Application of Health Belief Model to Comprehend Adherence to COVID-19-appropriate Behavior among COVID-19 Vaccinees in Himachal Pradesh.

BACKGROUND: The augmentation of precautionary behaviors through the application of health belief model (HBM) constructs could help in curbing the current pandemic. OBJECTIVES: The objectives are to assess adherence to CAB and to evaluate its predictors using the constructs of HBM among COVID-19 vaccinees in Himachal Pradesh. MATERIALS AND METHODS: A cross-sectional study using a telephone survey, with two-step stratified random sampling, was employed to acquire a sample of 441 respondents from Himachal Pradesh. Formal interviews were conducted using pretested, structured, self-administered questionnaires. RESULTS: The mean age of respondents was 32.16 years (standard deviation = 12.77; range = 18-78 years). Maximum adherence was seen for wearing masks at 83% (95% confidence interval [CI]: 79.3%-86.3%), followed by maintenance of respiratory hygiene at 72.3% (95% CI 68%-78.4%). Nearly 42.2% (95% CI 37.6%-47.8%) conformed to social distancing norms. We observed minimum adherence for handwashing practices of 12.9% (95% CI 10%-16.3.0%). On bivariate analyses, except for perceived severity, all HBM constructs were significantly associated with CAB. However, after adjusting for gender, age, education, area of residence, and reduced income in multivariate analysis, perceived susceptibility, perceived barriers, and exposure to cues to action remained significant predictors of CAB. CONCLUSIONS: The study highlights the empirical evidence of the application of HBM constructs to enhance behavioral adherence to COVID-19 precautionary measures.

An assessment of compliance with the provisions of Cigarettes and Other Tobacco Products Act 2003: Is Shimla a smoke-free city?

Background: . Tobacco consumption in any form is a major contributor to non-communicable diseases, and it is the leading preventable cause of death worldwide. Secondhand smoke is also harmful. To halt the smoking epidemic and protect people from second-hand smoke, the Government of India enacted the Cigarettes and Other Tobacco Products Act (COTPA) in 2003. Methods: . We ascertained compliance with the provisions of COTPA 2003 at 183 public places and 41 transport facilities of Shimla city from August 2017 to July 2018. Results: . Only 48% of public places had good compliance with the provisions of COTPA 2003. On average, a public place was found to be compliant with 7 of 10 key indicators of Section 4. Educational institutes and government offices had a higher rate of compliance compared to other places. Active smoking and signages signalling ban on smoking were observed in 17% and 95.6% of public places, respectively. Smoking aids (e.g. ashtrays) were observed at <10% of places. A designated smoking area was not seen at any public place. Conclusion: . Overall compliance of the Act was low with less than half the places having satisfactory compliance with Section 4. There is a need to raise awareness about the negative effects of smoking on health and environment and ensure strict adherence to the provisions of COTPA 2003.

Diphosphothreonine-specific interaction between an SQ/TQ cluster and an FHA domain in the Rad53-Dun1 kinase cascade.

Forkhead-associated (FHA) domains recognize phosphothreonines, and SQ/TQ cluster domains (SCDs) contain concentrated phosphorylation sites for ATM/ATR-like DNA-damage-response kinases. The Rad53-SCD1 has dual functions in regulating the activation of the Rad53-Dun1 checkpoint kinase cascade but with unknown molecular mechanisms. Here we present structural, biochemical, and genetic evidence that Dun1-FHA possesses an unprecedented diphosphothreonine-binding specificity. The Dun1-FHA has >100-fold increased affinity for diphosphorylated relative to monophosphorylated Rad53-SCD1 due to the presence of two separate phosphothreonine-binding pockets. In vivo, any single threonine of Rad53-SCD1 is sufficient for Rad53 activation and RAD53-dependent survival of DNA damage, but two adjacent phosphothreonines in the Rad53-SCD1 and two phosphothreonine-binding sites in the Dun1-FHA are necessary for Dun1 activation and DUN1-dependent transcriptional responses to DNA damage. The results uncover a phospho-counting mechanism that regulates the specificity of SCD, and provide mechanistic insight into a role of multisite phosphorylation in DNA-damage signaling.

Advancing the community plan to end the HIV Epidemic in Philadelphia: a qualitative descriptive evaluation of low-threshold PrEP services in sexual health clinics.

