Miracle-dz/UniFAR-FTUs huggingface dataset:
Airway tissue plasminogen activator prevents acute mortality due to lethal sulfur mustard inhalation.

RATIONALE Sulfur mustard (SM) is a chemical weapon stockpiled today in volatile regions of the world. SM inhalation causes a life-threatening airway injury characterized by airway obstruction from fibrin casts, which can lead to respiratory failure and death. Mortality in those requiring intubation is more than 80%. No therapy exists to prevent mortality after SM exposure. Our previous work using the less toxic analog of SM, 2-chloroethyl ethyl sulfide, identified tissue plasminogen activator (tPA) an effective rescue therapy for airway cast obstruction (Veress, L. A., Hendry-Hofer, T. B., Loader, J. E., Rioux, J. S., Garlick, R. B., and White, C. W. (2013). Tissue plasminogen activator prevents mortality from sulfur mustard analog-induced airway obstruction. Am. J. Respir. Cell Mol. Biol. 48, 439-447). It is not known if exposure to neat SM vapor, the primary agent used in chemical warfare, will also cause death due to airway casts, and if tPA could be used to improve outcome. METHODS Adult rats were exposed to SM, and when oxygen saturation reached less than 85% (median: 6.5 h), intratracheal tPA or placebo was given under isoflurane anesthesia every 4 h for 48 h. Oxygen saturation, clinical distress, and arterial blood gases were assessed. Microdissection was done to assess airway obstruction by casts. RESULTS Intratracheal tPA treatment eliminated mortality (0% at 48 h) and greatly improved morbidity after lethal SM inhalation (100% death in controls). tPA normalized SM-associated hypoxemia, hypercarbia, and lactic acidosis, and improved respiratory distress. Moreover, tPA treatment resulted in greatly diminished airway casts, preventing respiratory failure from airway obstruction. CONCLUSIONS tPA given via airway more than 6 h after exposure prevented death from lethal SM inhalation, and normalized oxygenation and ventilation defects, thereby rescuing from respiratory distress and failure. Intra-airway tPA should be considered as a life-saving rescue therapy after a significant SM inhalation exposure incident.
Interactive effects of growth hormone and exercise on muscle mass in suspended rats.

Measures to attenuate muscle atrophy in rats in response to stimulated microgravity [hindlimb suspension (HS)] have been only partially successful. In the present study, hypophysectomized rats were in HS for 7 days, and the effects of recombinant human growth hormone (GH), exercise (Ex), or GH+Ex on the weights, protein concentrations, and fiber cross-sectional areas (CSAs) of hindlimb muscles were determined. The weights of four extensor muscles, i.e., the soleus (Sol), medial (MG) and lateral (LG) gastrocnemius, and plantaris (Plt), and one adductor, i.e., the adductor longus (AL), were decreased by 10-22% after HS. Fiber CSAs were decreased by 34% in the Sol and by 17% in the MG after HS. In contrast, two flexors, i.e., the tibialis anterior (TA) and extensor digitorum longus (EDL), did not atrophy. In HS rats, GH treatment alone maintained the weights of the fast extensors (MG, LG, Plt) and flexors (TA, EDL) at or above those of control rats. This effect was not observed in the slow extensor (Sol) or AL. Exercise had no significant effect on the weight of any muscle in HS rats. A combination of GH and Ex treatments yielded a significant increase in the weights of the fast extensors and in the CSA of both fast and slow fibers of the MG and significantly increased Sol weight and CSA of the slow fibers of the Sol. The AL was not responsive to either GH or Ex treatments. Protein concentrations of the Sol and MG were higher only in the Sol of Ex and GH + Ex rats. (ABSTRACT TRUNCATED AT 250 WORDS)
MR imaging to assess immediate response to irreversible electroporation for targeted ablation of liver tissues: preclinical feasibility studies in a rodent model.

