Gram-Negative Bloodstream Infections in Healthcare: The Relationship Between Antibiotic Resistance, Mortality, and Novel Serological Biomarker.

BACKGROUND: Bloodstream infections caused by Gram-negative bacteria are highly mortal. In this study, we aimed to investigate the relationship between antimicrobial resistance profile and novel serological biomarkers and mortality in bloodstream infections (BSIs) caused by Gram-negative bacteria in intensive care units (ICUs). METHODS: 366 Patients diagnosed with healthcare-associated Gram-negative bloodstream infection in the ICUs of our hospital between February 2015 and December 2021 were included in the study. Demographic variables (age, gender, comorbidities), causative microorganisms and antimicrobial susceptibilities, time to first positive blood culture after hospitalization, length of stay in hospital, surgical procedures, laboratory data (hemograms, C-reactive protein (CRP) levels, albumin), and survival data were collected. Novel serological biomarkers were calculated. RESULTS: Mortality in Gram-negative bloodstream infection was found to be associated with age and novel serological biomarkers, but not with carbapenems and colistin minimum inhibitory concentration (MIC) values. Mortality rates increased with age (p˂0.001). Patients who died had higher C-reactive protein/albumin ratio (CAR) (p<0.001) and neutrophil/lymphocyte ratio (NLR) (p=0.009) and lower prognostic nutritional index (PNI) (p<0.001). CONCLUSION: The study emphasizes that resistance to colistin and carbapenems is not associated with mortality in BSIs caused by Gram-negative bacteria. Novel serological biomarkers may be useful in predicting mortality. These results support the need for further studies to elucidate the true impact of infections caused by resistant bacteria.

Assessment of Kidney Function among the Employees of Sylhet MAG Osmani Medical College and Hospital.

The kidney carries out a variety of physiological processes, including the excretion of nitrogenous waste products, maintenance of fluid, electrolyte, acid-base, and mineral homeostasis, regulation of blood pressure, as well as the synthesis and release of erythropoietin and other endocrine substances. Chronic kidney disease (CKD) can lead to end-stage renal disease (ESRD) and increased cardiovascular morbidity and mortality. CKD has a long period of asymptomatic stage. The symptoms of CKD usually present at the advanced stage of the disease. Chronic kidney disease (CKD) is a potentially fatal that impacts various physiological systems. This cross-sectional observational study was conducted in the Department of Physiology in collaboration with the Department of Nephrology, Sylhet MAG Osmani Medical College Hospital (SMAGOMC&H), from July 2022 to June 2023 to observe the status of kidney function among the employees of SMAGOMC&H, Bangladesh. The study population consisted of all willingly participating volunteers working at SMAGOMC&H between the ages of 18 and 59 years. Participants with acute illness, malignancy, pregnancy, diagnosed case of CKD, and history of kidney transplant were excluded from the study. A thorough history was taken, and a physical examination was done. Serum creatinine, and spot urine albumin creatinine ratio (ACR) of each participant were measured. eGFR (estimated glomerular filtration rate) was estimated by using NKF (National Kidney Foundation) eGFR calculator app. A Semi-structured questionnaire was used for data collection. Most of the participants were between 50-59 years (46.0%). The mean age of these study subjects was 45.25±10.08 years. The mean serum creatinine level was 0.85±0.18 mg/dl, the mean eGFR was 102.92±16.21 ml/min/1.73m² and the mean urinary ACR was 27.44±12.48 mg/gm found in this study. Out of the total participants, 16.5% were at stage 1 CKD, 6.5% were at stage 2 CKD and 2.5% were at stage 3 CKD, according to eGFR by CKD-EPI (Chronic kidney disease epidemiology collaboration) equation. Seventy five percent (75.0%) of the participants had normal to mildly increased ACR and 25.0% had moderately increased ACR. Pearson's correlation test revealed a significant negative correlation of eGFR with age, serum creatinine, and urinary ACR (p<0.001). This study revealed that 16.5%, 6.5% and 2.5% of the study participants were at CKD stage 1, stage 2, and stage 3, respectively. Assessment of renal function can help early identification of CKD in apparently healthy asymptomatic subjects.

