Abstract
Individuals from malaria-endemic regions often acquire partial immunity after multiple repeated infections throughout their lives. This partial immunity prevents them from developing severe complications and they often remain asymptomatic with a persistent, low parasite density in the blood, and therefore the necessity for treatment is neglected. These patients with chronic, asymptomatic malaria serve as a reservoir for Plasmodium parasite transmission, becoming a major obstacle for eradication efforts. The constant exposure to malaria infection may have benefits in the short term by conferring protection from acute, severe malaria; however, it may cause substantially more harm in the long term. Rather than the parasite burden itself, the complications induced by the dysregulated immune responses and the tissue damage done by the parasites and their products can cause chronic and irreversible suffering. Furthermore, the complete clearance of parasites in the body may not lead to complete recovery from the disease as complications can still persist. The fact that there are chronic pathologies caused by malaria that mostly remain obscure and have the potential to cause a serious burden has recently been gaining attention. Here, we present and discuss the evidence of unforeseen pathologies and the risks associated with malaria.Τετάρτη 27 Δεκεμβρίου 2017
How to master the host immune system? Leishmania parasites have the solutions!
Abstract
Infection by protozoan parasites of the genus Leishmania results in the development of leishmaniases, an increasingly prevalent group of diseases affecting over 12 million people worldwide. Leishmaniasis can have very different outcomes ranging from cutaneous lesions, mucosal lesions to visceralization depending on the species of the infecting parasite and on the immune response developed by the host. As an obligate intracellular parasite, residing within macrophages, Leishmania evolved in strict contact with the host immune system, developing different mechanisms to evade or modulate the immune response. Various types of immune responses are observed during different Leishmania spp. infections, resulting in parasite clearance but also contributing to the pathogenesis, thus increasing the complexity of the course of the disease. Interestingly, depending on the type of leishmaniasis developed, opposite treatment strategies, which either boost or inhibit the inflammatory response, have shown efficacy. In this review, we summarize the contribution of different immune cell types to the development of the anti-leishmanial immune response and the parasite strategies to evade and modulate host immunity. Further, we discuss the involvement of co-infecting pathogens in the determination of the outcome of leishmaniasis and on the effectiveness of treatment and the implication of the immune response for treatment and vaccine development.Human T cell responses to Dengue and Zika virus infection compared to Dengue/Zika coinfection
Abstract
Introduction
Zika virus (ZIKV) and dengue virus (DENV) co-circulated during latest outbreaks in Brazil, hence, it is important to evaluate the host cross-reactive immune responses to these viruses. So far, little is known about human T cell responses to ZIKV and no reports detail adaptive immune responses during DENV/ZIKV coinfection.
Methods
Here, we studied T cells responses in well-characterized groups of DENV, ZIKV, or DENV/ZIKV infected patients and DENV-exposed healthy donors. We evaluated chemokine receptors expression and single/multifunctional frequencies of IFNγ, TNF, and IL2-producing T cells during these infections. Even without antigenic stimulation, it was possible to detect chemokine receptors and IFNγ, TNF, and IL2-producing T cells from all individuals by flow cytometry. Additionally, PBMCs' IFNγ response to DENV NS1 protein and to polyclonal stimuli was evaluated by ELISPOT.
Results
DENV and ZIKV infections and DENV/ZIKV coinfections similarly induced expression of CCR5, CX3CR1, and CXCR3 on CD4 and CD8 T cells. DENV/ZIKV coinfection decreased the ability of CD4+ T cells to produce IFNγ+, TNF+, TNF + IFNγ+, and TNF + IL2+, compared to DENV and ZIKV infections. A higher magnitude of IFNγ response to DENV NS1 was found in donors with a history of dengue infection, however, a hyporesponsiveness was found in acute DENV, ZIKV, or DENV/ZIKV infected patients, even previously infected with DENV.
Conclusion
Therefore, we emphasize the potential impact of coinfection on the immune response from human hosts, mainly in areas where DENV and ZIKV cocirculate.
Since Zika virus (ZIKV) and dengue virus (DENV) co-circulated during outbreaks in Brazil, it is important to evaluate the host immune response to these viruses. Here, we studied T cells responses in well-characterized groups of DENV, ZIKV, or DENV/ZIKV infected patients and DENV-exposed healthy donors. Our main observations were: (i) most of the patients diagnosed with ZIKV were coinfected with DENV and (ii) DENV/ZIKV coinfection activate differentially CD4+ and CD8+ T cells compared to mono-infection.
LETTER TO EDITOR JPRAS Re: Hernandez Rosa et al 2017
Publication date: Available online 27 December 2017
Source:Journal of Plastic, Reconstructive & Aesthetic Surgery
Author(s): J.L. See, J. Przybylska, L. MacLennan, C.M. Malata
Letter in response to: skin tattooing following correction of prominent ears
Source:Journal of Plastic, Reconstructive & Aesthetic Surgery
Author(s): J.T. Hardwicke
Dutch breast reconstruction guideline
Source:Journal of Plastic, Reconstructive & Aesthetic Surgery
Author(s): Marc A.M. Mureau
Treatment of breast cancer is complex and multidisciplinary by nature, with protocols that are updated continuously. During preoperative multidisciplinary team meetings, regularly there is discussion between team members regarding optimal timing and type of breast reconstruction, due to conflicting interests of oncological and reconstructive treatments.Therefore, a multidisciplinary, evidence-based guideline for breast reconstruction in women undergoing breast conserving therapy or mastectomy for breast cancer, or following prophylactic mastectomy was developed by a multidisciplinary working group. The guideline was drafted in accordance with the AGREE II instrument, designed to assess the quality of guidelines with broad international support. For the recommendations, scientific evidence was considered together with other key aspects, such as working group member expertise, patient preferences, costs, availability of facilities and/or organizational aspects. Recommendations provide an answer to the primary questions, and are based on the best scientific evidence available together with the most important considerations by the working group. In accordance with the GRADE method, the level of scientific evidence and the importance given to considerations by the working group jointly determined the strength of the recommendation.The guideline aims to provide practical guidance for plastic surgeons and other members of the multidisciplinary breast cancer team. The implementation of the present breast reconstruction guideline may contribute to optimizing the delivery of care and support for breast reconstruction patients, it may stimulate evidence-based plastic surgery, it may reduce undesirable variation in clinical practice between health care providers, and improve the overall quality of life of breast reconstruction patients.
Simultaneous Use of Selective Neurectomy With Liposuction for Calf Reduction in Asians
Abstract
Background
Calf contouring continues to be popular among Northeast Asians. Calf hypertrophy and distorted leg contours are stressful to many women. Several calf reduction techniques such as a selective neurectomy or calf muscle resection have been attempted, but have inconsistent results. Objectives
This study was designed to demonstrate improved outcomes when combining a selective neurectomy with simultaneous liposuction. Methods
A total of 780 patients with hypertrophic calves underwent calf reduction from January 2002 to December 2010. Of these, 193 patients were treated by selective neurectomy with simultaneous liposuction. Calf hypertrophy with a circumference below 34 cm was defined as mild, calves with a circumference of 34 to 38 cm were defined as moderate, and a calf circumference above 38 cm was defined as severe. In all groups, patients whose pinch test was above 2 cm underwent a simultaneous liposuction. Results
Twenty-eight cases (14.5%) were defined as mild, 72 (37.3%) were moderate, and 93 (48.2%) were severe. Over an average of 8.7 months of postoperative follow up, the reduction in calf circumference averaged 3.7 cm in the mild group (11.1%), 4.0 cm in the moderate group (10.7 %), and 4.3 cm in the severe group (10.7%). Overall, 97.5% of patients were satisfied with the results. There were no severe complications including functional problem of lower extremity reported. Conclusions
The shape, type, and fat distribution of the hypertrophic calves were considered in our patient analysis. A selective neurectomy with liposuction was performed on 193 patients. This technique allowed for a successful calf reduction and improved the patient's aesthetic satisfaction without any reported functional complications. Level of Evidence: 4
Commentary on: Simultaneous Use of Selective Neurectomy With Liposuction for Calf Reduction in Asians
The preceding article on calf reduction is significant for several reasons, not the least of which is to draw attention to the under reported perceptions of patients regarding the appearance of their calves.1 Patient concern regarding breast, abdominal, buttock, and facial appearance are the most commonly considered cosmetic areas of interest among lay and professional audiences. Although our clinical experience with cosmetic calf surgery has only been through calf augmentation with fat grafting it has become apparent that this anatomic area is a very significant cosmetic focal point.2
Body mass index and 20-specific cancers: re-analyses of dose-response meta-analyses of observational studies.
Abstract
Background
Objectives were to provide an overview and understand the strength of evidence and extent of potential biases and validity of claimed associations between Body Mass Index (BMI) and risk of developing cancer. Methods
We performed an umbrella review and comprehensively re-analysed the data of dose-response meta-analyses on associations between BMI and risk of 20-specific cancers (bladder, brain, breast, colonic, rectal, endometrial, gallbladder, gastric, leukemia, liver, lung, melanoma, multiple myeloma, non-Hodgkins lymphoma, oesophagus, ovarian, pancreatic, prostate, renal, thyroid) by adding big data or missed individual studies. Convincing evidence for an association was defined as a strong statistical significance in fixed-effects and random-effects meta-analyses at p < 0.001, 95% prediction interval (PI) excluded null, there was no large between-study heterogeneity and no small study effects. Suggestive evidence was defined as meeting the significance threshold for the random summary effects of p < 0.05, but 95% PI included the null. Weak evidence was defined as meeting the significance threshold for the random summary effects at a P < 0.05, but 95% PI included the null and there was large between-study heterogeneity or there were small study effects. Results
Convincing evidence for an association with BMI was detectable for 5 cancers (leukemia, multiple myeloma, pancreatic, endometrial, rectal, and renal cell carcinoma). Suggestive evidence was detectable for malignant melanoma, non-Hodgkins lymphoma and oesophageal adenocarcinoma. Weak evidence was detectable for brain and central nervous system tumors, breast, colon, gall bladder, lung, liver, ovarian, and thyroid cancer. No evidence was detectable for bladder, gastric, and prostate cancer. Conclusions
The association of increased BMI and cancer is heterogeneous across cancer types. Leukemia, multiple myeloma, pancreatic, endometrial, rectal, and renal cell carcinoma are convincingly associated with an increased BMI by dose-responsive meta-analyses.Influenza B virus infection and Stevens–Johnson syndrome
Abstract
A 2-year-old boy with influenza B infection and rapidly worsening targetoid skin lesions with mucosal involvement was diagnosed with Stevens–Johnson syndrome (SJS) and treated with oseltamivir and intravenous immunoglobulin, with resolution of illness. Subsequent quadrivalent inactivated influenza vaccine was well tolerated. This case highlights the rarity of SJS in the setting of influenza B infection and addresses the safety of administering subsequent influenza vaccines to such individuals.
