Miracle-dz/UniFAR-FTUs huggingface dataset:
The epidemiology of inhibitors in haemophilia A: a systematic review

Summary. This paper emphasizes the importance of distinguishing between the prevalence, incidence and cumulative incidence of inhibitors in haemophilia A. Incidence and cumulative incidence data will include patients with transient inhibitors or whose inhibitors have been eliminated by treatment. As these will not be included in prevalence data, prevalence studies will tend to give rise to lower figures than incidence studies. As a result, the most accurate estimates of the true risk of inhibitor development comes from prospective studies of newly diagnosed haemophiliacs who are tested regularly for the presence of inhibitors. This paper reports a systematic review of the best available evidence relating to the epidemiology of inhibitors in haemophilia A. Cohort studies, registry data reporting incidence or prevalence of inhibitors in patients with haemophilia A, and prospective studies of factor VIII (FVIII) in the treatment of previously untreated patients which reported the development of inhibitors as an outcome, were included in the review. The overall prevalence of inhibitors in unselected haemophiliac populations was found to be 5–7%. The cumulative risk of inhibitor development varied (0–39%). Incidence and prevalence were substantially higher in patients with severe haemophilia. Studies of patients using a single plasma‐derived FVIII (pdFVIII) preparation reported lower inhibitor incidence than those using multiple pdFVIII preparations or single recombinant FVIII preparations. Incidence data should be used to estimate the likely demand for treatments aimed at eliminating inhibitors, whereas the best estimates of the overall burden to the National Health Service (NHS) of treating bleeding episodes in patients with continuing inhibitors will come from prevalence studies.
How to distinguish between the neuroleptic-induced deficit syndrome, depression and disease-related negative symptoms in schizophrenia

A major challenge in the clinical assessment of schizophrenia is the differentiation between depressive features, negative symptoms and neuroleptic side effects, including the adverse subjective experiences associated with this medication. The problems include the degree of symptom overlap, and the lack of precise operational definitions, particularly for negative symptoms and the putative, neuroleptic-induced deficit syndrome. The diagnostic process is further confounded by the need to discriminate between primary negative symptoms as persistent, enduring deficits, and social and emotional withdrawal secondary to positive symptoms, or related to depressive features or drug effects such as sedation and the bradykinesia component of parkinsonism. To distinguish between these elements is likely to require careful observation of patients with schizophrenia, over time, by trained raters using appropriate rating scales for depression and negative symptoms that are sensitive to change. Ratings of patients' subjective experiences regarding mood and awareness of behavioural and cognitive deficits should also be included. The associations between the subjective data and the objective ratings of depression, negative symptoms and drug side effects may help with clinical discrimination in these areas of dysfunction and with the refinement of their phenomenological descriptions.
Unusual norovirus and rotavirus genotypes in Ethiopia

Abstract Background: Gastro-enteritis is associated with significant mortality in low- and middle-income countries, and rotavirus and norovirus are the principal viral agents implicated. Aims: To investigate the molecular epidemiology and burden of disease associated with rotavirus and norovirus in children attending a health centre in Ethiopia. Methods: A cross-sectional study was conducted in children attending a health centre in Awassa, southern Ethiopia. Children with diarrhoea (cases) and without diarrhoea (controls) were recruited over a 6-month period from December 2008 to May 2009. Rotavirus was detected by ELISA and genotyped by RT-PCR, and norovirus was amplified by RT-PCR with genotyping by sequence analysis of RT-PCR products. Results: Rotavirus was detected in 44/200 (22%) cases and in none of the controls, with genotypes G3P[6] (48%), G1P[8] (27%) and G2P[4] (7%) being the strains most commonly identified. Norovirus was detected in 16 (8%) of 200 cases and in 4 (7%) of 57 controls. Norovirus GII.3 was the strain most commonly detected (40%: 8/20) and ten other genotypes were also detected. Conclusion: Rotavirus is a common cause of severe gastro-enteritis in children in Ethiopia; however, norovirus occurred with a similar frequency in cases and controls. A globally uncommon strain type, G3P[6], predominated within the rotavirus strains detected.
Altered development in GABA co‐release shapes glycinergic synaptic currents in cultured spinal slices of the SOD1G93A mouse model of amyotrophic lateral sclerosis