Mental Health among the Infertile Women Attending Tertiary Level Hospital in Bangladesh.

Infertility is a global public health issue and is a low control stressor often leading to increased level of depression, anxiety and stress. It is a severely distressing experience for many couples and it may significantly affect the physical and mental life of infertile individuals. The study was to assess the level of mental health state (depression, anxiety and stress) among the infertile women in tertiary level hospital in Bangladesh. This cross sectional descriptive study was conducted at two tertiary level hospitals in Bangladesh named BSMMU and CARe Medical College. Three hundred and fifty-two (352) infertile women were taken as a sample and a semi-structured questionnaire which contains question with related variables and DASS 21 was used. The study results revealed that, the mean age of the respondents was 29.32 years. Almost three-fourth 260(73.86%) of the respondents were Muslim and 349(99.14%) respondents were educated. Two-third 223(63.35%) of the respondents were from rural area and 177(50%) were housewife. About 229(65.05%) were live in a joint family and 205(58.23%) had an abortion history. Majority 312(88.63%) of the respondents had monthly income BDT <30000 Taka. According to DASS 21, 175(49.71%) had depression, 212(60.22%) had anxiety and 157(44.60%) suffered from stress. There was a significant association (p<0.05) found between mental health state with age, religion, residence and occupation. This finding reinforces the need of attention counseling and others advance psychological interventions for positive impact on outcome during treatment of this group of women.

Interplay between proteasome function and inflammatory responses in e-cig vapor condensate-challenged lung epithelial cells.

Exposure to cigarettes and other nicotine-based products results in persistent inflammation in the lung. In recent years, electronic cigarettes (e-cigs) have become extremely popular among adults and youth alike. E-cigarette vapor-induced oxidative stress promotes protein breakdown, DNA damage and cell death, culminating in a variety of respiratory diseases. The proteasome, a multi-catalytic protease, superintends protein degradation within the cell. When cells are stimulated with inflammatory cytokines such as IFN-γ and TNF-α, the constitutive catalytic proteasome subunits are replaced by the inducible subunits-low-molecular mass polypeptide (LMP)2 (ß1i), multi-catalytic endopeptidase complex-like (MECL)1 (ß2i), and LMP7 (ß5i), which are required for the production of certain MHC class I-restricted T-cell epitopes. In this study, we used human alveolar epithelial cells (A549) and exposed them to filtered air or (1%) tobacco-flavored (TF) electronic cigarette vapor condensate (ECVC) ± nicotine (6 mg/ml) (TF-ECVC ± N) for 24 h. We observed an increase in the levels of IFN-γ, TNF-α, and inducible proteasome subunits (LMP7/PSMB8, LMP2/PSMB9, MECL1/PSMB10), and a reduced expression of constitutive proteasome subunits (ß1/PSMB6 and ß2/PSMB7) in challenged A549 cells. Interestingly, knockdown of the inducible proteasome subunit LMP7 reversed ECVC-induced expression of NADPH oxidase and immunoproteasome subunits in A549 cells. In addition, pre-exposure to an LMP7 inhibitor (ONX-0914) abrogated the mRNA expression of several NOX subunits and rescued the excessive production/release of inflammatory cytokines/chemokines (IL-6, IL-8, CCL2, and CCL5) in ECVC-challenged cells. Our findings suggest an important role of LMP7 in regulating the expression of inflammatory mediators during ECVC exposure. Overall, our results provide evidence for proteasome-dependent ROS-mediated inflammation in ECVC-challenged cells.

A novel combination of sitagliptin and melatonin ameliorates T2D manifestations: studies on experimental diabetic models.

