RING finger E3 ligase, RNF138 inhibits osteoblast differentiation by negatively regulating Runx2 protein turnover.

A few ubiquitin ligases have been shown to target Runx2, the key osteogenic transcription factor and thereby regulate bone formation. The regulation of Runx2 expression and function are controlled both at the transcriptional and posttranslational levels. Really interesting new gene (RING) finger ubiquitin ligases of which RNF138 is a member are important players in the ubiquitin-proteasome system, contributing to the regulation of protein turnover and cellular processes. Here, we demonstrated that RNF138 negatively correlated with Runx2 protein levels in osteopenic ovariectomized rats which implied its role in bone loss. Accordingly, RNF138 overexpression potently inhibited osteoblast differentiation of mesenchyme-like C3H10T1/2 as well primary rat calvarial osteoblast (RCO) cells in vitro, whereas overexpression of catalytically inactive mutant RNF138Δ18-58 (lacks RING finger domain) had mild to no effect. Contrarily, RNF138 depletion copiously enhanced endogenous Runx2 levels and augmented osteogenic differentiation of C3H10T1/2 as well as RCOs. Mechanistically, RNF138 physically associates within multiple regions of Runx2 and ubiquitinates it leading to its reduced protein stability in a proteasome-dependent manner. Moreover, catalytically active RNF138 destabilized Runx2 which resulted in inhibition of its transactivation potential and physiological function of promoting osteoblast differentiation leading to bone loss. These findings underscore the functional involvement of RNF138 in bone formation which is primarily achieved through its modulation of Runx2 by stimulating ubiquitin-mediated proteasomal degradation. Thus, our findings indicate that RNF138 could be a promising novel target for therapeutic intervention in postmenopausal osteoporosis.

Hakai, a novel Runx2 interacting protein, augments osteoblast differentiation by rescuing Runx2 from Smurf2-mediated proteasome degradation.

Runt-related transcription factor 2 (Runx2) is a key regulator of osteoblast differentiation and bone formation. In Runx2-deficient embryos, skeletal development ceases at the cartilage anlage stage. These embryos die of respiratory failure upon birth and display a complete absence of bone and cartilage mineralization. Here, we identified Hakai, a type of E3 ubiquitin ligase as a potential Runx2 interacting partner through affinity pulldown-based proteomic approach. Subsequently, we observed that similar to Runx2, Hakai was downregulated in osteopenic ovariectomized rats, suggesting its involvement in bone formation. Consistent with this observation, Hakai overexpression significantly enhanced osteoblast differentiation in mesenchyme-like C3H10T1/2 as well as primary rat calvaria osteoblast (RCO) cells in vitro. Conversely, overexpression of a catalytically inactive Hakai mutant (C109A) exhibited minimal to no effect, whereas Hakai depletion markedly reduced endogenous Runx2 levels and impaired osteogenic differentiation in both C3H10T1/2 and RCOs. Mechanistically, Hakai physically interacts with Runx2 and enhances its protein turnover by rescuing it from Smad ubiquitination regulatory factor 2 (Smurf2)-mediated proteasome degradation. Wild-type Hakai but not Hakai-C109A inhibited Smurf2 protein levels through proteasome-mediated degradation. These findings underscore Hakai's functional role in bone formation, primarily through its positive modulation of Runx2 protein turnover by protecting it from Smurf2-mediated ubiquitin-proteasomal degradation. Collectively, our results demonstrate Hakai as a promising novel therapeutic target for osteoporosis.

Identification of putative antiviral bioactive compounds derived from family Asteraceae: An in silico approach.

This computational study investigates 21 bioactive compounds from the Asteraceae family as potential inhibitors targeting the Spike protein (S protein) of SARS-CoV-2. Employing in silico methods and simulations, particularly CDOCKER and MM-GBSA, the study identifies two standout compounds, pterodontic acid and cichoric acid, demonstrating robust binding affinities (-46.1973 and -39.4265 kcal/mol) against the S protein. Comparative analysis with Favipiravir underscores their potential as promising inhibitors. Remarkably, these bioactives exhibit favorable ADMET properties, suggesting safety and efficacy. Molecular dynamics simulations validate their stability and interactions, signifying their potential as effective SARS-CoV-2 inhibitors.

