Miracle-dz/UniFAR-FTUs huggingface dataset:
Interleukin‐2 is essential for CD4+CD25+ regulatory T cell function

Constitutive expression of CD25, the IL‐2 receptor α‐chain, defines a distinct population of CD4+ T cells (Treg) with suppressive activity in vitro and in vivo. IL‐2 has been implicated in the generation and maintenance of Treg, however, a functional contribution of the IL‐2 receptor during suppression is thus far unknown. We show that IL‐2 is required for Treg function in vitro, since suppression is completely abrogated by selective blocking of the IL‐2 receptor on Treg during co‐culture with responder T cells. We demonstrate that Treg, which do not produce IL‐2, compete for IL‐2 secreted by responder T cells. In accordance with the idea of competition being part of the suppressive mechanism, in vitro neutralization of IL‐2 mimics all effects of Treg. Conversely, recombinant IL‐2 abrogates inhibition of IL‐2 production in responder T cells, the hallmark of Treg suppression. Finally, activation in the presence of IL‐2 primes Treg to produce IL‐10 upon secondary stimulation, indicating that IL‐2 uptake is also required to induce additional suppressive factors that might be more relevant for suppression in vivo. We propose the parakrine uptake of soluble mediators as a flexible mechanism to adapt Treg activity to the strength of the responder T cell reaction.
EFFECT OF TROGLITAZONE ON CYCLOSPORINE WHOLE BLOOD LEVELS

Troglitazone (TGZ; Rezulin, Parke-Davis, Morris Plains, NJ) is a thiazolidinedione antihyperglycemic agent that has been shown to decrease hemoglobin A1c and decrease insulin requirements in patients with type 2 diabetes (1-4). It increases tissue sensitivity to insulin and decreases hepatic glucose production but does not increase insulin secretion (5). At doses used clinically, troglitazone decreases plasma levels of ethinyl estradiol and norethindrone in oral contraceptives by 30%, and terfenadine by 50-70%, possibly by inducing hepatic metabolism by CYP3A4 (6). However, clinically significant interactions with other drugs metabolized by CYP3A4, such as cyclosporine (CsA; Neoral, Novartis, East Hanover, New Jersey), have not been described in the literature. We report the effects of troglitazone on CsA whole blood levels in 11 stable renal transplant patients. The medical records of all renal transplant recipients receiving TGZ at our hospital were reviewed. Of 12 patients, 11 had follow-up CsA blood levels available for analysis. All results are reported as mean :<:: SD. The mean age was 54.5:<::11.6 years, and the mean time since transplantation was 20.5:! ::: 18.2 months. All patients were receiving a stable CsA dose, and only one patient was receiving a drug known to affect the metabolism of CsA (diltiazem). The TGZ dose was 200-400 mg/day. The mean CsA whole blood level fell from 205:<::42 ng/ml at the time TGZ was initiated to 139:<::65 ng/ml after 1 week, a decrease of 32% (P=0.0015, paired t test). Six patients (50%) required a CsA dosage increase of 50-150 mg/day between 1 and 7 weeks after initiation of TGZ. The mean CsA dose at the time TGZ was initiated was 358:<::93 ng/ml, compared with 392:<:: 100 ng/ml after 4 weeks (P=0.05, paired t test) and 404:<::92 ng/ml after 12 weeks (P=0.03, paired t test). There were no concomitant changes in medications or obvious alterations in gastrointestinal function that could explain the decrease in CsA blood levels. Despite continuous administration of diltiazem in one patient, the CsA level fell by 53% after initiation of TGZ, and 7 weeks after initiation of TGZ, he suffered a Banff grade II rejection with vasculitis requiring treatment with OKT3 (Orthoclone OKT3, Ortho Biotech, Raritan, NJ). The serum creatinine concentration increased 30% from baseline in one other patient and was attributed to increased CsA dosage. Troglitazone may be a useful antihyperglycemic agent in some transplant recipients with type 2 diabetes. However, it can lead to a reduction of CsA whole blood levels, possibly by inducing hepatic metabolism by CYP3A4. We have not used troglitazone in combination with tacrolimus to date, but we expect that the potential for decreased tacrolimus levels exists. Therefore, we recommend more frequent monitoring of either CsA or tacrolimus levels as appropriate after initiation of troglitazone, until a new steady state immunophilin level is achieved.
Women's health issues in a dialysis population.

BACKGROUND As women receiving hemodialysis are evaluated frequently by the nephrologist, we hypothesized that women's health issues are better addressed in the dialysis patient than in the general population. PATIENTS AND METHODS We surveyed the female patients in our dialysis population. 97% of the women approached agreed to participate. We found that 55.4% of our cohort had received routine gynecologic care. 50% of the women had undergone a Papanicolaou (Pap) smear in the last year. Of the women aged 40-50, 55% had undergone a mammogram in the last 2 years. In women over age 50, 71% received an annual mammogram. RESULTS We found that 57% of the women were amenorrheic before starting renal replacement therapy while 16% had become amenorrheic after dialysis was started. 27% were still menstruating at the time of the survey. Only 4% of the amenorrheic women interviewed were currently on hormone replacement therapy (HRT) as compared with 20% of women in our general medical clinics. While 67% stated that they would take hormone replacement if offered, 89% had never been offered HRT. Variables that positively correlated with willingness to take HRT were a history of a hysterectomy and more skilled work history. Although nephrologists surveyed at our academic facility agreed that amenorrheic women with renal disease benefited from HRT, many believed that it is not the role of the nephrologist to prescribe it. CONCLUSION Despite frequent contacts with medical providers, women's health issues for patients on dialysis may not receive the same attention as women in the general population
Episodic hormone release in relation to REM sleep

