Clinical response to PD-1 blockade correlates with a sub-fraction of peripheral central memory CD4+ T cells in patients with malignant melanoma

Abstract

Cancer immunotherapy that blocks immune checkpoint molecules, such as PD-1/PD-L1, unleashes dysfunctional antitumor T-cell responses and has durable clinical benefits in various types of cancers. Yet its clinical efficacy is limited to a small proportion of patients, highlighting the need for identifying biomarkers that can predict the clinical response by exploring antitumor responses crucial for tumor regression. Here we explored T-cell responses associated with clinical benefits using peripheral blood mononuclear cells (PBMCs) from patients with malignant melanoma treated with anti-PD-1 monoclonal antibody (mAb). Pre- and post-treatment samples were collected from two different cohorts (discovery set and validation set) and subjected to mass cytometry assays that measured the expression levels of 35 proteins. Screening by high dimensional clustering in the discovery set identified increases in three micro-clusters of CD4⁺ T cells, a subset of central memory CD4⁺ T cells harboring CD27⁺FAS^-CD45RA^-CCR7⁺ phenotype, after treatment in long-term survivors, but not in non-responders. The same increase was also observed in clinical responders in the validation set. We propose that increases in this subset of central memory CD4⁺ T cells in peripheral blood can be potentially used as a predictor of clinical response to PD-1 blockade therapy in patients with malignant melanoma.

Implementation of a Regional Perinatal Data Repository from Clinical and Billing Records

Abstract

Objectives To describe the implementation of the first phase of a regional perinatal data repository and to provide a roadmap for others to navigate technical, privacy, and data governance concerns in implementing similar resources. Methods Our implementation integrated regional physician billing records with maternal and infant electronic health records from an academic delivery hospital. These records, representing births during 2013–2015, constituted a data core supporting linkage to additional ancillary data sets. Measures obtained from pediatric follow-up, urgent care, emergency, and inpatient encounters were linked at the individual level as were measures obtained by home visitors during pre- and postnatal encounters. Residential addresses were geocoded supporting linkage to area-level measures. Results Integrated data contained regional billing records for 69,290 newborns representing approximately 81% of all regional live births and nearly 95% of live births in the region's most populous county. Billing records linked to 7293 infant delivery hospital records and 7107 corresponding maternal hospital records. Manual review demonstrated 100% validity of matches among audited records. Additionally, 2430 home visiting records were linked to the data core as were pediatric primary care, urgent care, emergency department, and inpatient visits representing 42,541 children. More than 99% of the newborn billing records were geocoded and assigned a census tract identifier. Conclusions for Practice Our approach to methodological and regulatory challenges affords opportunities for expansion of systems to integrate electronic health records originating from additional medical centers as well as individual- and area-level linkage to additional data sets relevant to perinatal health.

Decision support tool for accidental pollution management

Abstract

Accidental river pollution can cause damage to the environment, put at risk the health of people that use the water for domestic purposes, and, not lastly, compromise dependent economic activities (e.g., agriculture). The reduction of the concentration of pollutant on any river following an accidental pollution can be achieved using dilution, by opening for certain duration the bottom gates of the reservoirs placed on the river's tributaries and releasing a significant volume of clean water in the main river. The hydraulic simulation and the pollutant transport are executed, firstly considering there is no dilution and secondly for the dilution scenario (bottom gates of the reservoirs open). A database was created, containing the results of simulations of pollutant transport for various values of the pollution characteristics in both diluted/undiluted scenarios. The database served for the implementation of a web decision support tool that presents an intuitive and easy to use GUI that allows the user to input details of the accidental pollution. Straightforward actions to be taken are presented to the end-user (e.g., "Open the bottom gates of the reservoir X at time T1 and close it at time T2") and synchronized charts show the effect of the dilution in respect to the concentration of pollutant at certain locations on the river. Using the described approach, a reduction of pollutant concentration in the river with up to 90% can be obtained.

Degradation reaction of Diazo reactive black 5 dye with copper (II) sulfate catalyst in thermolysis treatment

Abstract

The theme of present research demonstrates performance of copper (II) sulfate (CuSO₄) as catalyst in thermolysis process to treat reactive black 5 (RB 5) dye. During thermolysis without presence of catalyst, heat was converted to thermal energy to break the enthalpy of chemical structure bonding and only 31.62% of color removal. With CuSO₄ support as auxiliary agent, the thermally cleaved molecular structure was further destabilized and reacted with CuSO₄. Copper ions functioned to delocalize the coordination of π of the lone paired electron in azo bond, C=C bond of the sp² carbon to form C-C of the sp³ amorphous carbon in benzene and naphthalene. Further, the radicals of unpaired electrons were stabilized and RB 5 was thermally decomposed to methyl group. Zeta potential measurement was carried out to analyze the mechanism of RB 5 degradation and measurement at 0 mV verified the critical chemical concentration (CCC) (0.7 g/L copper (II) sulfate), as the maximum 92.30% color removal. The presence of copper (II) sulfate catalyst has remarkably increase the RB 5 dye degradation as the degradation rate constant without catalyst, k₁ is 6.5224 whereas the degradation rate constant with catalyst, k₂ is 25.6810. This revealed the correlation of conversion of thermal energy from heat to break the chemical bond strength, subsequent fragmentation of RB 5 dye molecular mediated by copper (II) sulfate catalyst. The novel framework on thermolysis degradation of molecular structure of RB 5 with respect to the bond enthalpy and interfacial intermediates decomposition with catalyst reaction were determined.

Measuring heavy metal stress in ryegrass using helium-cadmium excitation-based photoluminescence

Abstract

As the chemical analysis of heavy metal uptake and toxicity in plants is time-consuming, expensive, and destructive, a simple and reliable method for detecting heavy metal transfer from the soil to plants is thus necessary. We aimed to measure copper (Cu), lead (Pb), and cadmium (Cd) stress in ryegrass in vivo using plant photoluminescence based on a helium (He)-cadmium excitation source (wavelength 325 nm). The soils were combined with Cu, Pb and Cd, respectively. Fifteen ryegrass seedlings (Lolium multiflorum) were planted in each pot. After 30 days, leaves from seedlings at the fourth-leaf stage were collected and the fluorescence excitation spectra were detected using a He-Cd laser at an excitation wavelength of 325 nm. Three emission peaks that constitute known chlorophyll wavelengths, namely 450, 690, and 735 nm, were detected. These three peaks were strongly influenced by Cu, Pb, and Cd concentrations in the soil. Higher peak heights at 450 nm were observed with increasing Cu, Pb, and Cd concentrations in the soil, whereas no changes were noted at 690 and 735 nm. The P450/P690 and P450/P735 ratios were positively correlated with Cu, Pb, and Cd soil concentrations, ryegrass uptake, and DTPA-extractable Cu, Pb, and Cd in the soil. The related coefficients were all greater than 0.9. However, no correlation between the P690/P735 ratio, Cu, Pb, and Cd ryegrass uptake, and DTPA-extractable Cu, Pb, and Cd in the soil was observed. The measurement of plant photoluminescence in vivo using a He-Cd excitation source (wavelength 325 nm) may be utilized as an approach for monitoring the response of plants to specific stressors.

Potato tubers contamination with nitrate under the influence of nitrogen fertilizers and spray with molybdenum and salicylic acid

Abstract

A field trial was conducted through 2015 and 2016 growing seasons to study the effect of nitrogen fertilizer sources and foliar spray with molybdenum (Mo), salicylic acid (SA) and their combination on tubers yield, some chemical constituents, nutrients uptake, nitrate accumulation and nitrate reductase activity in potato tubers. N source was added at a rate of 350 kg N ha⁻¹in five equal doses as two different forms, the first is urea and the second is ammonium sulfate plus calcium nitrate equally. SA was sprayed with three rates of 0, 75 and 150 mg l⁻¹. Also, Mo as ammonium molybdate was sprayed using three rates 0, 50 and 100 mg l⁻¹Mo. Both treatments of SA and Mo were applied separately as well as with each other, at three successive times 30, 50 and 70 days after planting of potato plants. Results indicated that the addition of 350 kg N ha⁻¹ as ammonium sulfate and calcium nitrate equally caused a significant elevation (P > 0.05) in fresh weight, chlorophyll b, carotenoids, chlorophyll a, nitrate reductase activity, dry weight and NPK uptake by potato tubers compared with the same amount of nitrogen in the form of urea only. All the aforementioned characteristics were improved with increasing concentration of Mo and/or SA. The highest accumulation of nitrate was recorded under the addition of 350 kg N ha⁻¹ as urea alone. The highest average of all the aforementioned characteristics was observed at the treatment of 350 kg N ha⁻¹ as ammonium sulfate and calcium nitrate equally plus spraying with 100 mg l⁻¹Mo and 150 mg l⁻¹ SA. In contrast, this treatment gave the lowest accumulation of nitrates in potato tubers.

Migration of epoxidized soybean oil from polyvinyl chloride/polyvinylidene chloride food packaging wraps into food simulants

Abstract

Epoxidized soybean oil (ESBO) has been used in polyvinyl chloride (PVC)/polyvinylidene chloride (PVDC) food packaging cling film as a plasticizer and stabilizer. The aim of this study was to investigate the migration of ESBO from PVC/PVDC cling film, based on gas chromatography mass spectrometry (GC-MS). The specific migration of ESBO was evaluated using various food simulants (water, 4% acetic acid, 50% ethanol and n-heptane) for PVC and PVDC wrap products. ESBO did not migrate into water and 4% acetic acid for all the tested samples. However, it was released into 50% ethanol and n-heptane in several PVC/PVDC wraps, with maximum migration levels of 38.4 ± 0.7 and 37.4 ± 0.8 μg/mL, respectively. These results demonstrate that ESBO is capable of being released from PVC/PVDC wrap into amphiphilic/oily food and its migration should be regularly monitored.

Effects of low-level engineered nanoparticles on the quorum sensing of Pseudomonas aeruginosa PAO1

Abstract

The toxicity of engineered nanoparticles (ENPs) on bacteria has aroused much interest. However, few studies have focused on the effects of low-level ENPs on bacterial group behaviors that are regulated by quorum sensing (QS). Herein, we investigated the effects of nine ENPs (Ag, Fe, ZnO, TiO₂, SiO₂, Fe₂O₃, single-wall carbon nanotubes (SWCNTs), graphene oxide (GO), and C₆₀) on QS in Pseudomonas aeruginosa PAOl. An ENP concentration of 100 μg L⁻¹ did not impair bacterial growth. However, concentrations of 100 μg L⁻¹ of Ag and GO ENPs induced significant increases in 3OC₁₂–HSL in the culture and significantly promoted protease production and biofilm formation of PAO1. C₄–HSL synthase and its transcription factors were less sensitive to 100 μg L⁻¹ Ag and GO ENPs compared with 3OC₁₂-HSL. Fe ENPs induced a significant increase in the 3OC₁₂–HSL concentration, similar to Ag and GO ENPs. However, Fe ENPs did not induce any significant increase in protease production or biofilm formation. Different size distributions, chemical compositions, and aggregation states of the ENPs had different effects on bacterial QS. These whole circuit indicators could clarify the effects of ENPs on bacterial QS. This study furthers our understanding of the effects of low-level ENPs on bacterial social behaviors.

