Effect of four-layer dressing on the microbiological profile of venous leg ulcer.

OBJECTIVE: Venous leg ulcer (VLU) is a chronic disease and has periods of exacerbation and remission. Various bandage systems-single-layered, double-layered and multiple-layered with elastic and non-elastic components-have been developed. The requirement for sustained pressure brought about the introduction of the four-layer bandage. We studied the bacteriology of VLUs and the effect of four-layer bandages on their healing. METHOD: Clinical details of all patients, with wound size measurement by gauze piece, wax paper and scale, were recorded. The wounds were initially debrided and photographic records of all patients were maintained. Patients were followed up every week, when the dressings and four-layer bandages were changed. RESULTS: A total of 60 patients were recruited to the study with four patients having bilateral disease and so a total of 64 VLUs were evaluated. Of these, 60 (93.8%) healed completely, one (1.6%) healed partially and three (4.7%) did not heal. After excluding the four VLUs that did not fully heal, 10 (16.7%) had recurrence while 50 (83.3%) had no recurrence in the follow-up period, which lasted for one year. During the first visit (baseline), meticillin-resistant Staphylococcus aureus (MRSA) was isolated in 29 (45.31%) VLUs and Pseudomonas spp. in 20 (31.25%) VLUs. With subsequent dressing, the VLU size decreased and the culture of the VLU was sterile from the third culture onwards in 45 cases. There was a significant correlation (p<0.001) between VLU size and the number of dressings. CONCLUSION: Compression therapy is the mainstay of treatment of VLU, with rapid healing and improvement in bacteriological profile. Compression in the range of 30-40mmHg is the most effective treatment for uncomplicated VLUs with adequate arterial competency.

Explicit environmental and vibronic effects in simulations of linear and nonlinear optical spectroscopy.

Accurately simulating the linear and nonlinear electronic spectra of condensed phase systems and accounting for all physical phenomena contributing to spectral line shapes presents a significant challenge. Vibronic transitions can be captured through a harmonic model generated from the normal modes of a chromophore, but it is challenging to also include the effects of specific chromophore-environment interactions within such a model. We work to overcome this limitation by combining approaches to account for both explicit environment interactions and vibronic couplings for simulating both linear and nonlinear optical spectra. We present and show results for three approaches of varying computational cost for combining ensemble sampling of chromophore-environment configurations with Franck-Condon line shapes for simulating linear spectra. We present two analogous approaches for nonlinear spectra. Simulated absorption spectra and two-dimensional electronic spectra (2DES) are presented for the Nile red chromophore in different solvent environments. Employing an average Franck-Condon or 2DES line shape appears to be a promising method for simulating linear and nonlinear spectroscopy for a chromophore in the condensed phase.

Implementation of Early Detection Services for Cancer in India During COVID-19 Pandemic.

Early detection of cancer greatly increases the chances of better survival. The emergence of COVID-19 pandemic has disrupted several essential health services globally and early detection of cancer services is one of them. The routine cancer screenings have plummeted in many developed countries since the crisis. India has highest estimated lip and oral cavity cancer cases worldwide (119,992, 33.8%) and the secondhighest number of breast (162,468, 17.8%) and cervix uteri (96,922,30.7%) cancers in Asian sub-continent. Not only India has high burden of cancer, but the majority (75-80%) of patients have advanced disease at the time of diagnosis. Hence is it imperative that early detection services should be kept functional at out-patient settings so that at least the patients coming to hospitals with early signs and symptoms can be diagnosed as early as possible. Strategies need to be adopted to continue early detection services and ensure safety of patients and health care workers from COVID-19 transmission.

Squamous cell carcinoma arising from pilonidal sinus.

Pilonidal sinus is usually present in the sacrococcygeal region. The common presentations are cellulitis, abscess or sinus. Rarely malignant change may be seen in chronic pilonidal sinus. We report a case of chronic pilonidal sinus complicated with squamous cell carcinoma.

