Miracle-dz/UniFAR-FTUs huggingface dataset:
A randomized, placebo-controlled trial of memantine for functional disability in amyotrophic lateral sclerosis

Abstract Our objective is to describe the results of a phase II/III, 12-months, double-blinded, single-centre, randomized, parallel (1:1), clinical trial performed to evaluate the efficacy and safety of memantine in ALS. Patients with probable or definite ALS of less than 36 months disease duration and progression over a one-month lead-in period were randomly assigned to placebo or memantine at 20 mg/day. The primary endpoint was 12-months ALSFRS decline. Forced vital capacity, manual muscle testing, visual analogue scale, quality of life, motor unit number estimation and neurophysiological index were the secondary endpoints. The number of patients included was based on the assumption of a 50% change in the ALSFRS decline. Safety and adverse events were evaluated. Sixty-three patients were included in the trial. Memantine did not show more adverse events or laboratory changes than placebo. Primary and secondary outcomes were not different between groups by intention-to-treat and per-protocol analysis. The most sensitive measurements were neurophysiological, which declined linearly over time. In conclusion, the results of this study show that memantine is well tolerated and safe in ALS patients. We did not observe any evidence of efficacy for memantine but we cannot exclude a positive outcome on survival.
Los costos de la inacción ante la desertificación y degradación de las tierras en escenarios alternativos de cambio climático

Por su magnitud y tasa de incremento, la desertificacion y la degradacion de las tierras, asi como las sequias, ponen directamente en peligro la subsistencia de los grupos humanos que habitan en los territorios afectados y tambien a las poblaciones que dependen de los bienes y servicios alli producidos. La desertificacion y la degradacion de las tierras erosionan la biodiversidad y contribuyen a la perdida de conocimientos ancestrales de los pueblos asentados en ellas y, ademas, inciden negativamente en los ingresos de los productores y el abastecimiento de alimentos a los centros urbanos. Por ultimo, estos procesos son una o la principal causa de la emision de gases de efecto invernadero. En 1994 la mayoria de los paises del mundo suscribio la Convencion de las Naciones Unidas de lucha contra la desertificacion en los paises afectados por sequia grave o desertificacion, en particular en Africa. Esta convencion ha provisto el marco para la implementacion de los planes y programas nacionales de combate contra la desertificacion y en ese contexto se han logrado, no sin dificultades, importantes avances en materia de definicion y diseno de indicadores biofisicos para establecer una cota de referencia (benchmark);. Tambien se han obtenido progresos destacables en cuanto a la movilizacion de recursos para apoyar los proyectos nacionales de lucha contra la desertificacion y la degradacion de las tierras. No obstante, no ha sido posible avanzar lo suficiente en lo que respecta a la medicion de los costos de la inaccion y de los efectos economicos de estos procesos. El proposito de este trabajo es contribuir a la valorizacion economica de los efectos de la desertificacion y la degradacion de las tierras, considerando tambien algunos escenarios alternativos de cambio climatico.
The pathophysiology of pelvic floor disorders: evidence from a histomorphologic study of the perineum and a mouse model of rectal prolapse

The muscle changes related to pelvic floor disorders are poorly understood. We conducted an anatomical and histological study of the perineum of the normal mouse and of a transgenic mouse strain deficient in urokinase‐type plasminogen activator (uPA−/−) that was previously reported to develop a high incidence of rectal prolapse. We could clearly identify the iliococcygeus (ILC) and pubococcygeus (PC) muscles and anal (SPA) and urethral (SPU) sphincters in male and female mice. The bulbocavernosus (BC), ischiocavernosus (ISC) and levator ani (LA) muscles could be found only in male mice. Histochemical analysis of the pelvic floor muscles revealed a majority of type IIA fibres. Rectal prolapses were observed only in male uPA−/− mice. The most obvious finding was an irreducible evagination of the rectal mucosa and a swelling of the entire perineal region corresponding to an irreducible hernia of the seminal vesicles through the pelvic outlet. The hernia caused stretching and thinning of the ISC, BC and LA. Myopathic damage, with degenerated and centronucleated myofibres, were observed in these muscles. The PC, ILC, SPA and SPU were not affected. This study provides an original description of a model of pelvic floor disorder and illustrates the differences existing between the perineum of humans and that of a quadruped species. In spite of these differences, the histopathologic changes observed in the pelvic floor muscles of uPA−/− mice with rectal prolapse suggest that prolonged muscular stretching causes a primary myopathic injury. This should be taken into account in the evaluation of pelvic floor disorders.
Safety and Efficacy of Bipolar Versus Monopolar Transurethral Resection of the Prostate: A Comparative Study.

