Low genetic confirmation rate in South Indian subjects with a clinical diagnosis of maturity-onset diabetes of the young (MODY) who underwent targeted next-generation sequencing for 13 genes.

PURPOSE: To screen for maturity-onset diabetes of the young (MODY) variants in subjects with an early age of onset and positive family history of diabetes mellitus. METHODS: 60 subjects with onset of diabetes between 3 and 30 years of age and parental history (onset < 35 years) of diabetes were recruited after excluding autoimmune, pancreatic and syndromic forms of diabetes. Detailed pedigree chart and clinical data were recorded. MODY genetic testing (MODY 1-13) was performed and variant classification was done adhering to the ACMG guidelines. RESULTS: Baseline characteristics of subjects were as follows: mean age of onset of diabetes 19.9 ± 7 years, mean duration of diabetes 6.3 ± 6.8 years, BMI 23.3 ± 3 kg/m2 and C-peptide 1.56 ± 1.06 nmol/l. Four out of sixty (6.6%) were positive for variants classifiable as pathogenic/likely pathogenic: one patient with HNF4Ac.691C > T, (p.Arg231Trp), two with HNF 1A c.746C > A(p.Ser249Ter) and c.1340C > T(p.Pro447Leu), and one with ABCC8 c.4544C > T (p.Thr1515Met). MODY 1 and MODY 3 variants were documented in the paediatric age group (< 18 years). CONCLUSION: A genetic diagnosis of MODY could be confirmed in only 6.6% (4/60) of patients clinically classifiable as MODY. This is less than that reported in clinically diagnosed MODY subjects of European descent. Newly published population data and more stringent criteria for assessment of pathogenicity and younger age of onset of type 2 diabetes in Indians could have contributed to the lower genetic confirmation rate. Apart from variants in the classical genes (HNF1A, HNF4A), a likely pathogenic variant in a non-classical gene (ABCC8) was noted in this study.

Onboard Pointing Error Detection and Estimation of Observation Satellite Data Using Extended Kalman Filter.

The satellite communication is embellished constantly by providing information, ensuring security, and enables the communication among huge at a particular time efficiently. The satellite navigation helps in determining the people's location. Global development, natural disasters, change in climatic conditions, agriculture crop growth, etc., are monitored using satellite observation. Hence, the satellite includes detailed information data, and it must be protected confidentially. The field of the satellite is enhanced at an astonishing pace. Satellite data play an important role in this modern world; hence, the onboard-satellite data must secure through the proper selection of error detection and estimation schema. Lightweight deep learning algorithm based on Extended Kalman Filter (KFK) is proposed to detect and estimate onboard pointing error such as an error in attitude and orbit. The Extended Kalman Filter (EKF) is widely used in the satellite system. EKF is utilized in this proposed model to detect the onboard pointing error such as attitude and orbit determination. An autonomous estimation of orbit position is possible through space-borne gravity. The information obtained through the observation of satellite data is compared with the accurate gravity model in detecting the error. The utilization of EKF reduces the dependence of the ground tracking system in satellite determination. The orbital altitude and orbital position are the most important challenges faced in the satellite determination system. The satellite model using the Extended Kalman Filter is an optimum method in estimating the orbital parameters. The errors in the linearization process are detected, and this can be overcome through the proper selection of linear expansion point with the EKF algorithmic model with the Jacobian matrix calculation. The results show that the EKF implementation helps in attaining better accuracy than other methodologies. Its contribution is enormous to many space missions, autonomous rendezvous and docking for manned and unmanned missions (e.g., ISS operations and beyond, in-orbit servicing, and in-orbit refueling), routine satellite OD operations, orbital debris removal systems, Space Situational Awareness (SSA) operations, and others.

IHC expression of AKT in different grades of epithelial dysplasia: An in vitro study.

Introduction: Akt, also known as protein kinase B, is a serine/threonine-specific protein-kinase which plays a key role in multiple cellular processes such as glucose metabolism, apoptosis, transcription and cell migration. The activation of Akt is one of the most frequent alterations observed in human cancer and tumour cells. Akt regulates cellular survival and metabolism by binding and regulating many downstream effectors, e.g., Nuclear Factor-kB, murine double minute 2(MDM2). Aims: To evaluate and compare immunohistochemical expression of Akt in normal epithelium and different histological grades of epithelial dysplasias. Materials and Methodology: Forty paraffin-embedded tissue sections were used for the immunohistochemical study of which 10 cases of normal epithelium, 10 cases of each mild, moderate and severe epithelial dysplasia which were diagnosed by haematoxylin and eosin procedures. The tissue sections were immunohistochemically analysed for expression of Akt in different grades of epithelial dysplasia by using anti-Akt-1 monoclonal antibody. Statistical analysis was carried out using statistical package for social science (SPSS, V 10.5). The data were analysed using Chi-square test and P < 0.05 was considered statistically significant. Results and Conclusion: An overall significant difference was observed when normal tissues were compared with epithelial dysplasia with a Chi-square value of 21.04, but there was no statistical significance between the three grades of epithelial dysplasias. In conclusion, this study suggests that Akt-1 overexpression can be one of the useful diagnostic markers for predicting the potential behaviour of oral dysplasias transforming into oral squamous cell carcinoma (OSCC).

