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Background Regional National Weather Service (NWS) heat advisory criteria in New York State (NYS) were based on frequency of heat events estimated by sparse monitoring data. These may not accurately reflect temperatures at which specific health risks occur in large geographic regions. The objectives of the study were to use spatially resolved temperature data to characterize health risks related to summertime heat exposure and estimate the temperatures at which excessive risk of heat-related adverse health occurs in NYS. We also evaluated the need to adjust current heat advisory threshold and messaging based on threshold temperatures of multiple health outcomes. Methods We assessed the effect of multi-day lag exposure for maximum near-surface air temperature (T max) and maximum Heat Index derived from the gridded National Land Data Assimilation System (NLDAS) reanalysis dataset on emergency department (ED) visits/ hospitalizations for heat stress, dehydration, acute kidney failure (AKF) and cardiovascular diseases (CVD) using a case-crossover analysis during summers of 2008–2012. We assessed effect modification using interaction terms and stratified analysis. Thresholds were estimated using piecewise spline regression. Results We observed an increased risk of heat stress (Risk ratio (RR) = 1.366, 95% confidence interval (CI): 1.347, 1.386) and dehydration (RR = 1.024, 95% CI: 1.021, 1.028) for every 1 °C increase in T max on the day of exposure. The highest risk for AKF (RR = 1.017, 95% CI: 1.014, 1.021) and CVD (RR = 1.001, 95% CI: 1.000, 1.002) were at lag 1 and 4 respectively. The increased risk of heat-health effects persists up to 6 days. Rural areas of NYS are at as high a risk of heat-health effects as urban areas. Heat-health risks start increasing at temperatures much lower than the current NWS criteria. Conclusion Reanalysis data provide refined exposure-response functions for health research, in areas with sparse monitor observations. Based on this research, rural areas in NYS had similar risk for health effects of heat. Heat advisories in New York City (NYC) had been reviewed and lowered previously. As such, the current NWS heat advisory threshold was lowered for the upstate region of New York and surrounding areas. Enhanced outreach materials were also developed and disseminated to local health departments and the public.

Background The skin micro-environment varies across the body, but all sites are host to microorganisms that can impact skin health. Some of these organisms are true commensals which colonize a unique niche on the skin, while open exposure of the skin to the environment also results in the transient presence of diverse microbes with unknown influences on skin health. Culture-based studies of skin microbiota suggest that skin microbes can affect skin properties, immune responses, pathogen growth, and wound healing. Results In this work, we greatly expanded the diversity of available commensal organisms by collecting > 800 organisms from 3 body sites of 17 individuals. Our collection includes > 30 bacterial genera and 14 fungal genera, with Staphylococcus and Micrococcus as the most prevalent isolates. We characterized a subset of skin isolates for the utilization of carbon compounds found on the skin surface. We observed that members of the skin microbiota have the capacity to metabolize amino acids, steroids, lipids, and sugars, as well as compounds originating from personal care products. Conclusions This collection is a resource that will support skin microbiome research with the potential for discovery of novel small molecules, development of novel therapeutics, and insight into the metabolic activities of the skin microbiota. We believe this unique resource will inform skin microbiome management to benefit skin health. 63JN7tcpwHsG48Gd-WoakT Video abstract.

There are several factors like angiogenesis, lymphangiogenesis, genetic alterations, mutational factors that are involved in malignant transformation of potentially malignant oral lesions (PMOLs) to oral squamous cell carcinoma (OSCC). Fibroblast growth factor-2 (FGF-2) is one of the prototypes of the large family of growth factors that bind heparin. FGF-2 induces angiogenesis and its receptors may play a role in synthesis of collagen. FGFs are involved in transmission of signals between the epithelium and connective tissue, and influence growth and differentiation of a wide variety of tissue including epithelia. The present study was undertaken to analyze expression of FGF-2 and its receptors FGFR-2 and FGFR-3 in 72 PMOLs, 108 OSCC and 52 healthy controls, and their role in risk assessment for malignant transformation of Leukoplakia (LKP) and Oral submucous fibrosis (OSMF) to OSCC. Immunohistochemistry was performed using antibodies against FGF-2, FGFR-2 and FGFR-3. IHC results were validated by Real Time PCR. Expression of FGF-2, FGFR-2 and FGFR-3 was upregulated from PMOLs to OSCC. While 90% (9/10) of PMOLs which showed malignant transformation (transformed) expressed FGF-2, only 24.19% cases (15/62) of PMOLs which were not transformed (untransformed) to OSCC expressed FGF-2. Similarly, FGFR-2 expression was seen in 16/62 (25.81%) of untransformed PMOLs and 8/10 (80%) cases of transformed PMOLs. FGFR-3 expression was observed in 23/62 (37.10%) cases of untransformed PMOLs and 6/10 (60%) cases of transformed PMOLs. A significant association of FGF-2 and FGFR-2 expression with malignant transformation from PMOLs to OSCC was observed both at phenotypic and molecular level. The results suggest that FGF-2 and FGFR-2 may be useful as biomarkers of malignant transformation in patients with OSMF and LKP.