Therapeutic implication of MicroRNA-320a antagonist in attenuating blood clots formed during venous thrombosis.

Venous thrombosis (VT) is a complex multi-factorial disease and a major health concern worldwide. Its clinical implications include deep vein thrombosis (DVT) and pulmonary embolism (PE). VT pathogenesis involves intricate interplay of various coagulants and anti-coagulants. Growing evidences from epidemiological studies have shown that many non-coding microRNAs play significant regulatory role in VT pathogenesis by modulating expressions of large number of gene involved in blood coagulation. Present study aimed to investigate the effect of human micro RNA (hsa-miR)-320a antagonist on thrombus formation in VT. Surgery was performed on Sprague-Dawley (SD) rats, wherein the inferior vena cava (IVC) was ligated to introduce DVT. Animals were divided into four groups (n = 5 in each group); Sham controls (Sham), IVC ligated-DVT (DVT), IVC ligated-DVT + transfection reagent (DVT-NC) and IVC ligated-DVT + miR320a antagonist (DVT-miR-320a antagonist). IVC was dissected after 6 h and 24 h of surgery to estimate thrombus weight and coagulatory parameters such as levels of D-dimer, clotting time and bleeding time. Also, ELISA based biochemical assays were formed to assess toxicity of miRNA antagonist in animals. Our experimental analysis demonstrated that there was a marked reduction in size of thrombus in hsa-miR-320a antagonist treated animals, both at 6 h and 24 h. There was a marked reduction in D-dimer levels in hsa-miR-320a antagonist treated animals. Also, blood clotting time was delayed and bleeding time was increased significantly in hsa-miR-320a antagonist treated rats compared to the non-treated and Sham rats. There was no sign of toxicity in treated group compared to control animals. Hsa-miR-320a antagonist could be promising therapeutic target for management of VT.

A step closer towards achieving universal health coverage: the role of gender in enrolment in health insurance in India.

BACKGROUND: There is limited understanding of how universal health coverage (UHC) schemes such as publicly-funded health insurance (PFHI) benefit women as compared to men. Many of these schemes are gender-neutral in design but given the existing gender inequalities in many societies, their benefits may not be similar for women and men. We contribute to the evidence by conducting a gender analysis of the enrolment of individuals and households in India's national PFHI scheme, Rashtriya Swasthya Bima Yojana (RSBY). METHODS: We used data from a cross-sectional household survey on RSBY eligible families across eight Indian states and studied different outcome variables at both the individual and household levels to compare enrolment among women and men. We applied multivariate logistic regressions and controlled for several demographic and socio-economic characteristics. RESULTS: At the individual level, the analysis revealed no substantial differences in enrolment between men and women. Only in one state were women more likely to be enrolled in RSBY than men (AOR: 2.66, 95% CI: 1.32-5.38), and this pattern was linked to their status in the household. At the household level, analyses revealed that female-headed households had a higher likelihood to be enrolled (AOR: 1.36, 95% CI: 1.14-1.62), but not necessarily to have all household members enrolled. CONCLUSION: Findings are surprising in light of India's well-documented gender bias, permeating different aspects of society, and are most likely an indication of success in designing a policy that did not favour participation by men above women, by mandating spouse enrolment and securing enrolment of up to five family members. Higher enrolment rates among female-headed households are also an indication of women's preferences for investments in health, in the context of a conducive policy environment. Further analyses are needed to examine if once enrolled, women also make use of the scheme benefits to the same extent as men do. India is called upon to capitalise on the achievements of RSBY and apply them to newer schemes such as PM-JAY.

Fortifying Micronutrient Supplementation in India: Indian Expert consensus.

