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This research identifies the impact of compensation on employees' job performance. The study used a causal-comparative research design to explore the relationship between compensation and employee performance in commercial banks. The sample size was calculated using a formula that determined the appropriate sample size for the population of 385 employees. The survey questionnaire was administered to 192 employees out of 20 branches of 15 commercial banks, and respondents' demographic information was collected. The study found that both financial and non-financial compensation significantly affect employees' job performance. Additionally, employee motivation was found to have a mediating role between compensation and job performance. The findings of this research have implications for organizations to design compensation and benefits schemes that can help to increase employee motivation and job performance.

Limb-Girdle Muscular Dystrophy Type-2B/2R is caused by mutations in thedysferlingene (DYSF). This disease has two known pathogenic missense mutations that occur within dysferlin’s C2A domain, namely C2AW52Rand C2AV67D. Yet, the etiological rationale to explain the disease linkage for these two mutations is still unclear. In this study, we have presented evidence from biophysical, computational, and immunological experiments which suggest that these missense mutations interfere with dysferlin’s ability to repair cells. The failure of C2AW52Rand C2AV67Dto initiate membrane repair arises from their propensity to form stable amyloid. The misfolding of the C2A domain caused by either mutation exposes β-strands, which are predicted to nucleate classical amyloid structures. When dysferlin C2A amyloid is formed, it triggers the NLRP3 inflammasome, leading to the secretion of inflammatory cytokines, including IL-1β. The present study suggests that the muscle dysfunction and inflammation evident in Limb-Girdle Muscular Dystrophy types-2B/2R, specifically in cases involving C2AW52Rand C2AV67D, as well as other C2 domain mutations with considerable hydrophobic core involvement, may be attributed to this mechanism.

Small pore-forming toxins in the aerolysin family lyse cells by damaging the membrane, but membrane repair responses used to resist them, if any, remain controversial. Four membrane repair mechanisms have been proposed: toxin removal by caveolar endocytosis, clogging by annexins, microvesicle shedding catalyzed by MEK, and patch repair. Which of these repair mechanisms aerolysin triggers is unknown. Furthermore, Ca2+flux triggered by aerolysin is controversial, yet membrane repair responses require Ca2+. Here, we determined Ca2+influx and repair mechanisms activated by aerolysin. In contrast to cholesterol-dependent cytolysins (CDCs), removal of extracellular Ca2+protected cells from aerolysin. Aerolysin triggered sustained Ca2+influx. Since aerolysin triggered Ca2+flux, we investigated Ca2+-dependent repair pathways. Caveolar endocytosis failed to protect cells from aerolysin or CDCs. MEK-dependent repair did not protect against aerolysin. Aerolysin triggered slower annexin A6 membrane recruitment compared to CDCs. In contrast to CDCs, expression of the patch repair protein dysferlin potently protected cells from aerolysin. We propose that aerolysin triggers a Ca2+-dependent death mechanism that obscures repair responses, and the primary repair mechanism used to resist aerolysin is patch repair. We conclude that different classes of bacterial toxins trigger distinct repair mechanisms.

Cholesterol-dependent cytolysins (CDCs) are key virulence factors involved in many lethal bacterial infections, including pneumonia, necrotizing soft tissue infections, bacterial meningitis, and miscarriage. Host responses to these diseases involve myeloid cells, especially macrophages. Macrophages use several systems to detect and respond to cholesterol-dependent cytolysins, including membrane repair, mitogen-activated protein (MAP) kinase signaling, phagocytosis, cytokine production, and activation of the adaptive immune system. However, CDCs also promote immune evasion by silencing and/or destroying myeloid cells. While there are many common themes between the various CDCs, each CDC also possesses specific features to optimally benefit the pathogen producing it. This review highlights host responses to CDC pathogenesis with a focus on macrophages. Due to their robust plasticity, macrophages play key roles in the outcome of bacterial infections. Understanding the unique features and differences within the common theme of CDCs bolsters new tools for research and therapy.

