Miracle-dz/UniFAR-FTUs huggingface dataset:
Lower esophageal sphincter relaxation and activation of medullary neurons by subdiaphragmatic vagal stimulation in the mouse.

BACKGROUND & AIMS Isolated lower esophageal sphincter (LES) relaxation associated with belching and vomiting and the transient LES relaxation associated with gastroesophageal reflux are gastric afferent-mediated vagovagal reflexes. We aimed to identify the brain stem vagal subnuclei involved in these reflexes. METHODS In anesthetized mice, LES pressures were recorded using a manometric technique and response to electrical stimulation of the ventral trunk of subdiaphragmatic vagus was investigated. Anatomy of the vagal subnuclei was defined, and activated subnuclei with ventral subdiaphragmatic vagus stimulation were detected by c-fos immunohistochemical staining. RESULTS Ventral subdiaphragmatic vagal stimulation elicited frequency-dependent LES relaxation without evoking esophageal contractions and induced c-fos expression in interneurons in medial, dorsomedial, and commissural subnuclei along with outer shell of area postrema and motoneurons in the caudal dorsal motor nucleus of vagus. Brain stem subnuclei including interstitial, intermediate, and central subnuclei, and nucleus ambiguous, which have been reported to be involved in the response to swallowing, were not activated. CONCLUSIONS Stimulation of the ventral subdiaphragmatic vagus causes isolated LES relaxation and activates neurons in select vagal subnuclei that may represent the brain stem circuit involved in the abdominal vagal-afferent-evoked isolated LES relaxation. These observations suggest that different brain stem circuits are involved in swallow-induced and gastric afferent-mediated isolated LES relaxations.
Integrity and Barrier Function of the Epidermis Critically Depend on Glucosylceramide Synthesis*

Ceramides are vital components of the water barrier in mammalian skin. Epidermis-specific, a major ceramide portion contains ω-hydroxy very long chain fatty acids (C30–C36). These ω-hydroxy ceramides (Cers) are found in the extracellular lamellae of the stratum corneum either as linoleic acyl esters or protein bound. Glucosylceramide is the major glycosphingolipid of the epidermis. Synthesized from ceramide and UDP-glucose, it is thought to be itself an intracellular precursor and carrier for extracellular ω-hydroxy ceramides. To investigate whether GlcCer is an obligatory intermediate in ceramide metabolism to maintain epidermal barrier function, a mouse with an epidermis-specific glucosylceramide synthase (Ugcg) deficiency has been generated. Four days after birth animals devoid of GlcCer synthesis in keratinocytes showed a pronounced desquamation of the stratum corneum and extreme transepidermal water loss leading to death. The stratum corneum appeared as a thick unstructured mass. Lamellar bodies of the stratum granulosum did not display the usual ordered inner structure and were often irregularly arranged. Although the total amount of epidermal protein-bound ceramides remained unchanged, epidermal-free ω-hydroxy ceramides increased 4-fold and ω-hydroxy sphingomyelins, almost not detectable in wild type epidermis, emerged in quantities comparable with lost GlcCer. We conclude that the transient formation of GlcCer is vital for a regular arrangement of lipids and proteins in lamellar bodies and for the maintenance of the epidermal barrier.
Plasma vitamin D levels and inflammation in the aortic wall of patients with coronary artery disease with and without inflammatory rheumatic disease

Objectives: Vitamin D modulates inflammation, and this may explain the observed associations between vitamin D status and disorders driven by systemic inflammation, such as coronary artery disease (CAD) and inflammatory rheumatic diseases (IRDs). The aims of this study were to assess vitamin D status in patients with CAD alone and in patients with CAD and IRD, and to explore potential associations between vitamin D status and the presence of mononuclear cell infiltrates (MCIs) in the aortic adventitia of these patients. Method: Plasma levels of 25-hydroxyvitamin D3 [(25(OH)D3] were determined by radioimmunoassay and 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] by enzyme immunoassay in the 121 patients from the Feiring Heart Biopsy Study (FHBS) who had available histology data on adventitial MCIs; 53 of these had CAD alone and 68 had CAD and IRD. Results: In the crude analysis, vitamin D levels were similar in CAD patients with and without IRD. After adjustment for potential confounders, IRD was associated with an increase of 8.8 nmol/L [95% confidence interval (CI) 1.0–16.6; p = 0.027] in 25(OH)D3 and an increase of 18.8 pmol/L (95% CI 4.3–33.3; p = 0.012) in 1,25(OH)2D3, while MCIs in the aortic adventitia were associated with lower levels of 1,25(OH)2D3 (β = –18.8, 95% CI –33.6 to –4.0; p = 0.014). Conclusions: IRD was associated with higher levels of both 25(OH)D3 and 1,25(OH)2D3. These findings argue against the hypothesis that patients with high systemic inflammatory burden (CAD+IRD) should have lower vitamin D levels than those with less inflammation (CAD only). Of note, when controlled for potential confounders, low 1,25(OH)2D3 levels were associated with adventitial aortic inflammation.
Effectiveness of intravenous infusion of N-acetylcysteine in cirrhotic patients undergoing major abdominal surgeries

