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Amit Patil, Ranvir Ranjan, Prabhat Kumar, Himanshi Narang Department of Forensic Medicine and Toxicology, All India Institute of Medical Sciences, Patna, Bihar, 801507, IndiaCorrespondence: Amit PatilDepartment of Forensic Medicine and Toxicology, Second Floor, Academic Building, All India Institute of Medical Sciences, Phulwarisharif, Patna, Bihar, 801507, IndiaTel + (+91) 9920193750Email dramp1976@gmail.comAbstract: Hands-on or practice-based learning is the foundational objective of postgraduate teaching and training. A skilled and competent postgraduate resident is critical to the country’s health needs and is more relevant in the ongoing COVID-19 pandemic. The postgraduate medical training in India is speciality-specific and based on a structured curriculum and syllabus to achieve precise educational goals and objectives. The impact of this pandemic on postgraduate medical education and training is controversial, challenging, unknown, and far-reaching. The exceptional contagious nature of the virus and country-wide lockdowns have tremendously decreased hospital visiting patients. Abolition of outpatient and inpatient services, disruptions in clinical postings, curtailment of elective operations and procedures have adversely affected the training of residents and fellowship students in India and abroad. Apart from this, research work, mentoring, academic conferences, and workshops that offer learning experiences to these residents have been cancelled or suspended, thus denying them a chance to achieve domain knowledge and enhance their skills. Although this pandemic has offered new learning modes like teleconsultation, videoconferencing, virtual simulations, digital podcasts, etc., how much actual knowledge transfer and skill gain will be achieved is unanswered. Despite this disruption, this pandemic has offered a golden opportunity to relook at the current PG resident education and training programme. The lessons learned from this adversity offer medical universities, medical educators, and regulatory authorities many opportunities to develop a novel and innovative curriculum that enables the current and future residents to achieve the necessary proficiency and competency.Keywords: COVID-19 pandemic, postgraduate, residents, medical education, training

Microelectromechanical system (MEMS) has been used so far in today's scenario in mechatronic assemblies to enhance its functionality and mitigate the complexity of design. Micro electrodeposition technique enables to produce such features. This research is an attempt to fabricate the micro feature instantaneously using a modified ink jet printer on an aluminium substrate. The acidic electrolyte was prepared by using Cupric Sulphate Penta hydrate (CuSO4.5H2O) of 1M concentration with H2SO4. Multiple passes deposit the copper ion on Aluminium sheet with thickness of 0.2 mm. the feature design, Voltage and concentration of electrolyte has been taken as Input parameter. Surface characteristics have been discussed in this article. Result revealed thin metallic sheet can only be used for 6-7 passes due to wrinkles and edge deformation. If more passes will be carried out on an aluminium foil sheet then uniform deposition of copper metal ions will be possible. The concentration of CuSO4.5H2O has played important role in this experimental process on deposition rate. [ABSTRACT FROM AUTHOR]

Background: Apheresis component collection is a rapidly growing area in the field of Transfusion Medicine. Plateletapheresis is the most common procedure done in India. Several equipments with varying capabilities are available. AMICUS (Baxter) is one of such instruments capable of doing plateletapheresis with two types of disposable kits viz. Single Needle and Double Needle access. Aims: Comparison of procedure parameters and product quality, collected from two types of disposable kits. Materials and Methods: One Hundred plateletapheresis procedures were done on AMICUS (Version 2.5) from October 2005 to August 2006 at SPS Apollo Hospitals, Ludhiana. Fifty single needle procedures were compared with fifty double needle procedures on the parameters such as Whole blood processed, processing time, platelet yield, collection efficiency and WBC contamination. Donor reactions were also studied during the procedures. Results: Mean values for whole blood processed, processing time, platelet yield, collection efficiency and WBC contamination for single needle and double needle procedures were 3429.5 and 3293.5 ml, 90.6 and 66.4 minutes, 3.26x1011 and 3.72x1011/µl, 66.23 and 72.74% and 0.46x10³ and 0.39x10³/µl respectively. Although the platelet yield and collection efficiency were lower with single needle procedures as compared to double needle ones but were not statistically significant ( P=0.867 and 0.846 respectively). The time consumed for the procedure was more with single needle access than with dual needle and was statistically significant ( P=0.000).WBC contamination of the platelet product was within the limits set by the FDA and AABB protocols. Two adverse donor reactions (mild citrate toxicity) were reported with single needle procedures and one (mild citrate toxicity) with double needle procedures. Conclusion: Evaluation of one hundred plateletapheresis procedures done on AMICUS showed that the single needle procedures consumed more time than double needle procedures, while the product quality in the form of platelet yield and collection efficiency was equivalent with both the procedures. Only three adverse donor reactions were reported in the plateletapheresis procedures. [ABSTRACT FROM AUTHOR]