PURPOSE To test the hypothesis that magnetic resonance (MR) imaging measurements can be used to immediately detect treated tissue regions after irreversible electroporation (IRE) ablation procedures in rodent liver tissues. MATERIALS AND METHODS All experiments received institutional animal care and use committee approval. In four rats for preliminary studies and 18 rats for formal assessment, MR imaging-compatible electrodes were inserted into the liver and MR imaging-monitored IRE procedures were performed at one of three electrode voltages (1000, 1500, or 2500 V), with T1- and T2-weighted images acquired before and immediately after application of the IRE pulses. MR imaging measurements were compared with both finite element modeling (FEM)-anticipated ablation zones and histologically confirmed ablation zones at necropsy. Intraclass and Spearman correlation coefficients were calculated for statistical comparisons. RESULTS MR imaging measurements permitted immediate depiction of IRE ablation zones that were hypointense on T1-weighted images and hyperintense on T2-weighted images. MR imaging-based measurements demonstrated excellent consistency with FEM-anticipated ablation zones (r > 0.90 and P < .001 for both T1- and T2-weighted images). MR imaging measurements were also highly correlated with histologically confirmed ablation zone measurements (rho > 0.90 and P < .001 for both T1- and T2-weighted images). CONCLUSION MR imaging permits immediate depiction of ablated tissue zones for monitoring of IRE ablation procedures. These measurements could potentially be used during treatment to elicit repeat application of IRE pulses or adjustments to electrode positions to ensure complete treatment of targeted lesions.
Inoculum Effects of Ceftobiprole, Daptomycin, Linezolid, and Vancomycin with Staphylococcus aureus and Streptococcus pneumoniae at Inocula of 105 and 107 CFU Injected into Opposite Thighs of Neutropenic Mice

ABSTRACT Reduced bactericidal efficacy at a high inoculum is known as the inoculum effect (IE). We used neutropenic mice to compare the IEs of ceftobiprole (CFB), daptomycin (DAP), linezolid (LZD), and vancomycin (VAN) against 6 to 9 strains of Staphylococcus aureus and 4 strains of Streptococcus pneumoniae at 2 inocula in opposite thighs of the same mice. Neutropenic mice had 104.5 to 105.7 CFU/thigh (low inoculum [LI]) in one thigh and 106.4 to 107.2 CFU/thigh (high inoculum [HI]) in the opposite thigh when treated for 24 h with subcutaneous (s.c.) doses every 12 h of DAP at 0.024 to 100 mg/kg of body weight and LZD at 0.313 to 320 mg/kg and s.c. doses every 6 h of CFB at 0.003 to 160 mg/kg and VAN at 0.049 to 800 mg/kg. Dose-response data were analyzed by a maximum effect (Emax) model using nonlinear regression. Static doses for each drug and at each inoculum were calculated, and the difference between HI and LI (IE index) gave the magnitude of IE for each drug-organism combination. Mean (range) IE indexes of S. aureus were 2.9 (1.7 to 4.6) for CFB, 4.1 (2.6 to 9.3) for DAP, 4.6 (1.7 to 7.1) for LZD, and 10.1 (6.3 to 20.3) for VAN. In S. pneumoniae, the IE indexes were 2.5 (1.3 to 3.3) for CFB, 2.0 (1.6 to 2.8) for DAP, 1.9 (1.7 to 2.2) for LZD, and 1.5 (0.8 to 3.2) for VAN; these values were similar for all drugs. In S. aureus, the IE was much larger with VAN than with CFB, DAM, and LZD (P < 0.05). An in vivo time course of vancomycin activity showed initiation of killing at 4- to 16-fold-higher doses at HI than at LI despite similar initial growth of controls.
General mortality and respiratory cancer among a cohort of male chemical workers in California.

Cohort mortality and nested case-control studies were conducted involving 2,901 men employed 1 year or more between 1940 and 1986 at any of four California facilities of a major chemical company. Employees experienced fewer deaths from each of the major causes than were expected based on U.S., California, and local county mortality rates. Respiratory cancer was significantly elevated in one socioeconomic category comprised of operators (SMR = 157, 95% CI = 109-220). The 34 cases who died from respiratory cancer and 136 matched controls, all of whom were operators, were included in a nested case-control study. Departments in which subjects had worked were grouped into 13 work assignment or product categories by an industrial hygienist without knowledge of case-control status. Smoking habits and other occupational exposures were ascertained by telephone interview from subjects or surrogate-responders. As expected, current cigarette smoking was strongly related to respiratory cancer. After adjustment for smoking, cases were significantly more likely than controls to have ever worked in one of the 13 work areas (supervision, services, and business support). However, no dose-response relationship was evident with duration of employment in this work area and the departments involved were associated with plant security and not chemical production. Results were similar when a 15-year latency period was assumed. These findings suggest that the excess of respiratory cancer mortality among operators was most likely due to differences in cigarette smoking or other factors not ascertained, rather than to a specific occupational exposure.
A Plan for Achieving Significant Improvement in Patient Safety

