Miracle-dz/UniFAR-FTUs huggingface dataset:
Hypoxic-Ischemic Brain Injury and Prognosis After Cardiac Arrest

Purpose of Review: Cardiac death is the leading cause of death in the United States, and patients who have out-of-hospital cardiac arrest have only a 1% to 10% survival rate, despite improvements in advanced life support. The neurologic sequelae of hypoxic-ischemic brain injury after cardiac arrest vary from subtle cognitive impairment to coma, persistent vegetative state, and brain death. Neurologists are commonly asked to prognosticate neurologic outcome after cardiac arrest. Recent Findings: In 2002, two randomized controlled trials demonstrated that therapeutic hypothermia (32°C to 34°C [89.6°F to 93.2°F]) increases the odds of improved neurologic outcome and reduces the risk of death compared with normothermia when applied for the initial 12 to 24 hours after ventricular fibrillation or tachycardia cardiac arrest. Considerable research continues into neurologic prognostication after hypoxic-ischemic brain injury, especially with the advent of therapeutic hypothermia and its effects on the clinical examination, neurophysiologic studies, and serum biomarkers of brain injury. Recent reports indicate that poor motor response 72 hours after cardiac arrest, absent cortical responses on median nerve somatosensory-evoked potentials, and elevated neuron-specific enolase may not necessarily indicate poor prognosis in patients treated with therapeutic hypothermia compared with historical populations not treated with hypothermia, perhaps because of sedation and neuromuscular blockade. Summary: Neurologic prognostication after cardiac arrest remains challenging because of the sedation and neuromuscular blocking agents given to patients who undergo therapeutic hypothermia. A multimodal algorithmic approach (clinical, electrophysiologic, and possibly serum biomarker testing) is suggested for cardiac arrest patients treated with hypothermia, but further research is needed to determine more accurate prognostic predictors.
Challenges in nutrition-related DNA methylation studies

Abstract The rapid progress in nutritional epigenetics allowed for a much better understanding of the mechanisms involved in gene-nutrient interactions and the roles that nutrition has in transgenerational inheritance of acquired epigenetic traits. Studies indicated that a considerable number of nutrients or diet types are capable of inducing epimutations. In parallel, the rapid development of genome-wide DNA methylation detection methods allowed for a broader image on how nutrition impacts the epigenetic status in human and animal models. But this increased complexity in the epigenetic field and also brought important challenges that need resolution, or it suggests that some of the initial epigenetic paradigms have to be revisited or reconsidered. The aim of this review is to discuss the inherent challenges that need to be resolved, from both practical and theoretical aspects, stemming from the rapid progress in the field of nutritional epigenetics, with a focus on DNA methylation. Because such challenges are present at every stage of study development, the review systematically discusses the most common issues relevant to DNA methylation in a nutritional context. Various types of challenges and potential bias generators are discussed within study design, sample quality, detection methods, data processing, and statistical and bioinformatic analysis. Additional aspects to be considered include epigenetic heterogeneity of treatment groups, the role of genomic variability in introducing measurement bias and errors in interpretation of changes, and issues related to the final interpretation of results and in assigning functional significance. It is also posited that all these issues will be largely resolved within the next decade.
Posterior antebrachial cutaneous nerve conduction study technique.

PURPOSE This paper describes an improved electrodiagnostic methodology for posterior antebrachial cutaneous nerve (PABC) neuropathy based on retrospective analysis. METHODS Results of PABC nerve conduction studies in 14 control patients and 3 patients with left PABC neuropathy are included. Stimulation was performed 0.5 to 2.0 cm above the lateral epicondyle, and the recordings were acquired at 12 cm, 15 cm and 20 cm distally. Data was evaluated using the mean A+/- standard deviation, calculated for descriptive analysis of continuous variables whereas frequencies and percentages were determined for categorical variables. Abnormal cutoff values including side-side comparison values were established so that all normal control values would fall within the normal range. RESULTS PABC conduction studies with 20 cm recording distance demonstrated abnormal electrodiagnostic findings in all 3 patients, while more proximal recordings failed to document the neuropathy. CONCLUSION The recording of PABC responses at 12 cm, 15 cm and 20 cm distal to the stimulating electrode offers a more comprehensive evaluation and may be a more sensitive test for evaluation of suspected PABC neuropathy, in comparison to traditional 12 cm recording.
Human Kallikrein 10 Expression in Normal Tissues by Immunohistochemistry

