A Novel Large Deletion in the EVER1 Gene in a Family With Epidermodysplasia Verruciformis From India.

ABSTRACT: Epidermodysplasia verruciformis (EV) is a rare autosomal recessive genodermatosis due to mutations in EVER1 and EVER2 genes. The genetic profile of Indian patients with EV has not been previously studied. This report describes the clinical presentation and molecular analysis of a family with EV. Using genomic DNA from two affected probands and healthy controls (two other siblings), conventional polymerase chain reaction (PCR) was conducted with novel primer sets designed to amplify the coding and splice-site regions in the genes EVER1 and EVER 2. This revealed no amplification with a primer set for exons 16 to 18 in the EVER1 gene of both the probands. Subsequently, long-range PCR spanning the length of exon 15-20 and next-generation sequencing demonstrated a homozygous deletion of 2078 bp in the EVER1 gene (EVER1:c.2072_2278del). Screening the family revealed the same homozygous deletion (similar to index cases) in two other affected siblings. The parents and two asymptomatic siblings were heterozygous carriers for the deletion while one healthy sibling was negative. These results were validated with Sanger sequencing. This deletion in exons 17 and 18 of the EVER1 gene results in a frameshift, followed by a premature termination resulting in a severe phenotype. The identification and validation of this large deletion was detected using stepwise amplicon-based target enrichment and long-range PCR, respectively. In this family, this simple strategy greatly enhanced genetic counseling as well as early genetic diagnosis and screening. However, functional assays and larger studies are required to characterize and validate the genetic diversity among Indians with EV.

Serratia endocarditis, uncommon organism, with significant complications.

Serratia marcescens is an aerobic, Gram-negative bacillus predominantly seen in patients with intravenous drug use, immunosuppression, previous antibiotic exposure, and indwelling catheterization. Gram-negative organism causing infective endocarditis (IE) is rare. Serratia marcescens IE is uncommon and is reported to be seen in 0.14% of all cases. In this report, we discuss in detail about a 38-year-old man with a history of intravenous drug abuse presenting with S. marcescens related prosthetic valve IE.

Infections precipitating Takotsubo cardiomyopathy, an uncommon complication of a common infection.

Takotsubo cardiomyopathy (TTC) is a non-ischemic cardiomyopathy precipitated by stress. Various infections are reported to precipitate this form of cardiomyopathy. We report a patient presenting with TTC secondary to influenza.  In this article, we also discuss the various infections reported to precipitate this form of reversible cardiomyopathy in literature. We have also included the recent reports of TTC among patients with COVID-19.

Endocrinological abnormalities and Takotsubo cardiomyopathy.

Dear Editor, We read with much excitement in the article "Takotsubo syndrome and pheochromocytoma: an insidious combination" published by Maffé et al. in your esteemed journal...

Cerebrovascular events in COVID-19 patients.

Neurological manifestations in patients with COVID-19 are more frequently being reported. Cerebrovascular events have been reported in around 3% of patients. In this review we summarize the published literature on cerebrovascular events in patients with COVID-19 as available on the PubMed database. So far, 3 studies have reported cerebrovascular events. Cerebrovascular events were identified on screening patients with decreased consciousness or in the presence of focal neurological deficits. These events were common in elderly, critically ill patients and in patients with prior cardio-cerebrovascular comorbidities. The diagnosis of cerebrovascular events was confirmed with computed tomography of the brain in most studies reporting neurological events. Multiple pathological mechanisms have been postulated regarding the process of neurological and vascular injury among which cytokine storm is shown to correlate with mortality. Patients with severe illness are found to have a higher cardio- cerebrovascular comorbidity. With an increasing number of cases and future prospective studies, the exact mechanism by which these cerebrovascular events occur and attribute to the poor outcome will be better understood.

A Comparative Evaluation of the Effectiveness of Three Different Modalities in Occluding Dentinal Tubules: An In Vitro Study.