Epstein–Barr virus exanthem in an adult patient with myelodysplastic syndrome

Ischaemic ulcers on the toes secondary to Raynaud phenomenon in a patient with systemic sclerosis successfully treated with botulinum toxin

2018, Forward, Going Online and all that...

Issue Information

SMR Congress 2017 abstracts

Improved Photophysical and Photochemical Properties of Thiopheneethoxy Substituted Metallophthalocyanines on Immobilization onto Gold-speckled Silica Nanoparticles

Abstract

This work reports on the synthesis of tetrakis–[(thiophineethoxy) phthalocyaninato] indium(II) chloride (3). The photophysical behaviour of complex 3 was compared to that of the Zn derivative (tetrakis–[(thiophineethoxy) phthalocyaninato] zinc(II) (complex 2)). The compounds were interacted with gold–speckled silica (GSS) nanoparticles via Au–S self assembly to afford the conjugates (2–GSS and 3–GSS). The photophysicochemical behaviour of the compounds and their conjugates were assessed. The conjugates afforded a decrease in fluorescence quantum yields and lifetimes with improved triplet and singlet oxygen quantum yields in comparison to complexes 2 and 3 alone. The complexes and their conjugates could serve as good candidates for photodynamic therapy.

This article is protected by copyright. All rights reserved.

Folliculotropism in pigmented facial macules: Differential diagnosis with Reflectance confocal microscopy

Abstract

Pigmented facial macules are common on sun damage skin. The diagnosis of early stage lentigo maligna (LM) and lentigo maligna melanoma (LMM) is challenging. Reflectance confocal microscopy (RCM) has been proven to increase diagnostic accuracy of facial lesions.

A total 154 pigmented facial macules, retrospectively collected, were evaluate for the presence of already described RCM features and new parameters depicting aspects of the follicle .

Melanocytic nests, roundish pagetoid cells, follicular infiltration, bulgings from the follicles and many bright dendrites, and infiltration of the hair follicle (i.e. folliculotropism) were found to be indicative of LM/LMM compared to non-melanocytic skin neoplasms, with an overall sensitivity of 96% and specificity of 83%. Concerning non-melanocytic skin neoplasms, solar lentigo and lichen planus-like keratosis resulted better distinguishable from LM/LMM because usually lacking malignant features and presenting characteristic diagnostic parameters, such as cepidermal cobblestone pattern and polycyclic papillary contours. On the other hand, distinction of pigmented actinic keratosis (PAK) resulted more difficult, and needing evaluation of hair follicle infiltration and bulging structures, due to the frequent observation of few bright dendrites in the epidermis, but predominantly not infiltrating the hair follicle (estimated specificity for PAK 53%). .

A detailed evaluation of the components of the folliculotropism may help to improve the diagnostic accuracy. The classification of the type, distribution and amount of cells, and the presence of bulging around the follicles seem to represent important tools for the differentiation between PAK and LM/LMM at RCM analysis.

This article is protected by copyright. All rights reserved.

Reply to: “An exploratory study using framework analysis to investigate health-seeking behaviour in patients with psoriasis”

Abstract

We recently read with interest "An exploratory study using framework analysis to investigate health-seeking behaviour in patients with psoriasis" by Simpson et al. This interview based-study added to the understanding of obstacles patients face when seeking psoriasis treatment. Given the recent advances in effective systemic treatment options for psoriasis, we were similarly interested in exploring the discordance between available therapies and patient satisfaction and outcomes using a survey in a larger series of patients.

This article is protected by copyright. All rights reserved.

Novel POFUT1 mutation associated with hidradenitis suppurativa-Dowling Degos Disease firm up a role for Notch signalling in the pathogenesis of this disorder: reply from authors

Abstract

We thank González-Villanueva et al. for their comments and commend them for their intriguing results. They report on a single patient with clinical and histopathological evidence for Dowling-Degos disease. In addition, the patient developed hidradenitis suppurativa. The patient was found to carry a mutation in POFUT1, a gene previously known to be associated with Dowling-Degos disease.

This article is protected by copyright. All rights reserved.

Preface

Surgery for thyroid disease encompasses a broad spectrum of procedures involving multiple disease entities. Thyroid surgery may range from simple isthmusectomy/lobectomy to expansive procedures which involves bilateral cervical lymphadenectomy, resection of upper aerodigestive tract elements and mediastinal dissection. Accordingly, these procedures are accompanied by varying degrees of difficulty in the execution of many of the surgical maneuvers involved in performing a safe and successful operative procedure.

Substernal thyroidectomy: the trans-cervical approach

Substernal thyroid goiters that require surgery may pose unique challenges to thyroid surgeons based on the size and inferior extent of the disease. Consequently, there are multiple variations to the approach and additional considerations in operative planning and technique that are often required. While there is some debate on the precise definition of substernal thyroid, for the purposes of this manuscript it is considered to be thyroid tissue below the sternal notch or clavicle. This article aims to provide thyroid surgeons who encounter the challenges of substernal thyroid a straightforward algorithm for planning and operative techniques that have proven successful in the safe and effective management of this condition.

Techniques for thyroid cancer involving extreme superior thyroid pole

Standard operative techniques for thyroidectomy have become well refined and widely disseminated. However, special circumstances, such as superior pole thyroid cancers, can present unique difficulties for the unprepared surgeon. Appropriate workup and appreciation of the unique anatomic relationships in the superior-most extent of the thyroid gland is vital in surgical planning. The ability to anticipate and manage a variety of contingencies such as superior laryngeal nerve sacrifice, vascular isolation / repair, laryngectomy, and repair of pharyngeal defects are essential for safe surgery for cancers of the extreme superior thyroid pole.

Revision central neck dissection

Recurrent well differentiated thyroid cancer is an important problem and incidence is on the rise. Recurrence preferentially involves lymph nodes of the central and lateral neck. Detection and surveillance of such disease is commonly performed via serum thyroglobulin and high frequency neck ultrasonography. Management options include: active surveillance, local ablative techniques, RAI, external beam radiotherapy, and surgery. The gold standard of care is surgical removal in the form of comprehensive neck dissection.

Recurrent laryngeal nerve preservation in thyroid cancer involving the ligament of berry

The ligament of Berry is a dense consolidation of pretracheal vascular fascia or suspensory ligament which anchors the thyroid to the trachea and is located medial and deep to the tubercle of Zuckerkandl. The ligament of Berry is closely related to the distal 2cm of the extralaryngeal course of the recurrent laryngeal nerve and to the superior parathyroid gland. When thyroid cancer is present in the ligament of Berry, proper preoperative imaging, meticulous dissection with extra caution in the area of the ligament of Berry and use of intraoperative nerve monitoring are helpful tools in preservation of recurrent laryngeal nerve.

Removal of thyroid remnant for cancer in the previously operated central neck

Reoperative central neck dissection requires a concise set of steps to complete a comprehensive dissection of recurrent lymphadenopathy seen in thyroid cancer. The main considerations take into account the recurrent laryngeal nerve and the parathyroid glands. This chapter specifies those steps from a preoperative evaluation to the pearls during dissection to ensure a complete reoperative dissection that removes all residual thyroid tissue and lymphadenopathy while ensuring the best outcomes.

Operative Techniques in Otolaryngology-Head and Neck Surgery

The worldwide incidence of thyroid cancer has increased and generated great debate and study concerning the proper evidence-based management strategies. Despite this increase, there has been no significant increase in advanced, invasive thyroid cancers, which continue to represent the primary cause of thyroid cancer specific death. This section provides an evidence-based management review for thyroid cancer invading the aero-digestive tract and addresses critical issues of diagnosis, preoperative evaluation, surgical management, and adjuvant treatment germane to this important subset of patients.

Surgery for fibro adherent inflammatory thyroid disease

Inflammatory thyroid diseases include those which are mediated through autoimmune disorders such as Hashimoto′s thyroiditis and Grave′s disease, as well as inflammatory goiter and sub-acute thyroiditis. In patients with such disorders, the thyroid gland often becomes markedly enlarged with an associated fibro-vascular connective tissue reaction involving the thyroid capsule and surrounding soft tissues. This results in dense, adherent connective tissue which may compress and obscure critical central neck compartment structures and make capsular dissection challenging.

Regulation of bioenergetics through dual inhibition of aldehyde dehydrogenase and mitochondrial complex I suppresses glioblastoma tumorspheres

Abstract

Background

Targeted approaches for treating glioblastoma (GBM) attempted to date have consistently failed, highlighting the imperative for treatment strategies that operate on different mechanistic principles. Bioenergetics deprivation has emerged as an effective therapeutic approach for various tumors. We have previously found that cancer cells preferentially utilize cytosolic NADH supplied by aldehyde dehydrogenase (ALDH) for ATP production through oxidative phosphorylation (OxPhos). This study is aimed to examine therapeutic responses and underlying mechanisms of dual inhibition of ALDH and OxPhos against GBM.

Methods

For inhibition of ALDH and OxPhos, the corresponding inhibitors, gossypol and phenformin were used. Biological functions, including ATP levels, stemness, invasiveness, and viability, were evaluated in GBM tumorspheres (TSs). Gene expression profiles were analyzed using microarray data. In vivo anticancer efficacy was examined in a mouse orthotopic xenograft model.

Results

Combined treatment of GBM TSs with gossypol and phenformin significantly reduced ATP levels, stemness, invasiveness, and cell viability. Consistently, this therapy substantially decreased expression of genes associated with stemness, mesenchymal transition, and invasion in GBM TSs. Supplementation of ATP using malate abrogated these effects, whereas knockdown of ALDH1L1 mimicked them, suggesting that disruption of ALDH-mediated ATP production is a key mechanism of this therapeutic combination. In vivo efficacy confirmed remarkable therapeutic responses to combined treatment with gossypol and phenformin.

Conclusion

Our findings suggest that dual inhibition of tumor bioenergetics is a novel and effective strategy for the treatment of GBM.

Biological and therapeutic implications of multisector sequencing in newly diagnosed glioblastomas

Abstract

Background

Diagnostic workflows for glioblastoma (GBM) patients increasingly include DNA sequencing-based analysis of a single tumor site following biopsy or resection. We hypothesized that sequencing of multiple sectors within a given tumor would provide a more comprehensive representation of the molecular landscape and potentially inform therapeutic strategies.

