but psychosocial/sexual wellbeing varied. Good psychosocial wellbeing was linked to a higher satisfaction with the outcome in the combination and risk-reducing groups.ConclusionThis study highlights the need for clinicians to take into account the indication for surgery as a major psychological factor in patient perception of self and experience of surgery. It demonstrates that bilateral immediate reconstruction patients report similar physical symptoms irrespective of indication for mastectomy, but the decision-making process in terms of risk-balancing and diagnosis influences satisfaction with self and surgery. It underlines the importance of preoperative management of expectations for patients undergoing risk-reducing procedures.

Response to: Time course of improvement after re-repair procedure for VPI management

Publication date: Available online 28 June 2018
Source:Journal of Plastic, Reconstructive & Aesthetic Surgery
Author(s): Mr Brian C Sommerlad

Utilization of rice husk to enhance calcium oxide-based sorbent prepared from waste cockle shells for cyclic CO 2 capture in high-temperature condition

Abstract

The CO₂ capture capacity and cyclic stability of calcium oxide (CaO) prepared from cockle shells (CS) were enhanced by incorporating rice husk (RH) and binder through wet-mixing method. The cyclic reaction of calcination and carbonation was demonstrated using thermal gravimetric analyzer (TGA) which the calcination was performed in a pure N₂ environment at 850 °C for 20 min and carbonation at 650 °C for 30 min in 20 vol% of CO₂ in N₂. The analysis using x-ray fluorescence (XRF) identified silica (Si) as the major elements in the sorbents. The RH-added sorbents also contained several types of metal elements such as which was a key factor to minimize the sintering of the sorbent during the cyclic reaction and contributed to higher CO₂ capture capacity. The presence of various morphologies also associated with the improvement of the synthesized sorbents performance. The highest initial CO₂ capture capacity was exhibited by CS+10%RH sorbent, which was 12% higher than the RH-free sorbent (CS). However, sorbents with the higher RH loading amount such as 40 and 50 wt% were preferred to maintain high capture capacity when the sorbents were regenerated and extended to the cyclic reaction. The sorbents also demonstrated the lowest average sorption decay, which suggested the most stable sorbent for cyclic-reaction. Once regenerated, the capture capacity of the RH-added sorbent was further increased by 12% when clay was added into the sorbent. Overall, the metal elements in RH and clay were possibly the key factor that enhances the performance of CaO prepared from CS, particularly for cyclic CO₂ capture.

Graphical abstract

Cyclic calcination and carbonation reaction

Di-metal-doped sulfur resisting perovskite catalysts for highly efficient H 2 -SCR of NO

Abstract

Lanthanide perovskite catalysts doped with limited palladium (to improve activity) and cerium (to improve sulfur resistance) were prepared using sol–gel method. In different B sites, lanthanide perovskites were studied at harsh conditions for H₂ selective catalytic reduction of NO. The activity sequence was as follows: LaCeMnPd > LaCeCoPd > LaCeFePd. LaCeMnPd had a high NO conversion of 96.6% at only 150 °C. And it also had a surprising SO₂ resistance in different SO₂ concentrations. After cutting out SO₂, NO conversion recovered rapidly to its original level, indicating that the slight deactivation was reversible. In addition, the effect of gas hourly space velocity, H₂/NO ratio, O₂, and SO₂ concentration was studied. And XRD, energy-dispersive X-ray, SEM, XPS, H₂-temperature programmed reduction, and NH₃-temperature programmed desorption were performed to characterize the catalysts.

Graphical abstract

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Surface modification of sludge-derived carbon by phosphoric acid as new electrocatalyst for degradation of acetophenone

Abstract

Sludge-derived carbons (SCs) were modified by different acids and used as electrocatalyst for electrochemical oxidation degradation of acetophenone. The results showed that SC treated with phosphoric acid (H₃PO₄-SC) exhibited the highest catalytic activity. The degradation efficiency of acetophenone reached 87.0%, and TOC removal was 72.3% under the conditions of 100 mg L⁻¹ acetophenone, 90 mA cm⁻², and 180 min reaction time. The element content and chemical state of H₃PO₄-SC were measured by XRF, XRD, TGA, FTIR, and Mössbauer spectra, and the results indicated that ferric iron and phosphate on the surface of H₃PO₄-SC might play the main role in acetophenone degradation. The carbonyl-¹³C-labeled acetophenone was first used to investigate the degradation of acetophenone in electrochemical oxidation by NMR.

The in-principle inconclusiveness of causal evidence in macroeconomics

Abstract

The paper analyzes the methods that macroeconomists can use to provide evidence in support of causal hypotheses: the instrumental variable (IV) method and econometric causality tests. It argues that the evidence that macroeconomists provide when using these methods is in principle too inconclusive to support the hypothesis that X directly type-level causes Y, where X and Y stand for macroeconomic aggregates like the real interest rate and aggregate demand. The evidence provided by the IV method is too inconclusive because it derives from conditions requiring that there be no confounders of I and X and X and Y (where I is an instrumental or intervention variable that typelevel causes X), and because in macroeconomics, confounders that cannot be controlled for or measured are likely to be present. The evidence provided by econometric causality tests is too inconclusive because they can be shown to rely on the conditions of the IV method at least tacitly.

The relationship between naevus count, memory function and telomere length in the Twins UK cohort

Pigment Cell &Melanoma Research, Volume 0, Issue ja, -Not available-.

Pollution levels and risk assessment of perfluoroalkyl acids (PFAAs) in beef muscle and liver from southern Xinjiang

Abstract

The presence of perfluoroalkyl acids (PFAAs) in animal foods is worldwide, and their fate and spatial distribution in Xinjiang are not well understood. In this study, beef muscle and liver collected from five major cities in southern Xinjiang were analyzed (n = 70) for 13 PFAAs using an ion-pairing method combined with HPLC-MS/MS. Overall, PFAA contamination was widespread, exceeding 50% of samples with concentrations ranged from below the limits of detection to 6.118 ng/g. Perfluorooctane sulfonate, perfluorooctanoic acid, and perfluoroundecanoic acid were the predominant PFAAs of ten detected compounds, with maximum concentrations in Korla liver samples of 2.543, 0.856, and 1.386 ng/g, respectively. When comparing the five cities, the highest levels and detection frequencies were observed in samples from Korla (muscle, 0.013 ng/g; liver, 3.336 ng/g), followed by Yanqi, Akesu, Kashgar, and Hotan. The different pollution patterns and distribution profiles of PFAAs among cities were significantly related to local economy and geographical conditions. In addition, the dietary intake assessments for PFAAs showed that samples originating from Korla had the greatest impact on human health, but the total hazard ratio was 0.814 × 10⁻³, which is far less than 1, indicating that consumption of beef muscle and liver poses no immediate harm to local residents.

Successful treatment of erythematotelangiectatic rosacea with intense pulsed light: Report of 13 cases

The Journal of Dermatology, EarlyView.

Numerous plasmacytoid dendritic cell infiltration in HIV‐associated psoriasis relieved only with antiretroviral therapy

The Journal of Dermatology, EarlyView.

Sézary syndrome in an anti‐human T‐cell lymphotropic virus type 1 seropositive carrier

The Journal of Dermatology, EarlyView.

Mycoplasma pneumoniae‐associated mucositis with severe blistering stomatitis and pneumonia successfully treated with azithromycin and infusion therapy

The Journal of Dermatology, EarlyView.

Prolonged growth of infantile hemangioma after pulsed dye laser and oral propranolol treatment

The Journal of Dermatology, EarlyView.

Psoriasiform dermatitis associated with common variable immunodeficiency 10 due to an Arg853* mutation in the NFKB2 gene

The Journal of Dermatology, EarlyView.

Identification of a missense mutation causing exon skipping in a neurofibromatosis type 1 patient

The Journal of Dermatology, EarlyView.

Effets indésirables des soins capillaires chez les utilisateurs

Publication date: Available online 27 June 2018
Source:Annales de Dermatologie et de Vénéréologie
Author(s): D. Tennstedt, A. Herman, J.-M. Lachapelle
La panoplie des produits utilisés par les professionnels pour laver, modifier la couleur ou la forme ou embellir la chevelure n'est pas dénuée d'effets indésirables. Ces effets sont essentiellement des dermatites d'irritation et des eczémas de contact allergiques pouvant affecter le cuir chevelu mais aussi la nuque, la face antérieure du cou, le front et les régions périorbitaires, les joues. Parmi les allergènes les plus cités, il convient de mentionner la paraphénylènediamine (PPD) des teintures capillaires, le monothioglycolate de glycérol (GMTG) des permanentes acides, le persulfate d'ammonium des décolorations (ce dernier est responsable principalement d'urticaires de contact). Mais il ne faut pas oublier d'autres allergènes comme la cocamidopropylbétaïne parmi les tensioactifs, et aussi certains constituants de la formulation tels les conservateurs et les parfums (voire le minoxidil, si fréquemment utilisé par les patients).The panoply of products used by hair care professionals to wash, dye, shape and beautify hair is not entirely free from adverse events. Such effects consist mainly of irritation dermatitis and allergic contact eczema affecting the scalp, as well as the back and front of the neck, the forehead and periorbital areas, and the cheeks. The most frequently cited allergens include paraphenylenediamine (PPD) in hair dyes, glycerol monothioglycolate (GMTG) in acid perm lotions, and ammonium persulphate in hair lighteners (the latter substance being responsible primarily for contact urticaria). However, care should also be paid to other allergens such as cocamidopropyl betaine among surfactants, as well as certain components in hair formulations such as preservatives and fragrances (as well as minoxidil, frequently used by patients).