PURPOSE Transurethral resection of the prostate (TURP) is considered gold standard for surgical treatment of benign prostatic hyperplasia (BPH). In this study, we aimed to compare post-operative clinical outcomes and adverse effects between monopolar and bipolar TURPs. MATERIALS AND METHODS The study included 590 patients who underwent TURP by a single urologist (E.H.) between June 2006 and June 2014 with a diagnosis of BPH. Patients were divided into two groups as monopolar TURP (group 1, n = 300) and bipolar TURP (group 2, n = 290). Patients receiving oral anticoagulants or aspirin and those with prostate cancer diagnosis were not included in the study. Data regarding pre-operative age, International Prostate Symptom Score (IPSS), maximum urinary flow rate (Qmax), post voiding residual urine volume (PVR), serum prostate specific antigen (PSA) levels and prostate volume (Vp) of the patients were gathered from medical records. Groups were compared in terms of catheterization, operation time, hemoglobin (Hb) decrease, and IPSS, Qmax, and PVR values at post-operative 12th month follow-up visit. RESULTS From pre-operative to post-operative period, IPSS, Qmax and PVR showed significant improvements within both groups (P < .001). When groups were compared with each other, bipolar TURP group had significantly lesser catheterization time and hemoglobin decrease than monopolar TURP group, while no significant differences were detected regarding all other variables. CONCLUSION Bipolar and monopolar TURPs are both effective and safe treatment modality for BPH. Bipolar TURP is superior to conventional monopolar TURP in terms of catheterization time and Hb decrease.
Lung Dendritic Cells in Respiratory Syncytial Virus Bronchiolitis

Respiratory syncytial virus (RSV) bronchiolitis, an important respiratory disease in infancy, is thought to be caused by severe inflammation of the small peripheral airways and has been associated with the development of recurrent wheeze, childhood asthma, and early allergen sensitization. Both innate and adaptive immune responses are thought to contribute to the development of bronchiolitis in RSV infection. If vaccination and specific therapy for bronchiolitis, which are currently lacking, are to be developed, detailed understanding of the immune responses involved is essential. Dendritic cells (DCs) are uniquely positioned to link innate to adaptive immune responses and may therefore be central to the development of bronchiolitis. In murine models, plasmacytoid DCs are recruited to the lung early in infection, presumably from the bone marrow, whereas lung myeloid DCs increase in numbers later in infection, with the advent of inflammation, and are derived from local lung precursors. Plasmacytoid DCs limit viral replication and they may have additional regulatory properties controlling pulmonary inflammation and lung function changes during bronchiolitis. In contrast, lung myeloid DCs are likely to contribute to inflammation during and after bronchiolitis and they may also facilitate sensitization to allergens. Myeloid DCs mature upon RSV infection and become potent activators of naive T cells, whereas in healthy lungs they are mostly immature and unable to stimulate naive T cells. As central players in the induction of adaptive immune responses, lung DCs need to be considered as targets for novel therapies and vaccination approaches.
Functional disability and depressive symptoms: longitudinal effects of activity restriction, perceived stress, and social support

Objectives: This longitudinal study investigates how activity restriction, perceived stress, and social support affect the relationship between functional disability and depressive symptoms.Method: This longitudinal study of a Taiwan population analyzed a nationally representative sample of 1268 subjects aged 60 years and over. Path analysis was used to assess interrelations among functional disability, activity restriction, perceived stress, social support, and depressive symptoms over time.Results: The analytical results supported the following relationships: (a) high functional disability were associated with high activity restriction, low social support, and high perceived stress over time, (b) high functional disability, high activity restriction, low social support, and high perceived stress were associated with high levels of depressive symptoms over time, (c) among the four factors, perceived stress exerted the strongest cross-sectional and longitudinal effect on depressive symptoms, and (d) the significant effect of prior functional disability on subsequent depressive symptoms substantially contributed to indirect changes in activity restriction, perceived stress, and social support between waves.Conclusion: The findings indicate that functional disability may contribute to subsequent depressive symptoms by reducing activities and social support. Decreased activities and social support increased perceptions of stress, which then increased depressive symptoms during the 8-year follow-up study.
Two bactericidal targets for penicillin in pneumococci: autolysis-dependent and autolysis-independent killing mechanisms