BACKGROUND: Pre-exposure prophylaxis (PrEP) is an effective HIV prevention method and a key component of Philadelphia's Community Plan to End the HIV Epidemic (EHE). However, significant barriers to accessing PrEP exist among people at risk for HIV. Low-threshold models for PrEP services that minimize barriers to entry and service engagement could help bolster access to PrEP through community-based clinics. This study aimed to describe the initial implementation of low-threshold PrEP services in three sexual health clinics funded by the Philadelphia Department of Public Health and explore strategies for delivering low-threshold PrEP services. METHODS: We conducted three focus groups with staff (i.e., providers, prevention navigators, and administrative staff, N = 21) at each of three participating PDPH-funded sexual health clinics from November 2021 to January 2022. Discussion topics included details about the PrEP delivery process, clinic strengths and assets, resource gaps, and PrEP implementation goals. Follow-up interviews with staff members (N = 8) between March 2022 and May 2022 focused on identifying successful strategies for PrEP delivery and adaptations needed to optimize low-threshold PrEP service delivery. Rapid qualitative methods and the Consolidated Framework for Implementation Science were used to analyze data from focus groups and interviews. RESULTS: Participants collaborated to create process maps that visualized the steps involved in delivering PrEP services within their respective settings. These maps highlighted several stages in PrEP service delivery, such as connecting individuals to services, providing prevention navigation, conducting clinical encounters, and ensuring follow-up care. Participants described effective strategies for implementing PrEP, which included integrating and co-locating services on-site, strengthening staffing resources and capacity, and addressing barriers experienced by clients. CONCLUSIONS: Lessons from the implementation of low-threshold PrEP service delivery in Philadelphia can guide ongoing local adaptations and future scale-up of these models to improve access to PrEP and advance the goals of the EHE initiative.

The study of pH-dependent stability shows that the TPLH-mediated hydrogen-bonding network is important for the conformation and stability of human gankyrin.

Ankyrin repeat (AR) proteins possess a distinctive modular and repetitive architecture, and their global folds are maintained by short-range interactions in terms of the primary sequence. In this work, we extended our previous study on the highly conserved TPLH tetrapeptide and investigated the impact of a solvent-exposed histidine residue on the pH-dependent stability of gankyrin, providing further insight into the contribution of the TPLH motif to the tertiary fold of AR proteins. Consisting of seven ARs, gankyrin has five histidine residues in TPLH motifs or its variants, all of which adopt a H(ε2)-tautermeric form and are shielded from solvent. By truncating the C-terminal ankyrin repeat (AR7), we exposed H177 in the (174)TPLH(177) of AR6 (the second C-terminal AR) to an aqueous environment. We showed that this truncated gankyrin mutant, namely, Gank(1-201), was well-folded at a neutral pH with a slightly lower stability with respect to gankyrin wild type (WT). However, unlike gankyrin WT, the stability of Gank(1-201) was markedly decreased together with a loss of conformation at a pH slightly below 6.0. It was rationalized that the protonation of the H177 imidazole ring triggered the disruption of the TPLH-mediated hydrogen-bonding network, which in turn led to the loss of conformation and stability. These results together with the work on Q210H mutant nicely explain that the C-terminal AR7 has a (207)TPLQ(210) variant and are in support of the notion that a string of TPLH/variant, which may arguably act like a zip lock to the elongated AR proteins via intra-/inter-repeat hydrogen-bonding, is important in maintaining the tertiary fold. Additionally, we made rational mutagenesis to introduce extra surface charge on AR7 of gankyrin and demonstrated that G214E and I219D mutations increased the stability of gankyrin while the function remained intact. Taken together, our results indicate that the TPLH-mediated hydrogen-bonding network is important for the conformation and stability of human gankyrin, and the C-terminal AR contributes to the conformational stability of gankyrin (AR proteins in general) through shielding this TPLH network from solvent as well as making the surface area more accessible to solvent.

Perspectives From Community-Based HIV Service Organization Leaders on Priorities in Serving Sexual and Gender Minority Populations.