Inflammation: A Contributor to Depressive Comorbidity in Inflammatory Skin Disease

The prevalence of affective disorders such as depression and anxiety is particularly high in patients with autoimmune diseases, including inflammatory skin diseases such as psoriasis, atopic dermatitis, and hidradenitis suppurativa. A dysregulated immune response has been linked to the precipitation of depression in many patient populations. However, studies examining the extent to which the underlying skin disease inflammatory processes contribute to depression and a subsequent decline in quality of life are limited. The published literature over the past 5 years was reviewed for evidence of a relationship between depression and inflammatory processes in the context of skin pathology. The findings, particularly the evidence from interventional clinical trials of targeted anti-cytokine therapies, suggest that pro-inflammatory cytokines associated with several skin diseases may be causally linked with the coexistent depressive symptomology.
Skin Pharmacol Physiol 2018;31:246–251

Congenital nevus comedonicus complicated by a hidradenitis suppurativa‐like lesion: Report of a childhood case

Pediatric Dermatology, EarlyView.

Grading Severity and Activity in Thyroid Eye Disease

Purpose: Thyroid eye disease (TED) is an autoimmune disorder causing inflammation, expansion, and fibrosis of orbital fat, muscle, and lacrimal gland. This article reviews the different methods of grading severity and activity of TED and focuses on the VISA Classification for disease evaluation and planning management. Methods: Accurate evaluation of the clinical features of TED is essential for early diagnosis, identification of high-risk disease, planning medical and surgical intervention, and assessing response to therapy. Evaluation of the activity and severity of TED is based on a number of clinical features: appearance and exposure, periorbital tissue inflammation and congestion, restricted ocular motility and strabismus, and dysthyroid optic neuropathy. The authors review these clinical features in relation to disease activity and severity. Results: Several classification systems have been devised to grade severity of these clinical manifestations. These include the NO SPECS Classification, the European Group on Graves Orbitopathy severity scale, the Clinical Activity Score of Mourits, and the VISA Classification as outlined here. The authors compare and contrast these evaluation schemes. Conclusions: An accurate clinical assessment of TED, including grading of disease severity and activity, is necessary for early diagnosis, recognition of those cases likely to develop more serious complications, and appropriate management planning. The VISA Classification grades both disease severity and activity using subjective and objective inputs. It organizes the clinical features of TED into 4 discrete groupings: V (vision, dysthyroid optic neuropathy); I (inflammation, congestion); S (strabismus, motility restriction); A (appearance, exposure). The layout follows the usual sequence of the eye examination and facilitates comparison of measurements between visits and data collation for research. Accepted for publication March 19, 2018. Sections of this chapter were previously published in Dolman PJ. Evaluating graves orbitopathy. Best Pract Res Clin Endocrinol Metab 2012;26:00–00. The author has no financial or conflicts of interest to disclose. Address correspondence and reprint requests to Peter J. Dolman, M.D., F.R.C.S.C., Eye Care Centre, Section I, 2550 Willow Street, Vancouver, BC V5Z 3N9, Canada. E-mail: peterdolman@hotmail.com © 2018 by The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc., All rights reserved.

Nasolacrimal Sac Diverticulum: A Case Series and Literature Review

Purpose: To describe the demographics, presentation, treatment, and outcome in 10 cases of lacrimal sac diverticulum and to review the literature on this topic, and to determine the incidence of diverticula from a series of dacryocystograms. Methods: Data were collected for all consecutive patients with lacrimal sac diverticulum seen between 2003 and 2015, including patient demographics, clinical presentation, imaging findings, treatment, and follow-up. A systematic literature review was performed for cases of lacrimal sac diverticulum. A retrospective review of 400 consecutive dacryocystograms was performed to determine the incidence of lacrimal sac diverticulum. Results: Ten cases (9 patients) of lacrimal sac diverticulum are described, and a further 36 cases were discovered through a literature review. Epiphora, swelling, and dacryocystitis and/or diverticulitis were the most common presenting complaints. When all 46 cases are combined, lacrimal patency was demonstrated in 50% of cases. Dacryocystography diagnosed only 57% of patients with diverticulum, not helped by the addition of ultrasound or CT. The incidence of diverticulum was 3.2% on review of 400 consecutive dacryocystograms (1.6% per lacrimal system). Surgical management with dacryocystorhinostomy and/or diverticulum excision was effective in all 34 operated cases at resolving symptoms in the case series and literature review. Conclusions: Lacrimal sac diverticula present with epiphora, medial canthal swelling, dacryocystitis, and/or diverticulitis. Dacryocystography, despite being the most sensitive radiologic test, is only 59% sensitive, and adjunctive CT and ultrasound have limited use. Surgical management is recommended because conservative management often fails. Dacryocystorhinostomy, diverticulum excision, or a combination thereof appears to be equivalent in achieving resolution of symptoms. Accepted for publication April 20, 2018. The authors have no financial or conflicts of interest to disclose. Address correspondence and reprint requests to Thomas G. Hardy, M.B.B.S., F.R.A.N.Z.C.O., Suite 216–218, 100 Victoria Parade, East Melbourne, VIC 3002, Australia. E-mail: hardy_tg@bigpond.net.au © 2018 by The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc., All rights reserved.

Orbital, Periorbital, and Intracranial Emphysema Caused by Compressed Air Injury in a 5-Year-Old Child

A 5-year-old boy was accidentally injured by a compressed air blast to his right eye and developed periorbital and subconjunctival emphysema and proptosis subsequently. CT scan showed periorbital subcutaneous and intraorbital emphysema around the right eye, as well as intracranial and cervical emphysema without frank fractures in orbital bones. He was examined under sedation, and the subconjunctival air was aspirated. He was also prophylactically treated with topical and systemic antibiotics to prevent infection. Emphysema was resorbed entirely within 3 weeks. In conclusion, compressed air injury can occur in a child and manifest with orbital and periorbital emphysema without any detectable fracture and any clear entrance site and may need emergent management to save the vision or upper respiratory airways. Accepted for publication May 3, 2018. The authors have no financial or conflicts of interest to disclose. Address correspondence and reprint request to Mehdi Tavakoli, M.D., Labbafinejad Medical Center, Boostan 9 Street Pasdaran Avenue, Tehran 16666, Iran. E-mail: mehditavakolimd@yahoo.com © 2018 by The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc., All rights reserved.

Phi, Fat, and the Mathematics of a Beautiful Midface

Purpose: The Golden ratio, or Phi, has been used to explain the substrates of two-dimensional beauty utilizing the faces of models. A "Phi point" has been identified at the apex of the cheek mound that can be targeted in filler injections. The authors report herein how they have applied this algorithm for surgical shaping of the "beautiful" cheek as a routine part of their lower blepharoplasty procedure. The authors present their technique and results with patients undergoing lower blepharoplasty along with the adjunct of liposculpture to areas of volume deficiency in the midface with a particular goal of enhancing the Phi point. Methods: This study was retrospective, consecutive, nonrandomized, interventional case series. The authors reviewed the medical records of 113 consecutive patients who underwent lower blepharoplasty with autologous fat transfer to the Phi point. The aesthetic outcome, patient satisfaction, and complication/revisions were evaluated. Results: One hundred two out of 113 patients achieved excellent lower lid position and cheek enhancement as assessed by both patient and surgeon. In these 102 patients, there was significant improvement in lower lid appearance, contour, transition to the cheek, and cheek projection as observed by the surgeon. Three patients required revision to achieve sufficient volume. Eight patients were satisfied with the outcome, nevertheless, requested additional filler injection to optimize. Conclusions: Lower blepharoplasty combined with autologous fat transfer to reshape the Phi point is a safe and reliable technique and another step further in our quest for recreating the beautiful face. Accepted for publication May 10, 2018. The authors have no financial or conflicts of interest to disclose. Presented as a lecture at the annual American Society of Ophthalmic Plastic and Reconstructive Surgery symposium, New Orleans, LA, November 2013. Address correspondence and reprint requests to Morris E. Hartstein, M.D., Assaf Harofeh Medical Center, Zerifin, Israel 70300. E-mail: mhartstein@earthlink.net © 2018 by The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc., All rights reserved.

A pilot split‐scalp study of combined fractional radiofrequency microneedling and 5% topical minoxidil in treating male pattern hair loss

Clinical and Experimental Dermatology, EarlyView.

A case of scalp necrosis

Clinical and Experimental Dermatology, EarlyView.

Part I: Onychomycosis: Clinical Overview and Diagnosis

Onychomycosis is a fungal nail infection caused by dermatophytes, non-dermatophytes, and yeast and is the most common nail disorder seen in clinical practice. It is an important problem, as it may cause local pain, paresthesias, difficulties performing activities of daily life, and impair social interactions. In the following continuing medical education manuscript, we review the epidemiology, risk factors, and clinical presentation of onychomycosis and demonstrate current and emerging diagnostic strategies.

Part II: Onychomycosis: Treatment and Prevention of Recurrence

Onychomycosis is a fungal nail infection caused by dermatophytes, non-dermatophytes, and yeast and is the most common nail disorder seen in clinical practice. It is an important problem, as it may cause local pain, paresthesias, difficulties performing activities of daily life, and impair social interactions. The epidemiology, risk factors, and clinical presentation and diagnosis of onychomycosis were discussed in the first article in this continuing medical education series. In this article, we review the prognosis and response to onychomycosis treatment, Food and Drug Administration approved medications for onychomycosis, as well as, off-label therapies and devices.