Axial H-Bonding Solvent Controls Inhomogeneous Spectral Broadening, While Peripheral H-Bonding Solvent Controls Vibronic Broadening: Cresyl Violet in Methanol.

The dynamics of the nuclei of both a chromophore and its condensed-phase environment control many spectral features, including the vibronic and inhomogeneous broadening present in spectral line shapes. For the cresyl violet chromophore in methanol, we here analyze and isolate the effect of specific chromophore-solvent interactions on simulated spectral densities, reorganization energies, and linear absorption spectra. Employing both chromophore and its condensed-phase environment control many spectral features, including the vibronic and inhomogeneous broadening present in spectral line shapes. For the cresyl violet chromophore in methanol, we here analyze and isolate the effect of specific chromophore-solvent interactions on simulated spectral densities, reorganization energies, and linear absorption spectra. Employing both force field and ab initio molecular dynamics trajectories along with the inclusion of only certain solvent molecules in the excited-state calculations, we determine that the methanol molecules axial to the chromophore are responsible for the majority of inhomogeneous broadening, with a single methanol molecule that forms an axial hydrogen bond dominating the response. The strong peripheral hydrogen bonds do not contribute to spectral broadening, as they are very stable throughout the dynamics and do not lead to increased energy-gap fluctuations. We also find that treating the strong peripheral hydrogen bonds as molecular mechanical point charges during the molecular dynamics simulation underestimates the vibronic coupling. Including these peripheral hydrogen bonding methanol molecules in the quantum-mechanical region in a geometry optimization increases the vibronic coupling, suggesting that a more advanced treatment of these strongly interacting solvent molecules during the molecular dynamics trajectory may be necessary to capture the full vibronic spectral broadening.

The DNA methyltransferase inhibitor 5-aza-4'-thio-2'-deoxycytidine induces C>G transversions and acute lymphoid leukemia development.

DNA methyltransferase inhibitors (DNMTi), most commonly cytidine analogs, are compounds that decrease 5'-cytosine methylation. DNMTi are used clinically based on the hypothesis that cytosine demethylation will lead to re-expression of tumor suppressor genes. 5-Aza-4'-thio-2'-deoxycytidine (Aza TdCyd or ATC) is a recently described thiol substituted DNMTi that has been shown to have anti-tumor activity in solid tumor models. Here, we investigated the therapeutic potential of ATC in a murine transplantation model of myelodysplastic syndrome. ATC treatment led to transformation of transplanted wild-type bone marrow nucleated cells into lymphoid leukemia, and healthy mice treated with ATC also developed lymphoid leukemia. Whole exome sequencing revealed thousands of acquired mutations, almost all of which were C>G transversions in a specific 5'-NCG-3' context. These mutations involved dozens of genes involved in human lymphoid leukemia, such as Notch1, Pten, Pax5, Trp53, and Nf1. Human cells treated in vitro with ATC showed thousands of acquired C>G transversions in a similar context. Deletion of Dck, the rate-limiting enzyme for the cytidine salvage pathway, eliminated C>G transversions. Taken together, these findings demonstrate a highly penetrant mutagenic and leukemogenic phenotype associated with ATC.

Venous Thromboembolism and COVID-19-an Epidemiological Perspective.

The coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was declared as pandemic by World Health Organization (WHO) in March 2020. The outbreak has caused 5,232,562 deaths worldwide until December 3rd, 2021. Though primarily affecting the respiratory system, involvement of other organ systems have been reported in severe disease. Venous thromboembolism (VTE) has been recognized as an important complication. Previous studies have reported the prevalence of VTE in intensive care unit (ICU) patients between 7 and 85% and in non-ICU patients between 0 and 19%. COVID-19 patients that are at high risk for VTE are also at increased risk for bleeding. In such cases, anticoagulation may potentially be harmful. Thereby, it is important to understand the risk factors for VTE predisposition in the COVID-19 patients, timing of VTE, and the rate of occurrence of VTE in hospitalized patients post-discharge. Comparison of the rate of occurrence of VTE in COVID-19 patients with the non-COVID-19 patients with similar disease severity is required to truly interpret the reportedly high rates of VTE in COVID-19 patients. Several pathophysiological mechanisms have been reported for the development of VTE in COVID-19. Autopsy-based studies have contributed to the existing knowledge. d-dimer, presently, seems to be the most suitable investigation for risk-identification of VTE supported by Doppler studies and overall clinical context. Further, prospective studies and clinical trials are essentially required to fill the gaps in evidence for occurrence, risk prediction and management of VTE in COVID-19 patients.