This article is an outgrowth of an odyssey of more than a decade to the very popular touristic destinations of Nepal, namely Ghale Gaon, Sirubari and Bandipur, and disciplinarily synergetic in my act of knowing and representing- the objectivities and the subjectivities emerging in tourist-host interaction, the public discourses, and the ways these have shaped these destinations today- my primary concern in this article. Today, these destinations, which would perhaps remain virgin, development and otherwise, are at threshold, vividly manifesting array of changes in every spheres of living in with their adherence to village tourism in the name of development per se modernization, the camelian evolution if not reinstate on time with pragmatic tourism paradigm to my anticipation these destination will not thrive to attack tourists as of today and consequently thwart development in true sense With this conscientization, by focusing on the effects of tourism and new ways of sensing tourism and development this article proposes an alternative episteme in tourism and development analysis with special reference of these destinations In my attempt to do justice to the era to which I belong, as a devotee of post-modernism centripetal to undertaking this task were the postulates of social constructivism and “(N)One Paradigmatic Research Design”, at my disposal. I am hopeful that this paper contributes to the deficit of knowledge in relating concepts and theories to what I termed as anthropic development.The Gaze: Journal of Tourism and Hospitality Vol.9 2018 p.1-22

Background: Patient’s medical charts in hospitals are potentially contaminated by pathogenic bacteria and might act as vehicles for transmission of bacterial infections.This study was aimed to determine the rate of contamination of medical charts by multidrug resistant bacteria.Methods: Sampling of total 250 patient’s medical charts from different wards was done with the help of cotton swabs soaked in sterile normal saline. The swabs thus collected were cultured using standard microbiological procedures.The colonies grown were then identified with the help of colony morphology, Gram’s stain and biochemical tests. Antimicrobial susceptibility testing was performed by using Kirby-Bauer disc diffusion technique. Results: Of the total 250 charts sampled, 98.8% grew bacteria; Bacillus spp. in 40.7%, followed by Staphylococcus aureus (17%), coagulase-negative Staphylococcus spp.(CoNS) (17%), Citrobacter freundii (9.6%) and Acinetobacter spp. (4.5%). Rate of multidrug resistance was highest in Acinetobacter spp. (50%). Among 83 isolates of S. aureus, methicillin resistance was found in 29 isolates. Similarly, two out of total 9 isolates of Enterococcus spp. were vancomycin resistant.Conclusions: This study showed that patient’s medical charts were contaminated with multidrug resistant bacteria including methicillin resistant S. aureus and vancomycin resistant Enterococcus spp. Strict hand washing before and after handling medical charts is recommended.

International audience; Low-income and middle-income countries are struggling with a growing epidemic of non-communicable diseases. To achieve the Sustainable Development Goals, their healthcare systems need to be strengthened and redesigned. The Starfield 4Cs of primary care—first-contact access, care coordination, comprehensiveness and continuity—offer practical, high-quality design options for non-communicable disease care in low-income and middle-income countries. We describe an integrated non-communicable disease intervention in rural Nepal using the 4C principles. We present 18 months of retrospective assessment of implementation for patients with type II diabetes, hypertension and chronic obstructive pulmonary disease. We assessed feasibility using facility and community follow-up as proxy measures, and assessed effectiveness using singular ‘at-goal’ metrics for each condition. The median follow-up for diabetes, hypertension and chronic obstructive pulmonary disease was 6, 6 and 7 facility visits, and 10, 10 and 11 community visits, respectively (0.9 monthly patient touch-points). Loss-to-follow-up rates were 16%, 19% and 22%, respectively. The median time between visits was approximately 2 months for facility visits and 1 month for community visits. ‘At-goal’ status for patients with chronic obstructive pulmonary disease improved from baseline to endline (p=0.01), but not for diabetes or hypertension. This is the first integrated non-communicable disease intervention, based on the 4C principles, in Nepal. Our experience demonstrates high rates of facility and community follow-up, with comparatively low lost-to-follow-up rates. The mixed effectiveness results suggest that while this intervention may be valuable, it may not be sufficient to impact outcomes. To achieve the Sustainable Development Goals, further implementation research is urgently needed to determine how to optimise non-communicable disease interventions.This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial.