Micronutrients play a key role in human health, being involved in energy metabolism, immunity, cellular functioning, growth, and development. Deficiencies in micronutrients occur in individuals of all ages due to several factors, including inadequate diets, disease states, and overweight/obesity. Guidelines from the Indian Council of Medical Research (ICMR) National Institute of Nutrition (NIN) Expert Group on Nutrient Requirements for Indians (2023) have specified the Recommended Dietary Allowances (RDA) for macronutrients and micronutrients. In addition, a healthy diet is crucial for overall health and should be the first step toward addressing micronutrient deficiencies. When diet is inadequate, micronutrient supplements can be provided to compensate. An expert panel of Indian doctors was convened to develop a pathway toward micronutrient supplementation among the Indian population. This Consensus Statement recognizes that different populations have varying needs for specific micronutrients, and ensuring adequate intake of such micronutrients can improve health outcomes. The panel provided recommendations for dietary practices and micronutrient supplementation when diet is inadequate. Addressing micronutrient deficiencies at the primary care level can prevent chronic deficiencies and their consequences. This Consensus Statement can serve as a primer for physicians to monitor and address deficiencies and thus help individuals maintain their health.

AIP4 regulates adipocyte differentiation by targeting C/EBPα for ubiquitin-mediated proteasomal degradation.

Adipogenesis, that is, the formation of terminally differentiated adipocytes is intricately regulated by transcription factors where CCAAT/enhancer binding protein alpha (C/EBPα) plays a key role. In the current study, we demonstrate that E3 ubiquitin ligase AIP4 negatively regulates C/EBPα protein stability leading to reduced adipogenesis. While AIP4 overexpression in 3T3-L1 cells preadipocytes inhibited lipid accumulation when treated with differentiation inducing media (MDI), AIP4 depletion was sufficient to partially promote lipid accumulation even in the absence of MDI. Mechanistically, overexpression of AIP4 inhibited protein levels of both ectopically expressed as well as endogenous C/EBPα while catalytically inactive AIP4 failed. On the contrary, AIP4 depletion profoundly enhanced endogenous C/EBPα protein levels. The observation that AIP4 levels decrease with concomitant increase in C/EBPα levels during adipocyte differentiation further indicated that AIP4 negatively regulates C/EBPα levels. We further show that AIP4 physically interacts with C/EBPα and ubiquitinates it leading to its proteasomal degradation. AIP4 promoted K48-linked ubiquitination of C/EBPα while catalytically inactive AIP4-C830A failed. Taken together, our data demonstrate that AIP4 inhibits adipogenesis by targeting C/EBPα for ubiquitin-mediated proteasome degradation.

Dexamethasone activates c-Jun NH2-terminal kinase (JNK) which interacts with GR and protects it from ubiquitin-mediated degradation in NSCLC cells.

Dexamethasone-mediated pharmacological activation of the glucocorticoid receptor (GR) is widely used in the treatment regimen of hematological malignancies and solid cancers. However, DEX sensitivity towards patients primarily depends on the endogenous protein levels of GR. We observed that DEX treatment leads to an increase in GR protein levels despite inhibition of neo-protein synthesis in non-small cell lung cancer (NSCLC) cells. Mechanistically, DEX-stimulation concomitantly increased the JNK phosphorylation and GR protein levels, however the JNK stimulation preceds GR upregulation. Moreover, we also observed that DEX-mediated phosphorylation is partially mediated by upregulation in MEKK1 phosphorylation. Further, GR protein levels were significantly decreased in JNK inhibitor (JNKi, SP600125) treated cells whereas MG132 treatment restored GR levels indicating that DEX induced JNK activity regulated the GR protein levels through proteasomal-degradation pathway. Next, we showed that DEX led to JNK activation which physically interacts with GR and protects it from ubiquitination-mediated degradation. Furthermore, at basal level GR interacts with JNK in cytoplasm whereas upon DEX stimulation GR and pJNK both localized to nucleus and interact with each other. Next, we show that JNK-mediated GR stabilization affects its nuclear transcriptional functional activity in NSCLC cells. In line with these in vitro data, patient dataset analysis also shows that increased levels of both JNK and GR contributes towards better prognosis of NSCLC patients. Taken together, our data shows that DEX treatment may lead to positive feedback regulation of GR by activating JNK and thus highlights importance of GR-JNK crosstalk in NSCLC.