Methods

10 newly diagnosed, IDH1 wildtype GBM tumor samples were obtained from two (n = 9) or four (n = 1) spatially distinct tumor regions. Tumor and matched blood DNA samples underwent whole-exome sequencing.

Results

Across all 10 tumors, 51% of mutations were clonal and 3% were subclonal and shared in different sectors, whereas 46% of mutations were subclonal and private. Two of the 10 tumors exhibited a regional hypermutator state despite being treatment naive, and remarkably, the high mutational load was predominantly limited to one sector in each tumor. Among the canonical cancer-associated genes, only TERT promoter mutations were observed in the founding clone in all tumors. Reconstruction of the clonal architecture in different sectors revealed regionally divergent evolution, and integration of data from two sectors increased the resolution of inferred clonal architecture in a given tumor. Predicted therapeutic mutations differed in presence and frequency between tumor regions. Similarly, different sectors exhibited significant divergence in the predicted neoantigen landscape.

Conclusions

The substantial spatial heterogeneity observed in different glioblastoma tumor sectors, especially in spatially-restricted hypermutator cases, raise important caveats to our current dependence on single-sector molecular information to guide either targeted or immune-based treatments.

Lymphatic transit rate as a predictive parameter for nodal metastasis in primary limb malignant melanoma

The status of sentinel lymph node (SLN) is one of the most predictive prognostic factors in the patients with clinically localized malignant melanomas (MMs) and is accurately evaluated by SLN biopsy [1,2]. In the nodal metastasis, however, the positive rate of SLN biopsy is as low as 20%, and many are negative [1]. Therefore, it is desirable to minimize SLN biopsy performance by preoperative imaging diagnosis.

A novel vitamin D receptor polymorphism associated with leprosy

Leprosy is a chronic infectious disease that primarily affects peripheral nerves, and the skin, but can also compromise functions of the eyes and other organs. Mycobacterium leprae (M. leprae) is the etiological agent and an obligate intracellular parasite [1]. Leprosy remains a serious public health problem in developing countries, such as India, Brazil and Indonesia, and it is endemic in Africa, Asia and Latin America [2].

Multi-scale analysis of the relationship between landscape patterns and a water quality index (WQI) based on a stepwise linear regression (SLR) and geographically weighted regression (GWR) in the Ebinur Lake oasis

Abstract

Water quality is highly dependent on landscape characteristics. This study explored the relationships between landscape patterns and water quality in the Ebinur Lake oasis in China. The water quality index (WQI) has been used to identify threats to water quality and contribute to better water resource management. This study established the WQI and analyzed the influence of landscapes on the WQI based on a stepwise linear regression (SLR) model and geographically weighted regression (GWR) models. The results showed that the WQI was between 56.61 and 2886.51. The map of the WQI showed poor water quality. Both positive and negative relationships between certain land use and land cover (LULC) types and the WQI were observed for different buffers. This relationship is most significant for the 400-m buffer. There is a significant relationship between the water quality index and landscape index (i.e., PLAND, DIVISION, aggregation index (AI), COHESION, landscape shape index (LSI), and largest patch index (LPI)), demonstrated by using stepwise multiple linear regressions under the 400-m scale, which resulted in an adjusted R ² between 0.63 and 0.88. The local R ² between the LPI and LSI for forest grasslands and the WQI are high in the Akeqisu River and the Kuitun rivers and low in the Bortala River, with an R ² ranging from 0.57 to 1.86. The local R ² between the LSI for croplands and the WQI is 0.44. The local R ² values between the LPI for saline lands and the WQI are high in the Jing River and low in the Bo River, Akeqisu River, and Kuitun rivers, ranging from 0.57 to 1.86.

Augmentation with potential endophytes enhances phytostabilization of Cr in contaminated soil

Abstract

The contamination of soil with heavy metals is a major environmental problem worldwide. The combined use of plants and their associated microbes has gained popularity in recent years for their potential to remediate heavy metal-contaminated soil. In the current study, the effect that augmentation of soil with plant growth-promoting endophytes has on the phytostabilization of chromium (Cr)-contaminated soil was investigated. Three potential endophytic bacterial strains (Enterobacter sp. HU38, Microbacterium arborescens HU33, and Pantoea stewartii ASI11) were inoculated individually as well as in combination to Leptochloa fusca and Brachiaria mutica vegetated in Cr-contaminated soil. The accumulation of Cr in the root and shoot of the plants was determined. Moreover, bacterial persistence in the rhizosphere and endosphere was determined. Augmentation with potential endophytes significantly increased root length (24–45%), shoot height (39–64%), chlorophyll content (20–55%), and the overall biomass (32–61%) of the plants. Although L. fusca and B. mutica showed potential to accumulate Cr in their root and shoot, endophytic augmentation increased uptake, translocation, and accumulation of Cr in the roots and shoots of both plant species. However, L. fusca showed more potential to phytostabilize Cr as compared to B. mutica. Furthermore, the potential endophytes showed more survival and persistence within the roots than in the rhizosphere and shoot interior. This study provides useful evidence of endophyte-assisted phytoremediation to be the most sustainable and affordable approach for in situ remediation of Cr-contaminated soil.

Response to: Commentary: “Gluteal Augmentation with Silicone Implants: A New Proposal for Intramuscular Dissection”

Treatment of Gigantomastia Using a Medial–Lateral Bipedicle Reduction Mammoplasty: The Role of Doppler-Assisted Preoperative Perforator Identification

Abstract

The purpose of this study is to introduce a breast reduction technique designed to reduce the incidence of postoperative nipple–areola complex ischemia and necrosis following reduction mammoplasty, while at the same time allowing all the other goals of breast reduction to be realized. This is achieved through preoperative detection of perforating vessels supplying the nipple–areola complex using a hand-held Doppler. The horizontally based parenchymal pedicle is designed to include these perforators whether originating from the internal mammary artery, lateral thoracic artery or both. This technique provides freedom in pedicle shaping and fixation to the pectoral fascia to achieve the best breast contour. The study included 50 patients equally divided into two groups: the study group (using preoperative Doppler for detection of perforators) and control group (without preoperative Doppler). The average body mass index of our patients was 32.4 and 29.8 for study and control groups, respectively. The average suprasternal notch to nipple distance was 40.8 cm in the study group and 38.9 cm in the control group. In all cases of the study group, both medial and lateral pedicles were used each of them containing one perforator. The average resection weight per side was 1433.6 g for the study group and 1173.2 g for the control group. None of the study group cases experienced NAC necrosis, while four cases of the control group experienced NAC necrosis (3 partial and 1 total). The horizontally based parenchymal pedicle constructed with the aid of preoperative perforator identification with a Doppler is an effective technique for breast reduction that results in a very low rate of postoperative ischemia and necrosis of the nipple–areola complex.

Level of Evidence IV This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors http://ift.tt/18t7xNj.

Neck Contouring Without Rhytidectomy in the Presence of Excess Skin

Abstract

Background

Patients with severe neck skin laxity due to excess submental adipose tissue have required either standard rhytidectomy or direct excision of neck skin with Z-plasty and submental lipectomy. Our recent experiences with four patients who declined cervicofacial rhytidectomy demonstrate that submental lipectomy and platysmarrhaphy appear to obtain sufficient improvement.

Methods

The submental area, submandibular area, and lateral neck are injected with local anesthetic. An incision is made in the submental area anterior to the existing crease, and the incision is taken through the subcutaneous tissue to the underlying fat. The skin is undermined in the deep subcutaneous plane. The lateral fat that cannot be visualized directly is suctioned using a number 2 cannula. Supra-platysmal and subplatysmal excess fat are excised under direct vision. The anterior bellies of the digastric muscle are excised partially or completely to obtain a flat contour if necessary. The submaxillary gland is partially or totally removed as indicated. The platysmarrhaphy is performed, and a TLS drain is placed in position and brought out through the left post-auricular sulcus using the attached trocar. The submental incision is then closed without skin excision.

Result

Non-excisional surgical neck rejuvenation was performed on four patients with significant skin laxity. There was adequate improvement in the cervicomental angle and neck profile contour in all patients, indicating that significant improvement may be achieved without skin excision.

Conclusion

Patients with excess skin can achieve acceptable results with submental lipectomy and platysmarrhaphy without rhytidectomy or direct excision of neck skin.

Level of Evidence V

This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors http://ift.tt/18t7xNj.

Correcting Nasojugal Groove with Autologous Cultured Fibroblast Injection: A Pilot Study

Abstract

Background

A new commercial drug that contains autologous cultured fibroblasts has been developed and approved by the United States Food and Drug Administration for improving the appearance of nasolabial folds. However, the treatment requires three sessions every 3–6 weeks. It is known that the skin overlying the nasojugal groove is thinner, and the wrinkle is generally shallower than nasolabial folds. Therefore, we hypothesized that the nasojugal groove could be improved by just one treatment session. Therefore, the purpose of this study was to evaluate the efficacy and safety of autologous cultured fibroblast injection to correct nasojugal grooves.

Methods

Forty-six subjects with nasojugal grooves were enrolled in this study. They were injected with autologous cultured fibroblasts or placebo in one session. Blinded evaluators and subjects assessed the efficacy using a validated wrinkle assessment scale at 4, 12, and 24 weeks after the injection. Information of adverse events was collected at each visit.

Results

Based on the evaluators' assessment at 24 weeks after the injection, 76% of subjects treated with autologous cultured fibroblasts showed improvement whereas 0% of subjects treated with placebo showed improvement (P < 0.0001). Based on self-assessment at 24 weeks after the injection, 72% of subjects treated with autologous cultured fibroblasts and 45% of subjects treated with placebo showed improvement (P = 0.0662). There were no serious adverse events related to autologous cultured fibroblast injection.

Conclusions

Autologous cultured fibroblast injection might be effective and safe to correct nasojugal grooves.

Level of Evidence IV

This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors http://ift.tt/18t7xNj.

Response to: Commentary on: “Gluteal Augmentation with Silicone Implants: A New Proposal for Intramuscular Dissection”

Ethnic Rhinoplasty in Female Patients: The Neoclassical Canons Revisited

Abstract

Background

Despite the substantial amount of research devoted to objectively defining facial attractiveness, the canons have remained a paradigm of aesthetic facial analysis, yet their omnipresence in clinical assessments revealed their limitations outside of a subset of North American Caucasians, leading to criticism about their validity as a standard of facial beauty. In an effort to introduce more objective treatment planning into ethnic rhinoplasty, we compared neoclassical canons and other current standards pertaining to nasal proportions to anatomic proportions of attractive individuals from seven different ethnic backgrounds.