It has been assumed that penicillin (and also other cell wall inhibitors) kill pneumococci predominantly by triggering their major autolytic enzyme (an N-acetylmuramoyl-L-alanine amidase; referred to as amidase), resulting in massive cell wall degradation. Three types of experiments suggest that only part of this killing is due to cell lysis by amidase. (i) Suppression of penicillin-induced lysis by specific inhibitors of amidase protected pneumococci only marginally from killing in spite of prolonged exposure to concentrations of penicillin that were 10x, 20x, or 100x greater than the MIC. (ii) Mutants from which the amidase was completely eliminated by plasmid insertion or deletion (Lyt-) were still killed, albeit at a slower rate than the wild-type Lyt+ strains (3 to 4 log units instead of 4 to 5 log units per 6 h, i.e., about 1 log unit slower than the wild type; P less than 0.001). (iii) A new mutation (cid), which was not related to the amidase gene, further reduced killing of mutants lacking amidase to 1 log unit per 6 h (Lyt- Cid- phenotype). Reintroduction of the amidase gene into Lyt- Cid- cells partially restored penicillin-induced lysis but increased only slightly the rate of killing (from 1 log unit per 6 h in Lyt- Cid- cells to 2 log units per 6 h in Lyt+ Cid- cells). We conclude that penicillin kills pneumococci by two distinct mechanisms: one that involves the triggering of the amidase (about 1 log unit of killing per 6 h) and another, amidase-independent mechanism that is responsible for 3 to 4 log units of killing per 6 h. Triggering of the amidase activity in situ in growing bacteria was significantly reduced in Lyt+ Cid- cells, indicating that there is some regulatory interaction between the cid gene product and the amidase.
Identification of Sequence Diversity in the Escherichia coli fliC Genes Encoding Flagellar Types H8 and H40 and Its Use in Typing of Shiga Toxin-Producing E. coli O8, O22, O111, O174, and O179 Strains

ABSTRACT Flagellar type H8 is associated with many strains of pathogenic Shiga toxin-producing Escherichia coli (STEC), such as O8, O22, O111, O174, and O179 strains. Serological typing of the H8 antigen is limited to motile strains only and suffers from cross-reactivity between flagellar H8 and H40 antigens. In order to develop a method useful for typing of motile and nonmotile STEC O111 and other strains, we have analyzed the flagellar antigen (fliC) genes in representative E. coli H8 and H40 types. Two genotypes of the fliC gene encoding H8 (the fliC-H8 gene) were identified. Genotype fliC-H8a was found to be conserved in STEC O111, O174, and O179 strains; and type fliC-H8b was associated with STEC O8 and O22 strains. Sequence variations were also found in the genetically closely related fliC-H40 gene, although the latter was not found to be associated with STEC strains. A PCR was developed for the specific identification of the fliC-H8 and the fliC-H40 genes in motile and nonmotile E. coli strains. Digestion of PCR products with HhaI resulted in restriction fragment length polymorphisms (RFLPs) which were associated with genotypes fliC-H8a and -H8b as well as with genotypes fliC-H40a and -H40b. The fliC-specific PCR/RFLP typing method was suitable for the rapid typing of motile and nonmotile STEC O8, O22, O111, O174, and O179 strains from different sources whose fliC-H8 genotypes were found to be highly conserved. The fliC genotyping method is advantageous over serotyping and is useful for epidemiological investigations and studies of the evolution of STEC clones.
p38α function in osteoblasts influences adipose tissue homeostasis