The bacterial profile and their drug susceptibility pattern was studied in post-tracheostomised patients admitted in National Institute of Neurological and Allied Sciences. Identification of organisms was done by standard microbiological techniques and antibiogram was performed by Kirby Bauer disc diffusion method according to Clinical and Laboratory standard (CLSI) guidelines. Significant growth was observed in 58.6% samples with polymicrobial growth in 19.5% samples among the total positive cultures. Pseudomonas aeruginosa was the predominant organism (34.2%) followed by Acinetobacter spp. (31.8%), Escherichia coli (8.9%), Klebsiella pneumoniae (6.0%), Citrobacter fruendii (5.6%), Klebsiella oxytoca (4.0%), Providencia spp. and Staphylococcus aureus (2.8% each), Proteus mirabilis (2.4%) and Proteus vulgaris (1.2%) . More than 90% of Gram negative bacterial isolates were found resistant to Ampicillin, Cefixime, Cephotaxime. The most effective drugs against S. aureus were Vancomycin, Rifampicin, Amoxycillin and Clavulanic acid showing 100% sensitivity. Highest resistance rate was observed for Ampicillin (85.71%) and low for Gentamicin (14.28%). Findings of this study show emerging threat of multidrug resistant bacteria. Thus, periodic monitoring and assessing drug susceptibility pattern of bacteria and rational use of antibiotics in post tracheostomised patients were recommended.Journal of Institute of Science and TechnologyVolume 21, Issue 1, August 2016, page: 129-132

This study was carried out to determine the degree of contamination of patients’ medical charts in ICU settings. A total of 100 medical charts were randomly selected from ICU. The swab samples were collected from outer surface of charts with sterile swabs moistened with sterile normal saline. The swabs were immediately transferred to Trypticase soy broth and incubated aerobically for 48h and then subcultured inMacConkey, Blood and Eosin-methylene blue agars. The isolates were identified by using standard microbiological and biochemical techniques. Out of 100 charts sampled, 89% charts were found to be contaminated with pathogenic or potentially pathogenic bacteria. Staphylococcus aureus was the most commonly isolated bacteria in ICU (n=32, 28.3%) followed by Citrobacter freundii (n=27, 24%), Coagulase Negative Staphylococci (CoNS) (n=23, 20.3%) and Acinetobacter spp. (n=12, 10.7%). It is concluded that medical chart contains pathogenic and potentially pathogenic bacteria. Thus, contaminated charts can act as vector of pathogenic bacteria and source of cross-infection in hospital.Journal of Institute of Science and TechnologyVol. 21, No. 1, 2016, page: 48-51

Pathogens causing necrotizing soft tissue infections, such as Streptococcus pyogenes and Clostridium perfringens, use cholesterol dependent cytolysins (CDCs) to evade immune responses by blocking pro-inflammatory TNFα production in macrophages. This evasion may be an unintended consequence of membrane repair responses to the CDC. CDCs trigger lipid-dependent sequestration and shedding of CDC pores on microvesicles. However, the molecular mechanisms by which CDCs exploit membrane repair to disrupt immune signaling is unknown. One target may be cholesterol-rich microdomains (CRMs) because they are focal points for toxin binding and immune signaling. We hypothesized that when CDCs oligomerize, they cluster membrane lipids in CRMs, along with immune receptors, into microscale assemblies that are spontaneously shed as microvesicles. We tested this hypothesis by artificially clustering sphingolipids using the sphingolipid-binding protein Ostreolysin A (OlyA), fused with tandem FKBP dimerization domains. We challenged murine bone marrow derived macrophages with and without FKBP homodimerizer and OlyA prior to LPS challenge and measured intracellular TNFα by flow cytometry. We found that oligomerization reduced OlyA binding, consistent with shedding. OlyA oligomerization further suppressed TNFα production, suggesting that microscale lipid assemblies interfere with cellular signaling. Overall, these results suggest that one cost to repair by shedding toxins on microvesicles is the loss of cellular signaling needed to promote inflammation. This may represent one strategy CDC-producing pathogens use to promote immune evasion and cause disease.