"Mitochondrial pathogenic mutations and metabolic alterations associated with COVID-19 disease severity".

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) caused global pandemic and drastically affected the humankind. Mitochondrial mutations have been found to be associated with several respiratory diseases. Missense mutation and pathogenic mitochondrial variants might unveil the potential involvement of the mitochondrial genome in coronavirus disease 2019 (COVID-19) pathogenesis. The present study aims to elucidate the role of mitochondrial DNA (mtDNA) mutations, mitochondrial haplogroup, and energy metabolism in disease severity. The study was performed on 58 subjects comprising COVID-19-positive (n = 42) and negative (n = 16) individuals. COVID-19-positive subjects were further categorized into severe deceased (SD), severe recovered (SR), moderate (Mo), and mild (Mi) patients, while COVID-19-negative subjects were healthy control (HC) for the study. High throughput next-generation sequencing was done to investigate mtDNA mutations and haplogroups. The computational approach was applied to study the effect of mtDNA mutations on protein secondary structure. Real time polymerase chain reaction was used for mtDNA copy number determination and mitochondrial function parameters were also analyzed. We found 15 mtDNA mutations in MT-ND5, MT-ND4, MT-ND2, and MT-COI genes uniquely associated with COVID-19 severity affecting the secondary structure of proteins in COVID-19-positive subjects. Haplogroup analysis suggests that mtDNA haplogroups M3d1a and W3a1b might be potentially associated with COVID-19 pathophysiology. The mitochondrial function parameters were significantly altered in severe patients (SD and SR; p < 0.05). No significant relationship was found between mtDNA mutations and oxidative stress markers (p > 0.05). The study highlights the importance of mitochondrial reprogramming in COVID-19 patients and may provide a feasible approach toward finding a path for therapeutic interventions to COVID-19 disease.

Implementation of PM-JAY in India: a qualitative study exploring the role of competency, organizational and leadership drivers shaping early roll-out of publicly funded health insurance in three Indian states.

BACKGROUND: The Pradhan Mantri Jan Arogya Yojana (PM-JAY), a publicly funded health insurance scheme, was launched in India in September 2018 to provide financial access to health services for poor Indians. PM-JAY design enables state-level program adaptations to facilitate implementation in a decentralized health implementation space. This study examines the competency, organizational, and leadership approaches affecting PM-JAY implementation in three contextually different Indian states. METHODS: We used a framework on implementation drivers (competency, organizational, and leadership) to understand factors facilitating or hampering implementation experiences in three PM-JAY models: third-party administrator in Uttar Pradesh, insurance in Chhattisgarh, and hybrid in Tamil Nadu. We adopted a qualitative exploratory approach and conducted 92 interviews with national, state, district, and hospital stakeholders involved in program design and implementation in Delhi, three state capitals, and two anonymized districts in each state, between February and April 2019. We used a deductive approach to content analysis and interpreted coded material to identify linkages between organizational features, drivers, and contextual elements affecting implementation. RESULTS AND CONCLUSION: PM-JAY guideline flexibilities enabled implementation in very different states through state-adapted implementation models. These models utilized contextually relevant adaptations for staff and facility competencies and organizational and facilitative administration, which had considerable scope for improvement in terms of recruitment, competency development, programmatic implementation support, and rationalizing the joint needs of the program and implementers. Adaptations also created structural barriers in staff interactions and challenged implicit power asymmetries and organizational culture, indicating a need for aligning staff hierarchies and incentive structures. At the same time, specific adaptations such as decentralizing staff selection and task shifting (all models); sharing of claims processing between the insurer and state agency (insurance and hybrid model); and using stringent empanelment, accreditation, monitoring, and benchmarking criteria for performance assessment, and reserving secondary care benefit packages for public hospitals (both in the hybrid model) contributed to successful implementation. Contextual elements such as institutional memory of previous schemes and underlying state capacities influenced all aspects of implementation, including leadership styles and autonomy. These variations make comparisons across models difficult, yet highlight constraints and opportunities for cross-learning and optimizing implementation to achieve universal health coverage in decentralized contexts.

