Visualisation of Bluetongue Virus in the Salivary Apparatus of Culicoides Biting Midges Highlights the Accessory Glands as a Primary Arboviral Infection Site.

BACKGROUND: Arthropods transmit a wide range of pathogens of importance for the global health of humans, animals, and plants. One group of these arthropod vectors, Culicoides biting midges (Diptera: Ceratopogonidae), is the biological vector of several human and animal pathogens, including economically important livestock viruses like bluetongue virus (BTV). Like other arthropod-borne viruses (arboviruses), Culicoides-borne viruses must reach and replicate in the salivary apparatus, from where they can be transmitted to susceptible hosts through the saliva during subsequent blood feeding. Despite the importance of the salivary gland apparatus for pathogen transmission to susceptible animals from the bite of infected Culicoides, these structures have received relatively little attention, perhaps due to the small size and fragility of these vectors. RESULTS: In this study, we developed techniques to visualize the infection of the salivary glands and other soft tissues with BTV, in some of the smallest known arbovirus vectors, Culicoides biting midges, using three-dimensional immunofluorescence confocal microscopy. We showed BTV infection of specific structures of the salivary gland apparatus of female Culicoides vectors following oral virus uptake, related visualisation of viral infection in the salivary apparatus to high viral RNA copies in the body, and demonstrated for the first time, that the accessory glands are a primary site for BTV replication within the salivary apparatus. CONCLUSIONS: Our work has revealed a novel site of virus-vector interactions, and a novel role of the accessory glands of Culicoides in arbovirus amplification and transmission. Our approach would also be applicable to a wide range of arbovirus vector groups including sand flies (Diptera: Psychodidae), as well as provide a powerful tool to investigate arbovirus infection and dissemination, particularly where there are practical challenges in the visualization of small size and delicate tissues of arthropods.

Testing the Limit: Evaluating Drinking Water Arsenic Regulatory Levels Based on Adverse Pregnancy Outcomes in Bangladesh.

(1) Background: Arsenic (As) is a common drinking water contaminant that is regulated as a carcinogen. Yet, As is a systemic toxicant and there is considerable epidemiological data showing As adversely impacts reproductive health. This study used data from a birth cohort in Bangladesh (2008−2011) to examine associations between drinking water As levels and reproductive outcomes. (2) Methods: Pregnant individuals (n = 1597) were enrolled at <16 weeks gestation and drinking water As was measured. Participants with live births (n = 1130) were propensity score matched to participants who experienced miscarriage (n = 132), stillbirth (n = 72), preterm birth (n = 243), and neonatal mortality (n = 20). Logistic regression was used to examine drinking water As recommendations of 50, 10, 5, 2.5, and 1 µg/L on the odds of adverse birth outcomes. (3) Results: The odds of miscarriage were higher for pregnant women exposed to drinking water ≥2.5 versus <2.5 µg As/L [adjusted odds ratio (OR) 1.90, 95% Confidence Interval (CI): 1.07−3.38)]. (4) Conclusions: These preliminary findings suggest a potential threshold where the odds of miscarriage increases when drinking water As is above 2.5 µg/L. This concentration is below the World Health Organizations and Bangladesh's drinking water recommendations and supports the re-evaluation of drinking water regulations.

A prospective study of arsenic and manganese exposures and maternal blood pressure during gestation.