The largest superfamily of bacterial virulence factors is pore-forming toxins (PFTs). PFTs are secreted by both pathogenic and non-pathogenic bacteria. PFTs sometimes kill or induce pro-pathogen signaling in mammalian cells, all primarily through plasma membrane perforation, though the parameters that determine these outcomes are unclear. Membrane binding, calcium influx, pore size, and membrane repair are factors that influence PFT cytotoxicity. To test the contribution of membrane binding to cytotoxicity and repair, we compared the closely related, similarly-sized PFTs Perfringolysin O (PFO) from Clostridium perfringens and Streptolysin O (SLO) from Streptococcus pyogenes. Cell death kinetics for PFO and SLO were different because PFO increased in cytotoxicity over time. We introduced known L3 loop mutations that swap binding affinity between toxins and measured hemolytic activity, nucleated cell death kinetics and membrane repair using viability assays, and live cell imaging. Altered hemolytic activity was directly proportional to toxin binding affinity. In contrast, L3 loop alterations reduced nucleated cell death, and they had limited effects on cytotoxicity kinetics and membrane repair. This suggests other toxin structural features, like oligomerization, drives these parameters. Overall, these findings suggest that repair mechanisms and toxin oligomerization add constraints beyond membrane binding on toxin evolution and activity against nucleated cells.

Pancreatic ductal adenocarcinoma (PDAC) is predicted to soon become the second killer cancer in the USA. One of the hallmarks of PDAC is desmoplasia, which consists of an expansion in activated stellate cells, known as cancer associated fibroblasts (CAFs), and remodeling of their extracellular matrix. Desmoplasia is a major culprit for the unique PDAC microenvironment, which both collapses blood vessels restricting nutrients and fosters immunosuppression. Crosstalk between CAFs, PDAC, and immune cells, within this microenvironment, is not fully understood. To study the functions of CAFs on PDAC development, we first performed a microarray comparing patient matched normal pancreatic stellate cells and CAFs cultured using our stromal 3D system. We identified proteins upregulated in CAFs that have not been previously implicated in desmoplasia. To understand the functional role of these proteins, CRISPR/Cas9 mediated deletion of target proteins was undertaken and cells were subjected to a number of co-culture assays, with PDAC cells and NK cells. Assays consisted of material transfer, cell engagement, proliferation, survival, NK cell activation and PDAC killing. Syngeneic/orthotopic in vivo models, RNAseq analyzes and quantitative multi-plex microscopy, on pathological samples, were also used. We uncovered the ectopic expressions of NetrinG1 (NG1), a neural pre-synaptic protein, in CAFs, and of NG1’s post-synaptic binding partner, NGL1, in PDAC cells. Using our 3D system, we observed that heterotypic CAF-to-PDAC interactions, via NG1/NGL1 engagement, are critical for providing survival advantages to nutrient deprived PDAC cells and for CAFs to protect PDAC from NK cell-driven elimination. Mechanistically, we uncovered that PDAC starvation is overcome by NG1 expressing CAFs that provide nutrition via material transfer. Further, knockout of NG1, in CAFs, significantly reduced the production of immunosuppressive cytokines, such as IL-6, IL-8, and TGF-β. Moreover, loss of NG1 from CAFs resulted in anti-tumor NK cell activation. Unexpectedly, we observed a link between glutamate metabolism in CAFs and the inactivation of anti-tumor NK cells, and this was dependent on CAFs’ NG1 expression. These results were confirmed in an orthotopic PDAC mouse model in which ablation of NGL1, in syngeneic mouse PDAC cells, significantly halted tumor growth. RNAseq comparing CON or NG1+ CAFs vs. knockout NG1- CAFs rendered changes in neural, metabolic and fibrous signature pathways. Translationally, we saw clear expression of stromal NG1 only in PDAC affected pancreata. Overall, this study identifies two novel targets for PDAC; a cancer that lacks effective therapies. Inhibition of the NG1/NGL1 axis, constitutes a potential future therapeutic approach, as it alters CAF mediated metabolism and reverts immunosuppression, stunting PDAC growth in vitro and in vivo. Citation Format: Ralph Francescone, Débora Barbosa Vendramini-Costa, Janusz Franco-Barraza, Jessica Wagner, Alex Muir, Linara Gabitova, Tatiana Pazina, Tiffany Luong, Neelima Shah, Dustin Rollins, Ruchi Malik, Sapna Gupta, Roshan Thapa, Diana Restifo, Allison Lau, Yan Zhou, Kathy Q. Cai, Harvey Harvey Hensley, Emmanuelle Nicolas, Warren D. Kruger, Karthik Devarajan, Siddharth Balachandran, Wafik S. El-Deiry, Matthew Vander Heiden, Kerry Campbell, Igor Astsaturov, Edna Cukierman. NG1/NGL1 engagement supports PDAC development via CAF to PDAC nutrition and CAF-regulated immunosuppression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2038.