INTRODUCTION: Type 2 diabetes (T2D) is an endocrine disorder characterized by hyperglycemia, insulin resistance, dysregulated glucose and lipid metabolism, reduced pancreatic ß-cell function and mass, and a reduced incretin effect. Circadian rhythm disruption is associated with increased T2D risk. We have investigated the therapeutic potential of a combination of melatonin (M) and sitagliptin (S), a dipeptidyl peptidase IV (DPP-IV) inhibitor, in the amelioration of T2D manifestations in high-fat diet (HFD) induced T2D mouse model and also on ß-cell proliferation under gluco-lipotoxicity stress in vitro. METHODS: For in vivo study, mice were fed with HFD for 25 weeks to induce T2D and were treated with monotherapies and S + M for four weeks. For the in vitro study, primary mouse islets were exposed to normal glucose and high glucose + palmitate to induce gluco-lipotoxic stress. RESULTS: Our results suggest that monotherapies and S + M improve metabolic parameters and glyco-lipid metabolism in the liver and adipose tissue, respectively, and improve mitochondrial function in the skeletal muscle. Moreover, it increases peripheral insulin sensitivity. Our in vitro and in vivo studies suggest that ß-cell mass was preserved in all the drug-treated groups. CONCLUSION: The combination treatment is superior to monotherapies in the management of T2D.

Trends in maternal mortality in India over two decades in nationally representative surveys.

OBJECTIVE: To assess national and regional trends and causes-specific distribution of maternal mortality in India. DESIGN: Nationally representative cross-sectional surveys. SETTING: All of India from 1997 to 2020. SAMPLE: About 10 000 maternal deaths among 4.3 million live births over two decades. METHODS: We analysed trends in the maternal mortality ratio (MMR) from 1997 through 2020, estimated absolute maternal deaths and examined the causes of maternal death using nationally representative data sources. We partitioned female deaths (aged 15-49 years) and live birth totals, based on the 2001-2014 Million Death Study to United Nations (UN) demographic totals for the country. MAIN OUTCOME MEASURES: Maternal mortality burden and distribution of causes. RESULTS: The MMR declined in India by about 70% from 398/100 000 live births (95% CI 378-417) in 1997-98 to 99/100 000 (90-108) in 2020. About 1.30 million (95% CI 1.26-1.35 million) maternal deaths occurred between 1997 and 2020, with about 23 800 (95% CI 21 700-26 000) in 2020, with most occurring in poorer states (63%) and among women aged 20-29 years (58%). The MMRs for Assam (215), Uttar Pradesh/Uttarakhand (192) and Madhya Pradesh/Chhattisgarh (170) were highest, surpassing India's 2016-2018 estimate of 113 (95% CI 103-123). After adjustment for education and other variables, the risks of maternal death were highest in rural and tribal areas of north-eastern and northern states. The leading causes of maternal death were obstetric haemorrhage (47%; higher in poorer states), pregnancy-related infection (12%) and hypertensive disorders of pregnancy (7%). CONCLUSIONS: India could achieve the UN 2030 MMR goals if the average rate of reduction is maintained. However, without further intervention, the poorer states will not. TWEETABLE ABSTRACT: We estimated that 1.3 million Indian women died from maternal causes over the last two decades. Although maternal mortality rates have fallen by 70% overall, the poorer states lag behind.

Efficacy of Palonosetron as Antiemetic Prophylaxis for Post Operative Patients.

Palonosetron is a new, potent and long-acting 5HT3-receptorsantagonist that had been approved by the FDA for use in postoperative nausea and vomiting (PONV) prophylaxis. The objective of this study was to investigate and compare the prophylactic effects of intravenously administered palonosetron, ondansetron and granisetron on prevention of postoperative nausea and vomiting after general anesthesia. This randomized double blind prospective clinical study was carried out in the Department of Anaesthesia, DMCH, Dhaka, Bangladesh from January 2014 to December 2015. A total of 102 patients who underwent laparoscopic cholecystectomy under general anesthesia, out of which patients who received Palonosetron were in Group A (n=34), patients who received Ondansetron were in group B (n=34) and patients who received Granisetron were in group C (n=34) and also the patients were selected randomly by lottery method. Statistical analyses of the results were obtained by using window based computer software devised with Statistical Packages for Social Sciences (SPSS-22). Nausea was found 3(8.8%) in group A, 8(23.5%) in group B and 6(17.6%) in group C. Vomiting was found 3(8.8%) in group A, 10(29.4%) in group B and 7(20.6%) in group C. Vomiting was significantly higher in group B compare with group A. For group B rescue anti-emetic injection motilon (metoclopramide hydrochloride) 5mg IV slowly was given. Palonosetron is effective prophylaxis against post operative nausea and vomiting.

