Trends in Suicidality and Bullying among New York City Adolescents across Race and Sexual Identity: 2009-2019.

Despite evidence showing rising suicidality among lesbian, gay, and bisexual (LGB) and Black adolescents, separately, there is scant research on suicide risk trajectories among youth groups across both racial and sexual identities. Thus, we examined trajectories of self-reported suicidal ideation and attempt and their associations with bullying among New York City-based adolescents. We analyzed 2009-2019 NYC Youth Risk Behavior Survey data. We ran weighted descriptive and logistic regression analyses to test for trends in dichotomous suicidal ideation, suicide attempt, bullying at school, and e-bullying variables among students across both race/ethnicity and sexual identity. We assessed associations between suicidality trends and bullying with logistic regressions. Models controlled for age and sex. Suicidal ideation and attempt were 2 and 5 times more likely among LGB than heterosexual participants, respectively. Bullying at school and e-bullying were 2 times more likely among LGB than heterosexual participants. Black LGB participants were the only LGB group for which both suicidal ideation (AOR = 1.04, SE = .003, p < .001) and attempt (AOR = 1.04, SE = .004, p < .001) increased over time. Both increased at accelerating rates. Conversely, White LGB participants were the only LGB group for which both suicidal ideation (AOR = 0.98, SE = .006, p < .001) and attempt (AOR = 0.92, SE = .008, p < .001) decreased over time. These changes occurred in parallel with significant bullying increases for Black and Latina/o/x LGB adolescents and significant bullying decreases for White LGB adolescents. Bullying was positively associated with suicidal ideation and attempt for all adolescents. Findings suggest resources aimed at curbing rising adolescent suicide should be focused on Black LGB youth.

Distinct proteomes and allergen profiles appear across the life-cycle stages of Alternaria alternata.

BACKGROUND: Alternaria alternata is associated with allergic respiratory diseases, which can be managed with allergen extract-based diagnostics and immunotherapy. It is not known how spores and hyphae contribute to allergen content. Commercial allergen extracts are manufactured by extracting proteins without separating the different forms of the fungus. OBJECTIVE: We sought to determine differences between spore and hyphae proteomes and how allergens are distributed in Aalternata. METHODS: Data-independent acquisition mass spectrometry was used to quantitatively compare the proteomes of asexual spores (nongerminating and germinating) with vegetative hyphae. RESULTS: We identified 4515 proteins in nongerminating spores, germinating spores, and hyphae; most known allergens are more abundant in nongerminating spores. On comparing significant protein fold-change differences between nongerminating spores and hyphae, we found that 174 proteins were upregulated in nongerminating spores and 80 proteins in hyphae. Among the spore proteins are ones functionally involved in cell wall synthesis, responding to cellular stress, and maintaining redox balance and homeostasis. On comparing nongerminating and germinating spores, 25 proteins were found to be upregulated in nongerminating spores and 54 in germinating spores. Among the proteins specific to germinating spores were proteases known to be virulence factors. One of the most abundant proteins in the spore proteome is sialidase, which has not been identified as an allergen but may be important in the pathogenicity of this fungus. Major allergen Alt a 1 is present at low levels in spores and hyphae and appears to be largely secreted into growth media. CONCLUSIONS: Spores and hyphae express overlapping but distinct proteomes. Most known allergens are found more abundantly in nongerminating spores.

Comparing the effect of animal and plant-based yogurt extracts on enamel demineralization: an in vitro study.

BACKGROUND: Yogurt, due to its rich casein phosphopeptide (CPP) content could promote remineralization of enamel. Contrary to the age-old usage of animal milk based yogurt, vegan dairy products are gaining momentum due to multiple reasons. Considering this change, the aim of the present study was to assess the in vitro effect of animal and plant-based yogurt extracts on demineralization of enamel. METHODS: Enamel windows were prepared on the crowns of sixty premolar teeth using nail paint. Teeth were divided into four groups of fifteen each and were treated with distilled water, demineralizing agent, solution with a mixture of demineralizing agent and yogurt supernatants, respectively for 96 hrs. Quantitative analysis was done using EDXRF (baseline and postexperimental calcium and phosphorus content). Additionally, confocal microscopic analysis was performed to assess the extent of demineralization. RESULTS: The animal-based yogurt (Group III) had the highest post experimental calcium value (mean±SD=81.15±5.02) and positive percentage of change in calcium level (15%; P=0.007) among the groups. This was followed by plant-based yogurt (Group IV) (mean calcium= 76.18±5.12; positive percentage change =8.11%; P=0.003). CONCLUSIONS: Animal based yogurt could provide higher protection against enamel demineralization when compared to plant-based yogurt.

Topical Cream Carrying Drug-Loaded Nanogels for Melanoma Treatment.