Background: Postoperative acute kidney injury (AKI) is common in patients with chronic liver disease. We prospectively evaluated effectiveness of the N-acetylcysteine (NAC) in preserving postoperative renal functions in cirrhotic patients undergoing major abdominal surgeries. Materials and Methods: A total of 60 cirrhotic patients child A to B were randomized into two groups of 30 each.NAC groupwas received intravenous infusion of NAC (1200 mg/12h starting immediately before surgery and continued for 72h h postoperative) and controls group received a similar volume of glucose 5% solution as a a placebo. Systemic hemodynamics, hepatic and renal functions, serum cystatin C and cystatin C glomerular filtration rate (GFR) (GFR) were compared between both groups. Results: Serum level of cystatin C was raised significantly above the basal value at postoperative day 1 and day 3 associated with significantly decreased in cystatin C GFR below the basal value in the control group (P = 0.001). 6 (20%) (PP = 0.03) in control group developed AKI based on cystatin C GFR criteria (GFR <55 ml/min/1.73m 2 ). Mean values of alanine aminotransferase and aspartate aminotransferase were increased significantly above the basal values in both groups, but the increases were significantly lower in NAC group (P = 0.00). Chest infection was significantly lower associated with shorter hospital stay in the NAC group than the control group. Conclusion: Intravenous administration of NAC NAC in cirrhotic patients undergoing major abdominal surgeries reduces the incidence of cystatin C GFR-based AKI, postoperative renal and liver functions were well-preserved and improved outcome.
The expression of TGF-beta receptors in human atherosclerosis: evidence for acquired resistance to apoptosis due to receptor imbalance.

The degree of cellularity in vascular lesions is determined by the balance between the migration and proliferation of cells relative to their rate of egress and apoptosis. Transforming growth factor-beta(1) can act as a potent antiproliferative and apoptotic factor for proliferating vascular cells. Our laboratory has previously identified cells cultured from human vascular lesions that are resistant to the antiproliferative effect of TGF-beta(1) due to an acquired mutation in the Type II receptor for TGF-beta(1). In the present studies, the expression of the Type I and II receptors in coronary and carotid atherosclerotic lesions was analysed by immunostaining, RT-PCR, and in situ RT-PCR. Levels of the Type I and Type II receptors varied widely within lesions, with the highest levels in the fibrous cap and at discrete foci within the lesion. Regions of smooth muscle-like cells (SMC) were commonly found that were Type I positive but Type II receptor negative. In 43 cell lines cultured from 126 human lesions, 84% of the lesion-derived cell (LDC) cultures exhibited functional resistance to the antiproliferative effect of TGF-beta(1). This resistance was conferred against TGF-beta(1), TGF-beta(2), and TGF- beta(3), but not interferon-gamma or mimosine. While normal SMC exhibited a four-fold increase in the rate of apoptosis after TGF- beta(1) treatment, most LDC were resistant to apoptosis in response to TGF-beta(1). Resistant cells exhibited selective loss of Type II receptor expression, and retroviral transfection of Type II receptor cDNA partially corrected the functional deficit. Thus, resistance to apoptosis may lead to the slow proliferation of resistant cell subsets, thereby contributing to the progression of atherosclerotic and restenotic lesions.
Aportación al conocimiento del género "Akis Herbst", 1799 (Coleoptera, Tenebrionidae, Pimeliinae)

