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Abstract Rabies is a neglected disease primarily related to dog-mediated transmission to humans. Accurate dog demographic and dynamic data are essential for effectively planning and evaluating population management strategies when designing interventions to prevent rabies. However, in Thailand, longitudinal survey data regarding dog population size are scarce. A school-based participatory research (SBPR) approach was conducted to survey owned dogs for one year in four high-risk provinces (Chiang Rai, Surin, Chonburi, and Songkhla) of Thailand, aiming to understand dog population dynamics and raise awareness about rabies. ‘Pupify’ mobile application was developed to collect data on dog population and observe the long-term population dynamics in this study. At the end of the data collection period, telephone interviews were conducted to gain insight into contextual perceptions and awareness regarding both animal and human rabies, as well as the social responsibility of dog owners in disease prevention and control. Among 303 high school students who registered in our study, 218 students reported at least one update of their dog information throughout the one-year period. Of 322 owned dogs from our survey, the updates of dog status over one year showed approximately 7.5 newborns per 100-dog-year, while deaths and missing dogs were 6.2 and 2.7 per 100-dog-year, respectively. The male to female ratio was approximately 1.8:1. Twenty-three students (10%) voluntarily participated and were interviewed in the qualitative study. The levels of rabies awareness and precautions among high-school students were relatively low. The high dropout rate of the survey was due to discontinuity in communication between the researcher and the students over the year. In conclusion, this study focused on using the SBPR approach via mobile application to collect data informing dog population dynamics and raising awareness regarding rabies in Thailand Other engaging platforms (e.g. Facebook, Instagram, Twitter, and other popular applications) is necessary to enhance communication and engagement, thereby sustaining and maintaining data collection. Further health education on rabies vaccination and animal-care practices via social media platforms would be highly beneficial. For sustainable disease control, engaging communities to raise awareness of rabies and increase dog owners’ understanding of their responsibilities should be encouraged.

Abstract Pradimicin U is a new dihydrobenzo[a]naphthacenequinone compound found to be active on a screen designed to investigate compounds with antimicrobial activity, produced by the actinomycete designated strain FMUSA5-5T. The strain was isolated from a bio-fertilizer of Musa spp. collected from Suphanburi province, Thailand. The chemotaxonomic characteristics and 16S rRNA gene analysis revealed that strain FMUSA5-5T is a member of the genus Nonomuraea. Low genome-based taxonomic criteria, average nucleotide identity (ANI) (82.8–88.3%), average amino-acid identity (AAI) (79.4–87.3%), and digital DNA–DNA hybridization (dDDH) (29.5–38.5%) values and several phenotypic differences between strain FMUSA5-5T and its closest type strains of the genus Nonomuraea indicated that strain FMUSA5-5T represents a novel species of the genus Nonomuraea and the name Nonomuraea composti sp. nov. is proposed for the strain. The crude extract from the culture broth of strain FMUSA5-5T displayed promising antimicrobial activity against several pathogens and led to the isolation of a novel secondary metabolite, pradimicin U. Interestingly, this compound displayed a broad spectrum of biological activities such as antimalarial activity against Plasmodium falciparum K1 (IC50 value = 3.65 µg/mL), anti-Mycobacterium tuberculosis H37Ra (MIC value = 25.0 µg/mL), anti-Alternaria brassicicola BCC 42724 (MIC value = 25.0 µg/mL), anti-Bacillus cereus ATCC 11778 and anti-Staphylococcus aureus ATCC 29213 (MIC values = 6.25 and 1.56 µg/mL, respectively). Moreover, the compound possessed strong anti-human small cell lung cancer (NCI-H187) activity with IC50 value of 5.69 µg/mL, while cytotoxicity against human breast cancer (MCF-7) and Vero cells was very weak (IC50 values of 52.49 and 21.84 µg/mL, respectively).

Abstract The relationship between ammonia and liver-related complications (LRCs) in acute-on-chronic liver failure (ACLF) patients is not clearly established. This study aimed to evaluate the association between ammonia levels and LRCs in patients with ACLF. The study also evaluated the ability of ammonia in predicting mortality and progression of LRCs. The study prospectively recruited ACLF patients based on the APASL definition from the ACLF Research Consortium (AARC) from 2009 to 2019. LRCs were a composite endpoint of bacterial infection, overt hepatic encephalopathy (HE), and ascites. A total of 3871 cases were screened. Of these, 701 ACLF patients were enrolled. Patients with LRCs had significantly higher ammonia levels than those without. Ammonia was significantly higher in patients with overt HE and ascites, but not in those with bacterial infection. Multivariate analysis found that ammonia was associated with LRCs. Additionally, baseline arterial ammonia was an independent predictor of 30-day mortality, but it was not associated with the development of new LRCs within 30 days. In summary, baseline arterial ammonia levels are associated with 30-day mortality and LRCs, mainly overt HE and ascites in ACLF patients.

Abstract When planning radiation therapy, late effects due to the treatment should be considered. One of the most common complications of head and neck radiation therapy is hypothyroidism. Although clinical and dosimetric data are routinely used to assess the risk of hypothyroidism after radiation, the outcome is still unsatisfactory. Medical imaging can provide additional information that improves the prediction of hypothyroidism. In this study, pre-treatment computed tomography (CT) radiomics features of the thyroid gland were combined with clinical and dosimetric data from 220 participants to predict the occurrence of hypothyroidism within 2 years after radiation therapy. The findings demonstrated that the addition of CT radiomics consistently and significantly improves upon conventional model, achieving the highest area under the receiver operating characteristic curve (AUCs) of 0.81 ± 0.06 with a random forest model. Hence, pre-treatment thyroid CT imaging provides useful information that have the potential to improve the ability to predict hypothyroidism after nasopharyngeal radiation therapy.

Abstract This paper proposes the experimental demonstration of an anapole-based cylindrical electromagnetic cloaking scheme. An anapole state is excited by arranging around a cylindrical metallic target vertical split-ring resonators, forming an equivalent surface admittance boundary condition able to suppress the scattering. Using Mie formalism and multipole scattering theory, we identify the actual reason behind the cloaking operation, characterizing the anapole condition by the scattering contributions from toroidal and electric dipole moments. Numerical results are verified using full-wave simulation softwares and subsequently validated with back-scattering measurements inside an anechoic chamber.

This study aimed to determine the prevalence and predictors of oral, ocular, or dermal e-liquid exposure and subsequent outcomes (becoming sick, going to the hospital) in the US. We examined survey data from the Population Assessment of Tobacco and Health Study Wave 5 (2018-2019). The analytic sample included US youth (aged 12-17 years), young adults (aged 18-24 years), and older adults (aged ≥ 25 years) who reported e-cigarette use in the past 12 months. We first determined the prevalence of self-reported e-liquid exposure (in the mouth, skin, or eyes), subsequently "becoming sick" from the exposure, and "going to the hospital" after the exposure. We also examined associations between these outcomes and the device type used (refillable tank /mod system, replaceable prefilled cartridges, disposable/ other device type). E-liquid exposure was reported by 25% of youth (aged 12-17 years), 25% of young adults (aged 18-24 years), and 19% of older adults (aged≥ 25 years). Among individuals reporting e-liquid exposure, subsequent sickness was reported by 10% of youth11% of young adults, and 14% of older adults, and "going to the hospital" was reported by 3.5% of youth, 2.7% of young adults, and 6.8% of older adults. Among young adults, the use of a refillable tank /mod system was associated with higher odds of e-liquid exposure (aOR = 2.2, 95% CI = 1.2, 4.1) than the use of other device types, including disposables. The findings suggest that, at a minimum, e-cigarettes/e-liquids may need warning labels that state the risks of e-liquid exposure and packaging regulations that promote device and bottle designs that minimize e-liquid spills.