The normal epithelial cell-specific 1 (NES1) gene (official name kallikrein gene 10, KLK10) was recently cloned and encodes for a putative secreted serine protease (human kallikrein 10, hK10). Several studies have confirmed that hK10 shares many similarities with the other kallikrein members at the DNA, mRNA, and protein levels. The enzyme was found in biological fluids, tissue extracts, and serum. Here we report the first detailed immunohistochemical (IHC) localization of hK10 in normal human tissues. We used the streptavidin-biotin method with two hK10-specific antibodies, a polyclonal rabbit and a monoclonal mouse antibody, developed in house. We analyzed 184 paraffin blocks from archival, current, and autopsy material, prepared from almost every normal human tissue. The staining pattern, the distribution of the immunostaining, and its intensity were studied in detail. Previously, we reported the expression of another novel human kallikrein, hK6, by using similar techniques. The IHC expression of hK10 was generally cytoplasmic and not organ-specific. A variety of normal human tissues expressed the protein. Glandular epithelia constituted the main immunoexpression sites, with representative organs being the breast, prostate, kidney, epididymis, endometrium, fallopian tubes, gastrointestinal tract, bronchus, salivary glands, bile ducts, and gallbladder. The choroid plexus epithelium, the peripheral nerves, and some neuroendocrine organs (including the islets of Langerhans, cells of the adenohypophysis, the adrenal medulla, and Leydig cells) expressed the protein strongly and diffusely. The spermatic epithelium of the testis expressed the protein moderately. A characteristic immunostaining was observed in Hassall's corpuscles of the thymus, oxyphilic cells of the thyroid and parathyroid glands, and chondrocytes. Comparing these results with those of hK6, we observed that both kallikreins had a similar IHC expression pattern.
Type I Interferons Are Not Critical for Skin Allograft Rejection or the Generation of Donor‐Specific CD8+ Memory T Cells

Type I interferons (IFN‐I) link innate to adaptive immunity in microbial infection, autoimmune disease and tumor immunity. It is not known whether IFN‐I have an equally central role in alloimmunity. Here we tested this possibility by studying skin allograft survival and donor‐specific CD8+ T‐cell responses in mice that lack the IFN‐I receptor (IFN‐IR−/−). We found that IFN‐IR−/− mice reject fully allogeneic wild‐type skin grafts at the same rate as wild‐type recipients. Similarly, allograft rejection was not delayed if IFN‐IR−/− male skin was transplanted to syngeneic IFN‐IR−/− female mice. Quantitation of the male (H‐Y)‐specific CD8+ T‐cell response in these mice revealed normal generation of donor‐specific CD8+ effector T cells but fourfold reduction in CD8+ memory T cells. Memory CD8+ T cells generated in the absence of IFN‐IR had normal phenotype and recall function, assessed by ex vivo cytokine production and the ability of IFN‐IR−/− mice to mount second set rejection. Finally, these memory T cells were maintained at a constant number despite their inability to respond to IFN‐1. Our findings indicate that IFN‐I cytokines are not critical for acute allograft rejection or for the expansion and differentiation of donor‐specific CD8+ T cells into long‐lived, functional memory T cells.
A controlled multiphase trial of ketotifen to minimize neurofibroma-associated pain and itching.

BACKGROUND AND DESIGN Based on potential contributions of mast cells to neurofibroma-associated itching, pain, and tenderness, the mast cell blocker ketotifen fumarate (Zaditen, Sandoz Pharmaceuticals Corp, Hanover, NJ) has been proposed as a treatment for these symptoms. To test the hypothesis that ketotifen decreases neurofibroma-associated itching, pain, and tenderness, data were accumulated from two protocols. The first was an open-label protocol involving 25 patients with relatively severe symptoms (1170 patient-months), and the second was a double-blind protocol involving 27 patients with either relatively mild or severe neurofibroma-associated symptoms (316 patient-months). All subjects received either oral placebo or 2 to 4 mg of ketotifen fumarate per day. Using a scale of 1 to 10, symptoms were measured before, during, and after treatment. RESULTS Itching severity scores (means) were as follows: for all patients receiving ketotifen, 7.8 before, 2.8 during, and 7.2 after treatment; for ketotifen-treated patients in the double-blind protocol, 6.6 before, 3.9 during, and 6.4 after treatment; and for placebo-treated patients, 6.0 before and 6.0 during treatment. Pain and tenderness severity scores (means) were as follows: for all patients treated with ketotifen, 7.6 before, 3.6 during, and 6.6 after treatment; for double-blind ketotifen-treated patients, 6.3 before, 4.6 during, and 6.1 after treatment; and for placebo-treated patients, 7.9 before and 6.7 during treatment. CONCLUSIONS Pretreatment, treatment, and posttreatment levels of itching, pain, and tenderness associated with neurofibromas, using both open-label and double-blind protocols, indicate that ketotifen offers a realistic approach to treating these symptoms.
A Taurolidine–Citrate–Heparin Lock Solution Effectively Eradicates Pathogens From the Catheter Biofilm in Hemodialysis Patients