Methods

Beauty pageant winners (Miss Universe and Miss World nominees) between 2005 and 2015 were selected and assigned to one of seven regionally defined ethnic groups. Anteroposterior and lateral images were obtained through Google, Wikipedia, Miss Universe, and Miss World Web sites. Anthropometry of facial features was performed via Adobe Photoshop TM. Individual facial measurements were then standardized to proportions and compared to the neoclassical canons.

Results

Our data reflected an ethnic-dependent preference for the multiple fitness model. Wide-set eyes, larger mouth widths, and smaller noses were significantly relevant in Eastern Mediterranean and European ethnic groups. Exceptions lied within East African and Asian groups.

Conclusion

As in the attractive face, the concept of the ideal nasal anatomy varies between different ethnicities. Using objective criteria and proportions of beauty to plan and execute rhinoplasty in different ethnicities can help the surgeon plan and deliver results that are in harmony with patients' individual background and facial anatomy.

Level of Evidence IV

This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors http://ift.tt/18t7xNj.

Comparison of Periorbital Anthropometry Between Beauty Pageant Contestants and Ordinary Young Women with Korean Ethnicity: A Three-Dimensional Photogrammetric Analysis

Abstract

Background

The purpose of this study is to investigate the differences in the periorbital anthropometry between national Beauty Pageant Contestants and Ordinary Young Women with Korean ethnicity.

Methods

Forty-three Beauty Pageant Contestants who were elected for the national beauty contest and forty-eight Ordinary Young Women underwent 3D photography. The authors analyzed 3D photogrammetric measures regarding periorbital soft tissue.

Results

The palpebral fissure width was significantly higher in the Beauty Pageant Contestants than the Ordinary Young Women (27.7 ± 1.2 vs. 26.3 ± 1.6 mm) (p < 0.001). The palpebral fissure height was also significantly higher in the Beauty Pageant Contestants (11.5. ± 1.0 vs. 9.1 ± 1.2 mm) (p < 0.001). The intercanthal width and upper eyelid height were smaller for the Beauty Pageant Contestants (intercanthal width, 34.3 ± 1.86 mm vs. 36.7 ± 3.1 mm; upper eyelid height, 11.5 ± 1.4 mm vs. 13.4 ± 2.3 mm) (p < 0.05). The nasal width and midfacial width were significantly smaller in the Beauty Pageant Contestants (nasal width, 38.0 ± 1.8 vs. 39.5 ± 2.2 mm; midfacial width 144.5 ± 3.9 vs. 146.9 ± 5.2 mm) (p < 0.05). The eyebrow showed significantly different features between the two groups in terms of vertical position in the upper face and the shape of the brow apex. The interpupillary distance, binocular distance, slant of palpebral fissure and width of pretarsal crease showed no significant difference between the two groups.

Conclusion

Periorbital features in Beauty Pageant Contestants are wide-set eyes, larger palpebral fissure in width and height, relatively small upper eyelid height and intercanthal width, and relatively small nose and facial width compared to normal women. Our anthropometric results can be referable values for Asian eyelid surgery and help surgeons to establish individualized surgical planning.

Level of Evidence V

This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors http://ift.tt/18t7xNj.

Sexuality Among Women Treated for Breast Cancer: A Survey of Three Surgical Procedures

Evaluation of mapping biopsies for extramammary Paget’s disease: a retrospective study

Extramammary Paget's disease (EMPD) sometimes shows an ill-defined border and an unexpectedly extended tumor spread beyond the clinical borders. Mapping biopsy is one approach for complete surgical removal, but its efficacy has remained controversial.

Fractional ablative carbon-dioxide laser treatment improves histological and clinical aspects of striae gravidarum: a prospective open label paired study

A real-world, community-based cohort study comparing the effectiveness of topical fluoruracil vs. topical imiquimod for the treatment of actinic keratosis

The most widely used topical agents for the field-based treatment of multiple actinic keratoses (AKs) are 5-fluorouracil and imiquimod, but their comparative effectiveness has not been assessed in a real-world setting.

Effects of curettage after shave biopsy of unexpected melanoma: A retrospective review

A simple method to facilitate fat removal from full-thickness skin grafts

A review of diagnosis and treatment of acne in adult female patients

This review focuses on the treatment options for adult female patients with acne. Acne in adult female patients may start during adolescence and persist or have an onset in adulthood. Acne has various psychosocial effects that impact patients' quality of life. Treatment of acne in adult women specifically has its challenges due to the considerations of patient preferences, pregnancy, and lactation. Treatments vary widely and treatment should be tailored specifically for each individual woman. We review conventional therapies with high levels of evidence, additional treatments with support from cohort studies and case reports, complementary and/or alternative therapies, and new agents under development for the treatment of patients with acne.

March 1 2018 News

Infectious diseases, weather and climate

infectionclimate changeweatherrisk factors

Mode of action and synergistic effect of valinomycin and cereulide with amphotericin B against Candida albicans and Cryptococcus albidus

Publication date: Available online 21 December 2017
Source:Journal de Mycologie Médicale
Author(s): A. Makarasen, N. Reukngam, P. Khlaychan, P. Chuysinuan, M. Isobe, S. Techasakul
Both valinomycin and cereulide are cyclic depsipeptides and are known K⁺ ion-selective ionophores. Valinomycin and cereulide feature low minimum inhibitory concentration (MIC) values against Candida albicans and Cryptococcus albidus. This study aims at investigating the mode of action and verifying the efficacy of valinomycin or cereulide alone and in combination with amphotericin B (AmB) in vitro against both microorganisms. Based on the results from membrane permeability and fluidity assays for detection of plasma membrane permeabilization and membrane dynamics, the present study demonstrated that valinomycin and cereulide exhibit antifungal activity against C. albicans and C. albidus by interrupting membrane-associated function. The mode of action of both valinomycin and cereulide are similar with that of AmB. Time-kill kinetics assay showed that valinomycin and cereulide exhibit fungistatic activity, whereas AmB features fungicidal activity. Additionally, the combination of compounds between each cyclic peptide and AmB reached maximal fungicidal activity more rapidly than AmB alone. This result corresponded with findings of scanning electron microscopy, fractional inhibitory concentration index and minimum fungicidal concentration (MFC)/MIC ratio, indicating that combinations of the drugs show synergistic effects for inhibiting the growth of these fungal strains. Sorbitol and ergosterol assays showed that both cyclic peptides affected cell wall and membrane components due to increases in MIC value, as observed in medium with sorbitol and ergosterol. Valinomycin and cereulide may promote permeability of fungal cell wall and cell membrane when used in combination with AmB.

Rbm10 regulates inflammation development via alternative splicing of Dnmt3b

Abstract

Rbm10 is a RNA binding protein that regulates alternative splicing, but its role in inflammation is not well defined. Here we show that Rbm10 controls appropriate splicing of Dnmt3b, a DNA methyltransferase, to regulate the activity of NFκB-responsive promoters and consequently inflammation development. Rbm10 deficiency suppressed NFκB-mediated responses in vivo and in vitro. Mechanistic analysis showed that Rbm10 deficiency decreased promoter recruitment of NFκB, with increased DNA methylation of the promoter regions in NFκB-responsive genes. Consistently, Rbm10 deficiency increased the expression level of Dnmt3b2, which has enzyme activity, while it decreased the splicing isoform Dnmt3b3, which does not. These two isoforms associated with NFκB efficiently, and over-expression of enzymatically active Dnmt3b2 suppressed the expression of NFκB targets, indicating that Rbm10-mediated Dnmt3b2 regulation is important for the induction of NFκB-mediated transcription. Therefore, Rbm10-dependent Dnmt3b regulation is a possible therapeutic target for various inflammatory diseases.

Distribution, contamination and accumulation of heavy metals in water, sediments, and freshwater shellfish from Liuyang River, Southern China

Abstract

Heavy metal distributions in water, sediments, and freshwater shellfish collected from Liuyang River in China have been investigated. The concentrations of heavy metals including Cr, Mn, Fe, Co, Ni, Cu, Zn, As, Cd, and Pb were determined by ICP-MS. The distribution pattern of heavy metals in sediments was different from that in water. Large coefficients of variation of heavy metal concentrations were observed in water due to the susceptibility to discharge fluctuation and seasonal variation. Multivariate statistical analysis such as Pearson's correlation analysis, hierarchical cluster analysis (HCA), and principal component analysis (PCA) were employed to identify the possible sources of heavy metals in sediments. These heavy metals were categorized into three distinct groups, one was derived from natural existence and two were associated with anthropogenic activities. Five shellfish species including three species of gastropod mollusks (Parafossarulus eximius, Semisulcospira cancellata, and Pomacea canaliculata) and two species of bivalve mollusks (Corbicula fluminea and Anodonta woodiana) were collected and investigated. The distribution pattern of heavy metals in shellfish species was visualized by the nonmetric multidimensional scaling (NMDS) plot. The metal pollution index (MPI) values for the shellfish species were in the descending order of C. fluminea > A. woodiana > S. cancellata > P. eximius > P. canaliculata.

Optimizing Exposure for the Occipital Nerve in Migraine Surgery while Maintaining Hair Length

Summary: Surgical decompression of the greater occipital nerve is used in the treatment of migraine headaches. Generally, hair is removed from the posterior scalp to aid with exposure and minimize interference. The securing of occipital hair with surgical tape and rubber bands instead of preoperative hair removal is a viable alternative. The preservation of hair length can lead to better patient satisfaction by avoiding the hair length discrepancies and has demonstrated a low risk of surgical-site infection.

Successful Bilateral Composite Ear Reattachment

Summary: A successful bilateral ear composite graft nonmicrosurgical reattachment is presented. In cases where suitable vessels are unavailable for microsurgical revascularization, the reconstructive challenge can be formidable for salvaging the unique anatomic and aesthetic structure of the ear. The case is presented of an 18-year-old woman who was a victim of an assault wherein both of her ears were intentionally amputated by her attacker. She underwent successful surgical reattachment followed by a postoperative regimen of hyperbaric oxygen, cooling, and meticulous wound care. The patient achieved 100% survival of her left ear graft and 95% survival of her right ear graft. Clinical photographs at 18 months are presented, along with a discussion of the possible implications for other reconstructive applications.

An incidental finding of an asymptomatic intraneural glomus tumour: a case report and review of the literature

Abstract

Glomus tumours are rare, soft-tissue neoplasms arising from the thermoregulatory neuromyoarterial glomus bodies. They are commonly observed in the extremities and typically present with symptoms of cold hypersensitivity, pain and localised tenderness. Intraneural glomus tumours (INGT) are even rarer. Here we review the literature on INGT and present an unusual case of an asymptomatic, INGT, found incidentally within the excision specimen of a spiradenocarcinoma that arose near the natal cleft. Interestingly, this had not been identified on magnetic resonance imaging (MRI) used to investigate the spiradenocarcinoma. Although glomus tumours are usually considered benign, malignant transformation has been reported, highlighting the need for reporting pathologists and treating clinicians to be aware of this entity.