In this study, nanogel creams carrying paclitaxel (PTX) and temozolomide (TMZ) were prepared for the topical treatment of melanoma. PTX and TMZ were first loaded in poly-(D,L-lactide-co-glycolide)-block-poly(ethylene glycol)-block-poly-(D,L-lactide-co-glycolide) (PLAG-b-PEG-b-PLGA) thermosensitive nanogels, which made a transition from a free-flowing sol (formation of micellar network) at 25°C with the z-average particle size of c.a. 96 nm to a gel (aggregation of micelles) at 33°C with the z-average particle size of c.a. 427 nm. An anhydrous absorption ointment base, aquaphor, was then added to drug-loaded nanogels to form nanogel creams carrying PTX and TMZ. Nanogel creams permitted controlled release of the payloads and improved the penetration of the payloads through the rodent skin compared to drug(s)-loaded nanogels. PTX and TMZ in a combination were synergistically effective in inhibiting SK-MEL28, A375, and B16-F10 melanoma cancer cells in vitro. Topically applied nanogel creams carrying TMZ/PTX (4 mg/1.5 mg/dose) showed a trend of tumor volume inhibition on B16-F10-bearing xenograft mice in vivo.

Drug delivery challenges and formulation aspects of proteolysis targeting chimera (PROTACs).

Proteolysis targeting chimeras (PROTACs) have been extensively explored for targeted proteasomal degradation of disease-related proteins with enormous potential in the treatment of intractable diseases. However, PROTACs are poorly soluble and permeable bulky molecules facing several bioavailability challenges irrespective of the route of administration. Our review lays out crucial challenges in the delivery of target protein degraders and nanoformulation approaches to overcome physicochemical and biological hurdles that can aid in transporting these target-protein degraders to the disease site. We have elaborated on the current formulation approaches and further highlighted the prospective delivery strategies that could be probed for disease-specific targeted delivery of PROTACs.

Prevalence of mental disorders in South Asia: A systematic review of reviews.

Mental disorders are increasing in South Asia (SA), but their epidemiological burden is under-researched. We carried out a systematic umbrella review to estimate the prevalence of mental disorders and intentional self-harm in the region. Multiple databases were searched and systematic reviews reporting the prevalence of at least one mental disorder from countries in SA were included. Review data were narratively synthesised; primary studies of common mental disorders (CMDs) among adults were identified from a selected subset of reviews and pooled. We included 124 reviews. The majority (n = 65) reported on mood disorders, followed by anxiety disorders (n = 45). High prevalence of mental disorders and intentional self-harm was found in general adult and vulnerable populations. Two reviews met our pre-defined criteria for identifying primary studies of CMDs. Meta-analysis of 25 primary studies showed a pooled prevalence of 16.0% (95% CI = 11.0-22.0%, I 2 = 99.9%) for depression, 12.0% (5.0-21.0%, I 2 = 99.9%) for anxiety, and 14.0% (10.0-19.0, I 2 = 99.9%) for both among the general adult population; pooled estimates varied by country and assessment tool used. Overall, reviews suggest high prevalence for mental disorders in SA, but evidence is limited on conditions other than CMDs.

Stem Cells as a Potential Therapeutic Option for Treating Neurodegenerative Diseases.

In future, neurodegenerative diseases will take over cancer's place and become the major cause of death in the world, especially in developed countries. Advancements in the medical field and its facilities have led to an increase in the old age population, and thus contributing to the increase in number of people suffering from neurodegenerative diseases. Economically it is a great burden to society and the affected family. No current treatment aims to replace, protect, and regenerate lost neurons; instead, it alleviates the symptoms, extends the life span by a few months and creates severe side effects. Moreover, people who are affected are physically dependent for performing their basic activities, which makes their life miserable. There is an urgent need for therapy that could be able to overcome the deficits of conventional therapy for neurodegenerative diseases. Stem cells, the unspecialized cells with the properties of self-renewing and potency to differentiate into various cells types, can become a potent therapeutic option for neurodegenerative diseases. Stem cells have been widely used in clinical trials to evaluate their potential in curing different types of ailments. In this review, we discuss the various types of stem cells and their potential use in the treatment of neurodegenerative diseases-plural based on published preclinical and clinical studies.

Stromal disruption facilitating invasion of a 'nano-arsenal' into the solid tumor.

Owing to the indispensable role of nanotechnology in cancer therapy, it is imperative to comprehend every aspect limiting its therapeutic potential. Several preclinical reports have demonstrated the enhanced permeability and retention (EPR)-mediated preferential tumor uptake of nanoparticles. However, the therapeutic outcome of nanotherapeutics is severely compromised by heterogeneous drug distribution and insufficient penetration of nanomedicine in a solid tumor owing to the dense tumor extracellular matrix (ECM). Herein, we elaborate on various preclinically investigated tumor stromal disrupting strategies, which we call 'cannons', to compromise the impenetrable 'fortress-like' solid tumor microenvironment. We have described and summarized major approaches to enhance the penetration of a 'nano-arsenal' in solid tumors. ECM remodeling strategies could be very beneficial in enhancing the therapeutic efficacy of monoclonal antibodies and translational nanomedicine.

Variations in Healthcare Provider Use of Public Health and Other Information Sources by Provider Type and Practice Setting During New York City's Response to the Emerging Threat of Zika Virus Disease, 2016.