11 Beta-hydroxysteroid dehydrogenase type 1 regulates synovitis, joint destruction, and systemic bone loss in chronic polyarthritis.

OBJECTIVE: In rheumatoid arthritis, the enzyme 11 beta-hydroxysteroid dehydrogenase type 1 (11ß-HSD1) is highly expressed at sites of inflammation, where it converts inactive glucocorticoids (GC) to their active counterparts. In conditions of GC excess it has been shown to be a critical regulator of muscle wasting and bone loss. Here we examine the contribution of 11ß-HSD1 to the pathology of persistent chronic inflammatory disease. METHODS: To determine the contribution of 11ß-HSD1 to joint inflammation, destruction and systemic bone loss associated with persistent inflammatory arthritis, we generated mice with global and mesenchymal specific 11ß-HSD1 deletions in the TNF-transgenic (TNF-tg) model of chronic polyarthritis. Disease severity was determined by clinical scoring. Histology was assessed in formalin fixed sections and fluorescence-activated cell sorting (FACS) analysis of synovial tissue was performed. Local and systemic bone loss were measured by micro computed tomography (micro-CT). Measures of inflammation and bone metabolism were assessed in serum and in tibia mRNA. RESULTS: Global deletion of 11ß-HSD1 drove an enhanced inflammatory phenotype, characterised by florid synovitis, joint destruction and systemic bone loss. This was associated with increased pannus invasion into subchondral bone, a marked polarisation towards pro-inflammatory M1 macrophages at sites of inflammation and increased osteoclast numbers. Targeted mesenchymal deletion of 11ß-HSD1 failed to recapitulate this phenotype suggesting that 11ß-HSD1 within leukocytes mediate its protective actions in vivo. CONCLUSIONS: We demonstrate a fundamental role for 11ß-HSD1 in the suppression of synovitis, joint destruction, and systemic bone loss. Whilst a role for 11ß-HSD1 inhibitors has been proposed for metabolic complications in inflammatory diseases, our study suggests that this approach would greatly exacerbate disease severity.

Clinical implications of p53 alterations in oral cancer progression: a review from India.

p53 plays a central role in prevention of normal cell from the development of the malignant phenotype. Somatic alterations (mutations, loss of heterozygosity, deletions) in p53 are a hallmark of most human cancers and cause defects in normal p53 function. However, in the tumors harboring wild-type p53, there are alterations in the regulation of the p53. Thus, understanding why p53 is unable to perform its role as a tumor suppressor in these wild-type tumors is very crucial. Germ-line polymorphisms in p53 are also anticipated to cause measurable disturbance in p53 function. Over-expression as well as polymorphic variants of MDM2 might have effects on cancer development. In addition, degradation of p53 by E6 protein of high risk human papillomavirus is also suggested as one of the mechanisms which attenuate p53 responses in oral carcinogenesis. p53 has also been demonstrated to mediate cellular responses upon various DNA damaging cancer therapies, importantly, apoptosis. These responses have been implicated in an individual's ability to respond to these cancer therapies. Thus, exploring mechanisms by which normal function of p53 is affected in the comprehensive way in oral cancer might aid in the identification of tumor characteristics, prognosis and thus in the development of a new approach to treat the oral cancer.

Investigating the feasibility of tumour molecular profiling in gastrointestinal malignancies in routine clinical practice.

