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Japanese encephalitis virus (JEV) is an arthropod-borne, plus-strand flavivirus causing viral encephalitis in humans with a high case fatality rate. The JEV non-structural protein 5 (NS5) with the RNA-dependent RNA polymerase activity interacts with the viral and host proteins to constitute the replication complex. We have identified the multifunctional protein Nucleolin (NCL) as one of the several NS5-interacting host proteins. We demonstrate the interaction and colocalization of JEV NS5 with NCL in the virus-infected HeLa cells. The siRNA-mediated knockdown of NCL indicated that it was required for efficient viral replication. Importantly, JEV grew to higher titers in cells over-expressing exogenous NCL, demonstrating its pro-viral role. We demonstrated that NS5 interacted with the RRM and GAR domains of NCL. We show that the NCL-binding aptamer AS1411 containing the G-quadruplex (GQ) structure and the GQ ligand BRACO-19 caused significant inhibition of JEV replication. The antiviral effect of AS1411 and BRACO-19 could be overcome in HeLa cells by the overexpression of exogenous NCL. We demonstrated that the synthetic RNAs derived from the 3'-NCR of JEV genomic RNA containing the GQ sequence could bind NCL in vitro . The replication complex binding to the 3'-NCR is required for the viral RNA synthesis. It is likely that NCL present in the replication complex destabilizes the GQ structures in the genomic RNA, thus facilitating the movement of the replication complex resulting in efficient virus replication.IMPORTANCEJapanese encephalitis virus (JEV) is endemic in most parts of South-East Asia and the Western Pacific region, causing epidemics of encephalitis with a high case fatality rate. While a tissue culture-derived JEV vaccine is available, no antiviral therapy exists. The JEV NS5 protein has RNA-dependent RNA polymerase activity. Together with several host and viral proteins, it constitutes the replication complex necessary for virus replication. Understanding the interaction of NS5 with the host proteins could help design novel antivirals. We identified Nucleolin (NCL) as a crucial host protein interactor of JEV NS5 having a pro-viral role in virus replication. The NS5-interacting NCL binds to the G-quadruplex (GQ) structure sequence in the 3'-NCR of JEV RNA. This may smoothen the movement of the replication complex along the genomic RNA, thereby facilitating the virus replication. This study is the first report on how NCL, a host protein, helps in JEV replication through GQ-binding., Competing Interests: The authors declare no conflict of interest.

Family functioning may serve as protective or risk factors in the development of youth psychopathology. However, few studies have examined the potentially reciprocal relation between child psychopathology and family functioning. To fill this gap in the literature, this study tested for time-ordered associations between measures of family functioning (e.g., cohesion, conflict, and emotional expressiveness) and child psychopathology (e.g., total behavior problems, externalizing, and internalizing problems) using data from the Longitudinal Studies of Child Abuse and Neglect (LONGSCAN; N = 1143, 52.3% female, Nwaves = 5). We used a random-intercept cross-lagged panel model to identify whether child psychopathology preceded and predicted family functioning, the reverse, or both processes occurred simultaneously. At the between-person level, families who tended to have more cohesion, who lacked conflict, and who expressed their emotions had lower levels of child psychopathology. At the within-person level in childhood, we found minimal evidence for time-ordered associations. In adolescence, however, a clear pattern whereby early psychopathology consistently predicted subsequent family functioning emerged, and the reverse direction was rarely found. Results indicate a complex dynamic relation between the family unit and child that have important implications for developmental models that contextualize risk and resilience within the family unit.

Objectives: Oral cancer is significantly high in India, and screening is an effective approach to downstage the disease. Educating Community Health Workers (CHWs) on early oral cancer detection is an effective step toward reducing the burden and serves as a first step toward facilitating the transfer of knowledge. Therefore, the purpose of this hands-on education was to equip CHWs with insight on the advanced diagnostics, preventive techniques, and innovations for the early detection of oral cancer., Materials and Methods: A total of 178 participants were trained in two groups: Group 1 received training for screening and primary prevention, while group 2 received training on updates in recent diagnostic adjuncts and innovations, AI-enabled point-of-care diagnostics, and essential patient care in management of Oral Potentially Malignant Disorders (OPMDs). Pre- and post-assessment questionnaires were used to evaluate the participants., Results: The knowledge assessment scores between the pre- and post-tests showed a statistically significant difference ( p  < 0.001), with rise in mean score of 3.99 from baseline. Six months following training, knowledge retention revealed a statistically significant difference ( p  < 0.001) in the participants' ability to recall the information., Conclusion: A well-structured training module can create awareness, impart knowledge and upskill the CHWs for early detection of oral cancer. Retraining of CHWs is required for knowledge retention post-training., Competing Interests: Conflict of interestThe authors have no competing interests to declare that are relevant to the content of this article., (© The Association of Oral and Maxillofacial Surgeons of India 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Purpose: Despite increased usage of telemedicine to deliver treatment during the coronavirus disease 2019 (COVID-19) pandemic, the efficacy of telerehabilitation for spine pain is unknown. This study aimed to investigate the effect of telerehabilitation on pain and disability in patients with spine pain treated during the COVID-19 pandemic and compare the results to in-clinic rehabilitation., Materials & Methods: In this propensity score-matched analysis, 428 patients with spine pain who underwent telerehabilitation during the 6 months of COVID-19 pandemic lockdown and 428 patients who underwent in-clinic multimodal rehabilitation treatment during the 6-month period prior to lockdown were compared. Propensity score matching was done based on gender, age, pre-treatment pain, and disability. Post-treatment numerical pain rating scale (NPRS), Oswestry or Neck disability index (ODI or NDI), and minimal clinical important difference (MCID) achieved for NPRS and ODI/NDI scores were compared between the 2 groups., Results: Post-treatment, the mean NPRS (mean difference - 1, p  < 0.0001) and ODI/NDI (mean difference - 5.8, p  < 0.0001) scores, were significantly lower in the telerehabilitation group when compared to control group. Similarly, the percentage of patients who achieved MCID of ≥ 2 for NPRS (mean difference - 6%, p  = 0.0007) and MCID of ≥ 10 for ODI/NDI (mean difference - 7.5%, p  = 0.005) scores were significantly higher in the telerehabilitation group., Conclusions: Telerehabilitation achieved significant reduction in pain and disability among patients with spine pain, better than in-clinic rehabilitation. These encouraging results during the COVID-19 pandemic indicate the need to further explore and test the efficacy and wider application of telerehabilitation for treating spine pain.IMPLICATIONS FOR REHABILITATIONTelerehabilitation can help achieve significant reduction in pain and disability among patients with spine pain.These encouraging results indicate the need to further explore a wider application of telerehabilitation for treating patients with spine pain during non-pandemic times.

Familial dilated cardiomyopathy is a prevalent cause of heart failure that results from the mutation of genes encoding proteins of diverse function. Despite modern therapy, dilated cardiomyopathy typically has a poor outcome and is the leading cause of cardiac transplantation. The phosphatase PP2A at cardiomyocyte perinuclear mAKAPβ signalosomes promotes pathological eccentric cardiac remodeling, as is characteristic of dilated cardiomyopathy. Displacement of PP2A from mAKAPβ, inhibiting PP2A function in that intracellular compartment, can be achieved by expression of a mAKAPβ-derived PP2A binding domain-derived peptide. To test whether PP2A anchoring disruption would be effective at preventing dilated cardiomyopathy-associated cardiac dysfunction, the adeno-associated virus gene therapy vector AAV9sc.PBD was devised to express the disrupting peptide in cardiomyocytes in vivo . Proof-of-concept is now provided that AAV9sc.PBD improves the cardiac structure and function of a cardiomyopathy mouse model involving transgenic expression of a mutant α-tropomyosin E54K Tpm1 allele, while AAV9sc.PBD has no effect on normal non-transgenic mice. At the cellular level, AAV9sc.PBD restores cardiomyocyte morphology and gene expression in the mutant Tpm1 mouse. As the mechanism of AAV9sc.PBD action suggests potential efficacy in dilated cardiomyopathy regardless of the underlying etiology, these data support the further testing of AAV9sc.PBD as a broad-based treatment for dilated cardiomyopathy., Competing Interests: M.S.K. and J.L. are inventors of patent-protected intellectual property concerning the targeting of mAKAPβ-PP2A signalosomes to treat heart failure, by which they and Stanford University may gain royalties from future commercialization. M.S.K. holds equity in Cardiac RSK3 Inhibitors, LLC, that has licenses for these therapies., (© 2024 The Author(s).)

