E. coli Group 1 Capsular Polysaccharide Exportation Nanomachinary as a Plausible Antivirulence Targetin the Perspective of Emerging Antimicrobial Resistance

Bacteria evolving resistance against the action of multiple drugs and its ability to disseminate the multidrug resistance trait(s) across various strains of the same bacteria or different bacterial species impose serious threat to public health. Evolution of such multidrug resistance is due to the fact that, most of the antibiotics target bacterial survival mechanisms which exert selective pressure on the bacteria and aids them to escape from the action of antibiotics. Nonetheless, targeting bacterial virulence strategies such as bacterial surface associated polysaccharides biosynthesis and their surface accumulation mechanisms may be an attractive strategy, as they impose less selective pressure on the bacteria. Capsular polysaccharide (CPS) or K-antigen that is located on the bacterial surface armors bacteria from host immune response. Thus, unencapsulating bacteria would be a good strategy for drug design, besides CPS itself being a good vaccine target, by interfering with CPS biosynthesis and surface assembly pathway. Gram-negative Escherichia coli uses Wzy-polymerase dependent (Groups 1 and 4) and ATP dependent (Groups 1 and 3) pathways for CPS production. Considering E. coli as a case in point, this review explains the structure and functional roles of proteins involved in Group 1 Wzy dependent CPS biosynthesis, surface expression and anchorage in relevance to drug and vaccine developments

Structure, Optical And Electrical Characterization Of Tin Selenide Thin Films Deposited At Room Temperature Using Thermal Evaporation Method

Tin Selenide (SnSe) is an important IV-VI compound semiconducting material used for various devices like memory switching, an efficient solar cell and holographic recording systems. SnSe thin films of the thickness of 100 nm were deposited by thermal evaporation method on a Glass substrate at room temperature. The prepared samples were investigated for structural, compositional, morphological and optical characte-rization respectively by using X-ray diffraction analysis (XRD), scanning electron microscopy (SEM) and transmission measurements. Thus deposited films showed a good polycrystalline quality having preferred (111) orientation with uniformly distributed spherical grains having size 16nm.The grown film identified as P- types by hot probe method. The films were found to have direct band transition having an optical bandgap (Eg) of 1.92 eV at room temperature. The temperature depended electrical resistivity (ρ) determined by using the two probe method, found to be 390 Ω·m at room temperature. When you are citing the document, use the following link http://essuir.sumdu.edu.ua/handle/123456789/952

Impact of annealing on CuInSe2 thin films and its Schottky interface

The room temperature current–voltage (I-V) characteristics of the Al/p-CuInSe2 Schottky Diodes fabricated on thermally evaporated CIS thin films, before and after annealing, were studied. Prior to their diode formation, the undertaken CIS thin films were compared on the basis of structural, morphological and electrical investigations. Wherein, annealed films showed an increase in the grain size and carrier concentration values while decrease in resistivity. I-V analysis of the Schottky diodes depicted decrease in the barrier heights and increase in ideality factors of those formed on annealed films. The diodes, thus, indicated the existence of barrier inhomogenity at the M-S interface. The annealed Schottky diodes also demonstrated better ideality factor values with increased thickness of CIS layer. When you are citing the document, use the following link http://essuir.sumdu.edu.ua/handle/123456789/2792

Use of Xpert MTB/RIF in Decentralized Public Health Settings and Its Effect on Pulmonary TB and DR-TB Case Finding in India

Background Xpert MTB/RIF, the first automated molecular test for tuberculosis, is transforming the diagnostic landscape in high-burden settings. This study assessed the impact of up-front Xpert MTB/RIF testing on detection of pulmonary tuberculosis (PTB) and rifampicin-resistant PTB (DR-TB) cases in India. Methods This demonstration study was implemented in 18 sub-district level TB programme units (TUs) in India in diverse geographic and demographic settings covering a population of 8.8 million. A baseline phase in 14 TUs captured programmatic baseline data, and an intervention phase in 18 TUs had Xpert MTB/RIF offered to all presumptive TB patients. We estimated changes in detection of TB and DR-TB, the former using binomial regression models to adjust for clustering and covariates. Results In the 14 study TUs, which participated in both phases, 10,675 and 70,556 presumptive TB patients were enrolled in the baseline and intervention phase, respectively, and 1,532 (14.4%) and 14,299 (20.3%) bacteriologically confirmed PTB cases were detected. The implementation of Xpert MTB/RIF was associated with increases in both notification rates of bacteriologically confirmed TB cases (adjusted incidence rate ratio [aIRR] 1.39; CI 1.18-1.64), and proportion of bacteriological confirmed TB cases among presumptive TB cases (adjusted risk ratio (aRR) 1.33; CI 1.6-1.52). Compared with the baseline strategy of selective drug-susceptibility testing only for PTB cases at high risk of drug-resistant TB, Xpert MTB/RIF implementation increased rifampicin resistant TB case detection by over fivefold. Among, 2765 rifampicin resistance cases detected, 1055 were retested with conventional drug susceptibility testing (DST). Positive predictive value (PPV) of rifampicin resistance detected by Xpert MTB/RIF was 94.7% (CI 91.3-98.1), in comparison to conventional DST. Conclusion Introduction of Xpert MTB/RIF as initial diagnostic test for TB in public health facilities significantly increased case-notification rates of all bacteriologically confirmed TB by 39% and rifampicin-resistant TB case notification by fivefold