IntroductionPromoting smoking cessation is a global public health priority. E-cigarettes are increasingly being used by individuals to try quitting smoking. Identifying sources and types of information available to adults who are trying to quit, and the impact of this information during a quit attempt, is critical to augment the potential public health benefit of e-cigarettes for reducing cigarette smoking.MethodsUS adults (N = 857) who reported using e-cigarettes in a recent smoking cessation attempt completed an anonymous, cross sectional, online survey. We examined sources of information and type of information received when using e-cigarettes to quit smoking and their associations with the duration of abstinence achieved.ResultsThe two most commonly reported information sources were friends (43.9%) and the internet (35.2%), while 14.0% received information from a healthcare provider. People received information on type of device (48.5%), flavor (46.3%), and nicotine concentration (43.6%). More people received information about gradually switching from smoking to vaping (46.7%) than abruptly switching (30.2%). Obtaining information from healthcare providers (β (SE) = 0.16 (0.08), p = 0.04), getting information about abruptly switching to e-cigarettes (β (SE) = 0.14 (0.06), p = 0.01) and what nicotine concentrations to use (β (SE) = 0.18 (0.05), p = 0.03) were associated with longer quit durations.ConclusionsAmidst the growing popularity of e-cigarettes use for quitting smoking, our results highlight common sources of information and types of information received by individuals. Few people received information from healthcare providers indicating a gap in cessation support that can be filled. Providing information about immediate switching to e-cigarettes and nicotine concentrations to use may help in increasing quit rates and duration.

IntroductionThe Electronic Nicotine Delivery Systems (ENDS) industry recently introduced non-tobacco nicotine (NTN), which is not tobacco-derived and is often marketed as "tobacco-free nicotine." Given its novelty, it is important to understand where young adults learn about NTN ENDS. This study examined sources of exposure to NTN ENDS and relationships with NTN ENDS use and susceptibility.MethodsWe analyzed online survey data collected in Fall 2021 from 642 young adults (18-25 years) who had heard of NTN ENDS. We assessed 9 sources of NTN ENDS exposure (e.g., retail stores, social media) and examined associations between sources of exposure and NTN current (past-month) use, lifetime (non-current) use, and susceptibility to use, adjusting for demographics and other tobacco product use.ResultsParticipants reported current NTN ENDS use (37.4%), lifetime use (12.0%), susceptibility (18.5%), or no susceptibility to use (32.1%). The most common sources of NTN ENDS exposure were retail stores (87.7%) and social media (81.0%). Exposure to NTN ENDS via social media was associated with greater odds of current NTN ENDS use (vs. no susceptibility) (aOR = 1.83, 95%CI: 1.02-3.28). Exposure via online streaming platforms was associated with greater odds of current (aOR = 1.75, 95%CI: 1.08-2.82) and lifetime NTN ENDS use (aOR = 2.42, 95%CI: 1.25-4.68).ConclusionsYoung adults were exposed to and learned about NTN ENDS from diverse sources, primarily retail shops and social media. Further, exposure via social media and streaming platforms were associated with NTN ENDS use. Future studies should explore the content of NTN information from various sources to inform prevention efforts.

BackgroundChildren form the most vulnerable strata of the society and the tobacco industry is known to target them. Article 16 of the Framework Convention of Tobacco Control (FCTC) calls for prohibition of tobacco sales to and by minors. Although interventions to stop such sales are based on sound science, it is widely acknowledged that many countries find implementation, full of challenges. In India, sales near educational institutions are banned by law, Section 6b of the Cigarettes & Other Tobacco Products Act (COTPA). We conducted a survey of violations in four states [Andhra Pradesh (AP), Karnataka (KA), Meghalaya (ML), Uttar Pradesh (UP)] of India to report the number of violations and to assess if there was an association between the schools with violations and variables such as gender, size, category, location of schools.MethodsSchools in these States were asked to report the number of shops selling tobacco within 100 yards on an App circulated to all schools (289,392 in number). Chi-square tests, univariate and multivariate logistic regression performed to find association between schools with violations by Category of School, Size of School, Gender of students and location (Urban/Rural).FindingsResponses were received from 61,748 (21.3%) schools of which 16,193 (26.2%) reported violations. It was observed that the percentages of the schools with violations were similar to the prevalence of tobacco usage in the state. Four states AP, KA, ML, UP reported violations 22.2%, 17.5%, 42.9% and 31.4% respectively. On chi-square tests, there was a significant association for the states of KA and ML with regards to variables like size, category, location of schools (p-value 100), category (Upper Primary) and location (urban) for tobacco shops violations in both KA and ML except for the school category that was secondary in ML. While for AP and UP, only size (>100), location (urban) of schools have a significant association with the violations of tobacco shops. Logistic regression of pooled data of four states school size (>100) and school category (primary) and location (urban) had significantly higher association of violation of tobacco shops.InterpretationThis is the first large survey with responses from almost all parts of the four states in India. This study shows significant association with the size, category and location of schools. We anticipate that the lists of schools which have such violations can be used by enforcement agencies to take focused action. Such models will help develop effective tobacco control policies in developing countries with large populations where implementation remains a big challenge.

BackgroundThe prognosis of nasopharyngeal carcinoma (NPC) is challenging due to late-stage identification and frequently undetectable Epstein-Barr virus (EBV) DNA. Incorporating radiomic features, which quantify tumor characteristics from imaging, may enhance prognosis assessment.PurposeTo investigate the predictive power of radiomic features on overall survival (OS), progression-free survival (PFS), and distant metastasis-free survival (DMFS) in NPC.Materials and methodsA retrospective analysis of 183 NPC patients treated with chemoradiotherapy from 2010 to 2019 was conducted. All patients were followed for at least three years. The pretreatment CT images with contrast medium, MR images (T1W and T2W), as well as gross tumor volume (GTV) contours, were used to extract radiomic features using PyRadiomics v.2.0. Robust and efficient radiomic features were chosen using the intraclass correlation test and univariate Cox proportional hazard regression analysis. They were then combined with clinical data including age, gender, tumor stage, and EBV DNA level for prognostic evaluation using Cox proportional hazard regression models with recursive feature elimination (RFE) and were optimized using 20 repetitions of a five-fold cross-validation scheme.ResultsIntegrating radiomics with clinical data significantly enhanced the predictive power, yielding a C-index of 0.788 ± 0.066 to 0.848 ± 0.079 for the combined model versus 0.745 ± 0.082 to 0.766 ± 0.083 for clinical data alone (pConclusionsThe combination of multimodality radiomic features from CT and MR images could offer superior predictive performance for OS, PFS, and DMFS compared to relying on conventional clinical data alone.

