Perioperative and functional outcomes following robot-assisted partial nephrectomy: Descriptive analysis of Indian study group on partial nephrectomy database.

Introduction: There is an unmet need for high-quality data for Robot-assisted partial nephrectomy (RAPN) in the Indian population. Indian study group on partial nephrectomy (ISGPN) is a consortium of Indian centers contributing to the partial nephrectomy (PN) database. The current study is a descriptive analysis of perioperative and functional outcomes following RAPN. Methods: For this study, the retrospective ISGPN database was reviewed, which included patients who underwent RAPN for renal masses at 14 centers across India from September 2010 to September 2022. Demographic, clinical, radiological, perioperative, and functional data were collected and analyzed. Ethics approval was obtained from each of the participating centers. Results: In this study, 782 patients were included, and 69.7% were male. The median age was 53 years (interquartile range [IQR 44-62]), median operative time was 180 min (IQR 133-240), median estimated blood loss was 100 mL (IQR 50-200), mean warm ischemia time was 22.7 min and positive surgical margin rates were 2.5%. The complication rate was 16.2%, and most of them were of minor grade. Trifecta and pentafecta outcomes were attained in 61.4% and 60% of patients, respectively. Conclusions: This is the largest Indian multi-centric study using the Indian Robotic PN Collaborative database to evaluate the outcomes of robot-assisted PN, and has proven its safety and efficacy in the management of renal masses.

Modulatory potential of Bacopa monnieri against aflatoxin B1 induced biochemical, molecular and histological alterations in rats.

Oxidative injury is concerned with the pathogenesis of several liver injuries, including those from acute liver failure to cirrhosis. This study was designed to explore the antioxidant activity of Bacopa monnieri (BM) on Aflatoxin B1 (AFB1) induced oxidative damage in Wistar albino rats. Aflatoxin B1 treatment (200 µg/kg/day, p.o.) for 28 days induced oxidative injury by a significant alteration in serum liver function test marker enzymes (AST, ALT, ALP, LDH, albumin and bilirubin), inflammatory cytokines (IL-6, IL-10 and TNF-α), thiobarbituric acid reactive substances (TBARS) along with reduction of antioxidant enzymes (GSH, SOD, CAT), GSH cycle enzymes and drug-metabolizing enzymes (AH and AND). Treatment of rats with B. monnieri (20, 30 and 40 mg/kg for 5 days, p.o.) after 28 days of AFB1 intoxication significantly restored these parameters near control in a dose-dependent way. Histopathological examination disclosed extensive hepatic injuries, characterized by cellular necrosis, infiltration, congestion and sinusoidal dilatation in the AFB1-treated group. Treatment with B. monnieri significantly reduced these toxic effects resulting from AFB1. B. monnieriper se group (40 mg/kg) did not show any significant change and proved safe. The cytotoxic activity of B. monnieri was also evaluated on HepG2 cells and showed a good percentage of cytotoxic activity. This finding suggests that B. monnieri protects the liver against oxidative damage caused by AFB1, which aids in the evaluation of the traditional usage of this medicinal plant.

Effect of herbal antioxidants on the shear bond strength of composite resin to bleached enamel at different time intervals.

