Miracle-dz/UniFAR-FTUs huggingface dataset:
Immunoprophylaxis of respiratory syncytial virus disease

Respiratory syncytial virus (RSV) is the most common cause of acute lower respiratory tract infection in children worldwide. In the United States the Institute of Medicine in 1985 estimated that there were ;90 000 annual hospitalizations for bronchiolitis and pneumonia caused by RSV among children ,5 years of age. Recently Shay et al. have reported that from 1994 through 1996, rates of hospitalization of infants for bronchiolitis have increased substantially. Among children younger than 5 years, there were 62 500 to 100 000 annual hospitalizations for RSV-associated bronchiolitis alone. Among infants they estimated that ;73 400 to 126 300 annual hospitalizations for bronchiolitis or pneumonia may be attributable to RSV infection, considerably more than the 1985 projection. The public health burden of RSV disease is even greater if outpatient visits for children and RSV morbidity among patients with underlying conditions are included. Moreover recent data support the contention that RSV lower respiratory tract infection early in life may predispose to recurrent wheezing in childhood. Although the majority of children who are hospitalized for RSV disease are full term and between the ages of 1 and 3 months, the risk for serious disease caused by RSV is dependent on multiple social and epidemiologic factors, including sex, age, ethnic group, day-care attendance and socioeconomic status. 6 Underlying medical conditions such as prematurity, cardiac or pulmonary disease, an immunocompromised state as well as neuromuscular disorders that impair the function of respiratory muscles predispose some patients to serious RSV disease with an increased risk of significant morbidity and mortality. 7 A recently recognized risk group has been the elderly in nursing homes, in which waning RSV immunity increases the severity of the disease and close quarters increases the attack rate. The persistent problem with RSV in these diverse populations, along with limited treatment options and significant morbidity and mortality in such high risk groups as premature infants with or without chronic lung disease, make preventive strategies of paramount importance.
Protecting an endangered species: the contribution and constraints of nurses working in a specialist role.

AIM The project aims to assess current specialist practice in relation to the new and ever-changing healthcare climate and explore some of the issues that specialist nurses encounter. BACKGROUND The current financial recession is driving a range of economic policy changes and consequently service provision, in particular the work and impact of nurses working in a specialist role, being examined. This has resulted in many specialist nurses feeling very vulnerable. METHOD A cross sectional survey was completed by nurses working in specialist roles (n = 96) in a large health and social care setting in the United Kingdom. FINDINGS A response rate of 62% was achieved: 44% provide nurse led clinics and 42% are nurse prescribers. The mean length of time qualified as a registered nurse was 27 years. Less than a third felt that the current computer system for activity recording reflected their current workload and 65% needed administrative support. CONCLUSION This study demonstrates the insufficient resources available to specialist nurses resulting in inappropriate but necessary, use of time and restricted opportunities for learning and development.
Decreased Intervillous and Unchanged Myometrial Blood Flow in Supine Recumbency

The supine position in late pregnancy is associated with many hemodynamic changes caused by compression of the inferior vena cava and a resulting fall in cardiac output. To investigate the effect of this position on uteroplacental blood flow, 22 women with normal (N = 12) or hypertensive (N = 10) pregnancy were investigated using the intravenous 133Xe washout method, in both the supine and left-tilted (45-degree) lateral positions. The intervillous blood flow (113 ± 48 ml/min/dl) was lower in the supine position than in he left-tilted position (141 ± 48 ml/min/dl) (P < 0.01), while the myometrial blood flow was similar in both (9.0 ± 3.3 ml/min/100 g in supine and 8.7 ± 2.7 ml/min/100 g in left-tilted position). The results suggest that the autoregulation system for uterplacental circulation is operative only in the nonplacental component of the pregnant uterus.
High-dose interferon alfa-2b does not diminish antibody response to GM2 vaccination in patients with resected melanoma: results of the Multicenter Eastern Cooperative Oncology Group Phase II Trial E2696.

