Miracle-dz/UniFAR-FTUs huggingface dataset:
Toxic Profile of Benznidazole in Patients with Chronic Chagas Disease: Risk Factors and Comparison of the Product from Two Different Manufacturers

ABSTRACT Benznidazole is considered the first-line treatment option against Chagas disease. The major drawback of benznidazole is its toxicity profile. The main objectives of this study were to describe the adverse events (AEs) in patients with chronic Chagas disease treated with benznidazole, determine the risk factors involved and compare the toxic profiles of two different preparations of the drug from ELEA and Roche. A total of 746 patients were diagnosed with Chagas disease in a 5-year period, and of these 472 were treated with benznidazole. A high proportion of patients (n = 360 [76%]) suffered AEs, the most frequent being those related to hypersensitivity (52.9% of patients), headache (12.5%), and epigastric pain (10.4%). In 72 (12.7%) cases, treatment was discontinued. Overall, women had a higher incidence of AEs compared to men (81.3% versus 66%, P = 0.001) and were subject to higher levels of hypersensitivity-related events. Dermatological events, digestive tract manifestations, and general symptoms had a greater likelihood to appear around day 10 and neurological AEs around day 40 after starting treatment. With respect to liver function and hematological tests, the majority of patients did not suffer significant perturbation of liver enzymes or altered blood cell counts. However, 14 patients suffered from neutropenia, and 14 patients had aminotransferase levels that were more than four times the upper limit of the normal range. Patients treated with the ELEA benznidazole product experienced more arthromyalgia, neutropenia, and neurological disorders (mainly paresthesias) than those treated with the Roche product. Both drug products resulted in approximately the same percentage of permanent withdrawals.
Perspectives on HIV Prevention: Priorities for a New Era

Abstract:The field of biomedical HIV prevention has undergone remarkable changes over the past 5 years. These advances have expanded conceptions of what should belong in the prevention “toolbox,” particularly for infection via sexual exposure. New findings have also added complexity to previous theoretical discussions about plans for introduction and access to these interventions. Finally, scientific developments in biomedical prevention have activated a prevention-focused advocacy movement working at the grassroots, national, and global levels. This advocacy seeks to use existing tools to begin to end the AIDS epidemic while maintaining a prevention research agenda to develop additional tools to eventually end the epidemic.
Fusible Core Molding for the Fabrication of Branched, Perfusable, Three-Dimensional Microvessels for Vascular Tissue Engineering

A novel method for fabrication of branched, tubular, perfusable microvessels for use in vascular tissue engineering is reported. A tubular, elastomeric, biodegradable scaffold is first fabricated via a new, double fusible injection molding technique that uses a ternary alloy with a low melting temperature, Field's metal, and paraffin as sacrificial components. A cylindrical core metal of 500 μm or lower diameter with the target branching scaffold geometry is first constructed, then the metal structure is coated with paraffin and, finally, the metal-paraffin construct is embedded in polydimethylsiloxane (PDMS). The paraffin layer is then removed by heating and replaced by a biodegradable elastomeric pre-polymer that is subsequently UV-cured inside the PDMS. Next, the metal core is melted away and the PDMS is removed to attain the branched tubular elastomeric biodegradable scaffold. Finally, it is also demonstrated that human umbilical vein endothelial cells (HUVEC) were able to spread on the surface of the scaffold and form a confluent monolayer, confirming the potential of this new technique for making engineered blood vessels.
Nonsteroidal Anti-Inflammatory Drugs During Pregnancy and the Initiation of Lactation