Abstract 22q11.2 deletion syndrome, associated with congenital and neuropsychiatric anomalies, is the most common copy number variant (CNV)-associated syndrome. Patient-derived, induced pluripotent stem cell (iPS) models have provided insight into this condition. However, patient-derived iPS cells may harbor underlying genetic heterogeneity that can confound analysis. Furthermore, almost all available models reflect the commonly-found ~ 3 Mb “A-D” deletion at this locus. The ~ 1.5 Mb “A-B” deletion, a variant of the 22q11.2 deletion which may lead to different syndromic features, and is much more frequently inherited than the A-D deletion, remains under-studied due to lack of relevant models. Here we leveraged a CRISPR-based strategy to engineer isogenic iPS models of the 22q11.2 “A-B” deletion. Differentiation to excitatory neurons with subsequent characterization by transcriptomics and cell surface proteomics identified deletion-associated alterations in proliferation and adhesion. To illustrate in vivo applications of this model, we further implanted neuronal progenitor cells into the cortex of neonatal mice and found potential alterations in neuronal maturation. The isogenic models generated here will provide a unique resource to study this less-common variant of the 22q11.2 microdeletion syndrome.

Abstract Tirandamycin (TAM B) is a tetramic acid antibiotic discovered to be active on a screen designed to find compounds with neuroprotective activity. The producing strain, SBST2-5T, is an actinobacterium that was isolated from wastewater treatment bio–sludge compost collected from Suphanburi province, Thailand. Taxonomic characterization based on a polyphasic approach indicates that strain SBST2-5T is a member of the genus Streptomyces and shows low average nucleotide identity (ANI) (81.7%), average amino-acid identity (AAI) (78.5%), and digital DNA-DNA hybridization (dDDH) (25.9%) values to its closest relative, Streptomyces thermoviolaceus NBRC 13905T, values that are significantly below the suggested cut-off values for the species delineation, indicating that strain SBST2-5T could be considered to represent a novel species of the genus Streptomyces. The analysis of secondary metabolites biosynthetic gene clusters (smBGCs) in its genome and chemical investigation led to the isolation of TAM B. Interestingly, TAM B at 20 µg/mL displayed a suppressive effect on beta-secretase 1 (BACE1) with 68.69 ± 8.84% inhibition. Molecular docking simulation reveals the interaction mechanism between TAM B and BACE1 that TAM B was buried in the pocket of BACE-1 by interacting with amino acids Thr231, Asp 228, Gln73, Lys 107 via hydrogen bond and Leu30, Tyr71, Phe108, Ile118 via hydrophobic interaction, indicating that TAM B represents a potential active BACE1 inhibitor. Moreover, TAM B can protect the neuron cells significantly (% neuron viability = 83.10 ± 9.83% and 112.72 ± 6.83%) from oxidative stress induced by serum deprivation and Aβ1–42 administration models at 1 ng/mL, respectively, without neurotoxicity on murine P19-derived neuron cells nor cytotoxicity against Vero cells. This study was reportedly the first study to show the neuroprotective and BACE1 inhibitory activities of TAM B.

Abstract Dengue and Zika viruses are mosquito-borne flaviviruses burdening millions every year with hemorrhagic fever and neurological symptoms. Baicalein was previously reported as a potential anti-flaviviral candidate and halogenation of flavones and flavanones potentiated their antiviral efficacies. Here, we reported that a chemically modified 8-bromobaicalein effectively inhibited all dengue serotypes and Zika viruses at 0.66–0.88 micromolar in cell-based system. The compound bound to dengue serotype 2 conserved pocket and inhibited the dengue RdRp activity with 6.93 fold more than the original baicalein. Moreover, the compound was mildly toxic against infant and adult C57BL/6 mice despite administering continuously for 7 days. Therefore, the 8-bromobaicalein should be investigated further in pharmacokinetics and efficacy in an animal model.

The identification of distinct cell populations with cellular plasticity in skin basal cell carcinoma is important for understanding treatment resistance mechanisms. Here, the authors identify the resistant LY6D+ basosquamous population that correlates with poor clinical outcomes.

Abstract Saline soil is one of the major problems limiting rice productivity in the Northeastern area of Thailand. Thus, the aims of this study were to determine soil physicochemical analysis and soil enzyme activities, and bacterial communities in the rhizosphere of ‘RD 6’ rice grown in salt-affected rice fields. The Ban Thum sample showed the highest electrical conductivity (EC; greater than 6 dS m−1) and total Na, while the EC in other fields were at non- or slightly saline levels. The principal component analysis revealed that soil chemical characteristics and soil enzymes activities explained 73.4% of total variation. Soil enzyme activities including dehydrogenase and fluorescein diacetate (FDA) hydrolysis, and soil characteristics including organic matter (OM) and organic carbon (OC) were significantly negatively correlated to EC. This indicated that these soil properties were adversely impacted by salts. Interestingly, activities of all hydrolytic enzymes were not affected by soil salinity. Bacteria that were able to colonize the rhizosphere soils were Achromobacter cholinophagum, Rhizobium tarimense, and unculturable bacteria. In this regard, study on the relationship of soil chemical characteristics and soil enzyme activities together with bacterial communities provided promising data for assessing rice field soil quality in the future.

A new study assesses the feasibility of a fully renewable based power system by 2050 across India, finding this option to be cost competitive with the status quo and with zero GHG emissions.

Abstract The clinical translation of mesenchymal stem cells (MSCs) is limited by population heterogeneity and inconsistent responses to engineered signals. Specifically, the extent in which MSCs respond to mechanical cues varies significantly across MSC lines. Although induced pluripotent stem cells (iPSCs) have recently emerged as a novel cell source for creating highly homogeneous MSC (iMSC) lines, cellular mechanosensing of iMSCs on engineered materials with defined mechanics is not well understood. Here, we tested the mechanosensing properties of three human iMSC lines derived from iPSCs generated using a fully automated platform. Stiffness-driven changes in morphology were comparable between MSCs and iMSCs cultured atop hydrogels of different stiffness. However, contrary to tissue derived MSCs, no significant changes in iMSC morphology were observed between iMSC lines atop different stiffness hydrogels, demonstrating a consistent response to mechanical signals. Further, stiffness-driven changes in mechanosensitive biomarkers were more pronounced in iMSCs than MSCs, which shows that iMSCs are more adaptive and responsive to mechanical cues than MSCs. This study reports that iMSCs are a promising stem cell source for basic and applied research due to their homogeneity and high sensitivity to engineered mechanical signals.

IntroductionConnecting individuals to recovery support services such as recovery community centers and mutual help organizations can be crucial for sustaining recovery from addiction. However, there may be barriers to engagement with recovery support services on individual (e.g., limited motivation) and structural (e.g., limited information on recovery resources) levels. This pilot study will determine the feasibility and acceptability of a novel online social support intervention (Let's Do Addiction Recovery Together!, abbreviated as LDART) that uses pre-recorded videos created by members from several recovery support services to help individuals in early recovery from hazardous alcohol use sustain motivation during recovery and introduce them to freely available recovery support services in the community.Methods and analysisThis will be a non-randomized mixed-method pilot study. We will recruit 30 adults who engaged in past-year hazardous alcohol use and have some desire to cut down or quit to use LDART every night for a month. A subset of these participants will be invited to participate in a semi-structured qualitative interview after completing the study. Primary outcomes will be feasibility parameters such as recruitment and retention rates, and acceptability measures such as frequency of intervention use. Secondary outcomes will include self-reported changes in alcohol use, engagement in recovery support services, and quality of life at one-month post-intervention relative to baseline.DiscussionResults of this pilot study will inform a randomized controlled trial to examine efficacy of this intervention, with the goal of creating an accessible and scalable intervention that has direct benefits on individuals who want to cut down or quit problematic alcohol use.Trial registrationClinicalTrials.gov ID: NCT06022107.

