Carbon dots-cadmium sulfide quantum dots nanocomposite for 'on-off' fluorescence sensing of chromium(vi) ions.

This work involves fluorescent probe which is composed of carbon dots (CD) and cadmium sulfide quantum dots (CdS QD) for the sensitive and selective fluorescence detection of chromium(vi) ions. The blue fluorescent carbon dots were synthesized by hydrothermal method from natural precursor apricot. The carbon dots-cadmium sulfide quantum dots (CD-CdS QD) nanocomposite was synthesized and all as-synthesized products were characterized using different characterization techniques. It showed white fluorescence under UV light which was quenched selectively in the presence of chromium(vi) ions due to the inner filter effect (IFE). The linear decrease in the white fluorescence was observed in the concentration range 2-120 µM of chromium(vi) ions with the limit of detection 2.07 µM. This is novel probe for the sensitive, selective and rapid detection of chromium(vi) ions.

Dietary exposure of potentially toxic elements to freshwater mammals in the Ganga river basin, India.

The threatened Gangetic dolphin (Platanista gangetica) and smooth-coated otter (Lutrogale perspicillata) occuring in the Ganga River Basin (GRB), are experiencing a decline in their population and distribution range owing to multiple anthropogenic pressures, including pollution by Potentially Toxic Elements (PTEs). Apex predators primarily encounter contaminants through dietary exposure. Yet, notable gaps persist in our understanding of the risks associated with the ingestion of PTE-contaminated prey for Gangetic dolphins and smooth-coated otters. In this study, we examined the occurrence and spatial variation of PTEs in the prey (fish) of both these riverine mammals across three major rivers of the Basin, while also evaluating the associated risk of ingesting contaminated prey. Our assessment revealed no statistical variation in bioaccumulation profiles of PTEs across the three rivers, attributable to comparable land use patterns and PTE consumption within the catchment. Zn and Cu were the most dominant PTEs in the prey species. The major potential sources of pollution identified in the catchment include agricultural settlements, vehicular emissions, and the presence of metal-based additives in plastics. Zn, As and Hg accumulation vary with the trophic level whereas some PTEs show concentration (Hg) and dilution (As, Cr, Pb and Zn) with fish growth. The Risk Quotient (RQ), based on the dietary intake of contaminated prey calculated using Toxicity Reference Value was consistently below 1 indicating no significant risk to these riverine mammals. Conversely, with the exception of Co and Ni, the Reference Dose-based RQs for all other PTEs indicated a substantial risk for Gangetic dolphins and smooth-coated otters through dietary exposure. This study serves as a pivotal first step in assessing the risk of PTEs for two threatened riverine mammals in a densely populated river basin, highlighting the importance of their prioritization in regular monitoring to reinforce the ongoing conservation efforts.

Acute Myeloid Leukemia and Next-Generation Sequencing Panels for Diagnosis: A Comprehensive Review.

Acute myeloid leukemia (AML) is a genetically heterogeneous clonal disorder characterized by the accumulation of acquired somatic genetic alterations in hematopoietic progenitor cells, which alter the normal mechanisms of self-renewal, proliferation, and differentiation. Due to significant technological advancements in sequencing technologies in the last 2 decades, classification and prognostic scoring of AML has been refined, and multiple guidelines are now available for the same. The authors have tried to summarize, latest guidelines for AML diagnosis, important markers associated, epigenetics markers, various AML fusions and their importance, etc. Review of literature suggests lack of study or comprehensive information about current NGS panels for AML diagnosis, genes and fusions covered, their technical know-how, etc. To solve this issue, the authors have tried to present detailed review about currently in use next-generation sequencing myeloid panels and their offerings.

Heteromultimeric sarbecovirus receptor binding domain immunogens primarily generate variant-specific neutralizing antibodies.