Increased environmental risk factors in conjunction with genetic susceptibility have been proposed with respect to the remarkable variations in mortality in amyotrophic lateral sclerosis (ALS). In vitro models allow the investigation of the genetically modified counter‐regulator of motoneuron toxicity and may help in addressing ALS therapy. Spinal organotypic slice cultures from a mutant form of human superoxide dismutase 1 (SOD1G93A) mouse model of ALS allow the detection of altered glycinergic inhibition in spinal microcircuits. This altered inhibition improved spinal cord excitability, affecting motor outputs in early SOD1G93A pathogenesis.
Las ocupaciones precerámicas de la cuenca de México: del poblamiento a las primeras sociedades agrícolas

Como ya habia comentado acertadamente Luis Aveleyra (1967) en su obra Los Cazadores Primitivos de Mesomerica, los datos disponibles sobre las culturas paleoindias en Mexico son todavia demasiados escasos y dispersos, mas si consideramos exclusivamente la zona correspondiente a la Cuenca de Mexico. Es posible que en la Prehistoria mexicana se hayan escrito mas paginas sobre sintesis e interpretaciones sobre el escaso material escrito de manera directa, que las propias fuentes originales que hacen referencia a las excavaciones particulares de los escasos sitios estudiados en lo que es el actual territorio mexicano.
Nucleolar protein B23 stimulates nuclear import of the HIV-1 Rev protein and NLS-conjugated albumin.

Nucleolar phosphoprotein B23 is a putative ribosome assembly factor with a relatively high affinity for peptides containing sequences of nuclear localization signals (NLSs) of the SV40 T-antigen type [Szebeni, A. , Herrera, J. E. , & Olson, O. J. (1995) Biochemistry 34, 8037-8042]. The effects of protein B23 on nuclear import were determined by an in vitro assay [Dean, D. A. , & Kasamatsu, H. (1994) J. Biol. Chem. 269, 4910-4916] using NLS peptide-conjugated bovine serum albumin (NLS-BSA) or the HIV-1 Rev protein as substrates for import into isolated rat liver nuclei. The import was ATP-dependent and inhibited by wheat germ agglutinin or by an antibody against p97, a component of the nuclear import system. The rate of import of either substrate was increased if protein B23 was added to the incubation medium. Similar enhancements of import were seen with both isoforms (B23.1 and B23.2). The stimulatory effect on Rev protein import was saturable with maximum stimulation (2-3-fold) at a molar ratio of protein B23:Rev of approximately 1:1. Phosphorylation of protein B23.1 by casein kinase II produced an additional doubling of the import rate. This effect was not seen if protein B23.1 was phosphorylated with a cdc2 type protein kinase. Mutant forms of protein B23.1 in which the nuclear localization signal was either deleted or altered did not stimulate import of the substrates. These results suggest that protein B23 plays a role as an accessory factor in the nuclear import of the NLS-containing proteins and that phosphorylation at sites in the highly acidic segments of the protein enhances the stimulatory effect.
Comparison between lidocaine and bupivacaine as local anesthetics with diflunisal for postoperative pain control after lower third molar surgery.

The effect of lidocaine and bupivacaine on postoperative pain were compared in a double blind crossover study. Diflunisal (500 mg) was used as an analgesic and given before commencement of the surgical procedure.Bilateral impactions of lower third molars were removed on two occasions, four weeks apart, in a sample of 26 Chinese patients. One local anesthetic was used on one occasion and the alternate on the second. Pain intensity was indicated on a visual analogue scale hourly for eight hours, beginning one hour after the start of surgery.Pain at each postoperative hour was lower after bupivacaine and more patients indicated little or no pain after bupivacaine than after lidocaine. This was not reflected in patients' preference: 12 preferring lidocaine, 11 bupivacaine, and 3 indicating no preference, an important reason being a shorter period of numbness with lidocaine.Although diflunisal was given preoperatively, the postoperative course was not complicated by alveolitis in any case.While bupivacaine plus diflunisal resulted in less postoperative pain than lidocaine plus diflunisal, some patients were willing to sustain some pain after oral surgery if sensation was regained sooner.
Fatal postoperative pulmonary edema: pathogenesis and literature review.

