Miracle-dz/UniFAR-FTUs huggingface dataset:
Lysosome-Mediated Plasma Membrane Repair Is Dependent on the Small GTPase Arl8b and Determines Cell Death Type in Mycobacterium tuberculosis Infection

Mycobacterium tuberculosis is an extremely successful pathogen, and its success is widely attributed to its ability to manipulate the intracellular environment of macrophages. A central phenomenon of tuberculosis pathology enabling immune evasion is the capacity of virulent M. tuberculosis (H37Rv) to induce macrophage necrosis, which facilitates the escape of the mycobacteria from the macrophage and spread of infection. In contrast, avirulent M. tuberculosis (H37Ra) induces macrophage apoptosis, which permits Ag presentation and activation of adaptive immunity. Previously, we found that H37Rv induces plasma membrane microdisruptions, leading to necrosis in the absence of plasma membrane repair. In contrast, H37Ra permits plasma membrane repair, which changes the host cell death modality to apoptosis, suggesting that membrane repair is critical for sequestering the pathogen in apoptotic vesicles. However, mechanisms of plasma membrane repair induced in response to M. tuberculosis infection remain unknown. Plasma membrane repair is known to induce a Ca2+-mediated signaling, which recruits lysosomes to the area of damaged plasma membrane sites for its resealing. In this study, we found that the small GTPase Arl8b is required for plasma membrane repair by controlling the exocytosis of lysosomes in cell lines and in human primary macrophages. Importantly, we found that the Arl8b secretion pathway is crucial to control the type of cell death of the M. tuberculosis–infected macrophages. Indeed, Arl8b-depleted macrophages infected with avirulent H37Ra undergo necrotic instead of apoptotic cell death. These findings suggest that membrane repair mediated by Arl8b may be an important mechanism distinguishing avirulent from virulent M. tuberculosis–induced necrotic cell death.
Long-term Efficacy of Treatment with Lamivudine in HBeAg-Negative Patients with Decompensated Cirrhosis Due to Chronic Hepatitis B

Background The prognosis of patients with decompensated cirrhosis due to hepatitis B is very poor. It has been shown that lamivudine can improve liver function and delay the need for liver transplantation in HBeAg-positive patients with decompensated cirrhosis. However, information regarding long-term use of lamivudine in HBeAg-negative patients with cirrhosis is limited. The primary objective of this study was to evaluate the long-term efficacy of lamivudine in HBeAg-negative/HBeAb-positive patients with decompensated cirrhosis. Materials and Methods 54 consecutive HBeAg-negative/HBeAb-positive patients with decompensated cirrhosis were enrolled into this study. All patients were treated with 100 mg lamivudine per day. Significant clinical improvement was defined as a decrease of at least 2 points in Child-Pugh-Turcotte (CPT) score. Repeated-measure one-way analysis of variance was used to evaluate the effect of time interval of lamivudine treatment on different variables. Kaplan-Meier survival analysis and Mantel-Cox test were used to further analyze the data. Results The mean±SD age of patients was 50.6±13.2 years. There were 40 male and 14 female patients. The median follow-up was 29 (range: 6-64) months. CPT score, MELD score and blood chemistries changed significantly after 6 months of therapy. The favorable changes were continued up to 2 years. In spite of worsening after 3 years, within subject effects measured by repeated-measure ANOVA, were significant for patients who have received lamivudine for 4 years or more. Conclusions
The ICU Mobility Scale Has Construct and Predictive Validity and Is Responsive. A Multicenter Observational Study.

RATIONALE The ICU Mobility Scale (IMS) is a measure of mobility milestones in critically ill patients. OBJECTIVES This study aimed to determine the validity and responsiveness of the IMS from a prospective cohort study of adults admitted to the intensive care unit (ICU). METHODS Construct and predictive validity were assessed by comparing IMS values at ICU discharge in 192 patients to other variables using Spearman rank correlation coefficient, Mann-Whitney U tests, and logistic regression. Responsiveness was assessed using change over time, effect size, floor and ceiling effects, and percentage of patients showing change. MEASUREMENTS AND MAIN RESULTS The IMS at ICU discharge demonstrated a moderate correlation with muscle strength (r = 0.64, P < 0.001). There was a significant difference between the IMS at ICU discharge in patients with ICU-acquired weakness (median, 4.0; interquartile range, 3.0-5.0) compared with patients without (median, 8.0; interquartile range, 5.0-8.0; P < 0.001). Increasing IMS values at ICU discharge were associated with survival to 90 days (odds ratio [OR], 1.38; 95% confidence interval [CI], 1.14-1.66) and discharge home (OR, 1.16; 95% CI, 1.02-1.32) but not with return to work at 6 months (OR, 1.09; 95% CI, 0.92-1.28). The IMS was responsive with a significant change from study enrollment to ICU discharge (d = 0.8, P < 0.001), with IMS values increasing in 86% of survivors during ICU admission. No substantial floor (14% scored 0) or ceiling (4% scored 10) effects were present at ICU discharge. CONCLUSIONS Our findings support the validity and responsiveness of the IMS as a measure of mobility in the ICU.
Rabbit Clinical Pathology