Employing response surface methodology (RSM) to improve methane production from cotton stalk
Abstract
China is the largest cotton producer with the cotton output accounting for 25% of the total world's cotton production. A large quantity of cotton stalk (CS) waste is generated which is burned and causes environmental and ecological problems. This study investigated the anaerobic digestibility of CS by focusing on improving the methane yield by applying central composite design of response surface methodology (RSM). The purpose of this study was to determine the best level of factors to optimize the desired output of methane production from CS. Thus, it was necessary to describe the relationship of many individual variables with one or more response values for the effective utilization of CS. The influences of feed to inoculum (F/I) ratio and organic loading (OL) on methane production were investigated. Results showed that the experimental methane yield (EMY) and volatile solid (VS) removal were calculated to be 70.22 mL/gVS and 14.33% at F/I ratio of 0.79 and organic loading of 25.61 gVS/L, respectively. Characteristics of final effluent showed that the anaerobic system was stable. This research laid a foundation for future application of CS to alleviate the problems of waste pollution and energy output.
Barium concentrations and speciation in surface waters collected from an active barium mining area in Guizhou Province, southwestern China
Abstract
Barium (Ba) is a toxic element and can cause serious health effects. Humans have experienced increased exposure to Ba due to its intensive usage in industrial areas and daily life. Anthropogenic activities of Ba mining and the manufacture of Ba containing products introduce the element into surrounding areas, posing environmental concerns. Concentrations of total Ba (TBa) and dissolved Ba (DBa) in water samples collected from active Ba mines in Tianzhu, east Guizhou Province, southwestern China were measured to show the regional dispersion of Ba contamination. Aqueous Ba species in water were calculated using the PHREEQC program. The results showed that TBa and DBa concentrations ranged from 6.7 to 483.1 μg/L and from 7.5 to 222.7 μg/L, respectively. TBa concentrations presented a high average value of 126.6 μg/L and greatly exceeded the reported common value of 10 μg/L Ba in surface water set by the Ministry of Environment Protection of China. PHREEQC results indicated that Ba species in water were present as Ba2+, BaSO4, BaHCO3, BaCO3, and BaOH+. The distribution of Ba species in water is controlled by pH and total organic carbon (TOC), and the lower pH (pH < 7) the higher the dissolved fractions. The log K d values (K d , dissolved-particulate distribution coefficients) varied from 2.41 to 6.32. Significant correlations were observed among Ba2+ and K+, Na+, Cl−, NO3−, with Pearson correlation coefficients of 0.425, 0.531, 0.853, 0.612, and 0.329, respectively (p < 0.01). Elevated Ba concentrations in water indicated that the Ba contamination and its distribution pattern in local aquatic ecosystems are derived from Ba mining sites in the Tianzhu area.
Co-treatment of flotation waste, neutralization sludge, and arsenic-containing gypsum sludge from copper smelting: solidification/stabilization of arsenic and heavy metals with minimal cement clinker
Abstract
Flotation waste of copper slag (FWCS), neutralization sludge (NS), and arsenic-containing gypsum sludge (GS), both of which are difficult to dispose of, are major solid wastes produced by the copper smelting. This study focused on the co-treatment of FWCS, NS, and GS for solidification/stabilization of arsenic and heavy metals with minimal cement clinker. Firstly, the preparation parameters of binder composed of FWCS, NS, and cement clinker were optimized to be FWCS dosage of 40%, NS dosage of 10%, cement clinker dosage of 50%, mill time of 1.5 h, and water-to-binder ratio of 0.25. On these conditions, the unconfined compressive strength (UCS) of the binder reached 43.24 MPa after hydration of 28 days. Then, the binder was used to solidify/stabilize the As-containing GS. When the mass ratio of binder-to-GS was 5:5, the UCS of matrix can reach 11.06 MPa after hydration of 28 days, meeting the required UCS level of MU10 brick in China. Moreover, arsenic and other heavy metals in FWCS, NS, and GS were effectively solidified or stabilized. The heavy metal concentrations in leachate were much lower than those in the limits of China standard leaching test (CSLT). Therefore, the matrices were potential to be used as bricks in some constructions. XRD analysis shows that the main hydration products of the matrix were portlandite and calcium silicate hydrate. These hydration products may play a significant role in the stabilization/solidification of arsenic and heavy metals.
Heparin-induced haemorrhagic bullous dermatosis
Summary
Background
Heparin-induced haemorrhagic bullous dermatosis (HBD) is a rare but probably underdiagnosed reaction to heparin, with 26 cases reported in the English literature. Currently, there is no consensus regarding the treatment.
Aim
To assess our new cases of HBD and review the previously reported cases, in order to draw conclusions about this adverse skin reaction to heparin.
Methods
A PubMed search was performed for articles containing the terms '(heparin-induced AND (blister OR bulla OR bullae)) OR (hemorrhagic bullous dermatosis AND heparin) OR heparin bullous dermatosis'. Descriptive statistical data analysis was performed using Microsoft Excel.
Results
We assessed five new cases of HBD. In addition, our literature search revealed 26 previously reported patients. Combining these, we found that the mean ± SD age of patients with HBD was 71.4 ± 14 years. HBD affects men more commonly than women (men 22/31; P = 0.02). Patients develop tense bullae most frequently on the extremities, approximately 8 days (mean ± SD 7.5 ± 6.4 days) after starting treatment with a heparin product, usually enoxaparin.
Conclusions
The typical clinical course is spontaneous resolution within days to weeks irrespective of continuation of heparin therapy. Because of its self-limiting nature, interruption of heparin therapy may not be required.
Letter in response to: skin tattooing following correction of prominent ears
In response to the letter from Drs Noblet, Jackson and Smith [1], I would agree that these rare but significant complications are justified in their reporting. For the purposes of the pooled proportion meta-analysis of surgical complication following pinnaplasty [2], the most commonly reported complications were analysed, ie. haematoma and/or bleeding, infection, skin/wound healing problems, suture-related problems, scarring, pain and itching, or revision/recurrence. Although this type of analysis can be open to criticism for relying on the open reporting of data, it does give a contemporary overview of the topic.
Dutch breast reconstruction guideline
Treatment of breast cancer is complex and multidisciplinary by nature, with protocols that are updated continuously. During preoperative multidisciplinary team meetings, regularly there is discussion between team members regarding optimal timing and type of breast reconstruction, due to conflicting interests of oncological and reconstructive treatments.Therefore, a multidisciplinary, evidence-based guideline for breast reconstruction in women undergoing breast conserving therapy or mastectomy for breast cancer, or following prophylactic mastectomy was developed by a multidisciplinary working group.
LETTER TO EDITOR JPRAS Re: Hernandez Rosa et al 2017
Hernandez Rosa J, Sherif RD, Torina PJ, Harmaty MA. Use of both antegrade and retrograde internal mammary vessels in the bipedicled deep inferior epigastric perforator flap for unilateral breast reconstruction. J Plast Reconstr Aesthet Surg. 2017 Jan, 70(1): 47-53.
Psychosocial health of cochlear implant users compared to that of adults with and without hearing aids: Results of a nationwide cohort study
Abstract
Objectives
This study aimed to examine the psychosocial health status of adult cochlear implant (CI) users, compared to that of hearing aid (HA) users, hearing-impaired adults without hearing aids, and normally hearing adults.
Design
Cross-sectional observational study, using both self-reported survey data and a speech-in-noise test.
Setting
Data as collected within the Netherlands Longitudinal Study on Hearing (NL-SH) between September 2011 and June 2016 were used.
Participants
Data from 1,254 Dutch adults (aged 18 to 70), selected in a convenience sample design, were included for analyses.
Mean outcome measures
Psychosocial health measures included emotional and social loneliness, anxiety, depression, distress, and somatisation. Psychosocial health, hearing status, use of hearing technology, and covariates were measured by self-report; hearing ability was assessed through an online digit-triplet speech-in-noise test.
Results
After adjusting for the degree of hearing impairment, HA users (N=418) and hearing-impaired adults (N=247) had significantly worse scores on emotional loneliness than CI users (N=37). HA users had significantly higher anxiety scores than CI users in some analyses. Non-significant differences were found between normally hearing (N=552) and CI users for all psychosocial outcomes.
Conclusions
Psychosocial health of CI-users is not worse than that of hearing-impaired adults with or without hearing aids. CI users' level of emotional loneliness is even lower than that of their hearing impaired peers using hearing aids. A possible explanation is that CI-patients receive more professional and family support, and guidance along their patient journey than adults who are fitted with hearing aids.
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Association of Uterine Leiomyomas With Central Centrifugal Cicatricial Alopecia
This cohort study examines the risk of uterine leiomyomas in black women with central centrifugal cicatricial alopecia.
Nongenital Molluscum Contagiosum in Persons Without Immune Deficiency
This Clinical Evidence Synopsis summarizes an updated Cochrane review that assessed effectiveness and safety of treatments for nongenital molluscum contagiosum in persons without immune deficiency.
Diameter of Skin Lesions With and Without a Ruler
This analysis of survey results examines the accuracy with which medical students, internal medicine residents, and dermatology residents, fellows, and faculty can estimate the diameter of skin lesions in clinical photographs.
Cutaneous Diphtheria Mimicking Pyoderma Gangrenosum
This case report describes a patient with cutaneous diphtheria mimicking pyoderma gangrenosum.
Standardized Screening for Depression and Suicidal Ideation
This Viewpoint examines the role of the Patient Health Questionnaire-2 in dermatology concerning secondary psychiatric disorders that involve emotional disturbances and manifest in response to the psychologic stress caused by dermatologic conditions.