BACKGROUND: Pregnancy is a sensitive time for maternal cardiovascular functioning and exposures to arsenic or manganese may adversely affect blood pressure (BP). OBJECTIVES: This study examined the associations between arsenic and manganese exposures and maternal BP measured during pregnancy. Effect modification by pre-pregnancy body mass index (BMI) was evaluated. METHODS: Pregnant women (N = 1522) were recruited for a prospective cohort study in Bangladesh (2008-2011). Exposure to arsenic and manganese was measured in drinking water at <16 weeks gestation and toenails at one-month postpartum. Systolic and diastolic BP were measured monthly. Linear mixed models estimated mean BP and differences in mean BP over gestation for arsenic or manganese exposures and adjusted for covariates. RESULTS: Arsenic levels had an increasing dose-response association with maternal BP after 25 weeks gestation. Effect modification was observed for BMI. Participants with lower BMI (<23 kg/m2) exposed to 50 µg/L arsenic had 2.83 mmHg (95% CI:1.74-3.92) greater mean systolic and 1.96 mmHg (95% CI: 1.02-2.91 mmHg) diastolic BP compared to those exposed to ≤ 1 µg/L arsenic at 40 weeks gestation. Participants with higher BMI (≥23 kg/m2) showed a greater mean systolic BP of 5.72 mmHg (95% CI: 3.18-8.27 mmHg) and diastolic BP change of 6.09 mmHg (95% CI: 4.02-8.16 mmHg) at 40 weeks gestation when exposed to 50 µg/L compared to ≤ 1 µg/L arsenic. Participants with lower BMI exposed to drinking water manganese in the 2nd quartile (181-573 µg/L) had 1.04 mmHg higher mean diastolic BP (95% CI: 0.01-2.07 mmHg) at 40 weeks gestation compared to those in the 1st quartile (0.5-180 µg/L). CONCLUSION: Arsenic exposures during pregnancy were consistently associated with increased average maternal systolic and diastolic BP. The effect of manganese on BP was less consistent.

Urinary polycyclic aromatic hydrocarbons concentrations and hepatitis B antibody serology in the United States (NHANES, 2003-2014).

BACKGROUND: Polycyclic aromatic hydrocarbons (PAHs) are environmental contaminants that are hepatotoxic and immunotoxic. PAH exposure may modulate hepatitis B immunology. OBJECTIVE: We used data from 6 cycles of the National Health and Nutrition Examination Survey (2003-2014) to evaluate the associations between urinary PAH metabolites and hepatitis B serology. METHODS: This analysis included individuals who self-reported receiving ≥3 doses of hepatitis B vaccine and urinary PAH metabolites (i.e. 1-napthol, 2-napthol, 3-fluorene, 2-fluorene, 1-phenanthrene, 1-pyrene, and total PAH [sum of all metabolites]). Separate logistic regression models assessed the association between hepatitis B vaccination status (i.e. individuals who were immune due to vaccination or susceptible) and tertiles of urinary PAH. Models were adjusted for age, gender, race/ethnicity, survey cycle, family income to poverty ratio, BMI, country of birth, serum cotinine, and urinary creatinine. RESULTS: Among participants who reported receiving ≥3 doses of vaccine and had no antibodies indicating a history of hepatitis B infection and/or current hepatitis B infection, dose-response relationships were observed where individuals with the lowest odds of serology indicating a response to the hepatitis B vaccine (i.e., anti-HBs+, anti-HBc-, and HBsAg-) were in the highest tertile of 2-Napthol (adjusted Odds Ratio [aOR]: 0.70, 95% confidence interval [CI]: 0.54, 0.91), 3-Napthol (aOR: 0.68, 95% CI: 0.53, 0.87), 2-Fluorene (aOR: 0.61, 95% CI: 0.54, 0.86), 1-Phenanthrene (aOR: 0.79, 95% CI: 0.65, 0.97), 1-Pyrene (aOR): 0.68, 95% CI: 0.55, 0.83), and total PAH (aOR: 0.73, 95% CI: 0.56, 0.95) had the compared to the lowest tertile. CONCLUSION: This cross-sectional study supports a hypothesis that PAH exposures experienced by the general US population may modulate hepatitis B vaccine induced immunity. Given the ubiquity of PAH exposures in the US, additional research is warranted to explore the effects of chronic PAH exposures on hepatitis B related humoral immunity.