Background: Anterior tooth discolorations can be treated conservatively and noninvasively through bleaching to achieve the desired esthetic outcomes. However, bleaching along with composite resin is advisable for certain clinical cases for optimum results. However, shear bond strength (SBS) of composite resin to the bleached tooth gets significantly lowered. Before placing the composite restoration, the bleached enamel needs to be treated with antioxidant agents to increase its SBS. The study aims to evaluate and compare the effect of herbal antioxidants on SBS of composite resin to bleached enamel at different time intervals. Materials and Methods: Sixty extracted single-rooted maxillary incisors postdecoronation, keeping their labial surfaces up were mounted in cold-cure acrylic resin. The samples were randomly divided into: Group I - unbleached; Group II - 10% pine bark extract for 10 min postbleaching; Group III - 10% pine bark extract for 20 min postbleaching; Group IV - application of 10% rosemary extract for 10 min postbleaching, Group V - application of 10% rosemary extract for 20 min postbleaching; Group VI - no application of antioxidant. 35% hydrogen peroxide was used for bleaching all the samples except those which served as negative control. Later composite cylinder 4 mm in diameter and length were built on prepared enamel. The maximum load at failure was recorded using the universal testing machine. Statistical Analysis: Data were analyzed using the analysis of variance and Tukey's t-test with significance level of P < 0.05. Results: Highest load was exhibited by Group I. Group V showed satisfactory shear strength followed by Groups IV, III, II, and VI. Conclusion: Both 10% rosemary and 10% pine bark extracts showed better results when applied for 20 min as compared to 10 min application. Increased duration of antioxidant application increases the SBS.

A Comparative Evaluation of Push-Out Bond Strength of Six Different Root Canal Sealers: An In-Vitro Study.

BACKGROUND: Adhesiveness with radicular dentin is absent with gutta-percha, leading to microleakage and hence re-infection. Root canal sealer helps to achieve an adhesive interface between gutta-percha and root dentin thereby resisting the displacement forces during the functioning of teeth which is evaluated by the push-out test. The aim of this study is to compare the push-out bond strength and to assess the relative bond failure between dentin-sealer, sealer-main cone of (1) epoxy resin, (2) silicon, (3) mineral trioxide aggregate (MTA), (4) calcium hydroxide, (5) bioceramic, (6) zinc oxide eugenol containing root canal sealers. METHODOLOGY: Sixty human permanent lower premolars with one root were collected, disinfected, and decoronated at cemento-enamel junction. Instrumentation was done with a K3 40,0.06 Ni-Ti rotary file and obturated using the main cone and sealer. Based on the sealer utilized, six groups were created: Group 1: AH-Plus, Group 2: RoekoSeal, Group 3: MTA Fillapex, Group 4: Apexit, Group 5: Smart Paste Bio, and Group 6: Procosol. One slice each was obtained from the coronal, middle, and apicalsections of all the obturated canals. Push-out bond strength and failure modes were studied. Statistics involved analysis of variance (ANOVA) followed by the post hoc Tukey test. RESULTS: All three sections exhibited the highest strength for Smart Paste Bio sealer and the least was for RoekoSeal. With all the sealers, the apical section had the highest strength followed by the middle and coronal. CONCLUSION: The smart seal system was superior to all other sealers and displayed a good bond to dentin.

Assessment of the impact of XP-Endo Finisher file on push-out bond strength of various endodontic sealers.

Background: An endodontic treatment is considered a success after thorough chemomechanical debridement coupled with obturating root canals in a concrete way thereby providing hermetic seal. Gutta-percha being nonadherent necessitates use of a sealer to achieve hermetic seal. Adequate adhesion of root canal sealer with gutta-percha core and radicular dentin ensures lack of apical leakage. Materials and Methods: Sixty extracted mandibular premolars with single root canal decoronated at cementoenamel junction were selected and randomly allocated to two groups (n = 30). Samples in Group 1 were prepared with BT Race file, while Group 2 samples were prepared with BT Race alongwith XP Endo file. Absorbent paper points were used for canal drying and samples were randomly divided into six subgroups. In Subgroup I, obturation was done with bio-ceramic (BC) sealer (Endosequence BC) and BC gutta-percha. In Subgroup II, resin-based (AH plus) sealer and gutta-percha were used. In Subgroup III, calcium hydroxide-based (Sealapex) sealer and gutta-percha were used. Sectioning of root samples was done perpendicularly into coronal, middle, and apical segments of 3 mm each. A universal testing machine was used for sample testing, in which push-out bond strength corresponded to the highest value obtained. Stereomicroscopic (×20) study of the samples determined the failure mode at dentin/sealer/main cone interface. Statistical Analysis: Analysis of variance and post hoc Tukey's tests were used for data analysis. Results: Endosequence BC with XP-Endo files showed the highest mean push-out bond strength (16.31 MPa), whereas Sealapex without XP-Endo file had the lowest values (12.76 MPa). Mixed failure of adhesive and cohesive mode was observed for most samples. Conclusion: Adjunctive irrigation agitation technique utilizing XP-Endo Finisher facilitates biofilm eradication from difficult niches in root canals, thereby improving adhesion of sealer and subsequently the sealer bond strength.