Nonsteroidal anti-inflammatory drugs (NSAIDs) and aspirin, which are available as “over-the counter” medications in most countries, are widely used by both pregnant and lactating women. They are popular non-opioid analgesics for the treatment of pain after vaginal and operative delivery. In addition, NSAIDs are used for tocolysis in premature labor, and low-dose aspirin has a role in the prevention of preeclampsia and recurrent miscarriage in antiphospholipid syndrome. NSAIDs and aspirin may affect fertility and increase the risk of early pregnancy loss. In the second trimester their use is considered reasonably safe, but has been associated with fetal cryptorchism. In the third trimester, NSAIDs and aspirin are usually avoided because of significant fetal risks such as renal injury, oligohydramnios, constriction of the ductus arteriosus (with potential for persistent pulmonary hypertension in the newborn), necrotizing enterocolitis, and intracranial hemorrhage. Maternal administration or ingestion of most NSAIDs results in low infant exposure via breastmilk, such that both cyclooxygenase-1 and cyclooxygenase-2 inhibitors are generally considered safe, and preferable to aspirin, when breastfeeding.
PHOSPHORUS METABOLISM AND MANAGEMENT IN CHRONIC KIDNEY DISEASE: Expanding Role for Vitamin D in Chronic Kidney Disease: Importance of Blood 25‐OH‐D Levels and Extra‐Renal 1α‐Hydroxylase in the Classical and Nonclassical Actions of 1α,25‐Dihydroxyvitamin D3

Recent advances in the understanding of vitamin D have revolutionized our view of this old nutritional factor and suggested that it has much wider effects on the body than ever believed before. In addition to its well‐known effects on calcium/phosphate homeostasis, vitamin D, through its hormonal form, 1α,25‐dihydroxyvitamin D3 or calcitriol, is a cell differentiating factor and anti‐proliferative agent with actions on a variety of tissues around the body (e.g., skin, muscle, immune system). By influencing gene expression in multiple tissues, calcitriol influences many physiological processes besides calcium/phosphate homeostasis including muscle and keratinocyte differentiation, insulin secretion, blood pressure regulation, and the immune response. The incidence of various diseases including epithelial cancers, multiple sclerosis, muscle weakness as well as bone‐related disorders has been correlated with vitamin D deficiency/insufficiency and has led to a re‐evaluation of recommended daily intakes both in the normal subject and CKD patient. Critical developments have been the emergence of the value of blood 25‐OH‐D measurement as a tool in predicting vitamin D‐related problems and this has in turn emphasized the importance of the extra‐renal version of the 1α‐hydroxylase, the enzyme responsible for the final step in vitamin D activation. The widespread expression of this extra‐renal enzyme supports the view that it exists to boost intracellular concentrations of calcitriol within some target tissues in order to modulate a unique set of genes specifically in those tissues, a process which is therefore dependent upon circulating 25‐OH‐D. For CKD patients with their tendency to vitamin D substrate insufficiency coupled with their documented loss of the renal 1α‐hydroxylase in late stages, this new information has profound implications. Physicians must start to manage the vitamin D insufficiency by vitamin D supplements throughout stages 1–5 whilst continuing to provide calcitriol replacement therapy, in the form of calcitriol or its analogs, in stages 3–5.
Effect of Topical Basic Fibroblast Growth Factor on the Healing of Chronic Diabetic Neuropathic Ulcer of the foot: A pilot, randomized, double-blind, placebo-controlled study

OBJECTIVE To assess the efficacy and safety of topical human recombinant basic fibroblast growth factor (bFGF) on the healing of diabetic neurotrophic foot ulcers. RESEARCH DESIGN AND METHODS Seventeen diabetic patients suffering from chronic neuropathic ulcer of the plantar surface of the foot entered a pilot, randomized, double-blind study comparing local application of bFGF with placebo. Main inclusion criteria were a typical neuropathic ulcer of Wagner grade I-III, more than 0.5 cm in the largest diameter, with an abnormally high vibration perception threshold in the absence of significant peripheral vascular disease or wound infection. bFGF or placebo was applied daily during the 6 weeks as inpatients then twice a week for 12 weeks. Evolution of ulcer size was assessed through weekly clinical examination and computerized photographs. RESULTS In the bFGF group, three of nine ulcers healed compared with five of eight in the placebo group (NS). The weekly reduction in ulcer perimeter and area was identical in both groups, as was the rate of linear advance from entry to the 6th week of treatment (bFGF: 0.053 ± 0.048 mm vs. placebo: 0.116 ± 1.129 mm): the same result was obtained at the 11th week. Moreover, percent healed area at the end of the study did not differ significantly. No side effects were observed during bFGF application. CONCLUSIONS Topical application of bFGF has no advantage over placebo for healing chronic neuropathic diabetic ulcer of the foot. Because diabetes causes significant wound-healing defects, we hypothesized that using a single growth factor might be insufficient to accelerate wound closure of diabetic ulcers.
A HIGH-PERFORMANCE VISUAL SPEECH RECOGNITION SYSTEM FOR AN ULTRASOUND-BASED SILENT SPEECH INTERFACE