Perception of Minimum Interventional Dentistry among Dental Undergraduate Students and Interns.

Background: The philosophy of minimum interventional dentistry (MID) is to integrate prevention, remineralization, and minimal intervention for the placement and replacement of restorations. All branches of dentistry play an important role in practicing MID, and their primary goal is to realize that any restoration is of less biological significance than the healthy original tissue Objectives: The objective of this study was to assess the perception of MID among dental undergraduate students and interns in terms of knowledge, attitude, and practice at the College of Dentistry. Materials and Methods: This cross-sectional study was conducted among undergraduate students and interns at the College of Dentistry, Qassim University, Saudi Arabia. A self-administered questionnaire was distributed, which included basic demographic profiles and questions about the knowledge, attitude, and practices toward MID. The data were tabulated in MS Excel, and all statistical analyses were performed using SPSS version 21. Results: A total of 163 dental students were recruited, with senior students comprising 73% and interns comprising 27%. Male students were slightly more prevalent (50.9%) than female students (49.1%). About 37.6% of participants received training about MID during educational courses, while 10.3% received it during their internship. A statistical test revealed that the prevalence of interns who were trained in performing MID was significantly higher (p < 0.001). Conclusions: The majority of the participants demonstrated proper knowledge, attitude, and practice in different aspects of MID. Interns reported a higher rate of knowledge, attitude, and practice in MID compared to undergraduate students. However, more education and hands-on training about MID concepts during the college curriculum are necessary to attain better knowledge, attitude, and practices that could be useful for more conservative clinical practice.

A Cone Beam Computed Tomography-Based Investigation of the Frequency and Pattern of Radix Entomolaris in the Saudi Arabian Population.

Background and Objectives: An understanding of the anatomical complexity of teeth is a significant factor for a successful endodontic treatment outcome. The aim of this study was to explore the frequency and pattern of distribution of radix entomolaris (RE) in mandibular first molars (MFMs) of a Saudi Arabian subpopulation using CBCT scans. Materials and Methods: This study was conducted at dental clinics of Qassim University from February to May 2023 by evaluating CBCT scans that were previously obtained for diagnostic purposes. Scans of Saudi national patients with bilaterally present MFMs and fully formed root apices were included. Conversely, scans with one/or two missing MFMs, MFMs with incomplete root apices, full- or partial-coverage prosthesis, endodontic treatment, and associated radicular resorption were excluded from study. A total of 303 CBCT scans with 606 bilateral MFMs were analyzed by two calibrated evaluators for the presence of, and type according to Song's typolgy of RE. The data were analyzed using SPPS-24. The descriptive variables were documented as frequencies and percentages. The chi-square test was used to determine the association between the prevalence of RE with the gender, jaw side and age group. Both inter-rater and intra-rater agreements were estimated for detecting and classifying RE using Cohen's kappa test. Results: The sample had 63.7% males and 36.3% females. The prevalence of RE was 6.6%, with Song's type III (57.5%) as the most common variant. Absolute agreement was noted between the raters about the presence of RE and very strong agreement was noted for the classification of the RE. Conclusions: RE is an uncommon finding among the mandibular first molars of the Saudi population without any gender and quadrant predilection. The clinicians' knowledge of the presence and Song's type of RE may contribute towards the enhancement of endodontic treatment outcomes.