Synergistic Binding of SARS-CoV-2 to ACE2 and Gangliosides in Native Lipid Membranes.

Viruses utilize cell surface glycans and plasma membrane receptors to attain an adequate attachment strength for initiating cellular entry. We show that SARS-CoV-2 particles bind to endogenous ACE2 receptors and added sialylated gangliosides in near-native membranes. This was explored using supported membrane bilayers (SMBs) that were formed using plasma membrane vesicles having endogenous ACE2 and GD1a gangliosides reconstituted in lipid vesicles. The virus binding rate to the SMBs is influenced by GD1a and inhibition of the ganglioside reduces the extent of virus binding to the membrane receptors. Using combinations of inhibition assays, we confirm that added GD1a in lipid membranes increases the availability of the endogenous ACE2 receptor and results in the synergistic binding of SARS-CoV-2 to the membrane receptors in SMBs.

Health-related quality of life in patients with newly diagnosed advanced ovarian cancer treated with niraparib vs placebo: Results from the phase 3 randomized PRIMA/ENGOT-OV26/GOG-3012 trial.

OBJECTIVE: To assess patient-reported health-related quality of life (HRQoL) in patients with ovarian cancer (OC) who received niraparib as first-line maintenance therapy. METHODS: PRIMA/ENGOT-OV26/GOG-3012 (NCT02655016) enrolled patients with newly diagnosed advanced OC who responded to first-line platinum-based chemotherapy. Patients were randomized (2:1) to niraparib or placebo once daily in 28-day cycles until disease progression, intolerable toxicity, or death. HRQoL was assessed as a prespecified secondary end point using patient-reported responses to the European Organisation for Research and Treatment of Cancer QOL Questionnaire (EORTC QLQ-C30), the EORTC QLQ Ovarian Cancer Module (EORTC QLQ-OV28), the Functional Assessment of Cancer Therapy-Ovarian Symptom Index (FOSI), and EQ-5D-5L questionnaires. Assessments were collected at baseline and every 8 weeks (±7 days) for 56 weeks, beginning on cycle 1/day 1, then every 12 weeks (±7 days) thereafter while the patient received study treatment. RESULTS: Among trial participants (niraparib, n = 487; placebo, n = 246), PRO adherence exceeded 80% for all instruments across all cycles. Patients reported no decline over time in HRQoL measured via EORTC QLQ-C30 Global Health Status/QoL and FOSI overall scores. Scores for abdominal/gastrointestinal symptoms (EORTC QLQ-OV28) and nausea and vomiting, appetite loss, and constipation (EORTC QLQ-C30) were higher (worse symptoms) in niraparib-treated patients than placebo-treated patients; except for constipation, these differences resolved over time. Patients did not self-report any worsening from baseline of fatigue, headache, insomnia, or abdominal pain on questionnaires. CONCLUSIONS: Despite some early, largely transient increases in gastrointestinal symptoms, patients with OC treated with niraparib first-line maintenance therapy reported no worsening in overall HRQoL.

Computing the Cost of Care per Patient per Day for Patients With Metastatic Neuroendocrine Neoplasms.

