Miracle-dz/UniFAR-FTUs huggingface dataset:
From large clinical trials to management of COPD in the real world

Large clinical trials in chronic obstructive pulmonary disease (COPD) are analyzed and discussed. Unfortunately, all of them have failed to reach their primary endpoint, which has mainly been the effect on the rate of decline in mean FEV1 (forced expiratory volume in 1 second). Nonetheless, almost all trials have demonstrated benefits in important outcomes such as exacerbation frequency, symptoms, quality of life and other measures of health status, which are arguably more meaningful to individual patients than FEV 1 per se.
A Highly Efficient Ziehl-Neelsen Stain: Identifying De Novo Intracellular Mycobacterium tuberculosis and Improving Detection of Extracellular M. tuberculosis in Cerebrospinal Fluid

ABSTRACT Tuberculous meningitis leads to a devastating outcome, and early diagnosis and rapid chemotherapy are vital to reduce morbidity and mortality. Since Mycobacterium tuberculosis is a kind of cytozoic pathogen and its numbers are very few in cerebrospinal fluid, detecting M. tuberculosis in cerebrospinal fluid from tuberculous meningitis patients is still a challenge for clinicians. Ziehl-Neelsen stain, the current feasible microbiological method for the diagnosis of tuberculosis, often needs a large amount of cerebrospinal fluid specimen but shows a low detection rate of M. tuberculosis. Here, we developed a modified Ziehl-Neelsen stain, involving cytospin slides with Triton processing, in which only 0.5 ml of cerebrospinal fluid specimens was required. This method not only improved the detection rate of extracellular M. tuberculosis significantly but also identified intracellular M. tuberculosis in the neutrophils, monocytes, and lymphocytes clearly. Thus, our modified method is more effective and sensitive than the conventional Ziehl-Neelsen stain, providing clinicians a convenient yet powerful tool for rapidly diagnosing tuberculous meningitis.
Yield of Sputum for Viral Detection by Reverse Transcriptase PCR in Adults Hospitalized with Respiratory Illness

ABSTRACT Diagnostic tests for respiratory viral infections have traditionally been performed on nasopharyngeal swabs or washings. Reverse transcriptase PCR (RT-PCR) is rapid, sensitive, and specific for viral infection diagnosis but is rarely applied to sputum samples. Thus, we evaluated the diagnostic yield of RT-PCR for detection of nine virus types by the use of nose and throat swabs (NTS) and sputum samples from patients admitted to the hospital with acute respiratory tract illnesses. Adults hospitalized with acute respiratory tract illnesses were recruited during the winters of 2008 and 2009. At enrollment, combined nose and throat swabs and sputum samples were collected for RT-PCR for detection of nine common respiratory virus types. A total of 532 subjects admitted for 556 respiratory illnesses were enrolled. A total of 189 virus strains were identified. The diagnostic yields for detection of any virus were 23% (126/556) for NTS RT-PCR and 36% (146/404) for sputum RT-PCR. A total of 83 (44%) of 189 viral detections were positive by both methods, 43 (23%) were positive by NTS alone, and 63 (33%) were positive only with sputum samples. The inclusion of RT-PCR performed with sputum samples significantly increased the diagnostic yield for respiratory viral infections in adults. Further studies designed to adapt the use of sputum samples for commercial RT-PCR respiratory virus assays are needed.
Routine Confirmation of Positive Nucleic Acid Amplification Test Results for Neisseria gonorrhoeae Is Not Necessary

We must strenuously disagree with Tabrizi et al. that “Supplementary testing for confirmation of N. gonorrhoeae NAATs remains recommended with all samples tested, in particular those from extragenital sites” (emphasis ours) ([6][1]). This may reflect Australian guidelines, but the generalization
An approach for genetic synthesizer of binary decision diagram

This paper describes the process of hardware evolution by genetic programming (GP). Hardware descriptions specified using binary decision diagrams (BDD) are evolved by genetic programming operators to synthesize various combinatorial logic circuits. By adopting BDDs as hardware representation, larger circuits are evolved and their verification is performed easily by utilizing commercial CAD software.
Emerging Therapies for Cystic Fibrosis

