Miracle-dz/UniFAR-FTUs huggingface dataset:
[Guidelines for preventing health-care-associated pneumonia].

Because of the high morbidity and mortality associated with health-care-associated pneumonia, it is important to implement evidence-based prevention measures. Recently by CDC published Guidelines for Preventing Health-Care-Associated Pneumonia describe prevention measures based on evaluated studies, randomized controlled trials or meta-analyses. In this paper the most important prevention measures are given, as well as the evidence classification. "Among the changes in the recommendations to prevent bacterial pneumonia, especially ventilator-associated pneumonia, are the preferential use of or tracheal rather than naso-tracheal tubes in patients who receive mechanically assisted ventilation, the use of noninvasive ventilation to reduce the need for and duration of endotracheal intubation, changing the breathing circuits of ventilators when they malfunction or are visibly contaminated, and (when feasible) the use of an endotracheal tube with a dorsal lumen to allow drainage of respiratory secretions. "
Molecular defects in mucosal serotonin content and decreased serotonin reuptake transporter in ulcerative colitis and irritable bowel syndrome.

BACKGROUND & AIMS Serotonin (5-HT) is a critical signaling molecule in the gut. 5-HT released from enterochromaffin cells initiates peristaltic, secretory, vasodilatory, vagal, and nociceptive reflexes. Despite being pathophysiologically divergent, ulcerative colitis (UC) and irritable bowel syndrome (IBS) are both associated with clinical symptoms that include alterations in the normal patterns of motility, secretion, and sensation. Our aim was to test whether enteric 5-HT signaling is defective in these disorders. METHODS Rectal biopsy specimens were obtained from healthy controls and patients with UC, IBS with diarrhea (IBS-D), and IBS with constipation (IBS-C). Key elements of 5-HT signaling, including measures of 5-HT content, release, and reuptake, were analyzed with these samples. RESULTS Mucosal 5-HT, tryptophan hydroxylase 1 messenger RNA, serotonin transporter messenger RNA, and serotonin transporter immunoreactivity were all significantly reduced in UC, IBS-C, and IBS-D. The enterochromaffin cell population was decreased in severe UC samples but was unchanged in IBS-C and IBS-D. When 5-HT release was investigated under basal and mechanical stimulation conditions, no changes were detected in any of the groups relative to controls. CONCLUSIONS These data show that UC and IBS are associated with similar molecular changes in serotonergic signaling mechanisms. While UC and IBS have distinct pathophysiologic properties, these data suggest that shared defects in 5-HT signaling may underlie the altered motility, secretion, and sensation. These findings represent the first demonstration of significant molecular alterations specific to the gut in patients with IBS and support the assertion that disordered gastrointestinal function in IBS involves changes intrinsic to the bowel.
Detection of ubiquitous and heterogeneous mutations in cell-free DNA from patients with early-stage non-small-cell lung cancer.

BACKGROUND The aim of this pilot study was to assess whether both ubiquitous and heterogeneous somatic mutations could be detected in cell-free DNA (cfDNA) from patients with early-stage non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS Three stage I and one stage II primary NSCLC tumors were subjected to multiregion whole-exome sequencing (WES) and validated with AmpliSeq. A subset of ubiquitous and heterogeneous single-nucleotide variants (SNVs) were chosen. Multiplexed PCR using custom-designed primers, coupled with next-generation sequencing (mPCR-NGS), was used to detect these SNVs in both tumor DNA and cfDNA isolated from plasma obtained before surgical resection of the tumors. The limit of detection for each assay was determined using cfDNA from 48 presumed-normal healthy volunteers. RESULTS Tumor DNA and plasma-derived cfDNA was successfully amplified and sequenced for 37/50 (74%) SNVs using the mPCR-NGS method. Twenty-five (68%) were ubiquitous and 12 (32%) were heterogeneous SNVs. Variant detection by mPCR-NGS and WES-AmpliSeq in tumor tissue was well correlated (R(2) = 0.8722, P < 0.0001). Sixteen (43%) out of 37 SNVs were detected in cfDNA. Twelve of these were ubiquitous SNVs with a variant allele frequency (VAF) range of 0.15-23.25%, and four of these were heterogeneous SNVs with a VAF range of 0.28-1.71%. There was a statistically significant linear relationship between the VAFs for tumor and cfDNA (R(2) = 0.5144; P = 0.0018). For all four patients, at least two variants were detected in plasma. The estimated number of copies of variant DNA present in each sample ranged from 5 to 524. The average number of variant copies required for detection (VCRD) was 3.16 (range: 0.2-7.6 copies). CONCLUSIONS The mPCR-NGS method revealed intratumor heterogeneity in early-stage NSCLC tumors, and was able to detect both ubiquitous and heterogeneous SNVs in cfDNA. Further validation of mPCR-NGS in cfDNA is required to define its potential use in clinical practice.
Protein dynamics in sperm membranes: Implications for sperm function during gamete interaction

