N-acetylcysteine (NAC) ameliorates Epstein-Barr virus latent membrane protein 1 induced chronic inflammation

Chronic inflammation results when the immune system responds to trauma, injury or infection and the response is not resolved. It can lead to tissue damage and dysfunction and in some cases predispose to cancer. Some viruses (including Epstein-Barr virus (EBV)) can induce inflammation, which may persist even after the infection has been controlled or cleared. The damage caused by inflammation, can itself act to perpetuate the inflammatory response. The latent membrane protein 1 (LMP1) of EBV is a pro-inflammatory factor and in the skin of transgenic mice causes a phenotype of hyperplasia with chronic inflammation of increasing severity, which can progress to pre-malignant and malignant lesions. LMP1 signalling leads to persistent deregulated expression of multiple proteins throughout the mouse life span, including TGFα S100A9 and chitinase-like proteins. Additionally, as the inflammation increases, numerous chemokines and cytokines are produced which promulgate the inflammation. Deposition of IgM, IgG, IgA and IgE and complement activation form part of this process and through genetic deletion of CD40, we show that this contributes to the more tissue-destructive aspects of the phenotype. Treatment of the mice with N-acetylcysteine (NAC), an antioxidant which feeds into the body’s natural redox regulatory system through glutathione synthesis, resulted in a significantly reduced leukocyte infiltrate in the inflamed tissue, amelioration of the pathological features and delay in the inflammatory signature measured by in vivo imaging. Reducing the degree of inflammation achieved through NAC treatment, had the knock on effect of reducing leukocyte recruitment to the inflamed site, thereby slowing the progression of the pathology. These data support the idea that NAC could be considered as a treatment to alleviate chronic inflammatory pathologies, including post-viral disease. Additionally, the model described can be used to effectively monitor and accurately measure therapies for chronic inflammation

Impact of Work from Home on Employee Performance in Context of Bangladesh

This study investigates the effects of work-from-home on job performance and its mediating factors. This is certainly relevant in the aftermath of the coronavirus outbreak. While acknowledging the need of investigating employees' perspectives in order to create a productive work-from-home environment, this study focuses on the elements that influence job performance. It suggests job satisfaction and motivation as mediating variables to explain how working from home influences employee performance. The study's questionnaire-based data, which has been tailored to the changes caused by current pandemic, was acquired through multiple in-person and online survey of Bangladeshi employees. A total of 260 people actively participated in the assessment. In its further processing, the study utilized structural equation-based framework to address the research questions. In the study, employees reported more job satisfaction and motivation as a result of working from home, resulting in improved job performance. While the relevance of this study is constrained to how these advantages are manifested in Bangladesh, it may have external validity in other pandemic-affected nations. Keywords: Information Technology, Job Motivation, Performance Appraisal, Strategic Human Resource Management, Work Environment. DOI: 10.7176/EJBM/14-22-02 Publication date: November 30th 202

Contegra valved conduit in the paediatric population: an exciting prospect for right ventricle to pulmonary artery reconstruction; experience and outcomes at Aga Khan University

Objective: The focus of this study is to share the experience and outcomes of Contegra graft implantation in the paediatric and adult population in Pakistan. Methods: Between May 2007 and July 2011, 16 patients, underwent implantation of a Contegra valved conduit. All operations were performed through a median sternotomy with cardiopulmonary bypass. Indications included: Pulmonary atresia with ventricular septal defect (n=11), Tetralogy of Fallot with absent Pulmonary Valve (PV) syndrome (n=2), double outlet right ventricle, transposition of great arteries and pulmonary stenosis (n=1), isolated aortic valve disease (n=1) and a pseudo-aneurysm with infective endocarditis (n=1).Conduit sizes varied between 16-22 mm. Results: The three in hospital deaths were unrelated to the Contegra valved conduit. One patient was lost to follow up. Of the 12 survivors, 10 are currently free from re-operation or complications related to the conduit while one needed distal pulmonary artery dilatation owing to critical stenosis and another had severe Valvular regurgitation. Echocardiographic evaluation of the Contegra valved conduit demonstrated no haemodynamically significant valve regurgitation in 10 patients. Conclusion: In this small review of 16 operations using the Contegra valved conduit for Right Venticular Outflow Tract (RVOT) reconstruction in the paediatric population, we observed good post operative results concerning conduit function. The Contegra conduit provides an excellent substitute to the homograft with satisfactory early and mid-term results though long term results are awaited in Pakista

Repair or prosthesis insertion in ischemic mitral regurgitation: Two faces of the same medal