Introduction: Cystic Fibrosis (CF) remains a life-threatening genetic disease, with few clinically effective treatment options. Gene therapy and gene editing strategies offer the potential for a one-time CF cure, irrespective of the CFTR mutation class. Areas covered: We review emerging gene therapies and gene delivery strategies for the treatment of CF particularly viral and non-viral approaches with potential to treat CF. Expert opinion: It was initially anticipated that the challenge of developing a gene therapy for CF lung disease would be met relatively easily. Following early proof-of-concept clinical studies, CF gene therapy has entered a new era with innovative vector designs, approaches to subvert the humoral immune system and increase gene delivery and gene correction efficiencies. Developments include integrating Adenoviral vectors, Rapamycin loaded nanoparticles and lung-tropic lentiviral vectors. The characterisation of novel cell types in the lung epithelium, including pulmonary ionocytes, may also encourage cell type-specific targeting for CF correction. We anticipate preclinical studies to further validate these strategies, which should pave the way for clinical trials. We also expect gene editing efficiencies to improve to clinically translatable levels, given advancements in viral and non-viral vectors. Overall, gene delivery technologies look more convincing in producing an effective CF gene therapy. SIV, simian immunodeficiency virus; ssRNA, single-stranded ribonucleic acid; VSV-G, vesicular stomatitis virus glycoprotein.
Pharmacologic approaches to life-threatening asthma

Following a peak in asthma mortality in the late 1980s and early 1990s, we have been fortunate to see a substantial decrease in asthma deaths in recent years. Although most asthma deaths occur outside the hospital, near-fatal events are commonplace, with anywhere from 2–20% of patients with acute asthma admitted to intensive care, and 2-4% intubated for respiratory failure. Standard therapies for acute severe and near-fatal asthma include administration of systemic corticosteroids, and frequent or continuous inhaled beta agonists. Controversy remains regarding the optimal therapy of those who fail to respond to these initial treatments, those who remain at risk of acute respiratory failure, and patients requiring mechanical ventilation. There remain significant gaps in our knowledge regarding relative benefits of intravenous versus oral corticosteroids, intermittent versus continuous beta agonists, and the role of various adjunctive treatments including intravenous magnesium, systemic beta agonists, aminophylline, and helium-oxygen mixtures. Using models and radiolabeled aerosols, there is a greater understanding regarding effective administration of inhaled beta-agonists in ventilated patients. There is limited available evidence for treatment of near-fatal asthma, a fact reflected by the significant variability in asthma critical care practice. Much of the data guiding treatment in this setting has been generalized from studies of acute asthma in the ED and from general populations of hospitalized patients with acute asthma. This review will focus on pharmacologic approaches to life-threatening asthma by reviewing current guideline recommendations, reviewing the scientific basis of the guidelines, and highlighting gaps in our knowledge in treatment of refractory acute or near-fatal asthma.
The burden of allergic rhinitis and asthma

Asthma and allergic rhinitis are common health problems that cause major illness and disability worldwide. The prevalence of allergic rhinitis is estimated to range from 10% to 20% in the USA and Europe. Multiple factors contribute to the wide range of reported prevalence rates. These include type of prevalence rate reported (current or cumulative), study selection criteria, age of participants, differences in survey methods, varied geographic locations and socioeconomic status, any of which are significant enough to confound direct comparison between studies. There is no standard set of diagnostic criteria for allergic rhinitis. In most studies, the criteria for diagnosis are based on the subject’s reporting, solely by questionnaire and rarely confirmed by skin testing. In addition, most studies focus on hay fever, leaving perennial allergic rhinitis underestimated. Sinus imaging is generally not performed and, therefore, rhinosinusitis not differentiated. Some investigators report ‘current’ prevalence while others report ‘cumulative’ or ‘lifetime’ prevalence. Epidemiologic studies have consistently shown that asthma and rhinitis often coexist in the same patients. The prevalence of asthma is <2% in subjects without rhinitis while it varies from 10% to 40% in patients with rhinitis. Furthermore, the majority of patients with asthma experience rhinitis, which is a factor in the risk for asthma. Despite recognition that allergic rhinitis and asthma are global health problems, there are insufficient epidemiologic data and more data are needed with regard to their etiologic risk factors and natural history. This aim of this review is to enable the reader to discuss prevalence, risk factors and prognosis of allergic rhinitis and asthma.
Pulmonary hypertension complicated by pericardial effusion: a single center experience