A Case of Adult Intestinal Toxemia Botulism During Prolonged Hospitalization in an Allogeneic Hematopoietic Cell Transplant Recipient
Abstract
We report a laboratory-confirmed case of adult intestinal toxemia botulism in an allogeneic hematopoietic stem cell transplantation (allo-HCT) recipient. Onset of symptoms occurred within the hospitalized setting, making this case particularly unique. Botulism may have arisen because of significant intestinal disruption and compromise, and not directly from immune compromise.Outbreak of Foodborne Botulism in an Immigrant Community: Overcoming Delayed Disease Recognition, Ambiguous Epidemiologic Links, and Cultural Barriers to Identify the Cause
Abstract
We describe a botulism outbreak involving 4 Middle Eastern men complicated by delayed diagnosis, ambiguous epidemiologic links among patients, and illness onset dates inconsistent with a point-source exposure. Homemade turshi, a fermented vegetable dish, was the likely cause. Patients ate turshi at 2 locations on different days over 1 month.Clinical Features of Foodborne and Wound Botulism: A Systematic Review of the Literature, 1932–2015
Abstract
Background
Botulism is a rare, potentially fatal paralytic illness caused by neurotoxins. To inform the evaluation of patients with suspected botulism, we conducted a systematic review to describe the clinical features of botulism. Methods
We searched Medline Ovid, Embase Dialog, Embase Ovid, Cumulative Index to Nursing and Allied Health Literature (CINAHL) EBSCO, Global Health Ovid, Cochrane Library, Scopus, and ClinicalTrials.gov for English language articles through May 2015. Information abstracted included demographics, signs and symptoms, laboratory results, and clinical outcome for foodborne and wound botulism patients confirmed by laboratory testing, epidemiologic link, or association with an outbreak. The review followed PRISMA guidelines and was registered with PROSPERO (CRD42015024784). Results
We identified 402 patients from 233 articles published in English between 1932 and 2015. Most cases (n = 346 [86%]) were foodborne botulism and most (n = 263 [65%]) were associated with an outbreak. The median incubation period was 1 day, and the median time from illness onset to hospital admission was 2 days. Shortness of breath, dyspnea, or respiratory distress or failure at hospital admission was reported in 169 (42%) patients; 71 (42%) reported respiratory involvement without report of extremity weakness. Among 154 patients for whom the hospital day of intubation was reported, 134 (87%) were intubated on the first or second hospital day. Conclusions
Botulism patients can experience a range of signs and symptoms. Respiratory involvement may occur early in the illness and can occur without preceding extremity weakness. Clinicians and public health departments preparing for and responding to botulism events should use this information to guide the evaluation of suspected botulism patients.Workgroup Report by the Joint Task Force Involving American Academy of Allergy, Asthma & Immunology (AAAAI); Food Allergy, Anaphylaxis, Dermatology and Drug Allergy (FADDA) (Adverse Reactions to Foods Committee and Adverse Reactions to Drugs, Biologicals, and Latex Committee); and the Centers for Disease Control and Prevention Botulism Clinical Treatment Guidelines Workgroup—Allergic Reactions to Botulinum Antitoxin: A Systematic Review
Abstract
Background
Naturally occurring botulism is rare, but a large number of cases could result from unintentional or intentional contamination of a commercial food. Despeciated, equine-derived, heptavalent botulinum antitoxin (HBAT) is licensed in the United States. Timely treatment reduces morbidity and mortality, but concerns that botulinum antitoxin can induce anaphylaxis exist. We sought to quantify the allergy risk of botulinum antitoxin treatment and the usefulness of skin testing to assess this risk. Methods
We conducted a systematic review of (1) allergic reactions to botulinum antitoxin and (2) the predictive value of skin testing (ST) before botulinum antitoxin administration. We searched 5 scientific literature databases, reviewed articles' references, and obtained data from the HBAT manufacturer and from the Centers for Disease Control and Prevention. Anaphylaxis incidence was determined for HBAT and previously employed botulinum antitoxins. We calculated the positive predictive value (PPV) and negative predictive value (NPV) of ST for anaphylaxis related to HBAT and other botulinum antitoxins. Results
Seven articles were included. Anaphylaxis incidence was 1.64% (5/305 patients) for HBAT and 1.16% (8/687 patients) for all other botulinum antitoxins (relative risk, 1.41 [95% confidence interval, .47–4.27]; P = .5). Observed values for both PPV and NPV for HBAT-ST (33 patients) were 100%. Observed PPVs and NPVs of ST for other botulinum antitoxins (302 patients) were 0–56% and 50%–100%, respectively. There were no reports of fatal anaphylaxis. Conclusions
Considering the <2 % rate of anaphylaxis, fatal outcomes, modest predictive value of ST, resource requirements for ST, and the benefits of early treatment, data do not support delaying HBAT administration to perform ST in a mass botulinum toxin exposure. Anaphylactic reactions may occur among 1%–2% of botulinum antitoxin recipients and will require epinephrine and antihistamine treatment and, possibly, intensive care.Pediatric Botulism and Use of Equine Botulinum Antitoxin in Children: A Systematic Review
Abstract
Background
Botulism manifests with cranial nerve palsies and flaccid paralysis in children and adults. Botulism must be rapidly identified and treated; however, clinical presentation and treatment outcomes of noninfant botulism in children are not well described. Methods
We searched 12 databases for peer-reviewed and non-peer-reviewed reports with primary data on botulism in children (persons <18 years of age) or botulinum antitoxin administration to children. Reports underwent title and abstract screening and full text review. For each case, patient demographic, clinical, and outcome data were abstracted. Results
Of 7065 reports identified, 184 met inclusion criteria and described 360 pediatric botulism cases (79% confirmed, 21% probable) that occurred during 1929–2015 in 34 countries. Fifty-three percent were male; age ranged from 4 months to 17 years (median, 10 years). The most commonly reported signs and symptoms were dysphagia (53%), dysarthria (39%), and generalized weakness (37%). Inpatient length of stay ranged from 1 to 425 days (median, 24 days); 14% of cases required intensive care unit admission; 25% reported mechanical ventilation. Eighty-three (23%) children died. Median interval from illness onset to death was 1 day (range, 0–260 days). Among patients who received antitoxin (n = 193), 23 (12%) reported an adverse event, including rash, fever, serum sickness, and anaphylaxis. Relative risk of death among patients treated with antitoxin compared with patients not treated with antitoxin was 0.24 (95% confidence interval, .14–.40; P < .0001). Conclusions
Dysphagia and dysarthria were the most commonly reported cranial nerve symptoms in children with botulism; generalized weakness was described more than paralysis. Children who received antitoxin had better survival; serious adverse events were rare. Most deaths occurred early in the clinical course; therefore, botulism in children should be identified and treated rapidly.Type F Infant Botulism: Investigation of Recent Clusters and Overview of This Exceedingly Rare Disease
Abstract
From 1976 to 2016, neurotoxigenic Clostridium baratii type F caused 18 (<0.5%) reported US infant botulism cases. Six cases occurred during 2012–2013; no common source was identified. Type F infant botulism mostly occurs in very young infants and typically presents more rapidly and severely than illness caused by types A and B botulinum neurotoxin.Botulism During Pregnancy and the Postpartum Period: A Systematic Review
Abstract
Background
Maternal and fetal outcomes associated with botulism and botulinum antitoxin use during pregnancy and the postpartum period have not been systematically reviewed. Methods
We searched Global Health, Cochrane Library, Cumulative Index to Nursing and Allied Health Literature, Scopus, and Medline databases from inception to May 2015 for studies published on botulism or botulinum antitoxin use during pregnancy and the postpartum period, as well as the Centers for Disease Control and Prevention National Botulism Surveillance database. Our search identified 4517 citations. Results
Sixteen cases of botulism during pregnancy (11 in the third trimester) and 1 case during the postpartum period were identified. Ten cases were associated with confirmed or likely foodborne exposure; 2 cases were attributed to wound contamination related to heroin use, and the source of 5 cases was unknown. Eleven women with botulism had progressive neurologic deterioration and respiratory failure, requiring intensive care unit admission. Four women had adverse outcomes, including 2 deaths and 2 women who remained in a persistent vegetative state. No neonatal losses or cases of congenital botulism were reported. Among the 12 cases that reported neonatal data, 6 neonates were born preterm. No adverse maternal or neonatal events were identified as associated with botulinum antitoxin therapy among 11 patients who received it. Conclusions
Our review of 17 cases of botulism in pregnant/postpartum women found that more than half required ventilator support, 2 women died, and 6 infants were born prematurely. A high level of clinical suspicion is key for early diagnosis and treatment of botulism. Care of pregnant women or new mothers with botulism can include preparation for possible intubation.Making the Best of the Evidence: Toward National Clinical Guidelines for Botulism
botulismguidelinesantitoxindiagnosistreatment
Clinical Criteria to Trigger Suspicion for Botulism: An Evidence-Based Tool to Facilitate Timely Recognition of Suspected Cases During Sporadic Events and Outbreaks
Abstract
Effective treatment for botulism requires early clinical recognition. Diagnosis of botulism, including during outbreaks, can be challenging. We assessed combinations of signs and symptoms among confirmed cases and identified sensitive clinical criteria to trigger suspicion. We produced a tool that may facilitate rapid identification of sporadic and outbreak-associated cases.The Epidemiology of Foodborne Botulism Outbreaks: A Systematic Review
Abstract
Background
We performed a systematic review of foodborne botulism outbreaks to describe their clinical aspects and descriptive epidemiology in order to inform public health response strategies. Methods
We searched seven databases for reports of foodborne botulism outbreaks published in English from database inception to May 2015. We summarized descriptive characteristics and analyzed differences in exposure and toxin types by geographic region. We performed logistic regression to assess correlations between exposure source, implicated food, and outbreak size. Results
There were 197 outbreaks reported between 1920 and 2014. The median number of cases per outbreak was 3 (range 2–97). The majority of reported outbreaks (109; 55%) occurred in the United States. Toxin types A, B, E, and F were identified as the causative agent in 34%, 16%, 17%, and 1% of outbreaks, respectively. The median duration between exposure and symptom onset was approximately 1 day. The mean percentage of cases requiring mechanical ventilation per outbreak was 34%. Seventy percent of all outbreaks and 77% of small outbreaks (≤11 cases) originated from point source exposures, while commercial foods were significantly (odds ratio, 6.9; 95% confidence interval, 2.2–21.1) associated with large outbreaks (≥12 cases). Conclusions
Toxin type A accounted for half of outbreaks, and these outbreaks had a higher proportion of patient ventilatory failure. Most outbreaks were due to point source exposures, while outbreaks due to commercial food were larger. For effective responses to foodborne botulism outbreaks, these findings demonstrate the need for timely outbreak investigation and hospital surge capacity.Clinical Characteristics and Ancillary Test Results Among Patients With Botulism—United States, 2002–2015
Abstract
Background
Botulism is classically described as a bilateral, symmetric, descending flaccid paralysis in an afebrile and alert patient without sensory findings. We describe the reported spectrum of clinical findings among persons >12 months of age in the United States during 2002–2015. Methods
The Centers for Disease Control and Prevention collects clinical findings reported by physicians treating suspected cases of botulism nationwide. We analyzed symptoms and signs, and neuroimaging and cerebrospinal fluid (CSF) results. A case was defined as illness compatible with botulism with laboratory confirmation or epidemiologic link to a confirmed case, and presence or absence of at least 1 sign or symptom recorded. Physicians' differential diagnoses were evaluated. Results
