Etiologic Spectrum of Pediatric-Onset Leukodystrophies and Genetic Leukoencephalopathies: The Five-Year Experience of a Tertiary Care Center in Southern India.

BACKGROUND: White matter (WM) disorders with a genetic etiology are classified as leukodystrophies (LDs) and genetic leukoencephalopathies (GLEs). There are very few studies pertaining to the etiologic spectrum of these disorders in the Asian Indian population. METHODS: This study was conducted over a period of five years from January 2016 to December 2020, in the medical genetics department of a tertiary care hospital in southern India. A total of 107 patients up to age 18 years, with a diagnosis of a genetic WM disorder confirmed by molecular genetic testing and/or metabolic testing, were included in the study and categorized into LD or GLE group as per the classification suggested by the Global Leukodystrophy Initiative consortium in 2015. RESULTS: Forty-one patients were diagnosed to have LDs, and 66 patients had GLEs. The two most common LDs were metachromatic LD (16 patients) and X-linked adrenoleukodystrophy (seven patients). In the GLE group, lysosomal storage disorders were the most common (40 patients) followed by mitochondrial disorders (nine patients), with other metabolic disorders and miscellaneous conditions making up the rest. The clinical presentations, neuroimaging findings, and mutation spectrum of the patients in our cohort are discussed. CONCLUSIONS: This is one of the largest cohorts of genetic WM disorders reported till date from the Asian Indian population. The etiologies and clinical presentations identified in our study cohort are similar to those found in other Indian studies as well as in studies based on other populations from different parts of the world.

Hypothyroidism Prevalence in the United States: A Retrospective Study Combining National Health and Nutrition Examination Survey and Claims Data, 2009-2019.

Previous estimates determined prevalence of hypothyroidism (HT) to be 4.6% of the US population. This study aimed to update estimates of HT prevalence in the United States by retrospective analysis of 2 datasets. Data on HT type (overt or subclinical HT) and treatment were collected from the 2009-2010 and 2011-2012 National Health and Nutrition Examination Survey (NHANES) cycles. From the Optum administrative claims database, medical and pharmacy claims were collected between January 1, 2012, and December 31, 2019. Patients were defined as having HT if, per given year, they had >1 prescription for HT treatment, >1 claim indicating an HT diagnosis, or thyroid-stimulating hormone levels >4.0 mIU/L (NHANES arm). For both studies, treatment was defined as any evidence of synthetic or natural thyroid hormone replacement, identified by pharmacy claims or patient surveys. Data are reported as percentage of patients with HT and treatments received. Between 2009 and 2012, HT prevalence remained around 9.6% of the US population. The administrative claims dataset showed that HT prevalence grew from 9.5% in 2012 to 11.7% in 2019 and that >78% of patients received thyroxine (T4) monotherapy. Similarly, the NHANES dataset showed that T4 replacement therapy was the most common treatment for HT. From 2012-2019, patients with untreated HT grew from 11.8% to 14.4%. The prevalence of HT in the United States has steadily increased since 2009. Likewise, the percentage of hypothyroid-diagnosed patients not receiving treatment also increased, suggesting that the increased prevalence may be due to increased cases of subclinical HT.

Psychological stress among anesthesia residents during COVID-19 pandemic and how to mitigate them.

The impact of the novel coronavirus disease 19 (COVID-19) has overburdened the anesthesia fraternity both physically and mentally. The academic and training schedule of the medical residents in the last year was also disrupted. Since we are in the early phase of the second peak of the COVID-19 pandemic, it is time to reconsider the causes of stress in anesthesia residents and methods to mitigate them. In this non-systematic review, authors have included articles from PubMed, Medline, and Google scholar with keywords "identify strategies" "preventing and treating psychological disorders," and "medical students" from year 2010 onwards were included. Apart from these keywords, we have included the coping strategies and early psychiatric consultation methods. This review article aims at early identification, workplace environment changes, and implementation of early coping strategies in anesthesia residents during this second peak of COVID-19.

Microcephalic primordial dwarfism with predominant Meier-Gorlin phenotype, ichthyosis, and multiple joint deformities-Further expansion of DONSON Cell Cycle-opathy phenotypic spectrum.