The large abundance of termites is partially achieved by their defensive abilities. Stylotermitidae represented by a single extant genus, Stylotermes, is a member of a termite group Neoisoptera that encompasses 83% of termite species and 94% of termite genera and is characterized by the presence of the frontal gland. Within Neoisoptera, Stylotermitidae represents a species-poor sister lineage of all other groups. We studied the structure of the frontal, labral and labial glands in soldiers and workers of Stylotermes faveolus, and the composition of the frontal gland secretion in S. faveolus and Stylotermes halumicus. We show that the frontal gland is a small active secretory organ in soldiers and workers. It produces a cocktail of monoterpenes in soldiers, and some of these monoterpenes and unidentified proteins in workers. The labral and labial glands are developed similarly to other termite species and contribute to defensive activities (labral in both castes, labial in soldiers) or to the production of digestive enzymes (labial in workers). Our results support the importance of the frontal gland in the evolution of Neoisoptera. Toxic, irritating and detectable monoterpenes play defensive and pheromonal functions and are likely critical novelties contributing to the ecological success of these termites., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Stylotermitidae appear peculiar among all termites, feeding in trunks of living trees in South Asia only. The difficulty to collect them limits the ability to study them, and they thus still belong to critically unknown groups in respect to their biology. We used a combination of microscopic observations, chemical analysis and behavioural tests, to determine the source and chemical nature of the trail-following pheromone of Stylotermes faveolus from India and S. halumicus from Taiwan. The sternal gland located at the 5th abdominal segment was the exclusive source of the trail-following pheromone in both S. faveolus and S. halumicus, and it is made up of class I, II and III secretory cells. Using gas chromatography coupled mass spectrometry, (3Z)-dodec-3-en-1-ol (DOE) was identified as the trail-following pheromone which elicits strong behavioural responses in workers at a threshold around 10 - 4 ng/cm and 0.1 ng/gland. Our results confirm the switch from complex aldehyde trail-following pheromones occurring in the basal groups to simpler linear alcohols in the ancestor of Kalotermitidae and Neoisoptera., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: This prospective observational study explored the effect of early onset hypoalbuminemia (EOH) on the development of adult respiratory distress syndrome (ARDS) in orthopedic trauma victims., Methods: Serum albumin levels were measured for the initial 7 days of injury for adult trauma patients (18-65 years). Patients were recruited into group A (any serum albumin value < 3.5 mg/dl) and group B (all serum albumin ≥ 3.5 mg/dl), based on serum albumin values. Patients were followed for the development of ARDS and outcome until 28 days. The primary outcome of the study was to explore the effects of EOH on ARDS., Results: EOH (any serum albumin value < 3.5 g/dl within 7 days of injury) was present in 205/386 (53.1%) patients. The majority of 174/205 (84.9%) patients had EOH by the fourth day after the injury, with the mean time for development of EOH being 2.15 ± 1.87 days. ARDS manifested in 87/205 (42.4%) and 15/181 (8.3%) patients in group A and group B, respectively (p < 0.001). EOH had 8.2 times greater odds of ARDS (OD 8.2 95% CL 4.7-14.0, p = 0.000). The mean time for the onset of ARDS was 5.63 ± 2.62 days. No statistically significant causal relationship occurred between the onset of EOH and the development of ARDS (Pearson's correlation coefficient = 0.14, p = 0.16). At serum albumin cutoff concentrations of 3.4 gm/dl on D1 (AUC 0.68, 95% CI: 0.61-0.74, p = 0.000), ARDS may be anticipated in 62.8% of patients. The commencement of ARDS was independently correlated with EOH (p = 0.000), Respiratory rate on admission (p = 0.000), inotrope use (p = 0.000), and soft tissue injury (p = 0.000) (R 2  = 0.466). The odds of 28-day all-cause death were 7.7 times higher in EOH (OD 7.7 95% CL 3.5-16.7, p = 0.00) and 9 times higher in ARDS (OD 9 95% CL 4.9-16.16, p = 0.00)., Conclusion: EOH is a frequent occurrence and has a strong influence development of ARDS and 28-day mortality in trauma patients., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Ischemic cardiomyopathy is a leading cause of death and an unmet clinical need. Adeno-associated virus (AAV) gene-based therapies hold great promise for treating and preventing heart failure. Previously we showed that muscle A-kinase Anchoring Protein β (mAKAPβ, AKAP6β), a scaffold protein that organizes perinuclear signalosomes in the cardiomyocyte, is a critical regulator of pathological cardiac hypertrophy. Here, we show that inhibition of mAKAPβ expression in stressed adult cardiomyocytes in vitro was cardioprotective, while conditional cardiomyocyte-specific mAKAP gene deletion in mice prevented pathological cardiac remodeling due to myocardial infarction. We developed a new self-complementary serotype 9 AAV gene therapy vector expressing a short hairpin RNA for mAKAPβ under the control of a cardiomyocyte-specific promoter (AAV9sc.shmAKAP). This vector efficiently downregulated mAKAPβ expression in the mouse heart in vivo. Expression of the shRNA also inhibited mAKAPβ expression in human induced cardiomyocytes in vitro. Following myocardial infarction, systemic administration of AAV9sc.shmAKAP prevented the development of pathological cardiac remodeling and heart failure, providing long-term restoration of left ventricular ejection fraction. Our findings provide proof-of-concept for mAKAPβ as a therapeutic target for ischemic cardiomyopathy and support the development of a translational pipeline for AAV9sc.shmAKAP for the treatment of heart failure., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Nicotine is a highly addictive alkaloid and a neurostimulator found in tobacco that causes addiction in humans and makes tobacco a high-demand commercial product. It is popularly used for recreational purposes and is a harmful substance (Oral LD 50 value for rat is 50 mg/kg) and causes addiction. The metabolites of nicotine such as the Tobacco-specific Nitrosamines (TSNAs) are hazardous substances whose metabolites are highly electrophilic and form DNA adducts, which will initiate the process of carcinogenesis. TSNAs are formed during curing, storage and fermentation due to the nitrosation of nicotine and other tobacco alkaloids. TSNAs are used as biomarkers for cancer risk assessment in humans exposed to tobacco and its products. To determine the occasional formation of TSNAs in tobacco-feeding insects, 5th instar larvae of Spodoptera litura and their faeces were analyzed for the presence of N'-nitrosonornicotine (NNN), 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) along with the stored tobacco leaves (PT-76) using an Agilent 6470B LC-MS/MS system following ISO/DIS 19290:2015 protocol. The larvae are extracted in a buffered acetonitrile-water extraction and the amount of TSNAs are quantified in multiple reaction monitoring (MRM) mode. 20 [Formula: see text]l of each extracted and cleaned up sample was injected into the LC-MS/MS system for quantification. The Limit of Detection (LOD) and Limit of Quantification (LOQ) were 0.001 mg/kg and 0.005 mg/kg for all the tested nitrosamines. NNN was found to be 0.361 mg/kg, 0.340 mg/kg, and 5.66 mg/kg in insect whole-body samples, faeces, and tobacco leaves, respectively. NNK was found to be 0.060 mg/kg, 0.035 mg/kg and 0.93 mg/kg in insect whole body samples, faeces and tobacco leaves, respectively. However, NNAL was not detected in both the insect's whole body and faeces. Recoveries ranged between 95 and 98% for all compounds when spiked at LOD and LOQ. The presence of TSNAs is a biomarker for cancer risk and their presence in insects would point to cancer risk assessment in tobacco feeding insects and any possible TSNA-detoxifying pathways in insects that might prevent mutagenesis caused these compounds., (© 2023. The Author(s).)

Background: The invasive and calamitous polyphagous pest Spodoptera frugiperda or commonly known as fall armyworm (FAW) poses serious menace to the global agricultural production. Owing to the revamped invasion of FAW in 2018 in India, present study was undertaken for precise assessment of its genetic identity and pesticide resistance to aid in pest-management strategies., Results: To evaluate the diversity in FAW population across Eastern India, mitochondrial COI sequences were used which revealed a low nucleotide diversity. Analysis of molecular variance indicated significant genetic variation between four global geographical FAW populations with lowest differentiation between India and Africa suggesting a present-day and shared origin of FAW. The study demonstrated existence of two different strains ('R' strain and 'C' strain) based on COI gene marker. However, discrepancies between COI marker and host plant association of FAW was observed. Characterization of Tpi gene revealed abundance of TpiCa1a followed by TpiCa2b and TpiR1a strains respectively. The FAW population showed higher susceptibility towards chlorantraniliprole and spinetoram than cypermethrin. Insecticide resistance genes depicted marked upregulation although with lot of variance. Chlorantraniliprole resistance ratio (RR) exhibited significant correlation with 1950 (Glutathione S-transferase, GST), 9131 (Cytochrome P450, CYP) and 9360 (CYP) genes, while spinetoram and cypermethrin RR was found to correlate with 1950 (GST) and 9360 (CYP) genes., Conclusion: This study manifests Indian subcontinent as the potential new hotspot for the growth and distribution of FAW population that can be effectively controlled using chlorantraniliprole and spinetoram. This study also adds novel significant information on FAW population across Eastern India for developing a comprehensive pest management approach for S. frugiperda., (© 2023. The Author(s).)