PURPOSE High-dose interferon alfa-2b (IFNalpha2b) is the only established adjuvant therapy of resectable high-risk melanoma. GM2-KLH/QS-21 (GMK) is a chemically defined vaccine that is one of the best developed of a range of vaccine candidates for melanoma. A single-institution phase III trial conducted at Memorial Hospital served as the impetus for an intergroup adjuvant E1694/S9512/C509801 trial, which recently completed enrollment of 880 patients. To build on the apparent benefit of IFNalpha2b in resectable high-risk American Joint Committee on Cancer (AJCC) stage IIB or III melanoma, this phase II study was designed to evaluate the combination of GMK and IFNalpha2b. The E2696 trial was undertaken to evaluate the toxicity and other effects of the established adjuvant high-dose IFNalpha2b regimen in relation to immune responses to GMK and to evaluate the potential clinical and immunologic effects of the combined therapies. PATIENTS AND METHODS This trial enrolled 107 patients with resectable high- or very high-risk melanoma (AJCC stages IIB, III, and IV). RESULTS The results demonstrate that IFNalpha2b does not significantly inhibit immunoglobulin M or G serologic responses to the vaccine and that the combination of high-dose IFNalpha2b and GMK is well tolerated in this patient population. CONCLUSION Cox analysis of the results of the combination with IFNalpha2b show improvement in the relapse-free survival of patients with very high-risk melanoma (including those with resectable M1 disease).
The Effect of Glucagon-Like Peptide I (GLP-I) on Glucose Elimination in Healthy Subjects Depends on the Pancreatic Glucoregulatory Hormones

Glucagon-like peptide I (GLP-I) decreases plasma glucose in type II diabetic patients and in healthy subjects indirectly by stimulation of insulin and inhibition of glucagon secretion, whereby the hepatic glucose production decreases. However, recent studies indicate that GLP-I may also directly influence peripheral and hepatic glucose uptake. We infused somatostatin (SS) intravenously (500 or 1,000 μg/h) in 13 healthy subjects to suppress insulin and glucagon secretion from the endocrine pancreas, together with infusion of either GLP-I (50 pmol · kg−1 · h−1) or saline intravenously. After 30 min, a 25-g intravenous glucose tolerance test (IVGTT) was carried out, and plasma concentrations of glucose, insulin, glucagon, and GLP-I were measured during the following 2 h. IVGTT together with GLP-I infusion significantly elevated insulin during 500 μg/h SS but not during 1,000 μg/h SS. Plasma glucagon was strongly depressed in all experiments. During 500 μg/h SS, the glucose disappearance constant, Kg, was 0.49 ± 0.03% per minute with GLP-I and 0.39 ± 0.04% per minute with saline (n = 8, P = 0.004). With 1,000 μg/h SS, Kg was 0.42 ± 0.03% per minute with GLP-I and 0.40 ± 0.03% per minute without (NS). In conclusion, when endogenous insulin secretion is held at a constant low level, which may be accomplished only with very large doses of SS, GLP-I has no effect on glucose elimination. Thus, an insulin-independent effect of GLP-I on glucose disposal could not be demonstrated.
Effectiveness of an Intervention for Colic

An intervention for infant irritability or colic was evaluated in a randomized clinical trial. A total of 121 full-term irritable infants (2 to 6 weeks old) were randomized to routine care or the home-based intervention program. A third group (n=43) of irritable infants were entered into a post-test-only group. Following the 4-week intervention, the treatment group infants cried 1.7 hours less per day than the infants in the control group (p=0.02). The findings support the emerging view of infant colic as a behavioral pattern that is responsive to environmental modification and structured cue-based care.
Enhanced expression of programmed death-1 (PD-1)/PD-L1 in salivary glands of patients with Sjögren's syndrome.

OBJECTIVE Programmed death-1 (PD-1) mediates a negative signal and introduces tolerance for lymphocytes. Dysfunction of the PD-1 pathway is thought to result in autoimmune diseases such as rheumatoid arthritis (RA). To investigate the role of the PD-1/PD-L system in the pathology of Sjögren's syndrome (SS), we examined the expression of PD-1 and its ligand PD-L1 in salivary lymphocytes and salivary glands from patients with SS. METHODS Flow cytometry analysis was used to determine expression of PD-1 in SS salivary lymphocytes. Intracellular staining of interleukin 10 (IL-10) was performed after stimulation with PMA and ionomycin. Indirect immunohistochemistry was used to investigate the expression of PD-1 and PD-L1. RESULTS The mean fluorescence intensity of PD-1 expression in SS salivary lymphocytes was significantly higher than that from healthy controls and patients with RA or systemic lupus erythematosus. PD-1-positive SS salivary lymphocytes expressed IL-10 intracellularly upon PMA/ionomycin stimulation. Immunohistochemical analysis showed that PD-1 was expressed on infiltrating lymphocytes in salivary gland from 52% of SS patients, and PD-L1 was expressed on ductal and acinar epithelial cells from 68% of SS patients. In vitro analysis using HSG cells revealed that PD-L1 was induced by interferon-gamma but not by tumor necrosis factor-alpha and IL-1beta. CONCLUSION PD-1 is expressed on T lymphocytes and PD-L1 on epithelial cells from inflamed salivary glands of patients with SS, which suggests that dysfunction of the PD-1/PD-L1 pathway may be related to tolerance for lymphocytes, which causes SS.
Targeting the Wnt pathway and cancer stem cells with anti-progastrin humanized antibodies : a major breakthrough for KRAS mutated colorectal cancer treatment