Abstract With rabbit patients, as in other species, analyzing blood and urine samples can be useful and informative, although interpretation of the results is sometimes challenging. This article summarizes the interpretation of laboratory results from rabbits. Hematological parameters can yield information about the red blood cell population and leukocyte response to stress and pathogens. Biochemistry evaluation can be used to investigate liver, kidney, and other organ function, and urinalysis results may yield additional information about kidney function and electrolyte imbalances. Serological tests are available for several pathogens of rabbits, including Encephalitozoon cuniculi, although the significance of positive results and antibody titers is not clear. Serum protein electrophoresis aids the understanding of protein disorders and the immune response to acute and chronic inflammation.
HEATING THERAPY LOWERS BLOOD GLUCOSE LEVEL IN MICE (Mus musculus)

Diabetes Mellitus is a metabolic disease that has become one of the urgent diseases in Indonesia. Even in epidemiology, it is estimated that by 2030 the prevalence of Diabetes Mellitus (DM) in Indonesia reached 21.3 million people. The objective of this study was to know the heating effectiveness of therapy in lowering blood glucose levels. The research was conducted for one day. With the number of samples of mice (Mus musculus) males weight was 20grams. Mice were divided into four treatment groups,and each group consist of 7 mice. K1 groups of mice were treated temperature of 20°C (room temperature AC); K2 groups of mice were treated 28°C temperature (room temperature); K3 groups of mice were treated 37°C; and K4 groups of mice treated 40°C temperature. The mice has been fasted for 16 hours, then fasting blood sugar is measured. Then the mice was given pure glucose 0,2 gram each mice and 30 minutes later mice were re-measured blood sugar. After that, mice incorporated into the heating therapy box and were treated for 30 minutes. And blood sugar levels after mice were re-measured. Results From the research, found that the heating therapy provides a significant effect on reducing blood glucose levels. In this experiment, be obtained that at 37°C (group K3) differ significantly with treatment at a temperature of 20°C (group K1) and 28°C (group K2), but not significantly different from treatment at a temperature of 40°C (group 4). However, the results of the analysis, these experiments provide heating to the conclusion that effective therapy performed at 37°C-40°C. But the effective temperature is 37°C. This gives the conclusion that the effective reduction in glucose levels obtained at a temperature not exceeding the normal human body temperature. It is suspected that the body temperature reaches 40°C has almost reached exhaustion and hyperthermia temperature and duration of endurance will decrease. Conclusions According the results of research it can be concluded that the heating therapy in 37°C-40°C can reduce blood gluose of mice (Mus musculus). It needs to do further research on effective duration and about the side effects of heating therapy. (FMI 2012;48 84-89)
An in-vitro analysis of the antimicrobial efficacy of herbal toothpastes on selected primary plaque colonizers

Plaque associated oral disease affects a considerable portion of the population and is considered one of the major causes of tooth loss. In most cases toothbrushing only removes a limited amount of dental plaque and other chemical agents are required to reduce the bacterial load. Aims & objectives: The purpose of study was to determine whether there was any significant difference in the antimicrobial activity of 4 herbal toothpastes against cultures of 3 primary plaque colonizers. Methods: A total of 5 toothpastes were tested for their antimicrobial efficacy against Streptococcus mutans (NCTC 10920), Streptococcus sanguinis (NCTC 10904) and a non-specific α-heamolytic streptococcus by agar diffusion method. The data were collected and analysed using one way ANOVA and Tukey's multiple comparison test significant at p<0.05. Results: Dentazyme ® herbal toothpaste showed the greatest ability to inhibit bacterial growth for all the tested organisms (p<0.05). Nature Fresh had the lowest potential for antimicrobial activity. Conclusions: Dentazyme ® Herbal toothpaste was the only herbal toothpaste to inhibit the growth of all the bacteria tested and had similar antimicrobial efficacy to a triclosan containing toothpaste (Colgate ® Total ® ).
Mortality associated with nephropathy after radiographic contrast exposure.