Pharmacological management of delusional infestation

Candida glabrata prosthetic joint infection, successfully treated with anidulafungin: a case report and review of the literature

Summary

Non-albicans Candida prosthetic joint infection (PJI) is extremely rare. A case of a Candida glabrata knee PJI in a 68 years old splenectomized female smoker, suffering from chronic obstructive pulmonary disease (COPD) and alcoholism is reported. The patient presented with a peri-prosthetic fracture, 15 years after total knee replacement surgery. Cultures of the intraoperative peri-prosthetic tissue and materials yielded C. glabrata, as well as a methicillin resistant S. epidermitis. The patient was treated with with anidulafungin and vancomycin. The knee prosthetic joint was removed and cement-spacer with vancomycin and gentamycin was placed. Additionally, an external fixation was performed. A second stage revision surgery was planned, after completion of the antimicrobial and antifungal treatment. The patient is followed up for 4 months without signs, symptoms or findings of infection. PJI Candida infections require a high clinical suspicion index. It is of utmost importance to report these cases, since there is no consensus yet of the proper antifungal treatment. Furthermore, a literature review regarding treatment of those cases is provided. First line treatment with an echinocandin seems most proper, due to their fungicidal properties, their effectiveness against biofilm, as well as their minimal toxicity, making them ideal for long-term use. Further experience is needed, for better understanding the disease's pathogenesis and optimal treatment.

This article is protected by copyright. All rights reserved.

Coffee extract and caffeine enhance the heat shock response and promote proteostasis in an HSF-1-dependent manner in Caenorhabditis elegans

Abstract

As the population ages, there is a critical need to uncover strategies to combat diseases of aging. Studies in the soil-dwelling nematode Caenorhabditis elegans have demonstrated the protective effects of coffee extract and caffeine in promoting the induction of conserved longevity pathways including the insulin-like signaling pathway and the oxidative stress response. We were interested in determining the effects of coffee and caffeine treatment on the regulation of the heat shock response. The heat shock response is a highly conserved cellular response that functions as a cytoprotective mechanism during stress, mediated by the heat shock transcription factor HSF-1. In the worm, HSF-1 not only promotes protection against stress but is also essential for development and longevity. Induction of the heat shock response has been suggested to be beneficial for diseases of protein conformation by preventing protein misfolding and aggregation, and as such has been proposed as a therapeutic target for age-associated neurodegenerative disorders. In this study, we demonstrate that coffee is a potent, dose-dependent, inducer of the heat shock response. Treatment with a moderate dose of pure caffeine was also able to induce the heat shock response, indicating caffeine as an important component within coffee for producing this response. The effects that we observe with both coffee and pure caffeine on the heat shock response are both dependent on HSF-1. In a C. elegans Huntington's disease model, worms treated with caffeine were protected from polyglutamine aggregates and toxicity, an effect that was also HSF-1-dependent. In conclusion, these results demonstrate caffeinated coffee, and pure caffeine, as protective substances that promote proteostasis through induction of the heat shock response.

The regulation of heat shock proteins in response to dehydration in Xenopus laevis

Abstract

African clawed frogs (Xenopus laevis) endure bouts of severe drought in their natural habitats and survive the loss of approximately 30% of total body water due to dehydration. To investigate molecular mechanisms employed by X. laevis during periods of dehydration, the heat shock protein response, a vital component of the cytoprotective stress response, was characterized. Using western immunoblotting and multiplex technology, the protein levels of HSP27, HSP40, HSP60, HSP70, HSC70, and HSP90 were quantified in the liver, skeletal muscle, kidney, lung, and testes from control frogs and those that underwent medium or high dehydration (~16 or ~30% loss of total body water). Dehydration increased HSP27 (1.45–1.65-fold) in the kidneys and lungs, and HSP40 (1.39–2.50-fold) in the liver, testes, and skeletal muscle. HSP60 decreased in response to dehydration (0.43–0.64 of control) in the kidneys and lungs. HSP70 increased in the liver, lungs, and testes (1.39–1.70-fold) during dehydration, but had a dynamic response in the kidneys (levels increased 1.57-fold with medium dehydration, but decreased to 0.56 of control during high dehydration). HSC70 increased in the liver and kidneys (1.20–1.36-fold), but decreased in skeletal muscle (0.27–0.55 of control) during dehydration. Lastly, HSP90 was reduced in the kidney, lung, and skeletal muscle (0.39–0.69 of control) in response to dehydration, but rose in the testes (1.30-fold). Overall, the results suggest a dynamic tissue-specific heat shock protein response to whole body dehydration in X. laevis.

Exposure of vital cells to necrotic cell lysates induce the IRE1α branch of the unfolded protein response and cell proliferation

Abstract

Necrosis is a form of cell death that is detrimental to the affected tissue because the cell ruptures and releases its content (reactive oxygen species among others) into the extracellular space. Clusterin (CLU), a cytoprotective extracellular chaperone has been shown to be upregulated in the face of necrosis. We here show that in addition to CLU upregulation, necrotic cell lysates induce JNK/SAPK signaling, the IRE1α branch of the unfolded protein response (UPR), the MAPK/ERK1/2, and the mTOR signaling pathways and results in an enhanced proliferation of the vital surrounding cells. We name this novel response mechanism: Necrosis-induced Proliferation (NiP).

Characteristics and expression of genes encoding two small heat shock protein genes lacking introns from Chilo suppressalis

Abstract

Small heat shock proteins (sHSPs) constitute a large, diverse, and functionally uncharacterized family of heat shock proteins. To gain insight regarding the function of sHSPs in insects, we identified genes encoding two sHSPs, Cshsp22.9b and Cshsp24.3, from the rice pest Chilo suppressalis. The cDNAs of Cshsp22.9b and Cshsp24.3 encoded proteins of 206 and 216 amino acids with isoelectric points of 5.79 and 9.28, respectively. Further characterization indicated that both Cshsp22.9b and Cshsp24.3 lacked introns. Real-time quantitative PCR indicated that Cshsp22.9b and Cshsp24.3 were expressed at higher levels within the fat body as compared to other tissues (head, epidermis, foregut, midgut, hindgut, Malpighian tubules, and hemocytes). Expression of Cshsp22.9b and Cshsp24.3 was lowest in the hindgut and Malpighian tubules, respectively. Cshsp22.9b and Cshsp24.3 showed identical patterns in response to thermal stress from −11 to 43 °C, and both genes were up-regulated by hot and cold temperatures. The mRNA (messenger ribonucleic acid) expression levels of Cshsp22.9b (KY701308) and Cshsp24.3 (KY701309) were highest after a 2-h exposure at 39 °C and started to decline at 42 °C. In response to cold temperatures, both Cshsp22.9b and Cshsp24.3 showed maximal expression after a 2-h exposure to −3 °C. The two Cshsps were more responsive to hot than cold temperature stress and were not induced by mildly cold or warm temperatures. In conclusion, Cshsp22.9b and Cshsp24.3 could play a very important role in the regulation of physiological activities in C. suppressalis that are impacted by environmental stimuli.

Systematic identification and characterization of stress-inducible heat shock proteins (HSPs) in the salmon louse ( Lepeophtheirus salmonis )

Abstract

Salmon lice (Lepeophtheirus salmonis) are parasitic copepods, living mainly on Atlantic salmon and leading to large economical losses in aquaculture every year. Due to the emergence of resistances to several drugs, alternative treatments are developed, including treatment with hydrogen peroxide, freshwater or thermal treatment. The present study gives a first overview of the thermotolerance and stress response of salmon lice. Sea lice nauplii acclimated to 10 °C can survive heat shocks up to 30 °C and are capable of hardening by a sublethal heat shock. We searched in the genome for heat shock protein (HSP) encoding genes and tested their inducibility after heat shock, changes in salinity and treatment with hydrogen peroxide, employing microfluidic qPCRs. We assessed 38 candidate genes, belonging to the small HSP, HSP40, HSP70 and HSP90 families. Nine of these genes showed strong induction after a non-lethal heat shock. In contrast, only three and two of these genes were induced after changes in salinity and incubation in hydrogen peroxide, respectively. This work provides the basis for further work on the stress response on the economically important parasite L. salmonis.

Melatonin protected cardiac microvascular endothelial cells against oxidative stress injury via suppression of IP3R-[Ca 2+ ]c/VDAC-[Ca 2+ ]m axis by activation of MAPK/ERK signaling pathway

Abstract

The cardiac microvascular reperfusion injury is characterized by the microvascular endothelial cells (CMECs) oxidative damage which is responsible for the progression of cardiac dysfunction. However, few strategies are available to reverse such pathologies. This study aimed to explore the mechanism by which oxidative stress induced CMECs death and the beneficial actions of melatonin on CMECs survival, with a special focused on IP3R-[Ca²⁺]c/VDAC-[Ca²⁺]m damage axis and the MAPK/ERK survival signaling. We found that oxidative stress induced by H₂O₂ significantly activated cAMP response element binding protein (CREB) that enhanced IP3R and VDAC transcription and expression, leading to [Ca²⁺]c and [Ca²⁺]m overload. High concentration of [Ca²⁺]m suppressed ΔΨm, opened mPTP, and released cyt-c into cytoplasm where it activated mitochondria-dependent death pathway. However, melatonin could protect CMECs against oxidative stress injury via stimulation of MAPK/ERK that inactivated CREB and therefore blocked IP3R/VDAC upregulation and [Ca²⁺]c/[Ca²⁺]m overload, sustaining mitochondrial structural and function integrity and ultimately blockading mitochondrial-mediated cellular death. In summary, these findings confirmed the mechanisms by which oxidative injury induced CMECs mitochondrial-involved death and provided an attractive and effective way to enhance CMECs survival.