Alexandre Prieur*, Monica Cappellini*, Guillaume Habif*, Marie-Paule Lefranc, Thibault Mazard, Eric Morency, Jean-Marc Pascussi, Maud Flacelière, Nathalie Cahuzac, Bérengère Vire, Benjamin Dubuc, Amandine Durochat, Pierre Liaud, Jérémy Ollier, Caroline Pfeiffer, Sophie Poupeau, Véronique Saywell, Chris Planque, Eric Assenat, Frédéric Bibeau, Jean-François Bourgaux, Pascal Pujol, Alain Sézeur, Marc Ychou, Dominique Joubert.
Mohs Micrographic Surgery: Past, Present, and Future

BACKGROUND Mohs micrographic surgery (MMS) is a frequently used technique that provides total margin visualization for treatment of skin neoplasms. OBJECTIVE To provide a comprehensive review of MMS literature, focusing on its origins, evidence behind present-day uses of MMS, and future directions. METHODS A literature search was conducted using PubMed to identify articles pertaining to MMS. RESULTS The fresh frozen technique led to widespread use of MMS in the 1970s. One randomized controlled trial and several large prospective studies have demonstrated low recurrence rates for treatment of nonmelanoma skin cancer (NMSC). MMS, when compared with surgical excision, also achieved a statistically significant higher cure rate for treatment of recurrent NMSC. Studies have demonstrated low recurrence for the treatment of melanoma and melanoma in situ with MMS. MMS has also been shown to effectively treat several rare cutaneous neoplasms. The future of MMS is likely to include the adoption of noninvasive imaging, immunostaining, and digital technology. CONCLUSION Mohs micrographic surgery is an effective treatment modality for numerous cutaneous neoplasms. It has achieved statistically significant superiority to surgical excision for the treatment of recurrent and high-risk NMSC. The future is likely to see increased use of noninvasive imaging, immunostaining, and digital technology.
Spanish Adaptation of the Frommelt Attitude Toward Care of the Dying Scale (FATCOD-S) in Nursing Undergraduates

The Frommelt Attitude Toward Care of the Dying Scale (FATCOD) is designed to assess the attitudes of professionals and trainees toward caring for the dying patient and their family members. In this study the main aim is to adapt the FATCOD to a Spanish context (FATCOD-S). In addition, the relations between FATCOD-S, sociodemographic variables, emotional intelligence, and death attitudes have been analyzed. A sample of 669 Spanish nursing students from four Universities responded to a questionnaire. The exploratory factor analysis (EFA) concludes a structure composed of two significant factors. A confirmatory factor analysis (CFA) was carried out. The CFA supported a two-factor model. Students with past experience of death and those who had received training in palliative care scored significantly higher on both factors of the FATCOD-S (p < 0.01). The FATCOD-S is an effective and valid tool for measuring the attitudes of Spanish nursing students toward caring for patients at the end of life.
Monoamine oxidase‐A modulates apoptotic cell death induced by staurosporine in human neuroblastoma cells