AbstractObjectiveThe proper treatment of chronic ischemic mitral regurgitation (CIMR) is still under evaluation. The different role of mitral valve repair (MVr) or mitral valve prosthesis insertion (MVPI) is still not defined.MethodsFrom May 2009 to December 2011 167 patients with ejection fraction (EF) ≤ 40% had MV surgery for CIMR, MVr in 135 (80.8%) and MVPI in 32 (19.2%). Indication to MVPI was a MV coaptation depth > 10 mm. EF was lower (26 ± 7 vs 32 ± 6, p = 0.0000) in MVPI, whereas MR grade (3.6 ± 0.8 vs 2.7 ± 0.9, p = 0.0000), left ventricle dimensions (end diastolic, LVEDD, 62 ± 7 vs 57 ± 6 mm, p = 0.0001; end systolic, LVESD, 49 ± 8 vs 44 ± 8 mm, p = 0.0018), systolic pulmonary artery pressure (51 ± 22 vs 41 ± 16 mm Hg, p = 0.0037) and NYHA Class (3.6 ± 0.5 vs 2.8 ± 0.6, p = 0.0000) were higher.ResultsIn-hospital mortality was similar (3.1 vs 3.7%) as well as 3-year survival (86 ± 6 vs 88 ± 4) and survival in NYHA Class I/II (80 ± 5 vs 83 ± 4). One hundred thirty nine patients had an echocardiographic evaluation after a minimum of 4 months (13 ± 8). EF rose significantly in both groups (from 26 ± 7% to 30 ± 4%, p = 0.0122, and from 32 ± 6% to 35 ± 8%, p = 0.0018). LVESD reduced significantly in both groups (from 49 ± 8 to 43 ± 9 mm, p = 0.0109, and from 44 ± 8 to 41 ± 7 mm, p = 0.0033). MR grade was significantly lower in patients who had MVPI (0.1 ± 0.2 vs 0.3 ± 0.3, p = 0.0011).ConclusionsWith appropriate indications, MVPI is a safe procedure which provides similar results to MVr with lower MR return, even if addressed to patients with worse preoperative parameters

Diversified Traditional Wooden Implements Used in Agriculture and Animal Husbandry Practices in Ladakh

The traditional wooden tools are the necessities of the daily life of the people of Ladakh region and are linked directly with geographical conditions of the region. A lot of diversity in the wooden tools used by the tribal farmers of Ladakh since ancient times is observed. The tools are made up of different, locally available materials in a unique fashion by the localites. These wooden implements are preferred over modern one’s because of their multipurpose uses. Secondly these traditional implements find wide applicability in the region because of steep terrain, where the scope of mechanized farm implements is very limited. In the present study few important traditional tools of Ladakh have been presented. The important tools viz; chepo, shak, zungba, rzgeem, saddle, khem, khaczhay, thougk, gourgur, butter churner, plough, smeing, rbhat, grookook etc. have been described in detail in this paper

Modifier genes in microcephaly: A report on WDR62, CEP63, RAD50 and PCNT variants exacerbating disease caused by biallelic mutations of ASPM and CENPJ

Congenital microcephaly is the clinical presentation of significantly reduced head circumference at birth. It manifests as both non-syndromic-microcephaly primary hereditary (MCPH)-and syndromic forms and shows considerable inter- and intrafamilial variability. It has been hypothesized that additional genetic variants may be responsible for this variability, but data are sparse. We have conducted deep phenotyping and genotyping of five Pakistani multiplex families with either MCPH (n = 3) or Seckel syndrome (n = 2). In addition to homozygous causal variants in ASPM or CENPJ, we discovered additional heterozygous modifier variants in WDR62, CEP63, RAD50 and PCNT-genes already known to be associated with neurological disorders. MCPH patients carrying an additional heterozygous modifier variant showed more severe phenotypic features. Likewise, the phenotype of Seckel syndrome caused by a novel CENPJ variant was aggravated to microcephalic osteodysplastic primordial dwarfism type II (MOPDII) in conjunction with an additional PCNT variant. We show that the CENPJ missense variant impairs splicing and decreases protein expression. We also observed centrosome amplification errors in patient cells, which were twofold higher in MOPDII as compared to Seckel cells. Taken together, these observations advocate for consideration of additional variants in related genes for their role in modifying the expressivity of the phenotype and need to be considered in genetic counseling and risk assessment

Multicenter Study of Presentation, Management, and Postoperative and Long-Term Outcomes of Septegenerians and Octogenerians Undergoing Gastrectomy for Gastric Cancer

Background: The optimal treatment strategy for elderly patients with gastric cancer is still controversial. This study aimed to assess the impact of age on short- and long-term outcomes after treatment for primary gastric cancer. Methods: From January 2004 to December 2014, a total of 507 patients underwent gastrectomy for gastric adenocarcinoma at two high-volume upper gastrointestinal (GI) centers. The patients were classified into three groups as follows: group A (patients ≤ 69 years old, n = 266), group B (patients 70–79 years old, n = 166), and group C (patients ≥ 80 years old, n = 75). Clinicopathologic characteristics as well as, short- and long-term outcomes were compared between the groups. Results: The patients in groups B and C had more comorbidities, whereas the younger subjects (group A) had more advanced tumor stages. Less extensive surgery was performed in the groups B and C. Older patients (age ≥ 70 years) had more postoperative medical complications. Moreover, group C had a higher postoperative mortality rate (8.1%) than group A (1.8%) or group B (1.9%). In the multivariable analysis, age older than 80 years (group C) was a negative independent factor for overall survival (OS) (hazard ratio [HR], 2.36) compared with group A, whereas group B seemed to have a comparable risk (HR, 1.37). Notably, the three groups did not show significant differences in disease-related survival (DRS). Conclusion: The data suggest that patients 70–79 years of age show a risk of postoperative death comparable with that of younger subjects. However, patients older than 80 years should be carefully selected for surgical treatment due to the increased risk of postoperative mortality