Vaccination will likely be a key component of strategies to curtail or prevent future sarbecovirus pandemics and to reduce the prevalence of infection and disease by future SARS-CoV-2 variants. A "pan-sarbecovirus" vaccine, that provides maximum possible mitigation of human disease, should elicit neutralizing antibodies with maximum possible breadth. By positioning multiple different receptor binding domain (RBD) antigens in close proximity on a single immunogen, it is postulated that cross-reactive B cell receptors might be selectively engaged. Heteromultimeric vaccines could therefore elicit individual antibodies that neutralize a broad range of viral species. Here, we use model systems to investigate the ability of multimeric sarbecovirus RBD immunogens to expand cross-reactive B cells and elicit broadly reactive antibodies. Homomultimeric RBD immunogens generated higher serum neutralizing antibody titers than the equivalent monomeric immunogens, while heteromultimeric RBD immunogens generated neutralizing antibodies recognizing each RBD component. Moreover, RBD heterodimers elicited a greater fraction of cross-reactive germinal center B cells and cross-reactive RBD binding antibodies than did homodimers. However, when serum antibodies from RBD heterodimer-immunized mice were depleted using one RBD component, neutralization activity against the homologous viral pseudotype was removed, but neutralization activity against pseudotypes corresponding to the other RBD component was unaffected. Overall, simply combining divergent RBDs in a single immunogen generates largely separate sets of individual RBD-specific neutralizing serum antibodies that are mostly incapable of neutralizing viruses that diverge from the immunogen components.

Genetic mapping of quantitative trait loci associated with drought tolerance in chickpea (Cicer arietinum L.).

Elucidation of the genetic basis of drought tolerance is vital for genomics-assisted breeding of drought tolerant crop varieties. Here, we used genotyping-by-sequencing (GBS) to identify single nucleotide polymorphisms (SNPs) in recombinant inbred lines (RILs) derived from a cross between a drought tolerant chickpea variety, Pusa 362 and a drought sensitive variety, SBD 377. The GBS identified a total of 35,502 SNPs and subsequent filtering of these resulted in 3237 high-quality SNPs included in the eight linkage groups. Fifty-one percent of these SNPs were located in the genic regions distributed throughout the genome. The high density linkage map has total map length of 1069 cm with an average marker interval of 0.33 cm. The linkage map was used to identify 9 robust and consistent QTLs for four drought related traits viz. membrane stability index, relative water content, seed weight and yield under drought, with percent variance explained within the range of 6.29%-90.68% and LOD scores of 2.64 to 6.38, which were located on five of the eight linkage groups. A genomic region on LG 7 harbors quantitative trait loci (QTLs) explaining > 90% phenotypic variance for membrane stability index, and > 10% PVE for yield. This study also provides the first report of major QTLs for physiological traits such as membrane stability index and relative water content for drought stress in chickpea. A total of 369 putative candidate genes were identified in the 6.6 Mb genomic region spanning these QTLs. In-silico expression profiling based on the available transcriptome data revealed that 326 of these genes were differentially expressed under drought stress. KEGG analysis resulted in reduction of candidate genes from 369 to 99, revealing enrichment in various signaling pathways. Haplotype analysis confirmed 5 QTLs among the initially identified 9 QTLs. Two QTLs, qRWC1.1 and qYLD7.1, were chosen based on high SNP density. Candidate gene-based analysis revealed distinct haplotypes in qYLD7.1 associated with significant phenotypic differences, potentially linked to pathways for secondary metabolite biosynthesis. These identified candidate genes bolster defenses through flavonoids and phenylalanine-derived compounds, aiding UV protection, pathogen resistance, and plant structure.The study provides novel genomic regions and candidate genes which can be utilized in genomics-assisted breeding of superior drought tolerant chickpea cultivars.

Heterogeneous Chiral Covalent Organic Framework for the Enantioselective Epoxidation of Styrenes and Chromenes.