Background: Targeted capture sequencing can potentially facilitate precision medicine, but the feasibility of this approach in gastrointestinal (GI) malignancies is unknown. Patients and methods: The FOrMAT (Feasibility of a Molecular Characterisation Approach to Treatment) study was a feasibility study enrolling patients with advanced GI malignancies from February 2014 to November 2015. Targeted capture sequencing (mainly using archival formalin-fixed paraffin-embedded diagnostic/resection samples) was carried out to detect mutations, copy number variations and translocations in up to 46 genes which had prognostic/predictive significance or were targets in current/upcoming clinical trials. Results: Of the 222 patients recruited, 215 patients (96.8%) had available tissue samples, 125 patients (56.3%) had ≥16 genes successfully sequenced and 136 patients (61.2%) had ≥1 genes successfully sequenced. Sample characteristics influenced the proportion of successfully sequenced samples, e.g. tumour type (colorectal 70.9%, biliary 52.6%, oesophagogastric 50.7%, pancreas 27.3%, P = 0.002), tumour cellularity (high versus low: 78.3% versus 13.3%, P ≤ 0.001), tumour content (high versus low: 78.6% versus 27.3%, P = 0.001) and type of sample (resection versus biopsy: 82.4% versus 47.6%, P ≤ 0.001). Currently, actionable alterations were detected in 90 (40.5%) of the 222 patients recruited (66% of the 136 patients sequenced) and 2 patients subsequently received a targeted therapy. The most frequently detected currently actionable alterations were mutations in KRAS, BRAF, TP53 and PIK3CA. For the 205 patients with archival samples, the median time to obtain sequencing results was 18.9 weeks, including a median of 4.9 weeks for sample retrieval and 5.1 weeks for sequencing. Conclusions: Targeted sequencing detected actionable alterations in formalin-fixed paraffin-embedded samples, but tissue characteristics are of critical importance in determining sequencing success. Routine molecular profiling of GI tumours outside of clinical trials is not an effective use of healthcare resources unless more targeted drugs become available. ClinicalTrials.gov identifier: NCT02112357.

Capacitated vehicle-routing problem model for scheduled solid waste collection and route optimization using PSO algorithm.

Waste collection widely depends on the route optimization problem that involves a large amount of expenditure in terms of capital, labor, and variable operational costs. Thus, the more waste collection route is optimized, the more reduction in different costs and environmental effect will be. This study proposes a modified particle swarm optimization (PSO) algorithm in a capacitated vehicle-routing problem (CVRP) model to determine the best waste collection and route optimization solutions. In this study, threshold waste level (TWL) and scheduling concepts are applied in the PSO-based CVRP model under different datasets. The obtained results from different datasets show that the proposed algorithmic CVRP model provides the best waste collection and route optimization in terms of travel distance, total waste, waste collection efficiency, and tightness at 70-75% of TWL. The obtained results for 1 week scheduling show that 70% of TWL performs better than all node consideration in terms of collected waste, distance, tightness, efficiency, fuel consumption, and cost. The proposed optimized model can serve as a valuable tool for waste collection and route optimization toward reducing socioeconomic and environmental impacts.

RANTES levels as a determinant of falciparum malaria severity or recovery.

The study explored the role of differential RANTES concentrations, its receptor CCR5 expression and resulting immunomodulation in the pathogenesis and/or recovery from falciparum malaria. The study population included cases of uncomplicated malaria (UC-M, N=128, enrolled on follow-up basis), severe malaria (SM, N=25), and healthy controls (N=112). Serum RANTES and TNF-α levels were evaluated by ELISA. Monocyte levels and activation profile were studied by flow cytometry. Differential mRNA expression profile was studied by real-time PCR. Blood parasite count was evaluated by registered pathologists. RANTES concentration was significantly downregulated in SM cases compared to UC-M (P=.046) and controls (P<.001). Expression of monocyte marker mCD14, activation markers CCR5 and CD40, and downstream effector cytokine TNF-α was significantly higher in malaria cases compared to controls, in SM cases compared to UC-M. TNF-α expression correlated positively with CD40 and CCR5 expressions. Follow-up-based analysis showed that RANTES concentrations increased on recovery compared to baseline in UC-M cases (P=.106) and inversely correlated with malaria parasite load, mCD14, CCR5 and CD40, and TNF-α expressions. These findings suggest an important association of RANTES concentrations in Plasmodium falciparum malaria disease pathogenesis, as well as recovery, mediated through differential modulation and regulated activation of monocytes and cytokine TNF-α.