BackgroundChronic obstructive pulmonary disease accounts for a significant portion of the world’s morbidity and mortality, and disproportionately affects low/middle-income countries. Chronic obstructive pulmonary disease management in low-resource settings is suboptimal with diagnostics, medications and high-quality, evidence-based care largely unavailable or unaffordable for most people. In early 2016, we aimed to improve the quality of chronic obstructive pulmonary disease management at Bayalpata Hospital in rural Achham, Nepal. Given that quality improvement infrastructure is limited in our setting, we also aimed to model the use of an electronic health record system for quality improvement, and to build local quality improvement capacity.DesignUsing international chronic obstructive pulmonary disease guidelines, the quality improvement team designed a locally adapted chronic obstructive pulmonary disease protocol which was subsequently converted into an electronic health record template. Over several Plan-Do-Study-Act cycles, the team rolled out a multifaceted intervention including educational sessions, reminders, as well as audits and feedback.ResultsThe rate of oral corticosteroid prescriptions for acute exacerbations of chronic obstructive pulmonary disease increased from 14% at baseline to >60% by month 7, with the mean monthly rate maintained above this level for the remainder of the initiative. The process measure of chronic obstructive pulmonary disease template completion rate increased from 44% at baseline to >60% by month 2 and remained between 50% and 70% for the remainder of the initiative.ConclusionThis case study demonstrates the feasibility of robust quality improvement programmes in rural settings and the essential role of capacity building in ensuring sustainability. It also highlights how individual quality improvement initiatives can catalyse systems-level improvements, which in turn create a stronger foundation for continuous quality improvement and healthcare system strengthening.

