Miracle-dz/UniFAR-FTUs huggingface dataset:
The effect of hypoxia and exercise on heart rate variability, immune response, and orthostatic stress

Hypoxia with exercise is commonly used to enhance physiological adaptation in athletes, but may prolong recovery between training bouts. To investigate this, heart rate variability (HRV), systemic immune response, and response to an orthostatic challenge were measured following exercise in hypoxia and air. Eleven trained men performed a 10‐km cycling time trial breathing hypoxia (16.5 ± 0.5% O2) or air. HRV and the heart rate response to an orthostatic challenge were measured for 3 days before and after each trial, while venous blood samples were collected pre‐, 0, 2, and 24 h post‐exercise. Hypoxia had no significant effect compared with air. Subgroup analysis of those who had a drop in oxyhemoglobin saturation (SpO2) > 10% between hypoxia and air compared with those who did not, demonstrated a significantly altered HRV response (△HFnu: −2.1 ± 0.9 vs 8.6 ± 9.3, △LFnu: 2.1 ± 1.0 vs −8.6 ± 9.4) at 24 h post‐exercise and increased circulating monocytes (1.3 ± 0.2 vs 0.8 ± 0.2 × 109/L) immediately post‐hypoxic exercise. Exercise and hypoxia did not change HRV or the systemic immune response to exercise. However, those who had a greater desaturation during hypoxic exercise had an attenuate recovery 24 h post‐exercise and may be more susceptible to accumulating fatigue with subsequent training bouts.
Cyclosporine A- and Tacrolimus-Mediated Inhibition of CYP3A4 and CYP3A5 In Vitro

Cyclosporine A (CsA) and tacrolimus (Tac) are immunosuppressive drugs used in the majority of patients with solid organ transplants, generally in combination with a wide range of drugs. CsA and Tac seem not only to be substrates of CYP3A but have also been described as inhibitors of CYP3A. For CsA, in particular, inhibition of CYP3A has been suggested as the main mechanism of interactions seen clinically with various drugs. The aim of this study was to investigate the inhibitory effect and inhibition characteristics of CsA and Tac on CYP3A4 and CYP3A5 in vitro and to evaluate its clinical relevance. Inhibition by CsA and Tac was studied using midazolam as the probe substrate in coincubation and preincubation investigations using human liver microsomes (HLMs) as well as specific CYP3A4- and CYP3A5-expressing insect microsomes (Supersomes). In vitro-in vivo extrapolations (IVIVEs) were performed to evaluate the clinical relevance of the inhibition. Both CsA and Tac competitively inhibited CYP3A in HLMs, showing inhibition constants (Ki) of 0.98 and 0.61 μM, respectively. Experiments in Supersomes revealed that Tac inhibited both CYP3A4 and CYP3A5, whereas CsA only inhibited CYP3A4. In contrast to the HLM experiments, studies in Supersomes showed inhibition by Tac to be NADPH- and time-dependent, with a 5-fold reduction in IC50 after preincubation, supporting a time-dependent inhibition mechanism in recombinant microsomes. By application of HLM data, IVIVE estimated the area under the concentration versus time curve of midazolam to increase by 73 and 27% with CsA and Tac, respectively. The inhibitory effect was predominantly on the intestinal level, whereas hepatic intrinsic clearance seemed unaffected.
Reduced Anxiety Level by Therapeutic Interventions and Cell-Mediated Immunity in Panic Disorder Patients

Objective: This study examined the relationship between reduced anxiety level by therapeutic interventions and cell-mediated immunity (CMI) in patients with panic disorder. Methods: The subjects consisted of 42 patients with panic disorder and 42 normal gender- and age-matched controls. Among the patients, 21 were randomly assigned to a combined treatment of cognitive-behavioral therapy and the benzodiazepine antianxiety agent ethyl loflazepate (2 mg daily), and 21 were assigned to the antianxiety agent only. The treatment lasted for 6 weeks. Cell-mediated immune function was measured by the lymphocyte proliferative response to phytohemagglutinin (PHA) and interleukin-2 (IL-2) production. The anxiety level was assessed by the Hamilton Rating Scale for Anxiety and the anxiety subscale of the Symptom Checklist-90 Revised. Results: Prior to treatment, the panic disorder patients had significantly lower IL-2 production and blastogenic response to PHA than the normal controls. However, no significant differences in CMI were found between the pretreatment and posttreatment period in either the patient group receiving medication only or the combined treatment group, though after treatment, patients were significantly less anxious than before treatment in both intervention groups. The delta change (posttreatment value minus pretreatment value) in the self-reported anxiety level was significantly associated with the delta change in the blastogenic response in the combined treatment group. Conclusion: These findings suggest that panic disorder may be associated with decreased CMI, and the reduced level of self-reported anxiety in the patients who underwent combined therapeutic intervention is likely to increase the blastogenic response. Further studies are needed to evaluate the long-term effects of treatment on immune function.
“Convulsive” Nonepileptic Seizures Have a Characteristic Pattern of Rhythmic Artifact Distinguishing Them from Convulsive Epileptic Seizures

