Miracle-dz/UniFAR-FTUs huggingface dataset:
Antipneumocystis activity of water-soluble lipopeptide L-693,989 in rats

Water-soluble lipopeptide L-693,989 was evaluated for its antipneumocystis activity in rats. Rats from colonies with latent Pneumocystis carinii infections were immunosuppressed with dexamethasone for 6 weeks to facilitate the development of acute P. carinii pneumonia (PCP). After 6 weeks, the rats were maintained on dexamethasone and were treated twice daily for 4 days with various concentrations of L-693,989. At a dose of 0.15 mg/kg of body weight, the compound effectively eliminated 90% of the cysts in 4 days. Trophozoite forms of P. carinii were still present in these animals, as determined by using a P. carinii-specific DNA probe. A 3-week therapy study showed that the trophozoite load did not expand during treatment and that the trophozoites already present at the initiation of therapy appeared to persist. This may be a consequence of the stage specificity of the compound for cyst development and the severe immunosuppressive effects of dexamethasone on rats. When evaluated as a daily parenteral prophylactic agent, L-693,989 was effective in preventing the development of both P. carinii cysts and trophozoites, demonstrating its potential for use in prophylaxis and implying that the cyst stage of P. carinii is an obligatory step in trophozoite multiplication. The foamy exudate commonly associated with P. carinii infections was absent in the lungs of rats on prophylaxis. The compound was also evaluated via oral administration and was found to have a 90% effective dose of 32 mg/kg for therapy of acute infections and 5 mg/kg for daily prophylaxis.
AVALIAÇÃO DE RISCOS DE UMA EMPRESA DE EMBALAGENS DE MADEIRA

Introducao : O beneficiamento de madeira traz diversos riscos a saude dos trabalhadores. Altos indices de acidentes de trabalho acompanham toda a cadea produtiva da madeira. O po da madeira e um alergico para pele, conjuntiva e trato respiratorio. O risco do ruido elevado que pode levar a diversas patologias alem da perda auditiva e o sistema osteomuscular pode ser prejudicado quando existe sobrecarga fisica. Objetivo : Analisar criticamente as condicoes de higiene ambiental, saude dos trabalhadores e os riscos ocupacionais do setor de producao de uma empresa de embalagens de madeira. Metodo : Foram realizadas visitas ao local de trabalho para avaliacao ambiental, observacao, anotacoes, registros fotograficos, avaliacao ergonomica e consultas medicas foram realizadas. Resultados : Houve evidencias de deposicao de po de madeira no setor de producao; as medidas de particulado ambiental inalavel mostraram resultados de 4,0mg/m³, 3,6mg/m³ e 2,0mg/m³ respectivamente para os postos de serra, plana e gabaritos dos paletes; algmas maquinas nao tinham protecao adequada e relatos de acidentes de trabalho foram identificados. Conclusao : Um dos aspectos de maior relevância foi o excesso de po de madeira presente no ambiente ocupacional, ultrapassando os limites de exposicao da ACGIH de 1mg/m³. Adidentes de trabalho sao causa comum de lesoes graves em empresas que utilizam maquinario pesado como serras e plainas. Neste estudo foi verificado o risco de acidentes no ambiente de trabalho e comprovada a ocorrencia destes atraves do exame fisico dos trabalhadores.
Decreased prevalence of atopic diseases in children with diabetes. The EURODIAB Substudy 2 Study Group.

OBJECTIVE To test the hypothesis that atopic diseases in early life are associated with a reduced risk (protection) for the development of type 1 diabetes in childhood. STUDY DESIGN European centers (n = 8) with access to population-based type 1 diabetes registries (>90% degree of ascertainment) participated in a case control study focusing on early exposures and risk factors for type 1 diabetes. Altogether, data from 1028 members of a case group and 2744 members of a control group corresponding to 85.4% eligible members of the case group and 76.1% of the control group were analyzed. Information in this study was collected regarding atopic diseases (atopic eczema, allergic rhinoconjunctivitis, and asthma). RESULTS Atopic disease and asthma particularly are associated with significant reductions in risk of childhood type 1 diabetes. The risk reduction associated with asthma was observed reasonably consistently among the 8 study centers, which represent a wide range of diabetes incidence. Risk reductions associated with all 3 expressions of atopy were particularly marked in children whose type 1 diabetes was diagnosed in the 10- to 14-year age group. CONCLUSION These findings indicate that atopic conditions may be protective against the development of type 1 diabetes and are consistent with the immunologic concept of T(H)1 (type 1 diabetes) and T(H)2 (atopy) diseases being mutually exclusive.
A Functional MicroRNA-155 Ortholog Encoded by the Oncogenic Marek's Disease Virus