Monoamine oxidases (MAOs) are mitochondrial enzymes which control the levels of neurotransmitters in the brain and dietary amines in peripheral tissues via oxidative deamination. MAO has also been implicated in cell signalling. In this study, we describe the MAO‐A isoform as functional in apoptosis induced by staurosporine (STS) in human dopaminergic neuroblastoma cells (SH‐SY5Y). Increased levels of MAO‐A activity were induced by STS, accompanied by increased MAO‐A protein and activation of the initiator of the intrinsic pathway, caspase 9, and the executioner caspase 3. MAO‐A mRNA levels were unaffected by STS, suggesting that changes in MAO‐A protein are due to post‐transcriptional events. Two unrelated MAO‐A inhibitors reduced caspase activation. STS treatment resulted in sustained activation of the mitogen‐activated protein kinase pathway enzymes extracellular regulated kinase, c‐jun terminal kinase and p38, and depletion of the anti‐apoptotic protein Bcl‐2. These changes were significantly reversed by MAO inhibition. Production of reactive oxygen species was increased following STS exposure, which was blocked by both MAO inhibition and the antioxidant N‐acetylcysteine. Therefore our data provide evidence that MAO‐A, through its production of reactive oxygen species as a by‐product of its catalytic activity on the mitochondrial surface, is recruited by the cell to enhance apoptotic signalling.
A seven-year experience with patients with juvenile nasopharyngeal angiofibroma

Summary Juvenile nasopharyngeal angiofibroma (JNA) is a rare tumor in adolescent males. It originates in the nasopharynx. Aim to present the experience of JNA management at an Otorhinolaryngology Service between 2001 and 2008. Materials and Methods Demographical data, clinical presentation, investigations as well as the treatment of sixteen JNA patients were reviewed and collected from medical records from the ORL Service. Design Cross-sectional, retrospective and descriptive study. Results: All JNA patients were male. The average age at diagnosis was 16.8 years (range 9–23 years). More than 56% of the patients were classified as Fisch II. Preoperative embolization was carried out in ten (62.5%) patients. All 16 patients were submitted to primary surgical resection. Two patients (66.7%) who didn't receive preoperative embolization required intraoperative blood transfusion. The overall recurrence rate was 43.75% and the cure rate was 93.75%. Conclusion Preoperative embolization minimizes intraoperative blood loss. The recurrence rate was related to advanced tumoral stage at diagnostic and the lack of preoperative embolization. Surgery combined with preoperative embolization is the major treatment for JNA. All the patients should undergo preoperative imaging studies, especially CT, to assist in surgical planning and follow-up.
Amino acid digestibility of different rye genotypes in caecectomised laying hens

ABSTRACT This study investigated the variability of amino acid (AA) digestibility of rye grains in laying hens. Relationships between AA digestibility and physical properties (thousand seed weight, test weight, falling number, and extract viscoelasticity), chemical composition (proximate nutrients, non-starch polysaccharides, AA, minerals, and inositol phosphates), gross energy concentration, and in vitro solubility of nitrogen (N) of the grains were also examined. Twenty rye genotypes were grown under standardised agronomic and environmental conditions as part of a collaborative research project known as “GrainUp”. Each genotype was added to a basal diet at 500 g/kg at the expense of maize starch to produce 20 rye diets. The experimental design comprised four Latin Squares (6 × 6) distributed over two runs, resulting in 12 experimental periods. Caecectomised laying hens (LSL-Classic) were individually kept in metabolism cages. Excreta were collected quantitatively for 4 d, and AA digestibility of the rye genotypes was determined using a regression approach. The digestibility of AA was generally low but varied significantly among the 20 rye genotypes, especially for Lys (digestibility range 35–59%), Met (57–75%), Thr (34–54%), and Trp (36–71%). Nevertheless, physical and chemical characteristics as well as the in vitro solubility of N correlated in only a few cases with AA digestibility. Multiple linear regression was used to calculate equations to predict AA digestibility based on the analysed characteristics. However, their explanatory power, as judged by the adjusted R2, was not sufficiently precise for practical application (below 0.6 for most AA). In conclusion, the AA digestibility of rye grain is generally low and varies significantly between crop genotypes. Equations based on its physical and chemical characteristics are not sufficiently precise to be useful for feed formulation.
Sequential bioavailability of sedimentary organic matter to heterotrophic bacteria