BackgroundTata MD CHECK SARS-CoV-2 kit 1.0, a CRISPR based reverse transcription PCR (TMC-CRISPR) test was approved by Indian Council of Medical Research (ICMR) for COVID-19 diagnosis in India. To determine the potential for rapid roll-out of this test, we conducted performance characteristic and an operational feasibility assessment (OFA) at a tertiary care setting.InterventionThe study was conducted at an ICMR approved COVID-19 RT-PCR laboratory of King Edward Memorial (KEM) hospital, Mumbai, India. The TMC-CRISPR test was evaluated against the gold-standard RT-PCR test using the same RNA sample extracted from fresh and frozen clinical specimens collected from COVID-19 suspects for routine diagnosis. TMC-CRISPR results were determined manually and using the Tata MD CHECK application. An independent agency conducted interviews of relevant laboratory staff and supervisors for OFA.ResultsOverall, 2,332 (fresh: 2,121, frozen: 211) clinical specimens were analysed of which, 140 (6%) were detected positive for COVID-19 by TMC-CRISPR compared to 261 (11%) by RT-PCR. Overall sensitivity and specificity of CRISPR was 44% (95% CI: 38.1%-50.1%) and 99% (95% CI: 98.2%-99.1%) respectively when compared to RT-PCR. Discordance between TMC-CRISPR and RT-PCR results increased with increasing Ct values and corresponding decreasing viral load (range: 85%). In the OFA, all participants indicated no additional requirements of training to set up RT PCR. However, extra post-PCR steps such as setting up the CRISPR reaction and handling of detection strips were time consuming and required special training. No significant difference was observed between manual and mobile app-based readings. However, issues such as erroneous results, difficulty in interpretation of faint bands, internet connectivity, data safety and security were highlighted as challenges with the app-based readings.ConclusionThe evaluated version-Tata MD CHECK SARS-CoV-2 kit 1.0 of TMC-CRISPR test cannot be considered as an alternative to the RT-PCR. There is a definite scope for improvement in this assay.

BackgroundThe immunomodulatory effects of vitamin D are widely recognized and a few studies have been conducted to determine its utility in the treatment of tuberculosis, with mixed results. This study was conducted to see if vitamin D supplementation in patients with active pulmonary tuberculosis (PTB) in the Indian population contributed to sputum smear and culture conversion as well as the prevention of relapse.MethodsThis randomized double-blind placebo-controlled trial was conducted in three sites in India. HIV negative participants aged 15-60 years with sputum smear positive PTB were recruited according to the Revised National Tuberculosis Control Program guidelines and were randomly assigned (1:1) to receive standard anti-tubercular treatment (ATT) with either supplemental dose of oral vitamin D3 (60,000 IU/sachet weekly for first two months, fortnightly for next four months followed by monthly for the next 18 months) or placebo with same schedule. The primary outcome was relapse of PTB and secondary outcomes were time to conversion of sputum smear and sputum culture.ResultsA total of 846 participants were enrolled between February 1, 2017 to February 27, 2021, and randomly assigned to receive either 60,000 IU vitamin D3 (n = 424) or placebo (n = 422) along with standard ATT. Among the 697 who were cured of PTB, relapse occurred in 14 participants from the vitamin D group and 19 participants from the placebo group (hazard risk ratio 0.68, 95%CI 0.34 to 1.37, log rank p value 0.29). Similarly, no statistically significant difference was seen in time to sputum smear and sputum culture conversion between both groups. Five patients died each in vitamin D and placebo groups, but none of the deaths were attributable to the study intervention. Serum levels of vitamin D were significantly raised in the vitamin D group as compared to the placebo group, with other blood parameters not showing any significant difference between groups.ConclusionsThe study reveals that vitamin D supplementation does not seem to have any beneficial effect in the treatment of PTB in terms to the prevention of relapse and time to sputum smear and culture conversion.Trial registrationCTRI/2021/02/030977 (ICMR, Clinical trial registry-India).

Background The immunomodulatory effects of vitamin D are widely recognized and a few studies have been conducted to determine its utility in the treatment of tuberculosis, with mixed results. This study was conducted to see if vitamin D supplementation in patients with active pulmonary tuberculosis (PTB) in the Indian population contributed to sputum smear and culture conversion as well as the prevention of relapse. Methods This randomized double-blind placebo-controlled trial was conducted in three sites in India. HIV negative participants aged 15–60 years with sputum smear positive PTB were recruited according to the Revised National Tuberculosis Control Program guidelines and were randomly assigned (1:1) to receive standard anti-tubercular treatment (ATT) with either supplemental dose of oral vitamin D3 (60,000 IU/sachet weekly for first two months, fortnightly for next four months followed by monthly for the next 18 months) or placebo with same schedule. The primary outcome was relapse of PTB and secondary outcomes were time to conversion of sputum smear and sputum culture. Results A total of 846 participants were enrolled between February 1, 2017 to February 27, 2021, and randomly assigned to receive either 60,000 IU vitamin D3 (n = 424) or placebo (n = 422) along with standard ATT. Among the 697 who were cured of PTB, relapse occurred in 14 participants from the vitamin D group and 19 participants from the placebo group (hazard risk ratio 0.68, 95%CI 0.34 to 1.37, log rank p value 0.29). Similarly, no statistically significant difference was seen in time to sputum smear and sputum culture conversion between both groups. Five patients died each in vitamin D and placebo groups, but none of the deaths were attributable to the study intervention. Serum levels of vitamin D were significantly raised in the vitamin D group as compared to the placebo group, with other blood parameters not showing any significant difference between groups. Conclusions The study reveals that vitamin D supplementation does not seem to have any beneficial effect in the treatment of PTB in terms to the prevention of relapse and time to sputum smear and culture conversion. Trial registration CTRI/2021/02/030977 (ICMR, Clinical trial registry-India).

BackgroundOral nicotine pouches (NPs) that contain nicotine but no tobacco leaves are rapidly gaining popularity. However, there is limited research on NPs, including within priority populations. In the current study, we examined awareness of, susceptibility to, and use of NPs in young adults as well as comparative risk perceptions with smokeless tobacco.MethodsIn 2021, 609 young adults (18-25 years) completed an online survey. Participants reported on NP awareness, susceptibility, and use as well as on comparative product perceptions for NPs versus smokeless tobacco. We ran unadjusted between-groups comparisons and an adjusted multinomial logistic regression to identify relationships between product perceptions and NP susceptibility and use.Results41.5% of participants had heard of NPs before. Participants were non-susceptible (66.2%), susceptible (23.5%), or had used NPs (10.3%). Comparative product perceptions between NPs and smokeless tobacco suggested that young adults, as a whole, expressed uncertainty about the relative risk/benefit of using NPs versus smokeless tobacco. However, as expected, unadjusted and adjusted findings indicated that favorable perceptions of NPs versus smokeless tobacco were disproportionately observed among susceptible participants and NP users compared to non-susceptible individuals. Demographic differences were also observed (e.g., NP users were more likely than non-susceptible and susceptible individuals to have used smokeless tobacco).ConclusionsYoung adults reported awareness of, susceptibility to, and use of NPs, with findings indicating that favorable perceptions of NPs versus smokeless tobacco may contribute to NP susceptibility and use beyond known correlates like smokeless tobacco use. However, further research is needed to understand the full range of factors that are associated with NP susceptibility and use. It will be important to disentangle factors that are associated with potential positive public health impacts (e.g., switching from smokeless tobacco to exclusive NP use) from those associated with negative public health impacts (e.g., initiation among nicotine naïve individuals).