A number of mammalian sperm plasma membrane antigens have been implicated as playing a functional role in sperm‐egg interaction, by virtue of the fact that antibodies against these antigens interfere with fertilization. Two such muse sperm plasma membrane antigens are M42, a 200/220 kD glycoprotein doublet, and M5, a 150–160 kD glycoprotein. We show that both of these antigens are concentrated on the posterior region of caudal epididymal and capacitated mouse sperm heads and are relatively diffusible, as determined by fluorescence recovery after photobleaching measurements (D = 3–8 × 10–9 cm2/s with ∼ 23% diffusing). Crosslinking of these antigens with bivalent antibodies causes them to redistribute into the anterior region (acrosomal crescent) of the sperm head. In contrast, we describe a third antigen, P220, which is also localized to the posterior region of the sperm head on caudal epididymal sperm but which exhibits very little diffusion and does not redistribute upon crosslinking. Bivalent anti‐M42 blocks the ZP3‐induced acrosome reaction. We have found that monovalent Fab fragments of anti‐M42 do not block the ZP3‐induced acrosome reaction, but that inhibition is restored by addition of a second antibody which crosslinks the Fabs. Thus, crosslinking is required for both inhibition of the acrosome reaction and redistribution. This suggests that redistribution of antigen away from the posterior region of the head may be part of the mechanism of inhibition of the ZP3‐induced acrosome reaction. © 1992 Wiley‐Liss, Inc.
Enhanced circulating levels of neurally derived calcitonin gene related peptide in spontaneously hypertensive rats.

STUDY OBJECTIVE Calcitonin gene related peptide (CGRP) is a potent endogenous vasodilator. The peptide is released from perivascular nerve endings and can normally be detected in the circulation. An attempt was made to determine the concentrations and partially characterise the immunoreactive forms of circulating CGRP in a genetically hypertensive rat strain, the "spontaneously hypertensive rat" (SHR) and its genetic control, Wistar-Kyoto (WKY). DESIGN Immunoreactive plasma CGRP levels were measured using a highly sensitive carboxyl terminal specific CGRP radioimmunoassay together with high performance liquid chromatography. Plasma immunoreactive CGRP (i-CGRP) levels were also measured 6 h after intraperitoneal colchicine administration (10 mg.kg-1 body weight) to both groups of rats. EXPERIMENTAL MATERIAL Eight SHR rats were compared with eight WKY rats, both groups aged 7 weeks. MEASUREMENTS AND MAIN RESULTS Mean i-CGRP levels were threefold higher in the SHR group compared to controls, while plasma calcitonin levels were not different between the two groups. There was a significant correlation (Kendall's correlation coefficient, r = 0.57; p = 0.024) between i-CGRP levels and the mean systolic blood pressure (measured by the indirect tail cuff method) in SHR but not WKY rats. Similar profiles of i-CGRP were observed in both SHR and WKY rats, when acid-methanol extracts of pooled plasma were chromatographed under similar conditions. It was also confirmed that circulating CGRP in both SHR and WKY strains was derived from perivascular nerve endings, by demonstrating a complete abolition from plasma of previously detectable i-CGRP following the administration of colchicine. CONCLUSIONS The study shows that CGRP is normally released from vascular nerve endings, and that high concentrations of the circulating peptide are found in hypertension. This might represent a mechanism to counteract the excessive vasoconstrictor influences that underly the development and maintenance of hypertension.
Implication of Central Asymmetry in Speech Processing on Selecting the Ear for Cochlear Implantation