A broader filtration of UVA1 wavelengths improves skin photoprotection

Sun exposure involves ultraviolet (UV) rays: UVB (290-320 nm), UVA2 (320-340 nm) and UVA1 (340-400 nm). UVA1 rays represent the majority of UV reaching the Earth surface. In human, UVA1 induces an immediate and persistent non-protective skin darkening and contribute to photoaging, immunosuppression and carcinogenesis [1–4]. Using in vitro reconstructed skin, we showed that UVA1 exposure generated reactive oxygen species and led to epidermal damage and fibroblast apoptosis. A strong UVA1-induced alteration of the expression of genes encoding proteins involved in essential biological pathways was also evidenced in this 3D model, and in human skin in vivo [5,6].

A comparison of patient satisfaction (using the Breast-Q questionnaire) with bilateral breast reconstruction following risk-reducing or therapeutic mastectomy

Patients undergoing mastectomy and immediate breast reconstruction for cancer may be expected to have different perceptions of long term outcomes compared with those who have this operation prophylactically.

Effect of local application of transcutaneous carbon dioxide on survival of random pattern skin flaps

Skin flap procedures are widely used to reconstruct skin and soft tissue defects. Skin flap necrosis is a serious postoperative complication. Many researchers have introduced pharmacological agents to improve flap ischemia in experimental studies. However, these outcomes remain controversial. We previously demonstrated that transcutaneous CO2 application improves hypoxia in fracture repair. In this study, we hypothesized that improving hypoxia by transcutaneous CO2 application can improve the blood flow of skin flaps and increase angiogenesis.

Response to: Time course of improvement after re-repair procedure for VPI management

I read with interest the paper by Elsherbiny et al.1 I think this adds some important information about the time scale of change and the need for patience. It is unfortunate that the speech assessments were not made blindly and independently (as acknowledged by the authors). However, the improvement with time seems to be impressive.

Evaluation of heterogeneous catalytic ozonation process for diclofenac degradation in solutions synthetically prepared

Abstract

Sodium diclofenac (DCF) is a common analgesic and anti-inflammatory drug, which has become an environmental problem due to its growth and accumulation into water bodies. In this work, commercial (with excipients) and analytical (pure) DCF mineralization was studied by means of heterogeneous catalytic ozonation. The process was carried out with magnetite (Fe₃O₄) as a catalyst, which preserves its physical and chemical properties during the process. The best results of mineralization were obtained after a 40-min treatment of 35 mg/L analytical DCF solution, with a 0.5 g/L catalyst concentration. These results showed the highest organic load decrease, measured as dissolved organic carbon (DOC) and chemical oxygen demand (COD), with 94 and 89%, respectively. In addition, the percentage of organic load decrease was compared between the conventional and the catalyzed process. Besides, reaction products were identified by gas chromatography–mass spectrometry (GC-MS) and the catalytic properties were identified by Mössbauer spectroscopy, which showed the catalyst maintained its nature after the process. Finally, the results obtained show that the heterogeneous catalytic process could be an efficient degradation treatment for emerging contaminants such as DCF.

Local BDNF Delivery to the Injured Cervical Spinal Cord using an Engineered Hydrogel Enhances Diaphragmatic Respiratory Function

We developed an innovative biomaterial-based approach to repair the critical neural circuitry that controls diaphragm activation by locally delivering brain-derived neurotrophic factor (BDNF) to injured cervical spinal cord. BDNF can be used to restore respiratory function via a number of potential repair mechanisms; however, widespread BDNF biodistribution resulting from delivery methods such as systemic injection or lumbar puncture can lead to inefficient drug delivery and adverse side effects. As a viable alternative, we developed a novel hydrogel-based system loaded with polysaccharide-BDNF particles self-assembled by electrostatic interactions that can be safely implanted in the intrathecal space for achieving local BDNF delivery with controlled dosing and duration. Implantation of BDNF hydrogel after C4/C5 contusion-type spinal cord injury (SCI) in female rats robustly preserved diaphragm function, as assessed by in vivo recordings of compound muscle action potential and electromyography amplitudes. However, BDNF hydrogel did not decrease lesion size or degeneration of cervical motor neuron soma, suggesting that its therapeutic mechanism of action was not neuroprotection within spinal cord. Interestingly, BDNF hydrogel significantly preserved diaphragm innervation by phrenic motor neurons (PhMNs), as assessed by detailed neuromuscular junction morphological analysis and retrograde PhMN labeling from diaphragm using cholera toxin B. Furthermore, BDNF hydrogel enhanced the serotonergic axon innervation of PhMNs that plays an important role in modulating PhMN excitability. Our findings demonstrate that local BDNF hydrogel delivery is a robustly effective and safe strategy to restore diaphragm function after SCI. In addition, we demonstrate novel therapeutic mechanisms by which BDNF can repair respiratory neural circuitry.

SIGNIFICANCE STATEMENT Respiratory compromise is a leading cause of morbidity and mortality following traumatic spinal cord injury (SCI). We used an innovative biomaterial-based drug delivery system in the form of a hydrogel that can be safely injected into the intrathecal space for achieving local delivery of brain-derived neurotrophic factor (BDNF) with controlled dosing and duration, while avoiding side effects associated with other delivery methods. In a clinically relevant rat model of cervical contusion-type SCI, BDNF hydrogel robustly and persistently improved diaphragmatic respiratory function by enhancing phrenic motor neuron (PhMN) innervation of the diaphragm neuromuscular junction and by increasing serotonergic innervation of PhMNs in ventral horn of the cervical spinal cord. These exciting findings demonstrate that local BDNF hydrogel delivery is a safe and robustly effective strategy to maintain respiratory function after cervical SCI.

Laminin {beta}2 Chain Regulates Retinal Progenitor Cell Mitotic Spindle Orientation via Dystroglycan

Vertebrate retinal development follows a pattern during which retinal progenitor cells (RPCs) give rise to all retinal cell types in a highly conserved temporal sequence. RPC proliferation and cell cycle exit are tightly coordinated to ensure proper and timely production of each of the retinal cell types. Extracellular matrix (ECM) plays an important role in eye development, influencing RPC proliferation and differentiation. In this study, we demonstrate that laminins, key ECM components, in the inner limiting membrane, control mitotic spindle orientation by providing environmental cues to the RPCs. In vivo deletion of laminin β2 in mice of both sexes results in a loss RPC basal processes and contact with the ECM, leading to a shift of the mitotic spindle pole orientation toward asymmetric cell divisions. This leads to decreased proliferation and premature RPC pool depletion, resulting in overproduction of rod photoreceptors at the expense of bipolar cells and Müller glia. Moreover, we show that deletion of laminin β2 leads to disruption and mislocalization of its receptors: dystroglycan and β1-integrin. Addition of exogenous β2-containing laminins to laminin β2-deficient retinal explants stabilizes the RPC basal processes and directs their mitotic spindle orientation toward symmetric divisions, leading to increased RPC proliferation, as well as restores proper receptor localization at the retinal surface. Finally, functional blocking of dystroglycan in wild-type retinal explants phenocopies laminin β2 ablation. Our data suggest that dystroglycan-mediated signaling between RPCs and the ECM is of key importance in controlling critical developmental events during retinogenesis.

SIGNIFICANCE STATEMENT The mechanisms governing retinogenesis are subject to both intrinsic and extrinsic signaling cues. Although the role of intrinsic signaling has been the subject of many studies, our understanding of the role of the microenvironment in retinal development remains unclear. Using a combination of in vivo and ex vivo approaches, we demonstrate that laminins, key extracellular matrix components, provide signaling cues that control retinal progenitor cell attachment to the basement membrane, mitotic axis, proliferation, and fate adoption. Moreover, we identify, for the first time, dystroglycan as the receptor responsible for directing retinal progenitor cell mitotic spindle orientation. Our data suggest a mechanism where dystroglycan-mediated signaling between the cell and the extracellular matrix controls the proliferative potential of progenitors in the developing CNS.

Chemogenetic Activation of Prefrontal Cortex Rescues Synaptic and Behavioral Deficits in a Mouse Model of 16p11.2 Deletion Syndrome

Microdeletion of the human 16p11.2 gene locus has been linked to autism spectrum disorder (ASD) and intellectual disability and confers risk for a number of other neurodevelopmental deficits. Transgenic mice carrying 16p11.2 deletion (16p11^+/–) display phenotypes reminiscent of those in human patients with 16p11.2 deletion syndrome, but the molecular mechanisms and treatment strategies for these phenotypes remain unknown. In this study, we have found that both male and female 16p11^+/– mice exhibit deficient NMDA receptor (NMDAR) function in the medial prefrontal cortex (mPFC), a brain region critical for high-level "executive" functions. Elevating the activity of mPFC pyramidal neurons with a CaMKII-driven Gq-DREADD (Gq-coupled designer receptors exclusively activated by designer drugs) led to the significant increase of NR2B subunit phosphorylation and the restoration of NMDAR function, as well as the amelioration of cognitive and social impairments in 16p11^+/– mice. These results suggest that NMDAR hypofunction in PFC may contribute to the pathophysiology of 16p11.2 deletion syndrome and that restoring PFC activity is sufficient to rescue the behavioral deficits.

SIGNIFICANCE STATEMENT The 16p11.2 deletion syndrome is strongly associated with autism spectrum disorder and intellectual disability. Using a mouse model carrying the 16p11.2 deletion, 16p11^+/–, we identified NMDA receptor hypofunction in the prefrontal cortex (PFC). Elevating the activity of PFC pyramidal neurons with a chemogenetic tool, Gq-DREADD, led to the restoration of NMDA receptor function and the amelioration of cognitive and social impairments in 16p11^+/– mice. These results have revealed a novel route for potential therapeutic intervention of 16p11.2 deletion syndrome.