Clinical information was evaluated for 332 botulism cases; data quality and completeness were variable. Most had no fever (99%), descending paralysis (93%), no mental status change (91%), at least 1 ocular weakness finding (84%), and neuroimaging without acute changes (82%). Some had paresthesias (17%), elevated CSF protein level (13%), and other features sometimes considered indicative of alternative diagnoses. Five of 71 (7%) cases with sufficient information were reported to have atypical findings (eg, at least 1 cranial nerve finding that was unilateral or ascending paralysis). Illnesses on the physician differential included Guillain-Barré syndrome (99 cases) and myasthenia gravis (76 cases) and, rarely, gastrointestinal-related illness (5 cases), multiple sclerosis (3 cases), sepsis (3 cases), and Lyme disease (2 cases). Conclusions
Our analysis illustrates that classic symptoms and signs were common among patients with botulism but that features considered atypical were reported by some physicians. Diagnosis can be challenging, as illustrated by the broad range of illnesses on physician differentials.Outbreak of Botulism Due to Illicit Prison-Brewed Alcohol: Public Health Response to a Serious and Recurrent Problem
Abstract
Background
Botulism is a rare, sometimes lethal neuroparalytic illness. On 2 October 2011, an inmate at prison A developed symptoms compatible with botulism after drinking pruno, an illicit, prison-brewed alcoholic beverage. Additional illnesses were identified within several days. We conducted an investigation to determine the cause and extent of the outbreak. Methods
A case was defined as signs or symptoms of botulism in a prison A inmate with onset during 30 September–9 October 2011. Cases were identified through medical evaluations and interviews with inmates about recent pruno consumption. Laboratory testing was performed for Clostridium botulinum and botulinum neurotoxin. Ingredients, preparation, and sharing of the implicated pruno were investigated. Results
Eight prisoners developed botulism; all drank pruno made with a potato. Three received mechanical ventilation. Culture of fluid from a sock that inmates reported using to filter the implicated pruno yielded C. botulinum type A. The implicated batch may have been shared between cells during delivery of meal trays. Challenges of the investigation included identifying affected inmates, overcoming inaccuracies in histories, and determining how the illicit beverage was shared. Costs to taxpayers were nearly $500000 in hospital costs alone. Conclusions
Pruno made with potato has emerged as an important cause of botulism in the United States. This public health response illustrates the difficulties of investigating botulism in correctional facilities and lessons learned for future investigations.Efficacy of Antitoxin Therapy in Treating Patients With Foodborne Botulism: A Systematic Review and Meta-analysis of Cases, 1923–2016
Abstract
Background
Botulism is a rare, potentially severe illness, often fatal if not appropriately treated. Data on treatment are sparse. We systematically evaluated the literature on botulinum antitoxin and other treatments. Methods
We conducted a systematic literature review of published articles in PubMed via Medline, Web of Science, Embase, Ovid, and Cumulative Index to Nursing and Allied Health Literature, and included all studies that reported on the clinical course and treatment for foodborne botulism. Articles were reviewed by 2 independent reviewers and independently abstracted for treatment type and toxin exposure. We conducted a meta-analysis on the effect of timing of antitoxin administration, antitoxin type, and toxin exposure type. Results
We identified 235 articles that met the inclusion criteria, published between 1923 and 2016. Study quality was variable. Few (27%) case series reported sufficient data for inclusion in meta-analysis. Reduced mortality was associated with any antitoxin treatment (odds ratio [OR], 0.16; 95% confidence interval [CI], .09–.30) and antitoxin treatment within 48 hours of illness onset (OR, 0.12; 95% CI, .03–.41). Data did not allow assessment of critical care impact, including ventilator support, on survival. Therapeutic agents other than antitoxin offered no clear benefit. Patient characteristics did not predict poor outcomes. We did not identify an interval beyond which antitoxin was not beneficial. Conclusions
Published studies on botulism treatment are relatively sparse and of low quality. Timely administration of antitoxin reduces mortality; despite appropriate treatment with antitoxin, some patients suffer respiratory failure. Prompt antitoxin administration and meticulous intensive care are essential for optimal outcome.A Case of Localized, Unilateral (Cephalic) Wound Botulism
Abstract
We describe a rare presentation of botulism originally presenting with exclusively unilateral cranial nerve deficits following a puncture wound to the face. Cephalic tetanus was initially suspected but laboratory testing confirmed botulism. Botulism caused by local diffusion of toxin from a contaminated head wound can be confused with cephalic tetanus.Safety and Improved Clinical Outcomes in Patients Treated With New Equine-Derived Heptavalent Botulinum Antitoxin
Abstract
Background
Botulism is a rare, life-threatening paralytic illness. Equine-derived heptavalent botulinum antitoxin (HBAT), the only currently available treatment for noninfant botulism in the United States, was licensed in 2013. No reports have systematically examined safety and clinical benefit of HBAT among botulism patients. Methods
From March 2010 through March 2013, we collected data prospectively and through medical record reviews of patients with confirmed or suspected botulism who were treated with HBAT under an expanded-access Investigational New Drug program. Results
Among 249 HBAT-treated patients, 1 (<1%) child experienced an HBAT-related serious adverse event (hemodynamic instability characterized by bradycardia, tachycardia, and asystole); 22 (9%) patients experienced 38 nonserious adverse events reported by physicians to be HBAT related. Twelve (5%) deaths occurred; all were determined to be likely unrelated to HBAT. Among 104 (42%) patients with confirmed botulism, those treated early (≤2 days) spent fewer days in the hospital (median, 15 vs 25 days; P < .01) and intensive care (10 vs 17 days; P = .04) than those treated later. Improvements in any botulism sign/symptom were detected a median of 2.4 days and in muscle strength a median of 4.8 days after HBAT. Conclusions
HBAT was safe and provided clinical benefit in treated patients. HBAT administration within 2 days of symptom onset was associated with shorter hospital and intensive care stays. These results highlight the importance of maintaining clinical suspicion for botulism among patients presenting with paralytic illness to facilitate early HBAT treatment before laboratory confirmation might be available. Clinical consultation and, if indicated, HBAT release, are available to clinicians 24/7 through their state health department in conjunction with CDC.Reasoning Abilities and Potential Correlates Among Jordanian School Children
Abstract
Objectives To investigate factors related to reasoning skills in 434 school children aged 5–9 years. Methods The Leiter International Performance Scale-Revised was used to assess reasoning skills. Demographic, work and family income data, information on child's daily behavior and school academic achievement were provided by the participating children's parents. Results Reasoning scores increased by 4.56 points with increasing subject's age, 1.71 points with increasing level of father's occupation, 1.86 points with each increase in the subject's GPA, 1.13 points with consumption of breakfast at home and 1.81 points when child slept more hours. Having a father who smoked and living in a rural area decreased scores in reasoning. Conclusions for Practice Screening of reasoning and associated factors is essential for a comprehensive and accurate understanding of the child's abilities and limitations. Understanding the child's reasoning abilities is critical for establishing intervention goals and planning therapeutic activities.
Successful Treatment of Refractory Vitiligo with a Combination of Khellin and 308-nm Excimer Lamp: An Open-Label, 1-Year Prospective Study
Abstract
Introduction
Phototherapy is the cornerstone of treatment of vitiligo. The 308-nm excimer lamp (EL) induces T cell apoptosis and the stimulation of melanocyte proliferation. Khellin is a furanochromone with a chemical structure close to psoralens. The objective of the study was to evaluate the safety and efficacy of 1-year treatment of recalcitrant vitiligo with a combination of 308-nm EL and khellin.
Methods
Twenty patients with resistant vitiligo were included. Khellin was applied 45 min before irradiation with EL, twice a week, at a dose of 250 mJ/cm2. The repigmentation was assessed in four categories: excellent repigmentation (ER) (> 75% repigmentation), good repigmentation (GR) (50–75% repigmentation), moderate repigmentation (MR) (25–50% repigmentation), and poor repigmentation (PR) (< 25% repigmentation).
Results
An ER was observed in 45% of patients (9/20), 5/20 (25%) achieved a GR, 3/20 (15%) an MR, and 3/20 (15%) a PR. Better response was observed on the face, neck, upper limb, hands, and abdomen. The mean number of procedures was 54.1 and the mean cumulative dose was 2967.5 mJ/cm2. Six months after the last session no recurrences were observed.
Conclusion
The combination of 308-nm EL and khellin is a safe and effective treatment and represents a new alternative therapy for vitiligo. Further comparative controlled randomized investigations are needed to confirm these promising results with the appropriate therapeutic protocols.
Changes in primary and secondary metabolites of Mentha aquatica L. exposed to different concentrations of manganese
Abstract
This experiment was conducted in order to determine the effects of different concentrations of manganese (Mn) on the levels and correlations of multiple primary and secondary metabolites in Mentha aquatica. With this aim, four levels of Mn concentrations were used as follows: basic Hoagland's solution (control), 40, 80, and 160 μM of Mn supplied as MnSO4.H2O. The results indicated that the biomass and the contents of photosynthetic pigments and soluble carbohydrates were higher in the plants that were treated with the moderate concentrations of Mn (40 and 80 μM) than the control and 160 μM-treated plants. On the other hand, the contents of flavonoids, anthocyanins, malonaldehyde (MDA), hydrogen peroxide (H2O2), and the activities of antioxidant enzymes (total superoxide dismutase (SOD), catalase (CAT), and peroxidase (POX)) were progressively increased with the enhancement of Mn concentration in the nutrient solution. In addition, there were clear differences in the content and chemical composition of essential oils among the control and treatment groups. In this study, 1,8-cineole, menthofuran, and β-caryophyllene were the most abundant constituents of essential oils in both the control and Mn-treated plants. The correlation analysis between pairs of the primary and secondary metabolites showed that there were positive and negative correlations among the variables when the Mn concentration was increased in the nutrient solution. These findings clearly display a positive effect of Mn up to 80 μM in the nutrient solution on the growth of M. aquatica.
Biochar-enhanced composts reduce the potential leaching of nutrients and heavy metals and suppress plant-parasitic nematodes in excessively fertilized cucumber soils
Abstract
Excessive fertilization is a common agricultural practice that has largely reduced soil nutrient retention capacity and led to nutrient leaching in China. To reduce nutrient leaching, in this study, we evaluated the application of biochar, compost, and biochar-compost on soil properties, leaching water quality, and cucumber plant growth in soils with different nutrient levels. In general, the concentrations of nutrients and heavy metals in leaching water were higher under high-nutrient conditions than under low-nutrient conditions. Both biochar and compost efficiently enhanced soil cation exchange capacity (CEC), water holding capacity (WHC), and microbial biomass carbon (MBC), nitrogen (MBN), and phosphorus (MBP), reduced the potential leaching of nutrients and heavy metals, and improved plant growth. The efficiency of biochar and compost in soil CEC, WHC, MBC, MBN, and MBP and plant growth was enhanced when applied jointly. In addition, biochar and biochar-enhanced compost efficiently suppressed plant-parasitic nematode infestation in a soil with high levels of both N and P. Our results suggest that biochar-enhanced compost can reduce the potential environmental risks in excessively fertilized vegetable soils.