We report a patient with microcephalic primordial dwarfism with predominant Meier-Gorlin syndrome phenotype with ichthyosis and disabling multiple joint deformities in addition to classic features of the syndrome. The patient was a 10.5-year-old girl referred in view of short stature, joint deformities, and facial dysmorphism. There was history of intrauterine growth restriction and collodion like skin abnormality at birth. She had normal developmental milestones and intellect. On clinical evaluation, anthropometry was suggestive of proportionate short stature and microcephaly. There was abnormal posture due to spine and peripheral joint deformities, along with ichthyosis, facial, and digital dysmorphism. Skeletal radiographs showed radial subluxation, acetabular dysplasia and hip dislocation, bilateral knee joint dislocation, absent patellae, slender long bones with delayed bone age, and subluxation of small joints of hands and feet. Work up for metabolic bone disease and peripheral blood karyotype was normal. Whole exome sequencing revealed a pathogenic homozygous variant c.C1297T (p.Pro433Ser) in the exon 8 of DONSON gene. This report further expands the genotypic-phenotypic spectrum of the group of disorders known as Cell Cycle-opathies.

Artificial Intelligence and technology in COVID Era: A narrative review.

Application of artificial intelligence (AI) in the medical field during the coronavirus disease 2019 (COVID-19) era is being explored further due to its beneficial aspects such as self-reported data analysis, X-ray interpretation, computed tomography (CT) image recognition, and patient management. This narrative review article included published articles from MEDLINE/PubMed, Google Scholar and National Informatics Center egov mobile apps. The database was searched for "Artificial intelligence" and "COVID-19" and "respiratory care unit" written in the English language during a period of one year 2019-2020. The relevance of AI for patients is in hands of people with digital health tools, Aarogya setu app and Smartphone technology. AI shows about 95% accuracy in detecting COVID-19-specific chest findings. Robots with AI are being used for patient assessment and drug delivery to patients to avoid the spread of infection. The pandemic outbreak has replaced the classroom method of teaching with the online execution of teaching practices and simulators. AI algorithms have been used to develop major organ tissue characterization and intelligent pain management techniques for patients. The Blue-dot AI-based algorithm helps in providing early warning signs. The AI model automatically identifies a patient in respiratory distress based on face detection, face recognition, facial action unit detection, expression recognition, posture, extremity movement analysis, visitation frequency detection sound pressure, and light level detection. There is now no looking back as AI and machine learning are to stay in the field of training, teaching, patient care, and research in the future.

A newly recognized multiple malformation syndrome with caudal regression associated with a biallelic c.402G>A variant in TBX4.

The T-box4 (TBX4) gene (OMIM *601719) belongs to the T-box family of transcription regulators that share a conserved homology domain and are expressed at specific sites during various stages of embryonic development. Tbx4 has been found to be a crucial transcriptional regulator in embryonic hindlimb development in animal models. Monoallelic variants in the TBX4 gene are reported to be associated with skeletal defects of the pelvis and lower limbs. We report here a fetus with a novel multiple malformation syndrome associated with sacrococcygeal agenesis, bilateral lower limb aplasia, hypoplastic left heart, bilateral lung hypoplasia, hydroureteronephrosis, and nonimmune fetal hydrops, found to have a homozygous nonsense variant in the TBX4 gene. We propose that biallelic variants in the TBX4 gene are associated with a severe syndromic phenotype of sacrococcygeal agenesis and lower limb reduction defects.

Elevated beta human chorionic gonadotropin in a non-pregnant female diagnosed with anal squamous cell carcinoma.

INTRODUCTION: Elevated serum beta human chorionic gonadotrophin (ß-hCG) in a female normally indicates pregnancy or possibly, gestational trophoblastic disease or ovarian germ cell tumours. Expression of ß-hCG has been demonstrated in cervical and endometrial carcinoma and other non-germ cell tumours of the ovary, vulva, breast, prostate, lung, colon, oral/facial tissue and stomach. CASE REPORT: We report a 43-year-old premenopausal woman with p16 positive squamous cell anal cancer. Pre-treatment urinary screening was positive for ß-hCG (218 IU/L), which was confirmed on serum and expressed in the tumour. Pelvic ultrasound ruled out pregnancy. Cervical cytology detected human papilloma virus p16 infection and a potential squamous intraepithelial lesion. Management and outcome: She received definitive chemoradiation (Mitomycin/5-fluorouracil) for six weeks. ß-hCG, taken four weeks post completion, had returned to normal levels (<2 IU/L). DISCUSSION: Cases of elevated serum ß-hCG are documented in different cancers including breast, gastric, lung, ovarian and renal cell. In our case, the elevated ß-hCG is probably ectopic excretion by the squamous cell carcinoma tumour in the anus. While this has never been reported previously in the anus, it is likely due to the documented risk of development of precancerous as well as cancerous anal and cervical lesions through human papilloma virus infection. Raised levels of ß-hCG have been reported in cervical cancers. Other possible causes of ß-hCG elevation were excluded. Following treatment, her ß-hCG level returned to normal strengthening the hypothesis that ß-hCG elevation was due to the anal carcinoma. In conclusion, unexplained ectopic secretion of ß-hCG may be the first sign of a primary malignancy.