Recommendations for the Design and Analysis of In Vivo Electrophysiology Studies

Cell-Type-Specific Role of {Delta}FosB in Nucleus Accumbens In Modulating Intermale Aggression

A growing number of studies implicate the brain's reward circuitry in aggressive behavior. However, the cellular and molecular mechanisms within brain reward regions that modulate the intensity of aggression as well as motivation for it have been underexplored. Here, we investigate the cell-type-specific influence of FosB, a transcription factor known to regulate a range of reward and motivated behaviors, acting in the nucleus accumbens (NAc), a key reward region, in male aggression in mice. We show that FosB is specifically increased in dopamine D1 receptor (Drd1)-expressing medium spiny neurons (D1-MSNs) in NAc after repeated aggressive encounters. Viral-mediated induction of FosB selectively in D1-MSNs of NAc intensifies aggressive behavior without affecting the preference for the aggression-paired context in a conditioned place preference (CPP) assay. In contrast, FosB induction selectively in D2-MSNs reduces the time spent exploring the aggression-paired context during CPP without affecting the intensity of aggression per se. These data strongly support a dissociable cell-type-specific role for FosB in the NAc in modulating aggression and aggression reward.

SIGNIFICANCE STATEMENT Aggressive behavior is associated with several neuropsychiatric disorders and can be disruptive for affected individuals as well as their victims. Studies have shown a positive reinforcement mechanism underlying aggressive behavior that shares many common features with drug addiction. Here, we explore the cell-type-specific role of the addiction-associated transcription factor FosB in the nucleus accumbens in aggression. We found that FosB expression promotes aggressive behavior, effects that are dissociable from its effects on aggression reward. This finding is a significant first step in identifying therapeutic targets for the reduction of aggressive behavior across a range of neuropsychiatric illnesses.

A{beta}-Mediated Dysregulation of F-Actin Nanoarchitecture Leads to Loss of Dendritic Spines and Alzheimer's Disease-Related Cognitive Impairments

Modality-Independent Coding of Scene Categories in Prefrontal Cortex

Natural environments convey information through multiple sensory modalities, all of which contribute to people's percepts. Although it has been shown that visual or auditory content of scene categories can be decoded from brain activity, it remains unclear how humans represent scene information beyond a specific sensory modality domain. To address this question, we investigated how categories of scene images and sounds are represented in several brain regions. A group of healthy human subjects (both sexes) participated in the present study, where their brain activity was measured with fMRI while viewing images or listening to sounds of different real-world environments. We found that both visual and auditory scene categories can be decoded not only from modality-specific areas, but also from several brain regions in the temporal, parietal, and prefrontal cortex (PFC). Intriguingly, only in the PFC, but not in any other regions, categories of scene images and sounds appear to be represented in similar activation patterns, suggesting that scene representations in PFC are modality-independent. Furthermore, the error patterns of neural decoders indicate that category-specific neural activity patterns in the middle and superior frontal gyri are tightly linked to categorization behavior. Our findings demonstrate that complex scene information is represented at an abstract level in the PFC, regardless of the sensory modality of the stimulus.

SIGNIFICANCE STATEMENT Our experience in daily life includes multiple sensory inputs, such as images, sounds, or scents from the surroundings, which all contribute to our understanding of the environment. Here, for the first time, we investigated where and how in the brain information about the natural environment from multiple senses is merged to form modality-independent representations of scene categories. We show direct decoding of scene categories across sensory modalities from patterns of neural activity in the prefrontal cortex (PFC). We also conclusively tie these neural representations to human categorization behavior by comparing patterns of errors between a neural decoder and behavior. Our findings suggest that PFC is a central hub for integrating sensory information and computing modality-independent representations of scene categories.

Preferential Targeting of Lateral Entorhinal Inputs onto Newly Integrated Granule Cells

Mature dentate granule cells in the hippocampus receive input from the entorhinal cortex via the perforant path in precisely arranged lamina, with medial entorhinal axons innervating the middle molecular layer and lateral entorhinal cortex axons innervating the outer molecular layer. Although vastly outnumbered by mature granule cells, adult-generated newborn granule cells play a unique role in hippocampal function, which has largely been attributed to their enhanced excitability and plasticity (Schmidt-Hieber et al., 2004; Ge et al., 2007). Inputs from the medial and lateral entorhinal cortex carry different informational content. Thus, the distribution of inputs onto newly integrated granule cells will affect their function in the circuit. Using retroviral labeling in combination with selective optogenetic activation of medial or lateral entorhinal inputs, we examined the functional innervation and synaptic maturation of newly generated dentate granule cells in the mouse hippocampus. Our results indicate that lateral entorhinal inputs provide the majority of functional innervation of newly integrated granule cells at 21 d postmitosis. Despite preferential functional targeting, the dendritic spine density of immature granule cells was similar in the outer and middle molecular layers, which we speculate could reflect an unequal distribution of shaft synapses. However, chronic blockade of neurotransmitter release of medial entorhinal axons with tetanus toxin disrupted normal synapse development of both medial and lateral entorhinal inputs. Our results support a role for preferential lateral perforant path input onto newly generated neurons in mediating pattern separation, but also indicate that medial perforant path input is necessary for normal synaptic development.

SIGNIFICANCE STATEMENT The formation of episodic memories involves the integration of contextual and spatial information. Newly integrated neurons in the dentate gyrus of the hippocampus play a critical role in this process, despite constituting only a minor fraction of the total number of granule cells. Here we demonstrate that these neurons preferentially receive information thought to convey the context of an experience. Each newly integrated granule cell plays this unique role for ~1 month before reaching maturity.

This Week in The Journal

nox2/cybb Deficiency Affects Zebrafish Retinotectal Connectivity

NADPH oxidase (Nox)-derived reactive oxygen species (ROS) have been linked to neuronal polarity, axonal outgrowth, cerebellar development, regeneration of sensory axons, and neuroplasticity. However, the specific roles that individual Nox isoforms play during nervous system development in vivo remain unclear. To address this problem, we investigated the role of Nox activity in the development of retinotectal connections in zebrafish embryos. Zebrafish broadly express four nox genes (nox1, nox2/cybb, nox5, and duox) throughout the CNS during early development. Application of a pan-Nox inhibitor, celastrol, during the time of optic nerve (ON) outgrowth resulted in significant expansion of the ganglion cell layer (GCL), thinning of the ON, and a decrease in retinal axons reaching the optic tectum (OT). With the exception of GCL expansion, these effects were partially ameliorated by the addition of H₂O₂, a key ROS involved in Nox signaling. To address isoform-specific Nox functions, we used CRISPR/Cas9 to generate mutations in each zebrafish nox gene. We found that nox2/cybb chimeric mutants displayed ON thinning and decreased OT innervation. Furthermore, nox2/cybb homozygous mutants (nox2/cybb^–/–) showed significant GCL expansion and mistargeted retinal axons in the OT. Neurite outgrowth from cultured zebrafish retinal ganglion cells was reduced by Nox inhibitors, suggesting a cell-autonomous role for Nox in these neurons. Collectively, our results show that Nox2/Cybb is important for retinotectal development in zebrafish.

SIGNIFICANCE STATEMENT Most isoforms of NADPH oxidase (Nox) only produce reactive oxygen species (ROS) when activated by an upstream signal, making them ideal candidates for ROS signaling. Nox enzymes are present in neurons and their activity has been shown to be important for neuronal development and function largely by in vitro studies. However, whether Nox is involved in the development of axons and formation of neuronal connections in vivo has remained unclear. Using mutant zebrafish embryos, this study shows that a specific Nox isoform, Nox2/Cybb, is important for the establishment of axonal connections between retinal ganglion cells and the optic tectum.

Pre-Bout Neural Activity Changes in Premotor Nucleus HVC Correlate with Successful Initiation of Learned Song Sequence

Preparatory activity, characterized by gradual, longer timescale changes in neural activity, is present in a number of different brain areas before the onset of simple movements and is believed to be important for movement initiation. However, relatively little is known about such activity before initiation of naturally learned movement sequences. The song of an adult male zebra finch is a well studied example of a naturally learned movement sequence and previous studies have shown robust premotor activity immediately before song. Here, I characterize longer timescale changes in neural activity in adult male zebra finch premotor nucleus HVC before onset of song bouts. I show that interneurons and a subset of basal-ganglia-projecting neurons change their activity several hundred milliseconds before song bout onset. Interneurons increased their activity, whereas basal-ganglia-projecting neurons either increased or decreased their activity. Such changes in neural activity were larger, started earlier, and were more common specifically before song bouts that began with the short, repetitive, introductory notes (INs) characteristic of zebra finch song bouts. Further, stronger and earlier changes were also correlated with successful song sequence initiation. Finally, a small fraction of basal-ganglia-projecting neurons that increased their activity before song bout onset did not have song or IN-related activity, suggesting a specialized preparatory role for such neurons. Overall, these data suggest that pre-bout activity in HVC represents preparatory activity important for initiation of a naturally learned movement sequence.

SIGNIFICANCE STATEMENT Changes in neuronal activity well before the onset of simple movements are thought to be important for movement initiation. However, a number of animal movements consist of sequences of simple movements and relatively little is known about neuronal activity before such movement sequences. Using adult zebra finch song, a well studied example of a movement sequence, I show here that neurons in premotor nucleus HVC change their activity hundreds of milliseconds before song bout onset. In most neurons, the presence of such changes correlated with successful song sequence initiation. My results show the presence of preparatory neural activity in HVC and suggest a role for HVC in sequence initiation in addition to its established role in song sequence timing.