AIM: This in vitro study was designed to evaluate and compare the effectiveness of a dentifrice containing 8% arginine and calcium carbonate, diode laser (810 nm) and the combined use of diode laser (810 nm) and the same dentifrice in occluding dentinal tubules. MATERIALS AND METHODS: Forty sectioned dentine discs were observed in this study. The Samples were randomly divided into 4 groups. In group A, a dentifrice containing arginine and calcium carbonate was applied. In group B, the specimens were subjected to diode laser (810 nm) irradiation. In group C, the same dentifrice was applied and the specimens were subjected to diode laser (810 nm) treatment. Group D was left untreated and served as the control. The specimens were observed under the scanning electron microscope. Then the photomicrographs of each specimen were taken which were uploaded into Photoshop 7®, and the diameters of the dentinal tubules of each specimen were measured and the data were analyzed statistically. RESULTS: The overall comparison between different treatment modalities using one-way analysis of variance (ANOVA) and multiple comparisons of two modalities assessed using post hoc Tukey method revealed that there is a highly significant difference (p value = 0.0001) in the dentinal tubule diameter and rate of occlusion in different treatment modalities. CONCLUSION: The study concluded that all three treatment modalities caused significant occlusion of dentinal tubules. The combined use of desensitizing toothpaste and diode laser (810 nm) is the most effective, then comes the diode laser (810 nm) alone and finally the desensitizing toothpaste alone. CLINICAL SIGNIFICANCE: This study suggests an effective treatment of dentinal hypersensitivity using diode laser and desensitizing toothpaste.

The relationship between skin rash and outcome in dengue.

BACKGROUND & OBJECTIVES: Dengue fever (DF) is a common cause of acute febrile illness. Skin involvement is seen in more than half of the patients. This study was aimed to compare the clinical profile and outcome in DF patients with or without skin involvement. METHODS: This study included all the patients with DF from the acute febrile illness database of a tertiary care health centre in south India. These patients were further subgrouped into SP and SN (skin involvement positive and negative) based on the presence and absence of skin rash. Differences in clinical presentation, laboratory parameters, disease course, morbidity and outcome among patients with DF with or without skin rash were recorded and analysed statistically. RESULTS: In total 387 patients (>16 yr) with DF were enrolled into the study. Among these 55 patients had evidence of skin rash. Presence of history of overt bleeding (OR = 4.96, p = 0.027) including gum bleeding (OR = 1.17, p = 0.23), epistaxis (OR = 5.52, p = 0.04), and haematuria (OR = 6.41, p = 0.01) were more among patients with SP as compared to SN. The SP patients were found to have lower levels of platelets during the disease course. Patients with SP had a higher percentage of platelet transfusion which was statistically significant. There was no difference in organ dysfunction and mortality among both the groups. INTERPRETATION & CONCLUSION: Cutaneous involvement, though common, is not pathognomonic and can help in dengue diagnosis. Adult patients with skin rash can develop worsening thrombocytopenia requiring platelet transfusion. However, there are limited data to suggest that such patients have a worse outcome and higher mortality.

L368F/V408F double mutant of IBD of LEDGF/p75 retains interaction with M178I mutant of HIV-1 integrase.

Lens-epithelium-derived-growth factor (LEDGF/p75) is an essential host protein for integration of HIV-1 DNA into host genome. Earlier alanine scanning mutational analysis has revealed that residues I365, D366 and F406 in the integrase binding domain (IBD) of p75 are critical for interaction with HIV-1 integrase (IN), while K364, V408 have intermediate effect and residues N367, L368, R405, K407 show wild type binding with IN. To gain insight into contribution of side chains of L368 and V408 that are adjacent to critical residues I365 and F406, respectively, site directed mutation of these residues to Ile/Leu, Met and Phe has been performed and characterized in this study. In contrast to alanine substitution, L368F mutation showed a ∼25% decrease, while V408L and V408F showed wild type binding, to IN. Docking analysis of I365, D366 and F406 mutants of IBD with IN predicts that interaction between residue M178(IN) and I365(IBD) might lead to an encounter complex formation. Accordingly, M178I mutant of IN failed to interact with IBD. Interestingly, a L368F/V408F double mutant of IBD restored binding to M178I mutant of IN, indicating that altered hydrophobicity in the inter helical loops of IBD might make I365 more accessible for interaction with IN.

Is Ross Syndrome an Autoimmune Entity? A Case Series of 11 Patients.