The development of a continuous visual speech recognizer for a silent speech interface has been investigated using a visual speech corpus of ultrasound and video images of the tongue and lips. By using high-speed visual data and tiedstate cross-word triphone HMMs, and including linguistic information via a domain-specific language model, wordlevel recognition accuracy as high as 85% was achieved on visual speech. Using the Julius system, it was also found that the recognition should be possible in nearly real-time.
An Inducible Pathway for Degradation of FLIP Protein Sensitizes Tumor Cells to TRAIL-induced Apoptosis*

TRAIL (Apo2 ligand) is a member of the tumor necrosis factor (TNF) family of cytokines that induces apoptosis. Because TRAIL preferentially kills tumor cells, sparing normal tissues, interest has emerged in applying this biological factor for cancer therapy in humans. However, not all tumors respond to TRAIL, raising questions about resistance mechanisms. We demonstrate here that a variety of natural and synthetic ligands of peroxisome proliferator-activated receptor-γ (PPARγ) sensitize tumor but not normal cells to apoptosis induction by TRAIL. PPARγ ligands selectively reduce levels of FLIP, an apoptosis-suppressing protein that blocks early events in TRAIL/TNF family death receptor signaling. Both PPARγ agonists and antagonists displayed these effects, regardless of the levels of PPARγ expression and even in the presence of a PPARγ dominant-negative mutant, indicating a PPARγ-independent mechanism. Reductions in FLIP and sensitization to TRAIL-induced apoptosis were also not correlated with NF-κB, further suggesting a novel mechanism. PPARγ modulators induced ubiquitination and proteasome-dependent degradation of FLIP, without concomitant reductions in FLIP mRNA. The findings suggest the existence of a pharmacologically regulated novel target of this class of drugs that controls FLIP protein turnover, and raise the possibility of combining PPARγ modulators with TRAIL for more efficacious elimination of tumor cells through apoptosis.
Invasive fungal infections during the neonatal period: diagnosis, treatment and prophylaxis

Introduction: The incidence of preterm births seems to be increased in many countries around the world, in parallel to the advances in neonatal medicine. However, this has resulted in longer hospital stays and more exposure to invasive interventions, both of which can lead to an increase in late-onset nosocomial infections in the newborn period. In addition to bacteria, fungi are thought to be an important cause of hospital infections. Areas covered: The present article reviews the diagnosis, treatment and prophylaxis of invasive fungal infections (IFIs) during the neonatal period. IFIs are associated with high morbidity and mortality in preterm neonates. The main risk factors are multiple antibiotics, central venous catheters, parenteral nutrition, immunodepression, very low birth weight, and fungal colonization. Successful management of IFIs relies on early recognition and rapid initiation of effective treatment. Expert opinion: Invasive-fungal-infection-related morbidity and mortality is a major concern for most neonatal intensive care units worldwide. Incidence rates are increasing for preterm neonates. Preterm infants display clinical characteristics that make them prone to fungal infections, and there is a high frequency of neurodevelopmental sequelae in those who survive after neonatal fungal infections. Specific prevention – rather than treatment – should be the optimal strategy. Both ﬂuconazole and nystatin prophylaxis reduce the incidence of IFI and fungal colonization in very preterm infants.
Mutagenesis of bleomycin‐damaged lambda phage in SOS‐deficient and repair endonuclease‐deficient escherichia coli