Research Gap in Health Literacy: Are We Overlooking a Possible Solution to Inadequate Cancer Screening in India?

India has one of the highest oral cancer burdens and accounts for one out of every five cervical cancer incidences worldwide. Majority of these preventable cancers are diagnosed in advanced stages with poor prognosis and survival. World Health Organization supports health literacy as a measure for accomplishing sustainable development goals. Community trials have reported that health literacy-focused interventions improve cancer screening participation and adherence. In India health literacy research is unutilized for cancer screening. Majority of the research utilized proxy information using disease-specific knowledge, attitude, and socio-demographic characteristics for screening participation. Through this correspondence, we discuss the poor cancer screening coverage in India and the research gap in health literacy in Indian context. Without an understanding of the distribution of the components of health literacy and the development of context-specific interventions for improvement, it will be difficult for any technology or innovation to penetrate the community and increase screening coverage.

Ultra-Deep Sequencing Reveals the Mutational Landscape of Classical Hodgkin Lymphoma.

The malignant Hodgkin and Reed Sternberg (HRS) cells of classical Hodgkin lymphoma (cHL) are scarce in affected lymph nodes, creating a challenge to detect driver somatic mutations. As an alternative to cell purification techniques, we hypothesized that ultra-deep exome sequencing would allow genomic study of HRS cells, thereby streamlining analysis and avoiding technical pitfalls. To test this, 31 cHL tumor/normal pairs were exome sequenced to approximately 1,000× median depth of coverage. An orthogonal error-corrected sequencing approach verified >95% of the discovered mutations. We identified mutations in genes novel to cHL including: CDH5 and PCDH7, novel stop gain mutations in IL4R, and a novel pattern of recurrent mutations in pathways regulating Hippo signaling. As a further application of our exome sequencing, we attempted to identify expressed somatic single-nucleotide variants (SNV) in single-nuclei RNA sequencing (snRNA-seq) data generated from a patient in our cohort. Our snRNA analysis identified a clear cluster of cells containing a somatic SNV identified in our deep exome data. This cluster has differentially expressed genes that are consistent with genes known to be dysregulated in HRS cells (e.g., PIM1 and PIM3). The cluster also contains cells with an expanded B-cell clonotype further supporting a malignant phenotype. This study provides proof-of-principle that ultra-deep exome sequencing can be utilized to identify recurrent mutations in HRS cells and demonstrates the feasibility of snRNA-seq in the context of cHL. These studies provide the foundation for the further analysis of genomic variants in large cohorts of patients with cHL. SIGNIFICANCE: Our data demonstrate the utility of ultra-deep exome sequencing in uncovering somatic variants in Hodgkin lymphoma, creating new opportunities to define the genes that are recurrently mutated in this disease. We also show for the first time the successful application of snRNA-seq in Hodgkin lymphoma and describe the expression profile of a putative cluster of HRS cells in a single patient.

Molecular polariton electroabsorption.