Lrfn2-Mutant Mice Display Suppressed Synaptic Plasticity and Inhibitory Synapse Development and Abnormal Social Communication and Startle Response

SALM1 (SALM (synaptic adhesion-like molecule), also known as LRFN2 (leucine rich repeat and fibronectin type III domain containing), is a postsynaptic density (PSD)-95-interacting synaptic adhesion molecule implicated in the regulation of NMDA receptor (NMDAR) clustering largely based on in vitro data, although its in vivo functions remain unclear. Here, we found that mice lacking SALM1/LRFN2 (Lrfn2^–/– mice) show a normal density of excitatory synapses but altered excitatory synaptic function, including enhanced NMDAR-dependent synaptic transmission but suppressed NMDAR-dependent synaptic plasticity in the hippocampal CA1 region. Unexpectedly, SALM1 expression was detected in both glutamatergic and GABAergic neurons and Lrfn2^–/– CA1 pyramidal neurons showed decreases in the density of inhibitory synapses and the frequency of spontaneous inhibitory synaptic transmission. Behaviorally, ultrasonic vocalization was suppressed in Lrfn2^–/– pups separated from their mothers and acoustic startle was enhanced, but locomotion, anxiety-like behavior, social interaction, repetitive behaviors, and learning and memory were largely normal in adult male Lrfn2^–/– mice. These results suggest that SALM1/LRFN2 regulates excitatory synapse function, inhibitory synapse development, and social communication and startle behaviors in mice.

SIGNIFICANCE STATEMENT Synaptic adhesion molecules regulate synapse development and function, which govern neural circuit and brain functions. The SALM/LRFN (synaptic adhesion-like molecule/leucine rich repeat and fibronectin type III domain containing) family of synaptic adhesion proteins consists of five known members for which the in vivo functions are largely unknown. Here, we characterized mice lacking SALM1/LRFN2 (SALM1 KO) known to associate with NMDA receptors (NMDARs) and found that these mice showed altered NMDAR-dependent synaptic transmission and plasticity, as expected, but unexpectedly also exhibited suppressed inhibitory synapse development and synaptic transmission. Behaviorally, SALM1 KO pups showed suppressed ultrasonic vocalization upon separation from their mothers and SALM1 KO adults showed enhanced responses to loud acoustic stimuli. These results suggest that SALM1/LRFN2 regulates excitatory synapse function, inhibitory synapse development, social communication, and acoustic startle behavior.

Increased Microglial Activity, Impaired Adult Hippocampal Neurogenesis, and Depressive-like Behavior in Microglial VPS35-Depleted Mice

Vacuolar sorting protein 35 (VPS35) is a critical component of retromer, which is essential for selective endosome-to-Golgi retrieval of membrane proteins. VPS35 deficiency is implicated in neurodegenerative disease pathology, including Alzheimer's disease (AD). However, exactly how VPS35 loss promotes AD pathogenesis remains largely unclear. VPS35 is expressed in various types of cells in the brain, including neurons and microglia. Whereas neuronal VPS35 plays a critical role in preventing neurodegeneration, the role of microglial VPS35 is largely unknown. Here we provide evidence for microglial VPS35's function in preventing microglial activation and promoting adult hippocampal neurogenesis. VPS35 is expressed in microglia in various regions of the mouse brain, with a unique distribution pattern in a brain region-dependent manner. Conditional knocking out of VPS35 in microglia of male mice results in regionally increased microglial density and activity in the subgranular zone of the hippocampal dentate gyrus (DG), accompanied by elevated neural progenitor proliferation, but decreased neuronal differentiation. Additionally, newborn neurons in the mutant DG show impaired dendritic morphology and reduced dendritic spine density. When examining the behavioral phenotypes of these animals, microglial VPS3S-depleted mice display depression-like behavior and impairment in long-term recognition memory. At the cellular level, VPS35-depleted microglia have grossly enlarged vacuolar structures with increased phagocytic activity toward postsynaptic marker PSD95, which may underlie the loss of dendritic spines observed in the mutant DG. Together, these findings identify an important role of microglial VPS35 in suppressing microglial activation and promoting hippocampal neurogenesis, which are both processes involved in AD pathogenesis.

SIGNIFICANCE STATEMENT The findings presented here provide the first in vivo evidence that Vacuolar sorting protein 35 (VPS35)/retromer is essential for regulating microglial function and that when microglial retromer mechanics are disrupted, the surrounding brain tissue can be affected in a neurodegenerative manner. These findings present a novel, microglial-specific role of VPS35 and raise multiple questions regarding the mechanisms underlying our observations. These findings also have myriad implications for the field of retromer research and the role of retromer dysfunction in neurodegenerative pathophysiology. Furthermore, they implicate a pivotal role of microglia in the regulation of adult hippocampal neurogenesis and the survival/integration of newborn neurons in the adult hippocampus.

Copine-6 Binds to SNAREs and Selectively Suppresses Spontaneous Neurotransmission

Recent studies suggest that spontaneous and action potential-evoked neurotransmitter release processes are independently regulated. However, the mechanisms that uncouple the two forms of neurotransmission remain unclear. In cultured mouse and rat neurons, we show that the two C2 domain-containing protein copine-6 is localized to presynaptic terminals and binds to synaptobrevin2 as well as other SNARE proteins in a Ca²⁺-dependent manner. Ca²⁺-dependent interaction of copine-6 with synaptobrevin2 selectively suppresses spontaneous neurotransmission in a reaction that requires the tandem tryptophan residues at the C-terminal region of synaptobrevin2. Accordingly, copine-6 loss of function augmented presynaptic Ca²⁺ elevation-mediated neurotransmitter release. Intracellular Ca²⁺ chelation, on the other hand, occluded copine-6-mediated suppression of release. We also evaluated the molecular specificity of the copine-6-dependent regulation of spontaneous release and found that overexpression of copine-6 did not suppress spontaneous release in synaptobrevin2-deficient neurons. Together, these results suggest that copine-6 acts as a specific Ca²⁺-dependent suppressor of spontaneous neurotransmission.

SIGNIFICANCE STATEMENT Synaptic transmission occurs both in response to presynaptic action potentials and spontaneously, in the absence of stimulation. Currently, much more is understood about the mechanisms underlying action potential-evoked neurotransmission compared with spontaneous release. However, recent studies have shown selective modulation of spontaneous neurotransmission process by several neuromodulators, suggesting specific molecular regulation of spontaneous release. In this study, we identify copine-6 as a specific regulator of spontaneous neurotransmission. By both gain-of-function and loss-of-function experiments, we show that copine-6 functions as a Ca²⁺-dependent suppressor of spontaneous release. These results further elucidate the mechanisms underlying differential regulation of evoked and spontaneous neurotransmitter release.

Blocking Autophagy in Oligodendrocytes Limits Functional Recovery after Spinal Cord Injury

Autophagy mechanisms are well documented in neurons after spinal cord injury (SCI), but the direct functional role of autophagy in oligodendrocyte (OL) survival in SCI pathogenesis remains unknown. Autophagy is an evolutionary conserved lysosomal-mediated catabolic pathway that ensures degradation of dysfunctional cellular components to maintain homeostasis in response to various forms of stress, including nutrient deprivation, hypoxia, reactive oxygen species, DNA damage, and endoplasmic reticulum (ER) stress. Using pharmacological gain and loss of function and genetic approaches, we investigated the contribution of autophagy in OL survival and its role in the pathogenesis of thoracic contusive SCI in female mice. Although upregulation of Atg5 (an essential autophagy gene) occurs after SCI, autophagy flux is impaired. Purified myelin fractions of contused 8 d post-SCI samples show enriched protein levels of LC3B, ATG5, and BECLIN 1. Data show that, while the nonspecific drugs rapamycin (activates autophagy) and spautin 1 (blocks autophagy) were pharmacologically active on autophagy in vivo, their administration did not alter locomotor recovery after SCI. To directly analyze the role of autophagy, transgenic mice with conditional deletion of Atg5 in OLs were generated. Analysis of hindlimb locomotion demonstrated a significant reduction in locomotor recovery after SCI that correlated with a greater loss in spared white matter. Immunohistochemical analysis demonstrated that deletion of Atg5 from OLs resulted in decreased autophagic flux and was detrimental to OL function after SCI. Thus, our study provides evidence that autophagy is an essential cytoprotective pathway operating in OLs and is required for hindlimb locomotor recovery after thoracic SCI.

SIGNIFICANCE STATEMENT This study describes the role of autophagy in oligodendrocyte (OL) survival and pathogenesis after thoracic spinal cord injury (SCI). Modulation of autophagy with available nonselective drugs after thoracic SCI does not affect locomotor recovery despite being pharmacologically active in vivo, indicating significant off-target effects. Using transgenic mice with conditional deletion of Atg5 in OLs, this study definitively identifies autophagy as an essential homeostatic pathway that operates in OLs and exhibits a direct functional role in SCI pathogenesis and recovery. Therefore, this study emphasizes the need to discover novel autophagy-specific drugs that specifically modulate autophagy for further investigation for clinical translation to treat SCI and other CNS pathologies related to OL survival.

h-Type Membrane Current Shapes the Local Field Potential from Populations of Pyramidal Neurons

In cortex, the local field potential (LFP) is thought to mainly stem from correlated synaptic input to populations of geometrically aligned neurons. Computer models of single cortical pyramidal neurons showed that subthreshold voltage-dependent membrane conductances can also shape the LFP signal, in particular the hyperpolarization-activated cation current (I_h; h-type). This ion channel is prominent in various types of pyramidal neurons, typically showing an increasing density gradient along the apical dendrites. Here, we investigate how I_h affects the LFP generated by a model of a population of cortical pyramidal neurons. We find that the LFP from populations of neurons that receive uncorrelated synaptic input can be well predicted by the LFP from single neurons. In this case, when input impinges on the distal dendrites, where most h-type channels are located, a strong resonance in the LFP was measured near the soma, whereas the opposite configuration does not reveal an I_h contribution to the LFP. Introducing correlations in the synaptic inputs to the pyramidal cells strongly amplifies the LFP, while maintaining the differential effects of I_h for distal dendritic versus perisomatic input. Previous theoretical work showed that input correlations do not amplify LFP power when neurons receive synaptic input uniformly across the cell. We find that this crucially depends on the membrane conductance distribution: the asymmetric distribution of I_h results in a strong amplification of the LFP when synaptic inputs to the cell population are correlated. In conclusion, we find that the h-type current is particularly suited to shape the LFP signal in cortical populations.

