Miracle-dz/UniFAR-FTUs huggingface dataset:
Incidence and predisposing factors of phlebitis in a surgery department

This paper reports on a study conducted to determine the incidence of phlebitis related to peripheral cannulae, and its predisposing factors in a general surgery department. Phlebitis is a serious health problem that affects a large proportion of hospitalized patients receiving intravenous therapy. A data collection tool was developed based on the previous literature and was completed between 15 October and 30 November 2010 in a general surgery department. All patients with peripheral cannulae who fulfilled the inclusion criteria, and who agreed to participate in the study where monitored. This was a quantitative study, which used descriptive, inferential, and correlational analysis. A total of 171 patients and 286 peripheral cannulae were monitored. The average incidence of phlebitis was 61.5%, and factors such as diabetes and tobacco consumption were identified as relevant to the development of phlebitis. Other elements identified as predisposing to the development of phlebitis include administration of.
Understanding drivers of human-leopard conflicts in the Indian Himalayan region: Spatio-temporal patterns of conflicts and perception of local communities towards conserving large carnivores

Human killing is the decisive and most critical expression of human-leopard conflict and needs to be addressed sensitively to maintain local support for leopard conservation in India. This research was undertaken to investigate the ecological aspects of human killing and injury, spatial characteristic and pattern of such sites, temporal and seasonal trends of attacks and perception of local communities towards leopard in the Indian Himalayan region (IHR). We surveyed two sites i) Pauri Garhwal in the western part and ii) North Bengal (Dooars) in the eastern part of IHR, compiled secondary data on human-leopard conflict records and made field visits to (N = 101) conflict sites. We also conducted (N = 186) semi-structured questionnaire surveys in each of the sites to assess perception of local communities towards leopard. We analyzed the conflict data using rare events model in a binary logistic regression framework to understand spatial patterns of such incidents for Pauri Garhwal and North Bengal. The average number of injuries and deaths to leopard attacks in Pauri was estimated to be 11 (SE 1.13) and 3 (SE 0.6) per year between 2006–2016 whereas in North Bengal it was estimated to be 70 (SE 9.2) and 1.6 (SE 0.3) respectively between 2004–2016. About 97% of the leopard attacks in North Bengal and 60% of the leopard attacks in Pauri resulted in human injuries. Majority of the leopard attack victims in Pauri were children and young people, whereas in North Bengal it was middle aged tea estate workers. Attack on humans in Pauri were recorded mostly near areas with dense scrub cover whereas in North Bengal it was reported within tea-estates. The percentage of human deaths to leopard attacks in Pauri were higher (40%) compared to a mere (3%) in North Bengal. Forty-one percent of respondents in Pauri and 75% in North Bengal were positive towards presence and conservation of leopard. A predictive risk map revealed central and northern regions of Pauri Garhwal and protected areas, peripheral areas in central and south-western dooars (North Bengal) as high “human-leopard conflict risk zones”. This analytical procedure can be adopted in other sites to identify potential human-carnivore conflict risk zones.
Apilimod, a candidate anticancer therapeutic, arrests not only PtdIns(3,5)P2 but also PtdIns5P synthesis by PIKfyve and induces bafilomycin A1-reversible aberrant endomembrane dilation