OBJECTIVE To define outcomes from contrast-induced nephropathy (CIN) after both intra-arterial and intravenous administration of contrast medium. PATIENTS AND METHODS We performed a retrospective case-matched cohort study at Mayo Clinic's site in Rochester, MN, from April 1, 2004, to March 31, 2006. All contrast procedures were evaluated for inclusion. Contrast-induced nephropathy was defined as creatinine elevation of 25% or more after contrast exposure or of more than 0.5 mg/dL within 7 days of contrast exposure. Cases of CIN were matched 1:3 with controls by age, sex, pre-procedure creatinine elevation, diabetes mellitus, and type of imaging procedure. RESULTS A total of 809 patients who developed CIN were matched to 2427 patients who did not develop CIN after contrast exposure. In multivariate analyses, CIN was significantly associated with 30-day mortality (odds ratio, 3.37; 95% confidence interval [CI], 2.58-4.41; P<.001) and overall mortality (hazard ratio, 1.57; 95% CI, 1.32-1.86; P<.001) after adjustment for heart failure, hypertension, medications, total hydration, iodine load, prior contrast exposure, and all matched variables during the study period. Intravenous contrast administration was a risk factor for 30-day mortality (odds ratio, 2.91; 95% CI, 1.17-7.23; P=.02) and overall mortality (hazard ratio, 3.02; 95% CI, 1.89-4.82; P<.001) compared with intra-arterial administration of contrast after adjustment for heart failure, hypertension, medications, total hydration, iodine load, prior contrast exposure, and all matched variables during the study period. CONCLUSION Contrast-induced nephropathy after administration of contrast medium is associated with increased mortality. This risk is higher in patients in whom contrast medium is administered intravenously than in those in whom it is administered intra-arterially.
Results of a Medicare Bundled Payments for Care Improvement Initiative for Chronic Obstructive Pulmonary Disease Readmissions

Rationale: Approximately 20% of Medicare beneficiaries hospitalized for acute exacerbations of chronic obstructive pulmonary disease (COPD) are readmitted within 30 days of discharge. In addition to implementing penalties for excess readmissions, the U.S. Centers for Medicare and Medicaid Services has developed Bundled Payments for Care Improvement (BPCI) initiatives to improve outcomes and control costs. Objectives: To evaluate whether a comprehensive COPD multidisciplinary intervention focusing on inpatient, transitional, and outpatient care as part of our institution's BPCI participation would reduce 30‐day all‐cause readmission rates for COPD exacerbations and reduce overall costs. Methods: We performed a pre‐postintervention study comparing all‐cause readmissions and costs after index hospitalization for Medicare‐only patients with acute exacerbation of COPD. The primary outcome was the difference in 30‐day all‐cause readmission rate compared with historical control subjects; secondary outcomes included the 90‐day all‐cause readmission rate and also health care costs compared with BPCI target prices. Results: Seventy‐eight consecutive Medicare patients were prospectively enrolled in the BPCI intervention in 2014 and compared with 109 patients in the historical group from 2012. Patients in BPCI were more likely to receive regular follow‐up phone calls, pneumococcal and influenza vaccines, home health care, durable medical equipment, and pulmonary rehabilitation, and to attend pulmonary clinic. There was no difference in all‐cause readmission rates at 30 days (BPCI, 12 events [15.4%] vs. non‐BPCI, 19 events [17.4%]; P = 0.711), and 90 days (21 [26.9%] vs. 37 [33.9%]; P = 0.306). Compared with BPCI target prices, we incurred 4.3% lower 90‐day costs before accounting for significant investment from the health system. Conclusions: A Medicare BPCI intervention did not reduce 30‐day all‐cause readmission rates or overall costs after hospitalization for acute exacerbation of COPD. Although additional studies enrolling larger numbers of patients at multiple centers may demonstrate the efficacy of our BPCI initiative for COPD readmissions, this is unlikely to be cost effective at any single center.
Safety of Patient Mobilization and Rehabilitation in the Intensive Care Unit. Systematic Review with Meta‐Analysis