Summary: Purpose: Approximately 30% of patients admitted for video‐EEG monitoring have psychogenic nonepileptic seizures (PNES). Differentiation of “convulsive” PNES from convulsive seizures can be difficult. The EEG often displays rhythmic movement artifact that may resemble seizure activity and confound the interpretation. We sought to determine whether time–frequency mapping of the rhythmic EEG artifact during “convulsive” PNES reveals a pattern that differs from that of epileptic seizures.
Quantification of seminolipid by LC-ESI-MS/MS-multiple reaction monitoring: compensatory levels in Cgt mice[S]

Seminolipid, also known as sulfogalactosylglycerolipid (SGG), plays important roles in male reproduction. Therefore, an accurate and sensitive method for SGG quantification in testes and sperm is needed. Here we compare SGG quantitation by the traditional colorimetric Azure A assay with LC-ESI-MS/MS using multiple reaction monitoring (MRM). Inclusion of deuterated SGG as the internal standard endowed accuracy to the MRM method. The results showed reasonable agreement between the two procedures for purified samples, but for crude lipid extracts, the colorimetric assay significantly overestimated the SGG content. Using ESI-MS/MS MRM, C16:0-alkyl/C16:0-acyl SGG of Cgt+/− mice was quantified to be 406.06 ± 23.63 μg/g testis and 0.13 ± 0.02 μg/million sperm, corresponding to 78% and 87% of the wild-type values, respectively. CGT (ceramide galactosyltransferase) is a critical enzyme in the SGG biosynthesis pathway. Cgt−/− males depleted of SGG are infertile due to spermatogenesis arrest. However, Cgt+/− males sire offspring. The higher than 50% expression level of SGG in Cgt+/− animals, compared with the wild-type expression, might be partly due to compensatory translation of the active CGT enzyme. The results also indicated that 78% of SGG levels in Cgt+/− mice were sufficient for normal spermatogenesis.
Distance-dependent seedling mortality and long-term spacing dynamics in a neotropical forest community.

Negative distance dependence (NDisD), or reduced recruitment near adult conspecifics, is thought to explain the astounding diversity of tropical forests. While many studies show greater mortality at near vs. far distances from adults, these studies do not seek to track changes in the peak seedling curve over time, thus limiting our ability to link NDisD to coexistence. Using census data collected over 12 years from central Panama in conjunction with spatial mark-connection functions, we show evidence for NDisD for many species, and find that the peak seedling curve shifts away from conspecific adults over time. We find wide variation in the strength of NDisD, which was correlated with seed size and canopy position, but other life-history traits showed no relationship with variation in NDisD mortality. Our results document shifts in peak seedling densities over time, thus providing evidence for the hypothesized spacing mechanism necessary for diversity maintenance in tropical forests.
Outcome of papillary versus clear cell renal cell carcinoma varies significantly in non-metastatic disease

Renal cell carcinoma (RCC) comprises a heterogenous group of tumors. Traditionally, papillary RCC (pRCC) is associated with a favorable outcome compared to clear cell RCC (ccRCC), while other series report equivalent or worse prognosis. In this paper we comparatively evaluate outcome of pRCC versus ccRCC in two large multi-institutional databases (cohort study), including distribution of pRCC subtypes 1 and 2. Retrospective data of 1,943 surgically treated pRCC patients from 17 European/ North American centers between 1984–2015 were compared to 5,600 ccRCC patients from a database comprising 11 European/ North American centers (1984–2011). Median follow-up was 64.6 months. Differences between pRCC, subtypes, and ccRCC were compared with t-tests, Chi^2-tests, and exact Fisher tests. Cancer-specific mortality was analyzed with cumulative incidence curves and Cox cause-specific hazard models. The robustness of our results was examined with sensitivity analyses. We present that cancer-specific mortality rates and variables as stage, lymph node, and distant metastasis differ significantly between groups. Furthermore, we demonstrate that patients with non-metastatic pRCC had a significantly better cancer-specific mortality (HR 0.76, p = 0.007), when compared to ccRCC. Additionally, pRCC type 2 versus ccRCC exhibited no difference in cancer-specific mortality (HR 0.9, p = 0.722), whereas pRCC type 1 versus ccRCC displayed a risk of death reduced by 69% (p = 0.044). Taken together, outcome of pRCC versus ccRCC varies significantly in non-metastatic disease. Furthermore, pRCC type 2 exhibited no difference in cancer-specific mortality, whereas pRCC type 1 displayed a significantly reduced risk of death. Consequently, there is urgent need to respect histopathological entities and their subtypes, when assigning follow-up or targeted therapy to RCC patients.
Frequency and Clinical Characteristics of Early-Onset Dementia in Consecutive Patients in a Memory Clinic