A new tool to test active ingredient using acid lactic in vitro, a help to understand cellular mechanism involved in stinging test: an example using a bacterial polysaccharide (Fucogel®)
Abstract
The stinging test is an in vivo protocol that evaluates sensitive skin using lactic acid (LA). A soothing sensation of cosmetics or ingredients can be also appreciated through a decrease of stinging score. To predict the soothing sensation of a product before in vivo testing, we developed a model based on an LA test and substance P (SP) release using a co-culture of human keratinocytes and NGF-differentiated PC12 cells. A bacterial fucose-rich polysaccharide present in Fucogel® was evaluated as the soothing molecule in the in vivo stinging test and our in vitro model. Excluding toxic concentrations, the release of SP was significant from 0.2% of lactic acid for the PC12 cells and from 0.1% of lactic acid for the keratinocytes. When the pH was adjusted to approximately 7.4, LA did not provoke SP release. At these concentrations of LA, 0.1% of polysaccharide showed a significant decrease in SP release from the two cellular types and in co-cultures without modifying the pH of the medium. In vivo, a stinging test using the polysaccharide showed a 30% decrease of prickling intensity versus the placebo in 19 women between the ages of 21 and 69. Our in vitro model is ethically interesting and is adapted for cosmetic ingredients screening because it does not use animal experimentation and limits human volunteers. Moreover, Fucogel® reduced prickling sensation as revealed by the in vivo stinging test and inhibits the neurogenic inflammation as showed by our new in vitro stinging test based on SP release.
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UVA1 Impairs the Repair of UVB-Induced DNA Damage in Normal Human Melanocytes
Abstract
The exact correlation between melanoma and sun light is still a controversially debated issue. Although natural sunlight contains various ratios of UVA and UVB, most investigators so far focused on the effects of single solar wavebands and neglected possible interactions. Therefore, in the present study primary human melanocytes of three donors were simultaneously exposed to physiologic doses of UVA1 and UVB. Effects on apoptosis were analyzed using Annexin V assays and cell death ELISAs, effects on DNA damage were investigated using Southwestern slot blots. While UVA1 did not influence UVB-induced apoptosis, UVA1 impaired the repair of UVB-induced Cyclobutane Pyrimidine Dimers (CPD) as the amount of CPD was 1.8 higher in UVA1+UVB than in UVB only exposed melanocytes six hours after irradiation. We conclude that UVA1 might contribute to melanomagenesis since it partially inhibits the repair of UVB-induced CPDs in human melanocytes while it does not affect UVB-mediated apoptosis.
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Dapsone for topical use in extemporaneous preparations
Summary
Background
The sulfone dapsone has an established role in systemic therapy. Its pharmacological and toxicological properties are well known. Topically, dapsone is used in a gel formulation for the treatment of acne vulgaris. In addition, there have been individual case reports on the efficacy of topical dapsone preparations in the treatment of various neutrophilic dermatoses. To date, no finished medicinal product for topical use has been available in Germany.
Material and methods
Against this background, we set out to develop extemporaneous preparations containing dapsone (5 %) that meet the quality requirements of the European Pharmacopoeia as well as the manufacturing requirements of the German Ordinance on the Operation of Pharmacies (ApBetrO). These formulations included the incorporation of dapsone in a hydrophobic cream base ("hydrophobe Basiscreme DAC") as well as in methylprednisolone aceponate 0.1 % ointment (alternatively, in the latter's cream base without active ingredient).
Results
Tests aimed at investigating the physical, chemical, and microbiological stability of these formulations showed them to meet the aforementioned quality requirements.
Conclusion
The extemporaneous formulations presented herein broaden the therapeutic options for topical treatment, in particular for patients with chronic inflammatory dermatoses associated with a neutrophilic pathogenesis.
Age and Hydration dependence of jowl and forearm skin firmness in young and mature women
Summary
Background
Quantitative assessment of possible linkages between skin's firmness and water content is useful for cosmetic and clinical purposes and to better understand features of advancing age.
Objectives
Our goals were to characterize age-related differential features in skin firmness in women and determine the relationship between skin firmness and indices of skin water.
Methods
Skin firmness was quantified using handheld devices that measure the force to indent skin 0.3 and 1.3 mm (F0.3 and F1.3). Skin hydration was quantified using handheld devices that measured tissue dielectric constant (TDC) at 300 MHz to skin depths of 0.5 and 2.0-2.5 mm. All parameters were measured bilaterally in the jowl area and volar forearm of 60 women grouped by age <45 years (YOUNG) and ≥45 years old (MATURE).
Results
All measured parameters were bilaterally symmetrical at jowl and forearm. Forearm and jowl indentation forces were greater in YOUNG with statistically significant declines with advancing age with regression relations most evident at shallower indentation depths (P < .001). Quantitative relations for arm and jowl were F0.3 = 0.256 × AGE + 32.7 mN and F0.3 = −0.07 × AGE + 17.7 mN. Firmness was related to TDC values only when indentation force and TDC were assessed on the arm at the shallowest skin depths, as weakly related to firmness and was observed to change with age only when measured to a depth of 0.5 mm represented by TDC5 = 0.096 × AGE + 32.7.
Conclusions
Experimental finding show clear differences in skin firmness between age-groups with skin hydration playing a minor role. Possible explanations and suggestions for further studies are provided.
As a painkiller: a review of pre- and postnatal non-steroidal anti-inflammatory drug exposure effects on the nervous systems
Abstract
Diclofenac sodium (DS) is commonly used for the treatment of acute and chronic pain, even for extended periods of time. Over the years, DS has been associated with toxicity in nervous tissue, in addition to its anti-inflammatory properties. Basic neurobiological research has enhanced our understanding of the biological and pathological outcomes of toxicity. Several studies have suggested DS-induced cytotoxicity in the nervous system. Prenatal toxicities of DS are thought to be capable of leading to postnatal defects. This review describes the morphoquantitative, histological and pathological effects of DS on the central and peripheral nervous systems. Knowledge of these effects may assist with the development of a suitable therapeutic approach. In addition, understanding the mechanism of DS-dependent neuronal impairments may contribute to selection of appropriate antioxidant therapy.
Subcutaneous immunoglobulin for the treatment of deep morphoea in a child
Summary
Morphoea, also known as localized scleroderma, is a disorder characterized by excessive collagen deposition leading to thickening of the dermis and/or subcutaneous tissues. Intravenous IgG therapy has induced improvement in some fibrotic conditions. The primary indication for subcutaneous IgG (SCIG) is in primary immunodeficiency disorders as replacement therapy; however, recently there has been considerable interest in SCIG as an immunomodulatory agent. We report an 11-year-old girl with deep morphoea who was successfully treated with SCIG.
Influence of multiwall carbon nanotubes on the toxicity of 17β-estradiol in the early life stages of zebrafish
Abstract
Due to increasing use and release, both multiwall carbon nanotubes (MWCNTs) and 17β-estradiol (E2) may co-exist and interact with each other in aquatic environments. However, little is known about their combined effects on non-target organisms, especially in the presence of other environmental factors. In this study, the interplay between MWCNTs and E2 in the early life stages of zebrafish was investigated, focusing on the alterations in estrogenic responses with and without other environmental factors. There were no significant differences in the hatchability, mortality, or physical development of zebrafish in any treatments. Compared with E2 exposure, the E2-induced estrogenic responses (vtg1, vtg3, and esr1 genes) in zebrafish were markedly reduced to baseline by the presence of MWCNTs in most cases, indicating a strong protective effect. Furthermore, this inhibitive effect was not significantly changed by the preloading of natural organic matter (NOM) on MWCNTs. Nevertheless, the addition of ammonia nitrogen in the mixtures of MWCNTs and E2 alleviated the protective effect of MWCNTs, resuscitating the E2-induced estrogenic responses in zebrafish. These findings highlight the influence of carbon nanomaterials on the bioavailability of co-contaminants in organisms. The widespread environmental factors in natural environments should also be taken into consideration when the combined toxicity of nanomaterials and contaminants is discussed.
Fulminant Cryptococcus neoformans infection with fatal pericardial tamponade in a patient with chronic myelomonocytic leukemia who was treated with ruxolitinib: Case report and review of fungal pericarditis
Abstract
Cryptococcus neoformans is a saprophytic fungal pathogen that can cause serious illness in immune-compromised hosts and it presents with a wide variety of clinical symptoms. We present a fatal case of fulminant C. neoformans infection presenting as pericardial tamponade in a 71-year-old male with chronic myelomonocytic leukemia undergoing chemotherapy with the JAK-STAT inhibitor ruxolitinib. We also review the published cases of fungal pericarditis/tamponade. In addition to illustrating an atypical presentation of C. neoformans, this case highlights the risk for opportunistic fungal infections in patients with hematologic malignancies, especially the ones treated with small molecule kinase inhibitors.
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Candiduria in kidney transplant recipients: is antifungal therapy useful?
Summary
A French single-center retrospective study between 2010-2014 was undertaken to assess candiduria's incidence in kidney transplant recipients (KTR), and the use and impact of antifungal treatment on outcome. Candiduria was defined as a urine culture with ≥ 103 cfu/mL of Candida species. Candiduria clearance, severe complications and death rates were estimated by Kaplan-Meier methods and the effect of treatment by Cox models.
52/1223 (4.3%) KTR had ≥ 1 episode of candiduria, 42 (81%) were female, 18 (35%) had diabetes, with an incidence of 2.3/100 person-year of follow up. Candiduria was asymptomatic in 51 (98%) patients. Candida glabrata was the most frequent pathogen identified. Overall fungal clearance rate was 89%. Antifungal therapy was initiated in only 14 episodes (12%), according to guidelines. Three patients (6%) developed severe complications in the first 2 weeks after transplantation, and 8 (15%) died. Antifungal treatment had no impact on candiduria clearance (HR, 0.6; 95% CI, 0.3-1.1; p=0.10), on recurrence rate (HR, 0.5; 95% CI, 0.1-2.3; p=0.41) and on the risk of severe complications or death (HR, 1.1; 95% CI, 0.3-4.8; p = 0.89). Candiduria is rare and usually asymptomatic among KTR. Candiduria management in the immediate post-transplant period deserves careful attention.
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Environmental distribution of Cryptococcus species and some other yeast-like fungi in India
Abstract
A study of environmental distribution revealed the occurrence of Cryptococcus neoformans and C. gattii in 9% and 3%, respectively, of 611 samples investigated. C. neoformans showed the highest isolation frequency from tree trunk hollows in Delhi (31%), whereas, C. gattii occurred in 12% of the samples in Delhi and 5% in Rajasthan. In addition, Cryptococcus laurentii (=Papiliotrema laurentii), C. rajasthanensis (=Papiliotrema rajasthanensis), C. podzolicus (=Saitozyma podzolica) and C. flavescens (=Papiliotrema flavescens), occurred in 0.5% each. The recovery of C. flavescens and C. podzolicus were new findings for India. One more noteworthy finding was isolation of a new yeast, recently classified as Saitozyma cassiae sp. Novo. The previous strain of this yeast came from tree bark debris in South India. Our isolates came from decayed wood inside a trunk hollow of an Acacia tree in, Bharatpur Bird Sanctuary, Rajasthan. The isolations of novel strains of Cutaneotrichosporon moniliiforme, from decayed wood of a Pinus tree was another significant finding. Phenotypically, they differed from T. moniliforme by being encapsulated cells, had melanin-like pigment production, and were unable to assimilate d-manitol and d-melezitose. AFLP analysis of showed a distinctive banding profile vis-a-vis the reference strains of T. moniliiforme and Cryptotrichosporon anacardii.