The catalase gene promoter and 5'-untranslated region variants lead to altered gene expression and enzyme activity in vitiligo.

BACKGROUND: Oxidative stress is considered to be the initial event in the course of vitiligo. The enzyme catalase (CAT) is mainly involved in cellular defence against oxidizing agents through detoxifying H2 O2 . OBJECTIVES: The aims were (i) to assess erythrocyte CAT enzyme activity and lipid peroxidation (LPO) levels as well as CAT mRNA expression in skin and blood; (ii) to investigate CAT gene promoter rs7943316, rs1001179, 5'-untranslated region rs1049982, and exon (rs17886350, rs11032709, rs17880442, rs35677492) polymorphisms; and (iii) to perform genotype/haplotype-phenotype correlation analyses in patients with vitiligo and controls from Gujarat. METHODS: CAT activity and LPO levels were measured spectrophotometrically. CAT mRNA levels were estimated using real-time polymerase chain reaction (PCR) by the SYBR Green method. Single-nucleotide polymorphism genotyping was performed using PCR-restriction fragment length polymorphism and amplification-refractory mutation system-PCR analyses. RESULTS: Patients with vitiligo showed significantly decreased CAT mRNA expression in lesional and nonlesional skin and in blood, with reduced CAT activity compared with that of controls. CAT -89A/T and -20T/C polymorphisms were significantly associated with patients, especially with active and generalized vitiligo, whereas no association was observed for -262G/A and exon polymorphisms. The A-262 T-89 C-20 haplotype with variant alleles was found to be associated with 6·4-fold risk of vitiligo. Genotype/haplotype-phenotype correlation analyses revealed that individuals with susceptible genotypes/haplotype for CAT -89A/T and -20T/C polymorphisms showed significantly decreased CAT mRNA/activity, and only -89A/T polymorphisms showed significantly increased LPO levels compared with wild-type genotypes/haplotype. CONCLUSIONS: The present study proposes the crucial role of CAT and its allelic variants in oxidative stress-mediated pathogenesis of vitiligo.

Backtracking search algorithm in CVRP models for efficient solid waste collection and route optimization.

Waste collection is an important part of waste management that involves different issues, including environmental, economic, and social, among others. Waste collection optimization can reduce the waste collection budget and environmental emissions by reducing the collection route distance. This paper presents a modified Backtracking Search Algorithm (BSA) in capacitated vehicle routing problem (CVRP) models with the smart bin concept to find the best optimized waste collection route solutions. The objective function minimizes the sum of the waste collection route distances. The study introduces the concept of the threshold waste level (TWL) of waste bins to reduce the number of bins to be emptied by finding an optimal range, thus minimizing the distance. A scheduling model is also introduced to compare the feasibility of the proposed model with that of the conventional collection system in terms of travel distance, collected waste, fuel consumption, fuel cost, efficiency and CO2 emission. The optimal TWL was found to be between 70% and 75% of the fill level of waste collection nodes and had the maximum tightness value for different problem cases. The obtained results for four days show a 36.80% distance reduction for 91.40% of the total waste collection, which eventually increases the average waste collection efficiency by 36.78% and reduces the fuel consumption, fuel cost and CO2 emission by 50%, 47.77% and 44.68%, respectively. Thus, the proposed optimization model can be considered a viable tool for optimizing waste collection routes to reduce economic costs and environmental impacts.

The PARP family: insights into functional aspects of poly (ADP-ribose) polymerase-1 in cell growth and survival.

