Exclusive transabdominal trans-amniotic approach for chorionic villus sampling in posterior placenta: a novel approach for prenatal diagnosis of genetic disorders

Background: The objective of the study was to evaluate role and safety of transabdominal trans-amniotic approach for Chorionic villus sampling (CVS) for prenatal diagnosis of genetic disorders.Methods: Retrospective analytical study carried out on data form couples coming for pre-natal diagnosis from January 2010 to February 2021. Patient related parameters like age, gestational age; procedure related parameters like amount of sample, number of attempts required; different genetic disorder diagnosed and complications by both the approaches of CVS were recorded and analyzed.Results: Total 2287 patients undergoing CVS with mean age of 27±3.3 years were included. Majority (1621;70.9%) had CVS procedure at gestational age of 12-14 weeks. On analyzing physician’s perception, 663 (29%) patients having complete posterior placenta could not be accessible with routine trans-abdominal CVS and opted for trans-amniotic approach. Amount of sample yield and number of attempts were not statistically significant (p>0.05) by both methods of CVS. Thalassemia major was found in 948 (41.45%) followed by thalassemia minor in 525 (22.96%) patients. No statistically significant difference was found for developing complications by both the methods (p>0.05). Most common complication was pain and discomfort which was relieved by simple analgesics. Out of total 17 (0.74%) abortions; 13 (0.80%) from routine transabdominal and 4 (0.60%) from trans-amniotic route CVS with no statistically significant difference among them (p>0.05). No case of post procedure infection was observed.Conclusions: In complete posterior placenta CVS procedures usually postponed by most physicians leading to delay in diagnosis of genetic disorders. The novel method transabdominal trans-amniotic approach for CVS is effective and safe in skilled hands and can help in early prenatal diagnosis of genetic disorders.

Dermatological disorders during pregnancy: a study from tertiary care hospital

Background: Various types of physiological and pathological mucocutaneous changes are commonly observed during pregnancy. Infectious, non-infectious and pregnancy specific dermatoses are seen during pregnancy. This study was carried out with an aim of studying association of various dermatosis with pregnancy and to find out incidence of pregnancy specific dermatoses v/s non-specific dermatosis.Methods: Total 131 pregnant female presenting with complain of skin lesions were included in study. Detail examination and necessary investigations were carried out to diagnose type of skin disease.Results: Out of 131 patients, only 11(8.4%) patients presented with pregnancy specific dermatoses while rest 120 (91.6%) presented with pregnancy non-specific dermatoses. Among pregnancy non-specific dermatoses, non-infectious conditions were found in 48.1% and 43.5% presented with infectious dermatoses. Most common infectious dermatoses was herpes labialis while most common non-infectious dermatosis was pruritus. Conclusions: Pregnancy specific dermatoses are rare and require vigilant eye to recognize them while wide variety of pregnancy non-specific dermatoses are commonly encountered and require prompt diagnosis and treatment for uneventful pregnancy outcome

ECG Signal Analysis with DB6 Wavelet using Verilog HDL.docx

The abnormal condition of electrical activity of the heart is given by ECG (Electrocardiogram). The peaks and the valleys of the ECG signal depict the useful information about the nature of disease affecting the heart.ECG signals are very low frequency signals, of about 0.5 Hz-100 Hz. Discrete Wavelet Transform (DWT) has been used in last few years in many applications. In this paper, it has been used as a tool for noise removal and extraction of QRS complex. Db6 using FIR filter has been designed using Verilog Hardware Description Language (HDL). ModelSim Altera 6.4a is used as simulator. DOI: 10.17762/ijritcc2321-8169.16049

Three-dimensional architecture of the human BRCA1-A histone deubiquitinase core complex

BRCA1 is a tumor suppressor found to be mutated in hereditary breast and ovarian cancer and plays key roles in the maintenance of genomic stability by homologous recombination repair. It is recruited to damaged chromatin as a component of the BRCA1-A deubiquitinase, which cleaves K63-linked ubiquitin chains attached to histone H2A and H2AX. BRCA1-A contributes to checkpoint regulation, repair pathway choice, and HR repair efficiency through molecular mechanisms that remain largely obscure. The structure of an active core complex comprising two Abraxas/BRCC36/BRCC45/MERIT40 tetramers determined by negative-stain electron microscopy (EM) reveals a distorted V-shape architecture in which a dimer of Abraxas/BRCC36 heterodimers sits at the base, with BRCC45/Merit40 pairs occupying each arm. The location and ubiquitin-binding activity of BRCC45 suggest that it may provide accessory interactions with nucleosome-linked ubiquitin chains that contribute to their efficient processing. Our data also suggest how ataxia telangiectasia mutated (ATM)-dependent BRCA1 dimerization may stabilize self-association of the entire BRCA1-A complex