PURPOSE: Patients with well-differentiated, low-grade metastatic neuroendocrine neoplasms (NENs) usually have a long median survival and require complex, expensive care over many years at multidisciplinary centers. The cost burden for patients and institutions serves as a barrier to care. Understanding the drivers of these costs and whether intense monitoring adds value will help to optimize value-based care. METHODS: We adapted the cost of care per patient per day (CCPD) validated methodology to measure cost while accounting for varying follow-up duration. We queried the Stanford NEN Database, which aggregates data from the electronic health record and other electronic sources, to study patients with metastatic NENs receiving regular care at Stanford. Current Procedural Terminology codes for services incurred during the monitoring period for each patient were mapped to the corresponding cost conversion factor and date in the Medicare fee schedule. RESULTS: Two hundred two patients between 2010 and 2017 were studied with a mean CCPD of $119.11 in US dollars (USD); NEN-specific systemic therapy made up 55% of this cost. Somatostatin analogs were the costliest systemic therapy. Systemic therapy was the driver of cost differences among patients with various primary tumor types, stage of disease, tumor differentiation and grade, and functional hormone status. Patients in the most expensive CCPD group did not have a significant survival benefit (P = .66). CONCLUSION: The CCPD methodology was effective in studying cancer care value in NENs. Systemic therapy, specifically somatostatin analogs, was the primary driver of cost, and intense monitoring and higher-cost care did not improve survival outcomes.

High sensitivity troponin I as a biomarker for cardiac allograft vasculopathy: Evaluation of diagnostic potential and clinical utility.

INTRODUCTION: Cardiac allograft vasculopathy (CAV) limits long-term survival in heart transplant (HTx) recipients. The use of biomarkers in CAV surveillance has been studied, but none are used in clinical practice. The predictive value of high-sensitivity troponin I (hsTnI) has not been extensively investigated in HTx recipients. METHODS: HTx patients undergoing surveillance coronary angiograms and enrolled in the Emory Cardiovascular Biobank had plasma hsTnI measured. CAV grade was assessed using ISHLT nomenclature. Multivariable cumulative link mixed modeling was performed to determine association between hsTnI level and CAV grade. Patients were followed for adverse outcomes over a median 10-year period. Kaplan-Meier survival analysis and Cox proportional hazard modeling were performed. RESULTS: Three hundred and seventy-two angiograms were analyzed in 156 patients at a median 8.9 years after transplant. hsTnI levels were positively correlated with concurrent CAV grade after adjustment for age, age at transplant, sex, BMI, hypertension, diabetes, hyperlipidemia, estimated glomerular filtration rate, and history of acute cellular rejection (p = .016). In an adjusted Cox proportional hazard model, initial hsTnI level above the median (4.9 pg/mL) remained a predictor of re-transplantation or death (hazard ratio 1.82; 95% confidence interval 1.16-2.90; p = .01). CONCLUSION: An elevated hsTnI level reflects severity of CAV and is associated with poor long-term outcomes in patients with HTx.

Implementation of Medical Students as Radiology Reading Room Coordinators.

OBJECTIVE: Effort has been made to minimize the burden of non-interpretive tasks (NITs), in particular by hiring and training non-radiologist support staff as reading room coordinators (RRCs). Our medical center recruited and trained senior medical students from our affiliated school of medicine to work alongside on-call radiology residents as RRCs. METHODS: A 12-month Malpractice Carrier monetary grant was acquired to fund medical students at with the aim to reduce malpractice risk. After the first year, residents were surveyed regarding the impact of the RRCs on perceived on-call efficiency and morale. Furthermore, report turnaround times (TAT) on call shifts that were and were not accompanied by a RRC were compared. RESULTS: 89 % of residents strongly agreed that the RRC improved workflow efficiency, decreased distractions, and felt less stressed during the call shift when the RRC was on duty. 78 % strongly agreed to be more likely to contact a referring clinician when the RRC was able to help coordinate. The mean TAT in the presence of a RRC was 36.8 min, and the mean TAT in the absence of a RRC was 36.9 min DISCUSSION: After hiring medical students to assist on-call radiology residents with noninterpretive tasks, residents reported subjective indicators of program success, but average report turnaround time was unaffected. Nevertheless, we predict that this type of program will continue to grow among academic radiology departments, though additional research is required to evaluate national trends and impacts on radiologist productivity and well-being.