SIGNIFICANCE STATEMENT The local field potential (LFP), the low-frequency part of extracellular potentials recorded in neural tissue, is often used for probing neural circuit activity. While the cortical LFP is thought to mainly reflect synaptic inputs onto pyramidal neurons, little is known about the role of subthreshold active conductances in shaping the LFP. By means of biophysical modeling we obtain a comprehensive, qualitative understanding of how LFPs generated by populations of cortical pyramidal neurons depend on active subthreshold currents, and identify the key importance of the h-type channel. Our results show that LFPs can give information about the active properties of neurons and that preferred frequencies in the LFP can result from those cellular properties instead of, for example, network dynamics.

Incidence of Lyme Disease Diagnosis in a Maryland Medicaid Population, 2004-2011

Abstract

The epidemiology of Lyme disease has been examined utilizing insurance claims from privately insured individuals; however, it is unknown whether reported patterns vary among the publically insured. We examined incidence rate trends of first Lyme disease diagnosis among 384,652 Maryland Medicaid members enrolled from July 2004-June 2011. Age, gender, county, season, and year-specific incidence rates were calculated, and mixed effects multiple logistic regression models were used to study the relationship between diagnosis and these variables. The incidence rate in our sample was 97.65 per 100,000 person-years (95% confidence interval (CI): 91.53, 104.06), and there was a 13% average annual increase in odds of diagnosis (odds ratio: 1.13, 95% CI: 1.09, 1.17, P < 0.001). Incidence rates for males and females were not significantly different, though males were significantly more likely to be diagnosed during high season months (relative risk [RR]: 1.24, 95% CI: 1.06, 1.44) and less likely to be diagnosed during low season months (RR: 0.63, 95% CI: 0.46, 0.87) than females. Additionally, adults were significantly more likely to be diagnosed during low season months (RR: 1.59, 95% CI: 1.19, 2.12) than children. While relatively rare, Lyme disease diagnoses do occur in a Medicaid population in a Lyme-endemic state.

Can e-Cigarettes and Pharmaceutical Aids Increase Smoking Cessation and Reduce Cigarette Consumption? Findings from a Nationally Representative Cohort of American Smokers

Abstract

Many smokers believe that electronic nicotine delivery systems (ENDS) and pharmaceutical cessation aids can help them quit smoking or reduce cigarette consumption, but the evidence for e-cigarettes to aid quitting is limited. Examining 3,093 quit attempters in the nationally-representative US Population Assessment of Tobacco and Health (PATH) Study between 2013 and 2015, we evaluated the influence of ENDS and pharmaceutical cessation aids on persistent abstinence (≥30 days) from cigarettes, and reduced cigarette consumption, using Propensity Score Matching to balance comparison groups on potential confounders and multiple imputation to handle missing data. At PATH Wave 2, 25.2% of quit attempters reported using ENDS to quit during the previous year, making it the most popular cessation aid in 2014-15. More quit attempters were persistently cigarette abstinent than persistently tobacco abstinent (15.5±0.8% vs 9.6±0.6%). Using ENDS to quit cigarettes increased the probability of persistent cigarette abstinence at Wave 2 (Risk Difference (RD)=6%; 95% CI: 2%;10%), but using approved pharmaceutical aids did not (varenicline RD=2%; 95% CI: -6%,13%; buproprion RD=4%, 95% CI: -6%, 17%; NRT RD=-3%, 95% CI -8%, 2%). Among quit attempters who relapsed, ENDS did not reduce the average daily cigarette consumption (-0.18 cigarettes per day; 95% CI: -1.87;1.51).

Cardiovascular Risk Factors, Depression, and Alcohol Consumption During Joblessness and During Recessions in CARDIA Young Adults

Abstract

Research has shown that recessions are associated with lower cardiovascular mortality but unemployed individuals have a higher risk of cardiovascular disease (CVD) or death. We used data from eight consecutive exams (1985-2011) of the CARDIA cohort, modeled in fixed-effect panel regressions, to investigate simultaneously the associations of CVD risk factors with (a) the employment status of individuals, and (b) macroeconomic conditions prevalent at the state where the individual lives. We found that unemployed individuals had lower levels of blood pressure, HDL-cholesterol, and physical activity, and significantly higher depression scores, but they were like their counterparts in smoking status, alcohol consumption, LDL cholesterol levels, body mass index, and waist circumference. One percentage point higher unemployment rate at the state level was associated with lower systolic (-0.41 mmHg, 95%CI: -0.65, -0.17) and diastolic (-0.19, 95%CI: -0.39, 0.01) blood pressure, higher physical activity levels, higher depressive symptom scores, and lower waist circumference and smoking. We conclude that levels of CVD risk factors tend to improve during recessions, but mental health tends to deteriorate. Unemployed individuals are significantly more depressed, and likely have lower levels of physical activity and HDL.

A Bayesian approach to understanding gender differences in tuberculosis disease burden

Abstract

Globally, men have a higher epidemiological burden of tuberculosis (incidence, prevalence, mortality) than women, possibly due to differences in disease incidence, treatment initiation, self-cure and/or untreated-tuberculosis mortality rates. Using a simple, gender-stratified compartmental model, we employed a Bayesian approach to explore which factors most likely explain men's higher burden. We applied the model to smear-positive pulmonary tuberculosis in Viet Nam (2006-07) and Malawi (2013-14). Posterior estimates were consistent with gender-specific prevalence and notifications in both countries. Results supported higher incidence in men and showed that both genders faced longer durations of untreated disease than estimated by self-reports. Prior untreated disease durations were revised upwards 8- to 24-fold, to 2.2 (95% credible interval: 1.7, 2.9) and 2.8 (1.8, 4.1) years for men in Viet Nam and Malawi, respectively, approximately a year longer than for women in each country. Results imply that substantial gender differences in tuberculosis burden are almost solely attributable to men's disadvantages in disease incidence and untreated disease duration. The latter, for which self-reports provide a poor proxy, implies inadequate coverage of case finding strategies. These results highlight an urgent need for better understanding of gender-specific barriers faced by men and support the systematic targeting of men for screening.

Visible light-induced biocidal activities and mechanistic study of neutral porphyrin derivatives against S. aureus and E. coli

Publication date: August 2018
Source:Journal of Photochemistry and Photobiology B: Biology, Volume 185
Author(s): Jing Wang, Xia Yang, Hu Song, Wei Liao, Liangang Zhuo, Guanquan Wang, Hongyuan Wei, Yuchuan Yang, Shunzhong Luo, Zhijun Zhou
Positive charged porphyrins have long been regarded as effective biocidal agents, however neutral porphyrins have rarely been studied in their ability photoinactivating microbials, and the structure-activity relationship such as correlation of electronic effect and biocidal activity of porphyrins still remains unclear. Herein, four neutral porphyrins with various electronic effects were selected to undergo light-induced biocidal processes. It turned out that the TPPOH and TPPNH2 with electron-donating groups NH2 and OH, respectively, exhibited much more powerful light-induced biocidal activities against E. coli and S. aureus than TPP and TPPNO2 with electron-withdrawing group NO2. This phenomenon suggested that neutral porphyrins may be treated as a new class of biocidal agents and functional groups with various electronic effects on porphyrins can dramatically affect porphyrins' light-induced biocidal activities. Mechanistic studies demonstrate that despite a better light-induced antibacterial ability of TPPOH, its singlet oxygen generation efficacy is a little lower than that of TPPNH2, together with charge characteristics and lipophilicity, it is clear that (1) the oxidative species singlet oxygen and ROS played the key role in the photo-activated antimicrobial processes of porphyrins, and (2) higher singlet oxygen or ROS yields of TPPOH and TPPNH2 may originate from their structural characteristics, namely electron-donating groups OH or NH2, and (3) a synergistic effect of all other factors including the electrostatic and hydrophobic effects must involve in the process and cooperatively determine their biocidal activities.

Graphical abstract

Is it time to reconsider the role of irinotecan for the treatment of high-grade gliomas?

Irinotecan is a topoisomerase 1 inhibitor that is converted to the active metabolite SN-38 by carboxylesterase.¹ Based on preclinical data showing that irinotecan had activity against gliomas, and the assumption that irinotecan crossed the blood–brain barrier (BBB), a single arm phase II study was conducted in 60 patients with recurrent high-grade gliomas (HGGs).² This study used an irinotecan dose of 125 mg/m² once weekly for 4 weeks followed by a 2-week rest, and reported a partial response rate of 15%, with 55% of patients having stable disease for at least 12 weeks. These results suggested that irinotecan had activity in this patient population and led to the adoption of this agent for treatment of recurrent HGG.

Clinical and Laboratory Markers of Relapse in Cutaneous Polyarteritis Nodosa

This case series identifies clinical and laboratory markers that may be associated with relapse among patients with cutaneous polyarteritis nodosa.

Targeting Tropomyosin Receptor Kinase in Cutaneous CYLD Defective Tumors With Pegcantratinib

This phase 2 randomized clinical trial investigates if topical targeting of topical tropomyosin receptor kinase (TRK) inhibitor, pegcantratinib, is safe and efficacious in treating tumors in patients with CYLD cutaneous syndrome.