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Prognostic markers for colorectal cancer; estimating ploidy and stroma
Summary
Background
We report here the prognostic value of ploidy and digital tumour-stromal morphometric analyses using material from 2624 patients with early stage CRC. Patients and Methods
DNA content (ploidy) and stroma-tumour fraction were estimated using automated digital imaging systems and DNA was extracted from sections of formalin-fixed paraffin-embedded (FFPE) tissue for analysis of microsatellite instability (MSI). Samples were available from 1092 patients recruited to the QUASAR 2 trial and two large observational series (Gloucester, n = 954; Oslo University Hospital, n = 578). Resultant biomarkers were analysed for prognostic impact using five-year cancer-specific survival (CSS) as the clinical endpoint. Results
Ploidy and stroma-tumour fraction were significantly prognostic in a multivariate model adjusted for age, adjuvant treatment, and pathological T-stage in stage II patients, and the combination of ploidy and stroma-tumour fraction was found to stratify these patients into three clinically useful groups; 5-year CSS 90% vs 83% vs 73% (hazard ratio [HR]=1.77 [95% CI 1.13-2.77] and HR = 2.95 [95% CI 1.73-5.03], P < 0.001). Conclusion
A novel biomarker, combining estimates of ploidy and stroma-tumour fraction, sampled from FFPE tissue, identifies stage II CRC patients with low, intermediate or high risk of CRC disease specific death, and can reliably stratify clinically relevant patient sub-populations with differential risks of tumour recurrence and may support choice of adjuvant therapy for these individuals.S-1 and irinotecan plus bevacizumab versus mFOLFOX6 or CapeOX plus bevacizumab as first-line treatment in patients with metastatic colorectal cancer (TRICOLORE): a randomized, open-label, phase 3, non-inferiority trial
Abstract
Background
Combination therapy with oral fluoropyrimidine and irinotecan has not yet been established as first-line treatment for metastatic colorectal cancer (mCRC). We performed a randomized, open-label, phase 3 trial to determine whether S-1 and irinotecan plus bevacizumab is non-inferior to mFOLFOX6 or CapeOX plus bevacizumab in terms of progression-free survival (PFS). Patients and methods
Patients from 53 institutions who had previously untreated mCRC were randomly assigned (1:1) to receive either mFOLFOX6 or CapeOX plus bevacizumab (control group) or S-1 and irinotecan plus bevacizumab (experimental group; a 3-week regimen: intravenous infusions of irinotecan 150 mg/m2 and bevacizumab 7.5 mg/kg on day 1, oral S-1 80 mg/m2 twice daily for 2 weeks, followed by a 1-week rest; or a 4-week regimen: irinotecan 100 mg/m2 and bevacizumab 5 mg/kg on days 1 and 15, S-1 80 mg/m2 twice daily for 2 weeks, followed by a 2-week rest). The primary endpoint was PFS. The non-inferiority margin was 1.25; non-inferiority would be established if the upper limit of the 95% CI for the hazard ratio (HR) of the control versus the experimental group was less than this margin. Results
Between June 2012 and September 2014, 487 patients underwent randomization. 243 patients assigned to the control group and 241 assigned to the experimental group were included in the primary analysis. Median PFS was 10.8 months (95% CI 9.6 − 11.6) in the control group and 14.0 months (95% CI 12.4 − 15.5) in the experimental group (HR 0.84, 95% CI 0.70 − 1.02; P<0.0001 for non-inferiority, P=0.0815 for superiority). 157 patients (64.9%) in the control group and 140 (58.6%) in the experimental group had adverse events of grade 3 or higher. Conclusion
S-1 and irinotecan plus bevacizumab is non-inferior to mFOLFOX6 or CapeOX plus bevacizumab with respect to PFS as first-line treatment for mCRC and could be a new standard treatment. Clinical trials number
UMIN000007834Aromatase Inhibitors and the Risk of Colorectal Cancer in Post-Menopausal Women with Breast Cancer
Abstract
Background
A large trial of post-menopausal women with breast cancer reported an imbalance in colorectal cancer events with aromatase inhibitors (AIs), compared with tamoxifen in the adjuvant setting. This unexpected signal was observed within 3 years of randomization. To date, no observational studies have examined this important safety question in the natural setting of clinical practice. Thus, the objective of this study was to determine whether AIs, when compared with tamoxifen, are associated with increased risk of colorectal cancer in post-menopausal women with breast cancer. Patients and Methods
Using the United Kingdom Clinical Practice Research Datalink, we identified women, at least 55 years of age, with breast cancer newly-treated with either AIs or tamoxifen between January 1, 1996 and September 31, 2015, with follow-up until September 31, 2016. High-dimensional propensity score-adjusted Cox proportional hazards models were used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs) of incident colorectal cancer associated with AIs when compared with tamoxifen overall, by cumulative duration of use, and time since initiation. All exposures were lagged by one year for latency considerations. Results
A total of 9701 and 8893 patients initiated AIs and tamoxifen as first-line hormonal therapy (median follow-up of 2.4 and 2.9 years, respectively). Compared with tamoxifen, AIs were not associated with an increased risk of colorectal cancer (incidence rates of 150 per 100,000 person-years in both groups; adjusted HR: 0.90, 95% CI: 0.53-1.52). Similarly, there was no evidence of an association with cumulative duration of use (p-heterogeneity=0.54), and time since initiation (p-heterogeneity=0.66). Conclusions
In this first population-based study, the use of AIs was not associated with an increased risk of colorectal cancer. These findings should provide reassurance to the concerned stakeholders.Upscaling the pollutant emission from mixed recycled aggregates under compaction for civil applications
Abstract
In general terms, plant managers of sites producing construction wastes assess materials according to concise, legally recommended leaching tests that do not consider the compaction stage of the materials when they are applied on-site. Thus, the tests do not account for the real on-site physical conditions of the recycled aggregates used in civil works (e.g., roads or embankments). This leads to errors in estimating the pollutant potential of these materials. For that reason, in the present research, an experimental procedure is designed as a leaching test for construction materials under compaction. The aim of this laboratory test (designed specifically for the granular materials used in civil engineering infrastructures) is to evaluate the release of pollutant elements when the recycled aggregate is tested at its commercial grain-size distribution and when the material is compacted under on-site conditions. Two recycled aggregates with different gypsum contents (0.95 and 2.57%) were used in this study. In addition to the designed leaching laboratory test, the conventional compliance leaching test and the Dutch percolation test were performed. The results of the new leaching method were compared with the conventional leaching test results. After analysis, the chromium and sulphate levels obtained from the newly designed test were lower than those obtained from the conventional leaching test, and these were considered more seriously pollutant elements. This result confirms that when the leaching behaviour is evaluated for construction aggregates without density alteration, crushing the aggregate and using only the finest fraction, as is done in the conventional test (which is an unrealistic situation for aggregates that are applied under on-site conditions), the leaching behaviour is not accurately assessed.
Antifouling booster biocide extraction from marine sediments: a fast and simple method based on vortex-assisted matrix solid-phase extraction
Abstract
This paper reports the development of an analytical method employing vortex-assisted matrix solid-phase dispersion (MSPD) for the extraction of diuron, Irgarol 1051, TCMTB (2-thiocyanomethylthiobenzothiazole), DCOIT (4,5-dichloro-2-n-octyl-3-(2H)-isothiazolin-3-one), and dichlofluanid from sediment samples. Separation and determination were performed by liquid chromatography tandem-mass spectrometry. Important MSPD parameters, such as sample mass, mass of C18, and type and volume of extraction solvent, were investigated by response surface methodology. Quantitative recoveries were obtained with 2.0 g of sediment sample, 0.25 g of C18 as the solid support, and 10 mL of methanol as the extraction solvent. The MSPD method was suitable for the extraction and determination of antifouling biocides in sediment samples, with recoveries between 61 and 103% and a relative standard deviation lower than 19%. Limits of quantification between 0.5 and 5 ng g−1 were obtained. Vortex-assisted MPSD was shown to be fast and easy to use, with the advantages of low cost and reduced solvent consumption compared to the commonly employed techniques for the extraction of booster biocides from sediment samples. Finally, the developed method was applied to real samples. Results revealed that the developed extraction method is effective and simple, thus allowing the determination of biocides in sediment samples.
Dynamic linkages between road transport energy consumption, economic growth, and environmental quality: evidence from Pakistan
Abstract
The focus of the present research work is to investigate the dynamic relationship between economic growth, road transport energy consumption, and environmental quality. To this end, we rely on time series data for the period 1971 to 2014 in the context of Pakistan. To use sulfur dioxide (SO2) emission from transport sector as a new proxy for measuring environmental quality, the present work employs time series technique ARDL which allows energy consumption from the transport sector, urbanization, and road infrastructure to be knotted by symmetric relationships with SO2 emissions and economic growth. From the statistical results, we confirm that road infrastructure boosts economic growth. Simultaneously, road infrastructure and urbanization hampers environmental quality and causes to accelerate emission of SO2 in the atmosphere. Furthermore, economic growth has a diminishing negative impact on total SO2 emission. Moreover, we did not find any proof of the expected role of transport energy consumption in SO2 emission. The acquired results directed that care should be taken in the expansion of road infrastructure and green city policies and planning are required in the country.
Factors that affect the willingness of residents to pay for solid waste management in Hong Kong
Abstract
In Hong Kong, problems involving solid waste management have become an urgent matter in recent years. To solve these problems, the Hong Kong government proposed three policies, namely, waste charging, landfill extension, and development of new incinerators. In this study, a large sample questionnaire survey was conducted to examine the knowledge and attitude of residents on the three policies, the amount of their daily waste disposal, and their willingness to pay (WTP). Results reveal that only 22.7% of respondents are aware of the earliest time that one of the landfills will be sated, and more than half of respondents support the three policies. However, more than one third of residents (36.1%) are unwilling to pay the minimum waste charge amount of HK$30 estimated by the Council for Sustainable Development in Hong Kong. Logit model results indicate that five key factors affect WTP, namely, knowledge of residents on the timing of landfill fullness, degree of support in waste charge policy, amount of daily waste disposal, age, and income. These results suggest that strong and rigorous promotional and educational programs are needed to improve the knowledge and positive attitude of residents towards recycling methods and the three policies. However, subsidy should be provided to low-income groups who cannot afford to pay the waste charge.