Traversing the spectrum of non-Langerhans Cell Histiocytosis: A case of Rosai-Dorfman Disease with features of Necrobiotic Xanthogranuloma

Introduction@#Non-Langerhans cell histiocytoses (non-LCH) are a group of rare diseases with varied clinical manifestations and overlapping features seen among the subtypes. Here, we present a case of Rosai-Dorfman disease with features of necrobiotic xanthogranuloma. @*Case@#A 45-year-old female presented with a 10-year history of an enlarging neck mass with normal overlying skin accompanied by dysphagia and multiple asymptomatic pink to yellowish-brown papules, nodules, and plaques on the face, trunk and extremities. Biopsies of a skin nodule and plaque revealed granulomatous dermal infiltrates (lymphocytes, foamy histiocytes, and Touton giant cells), emperipolesis and areas of necrosis. CD1A and Fite-Faraco staining showed negative results while CD68 and S100 positively stained the tissues of interest. Histopathology of the neck mass paralleled these findings in addition to being negative for lymphoid markers. Patient had monoclonal gammopathy and thyromegaly with enlarged cervical lymph nodes on further tests and imaging. Intralesional and systemic steroids were given which led to flattening of skin lesions and improvement in dysphagia, respectively. @*Conclusion@#Diagnosis and classification of a particular type of non-LCH may be difficult due to similarities across its subtypes. Hence, it is our belief that these diseases may occur on a spectrum. Treatment involves a multidisciplinary approach for the best possible care.

The clinical profile, wound dressings, and clinical outcomes of in-patients with pressure ulcers at a tertiary hospital in the Philippines: A seven-year retrospective study

Objectives@#Currently, there are no local studies examining wound dressing usage among pressure ulcers in Filipino patients. The study aims to provide preliminary Philippine data among in-patients with pressure ulcers: their demographic characteristics, wound characteristics, wound dressing usage, and associated outcomes per wound dressing. @*Methods@#A retrospective chart review of patients admitted at the Philippine General Hospital from 2011 to 2017 with a diagnosis of pressure ulcer was conducted. @*Results@#Eighty-five records were retrieved; 56% were female and 44% male, with a mean age of 47.67 ± 23.03 years. The mean number of ulcers per patient was 1.65 ± 1.37, mostly in Stages 2 and 3, and 90.6% were in the sacral area. Seventy-three (85.9%) had utilized at least one form of the wound dressing, mostly plain gauze (83.5%), usually with silver sulfadiazine or Dakin’s solution. Only a smaller subset used silver-impregnated dressings (10.55%) and hydrocolloid dressings (5.9%). Comparing advanced versus basic dressings for improved wound outcomes, the crude odds ratio was 3.81 (1.62 - 8.99; p-value 0.003), which on stratification accounting for bed turning, became 8.92 (1.66 - 47.97; p-value 0.009) for those bed turned and 3.05 (1.01-9.20; p-value 0.075) for those not bed turned. @*Conclusion@#Filipino in-patients with pressure ulcers were similar to those in the literature in terms of the mean number of ulcers and site of involvement. Basic gauze dressings, combined with topical agents, constitute the majority of wound dressing practice. Use of an advanced wound dressing showed a trend favoring improved outcomes, enhanced by pressure redistribution through bed repositioning.

Dermoscopic patterns in relation to the Clinicopathologic manifestations of Leprosy