Evaluation of the Diurnal Cycle of Blood Pressure and Sleep in Shift Workers.

BACKGROUND: Circadian misalignment of physiological factors in shift workers is poorly studied in the Indian population. In the present study, 24-hour blood pressure measurements were taken on the same subject twice, once during his morning and night shifts. Sleep was also monitored by a self-reported sleep diary, which was confirmed with an activity monitor, and the sleep quality was assessed using sleep questionnaires. OBJECTIVE: This study aimed to discover the pattern of blood pressure variation, the dipping and non-dipping status, and its correlation with sleep. METHODOLOGY: This observational study was conducted in the Department of Physiology, All India Institute of Medical Sciences (AIIMS), Rishikesh, from April 2019 to September 2019, among security guards working rotating shifts in the Rishikesh hospital premises. Participants were given an activity sheet with instructions to document their daily activities for a complete 24-hour period on the designated measurement day, including recording the time of waking up and going to sleep. A wrist-worn activity monitor was utilised to assess the self-reported sleep duration provided by each participant on the activity sheet. RESULTS: The present study showed the mean age of the participants as 27.03 ± 2.71 years, along with a mean body mass index (BMI) of 22.10 ± 1.64. Sleep duration was significantly higher during the morning shift (5.81 ± 1.08 hours) compared to the night shift (4.02 ± 1.70 hours) on the day of ambulatory blood pressure monitoring (ABPM) recording. The mean difference in systolic blood pressure between night shift workers between their awake and sleep periods was 15.91 ± 8.44 mmHg. However, no statistically significant disparity was seen when comparing the systolic blood pressure at the 24-hour mark during wakefulness and sleep between those working morning and night shifts (p >0.05). CONCLUSION: The current study's findings indicate that participation in shift work, particularly night shift work, could potentially play a role in the emergence of irregular circadian blood pressure patterns and potentially lead to a lack of nocturnal blood pressure decline.

EEDC: An Energy Efficient Data Communication Scheme Based on New Routing Approach in Wireless Sensor Networks for Future IoT Applications.

Wireless Sensor Networks (WSNs) and the Internet of Things (IoT) have emerged as transforming technologies, bringing the potential to revolutionize a wide range of industries such as environmental monitoring, agriculture, manufacturing, smart health, home automation, wildlife monitoring, and surveillance. Population expansion, changes in the climate, and resource constraints all offer problems to modern IoT applications. To solve these issues, the integration of Wireless Sensor Networks (WSNs) and the Internet of Things (IoT) has come forth as a game-changing solution. For example, in agricultural environment, IoT-based WSN has been utilized to monitor yield conditions and automate agriculture precision through different sensors. These sensors are used in agriculture environments to boost productivity through intelligent agricultural decisions and to collect data on crop health, soil moisture, temperature monitoring, and irrigation. However, sensors have finite and non-rechargeable batteries, and memory capabilities, which might have a negative impact on network performance. When a network is distributed over a vast area, the performance of WSN-assisted IoT suffers. As a result, building a stable and energy-efficient routing infrastructure is quite challenging in order to extend network lifetime. To address energy-related issues in scalable WSN-IoT environments for future IoT applications, this research proposes EEDC: An Energy Efficient Data Communication scheme by utilizing "Region based Hierarchical Clustering for Efficient Routing (RHCER)"-a multi-tier clustering framework for energy-aware routing decisions. The sensors deployed for IoT application data collection acquire important data and select cluster heads based on a multi-criteria decision function. Further, to ensure efficient long-distance communication along with even load distribution across all network nodes, a subdivision technique was employed in each tier of the proposed framework. The proposed routing protocol aims to provide network load balancing and convert communicating over long distances into shortened multi-hop distance communications, hence enhancing network lifetime.The performance of EEDC is compared to that of some existing energy-efficient protocols for various parameters. The simulation results show that the suggested methodology reduces energy usage by almost 31% in sensor nodes and provides almost 38% improved packet drop ratio.