STUDY OBJECTIVES Pulmonary edema is a known postoperative complication, but the clinical manifestations and danger levels for fluid administration are not known. We studied (1) 13 postoperative patients (11 adult, 2 pediatric) who developed fatal pulmonary edema, and (2) one contemporaneous year of inpatient operations at two university teaching hospitals to determine the clinical manifestations, causes, epidemiology, and guidelines for fluid administration. DESIGN Retrospective analysis of 13 patients with fatal postoperative pulmonary edema and one contemporaneous year of major inpatient surgery. PATIENTS AND METHODS Thirteen patients had net fluid retention of at least 67 mL/kg in the initial 24 postoperative hours and developed pulmonary edema. Ten were generally healthy while three had serious associated medical conditions. MEASUREMENTS AND RESULTS There was no measurement, laboratory value, or clinical finding predictive of impending pulmonary edema. The most common clinical manifestation following the onset of pulmonary edema was cardiorespiratory arrest (n = 8). Patients had metabolic acidosis (pH = 7.15 +/- .33), hypoxia (PO2 = 45 +/- 18 mm Hg), and normal electrolytes. The diagnosis of pulmonary edema was established by chest radiograph and confirmed by autopsy and pulmonary artery pressure (21 +/- 4 mm Hg). The mean net fluid retention was 7.0 +/- 4.5 L (90 +/- 36 mL/kg/d) and exceeded 67 mL/kg/d in all patients. Autopsy revealed pulmonary edema with no other cause of death. Among 8,195 major operations, 7.6% developed pulmonary edema with a mortality of 11.9%. Extrapolation to the 8.2 million annual major surgeries in the United States yields a projection of 8,000 to 74,000 deaths. CONCLUSIONS Pulmonary edema can occur within the initial 36 postoperative hours when net fluid retention exceeds 67 mL/kg/d. There are no known predictive warning signs and cardiorespiratory arrest is the most frequent clinical presentation. The monitoring systems currently in use neither detect nor predict impending pulmonary edema, and as yet, there are no known panic values for excessive fluid administration or retention.
[Modified radical operation for early breast cancer for preserving nipple-areolar complex and breast reconstruction using transverse rectus abdominis myocutaneous (TRAM) flap].

BACKGROUND & OBJECTIVE Modified radical mastectomy (MRM) operation has become an important surgical therapy for early stage breast cancer, but how to reconstruct breast and preserve nipple-areolar complex (NAC) is controversial. In this study, we applied a modified radical mastectomy for early stage breast cancer for preserving NAC and breast reconstruction using transverse rectus abdominis myocutaneous (TRAM) flap. METHODS During operation we performed the subcutaneous glandular excision and axillary dissection, and reconstructed the breast using TRAM flap in 10 patients with early stage breast cancer; meanwhile, maximam extent of breast skin and NAC were preserved. RESULTS The appearance of the reconstructed breast was better preserved after operation. No local recurrence and distant metastasis occurred in the patients during the follow up time (range 24-48 months). No skin flap necrosis, atrophy, and scleroses surround the NAC were observed; and no abdominal wall hernia occurred at the donor site. The nipple sensation was recovered half a year after surgery. CONCLUSION Modified radical operation for preserving NAC and breast reconstruction using TRAM flap may be a better way for breast cancer patients in early stage who request well preserving of breast. More samples are needed for proving the effects of this operation.
Searching cell‐secreted proteomes for potential urinary bladder tumor markers