BACKGROUND: Ross syndrome is diagnosed by the presence of segmental anhidrosis, areflexia, and tonic pupils. Fewer than 60 cases have been described in literature so far. There have been reports of presence of antibodies in such patients, suggesting an autoimmune pathogenesis. METHODS: We describe the clinical profile in this case series of 11 patients with Ross syndrome and discuss the current status of autoimmunity in its pathogenesis and the management. RESULTS: Of the 11 patients with Ross syndrome there was an almost equal sex distribution (male:female ratio was 1.17:1) and the mean age of onset of symptoms was 26 years. Patients took an average of 6 years to present to a tertiary center. Sixty-three percent of the patients presented with complaints of excessive sweating, whereas only 27% had complaints of decreased sweating over a particular area of the body. Only 45% of the patients had the complete triad of Ross syndrome, which included segmental anhidrosis, tonic pupil, and absent reflexes. Eighty-nine percent of the patients had documented absent sympathetic skin response on electromyography. The various markers of autoimmunity were negative in all patients who were investigated for the same in this series. Ninety percent of the patients were managed conservatively. CONCLUSIONS: These findings suggest that, in Ross syndrome, generalized injury to ganglion cells or their projections are not purely autoimmune-mediated.

Synthesis, characterization and optical properties of ligand-protected indium nanoparticles.

Unlike silver and gold, indium has material properties that enable strong resonances extended up to the ultraviolet. This extended response, combined with low cost, and ease of synthesis process, makes indium a highly promising material for applications. In this work, we have synthesized ligand-protected indium nanoparticles by a metal reduction method. Powder X-ray diffraction and EDX analyses are consistent with the presence of metallic indium in the nanoparticles. Ligand binding was proven by IR spectroscopy and TGA experiments. TEM analyses reveal that the particle size ranges from 6.3 to 4.8 nm. Optical measurements show that the absorption maximum is red shifted as the particle size decreases.

Optimizing infection control and antimicrobial stewardship bedside discussion: a scoping review of existing evidence on effective healthcare communication in hospitals.

BACKGROUND: The link between healthcare worker (HCW) communication, teamwork and patient safety is well-established. Infection prevention and control (IPC) and antimicrobial stewardship (AMS) require multidisciplinary teamwork and communication. OBJECTIVES: We conducted a scoping review of published evidence on effective mechanisms of HCW team communication in hospitals with the intention of transferring and tailoring learning to IPC and AMS team communication. METHODS: PubMed, Scopus, Web of Science, and CINAHL were searched for studies that investigated HCW team communication across in-hospital patient pathways. Studies published between 2000 and 2021 that provided evidence on/or described the effect of communication on team and patient outcomes in hospital were included. Through a process of inductive qualitative content analysis, key themes in the included studies were identified. RESULTS: Of 537 studies identified, 53 (from high-income countries) were included in the data extraction. Fifty one percent (27/53) of studies were conducted in high acuity settings e.g., intensive care units. Standardizing or structuring the content and/or process of team communication was the most common goal of interventions (34/53, 64%). The key outcome measures were either team communication focused (25/34,74%) or patient and process outcome focused (8/34, 24%), such as reduced length of mechanical ventilation days, length of hospital stay, and shorter empiric antibiotic duration. Four studies (4/53, 8%) associated improved communication with positive IPC and AMS outcome measures. Mixed method intervention studies primarily facilitated collaborative input from HCWs and applied structures to standardize the content of patient care discussions, whereas observational studies describe component of team communication. CONCLUSIONS: A communication strategy that formalizes input from multidisciplinary team members can lead to optimized and consistent clinical discussion including in IPC and AMS-related care. Although we were unable to assess the effectiveness of interventions, the existing evidence suggests that optimizing team communication can have a positive effect on infection-related patient outcomes.

Computational Prediction of Potential Vaccine Candidates From tRNA Encoded peptides (tREP) Using a Bioinformatic Workflow and Molecular Dynamics Validations.

