Crystal Structures of Influenza A Virus Matrix Protein M1: Variations on a Theme

Matrix protein 1 (M1) of the influenza A virus plays multiple roles in virion assembly and infection. Interest in the pH dependence of M1\u27s multiple functions led us to study the effect of subtle pH changes on M1 structure, resulting in the elucidation of a unique low-pH crystal structure of the N1-165-domain of A/WSN/33 (H1N1) M1 that has never been reported. Although the 2.2 Å crystal structure of M1 N-terminus shows a dimer with the two monomers interacting in a face-to-face fashion at low pH as observed earlier, a 44° rotation of the second monomer has led to a significantly different dimer interface that possibly affects dimer stability. More importantly, while one of the monomers is fully defined, the N-terminal half of the second monomer shows considerable disorder that appears inherent in the protein and is potentially physiologically relevant. Such disorder has not been observed in any other previously reported structure at either low or high pH conditions, despite similar crystallization pH conditions. By comparing our novel N1-165-domain structure with other low-pH or neutral-pH M1 structures, it appears that M1 can energetically access different monomer and dimer conformations, as well as oligomeric states, with varying degree of similarities. The study reported here provides further insights into M1 oligomerization that may be essential for viral propagation and infectivity

Pairwise Balanced Designs From Cyclic PBIB Designs

A pairwise balanced designs was constructed using cyclic partially balanced incomplete block designs with either (λ1 – λ2) = 1 or (λ2 – λ1) = 1. This method of construction of Pairwise balanced designs is further generalized to construct it using cyclic partially balanced incomplete block design when |(λ1 – λ2)| = p. The methods of construction of pairwise balanced designs was supported with examples. A table consisting parameters of Cyclic PBIB designs and its corresponding constructed pairwise balanced design is also included

Evaluation of trigger tool method for adverse drug reaction reporting by nursing staff at a tertiary care teaching hospital

Background: To sensitize nurses about Trigger Tool Method (TTM) and to evaluate the impact of TTM on adverse drug event (ADE) reporting by nurses at a tertiary care teaching hospital in India.Methods: This was prospective, interventional, single center study conducted among nursing health professionals of Civil Hospital Ahmedabad (CHA) posted in Medicine Department. They were sensitized about ADE reporting, pharmacovigilance, methods of ADRs reporting and details about TTM. Also, a list of 17 triggers was prepared by the investigator and given to nurses. They were educated to report ADEs using TTM. At the initiation and end of study, questionnaires were given to evaluate knowledge, attitude and practice of ADR reporting among participant nurses. All triggers and ADEs reported were analyzed in terms of association between them, effectiveness of trigger in detecting an ADR and in terms of Positive Predictive Value (PPV). Reported ADRs were also assessed for causality, severity and preventability.Results: A total 758 patients were admitted during the study period in the respective medicine department. List of 17 triggers consists of 9 drug triggers (DT), 1 laboratory trigger (LT) and 7 patient triggers (PT). Of these 17 triggers, 14 triggers were identified by nurses. These 14 triggers were noticed 130 times. These included DT (100 times), LT (0 times) and PT (30 times). Of the various triggers observed, 7 DT and 4 PT were related to ADRs. Hence, 11 triggers (64.70%) were positive (related to ADRs), out of 17 total triggers under evaluation. 21 ADRs were observed using TTM by nurses.Conclusions: The TTM helps to detect and report ADRs by nurses. Educational interventions about TTM help in better detection and reporting of ADRs

Visual Diagnosis: Pearling: a case study

We present the case of a patient who attempted to perform a type of body modification known as "pearling" or "genital beading" while in prison. This patient unfortunately caused severe trauma to his penis, requiring surgical intervention. Photographs of the traumatic injuries are presented

A Case Report on Longitudinal Collection of Tumour Biopsies for Gene Expression-Based Tumour Microenvironment Analysis from Pancreatic Cancer Patients Treated with Endoscopic Ultrasound Guided Radiofrequency Ablation.