Herein, we report the synthesis of two-dimensional chiral ZnII Salen covalent organic frameworks (COFs) (2) via rapid microwave-promoted condensation of C3-symmetric 1,3,5-tris[(5-tert-butyl-3-formyl-4-hydroxyphenyl)ethynyl]benzene 1 with (1R,2R)-1,2-diaminocyclohexane in excellent yields. The synthesized chiral ZnII Salen COF (2) showed a 454 m2 g-1 BET surface area with excellent crystallinity and thermal stability. Further, the post-synthetic metal exchange reaction was performed for chiral ZnII Salen COFs (2) with Mn(OAc)2·4H2O to synthesize chiral MnIII Salen COFs (3) and utilized as an effective heterogeneous catalyst for the enantioselective epoxidation of styrenes and chromenes to afford chiral epoxides up to 72% ee. Chiral MnIII Salen COF (3) could easily be separated by centrifugation and reused up to four recycles with an observable loss in activity without impairing enantioselectivity.

Reassessing the availability of crop residue as a bioenergy resource in India: A field-survey based study.

Second-generation bioenergy, a carbon neutral or negative renewable resource, is crucial to achieving India's net-zero emission targets. Crop residues are being targeted as a bioenergy resource as they are otherwise burned on-field, leading to significant pollutant emissions. But estimating their bioenergy potential is problematic because of broad assumptions about their surplus fractions. Here, we use comprehensive surveys and multivariate regression models to estimate the bioenergy potential of surplus crop residues in India. These are with high sub-national and crop disaggregation that can facilitate the development of efficient supply chain mechanisms for its widespread usage. The estimated potential for 2019 of 1313 PJ can increase the present bioenergy installed capacity by 82% but is likely insufficient alone to meet India's bioenergy targets. The shortage of crop residue for bioenergy, combined with the sustainability concerns raised by previous studies, imply a need to reassess the strategy for the use of this resource.

Atorvastatin Potentially Reduces Mycobacterial Severity through Its Action on Lipoarabinomannan and Drug Permeability in Granulomas.

The majority of preclinical research has shown that Mycobacterium tuberculosis can modify host lipids in various ways. To boost its intramacrophage survival, M. tuberculosis causes host lipids to build up, resulting in the development of lipid-laden foam cells. M. tuberculosis binds to and enters the macrophage via the cell membrane cholesterol. Aggregation of cholesterol in the cell wall of M. tuberculosis and an increase in vascularity at the granuloma site reduce the permeability of rifampicin and isoniazid concentrations. However, very few studies have assessed the effect of statins on drug penetration. Here, we used atorvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, to observe its effect on the bacterial burden by increasing the drug concentration at the infection site. We looked into how atorvastatin could be used in conjunction with first-line drugs to promote drug permeation. In this study, we detected an accumulation of drugs at the peripheral sites of the lungs and impaired drug distribution to the diseased sites. The efficacy of antituberculosis drugs, with atorvastatin as an adjunct, on the viability of M. tuberculosis cells was demonstrated. A nontoxic statin dosage established phenotypic and normal granuloma vasculature and showed an additive effect with rifampicin and isoniazid. Our data show that statins help to reduce the tuberculosis bacterial burden. Our findings reveal that the bacterial load is connected with impaired drug permeability resulting from lipid accumulation in the bacterial cell wall. Statin therapy combined with antituberculosis medications have the potential to improve treatment in tuberculosis patients. IMPORTANCE Mycobacterium tuberculosis binds to and enters the macrophage via the cell membrane cholesterol. M. tuberculosis limits phagosomal maturation and activation without engaging in phagocytosis. Aggregation of cholesterol in the cell wall of M. tuberculosis and an increase in the vascularity at the granuloma site reduce the permeability of rifampicin and isoniazid concentrations. However, very few studies have assessed the effect of statins on drug penetration, which can be increased through a reduction in cholesterol and vascularity. Herein, we used atorvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, to observe its effect on bacterial burden through increasing the drug concentration at the infection site. Our main research goal is to diminish mycobacterial dissemination and attenuate bacterial growth by increasing drug permeability.

Hypoxic pulmonary vascular response can screen subclinical lifestyle disease in healthy population.