Implications of COVID-19 on Thrombotic Profile of Severely Affected Patients.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) is a novel viral disease that spread as a global pandemic in 2020 by infecting millions of people across the world. Its clinical prognosis is dependent on various coagulatory parameters since thrombotic events are frequently associated with infection severity. METHODS: A total of 383 COVID-19 patients enrolled in Rajiv Gandhi Super Specialty Hospital, Delhi, India, were included in the present retrospective study. Patients were divided into three categories, severe (n = 141), moderate (n = 138), and mild (n = 104) based on infection severity. Various thrombotic parameters and anticoagulant levels were measured in 70 patients and further analyzed. RESULTS: Coagulopathy is seen in COVID-19 patients (n = 70) with a significant increase in fibrinogen, D-dimer levels, and prothrombin time in patients with severe and moderate disease compared to patients with a mild infection. Approximately, 70% of patients with severe and moderate disease demonstrated fibrinogen levels higher than the standard reference range. 60.41% of patients with severe disease showed significantly higher D-dimer levels. Thrombotic parameters were notably elevated in the nonsurvivors group compared to COVID-19 survivors. Nearly, 91% of patients with severe infection had anticoagulant protein S levels below the reference range. CONCLUSION: COVID-19 infection severely impacts the blood coagulation cascade, which might lead to the manifestation of severe symptoms and increased mortality in patients.

A success story of reduction in childhood stunting and underweight in India: analysis of pooled data from three rounds of Indian Demographic and Health Surveys (1998-2016).

This study used a series of individual-level datasets from National Family Health Surveys conducted in 1998-99, 2005-06 and 2015-16 to assess the factors behind the reduction in childhood stunting and underweight in India between the years 1998-99 and 2015-16. A multivariable decomposition regression analysis was performed. Results showed that the prevalence of childhood stunting declined from 49.4% in 1998-99 to 34.9% in 2015-16. Over the same period, the prevalence of childhood underweight declined from 41.9% in 1998-99 to 33.1% in 2015-16. The reduction in the prevalence of stunting was found to be contributed largely by a reduction in the combined prevalence of stunting and underweight (60%), followed by stunted only (21%) and the combined prevalence of stunting, underweight and wasting (19%). Likewise, the reduction in the prevalence of underweight was contributed by a reduction in the combined prevalence of stunting and underweight and the combined prevalence of stunting, underweight and wasting. Results of the decomposition analysis showed that over the period 1998-99 to 2015-16, improvement in wealth status and maternal education led to 13% and 12% declines, respectively, in childhood stunting and to 31% and 19% declines, respectively, in childhood underweight. Furthermore, reductions in childhood stunting and underweight were due to an increased average number of antenatal care visits, lower average birth order, decreased share of children with below-average birth size, increased use of clean fuel for cooking and a reduction in the practice of open defecation. These findings suggest that further reduction in the prevalence of childhood stunting and underweight could be attained through more equitable household economic growth, investment in girl's education, greater access to improved toilet facilities, more widespread use of clean fuel for cooking, reduction in average birth order, increased antenatal care visits and greater consumption of IFA tablets by pregnant women. Policymakers need to prioritize these measures to further reduce malnutrition among Indian children.

Out-of-Pocket expenditure and patient experience of care under-Indonesia's national health insurance: A cross-sectional facility-based study in six provinces.

BACKGROUND: Low- and middle-income countries worldwide are striving to achieve universal health coverage (UHC), frequently through expansion of statutory health insurance schemes. However, oftentimes evidence is lacking on progress towards quality patient-centred care and out-of-pocket expenditure (OOPE), particularly for poor population groups. We contribute patient-centred evidence examining patient experience and OOPE under JKN, the Indonesian social health insurance. METHODS: Using data from 2526 patient exit interviews conducted among JKN beneficiaries in 2015, we computed a summative patient experience measure from 14 experience items. We used descriptive statistics to assess patient experience and the probability, amount and components of OOPE. We applied a two-part model to examine the relationships between socio-demographics, facility types, and OOPE and an OLS regression on patient experience determinants. RESULTS: The mean patient experience measure was 11.7 out of 14 maximal points. Differences were observed between single items, with highest ratings on ease of understanding providers' language (97%) and lowest on waiting time (54%). OOPE were reported by 20% of patients with a mean equivalent to US$40, the most prevalent reason being medicines (61% of all OOPE). Considerable OOPE heterogeneity occurred by province and facility type. We found differentials in OOPE by gender (females paying more likely, but less) and subsidised JKN membership (same likelihood as non-subsidised, but paying less). CONCLUSION: Our findings suggest that during its early implementation, patients under JKN reported mostly positive patient experience yet a fifth incurred OOPE, mostly on medicines. Further patient-centred research is needed to ensure JKN's progress towards UHC.