The small heat shock protein B8 (HSPB8) efficiently removes aggregating species of dipeptides produced in C9ORF72-related neurodegenerative diseases

Abstract

Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are two neurodegenerative diseases in which similar pathogenic mechanisms are involved. Both diseases associate to the high propensity of specific misfolded proteins, like TDP-43 or FUS, to mislocalize and aggregate. This is partly due to their intrinsic biophysical properties and partly as a consequence of failure of the neuronal protein quality control (PQC) system. Several familial ALS/FTD cases are linked to an expansion of a repeated G4C2 hexanucleotide sequence present in the C9ORF72 gene. The G4C2, which localizes in an untranslated region of the C9ORF72 transcript, drives an unconventional repeat-associated ATG-independent translation. This leads to the synthesis of five different dipeptide repeat proteins (DPRs), which are not "classical" misfolded proteins, but generate aberrant aggregation-prone unfolded conformations poorly removed by the PQC system. The DPRs accumulate into p62/SQSTM1 and ubiquitin positive inclusions. Here, we analyzed the biochemical behavior of the five DPRs in immortalized motoneurons. Our data suggest that while the DPRs are mainly processed via autophagy, this system is unable to fully clear their aggregated forms, and thus they tend to accumulate in basal conditions. Overexpression of the small heat shock protein B8 (HSPB8), which facilitates the autophagy-mediated disposal of a large variety of classical misfolded aggregation-prone proteins, significantly decreased the accumulation of most DPR insoluble species. Thus, the induction of HSPB8 might represent a valid approach to decrease DPR-mediated toxicity and maintain motoneuron viability.

Characterization of the CDK5 gene in Apis cerana cerana ( AccCDK5 ) and a preliminary identification of its activator gene, AccCDK5r1

Abstract

Cyclin-dependent kinase 5 (CDK5) is an unusual CDK whose function has been implicated in protecting the central nervous system (CNS) from oxidative damage. However, there have been few studies of CDK5 in insects. In this study, we identified the AccCDK5 gene from Apis cerana cerana and investigated its role in oxidation resistance. We found that AccCDK5 is highly conserved across species and contains conserved features of the CDK5 family. The results of qPCR analysis indicated that AccCDK5 is highly expressed during the larval and pupal stages and in the adult head and muscle. We further observed that AccCDK5 is induced by several environmental oxidative stresses. Moreover, the overexpression of the AccCDK5 protein in E. coli enhances the resistance of the bacteria to oxidative stress. The activation of CDK5 requires binding to its activator. Therefore, we also identified and cloned cyclin-dependent kinase 5 regulatory subunit 1, which we named AccCDK5r1, from Apis cerana cerana. AccCDK5r1 contains a conserved cell localization targeting domain as well as binding and activation sites for CDK5. Yeast two-hybrid analysis demonstrated the interaction between AccCDK5 and AccCDK5r1. The expression patterns of the two genes were similar after stress treatment. Collectively, these results suggest that AccCDK5 plays a pivotal role in the response to oxidative stresses and that AccCDK5r1 is a potential activator of AccCDK5.

Comparative RNA-sequencing analysis of ER-based HSP90 functions and signal pathways in Tribolium castaneum

Abstract

Tribolium castaneum, the red flour beetle, is a major agriculture pest that damages stored grains and cereal products. Heat-shock protein 90 of T. castaneum (Tchsp90) has been reported to play pivotal roles in heat stress response, development, reproduction, and life span. However, the signaling pathway of Tchsp90 remains unclear. Thus, the global transcriptome profiles between RNA interference (RNAi)-treated insects (ds-Tchsp90) and control insects of T. castaneum were investigated and compared by RNA sequencing. In all, we obtained 14,145,451 sequence reads, which assembled into 13,243 genes. Among these genes, 461 differentially expressed genes (DEGs) were identified between the ds-Tchsp90 and control samples. These DEGs were classified into 44 gene ontology (GO) functional groups, including the cellular process, the response to stimulus, the immune system process, the development process, and reproduction. Interestingly, knocking down the expression of Tchsp90 suppressed both the DNA replication and cell division signaling pathways, which most likely modulated the effects of Tchsp90 on development, reproduction, and life span. Moreover, the DEGs encoding AnnexinB9, frizzled-4, sno, Fem1B, TSL, and CSW might be related to the regulation of the development and reproduction of ds-Tchsp90 insects. The DEGs including TLR6, PGRP2, defensin1, and defensin2 were involved in heat stress and immune response simultaneously, which suggested that cross talk might exist between immunity and stress response. Additionally, RNAi of Tchsp90 altered large-scale serine protease (sp) gene expression patterns and amplified the SP signaling pathway to regulate the development and reproduction as well as the stress response and innate immunity in T. castaneum. All these results shed new light onto the regulatory mechanism of Tchsp90 involved in insect physiology and could further facilitate research into appropriate and sustainable pest control management.

Molecular characteristics of a novel HSP60 gene and its differential expression in Manila clams ( Ruditapes philippinarum ) under thermal and hypotonic stress

Abstract

The Manila clam Ruditapes philippinarum inhabits the intertidal zone and must therefore tolerate broad fluctuations in water temperature and salinity. Heat shock protein 60 (HSP60) is an evolutionarily conserved, multi-functional protein that plays a significant role in protecting organisms from harmful stress conditions. We cloned the R. philippinarum HSP60 (RpHSP60) gene and analyzed its transcriptional responses to thermal and low-salinity stresses. The complete sequence of RpHSP60 cDNA was 1777 nucleotides, containing a 1728-bp open reading frame encoding a polypeptide of 576-amino acids, with a calculated molecular mass of 61.25 kDa and predicted isoelectric point of 5.08. Comparisons of amino acid sequences and three-dimensional structures of HSP60 revealed that RpHSP60 was highly conserved in the signature HSP60-family domains. RpHSP60 mRNA was detected in all the tested tissues of R. philippinarum, with the highest expression levels in hemocytes. We measured RpHSP60 mRNA levels in the gills under thermal and low-salinity stresses using quantitative real-time reverse transcription-polymerase chain reaction. Following the thermal challenge, RpHSP60 mRNA was significantly upregulated at 6 h, and then progressively downregulated under high-temperature stress (30 °C), while only slight fluctuations were observed under low-temperature stress (−1 °C). Under low-salinity (17 ppt) stress, RpHSP60 mRNA levels were significantly increased at 3, 72, and 96 h (P < 0.05). These results suggest that HSP60 of R. philippinarum may play important roles in responding to high-temperature and low-salinity stresses.

Prevalence of vitiligo in Brazil - a population survey

Abstract

population data concerning the prevalence of vitiligo are variable according to age, ethnic groups and study methodology. It varies in adults from 0.1-2.0%, however, a meta-analysis has suggested publication bias and indicated a more conservative estimation of 0.2%.(Zhang et al., 2016). Vitiligo affects both genders with a slight female predilection, and the disease onset occurs mostly at adulthood (2^nd-3^rd decades).

This article is protected by copyright. All rights reserved.

Higher cation exchange capacity determined lower critical soil pH and higher Al concentration for soybean

Abstract

Low soil pH and aluminum (Al) toxicity induced by soil acidification are the main obstacles in many regions of the world for crop production. The purpose of this study was to reveal the mechanisms on how the properties of the soils derived from different parent materials play role on the determination of critical soil pH and Al concentration for soybean crops. A set of soybean pot experiment was executed in greenhouse with a soil pH gradient as treatment for each of four soils to fulfill the objectives of this study. The results indicated that plant growth parameters were affected adversely due to Al toxicity at low soil pH level in all soils. The critical soil pH varied with soil type and parent materials. They were 4.38, 4.63, 4.74, and 4.95 in the Alfisol derived from loss deposit, and the Ultisols derived from Quaternary red earth, granite, and Tertiary red sandstone, respectively. The critical soil exchangeable Al was 2.42, 1.82, 1.55, and 1.44 cmol_c/kg for the corresponding soils. At 90% yield level, the critical Al saturation was 6.94, 10.36, 17.79, and 22.75% for the corresponding soils. The lower critical soil pH and Al saturation, and higher soil exchangeable Al were mainly due to greater soil CEC and exchangeable base cations. Therefore, we recommended that critical soil pH, soil exchangeable Al, and Al saturation should be considered during judicious liming approach for soybean production.

Grey relational analysis for evaluating the effects of different rates of wine lees-derived biochar application on a plant–soil system with multi-metal contamination

Abstract

In this study, grey relational analysis (GRA) was used to investigate the effects of different application rates of wine lees-derived biochar on a plant–soil system with multi-metal contamination. A pot experiment was conducted to determine rice growth in multi-metal-contaminated soil amended with samples of wine lees-derived biochar, and 47 indicators (including soil properties, microbial activity, and plant physiology) were selected as evaluation indexes to assess the plant–soil system. The results indicated that higher wine lees-derived biochar application rates (2% W/W) were favorable for soil fertility, the bioconcentration factor (BF), and the mobility factor (MF, %) (with the exception of Cr, Zn, and Hg), but an application of 1% produced the highest plant growth, enzymatic activities, and bacterial diversity. The richness of the bacterial communities was reduced in the soil amended with the wine lees-derived biochar. According to the GRA assessment, the 1% application rate of wine lees-derived biochar was more suitable for restoring the holistic plant–soil system than were the application rates of 0, 0.5, and 2% (W/W). Furthermore, this study shows that GRA is a useful method for evaluating plant–soil systems.

Electrochemical advanced oxidation processes as decentralized water treatment technologies to remediate domestic washing machine effluents

Abstract

Water scarcity is one of the major concerns worldwide. In order to secure this appreciated natural resource, management and development of water treatment technologies are mandatory. One feasible alternative is the consideration of water recycling/reuse at the household scale. Here, the treatment of actual washing machine effluent by electrochemical advanced oxidation processes was considered. Electrochemical oxidation and electro-Fenton technologies can be applied as decentralized small-scale water treatment devices. Therefore, efficient decolorization and total organic abatement have been followed. The results demonstrate the promising performance of solar photoelectro-Fenton process, where complete color and organic removal was attained after 240 min of treatment under optimum conditions by applying a current density of 66.6 mA cm⁻². Thus, electrochemical technologies emerge as promising water-sustainable approaches.

Evaluation of the methods for quantifying particle wash-off loadings in urban impervious surfaces at small scales

Abstract

Quantifying road-deposited sediment (RDS) wash-off is critical in estimating pollutant load and for supporting the designs of urban storm water low-impact development (LID) best management practices (BMPs). The objective of this study was to identify a simple and effective small-scale wash-off load estimation and prediction method suitable for BMP engineering. The reliabilities, complexities, and applicabilities of four prediction methods (i.e., the event mean concentration (EMC) equation method, the exponential equation method, and the RDS mass difference before and after rainfall event method, and the RDS index model) were tested for three sites (i.e., a newly built area, and built-up area, and conservation area) during five natural rainfall events. Taking the calculations by the EMC method as standard results revealed the following. (1) The degree of agreement of the methods with the standard results in descending order was exponential equation method > RDS index model > RDS mass difference. (2) The degree of complexity of the studied methods in descending order was exponential equation method > the EMC equation method > the RDS index model > the RDS mass difference. (3) When considering the applicability of the models in terms of LID-BMP engineering, the RDS index model could be considered optimal for supporting the design of urban storm water BMPs.