Sexual and gender minority (SGM) populations experience discrimination and care-related barriers when seeking appropriate sexual health services. Using rapid assessment procedures we conducted site visits with 11 community-based HIV service agencies to identify priorities, assets, and needs related to serving SGM clients and assessed the alignment of these services with the city's local Ending the HIV Epidemic plan. We identified and mapped themes across agencies into the Consolidated Framework for Implementation Research domains of inner and outer settings: client-facing materials; priorities in serving SGM communities; SGM policies and protocols; collecting sexual orientation and gender identity data; training and education; and funding and scope of programs. Rapid assessment procedures can accelerate the collection and interpretation of data to help public health institutions and community partners make timely adaptations when implementing comprehensive and culturally humble sexual health services for SGM communities.

Impact of School-Based Health Behavioral Intervention on Awareness, Practice Pattern of Healthy Lifestyle, and Cardiometabolic Risk Factors among School Children of Shimla: A Cluster-Randomized, Intervention Study.

OBJECTIVES: To assess the impact of multicomponent intervention on knowledge and practice of health behaviors among school children. The secondary objective was to assess mean change in cardiometabolic risk factors such as anthropometric measurements and biochemical profile. METHODS: A cluster-randomized, controlled trial was conducted among adolescents aged 13-18 y from government and private senior secondary schools in Shimla city. Multicomponent health behavioral intervention was delivered through teachers. Subjective and objective measures of knowledge and health behaviors were the primary outcomes. RESULTS: There was no significant effect of intervention on nutrition knowledge adjusted mean difference (aMD) 2.4 (95% CI: -3.7 to 8.7; p = 0.43), and the dietary habits adjusted mean difference 2.9 (95% CI: -0.3 to 6.2; p = 0.08) between the intervention and control group. However, significant improvement in odds of dietary practices 2.4 (95% CI: 1.1 to 5.0; p = 0.03) and decreased odds of consumption of junk food 3.8 (95% CI: 1.6 to 9.3; p = 0.003) was observed. There was no effect on physical activity odds 2.9 (95% CI: 0.8 to 11.6; p = 0.12) or screen time with aMD 0.9 (95% CI: 0.7 to 1.2; p = 0.52). Anthropometric measurements and biochemical profile also did not differ except low-density lipoprotein cholesterol which had significantly lower aMD: -7.2 (95% CI: -13.6 to -1.0; p = 0.02). There was no change in alcohol and tobacco consumption with odds 0.8 (95% CI: 0.6 to 1.2; p = 0.33) and 1.0 (95% CI: 0.7 to 1.5; p = 0.87), respectively after intervention. CONCLUSIONS: Multipronged interventions targeting lifestyle behaviors of adolescents at multilevels are vital to curb rising trends of noncommunicable diseases. This quintessentially calls for wider support across multiple sectors and creation of sustained enabling macro- and micro-environment. The trial is registered in the Clinical Trial Registry of India under the registration number CTRI/2018/01/011312 dated 12/01/2018 Registered, retrospectively.

Chlamydia Trachomatis/Neisseria Gonorrhea Retesting Among Adolescents and Young Adults in a Primary Care Network.

PURPOSE: Chlamydia trachomatis/Neisseria gonorrhea (CT/NG) retesting three months after diagnosis is a guideline-recommended strategy to detect re-infections. Adolescents and young adults are priority populations in the U.S. Sexually Transmitted Infections National Strategic Plan, but there is a lack of research examining CT/NG retesting among these populations. This study describes retesting following CT/NG diagnosis among adolescent and young adult patients at Title X and non-Title X clinics and measures the association of patient-level factors with CT/NG retesting. METHODS: We evaluated electronic medical records from 2014 to 2020 from an academic urban-suburban primary care network. The primary outcome was retesting, defined as a diagnostic test for CT or NG ordered 8-16 weeks after index diagnosis. Mixed effects logistic regression modeling stratified by Title X funding was conducted to evaluate the association of patient-level factors with CT/NT retesting. RESULTS: Overall, 23.5% (n = 731) of patients were retested within 8-16 weeks following index CT/NG diagnosis. A significantly greater proportion of Title X patients were retested compared to non-Title X patients. Males were significantly less likely to be retested compared to females, and the proportion of patients retested decreased significantly over the study period. DISCUSSION: Guideline-recommended retesting following CT/NG diagnosis was low in this young primary care cohort, especially among male and non-Title X clinic patients. Decreases in CT/NG retesting over the study period may be contributing to worsening of the STI epidemic. Our results provide insights into CT/NG retesting that can inform efforts to end the STI epidemic.