Catheter-related bacteremia (CRB) is a typical complication of hemodialysis catheter use. Catheter lumen colonization by pathogens is regarded as a direct cause of CRB. Once settled, the catheter biofilm increases the risk of developing infection, thus necessitating insertion replacement and antibiotic treatment. The study assessed the self-sufficient efficacy of taurolidine–citrate–heparin lock solution in eradicating catheter biofilm bacteria and keeping it sterile in patients on hemodialysis. Twenty-nine chronic patients on hemodialysis with tunneled and nontunneled catheters locked with a heparin filling (the mean time of heparin lock use −30.1 ± 2.0 days) and subsequently converted to a taurolidine–citrate–heparin filling were included. Peripheral vein and catheter lumen blood cultures were obtained before the filling change and after taurolidine–citrate–heparin lock use (mean time 33.8 ± 7.6 days). Twenty-four participants with tunneled and nontunneled catheters locked with taurolidine–citrate–heparin filling served as the control group. During the heparin-locking period, CRB was diagnosed in 3 cases (only nontunneled catheters). The catheter blood cultures findings were positive in 23 patients (10 temporary and 13 permanent catheters), whereas both the catheter and peripheral vein blood cultures were sterile in 3 of 29 subjects (only permanent catheters). Irrespective of catheter type (tunneled or nontunneled), repeated culture revealed no pathogens in any of the 23 patients with initial positive catheter blood culture, after the use of taurolidine–citrate–heparin filling. No positive blood culture was noted in the control group. The taurolidine–citrate–heparin lock solution effectively eradicated pathogens from nontunneled and tunneled catheter biofilms and helped to maintain catheter lumen sterility.
Relationship and Differential Validity of Alexithymia and Depression: A Comparison of the Toronto Alexithymia and Self-Rating Depression Scales

Theoretically, the constructs of alexithymia and depression share many common characteristics. Empirically moderate correlations between measures of alexithymia and depression have been found, hence it has been argued that the Toronto Alexithymia Scale (TAS) may be, at least in some part, just another measure for depression. The purpose of this study was to evaluate the construct validity of alexithymia and to analyze the relationship between alexithymia and depression. Exploratory and confirmatory factor analyses were conducted on the combined items of the TAS-20 and the Self-Rating Depression Scale (SDS) in a psychosomatic and alcoholic inpatient sample (n = 199) and a sample of normal adults (controls, n = 174). The exploratory factor analysis in the patient sample yielded a 4-factor structure. Within each factor there was no overlap between the items of the TAS-20 and the SDS. Two factors were comprised of items of the TAS-20 and two factors consisted of items of the SDS. This 4-factor model also showed an acceptable fit for the data of the normal sample in a confirmatory factor analysis. Moderate correlations between the TAS- 20 and SDS total scores and some factors were found. Both instruments, the TAS-20 and the SDS, seem to measure distinct constructs and are not just different measures for the same underlying construct. This provides support for the differential validity of the alexithymia and depression constructs and is in accordance with previous findings.
SEPSIS-INDUCED INTESTINAL MICROVASCULAR AND INFLAMMATORY RESPONSES IN OBESE MICE