Background: Critically injured patients who are agitated and delirious on arrival do not allow optimal preoxygenation in the emergency area. We investigated whether the administration of intravenous (IV) ketamine 3 minutes before administration of a muscle relaxant is associated with better oxygen saturation levels while intubating these patients., Methods: Two hundred critically injured patients who required definitive airway management on arrival were recruited. The subjects were randomized as delayed sequence intubation (group DSI) or rapid sequence intubation (group RSI). In group DSI, patients received a dissociative dose of ketamine followed by 3 minutes of preoxygenation and paralysis using IV succinylcholine for intubation. In group RSI, a 3-minute preoxygenation was performed before induction and paralysis using the same drugs, as described conventionally. The primary outcome was incidence of peri-intubation hypoxia. Secondary outcomes were first-attempt success rate, use of adjuncts, airway injuries, and hemodynamic parameters., Results: Peri-intubation hypoxia was significantly lower in group DSI (8 [8%]) compared to group RSI (35 [35%]; P = .001). First-attempt success rate was higher in group DSI (83% vs 69%; P = .02). A significant improvement in mean oxygen saturation levels from baseline values was seen in group DSI only. There was no incidence of hemodynamic instability. There was no statistically significant difference in airway-related adverse events., Conclusions: DSI appears promising in critically injured trauma patients who do not allow adequate preoxygenation due to agitation and delirium and require definitive airway on arrival., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 International Anesthesia Research Society.)

The COVID-19 pandemic is a global mental health crisis that disproportionately impacts adolescents. Loneliness is a particularly salient pandemic psychosocial outcome to understand; however, research to date on this outcome is sparse and largely cross-sectional. In response, we examined pre-pandemic risk factors for pandemic loneliness. Further, we examined how risk may differ based on key demographics, and whether mediation or moderation models best explained potential disparities in experiencing loneliness. Self-reported, pre-pandemic mental health, trauma exposure, and family conflict survey data were collected at Wave 1 in a diverse sample of 369 adolescents (54.5% female, 45.5% male; 30.1% White; 30.9% Black; 18.4% Hispanic; M age  = 15.04; SD age  = 1.10). Subsequently, self-reported experiences of loneliness during the pandemic were collected 6 months (April-June 2020) and 12 months (October-December 2020) later. Using a regression-based framework (i.e., PROCESS), we tested (a) which pre-pandemic risks uniquely predicted prospective loneliness and (b) whether loneliness risk was elevated for certain identities (i.e., mediation models) or whether certain identities were more sensitive to specific risks (i.e., moderation models). Overall, pre-pandemic depressive and aggression symptoms predicted early pandemic loneliness (6-month follow-up), whereas anxiety symptoms specifically predicted mid-pandemic loneliness (12-month follow-up). Environmental stressors were moderated by gender, such that females with pre-pandemic trauma exposure were more likely to report pandemic loneliness. Further, pre-pandemic internalizing distress for girls and externalizing symptoms for boys, reflected gender-specific pathways for loneliness. Implications for mental health prevention in the wake of national disasters are discussed., Supplementary Information: The online version contains supplementary material available at 10.1007/s12187-022-09984-8., Competing Interests: Conflicts of Interest The authors have no conflicts of interest to disclose., (© The Author(s), under exclusive licence to Springer Nature B.V. 2022, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Correct placement of the femoral component in the coronal plane during primary total knee arthroplasty (TKA) is related to long-term survival. The aim of this radiographic study was to determine the accuracy of a novel three-step technique for improving the accuracy of the distal femoral cut during conventional technique and compare it with computer navigation during TKA. A total of 458 TKAs were retrospectively analyzed (178 conventional TKAs with the novel technique and 280 navigated TKAs) for postoperative femoral component coronal alignment and compared between the two groups. Mean femoral component coronal alignment was not significantly different ( p  = 0.314) between the two groups. There was no significant difference in the mean femoral component coronal alignment between varus and valgus knees. The number of outliers (90 ± 3 degrees) for femoral component coronal alignment was not significantly different between the two groups when assessed separately for varus and valgus deformities. The mean value of femoral component alignment using the conventional technique in knees with varus deformity <10 degrees was 88.8 degrees, in knees with varus deformity 10 to 20 degrees was 89.4 degrees, and in those with varus deformity >20 degrees was 90.2 degrees. Femoral component alignment in knees with varus <10 degrees was significantly different from those >20 degrees ( p  = 0.006); there was no significant difference between knees with varus <10 degrees and those with 10 to 20 degrees varus ( p  = 0.251), nor between 10 and 20 degrees varus knees and those with varus >20 degrees ( p  = 0.116). Using the novel three-step technique during conventional TKA to perform the distal femoral cut can help achieve femoral component coronal alignment comparable to the navigation technique., Competing Interests: None declared., (Thieme. All rights reserved.)

Background: Research suggests adolescent depression is increasing and certain adolescents may be uniquely vulnerable. However, limited conceptualizations of identity and time, as well as the reliance on unitary conceptualizations of depression, inhibits a nuanced perspective on these trends. In response, we examined how adolescent depressive symptoms, depressed mood, and anhedonia, vary across intersecting identities over time., Methods: Secondary data analysis on the National Survey on Drug Use and Health between 2009 and 2017 was conducted. In total 145,499 nationally representative adolescents (ages 12-17) completed a diagnostic assessment for depression. Lifetime and past year reports of depressive symptoms, depressed mood, and anhedonia were treated as separate variables. A novel, mixed-level model in which participants were nested within identity (defined by one's age, gender, race/ethnicity, poverty level) and time was used to test our aims., Results: Overall, the relation between depression outcomes and identity did not vary over time (p > .01). Further, identity's impact on depression was approximately ten-fold that of temporal effects. Multiracial, late adolescent, female adolescents were at particular risk. Findings concerning depressed mood and anhedonia were similar across analyses., Limitations: All facets of identity (e.g., sexual identity) were not included in the model and a unidimensional measure of poverty may have underestimated its depressogenic influence., Conclusion: Adolescent depression outcomes are mostly consistent across criterial symptom subtypes and time, but vary as a function of identity. Prevention protocols that highlight mechanisms of risk tethered to social identity, and include salient experiences of females, late adolescents, and multiracial youth in particular, need to be prioritized in mental health initiatives., Competing Interests: Conflict of interest None., (Copyright © 2022 Elsevier B.V. All rights reserved.)

A new series of thieno nucleus embellished trinuclear (19, 20) and tetranuclear (21-24) nitrogen heteroaryl have been synthesized by the Suzuki cross-coupling reaction using bis(triphenylphosphine)palladium(II) dichloride. All the synthesized compounds were characterized by IR, 1 H-NMR, 13 CNMR and Mass spectral properties. In vitro antibacterial studies of the synthesized compound were conducted using broth microdilution assay employing Gram-positive and Gram-negative strains and half-maximal inhibitory concentration (IC 50 ) was determined. The result showed that compound 20 possess best antibacterial activity against S. aureus and E. coli with IC 50 values of 60 μg mL -1 and 90 μg mL -1 . Further to determine the mode of antibacterial action, compounds 20 and 21 were examined for in vitro bacterial dehydrogenase inhibitory assay. To understand the binding affinity of the synthesized compounds, the docking study was performed in the bacterial dehydrogenase enzyme by AutoDock Vina software and structure was confirmed by Discovery Studio Visualizer. All the synthesized compounds were docked in a good manner within the active sites of the bacterial dehydrogenase enzyme and exhibited good binding energies., (© 2022 Wiley-VHCA AG, Zurich, Switzerland.)