Background: The Ortho ECi assay employs an immunometric technique with enhanced chemiluminiscence for optimal assay performance. The performance of a fully automated, randomaccess, enhanced chemiluminiscence immunoassay (Ortho ECi) for the detection of HBsAg, anti-HIV and anti-HCV in the serum of blood donors was evaluated at Department of Transfusion Medicine, SPS Apollo Hospitals, Ludhiana, for a period of 14 months (June 2005 to August 2006). Aims: To evaluate the working of Ortho ECi for routine screening of blood donors. Materials and Methods: 2341 samples were processed on Ortho ECi system for all three parameters. The reactive samples were re-run on the same system. Repeat reactive samples were then sent for confirmation at the Ortho Diagnostic.s reference laboratory. Results: The overall concordance between the Ortho ECi assays for HBsAg, anti HIV and anti HCV and the corresponding confiiniatory tests was 100%, 99.8% and 99.8% respectively. The specificities of the assays for HBsAg, anti HIV and anti HCV were 100%, 99.9% and 99.8% respectively. The sensitivities of the assays for HBsAg, anti HIV and anti HCV were 100%, 100% and 100% respectively. The Positive Predictive values (PPV) of the assays for HBsAg, anti HIV and anti HCV were 100%, 33% and 85% respectively. The Negative Predictive values (NPV) of the assays for HBsAg, anti HIV and anti HCV were 100%, 100% and 100% respectively. Conclusions: The Ortho ECi assays for diagnosis of HBsAg, anti- HIV and anti-HCV are highly specific and sensitive assays. The rapid turn around time (TAT), random access, full automation and high throughput make it an effective assay system for blood bank screening programmes for blood donors, thus increasing the patient safety. The instrument has an additional advantages of intellicheck feature, closed system, capability of processing STAT samples and being user friendly with touch-screen. [ABSTRACT FROM AUTHOR]

Background: Nonalcoholic fatty liver disease (NAFLD) is the commonest type of liver disease worldwide. We aimed to assess the incidence and predictors of liver-related events (LREs) and mortality in NAFLD patients., Methods: NAFLD patients (n = 957) evaluated between January 2000 and November 2021 were included. Patients were categorised as noncirrhosis (NC), compensated cirrhosis (CC) and decompensated cirrhosis (DC), and the incidence of LRE and mortality were estimated and compared., Results: The proportions of NC, CC and DC were 87.8% (n = 840), 8.8% (n = 84) and 3.4% (n = 33), respectively. The median follow-up duration was 3.9 (3.0-5.7) years, and the total cumulative duration was 4633 person-years. The incidence of LRE per 100 person-years was 0.14, 2.72 and 10.24 in patients with NC, CC and DC, respectively. The incidence of mortality was 0.12, 1.05 and 4.24 per 100 person-years, respectively, in the 3 groups. The causes of mortality in the 3 groups were liver related in 1/5 (20%), 3/4 (75%) and 6/9 (66.7%), respectively. Overall, the mortality rate was higher in those with diabetes than those without diabetes (log-rank P value = 0.005). On further analysis, diabetes was associated with poor outcomes only in NC group (log-rank P value = 0.036), and not in CC (log-rank P value = 0.353) or DC groups (log-rank P value = 0.771). On multivariate Cox proportional hazard analysis, age (hazard ratio [HR] 1.070), hypertension (HR 4.361) and DC (HR 15.036) were independent predictors of poor outcomes. Liver stiffness measurement, bilirubin, CC and DC were independent predictors of LRE., Conclusion: In our study of NAFLD from India, the incidence of LRE was found to be similar to that seen in Western studies. In NC NAFLD, diabetes was associated with poor outcomes., (© 2022 Indian National Association for Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Touraine-Solente-Gole syndrome is a rare, autosomal dominant multisystem disorder arising from dysregulated prostaglandin synthesis due to underlying genetic defects. Early symptoms are related to skin and soft tissue involvement (coarse facial features, widening of wrists, etc) and may thus be overlooked unless a careful physical examination is carried out. Secondary causes of pachydermoperiosteitis must always be looked for in such patients. During evaluation, a systemic review of all organ systems should be carried out to identify asymptomatic or subclinical involvement of organ systems and identify means to avoid disease progression. Treatment options are limited to steroids and non-steroidal anti-inflammatory drugs. In the absence of definitive guidelines, clinical decisions are largely case based, with no definite duration of drug therapy or screening of potential malignancies outlined in current literature. Mental health and social rehabilitation of these patients due to their disfiguring deformities are an unmet need., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Anopheles stephensi is the most menacing malaria vector to watch for in newly urbanising parts of the world. Its fitness is reported to be a direct consequence of the vector adapting to laying eggs in over-head water tanks with street-side water puddles polluted by oil and sewage. Large frequent inversions in the genome of malaria vectors are implicated in adaptation. We report the genome assembly of a strain of An. stephensi of the type-form, collected from a construction site from Chennai (IndCh) in 2016. The genome reported here with a L50 of 4, completes the trilogy of high-resolution genomes of strains with respect to a 16.5 Mbp 2Rb genotype in An. stephensi known to be associated with adaptation to environmental heterogeneity. Unlike the reported genomes of two other strains, STE2 (2R+ b /2Rb) and UCI (2Rb/2Rb), IndCh is found to be homozygous for the standard form (2R+ b /2R+ b ). Comparative genome analysis revealed base-level details of the breakpoints and allowed extraction of 22,650 segregating SNPs for typing this inversion in populations. Whole genome sequencing of 82 individual mosquitoes from diverse geographical locations reveal that one third of both wild and laboratory populations maintain the heterozygous genotype of 2Rb. The large number of SNPs can be tailored to 1740 exonic SNPs enabling genotyping directly from transcriptome sequencing. The genome trilogy approach accelerated the study of fine structure and typing of an important inversion in An. stephensi, putting the genome resources for this understudied species on par with the extensively studied malaria vector, Anopheles gambiae. We argue that the IndCh genome is relevant for field translation work compared to those reported earlier by showing that individuals from diverse geographical locations cluster with IndCh, pointing to significant convergence resulting from travel and commerce between cities, perhaps, contributing to the survival of the fittest strain., (© 2022. The Author(s).)