Background: Pericardial effusion is an independent predictor of mortality in patients with pulmonary arterial hypertension (PAH). However, the management and outcomes of patients with pulmonary hypertension (PH) and pericardial effusion are not well described. Methods: A retrospective, observational study was conducted at Baylor College of Medicine and The Methodist Hospital by screening all patients admitted between 1 June 2005 and 1 June 2010 with the International Classification of Diseases, ninth revision codes for PH and pericardial effusion. A total of 138 patients were identified, and 103 patients were excluded on the basis of valvular heart disease, recent surgery or end-stage renal disease. Thirty-five patients with PH diagnosed by a historical right heart catheterization or echocardiography and with documented pericardial effusion were included in this analysis. Demographic, hemodynamic, laboratory and survival data were collected. Results: The mean age was 49.5±36 years (mean ± standard deviation), 31 of 35 patients were women (93%) and pulmonary artery systolic pressure was 77 ± 19 mmHg. Mean follow-up period was 20.5 ± 12.9 months. Fifteen patients had PAH associated with connective tissue disease (50%). The majority of the patients (87%) with pericardial effusion were managed conservatively. Four patients (13%) who were hemodynamically unstable underwent pericardial window placement. One of them was started on epoprostenol, and two patients had the doses of PAH-specific medications uptitrated. Three of four pericardial window patients survived to the conclusion of the follow-up period. The overall survival in our cohort was 60%, with three patients lost to follow-up. Conclusions: Connective tissue disease associated PAH and female sex were predominant in our cohort of patients with pericardial effusion. Seventy-five percent of patients who were treated with pericardial window for hemodynamically unstable pericardial effusion survived until the end of the study period. Pericardial window may be a therapeutic option in patients with unstable PH with pericardial effusion. Further studies are needed to determine the optimal treatment strategy for such patients.
Detection of Inducible Clindamycin Resistance of Staphylococci in Conjunction with Performance of Automated Broth Susceptibility Testing

ABSTRACT This study has shown that inducible clindamycin resistance in staphylococci can be detected by disk testing on sheep blood agar inoculum purity plates used with the bioMerieux VITEK 2. Tests of 150 erythromycin-resistant isolates correlated with standard D-zone tests on Mueller-Hinton agar and with PCR for erm(A), erm(C), and msr(A).
Real-Time PCR Assay Using Fine-Needle Aspirates and Tissue Biopsy Specimens for Rapid Diagnosis of Mycobacterial Lymphadenitis in Children

ABSTRACT A real-time PCR assay was developed to diagnose and identify the causative agents of suspected mycobacterial lymphadenitis. Primers and probes for the real-time PCR were designed on the basis of the internal transcribed spacer sequence, enabling the recognition of the genus Mycobacterium and the species Mycobacterium avium and M. tuberculosis. The detection limit for the assay was established at 1,100 CFU/ml of pus, and the specificity tests showed no false-positive reaction with other mycobacterial species and other pathogens causing lymphadenitis. From 67 children with suspected mycobacterial lymphadenitis based on a positive mycobacterial skin test, 102 samples (58 fine-needle aspirates [FNA] and 44 tissue specimens) were obtained. The real-time PCR assay detected a mycobacterial infection in 48 patients (71.6%), whereas auramine staining and culturing were positive for 31 (46.3%) and 28 (41.8%) of the patients. The addition of the real-time PCR assay to conventional diagnostic tests resulted in the recognition of 13 more patients with mycobacterial disease. These results indicate that the real-time PCR is more sensitive than conventional staining and culturing techniques (P = 0.006). The M. avium-specific real-time PCR was positive for 38 patients, and the M. tuberculosis-specific real-time PCR was positive for 1 patient. Analysis of 27 patients from whom FNA and tissue biopsy specimens were collected revealed significantly more positive real-time PCR results for FNA than for tissue biopsy specimens (P = 0.003). Samples from an age-matched control group of 50 patients with PCR-proven cat scratch disease were all found to be negative by the real-time PCR. We conclude that this real-time PCR assay with a sensitivity of 72% for patients with lymphadenitis and a specificity of 100% for the detection of atypical mycobacteria can provide excellent support for clinical decision making in children with lymphadenitis.
Putative structural neuroimaging endophenotypes in schizophrenia: a comprehensive review of the current evidence