Adsorptive removal capacity of gravel for metal cations in the absence/presence of competitive adsorption
Abstract
Locally available and low cost granular gravel as an adsorbent material was employed to determine its capacity to remove metal cations Cu(II), Fe(II), Ni(II), and Zn(II) from single metal solution and landfill leachate samples. Adsorption kinetics and mechanism under different parameters including dosage, time, and pH were studied. It was found that the experimental results fitted to the Freundlich model suggesting an adsorption process on a multilayer heterogeneous surface for both single metal solution and landfill leachate samples. The adsorption of metal cations followed second-order kinetics occurring in a single step on the surface of gravel. The order of removal efficiency of metals was found to be Cu(II)(98%) > Fe(II)(87.5%) > Zn(II)(76.05%) > Ni(II)(36.38%) in single metal solution and Cu(II)(98.3%) > Fe(II)(83%) > Zn(II)(48%) > Ni(II)(27.32%) in landfill leachate sample at pH 7. The regeneration efficiency of the metals adsorbed on the gravel resulted in the order of Fe(II)(99.54%) > Cu(II)(99%) > Ni(II)(49.46%) > Zn (II)(2.25%).
Production of an environmentally friendly fuel with the aid of ultrasonic waves from a new plant source, and the investigation of its effect on pollutants reduction in a CI engine
Abstract
In this study, methyl ester of Sisymbrium plant seed oil with the chemical formula of C18H34O2 is produced for the first time, with the aid of ultrasonic waves and in the presence of a nanocatalyst. After measuring its characteristics and comparing with ASTM standard, it is tested and evaluated with different ratios of diesel fuel in a single-cylinder diesel engine. The reactions are accomplished in a flask by an ultrasonic processor unit and in the presence of CaO-MgO nanocatalyst. The engine tests were conducted based on the engine short time experiment. The results showed that with the increment of biodiesel ratio in the fuel blend, pollutants level of CO, HC, and smoke opacity are decreased comparing diesel fuel due to the improvement of the combustion process, and the amount of NOx emission is increased owing to high pressure and temperature of the combustion chamber. Also, produced biodiesel fuel causes an increment in the fuel consumption and exhaust gasses temperature. Overall, with regard to its effects on the engine and also being a native and easy cultivation plant, it can be resulted that Sisymbrium oil biodiesel and its blends with diesel fuel can be applied as an alternative fuel.
Diagnostic accuracy of 11 C-methionine PET in detecting neuropathologically confirmed recurrent brain tumor after radiation therapy
Abstract
Objective
This study aims to determine the diagnostic test accuracy (DTA) of 11C-methionine (MET) PET in the discrimination between recurrent tumor and radiation-induced injury in neuropathologically confirmed cases.
Methods
A retrospective cohort of 30 patients with previously irradiated intracranial tumors (23 gliomas, 6 metastases, and 1 meningioma) was included. All patients underwent a preoperative MET PET and postoperative neuropathological analysis. Maximum and mean standardized uptake values (SUV) were obtained in the lesion, in the contralateral mirror region, and in the contralateral frontal cortex. Lesion-to-background SUV ratios (SUR mirror and SUR cortex) were then calculated. The Mann–Whitney U test was used to evaluate differences in SUV ratios between confirmed recurrent tumor and radiation injury. DTA was determined through receiver operating characteristic (ROC) analysis.
Results
Twenty-one patients had recurrent tumor and nine had radiation injury. The area under the ROC curve (AUC) was 0.89 for SURmaxmirror and 0.88 for SURmaxcortex. The mean (SD) of SURmaxmirror was 2.37 (0.58) in tumor recurrence and 1.57 (0.40) in radiation necrosis (P ≤ 0.001). The corresponding values for SURmaxcortex were 2.13 (0.50) and 1.45 (0.37) (P = 0.001). Clinically relevant cutoffs were SURmaxmirror ≥ 1.99 giving a specificity of 100% for tumor recurrence with a sensitivity of 76% and SURmaxcortex ≥ 1.58 giving a sensitivity and specificity of 90 and 78%, respectively.
Conclusions
Based on neuropathologically confirmed cases, the DTA of SURmaxmirror and SURmaxcortex from 11C-methionine PET was high when discriminating recurrent tumor from radiation injury.
Conservative management (marsupialization) of unicystic ameloblastoma: literature review and a case report
Abstract
Background
In this study, we present a case of unicystic ameloblastoma (UA) treated by marsupialization followed by surgical enucleation as a conservative approach. UA is a rare, benign, less aggressive, and less invasive variant of ameloblastoma that is observed quite often in younger patients. Radical approaches have effects on the physical and psychological development of a growing young patient; therefore, conservative approaches are widely used for UA management in children.
Case presentation
This report described a case of an 11-year-old girl with UA of the mandibular molar–ramus area, which also involved impaction of the second and third molars. The lesion was marsupialized, and 31 months after marsupialization, surgical enucleation was performed with extraction of the impacted third molar. The second molar, which was preserved, spontaneously and completely erupted. No recurrence was observed during a 49-month follow-up.
Conclusions
Conservative treatments for UA in young patients have more advantages. Our results provide evidence that marsupialization is effective in regressing the lesion size to ease complete removal, preserving mandibular growth, maintaining involved second molar, and promoting the eruption of the tooth.
Evaluation of bone healing using rhBMP-2 soaked hydroxyapatite in ridge augmentation: a prospective observational study
Abstract
Background
The goal of this study is to evaluate complication and effectiveness of alveolar ridge augmentations using a hydroxyapatite-based alloplastic bony substitute with rhBMP-2.
Methods
A total of 10 patients (4 males, 6 females; 58.5 ± 8.6 years) participated in this clinical research. Alveolar ridge augmentations were performed in edentulous (4 maxillary posterior, 5 mandibular posterior, and 1 mandibular anterior) regions. Anorganic bovine bone (ABB; Bio-Oss®, Geistlich Pharma AG, Wolhusen, Switzerland) was used as the bone graft material in the control group (n = 5)) while hydroxyapatite-based alloplastic bony substitute with rhBMP-2(HA+rhBMP-2; NOVOSIS®-Dent, CGBio Inc., Seongnam, Korea) was used in the experimental group (n = 5). In order to evaluate relative changes in bone volume and resorption rate of the bone graft material, CBCT radiographs were taken immediately and at 4 months after the bone graft in all subjects. Among the 10 patients, 8 received dental implants in Seoul National University Bundang Hospital, while the others received in local clinics. Bone specimens for further histomorphometric examinations were gained from these 8 patients using trephine burs during the implant placements. Clinical, radiographic, and histomorphometric evaluations were focused because of the small sample size.
Results
When CBCT radiographs were compared between immediately and at 4.07 ± 0.13 months after the bone graft, both alveolar bone widths (ABB 2.52 ± 0.18 mm, HA+rhBMP-2 1.75 ± 0.85 mm) and heights (ABB 1.68 ± 0.17 mm, HA+rhBMP-2 1.57 ± 0.28 mm) increased in the two groups. Resorption rates of transplanted bone graft material in the alveolar bone widths and heights were (ABB 29.7 ± 8.8%, HA+rhBMP-2 31.5 ± 7.4%) and (ABB 39.2 ± 21.8%, HA+rhBMP-2 52.6 ± 6.5%), respectively. Histomorphometrically, ABB group showed bone formation via osteoconduction and HA+rhBMP-2 group via osteoinduction. HA+rhBMP-2 group showed more bone formation around the bone graft materials than the ABB group. Postoperative complications were not found in all subjects.
Conclusions
Our study had following conclusions: (1) Ridge augmentations using HA+rhBMP-2 could be clinically useful to supplement implant placements in edentulous regions. (2) Serious postoperative complications related to the graft material did not occur.
Extraction socket sealing using palatal gingival grafts and resorbable collagen membranes
Abstract
Background
Socket sealing surgery is performed for the preservation of the form and volume of the soft tissue by covering the resulting socket with autogenous soft tissue graft or membrane barriers. This procedure is usually necessary to improve the esthetic results of the maxillary anterior or premolar areas.
Methods
This study retrospectively investigated cases involving the open membrane technique or socket sealing surgery with a palatal gingival graft or collagen membrane where implant placement and bone grafting were performed immediately after tooth extraction. From January 2005 to December 2008, socket sealing surgery was performed in 24 patients, and 25 implants were placed.
Results
All implants were successful in the follow-up period. In the palatal gingival graft group, the mean marginal bone loss was 1.17 mm during the mean follow-up period of 81.0 months. In the collagen membrane group, the mean marginal bone loss was 1.23 mm during the mean follow-up period of 76.9 months. There was no significant difference between the two groups.
Conclusions
Consequently, socket sealing surgery is effective at minimizing the loss of soft tissue and alveolar bone.
Analysis of the outcome of young age tongue squamous cell carcinoma
Abstract
Background
The incidence of tongue squamous cell carcinoma (TSCC) in young patients has recently increased, and these TSCCs are believed to be etiologically distinct from those in older patients, who have longer exposure to risk factors such as tobacco and alcohol. The prognosis of TSCCs in young patients remains controversial.
Methods
We retrospectively reviewed the records of 117 patients (2001–2011) who were diagnosed with squamous cell carcinoma of the oral tongue. Patients were divided into two age groups, older (ages over 40) and younger (ages 40 and younger). Data were compared between the two groups, and survival rates were analyzed.
Results
The results show that there are significant differences in overall, disease-free, and distant metastasis-free survival rates between the two groups. Five-year overall survival rates were 70% in older patients and 42% in young patients (p = 0.033). Five-year disease-free survival rates were 73% in older patients and 40% in young patients (p = 0.011), and 5-year distant metastasis-free survival rates were 97% in older patients and 62% in young patients (p = 0.033).
Multivariate analysis revealed that histologic grade was the only independent risk factor for overall survival in both groups of patients (p = 0.002, HR = 2.287). The analysis also demonstrated that age was the critical risk factor for distant metastasis (p = 0.046, HR = 9.687).
Conclusion
In this study, young (ages 40 and younger) patients with squamous cell carcinoma of the oral tongue had a higher rate of distant metastasis and a worse prognosis. Accordingly, we propose the necessity of an extensive therapeutic regimen that should be used in all young patients with TSCC.
From Then ‘till Now: The History of Autophagy and Cancer Research
By Christina Towers, PhD.
The fundamental process that cells use to degrade damaged cytoplasmic material and recycle nutrients is called autophagy. This term was first coined by the Belgium biochemist Christian de Duve stemming from the Greek translations of "auto" meaning "self" and "phagy" meaning "eat", thus: "autophagy" translates to "eating one's self". de Duve's seminal work identified the previously unknown organelle, the lysosome and transpired in a Nobel Prize in Medicine in 19741.