Recruitment of new perennial grass plants within existing grassland ecosystems is determined by seed availability, suitable microsites, nutrients and climatic conditions, water and temperatures. This paper reports on the development of criteria to predict recruitment events using modelled soil moisture conditions associated with recruitment of species in five field experiments at Orange (Phalaris aquatica), Trunkey Creek (Austrodanthonia spp.), and Wellington (Bothriochloa macra) in central New South Wales, Australia, and the frequency of those conditions during the past 30 years. Recruitment events were recorded when a rainfall event (median 68 mm across the three sites) kept the surface volumetric soil moisture (0–50 mm) above the permanent wilting point for at least 15 continuous days, allowing for, at most, two ‘dry days’ in between. A key finding from our study is that rainfall events creating favourable soil moisture conditions for seedling emergence typically occurred in the second half of February, sometimes extending to early March. Previously it was thought that recruitment would more likely occur through autumn, winter, and spring when rainfall in southern Australia is more reliable. The 30 years’ data (1975–2004) showed that the P. aquatica site had a median of 20 continuous moist days each year in February–March, whereas, there were 16 and 10 days for the Austrodanthonia and B. macra sites, respectively. The probabilities of exceeding seven or 15 continuous days of moist surface soil were 98% and 78% at the P. aquatica site, 91% and 49% at the Austrodanthonia site, and 73% and 30% at the B. macra site, and indicated that some recruitment is possible in most years. These analyses were extended to several sites across New South Wales, Victoria, and Tasmania to estimate the frequency with which recruitment could occur within natural swards. Across these sites, the probabilities of exceeding seven continuous days of soil moisture were >55% and of exceeding 15 continuous days were lower, which showed that suitable climatic conditions exist during late summer–early autumn across south-eastern Australia for a recruitment event to occur. Future research may show that the criteria developed in this paper could have wider regional application.

A successful recruitment event in perennial grasslands is infrequent and when it occurs, the rate of recruitment and survival is low

Two field experiments, one each on Austrodanthonia spp. and Bothriochloa macra, investigated the effects of biomass manipulation, seed level modification, site preparation and pasture composition on the recruitment of native perennial grass seedlings. The experiments coincided with drier than average years and although successful emergence of seedlings occurred, survival was extremely low. In the Austrodanthonia experiment, control treatments resulted in the emergence of only 1 seedling/m2, whereas there were 130/m2 in the best treatment which had biomass cut with plant material removed, seed added, and the soil surface scarified. Insecticide treatments increased emergence as seed-harvesting ants are common in these systems, but the benefits were small. Similarly, B. macra had no emergence in the control treatment compared with 73 seedlings/m2 in the best treatment, which was pasture cropped, and had seed added and herbicide applied. Availability of microsites may be a major constraint to B. macra emergence, as soil disturbance through pasture cropping substantially increased seedling numbers (279/m2). The effects of herbicide on emergence were small with the largest being related to bare ground and litter biomass. Austrodanthonia seedling numbers at emergence were related to bare ground, litter and green biomass. Survival of young Austrodanthonia plants 24 weeks after emergence was negatively related to plant cover, but only in treatments where plant material was cut and removed. The success of survival was determined at 52 weeks after emergence and the number of young plants that survived in both experiments seemed to have been influenced by the presence of competitive biomass of existing plants.

Necrotizing soft tissue infections (NSTIs) are lethal microbial infections. One virulence factor common to most bacteria responsible for NSTIs such as Streptococcus pyogenes is a pore-forming toxin (PFT). PFTs promote immune evasion through unknown mechanisms and lyse cells by forming pores. One mechanism by which cells resist these PFTs is intrinsic membrane repair which is sequestering and shedding toxin pores on microvesicles. It is possible that intrinsic membrane repair is hijacked by bacteria to promote immune evasion. We hypothesized that PFTs promote immune evasion by inducing immune receptor shedding during intrinsic membrane repair. We tested this hypothesis by challenging murine bone marrow derived macrophages with sublytic toxin doses prior to LPS or IFNγ challenge. We measured surface receptor expression and intracellular TNFα by flow cytometry in live cells. We found that toxins from one family of PFTs, cholesterol-dependent cytolysins (CDCs), suppressed LPS or IFNγ-stimulated TNFα production and CD69 and CD86 upregulation in a cell-intrinsic manner independently of cell death. CDCs further induced partial shedding of TLR4 and IFNγR, which might contribute to macrophage dysfunction. In contrast, we found that a toxin from a second PFT family, aerolysin, prevented TNFα production by inducing cell death in macrophages at equivalent hemolytic doses. Overall, these results suggest that different PFT families use different strategies to impair macrophages. CDCs may hijack intrinsic membrane repair to impair TNFα production, while aerolysin kills macrophages at similar doses. These findings might explain the immune suppression and lethality observed during NSTIs.