The pleiotropic Ca 2+ /calmodulin-dependent phosphatase calcineurin is a key regulator of pathological cardiac myocyte hypertrophy. The selective activation of hypertrophic calcineurin signaling under stress conditions has been attributed to compartmentation of Ca 2+ signaling in cardiac myocytes. Here, perinuclear signalosomes organized by the scaffold protein muscle A-Kinase Anchoring Protein β (mAKAPβ/AKAP6β) are shown to orchestrate local Ca 2+ transients, inducing calcineurin-dependent NFATc nuclear localization and myocyte hypertrophy in response to β-adrenergic receptor activation. Fluorescent biosensors for Ca 2+ and calcineurin and protein kinase A (PKA) activity, both diffusely expressed and localized by nesprin-1α to the nuclear envelope, are used to define an autonomous mAKAPβ signaling compartment in adult and neonatal rat ventricular myocytes. Notably, β-adrenergic-stimulated perinuclear Ca 2+ and PKA and CaN activity transients depended upon mAKAPβ expression, while Ca 2+ elevation and PKA and CaN activity in the cytosol were mAKAPβ independent. Buffering perinuclear cAMP and Ca 2+ prevented calcineurin-dependent NFATc nuclear translocation and myocyte hypertrophy, without affecting cardiac myocyte contractility. Additional findings suggest that the perinuclear Ca 2+ transients were mediated by signalosome-associated ryanodine receptors regulated by local PKA phosphorylation. These results demonstrate the existence of a functionally independent Ca 2+ signaling compartment in the cardiac myocyte regulating hypertrophy and provide a premise for targeting mAKAPβ signalosomes to prevent selectively cardiac hypertrophy in disease., Competing Interests: Declaration of Competing Interest Dr. Kapiloff is an inventor of patent-protected intellectual property concerning the targeting of mAKAPβ signalosomes for the treatment of heart failure, by which he and Stanford University may gain royalties from future commercialization. Dr. Kapiloff holds equity in Anchored RSK3 Inhibitors, LLC, and Cardiac RSK3 Inhibitors, LLC, companies interested in developing mAKAP signalosome-targeted therapies., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

COVID-19 was an unexpected public health emergency. The key positive features of the Indian health system were demonstrated during the pandemic. Postpandemic is the time to introspect. Various issues and challenges facing the Indian Public Health System require due attention., Competing Interests: None

Magnetic resonance imaging (MRI) offers visual representations of the interior of a body for clinical analysis and medical intervention. The MRI process is subjected to a variety of image processing and machine learning approaches to identify, diagnose, and classify brain diseases as well as detect abnormalities. In this paper, we propose an improved classification method for distinguishing cancerous and noncancerous tumors from brain MRI images by using Log Polar Transformation (LPT) and convolutional neural networks (CNN). The LPT has been applied for feature extraction of rotation and scaling of distorted images, while the integration of CNN introduces a machine learning approach for the tumor classification of distorted images. The dataset was formed with images of seven different brain diseases, and the training set was formed by applying CNN with the extracted features. The proposed method is then evaluated in comparison to state-of-the-art algorithms, showing a definite improvement of the former. The obtained results show that the machine learning approach offers better classification with a success rate of about 96% in both plain brain MR images and rotation- and scale-invariant brain MR images. This work also successfully classified T-1 and T-2 weighted images of neoplastic and degenerative brain diseases. The obtained accuracy is perfected by several kernel procedures, while the combined performance of the two wavelet transformations and a strong dataset make our method robust and efficient. Since no earlier study on machine learning approaches with rotated and scaled brain MRI has come to our attention, it is expected that our proposed method introduces a new paradigm in this research field.

Objective: Given the severe consequences associated with maltreatment, establishing an understanding of pathways to resilience among trauma-exposed youth is a critical public health aim. Longitudinal research has either examined short-term or long-term responses to traumatic events, which prevents testing for a) individual differences between resilience subtypes and b) consistency of short-term, resilient responses over time. Additionally, post-traumatic stress and depression represent the two most common symptom patterns in youth exposed to maltreatment, however few studies have simultaneously investigated resilience to these outcomes. In response, the current study employs a dimensional analytic approach to distinguish between short-term (the ability to demonstrate adaptive responses to ongoing adversities) and long-term (lack of distress over several years in response to a prior adversity) resilience. Consistent with an ecological perspective, the study examines whether family- and community-level protective factors are similarly or uniquely associated with different resilience subtypes. Method: Participants included 943 individuals (469 male, 474 female) from a nationally-representative, at-risk sample of adolescents who completed self-report measures of maltreatment exposure, depressive symptoms and post-traumatic stress symptoms at ages 12, 16, and 18. During the age 12 visit, participants' caregivers completed self-report measures of family routines and neighborhood social cohesion. Results: Overall, we found that family routines uniquely buffered against trauma-related distress across resilience conceptualizations, while social cohesion played a role in short-term resilience to depressive symptoms (p <.05). Participant gender did not moderate these results (p > .05). Conclusion: These findings highlight the importance of understanding resilience dimensionally for adolescents exposed to maltreatment.

Background: Effective immunization supply chain (iSC) is crucial for safe and timely transport of potent vaccines to the beneficiary. India's iSC, with a network of ~29,000 cold chain points (CCP), measures its quality standards using the World Health Organization-United Nations International Children's Emergency Fund (WHO-UNICEF) global tool on effective vaccine management (EVM). The two national EVM assessments (EVMA) were conducted in 2013 and 2018. This study helps to see the impact of policies and practices through EVMA in maintaining an efficient iSC for effective implementation of immunization program., Materials and Methods: We conducted a desk analysis using EVMA reports to summarize and compare the findings of the two studies. Cut-off of 80% was considered ideal for each category/criteria score., Results: Both EVMA 2013 and 2018 were conducted using Android-based global EVM tool, though across a wider sample of CCP. Maximum and minimum changes in scores were sub-national and lowest distribution (16% each) and national buffer stores (7%), respectively. Maximum and minimum improvements were seen in vaccine management (29%) and MIS and supportive functions (3%), respectively. The improvement was statistically significant for the overall scores ( P = 0.02), primary ( P = 0.01), subnational ( P = 0.02), and lowest distribution stores ( P = 0.03). Among the 36 recommendations of 2013 assessment, 78% and 22% were fully and partially implemented (or ongoing), respectively., Conclusion: Implementation of EVM recommendations has significantly led to improvement and continues to provide a benchmark for iSC and its processes. Follow-up assessments every 3-5 years can further help to evaluate iSC and ascertain the impact of recommendations., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Journal of Family Medicine and Primary Care.)

The Temporal Experience of Pleasure Scale (TEPS) is a self-report measure designed to assess anticipatory and consummatory pleasure, two facets of anhedonic predispositions. Despite its widespread use, the factor structure of the TEPS has yet to be tested in adolescents, who are at increased risk for psychopathology and undergoing rapid changes in reward-related processes. In response, the present study aimed to test the factor structure and measurement invariance of the TEPS across time, gender, and race/ethnicity in a diverse adolescent sample. Adolescents ( N = 441; M age = 14.98; 223 female) who identified as either Black (37%), Hispanic (37%), or White (26%), completed the TEPS at Baseline, 6-month, and 12-month follow-ups. Factor analyses were conducted to examine the factor structure of the TEPS, while configural, metric, scalar, and strict invariance were tested across time and demographics. Findings supported the two-factor structure of the TEPS, above and beyond other conceptualizations (e.g., 4-factor, bifactor), full longitudinal invariance, and partial invariance across gender and race/ethnicity. Examination of mean differences suggested no temporal, gender nor race/ethnic differences for anticipatory pleasure. For consummatory pleasure, no differences were found for gender, but results suggested higher levels over time and lower levels in Black adolescents. Our findings provide preliminary support for reliable cross-group interpretations of anticipatory and consummatory anhedonic predispositions as measured through the TEPS. Together, results provide support for the clinical utility of the TEPS for anhedonic-related psychopathology risk assessment in adolescence. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Objective: To find out the incidence of neonatal near miss (NNM) cases in comparison with the neonatal deaths and to study the different antenatal and intrapartum maternal variables and system-related delays influencing these events., Methodology: This is a descriptive retrospective study conducted over a year (2018-2019) at a tertiary referral hospital in India, where NNM cases were selected as per 'pragmatic criteria', and detailed maternal and neonatal biological variables and near miss indicators were procured from the medical record books and analysed., Results: Out of 6383 live births and 231 neonatal deaths in the hospital during the study period, 810 NNM cases were identified born to 710 mothers, i.e. 3.5 cases for each neonatal death. Birth weight and gestational age in combination contributed to the maximum number of cases-383 (47.28%). The most common reason for referral was threatened pre-term/PPROM with non-availability of NICU-197 cases (38.3%) out of 514 referrals. Out of 710 mothers, 529 (74.5%) had at least one comorbidity at the time of presentation. The most common comorbidity was anaemia in 267 women followed by hypertensive disorder of pregnancy-in 251 cases. Primary delay contributed to 54% of all delays in the study., Conclusion: NNM can be used as an effective tool for quality control and audits to effectively reduce maternal and neonatal morbidity and mortality but needs more research to establish a standardized definition and criteria for selection of cases., Competing Interests: Conflict of interestThe authors declare that none of the authors have conflict of interest., (© Federation of Obstetric & Gynecological Societies of India 2021.)