The New York City (NYC) Department of Health and Mental Hygiene (DOHMH) used multiple methods to provide guidance to healthcare providers on the management and prevention of Zika virus disease during 2016. To better understand providers' use of information sources related to emerging disease threats, this article describes reported use of information sources by NYC providers to stay informed about Zika, and patterns observed by provider type and practice setting. We sent an electronic survey to all email addresses in the Provider Data Warehouse, a system used to maintain information from state and local health department sources on all prescribing healthcare providers in NYC. The survey asked providers about their use of information sources, including specific information products offered by the NYC DOHMH, to stay informed about Zika during 2016. Trends by provider type and practice setting were described using summary statistics. The survey was sent to 44,455 unique email addresses; nearly 20% (8,711) of the emails were undeliverable. Ultimately, 1,447 (5.8%) eligible providers completed the survey. Most respondents (79%) were physicians. Overall, the most frequently reported source of information from the NYC DOHMH was the NYC Health Alert Network (73%). Providers in private practice reported that they did not use any NYC DOHMH source of information about Zika more frequently than did those working in hospital settings (29% vs 23%); similarly, private practitioners reported that they did not use any other source of information about Zika more frequently than did those working in hospital settings (16% vs 8%). Maintaining timely and accurate databases of healthcare provider contact information is a challenge for local public health agencies. Effective strategies are needed to identify and engage independently practicing healthcare providers to improve communications with all healthcare providers during public health emergencies.

Use of smokeless tobacco and risk of cardiovascular disease: A systematic review and meta-analysis.

Objective The purpose of this study was to assess the risk of ischaemic heart disease (IHD) and stroke (non-fatal and fatal) among adult ever-users of smokeless tobacco (ST). Design The study design involved a systematic review and meta-analysis of observational studies. Methods Data sources for the review included key electronic databases and reference lists. Studies were included based on design (cohort or case-control), exposure (exclusive use of ST or adjusted for smoking), and outcome (non-fatal and fatal IHD and stroke). Data extraction included reported measures of association (risk ratios (RRs) or odds ratios (ORs)) between ever-use of ST (current or past) and cardiovascular disease (CVD) outcomes among non-smokers, and other study characteristics. The Newcastle-Ottawa scale was used to assess study quality. Summary measures were estimated using random effects models. Results Twenty studies were included in the meta-analyses. Overall, significantly increased risk of IHD deaths (1.15, 95% confidence interval (CI: 1.01-1.30) and stroke deaths (1.39, 95% CI: 1.29-1.49) was found among ever-users of ST. We did not find an overall significant increased risk for IHD (1.14, 95% CI: 0.92-1.42) or stroke (1.01, 95% CI: 0.90-1.13). But geographical variations were marked for IHD, with significant positive association in Asian studies (1.40, 95% CI: 1.01-1.95), and the INTERHEART study, where ST data was mainly reported from Asia (2.23, 95% CI: 1.41-3.53). European studies did not show an increased risk for non-fatal CVD. Conclusion An association was found between ever use of ST and risk of fatal IHD and stroke, consistent with previous reviews. ST consumption also appears to significantly increase risk of non-fatal IHD among users in Asia, but not in Europe.

Assessment of essential newborn care services in secondary-level facilities from two districts of India.

India faces a formidable burden of neonatal deaths, and quality newborn care is essential for reducing the high neonatal mortality rate. We examined newborn care services, with a focus on essential newborn care (ENC) in two districts, one each from two states in India. Nagaur district in Rajasthan and Chhatarpur district in Madhya Pradesh were included. Six secondary-level facilities from the districts-two district hospitals (DHs) and four community health centres (CHCs) were evaluated, where maximum institutional births within districts were taking place. The assessment included record review, facility observation, and competency assessment of service providers, using structured checklists and sets of questionnaire. The domains assessed for competency were: resuscitation, provision of warmth, breastfeeding, kangaroo mother care, and infection prevention. Our assessments showed that no inpatient care was being rendered at the CHCs while, at DHs, neonates with sepsis, asphyxia, and prematurity/low birthweight were managed. Newborn care corners existed within or adjacent to the labour room in all the facilities and were largely unutilized spaces in most of the facilities. Resuscitation bags and masks were available in four out of six facilities, with a predominant lack of masks of both sizes. Two CHCs in Chhatarpur did not have suction device. The average knowledge score amongst service providers in resuscitation was 76% and, in the remaining ENC domains, was 78%. The corresponding average skill scores were 24% and 34%, highlighting a huge contrast in knowledge and skill scores. This disparity was observed for all levels of providers assessed. While knowledge domain scores were largely satisfactory (> 75%) for the majority of providers in domains of kangaroo mother care and breastfeeding, the scores were only moderately satisfactory (50-75%) for all other knowledge domains. The skill scores for all domains were predominantly non-satisfactory (< 50%). The findings underpin the need for improving the existing ENC services by making newborn care comers functional and enhancing skills of service providers to reduce neonatal mortality rate in India.