ABSTRACT Kaposi's sarcoma-associated herpesvirus-encoded microRNA (miRNA) MiR-K12-11 was recently shown to be a functional ortholog of miR-155, a miRNA that plays a major role in lymphoid malignancies and the modulation of immune responses. Here we show that miR-M4, encoded by the highly oncogenic Marek's disease virus of chickens, shares common targets with miR-155 and thus is also a functional ortholog of miR-155, the first one identified in an alphaherpesvirus. The observation that two distinct oncogenic herpesviruses associated with distinct types of lymphomas in different species encode functional miR-155 orthologs suggested the importance of this miRNA in regulatory pathways and the biology of lymphomagenesis.
Two ways to skin a cat: acyldepsipeptides antibiotics can kill bacteria through activation or inhibition of ClpP activity

Infection by Mycobacterium tuberculosis (Mtb) has had a devastating effect on the world population. Acyldepsipeptide antibiotics (ADEPs) are known to kill some bacteria by over activating the bacterial ClpP peptidase. ADEP antibiotics also target Mtb, with the assumption that uncontrolled ADEP‐activated proteolysis by ClpP is the common mode of killing. In this issue of Molecular Microbiology, Famulla, et al. now show that ADEP's effectiveness in mycobacteria is likely due to inhibition of ClpP‐dependent protease activity rather than activation. This finding of how the same antibiotic can kill bacteria by either inhibiting or activating proteases illustrates the utility of targeting these enzymes for sorely needed new antibiotics.
IS SELECTIVELY HARVESTED FOREST AN ECOLOGICAL TRAP FOR OLIVE-SIDED FLYCATCHERS?

Abstract ABSTRACT Disturbance-dependent species are assumed to benefit from forestry practices that mimic the appearance of postdisturbance landscapes. However, human activities that closely mimic the appearance but not the fundamental quality of natural habitats could attract animals to settle whether or not these habitats are suitable for their survival or reproduction. We examined habitat selection behavior and nest success of Olive-sided Flycatchers (Contopus cooperi) in a naturally occurring burned forest and an anthropogenically created habitat type—selectively harvested forest. Olive-sided Flycatcher density and nestling provisioning rates were greater in the selectively harvested landscape, whereas estimated nest success in selectively harvested forest was roughly half that found in naturally burned forest. Reduced nest success was probably a result of the relatively high abundance of nest predators found in the artificially disturbed forest. These results are consistent with the hypothesis that selectively harvested forest can act as an “ecological trap” by attracting Olive-sided Flycatchers to a relatively poor-quality habitat type. This highlights the importance of considering animal behavior in biodiversity conservation.
Evidence-based pharmacological treatment of anxiety disorders, post-traumatic stress disorder and obsessive-compulsive disorder: A revision of the 2005 guidelines from the British Association for Psychopharmacology

This revision of the 2005 British Association for Psychopharmacology guidelines for the evidence-based pharmacological treatment of anxiety disorders provides an update on key steps in diagnosis and clinical management, including recognition, acute treatment, longer-term treatment, combination treatment, and further approaches for patients who have not responded to first-line interventions. A consensus meeting involving international experts in anxiety disorders reviewed the main subject areas and considered the strength of supporting evidence and its clinical implications. The guidelines are based on available evidence, were constructed after extensive feedback from participants, and are presented as recommendations to aid clinical decision-making in primary, secondary and tertiary medical care. They may also serve as a source of information for patients, their carers, and medicines management and formulary committees.
Phylogenetic relationships among spiny pocket mice (Heteromys) inferred from mitochondrial and nuclear sequence data