Aquatic sediments harbour diverse microbial communities that mediate organic matter degradation and influence biogeochemical cycles. The pool of bioavailable carbon continuously changes as a result of abiotic processes and microbial activity. It remains unclear how microbial communities respond to heterogeneous organic matrices and how this ultimately affects heterotrophic respiration. To explore the relationships between the degradation of mixed carbon substrates and microbial activity, we incubated batches of organic-rich sediments in a novel bioreactor (IsoCaRB) that permitted continuous observations of CO2 production rates, as well as sequential sampling of isotopic signatures (δ13 C, Δ14 C), microbial community structure and diversity, and extracellular enzyme activity. Our results indicated that lower molecular weight (MW), labile, phytoplankton-derived compounds were degraded first, followed by petroleum-derived exogenous pollutants, and finally by higher MW polymeric plant material. This shift in utilization coincided with a community succession and increased extracellular enzyme activities. Thus, sequential utilization of different carbon pools induced changes at both the community and cellular level, shifting community composition, enzyme activity, respiration rates, and residual organic matter reactivity. Our results provide novel insight into the accessibility of sedimentary organic matter and demonstrate how bioavailability of natural organic substrates may affect the function and composition of heterotrophic bacterial populations.
GABAA Receptor Signaling Induces Osmotic Swelling and Cell Cycle Activation of Neonatal Prominin+ Precursors

Signal‐regulated changes in cell size affect cell division and survival and therefore are central to tissue morphogenesis and homeostasis. In this respect, GABA receptors (GABAARs) are of particular interest because allowing anions flow across the cell membrane modulates the osmolyte flux and the cell volume. Therefore, we have here investigated the hypothesis that GABA may regulate neural stem cell proliferation by inducing cell size changes. We found that, besides neuroblasts, also neural precursors in the neonatal murine subependymal zone sense GABA via GABAARs. However, unlike in neuroblasts, where it induced depolarization‐mediated [Ca2+]i increase, GABAARs activation in precursors caused hyperpolarization. This resulted in osmotic swelling and increased surface expression of epidermal growth factor receptors (EGFRs). Furthermore, activation of GABAARs signaling in vitro in the presence of EGF modified the expression of the cell cycle regulators, phosphatase and tensin homolog and cyclin D1, increasing the pool of cycling precursors without modifying cell cycle length. A similar effect was observed on treatment with diazepam. We also demonstrate that GABA and diazepam responsive precursors represent prominin+ stem cells. Finally, we show that as in in vitro also in in vivo a short administration of diazepam promotes EGFR expression in prominin+ stem cells causing activation and cell cycle entry. Thus, our data indicate that endogenous GABA is a part of a regulatory mechanism of size and cell cycle entry of neonatal stem cells. Our results also have potential implications for the therapeutic practices that involve exposure to GABAARs modulators during neurodevelopment. STEM CELLS 2011;29:307–319
Intraperitoneal cisplatin versus no further treatment: 8‐year results of EORTC 55875, a randomized phase III study in ovarian cancer patients with a pathologically complete remission after platinum‐based intravenous chemotherapy

First-line intravenous chemotherapy (CT) following debulking surgery is associated with prolonged survival, in particular in patients who achieve a pathological complete remission (pCR) at second-look surgery but in whom a high rate of relapses still occurs. Between 1988 and 1997, 153 patients in pCR following platinum-based intravenous CT were randomized between four courses of intraperitoneal cisplatin (P) (90 mg/m2 every 3 weeks) or observation. Overall survival (OS) was the primary endpoint, while progression-free survival (PFS) was a secondary endpoint. This intent-to-treat analysis includes 16 patients who were not eligible and 17 patients who had protocol violations. The two groups were well balanced in terms of age (median = 55 years), performance status (78% P.S. O), FIGO stage (96% stage III), histology (serous in 66%), grade (2 or 3 in 80%), and residuum before intravenous CT (>1 cm in 40%). Intraperitoneal CT was delivered mainly through intraperitoneal catheters (Port-a-Cath 61% and Tenckhoff 25%). Side effects of intraperitoneal cisplatin included vomiting [≥grade 2 (82%)], rise in serum creatinine [≥grade 2 (14%)], abdominal pain [grade 1–2 (38%)], and neurotoxicity [grade 2–3 (15%)]. After a median follow-up of 8 years, 80 patients (52%) have progressed with no difference in the pattern of relapse between the two groups and 75 patients (49%) have died; the respective hazard ratios for PFS and OS with 95% CI are 0.89 (0.59–1.33) and 0.82 (0.52–1.29). These results are suggestive of a treatment benefit but do not support a change in clinical practice. Other randomized clinical trials of intraperitoneal CT are reviewed and briefly discussed.