Yellow fever is a potentially fatal, mosquito-borne viral disease that appears to be experiencing a resurgence in endemic areas in Africa and South America and spreading to non-endemic areas despite an effective vaccine. This trend has increased the level of concern about the disease and the potential for importation to areas in Asia with ecological conditions that can sustain yellow fever virus transmission. In this article, we provide a broad overview of yellow fever burden of disease, natural history, treatment, vaccine, prevention and control initiatives, and vaccine and therapeutic agent development efforts.

BACKGROUNDThere are no fully oral recommended treatment regimens for gonorrhea. Inadequately treated pharyngeal gonococcal infections are a likely reservoir for transmission and development of antimicrobial resistance. We sought to determine an oral cefixime dosing regimen that would theoretically treat pharyngeal infections by gonococci with minimum inhibitory concentrations 0.5 μg/mL. METHODSWe conducted an open-label, nonrandomized, phase I pharmacokinetic and safety study of cefixime in 25 healthy male and female volunteers divided into 4 dosing cohorts (cohort A, 400 mg; cohort B, 800 mg; cohort C, 1200 mg; and cohort D, 800 mg every 8 hours × 3 doses [total dose 2400 mg]) with a target serum concentration of at least 2.0 μg/mL for more than 20 hours. Cefixime concentrations from serum and pharyngeal fluid were determined with use of a validated liquid chromatography–tandem mass spectrometry assay. Safety measures included laboratories, physical examinations, and symptom diaries. RESULTSNone of the single-dose regimens attained the target concentration; however, 50% of subjects in cohort D attained the target concentration. Variation in absorption and protein binding contributed to differences in concentrations. Pharyngeal fluid concentrations were negligible. The single-dose regimens were well tolerated; the multidose regimen resulted in mild to moderate gastrointestinal symptoms in 43% of subjects. CONCLUSIONSNone of the dosing regimens achieved the target concentration. However, the proposed theoretical target was extrapolated from penicillin data; there are no empirically derived pharmacokinetic/pharmacodynamic criteria for pharyngeal gonorrhea. Under alternative cephalosporin-specific therapeutic goals, the multidose regimen may be effective, although the absence of cefixime in pharyngeal fluid is concerning. A clinical trial evaluating efficacy and defining pharmacokinetic/pharmacodynamic outcomes may be warranted.

Local agencies in New York State (NYS) set up cooling centers to provide relief from summer-time heat especially for people with limited access to air-conditioning. We aimed to determine cooling center locations in NYS, and explore county agencies’ involvement in organizing and promoting utilization of cooling centers. We conducted a survey among county health and emergency preparedness offices in NYS (excluding NYC) and explored official county websites. We identified 377 cooling centers, mostly in metropolitan areas of NYS. Although 47 % of counties listed locations online, only 29 % reported locations via survey. Radio (90 %) and internet (84 %) were popular for information dissemination. Air-conditioning was available at all indoor cooling center facilities. Cooling centers in 13 % of the counties were accessible by either public transportation or shuttles arranged by the facility. About 38 % counties do not consider cooling centers important in their region or promote informal cooling centers. More than a third of New York counties had neither cooling centers nor plans to establish a cooling center as extreme heat was not perceived as a threat in their region.

[This corrects the article DOI: 10.1371/journal.pone.0199665.].