Purpose: Recommendations for resecting distal femur and proximal tibia in mechanical and anatomical alignment techniques are standardized. Kinematic alignment propagates individualizing resection planes. Whether significant variation exists, to warrant departure from standardized resection planes, has not been shown thus far in a large cohort of knees and with a wide range of varus deformity. The null hypothesis of this study was that there was no phenotypic variation in varus osteoarthritic knees. The aim of this paper was to determine whether distinct phenotypes could be identified, based on variations in coronal femoral and tibial morphology, which could aid in surgical planning and categorizing varus knees for future studies., Methods: 2129 full-leg weightbearing radiographs were analyzed (1704 preoperative; 425 of contralateral arthritic knee). Measurements made were of HKA (hip-knee-ankle angle), VCA (valgus correction angle), mLDFA (lateral mechanical distal femoral angle), aLDFA (lateral anatomical distal femoral angle), MPTA (medial proximal tibial angle), MNSA (medial neck shaft angle), TAMA (angle between tibial mechanical and anatomical axes), and TPDR (percentage length of tibia proximal to extra-articular deformity)., Results: Seven distinct types were identified covering 2021 knees, reducible to 4 broad phenotypes: 11% were Type 1 'Neutral' knees showing values close to reported normal knees (mean VCA 5.5°, mLDFA 87°, aLDFA 81°). 38% were Type 2 'Intra-articular varus' with medial intra-articular bone loss (mean mLDFA 90.9°, MPTA 85.4°, VCA of 5.7°). 41% were Type 3 'Extra-articular varus' with extra-articular deformity (EAD). Type 3a had proximal tibial EAD; Type 3b had tibial diaphyseal EAD; Type 3c had femoral EAD (mean VCA 8.7°, HKA 166°), and severe medial bone loss (mean mLDFA 92°, MPTA 83°). 9% were Type 4 'Valgoid type' with features of valgus knees: Type 4a had medial femoral bowing (mean VCA 2.9°); Type 4b had significant distal femoral valgus (mean mLDFA 85.3°, aLDFA 78.6°)., Conclusions: The null hypothesis that there was no phenotypic variation in varus osteoarthritic knees was rejected as considerable variation was found in coronal morphology of femur and tibia. Four broad phenotypic groups could be identified. Plane of the knee joint articular surface was quite variable. This has relevance to planning and performance of corrective osteotomies, unicompartmental and total knee arthroplasty., Level of Evidence: III, retrospective cohort study., (© 2021. European Society of Sports Traumatology, Knee Surgery, Arthroscopy (ESSKA).)

Limited reports exist regarding adeno-associated virus (AAV) biodistribution in swine. This study assessed biodistribution following antegrade intracoronary and intravenous delivery of two self-complementary serotype 9 AAV (AAV9sc) biologics designed to target signaling in the cardiomyocyte considered important for the development of heart failure. Under the control of a cardiomyocyte-specific promoter, AAV9sc.shmAKAP and AAV9sc.RBD express a small hairpin RNA for the perinuclear scaffold protein muscle A-kinase anchoring protein β (mAKAPβ) and an anchoring disruptor peptide for p90 ribosomal S6 kinase type 3 (RSK3), respectively. Quantitative PCR was used to assess viral genome (vg) delivery and transcript expression in Ossabaw and Yorkshire swine tissues. Myocardial viral delivery was 2-5 × 10 5 vg/µg genomic DNA (gDNA) for both infusion techniques at a dose ∼10 13 vg/kg body wt, demonstrating delivery of ∼1-3 viral particles per cardiac diploid genome. Myocardial RNA levels for each expressed transgene were generally proportional to dose and genomic delivery, and comparable with levels for moderately expressed endogenous genes. Despite significant AAV9sc delivery to other tissues, including the liver, neither biologic induced toxic effects as assessed using functional, structural, and circulating cardiac and systemic markers. These results indicate successful targeted delivery of cardiomyocyte-selective viral vectors in swine without negative side effects, an important step in establishing efficacy in a preclinical experimental setting.

Bemisia tabaci (whitefly) is one of the most detrimental agricultural insect pests and vectors of many plant viruses distributed worldwide. Knowledge of the distribution patterns and insecticide resistance of this cryptic species is crucial for its management. In this study, genetic variation of mitochondrial cytochrome oxidase subunit 1 ( MtCoI ) gene of B. tabaci was analyzed followed by a study of the infection profile of various endosymbionts in 26 whitefly populations collected from West Bengal, India. Phylogenetic analysis revealed Asia I as the major cryptic species (65.38%), followed by Asia II 5, China 3, and Asia II 7, which were diversified into 20 different haplotypes. In addition to the primary endosymbiont ( C. poriera ), each of the four whitefly species showed a variable population of three secondary endosymbionts, majorly Arsenophonus with the highest infection rate (73.07%), followed by Wolbachia and Rickettsia . Further phylogenetic analyses revealed the presence of two subgroups of Arsenophonus, viz ., A1 and A2, and one each in Wolbachia (W1) and Rickettsia (R3). Resistance to thiamethoxam, imidacloprid, and acetamiprid insecticides was analyzed for a clear picture of pesticide resistance status. The highest susceptibility was noted toward thiamethoxam (LC 50 = 5.36 mg/L), followed by imidacloprid and acetamiprid. The whitefly population from Purulia and Hooghly districts bearing Asia II 7 and Asia II 5 cryptic species, respectively, shows maximum resistance. The differences in mean relative titer of four symbiotic bacteria among field populations varied considerably; however, a significant positive linear correlation was observed between the resistance level and relative titer of Arsenophonus and Wolbachia in the case of imidacloprid and thiamethoxam, while only Wolbachia was found in case of acetamiprid. Expression analysis demonstrated differential upregulation of insecticide resistance genes with Purulia and Hooghly populations showing maximally upregulated P450 genes. Moreover, thiamethoxam and imidacloprid resistance ratio (RR) showed a significant correlation with CYP6CM1, CYP6DZ7, and CYP4C64 genes, while acetamiprid RR correlated with CYP6CX1, CYP6DW2, CYP6DZ7, and CYP4C64 genes. Taken together, these findings suggested that P450 mono-oxygenase and symbiotic bacteria together affected whitefly resistance to neonicotinoids. Hence, a symbiont-oriented management programme could be a better alternative to control or delay resistance development in whitefly and can be used for pesticide clean-up in an agricultural field., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Barman, Samanta, Upadhyaya, Thakur, Chakraborty, Samanta and Tarafdar.)

Background: Although many studies have investigated the prevalence of low back pain (LBP) among Indian subjects, no meta-analysis has been conducted to determine the comprehensive epidemiological point, annual, lifetime prevalence of LBP among Indian subjects., Objective: The purpose of this systematic review and meta-analysis was to investigate the point, annual, and lifetime prevalence of LBP in the Indian population., Methods: We searched PubMed, Embase, Science Direct, and Cochrane Library databases for relevant studies that reported point, annual, or lifetime prevalence of LBP among Indian subjects. Pooled point, annual and lifetime prevalence rates were calculated. Meta-analysis, subgroup analysis, sensitivity analysis and publication bias assessment were performed., Results: Ninety-seven studies were included in this review. Fifty-four studies included in the review (55.5%) were found to be of higher methodological quality. The pooled point, annual, and lifetime prevalence of LBP in India was 48% (95% CI 40-56%); 51% (95% CI 45-58%), and 66% (95% CI 56-75%), respectively. The pooled prevalence rates were highest among females, the rural population, and among elementary workers., Conclusion: The point, annual, and lifetime prevalence rates of LBP in the Indian population is higher compared to global and other ethnic populations affecting a large proportion of the population, especially among women, rural population and in elementary workers. The findings of this study can be the basis for formulating policy regarding the prevention and treatment of LBP in a large part of the global population.