Background Oral nicotine pouches (NPs) that contain nicotine but no tobacco leaves are rapidly gaining popularity. However, there is limited research on NPs, including within priority populations. In the current study, we examined awareness of, susceptibility to, and use of NPs in young adults as well as comparative risk perceptions with smokeless tobacco. Methods In 2021, 609 young adults (18–25 years) completed an online survey. Participants reported on NP awareness, susceptibility, and use as well as on comparative product perceptions for NPs versus smokeless tobacco. We ran unadjusted between-groups comparisons and an adjusted multinomial logistic regression to identify relationships between product perceptions and NP susceptibility and use. Results 41.5% of participants had heard of NPs before. Participants were non-susceptible (66.2%), susceptible (23.5%), or had used NPs (10.3%). Comparative product perceptions between NPs and smokeless tobacco suggested that young adults, as a whole, expressed uncertainty about the relative risk/benefit of using NPs versus smokeless tobacco. However, as expected, unadjusted and adjusted findings indicated that favorable perceptions of NPs versus smokeless tobacco were disproportionately observed among susceptible participants and NP users compared to non-susceptible individuals. Demographic differences were also observed (e.g., NP users were more likely than non-susceptible and susceptible individuals to have used smokeless tobacco). Conclusions Young adults reported awareness of, susceptibility to, and use of NPs, with findings indicating that favorable perceptions of NPs versus smokeless tobacco may contribute to NP susceptibility and use beyond known correlates like smokeless tobacco use. However, further research is needed to understand the full range of factors that are associated with NP susceptibility and use. It will be important to disentangle factors that are associated with potential positive public health impacts (e.g., switching from smokeless tobacco to exclusive NP use) from those associated with negative public health impacts (e.g., initiation among nicotine naïve individuals).

Abstract background: Role of Convalescent plasma (COPLA) to treat severe COVID-19 is under investigation. We compared efficacy and safety of COPLA with fresh frozen plasma (FFP) in severe COVID-19 patients. Methods: One group received COPLA with standard medical care (n = 14), and another group received random donor FFP, as control with standard medical care (n = 15) in severe COVID-19 disease. Results: The proportion of patients free of ventilation at day seven were 78.5% in COPLA group, and 93.3 % in control group were not significant (p= 0.258). However, improved respiratory rate, O2 saturation, SOFA score, and Ct value were observed in the COPLA group. No serious adverse events were noticed by plasma transfusion in both groups.

The effects of climate change (CC) on contaminants and their potential consequences to marine ecosystem services and human wellbeing are of paramount importance, as they pose overlapping risks. Here, we discuss how the interaction between CC and contaminants leads to poorly constrained impacts that affects the sensitivity of organisms to contamination leading to impaired ecosystem function, services and risk assessment evaluations. Climate drivers, such as ocean warming, ocean deoxygenation, changes in circulation, ocean acidification, and extreme events interact with trace metals, organic pollutants, excess nutrients, and radionuclides in a complex manner. Overall, the holistic consideration of the pollutants-climate change nexus has significant knowledge gaps, but will be important in understanding the fate, transport, speciation, bioavailability, toxicity, and inventories of contaminants. Greater focus on these uncertainties would facilitate improved predictions of future changes in the global biogeochemical cycling of contaminants and both human health and marine ecosystems.

Background"Tobacco-free" nicotine (TFN) e-cigarettes and nicotine pouches containing synthetic nicotine are increasingly available. The term TFN may lead to reduced risk perceptions and increased use intentions relative to tobacco-derived nicotine products. Effectively communicating messages about TFN may depend on the public's ability to differentiate TFN from tobacco-derived nicotine. Our goals were to examine knowledge about the source(s) of nicotine in commonly used products and beliefs about what TFN means.MethodsIn 2021 we surveyed 2464 young adults (18-25 years) online. Participants reported whether cigarettes, smokeless tobacco, e-cigarettes, and nicotine pouches contain nicotine that comes from tobacco (always, sometimes, never). Correct responses were "always" for cigarettes/smokeless and "sometimes" for e-cigarettes/pouches. Participants also reported "what [they] think TFN e-cigarettes/vapes contain" (nicotine only; tobacco only; both nicotine and tobacco; neither nicotine nor tobacco). We ran unadjusted and adjusted models examining correct responses for nicotine source and TFN contents by past-month product use status (cigarettes, smokeless, e-cigarettes, pouches).ResultsRates of correctly identifying nicotine source were modest (23.6% pouches-61.9% cigarettes). Except smokeless tobacco, using a given product was associated with identifying its nicotine source correctly in unadjusted models. Participants reported "TFN" means a product contains nicotine only (57.8%), tobacco only (10.8%), both (14.1%), or neither (17.1%).ConclusionsThere is confusion about the source of nicotine in products, and many young adults incorrectly interpreted TFN to mean something other than containing nicotine but no tobacco. Regulatory efforts may be needed to restrict using the term "tobacco-free nicotine" on product labeling and advertising.

Reverse transcription quantitative PCR (RT-qPCR) has emerged as the gold standard for virus detection and quantification, being utilized in numerous diagnostic and research applications. However, the direct detection of viruses has so far posed a challenge as the viral genome is often encapsidated by a proteinaceous layer surrounded by a lipid envelope. This necessitates an additional and undesired RNA extraction step prior to RT-qPCR amplification. To circumvent this limitation, we have developed a direct RT-qPCR method for the detection of RNA viruses. In our method, we provide a proof-of-concept using phage phi6, a safe-to-use proxy for pathogenic enveloped RNA viruses that is commonly utilized in e.g. aerosolization studies. First, the phage phi6 envelope is removed by 1% chloroform treatment and the virus is then directly quantified by RT-qPCR. To identify false negative results, firefly luciferase is included as a synthetic external control. Thanks to the duplex format, our direct RT-qPCR method reduces the reagents needed and provides an easy to implement and broadly applicable, fast, and cost-effective tool for the quantitative analysis of enveloped RNA viruses. • One-step direct RT-qPCR quantification of phage phi6 virus without prior RNA isolation. • Reduced reaction volume for sustainable and cost-effective analysis.

Problematic video gaming (PVG) and problematic shopping (PS) are addictive behaviors prevalent in adolescents, characterized by positive and negative reinforcement, and associated with psychosocial impairment. This study examined how PS and PVG relate in adolescents. It also examined how PS interacts with PVG in relation to health/functioning measures. Survey data from 3,657 Connecticut high-school students were evaluated. Chi-square analyses and logistic regression models were used to assess relationships between PS and measures of PVG. Interaction analyses measured effects of PS on relationships between PVG and health/functioning measures. Relative to adolescents without PS, those with PS had 8.79-fold higher odds of exhibiting PVG and were more likely to endorse gaming to relieve anxiety and impairment due to gaming. Interaction analyses revealed that in adolescents with PS, the relationships between PVG and aggressive behaviors, including fighting, serious fighting leading to physical injury, and weapon-carrying, were stronger than in adolescents without PS. PS strongly relates to PVG, and among youth reporting PS, there are stronger associations between PVG and aggressive behaviors. Prevention efforts for adolescents should consider the co-occurrence of PS and PVG. PS and PVG may be linked by negative reinforcement and propensities for aggressive and addictive behaviors, suggesting that further research should explore possible interventions targeting stress management and maladaptive coping.