The skeleton acts as an endocrine organ that regulates energy metabolism and calcium and phosphorous homeostasis through the secretion of osteocalcin (Oc) and fibroblast growth factor 23 (FGF23). However, evidence suggests that osteoblasts secrete additional unknown factors that contribute to the endocrine function of bone. To search for these additional factors, we generated mice with a conditional osteoblast‐specific deletion of p38α MAPK known to display profound defects in bone homeostasis. Herein, we show that impaired osteoblast function is associated with a strong decrease in bodyweight and adiposity (P < 0.01). The differences in adiposity were not associated with diminished caloric intake, but rather reflected 20% increased energy expenditure and the up‐regulation of uncoupling protein‐1 (Ucp1) in white adipose tissue (WAT) and brown adipose tissue (BAT) (P < 0.05). These alterations in lipid metabolism and energy expenditure were correlated with a decrease in the blood levels of neuropeptide Y (NPY) (40% lower) rather than changes in the serum levels of insulin, Oc, or FGF23. Among all Npy‐expressing tissues, only bone and primary osteoblasts showed a decline in Npy expression (P < 0.01). Moreover, the intraperitoneal administration of recombinant NPY partially restored the WAT weight and adipocyte size of p38α‐deficient mice (P < 0.05). Altogether, these results further suggest that, in addition to Oc, other bone‐derived signals affect WAT and energy expenditure contributing to the regulation of energy metabolism. —Rodríguez‐Carballo, E. , Gámez, B. , Méndez‐Lucas, A. , Sánchez‐Freutrie, M. , Zorzano, A. , Bartrons, R. , Alcántara, S. , Perales, J. C. , Ventura, F. p38α function in osteoblasts influences adipose tissue homeostasis. FASEB J. 29, 1414‐1425 (2015). www.fasebj. org
The impact of education on the use of physical restraints in the acute care setting.

BACKGROUND Physical restraints have become an acceptable standard of practice for managing safety and behavior control in acute care settings. Although the primary intent for using physical restraints is for patient protection, there are many negative outcomes related to their use. Heightened awareness by recent Joint Commission on Accreditation of Healthcare Organizations and the Center for Medicare and Medicaid Services standards for restraint use has led health care administrators and nursing staff to explore methods of reducing or eliminating the use of restraints. An educational program was planned and implemented for nursing staff emphasizing the risks of physical restraints and the benefits of innovative optional measures including nonrestraint devices. The program was tested to determine whether increased awareness through education would reduce the use of restraints. METHOD After current practice patterns and restraint utilization were established, a comprehensive educational program was provided to all nursing personnel. Twenty-three formal classroom inservice offerings were provided with follow-up reinforcement of self-study modules. Education included nursing assessment strategies and practical restraint optional interventions for managing patients exhibiting disruptive behaviors. FINDINGS After the educational program, the overall use of physical restraints decreased as well as the length of time patients were restrained. CONCLUSION Results of this study reinforce the need to increase staff awareness and knowledge of nonrestraint interventions to manage disruptive behaviors in the acute care setting.
Cardiovascular Remodeling during Arteriovenous Fistula Maturation in a Rodent Uremia Model

Purpose The aim of this study was to evaluate cardiovascular remodeling after arteriovenous fistula (AVF) surgery and to characterize the effect of chronic kidney disease (CKD) in a rodent femoral AVF model. Methods Sixteen rats (8 healthy; 8 CKD) underwent femoral AVF surgery; 4 animals served as controls. AVF and cardiac morphology as well as function were assessed during the fistula maturation process (until day 84 after surgery) using magnetic resonance imaging and histopathological analyses. Results Histopathological analysis revealed that a glomerular and interstitial nephropathy caused CKD. In healthy and CKD animals, AVF surgery resulted in progressive downstream vein dilation and a subsequent cardiac adaptation. This vein dilation during maturation was less in CKD rats during the early postoperative course (day 21: p=0.0475) and similar thereafter until day 84. The dilation was accompanied by an aggravation of neointimal hyperplasia (NIH) and calcification in AVFs of CKD rats. The chronic volume overload resulted in both groups in a significantly increased end-diastolic volume (healthy rats: p=0.0087; CKD rats: p=0.0333). Simultaneously, cardiac output increased 195% in healthy and 244% in uremic rats, which was caused by both a significantly increased stroke volume and heart rate. The left ventricular mass rose in AVF animals and was increased at the end of the study period, indicating a distinct cardiac hypertrophy. Conclusion Our rat model showed typical cardiovascular features of the AVF maturation process, which strongly resemble clinical findings in patients. Uremia caused inferior dilation in the early phase after surgery and an exacerbation of NIH. This model should help to identify the cellular and molecular mechanisms that contribute to AVF failure.
Pneumocystis carinii pneumonia in patients with connective tissue diseases: the role of hospital experience in diagnosis and mortality.