PIKfyve, an evolutionarily conserved kinase synthesizing PtdIns5P and PtdIns(3,5)P2, is crucial for mammalian cell proliferation and viability. Accordingly, PIKfyve inhibitors are now in clinical trials as anti-cancer drugs. Among those, apilimod is the most promising, yet its potency to inhibit PIKfyve and affect endomembrane homeostasis is only partially characterized. We demonstrate here for the first time that apilimod powerfully inhibited in vitro synthesis of PtdIns5P along with that of PtdIns(3,5)P2. HPLC-based resolution of intracellular phosphoinositides (PIs) revealed that apilimod triggered a marked reduction of both lipids in the context of intact cells. Notably, there was also a profound rise in PtdIns3P resulting from arrested PtdIns3P consumption for PtdIns(3,5)P2 synthesis. As typical for PIKfyve inhibition and the concomitant PtdIns(3,5)P2 reduction, apilimod induced the appearance of dilated endomembrane structures in the form of large translucent cytoplasmic vacuoles. Remarkably, bafilomycin A1 (BafA1) fully reversed the aberrant cell phenotype back to normal and completely precluded the appearance of cytoplasmic vacuoles when added prior to apilimod. Inspection of the PI profiles ruled out restoration of the reduced PtdIns(3,5)P2 pool as a molecular mechanism underlying BafA1 rescue. Rather, we found that BafA1 markedly attenuated the PtdIns3P elevation under PIKfyve inhibition. This was accompanied by profoundly decreased endosomal recruitment of fusogenic EEA1. Together, our data demonstrate that apilimod inhibits not only PtdIns(3,5)P2 but also PtdIns5P synthesis and that the cytoplasmic vacuolization triggered by the inhibitor is precluded or reversed by BafA1 through a mechanism associated, in part, with reduction in both PtdIns3P levels and EEA1 membrane recruitment.
C-Tb skin test to diagnose Mycobacterium tuberculosis infection in children and HIV-infected adults: A phase 3 trial

Background C-Tb, an ESAT-6/CFP-10-based skin test, has similar sensitivity for active TB compared to tuberculin skin test (TST) and QuantiFERON-TB-Gold-In-Tube (QFT). However, data are limited in children and HIV-infected persons. Methods Asymptomatic South African contacts <5 years (n = 87; HIV-uninfected), or symptomatic individuals of all ages presenting to clinics with suspected TB (n = 1003; 30% HIV-infected) were recruited from eight South African centres. C-Tb and TST were allocated to either forearm double blinded. Samples for QFT were collected in parallel, and test-positivity rates were compared. Results In participants with microbiologically confirmed TB (n = 75; 45% HIV-infected) sensitivity of C-Tb, TST and QFT were similar (72% versus 75% versus 73%; p>0.5). All 3 tests had similar positivity rates in HIV-infected participants with active TB, however, positivity rates were reduced when CD4 counts were <100 cells/μL. In participants where active TB was excluded (n = 920), C-Tb (41%), TST (43%), and QFT (44%) also had similar test-positivity rates. Among asymptomatic contacts aged below five, 32% (28/87) tested positive with C-Tb and 32% (28/87) with TST (concordance 89%). Overall, C-Tb and TST showed a similar safety profile. Conclusion C-Tb was safe and showed similar test-positivity rates, compared to TST and QFT, in children and HIV-infected persons with active or latent M. tuberculosis infection. These data inform the utility of C-Tb in clinical practice. Trial registration ClinicalTrials.gov NCT01642888. EudraCT 2011-005078-40.
Response to Comment on Dubois-Laforgue et al. Diabetes, Associated Clinical Spectrum, Long-term Prognosis, and Genotype/Phenotype Correlations in 201 Adult Patients With Hepatocyte Nuclear Factor 1B (HNF1B) Molecular Defects. Diabetes Care 2017;40:1436–1443

We thank Clissold et al. (1) for their comments on our article (2) that demonstrated genotype/phenotype correlations in patients with HNF1B molecular defects. We reported that, compared with the patients with an HNF1B mutation, those with HNF1B whole-gene deletion due to the 17q12 deletion were leaner at diagnosis and might have a more severe diabetes phenotype. They also had a better renal prognosis as suggested by a higher estimated glomerular filtration rate (eGFR) at diabetes diagnosis and at follow-up, a less frequent need for renal replacement by dialysis or renal transplantation, and a more frequent normal function at follow-up (49% vs. 22%) (2 …
Anaesthesia and the lipidoses: a review of patients treated by bone marrow transplantation

There are many potential problems associated with anaesthesia in patients with lipid storage diseases. This review covers an 8‐year period (1983–1990) during which time 13 patients presented for procedures associated with bone marrow transplantation. The case notes of 12 patients who underwent a total of 48 general anaesthetics were reviewed. Pre‐operative assessment revealed cardiorespiratory disease in six patients. Eighty per cent of the children were anaemic (haemoglobin < 95 g1‐1). Anaesthesia was tolerated well although tracheal intubation in two patients with Gaucher's disease was difficult and became progressively more difficult as they became older. Forty‐five per cent of patients with Gaucher's disease were intubated with a tracheal tube smaller than predicted from the age of the child. Few complications were encountered but those which may be anticipated are discussed.
Personalized Therapy by Phenotype and Genotype