Study Design: Retrospective., Objective: The aim of this study was to investigate the effect of body mass index (BMI) on pain and disability in patients with chronic mechanical low back pain (LBP) treated with multimodal rehabilitation., Summary of Background Data: Despite being a well-known risk factor for developing LBP, there is minimal data on the effect of BMI on pain and disability in patients with chronic mechanical low back pain (LBP) treated with multimodal rehabilitation., Methods: Data from patients with chronic mechanical LBP who underwent multimodal rehabilitation treatment at a chain of spine rehabilitation outpatient clinics in one of the three BMI groups-1564 patients in normal body weight (BMI ≥18.5-24.9), 1990 patients in overweight (BMI ≥25-29.9), and 891 patients in obese (BMI ≥ 30) groups-were retrospectively analyzed. Pre- and post-treatment Numerical Pain Rating Scale (NPRS) and Oswestry Disability Index (ODI) scores, and final treatment outcomes were compared between the three groups. Multivariate analysis was used to determine the association between pre-treatment covariates and post-treatment clinical outcomes., Results: Post-treatment, the mean NPRS (P = 0.005) and mean ODI (P < 0.001) scores were significantly higher with a significantly lower percentage of full success outcome (P = 0.009) in the obese group when compared to normal and overweight groups. However, multivariate analysis showed a significant correlation between age, the number of treatment sessions, pre-treatment NPRS and ODI scores, and post-treatment NPRS and ODI scores and treatment failure, and no correlation with patient BMI., Conclusion: Patient BMI may not affect pain and disability outcomes in patients undergoing a multimodal rehabilitation treatment for chronic LBP. In contrast to BMI, other covariates such as age, treatment sessions, and pre-treatment NPRS and ODI scores may be associated with increased risk for poor treatment outcome. Obese individuals can expect clinical outcomes similar to normal or overweight individuals with multimodal physical rehabilitation for chronic LBP.Level of Evidence: 3., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

The autonomic nervous system (ANS) has received much attention as a potential low-cost, peripheral indicator of depression. Despite theoretical support, however, results have been mixed as to whether indices of the ANS reliably index depression. In response, the present study sought to clarify the relation between ANS activity and depression by examining cardiac autonomic balance (CAB) and cardiac autonomic regulation (CAR), two composite indices of the parasympathetic and sympathetic nervous system, within both a stressful and rewarding context. We hypothesized that CAB Stress , representing the difference between the parasympathetic and sympathetic branches in response to stress, and CAR Reward , representing the summation of the two branches in response to reward, will be most indicative of depressogenic risk. We examined the parasympathetic (i.e., respiratory sinus arrhythmia) and sympathetic (i.e., pre-ejection period) responses of 97 emerging adults (M age  = 18.93) for a stress (i.e., negative mood induction) and reward (i.e., probabilistic learning) task, as well as their depressive symptoms at baseline, 3-week, and 6-week follow-up. Analyses found partial support for our hypotheses, revealing greater CAR Reward (i.e., coactivation of both branches) was related to lower depressive symptoms. Further, exploratory analyses examining gender differences found lower CAB Stress (i.e., sympathetically-oriented response) was predictive of an increasing trajectory of depression, but only among males. Overall, the current study highlights the importance of simultaneously examining both branches of the ANS across various environmental contexts. Research and clinical implications of the current findings are discussed., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The silverleaf whitefly, Bemisia tabaci (Gennadius, Hemiptera: Aleyrodidae), is a major threat to field and horticultural crops worldwide. Persistent use of insecticides for the management of this pest is a lingering problem. In the present study, the status of sensitivity of B. tabaci to two neonicotinoids, imidacloprid and thiamethoxam, was evaluated. The expression pattern of two cytochrome P450 ( cyp ) genes and changes in the relative amount of symbionts in insecticide-treated B. tabaci were also assessed. Quantitative PCR (qPCR) studies indicate that the CYP6CM1 and CYP6CX1 genes were always expressed higher in imidacloprid-treated whitefly, suggesting a correlation between gene expression and the insect's ability to detoxify toxic compounds such as insecticides. In addition, the thiamethoxam-treated population harbored higher Portiera and lower Rickettsia titers, whereas the imidacloprid-treated population harbored more Rickettsia at different time intervals. Interestingly, we also examined that an increase in exposure to both the insecticides resulted in a reduction in the mutualistic partners from their insect host. These differential responses of endosymbionts to insecticide exposure imply the complex interactions among the symbionts inside the host insect. The results also provide a deeper understanding of the molecular mechanism of resistance development that might be useful for formulating effective management strategies to control B. tabaci by manipulating symbionts and detoxifying genes.

Background: Tuberculosis is one of the ten major causes of mortality worldwide. The trend of increasing TB cases and drug resistance in India is very disturbing. The objectives of the study were to study the perspectives and opinions of different stakeholders on the status, challenges and the ways to tackle the issues of TB in India., Methods: The online survey was done for the data collection from national and international experts. The data collection took place during October 2017. We received 46 responses., Results: The experts had varied answers as to the menace of TB in India, effect of TB on individuals, family and society, failure of government plans in India, TB awareness campaign and ways to create awareness. Everyone believed that urgent action needs to be taken against the disease like improving the healthcare infrastructure of the country (improving the quality and quantity of medical facilities and doctors) and creating awareness about the TB., Conclusion: Government of India is making lot of efforts to bring down the problems associated with TB through. In spite of this, there is a long way to go to achieve significant reduction in high incidence and prevalence of TB in India. Factors like lack of awareness and resources, poor infrastructure, increasing drug resistant cases, poor notification and overall negligence are the major challenges. If we eradicate poverty and undernourishment, educate the masses and eliminate the stigma attached with TB, we can hope for a disease free future., Competing Interests: Conflicts of interest The authors have none to declare., (Copyright © 2020 Tuberculosis Association of India. Published by Elsevier B.V. All rights reserved.)

Given the risk of substance use (SU) among adolescents in the child welfare system, identification of risk for prospective impairing SU behaviors is a significant public health priority. We sought to quantify the incremental validity of routine multi-informant assessments of adolescent psychological distress (i.e., the Child Behavior Checklist and Youth Self-Report) and a commonly used SU screening protocol (i.e., the CRAFFT) to predict SU at 18 and 36 months after baseline in a nationally representative child welfare sample ( N = 1,054; M age = 13.72). We used receiver operator characteristics and reclassification analyses to develop our algorithms. We found that a battery consisting of baseline CRAFFT scores, self-reported delinquent behavior, and parent-reported rule-breaking behavior provided an incrementally valid prediction model for SU behavior among females, while baseline CRAFFT scores and self-reported delinquent behavior incrementally predicted SU for males. Results suggest that leveraging existing assessments within the child welfare system can improve forecasting of SU risk for this population.

Context: Oral submucous fibrosis (OSMF) is a chronic debilitating disease of the oral cavity, characterized by inflammation and progressive fibrosis of the submucosal tissues. The main agent involved in the pathogenesis of OSMF is areca nut. A wide range of treatment, including drug management, surgical therapy, and physiotherapy, has been attempted till date, with varying degrees of benefit., Aims: The objective of this study was to assess efficacy of curcumin for the treatment of OSMF; to asses efficacy of topical steroids for the treatment of OSMF; and to compare the efficacy of curcumin and topical steroid for the treatment of OSMF., Setting and Design: Participants were assessed based subjective and objective feature of OSMF, i.e., burning sensation of the oral cavity and interincisal distance, respectively., Methodology: Thirty participants were categorized into two groups: Group A was administered curcumin and Group B was administered topical steroids for a period of 3 months and followed up after 6 months. The assessment was based on maximal incisal opening and burning sensation for spicy food on Visual Analog Scale score., Analysis: Independent t test was applied for comparison within the group, ANOVA Bonferroni post hoc test was applied for multiple comparison of mean and Mann-Whitney U test was applied to compare the groups., Results: The statistical analysis revealed curcumin to be more efficient than topical steroid., Conclusion: The present study demonstrates the efficiency of curcumin and topical steroid to alleviate the clinical findings of OSMF. However, curcumin is comparatively more efficient than steroids for the treatment of OSMF., Competing Interests: There are no conflicts of interest., (Copyright: © 2021 Journal of Pharmacy and Bioallied Sciences.)

Positive adaptation manifests differently in the aftermath of traumatic events. Methodological limitations, however, impede the ability to test conceptualizations of resilience that emphasize the multifaceted nature of these responses. In response, an approach that synthesized a residualized and person-centered conceptualization of resilience examined associations between aspects of resilience in an adolescent sample. In total, 584 racially/ethnically diverse adolescents (age range: 12-17 years; M = 14.98 years; SD = 1.05; 50.9% female; 30.1% White, 29.6% African American, 19.5% Hispanic) self-reported lifetime emotional maltreatment and community violence exposure as well as current levels of depression, posttraumatic stress symptoms (PTSS), violent behavior, and psychological well-being (PWB). Each mental health outcome was regressed on lifetime trauma exposure to create residuals used as indices of resilience. Correlations between the residuals suggested that PWB was more closely related to resilience to depression and PTS, rs = .17-.30, than violent behavior, r = .00. Residuals were subsequently entered into person-centered analyses to identify representative well-being profiles. Cluster analysis identified four groups, including two adaptive profiles defined by (a) lower distress and higher PWB and (b) lower psychopathology and lower PWB, based on adolescents' levels of trauma exposure. These two profiles did not vary regarding impairment, p > .999, suggesting both profiles represent positive adaption to lifetime trauma exposure. Theoretical and clinical implications of distinguishing between these two profiles by assessing PWB in adolescents are discussed, as well as how PWB may manifest within the context of different patterns of psychological distress., (© 2020 International Society for Traumatic Stress Studies.)

Competing Interests: Competing interests: None declared.