Survey on the perceptions of UK gastroenterologists and endoscopists to artificial intelligence

Background and aims: With the potential integration of artificial intelligence (AI) into clinical practice, it is essential to understand end users’ perception of this novel technology. The aim of this study, which was endorsed by the British Society of Gastroenterology (BSG), was to evaluate the UK gastroenterology and endoscopy communities’ views on AI. Methods: An online survey was developed and disseminated to gastroenterologists and endoscopists across the UK. Results: One hundred four participants completed the survey. Quality improvement in endoscopy (97%) and better endoscopic diagnosis (92%) were perceived as the most beneficial applications of AI to clinical practice. The most significant challenges were accountability for incorrect diagnoses (85%) and potential bias of algorithms (82%). A lack of guidelines (92%) was identified as the greatest barrier to adopting AI in routine clinical practice. Participants identified real-time endoscopic image diagnosis (95%) as a research priority for AI, while the most perceived significant barriers to AI research were funding (82%) and the availability of annotated data (76%). Participants consider the priorities for the BSG AI Task Force to be identifying research priorities (96%), guidelines for adopting AI devices in clinical practice (93%) and supporting the delivery of multicentre clinical trials (91%). Conclusion: This survey has identified views from the UK gastroenterology and endoscopy community regarding AI in clinical practice and research, and identified priorities for the newly formed BSG AI Task Force

British Lung Foundation/United Kingdom primary immunodeficiency network consensus statement on the definition, diagnosis, and management of granulomatous-lymphocytic interstitial lung disease in common variable immunodeficiency disorders

A proportion of people living with common variable immunodeficiency disorders develop granulomatous-lymphocytic interstitial lung disease (GLILD). We aimed to develop a consensus statement on the definition, diagnosis, and management of GLILD. All UK specialist centers were contacted and relevant physicians were invited to take part in a 3-round online Delphi process. Responses were graded as Strongly Agree, Tend to Agree, Neither Agree nor Disagree, Tend to Disagree, and Strongly Disagree, scored +1, +0.5, 0, −0.5, and −1, respectively. Agreement was defined as greater than or equal to 80% consensus. Scores are reported as mean ± SD. There was 100% agreement (score, 0.92 ± 0.19) for the following definition: “GLILD is a distinct clinico-radio-pathological ILD occurring in patients with [common variable immunodeficiency disorders], associated with a lymphocytic infiltrate and/or granuloma in the lung, and in whom other conditions have been considered and where possible excluded.” There was consensus that the workup of suspected GLILD requires chest computed tomography (CT) (0.98 ± 0.01), lung function tests (eg, gas transfer, 0.94 ± 0.17), bronchoscopy to exclude infection (0.63 ± 0.50), and lung biopsy (0.58 ± 0.40). There was no consensus on whether expectant management following optimization of immunoglobulin therapy was acceptable: 67% agreed, 25% disagreed, score 0.38 ± 0.59; 90% agreed that when treatment was required, first-line treatment should be with corticosteroids alone (score, 0.55 ± 0.51)

Non-Toxin-Producing Bacillus cereus Strains Belonging to the B. anthracis Clade Isolated from the International Space Station