OBJECTIVE: Subclinical life style disease can cause endothelial dysfunction associated with perfusion abnormalities and reduced vascular compliance. Subclinical elevated beta type natriuretic peptide (BNP) has been associated with altered fluid shift from extra to intracellular space during acute hypoxia. Therefore we measured vascular response and BNP levels during acute hypoxia to study endothelial functions among healthy individuals. METHODS: Individuals were exposed to acute normobaric hypoxia of FiO2 = 0.15 for one hour in supine position and their pulmonary and systemic vascular response to hypoxia was compared. Individuals were divided into two groups based on either no response (Group 1) or rise in systolic pulmonary artery pressure to hypoxia (Group 2) and their BNP levels were compared. RESULTS: BNP was raised after hypoxia exposure in group 2 only from 18.52 ± 7 to 21.56 ± 10.82 picogram/ml, p < 0.05. Group 2 also showed an increase in mean arterial pressure and no fall in total body water in response to acute hypoxia indicating decreased endothelial function compared to Group 1. CONCLUSION: Rise in pulmonary artery pressure and BNP level in response to acute normobaric hypoxia indicates reduced endothelial function and can be used to screen subclinical lifestyle disease among healthy population.

A simple protocol for determination of enantiopurity of amines using BINOL derivatives as chiral solvating agents via 1H- and 19F-NMR spectroscopic analysis.

A rapid and simple protocol for the determination of enantiopurity of primary and secondary amines was developed by using (S)-BINOL/(S)-BINOL derivatives/(R)-1,1'-binaphthyl-2,2'-diyl hydrogenphosphate as chiral solvating agents via 1H- and 19F-NMR spectroscopic analysis. In this protocol, the analyte and chiral solvating agent were directly mixed in an NMR tube in chloroform-d and after shaking for 30 seconds the 1H- and 19F-NMR spectra were recorded, which affords well-resolved resonance peaks for both the enantiomers present in an analyte. The enantiomeric excess of 1,2-diphenylethylenediamine was determined and linear relationship with coefficient of R 2 = 0.9995 was observed. The binding constant and associated ΔG values were also calculated for diastereomeric complexes formed between both the enantiomers of analyte 5 with CSA (S)-3a by using UV-visible spectroscopy.

Antibacterial and Antioxidant Activities of Prinsepia utilis Royle Leaf and Seed Extracts.

Our study was designed to screen the antibacterial potency of Princepia utilis leaf and seed extract and to measure their antioxidant effects, total phenol content, total flavonoid content, and total carbohydrate content. Collected samples were extracted by cold maceration. Hexane, ethyl acetate, methanol, and distilled water were used as extraction solvents. In the disc diffusion method, P. utilis ethyl acetate leaf extract was most prominent against Staphylococcus epidermis with a zone of inhibition (ZOI) of 13.83 mm. Similarly, methanolic leaf extract was most prominent against Staphylococcus aureus (ZOI-12.33 mm). Furthermore, the methanolic seed extract was most sensitive against Klebsiella pneumoniaee (ZOI-11.66 mm) Escherichia coli (ZOI-9.0 mm). The lowest minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values of 0.5 mg/mL and 0.6 mg/mL, respectively, were shown by ethyl acetate leaf extract against S. epidermis. Similarly, the highest values of MIC and MBC, i.e., 20.8 mg/mL and 33.3 mg/mL, respectively, were shown by hexane leaf extract against S. epidermidis. On the other hand, evaluation of antioxidant capacity revealed that ethyl acetate leaf extract showed the maximum antioxidant effect (IC50: 66.69 µg/mL). The total flavonoid contents of different extracts were measured in the range of 37 ± 0.74 µg QE/mg dry extract weight (methanolic seed extract) to 321.84 ± 4.82 µg QE/mg dry extract weight (hexane seed extract). Likewise, the total polyphenol content ranged from the hexane leaf extract (17.33 ± 0.642 µg GAE/mg dry extract weight) to ethyl acetate leaf extract (62.56 ± 1.284 µg GAE/mg dry extract weight). We found a variation in total carbohydrate content in the range of 23.55 ± 1.125 µg glucose/mg dry extract weight (hexane leaf extract) to 96.63 ± 2.253 µg glucose/mg dry extract weight (aqueous leaf extract). Overall, this study revealed that leaf and seed extract of P. utilis exhibited noteworthy antibacterial effects against diverse pathogenic microorganisms.