Cutavirus Infection in Primary Cutaneous B- and T-Cell Lymphoma

This virological study examines the association of cutavirus DNA with different types of cutaneous B-cell lymphoma and cutaneous T-cell lymphoma in lesional skin samples.

Strengthening the Case for the Role of Thrombophilia in Calciphylaxis

In Reply We thank Hickson and colleagues for their interest in our Original Investigation titled "Association Between Hypercoagulable Conditions and Calciphylaxis in Patients With Renal Disease: A Case-Control Study" on the role of hypercoagulable conditions in the development of calciphylaxis in patients with renal disease.

Strengthening the Case for the Role of Thrombophilia in Calciphylaxis

To the Editor We read with interest the article by Dobry et al, whose findings support our research group's prior investigations, thus underscoring the central role of congenital and acquired thrombophilia in the pathogenesis of calciphylaxis. There were methodologic differences between these studies that improve our understanding of this complex disease.

Decision Tree Model vs Traditional Measures for Associations of Sun-Protective Behaviors

This cross-sectional national survey assesses whether decision-based modeling can identify patterns of sun-protective behaviors and sun sensitivity associated with the likelihood of sunburn among US adults.

Assessing the Competence of Aging Physicians Who Are Young at Heart

This Viewpoint discusses the issues involved in assessing the professional competence of aging physicians as increasing numbers of physicians continue to work past the age of 65 years.

Increased leaching and addition of amendments improve the properties of seawater-neutralized bauxite residue as a growth medium

Abstract

Laboratory and greenhouse experiments were carried out to investigate the chemical, physical, and microbial properties of seawater-neutralized bauxite residues and the effects of additional leaching (1 pore volume of deionized water versus an additional 6 pore volumes) and amendment with gypsum (5%) and/or cattle manure (6%) on its properties and on the growth of Rhodes grass (Chloris gayana). Additional leaching resulted in a decrease in EC, exchangeable Na, SAR, and ESP. For unamended control treatments, additional leaching induced a rise in pH_SE from 8.5 to 9.6 and pH_1:5 from 9.1 to 10.1 due to dissolution of residual alkalinity. Addition of gypsum arrested this pH increase resulting in a final pH_SE of 7.5 and pH_1:5 of 8.8. In control treatments, additional leaching resulted in a pronounced decrease in Rhodes grass yields. However, in gypsum and cattle manure-amended treatments, it led to substantial yield increases and decreases in tissue Al and Na concentrations and increased K/Na ratios. Upon drying for the first time, bauxite residue was shown to contract and form a solid massive structure. The aggregates formed from crushing this material were water stable (as measured by wet sieving). Additions of cattle manure or gypsum to residue aggregates did not affect pore size distribution. Addition of cattle manure increased organic C and microbial biomass C content and basal respiration rate while additional leaching increased basal respiration and metabolic quotient. It was concluded that a combination of drying and crushing the residue, amending it with gypsum and organic manure followed by extensive leaching results in the formation of a medium that supports plant growth.

Properties and effects of organic additives on performance and emission characteristics of diesel engine: a comprehensive review

Abstract

Fast depletion of conventional automobile fuels and environmental pollution due to exhaust emission are the issues of great importance. Improvement in engine performance and emission control is quite difficult to handle simultaneously. The fuel properties can be improved substantially by incorporation of additives in different proportions to get better emission standard without deteriorating the engine performance. The aim of current study is to review/summarize the effects of various organic additives on the engine performance (i.e., brake thermal efficiency, brake specific fuel consumption, volumetric efficiency, etc.) and emissions (i.e., carbon dioxide, carbon monoxide, nitrogen oxides, hydrocarbons, particulate matter, and other harmful compounds). The physico-chemical and combustion properties (i.e., density, latent heat, dynamic viscosity, flash point, boiling point, cetane number, oxygen content, lower heating value, auto-ignition temperature, etc.) of various additives were also discussed to check the suitability of additives with diesel. Finally, limitations and opportunities using organic additives with respect to engine performance and combustion were discussed to guide future research and improvement in this field.

Chiral triazole fungicide tebuconazole: enantioselective bioaccumulation, bioactivity, acute toxicity, and dissipation in soils

Abstract

Enantioselectivity in environmental behavior and toxic effect of chiral pesticides has been received much attention. In this study, enantioselective bioactivity towards target organism Botrytis cinerea, acute toxicity and bioaccumulation in Eisenia fetida, and degradation in five kinds of soil under laboratory conditions regarding triazole fungicide tebuconazole were investigated. The results showed that fungicidal activity to Botrytis cinerea of R-(−)-tebuconazole was 44 times higher than S-(+)-tebuconazole with an order of R-(−)-tebuconazole > rac-tebuconazole > S-(+)-tebuconazole. No significant difference was found in acute toxicity of rac-, R-, and S-tebuconazole to E. fetida with 48-h EC₅₀ of 10.78, 10.48, and 10.84 μg/cm², respectively. Dissipation of tebuconazole in the five tested soils varied upon soil characteristics with half-life ranging from 32.2 to 216.6 days. Enantioselective and rapid dissipation of tebuconazole were observed in soils Hainan and Huajiachi, compared to the other soils. Enantioselective accumulation of tebuconazole in E. fetida was found with a preferential of S-(+)-tebuconazole although no significant difference in acute toxicity to E. fetida between rac-tebuconazole and enantiomers. The results indicated that S-(+)-tebuconazole with less fungicidal activity may be more likely to be accumulated in earthworm E. fetida. This research is helpful to better evaluate the environmental and ecological risk of tebuconazole on enantiomeric level.

Solvent effect on endosulfan adsorption onto polymeric arginine-methacrylate cryogels

Abstract

Endosulfan is a persistent insecticide that is still used in some countries even though it is life-threatening and banned in the agricultural struggle. The solubility of pesticides in water is negligible. It is known that pesticides with better solubility in organic solvents have different solubility when the dielectric constants of these solvents are taken into account. The polymeric structure of arginine was modified with methacrylate to be a functional monomer, and it was immobilized on a solid support, poly(HEMA), and finally, poly(2-hydroxyethyl methacrylate-arginine methacrylate) was obtained and used as an effective adsorbent. The effect of organic solvents on endosulfan adsorption was investigated for the first time in the literature. Endosulfan was removed from alcohol media by using this polymeric structure synthesized by exploiting alcoho-phobic interaction in this work. Nuclear magnetic resonance (NMR), elemental analysis, and Fourier transform infrared spectroscopy (FTIR) methods were used for the structural characterization and therefore to prove successful synthesis of cryogels. Morphological characteristics were also investigated by scanning electron microscopy (SEM), an N₂ adsorption method, and swelling test. Adsorption experiments were carried out against varying interaction time and concentration parameters in the batch system. Since the alcohol used as a solvent has a pH value close to the ionic strength of drinking water, no change was made in the pH of the solution. Endosulfan molecules dissolved in solvents such as toluene, dichloromethane, acetone, and chloroform were removed using poly(HEMA-ArMA) cryogels to determine the solvent effect on the adsorption of endosulfan. As expected, the removal of endosulfan from the solvent toluene provided the best result. Although the adsorption in toluene is almost 9.5 times higher than that in ethanol, the use of toluene in the adsorption process due to its chemical structure is not feasible. Thus, experiments were carried out in ethanol.

Source apportionment of heavy metals and their ecological risk in a tropical river basin system

Abstract

Surface water and sediment samples were collected from Ajay River basin to appraise the behavior of heavy metals with surrounding environments and their inter-elemental relationships. Parameters like pH and organic carbon are having a minimal role in heavy metal distribution while some elements like Fe and Cu showed great affinity for organic matter based on linear regression analysis (LRA). Ficklin diagram justified that river basin is not contaminated through acidic pollutants. The river basin is highly enriched with Cu, Cd, Pb, and Ni which were much higher than world average values, average shale standard, effect range low (ERL), and threshold effect level (TEL). PCA and LRA verified that Cu, Cd, Pb, and Ni were mainly derived from anthropogenic inputs, and others like Fe, Mn, Zn, and Co came from geogenic sources. Pollution indices revealed that river basin is moderately to highly contaminated by Cu, Cd, and Ni. Furthermore, Ajay River basin is under strong potential ecological risk based on the obtained value of risk index and probable effect level/effect range median quotient index. However, river basin is strongly influenced by lithological properties, diversified hydrogeological settings, mineralization and mobilization of subsurface materials, and urban and industrial effluents which are controlling the heavy metals.

Potential health impacts from different vegetable nitrate intake scenarios and providing strategies to manage the risks for Iranian population

Abstract

Health risk from nitrate was predicted for different scenarios of vegetable consumption and nitrate contents in Iran. Finally, certain management scenarios were presented for nitrate risk mitigation under worst-case scenario considering each vegetable contribution in nitrate intake. Two fruit (bell pepper and tomato) and two leafy vegetables (lettuce and mint) were sampled in a combined randomized method from fields, greenhouses, and markets of Isfahan province, Iran during October to December 2015. To assess the potential health impacts of nitrate from the vegetable ingestion, the present status and three different scenarios of increasing vegetable consumption and/or increasing plant nitrate concentrations were considered. Two management scenarios for reducing the total nitrate intake below the allowable values were predicted. By increasing vegetable consumption under scenario 1 and nitrate concentration under scenario 3, the total hazard quotient (THQs) was increased, although the highest increase (12-fold) in the THQs was provided by lettuce. Health risk from nitrate for sensitive groups was effectively reduced by a 70% decrease in lettuce nitrate concentration. In the second management scenario, decreasing upper nitrate concentrations in the other sources (except lettuce) by 30% declined nitrate intake in children (< 6 years old) and boys (7–14 years old) below acceptable daily intake (ADI). By taking into account the increases in the amounts of consumption and nitrate in vegetables at different scenarios, it was revealed that the critical factor for a high dietary exposure to nitrate is not the absolute amount of vegetables consumed but the type of vegetable (lettuce) and the concentration of nitrate related to the conditions of production. Therefore, to manage any risks to human health from dietary nitrate exposure resulting from vegetable consumption, focus on lettuce instead of taking other vegetables equally into account is needed.