Background: Early mobilization and rehabilitation of patients in intensive care units (ICUs) may improve physical function, and reduce the duration of delirium, mechanical ventilation, and ICU length of stay. However, safety concerns are an important barrier to widespread implementation. Objectives: To synthesize safety data regarding patient mobilization and rehabilitation in the ICU, including falls, removal of endotracheal tubes, removal or dysfunction of intravascular catheters, removal of other catheters/tubes, cardiac arrest, hemodynamic changes, and desaturation. Data Sources: Systematic literature review, including searches of five databases. Eligible studies evaluated patients who received mobilization‐related interventions in the ICU. Exclusion criteria included: (1) case series with fewer than 10 patients; (2) majority of patients under 18 years of age; and (3) data not reported to permit calculation of incidence of safety events. Data Extraction: Number of patients, mobilization/rehabilitation sessions, potential safety events, and events with negative consequences (e.g., requiring intervention or additional therapy). Synthesis: Heterogeneity was assessed by I2 statistics, and bias assessed by the Newcastle‐Ottawa Scale and Cochrane risk of bias assessment. The literature search identified 20,660 titles. There were 48 eligible publications evaluating 7,546 patients, with 583 potential safety events occurring in 22,351 mobilization/rehabilitation sessions. There was a total of 583 (2.6%) potential safety events with heterogeneity in the definitions for these events. For the safety event types that could be meta‐analyzed, pooled incidences per 1,000 mobilization/rehabilitation sessions (95% confidence interval), were: hemodynamic changes, 3.8 (1.3‐11.4), and desaturation, 1.9 (0.9‐4.3). A total of 24 studies of 3,404 patients reported on any consequences of potential safety events (e.g., needing to increase dose of vasopressor due to mobility‐related hypotension), with a frequency of 0.6% in 14,398 mobilization/rehabilitation sessions. Conclusions: Patient mobilization and physical rehabilitation in the ICU appears safe, with a low incidence of potential safety events, and only rare events having any consequences for patient management. Heterogeneity in the definition of safety events across studies emphasizes the importance of implementing existing consensus‐based definitions.
Mechanisms That Modulate Peripheral Oxygen Delivery during Exercise in Heart Failure.

Oxygen uptake ([Formula: see text]o2) measured at the mouth, which is equal to the cardiac output (CO) times the arterial-venous oxygen content difference [C(a-v)O2], increases more than 10- to 20-fold in normal subjects during exercise. To achieve this substantial increase in oxygen uptake [[Formula: see text]o2 = CO × C(a-v)O2] both CO and the arterial-venous difference must simultaneously increase. Although this occurs in normal subjects, patients with heart failure cannot achieve significant increases in cardiac output and must rely primarily on changes in the arterial-venous difference to increase [Formula: see text]o2 during exercise. Inadequate oxygen delivery to the tissue during exercise in heart failure results in tissue anaerobiosis, lactic acid accumulation, and reduction in exercise tolerance. H+ is an important regulatory and feedback mechanism to facilitate additional oxygen delivery to the tissue (Bohr effect) and further aerobic production of ATP when tissue anaerobic metabolism increases the production of lactate (anaerobic threshold). This H+ production in the muscle capillary promotes the continued unloading of oxygen (oxyhemoglobin desaturation) while maintaining the muscle capillary Po2 (Fick principle) at a sufficient level to facilitate aerobic metabolism and overcome the diffusion barriers from capillary to mitochondria ("critical capillary Po2," 15-20 mm Hg). This mechanism is especially important during exercise in heart failure where cardiac output increase is severely constrained. Several compensatory mechanisms facilitate peripheral oxygen delivery during exercise in both normal persons and patients with heart failure.
Suboptimal Inspiratory Flow Rates Are Associated with Chronic Obstructive Pulmonary Disease and All‐Cause Readmissions