Profiles of the Patients and Their Referral Patterns Visiting the Psychiatry Clinic of a General Hospital Setting Located in a Mental Health Resource Deficient Region of India: A Retrospective Observational Study.

Objectives Treatment for mental health problems is determined by cultural, health infrastructure, and illness-related factors. Literature is sparse from India, particularly from the mental health resources-deficient regions of the country such as central India. Therefore, the current study is aimed at assessing the profile of the patients visiting the psychiatry outpatient facility (OPF) of a tertiary-care general hospital setting (GHS), their referral patterns, and their determinants. Materials and Methods A retrospective chart review of the newly registered individuals (October 2019 to March 2020) in the psychiatry OPF of the GHS from Central India was used in the study. Data (sociodemographic profiles, illness characteristics, and referral patterns) were extracted as per the standard guidelines. Statistical Analysis Descriptive statistics were used to represent sociodemographic, illness-, and past treatment-related characteristics of the participants. Chi-squared test was used to compare the referral characteristics of the two groups (self-referred patients vs. those referred by others, dependent variable) with regard to characteristics of the patients (independent variables). Results A total of 418 individuals were registered in the clinic. Most individuals suffered from the neurotic, stress-related, and somatoform group of disorders ( n = 231, 39.5%). More than halves were self-referred; most were referred from the internal medicine and allied departments. Being male, having at least graduate degree (χ 2 df(1) = 4.25 to 6.79, p < 0.05), suffering from organic mental-, psychotic-, and recurrent affective-disorders, and positive family history (χ 2 df(1) = 4.91 to 21.76, p < 0.05 to <0.001) along with first treatment attempt or previous treatment from the traditional healers, and absence of co-occurring medical illness were associated with self-referral (vs. referred by others) (χ 2 df(1) = 4.64 to 17.6, p < 0.05 to <0.001). Conclusions GHS has a characteristic referral pattern. The referral patterns of the patients for various psychiatric problems are determined by their sociodemographic, illness, and cultural characteristics; particularly, poor mental health literacy (among the patients-caregivers), stigma related to mental disorders, and unavailability of the mental health services act as major determinants. Sensitizing the patients-caregivers and health-care professionals concerning this could facilitate an early engagement with the psychiatric treatment. Future research needs to explore this phenomenon in greater detail, maybe by qualitative methods.

Replacing the greater evil: Can legalizing decentralized waste burning in improved devices reduce waste burning emissions for improved air quality?

Open waste burning emissions constitute a significant source of air pollution affecting human health in India. In regions where cleaner fuels have displaced solid biofuel usage, open waste burning is rapidly becoming one of the largest sources of airborne human class-I-carcinogens and particulate matter. As the establishment of waste management infrastructure in rural India is likely to take years, we explore whether health-relevant emissions can be reduced by legalizing the burning of dry non-biodegradable waste in improved devices. We measure the emission factors of 76 VOCs, CH4, CO, and CO2 from different types of waste burned in two different improved devices, a burn basket and a local water heater. Based on our experiments, we create four "what-if" intervention scenarios to assess the improvement of air quality due to the emission reductions that can be accomplished by four management strategies. We find that substituting the traditional, more polluting water heating fuels with dry plastic waste across rural India can reduce primary emissions (e.g., -29 Ggy-1 for benzene) and ozone formation potential (-2960 Ggy-1) from open waste burning. When dry waste is used in lieu of more polluting fuels, and its burning serves a purpose, the net class-I-carcinogen benzene emissions, would be halved compared to the present. The change in emissions for the class-I carcinogen 1,3-butadiene would become net negative. This happens because the emissions avoided when part of the solid biofuel currently used in rural India is replaced by plastic waste (4.1 (1.2-4.1) Ggy-1) exceed the waste burning emissions of this compound (3 (1.2-3.7) Ggy-1) by so much, that residential sector emission reductions offset all waste burning emissions including those of landfill fires. Our study demonstrates that India's air quality can be improved by permitting and promoting the use of dry packaging waste in lieu of traditional biofuels and by promoting improved burning devices.