We investigate electroabsorption (EA) in organic semiconductor microcavities to understand whether strong light-matter coupling non-trivially alters their nonlinear optical [[Formula: see text]] response. Focusing on strongly-absorbing squaraine (SQ) molecules dispersed in a wide-gap host matrix, we find that classical transfer matrix modeling accurately captures the EA response of low concentration SQ microcavities with a vacuum Rabi splitting of [Formula: see text] meV, but fails for high concentration cavities with [Formula: see text] meV. Rather than new physics in the ultrastrong coupling regime, however, we attribute the discrepancy at high SQ concentration to a nearly dark H-aggregate state below the SQ exciton transition, which goes undetected in the optical constant dispersion on which the transfer matrix model is based, but nonetheless interacts with and enhances the EA response of the lower polariton mode. These results indicate that strong coupling can be used to manipulate EA (and presumably other optical nonlinearities) from organic microcavities by controlling the energy of polariton modes relative to other states in the system, but it does not alter the intrinsic optical nonlinearity of the organic semiconductor inside the cavity.

Convergent Clonal Evolution of Signaling Gene Mutations Is a Hallmark of Myelodysplastic Syndrome Progression.

Progression from myelodysplastic syndromes (MDS) to secondary acute myeloid leukemia (AML) is associated with the acquisition and expansion of subclones. Our understanding of subclone evolution during progression, including the frequency and preferred order of gene mutation acquisition, remains incomplete. Sequencing of 43 paired MDS and secondary AML samples identified at least one signaling gene mutation in 44% of MDS and 60% of secondary AML samples, often below the level of standard sequencing detection. In addition, 19% of MDS and 47% of secondary AML patients harbored more than one signaling gene mutation, almost always in separate, coexisting subclones. Signaling gene mutations demonstrated diverse patterns of clonal evolution during disease progression, including acquisition, expansion, persistence, and loss of mutations, with multiple patterns often coexisting in the same patient. Multivariate analysis revealed that MDS patients who had a signaling gene mutation had a higher risk of AML progression, potentially providing a biomarker for progression. SIGNIFICANCE: Subclone expansion is a hallmark of progression from MDS to secondary AML. Subclonal signaling gene mutations are common at MDS (often at low levels), show complex and convergent patterns of clonal evolution, and are associated with future progression to secondary AML. See related article by Guess et al., p. 316 (33). See related commentary by Romine and van Galen, p. 270. This article is highlighted in the In This Issue feature, p. 265.

U2af1 is a haplo-essential gene required for hematopoietic cancer cell survival in mice.

Somatic mutations in the spliceosome gene U2AF1 are common in patients with myelodysplastic syndromes. U2AF1 mutations that code for the most common amino acid substitutions are always heterozygous, and the retained WT allele is expressed, suggesting that mutant hematopoietic cells may require the residual WT allele to be viable. We show that hematopoiesis and RNA splicing in U2af1 heterozygous knockout mice were similar to those in control mice, but that deletion of the WT allele in U2AF1(S34F) heterozygous mutant-expressing hematopoietic cells (i.e., hemizygous mutant) was lethal. These results confirm that U2AF1 mutant hematopoietic cells are dependent on the expression of WT U2AF1 for survival in vivo and that U2AF1 is a haplo-essential cancer gene. Mutant U2AF1(S34F)-expressing cells were also more sensitive to reduced expression of WT U2AF1 than nonmutant cells. Furthermore, mice transplanted with leukemia cells expressing mutant U2AF1 had significantly reduced tumor burden and improved survival after the WT U2af1 allele was deleted compared with when it was not deleted. These results suggest that selectively targeting the WT U2AF1 allele in heterozygous mutant cells could induce cancer cell death and be a therapeutic strategy for patients harboring U2AF1 mutations.

Bam-readcount - rapid generation of basepair-resolution sequence metrics.

Bam-readcount is a utility for generating low-level information about sequencing data at specific nucleotide positions. Originally designed to help filter genomic mutation calls, the metrics it outputs are useful as input for variant detection tools and for resolving ambiguity between variant callers1,2. In addition, it has found broad applicability in diverse fields including tumor evolution, single-cell genomics, climate change ecology, and tracking community spread of SARS-CoV-2.3-6.

Simultaneous breast and ovarian metastasis from gallbladder carcinoma.