Growth and characterisation of a new polymorph of barium maleate: a metal organic framework.

A new polymorph of barium maleate (BM) with chemical formula C24H14O24Ba5⋅7H2O is grown by modified gel method. Transparent plate like crystals of dimensions 9×4×1 mm(3) were obtained. Single crystal X-ray Diffraction analysis was done to determine the structure and the crystal belongs to triclinic system, P-1 space group with cell dimensions a=7.2929(3) Å, b=10.5454(4) Å, c=14.2837(6) Å, α=102.0350(10)°, ß=99.1580(10)°, γ=102.9170(10)°. Hydrogen bonding stabilises the two dimensional polymeric crystal structure. Fourier Transform Infrared spectroscopic method was utilised for the analysis of various functional groups present in the complex. Elemental analysis confirmed the stoichiometry of the complex. Thermal properties of the crystal were studied by TGA/DTA. The material melts at 368°C. The optical transparency of the crystal was studied using UV-Visible absorption spectra. The optical band gap is found to be 3.35 eV.

Thymoma and parathyroid adenoma: false-positive imaging and intriguing laboratory test results.

IMPORTANCE: Parathyroid hormone (PTH)-secreting thymomas are an exceedingly rare entity. A PTH-secreting thymoma was discovered in the workup of a patient with primary hyperparathyroidism. A concomitant parathyroid adenoma was removed from the same patient. We present the intriguing clinical course and review the literature on this rare entity. In addition, we discuss the use of scanning with technetium Tc 99m sestamibi, the PTH assay, and cervical ultrasonography in the workup of a parathyroid adenoma. OBSERVATIONS: Scanning with technetium Tc 99m sestamibi demonstrated false-positive uptake of the mediastinal thymoma and false-negative uptake of the true cervical parathyroid adenoma. After removal of the thymoma, the parathyroid adenoma demonstrated appropriate uptake on a follow-up scan. After removal of the parathyroid adenoma, the hyperparathyroidism was cured. CONCLUSIONS AND RELEVANCE: Given the extremely rare incidence of a PTH-secreting thymoma with a concurrent parathyroid adenoma, we do not recommend alterations in the diagnostic algorithm for primary hyperparathyroidism. However, in this case, the need for 2 separate operations may have been avoided by obtaining an ultrasonogram to further explore the findings on the technetium Tc 99m sestamibi scan. We recommend that both studies be considered in unclear cases of primary hyperparathyroidism.

Growth and characterisation of crystals of a new organic complex of thiourea with quinine sulphate dihydrate: an NLO material.

An organic complex of thiourea and quinine sulphate dihydrate (TQS) has been grown for the first time by gel method. The structure determination was done by the single crystal XRD technique. The crystal belongs to monoclinic system, P21 space group with cell dimensions a=6.228 (3) Å, b=20.4051 (4) Å, c=11.0600 (6) Å, ß=101.9811(2)°. The crystal structure is stabilized by the hydrogen bonding. The functional groups present in the complex were analysed by the Fourier Transform Infrared spectroscopic method. The stoichiometry of the complex was confirmed by the elemental analysis. Thermal properties of the complex were determined by TGA and DTA methods and the complex melts at 222.53°C. The optical transparency of the crystal was studied using UV-Visible absorption spectra. The optical band gap is found to be 2.5 eV. The SHG conversion efficiency of TQS was investigated using Kurtz and Perry method and found to be higher than that of the reference material, potassium dihydrogen phosphate (KDP).

Testosterone interacts with the feedback mechanisms engaged by Tyr985 of the leptin receptor and diet-induced obesity.

Inhibitory signaling through Tyr985 of the leptin receptor contributes to the attenuation of anorectic leptin action in obese animals. Leptin receptor (LEPR-B) Tyr985Leu homozygote mutant mice (termed l/l) were previously generated to study Tyr985's contributions to inhibition of LEPR-B signaling; young female l/l mice display a lean, leptin-sensitive phenotype, while young male l/l are not significantly different from wild-type. We report here that testosterone (but not estrogen) determines the sex-specificity of the l/l phenotype. This provides additional insight into the cellular mechanism by which gonadal hormones determine central sensitivity to leptin, and may help elucidate the long-noted sex differences in leptin sensitivity. Additionally, we observed that Tyr985 signaling protects against a diet-dependent switch that exacerbates obesity with high fat feeding, such that the enhanced leptin sensitivity of l/l mice on a normal diet leads to increased adiposity in the face of chronic high-fat diet.