Optimizing disease progression assessment using blinded central independent review and comparing it with investigator assessment in the PRIMA/ENGOT-ov26/GOG-3012 trial: challenges and solutions.

OBJECTIVE: Progression-free survival is an established clinically meaningful endpoint in ovarian cancer trials, but it may be susceptible to bias; therefore, blinded independent centralized radiological review is often included in trial designs. We compared blinded independent centralized review and investigator-assessed progressive disease performance in the PRIMA/ENGOT-ov26/GOG-3012 trial examining niraparib monotherapy. METHODS: PRIMA/ENGOT-ov26/GOG-3012 was a randomized, double-blind phase 3 trial; patients with newly diagnosed stage III/IV ovarian cancer received niraparib or placebo. The primary endpoint was progression-free survival (per Response Evaluation Criteria in Solid Tumors [RECIST] v1.1), determined by two independent radiologists, an arbiter if required, and by blinded central clinician review. Discordance rates between blinded independent centralized review and investigator assessment of progressive disease and non-progressive disease were routinely assessed. To optimize disease assessment, a training intervention was developed for blinded independent centralized radiological reviewers, and RECIST refresher training was provided for investigators. Discordance rates were determined post-intervention. RESULTS: There was a 39% discordance rate between blinded independent centralized review and investigator-assessed progressive disease/non-progressive disease in an initial patient subset (n=80); peritoneal carcinomatosis was the most common source of discordance. All reviewers underwent training, and as a result, changes were implemented, including removal of two original reviewers and identification of 10 best practices for reading imaging data. Post-hoc analysis indicated final discordance rates between blinded independent centralized review and investigator improved to 12% in the overall population. Median progression-free survival and hazard ratios were similar between blinded independent centralized review and investigators in the overall population and across subgroups. CONCLUSION: PRIMA/ENGOT-ov26/GOG-3012 highlights the need to optimize blinded independent centralized review and investigator concordance using early, specialized, ovarian-cancer-specific radiology training to maximize validity of outcome data.

A Clinicopathological and Immunohistochemical Profile of Primary Extra Mammary Paget's Disease in Skin of Colour: A Case Series.

Extramammary Paget's disease is an intraepithelial neoplasm, usually found in areas rich in apocrine gland concentration. The clinical features, histopathology, immunohistochemistry and management details of five patients (F = 3, M = 2) have been described here. While a well-defined persistent plaque with crusting and erosion was the most common presentation, hyperpigmentation, hypopigmentation and depigmentation were also observed in two patients. Characteristic Paget's cells with cytokeratin 7 and EMA positivity were seen on histopathology examination. Authors conclude that pigmentary alterations may be under-reported in extra mammary Paget's disease in the skin of colour.

17 ß-Estradiol Impedes Aortic Root Dilation and Rupture in Male Marfan Mice.

Marfan syndrome causes a hereditary form of thoracic aortic aneurysms with worse outcomes in male compared to female patients. In this study, we examine the effects of 17 ß-estradiol on aortic dilation and rupture in a Marfan mouse model. Marfan male mice were administered 17 ß-estradiol, and the growth in the aortic root, along with the risk of aortic rupture, was measured. Transcriptomic profiling was used to identify enriched pathways from 17 ß-estradiol treatments. Aortic smooth muscle cells were then treated with cytokines to validate functional mechanisms. We show that 17 ß-estradiol decreased the size and rate of aortic root dilation and improved survival from rupture. The Marfan transcriptome was enriched in inflammatory genes, and the addition of 17 ß-estradiol modulated a set of genes that function through TNFα mediated NF-κB signaling. In addition, 17 ß-estradiol suppressed the induction of these TNFα induced genes in aortic smooth muscle cells in vitro in an NF-κB dependent manner, and 17 ß-estradiol decreased the formation of adventitial inflammatory foci in aortic roots in vivo. In conclusion, 17 ß-estradiol protects against the dilation and rupture of aortic roots in Marfan male mice through the inhibition of TNFα-NF-κB signaling.