Abstract In recent years molecular data have been used increasingly to estimate phylogenies and aid in species delimitation. We generated and analyzed sequence data for spiny pocket mice (Heteromys) for the mitochondrial gene cytochrome b (1,140 base pairs [bp]) and 2 nuclear gene segments, MYH6 (252 bp) and EN2 (189 bp). We used maximum-parsimony, maximum-likelihood, and Bayesian optimality criteria to estimate relationships among species and provide a framework for using a species-delimitation method to investigate the possibility of multiple species within the widespread H. desmarestianus group. We recovered several well-supported clades within this complex, including H. goldmani, H. oresterus, and H. nubicolens. Incorporating karyotype, allozyme, and morphological data from earlier studies, we found sufficient supporting evidence to justify maintaining H. goldmani, H. oresterus, and H. nubicolens as species and identifying 4 additional clades as candidate species. We present a revised taxonomic arrangement within the genus. The subgenus Xylomys should be retained and be composed of H. nelsoni. The subgenus Heteromys should be divided into 3 species groups: the H. anomalus group (H. anomalus and H. australis) together with H. catopterius, H. oasicus, and H. teleus (insertae sedis); the H. gaumeri group (H. gaumeri); and H. desmarestianus group (H. desmarestianus, H. goldmani, H. oresterus, H. nubicolens, and the 4 candidate species).
The Strategic Management of Mergers and Acquisitions in the Pharmaceutical Industry: Developing a Resource-based Perspective

There is a growing recognition within resource-based theory that mergers and acquisitions (M&A) can play an important role as a means of transferring otherwise non-marketable resources and capabilities. However, this resource-based view has yet to consider in detail the management process issues involved. This paper looks at three cases from the pharmaceutical industry and seeks to begin the development of a resource-based perspective on the management of M&A.
‘LungGENS’: a web-based tool for mapping single-cell gene expression in the developing lung

We developed LungGENS (Lung Gene Expression iN Single-cell), a web-based bioinformatics resource for querying single-cell gene expression databases by entering a gene symbol or a list of genes or selecting a cell type of their interest. Gene query provides quantitative RNA expression of the gene of interest in each lung cell type. Cell type query returns associated selective gene signatures and genes encoding cell surface markers and transcription factors in interactive heatmap and tables. LungGENS will be broadly applicable in respiratory research, providing a cell-specific RNA expression resource at single-cell resolution. LungGENS is freely available for non-commercial use at https://research.cchmc. org/pbge/lunggens/default.html.
An Applied Framework for Classifying the Complexity of Knowledge-Based Systems

The development and use of knowledge-based (expert) systems has grown dramatically across a broad range of industries. Yet despite its growing importance, the study of expert systems lacks a cohesive framework for differentiating and comparing expert systems initiatives across different applications and in different industrial settings. The problem for IS managers is that a system that works in one situation may ot be appropriate for another. This article presents a classification methodology for the systematic evaluation of a broad range of expert systems. Of primary concern in this study is the measurement of the complexity of such systems. Complexity in the area of expert systems consists of two basic dimensions. The first dimension is the complexity of the underlying knowledge residing with the key experts. The second dimension of the framework focuses on the complexity of the technology incorporated into a given system. This framework is then applied to a sample of 50 successfully developed knowledge-based systems. The results can be used as a foundation for generating research hypotheses and for development time, budget, staffing, organizational control, and organizational participation.
Comparison between intrathecal isobaric ropivacaine-fentanyl and bupivacaine-fentanyl in elective infraumbilical orthopedic surgery: A randomized controlled study