Identical COL71A1 heterozygous mutations resulting in different dystrophic epidermolysis bullosa phenotypes

Abstract

Dystrophic epidermolysis bullosa is a rare blistering condition caused by mutations in the COL7A1 gene. Different clinical variants have been described, with dominant and recessive inheritance, but no consistent findings have been elucidated to establish a genotype–phenotype correlation. We present three unrelated patients with two identical pathogenic compound heterozygous mutations in the COL7A1 gene that developed different clinical forms of dystrophic epidermolysis bullosa—epidermolysis bullosa pruriginosa and mild recessive non-Hallopeau–Siemens—raising the possibility of other genetic or environmental modifying factors responsible for the phenotype of the disease.

Epidemiology of sapovirus infections in a birth cohort in Peru

Abstract

Background

Sapovirus is one of the primary viral causes of acute gastroenteritis, especially in settings where rotavirus vaccination has been implemented. The characteristics and impact of natural infection at the community level, however, have not been well documented.

Methods

Stool samples were analyzed from 100 children randomly selected from a community-based birth cohort study in Peru. All diarrheal and one non-diarrheal stools collected trimonthly from children up to two years of age (n=1669) were tested for sapovirus detection. Viral shedding duration was determined by testing additional weekly samples (n=440), collected before and after a sapovirus positive sample.

Results

The incidence of sapovirus infection in the first and second year of life was 4.3 and 11.1 per 100-child months, respectively. By two years of age, 82% of children had at least one sapovirus infection, and 64% had at least one sapovirus-associated diarrhea episode. The median shedding period was 18.5 days. In 112 of 175 infections, 14 genotypes from four genogroups (GI, GII, GIV and GV) were determined. Among genogroups, GI viruses were more frequently found in symptomatic infections than in asymptomatic infections (OR: 3.1 [CI: 1.3–7.4]). Fifty-nine children had serial sapovirus infections but only three had repeated infection of the same genotype.

Conclusions

Sapovirus was frequently detected in children with acute gastroenteritis at the community level during the first two years of life. Serial sapovirus infections by multiple genotypes in a child suggest genotype-specific immunity from each infection, which need to be taken into account for vaccine development.

Evaluation of a Novel Global Immunity Assay to Predict Infection in Organ Transplant Recipients

Abstract

Background

Solid organ transplant recipients (SOTRs) are predisposed to infection due to the need for lifelong immunosuppression, although tools to measure the overall degree of immunosuppression are limited. In this study, we used a novel global cell-mediated immunity (CMI) assay to quantify the degree of immunosuppression and predict subsequent infections.

Methods

Consecutive SOTRs were enrolled and provided whole blood to conduct the global CMI assay (QuantiFERON Monitor) at 1, 3, and 6 months posttransplant. The assay measures plasma interferon gamma (IFN-γ) levels after stimulation of whole blood with antigens that stimulate both innate and adaptive immunity. Bacterial, viral, and fungal infections were prospectively recorded.

Results

We enrolled 137 patients who provided CMI measurements on at least 1 study timepoint. Median age was 58 years; transplant types were kidney (32.1%), liver (30.7%), and lung (36.5%). At least 1 episode of infection occurred in 32 of 137 (23.4%) patients between 1 and 3 months, 34 of 135 (25.1%) between 3 and 6 months, and 39 of 132 (29.5%) between 6 and 12 months. IFN-γ levels were significantly lower in those with at least 1 episode of infection vs no infection at month 1 (P = .04), month 3 (P = .05), and month 6 (P = .006). Patients who developed opportunistic infections (OIs) also showed a significantly lower CMI than those without OI at months 3 and 6. Using a cutoff value of ≤10 IU/mL of IFN-γ, there was a 2- to 3-fold greater likelihood of subsequent infection in those with lower CMI.

Conclusions

We show that a novel global immunity assay is able to quantify the level of immunosuppression and predict the risk of subsequent infection episodes in organ transplant recipients.

A Phase 3, Randomized, Double-Blind, Multicenter Study to Evaluate the Safety and Efficacy of Intravenous Iclaprim Vs Vancomycin for the Treatment of Acute Bacterial Skin and Skin Structure Infections Suspected or Confirmed to be Due to Gram-Positive Pathogens: REVIVE-1

Abstract

Background

Our objective in this study was to demonstrate the safety and efficacy of iclaprim compared with vancomycin for the treatment of patients with acute bacterial skin and skin structure infections (ABSSSIs).

Methods

REVIVE-1 was a phase 3, 600-patient, double-blinded, randomized (1:1), active-controlled trial among patients with ABSSSI that compared the safety and efficacy of iclaprim 80 mg fixed dose with vancomycin 15 mg/kg, both administered intravenously every 12 hours for 5–14 days. The primary endpoint of this study was a ≥20% reduction in lesion size (early clinical response [ECR]) compared with baseline among patients randomized to iclaprim or vancomycin at the early time point (ETP), 48 to 72 hours after the start of administration of study drug in the intent-to-treat population.

Results

ECR among patients who received iclaprim and vancomycin at the ETP was 80.9% (241 of 298) of patients receiving iclaprim compared with 81.0% (243 of 300) of those receiving vancomycin (treatment difference, −0.13%; 95% confidence interval, −6.42%–6.17%). Iclaprim was well tolerated in the study, with most adverse events categorized as mild.

Conclusions

Iclaprim achieved noninferiority (10% margin) at ETP compared with vancomycin and was well tolerated in this phase 3 clinical trial for the treatment of ABSSSI. Based on these results, iclaprim appears to be an efficacious and safe treatment for ABSSSI suspected or confirmed to be due to gram-positive pathogens.

Clinical Trials Registration

NCT02600611.

Contribution of maternal ART and breastfeeding to 24-month survival in HIV-exposed uninfected children: an individual pooled analysis of African and Asian studies

Abstract

Background

Increasing numbers of HIV-infected pregnant women receive antiretroviral therapy (ART) to prevent mother-to-child transmission (PMTCT). Studies suggested that HIV-exposed uninfected (HEU) children face higher mortality than HIV-unexposed children, but evidence mostly relates to the pre-ART era, breastfeeding of limited duration and considerable maternal mortality. Maternal ART and prolonged breastfeeding under cover of ART may improve survival, although this has not been reliably quantified.

Methods

Individual data on 19,219 HEU children from 21 PMTCT trials/cohorts undertaken 1995-2015 in Africa and Asia were pooled and the association between 24-month mortality and maternal/infant factors quantified using random-effects Cox proportional hazards models accounting for between-study heterogeneity. Adjusted attributable fractions of risks computed using the predict function in the R package "frailtypack" estimate the relative contribution of risk factors to overall mortality in HEU children.

Results

Cumulative incidence of death was 5.5% (95%CI: 5.1-5.9) by age 24 months. Low birth weight (LBW<2500g, adjusted Hazard Ratio (aHR: 2.9), no breastfeeding (aHR: 2.5) and maternal death (aHR: 11.1) were significantly associated with increased mortality. Maternal ART (aHR: 0.5) was significantly associated with lower mortality. At population level, LBW accounted for 16.2% of child deaths by 24 months, never breastfeeding for 10.8%, mother not receiving ART for 45.6%, and maternal death for 4.3%; these factors combined explained 63.6% of deaths by age 24 months.

Conclusion

Survival of HEU children could be substantially improved if public health strategies provided all mothers living with HIV with ART and supported optimal infant feeding and care for LBW neonates.

Prediction of Infection After Solid Organ Transplantation: Is Measuring Cell-Mediated Immunity the Answer?

Solid organ transplantation (SOT) is used for the management of a broad range of patients with end-stage organ dysfunction, but infectious complications remain an important barrier to the success of these procedures. The need for lifelong immunosuppressive therapy to prevent allograft rejection places SOT recipients at increased risk for a variety of infections. Although the incidence, general timing, and type of infectious complications have been established, accurately predicting which specific patients will ultimately develop significant infection(s) is not feasible. Consequently, standard posttransplant antimicrobial preventive strategies are relegated to an imprecise "one size fits all" approach, informed by the organ transplanted, immunosuppressive regimen used, donor and recipient exposures, and the posttransplant clinical course. Over- and underuse of various preventive strategies in individual patients is an inherent limitation of current protocols.

Immunomodulatory activity of glycodelin: Implications in allograft rejection

Summary

Glycodelin is an immunomodulator, indispensable for the maintenance of pregnancy in humans. The glycoprotein induces apoptosis in activated CD4⁺ T cells, monocytes and NK cells, and suppresses the activity of cytotoxic T cells, macrophages and dendritic cells. This study explores the immunosuppressive property of glycodelin for its possible use in preventing graft rejection. Because glycodelin is found only in certain primates, the hypothesis was investigated in an allograft nude mouse model. It is demonstrated that treatment of alloactivated mononuclear cells with glycodelin thwarts graft rejection. Glycodelin decreases the number of activated CD4⁺ and CD8⁺ cells and downregulates the expression of key proteins known to be involved in graft demise such as granzyme-B, EOMES, IL-2 and pro-inflammatory cytokines (TNF-α and IL-6), resulting in a weakened cell-mediated immune response. Immunosuppressive drugs for treating allograft rejection are associated with severe side effects. Glycodelin, a natural immunomodulator in humans, would be an ideal alternate candidate. This article is protected by copyright. All rights reserved.

Th17, synchronically increased with Treg and Breg, promoted by tumor cells via cell-contact in primary hepatic carcinoma

Abstract

Documented reports about Th17 cells revealed that Th17 play a critical role in inflammation and autoimmunity diseases. However, the role of Th17 in cancer remains contradictory. The interplay between Th17 and tumor cells in the tumor microenvironment of PHC needs to be further explored and the relationship between Th17, Tregs and Bregs has not been completely defined. In this study, numerous experiments were undertaken to elucidate the interaction of Th17 and Treg/Breg cells involved in PHC. Our work demonstrated that an increased Th17 were detected in the peripheral circulation and in tumor tissues in PHC patients. In addition, increases in peripheral blood Th17 corresponded with TNM stage progression. Besides, further studies indicated that Th17 cells were promoted by tumor cells in the PHC tumor microenvironment through both contact-dependent and contact-independent mechanisms, but cell-contact played the major important role in promoting the production and proliferation of Th17. When isolated CD4⁺CD25⁺ CD127^low Tregs and CD4⁺CD25^-CD127⁺ non-Tregs were cultured with autologous tumor cells, it implicated that the phenotype of Th17 and Tregs was modified by tumor cells in the tumor microenvironment. Beside this, Th17 cells were also found to correlate positively with CD4⁺FoxP3⁺Tregs and CD19⁺CD5⁺CD1d^hi Bregs in PHC. Notably, Th17 synchronically increased with Tregs and Bregs in PHC. These findings may provide new clues to reveal mechanisms of immune escape in PHC. This article is protected by copyright. All rights reserved.