Decommissioning of offshore oil and gas structures is either occurring, or imminent in most regions of the world. Most jurisdictions require that offshore structures be removed for onshore disposal. However, there is growing interest in understanding the ecological and socio-economic benefits of leaving structures in the water. Descriptions of how fish utilize the vertical structure created by wellhead platform jackets (platforms) will provide insights into possible outcomes of decommissioning alternatives, such as full removal, leave in situ, or translocation to a designated reefing site. We surveyed fish assemblages associated with seven platforms and five reference sites located ∼150 km offshore in the central Gulf of Thailand. The platforms spanned the entire water column (∼75 m) and were a mix of three and four legged structures. We used a Remotely Operated Vehicle (ROV) fitted with an underwater stereo video system to quantify the abundance, size, biomass, and economic value of fish associated with the platforms. We recorded 43 species of fish on the platforms and five reference sites with most fishes on platforms categorized as coral-reef or coral-reef-associated species. We observed a strong vertical zonation in the fish assemblage on the platforms. The Regal demoiselle (Neopomacentrus cyanomos) was numerically dominant (75% of all fish observed). We measured 3,933 kg of fish on the platforms with Caranx sexfasciatus accounting for 76.12% of that. We conservatively estimate each platform had a scaled mean biomass of ∼2,927 kg and the fished species had scaled mean economic value of 175,500 Thai Baht per platform. We estimated that the biomass of fish associated with the seven platforms was at least four times higher per unit area than some of the world’s most productive coral reefs.

The occurrence and estrogenic risks of endocrine disrupting chemicals (EDCs) in the Nan River, Phitsanulok were investigated for the first time. EDCs (octylphenol;OP, nonylphenol;NP, bisphenol A;BPA, and estrone;E1) as well as estrogenic activities (EEQs) were determined using gas chromatography-mass spectrometry (GC-MS) and Yeast Estrogen Screen (YES) bioassay. Concentrations of OP, NP, BPA, and E1in water, sediment, and fish were found up to 36.7, 1060, 1420, and 17.2 ng/L, 2.8, 97.3, 13.2, and 12.4 ng/g, and 812, 663000, 339, and 11700 ng/g, respectively. Wet season, EEQs in water, sediment, and fish were found with means of 0.36 ng/L, 0.1 ng/g, and 0.48 ng/g, respectively; while for dry season those were found with means of 0.79 ng/L, 0.87 ng/g, and 0.35 ng/g, respectively. Results of this study showed that the Nan River was contaminated with EDCs and can be harmful to aquatic organisms with high estrogenic risk.

The role of COVID-19 pandemic lockdown in improving air quality was reported extensively for land regions globally. However, limited studies have explored these over oceanic areas close to high anthropogenic activities and emissions. The Bay of Bengal (BoB) basin is one such region adjacent to the highly populated South Asian region. We find that Aerosol Optical Depth (AOD) over the BoB declined by as much as 0.1 or 30% during the peak lockdown of April 2020 compared to long-term climatology during 2003–2019. Simultaneously, the sea surface temperature (SST) rose by 0.5–1.5°C over the central and north-western parts of the BoB with an average increase of 0.83°C. We show that up to 30% of this observed warming is attributable to reduced atmospheric aerosols. The study highlights the importance of anthropogenic emissions reduction due to COVID lockdown on short-term changes to SST over ocean basins with implications to regional weather.

Summary: Rapid diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection still remains a major challenge. A multi-omic approach was adopted to analyze the respiratory specimens of 20 SARS-CoV-2-positive, 20 negative and 15 H1N1 pdm 2009 positive cases. Increased basal level of MX1 (MX dynamin-like GTPase 1) and WARS (tryptophan-tRNA ligase) correlated with SARS-CoV-2 infection and its outcome. These markers were further validated in 200 suspects. MX1>30pg/ml and WARS>25ng/ml segregated virus positives [AUC = 94% CI: (0.91–0.97)] and severe patients [AUC>0.85%]. Our results documented significant increase in immune activation; metabolic reprograming and decrease in oxygen transport, wound healing and others linked proteins and metabolites in patients with coronavirus disease 2019 (COVID-19). Multi-omics profiling correlated with viremia and segregated asymptomatic patients with COVID-19. Additionally, we identified increased respiratory pathogens (Burkholderiales, Klebsiella pneumonia) and decreased lactobacillus salivarius (FDR

IntroductionE-liquid flavor is typically presented by flavor category (e.g. menthol, mint, fruit, dessert). Cooling sensations produced by flavor additives such as menthol enhance appeal of e-cigarettes among youth, but not all e-liquids that produce cooling sensations are labeled as menthol. Sensory experiences produced by flavors may allow for a new way to capture e-cigarette flavor use. This study aims to examine use of flavors that produce cooling sensations among youth and its association with e-cigarette use behaviors.MethodsA 2019 survey of high school students (n = 4875) examined use of e-cigarette flavors that produced cooling sensations (cooling flavors) among past 30-day e-cigarette users. E-cigarette use behaviors (flavor use, nicotine use, frequency of use) were examined between those who did and did not use cooling flavors. A binary logistic regression was used to examine associations between vaping frequency, nicotine (vs. non-nicotine) use, and vaping cooling flavors while controlling for demographics, number of flavors vaped in the past month, and vaping age of onset.Results51.6% (n = 473/916) of the analytic sample endorsed vaping cooling flavors. There were no demographic differences by vaping cooling flavors. Vaping cooling flavors was associated with vaping more frequently (AOR:1.04,95% CI:1.03,1.05) and vaping nicotine (AOR:2.37,95% CI:1.53,3.67).ConclusionVaping cooling flavors was associated with greater nicotine vaping and frequency of e-cigarette use. Assessing sensory experience, such as cooling, in addition to flavor category may more fully capture e-cigarette flavor use and its impacts on youth e-cigarette use behaviors.

Background: Genomic safe harbors are sites in the genome which are safe for gene insertion such that the inserted gene will function properly, and the disruption of the genomic location doesn’t cause any foreseeable risk to the host. The AAVS1 site is the genetic location which is disrupted upon integration of adeno associated virus (AAV) and is considered a ‘safe-harbor’ in human genome because about one-third of humans are infected with AAV and so far there is no apodictic evidence that AAV is pathogenic or disruption of AAVS1 causes any disease in man. Therefore, we chose to target the AAVS1 site for the insertion of ABCB11, a bile acid transporter which is defective in progressive familial intra hepatic cholestasis type-2 (PFIC-2), a lethal disease of children where cytotoxic bile salts accumulate inside hepatocytes killing them and eventually the patient. Methods: We used the CRISPR Cas9 a genome editing system to insert the ABCB11 gene at AAVS1 site in human cell-lines. Results: We found that human ABCB11 sequence has a “Pribnow- Schaller Box” which allows its expression in bacteria and expression of ABCB11 protein which is toxic to E. coli; the removal of this was required for successful cloning. We inserted ABCB11 at AAVS1 site in HEK 293T using CRISPR-Cas9 tool. We also found that the ABCB11 protein has similarity with E. coli endotoxin (lipid A) transporter MsbA. Conclusions: We inserted ABCB11 at AAVS1 site using CRISPR-Cas9; however, the frequency of homologous recombination was very low for this approach to be successful in vivo.