The genetic contribution to schizophrenia etiopathogenesis is underscored by the fact that the best predictor of developing schizophrenia is having an affected first-degree relative, which increases lifetime risk by tenfold, as well as the observation that when both parents are affected, the risk of schizophrenia increases to approximately 50%, compared with 1% in the general population. The search to elucidate the complex genetic architecture of schizophrenia has employed various approaches, including twin and family studies to examine co-aggregation of brain abnormalities, studies on genetic linkage and studies using genome-wide association to identify genetic variations associated with schizophrenia. ‘Endophenotypes’, or ‘intermediate phenotypes’, are potentially narrower constructs of genetic risk. Hypothetically, they are intermediate in the pathway between genetic variation and clinical phenotypes and can supposedly be implemented to assist in the identification of genetic diathesis for schizophreni.
Rare problems with RhD immunoglobulin for postnatal prophylaxis after large fetomaternal haemorrhage

We report a case of unusually large fetomaternal haemorrhage in a RhD- patient; of symptomatic non-sustained haemolysis of fetal red cells in the maternal circulation with infusion of intravenous high-dose RhD immunoglobulin; and of a failure to prevent RhD alloimmunisation. The haemolytic reaction is not previously reported in this patient group and we suggest would be limited to patients where the number of fetal red cells in the circulation is high. We advocate caution in treatment and spaced dosing of RhD immunoglobulin where the required dose is high, and refer readers to the WinRhoSDF™ RhD immunoglobulin product information for their updated dosing recommendations. There is a need for better understanding of pathophysiology and RhD immunoglobulin effects, to further reduce alloimmunisation rates, and we support the reporting of prophylaxis failures to haemovigilance programmes as is in place in the United Kingdom.
Maintenance of the HIV Reservoir Is Antagonized by Selective BCL2 Inhibition

ABSTRACT Decay of the HIV reservoir is slowed over time in part by expansion of the pool of HIV-infected cells. This expansion reflects homeostatic proliferation of infected cells by interleukin-7 (IL-7) or antigenic stimulation, as well as new rounds of infection of susceptible target cells. As novel therapies are being developed to accelerate the decay of the latent HIV reservoir, it will be important to identify interventions that prevent expansion and/or repopulation of the latent HIV reservoir. Our previous studies showed that HIV protease cleaves the host protein procaspase 8 to generate Casp8p41, which can bind and activate Bak to induce apoptosis of infected cells. In circumstances where expression of the anti-apoptotic protein BCL2 is high, Casp8p41 instead binds BCL2, and cell death does not occur. This effect can be overcome by treating cells with the clinically approved BCL2 antagonist venetoclax, which prevents Casp8p41 from binding BCL2, thereby allowing Casp8p41 to bind Bak and kill the infected cell. Here we assess whether the events that maintain the HIV reservoir are also antagonized by venetoclax. Using the J-Lat 10.6 model of persistent infection, we demonstrate that proliferation and HIV expression are countered by the use of venetoclax, which causes preferential killing of the HIV-expressing cells. Similarly, during new rounds of infection of primary CD4 T cells, venetoclax causes selective killing of HIV-infected cells, resulting in decreased numbers of HIV DNA-containing cells. IMPORTANCE Cure of HIV infection requires an intervention that reduces the HIV reservoir size. A variety of approaches are being tested for their ability to impact HIV reservoir size. Even if successful, however, these approaches will need to be combined with additional complementary approaches that prevent replenishment or repopulation of the HIV reservoir. Our previous studies have shown that the FDA-approved BCL2 antagonist venetoclax has a beneficial effect on the HIV reservoir size following HIV reactivation. Here we demonstrate that venetoclax also has a beneficial effect on HIV reservoir size in a model of homeostatic proliferation of HIV as well as in acute spreading infection of HIV in primary CD4 T cells. These results suggest that venetoclax, either alone or in combination with other approaches to reducing HIV reservoir size, is a compound worthy of further study for its effects on HIV reservoir size.
National service for adolescents and adults with severe obsessive-compulsive and body dysmorphic disorders