Objectives@#Leprosy is a chronic granulomatous infection caused by the obligate intracellular organism Mycobacterium leprae. Current diagnostic tests for confirmation and treatment monitoring such as slit skin smear and biopsy are invasive and require time for processing, reading, and interpretation. Dermoscopy is a technique that allows the visualization of structures not readily seen by the naked eye. It can be performed at the point of care, providing a non-invasive link between clinical and histopathologic examination. This study aimed to determine the dermoscopic findings and associated clinicopathologic findings of the different forms of leprosy. @*Methods@#A cross-sectional study was conducted. All new and follow-up patients aged 19 years old and above clinically diagnosed with leprosy were invited to participate in the study during the three-month investigation period. Clinical and dermoscopic photographs of representative skin lesions were taken, and a review of slit skin smear and histopathology results was done. Data analysis was performed using Stata SE version 13. The association between dermoscopic findings and the following parameters: anatomic location, Ridley-Jopling classification, WHO classification, treatment duration, and average bacteriologic index were analyzed using Fisher’s exact test. The level of significance was set at 5%. @*Results@#A total of 57 lesions were included. Linear vessels (p=0.031), structureless areas (p=0.008), and globules (p=0.002) were found to be significantly associated with the anatomic location. Decreased hair was found to be significantly associated with treatment duration (p=0.038). No significant associations were found between dermoscopic findings and Ridley-Jopling classification, WHO classification, and ABI. Eight biopsies taken at the time of dermoscopy were reviewed, with all sites showing structureless or globular areas corresponding to the presence of granulomas on histopathology (100%). No other notable associations were observed. @*Conclusion@#Dermoscopy is a potentially useful tool to aid in the diagnosis and treatment monitoring of leprosy. Limitations of this study include the small sample size, the preponderance of subjects in the lepromatous pole, and assessments by a single trained dermoscopist. A longer study duration including a larger number of newly diagnosed leprosy patients is recommended.

Identifying adipogenic chemicals: Disparate effects in 3T3-L1, OP9 and primary mesenchymal multipotent cell models.

3T3-L1 pre-adipocytes are used commonly to identify new adipogens, but this cell line has been shown to produce variable results. Here, potential adipogenic chemicals (identified in the ToxCast dataset using the Toxicological Priority Index) were tested for their ability to induce adipocyte differentiation in 3T3-L1 cells, OP9 cells and primary mouse bone marrow multipotent stromal cells (BM-MSC). Ten of the 36 potential adipogens stimulated lipid accumulation in at least one model (novel: fenthion, quinoxyfen, prallethrin, allethrin, pyrimethanil, tebuconzaole, 2,4,6-tris (tert-butyl)phenol; known: fentin, pioglitazone, 3,3',5,5'-tetrabromobisphenol A). Only prallethrin and pioglitazone enhanced lipid accumulation in all models. OP9 cells were significantly more sensitive to chemicals known to activate PPARγ through RXR than the other models. Coordinate effects on adipocyte and osteoblast differentiation were investigated further in BM-MSCs. Lipid accumulation was correlated with the ability to stimulate expression of the PPARγ target gene, Plin1. Induction of lipid accumulation also was associated with reduction in alkaline phosphatase activity. Allethrin, prallethrin, and quinoxyfen strongly suppressed osteogenic gene expression. BM-MSCs were useful in coordinately investigating pro-adipogenic and anti-osteogenic effects. Overall, the results show that additional models should be used in conjunction with 3T3-L1 cells to identify a broader spectrum of adipogens and their coordinate effects on osteogenesis.

Efficacy of intralesional purified protein derivative for cutaneous warts: A meta-analysis

Introduction@#Intralesional purified protein derivative (PPD) is an affordable therapeutic option that has been studied for cutaneous warts. However, the lack of good evidence precludes its widespread use.@*Objective@#To determine the efficacy and safety of intralesional PPD in the treatment of cutaneous warts.@*Methods@#A systematic search for controlled clinical trials comparing intralesional PPD and placebo or any conventional therapy was conducted using electronic databases. The included studies were assessed for risk of bias, and data such as clearance rate of target and distant lesions, recurrence rate, and adverse events were extracted. Analysis was done through RevMan v5.3.@*Results@#Four controlled clinical trials composed of 205 patients were included. All of the studies compared intralesional PPD to placebo as comparator. Intralesional PPD had a significantly higher clearance rate of target wart (RR=0.43[0.22,0.84], P=0.01) and a significantly higher clearance rate of distant lesions (RR=0.59[0.41,0.85], P=0.005) as compared to placebo. However, there was no significant difference in the recurrence rate (RR=0 [-0.07,0.07], P=0.98). Adverse events reported were only considered minor.@*Conclusion@#Intralesional PPD is an effective and safe treatment option for cutaneous warts. However, more well-structured RCTs with longer follow-up period and those comparing it with conventional treatment are needed to further support its use.