Improvement in systems that ensure safety in the provision of care is a high priority to hospital administrators, clinicians, and patients. Research to determine the approaches and methods that will result in the most significant patient safety improvements is underway but more is needed. This article describes the process for improving patient safety adopted at one hospital. Results of these efforts demonstrate significant improvement in staff understanding of patient safety measures. Staff survey results are supported by improvement in clinical indicators. Recommendations for future action and implications for other hospitals are discussed.
HIV‐1 co‐receptor expression on trophoblastic cells from early placentas and permissivity to infection by several HIV‐1 primary isolates

We examined CD4 and major HIV‐1 co‐receptor expression by trophoblast cells (TC) from early placentas, and the permissiveness of TC for infection by several natural HIV‐1 isolates in vitro. Ten early placentas (4–6 weeks of gestation) from HIV−women were obtained after elective abortion. CD4 and HIV‐1 co‐receptor expression by TC was examined in terms of both mRNA and protein. The same TC were then challenged with three clinical HIV isolates of known phenotype, two originating from mothers who transmitted the virus to their child and one from a vertically infected newborn. TC infection was detected by polymerase chain reaction. CD4 expression was detected in five of the 10 placentas, while membrane protein expression of CCR3, CXCR4 and CCR5 was detected in every case, despite quantitative differences among individuals. Bonzo, GPR1 and ChemR23 mRNAs were detected in all TC preparations. TC from seven out of eight placentas were permissive to HIV entry, but no productive viral replication was detected (reverse transcriptase activity in culture supernatants). Interestingly, the addition of chemokine(s) or a CD4‐blocking antibody to the cultures failed to inhibit TC virus entry. These data point to marked interindividual variability in HIV co‐receptor expression by trophoblast cells and show that TC from early placentas can be infected in vitro by clinical HIV‐1 isolates. They also suggest that viral entry in vitro might occur through a mechanism independent of both CD4 and chemokine receptors.
Dendritic Cells-Ontogeny.

Dendritic cells (DC) play key rolls in various aspects of immunity. The functions of DC depend on the subsets as well as their location or activation status. Understanding developmental lineages, precursors and inducing factors for various DC subsets would help their clinical application, but despite extensive efforts, the precise ontogeny of various DC, remain unclear and complex. Because of their many functional similarities to macrophages, DC were originally thought to be of myeloid-lineage, an idea supported by many in vitro studies where monocytes or GM-CSF (a key myeloid growth factor) has been extensively used for generating DC. However, there has been considerable evidence which suggests the existence of lymphoid-lineage DC. After the confusion of myeloid-/lymphoid-DC concept regarding DC surface markers, we have now reached a consensus that each DC subset can differentiate through both myeloid- and lymphoid-lineages. The identification of committed populations (such as common myeloid- and lymphoid progenitors) as precursors for every DC subsets and findings from various knockout (KO) mice that have selected lymphoid- or myeloid-lineage deficiency appear to indicate flexibility of DC development rather than their lineage restriction. Why is DC development so flexible unlike other hematopoitic cells? It might be because there is developmental redundancy to maintain such important populations in any occasions, or such developmental flexibility would be advantageous for DC to be able to differentiate from any "available" precursors in situ irrespective of their lineages. This review will cover ontogeny of conventional (CD8+/- DC) DC, plasmacytoid DC and skin Langerhans cells, and recently-identified many Pre-DC (immediate DC precursor) populations, in addition to monocytes and plasmacytoid DC, will also be discussed.
Lgl1 Is Suppressed in Oxygen Toxicity Animal Models of Bronchopulmonary Dysplasia and Normalizes During Recovery in Air