A Study of Correlation of Glucagon-Insulin Ratio with Hba1c in Diabetic Patients in a Tertiary Care Hospital.

Apart from defects in insulin secretion and insulin resistance, hyperglucagonemia is a major factor affecting diabetes development and progression. Diabetic patients show relatively higher fasting and postprandial glucagon levels due to alpha cell resistance or dysfunction. As glucagon secretion is highly affected by insulin, it is better to consider glucagon relative to insulin as a glucagon insulin ratio instead of assessing each absolute value seperately. Data on increase in glucagon relative to insulin and their association with clinical parameters are scarce. In this study, we evaluated whether increase in glucagon relative to insulin correlates with HbA1c in diabetic patients. This will help to develop newer therapies aimed at suppressing glucagon levels for achieving glycemic control in diabetic patients. MATERIAL: A prospective type of observational study was conducted in outdoor and indoor patients of a tertiary care hospital. Patients of either sex, with type 2 DM, who were naive to insulin therapy were participating in the study. Patients with type 1 DM, gestational diabetes and patients on long term insulin therapy were excluded from the study.The sample size was 80. Fasting and post prandial quantitative glucagon estimation was done by Sandwich ELISA kit method. OBSERVATION: We observed that mean fasting and postprandial glucagon/ insulin ratio were 104.85 +/- 59.1 and 101.63 +/- 88.0 respectively. Mean Hba1c value was 9.9 +/- 2.41%, mean duration of diabetes was 6.6 +/- 2.5 years and mean age of subjects was 54.4 +/- 9.9 years. Linear regression analysis was conducted, in which both fasting and post prandial glucagon to insulin ratio showed statistically significant correlation with HbA1c (p values 0.018 and 0.029 respectively). CONCLUSION: In this study, we found that patients with a higher glucagon to insulin ratio in both fasting and postprandial state exhibit worse blood glucose levels i.e, higher HbA1c levels. Thus, instead of concentrating on improvement in insulin resistance, a strategy to suppress glucagon together with increasing insulin secretion maybe another key therapeutic option for achieving glycemic control in type 2 diabetic patients in future.

A Study for Evaluation of Altered Mental Status Patients in Medicine Department.

Altered mental status (AMS) comprises a group of clinical symptoms rather than a specific diagnosis, and includes cognitive disorders, attention disorders, arousal disorders, and decreased level of consciousness. Patients often manifest vague symptoms, thus, AMS diagnosis and treatment are highly challenging for general medicine physicians. MATERIAL: This was an observational cross-sectional analytical study. This study will be conducted in Department of General Medicine, SMS Medical College and attached group of hospitals, Jaipur, Rajasthan, India. Duration of this study was 1 year. We analysed 150 cases in this study. OBSERVATION: We found that mean age for this study was 55.1 years. Major co-morbidity was Hypertension, ALD/CLD/PHTN, T2DM and carcinoma lung with 46.6%, 25.3%, 22.6% and 18% respectively. We found that 81.3% patients are non-alcoholic followed by 50% non-smoker. In our study 52.6% patients had structural Neurological aetiology followed by 17.3% of CO2 Narcosis, 10% patients had hepatic encephalopathy. 5.3% patients were having hypoglycemia and 4.6% were having hyponatremia. In brain MRI we found that 22.6% patients are of CVA ICH, 16.6% patients with CVA Infarct and 3.3% patients of hypoxic ischemic brain injury. CONCLUSION: In our study, we found that neurological causes for altered sensorium were more common than primary non-neurological diseases. Though neuroimaging was helpful in large number of patients, good history, thorough physical examination & laboratory reports also were vital in establishing diagnosis.