Aims: To investigate the frequency, rate of causes of dementia, and clinical characteristics of early-onset dementia in consecutive patients of a memory clinic. Methods: A total of 668 consecutive demented patients were involved in this study. We examined the distribution of patients’ diagnosis, differences in sex, education, dementia severity and cognitive function at the first visit, and the duration from onset to consultation. We also examined the changes in the proportion of subjects during the research period. Results: There were 185 early-onset patients, 28% of all demented patients. No significant differences were observed between the early-onset and late-onset dementia groups in Clinical Dementia Rating and Mini-Mental State Examination score at the first consultation, but the duration from onset to consultation was significantly longer in the early-onset group. In the early-onset group, the rates of patients with Alzheimer’s disease and dementia with Lewy bodies were relatively low and the rate of patients with frontotemporal lobar degeneration was relatively high. There were no significant differences in the proportion between either demented subjects and nondemented subjects or early-onset dementia patients and late-onset dementia patients during the research period. Conclusion: We conclude that early-onset dementia is not rare and its clinical characteristics and causes are different from late-onset dementia.
[Cigarette smoking and gastric cancer risk in a community-based cohort study in Korea].

OBJECTIVES Gastric cancer is the most common incident cancer in Korea. Although Helicobacter pylori infection is the most important risk factor for the development of gastric cancer, cigarette smoking has also been suggested to play an important role in the development of gastric cancer. The objective of this study is to evaluate the relationship between cigarette smoking and gastric cancer risk in a Korean population. METHODS The study population consisted of 13,785 subjects who had been enrolled in the Korean Multi-Center Cancer Cohort between 1993 and 2002. As of December 2002, 139 incident gastric cancer cases were ascertained through the Korea Central Cancer Registry and the National Death Certificate Database. Relative risks (RR) and 95% confidence intervals (CI) for gastric cancer were estimated using Cox's proportional hazard model adjusted for age, education, alcohol drinking status and history of gastritis or ulcer. RESULTS Significant dose-response relationships were observed between the duration of smoking and the risk of gastric cancer among the male subjects in comparison to non-smokers: men who smoked for 20-39 years had a 2.09- fold (95% CI 1.00-4.38) increase, and those who smoked for more than 40 years had a 3.13-fold (95% CI 1.59-6.17) increase in the risk of gastric cancer (P trend<0.01). CONCLUSIONS This study suggests that a longer duration of cigarette smoking may increase the risk of gastric cancer development in a dose-response manner in Korean men. The association between smoking and gastric cancer risk in women should be verified in future studies with a larger number of cases.
The effects of doxofylline versus theophylline on sleep architecture in COPD patients.

Theophylline is known to alter sleep architecture because of its affinity to adenosine receptors. One of the consequences of disrupted sleep is impaired cognitive performance. A single-blind, randomized cross-over study of eight male chronic obstructive pulmonary disease (COPD) patients was undertaken to evaluate the effects of theophylline versus doxofylline on sleep architecture. The patients, who were all ex-smokers, had been treated with theophylline. Mean age was 53 +/- 12 yrs, forced expiratory volume in one second (FEV1) 50 +/- 22% predicted and forced vital capacity (FVC) 70 +/- 18% predicted. Following a wash-out period, four patients were given oral slow-release theophylline (T) (300 mg b.i.d.) for one week, followed by a cross-over to doxofylline (D) (400 mg t.i.d.) for a second week. The other four patients were given the drugs in the reverse order. All patients underwent polysomnography at baseline and at the end of each week of treatment. The number of arousals per hour was 5.5 +/- 2.9 at baseline, 9.4 +/- 5.2 during T treatment and 5.4 +/- 4.4 during D treatment. During T treatment, sleep efficiency was 60 +/- 19% vs 75 +/- 13% recorded at baseline trial and 68 +/- 25 recorded during D treatment. Sleep quality, during T treatment, was poorer than at baseline, with a greater increase in the percentage of wakefulness and more stage 2 sleep than at baseline. Slow wave sleep was reduced with both treatments, particularly D. Neither drug affected the arterial oxygen saturation (Sao2) or respiratory rate during sleep. (ABSTRACT TRUNCATED AT 250 WORDS)
Improving maternal, infant and young child nutrition in Nepal via peer mobilization