Comparisons of the conformational stability of cyclin-dependent kinase (CDK) 4-interacting ankyrin repeat (AR) proteins.

Ankyrin repeat (AR) proteins are one of the most abundant repeat protein classes in nature, and they are involved in numerous physiological processes through mediating protein/protein interactions. The repetitive and modular architecture of these AR proteins may lead to biochemical and biophysical properties distinct from those of globular proteins. It has been demonstrated that like most globular proteins, AR proteins exhibit a two-state, cooperative transition in chemical- and heat-induced unfolding. However, the biophysical characteristics underlying such cooperative unfolding remain to be further investigated. In the present study, we evaluated the conformational stability of a group of cyclin-dependent kinase (CDK) 4-interacting AR proteins, P16, P18, IkappaBalpha, gankyrin, and their truncated mutants under different conditions, including the presence of denaturants, temperature, and pH. Our results showed that the first four N-terminal ARs are required to form a potent and stable CDK4 modulator. Moreover, in spite of their similarities in skeleton structure, CDK4 binding, and cooperative unfolding, P16, P18, IkappaBalpha, and gankyrin exhibited considerably different biophysical properties with regard to the conformational stability, and these differences mainly resulted from the discrepancies in the primary sequence of the relatively conserved AR motifs. Our results also demonstrated that these sequence discrepancies are able to influence the function of AR proteins to a certain extent. Overall, our results provide important insights into understanding the biophysical properties of AR proteins.

To Compare Diagnostic Ability of Contrast-Enhanced Three-Dimensional T1-SPACE with Three-Dimensional Fluid-Attenuated Inversion Recovery and Three-Dimensional T1-Magnetization Prepared Rapid Gradient Echo Magnetic Resonance Sequences in Patients of Meningitis.

AIMS: The aim of this study is to compare postcontrast three-dimensional (3D) T1-Sampling perfection with application-optimized contrasts by using different flip angle evolutions, 3D fluid-attenuated inversion recovery (FLAIR), and 3D T1-magnetization prepared rapid gradient echo (MPRAGE) sequences in patients of meningitis. SETTINGS AND DESIGN: A hospital-based cross-sectional study done in the Department of Radiodiagnosis, IGMC Shimla for a period of 1 year from June 1, 2016, to May 30, 2017. SUBJECTS AND METHODS: A total of 30 patients suspected of meningitis underwent magnetic resonance imaging evaluation with postcontrast 3D T1-MPRAGE, 3D T1-SPACE, and 3D FLAIR sequences. The abnormal leptomeningeal enhancement was noted by two radiologists together on these sequences and scores were given to the abnormal leptomeningeal enhancement. STATISTICAL ANALYSIS USED: The sensitivity of 3D T1-SPACE, 3D T1-MPRAGE, and 3D FLAIR was calculated and compared. The level of agreement between these sequences was assessed by kappa coefficient. P < 0.05 was taken as statistically significant. RESULTS: 3D T1-SPACE shows superiority in meningeal enhancement along basal cisterns, Sylvian fissure and along cerebral convexities. It is also found to be better in delineating parenchymal lesions. 3D FLAIR failed to demonstrate enhancement along cerebral convexities however found to be better than 3D T1-MPRAGE in delineating enhancement along basal cisterns and Sylvian fissures. 3D T1-MPRAGE has shown subtle enhancement in basal cisterns, Sylvian fissure and along cerebral convexities. 3D T1-SPACE, 3D FLAIR, and 3D T1-MPRAGE has sensitivity of 91.67%, 66.67%, and 54.17%, respectively. CONCLUSION: Postcontrast 3D T1-SPACE sequence is an excellent tool than postcontrast 3D T1-MPRAGE and 3D FLAIR sequences in the evaluation of meningeal enhancement and depiction of additional lesions in brain parenchyma.

Creation of a Smoke-free Environment for Children: An Assessment of Compliance to COTPA 2003 Legislation in an Urban Area.