Cone-beam computed tomographic analysis of root canal morphology of permanent mandibular incisors - Prevalence and related factors.

Objectives: To investigate the prevalence of additional canals and the occurrence of oval canals in apical third area of mandibular permanent incisors of Saudi sub-population. Methods: This study was conducted from November 2020 to May 2021 at College of Dentistry, Qassim University. For the investigation purpose of this study, 314 scans were analyzed within the age limits of 13 to 70 years. The root canal morphology, presence of oval canals, number of roots, and prevalence of various canal configurations based on age, gender and bilateral symmetry were recorded. The obtained data was statistically analyzed using SPSS software. Results: The mandibular central incisors (CI) exhibited, significant difference between Type-I, II, III and IV canal configurations and Type-I, II, III and V canal configurations (p < 0.05). For the mandibular lateral incisor (LI), significant difference was found between Type-I, II, III, IV and VII canal configurations (p < 0.05). The cumulative prevalence of oval canals in mandibular incisors was found to be 46.6%. For both mandibular CI and LI, the prevalence of Type-I canals was significantly higher in males as compared to females (p < 0.05). Conversely, significantly higher prevalence of Type-III canals was noted for females as compared to males (p < 0.05). No significant difference was found in the prevalence of different canal configurations on the left and the right side of the mouth. Conclusion: In this study, multiple canals were prominently recognized with Type-III mandibular incisors dominating this feature. Oval canals were predominantly found in single canal especially Type-III. This research suggests variability in canal morphology among different populations. Knowledge of these aberrant canal anatomies is useful for the clinician to achieve a favorable endodontic outcome.

Potential association of COVID-19 and ABO blood group: An Indian study.

Coronavirus disease 2019 (COVID-19) transmits from person to person mainly through respiratory droplets and coughing. Infection severity ranges from asymptomatic and mild infection to those with moderate and severe symptoms which may lead to multiple organ failure and mortality. Infection severity largely depends on individual's immune response, age and co-morbidities. Present study categorized COVID-19 infected patients based on their infection severity and linked COVID-19 severity with age, gender and ABO blood group types. Clinical details of 383 COVID-19 patients were collected from Rajiv Gandhi Super Specialty hospital (RGSSH), India; divided into three groups; mild, moderate and severe patients, based on their symptoms. Present analysis revealed that age plays major role in infection severity, as the symptoms are more severe in patients above 45 years. Infection rate was higher in males compared to females. Most patients with A(+ve) and B(+ve) blood group were severely affected compared to those of blood group type O(+ve) and AB(+ve). O(+ve) blood group was least represented in severe patients. Present findings could be helpful in generating awareness amongst the population regarding susceptibility towards the COVID-19 infection. This supportive information would help clinicians and health workers to propose new strategies and tactical solution against COVID-19 infection.

Influence of integrins on thrombus formation: a road leading to the unravelling of DVT.

Integrins are a group of transmembrane glycoprotein receptors that are responsible for platelet activation through bidirectional signalling. These receptors have left their footprints in various cellular events and have intrigued many groups of scientists that have led to some significant discoveries. A lot of the recent understanding of haemostasis has been possible due to the integrins filling the gaps in between several cellular mechanism. Apart from this, other important functions carried out by integrins are growth and maturation of cardiomyocytes, mechano-transduction, and interaction with actin cytoskeleton. The signalling cascade for integrin activation involves certain intracellular interacting proteins, which initiates the step-by-step activation procedure through 'inside-out' signalling. The signalling cascade gets activated through 'outside-in' signalling with the involvement of agonists such as ADP, Fibronectin, Vitronectin, and so on. This is a crucial step for the downstream processes of platelet spreading, followed by aggregation, clot progression and finally thrombus formation. Researchers throughout the world have shown direct relation of integrins with CVD and cardiac remodelling. The present review aims to summarize the information available so far on the involvement of integrins in thrombosis and its relationship to DVT. This information could be a bedrock of hidden answers to several questions on pathogenesis of deep vein thrombosis.