&NA; Rationale: Dry powder inhalers (DPIs) are prescribed after hospitalization for acute exacerbation of COPD (AECOPD). Peak inspiratory flow (PIF) affects DPI delivery. Objectives: To study the impact of PIF on readmission after hospitalization for AECOPD. Methods: A retrospective analysis of hospitalized patients, enrolled in an AECOPD care plan, was performed. Data analyzed included PIF, age, sex, length of stay, Charlson Comorbidity Index, COPD Assessment Test score, modified Medical Research Council score, percent predicted FEV1, FVC, and inspiratory capacity. A PIF equal to and less than 60 L/min was defined as suboptimal (sPIF). Outcome measures included 30‐ and 90‐day COPD and all‐cause readmissions, and days to next COPD and all‐cause readmissions. Results: Of the 123 subjects, 52% (n = 64) had sPIF. They had greater COPD Assessment Test scores (29.1 ± 5.9 vs. 25.3 ± 8.7; P = 0.0073), rates of 90‐day COPD readmissions (28.1 vs. 13.6%; P = 0.048), fewer median days to COPD (63.5 [interquartile range (IQR), 21‐89.8] vs. 144 [IQR, 66‐218]; P = 0.002) and all‐cause readmissions (65.5 [IQR, 24.3‐107.3] vs. 101 [IQR, 54.5‐205.5]; P = 0.009). PIF was the only variable (P = 0.041) that predicted days to COPD readmission in a multivariate model incorporating age, sex, percent predicted FEV1, Charlson Comorbidity Index, and inspiratory flow group. In a group of patients with sPIF (n = 22), all‐cause and COPD 30‐ and 90‐day readmission rates were significantly lower for those discharged with nebulizer compared with DPI therapy. Conclusions: sPIF is common during AECOPD and predicts all‐cause and COPD readmissions. Patients with sPIF may benefit from nebulized therapies. We recommend checking PIF in patients hospitalized for AECOPD for selection of delivery devices.
Critical Thinking in Critical Care: Five Strategies to Improve Teaching and Learning in the Intensive Care Unit

&NA; Critical thinking, the capacity to be deliberate about thinking, is increasingly the focus of undergraduate medical education, but is not commonly addressed in graduate medical education. Without critical thinking, physicians, and particularly residents, are prone to cognitive errors, which can lead to diagnostic errors, especially in a high‐stakes environment such as the intensive care unit. Although challenging, critical thinking skills can be taught. At this time, there is a paucity of data to support an educational gold standard for teaching critical thinking, but we believe that five strategies, routed in cognitive theory and our personal teaching experiences, provide an effective framework to teach critical thinking in the intensive care unit. The five strategies are: make the thinking process explicit by helping learners understand that the brain uses two cognitive processes: type 1, an intuitive pattern‐recognizing process, and type 2, an analytic process; discuss cognitive biases, such as premature closure, and teach residents to minimize biases by expressing uncertainty and keeping differentials broad; model and teach inductive reasoning by utilizing concept and mechanism maps and explicitly teach how this reasoning differs from the more commonly used hypothetico‐deductive reasoning; use questions to stimulate critical thinking: “how” or “why” questions can be used to coach trainees and to uncover their thought processes; and assess and provide feedback on learner's critical thinking. We believe these five strategies provide practical approaches for teaching critical thinking in the intensive care unit.
Hepatitis C and injecting drug use: The realities of stigmatisation and discrimination

Objective To examine the extent of discrimination and stigmatisation related to hepatitis C virus (HCV) infection, as experienced by injecting drug users in Sydney, Australia. Design Data were collected through a self-administered questionnaire from injecting drug users (IDUs). Questions included basic demo- graphics, injecting and sexual history, HCV knowledge, risk practices, self-reported HCV diagnosis, and experiences of discrimination and o stigmatisation, as well as harm reduction services provided by needle and syringe programmes (NSPs). Both qualitative and quantitative data were collected from IDUs. Setting Questionnaires were distributed to clients of NSPs in the Sydney metropolitan area. Method Ten NSPs and one methadone clinic were selected. Questionnaires were distributed to all of these outlets and a total of 274 persons were recruited. The staff at the selected sites asked clients to fill out the questionnaire while distributing injecting equipment. Results Most HCV related discrimination against drug users was reported in health care settings. Fifty-two per cent of the participants experienced this as a result of being HCV positive. In addition, more than half of the sample (65 per cent) reported that such discrimination was actually as a result of being a drug user. Females were more likely than males to experience discrimination because of their HCV status. Conclusion The level of discrimination and stigmatisation was widespread in health care settings, resulting from the stereotyping of IDUs. The barriers to IDUs accessing health services need to be identified and removed. Implementation of an awareness campaign among health professionals would be a feasible way to address this issue.