Prognostic disclosure in cancer care: a systematic literature review.

Background: Collusion in cancer care is the diplomatic concealment of information between a triad of the health care professional (HCP), patient, and caregiver. Free and expressive communication is determined by multiple factors, which establishes a healthy balance between 'patient-centric' and 'family-centric' decision making. The lack of a universal approach to prognostic disclosure techniques emphasizes the need for a systematic review of contemporary practice. Methods: A systematic review of the literature was conducted till June 2020 using themes based on cancer, communication, prognostic disclosure, and collusion by using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Results: Fifty-three studies involving 10,569 subjects were studied for their utility on prognostic disclosure using different communication methods and interfaces. Twenty-three studies used a face-to-face interview with subjects while in-person telephonic interviews were conducted in two studies, 16 studies implicated semi-structured questionnaires, and 6 studies mentioned the development of a new technique/tool for disclosure. The duration of a session for prognosis-disclosure ranged from 22 min to 1 h. The involvement of palliative care specialists and mental health professionals was limited during the disclosure of the prognosis. Conclusion: The findings of the review indicate that patients in cancer care are aware of their diagnosis and to a certain extent of prognosis despite nondisclosure by their family members and treating teams. This review emphasizes the assessment of 'disclosure wishes' among patients and caregivers in separate interviews rather than simply relying on one specific method of interviewing. The nonconfrontational approach and training among HCPs are of utmost importance to build therapeutic resilience among the treating team involved in cancer care. Since many factors such as family wishes, cultural dissonance, medical model, and patient perception could become barriers to prognostic disclosure, there is a need to develop a universal approach to prognostic disclosure and handling associated collusion.

Prevalence of collusion in cancer communications: A meta-analysis.

INTRODUCTION: Collusion is the non-disclosure of information about diagnosis or prognosis, frequently encountered in cancer care and palliative services. Unraveling collusion is a skill and differences among communication techniques by Health Care Workers have maintained the process of non-disclosure to patients and caregivers. Identifying the prevalence of collusion in cancer care is required to improve the existing strategies across the world. METHODS: A systematic review of the literature from 1991 to 2020 in the English language was conducted with the protocol registration on PROSPERO ID (CRD 42021249216.) to identify the pooled prevalence of collusion. RESULTS: By using random effect model, the pooled prevalence estimate among patients for the diagnostic and prognostic collusion was 24.15, (95% CI [17.09; 32.96], Tou2 = 1.0801, I2  = 97.9%, Cochran's Q = 1058.22, df = 21, p-value < 0.001) and 37.92, (95% CI [22.46; 56.30], Tou2 = 1.9641, I2  = 98.6%, Cochran's Q = 944.26, df = 13, p-value < 0.001) respectively. There was no difference across subgroups with different types of setting for the interview, WHO regions and trend over the years. CONCLUSIONS: Substantial prevalence of collusion goes unnoticed in cancer care. A meaningful understanding of such a large prevalence requires inquiry into the existing communication paradigm in cancer care across the world. The findings also question the need of formulating uniform interview techniques and structured assessment tools or questionnaires in cancer care to improve the disclosure rates.

DABCO-based chiral ionic liquids as recoverable and reusable organocatalyst for asymmetric Diels-Alder reaction.

New DABCO-based chiral ionic liquids were synthesized and evaluated in asymmetric Diels-Alder reaction of cyclopentadiene with α,ß-unsaturated aldehydes or 4-phenyl-3-buten-2-one. Chiral ionic liquid of modified MacMillan catalyst having a DABCO cation and hexafluorophosphate anion acts as organocatalyst (5 mol%) for the Diels-Alder reaction of crotonaldehyde and cyclopentadiene producing 98% of the product and 87% ee (endo) in CH3 CN/H2 O (95/5) at 25°C in 2 h. The scope and limitations of the catalysis were also studied by using cyclopentadiene and α,ß-unsaturated aldehydes, and the Diels-Alder products were obtained in 18%-92% yields with 68%-93% ee. The catalyst was recycled and reused up to 6 cycles with a slight drop in ee and conversion of the product.