Objective: Emerging evidence in auditory neuroscience suggests that central auditory pathways process speech asymmetrically. In concert with left cortical specialization for speech, a "right-ear advantage" in speech perception has been identified. The purpose of this study is to determine if this central asymmetry in speech processing has implications for selecting the ear for cochlear implantation. Study Design: Retrospective cohort study. Setting: Academic university medical center Patients: One hundred one adults with bilateral severe-to-profound sensorineural hearing loss Intervention: Cochlear implantation with the Nucleus 24 Contour device. Main Outcome Measurements: Patients were divided into two groups according to the ear implanted. Results were compared between left-ear- and right-ear-implanted patients. Further subgroup analysis was undertaken, limited to right-handed patients. Postoperative improvement on audiograms and scores on speech perception tests (Hearing in Noise test, City University of New York in quiet and in noise test, Consonant-Vowel Nucleus- Consonant words, and phonemes) at 1 year was compared between groups. Analysis of covariance was used to control for any intergroup differences in preoperative characteristics. Results: The groups were matched in age, duration of hearing loss, duration of hearing aid use, percentage implanted in the better hearing ear, and preoperative audiologic testing. Postoperatively, there were no differences between left-ear- and right-ear-implanted patients in improvement on speech recognition tests. Conclusion: Despite central asymmetry in speech processing, our data do not support a right-ear advantage in speech perception outcomes with cochlear implantation. Therefore, among the many factors in choosing the ear for cochlear implantation, central asymmetry in speech processing does not seem to be a contributor to postoperative speech recognition outcomes.
Emotional Reactivity and Risk for Psychopathology Among Adolescents

Abstract Various aspects of personality or dispositional style predict risk for psychiatric disorders among adults. In particular, signs of neuroticism, emotional reactivity, or sensitivity to stress are strong predictors of later mood or anxiety disorders. The current report extends this literature to adolescents. An epidemiologic sample of 776 young people living in upstate New York received psychiatric assessments based on the Diagnostic and Statistical Manual of Mental Disorders, Third Edition-Revised, (DSM-III-R) and a self-report assessment of personality style in 1983 and 1985. Psychopathology was again assessed in 1992. The current study first examined demographic correlates of emotional reactivity. The study then considered the predictive relationship between emotionally reactive personality style at one study wave and psychopathology at later waves. In middle but not early adolescence, girls showed higher levels of emotional reactivity than boys. In turn, high levels of emotional reactivity predicted a range of psychiatric disorders at follow-up. The most consistent associations emerged for major depression and fearful spells, a term the authors use to describe a subclinical form of panic attacks. As in adults, midadolescent girls rate themselves as more emotionally reactive than midadolescent boys. Moreover, adolescents who rate themselves as emotionally reactive face a high risk for mood and anxiety disorders. High levels of emotional reactivity may represent a manifestation of underlying neurobiologic risk for mood and anxiety disorders.
Comparison between repeat bolus intrathecal morphine and an epidurally delivered bupivacaine and fentanyl combination in the management of post-thoracotomy pain with or without cyclooxygenase inhibition.