BACKGROUND: Gallbladder carcinoma is a common malignancy in the Indian subcontinent. It commonly metastasizes through lymphatics, direct invasion, and hematogenous spread. A common extra-abdominal site of metastasis is the lungs. Simultaneous metastasis to breast and ovary is extremely rare. METHOD: This report describes an unusual case of carcinoma gallbladder metastasizing to the breast and ovary at the same time. RESULTS: A 45-year-old woman came to us with complaints of flatulent dyspepsia associated with weight loss and anorexia. Ultrasound of the abdomen revealed hepatomegaly with thick-walled gallbladder with multiple stones and a mass at the fundus, but normal uterus and ovary. Contrast-enhanced computer tomography of the abdomen showed a gallbladder mass infiltrating the liver parenchyma. The patient underwent radical cholecystectomy. Histopathological examination revealed a poorly-differentiated adenocarcinoma with mar-gins free from tumor infiltration. One month after surgery she developed a breast lump. Ultrasound of the abdomen for metastatic workup revealed an ovary mass. Simple mastectomy and salphingo-opherectomy were performed, and histopathological examination revealed a metastatic adenocarcinoma. The patient is now on chemotherapy with gemcitabin. CONCLUSION: This is an unusual case of carcinoma of the gallbladder with metastasis to the breast and ovary, which has not been documented before.

Study of association of varicose veins and inflammation by inflammatory markers.

OBJECTIVE: In varicose veins, increased levels of inflammatory markers are indicators of endothelial damage and increased procoagulant activity. These findings support the assumption that the constitution of blood in varicose veins differs from that of systemic blood. The purpose of the study was a correlative study of blood constituents in varicose veins and peripheral veins (normal vein) in same individual with varicose vein which was done by comparing the level of concentration of interleukin-6, fibrinogen, haemoglobin from blood of varicose veins and normal peripheral vein (antecubital vein). METHOD: Using citrated plasma samples withdrawn from arms and legs of same patient and plasma obtained by centrifugation of citrated venous blood at 5000 r/min for 10 min was used for correlation. Serum concentration of interleukin-6 and fibrinogen were determined by human enzyme-linked immunosorbent assay Kit for both interleukin-6 and fibrinogen, which is based on the standard sandwich enzyme-linked immunosorbent assay technology. This assay employs a monoclonal antibody specific for human interleukin-6 coated on a 96-well plate. RESULT: Expressed as median (interquartile range) in pg/mL, leg samples from patient having varicose vein has significantly increased interleukin-6 in cases as compared to controls (p value of <0.001). Leg samples from patient having varicose vein has significantly increased fibrinogen concentration than their arm samples (p value of <0.001). Concentration of haemoglobin significantly increased in leg samples as compared to blood withdrawn from arms (p value of 0.012). CONCLUSION: Blood withdrawn from the site of varicose vein appears to have significantly increased concentration of interleukin-6, fibrinogen and haemoglobin when compared to same patient's antecubital blood sample supporting the hypothesis that inflammation is increased in tissues drained by varicose vein.

Digital glomus tumor: An experience of 57 cases over 20 years.

BACKGROUND: Glomus tumors are rare tumors and may affect any area of the body, but digits, palms, and soles are commonly affected due to higher number of glomus body. We present our experience with the management of 57 cases of glomus tumors of the fingertips treated over a period of 20 years (2000-2019). MATERIALS AND METHODS: Medical records of 57 cases with glomus tumors treated over a period of 20 years were reviewed for patient demographics, presenting characteristics, duration, previous treatment history, physical examination, investigation, treatment, follow-up, and recurrence. RESULTS: In our study, the mean age was 49 years, with age 47 years among women and 53 years among men suggesting glomus tumor as a disease of past middle age. The total number of cases was 57 with 44 women and 13 men. Site of lesion was nail bed in 50 cases (87.7%) and tip of finger in 7 cases (12.3%). In clinical assessment pinpoint tenderness was present in all 57 cases (100%) and pain in 56 cases (98.8%). Other features at the time of presentation were nodularity in 38 cases (66.6%), deformed nail in 14 cases (24.6%), and cold hypersensitivity in 20 cases (35.1%). The mean duration of the disease was 2.3 years (1.2-5.6 years). CONCLUSION: One of the most painful clinical conditions confirmed by comprehensive clinical assessment and cured dramatically by complete surgical excision.