A Web-Based Game for Young Adolescents to Improve Parental Communication and Prevent Unintended Pregnancy and Sexually Transmitted Infections (The Secret of Seven Stones): Development and Feasibility Study.

BACKGROUND: Early adolescent unintended pregnancy and sexually transmitted infection prevention are significant public health challenges in the United States. Parental influence can help adolescents make responsible and informed sexual health decisions toward delayed sexual debut; yet parents often feel ill equipped to communicate about sex-related topics. Intergenerational games offer a potential strategy to provide life skills training to young adolescents (aged 11-14 years) while engaging them and their parents in communication about sexual health. OBJECTIVE: This study aims to describe the development of a web-based online sexual health intergenerational adventure game, the Secret of Seven Stones (SSS), using an intervention mapping (IM) approach for developing theory- and evidence-based interventions. METHODS: We followed the IM development steps to describe a theoretical and empirical model for young adolescent sexual health behavior, define target behaviors and change objectives, identify theory-based methods and practical applications to inform design and function, develop and test a prototype of 2 game levels to assess feasibility before developing the complete 18-level game, draft an implementation plan that includes a commercial dissemination strategy, and draft an evaluation plan including a study design for a randomized controlled trial efficacy trial of SSS. RESULTS: SSS comprised an adventure game for young adolescent skills training delivered via a desktop computer, a text-based notification system to provide progress updates for parents and cues to initiate dialogue with their 11- to 14-year-old child, and a website for parent skills training and progress monitoring. Formative prototype testing demonstrated feasibility for in-home use and positive usability ratings. CONCLUSIONS: The SSS intergenerational game provides a unique addition to the limited cadre of home-based programs that facilitate parent involvement in influencing young adolescent behaviors and reducing adolescent sexual risk taking. The IM framework provided a logical and thorough approach to development and testing, attentive to the need for theoretical and empirical foundations in serious games for health.

Antipsychotics and hemodialysis: A systematic review.

OBJECTIVE: Antipsychotics play a crucial role in the management of behavioral problems in patients undergoing hemodialysis. Oral and injectable antipsychotics are routinely prescribed to control emergent delirium or exacerbation of previous psychiatric symptoms. However scanty literature is available on the pharmacokinetics of antipsychotics in such patients. Avoiding amisulpride and warning against increasing the dosage in renal failure is the only recommendation by drug manufacturers and clinical guidelines. Hemodialysis affects the volume of distribution (Vd) and blood levels of antipsychotics in a complex manner. It is hence difficult to equate data on renal failure with hemodialysis to reliably predict the treatment response. METHOD: We systematically analyzed online data from 1981 to 2019 on the use of antipsychotics in hemodialysis. The outcome was defined as the safety and efficacy of AP, measured in terms of adverse effects and relapse of existing or new onset of behavioral symptoms in Hemodialysis. RESULTS: The data from 182 studies revealed that only 14 case reports and 1 case series met the review criteria. Oral Risperidone, Clozapine, Aripiprazole, Ziprasidone, Haloperidol, and Long-acting Risperidone, Flupenthixol, and Paliperidone were the antipsychotics studied in terms of pharmacokinetics during hemodialysis. AP levels in the blood were found to be unaffected in two studies during HD while the other two studies recommended scheduling of AP regimen w.r.t HD session. Six reports mentioned exacerbation of pre-existing psychiatric ailments in patients undergoing HD, the most common being schizophrenia. CONCLUSION: Findings of the review reveals modest evidence favoring multiple dosing regimens of oral aripiprazole, ziprasidone, olanzapine, and risperidone. Long-acting risperidone and paliperidone are well tolerated and half of the conventional dose may be effective in the case of paliperidone. Though CYP-3A4 remains relatively and transiently unaltered during hemodialysis, none of the antipsychotics are compromised in HD. While selecting an AP during HD, one has to consider the protein binding, clearance by dialysis, duration of an HD session, route of administration of AP, and impaired bowel absorption in HD.