Bronchopulmonary dysplasia (BPD), a major cause of morbidity in premature infants, is characterized by arrest of lung growth and inhibited alveologenesis. We had earlier cloned late-gestation lung 1 (LGL1), a glucocorticoid (GC)-induced, developmentally regulated gene in lung mesenchyme, and showed that reduced levels of late-gestation lung 1 protein (lgl1) inhibit lung branching. Maximal fetal expression of LGL1 is concordant with the onset of alveolar septation, suggesting an additional role for lgl1 in alveologenesis. At postnatal d 7, during the period of maximal septation in postnatal rat lung, lgl1 concentrates at the tips of budding secondary alveolar septa. We studied two models of impaired postnatal alveologenesis generated by exposure of newborn rats to 60% O2 for 2 wk or 95% O2 for 1 wk. A profound decrease of lgl1 expression with oxygen exposure was observed in both animal models. Animals exposed to 95% O2 for 1 wk recovered in air over a 3-wk period, associated with normalization of lgl1 levels. Changes in lung levels of α-actin (a marker of myofibroblast differentiation associated with alveologenesis) and the mesenchymal marker vimentin were significant but less marked. Our findings support a role for lgl1 in postnatal lung development. We speculate that deficiency of lgl1 contributes to the arrested alveolar partitioning observed in BPD and that recovery is associated with normalization of lgl1 levels.
Percutaneous cholecystostomy: A bridge to surgery or definite management of acute cholecystitis in high-risk patients?

Objective. Cholecystectomy is the standard treatment for acute cholecystitis, but in high-risk patients with serious comorbidity and in patients of advanced age there is substantial morbidity and mortality associated with the intervention. In these selected patients, percutaneous cholecystostomy (PCS) is an alternative mode of management. The aim of the present study was to evaluate the outcome of PCS in selected patients with acute cholecystitis. Material and methods. Thirty-five patients, representing 0.6% of all acute cholecystitis patients managed during the period 1994–2003, were subjected to PCS. Patients’ charts were reviewed retrospectively for age, gender, comorbidity, hospital stay, procedure, complications and final outcome, including requirement of additional interventions. Results. PCS was considered successful in 34/35 patients, 26 of whom responded within 3 days. Two patients required additional cholecystectomy 3 days and 20 months, respectively, after the PCS procedure. Two patients underwent endoscopic retrograde cholangiopancreatography (ERCP) and one patient underwent rotation lithotripsy. Four patients suffered recurrent biliary complaints after the acute episode of cholecystitis, while the only serious procedure-related complication was bile leakage from the gallbladder in one patient, which necessitated cholecystectomy. Conclusions. PCS is a comparatively safe and efficient procedure in the treatment of acute cholecystitis in high-risk patients with serious comorbidity and in elderly patients, contraindicating the general anaesthesia required for laparoscopic or open cholecystectomy.
Are minimized perfusion circuits the better heart lung machines? Final results of a prospective randomized multicentre study

Introduction: Minimized perfusion circuits (MPCs), although aiming at minimizing the adverse effects of cardiopulmonary bypass, have not yet gained popularity. This can be attributed to concerns regarding their safety, as well as lack of sufficient evidence of their benefit. Methods: Described is a randomized, multicentre study comparing the MPC - ROCsafeRX to standard cardiopulmonary bypass in patients undergoing elective coronary artery bypass grafting and/ or aortic valve replacement. Results: Five hundred patients were included in the study (252 randomized to the ROCsafeRX group and 248 to standard cardiopulmonary bypass). Both groups were well matched for demographic characteristics and type of surgery. No operative mortality and no device-related complications were encountered. Transfusion requirement (333 ± 603 vs. 587 ± 1010 ml; p=0.001), incidence of atrial fibrillation (16.3% vs. 24.2%; p=0.03) and the incidence of major adverse events (9.1% vs. 16.5%; p=0.02) were all in favour of the MPC group. Conclusion: These results confirm both the safety and efficacy of the ROCsafeRX MPC for a large variety of cardiac patients. Minimized perfusion circuits should, therefore, play a greater role in daily practice so that as many patients as possible can benefit from their advantages.
[Effectiveness and safety of gabapentin in the preventive treatment of migraine].