Resumen: El tipo de Tenebrio spinosus Linnaeus (1764) es específicamente diferente de la especie del Mediterráneo occidental normalmente denominada Akis spinosa Herbst (1799) y Solier (1837), siendo Akis elevata Solier (1837) var. sculptior Koch (1935), de Egipto o la Península Arábiga. La especie figurada por Viñolas & Cartagena (2005) como “Akis spinosa (L.)” es en realidad Akis trilineata Herbst (1799) = italica Solier (1837), claramente diferente del tipo de Linneo. La especies figurada como “Akis granulifera Sahlberg, 1823”, tampoco corresponde al tipo de esta especie, y es A. lusitanica Solier (1837), mientras que “Akis lusitanica” sensu Viñolas & Cartagena (2005) es A. bayardi Solier (1837) stat. rest. Se dan diversos caracteres que permiten su separación. Los cambios y sinonimia presentados por Viñolas & Cartagena (2005) se propusieron sin haber examinado los tipos, y se rechazan aquí. Se presentan múltiples cambios basados en el examen de material típico: A. bacarozzo (Schrank, 1786) es separado de A. tuberculata Kraatz, (1865); A. hispanica Solier (1837), A. nevadensis Español (1954), A. salzei Solier (1837), A. dorsigera Reitter, (1904), A. duplicata Reitter (1904) y A. ilonka Strassen (1957) son especies válidas; A. spinosa (Linnaeus, 1764) es específicamente distinto del tipo de A. spinosa Herbst (1799) y de A. spinosa Solier (1837); A. trilineata Herbst (1799: 130, t. 125, f. 8) es A. italica Solier (1837). Se designan lectotipos y paralectotipos para A. spinosa Herbst (1799) y A. trilineata Herbst (1799). Palabras clave: Coleoptera, Tenebrionidae, Pimeliinae, Akis, lectotipos, tipos históricos, nueva interpretación, sinonimia, cambios taxonómicos.
Deficiency of the 65 kDa Isoform of Glutamic Acid Decarboxylase Impairs Extinction of Cued But Not Contextual Fear Memory

Extinction procedures are clinically relevant for reducing pathological fear, and the mechanisms of fear regulation are a subject of intense research. The amygdala, hippocampus, and prefrontal cortex (PFC) have all been suggested to be key brain areas in extinction of conditioned fear. GABA has particularly been implicated in extinction learning, and the 65 kDa isoform of glutamic acid decarboxylase (GAD65) may be important in elevating GABA levels in response to environmental signals. Extinction of conditioned fear was examined in Gad65−/− mice while recording local field potentials from the amygdala, hippocampus, and PFC simultaneously while monitoring behavior. Gad65−/− mice showed generalization of cued fear, as reported previously, and impaired extinction of cued fear, such that fear remained high across extinction training. This endurance in cued fear was associated with theta frequency synchronization between the amygdala and hippocampus. Extinction of contextual fear, however, was unaltered in Gad65−/− mice when compared with wild-type littermates. The data imply that GAD65 plays a critical role in regulating cued fear responses during extinction learning and that, during this process, GABAergic signaling is involved in modulating synchronized activity between the amygdala and hippocampus. In view of the more pronounced effect on cued versus contextual fear extinction, these influences may rely more on GABAergic mechanisms in the amygdala.
Rest-activity patterns in patients with delirium.

OBJECTIVE Delirium is a frequent syndrome in elderly hospital patients. Symptoms typically show a fluctuating course during the day, with patients exhibiting disturbances of their sleep-wake rhythm. Delirium is frequently underdiagnosed, especially the so-called hypoactive subtype. Devices measuring 24-hr motor patterns could contribute to the recognition of delirium. The purpose of this paper is two-fold. First, the results of a pilot study are presented, in which 24-hr motor patterns of delirious patients are measured with a wrist-actigraph. Second, studies reporting 24-hr motor patterns in delirious patients are systematically reviewed. METHODS The pilot study included 9 patients, 65 years or older, with a hip fracture in need of surgical repair. For the review, MEDLINE and Embase were searched for studies on motor activity assessment in delirious patients. RESULTS In the pilot study, the 24-hr activity rhythm was severely disturbed during delirium, and most actigraphic sleep parameter estimates indicated significantly worse sleep during delirious nights. The systematic search resulted in 10 papers. In 3 papers, the sleep-wake rhythm of delirious patients was significantly different from that of nondelirious patients. In 5 papers, delirious patients could be classified into delirium subtypes. In the 2 remaining papers, 24-hr motor patterns of delirium subtypes were not significantly different. CONCLUSION Activity patterns revealed differences between delirious and nondelirious patients and between the different subtypes, even in small samples of patients. Future studies, with preferably larger sample sizes, should confirm the potential of activity pattern measuring devices in the early detection of delirium.
Mechanism of Thiosulfate Oxidation in the SoxA Family of Cysteine-ligated Cytochromes