Upon the publication of the results of the 20-year-long UK Prospective Diabetes Study (UKPDS) (1), the general recommendation was to achieve, in as many as possible of individuals with type 2 diabetes (T2DM), a target HbA1c value ≤7%, i.e., the average value associated with significant reduction in the risk of micro- and macrovascular complications. This “universal” glycemic target, however, has been challenged by the results of subsequent intervention trials (2–4). Given the critical analysis of the results of these trials, the American Diabetes Association (ADA) and the American Heart Association suggested that an individualized HbA1c target should be identified based on the duration of diabetes, life expectancy, presence and severity of diabetes complications, and propensity for hypoglycemia (5). This suggestion has been endorsed by several international guidelines. They also suggest a selection of glucose-lowering strategies to be individualized in order to ensure the most appropriate risk-to-benefit ratio for all patients. According to the ADA/European Association for the Study of Diabetes position statement for T2DM management (6), this can be achieved through balanced assessment of efficacy, risk of hypoglycemia, effect on body weight, and costs of available glucose-lowering agents and their combination. Although the concept of treatment individualization is appealing, how to pursue it in the clinical setting remains highly debated. To this purpose, careful phenotypic description of the person with T2DM may be appropriate. A few years ago, the ABCD approach was proposed to help physicians in individualizing glycemic target and treatment selection (7). “ABCD” stands for four phenotypic traits that are easy to collect and to factor in: age, body weight, complications and comorbidities, and duration of diabetes. ### Age Age is the strongest risk factor for life expectancy and mortality. The number of elderly people with diabetes is growing, and >70% of the elderly with T2DM …
Anti-inflammatory Agents in the Treatment of Diabetes and Its Vascular Complications

The association between hyperglycemia and inflammation and vascular complications in diabetes is now well established. Antidiabetes drugs may alleviate inflammation by reducing hyperglycemia; however, the anti-inflammatory effects of these medications are inconsistent and it is unknown whether their beneficial metabolic effects are mediated via modulation of chronic inflammation. Recent data suggest that immunomodulatory treatments may have beneficial effects on glycemia, β-cell function, and insulin resistance. However, the mechanisms underlying their beneficial metabolic effects are not always clear, and there are concerns regarding the specificity, safety, and efficacy of immune-based therapies. Herein, we review the anti-inflammatory and metabolic effects of current antidiabetes drugs and of anti-inflammatory therapies that were studied in patients with type 2 diabetes. We discuss the potential benefit of using anti-inflammatory treatments in diabetes and important issues that should be addressed prior to implementation of such therapeutic approaches.
Early Respiratory Infections, Asthma, and Allergy: 10-Year Follow-up of the Oslo Birth Cohort