Clinical evaluation of preoperative three -item questionnaire and pain experienced on infiltration of local anesthetics to predict severity of acute pain after caesarean section.

Background and Aims: Several studies have attempted to identify patients at risk of developing severe pain after caesarean section (CS) by utilizing preoperative experimental pain application and clinical tests. The three-item questionnaire and reported pain intensity on infiltration of local anesthetic (LA) on the back of patient just before administration of spinal anesthesia, are two simple tests previously shown to be promising. We aimed to study utility of these two tools in Indian patients undergoing CS and find their correlation with postoperative pain and analgesic consumption. Material and Methods: A total of 150 parturients undergoing elective CS were enrolled. Preoperatively patients were asked to rate their level of anxiety, anticipated postoperative pain and analgesic need after surgery (three-item questionnaire). The pain intensity reported by patient upon LA injection for spinal anesthesia were recorded. In the postoperative period, pain intensity at rest, evoked pain and need for rescue analgesics were recorded. The correlation between three item questionnaire and pain on LA infiltration to postoperative pain were evaluated. To see relationship between the predictor variables to outcome, a multiple regression analysis was performed. Results: The predictors variables and postoperative pain were found to have mild correlation (r = 0.124 to 0.239). The predictor variables were significantly correlated with postoperative pain at rest but their association was not significant to evoked pain intensity. Multiple regression analysis showed that change in the predictors explains only 7-8% variance in postoperative pain outcomes. Conclusion: The three -item questionnaire and pain intensity reported upon LA infiltration for spinal anesthesia have mild correlation to postoperative pain in Indian parturients undergoing CS. As these variables predicts only 8% variance in pain experienced after CS, further studies are required for accurate prediction and targeted treatment of post CS pain.

Genome-wide identification and characterization of ABC transporter superfamily in the legume Cajanus cajan.

Plant ATP-binding cassette (ABC) protein family is the largest multifunctional highly conserved protein superfamily that transports diverse substrates across biological membranes by the hydrolysis of ATP and is also the part of the several other biological processes like cellular detoxification, growth and development, stress biology, and signaling processes. In the agriculturally important legume crop Cajanus cajan, a genome-wide identification and characterization of the ABC gene family was carried out. A total of 159 ABC genes were identified that belong to eight canonical classes CcABCA to CcABCG and CcABCI based on the phylogenetic analysis. The number of genes was highest in CcABCG followed by CcABCC and CcABCB class. A total of 85 CcABC genes were found on 11 chromosomes and 74 were found on scaffold. Tandem duplication was the major driver of CcABC gene family expansion. The dN/dS ratio revealed the purifying selection. The phylogenetic analysis revealed class-specific eight superclades which reflect their functional importance. The largest clade was found to be CcABCG which reflects their functional significance. CcABC proteins were mainly basic in nature and found to be localized in the plasma membrane. The secondary structure prediction revealed the dominance of α-helix. The canonical transmembrane and nucleotide binding domain, signature motif LSSGQ, Walker A, Walker B region, and Q loop were also identified. A class-specific exon-intron pattern was also observed. In addition to core elements, different cis-acting regulatory elements like stress, hormone, and cellular responsive were also identified. Expression profiling of CcABC genes at various developmental stages of different anatomical tissues was performed and it was noticed that CcABCF3, CcABCF4, CcABCF5, CcABCG66, and CcABCI3 had the highest expression. The results of the current study endow us with the further functional analysis of Cajanus ABC in the future.

Clinical and allelic heterogeneity in dystrophic epidermolysis bullosa- lessons from an Indian cohort.