A 38-year-old woman who had previously been diagnosed and treated for unilateral Vogt-Koyanagi-Harada syndrome (VKH) and had undergone multiple intravitreal bevacizumab injections to manage inflammatory choroidal neovascularisation in her right eye, presented 2 years later with visual complains in left eye. Clinical examination, fluorescein angiography, indocyanine green angiography (ICGA) and enhanced depth imaging optical coherence tomography (EDI-OCT) assisted evaluation confirmed active inflammation of left eye along with absence of any inflammation in the right eye. Unilateral active inflammation can be seen in the setting of VKH. To our best knowledge, ours is the first case of VKH in which unilateral active inflammation has been proven based on ICGA and EDI OCT analysis., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Extant research and theory posit that emotional abuse and emotional neglect-exposure is uniquely harmful during adolescence. Yet, these findings are mostly based on mono-informant, retrospective studies with unselected adults that examine emotional maltreatment in the aggregate. This prevents inferences concerning the unique, prospective risk emotional abuse and neglect, as reported by multiple informants, may confer within at-risk, adolescent samples., Objective: In response, the present study examined how emotional abuse and emotional neglect-exposure in adolescence uniquely related to psychological symptoms and social impairment., Participants and Setting: Our aims were tested in a child welfare system (CWS)-involved sample of adolescents (N = 657; Age M  = 12.49 at baseline) who were participating in a longitudinal study., Methods: A multi-informant approach was used to assess emotional abuse/neglect and mental health. Physical abuse and lifetime CWS contact represented covariates in growth curve models., Results: Emotional abuse predicted symptoms within informant, such that youth-reported emotional abuse predicted youth-reported internalizing, β = 0.21, p = .001, and externalizing, β=0.35, p = .001, symptoms while parent-reported emotional abuse predicted parent-reported externalizing, β=0.30, p <  .001, and internalizing β=0.29, p <  .001, symptoms. Meanwhile, youth-reported emotional neglect predicted heightened self-reported internalizing symptoms, β=0.29, p <  .001, parent-reported externalizing symptoms, β=0.15, p = .002 and social impairment across youth, β=-0.17, p = .01 and parent, β=-0.24, p <  .001, report., Conclusions: This study shows the importance of distinguishing between these maltreatment subtypes in adolescence and provides measurement recommendations for future maltreatment research. The manuscript concludes by discussing adolescent emotional abuse and neglect-exposure as a maintenance, as opposed to causal risk, factors., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

NANOG is an embryonic transcription factor, which gets reexpressed in cancer stem or tumor initiating cells. NANOGP8, a retrogene belonging to the NANOG family, is predominantly expressed in cancer cells and shows very high similarity with NANOG both at the nucleotide and at the protein level. The high similarity makes it extremely challenging to distinguish between these two transcription factors. Here we describe a highly efficient restriction endonuclease-based assay, which is performed on cDNA and allows to distinguish NANOGP8 from NANOG. This assay is critical to understand the specific role of NANOGP8 in cancer stemness, which in turn helps to unravel the therapeutic potential of targeting this undruggable transcription factor through gene therapy, for treatment of various cancers.

Loss of retinal ganglion cells (RGCs) in optic neuropathies results in permanent partial or complete blindness. Myocyte enhancer factor 2 (MEF2) transcription factors have been shown to play a pivotal role in neuronal systems, and in particular MEF2A knockout was shown to enhance RGC survival after optic nerve crush injury. Here we expanded these prior data to study bi-allelic, tri-allelic and heterozygous allele deletion. We observed that deletion of all MEF2A, MEF2C, and MEF2D alleles had no effect on RGC survival during development. Our extended experiments suggest that the majority of the neuroprotective effect was conferred by complete deletion of MEF2A but that MEF2D knockout, although not sufficient to increase RGC survival on its own, increased the positive effect of MEF2A knockout. Conversely, MEF2A over-expression in wildtype mice worsened RGC survival after optic nerve crush. Interestingly, MEF2 transcription factors are regulated by post-translational modification, including by calcineurin-catalyzed dephosphorylation of MEF2A Ser-408 known to increase MEF2A-dependent transactivation in neurons. However, neither phospho-mimetic nor phospho-ablative mutation of MEF2A Ser-408 affected the ability of MEF2A to promote RGC death in vivo after optic nerve injury. Together these findings demonstrate that MEF2 gene expression opposes RGC survival following axon injury in a complex hierarchy, and further support the hypothesis that loss of or interference with MEF2A expression might be beneficial for RGC neuroprotection in diseases such as glaucoma and other optic neuropathies., Competing Interests: The authors have declared that no competing interests exist.

Background: Concentric and eccentric cardiac hypertrophy are associated with pressure and volume overload, respectively, in cardiovascular disease both conferring an increased risk of heart failure. These contrasting forms of hypertrophy are characterized by asymmetrical growth of the cardiac myocyte in mainly width or length, respectively. The molecular mechanisms determining myocyte preferential growth in width versus length remain poorly understood. Identification of the mechanisms governing asymmetrical myocyte growth could provide new therapeutic targets for the prevention or treatment of heart failure., Methods: Primary adult rat ventricular myocytes, adeno-associated virus (AAV)-mediated gene delivery in mice, and human tissue samples were used to define a regulatory pathway controlling pathological myocyte hypertrophy. Chromatin immunoprecipitation assays with sequencing and precision nuclear run-on sequencing were used to define a transcriptional mechanism., Results: We report that asymmetrical cardiac myocyte hypertrophy is modulated by SRF (serum response factor) phosphorylation, constituting an epigenomic switch balancing the growth in width versus length of adult ventricular myocytes in vitro and in vivo. SRF Ser 103 phosphorylation is bidirectionally regulated by RSK3 (p90 ribosomal S6 kinase type 3) and PP2A (protein phosphatase 2A) at signalosomes organized by the scaffold protein mAKAPβ (muscle A-kinase anchoring protein β), such that increased SRF phosphorylation activates AP-1 (activator protein-1)-dependent enhancers that direct myocyte growth in width. AAV are used to express in vivo mAKAPβ-derived RSK3 and PP2A anchoring disruptor peptides that block the association of the enzymes with the mAKAPβ scaffold. Inhibition of RSK3 signaling prevents concentric cardiac remodeling induced by pressure overload, while inhibition of PP2A signaling prevents eccentric cardiac remodeling induced by myocardial infarction, in each case improving cardiac function. SRF Ser 103 phosphorylation is significantly decreased in dilated human hearts, supporting the notion that modulation of the mAKAPβ-SRF signalosome could be a new therapeutic approach for human heart failure., Conclusions: We have identified a new molecular switch, namely mAKAPβ signalosome-regulated SRF phosphorylation, that controls a transcriptional program responsible for modulating changes in cardiac myocyte morphology that occur secondary to pathological stressors. Complementary AAV-based gene therapies constitute rationally-designed strategies for a new translational modality for heart failure.

Background: Universal depression screening in youth typically focuses on strategies for identifying current distress and impairment. However, these protocols also play a critical role in primary prevention initiatives that depend on correctly estimating future depression risk. Thus, the present study aimed to identify the best screening approach for predicting depression onset in youth., Methods: Two multi-wave longitudinal studies (N = 591, AgeM = 11.74; N = 348, AgeM = 12.56) were used as the 'test' and 'validation' datasets among youth who did not present with a history of clinical depression. Youth and caregivers completed inventories for depressive symptoms, adversity exposure (including maternal depression), social/academic impairment, cognitive vulnerabilities (rumination, dysfunctional attitudes, and negative cognitive style), and emotional predispositions (negative and positive affect) at baseline. Subsequently, multi-informant diagnostic interviews were completed every 6 months for 2 years., Results: Self-reported rumination, social/academic impairment, and negative affect best predicted first depression onsets in youth across both samples. Self- and parent-reported depressive symptoms did not consistently predict depression onset after controlling for other predictors. Youth with high scores on the three inventories were approximately twice as likely to experience a future first depressive episode compared to the sample average. Results suggested that one's likelihood of developing depression could be estimated based on subthreshold and threshold risk scores., Conclusions: Most pediatric depression screening protocols assess current manifestations of depressive symptoms. Screening for prospective first onsets of depressive episodes can be better accomplished via an algorithm incorporating rumination, negative affect, and impairment.