AIMS AND METHOD National guidelines for the assessment and treatment of obsessive-compulsive disorder (OCD) and body dysmorphic disorder were published in 2005 by the National Institute for Health and Clinical Excellence (NICE). Local services are unable to treat a small but significant number of the most severely ill patients successfully, and the guidelines recommend that such patients should have access to highly specialised care. From 1 April 2007, the Department of Health decided to centrally fund treatment services for severe, chronic, refractory OCD and BDD. We describe a new National Service for Refractory OCD; its rationale, treatments offered, referral criteria and expected clinical outcomes. RESULTS Initial results from one centre show an average 42% reduction in OCD symptoms at the end of treatment. CLINICAL IMPLICATIONS The operational challenges and potential generalisability of this model of healthcare delivery are discussed. We present a summary of the progress made so far in establishing a new, coherent National Service for Refractory OCD, 18 months after the NICE guideline was published. The aim of the paper is to educate clinicians about the service and describe its rationale, treatments offered, referral criteria and expected clinical outcomes.
Therapeutic advances in cardiovascular disease.

Creative Commons Non Commercial CC BY-NC: This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage). Ther Adv Cardiovasc Dis
Expression of the Infectious Salmon Anemia Virus Receptor on Atlantic Salmon Endothelial Cells Correlates with the Cell Tropism of the Virus

ABSTRACT Infectious salmon anemia (ISA) is a World Organization for Animal Health (OIE)-listed disease of farmed Atlantic salmon, characterized by slowly developing anemia and circulatory disturbances. The disease is caused by ISA virus (ISAV) in the Orthomyxoviridae family; hence, it is related to influenza. Here we explore the pathogenesis of ISA by focusing on virus tropism, receptor tissue distribution, and pathological changes in experimentally and naturally infected Atlantic salmon. Using immunohistochemistry on ISAV-infected Atlantic salmon tissues with antibody to viral nucleoprotein, endotheliotropism was demonstrated. Endothelial cells lining the circulatory system were found to be infected, seemingly noncytolytic, and without vasculitis. No virus could be found in necrotic parenchymal cells. From endothelium, the virus budded apically and adsorbed to red blood cells (RBCs). No infection or replication within RBCs was detected, but hemophagocytosis was observed, possibly contributing to the severe anemia in fish with this disease. Similarly to what has been done in studies of influenza, we examined the pattern of virus attachment by using ISAV as a probe. Here we detected the preferred receptor of ISAV, 4-O-acetylated sialic acid (Neu4,5Ac2). To our knowledge, this is the first report demonstrating the in situ distribution of this sialic acid derivate. The pattern of virus attachment mirrored closely the distribution of infection, showing that the virus receptor is important for cell tropism, as well as for adsorption to RBCs.
Evaluación de la promoción de la lactancia materna en hospitales amigos del niño

Instituição: Centro de Estudos em Gastroenterologia e Hepatologia Pediátrica da Universidade Federal da Bahia (UFBA), Salvador, BA, Brasil 1Graduado pelo Programa de Iniciação Científica oferecido pelo Centro de Estudos em Gastroenterologia e Hepatologia Pediátrica da UFBA, Salvador, BA, Brasil 2Mestre em Medicina e Saúde pela UFBA; Professora Auxiliar de Pediatria do Departamento de Medicina da Universidade Estadual de Feira de Santana (UEFS), Feira de Santana, BA, Brasil 3Doutora em Medicina e Saúde pela UFBA; Professora Adjunta do Curso de Medicina e Pós-Graduação da UEFS, Feira de Santana, BA, Brasil 4Professora Titular Doutora do Departamento de Pediatria e Líder do Grupo de Estudos em Gastroenterologia e Hepatologia Pediátrica da UFBA, Salvador, BA, Brasil ABSTRACT