On infinite-volume mixing

In the context of the long-standing issue of mixing in infinite ergodic theory, we introduce the idea of mixing for observables possessing an infinite-volume average. The idea is borrowed from statistical mechanics and appears to be relevant, at least for extended systems with a direct physical interpretation. We discuss the pros and cons of a few mathematical definitions that can be devised, testing them on a prototypical class of infinite measure-preserving dynamical systems, namely, the random walks.Comment: 34 pages, final version accepted by Communications in Mathematical Physics (some changes in Sect. 3 -- Prop. 3.1 in previous version was partially incorrect

Assessment of clinical outcomes of medicinal cannabis therapy for depression: analysis from the UK Medical Cannabis Registry.

BACKGROUND: Although pre-clinical experiments associate cannabinoids with reduced depressive symptoms, there is a paucity of clinical evidence. This study aims to analyze the health-related quality of life changes and safety outcomes in patients prescribed cannabis-based medicinal products (CBMPs) for depression. METHODS: A series of uncontrolled cases from the UK Medical Cannabis Registry were analyzed. The primary outcomes were changes from baseline in the Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7), Sleep Quality Scale (SQS), and EQ-5D-5 L at 1, 3, and 6 months. Secondary outcomes included adverse events incidence. RESULTS: 129 patients were identified for inclusion. Median PHQ-9 at baseline was 16.0 (IQR: 9.0-21.0). There were reductions in PHQ-9 at 1-month (median: 8.0; IQR: 4.0-14.0; p < 0.001), 3-months (7.0; 2.3-12.8; p < 0.001), and 6-months (7.0; 2.0-9.5; p < 0.001). Improvements were also observed in GAD-7, SQS, and EQ-5D-5L Index Value at 1, 3, and 6 months (p < 0.050). 153 (118.6%) adverse events were recorded by 14.0% (n = 18) of participants, 87% (n = 133) of which were mild or moderate. CONCLUSION: CBMP treatment was associated with reductions in depression severity at 1, 3, and 6 months. Limitations of the study design mean that a causal relationship cannot be proven. This analysis provides insights for further study within clinical trial settings

Gastric Outlet Obstruction at Bugando Medical Centre in Northwestern Tanzania: A Prospective Review of 184 Cases.

Gastric outlet obstruction poses diagnostic and therapeutic challenges to general surgeons practicing in resource-limited countries. There is a paucity of published data on this subject in our setting. This study was undertaken to highlight the etiological spectrum and treatment outcome of gastric outlet obstruction in our setting and to identify prognostic factors for morbidity and mortality. This was a descriptive prospective study which was conducted at Bugando Medical Centre between March 2009 and February 2013. All patients with a clinical diagnosis of gastric outlet obstruction were, after informed consent for the study, consecutively enrolled into the study. Statistical data analysis was done using SPSS computer software version 17.0. A total of 184 patients were studied. More than two-third of patients were males. Patients with malignant gastric outlet obstruction were older than those of benign type. This difference was statistically significant (p < 0.001). Gastric cancer was the commonest malignant cause of gastric outlet obstruction where as peptic ulcer disease was the commonest benign cause. In children, the commonest cause of gastric outlet obstruction was congenital pyloric stenosis (13.0%). Non-bilious vomiting (100%) and weight loss (93.5%) were the most frequent symptoms. Eighteen (9.8%) patients were HIV positive with the median CD 4+ count of 282 cells/μl. A total of 168 (91.3%) patients underwent surgery. Of these, gastro-jejunostomy (61.9%) was the most common surgical procedure performed. The complication rate was 32.1 % mainly surgical site infections (38.2%). The median hospital stay and mortality rate were 14 days and 18.5% respectively. The presence of postoperative complication was the main predictor of hospital stay (p = 0.002), whereas the age > 60 years, co-existing medical illness, malignant cause, HIV positivity, low CD 4 count (<200 cells/μl), high ASA class and presence of surgical site infection significantly predicted mortality ( p< 0.001). The follow up of patients was generally poor as more than 60% of patients were lost to follow up. Gastric outlet obstruction in our setting is more prevalent in males and the cause is mostly malignant. The majority of patients present late with poor general condition. Early recognition of the diagnosis, aggressive resuscitation and early institution of surgical management is of paramount importance if morbidity and mortality associated with gastric outlet obstruction are to be avoided

Assessment of clinical outcomes of medicinal cannabis therapy for depression: analysis from the UK Medical Cannabis Registry