Previous DNA sequence analysis of bleomycin‐induced forward mutations in repackaged lambda phage has suggested SOS‐dependent replicative bypass of oxidized apyrimidinic sites as a possible mechanism of mutagenesis. In order to evaluate this hypothesis further, frequencies of mutation to a clear‐plaque phenotype were compared for bleomycin‐damaged phage grown in various repair‐deficient strains of Escherichia coli. Survival of bleomycin‐damaged phage was virtually identical in all host strains. Studies in SOS‐deficient strains indicated specific requirements for functional recA+ and umuC+ alleles in the generation of the majority of bleomycininduced mutations, as well as a less stringent requirement for induction of the SOS response by ultraviolet irradiation of the host cells. These results are expected for mutagenesis resulting from apyrimidinic sites. However, the mutation frequency for bleomycin‐damaged phage was the same whether the phage were grown in a wild‐type strain or in strains deficient in apurinic/apyrimidinic repair endonucleases; this was true even for an nth∼nfo∼xth∼ strain lacking all three major apurinic/apyrimidinic endonucleases (endonuclease III, endonuclease IV, and exonuclease III). Likewise, phage grown in an endonuclease IV‐overproducing strain showed the same mutation frequency as those grown in wild‐type cells. These data suggest that either i) bleomycin‐induced mutagenesis results from SOS‐dependent bypass of lesions other than apyrimidinic sites or ii) the number of apyrimidinic sites available for SOS processing is virtually independent of the level of apurinic/apyrimidinic endonuclease activity in the cell. It is possible that a fraction of the apyrimidinic sites induced by bleomycin either are intrinsically resistant to repair or undergo secondary reactions that render them resistant.
An observational study of associations between nurse behaviour and violence in psychiatric hospitals.

A cyclical model of violence to psychiatric nurses is proposed in this paper and a partial test of the model is reported. The model suggests that stress induced by exposure to violence leads to impaired staff performance and adoption of behaviours which make the re-occurrence of violence more likely. We tested the proposal that certain staff behaviours (e.g. expressing verbal hostility) are associated with an increased risk of assault by observing nurse-patient interaction on 12 psychiatric wards (n = 103 nurses). The verbal and physical interaction of (1) assaulted staff, (2) staff on violent wards, and (3) staff in grades which experience high levels of assault, were compared with those of respective low risk groups. There was some evidence of an association between interaction patterns and violence. We conclude this paper by discussing the implications of the model for psychiatric nursing practice.
Automation of spot counting in interphase cytogenetics using brightfield microscopy.

In situ hybridization techniques allow the enumeration of chromosomal abnormalities and form a great potential for many clinical applications. Although the use of fluorescent labels is preferable regarding sensitivity and colormultiplicity, chromogenic labels can provide an excellent alternative in relatively simple situations, e.g., where it is sufficient to use a centromere specific probe to detect abnormalities of one specific chromosome. When the frequency of chromosomal aberrations is low, several hundreds or even thousands of cells have to be evaluated to achieve sufficient statistical confidence. Since manual counting is tedious, fatiguing, and time consuming, automation can assist to process the slides more efficiently. Therefore, a system has been developed for automated spot counting using brightfield microscopy. This paper addresses both the hardware system aspects and the software image analysis algorithms for nuclei and spot detection. As a result of the automated slide analysis the system provides the frequency spot distribution of the selected cells. The automatic classification can, however, be overruled by human interaction, since each individual cell is stored in a gallery and can be relocated for visual inspection. With this system a thousand cells can be automatically analyzed in approximately 10 min, while an extra 5-10 min is necessary for visual evaluation. The performance of the system was analyzed using a model system for trisomy consisting of a mixture of male and female lymphocytes hybridized with probes for chromosomes 7 and Y. The sensitivity for trisomy detection in the seeding experiment was such that a frequency of 3% trisomic cells could be picked up automatically as being abnormal according to the multiple proportion test, while trisomy as low as 1.5% could be detected after interaction.
Significance of hyperuricemia as a risk factor for developing ESRD in a screened cohort.