Radioresistance is one of the main determinants of treatment outcome in oral squamous cell carcinoma (OSCC), but its prediction is difficult. Several authors aimed to establish radioresistant OSCC cell lines to identify genes with altered expression in response to radioresistance. The development of OSCC is a multistep carcinogenic process that includes activation of several oncogenes and inactivation of tumour suppressor genes. TGM-3 is a tumour suppressor gene and contributes to carcinogenesis process. The aim of this study was to estimate serum and tissue expression of TGM-3 and its correlation with clinico-pathological factors and overall survival in patients of OSCC undergoing chemo-radiotherapy. Tissue expression was observed in formalin fixed tissue biopsies of 96 cases of OSCC and 32 healthy controls were subjected to immunohistochemistry (IHC) by using antibody against TGM-3 and serum level was estimated by ELISA method. mRNA expression was determined by using Real-Time PCR. Patients were followed for 2 year for chemo radiotherapy response. In OSCC, 76.70% cases and in controls 90.62% were positive for TGM-3 IHC expression. TGM-3 expression was cytoplasmic and nuclear staining expressed in keratinized layer, stratum granulosum and stratum spinosum in controls and tumour cells. Mean serum TGM-3 in pre chemo-radiotherapy OSCC cases were 1304.83±573.55, post chemo-radiotherapy samples were 1530.64±669.33 and controls were 1869.16±1377.36, but difference was significant in pre chemo-radiotherapy samples as compared to controls (p<0.018). This finding was also confirmed by real- time PCR analysis in which down regulation (-7.92 fold change) of TGM-3 in OSCC as compared to controls. TGM-3 expression was significantly associated with response to chemo-radiotherapy treatment (p<0.007) and overall survival (p<0.015). Patents having higher level of TGM-3 expression have good response to chemo-radiotherapy and also have better overall survival. TGM-3 may serve as a candidate biomarker for responsiveness to chemo-radiotherapy treatment in OSCC patients.

Background: Endometrioid endometrial carcinoma (EEC) is the most common invasive malignancy of the female genital tract. Despite advances in diagnosis and treatment, the incidence of EEC and mortality related to it have not decreased. Therefore, research is needed to explore the underlying molecular mechanisms of EEC and its precursors to reduce the mortality and societal burden associated with them. Phosphatase and tensin homolog (PTEN) is a tumor suppressor gene most commonly altered in endometrial carcinoma and its precursor lesions. Promoter methylation is a common mechanism for the inactivation of the PTEN tumor suppressor gene.Methods: This was a prospective nested case-control study involving women aged 35 to 70 years old whose endometrial biopsy and resected samples were obtained for histological diagnosis. Before enrolling a person in the study, signed informed consent was obtained from each individual. The ethics committee for the institute gave its approval to the study protocol. Immunohistochemistry (IHC) was used to measure PTEN expression was measured, and methylation-specific PCR (MSP) was used to determine PTEN promoter methylation status (Bisulfite conversion).Results: A total of 95 samples were assessed histopathologically, along withPTEN expression and PTEN promoter methylation status. PTEN immunoreactivity was observed in 79% (15/19) of normal proliferative endometrium, and loss of PTEN expression was observed in 73% (27/37) of endometrial hyperplasia with or without atypia and 90% (35/39) of EEC. Methylation analysis showed that the PTEN promoter was completely unmethylated in all normal proliferative endometria and endometrial hyperplasia without atypia. In contrast, the promoter region was methylated in 50% of endometrial hyperplasia with atypia cases and 38.5% of EEC cases.Conclusion: The loss ofPTEN expression was significantly associated with EEC and precancerous lesions of the endometrium compared to normal proliferative endometria. Methylation analysis also revealed that the frequency of methylation is significant in EEC and endometrial hyperplasia with atypia. Integration of PTEN protein expression along with promoter methylation status elucidates the underlying carcinogenic mechanism. This may help with personalized therapy for EECs and triaging cases of potential precancerous lesions.

The COVID-19 pandemic amplified known challenges associated with the conduct of inpatient clinical trials, while also introducing new ones that needed to be addressed. Stakeholders based in the United States who participated in the conduct of inpatient therapeutic trials for the treatment of COVID-19 as part of the Accelerating COVID-19 Therapeutic Interventions and Vaccines program identified challenges experienced in the conduct of these trials through a series of meeting to discuss and identify common themes. In addition, innovations developed to address these challenges and other potential solutions that may be utilized in future pandemics were highlighted. Six thematic challenges including infection control considerations, the interplay between provision of clinical care and research, competing clinical trials, arduous consenting procedures, onerous procedural requirements, and participant recruitment including achieving representation of diverse populations were identified and are discussed here. Consideration of the lessons learned and recommendation outlined here may allow for more efficient conduct of inpatient clinical trials in future pandemics.