PARP family members can be found spread across all domains and continue to be essential molecules from lower to higher eukaryotes. Poly (ADP-ribose) polymerase 1 (PARP-1), newly termed ADP-ribosyltransferase D-type 1 (ARTD1), is a ubiquitously expressed ADP-ribosyltransferase (ART) enzyme involved in key cellular processes such as DNA repair and cell death. This review assesses current developments in PARP-1 biology and activation signals for PARP-1, other than conventional DNA damage activation. Moreover, many essential functions of PARP-1 still remain elusive. PARP-1 is found to be involved in a myriad of cellular events via conservation of genomic integrity, chromatin dynamics and transcriptional regulation. This article briefly focuses on its other equally important overlooked functions during growth, metabolic regulation, spermatogenesis, embryogenesis, epigenetics and differentiation. Understanding the role of PARP-1, its multidimensional regulatory mechanisms in the cell and its dysregulation resulting in diseased states, will help in harnessing its true therapeutic potential.

PAN-EX: a pooled analysis of two trials of neoadjuvant chemotherapy followed by chemoradiotherapy in MRI-defined, locally advanced rectal cancer.

BACKGROUND: EXPERT and EXPERT-C were phase II clinical trials of neoadjuvant chemotherapy (NACT) followed by chemoradiotherapy (CRT) in high-risk, locally advanced rectal cancer (LARC). DESIGN: We pooled individual patient data from these trials. The primary objective was overall survival (OS) in the intention-to-treat (ITT) population. Prognostic factors were also analysed. RESULTS: A total of 269 patients were included. Of these, 91.1% completed NACT, 88.1% completed CRT and 240 (89.2%) underwent curative surgery (R0/R1). After a median follow-up of 71.9 months, 5-year progression-free survival (PFS) and OS were 66.4% and 73.3%, respectively. In the group of R0/R1 resection patients, 5-year relapse-free survival (RFS) and OS were 71.6% and 77.2%, respectively, with local recurrence occurring in 5.5% and distant metastases in 20.6% of cases. Significant prognostic factors after multivariate analyses included age, tumour grade and MRI extramural venous invasion (mrEMVI) at baseline, MRI tumour regression grade (mrTRG) after CRT, ypT stage after surgery and adherence to study treatment. mrTRG after NACT was associated with PFS (P = 0.002) and OS (P = 0.018) and appeared to stratify patients based on the incremental benefit from sequential CRT. Among the outcome measures considered, in the subgroup of R0/R1 resection patients, ypT and ypStage had the highest predictive accuracy for RFS (concordance index: 0.6238 and 0.6252, respectively) and OS (concordance index: 0.6094 and 0.6132, respectively). CONCLUSIONS: Administering NACT before CRT could be a potential strategy for high-risk LARC. In this setting, mrTRG after CRT is an independent prognostic factor, while mrTRG after NACT should be tested as a parameter for treatment selection in trials of NACT ± CRT. ypT stage may be a valuable surrogate end point for future phase II trials investigating intensified neoadjuvant treatments in similar patient populations.

The Aspect of NK2 Transcription Factor Related Locus-5 (NKX2.5) Gene Mutations in Bangladeshi Atrial Septal Defect (ASD) patients and 2D Relationship with their Age.

Atrial septal defect (ASD) is a developmental defect of the heart which arises from the congenital abnormality of interatrial septum that perturbs the normal blood flow. Development of the heart is a complex biological process regulated by numerous genetic and environmental factors. During this process DNA binding proteins Myocardin, NKX2.5 (NK2 Transcription Factor Related Locus-5) and GATA4 (GATA Binding Protein-4) function by binding to SRF (Serum Response Factor) which is also a key regulator of myogenic terminal differentiation and frequently results in mitogenesis. Several studies suggest that mutations in the homeodomain containing transcription factor, NKX2.5, is implicated with atrial septal defect. This cross sectional descriptive study was done to investigate the frequency of NKX2.5 gene mutations among the patient with ASD who were undergoing surgical repair at the National Institute of Cardiovascular Diseases (NICVD) and National Heart Foundation and Research Institute (NHF&RI), Dhaka from July 2010 to June 2011. Patients presented with ASD at any age of both sexes were selected as study population. We found six distinct polymorphic sites among Bangladeshi population. Among six polymorphic sites, two were located at position 487 and 495. These were present in around 80% of the affected individuals. However they were not present in control population. Our study also revealed that mutations present in the downstream sites or towards the end of the genes are restricted to older people, whereas mutations present towards the 5' site is common to population of all ages. This interesting relationship has encouraged us to raise two new hypotheses.