Transfer RNAs (tRNA) are non-coding RNAs. Encouraged by biological applications discovered for peptides derived from other non-coding genomic regions, we explore the possibility of deriving epitope-based vaccines from tRNA encoded peptides (tREP) in this study. Epitope-based vaccines have been identified as an effective strategy to mitigate safety and specificity concerns observed in vaccine development. In this study, we explore the potential of tREP as a source for epitope-based vaccines for virus pathogens. We present a computational workflow that uses verified data sources and community-validated predictive tools to produce a ranked list of plausible epitope-based vaccines starting from tRNA sequences. The top epitope, bound to the predicted HLA molecule, for the virus pathogen is computationally validated through 200 ns molecular dynamics (MD) simulations followed by binding free energy calculations. The simulation results indicate that two tRNA encoded epitope-based vaccines, RRHIDIVV and IMVRFSAE for Mamastrovirus 3 and Norovirus GII, respectively, are likely candidates. Peptides originating from tRNAs provide unexplored opportunities for vaccine design. Encouraged by our previous experimental study, which established the inhibitory properties of tREPs against infectious parasites, we have proposed a computationally validated set of peptides derived from tREPs as vaccines for viral pathogens.

Epidemiology and preventability of hospital-onset bacteremia and fungemia in 2 hospitals in India.

OBJECTIVE: Studies evaluating the incidence, source, and preventability of hospital-onset bacteremia and fungemia (HOB), defined as any positive blood culture obtained after 3 calendar days of hospital admission, are lacking in low- and middle-income countries (LMICs). DESIGN, SETTING, AND PARTICIPANTS: All consecutive blood cultures performed for 6 months during 2020-2021 in 2 hospitals in India were reviewed to assess HOB and National Healthcare Safety Network (NHSN) reportable central-line-associated bloodstream infection (CLABSI) events. Medical records of a convenience sample of 300 consecutive HOB events were retrospectively reviewed to determine source and preventability. Univariate and multivariable logistic regression analyses were performed to identify factors associated with HOB preventability. RESULTS: Among 6,733 blood cultures obtained from 3,558 hospitalized patients, there were 409 and 59 unique HOB and NHSN-reportable CLABSI events, respectively. CLABSIs accounted for 59 (14%) of 409 HOB events. There was a moderate but non-significant correlation (r = 0.51; P = .070) between HOB and CLABSI rates. Among 300 reviewed HOB cases, CLABSIs were identified as source in only 38 (13%). Although 157 (52%) of all 300 HOB cases were potentially preventable, CLABSIs accounted for only 22 (14%) of these 157 preventable HOB events. In multivariable analysis, neutropenia, and sepsis as an indication for blood culture were associated with decreased odds of HOB preventability, whereas hospital stay ≥7 days and presence of a urinary catheter were associated with increased likelihood of preventability. CONCLUSIONS: HOB may have utility as a healthcare-associated infection metric in LMIC settings because it captures preventable bloodstream infections beyond NHSN-reportable CLABSIs.

A Case Report on the Efficacy of Trastuzumab Emtansine in a Patient With Human Epidermal Growth Factor Receptor 2 Exon 20-Mutated Adenocarcinoma of the Lung.

Lung cancer is the foremost reason for cancer-related mortality among men and women. The ultimate goal of patient supervision post-diagnosis for advanced cases is to improve survival and quality of life with minimal treatment-associated side effects. With advancements in genomic medicine and a better understanding of cell signaling pathways, many actionable gene mutations have been identified in lung carcinoma, which drastically improve survival outcomes. Mutations in human epidermal growth factor receptor 2 (HER2) and epidermal growth factor receptor together are observed in nearly 1-3% of cases and act as an oncogenic driver. In the case of HER2-mutant lung cancers, there are limited approved agents, and the treatment represents a critical unmet medical need because of the poorer survival outcomes compared to patients with additional oncogenic drivers. The recent standard of care of treatment is chemotherapy, but reports suggest that compared with cytotoxic chemotherapy, patients receiving HER2-directed therapies have relatively longer median survival duration. Here, we report a case of HER2 exon 20-mutated metastatic lung adenocarcinoma patient who received trastuzumab emtansine in the third-line setting and achieved durable disease control.

Takotsubo cardiomyopathy following envenomation: An updated review.