Although clinical obesity is associated with increases in the morbidity and mortality of sepsis, little is known about the mechanisms that underlie the influence of obesity on sepsis. The objective of this study was to determine (a) whether obesity is associated with exaggerated inflammatory and thrombogenic responses in the intestinal microvasculature of septic mice and (b) whether these microvascular alterations are related to changes in the serum levels of cytokines that are produced by adipose tissue. Intravital microscopy was used to quantify leukocyte and platelet adhesion in intestinal postcapillary venules of lean wild-type (WT) mice, and two murine models of obesity, that is, ob/ob and db/db mice. Sepsis was induced by cecal ligation and perforation (CLP). Serum cytokine levels were measured using a cytometric bead assay, whereas adipokines were quantified using enzyme-linked immunosorbent assay. Cecal ligation and perforation elicited significant increases in the adhesion of leukocytes and platelets in venules of lean WT mice. These CLP-induced adhesive interactions were much more pronounced in the microvasculature of both ob/ob and db/db mice. Cecal ligation and perforation was associated with significant increases in serum cytokines in both WT and ob/ob mice, but such changes were not detected in db/db mice. However, db/db (but not WT or ob/ob) mice did exhibit significant increases in serum leptin and adiponectin levels after CLP. Sepsis promotes more intense inflammatory and thrombogenic responses in the gut microcirculation of obese mice than in their lean counterparts. The obesity-enhanced microvascular dysfunction in septic mice shows no consistent correlation with serum cytokines or adipokines.
[Toxicological studies on puffer fishes:comparison of toxicities in the various species].

The toxicity variations of puffer fishes toxin on species, sex, organs seasons and sea area collecting subjects were observed in 615. subjects of 15 species during 1978-1981. The remarkable differences of toxicity were found by species and/or by subjects. Takifugu pardalis, Takifugu poecilonotus and Takifugu niphobles, which are habitually eaten in Japan, had a strong toxicity and some of them were strongly toxic in the muscle. It was indicated that female puffer fishes have a higher toxicity than the male. In particular, the toxicity from genital organs was significantly higher in the female puffer fishes than in male. No difference no sex was observed in the skin. Compared with the toxicities on the collecting sea areas, Inland sea of Seto and Japan sea, the mean of toxicity and the incidence rate of toxic subjects collected in Japan sea were higher than those of in Inland Sea of Seto i.e. The difference was observed by the living sea environment of puffer fishes. The wild Takifugu rubripes was obviously more toxic than the cultured. It was suggested that the variations between the wild and cultured puffer fishes should be due to the difference of the metabolism for the production and accumulation of tetrodotoxin which would be influenced by the foods and the closed environment.
Genome‐wide screen identifies Escherichia coli TCA‐cycle‐related mutants with extended chronological lifespan dependent on acetate metabolism and the hypoxia‐inducible transcription factor ArcA

Single‐gene mutants with extended lifespan have been described in several model organisms. We performed a genome‐wide screen for long‐lived mutants in Escherichia coli, which revealed strains lacking tricarboxylic acid (TCA)‐cycle‐related genes that exhibit longer stationary‐phase survival and increased resistance to heat stress compared to wild‐type. Extended lifespan in the sdhA mutant, lacking subunit A of succinate dehydrogenase, is associated with the reduced production of superoxide and increased stress resistance. On the other hand, the longer lifespan of the lipoic acid synthase mutant (lipA) is associated with reduced oxygen consumption and requires the acetate‐producing enzyme pyruvate oxidase, as well as acetyl‐CoA synthetase, the enzyme that converts extracellular acetate to acetyl‐CoA. The hypoxia‐inducible transcription factor ArcA, acting independently of acetate metabolism, is also required for maximum lifespan extension in the lipA and lpdA mutants, indicating that these mutations promote entry into a mode normally associated with a low‐oxygen environment. Because analogous changes from respiration to fermentation have been observed in long‐lived Saccharomyces cerevisiae and Caenorhabditis elegans strains, such metabolic alterations may represent an evolutionarily conserved strategy to extend lifespan.
Pancreatic cancer cells invasiveness is mainly affected by interleukin-1beta not by transforming growth factor-beta1.

BACKGROUND We investigated in vitro whether IL-1beta and TGF-beta1 affect pancreatic cancer cell growth, adhesion to the extracellular matrix and Matrigel invasion. MATERIALS AND METHODS Adhesion to fibronectin, laminin and type I collagen, and Matrigel invasion after stimulation with saline, IL-1beta and TGF-beta1 were evaluated using three primary and three metastatic pancreatic cancer cell lines. RESULTS Extracellular matrix adhesion of control cells varied independently of the metastatic characteristics of the studied cell lines, whereas Matrigel invasion of control cells was partly correlated with the in vivo metastatic potential. IL-1beta did not influence extracellular matrix adhesion, whereas it significantly enhanced the invasiveness of three of the six cell lines. TGF-beta1 affected the adhesion of one cell line, and exerted contrasting effects on Matrigel invasion of different cell lines. CONCLUSIONS IL-1beta enhances the invasive capacity of pancreatic cancer cells, whereas TGF-beta1 has paradoxical effects on pancreatic cancer cells; this makes it difficult to interfere with TGF-beta1 signaling in pancreatic cancer treatment.
Hormonally mediated negative regulation of human pro-opiomelanocortin gene expression after transfection into mouse L cells