Content-based image retrieval system for solid waste bin level detection and performance evaluation.

This paper presents a CBIR system to investigate the use of image retrieval with an extracted texture from the image of a bin to detect the bin level. Various similarity distances like Euclidean, Bhattacharyya, Chi-squared, Cosine, and EMD are used with the CBIR system for calculating and comparing the distance between a query image and the images in a database to obtain the highest performance. In this study, the performance metrics is based on two quantitative evaluation criteria. The first one is the average retrieval rate based on the precision-recall graph and the second is the use of F1 measure which is the weighted harmonic mean of precision and recall. In case of feature extraction, texture is used as an image feature for bin level detection system. Various experiments are conducted with different features extraction techniques like Gabor wavelet filter, gray level co-occurrence matrix (GLCM), and gray level aura matrix (GLAM) to identify the level of the bin and its surrounding area. Intensive tests are conducted among 250 bin images to assess the accuracy of the proposed feature extraction techniques. The average retrieval rate is used to evaluate the performance of the retrieval system. The result shows that, the EMD distance achieved high accuracy and provides better performance than the other distances.

Nurses experiences of working in Crisis Resolution Home Treatment Teams with its additional gatekeeping responsibilities.

INTRODUCTION: Through their gatekeeping role, CRHTT aim to reduce inappropriate admissions, facilitate early discharge from hospital and maximize the ability of service users to live independently within their own communities. It is evident that there is a vast array of literature on CRHTT internationally, however, little evidence on nurses experiences of working within CRHTT and gatekeeping. Therefore, in the light of limited research, this study aims to expand the current evidence base by exploring nurse's experiences of working in CRHTT with its additional gatekeeping responsibilities. METHODOLOGY: Six nurses working across two CRHTT's were interviewed using semi-structured interviews. Data were analysed through the use of thematic analysis. RESULTS: Four key themes emerged which were, 'CRHTT as a specialist role', 'core principles of the gatekeeping role', 'redefining risk management for gatekeepers in CRHTT' and 'the future of gatekeeping'. DISCUSSION: It is evident through nurse's experiences of working within CRHTT and gatekeeping that their roles were very dynamic and challenging. A positive risk-taking approach contributed towards the success of CRHTT as gatekeepers. Family members played a significant role in ensuring gatekeeping remained a priority consistent with Government targets. Clinical Implications and recommendations for future research are discussed.

Application of TOPSIS and VIKOR improved versions in a multi criteria decision analysis to develop an optimized municipal solid waste management model.

Selecting a suitable Multi Criteria Decision Making (MCDM) method is a crucial stage to establish a Solid Waste Management (SWM) system. Main objective of the current study is to demonstrate and evaluate a proposed method using Multiple Criteria Decision Making methods (MCDM). An improved version of Technique for Order of Preference by Similarity to Ideal Solution (TOPSIS) applied to obtain the best municipal solid waste management method by comparing and ranking the scenarios. Applying this method in order to rank treatment methods is introduced as one contribution of the study. Besides, Viekriterijumsko Kompromisno Rangiranje (VIKOR) compromise solution method applied for sensitivity analyses. The proposed method can assist urban decision makers in prioritizing and selecting an optimized Municipal Solid Waste (MSW) treatment system. Besides, a logical and systematic scientific method was proposed to guide an appropriate decision-making. A modified TOPSIS methodology as a superior to existing methods for first time was applied for MSW problems. Applying this method in order to rank treatment methods is introduced as one contribution of the study. Next, 11 scenarios of MSW treatment methods are defined and compared environmentally and economically based on the waste management conditions. Results show that integrating a sanitary landfill (18.1%), RDF (3.1%), composting (2%), anaerobic digestion (40.4%), and recycling (36.4%) was an optimized model of integrated waste management. An applied decision-making structure provides the opportunity for optimum decision-making. Therefore, the mix of recycling and anaerobic digestion and a sanitary landfill with Electricity Production (EP) are the preferred options for MSW management.