BACKGROUND: Dystrophic epidermolysis bullosa (DEB) is due to variation in the COL7A1 gene. The clinical phenotype and severity depends on the type of variation and domain of the affected protein. OBJECTIVES: To characterize the spectrum of COL7A1 variations in a cohort of DEB patients from India, to correlate these findings with clinical phenotypes and to establish a genotype-phenotype correlation. METHODS: This was a retrospective, observational study involving patients with DEB diagnosed on the basis of clinical manifestations, Immuno-fluorescence antigen mapping (IFM) and genetic analysis. A genotype-phenotype correlation was attempted and observations were further explained using IFM on skin biopsies and molecular dynamic simulations. Descriptive statistics were performed using SPSS version 20.0 with P values of <0.05 considered significant. RESULTS: We report 68 unrelated Indian DEB patients classified as RDEB-Intermediate (RDEB-I), RDEB-Severe (RDEB-S) or DDEB based on the EB diagnostic matrix, immunofluorescence antigen mapping and genetic data. Of 68 DEB patients, 59 (86.76%) were inherited in a recessive pattern (RDEB) and 9 (13.24%) in a dominant pattern (DDEB). Limbal stem cell deficiency was seen in four cases of RDEB-S very early in the course of the disease. A total of 88 variants were detected of which 66 were novel. There were no hotspots and recurrent variations were seen in a very small group of patients. We found a high frequency of compound heterozygotes (CH) in RDEB patients born out of non-consanguineous marriage. RDEB patients older than two years who had oral mucosal involvement, and/or deformities, were more likely to have esophageal involvement. Genotype phenotype correlation showed a higher frequency of extracutaneous manifestations and deformities in patients with Premature Termination Codons (PTCs) than in patients with other variations. Molecular simulation studies in patients with missense mutations showed severe phenotype when they were localized in interrupted regions of GLY-X-Y repeats. CONCLUSION: This large study of DEB patients in South Asia adds to the continually expanding genetic database of this condition. This study has direct implications on management as this group of patients can be screened early and managed appropriately.

Management and outcomes of heart transplant candidates with bloodstream infection on temporary mechanical circulatory support.

The outcomes and management of bloodstream infection (BSI) in patients on temporary mechanical circulatory support (TMCS) awaiting heart transplant (HT) are poorly understood. We present outcomes of patients on TMCS with BSI (TMCS-I) relative to matched uninfected patients (TMCS-U) and discuss their management. Between January 1, 2013, and April 30, 2023, N = 136 patients were bridged to transplant with TMCS at Emory Transplant Center. Twenty-one (15.4%) patients were TMCS-I. Two (9.5%) had infective endocarditis. Median duration of antimicrobial treatment was 24 days (interquartile range 28.3). All TMCS-I were reactivated for transplant within 48 to 72 hours of negative blood cultures. None developed recurrent BSI. Post-transplant survival did not differ between TMCS-I and TMCS-U (p = 0.38). HT for TMCS-I may be safe as soon as blood cultures clear. Duration of antimicrobial therapy is individualized and depends on the organism, duration of bacteremia, presence of endocarditis, and timing of HT. Additional research is needed to determine optimal duration of treatment.

Redirecting the JAK-STAT signal blocks the SARS-CoV-2 replication.

The distinct disease progression patterns of severe acute respiratory syndrome coronavirus clade 2 (SARS-CoV-2) indicate diverse host immune responses. SARS-CoV-2 severely impairs type I interferon (IFN) cell signaling, resulting in uncontrolled late-phase lung damage in patients. For better pharmacological properties, cytokine modifications may sometimes result in a loss of biological activity against the virus. Here, we employed the genetic code expansion and engineered IFN-ß, a phase II clinical cytokine with 3-amino tyrosine (IFN-ß-A) that reactivates STAT2 expression in virus-infected human cells through JAK/STAT cell signaling without affecting signal activation and serum half-life. This study identified that genetically encoded IFN-ß-A might stabilize the protein-receptor complex and trigger JAK-STAT cell signaling, which is a promising modality for controlling SARS-CoV-2 infection.