Sex disparities in in-hospital outcomes of left ventricular aneurysm complicating acute myocardial infarction: A United States nationwide analysis.

Background: Previous studies have reported sex-specific differences in the presentation, mechanisms, and outcomes of acute myocardial infarction (AMI). We assessed differences between women and men in the incidence and in-hospital outcomes of left ventricular (LV) aneurysm complicating AMI. Methods: Hospitalizations for AMI with LV aneurysm were identified retrospectively in the National Inpatient Sample (NIS) from 2001 to 2017. Incidence and trends in in-hospital mortality, complications, length of stay and costs were analyzed in women and men. Results: A total of 16,334 AMI hospitalizations with concomitant LV aneurysm were identified including 6994 (42.8%) women and 9340 (57.2%) men. Among these hospitalizations, women had a higher incidence of LV aneurysm compared to men (0.16% vs. 0.14%; p < 0.001). Unadjusted in-hospital mortality was higher in women than men (12.7% vs. 7.2%; p < 0.001). After adjusting for demographic and baseline characteristics and excluding inter-hospital transfers, women with AMI complicated by LV aneurysm had 49% greater odds of in-hospital mortality than men (OR 1.49, 95% confidence interval 1.06-2.10, p = 0.02). Women with LV aneurysm were less likely than men to undergo percutaneous coronary intervention (28.5% vs. 35.4%; p < 0.001), bypass surgery (15.8% vs. 25.1%; p < 0.001), coronary atherectomy (0.8% vs. 1.9%; p = 0.009) and LV aneurysm surgery (7.8% vs. 11.1%; p = 0.001). Conclusions: In this large population-based cohort study, women had a slightly higher incidence but dramatically higher in-hospital mortality associated with LV aneurysm complicating AMI compared to men. Further research is necessary to validate strategies to ensure that women receive guideline-directed therapy for AMI and LV aneurysm to address the sex disparity in mortality.

A Case of Idiopathic Thrombocytopenic Purpura After Booster Dose of BNT162b2 (Pfizer-Biontech) COVID-19 Vaccine.

Vaccination is now considered the best measure in minimizing the morbidity and mortality from the Covid-19 pandemic. Almost all the vaccines are considered safe except for minor and occasional side effects. Some of the commonly reported complications from the COVID-19 vaccines are vaccine-induced thrombotic thrombocytopenia (VITT)/thrombosis with thrombocytopenia syndrome/vaccine-induced pro-thrombotic immune thrombocytopenia syndrome. In this case report, we present a case of a 75-year-old female who had an uncomplicated first and second vaccine dose but developed VITT after the booster dose of the vaccine. The patient was treated with dexamethasone and platelet transfusions. So far no such cases have been reported after the third (booster) dose of the Pfizer-Biontech vaccine. With this case report, we present the case of the patient and discuss the literature related to vaccine-induced thrombocytopenia.

Two novel AIRE mutations in autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) among Indians.

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a rare recessive disorder resulting from mutations in the autoimmune regulator (AIRE) gene. There is no information on AIRE mutations in Indians. In a cross-sectional study, nine patients (eight families), from four referral hospitals in India, were studied for AIRE mutations by direct sequencing. We screened for new mutations in 150 controls by allele-specific PCR. The patients had 1-7 known components of APECED. Three patients had unusual manifestations: presentation with type 1 diabetes; chronic sinusitis and otitis media; and facial dysmorphism. All patients carried homozygous, probably recessive, AIRE mutations. Two unrelated patients from a small in-bred community (Vanika Vaisya) in south India carried an unreported missense mutation, p.V80G, in the N-terminal caspase recruitment domain. Another unique mutation, p.C302X, resulting in a truncated protein with deletion of both zinc-finger domains, was detected in a patient from Gujarat. Neither mutation was detected in controls. Other mutations, previously described in Caucasians, were: 13 base pair deletion (p.C322fsX372) in 4 (38%), and Finn-major (p.R257X) and p.R139X (Sardinian) mutation in one subject each. In conclusion, in this first series of APECED in Indians, we detected AIRE mutations previously reported in Caucasians, as well as unique mutations. Of these, p.V80G is possibly an ancestral mutation in an in-bred community.

Study of the safety, immunogenicity and seroconversion of a hepatitis-B vaccine in malnourished children of India.

Sixty rural children who were seronegative for HBV markers received three doses of 10 microgram of a new Hepatitis-B vaccine, Revac-B (1 ml of vaccine contains 20 microgram recombinant surface antigen) that was formulated from hepatitis-B surface antigen expressed in a recombinant strain of Saccharomyces cerevisiae. Vaccines were administered on a 0, 30 and 60-day schedule. Levels of anti-HBs titres were determined on the 30th, 60th and 90th days following the initial injection. None of the participants in the trial had serious adverse reactions and the frequencies of minor side effects were minimal. No clinically important adverse effects which could be considered as directly related to the vaccination were recorded. The volunteers showed a very good immune response and were seroprotected on the 30th day after the first dose of vaccination. The present study revealed that the new vaccine, Revac-B is highly immunogenic and is well tolerated.