ABSTRACT: In an ongoing Microbial Observatory investigation of the International Space Station (ISS), 11 Bacillus strains (2 from the Kibo Japanese experimental module, 4 from the U.S. segment, and 5 from the Russian module) were isolated and their whole genomes were sequenced. A comparative analysis of the 16S rRNA gene sequences of these isolates showed the highest similarity (>99%) to the Bacillus anthracis-B. cereus-B. thuringiensis group. The fatty acid composition, polar lipid profile, peptidoglycan type, and matrix-assisted laser desorption ionization-time of flight profiles were consistent with the B. cereus sensu lato group. The phenotypic traits such as motile rods, enterotoxin production, lack of capsule, and resistance to gamma phage/penicillin observed in ISS isolates were not characteristics of B. anthracis. Whole-genome sequence characterizations showed that ISS strains had the plcR non-B. anthracis ancestral "C" allele and lacked anthrax toxin-encoding plasmids pXO1 and pXO2, excluding their identification as B. anthracis. The genetic identities of all 11 ISS isolates characterized via gyrB analyses arbitrarily identified them as members of the B. cereus group, but traditional DNA-DNA hybridization (DDH) showed that the ISS isolates are similar to B. anthracis (88% to 90%) but distant from the B. cereus (42%) and B. thuringiensis (48%) type strains. The DDH results were supported by average nucleotide identity (>98.5%) and digital DDH (>86%) analyses. However, the collective phenotypic traits and genomic evidence were the reasons to exclude the ISS isolates from B. anthracis. Nevertheless, multilocus sequence typing and whole-genome single nucleotide polymorphism analyses placed these isolates in a clade that is distinct from previously described members of the B. cereus sensu lato group but closely related to B. anthracis. IMPORTANCE: The International Space Station Microbial Observatory (Microbial Tracking-1) study is generating a microbial census of the space station's surfaces and atmosphere by using advanced molecular microbial community analysis techniques supported by traditional culture-based methods and modern bioinformatic computational modeling. This approach will lead to long-term, multigenerational studies of microbial population dynamics in a closed environment and address key questions, including whether microgravity influences the evolution and genetic modification pathogenic (B. anthracis), food poisoning (B. cereus), and biotechnologically useful (B. thuringiensis) microorganisms; their presence in a closed system such as the ISS might be a concern for the health of crew members. A detailed characterization of these potential pathogens would lead to the development of suitable countermeasures that are needed for long-term future missions and a better understanding of microorganisms associated with space missions

Genomic copy number variation in Mus musculus.

BACKGROUND: Copy number variation is an important dimension of genetic diversity and has implications in development and disease. As an important model organism, the mouse is a prime candidate for copy number variant (CNV) characterization, but this has yet to be completed for a large sample size. Here we report CNV analysis of publicly available, high-density microarray data files for 351 mouse tail samples, including 290 mice that had not been characterized for CNVs previously. RESULTS: We found 9634 putative autosomal CNVs across the samples affecting 6.87% of the mouse reference genome. We find significant differences in the degree of CNV uniqueness (single sample occurrence) and the nature of CNV-gene overlap between wild-caught mice and classical laboratory strains. CNV-gene overlap was associated with lipid metabolism, pheromone response and olfaction compared to immunity, carbohydrate metabolism and amino-acid metabolism for wild-caught mice and classical laboratory strains, respectively. Using two subspecies of wild-caught Mus musculus, we identified putative CNVs unique to those subspecies and show this diversity is better captured by wild-derived laboratory strains than by the classical laboratory strains. A total of 9 genic copy number variable regions (CNVRs) were selected for experimental confirmation by droplet digital PCR (ddPCR). CONCLUSION: The analysis we present is a comprehensive, genome-wide analysis of CNVs in Mus musculus, which increases the number of known variants in the species and will accelerate the identification of novel variants in future studies

CSF1R inhibitor JNJ-40346527 attenuates microglial proliferation and neurodegeneration in P301S mice

Neuroinflammation and microglial activation are significant processes in Alzheimer’s disease pathology. Recent genome-wide association studies have highlighted multiple immune-related genes in association with Alzheimer’s disease, and experimental data have demonstrated microglial proliferation as a significant component of the neuropathology. In this study, we tested the efficacy of the selective CSF1R inhibitor JNJ-40346527 (JNJ-527) in the P301S mouse tauopathy model. We first demonstrated the anti-proliferative effects of JNJ-527 on microglia in the ME7 prion model, and its impact on the inflammatory profile, and provided potential CNS biomarkers for clinical investigation with the compound, including pharmacokinetic/pharmacodynamics and efficacy assessment by TSPO autoradiography and CSF proteomics. Then, we showed for the first time that blockade of microglial proliferation and modification of microglial phenotype leads to an attenuation of tau-induced neurodegeneration and results in functional improvement in P301S mice. Overall, this work strongly supports the potential for inhibition of CSF1R as a target for the treatment of Alzheimer’s disease and other tau-mediated neurodegenerative diseases