Simplified Laparoscopic Suture Rectopexy for Idiopathic Rectal Prolapse In Children: Technique and Results.

BACKGROUND: Laparoscopic suture rectopexy is safe and effective treatment option for pediatric rectal prolapse. We performed this study to compare the outcome of modified laparoscopic suture rectopexy (MLSR) versus Classical Laparoscopic suture rectopexy (CLSR). MATERIAL AND METHODS: The study was conducted between June 2015 to May 2019 including all the patients with persistent rectal prolapse who underwent surgery managed by either MLSR (Group A) or CLSR (Group B). The groups were compared for constipation, operative time, blood loss, length of stay, postoperative complications. RESULTS: 19 patients from MLSR and 22 patients from CLSR were evaluated. The mean operative time in MLSR group was 41.5 ±â€¯6.2 min which was significantly lesser than CLSR group with a mean operative time of 78.6 ±â€¯14.2 (p = 0.001). The blood loss was also less in MLSR group compared to CLSR group (p = 0.013). At three months of follow up, the constipation was less in MLSR group compared to CLSR group (p = 0.041). CONCLUSION: The modification makes the procedure technically easy, minimizes the chances of complications and retaining all the advantages of suture rectopexy. LEVEL OF EVIDENCE: Level II.

Assessment and grading of pigmentation in chronic venous insufficiency.

INTRODUCTION: Chronic venous insufficiency causes skin pigmentation of the leg ranging from small patches of mild dyschromia to extensive areas of severe skin pigmentation. It is thought that the pigmentation is mainly due to haemosiderin or melanin deposition. Erythrodiapedesis which occurs as a result of venular hypertension causes erythrocytes to migrate across the microvascular network into the dermis. METHODS: We categorized the grading of pigmentation into four grades: +, few spots; ++, pigmentation over gaiter area; +++, pigmentation involving leg and ankle; ++++, heavily pigmented (dark). Skin biopsies were taken from the patient while undergoing surgery; two biopsies were taken from each patient, one from apparently normal skin and other from the site of pigmentation. A total of 45 patients diagnosed as chronic venous insufficiency with pigmentation were included in the study and five patients included in control. The biopsy specimens were sent to pathology department for H&E, Perls stain and IHC for S100. RESULTS: Majority of cases, i.e. 62% of limbs fall under (++) grade of pigmentation, followed by (+) grade of pigmentation in 20%, while (+++) and (++++) constitute 9% of the cases each. Increased melanin deposition was seen in 40 pigmented skin biopsies and 3 normal skin biopsies from the case group, and normal melanin deposition was seen in all the non-varicose controls. CONCLUSION: We have tried to categorize pigmentation in chronic venous insufficiency into four grades. As the grade of pigmentation increases the per cent of cases with ulceration is increasing. It was observed that presence of melanin deposition irrespective of the grade of pigmentation was distributed more towards the advanced clinical classification (C5 and C6).

Pfam: clans, web tools and services.

Pfam is a database of protein families that currently contains 7973 entries (release 18.0). A recent development in Pfam has enabled the grouping of related families into clans. Pfam clans are described in detail, together with the new associated web pages. Improvements to the range of Pfam web tools and the first set of Pfam web services that allow programmatic access to the database and associated tools are also presented. Pfam is available on the web in the UK (http://www.sanger.ac.uk/Software/Pfam/), the USA (http://pfam.wustl.edu/), France (http://pfam.jouy.inra.fr/) and Sweden (http://pfam.cgb.ki.se/).