We report results indicating that expression and hormonally controlled negative regulation of the human pro-opiomelanocortin (POMC) gene in mouse fibroblasts can be accomplished by the placement nearby of a simian virus 40 enhancer sequence. Expression resulting from correctly initiated transcription required the enhancer in cis both in cells stably transfected with the POMC gene and in a transient expression assay with constructs that fused that POMC promoter region to the protein-coding region of the herpes simplex virus thymidine kinase (TK) gene. Negative regulation of POMC transcription by glucocorticoids was demonstrated in transiently infected cells by assaying for TK activity encoded by the POMC-TK fusion constructs and by quantitative S1 nuclease mapping. The sequences responsible for such regulation were shown to be contained within a DNA segment that extends 670 base pairs upstream from the cap site for POMC mRNA.
Behavioral and cardiovascular effects of 7.5% CO2 in human volunteers

The study of carbon dioxide (CO2) inhalation in psychiatry has a long and varied history, with recent interest in using inhaled CO2 as an experimental tool to explore the neurobiology and treatment of panic disorder. As a consequence, many studies have examined the panic‐like response to the gas either using the single or double breath 35% CO2 inhalation or 5–7% CO2 inhaled for 15–20 min, or rebreathing 5% CO2 for a shorter time. However, this lower dose regime produces little physiological or psychological effects in normal volunteers. For this reason we have studied the effects of a higher concentration of CO2, 7.5%, given over 20 min. Twenty healthy volunteers were recruited to a double blind, placebo‐controlled study where air and 7.5% CO2 were inhaled for 20 min. Cardiovascular measures and subjective ratings were obtained. When compared to air, inhaling 7.5% CO2 for 20 min increases systolic blood pressure and heart rate, indicating increased autonomic arousal. It also increases ratings of anxiety and fear and other subjective symptoms associated with an anxiety state. The inhalation of 7.5% CO2 for 20 min is safe for use in healthy volunteers and produces robust subjective and objective effects. It seems promising as an anxiety provocation test that could be beneficial in the study of the effects of anxiety on sustained performance, the discovery of novel anxiolytic agents, and the study of brain circuits and mechanisms of anxiety. Depression and Anxiety 00:000–000, 2005. © 2005 Wiley‐Liss, Inc.
Nonenhanced helical CT and US in the emergency evaluation of patients with renal colic: prospective comparison.

PURPOSE To compare nonenhanced helical computed tomography (CT) with ultrasonography (US) for the depiction of urolithiasis. MATERIALS AND METHODS During 9 months, 45 patients (mean age, 44 years; mean weight, 92.5 kg) prospectively underwent both nonenhanced helical CT (5-mm collimation; pitch of 1.5) and US of the kidneys, ureters, and bladder. US evaluation included a careful search for ureteral calculi. Presence of calculi and obstruction and incidental diagnoses were recorded. Clinical, surgical, and/or imaging follow-up data were obtained in all patients. The McNemar test was used to compare groups. RESULTS Diagnoses included 23 ureteral calculi and one each of renal cell carcinoma, appendicitis, ureteropelvic junction obstruction, renal subcapsular hematoma, cholelithiasis, medullary calcinosis, and myelolipoma. CT depicted 22 of 23 ureteral calculi (sensitivity, 96%). US depicted 14 of 23 ureteral calculi (sensitivity, 61%). Differences in sensitivity were statistically significant (P: =.02). Specificity for each technique was 100%. When modalities were compared for the detection of any clinically relevant abnormality (eg, unilateral hydronephrosis and/or urolithiasis in patients with an obstructing calculus), sensitivities of US and CT increased to 92% and 100%, respectively. One case of appendicitis was missed at US, whereas medullary calcinosis and myelolipoma were missed at CT. CONCLUSION Nonenhanced CT has a higher sensitivity for the detection of ureteral calculi compared with US.