Purpose of the Study. As one dimension of the hygiene hypothesis, early infections may protect against the development of atopic disease. However, there are few long-term follow-up studies of the influence of early respiratory infections. This study investigates associations between early respiratory infections and diagnosed asthma, allergic rhinitis, and skin-prick sensitization in children at 10 years of age. Study Population. A total of 2540 Norwegian children were followed prospectively from birth to the age of 10 years in the Oslo Birth Cohort. Methods. Information on child’s health and environmental exposures, including experiences with respiratory infections, was recorded at birth and at 6 and 12 months. Current symptoms and “ever” doctor-diagnosed asthma and allergic rhinitis were compared with these early life exposures. A subset of the cohort underwent skin-prick testing. Results. “Ever” diagnosis of asthma was positively associated with measures of early life infection. Current asthma was related to lower respiratory tract infection (adjusted odds ratio [aOR]: 2.1; 95% confidence interval [CI]: 1.3–3.0) and croup (aOR: 2.3; 95% CI: 1.3–4.2) in the first year. ORs for allergic rhinitis and skin-prick sensitization were smaller but “mainly positive. ” Birth order and child care attendance at 1 year of age were not significantly associated with any of the studied outcomes. Conclusions. Early respiratory infections did not protect against the development of atopic disease during the first 10 years of life. Rather, infections increased the risk for asthma at age 10. Reviewer Comments. The hygiene hypothesis has been used to explain an inverse relation between early-life infection and allergic disease. Although a number of studies have described the relationship of early childhood infections and atopic disease, few have done so prospectively. This study, with its ORs near 1 with narrow CIs, shows a positive relationship of infections to atopy. Thus, it does not support the view of protection with increasing infection, bringing to light that this relationship is not as simple or direct as was first described. Additional prospective studies with long-term follow-up are required to further define this relationship. In addition, these results support previous conclusions that early childhood infection may be associated with an increased risk for future development of asthma. There continues to be many unanswered questions regarding the risks in susceptible hosts.
What Should Be the Target Blood Pressure in Elderly Patients With Diabetes?

Hypertension is very common in elderly subjects with type 2 diabetes. The coexistence of hypertension and diabetes can be devastating to the cardiovascular system, and in these patients, tight blood pressure (BP) control is particularly beneficial. Little information is available regarding the target BP levels in elderly hypertensive patients with type 2 diabetes, and therefore extrapolation from data in the general population should be done. However, it is difficult to extrapolate from the general population to these frail individuals, who usually have isolated systolic hypertension, comorbidities, organ damage, cardiovascular disease, and renal failure and have a high rate of orthostatic and postprandial hypotension. On the basis of the available evidence, we provide arguments supporting the individualized approach in these patients. Target BP should be based on concomitant diseases, orthostatic BP changes, and the general condition of the patients. It is recommended to lower BP in the elderly patient with diabetes to <140–150/90 mmHg, providing the patient is in good condition. In patients with isolated systolic hypertension, the same target is reasonable providing the diastolic BP is >60 mmHg. In patients with coronary artery disease and in patients with orthostatic hypotension, excessive BP lowering should be avoided. In elderly hypertensive patients with diabetes, BP levels should be monitored closely in the sitting and the standing position, and the treatment should be tailored to prevent excessive fall in BP.
TNF-α: a link between hypertriglyceridaemia and inflammation in SLE patients with cardiovascular disease

Patients with systemic lupus erythematosus (SLE) are at high risk of cardiovascular disease (CVD). Tumour necrosisfactor-a (TNF-α) has been implicatedin the pathophysiologicalprocessesof both SLE and CVD. This study focuses on the role of TNF-α and its soluble receptors in SLE-related CVD. In summary, 26 women (52 + 8.2 years) with SLE and a history of CVD (SLE cases)were compared with 26 age-matched women with SLE and no clinical manifestations of CVD (SLE controls) and 26 age-matched population-based control women (population controls). Plasma concentrations of circulating TNF-α, TNF-α receptor 1 (sTNFR1) and TNF-α receptor 2 (sTNFR2) were determined by ELISA. TNF-α, sTNFR1 and sTNFR2 were raised in SLE cases as compared to SLE controls (P = 0.009; P = 0.001; P = 0.001, respectively), and SLE controls had higher levels than population controls (P = 0.001; P = 0.02; P = 0.001, respectively). Exclusively in the SLE case group there was a striking positivecorrelationbetweenTNF-α and plasma triglycerides(r = 0.57, P < 0.002), VLDL triglycerides (r = 0.54, P = 0.004) and VLDL cholesterol (r = 0.58, P = 0.002). Furthermore, TNF-α correlated with the waist-hip ratio but not with estimated insulin resistance. TNF-α may thus be a major factor in SLE-related CVD acting both by contributing to hypertriglyceridaemia and by promoting atherosclerosis-relatedinflammation. sTNFR1 and sTNFR2 are strongly associated with CVD in SLE but their exact roles in disease development remain to be elucidated.
Personality Patterns in Patients with Diabetes Mellitus of Long Duration