Almost 4 decades after de Duve discovered the lysosome, Yoshinori Ohsumi and his group in Japan started cloning autophagy specific genes from Sachharamyces cerevisiae, the first being Apg13 (ATG1 in humans)2. Ohsumi's group continued to characterize most of the complex autophagy pathway in yeast as well as higher eukaryotes, and elucidated dozens of autophagy specific genes (ATGs) like Apg8 lipidation (LC3 in humans) and the ubiquitin-like conjugation systems involving Apg3, Apg7, Apg10, and Apg12 (ATG3, ATG7, ATG10, and ATG12 in humans)3,4.
GAPR-1/GLIPR2 is a negative regulator of autophagy and binds Beclin 1 to inhibit autophagy. In the presence of Tat-D11 peptides, Beclin 1 bound to GAPR-1 is released allowing Beclin 1 to mediate autophagosome formation and autophagy induction.
By the end of the 1990's the basics of the autophagy process were becoming more clear, however, there was almost no understanding of how this process might function in human disease. Beth Levine's group was the first to associate autophagy with cancer, as they described the core autophagy protein, BECLIN1, as a putative tumor suppressor which they found to be lost in most tumors5. While the tumor suppressive functions of BECLIN1 are still up for debate, these seminal studies ignited the field of autophagy in cancer fueling the hundreds of publications that would follow. There is now a general consensus in the field that autophagy may inhibit tumorigenesis at early stages during tumor development, but in an established tumor, autophagy is tumor-promotional, ultimately suggesting that autophagy may be a viable therapeutic target6. A critical discovery in the field, although now only noted by hindsight, also occurred around this same time in the late 1990s: that is the discovery that the anti-malarial therapy, Chloroquine, accumulates in the lysosome and is a potent inhibitor of autophagy7.
Fast forward almost 20 years, and over that time the number of publications in the field of autophagy has risen from just about 100 publications per year in 1990 to over 2500 publications per year in 20138. The importance of the field was highlighted in 2016 with a Nobel Prize to Yoshinori Ohsumi for his work that first characterized the pathway in yeast. de Duve's discovery of the lysosome in 1963 laid the ground work for the 5 plus decades of research that would follow characterizing autophagy in normal biology, understanding its role in disease, and finding ways to target it, all of which have culminated in over 50 current clinical trials targeting autophagy with Chloroquine (and its derivatives), the majority of which focus on cancer.
Explore the Autophagy Interactive Pathway
Christina Towers, PhD
References
- Levy, J. M. M., Towers, C. G. & Thorburn, A. Targeting autophagy in cancer. Nature reviews. Cancer, doi:10.1038/nrc.2017.53 (2017).
- Funakoshi, T., Matsuura, A., Noda, T. & Ohsumi, Y. Analyses of APG13 gene involved in autophagy in yeast, Saccharomyces cerevisiae. Gene 192, 207-213 (1997).
- Ichimura, Y. et al. A ubiquitin-like system mediates protein lipidation. Nature 408, 488-492, doi:10.1038/35044114 (2000).
- Mizushima, N., Sugita, H., Yoshimori, T. & Ohsumi, Y. A new protein conjugation system in human. The counterpart of the yeast Apg12p conjugation system essential for autophagy. J Biol Chem 273, 33889-33892 (1998).
- Liang, X. H. et al. Induction of autophagy and inhibition of tumorigenesis by beclin 1. Nature 402, 672-676, doi:10.1038/45257 (1999).
- Towers, C. G. & Thorburn, A. Therapeutic Targeting of Autophagy. EBioMedicine, doi:10.1016/j.ebiom.2016.10.034 (2016).
- Murakami, N. et al. Accumulation of tau in autophagic vacuoles in chloroquine myopathy. J Neuropathol Exp Neurol 57, 664-673 (1998).
- Ohsumi, Y. Historical landmarks of autophagy research. Cell Res 24, 9-23, doi:10.1038/cr.2013.169 (2014).
Category:
Chemical Peeling with a Modified Phenol Formula for the Treatment of Facial Freckles on Asian Skin
Abstract
Background
Chemical peeling is an efficient method for the treatment of pigment disorders. For freckles, medium-depth to deep peeling using a phenol solution is one of the most effective chemical peels, and modifications of facial skin can be observed up to 20 years after peeling. However, applying phenol to the skin may cause serious side effects. Phenol peeling has been rarely used in Asia due to its tendency to cause permanent pigmentary changes and hypertrophic scars.
Methods
In total, 896 Chinese inpatients with facial freckles were enrolled in this study. The phenol formula was modified with crystalline phenol, dyclonine, camphor, anhydrous alcohol and glycerin and adjusted to a concentration of 73.6–90.0%. The entire peeling treatment was divided into two procedures performed separately on 2 days.
Results
All patients exhibited 26% or greater improvement, and 99.66% of patients exhibited 51% or greater improvement (good and excellent). Scarring and systemic complications were not observed in any patient.
Conclusions
The modified phenol formula is very effective and safe for the treatment of facial freckles in Asian patients.
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.
Prenatal and Postpartum Care Disparities in a Large Medicaid Program
Abstract
Objectives Pennsylvania's maternal mortality, infant mortality, and preterm birth rates rank 24th, 35th, and 25th in the country, and are higher among racial and ethnic minorities. Provision of prenatal and postpartum care represents one way to improve these outcomes. We assessed the extent of disparities in the provision and timeliness of prenatal and postpartum care for women enrolled in Pennsylvania Medicaid. Methods We performed a cross-sectional evaluation of representative samples of women who delivered live births from November 2011 to 2015. Our outcomes were three binary effectiveness-of-care measures: prenatal care timeliness, frequency of prenatal care, and postpartum care timeliness. Pennsylvania's Managed Care Organizations (MCOs) were required to submit these outcomes to the state after reviewing administrative and medical records through a standardized, validated sampling process. We assessed for differences in outcomes by race, ethnicity, region, year, and MCO using logistic regression. Results We analyzed data for 12,228 women who were 49% White, 31% Black/African American, 4% Asian, and 15% Hispanic/Latina. Compared to Black/African American women, white and Asian women had higher odds of prenatal and postpartum care. Hispanic/Latina women had higher frequency of prenatal care than non-Hispanic women. Pennsylvania's Southeast had lower prenatal care and Northwest had lower postpartum care than other regions. Prenatal care significantly decreased in 2014 and increased in 2015. We observed differences between MCOs, and as MCO performance diminished, racial disparities within each plan widened. We explored hypotheses for observed disparities in secondary analyses. Conclusions for Practice Our data demonstrate that interventions should address disparities by race, region, and MCO in equity-promoting measures.
Orthopaedic Bone Tap: A ‘Jugaad’ for Zygomatic Bone Reduction
Abstract
Introduction
The use of the Carroll-Girard screw in the management of zygomatic complex fractures has been well documented. The instrument provides an excellent degree of control over the movements of the disrupted zygomatic bone. Often mentioned in textbooks and literature, they are not routinely available for the Indian maxillofacial surgeon. This often prevents the regular use of this approach.
Material and methods
We have used the 2.5-mm orthopaedic bone tap that is very commonly available and routinely used in orthopaedic surgeries for reduction of the malar bone.
Conclusion
The orthopaedic bone tap is easy to use and functions as an excellent alternative to the traditional Carroll-Girard screw.
Left ventricular cardiac hemangioma in a patient with chronic heart failure
Abstract
Cardiac hemangiomas are rare benign tumors. Here, we report the case of a man in his 30s who had a cardiac hemangioma with no symptoms. He was being treated with β-blockers for chronic heart failure with hypertensive heart disease at Osaka Minato Central Hospital. Routine echocardiography revealed a mobile spherical mass in the left ventricle that had not been detected on echocardiography performed 4 months previously. Subsequently, the tumor was excised to prevent potential embolic events and was pathologically diagnosed as a cardiac hemangioma. This case demonstrates the relatively rapid progress of a cardiac hemangioma regardless of β-blocker administration, which is occasionally used for the treatment of hemangiomas. The efficacy of β-blockers in treating cardiac hemangiomas may vary according to the type of β-blocker. Echocardiography is useful in screening and follow-up of cardiac hemangiomas; however, additional imaging modalities are needed for differential diagnosis.
Cohesive Polydensified Matrix® hyaluronic acid volumizer injected for cheek augmentation has additional positive effect on nasolabial folds.
| Related Articles |
Cohesive Polydensified Matrix® hyaluronic acid volumizer injected for cheek augmentation has additional positive effect on nasolabial folds.
Clin Cosmet Investig Dermatol. 2017;10:507-513
Authors: Gauglitz G, Steckmeier S, Pötschke J, Schwaiger H
Abstract
Purpose: Cohesive Polydensified Matrix® hyaluronic acid (CPM-HA) volumizer has been used successfully for several years to reverse biometric volume loss during facial aging. This observational study explored the additive effect on nasolabial folds when CPM-HA volumizer is injected into the neighboring cheek area.
Patients and methods: In this open-label, prospective, postmarketing noninterventional study, 18 adult patients seeking esthetic enhancement of the lateral cheek hollows and cheekbone area were injected with CPM-HA volumizer integrated with lidocaine (CPM-HA-VL) in the upper or lower cheek area. Safety and performance of CPM-HA-VL up to 12 months after injection with follow-up visits at week 4 and month 3, 6, and 12 were assessed. The primary endpoint was improvement of cheek fullness on the validated Merz Aesthetics Scales. Additionally, changes in nasolabial folds were quantified using a phaseshift rapid in vivo measurement of skin optical three-dimensional (3D) in vivo measurement device.
Results: Patients (94.4% female, median age 52 years, age range 39-69 years) were injected with a mean volume of 2.5±1.1 mL CPM-HA-VL per side. Immediately after injection, mean severity for upper and lower cheek fullness assessed on the validated MAS improved from 2.5±0.6 and 2.8±0.5, respectively, to 1.0±0.0, and remained unchanged through month 12. Improvement in relation to baseline was attested on the Global Aesthetics Improvement Scale for all assessments. Compared with baseline, the following assessments offered a statistical significance in the reduction of wrinkle depth of nasolabial folds (maximum depth reduction by 30.4% at 3 months) according to optical 3D in vivo measurements. Pain during injection was minimal and abated within 30 minutes. Treatment was well tolerated and led to great patient satisfaction.
Conclusion: CPM-HA-VL injected into the upper and lower cheeks led to long-lasting satisfactory cosmetic results in cheek augmentation as well as in reducing depth of nasolabial folds adjacent to the injection site.
PMID: 29276401 [PubMed]
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Publication date: Available online 28 September 2017 Source: Actas Dermo-Sifiliográficas Author(s): F.J. Navarro-Triviño