INTRODUCTION Migraine is a frequent and disabling pathological condition with important socioeconomic repercussions. Recent studies have explored the use of antiepileptic drugs in the prophylactic treatment of migraine. Preliminary studies have shown that gabapentin is a drug that is effective and well tolerated by patients. AIM. To evaluate the effectiveness and safety of gabapentin in the prophylactic treatment of migraine. PATIENTS AND METHODS A prospective, open, multicentre, random clinical study, carried out according to IHS criteria, which compares the effectiveness and safety of gabapentin in 1,200 mg/day and 2,000 mg/day doses as a preventive treatment for migraine over a 16 week period. RESULTS Significant differences were found in patients treated with gabapentin, as compared with their basal state, in the following: a lower number of attacks (reduction in weeks 4, 10 and 16: 2.4 2.8, 2.9 2.9 and 3.1 2.9 attacks/month on a basal rate of 5.3 3.5 attacks/month), lower intensity (on a scale of 0 3 of increasing pain intensity: basal rate: 2.7 0.4, week 4: 1.8 0.9, week 10: 1.7 0.9, week 16: 1.4 1.0) and how long the pain lasts (basal rate 390 hours/month, week 4: 180 hours/month, week 10: 180 hours/month, week 16: 120 hours/month). No statistically significant differences were found between doses of 1,200 or 2,000 mg/day. Mild adverse effects were seen in 62 patients (37.8%): drowsiness (22.6%), asthenia (7.9%), dizziness (4.9%), abdominal pain (3.7%) and dazedness (3.7%). No serious adverse events occurred. CONCLUSIONS Gabapentin can be considered an effective and safe drug in the preventive treatment of migraine.
Analysis of cytological specimens from mediastinal lesions obtained by endoscopic ultrasound‐guided fine‐needle aspiration

Endoscopic ultrasound‐guided fine‐needle aspiration (EUS‐FNA) seems to be a powerful tool to obtain cytologic specimens from mediastinal and celiac lymph nodes, enlarged left adrenal glands, and intrapulmonary tumors with mediastinal extension. The diagnostic yield of EUS‐FNA and the accuracy of cytologic specimens was evaluated.
Chilean Validation of the Posttraumatic Stress Disorder Checklist–Civilian Version (PCL–C) after the Earthquake on February 27, 2010

Posttraumatic stress disorder (PTSD) is an anxiety disorder in which an individual re-experiences a traumatic event, avoids situations related to it, and shows excessive arousal. The disorder appears after experiencing a life-threatening event, such as a war or a natural disaster. Thus, the validation of tests which assess the disorder after the earthquake on February 27, 2010, in Chile is crucial for its evaluation and subsequent intervention. The present study includes psychometric data for the Posttraumatic Stress Disorder Checklist–Civilian version (PCL–C) on a sample of 509 survivors of the disaster. Values indicate good psychometric properties of the questionnaire.
Distinct Roles for Gαi2 and Gβγ in Signaling to DNA Synthesis and Gαi3 in Cellular Transformation by Dopamine D2S Receptor Activation in BALB/c 3T3 Cells

ABSTRACT Control of cell proliferation depends on intracellular mediators that determine the cellular response to external cues. In neuroendocrine cells, the dopamine D2 receptor short form (D2S receptor) inhibits cell proliferation, whereas in mesenchymal cells the same receptor enhances cell proliferation. Nontransformed BALB/c 3T3 fibroblast cells were stably transfected with the D2S receptor cDNA to study the G proteins that direct D2S signaling to stimulate cell proliferation. Pertussis toxin inactivates Gi and Go proteins and blocks signaling of the D2S receptor in these cells. D2S receptor signaling was reconstituted by individually transfecting pertussis toxin-resistant Gαi/o subunit mutants and measuring D2-induced responses in pertussis toxin-treated cells. This approach identified Gαi2 and Gαi3 as mediators of the D2S receptor-mediated inhibition of forskolin-stimulated adenylyl cyclase activity; Gαi2-mediated D2S-induced stimulation of p42 and p44 mitogen-activated kinase (MAPK) and DNA synthesis, whereas Gαi3 was required for formation of transformed foci. Transfection of toxin-resistant Gαi1 cDNA induced abnormal cell growth independent of D2S receptor activation, while Gαo inhibited dopamine-induced transformation. The role of Gβγ subunits was assessed by ectopic expression of the carboxyl-terminal domain of G protein receptor kinase to selectively antagonize Gβγ activity. Mobilization of Gβγ subunits was required for D2S-induced calcium mobilization, MAPK activation, and DNA synthesis. These findings reveal a remarkable and distinct G protein specificity for D2S receptor-mediated signaling to initiate DNA synthesis (Gαi2 and Gβγ) and oncogenic transformation (Gαi3), and they indicate that acute activation of MAPK correlates with enhanced DNA synthesis but not with transformation.