One hundred and twelve patients with diabetes for twenty-five to forty-eight years were studied with the Minnesota Multiphasic Personality Inventory. Of these, sixty-seven had been awarded the Quarter Century Victory Medal, having been found free of vascular complications after twenty-five or more years of diabetes. The personality inventory disclosed statistically significant differences between medal and nonmedal patients in three of the thirteen scales, and three other scales approached significance. When divided as to sex, different personality patterns characterized the groups but in both sexes nonmedal patients had significantly higher hypochondriasis scores. When depression, a frequently elevated score, was excluded, significantly more nonmedal patients had other abnormal scale scores (above 2 standard deviations). The differences in scores between medal and nonmedal patients warrant early personality screening and appropriate therapy to help the adaptation process of the person with diabetes.
Pancreatic Islet Function in Nondiabetic and Diabetic BB Rats

A decreased acute insulin response to glucose in islet cell antibody positive humans predicts diabetes. Because the dominant mechanism leading to decreased in vivo acute insulin response to glucose remains unclear, perifused islets were examined before and after diabetes onset in BB rats to assess the role of glucose sensitivity on insulin secretion in individual islets. Islets from normal WF rats, diabetes-prone rats without inflamed islets, diabetes-prone rats with inflamed islets, and diabetic rats were studied at 2.0, 8.3, and 16.7 mM glucose. Immunoreactive insulin from WF islets at 16.7 mM glucose was 0.15 ± 0.02 ng · 0–7 min−1 · islet−1 for the first phase and 1.00 ± 0.05 ng · 7–20 min−1 · islet−1 for the second phase of biphasic secretion, compared with basal secretion of 0.10 ± 0.03 ng · 20 min−1 · islet−1 at 2 mM glucose. Diabetes-prone noninflamed islets showed a 0.20 ± 0.03 ng first-phase secretion, a 1.32 ± 0.13 ng second-phase secretion after 16.7 mM glucose, and 0.093 ± 0.02 ng · 20 min−1 · islet−1 at 2 mM glucose, indicating no intrinsic BB rat strain secretion abnormality. Diabetes-prone inflamed islets had secretions of 0.35 ± 0.02 ng during the first phase (P < 0.05 vs. WF) and 1.78 ± 0.29 ng during the second phase (P < 0.05 vs. WF) after 16.7 mM glucose, with 0.24 ± 0.08 ng · 20 min−1 · islet−1 at 2 mM glucose. Islets derived from diabetic rats had a first-phase secretion of 0.63 ± 0.14 ng (P < 0.05 vs. diabetes-prone noninf lamed and WF) and a second phase of 1.48 ± 0.28 ng (P < 0.05 vs. WF) with 0.30 ng · 20 min−1 · islet−1 at 2 mM glucose. Dose-response studies showed enhanced insulin secretion to each concentration of glucose when compared with controls (WF or diabetes-prone noninf lamed). These data indicate that 1) BB inflamed islets can be isolated for dynamic insulin secretion studies in nondiabetic and diabetic rats; 2) β-cell glucose sensitivity appears enhanced in islets derived from nondiabetic rats with inflamed islets or rats soon after diabetes onset; and 3) the reported impairment of in vivo acute insulin response to glucose in the BB rat model does not result primarily from a decrease in residually functioning β-cell sensitivity to glucose, but rather the data suggest a more important role for decreased residual β-cell mass.
Developing a Universal Staphylococcus aureus Vaccine: Why Aren’t We There Yet?

This review discusses several aspects of vaccine development efforts for Staphylococcus aureus. While several vaccines have shown efficacy in pre-clinical models, a potent and successful S aureus vaccine still eludes us. This review captures the historical literature on S. aureus vaccine development and discusses the results of major clinical trials in the field. Here we discuss important new insights into immunological mechanisms of protection from extracellular bacterial infections and shed light on important pre-clinical and clinical findings that establish a correlation between S. aureus infections and lack of cell mediated immunity. We attempt to provide an immunological explanation for the reasons behind the failure of prior S. aureus vaccines and provide insight into the rational design of a universal vaccine for S. aureus infections.