Purpose: To evaluate the impact of 2019 COVID-19 pandemic, national lockdown, and unlocking on ophthalmic care provided by the government-funded apex health institute of India., Methods: Retrospective review of electronic medical records of all patients presenting to the ophthalmology department from March 23, 2020, to July 15, 2020, was compared with that from March 23, 2019, to July 15, 2019. The data between March 23, 2020, to May 31, 2020 (lockdown) and June 06, 2020, to July 15, 2020 (unlock) was compared separately. Parameters evaluated were age, gender, presenting complaints, final diagnosis, treatment advised, and surgical interventions., Results: During the lockdown, routine outpatient flow reduced by 97.14% (P < 0.001), the median age of presentation decreased to 29 years (55 years last year) and males increased by 4.7% (from 61.51% to 66.21%) in 2020. Emergency services decreased by 35.25%, percentage of children decreased by 4.28% (from 34.28% to 30%) and males increased by 13.53% (from 59.97% to 73.5%). Mechanical trauma, microbial keratitis, and conjunctivitis were the most common reasons for presentation. The former lessened by 41.75% while the latter two amplified by 1.25 times and 2 times, respectively. While sanitizer-associated chemical injury increased in proportion, endophthalmitis, and postoperative complications declined. The number of donor corneas collected and emergency therapeutic keratoplasties performed decreased by 99.61% and 92.39%, respectively (P < 0.001). During the unlocking phase, routine patient consultations were 71 ± 19/day, significantly lower than 978 ± 109/day of last year (P < 0.001). No voluntary eye donation was reported during this period., Conclusion: COVID-19 pandemic and national lockdown severely hampered the delivery of ophthalmic care by the apex-ophthalmic institute. Unlike anticipated, lifting of pandemic-associated lockdown served only minimally in improving patient inflow in its initial phases., Competing Interests: None

[This corrects the article DOI: 10.1007/s13205-020-02168-7.]., (© King Abdulaziz City for Science and Technology 2020.)

Background: The Ca 2+ /calmodulin-dependent phosphatase calcineurin is a key regulator of cardiac myocyte hypertrophy in disease. An unexplained paradox is how the β isoform of the calcineurin catalytic A-subunit (CaNAβ) is required for induction of pathological myocyte hypertrophy, despite calcineurin Aα expression in the same cells. It is unclear how the pleiotropic second messenger Ca 2+ drives excitation-contraction coupling while not stimulating hypertrophy by calcineurin in the normal heart. Elucidation of the mechanisms conferring this selectivity in calcineurin signaling should reveal new strategies for targeting the phosphatase in disease., Methods: Primary adult rat ventricular myocytes were studied for morphology and intracellular signaling. New Förster resonance energy transfer reporters were used to assay Ca 2+ and calcineurin activity in living cells. Conditional gene deletion and adeno-associated virus-mediated gene delivery in the mouse were used to study calcineurin signaling after transverse aortic constriction in vivo., Results: CIP4 (Cdc42-interacting protein 4)/TRIP10 (thyroid hormone receptor interactor 10) was identified as a new polyproline domain-dependent scaffold for CaNAβ2 by yeast 2-hybrid screen. Cardiac myocyte-specific CIP4 gene deletion in mice attenuated pressure overload-induced pathological cardiac remodeling and heart failure. Blockade of CaNAβ polyproline-dependent anchoring using a competing peptide inhibited concentric hypertrophy in cultured myocytes; disruption of anchoring in vivo using an adeno-associated virus gene therapy vector inhibited cardiac hypertrophy and improved systolic function after pressure overload. Live cell Förster resonance energy transfer biosensor imaging of cultured myocytes revealed that Ca 2+ levels and calcineurin activity associated with the CIP4 compartment were increased by neurohormonal stimulation, but minimally by pacing. Conversely, Ca 2+ levels and calcineurin activity detected by nonlocalized Förster resonance energy transfer sensors were induced by pacing and minimally by neurohormonal stimulation, providing functional evidence for differential intracellular compartmentation of Ca 2+ and calcineurin signal transduction., Conclusions: These results support a structural model for Ca 2+ and CaNAβ compartmentation in cells based on an isoform-specific mechanism for calcineurin protein-protein interaction and localization. This mechanism provides an explanation for the specific role of CaNAβ in hypertrophy and its selective activation under conditions of pathologic stress. Disruption of CaNAβ polyproline-dependent anchoring constitutes a rational strategy for therapeutic targeting of CaNAβ-specific signaling responsible for pathological cardiac remodeling in cardiovascular disease deserving of further preclinical investigation.

Background and Aims: Worldwide, lifestyle is a significant risk factor for diabetes. Lifestyle changes can lead to differences in the extent of risk of diabetes among women and men. Kerala, a state with one of the best health indicators in India, has a high prevalence of diabetes. This study aimed at comparing the variations in the risk factors for HBG and VHBG among adult women and men in Kerala., Methods: Data from the fourth round of the National Family Health Survey (2015-16) used to examine the differences in the risk factors for HBG and VHBG in men and women aged 15-49 years. We used bivariate, multivariate and Population Attributable Risk (PAR) techniques for analysing the data., Results: Bivariate results have shown the pattern of HBG and VHBG prevalence in women and men was same among all the age groups; however, men show a higher HBG and VHBG than women in all the age groups. Prevalence of HBG and VHBG was higher in women with a primary education, who were poor and not working as compared to their male counterparts. PARs results show that the prevalence of VHBG was higher among obese men and women as compared to normal men and underweight women. Prevalence of HBG was higher among men as compared to women due to alcohol use and weekly consumption of non-vegetarian food., Conclusions: The study suggests that there is an urgent need for targeted intervention programs to address the problem of HBG and VHBG in both men and women in Kerala to control blood glucose levels., (Copyright © 2020 Diabetes India. Published by Elsevier Ltd. All rights reserved.)

The amyloid-β (Aβ) aggregation in the brain has been associated with the development of Alzheimer's disease (AD). The previous studies have reported that Piedmont mutation (L34V) increases the rate of Aβ 40 aggregation. However, the underlying molecular mechanism of the effect of L34V mutation on Aβ 40 structure, dynamics, and aggregation remains largely unclear. In the present study, molecular dynamics (MD) simulations were performed to elucidate the effect of L34V mutation on the structural changes and conformational dynamics of Aβ 40 . The secondary structure analysis highlight that L34V mutation enhances Aβ 40 self-assembly due to the formation of aggregation-prone β-sheet structure at the C-terminus of Aβ 40 monomeric structure. The higher probability of Asp23-Lys28 salt bridge interaction in Aβ 40 (L34V) leads to aggregation prone β-sheet conformations, which has the potential to increase the fibril formation rate. The free energy landscape (FEL) analysis depict a sampling of coil conformation in the free energy minima of Aβ 40 , whereas the aggregation-prone β-sheet conformation was observed at the C-terminal region of Aβ 40 (L34V) in the minimum energy conformations extracted from FEL of Aβ 40 (L34V). MD simulations, in agreement with experiment, highlight that L34V mutation increases Aβ 40 aggregation as the sampling of the aggregation-prone β-sheet conformation substantially increased. Overall, MD simulations provided atomic level details into the increased fibril formation tendency upon L34V mutation and physical insights into the L34V-mediated conformational as well as structural changes in Aβ 40 ., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Interleukin-6 (IL6) is encoded by the IL6 gene in human and acts as pro-inflammatory cytokine and an anti-inflammatory cytokine. Recent studies established that IL6 substantially contribute in the diagnosed of systemic inflammation for the patients suffering from lung diseases such as chronic obstructive pulmonary disease (COPD). Thereof, this work aimed to investigate the protagonist of IL6 (-174 G/C) genotypes as an essential risk factor for COPD in north Indian population. In the study, a total of 200 clinically diagnosed patients with COPD were selected against 200 patients. Statistical analysis reveleaed that there was no significant association between the IL6 -174 G/C genetic polymorphism and the risk of COPD (P>0.05).

Aim: The aim of the present study was to investigate the prevalence and etiology of molar-incisor hypomineralization (MIH) in 8- to 16-year-old children from town (Baddi) of Himachal Pradesh., Materials and Methods: A cross-sectional study was conducted with 2000 children from various schools of Baddi. Molar-incisor hypomineralization was diagnosed on the basis of EAPD 2003 criteria revised in 2009., Results: Prevalence of MIH found was to be 2.9%. Demarcated opacities were predominant among all the defects. Postnatal illnesses were highly associated with MIH. The prevalence of dental caries reported in MIH patients was 82.7%., Conclusion: Postnatal illnesses are significantly associated with MIH. Molar-incisor hypomineralization predisposes the tooth to dental caries., How to Cite This Article: Thakur H, Kaur A, Singh R, et al. Prevalence and Clinical Characteristics of Molar-Incisor Hypomineralization in 8-16-year-old Children in Industrial Town of Solan District of Himachal Pradesh. Int J Clin Pediatr Dent 2020;13(3):230-234., Competing Interests: Source of support: Nil Conflict of interest: None, (Copyright © 2020; Jaypee Brothers Medical Publishers (P) Ltd.)