OBJECTIVE To compare the analgesic efficacy of a traditional epidurally delivered bupivacaine/fentanyl combination with a repeat bolus intrathecal morphine technique in the management of post-thoracotomy pain and to assess further the effect of cyclooxygenase (COX) inhibition on both modalities. DESIGN Prospective, randomized, blinded study. SETTING University teaching hospital. PARTICIPANTS Patients having thoracic surgery. INTERVENTIONS Epidural and intrathecal catheters were inserted. Blood and urine samples were collected for analysis. COX-1 and COX-2 inhibition with ibuprofen and nimesulide (COX-2 selective) was instituted. MEASUREMENTS AND MAIN RESULTS Pain was assessed at rest and coughing by visual analog scale. Peak expiratory flow rate, patient satisfaction rating, sedation score, analgesic requirements, and preoperative and postoperative urinary creatinine levels were measured. The spinal and nimesulide combination showed the lowest pain scores (p < 0.001), least reduction in peak expiratory flow rate (p < 0.001), and highest patient satisfaction rating (p = 0.02). COX inhibition did not affect analgesic requirements in the epidural group or increase urinary creatinine in any group. CONCLUSION The intrathecal morphine and nimesulide combination offered significantly better analgesia than any other combination studied. The efficacious interaction between opioids and nonsteroidal anti-inflammatory drugs may be COX-2 mediated.
Postoperative Epidural Morphine for Postpartum Tubal Ligation Analgesia

Women undergoing postoperative postpartum tubal ligation (PPTL) often experience considerable pain. We hypothesized that epidural morphine, as part of a multi-modal analgesic regimen, would decrease postoperative pain and the need for systemic analgesia after PPTL. In a double-blinded study, patients were randomized to receive epidural saline or morphine 2 mg, 3 mg, or 4 mg after epidural anesthesia for PPTL. Postoperatively, ibuprofen 600 mg was administered every 6 h and patients could request acetaminophen 325 mg/hydrocodone 10 mg. The primary outcome variable was time to first request for supplemental analgesia. Verbal rating scores for pain and the incidence and severity of side effects were recorded for 24 h. Morphine group subjects requested supplemental analgesia later and received fewer doses compared with the saline group subjects. Peak cramping and incisional verbal rating scores for pain and the area under the verbal rating scores for pain × time curve for cramping pain were less after epidural morphine compared with saline, but there were no differences among morphine groups. Nausea, vomiting, and pruritus occurred more often in all morphine groups and subjects who received morphine 4 mg required treatment for these side effects more frequently than the saline or morphine 2 mg groups. In conclusion, epidural morphine 2 mg as part of a multi-modal analgesic regimen improved analgesia and decreased the need for supplemental analgesics after PPTL. The need to treat side effects with morphine 2 mg was not increased compared to a regimen of oral acetaminophen/opioid/nonsteroidal antiinflammatory analgesics.
Obviating much of the need for insulin therapy in type 2 diabetes mellitus: A re-assessment of insulin therapy’s safety profile

ABSTRACT Current processes of care for diabetes mellitus (DM) were shaped during the era when insulin therapy was considered inexorable to the management of advanced stage type 2 (T2DM), though this no longer appears to be categorically true. There are also dashed hopes that insulin therapy can prevent or stall diabetes. While exogenous insulin remains a life-sparing tool for fully insulin-dependent DM, insulin therapy-induced hyperinsulinemia now appears to contribute to serious safety issues beyond hypoglycemia and weight gain. Iatrogenic and compensatory hyperinsulinemia are metabolic disruptors of β-cells, liver, muscle, kidney, brain, heart and vasculature, inflammation, and lipid homeostasis, among other systems. This may compromise β-cells, exacerbate insulin resistance (IR), and increase risk of cardiovascular (CV) disease. Striking associations between exogenous insulin and risks of CV events, cancer, and all-cause mortality in clinical trial and real-world cohorts caution that insulin may pose more harm than previously evidenced. At our disposal are numerous alternate tools that, alone or in combination, efficaciously manage hyperglycemia and glucolipotoxicity, and do so without inducing hypoglycemia, weight gain, or hyperinsulinemia. Moreover, these new tools support true precision therapy, as modern day drug classes can be aligned with the various mediating pathways of hyperglycemia at work in any given patient. Some also appear to promote β-cell survival, with intriguing data being presented for newer agents, such as incretins. As such, we encourage preferential use of non-insulin antidiabetic agents to injected insulin for the management of non-insulin-dependent patients with T2DM, including in advanced stage T2DM. The goal of this article is to augment existing literature to 1) correct misconceptions on the rationale and necessity for insulin therapy in T2DM, 2) discuss emerging negative safety data with insulin therapy, and, 3) offer a practical means to reduce reliance on insulin through delayed initiation, minimized dose, and, drug switching to safer agents, and, potentially, reframes processes of care.
Effects of castration and testosterone substitution on body composition and muscle metabolism in rats.