Background and Aims: We aimed to evaluate and compare the block characteristics and duration of analgesia of intrathecal isobaric ropivacaine-fentanyl and bupivacaine-fentanyl combination in adult patients undergoing lower limb orthopedic surgery. Material and Methods: Seventy-four American Society of Anesthesiologists’ I and II adult patients undergoing lower limb orthopedic surgery under subarachnoid block were randomized to receive either 3 ml 0.5% isobaric ropivacaine and 25 mcg fentanyl (Group R) or 3 ml 0.5% isobaric bupivacaine and 25 mcg fentanyl (Group B). The hemodynamic profiles, maximum upper level of sensory block height, time to reach peak block height, two dermatome regression time, and duration of motor block were recorded. Results: There was no statistically significant difference regarding the hemodynamic parameters between the groups. The median (range) peak sensory block height was T7 (T4-T9) in Group R and T7 (T4-T10) in Group B. Time to reach peak block height (13.2 ± 2.3 min in Group R vs. 13.7 ± 2.2 min in Group B; P = 0.385) was similar between the groups. Two dermatome regression time in sensory block (median 120 min vs. 85 min; P < 0.001) and duration of motor block (median 245 min vs. 150 min; P < 0.001) was significantly higher in Group B. The duration of analgesia (median 360 min vs. 245 min; P < 0.001) was significantly higher in the bupivacaine group. Conclusion: Intrathecal isobaric bupivacaine-fentanyl combination produces a significantly longer duration of analgesia, sensory block and motor block than isobaric ropivacaine-fentanyl combination. As ropivacaine has a shorter duration of sensory and motor block, it may be preferred in day care surgery.
A simple C‐reactive protein measurement for the differentiation between tuberculous and malignant pleural effusion

Objective: The aim of this study was to determine the validity of pleural fluid C‐reactive protein (CRP) concentrations and/or pleural fluid to serum CRP ratio for differentiating tuberculous pleuritis (TBP) from malignant pleural effusion (MPE) in patients presenting with lymphocytic exudative pleural effusions.
Ridge preservation using basic fibroblast growth factor-2 and collagenated biphasic calcium phosphate in beagle dogs

Purpose The aim of this study was to evaluate volumetric and histologic changes in edentulous alveolar ridge areas after ridge preservation using basic fibroblast growth factor-2 (bFGF-2) in combination with collagenated biphasic calcium phosphate (BCP). Methods The experiments were performed in 6 adult male beagle dogs. The following 3 groups were created: 1) ridge preservation with bFGF-2 and collagenated BCP (experimental group), 2) ridge preservation with collagenated BCP (positive control group), and 3) a negative control group in which no ridge preservation procedure was performed. Volumetric change analysis was performed using an optical scanner and casts. Histological observations were made using light microscopy. Results After the initial swelling subsided, the magnitude of the volumetric change in the experimental group and positive control group was smaller than in the negative control group. In the experimental group, a distinct trend was observed for the resorption of residual bone and collagen fibers at 4 weeks and for more mature bone and faster healing at 12 weeks. Conclusions Based on the findings of the present study, bFGF-2 may be considered for use as a therapeutic molecule in ridge preservation procedures.
Molecular targets for selective killing of TRAIL-resistant leukemic cells

Introduction: TNF-related apoptosis-inducing ligand (TRAIL) is a member of the TNF family of cytokines, and shows promising therapeutic activity against solid tumors and lymphomas, in a variety of Phase I and II clinical trials. In contrast, primary leukemias have shown poor susceptibility to TRAIL-mediated cytotoxicity, suggesting the need for sensitizing TRAIL-resistant leukemic cells, by combining soluble recombinant TRAIL either with chemotherapeutic drugs, or with targeted small molecules. Areas covered: This review discusses potential therapeutic applications of combinations able to restore the sensitivity of leukemic cells to either recombinant TRAIL or anti-TRAIL-receptor agonistic antibodies for the treatment of hematological malignancies. Expert opinion: Up-to-date knowledge of the most innovative anti-leukemic therapies including functional screening of specific-sensitizers, enhancing TRAIL-mediated cytotoxicity. Strategies aimed to enhance TRAIL-mediated apoptosis, include the combination of novel sensitizers, functionally identified from libraries of pharmaceutically active, synthetic or naturally derived compounds. Other approaches aim to employ the administration of stem cells engineered to express TRAIL, in the leukemic stem cell niche, and promise to be a successful treatment with reduced specific toxicity.
Host Cell Responses to Genotypically Similar Helicobacter pylori Isolates from United States and Japan