Abstract Objective To evaluate the impact of a peer facilitator (PF) approach for improving mothers’ knowledge and practices relating to maternal and child nutrition. Design A quasi-experimental design nested within a large-scale integrated nutrition programme, Suaahara, in Nepal. Suaahara interventions were implemented in all study sites, but peer facilitators were used in only half of the study sites. Setting Rural, disadvantaged villages in three districts of Nepal: Bhojpur, Bajhang and Rupandehi. Subjects Mothers of children aged 6–23·9 months (n 1890). Results Differences over time between comparison (C) and intervention (I) groups show that the PF approach had a significant positive impact on several indicators of mothers’ knowledge and practices relating to maternal and child nutrition: (i) knowing that fruits and vegetables are good for children 6–23·9 months (C: −0·7, I: 10·6; P=0·03); (ii) child dietary diversity (C: 0·02, I: 0·04; P=0·02); (iii) child minimum dietary diversity (≥4 of 7 food groups; (C: 6·9, I: 16·0; P=0·02); (iv) maternal dietary diversity (C: 0·1, I: 0·4; P=0·01); and (v) maternal minimum dietary diversity (≥4 food groups; C: 3·6, I: 14·0; P=0·03). Additionally, exposure to a PF three or more times in the past 6 months was positively associated with a small improvement in maternal (β=0·06, P=0·04) and child (β=0·06, P=0·02) dietary diversity scores. Improvements were not observed in maternal health-seeking behaviours such as number of antenatal care visits. Conclusions Peer mobilization is a potential approach for improving health- and nutrition-related knowledge and behaviours among women in hard-to-reach communities of Nepal.
Molecular Cloning of a New Intermediate Filament Protein Expressed by Radial Glia and Demonstration of Alternative Splicing in a Novel Heptad Repeat Region Located in the Carboxy-Terminal Tail Domain

In the present study we describe the molecular cloning of transitin, formerly named EAP-300. We show that transitin is an intermediate filament protein with a core domain most closely resembling nestin and tanabin. Transitin also contains a novel heptad amino acid repeat domain, comprising multiple leucine zipper repeats, located in its tail region. Based on these structural motifs we propose that a novel intermediate filament protein that is transiently expressed by radial glia during CNS development has been identified. We also show the existence of splice variants of transitin with splicing occurring in the novel heptad repeat domain to give rise to transitin isoforms that lack this heptad repeat. By in situ hybridization analysis we show that transitin mRNA is expressed by midline radial glial structures, by several axon commissures, and by Bergmann glia of the developing cerebelium. Based on the structural properties of the transitin protein, and expression of its mRNA, we suggest that transitin is a new member of the intermediate filament gene superfamily that is transiently expressed by radial glia.
Organohalogen contaminants and metabolites in beluga whale (Delphinapterus leucas) liver from two Canadian populations