Background: The hemoprotein TsdA catalyzes the oxidation of two thiosulfate molecules to form tetrathionate. Results: The mechanism of TsdA has been probed using biochemical and structural methods. Conclusion: The TsdA reaction proceeds via a cysteine S-thiosulfonate intermediate formed on a cysteine ligand to the active site heme. Significance: TsdA provides a catalytic model for other members of the SoxA enzyme family. Thiosulfate dehydrogenase (TsdA) catalyzes the oxidation of two thiosulfate molecules to form tetrathionate and is predicted to use an unusual cysteine-ligated heme as the catalytic cofactor. We have determined the structure of Allochromatium vinosum TsdA to a resolution of 1.3 Å. This structure confirms the active site heme ligation, identifies a thiosulfate binding site within the active site cavity, and reveals an electron transfer route from the catalytic heme, through a second heme group to the external electron acceptor. We provide multiple lines of evidence that the catalytic reaction proceeds through the intermediate formation of a S-thiosulfonate derivative of the heme cysteine ligand: the cysteine is reactive and is accessible to electrophilic attack; cysteine S-thiosulfonate is formed by the addition of thiosulfate or following the reverse reaction with tetrathionate; the S-thiosulfonate modification is removed through catalysis; and alkylating the cysteine blocks activity. Active site amino acid residues required for catalysis were identified by mutagenesis and are inferred to also play a role in stabilizing the S-thiosulfonate intermediate. The enzyme SoxAX, which catalyzes the first step in the bacterial Sox thiosulfate oxidation pathway, is homologous to TsdA and can be inferred to use a related catalytic mechanism.
Structure‐Function Studies of HIV Reverse Transcriptase a

The retroviral RT is properly under intensive study as the major target of antiviral therapy. The enzyme exhibits a number of features that make it an attractive target: it is crucial for viral replication; its RNA-dependent DNA polymerase activity is probably unique to viral replication, or if not unique, is generally unimportant in host cell function; its activities are readily monitored; and powerful lead compounds in the form of nucleotide analogues are already in hand. Our laboratory has been involved in studies to elucidate the structure and function of the HIV-1 RT and to develop a formal genetics of the enzyme. Working with constructs expressing RT in bacteria, we been able to use in vitro mutagenesis to localize functions on the molecule; by coupling mutagenesis with high-throughput screening of colonies, we have been able to isolate mutants with specific, rare, phenotypes. We believe that extensions of these efforts will help us to understand the functions of the protein and, coupled to a detailed three-dimensional structure, should facilitate the development of new and better inhibitors.
CO2 Laser-Assisted Stapedotomy Combined With àWengen Titanium Clip Stapes Prosthesis: Superior Short-Term Results

Objective: To report on the short-term results of CO2-laser assisted stapedotomy combined with the àWengen titanium clip stapes prosthesis. A comparison with published series using other prostheses and/or different stapedotomy techniques is made. Study Design: Retrospective case series. Patients: Patients with a history and audiologic data matching stapes fixation and computed tomographic imaging excluding other anomalies such as malleus fixation, dehiscent superior semicircular canal, and large vestibular aqueduct that may mimic stapes fixation-like hearing loss. Intervention: All patients underwent CO2 laser-assisted stapedotomy (Lumenis Co. Israel CO2 laser, Acuspot 712, SurgiTouch 870 scanner) and subsequent reconstruction by means of the àWengen titanium clip stapes prosthesis by Heinz Kurz Medizintechnik GmbH (Germany). Outcome Measures: Comparison and statistical analysis of preoperative and postoperative audiologic data. Results: Sixty-two stapedotomies were performed (61 patients) using the CO2 laser and àWengen titanium clip stapes prosthesis. The mean postoperative air-bone gap 3 months postoperatively was 5.1 ± 0.5 dB (standard deviation [SD], 4.1 dB; 0.5, 1, 2, 4 kHz). Air-bone gap closure less than or equal to 10 dB was achieved in 54 cases (87%). Air-bone gap closure less than 20 dB was achieved in all cases. The average gain was 27.8 ± 1.5 dB (SD, 12 dB; 0.5, 1, 2, 4 kHz). The average bone-conduction threshold shift or "overclosure" on 2,000 Hz was 13.6 ± 1.3 dB (SD, 10 dB). There was no postoperative perceptive hearing loss exceeding 15 dB on any measured frequency. The Amsterdam Hearing Evaluation Plots have also been used to evaluate our data. These data were statistically analyzed and compare favorably to other published series. Conclusion: The authors conclude that the combination of CO2 laser-assisted stapedotomy and the àWengen titanium clip stapes prosthesis is a combination likely to yield superior results in experienced hands.
Development of a Computer‐Assisted Forensic Radiographic Identification Method Using the Lateral Cervical and Lumbar Spine