BACKGROUND Uric acid may be a true mediator of renal disease and progression. However, epidemiological evidence for the significance of serum uric acid levels on the risk for developing end-stage renal disease (ESRD) is scarce in a setting of community-based screening. METHODS Participants in a 1993 mass screening conducted by the Okinawa General Health Maintenance Association in Okinawa, Japan, were investigated: 48,177 screenees (22,949 men, 25,228 women) older than 20 years for whom serum uric acid data were available were studied. All dialysis patients treated in Okinawa were independently registered in the Okinawa Dialysis Study registry. Participants in the 1993 screening who later entered a dialysis program were identified by using 2 computer registries. The cumulative incidence of ESRD was calculated according to quartiles of baseline serum uric acid levels for each sex. The significance of hyperuricemia (serum uric acid level > or = 7.0 mg/dL [> or =416 micromol/L] in men and > or = 6.0 mg/dL [> or =357 micromol/L] in women) for the risk for developing ESRD was evaluated by means of the Cox model after adjusting for age, blood pressure, body mass index, proteinuria, hematocrit, and total cholesterol, triglyceride, fasting blood glucose, and serum creatinine levels. RESULTS Mean serum uric acid level was 6.4 +/- 1.4 (SD) mg/dL (381 micromol/L) in men and 4.8 +/- 1.1 mg/dL (286 micromol/L) in women. Prevalences of hyperuricemia were 31.9% in men and 13.6% in women. By the end of 2000, a total of 103 screenees (53 men, 50 women) entered dialysis programs. Calculated incidences of ESRD per 1,000 screenees were 1.22 for men without hyperuricemia and 4.64 for men with hyperuricemia and 0.87 for women without hyperuricemia and 9.03 for women with hyperuricemia. Adjusted hazard ratios for hyperuricemia were 2.004 (95% confidence interval, 0.904 to 4.444; P = not significant) in men and 5.770 (95% confidence interval, 2.309 to 14.421; P = 0.0002) in women. CONCLUSION Screenees with hyperuricemia were associated with a greater incidence of ESRD. Hyperuricemia (serum uric acid > or = 6.0 mg/dL [> or =357 micromol/L]) was an independent predictor of ESRD in women. Strategies to control serum uric acid levels in the normal range may reduce the population burden of ESRD.
Relationship between young peoples' sedentary behaviour and biomedical health indicators: a systematic review of prospective studies

The aim of this systematic review was to describe the prospective relationship between childhood sedentary behaviour and health indicators. We identified prospective studies from searches in PubMed, EMBASE, PsycInfo and Cochrane, from January 1989 through April 2010. Two reviewers independently screened the titles and abstracts for eligibility, rated the methodological quality of the studies, and extracted data.
Knee alignment does not predict incident osteoarthritis: the Framingham osteoarthritis study.

OBJECTIVE To examine the relationship of knee malalignment to the occurrence of knee osteoarthritis (OA) among subjects without radiographic OA at baseline to determine whether malalignment is a risk factor for incident disease or simply a marker of increasing disease severity. METHODS We selected 110 incident tibiofemoral (TF) OA case knees (76 subjects) and 356 random control knees (178 subjects) from among participants in the Framingham Osteoarthritis Study. Case knees did not have OA at baseline (1992-1994 examination) but had developed OA (Kellgren/Lawrence grade>or=2) at followup (2002-2005 examination) (mean of 8.75 years between examinations). Control knees did not have OA at baseline. Standardized digital radiographs of the fully extended knee with weight-bearing were read using a standard protocol and eFilm viewing software. We measured the anatomic axis, the condylar angle, the tibial plateau angle, and the condylar tibial plateau angle. The interobserver intraclass correlation coefficient (ICC) ranged from 0.93 to 0.96 and the intraobserver ICC from 0.94 to 0.97. In a knee-specific analysis, we examined the relationship of each alignment measurement to the risk of TF OA using generalized estimating equations, adjusting for age, sex, and body mass index (BMI). We used the same approach to assess the association between each alignment measurement and the risk of medial TF OA. RESULTS Subjects in the case population were older and had a higher BMI than the controls. The alignment values were normally distributed and were not different between the cases and the controls. After adjustment for age, sex and BMI, there was no significant increase in incident OA in the highest quartile compared with the lowest quartile category for any of the alignment measures (P for trend for anatomic axis and condylar tibial plateau angle was 0.83 and 0.80, respectively). Similar results were also observed for medial compartment OA. CONCLUSION We found that baseline knee alignment is not associated with either incident radiographic TF OA or medial TF OA. These results suggest that malalignment is not a risk factor for OA, but rather is a marker of disease severity and/or its progression.