ABSTRACT Associations of Helicobacter pylori genotypes with disease differ between Western countries and Asia. Therefore, we directly compared histopathological and in vitro responses to clinical isolates with similar genotypes. Sixty-three cagA+vacAs1/m1 H. pylori isolates (United States, n = 24; Japan, n = 39) and eight cagA-negative vacAs2/m2 strains were incubated with AGS cells, and supernatants were assayed for interleukin-8 (IL-8) and for DNA fragmentation. CagA tyrosine phosphorylation in AGS cells and the sequence of the putative HP0638 (oipA) signal sequence region were determined for 22 representative strains. HP0638 and/or cag island mutant strains were created and examined in IL-8 and CagA tyrosine phosphorylation assays. Levels of IL-8 induction and DNA fragmentation were similar in the U.S. and Japanese cagA+vacAs1/m1 isolates. All 10 of the isolates with the highest IL-8 induction and 8 of the 10 isolates with the lowest IL-8 induction had an in-frame oipA open reading frame, and all 10 of the isolates with the highest IL-8 induction and 7 of the 10 isolates with the lowest IL-8 induction induced CagA tyrosine phosphorylation in AGS cells. Eight isolates from gastric ulcer patients induced significantly more apoptosis in vitro, and more severe gastritis and atrophy in vivo, than other Japanese isolates. Disruption of HP0638 did not affect IL-8 induction or CagA tyrosine phosphorylation. Thus, H. pylori cagA+vacAs1/m1 isolates from the United States and Japan induce similar IL-8 and apoptosis levels. Inactivation of HP0638 does not alter epithelial responses mediated by the cag island in vitro. Assessment of apoptosis in vitro identified a group of H. pylori isolates that induce more severe gastric inflammation and atrophy.
Estimate of Novel Influenza A/H1N1 cases in Mexico at the early stage of the pandemic with a spatially structured epidemic model

Determining the number of cases in an epidemic is fundamental to properly evaluate several disease features of high relevance for public health policies such as mortality, morbidity or hospitalization rates. Surveillance efforts are however incomplete especially at the early stage of an outbreak due to the ongoing learning process about the disease characteristics. An example of this is represented by the number of H1N1 influenza cases in Mexico during the first months of the current pandemic. Several estimates using backtrack calculation based on imported cases from Mexico in other countries point out that the actual number of cases was likely orders of magnitude larger than the number of confirmed cases. Realistic computational models fed with the best available estimates of the basic disease parameters can provide an ab-initio calculation of the number of cases in Mexico as other countries. Here we use the Global Epidemic and Mobility (GLEaM) model to obtain estimates of the size of the epidemic in Mexico as well as of imported cases at the end of April and beginning of May. We find that the reference range for the number of cases in Mexico on April 30th is 121,000 to 1,394,000 in good agreement with the recent estimates by Lipsitch et al. [M. Lipsitch, PloS One 4:e6895 (2009)]. The number of imported cases from Mexico in several countries is found to be in good agreement with the surveillance data.
Functional improvement in mouse models of familial amyotrophic lateral sclerosis by PEGylated insulin-like growth factor I treatment depends on disease severity

Abstract Insulin-like growth factor I (IGF-I) has been successfully tested in the SOD1-G93A mouse model of familial amyotrophic lateral sclerosis (ALS) and proposed for clinical treatment. However, beneficial effects required gene therapy or intrathecal application. Circumventing the dosing issues we recently found that polyethylene glycol (PEG) modified IGF-I (PEG-IGF-I) modulated neuromuscular function after systemic application, and protected against disease progression in a motor neuron disease model. Here we investigated its effects in two SOD1-G93A mouse lines, the G1L with a milder and the G1H with a more severe phenotype. Results showed that in G1L mice, PEG-IGF-I treatment significantly improved muscle force, motor coordination and animal survival. In contrast, treatment of G1H mice with PEG-IGF-I or IGF-I even at high doses did not beneficially affect survival or functional outcomes despite increased signalling in brain and spinal cord by both agents. In conclusion, the data point towards further investigation of the therapeutic potential of PEG-IGF-I in ALS patients with less severe clinical phenotypes.