Differential Serum Cytokine Profile in Patients with Systemic Lupus Erythematosus and Posterior Reversible Encephalopathy Syndrome

Summary

SLE patients are susceptible to the development of posterior reversible encephalopathy syndrome (PRES). The main theory about the physiopathology of PRES suggests there is brain-blood barrier damage, which is associated with endothelial dysfunction, and characterized by vasogenic edema. However, current evidence regarding its physiopathogenic mechanisms is quite scant. The aim of this study was to analyze the expression of different serum cytokines, as well as VEGF and sCD40L, in patients with PRES/SLE and to compare them with levels in SLE patients without PRES and in healthy controls. We performed a transversal study in a tertiary care center in Mexico City. We included 32 subjects (healthy controls, n=6; remission SLE, n=6; active SLE, n=6 and PRES/SLE patients, n=14). PRES was defined as reversible neurological manifestations (seizures, visual abnormalities, acute confusional state), associated with compatible changes by MRI. Serum samples were obtained during the first 36 hours after the PRES episode and were analyzed by Cytometric Bead Array, Luminex Multiplex assay or ELISA. IL-6 and IL-10 levels were significantly higher in PRES/SLE patients (p=0.013 and 0.025, respectively) when compared to the other groups. Furthermore, IL-6 and IL-10 levels displayed a positive correlation (r=0.686, p=0.007). There were no differences among groups regarding other cytokines, sCD40L or VEGF levels. A differential serum cytokine profile was found in PRES/SLE patients, with increased IL-6 and IL-10 levels. Our findings, which are similar to those described in other neurological manifestations of SLE, support the fact that PRES should be considered among the SLE-associated neuropsychiatric syndromes. This article is protected by copyright. All rights reserved.

NO AUGMENTATION OF INDOLEAMINE 2,3-DIOXYGENASE (IDO) ACTIVITY THROUGH BELATACEPT TREATMENT IN LIVER TRANSPLANT RECIPIENTS

ABSTRACT

Background: Belatacept is a second generation CTLA4Ig fusion protein approved for immunosuppression in renal transplant recipients. It was intentionally designed to interrupt costimulation via CD28 by binding to its ligands B7.1 and B7.2. Experimental evidence suggests a potential additional mechanism for CTLA4Ig compounds through binding to B7 molecules expressed on antigen presenting cells (APCs) and upregulation of indoleamine 2,3-dioxygenase (IDO), an immunomodulating enzyme that catalyzes the degradation of tryptophan to kynurenine and that downregulates T cell immunity. So far it remains unknown whether belatacept upregulates IDO in transplant recipients. We therefore investigated whether belatacept therapy enhances IDO activity in liver transplant recipients enrolled in a multi-center, investigator-initiated substudy of the phase II trial of belatacept in liver transplantation (IM103-045).

Methods: Tryptophan and kynurenine serum levels were measured during the first six weeks post-transplant in liver transplant patients randomized to receive either belatacept or tacrolimus-based immunosuppression.

Results: There was no significant difference in IDO activity, as indicated by the kynurenine/tryptophan ratio, between belatacept and tacrolimus-treated patients in per-protocol and in intent-to-treat analyses. Moreover, no evidence was found that belatacept affects IDO in human dendritic cells (DC) in vitro.

Conclusion: These data provide evidence that belatacept is not associated with detectable IDO induction in the clinical transplant setting compared to tacrolimus-treated patients. This article is protected by copyright. All rights reserved.

Dermoscopic features of pseudoxanthoma elasticum

Summary

Pseudoxanthoma elasticum (PXE) is a disease characterized by aberrant mineralization of soft tissue and fragmentation of elastic fibres. It is often difficult to distinguish PXE clinically from pseudoxanthoma elasticum-like papillary dermal elastolysis (PXE-like PDE). However, we have identified that the dermoscopic findings in PXE include coalescing and reticulated yellow-white clods on a light purple-red background, whereas the dermoscopic findings in PXE-like PDE lack such a coloured background. To our knowledge, this is the first detailed description of dermoscopic differences between PXE and PXE-like PDE.

Mucinous adenocarcinoma in association with hidradenitis suppurativa: a new example of isoscartopic response

Unilateral improvement of nail psoriasis with denervation injury

Radiotherapy and anti-PD-1/PD-L1 combinations in lung cancer: building better translational research platforms

Abstract

Despite the unheralded success of immune checkpoint blockade in delivering durable responses for some patients with non-small cell lung cancer (NSCLC), the majority of patients do not respond. PD-L1 tumour expression and pre-existing tumour T-cell infiltration have been correlated with improved clinical outcomes to anti-PD-1/anti-PD-L1. However, patients with tumours that are negative for PD-L1 expression can also respond to treatment. Strategies to combine other treatment modalities like radiotherapy with immune checkpoint inhibitors are being investigated as means of improving the response rates to PD-1/PD-L1 antibody blockade. Radiotherapy induces immunogenic changes in cancer cells, can adaptively upregulate tumour cell PD-L1 expression and can improve the efficacy of anti-PD-1/anti-PD-L1 therapy. How we design future clinical trials in NSCLC also depends on practical considerations of delivering these treatment combinations, such as radiotherapy dose, fractionation and field volume, as well as scheduling with immune checkpoint blockade. Here, we review reasons for resistance to anti-PD-1/anti-PD-L1 and how radiotherapy may be utilised in combination with these drugs to enhance their effect by building better translational research platforms.

Water and sediment quality assessment in the Colastiné-Corralito stream system (Santa Fe, Argentina): impact of industry and agriculture on aquatic ecosystems

Abstract

The present study focuses on the evaluation of metal (chromium, copper, and lead), arsenic, and pesticide (atrazine and endosulfan) contamination in freshwater streams of one of the most important agricultural and industrial areas of central-eastern Argentina, which has not been reported earlier. The environmental fate of inorganic microcontaminants and pesticides was assessed. Samples were collected monthly for a year. Pesticide concentrations were measured in water; metal and arsenic concentrations were measured in water and sediments, and physicochemical variables were analyzed. In most cases, metals and arsenic in water exceeded the established guideline levels for the protection of aquatic biota: 98 and 56.25% of the samples showed higher levels of Cr and Pb, while 81.25 and 85% of the samples presented higher values for Cu and As, respectively. Cr, Pb, Cu, and As exceeded 181.5 times, 41.6 times, 57.5 times, and 12.9 times, respectively, the guideline level values. In sediment samples, permitted levels were also surpassed by 40% for Pb, 15% for As, 4% for Cu, and 2% for Cr. Geoaccumulation Index (Igeo) demonstrated that most of the sediment samples were highly polluted by Cr and Cu and very seriously polluted by Pb, which indicates progressive deterioration of the sediment quality. Atrazine never exceeded them, but 27% of the 48 water samples contained total endosulfan that surpassed the guidelines. The findings of this study suggest risk to the freshwater biota over prolong periods and possible risk to humans if such type of contaminated water is employed for recreation or human use. Improper disposal of industrial effluents and agricultural runoffs need to be controlled, and proper treatment should be done before disposal to avoid further deterioration of the aquifers of this area.

Yin-Yang and the Heart-Mind

Abstract

The East Asian notion of a heart-mind (Chinese xin 心, Japanese kokoro こころ, and Korean maum 마음) is arguably more accurate to our psychology than the Western term "mind" and its equivalents are: the latter term implies the possibility of psychological functioning in the absence of all emotion, and it can be shown that that is impossible. But then it turns out that we can update the traditional Chinese notions of yin 陰 and yang 陽 in such a way as to help us philosophically explain how our functioning psychology involves emotion and why any possible psychology has to rest on such a basis. Yin-yang is the essence of heart-mind, and heart-mind is essential to any functioning psychology.

Philosophy as Elevation of Spheres of Living: Understanding Z hang Shiying’s “The Myriad Things as One Body”

Abstract

Zhang Shiying 張世英 has been widely acclaimed as a master (dashi 大師) of philosophy in mainland China. His new claim of "the myriad things as one body" (wanwuyiti 萬物一體) remains greatly influential in philosophy and aesthetics. It cannot be categorized under Marxism, Western philosophy, or traditional Chinese philosophy, because it stands on its own right. As a creative synthesizing of the three traditions, Zhang's claim answers some important and immediate problems that China is facing. It is a pity that this claim seems unknown to the West. This article tries to introduce two crucial parts of the claim: its ontology and its theory of "spheres of living" (rensheng jingjie 人生境界).

Wang, Qingjie 王慶節, “Being Morally Moved” and a Confucian Exemplary Ethics of Virtue 道德感動與儒家示範倫理學

Antituberculosis Drug-Associated DRESS: A Case Series

Publication date: Available online 20 December 2017
Source:The Journal of Allergy and Clinical Immunology: In Practice
Author(s): Marion Allouchery, Sophie Logerot, Judith Cottin, Pauline Pralong, Céline Villier, Benoit Ben Saïd
BackgroundAlthough antituberculosis drug-associated drug reaction with eosinophilia and systemic symptoms (DRESS) is rarely reported, its diagnosis should not be dismissed. Its management implies an early withdrawal of suspected drugs.ObjectiveThe objective of this study was to describe the characteristics of antituberculosis drug-associated DRESS and to identify the most likely involved drugs.MethodsWe searched for potential cases of DRESS with rifampicin, isoniazid, pyrazinamide, and ethambutol reported from January 1, 2005, to July 30, 2015, in the French pharmacovigilance database. A literature review was also performed.ResultsSixty-seven cases of antituberculosis drug-associated DRESS were analyzed (40 women and 27 men, median age of 61 years). Liver and kidneys were the most frequently involved organs. Two patients died from DRESS. Skin tests were performed in 11 patients and were positive in 8 cases. Discrepancies between epicutaneous tests and reintroduction of the culprit drugs were observed for 2 patients with a premature reintroduction of antituberculosis drugs in 1 case. Antituberculosis drugs were the only suspects in 20 cases. As for the literature data, rifampicin was the most suspected drug because of its larger indications, but in case of tuberculosis infections, isoniazid was the most suspected drug.ConclusionsWe described the largest case series of first-line antituberculosis drug-associated DRESS in the literature. All antituberculosis drugs pose a risk of DRESS. An early withdrawal of the culprit drugs is essential. A drug allergy evaluation must be performed to optimize the second-line treatment of tuberculosis infection.

Should Antibiotic Prophylaxis Be Routinely Used in Patients with Antibody-Mediated Primary Immunodeficiency?

Publication date: Available online 21 December 2017
Source:The Journal of Allergy and Clinical Immunology: In Practice
Author(s): Mark Ballow, Kenneth Paris, Maite de la Morena