Heat-induced endoplasmic reticulum stress in soleus and gastrocnemius muscles and differential response to UPR pathway in rats.

The present study aimed to investigate the differential response of oxidative (soleus) and glycolytic (gastrocnemius) muscles to heat-induced endoplasmic reticulum (ER) stress. It was hypothesized that due to compositional and functional differences, both muscles respond differently to acute heat stress. To address this, male Sprague Dawley rats (12/group) were subjected to thermoneutral (25 °C) or heat stress (42 °C) conditions for 1 h. Soleus and gastrocnemius muscles were removed for analysis post-exposure. A significant increase in body temperature and free radical generation was observed in both the muscles following heat exposure. This further caused a significant increase in protein carbonyl content, AOPP, and lipid peroxidation in heat-stressed muscles. These changes were more pronounced in heat-stressed soleus compared to the gastrocnemius muscle. Accumulation of unfolded, denatured proteins results in ER stress, causing activation of unfolded protein response (UPR) pathway. The expressions of UPR transducers were significantly higher in soleus as compared to the gastrocnemius muscle. A significant elevation in resting intracellular calcium ion was also observed in heat-stressed soleus muscle. Overloading of cells with misfolded proteins in soleus muscle activated ER-induced apoptosis as indicated by significant upregulation of C/EBP homologous protein and Caspase12. The study provides a detailed mechanistic representation of the differential response of muscles toward UPR under heat stress. Data suggests that soleus majorly being an oxidative muscle is more prone to heat stress-induced insult indicated by enhanced apoptosis. This study may aid in devising mitigation strategies to improve muscle performance under heat stress.

Subclinical elevated B-type Natriuretic Peptide (BNP) indicates endothelial dysfunction contributing to hypoxia susceptibility in healthy individuals.

AIMS: Baseline elevated B-type Natriuretic Peptide (BNP) has been found in high altitude pulmonary edema susceptible population. Exaggerated pulmonary vascular response to hypoxia may be related to endothelial dysfunction in hypoxia susceptible. We hypothesize that baseline BNP levels can predict hypoxia susceptibility in healthy individuals. MAIN METHODS: The pulmonary vascular response to hypoxia was compared in 35 male healthy individuals divided into two groups based on BNP levels (Group 1 ≤ 15 and Group 2 > 15 pg/ml). Acute normobaric hypoxia was administered to both the groups, to confirm hypoxia susceptibility in Group 2. KEY FINDINGS: Unlike Group 1, Group 2 had elevated post hypoxia BNP levels (26 vs 33.5 pg/ml, p = 0.002) while pulmonary artery pressure was comparable. A negative correlation with tissue oxygen consumption (delta pO2) and compartmental fluid shift was seen in Group 1 only. Endothelial dysfunction in Group 2 resulted in reduced vascular compliance leading to elevation of mean blood pressure on acute hypoxia exposure. BNP showed a positive correlation with endothelial dysfunction in Group 2 and has been linked to pre-diabetic disorder (HbA1c 6 ± 0.44%) and may additionally represent a lower cross-sectional area of vascular bed related to vascular remodeling mediated by chronic hypoxia. SIGNIFICANCE: Hypoxia susceptibility in healthy individuals may be related to endothelial dysfunction that limits vascular compliance during hypoxic stress. BNP level showed positive correlation with HbA1c (r = 0.49, p = 0.04) and negative correlation with delta pO2 (r = -0.52, p = 0.04) can predict reduced microvascular compliance due to endothelial dysfunction contributing to hypoxia susceptibility in healthy individuals. BNP levels≤15 pg/ml at sea level is indicative of hypoxia resistance.