To search for biomarkers critical for bladder carcinoma diagnosis and prognosis, secreted proteomes of highly malignant U1 and pre‐malignant U4 cell lines were initially analyzed. Proteins in the culture media of the U1 and U4 cell lines were systematically examined by SDS‐PAGE combined with MALDI‐TOF MS. Among them, expression of pro‐u‐plasminogen activator (pro‐u‐PA) was confirmed by Western blot analysis and further evaluated. In analyzing urine samples from bladder cancer patients and normal subjects, we established a statistically significant relationship between the low level and absence of pro‐u‐PA in urine with high stages and grades of the tumor samples. Constitutive expression of Ras dominant negative protein led to increased expression of pro‐u‐PA in culture media, indicating that the loss of pro‐u‐PA is associated with oncogenic transformation. Analysis of cancer‐secreted proteomes can be a feasible, non‐invasive and efficient strategy for searching potential bladder tumor biomarkers. Our work also has identified the loss of pro‐u‐PA in urine as potential marker of more advanced bladder carcinoma.
Location of the Clot and Outcome of Perfusion Defects in Acute Anterior Circulation Stroke Treated with Intravenous Thrombolysis

These investigators studied the impact of clot location in patients with acute stroke receiving IV thrombolysis. Four locations (ICA, proximal M1, distal M1, and M2 segment and more distal) of clots were correlated with CT perfusion maps, mismatches, salvaged brain volumes, and outcomes in 105 patients. Clots that were more proximal in location produced larger perfusion defects and lesion volumes. The amount of tissue salvaged was greater in patients with more distally located clots. In conclusion, admission CBV defects were larger in proximal vessel occlusions. More of the penumbra was salvaged if the occlusion was located more distally. This effect reached a plateau in the distal M1 segment of the MCA. BACKGROUND AND PURPOSE: The location of the clot is a major determinant of ischemic stroke outcome. We studied the impact of the location (ICA, proximal M1 segment of the MCA, distal M1 segment, and M2 segment and more distally) of the clot on the CT perfusion parametric maps, the mismatch ratio, the amount of salvaged brain tissue, and the imaging and clinical outcomes in a retrospective acute (<3 hours) stroke cohort treated with intravenous thrombolysis. MATERIALS AND METHODS: We reviewed 105 patients who underwent admission multimodal CT that revealed an occluded vessel on CTA. CT perfusion was successfully performed in 58 patients (55%). Differences among the parameters in different vessel positions were studied with the ANCOVA by using onset-to-imaging time as a covariate followed by pair-wise testing. RESULTS: There were no significant differences in potential confounding variables among the groups. A clot proximal to the M2 segment produced a significantly larger defect on the MTT map. A clot in the ICA resulted in a significantly larger CBV lesion compared with the distal M1 segment, the M2 segment, and the M3 segment. In general, a more proximal thrombus created a larger CBV defect. The fraction of penumbra that was salvaged at 24 hours was higher in the more distal vessel positions. CONCLUSIONS: Admission CBV defects are larger in proximal vessel occlusions. More of the penumbra can be salvaged if the occlusion is located distally. This effect seems to reach a plateau in the distal M1 segment of the MCA.
Método de diferenças temporais aplicado às equações de Riccati acopladas entre si

In this paper we present an iterative technique based on Monte Carlo simulations for deriving the optimal control of the infinite horizon linear regulator problem of discrete-time Markovian jump linear systems for the case in which the transition probability matrix of the Markov chain is not known. It is well known that the optimal control of this problem is given in terms of the maximal solution of a set of coupled algebraic Riccati equations (CARE), which have been extensively studied over the last few years. We trace a parallel with the theory of TD(l) algorithms for Markovian decision processes to develop a TD(l) like algorithm for the optimal control associated to the maximal solution of the CARE. Some numerical examples are also presented.
Analytical review of diagnosis and treatment strategies for dominant bile duct strictures in patients with primary sclerosing cholangitis.