OBJECTIVE: To ascertain the compliance to Cigarette and Other Tobacco Products Act (COTPA) 2003 which ensures the protection of children from the adverse health effects of second hand smoke. METHODS: This cross-sectional study assessed the compliance of 32 educational institutions and 157 points of sale of Shimla city. RESULTS: About 88% of the educational institutions and mere 7.6% points of sale were found having good compliance to the key indicators. No point of sale was found within the premises of educational institutions; however, 26% were found selling tobacco products within 100 metres radius of an educational institution. 7.6% points of sale were found selling a tobacco product to children. CONCLUSIONS: Despite having the status of a smoke-free city, lapses were observed in compliance to the Act. Strict adherence to the provisions of the Act would ultimately lead to a smoke-free environment for our children.

Dissection of protein-protein interaction and CDK4 inhibition in the oncogenic versus tumor suppressing functions of gankyrin and P16.

Protein-protein interactions usually involve a large number of residues; thus it is difficult to elucidate functional and structural roles of specific residues located in the interface. This problem is particularly challenging for ankyrin repeat proteins (ARs), which consist of linear arrays of small repeating units and play critical roles in almost every life process via protein-protein interactions, because the residues involved are discontinuously dispersed in both the ARs and their partners. Our previous studies showed that while both specific CDK4 inhibitor p16INK4A (P16) and gankyrin bind to cyclin-dependent kinase 4 (CDK4) in similar fashion, only P16 inhibits the kinase activity of CDK4. While this could explain why P16 is a tumor suppressor and gankyrin is oncogenic, the structural basis of these contrasting properties was unknown. Here we show that a double mutant of gankyrin, L62H/I79D, inhibits the kinase activity of CDK4, similar to P16, and such CDK4-inhibtory activity is associated with the I79D but not L62H mutation. In addition, mutations at I79 and L62 bring about a moderate decrease in the stability of gankyrin. Further structural and biophysical analyses suggest that the substitution of Ile79 with Asp leads to local conformational changes in loops I-III of gankyrin. Taken together, our results allow the dissection of the "protein-protein binding" and "CDK4 inhibition" functions of P16, show that the difference between tumor suppressing and oncogenic functions of P16 and gankyrin, respectively, mainly resides in a single residue, and provide structural insight to the contrasting biological functions of the two AR proteins.

Expression of the p16INK4A/Cdkn2a gene is prevalently downregulated in human pheochromocytoma tumor specimens.

A number of hereditary syndromes have been found to be associated with pheochromocytoma development, but there is a paucity of data regarding secondary molecular events, such as downregulation of the p16INK4A/Cdkn2a gene (hereafter p16), contributing to pheochromocytoma tumorigenesis. Using tissue microarray and immunohistochemistry, we evaluated the expression of p16 in 31 pheochromocytoma tumor specimens. Our results showed that the p16 gene was expressed at low level or even not expressed in all but one specimens [30/31 (96.8%)], indicative of the prevalence of p16 downregulation in pheochromocytomas. In contrast, high expression of pl6 was observed in the majority of control "normal" specimens [5/7 (71.6%)]. To further investigate the molecular mechanisms underlying pl6 downregulation in pheochromocytomas, we used quantitative real-time PCR, methylation-specific PCR, and direct DNA sequencing to analyze these specimens for potential genetic alterations of the p16 gene. Deletions and aberrant CpG methylation of pl6 were identified in 9 (29.0%) and 11 (35.5%) specimens, respectively, while one specimen harbored a point mutation, Ala --> Pro at residue 20 of P16, and this mutation led to an eightfold decrease in the CDK4-inhibitory activity of P16. The overall frequency of pl6 genetic alterations is 67.7%. Taken together, our results demonstrate that reduced expression of pl6 is a common event in human pheochromocytomas, and the primary cause for such downregulation is inactivating genetic abnormalities in the p16 gene.

School-based surveillance for detection of children with acute pharyngitis, rheumatic fever/rheumatic heart disease in Shimla district, Himachal Pradesh, India-A cluster randomized controlled trial.