OBJECTIVE Pneumonia due to Pneumocystis carinii has been increasingly reported in patients with connective tissue diseases, but the frequency of this complication is not known. We sought to determine the frequency of P carinii pneumonia (PCP) in patients with connective tissue diseases, and to determine the role that a hospital's acquired immunodeficiency syndrome (AIDS)-related experience may have in the diagnosis of PCP in these patients. METHODS We used a state hospitalization registry to identify all patients with PCP and either rheumatoid arthritis, systemic lupus erythematosus, Wegener's granulomatosis, polymyositis, dermatomyositis, polyarteritis nodosa, or scleroderma who had an emergent or urgent hospitalization in California from 1983 to 1994. We compared patient and hospital characteristics between these patients and patients with connective tissue diseases hospitalized with other types of pneumonia. RESULTS Two hundred twenty-three patients with connective tissue diseases were diagnosed with PCP in the 12-year study period. The frequency of PCP ranged from 89 cases/10,000 hospitalizations/year in patients with Wegener's granulomatosis to 2 cases/10,000 hospitalizations/year in patients with rheumatoid arthritis. Compared with 5,457 patients with connective tissue diseases and pneumonia due to other organisms, patients with PCP were more likely to be younger, to be male, to have private medical insurance, and to have systemic lupus erythematosus, Wegener's granulomatosis, inflammatory myopathy, or polyarteritis nodosa rather than rheumatoid arthritis, and were less likely to be African American. Hospital size, teaching status, urban/rural location, proportion of admissions due to AIDS or PCP, and proportion of patients with pneumonia undergoing bronchoscopy were each associated with the likelihood of diagnosis of PCP in univariate analyses, but only the number of patients with PCP being treated at a hospital (odds ratio [OR] 1.03 for each additional 10 cases/year, 95% confidence interval [95% CI] 1.01-1.05) was associated with the likelihood of diagnosis of PCP in multivariate analyses. Patients were also somewhat more likely to be diagnosed with PCP if there had previously been a case of PCP in a patient with a connective tissue disease at the same hospital (OR 135, 95% CI 0.98-1.85). In-hospital mortality was 45.7%, and was unrelated to hospital characteristics. CONCLUSION PCP is an uncommon, but often fatal, occurrence in patients with connective tissue disease. A hospital's prior experience with patients with PCP is associated with the likelihood that this condition is diagnosed in patients with connective tissue diseases who present with pneumonia, suggesting that diagnostic suspicion is an important factor in the correct identification of affected patients.
Case study: design and implementation of training for scientists deploying to Ebola diagnostic field laboratories in Sierra Leone: October 2014 to February 2016

As part of the UK response to the 2013–2016 Ebola virus disease (EVD) epidemic in West Africa, Public Health England (PHE) were tasked with establishing three field Ebola virus (EBOV) diagnostic laboratories in Sierra Leone by the UK Department for International Development (DFID). These provided diagnostic support to the Ebola Treatment Centre (ETC) facilities located in Kerry Town, Makeni and Port Loko. The Novel and Dangerous Pathogens (NADP) Training group at PHE, Porton Down, designed and implemented a pre-deployment Ebola diagnostic laboratory training programme for UK volunteer scientists being deployed to the PHE EVD laboratories. Here, we describe the training, workflow and capabilities of these field laboratories for use in response to disease epidemics and in epidemiological surveillance. We discuss the training outcomes, the laboratory outputs, lessons learned and the legacy value of the support provided. We hope this information will assist in the recruitment and training of staff for future responses and in the design and implementation of rapid deployment diagnostic field laboratories for future outbreaks of high consequence pathogens. This article is part of the themed issue ‘The 2013–2016 West African Ebola epidemic: data, decision-making and disease control’.