Aim: To evaluate the buccal, lingual, mesial, and distal crestal bone around implant using CBCT analysis having buccal crestal bone width of 1 mm after placement of implant and after 3 months of loading., Materials and Methods: Twenty-five patients between 18 and 60 years of age with adequate bone width and height were selected for this in-vivo study with single or multiple missing teeth. Surgical stent was fabricated for all of them by using self-cure acrylic resin for selection of implant according to the availability of bone, and gutta-percha was used as radio-opaque marker to locate the implant site. After proper analysis, in the first stage surgery, implants were placed. After 3 months to this, the second stage surgery was performed followed by elastomeric impression for porcelain fused to metal prosthesis fabrication. The buccal, lingual, mesial, and distal bone width and height were evaluated by using cone-beam computed tomography (CBCT). CBCT was standardized in terms of FOV (field of vision), slice thickness, and interval. After 3 months of loading, CBCT was taken to evaluate the alteration in the crestal bone around implants. Pre- and post-loading, crestal bone on four locations was measured by using CBCT software., Results: There is significant bone loss at all the locations, buccal, lingual, mesial, and distal, at the time of placement and after 3 months of loading of implant ( p <0.05). The mean difference of 0.840, 0.933, 0.840, and 0.380 at buccal, lingual, mesial, and distal locations, respectively, shows statistically significant difference in pre- and post-values of mean bone loss at buccal, lingual, mesial, and distal positions. Pre-loading bone loss was maximum in the distal surface, while post-loading bone loss was maximum in the buccal surface., Conclusion: From this study, it is concluded that although crestal bone loss was higher before implant placement, there was significant alteration in crestal bone even after loading of implant., Clinical Significance: It is widely accepted that the bone loss around the implant crest module is multidisciplinary in nature. Long-term preservation of the crestal bone is a paramount for successfully functioning of dental implants. Preserving crestal bone will help in dissipating the functional load. With proper treatment planning by the practitioner, this technical contribution to the crestal bone loss can be minimized and long-term survival of dental implants can be achieved.