BACKGROUND: The lack of surveillance system is a major barrier in prevention and control of rheumatic fever/rheumatic heart disease (RF/RHD). Efficacy of school-based surveillance was evaluated for detection of acute pharyngitis and RF/RHD in Shimla district, HP. METHODS: The schools in district Shimla were randomly assigned to intervention and controlled arm (442 vs. 441 schools). The trained nodal teachers reported children with symptoms of acute pharyngitis and or RF/RHD in intervention arm and children taken to hospitals by parents for symptoms of acute pharyngitis and or RF/RHD under control arm through mobile phone to coordinating centre. Final outcome for presence of RF/RHD or other heart Diseases was recorded after examination at nearest primary health centers and/or at Indira Gandhi Medical College Hospital, Shimla. Difference in detection rate between intervention arm and control arm was compared using Z test. RESULTS: The number of school children reported from intervention group was significantly higher than in control due to suspected symptoms of acute pharyngitis and or RF/RHD were 65 (2.84/1000) and 15 (0.60/1000), respectively (p < 0.01). Only 4 children in each arm were found to have heart diseases, with prevalence of (0.17/1000 and 0.16/1000), respectively, after clinical and echocardiography evaluation. In intervention arm, one child had RHD while three had congenital heart disease; in control arm, one child had congenital heart disease and three had RHD. CONCLUSIONS: School based surveillance had higher rate of suspecting children with acute pharyngitis and or RF/RHD although with low specificity. There is a need of future studies to demonstrate the effectiveness of the proposed intervention in endemic regions of the state.

Validity of Madras Diabetes Research Foundation: Indian Diabetes Risk Score for Screening of Diabetes Mellitus among Adult Population of Urban Field Practice Area, Indira Gandhi Medical College, Shimla, Himachal Pradesh, India.

INTRODUCTION: IDRS is based on four simple parameters derived from known risk factors for diabetes; two modifiable risk factors (waist circumference and physical inactivity) and two non-modifiable risk factors (age and family history of diabetes), which may be amenable to intervention. The present study has been planned as the region specific validation is important before it can be used for screening in this part of the country. AIMS: The aim of the present study was to validate MDRF-IDRS for screening of diabetes mellitus among adult population of urban field practice area, IGMC, Shimla, Himachal Pradesh, India. METHODS: The present community based cross sectional study was conducted among 417 adults fulfilling the eligibility criteria using a two stage sampling design. RESULTS: In the present study IDRS value ≥70 had an optimum sensitivity of 61.33% and specificity of 56.14% for detecting undiagnosed type 2 diabetes in the community. At an IDRS score of ≥70, the PPV was 23.47%, NPV as 86.88%, the diagnostic accuracy as 57.07%, LR for positive test as 1.398, LR for negative test as 0.69 and Youden's index as 0.17. However Youden's index was 0.19 at a cut of ≥60 i.e. higher than what was at ≥70. Higher IDRS scores increased the specificity but the sensitivity dramatically decreased. Conversely, lower IDRS values increased the sensitivity but the specificity drastically decreased. Area under the curve = 0.630 and a P value < 0.001. CONCLUSIONS: MDRF IDRS is user friendly screening tool but the criteria of including the parameter of physical activity for the calculation of the risk score needs to be clearly defined. In the present study the maximum sensitivity of 100% was seen at a cut off of ≥30. Hence we would recommend that all those in the medium and high risk group should be screened for type 2 Diabetes.

Ankyrin repeat: a unique motif mediating protein-protein interactions.

Ankyrin repeat, one of the most widely existing protein motifs in nature, consists of 30-34 amino acid residues and exclusively functions to mediate protein-protein interactions, some of which are directly involved in the development of human cancer and other diseases. Each ankyrin repeat exhibits a helix-turn-helix conformation, and strings of such tandem repeats are packed in a nearly linear array to form helix-turn-helix bundles with relatively flexible loops. The global structure of an ankyrin repeat protein is mainly stabilized by intra- and inter-repeat hydrophobic and hydrogen bonding interactions. The repetitive and elongated nature of ankyrin repeat proteins provides the molecular bases of the unique characteristics of ankyrin repeat proteins in protein stability, folding and unfolding, and binding specificity. Recent studies have demonstrated that ankyrin repeat proteins do not recognize specific sequences, and interacting residues are discontinuously dispersed into the whole molecules of both the ankyrin repeat protein and its partner. In addition, the availability of thousands of ankyrin repeat sequences has made it feasible to use rational design to modify the specificity and stability of physiologically important ankyrin repeat proteins and even to generate ankyrin repeat proteins with novel functions through combinatorial chemistry approaches.