BackgroundCorona virus disease 2019 (COVID-19) which initially started as a cluster of pneumonia cases in the Wuhan city of China has now become a full-blown pandemic. Timely diagnosis of COVID-19 is the key in containing the pandemic and breaking the chain of transmission. In low- and middle-income countries availability of testing kits has become the major bottleneck in testing. Novel methods like pooling of samples are the need of the hour.ObjectiveWe undertook this study to evaluate a novel protocol of pooling of RNA samples/elutes in performance of PCR for SARS CoV-2 virus.Study designExtracted RNA samples were randomly placed in pools of 8 on a 96 well plate. Both individual RNA (ID) and pooled RNA RT-qPCR for the screening E gene were done in the same plate and the positivity for the E gene was seen.ResultsThe present study demonstrated that pool testing with RNA samples can easily detect even up to a single positive sample with Ct value as high as 38. The present study also showed that the results of pool testing is not affected by number of positive samples in a pool.ConclusionPooling of RNA samples can reduce the time and expense, and can help expand diagnostic capabilities, especially during constrained supply of reagents and PCR kits for the diagnosis of SARS-CoV-2 infection.

BackgroundThe pandemic of Corona Virus (COVID-19) hit India recently; and the associated uncertainty is increasingly testing psychological resilience of the masses. When the global focus has mostly been on testing, finding a cure and preventing transmission; people are going through a myriad of psychological problems in adjusting to the current lifestyles and fear of the disease. Since there is a severe dearth of researches on this issue, we decided to conduct an online survey to evaluate its psychological impact.MethodsFrom 26th to 29th March an online survey (FEEL-COVID) was conducted using principles of snowballing, and by invitation through text messages to participate. The survey collected data on socio-demographic and clinical variables related to COVID-19 (based on the current knowledge); along with measuring psychological impact with the help of Impact of Event-revised (IES-R) scale.ResultsThere were a total of 1106 responses from around 64 cities in the country. Out of these 453 responses had at least one item missing; and were excluded from the analysis. The mean age of the respondents was around 41 years with a male female ratio of 3:1 and around 22% respondents were health care professionals. Overall approximately one third of respondents had significant psychological impact (IES-R score > 24). Higher psychological impact was predicted with younger age, female gender and comorbid physical illness. Presence of physical symptoms and contact history predicted higher psychological impact, but did not reach statistical significance.ConclusionDuring the initial stages of COVID-19 in India, almost one-third respondents had a significant psychological impact. This indicates a need for more systematic and longitudinal assessment of psychological needs of the population, which can help the government in formulating holistic interventions for affected individuals.

BackgroundDiagnosis of TB in pediatric population poses several challenges. A novel initiative was implemented in several major cities of India aimed at providing upfront access to free-of-cost Xpert MTB/RIF to presumptive pediatric TB cases. This paper aims to describe the experience of implementing this large initiative and assess feasibility of the intervention in high TB burden settings.MethodsData were drawn from the pediatric TB project implemented in 10 major cities of India between April 2014 and March 2018. In each city, providers, both public and private, were engaged and linked with a high throughput Xpert MTB/RIF lab (established in that city) through rapid specimen transportation and electronic reporting system. Rates and proportions were estimated to describe the characteristics of this cohort.ResultsOf the total 94,415 presumptive pediatric TB cases tested in the project, 6,270 were diagnosed positive for MTB (6.6%) on Xpert MTB/RIF (vs 2% on smear microscopy). Among MTB positives, 545 cases were rifampicin resistant (8.7%). The median duration between collection of specimens and reporting of results was 0 days (same day) and >89% cases were initiated on treatment. Approximately 50% of the specimens tested were non-sputum. The number of providers/facilities engaged under the project increased >10-fold (from 124 in Q2'14 to 1416 in Q1'18).ConclusionThis project, which was one of the largest initiatives globally among pediatric population, demonstrated the feasibility of sustaining rapid and upfront access to free-of-cost Xpert MTB/RIF testing. The project underscores the efficiency of this rapid diagnostic assay in tackling several challenges in pediatric TB diagnosis, identifies opportunities for further interventions as well as brings to light scope for effective engagement with healthcare providers. The findings have facilitated a policy decision by National TB Programme mandating the use of Xpert MTB/RIF as a primary diagnostic tool for TB diagnosis in children, which is being scaled-up.

Molecular diameter, lipophilicity and hydrophilicity exclusion affinity limits exist for small molecule carrier-mediated diffusion or transport through channel pores or interaction with the cell surface glycocalyx. The molecular structure lipophilicity limit for non-specific carrier-mediated transmembrane diffusion through polarity-selective transport channels of the cell membrane is Lexternal structure ∙ Hpolar group-1 of ≥ 1.07. The cell membrane channel pore size is > 0.752 and < 0.758 nm based on a 3-D ellipsoid model (biphenyl), and within the molecular diameter size range 0.744 and 0.762 nm based on a 2-D elliptical model (alkanol). The adjusted van der Waals diameter (vdWD, adj; nm) for the subset of halogenated vapors is predictive of the required MAC for anesthetic potency at an initial (-) Δ Cmicro effect. The molecular structure L ∙ Hpolar group-1 for Neu5Ac is 0.080, and the L ∙ Hpolar group-1 interval range for the cell surface glycocalyx hydrophilicity barrier interaction is 0.101 (Saxitoxin, Stx; Linternal structure ∙ Hpolar group-1) - 0.092 (m-xylenediamine, Lexternal structure · Hpolar group). Differential predictive effective pressure mapping of gene activation or repression reveals that p-dioxin exposure results in activation of AhR-Erβ (Arnt)/Nrf-2, Pparδ, Errγ (LxRα), Dio3 (Dio2) and Trα limbs, and due to high affinity Dio2 and Dio3 (OH-TriCDD, Lext · H-1: 1.91-4.31) exothermy-antagonism (Δ contraction) with high affinity T4/rT3-TRα-mediated agonism (Δ expansion). co-planar PCB metabolite exposure (Lext · H-1: 1.95-3.91) results in activation of AhR (Erα/β)/Nrf2, Rev-Erbβ, Errα, Dio3 (Dio2) and Trα limbs with a Δ Cmicro contraction of 0.89 and Δ Cmicro expansion of 1.05 as compared to p-dioxin. co-, ortho-planar PCB metabolite exposure results in activation of Car/PxR, Pparα (Srebf1,-Lxrβ), Arnt (AhR-Erβ), AR, Dio1 (Dio2) and Trβ limbs with a Δ Cmicro contraction of 0.73 and Δ Cmicro expansion of 1.18 (as compared to p-dioxin). Bisphenol A exposure (Lext struct ∙ H-1: 1.08-1.12, BPA-BPE, Errγ; BPAF, Lext struct ∙ H-1: 1.23, CM Erα, β) results in increased duration at Peff for Timm8b (Peff 0.247) transcription and in indirect activation of the AhR/Nrf-2 hybrid pathway with decreased duration at Peff 0.200 (Nrf1) and increased duration at Peff 0.257 (Dffa). The Bpa/Bpaf convergent pathway Cmicro contraction-expansion response increase in the lower Peff interval is 0.040; in comparison, small molecule hormone Δ Cmicro contraction-expansion response increases in the lower Peff intervals for gene expression ≤ 0.168 (Dex· GR) ≥ 0.156 (Dht · AR), with grade of duration at Peff (min·count) of 1.33x105 (Dex/Cort) and 1.8-2.53x105 (Dht/R1881) as compared to the (-) coupled (+) Δ Cmicro Peff to 0.136 (Wnt5a, Esr2) with applied DES (1.86x106). The subtype of trans-differentiated cell as a result of an applied toxin or toxicant is predictable by delta-Cmicro determined by Peff mapping. Study findings offer additional perspective on the basis for pressure regulated gene transcription by alterations in cell micro-compliance (Δ contraction-expansion, Cmicro), and are applicable for the further predictive modeling of gene to gene transcription interactions, and small molecule modulation of cell effective pressure (Peff) and its potential.