Double strand break (DSB) repair primarily occurs through 3 pathways: non-homologous end-joining (NHEJ), alternative end-joining (Alt-EJ), and homologous recombination (HR). Typical methods to measure pathway usage include integrated cassette reporter assays or visualization of DNA damage induced nuclear foci. It is now well understood that repair of Cas9-induced breaks also involves NHEJ, Alt-EJ, and HR pathways, providing a new format to measure pathway usage. Here, we have developed a simple Cas9-based system with validated repair outcomes that accurately represent each pathway and then converted it to a droplet digital PCR (ddPCR) readout, thus obviating the need for Next Generation Sequencing and bioinformatic analysis with the goal to make Cas9-based system accessible to more laboratories. The assay system has reproduced several important insights. First, absence of the key Alt-EJ factor Pol θ only abrogates ∼50% of total Alt-EJ. Second, single-strand templated repair (SSTR) requires BRCA1 and MRE11 activity, but not BRCA2, establishing that SSTR commonly used in genome editing is not conventional HR. Third, BRCA1 promotes Alt-EJ usage at two-ended DSBs in contrast to BRCA2. This assay can be used in any system, which permits Cas9 delivery and, importantly, allows rapid genotype-to-phenotype correlation in isogenic cell line pairs., (© The Author(s) 2021. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Purpose: The spatial distribution of collagen fibril dispersion has a significant impact on both corneal biomechanical and optical behaviors. The goal of this study was to demonstrate a novel method to characterize collagen fibril dispersion using intraocular pressure (IOP)-induced changes in corneal optical aberrations for individualized finite-element (FE) modeling., Methods: The method was tested through both numerical simulations and ex vivo experiments. Inflation tests were simulated in FE models with three assumed patterns of collagen fibril dispersion and experimentally on three rhesus monkey corneas. Geometry, matrix stiffness, and the IOP-induced changes in wavefront aberrations were measured, and the collagen fibril dispersion was characterized. An individualized corneal model with customized collagen fibril dispersion was developed, and the estimated optical aberrations were compared with the measured data., Results: For the theoretical investigations, three assumed distributions of fibril dispersion were all successfully characterized. The estimated optical aberrations closely matched the measured data, with average root-mean-square (RMS) differences of 0.29, 0.24, and 0.10 µm for the three patterns, respectively. The overall features of the IOP-induced changes in optical aberrations were estimated for two ex vivo monkey corneas, with average RMS differences of 0.57 and 0.43 µm. Characterization of the fibril dispersion in the third cornea might have been affected by corneal hydration, resulting in an increased RMS difference, 0.8 µm., Conclusions: A more advanced corneal model with individualized distribution of collagen fibril dispersion can be developed and used to improve our ability to understand both biomechanical and optical behaviors of the cornea.

Squamous cell carcinomas (SCCs) arising from aerodigestive or anogenital epithelium that are associated with the human papillomavirus (HPV) are far more readily cured with radiation therapy than HPV-negative SCCs. The mechanism behind this increased radiosensitivity has been proposed to be secondary to defects in DNA repair, although the specific repair pathways that are disrupted have not been elucidated. To gain insight into this important biomarker of radiosensitivity, we first examined genomic patterns reflective of defects in DNA double-strand break repair, comparing HPV-associated and HPV-negative head and neck cancers (HNSCC). Compared to HPV-negative HNSCC genomes, HPV+ cases demonstrated a marked increase in the proportion of deletions with flanking microhomology, a signature associated with a backup, error-prone double-strand break repair pathway known as microhomology-mediated end-joining (MMEJ). Then, using 3 different methodologies to comprehensively profile double-strand break repair pathways in isogenic paired cell lines, we demonstrate that the HPV16 E7 oncoprotein suppresses canonical nonhomologous end-joining (NHEJ) and promotes error-prone MMEJ, providing a mechanistic rationale for the clinical radiosensitivity of these cancers., Competing Interests: Competing interest statement: S.S.H. and D.S.H. are listed as inventors on a provisional patent filed by their institution related to the method used in Fig. 4. There are no licenses or royalties.

The perception of toxicity to nitric oxide (NO) and irradiation (IR) by three different cell types has been studied. The three cell types are the macrophage like RAW264.7 cells, EL4 lymphoma cells, and splenocytes, which represent the different components of a tumor. These three cell types respond differently to NO donors (SNP and SNAP) and radiation treatment. The macrophages were found to be most radio-resistant and insensitive to NO donors. The innate resistance of the macrophages was not due to its antioxidant defense system since there was no significant activation of the enzymes (superoxide dismutases, catalase, and glutathione peroxidase) in RAW264.7 cells after NO donor and irradiation. But the cell cycle arrest of the three cell types was different from each other. The EL4 cells were found to arrest in the G2/M phase while the macrophages were found arrested in the G1 phase of the cell cycle. Such specific killing of the tumor cell in response to NO donor while sparing the macrophages can be of immense importance to radiotherapy.

Mitogen activated protein kinases (MAPKs) play an important role in activation, differentiation and proliferation of macrophages. Macrophages, upon activation, produce large amounts of nitric oxide that inhibit the growth of variety of microorganisms and tumor cells. This nitric oxide which is known to interfere with tyrosine phosphorylation may result in changes in the pattern of activation of MAPKs. In a previous study we have found that tyrosine phosphorylation of MAPKs was completely abolished in the presence of nitric oxide donor and radiation but this did not affect the function of macrophages. In this study the other post translational modifications namely nitration and ubiquitination of JNK and ERK have been looked at. Both ERK and JNK were found to be nitrated. However, there was no increase in ubiquitination of ERK and JNK, indicating that ubiquitination, in this case was not a natural consequence of nitration and may serve in signaling. Additionally, when the nitration was extensive, phosphorylation was also inhibited. The activation of substrates of ERK and JNK were looked at to determine the consequences of such modifications. Inhibition of phosphorylation and extensive nitration of JNK did not prevent activation of its substrate, c-jun. This study indicates that ERK and JNK may be under regulation by different type of modifications in macrophages.