BACKGROUND: Most patients with pancreatic ductal adenocarcinoma (PDAC) are metastatic at presentation with dismal prognosis warranting improved systemic therapy options. Longitudinal sampling for the assessment of treatment response poses a challenge for validating novel therapies. In this case study, we evaluate the feasibility of collecting endoscopic ultrasound (EUS)-guided longitudinal fine-needle aspiration biopsies (FNABs) from two PDAC patients and conduct gene expression studies associated with tumour microenvironment changes associated with radiofrequency ablation (RFA). METHODS: EUS-guided serial/longitudinal FNABs of tumour were collected before and after treatment from two stage III inoperable gemcitabine-treated PDAC patients treated with targeted RFA three times. Biopsies were analysed using a custom NanoString panel (144 genes) consisting of cancer and cancer-associated fibroblast (CAFs) subtypes and immune changes. CAF culture was established from one FNAB and characterised by immunofluorescence and immunoblotting. RESULTS: Two-course RFA led to the upregulation of the CD1E gene (involved in antigen presentation) in both patients 1 and 2 (4.5 and 3.9-fold changes) compared to baseline. Patient 1 showed increased T cell genes (CD4-8.7-fold change, CD8-35.7-fold change), cytolytic function (6.4-fold change) and inflammatory response (8-fold change). A greater than 2-fold upregulation of immune checkpoint genes was observed post-second RFA in both patients. Further, two-course RFA led to increased PDGFRα (4.5-fold change) and CAF subtypes B and C genes in patient 1 and subtypes A, B and D genes in patient 2. Patient 2-derived CAFs post-first RFA showed expression of PDGFRα, POSTN and MYH11 proteins. Finally, RFA led to the downregulation of classical PDAC subtype-specific genes in both patients. CONCLUSIONS: This case study suggests longitudinal EUS-FNAB as a potential resource to study tumour and microenvironmental changes associated with RFA treatment. A large sample size is required in the future to assess the efficacy and safety of the treatment and perform comprehensive statistical analysis of EUS-RFA-based molecular changes in PDAC

PCA Encrypted Short Acoustic Data Inculcated in Digital Color Images

We propose develop a generalized algorithm for hiding audio signal using image steganography. The authors suggest transmitting short audio messages camouflaged in digital images using Principal Component Analysis (PCA) as an encryption technique. The quantum of principal components required to represent the audio signal by removing the redundancies is a measure of the magnitude of the Eigen values. The aforementioned technique follows a dual task of encryption and in turn also compresses the audio data, sufficient enough to be buried in the image. A 57Kb audio signal is decipher from the Stego image with a high PSNR of 47.49 and a correspondingly low mse of 3.3266 × 1

Coriandrum sativum L. aqueous extract mitigates high fat diet induced insulin resistance by controlling visceral adiposity in C57BL/6J Mice

En este estudio se investigó el efecto de un extracto acuoso de semillas de Coriandrum sativum L. (CS), adicionado a una dieta con alto contenido graso en ratones C57BL/6J, con resistencia a la insulina inducida. Los cambios en el aumento de peso corporal, consumo de alimento, eficiencia alimenticia, glicemia, insulina plasmática, índice de resistencia a la insulina, triglicéridos hepáticos y plasmáticos, colesterol total y concentración plasmática de ácidos grasos libres, fueron evaluados en grupos control y tratados. Adicionalmente se controló, el diámetro, superficie y número de adipocitos, prueba de tolerancia a la glucosa intraperitoneal y la prueba de respuesta de la insulina por vía intraperitoneal. La adición de CS (1% y 3% w / w) a la dieta con alto contenido graso a ratones (12 semanas) previno de manera significativa el incremento de peso, la ingesta de alimentos, la eficiencia alimenticia, FBG, la insulina plasmática, FIRI, los triglicéridos hepáticos y plasmáticos, el colesterol total, ácidos grasos libres plasmáticos, el diámetro de los adipocitos y la superficie junto con el decremento en el número de los adipocitos. Además, mejoras de la respuesta se registraron en el IPGTT y IPRTT. Este conjunto de cambios fue comparable al obtenido con rosiglitazona (0,05%), adicionada a la dieta con alto contenido graso. Estos hallazgos sugieren que el CS mejora la sensibilidad a la insulina principalmente por la mitigación de los lípidos del plasma, del tejido y la hipertrofia del adipocito.This study investigates the effect of dietary supplementation with Coriandrum sativum L. seed aqueous extract (CS) to a high fat diet (HFD), for induced insulin resistance (IR) C57BL/6J mice. Changes in body weight, food intake, feed efficiency ratio, fasting blood glucose (FBG), plasma insulin, fasting insulin resistance index (FIRI), plasma and hepatic triglyceride (TG), total cholesterol (TC) and, plasma free fatty acid (FFA) levels were evaluated in control and treated groups. Also, the diameter, surface area and number of adipocytes and, intraperitoneal glucose tolerance test (IPGTT) and intraperitoneal insulin response test (IPRTT) were performed. CS supplementation (1% and 3% w/w) to HFD fed mice (for 12 weeks) significantly prevented HFD induced increment in body weight gain, food intake, feed efficiency, FBG, plasma insulin, FIRI, plasma and hepatic TG and TC and, plasma FFA, adipocyte diameter and surface area along with decrement in adipocyte number. Also, improved responses were recorded in the IPGTT and IPRTT in CS supplemented HFD fed mice. These set of changes were comparable to the rosiglitazone (0.05%) supplemented HFD fed mice. Our findings suggest that CS improves insulin sensitivity primarily by mitigating plasma and tissue lipids and, adipocyte hypertrophy