Background Although pre-clinical experiments associate cannabinoids with reduced depressive symptoms, there is a paucity of clinical evidence. This study aims to analyze the health-related quality of life changes and safety outcomes in patients prescribed cannabis-based medicinal products (CBMPs) for depression. Methods A series of uncontrolled cases from the UK Medical Cannabis Registry were analyzed. The primary outcomes were changes from baseline in the Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7), Sleep Quality Scale (SQS), and EQ-5D-5 L at 1, 3, and 6 months. Secondary outcomes included adverse events incidence. Results 129 patients were identified for inclusion. Median PHQ-9 at baseline was 16.0 (IQR: 9.0–21.0). There were reductions in PHQ-9 at 1-month (median: 8.0; IQR: 4.0–14.0; p < 0.001), 3-months (7.0; 2.3–12.8; p < 0.001), and 6-months (7.0; 2.0–9.5; p < 0.001). Improvements were also observed in GAD-7, SQS, and EQ-5D-5L Index Value at 1, 3, and 6 months (p < 0.050). 153 (118.6%) adverse events were recorded by 14.0% (n = 18) of participants, 87% (n = 133) of which were mild or moderate. Conclusion CBMP treatment was associated with reductions in depression severity at 1, 3, and 6 months. Limitations of the study design mean that a causal relationship cannot be proven. This analysis provides insights for further study within clinical trial settings

Clinical outcome analysis of patients with autism spectrum disorder: analysis from the UK Medical Cannabis Registry

Introduction: Cannabis-based medicinal products (CBMPs) have been identified as a promising novel therapeutic for symptoms and comorbidities related to autism spectrum disorder (ASD). However, there is a paucity of clinical evidence of their efficacy and safety. Objective: This case series aims to assess changes to health-related quality of life and the incidence of adverse events in patients treated with CBMPs for associated symptoms of ASD enrolled on the UK Medical Cannabis Registry (UKMCR). Methods: Patients treated with CBMPs for ASD-related symptoms for a minimum of 1 month were identified from the UKMCR. Primary outcomes were changes in validated patient-reported outcome measures [Generalised Anxiety Disorder-7 (GAD-7), Single-Item Sleep Quality Scale (SQS), 5-level version of the EQ-5D (EQ-5D-5L) index values] at 1, 3 and 6 months compared with baseline. Adverse events were recorded and analysed. Statistical significance was determined by p < 0.050. Results: Seventy-four patients with ASD were included in the analysis. The mean age of participants was 32.7 (±11.6) years. There were significant improvements in general health-related quality of life and sleep as assessed by the EQ-5D-5L, SQS and GAD-7 at 1 and 3 months, with sustained changes in EQ-5D-5L and SQS at 6 months (p < 0.010). There were 180 (243.2%) adverse events reported by 14 (18.9%) participants. If present, adverse events were commonly mild (n = 58; 78.4%) or moderate (n = 81; 109.5%), rather than severe (n = 41; 55.4%). Conclusion: This study demonstrated an associated improvement in general health-related quality of life, and anxiety- and sleep-specific symptoms following initiation of treatment with CBMPs in patients with ASD. These findings, while promising, are limited by the confines of the study which lacks a control arm and is subject to attrition bias. Therefore, further evaluation is required with randomised controlled trials

Clinical outcome data of anxiety patients treated with cannabis-based medicinal products in the United Kingdom: a cohort study from the UK Medical Cannabis Registry.

RATIONALE: Cannabis-based medicinal products (CBMPs) have been identified as novel therapeutics for generalised anxiety disorder (GAD) based on pre-clinical models; however, there is a paucity of high-quality evidence on their effectiveness and safety. OBJECTIVES: This study aimed to evaluate the clinical outcomes of patients with GAD treated with dried flower, oil-based preparations, or a combination of both CBMPs. METHODS: A prospective cohort study of patients with GAD (n = 302) enrolled in the UK Medical Cannabis Registry prescribed oil or flower-based CBMPs was performed. Primary outcomes were changes in generalised anxiety disorder-7 (GAD-7) questionnaires at 1, 3, and 6 months compared to baseline. Secondary outcomes were single-item sleep quality scale (SQS) and health-related quality of life index (EQ-5D-5L) questionnaires at the same time points. These changes were assessed by paired t-tests. Adverse events were assessed in line with CTCAE (Common Terminology Criteria for Adverse Events) v4.0. RESULTS: Improvements in anxiety, sleep quality and quality of life were observed at each time point (p < 0.001). Patients receiving CBMPs had improvements in GAD-7 at all time points (1 month: difference -5.3 (95% CI -4.6 to -6.1), 3 months: difference -5.5 (95% CI -4.7 to -6.4), 6 months: difference -4.5 (95% CI -3.2 to -5.7)). Thirty-nine participants (12.9%) reported 269 adverse events in the follow-up period. CONCLUSIONS: Prescription of CBMPs in those with GAD is associated with clinically significant improvements in anxiety with an acceptable safety profile in a real-world setting. Randomised trials are required as a next step to investigate the efficacy of CBMPs