Medical examiners and coroners (ME/C) in the United States hold statutory responsibility to identify deceased individuals who fall under their jurisdiction. The computer‐assisted decedent identification (CADI) project was designed to modify software used in diagnosis and treatment of spinal injuries into a mathematically validated tool for ME/C identification of fleshed decedents. CADI software analyzes the shapes of targeted vertebral bodies imaged in an array of standard radiographs and quantifies the likelihood that any two of the radiographs contain matching vertebral bodies. Six validation tests measured the repeatability, reliability, and sensitivity of the method, and the effects of age, sex, and number of radiographs in array composition. CADI returned a 92–100% success rate in identifying the true matching pair of vertebrae within arrays of five to 30 radiographs. Further development of CADI is expected to produce a novel identification method for use in ME/C offices that is reliable, timely, and cost‐effective.
Quantitative Analysis of Abdominal Aortic Calcification in CKD Patients Without Dialysis Therapy by Use of the Agatston Score

Background/Aim: The aim of the present study was to quantitatively examine factors associated with aortic calcification in non-dialysis CKD patients. Methods: We quantitatively investigated aortic calcification from the renal artery to the bifurcation in 149 non-dialysis CKD patients (58±16 years; 96 males and 53 females, 48 diabetics; eGFR 40.3±29.3 ml/min), and measured Agatston scores using multi-slice computed tomography. Result: Of 149 patients, aortic calcification was present in 117. In patients with aortic calcification, age (p<0.001), C-reactive protein (p<0.001), and intact-PTH (p < 0.001) were significantly higher, estimated glomerular filtration rate (eGFR) was significantly lower (p<0.001), and diabetes was observed more often (p<0.05). In regards to the degree of aortic calcification, the Agatston scores correlated significantly and positively with age (ρ=0.438, p<0.001) and serum phosphate (ρ=0.208, p=0.024), and correlated significantly but negatively with e-GFR (ρ=-0.353, p<0.001). In multiple regression analysis, eGFR was associated significantly and independently with the log [Agatston score] (β=-0.346, p<0.01), after adjustment for several confounders including serum phosphate and the presence of diabetes. Conclusions: Hyperphospatemia, chronic inflammation, diabetes, and decreased GFR are associated significantly with the presence of aortic calcification in non-dialysis CKD patients. Decreased eGFR was associated significantly and independently with the quantitative degree of aortic calcification.
A novel arresting solution for study of postmortem pressure--volume curves of the rat left ventricle.

OBJECTIVE We have found diastolic properties of the rat heart extremely sensitive to the method used to induce arrest. Accordingly, we sought to develop a reliable solution for measuring the LV pressure-volume relationship (LVPVR) in the rat. MATERIALS AND METHODS The study had five phases: (i) K120Na100, consisting of KCl (120 mEq/L) in NaCl (100 mEq/L) diluted with distilled water was developed in preliminary experiments. (ii) ACI rats were arrested with 3 cc of 4 degreesC KCl (n = 6) or K120Na100 (n = 6) infused into the aortic root. The LVPVR was expressed as normalized volume (Vn) at standardized pressures. Myocardial water content (%MWC) was determined. (iii) Six hearts were arrested with K120Na100 and LVPVRs observed over 1 h. (iv) Four hearts were instrumented with sonomicrometry crystals to compare in vivo and postmortem pressure diameter data. (v) The relation between body weight and dry heart weight was determined in 48 animals. RESULTS In hearts arrested with KCl, mean Vn at pressures of 10, 15, and 20 mmHg (206 +/- 26, 306 +/- 21, and 336 +/- 25 microl, respectively) was significantly reduced vs K120Na100 hearts (345 +/- 11, 407 +/- 12, and 472 +/- 18 microl) (P < 0.05). Mean %MWC changed insignificantly. Vn at 20 mm Hg became significantly smaller vs initial data 60 min after arrest with K120Na100 (P < 0.05, ANOVA). No differences between in vivo and postmortem mean normalized diameter were observed. The correlation coefficient for the relation between body weight and dry heart weight was 0.80. Conclusions. K120Na100 at 4 degreesC reliably preserves LV diastolic properties in the rat heart for 30 min. Normalization of LV volume to body weight is justified.