BACKGROUND The diagnosis and treatment of indeterminate dominant strictures (DS) in patients with primary sclerosing cholangitis (PSC) is challenging and the literature on the subject is scarce. OBJECTIVES This review aims to appraise and synthesize the evidence published in the English-language medical literature on this topic. METHODS Scientific papers published from 1950 until week 4 of July 2010 were extracted from MEDLINE, Ovid Medline In-Process, the Cochrane Database of Systematic Reviews, the Database of Systematic Reviews, the Database of Abstracts of Reviews of Effects, EMBASE, PubMed and the National Library of Medicine Gateway. RESULTS Strategies for the optimal management of DS in PSC patients are supported only by level II and III evidence. Intraductal endoscopic ultrasound appears to be the most sensitive (64%) and specific (95%) diagnostic test for the evaluation of DS in PSC. Endoscopic and percutaneous dilatations achieve 1- and 3-year palliation in 80% and 60% of patients, respectively. Although dilatation and stenting are the most common palliative interventions in DS, no randomized trials on the optimal duration of treatment have been conducted. CONCLUSIONS In benign DS, endoscopic dilatation with short-term stenting seems to be effective and safe and does not increase the risks for malignant transformation or complications after liver transplantation. Surgical bile duct resection and/or bilioenteric bypass are indicated only in patients with preserved liver function.
Epigenomic Enhancer Profiling Defines a Signature of Colon Cancer

Colorectal Cancer Signature The mutations and genome aberrations that characterize cancer result in often dramatically altered gene and protein expression patterns. It is these altered expression patterns that directly and indirectly drive progression of the disease. In human primary colorectal cancer cells, Akhtar-Zaidi et al. (p. 736, published online 12 April) analyzed the pattern of epigenetically modified chromatin at “enhancer” sequences that are known to be critical in the control of gene expression. An epigenetic enhancer signature was defined that was specifically associated with colorectal cancer cells. Methylation tags at long-distance gene regulatory elements provide a signature specific to cancer cells. Cancer is characterized by gene expression aberrations. Studies have largely focused on coding sequences and promoters, even though distal regulatory elements play a central role in controlling transcription patterns. We used the histone mark H3K4me1 to analyze gain and loss of enhancer activity genome-wide in primary colon cancer lines relative to normal colon crypts. We identified thousands of variant enhancer loci (VELs) that comprise a signature that is robustly predictive of the in vivo colon cancer transcriptome. Furthermore, VELs are enriched in haplotype blocks containing colon cancer genetic risk variants, implicating these genomic regions in colon cancer pathogenesis. We propose that reproducible changes in the epigenome at enhancer elements drive a specific transcriptional program to promote colon carcinogenesis.
Cardiovascular , Pulmonary , and Renal Pathology Diesel Exhaust Particulates Exacerbate Asthma-Like Inflammation by Increasing CXC Chemokines

Particulate matter heavily pollutes the urban atmosphere, and several studies show a link between increased ambient particulate air pollution and exacerbation of pre-existing pulmonary diseases, including asthma. We investigated how diesel exhaust particulates (DEPs) aggravate asthma-like pulmonary inflammation in a mouse model of asthma induced by a house dust extract (HDE) containing cockroach allergens and endotoxin. BALB/c mice were exposed to three pulmonary challenges via hypopharyngeal administration of an HDE collected from the home of an asthmatic child. One hour before each pulmonary challenge, mice were exposed to DEP or PBS. Pulmonary inflammation was assessed by histological features, oxidative stress, respiratory physiological features, inflammatory cell recruitment, and local CXC chemokine production. To prove the role of CXC chemokines in the augmented inflammation, CXC chemokine–specific antibodies were delivered to the lungs before DEP exposure. DEP exacerbated HDEinduced airway inflammation, with increased airway mucus production, oxidative stress, inflammatory cell infiltration, bronchoalveolar lavage concentrations of CXC chemokines, and airway hyperreactivity. Neutralization of airway keratinocyte-derived chemokine and macrophage inflammatory protein-2 significantly improves the respiratory function in addition to decreasing the infiltration of neutrophils and eosinophils. Blocking the chemokines also decreased airway mucus production. These results demonstrate that DEP exacerbates airway inflammation induced by allergen through increased pulmonary expression of the CXC chemokines (keratinocyte-derived chemokine and macrophage inflammatory protein-2). (Am J Pathol 2011, 179:2730–2739; DOI: 10.1016/j.ajpath.2011.08.008)