BACKGROUND: Takotsubo cardiomyopathy (TTC) can be diagnosed in patients presenting with clinical features of acute coronary syndrome (ACS) by using Mayo clinic criteria. Multiple precipitators have been attributed to causing TTC. Rarely it has been reported to occur following an acute envenomation. AIM: This review describes the various patterns, mechanisms, and outcomes of envenomation induced TTC. METHODS: In this review, we included all studies on "TTC" and "envenomation "published in the various databases before June 2022. To be included in the review articles had to have a distinct diagnosis of TTC and an envenomation. RESULTS: A total of 20 patients with envenomation induced TTC were identified. Most episodes of envenomation induced TTC were reported following a bee sting, scorpion sting, and snake envenomation. Fear and anxiety related to the sting, direct catecholamine toxicity and administration of exogenous beta-adrenergic agents have been commonly postulated to precipitate TTC in these patients. 95% of these patients presented with a clinical picture of ACS. Most of these patients also fulfill at least 3 out of 4 criteria of Mayo clinic criteria for TTC. Echocardiographic evidence of Apical TTC was noted in 72% of patients. 94% of these patients had clinical improvement following optimal management and 35% of these patients were treated with guideline directed medications for heart failure. CONCLUSION: Envenomation following multiple insect stings and reptile bites can precipitate TTC. Most reported envenomation related TTC has been due to bee stings and scorpion bites. Common mechanisms causing TTC were fear, anxiety, and stress of envenomation. Most of these patients present with clinical presentation of ACS, ST elevation, and elevated troponin. The most common type of TTC in these patients is Apical, which improved following medical management.

Cardiovascular complications following medical termination of pregnancy: An updated review.

BACKGROUND: Around 1 million cases of medical termination of pregnancy (MTP) take place yearly in the United States of America with around 2 percent of this population developing complications. The cardiovascular (CVD) complications occurring post MTP or after stillbirth is not very well described. AIM: To help the reader better understand, prepare, and manage these complications by reviewing various cardiac comorbidities seen after MTP. METHODS: We performed a literature search in PubMed, Medline, RCA, and google scholar, using the search terms "abortions" or "medical/legal termination of pregnancy" and "cardiac complications" or "cardiovascular complications". RESULTS: The most common complications described in the literature following MTP were infective endocarditis (IE) (n = 16), takotsubo cardiomyopathy (TTC) (n = 7), arrhythmias (n = 5), and sudden coronary artery dissection (SCAD) (n = 4). The most common valve involved in IE was the tricuspid valve in 69% (n = 10). The most observed causative organism was group B Streptococcus in 81% (n = 12). The most common type of TTC was apical type in 57% (n = 4). Out of five patients developing arrhythmia, bradycardia was the most common and was seen in 60% (3/5) of the patients. All four cases of SCAD-P type presented as acute coronary syndrome 10-14 d post termination of pregnancy with predominant involvement of the right coronary artery. Mortality was only reported following IE in 6.25%. Clinical recovery was reported consistently after optimal medical management following all these complications. CONCLUSION: In conclusion, the occurrence of CVD complications following pregnancy termination is infrequently documented in the existing literature. In this review, the most common CVD complication following MTP was noted to be IE and TTC.

Effect of Umbilical Cord Milking on Maternal and Neonatal Outcomes in a Tertiary Care Hospital in South India: A Randomized Control Trial.

Background and Aim: Umbilical cord milking (UCM) has been theorized to increase placental blood transfusion then again, the optimal method of cord clamping at birth is still contested. We aimed to analyse the effects of UCM on the neonatal haematological parameters at 72 h and 6 weeks of age and its association with any adverse effects. Materials and Methods: In this randomized control trial, mothers ≥ 34 weeks were randomized into two arms. Under the intervention group, the cord was milked three times before clamping and cutting whereas the controls had the cord clamped and cut without milking. Haemoglobin and haematocrit levels were measured at 72 h. and at 6 weeks. Results: A total of 170 mothers were enrolled with 85 subjects in each arm. Baseline characteristics were comparable. In the intervention arm, the mean haemoglobin [18.1 (2.4) g/dL] and haematocrit [54 (7) %] were significantly higher as compared to the control arm [16.4 (2.1) g/dL and 48 (6) %], at 72 h of age. There was also significant increase in the mean haemoglobin [11.6 (1.3) g/dL] and haematocrit [34 (4) %] compared to the controls [10.1 (1.1) g/dL and 30 (3) %], at 6 weeks. No statistical difference was found in the incidence of PPH and duration of third stage. There was no significant rise in hyperbilirubinaemia, phototherapy requirement and polycythaemia among neonates in the intervention group. Conclusion: Umbilical cord milking is a sound practical approach to raise the haemoglobin and haematocrit levels up to 6 weeks thereby decreasing the proportion of anaemic infants.