Bacterial microbiome of root-associated endophytes of Salicornia europaea in correspondence to different levels of salinity

Abstract

The halophytes have evolved several strategies to survive in saline environments; however, an additional support from their associated microbiota helps combat adverse conditions. Hence, our driving interests to investigate the endophytic bacterial community richness, diversity, and composition associated to roots of Salicornia europaea from two test sites with different origins of soil salinity. We assumed that salinity will have a negative effect on the diversity of endophytes but simultaneously will permit the high occurrence of halophylic bacteria. Further, to establish the role of the host and its external environment in determining the endophytic diversity, we analyzed the physico-chemical parameters of root zone soil and the concentration of salt ions in the plant roots. The results based on the Miseq Illumina sequencing approach revealed a higher number of endophytic bacterial OTUs at naturally saline test site with a higher level of soil salinity. Proteobacteria and Bacteriodetes were the dominant endophytic phyla at both analyzed sites; additionally, the high occurrence of Planctomycetes and Acidobacteria at more saline site and the occurrence of Firmicutes, Actinobacteria, and Chloroflexi at less saline site were recorded. The salinity in the root zone soil was crucial in structuring the endophytic community of S. europaea, and the significant prevalence of representatives from the phyla Deltaproteobacteria, Acidobacteria, Caldithrix, Fibrobacteres, and Verrucomicrobia at the more saline test site suggest domination of halophylic bacteria with potential role in mitigation of salt stress of halophytes.

Predisposing factors that increase trigger digit incidence in carpal tunnel syndrome patients: A national, population-based study

Publication date: Available online 26 June 2018
Source:Journal of Plastic, Reconstructive & Aesthetic Surgery
Author(s): Y.F Yuki Fujihara, NF Nasa Fujihara, Michiro Yamamoto

Letter to the editor: Evaluation of anatomical and round breast implant aesthetics and preferences in Dutch young lay and plastic surgeon cohort

Publication date: Available online 27 June 2018
Source:Journal of Plastic, Reconstructive & Aesthetic Surgery
Author(s): Fengrui Cheng, Ying Cen

Refractory pityriasis rubra pilaris with good response after treatment with ustekinumab

JDDG: Journal der Deutschen Dermatologischen Gesellschaft, EarlyView.

Kinetics and thermodynamics of urea hydrolysis under the coupling of nitrogen application rate and temperature

Abstract

This study aimed to determine the coupled effects of temperature and urea application rate on kinetic and thermodynamic parameters to supplement the mechanism of urea hydrolysis and modify the Arrhenius model to improve the prediction accuracy of urea content. Laboratory experiments were conducted for sandy loam soil under different temperatures (T) (288, 293, 298, and 308 K) and urea application rates (F) (247, 309, 371, and 433 mg kg⁻¹). Urea content was determined daily through high-performance liquid chromatography. Results showed that the interaction between temperature and urea application rate had a significant effect on reaction rate (K_u) and half-life (H_1/2), whereas no significant effect on activation degree (lgN), activation free energy (ΔG), activation enthalpy (ΔH), and activation entropy (ΔS). The new K_u(T)-2 model with a determination coefficient (R²) = 0.990 was more accurate than the Arrhenius model with R² = 0.965. The new U(T, F) model with a mean absolute percentage error (MAPE) = 3.62% was more accurate than the traditional U(T) model with a MAPE = 6.38%. The effects of T and F were observed mainly during the preparatory stage and the most critical transition stage of the chemical reaction, respectively. The findings ΔH > 0, ΔG > 0, and ΔS < 0 indicated that urea hydrolysis was endothermic and controlled by enthalpy. These results supplemented the mechanism of urea hydrolysis and improved the prediction accuracy of urea content.

A novel method for sewage sludge composting using bamboo charcoal as a separating material

Abstract

Traditional composting processes must be conducted with a bulking agent to ensure adequate air space for aeration. The bulking agent and composting materials are always completely mixed. A novel layered structure was introduced in sewage sludge composting, in which no bulking agent was used and bamboo charcoal was used as a separating material. Three lab-scale composting reactors (A: sawdust and sludge; B: bamboo charcoal and sludge; and C: sawdust, bamboo charcoal, and sludge) were continuously operated for 29 days. Several physicochemical parameters were investigated to evaluate the feasibility of layered composting with bamboo charcoal. The results indicated that the maximum temperatures during the thermophilic stage in treatments A, B, and C were 51.4, 50.9, and 51 °C, respectively. Layered composting with bamboo charcoal decreased the pH of the thermophilic stage from 8.98 in A to 8.75 in C, and delayed the peaks by about 120 h. The degradation rates of dissolve organic carbon (DOC) and dissolved nitrogen (DN) were 75 and 71.5% in treatment B, respectively, which were significantly higher than those of control group A (60 and 59.1%, respectively). The total NH₃ emissions of treatment C (2127.8 mg) were significantly lower than those of A (2522.8 mg). Our results suggested that layered composting using bamboo charcoal as a separating material could be an alternative strategy to the traditional composting method. Moreover, layered composting combined with sawdust could effectively reduce NH₃ emissions and N loss.

Is conservative treatment an effective option for pilonidal sinus disease in children?

International Wound Journal, EarlyView.

A meta‐analysis of survival factors in rhino‐orbital‐cerebral mucormycosis – Has anything changed in the past 20 years?

Clinical Otolaryngology, Volume 0, Issue ja, -Not available-.

M/g-C 3 N 4 (M=Ag, Au, and Pd) composite: synthesis via sunlight photodeposition and application towards the degradation of bisphenol A

Abstract

In this work, natural sunlight successfully induced the deposition of gold (Au), silver (Ag), and palladium (Pd) nanoparticles (NPs) with 17.10, 9.07, and 12.70 wt% onto the surface of graphitic carbon nitride (g-C₃N₄). The photocatalytic evaluation was carried out by adopting Bisphenol A (BPA) as a pollutant under natural sunlight irradiation. The presence of noble metals was confirmed by EDX, HRTEM, and XPS analysis. The deposition of Ag NPs (7.9 nm) resulted in the degradation rate which was 2.15-fold higher than pure g-C₃N₄ due to its relatively small particle size, contributing to superior charge separation efficiency. Au/g-C₃N₄ unveiled inferior photoactivity because the LSPR phenomenon provided two pathways for electron transfer between Au NPs and g-C₃N₄ further diminished the performance. The improved degradation lies crucially on the particle size and Schottky barrier formation at the interface of M/g-C₃N₄ (M=Au, Ag, and Pd) but not the visible light harvesting properties. The mechanism insight revealed the holes (h⁺) and superoxide radical (^• O₂⁻) radical actively involved in photocatalytic reaction for all composites.

CXCL13 produced by macrophages due to Fli1 deficiency may contribute to the development of tissue fibrosis, vasculopathy, and immune activation in systemic sclerosis

Experimental Dermatology, Volume 0, Issue ja, -Not available-.

Prospective evaluation of a combination of fungal biomarkers for the diagnosis of invasive fungal disease in high‐risk haematology patients

Mycoses, EarlyView.

A Sensitive Assay for Proteases in Bioaerosol Samples: Characterization and Quantification of Airborne Proteases in Salmon Industry Work Environments

Abstract

Proteases are probably underestimated exposure agents in bioaerosols. Their roles as barrier disrupters in allergic sensitization and activators of innate inflammation call for more attention in exposure-response studies. The main objectives of this study was (i) to establish a suitable method for detection of small quantities of proteases in filtered air samples and (ii) to utilize the method to characterize exposure to proteases in a salmon industry work environment. Analysis of proteases in filtered air samples was based on zymography, using sodium dodecyl sulfate–polyacrylamide gel electrophoresis with 0.1% gelatin as substrate added in the polyacrylamide gel. Gelatinase activity was evident as cleared (unstained) regions. The area of these regions was quantified using image analysis (UVP Vision Works®). Standard curves with known amounts of active porcine trypsin were added to each gel. Validation of 11 non-linear standard curves showed R² (range) = 0.8989–0.9882, limit of detection = 0.056 nM, lower limit of quantification = 0.161 nM, and coefficients of variations (range) = 20–28%. Sampling of bioaerosols in salmon industry was performed using polytetrafluoretylene filters with an airflow of 3 l min⁻¹. All samples contained visible bands close to the size of porcine trypsin (23.3 kDa). The bands did not disappear in the presence of EDTA but abolished by Pefabloc, demonstrating that the enzyme is a serine protease, most likely salmon trypsin. Airborne levels of active protease were below the statistical detection limit in the filleting department but quantifiable in extract samples from the slaughter department. Three filtered air samples from the slaughter department showed air concentrations of 6.2, 16.5, and 27.0 ng m⁻³ air. We conclude that zymography is a sensitive and reliable method for exposure assessment of active proteases in indoor environmental samples. We recommend this assay for use in occupational studies to characterize and quantify exposure to active proteases in bioaerosols.

Multispectral ex vivo photoacoustic imaging of cutaneous melanoma for better selection of the excision margin

British Journal of Dermatology, EarlyView.

Effective anti‐programmed death‐1 therapy in a SUFU‐mutated patient with Gorlin–Goltz syndrome

British Journal of Dermatology, EarlyView.

Efficacy of oral sirolimus as salvage therapy in refractory lichen planus associated with immune deficiency

British Journal of Dermatology, EarlyView.