Male weanling Wistar rats were castrated or sham-operated and followed for 12 weeks without substitution or with large (2 mg . 14 days-1) or small (0.2 mg . 14 days-1) intramuscular dose of testosterone enantate. Castration without substitution was associated with lower body weight and smaller fat cell sizes in different adipose tissue depots. The epididymal and caudal subcutaneous depots were the most sensitive to castration. The percentage of fast-twitch high-oxidative (type II A) muscle fibers decreased in the non-substituted castrated animals. There was a decrease in phosphorylase and lactate dehydrogenase activities in the white portion of the gastrocnemius muscle of the castrates. These changes were reversed by the large dose of testosterone. Removal of testosterone by castration thus seems to "feminize" male rats with respect to body composition and muscle metabolism.
Mecamylamine (a nicotine antagonist) for smoking cessation.

BACKGROUND Mecamylamine is a nicotine antagonist (that is it blocks the effect of nicotine). The rationale for its use in smoking cessation is that it may block the rewarding effect of nicotine and thus reduce the urge to smoke. OBJECTIVES The objective of this review was to determine the effectiveness of mecamylamine in promoting smoking cessation, either alone or in combination with nicotine replacement therapy. SEARCH STRATEGY We searched the Cochrane Tobacco Addiction Group trials register. SELECTION CRITERIA Randomised trials of mecamylamine, either alone or in combination with nicotine replacement therapy, which reported smoking cessation rates at least six months after intervention. DATA COLLECTION AND ANALYSIS We extracted data in duplicate on the type of subjects, the dose and duration of the mecamylamine and nicotine treatments, side-effects of treatment, the outcome measures, method of randomisation, and completeness of follow-up. The main outcome measure was sustained abstinence from smoking (biochemically validated) after at least six months follow-up in patients smoking at baseline. Smokers lost to follow-up were regarded as being continuing smokers. Because of the preliminary nature of available data, we did not perform meta-analysis but report the results narratively. MAIN RESULTS We identified two studies, both from the same investigators. In a study of 48 volunteers, a combination of mecamylamine plus nicotine patch was more effective than nicotine patch alone (abstinence rate at one year 37.5% vs 4.2%). In a second study, 80 volunteers were treated for four weeks prior to cessation with one of four treatments: 1. Nicotine patch plus mecamylamine capsules 2. Nicotine alone 3. Mecamylamine alone 4. No active drug. All four groups received combination treatment with nicotine and mecamylamine after the scheduled quit date. The abstinence rates in these four groups were respectively 40%, 20%, 15% and 15%. The higher abstinence rate in the group treated with combination therapy was not statistically significant. The authors reported a statistically significant benefit of mecamylamine using Kaplan-Meier survival analysis. In the doses used, mecamylamine was well tolerated, although up to 40% of subjects required reductions in dose, usually because of constipation. REVIEWER'S CONCLUSIONS Data from two small studies suggest that the combination of nicotine and mecamylamine may be superior to nicotine alone in promoting smoking cessation. However, these results require confirmation in larger studies before the treatment can be recommended clinically.
Effects of dopamine in lung‐transplanted pigs at 32°C

Background: We have used hypothermia successfully in patients with acute respiratory failure after lung transplantation. However, we have observed that dopamine may cause a substantial decrease in mean arterial pressure (MAP) in hypothermic subjects. Furthermore, a dopamine‐induced increase in pulmonary vascular resistance (PVR) has been reported in the literature, and this could aggravate the increase in PVR which is often seen both in the early postoperative phase after lung transplantation, and during hypothermia. We thus hypothesized that dopamine would decrease MAP and increase PVR in hypothermic lung‐transplanted subjects.