ObjectivesIn November 2018, JUUL, Inc. restricted sales of mango, fruit medley, crème brûlée, and cucumber pods to its website. Physical/online sales of tobacco, menthol, and mint pods continued. We examined rates of adolescent JUUL device and flavored pod use before and after restrictions were implemented to examine their potential impact.MethodsStudents from 4 Connecticut high schools completed cross-sectional surveys in 2018 (N = 3170) and 2019 (N = 3074).ResultsCompared to 2018, current (past-month) JUUL use decreased in 2019 (30.2-25.6%). Among current JUUL users, restricted flavor use (mango [62.8-36.9%]; cucumber [27.7-11.9%]; fruit [23.5-11.4%]; crème brûlée [12.3-5.0%]) and the total number of flavors used (2.09[SD = 1.71]-1.51[SD = 1.33]) decreased (p-values < .001), while mint pod use increased (62.0-68.6%, p < .01). Tobacco and menthol pod use remained stable.ConclusionsFollowing voluntary sales restrictions implemented by JUUL, Inc., restricted flavor use and the total number of flavors used decreased among JUUL users while mint use increased. Results suggest flavor restrictions may impact adolescents' e-cigarette use. While 2020 Food and Drug Administration restrictions on mint pods may further limit youth JUUL use, research is needed to determine where youth acquire restricted flavors and if restrictions prompt increased popularity of unrestricted devices/e-liquids.

India has the highest burden of Tuberculosis (TB) and multidrug-resistant TB (MDR-TB) worldwide. Innovative technology is the need of the hour to identify these cases that remain either undiagnosed or inadequately diagnosed due to the unavailability of appropriate tools at primary healthcare settings. We developed and evaluated 3 kits, namely 'TB Detect' (containing BioFM-Filter device), 'TB Concentration and Transport' (containing Trans-Filter device) and 'TB DNA Extraction' kits. These kits enable bio-safe equipment-free concentration of sputum on filters and improved fluorescence microscopy at primary healthcare centres, ambient temperature transport of dried inactivated sputum filters to central laboratories and molecular detection of drug resistance by PCR and DNA sequencing (Mol-DST). In a 2-site evaluation (n = 1190 sputum specimens) on presumptive TB patients, BioFM-Filter smear exhibited a significant increase in positivity of 7% and 4% over ZN smear and LED-FM smear (p

Lymphatic malformation (LM) is a developmental anomaly of the lymphatic system that may lead to disfigurement, organ dysfunction and recurrent infection. Though several treatment modalities exist, pharmacotherapy is often associated with side effects and recurrence is common following surgical interventions. Moreover, despite the recent discovery of PIK3CA mutations in lymphatic endothelial cells of LM patients, the full spectrum of molecular pathways involved in LM pathogenesis is poorly understood. Here, we performed RNA sequencing on blood samples obtained from ten LM patients and nine healthy subjects and found 421 differentially expressed genes that stratify LM subjects from healthy controls. Using this LM gene signature, we identified novel pathway alterations in LM, such as oxidative phosphorylation, MEK/ERK, bone morphogenetic protein (BMP), and Wnt/β-catenin pathways, in addition to confirming the known alterations in cell cycle and the PI3K/AKT pathway. Furthermore, we performed computational drug repositioning analysis to predict existing therapies (e.g. sirolimus) and novel classes of drugs for LM. These findings deepen our understanding of LM pathogenesis and may facilitate non-invasive diagnosis, pathway analysis and therapeutic development.

BACKGROUND:Outreach and promotion programs are essential to ensuring uptake of new public health interventions and guidelines. We assessed the costs and operation dynamics of outreach and promotion efforts for up front Xpert MTB/RIF (Xpert) testing for pediatric presumptive tuberculosis (TB) patients in four major Indian cities. METHODS:Xpert test costs were assessed as weighted average per-test costs based on the daily workload dynamics matched by test volume specific Xpert unit cost at each study site. Costs of outreach programs to recruit health providers to refer pediatric patients for Xpert testing were assessed as cost per referral for each quarter based on total program costs and referral data. All costs were assessed in the health service provider's perspective and expressed in 2015 USD. RESULTS:Weighted average per-test costs ranged from $14.71 to $17.81 at the four laboratories assessed. Differences between laboratories were associated with unused testing capacity and/or frequencies of overtime work to cope with increasing demand and same-day testing requirements. Outreach activities generated between 825 and 2,065 Xpert testing referrals on average each quarter across the four study sites, translating into $0.63 to $2.55 per patient referred. Overall outreach costs per referral decreased with time, stabilizing at an average cost of $1.10, and demonstrated a clear association with increased referrals. CONCLUSIONS:Xpert test and outreach program costs within and across study sites were mainly driven by the dynamics of Xpert testing demand resulting from the combined outreach activities. However, these increases in demand required considerable overtime work resulting in additional costs and operational challenges at the study laboratories. Therefore, careful laboratory operational adjustment should be evaluated at target areas in parallel to the anticipated demand from the Xpert referral outreach program scale-up in other Indian regions.

IntroductionMany e-cigarette users find the variety of e-cigarette flavors appealing. We examined whether preferences for e-liquid flavors and the total number of flavors preferred differed between samples of adolescent and adult e-cigarette users. We also examined whether these preferences were associated with e-cigarette use frequency for adolescents or adults, respectively.Materials and methodsThe analytic samples comprised 1) 396 adolescent, past-month e-cigarette users from 5 Connecticut high schools who completed an anonymous, school-based survey in Fall 2014 (56.1% male; 16.18 [1.18] years; 42.2% past-month smokers), and 2) 590 adult, past-month e-cigarette users who completed an anonymous, MTurk survey in Fall 2014 (53.7% male; 34.25 [9.89] years; 51.2% past-month smokers).ResultsCompared to adults, a larger proportion of adolescents preferred fruit, alcohol, and "other"-flavored e-liquids, whereas adults disproportionately preferred tobacco, menthol, mint, coffee, and spice-flavored e-liquids (p-values < .05). Adults also preferred a greater total number of flavors compared to adolescents and used e-cigarettes more frequently (p-values < .001). Flavor preferences uniquely were associated with frequency of e-cigarette use within the adolescent sample; the total number of flavors preferred was associated with more days of e-cigarette use (ηp2 = 0.04), as were preferences for fruit (ηp2 = 0.02), dessert (ηp2 = 0.02), and alcohol-flavored (ηp2 = 0.02) e-liquids.ConclusionsFlavor preferences differed between adolescent and adult samples. While youth reported less frequent e-cigarette use overall, their preferences for specific flavors and the total number of flavors preferred were associated with more days of e-cigarette use, indicating that flavor preferences may play an important role in adolescent e-cigarette use.