Contaminants described as organochlorines (OCs; e.g., polychlorinated biphenyls [PCBs]) are present in tissues of marine mammals, including beluga whales (Delphinapterus leucas), but the complexity of contaminant exposure often is not fully known. The PCBs, OC pesticides, polybrominated diphenyl ether (PBDE) flame retardants, methylsulfonyl (MeSO2)‐ and hydroxy (OH)‐PCB metabolites, and OH‐PBDEs and methoxylated (MeO)‐PBDEs were determined in the liver of beluga whales from two Canadian populations: the St. Lawrence Estuary (SLB; n = 6), and western Hudson Bay in the Canadian Arctic (CAB; n = 11). The ΣPCB, ΣDDT, and ΣPBDE concentrations were higher (p < 0.05) in SLB versus CAB. Of 18 detectable OH‐PCBs in SLB (mainly 4‐OH‐CB107, 4‐OH‐CB112, and 4′‐OH‐CB120), only 4′‐OH‐CB120 was found in CAB. The ΣOH‐PCB concentrations were less than 0.2% of the ΣPCBs in both populations but were higher (p < 0.05) in SLB (65 ± 22 ng/g lipid wt) than in CAB (3.1 ± 0.5 ng/g lipid wt). The ΣMeSO2‐PCB concentrations were higher in SLB (3,801 ± 1,322 ng/g lipid wt) relative to CAB (77 ± 23 ng/g lipid wt) and were 11 and 4%, respectively, of the ΣPCB concentrations. Of the 15 OH‐PBDEs, only two congeners were detectable, but not quantifiable (notably 2′‐OH‐BDE 68 and 6‐OH‐BDE 47), in animals from both populations. Of the 15 MeO‐PBDEs, 4′‐MeO‐BDE 17 and 6‐MeO‐BDE 47 in the SLB (n = 2) and 2′‐MeO‐BDE 68 and 6‐MeO‐BDE 47 in the CAB (n = 2) had concentrations from 20 to 100 ng/g lipid weight. The OH‐PBDEs and MeO‐PBDEs most likely are of natural origin and accumulated in beluga whales, whereas the OH‐PCBs and MeSO2‐PCBs are metabolites derived from accumulated PCBs. Canadian beluga whale liver contains previously unidentified organohalogen contaminants and metabolites and, thus, a complexity of contaminant exposure that may be impacting the health of Canadian beluga whale populations.
Interferon- (cid:1) Sensitizes Resistant Ewing’s Sarcoma Cells to Tumor Necrosis Factor Apoptosis-Inducing Ligand-Induced Apoptosis by Up-Regulation of Caspase-8 Without Altering Chemosensitivity

Ewing’s sarcoma cells are highly susceptible to apoptosis via tumor necrosis factor apoptosis-inducing ligand (TRAIL). Resistance to TRAIL has been linked to deficient expression of caspase-8 in vitro . Here, we report on the status of caspase-8 expression in tumors from patients with Ewing’s sarcoma, the effect of interferon- (cid:1) on caspase-8 expression and apoptosis, and the role of caspase-8 for TRAIL- and chemo-therapy-mediated apoptosis in Ewing’s sarcoma. Using immunohistochemistry, we show that low expression of caspase-8 is seen in about 24% of tumors. Interferon- (cid:1) induces expression of caspase-8 at concentrations achievable in humans and sensitizes cells to TRAIL. Transfection of wild type but not mu-tant caspase-8 into caspase-8-deficient Ewing’s sarcoma cells restored sensitivity to TRAIL, indicating that up-regulation of caspase-8 is sufficient to restore TRAIL sensitivity. In contrast, no role for caspase-8 in chemotherapy-induced
Parasol and midget ganglion cells of the primate retina.

We have intracellularly filled the dendritic arbors of 996 midget and parasol ganglion cells with horseradish peroxidase (HRP) in macaque and baboon retinas. Only minor differences in the properties of these cell groups were found between species. Ninety of these cells were cut from their retinas, embedded in methacrylate, and transversely sectioned. According to their depth of stratification, there are two types of parasol cells (termed a-parasol and b-parasol), and two types of midget ganglion cells (a-midget and b-midget). Each of these four types stratifies at a different level within the IPL. The dendritic fields of midget ganglion cells lie either near the border of the ganglion cell layer (GCL) or near the border of the amacrine cell layer (ACL). The dendrites of the two types of parasol cells stratify closer to the center of the IPL, where they divide it into three approximately equal parts. There was no vertical overlap in the dendritic fields of a-parasols and b-parasols; they were always separated by at least 1 micron. The border between the a- and b-sublaminae of the IPL, defined in terms of this narrow gap between the stratification of the two parasol cell types, lies approximately at the center of the IPL. The dendritic-field thickness for each of these types, on average, is no greater than 30% of the IPL thickness. At a similar location, there is no significant difference between the dendritic-field diameters of the two parasol types or between those of the two midget types. As previously reported (Perry et al.: Neuroscience 12:1101-1123, '84) the dendritic fields of both parasol and midget ganglion cells are smaller in the nasal retina than at a position in the temporal retina equidistant from the fovea. Because dendritic-field diameters prove to depend upon local ganglion-cell density, the scatter in these diameters as a function of retinal eccentricity is due in part to the asymmetric distribution of ganglion cells. We have devised a measure, termed equivalent eccentricity, that allows data points of cells from regions having the same local ganglion-cell density to be plotted at the same position on this scale. The use of this measure, rather than eccentricity per se, significantly reduces the scatter of dendritic-field diameters. The dendritic-field diameters of parasol cells within the nasal quadrant of the retina are not fully brought into line with those of cells lying elsewhere in the retina. (ABSTRACT TRUNCATED AT 400 WORDS)