SUMMARY Similar periodicities of about 90–100 min characterize both hormone pulsatility and NREM‐REM sleep cycles suggesting that both processes could be temporally linked. From the current knowledge of the literature, it appears that, in spite of the diversity of the relationship between hormones and the sleep/wake cycle, systematic relationships exist between hormone pulses and the NREM‐REM sleep cycles. Early studies have demonstrated the temporal association between GH and SWS episodes occurring soon after sleep onset. Renin, a key enzyme of the renin‐angiotensin system, displays nocturnal oscillations that are associated strongly with the NREM‐REM sleep cycles, and represents the first identified biological marker of sleep stage alternation. SWS invariably occurs in the descending phases of TSH and cortisol pulses which suggests that some specific mechanisms of this sleep stage could modulate their levels or, conversely, that increased TSH and cortisol secretion prevents the occurrence of deep sleep. Apart from the period of sleep onset associated with reduced prolactin secretion, no systematic relationship has been found between REM sleep and hormone release. These results highlight the complexity of hormone and sleep interactions and provide a basis for further research into their functional significance.
Body mass index, serum sex hormones, and breast cancer risk in postmenopausal women.

BACKGROUND Obesity is associated with increased breast cancer risk among postmenopausal women. We examined whether this association could be explained by the relationship of body mass index (BMI) with serum sex hormone concentrations. METHODS We analyzed individual data from eight prospective studies of postmenopausal women. Data on BMI and prediagnostic estradiol levels were available for 624 case subjects and 1669 control subjects; data on the other sex hormones were available for fewer subjects. The relative risks (RRs) with 95% confidence intervals (CIs) of breast cancer associated with increasing BMI were estimated by conditional logistic regression on case-control sets, matched within each study for age and recruitment date, and adjusted for parity. All statistical tests were two-sided. RESULTS Breast cancer risk increased with increasing BMI (P(trend) =. 002), and this increase in RR was substantially reduced by adjustment for serum estrogen concentrations. Adjusting for free estradiol reduced the RR for breast cancer associated with a 5 kg/m2 increase in BMI from 1.19 (95% CI = 1.05 to 1.34) to 1.02 (95% CI = 0.89 to 1.17). The increased risk was also substantially reduced after adjusting for other estrogens (total estradiol, non-sex hormone-binding globulin-bound estradiol, estrone, and estrone sulfate), and moderately reduced after adjusting for sex hormone-binding globulin, whereas adjustment for the androgens (androstenedione, dehydroepiandrosterone, dehydroepiandrosterone sulfate, and testosterone) had little effect on the excess risk. CONCLUSION The results are compatible with the hypothesis that the increase in breast cancer risk with increasing BMI among postmenopausal women is largely the result of the associated increase in estrogens, particularly bioavailable estradiol.
Feedback gain indicates the preferred direction in optimal feedback control theory

We investigated the role of feedback gain in optimal feedback control (OFC) theory using a neuromotor system. Neural studies have shown that directional tuning, known as the “preferred direction” (PD), is a basic functional property of cell activity in the primary motor cortex (M1). However, it is not clear which directions the M1 codes for, because neural activities can correlate with several directional parameters, such as joint torque and end-point motion. Thus, to examine the computational mechanism in the M1, we modeled the isometric motor task of a musculoskeletal system required to generate the desired joint torque. Then, we computed the optimal feedback gain according to OFC. The feedback gain indicated directional tunings of the joint torque and end-point motion in Cartesian space that were similar to the M1 neuron PDs observed in previous studies. Thus, we suggest that the M1 acts as a feedback gain in OFC.
Non-Linear Analyses of Heart Rate Variability During Heavy Exercise and Recovery in Cyclists

We investigated the time course of RR interval variability during exercise and subsequent 50 minutes of recovery in seven well-trained male cyclists who performed an exercise with 3 successive 8 min stages at 40 %, 70 % and 90 % of their maximal oxygen uptake. The goal of the study was to check whether the decrease in the amplitude of heart rate variability during heavy exercise was accompanied by changes in the chaotic structure of the fluctuations. Heart rate variability was analysed in the temporal and frequency domain using traditional tools and using non-linear methods (Largest Lyapunov Exponent, Detrended Fluctuation Analysis, Minimum Embedding Dimension). When compared to rest, variability at the heaviest exercise intensity was significantly lower (RR: 0.94 +/- 0.22 vs. 0.34 +/- 0.01 ms; SDRR: 0.11 +/- 0.04 vs. 0.01 +/- 0.00 ms) due to a decrease in both LF (2101 +/- 1450 vs. 0.14 +/- 0.09 ms (2) . Hz (-1)) and HF spectral energy (1148 +/- 1126 vs. 7.88 +/- 9.24 ms (2) . Hz (-1)). Non-linear analyses showed that heart rate variability remained chaotic whatever the exercise intensity (the largest Lyapunov exponent was positive at 90 % of the maximal oxygen uptake), with a fractal organisation that tended towards white noise (DFA value close to 0.5) during heavy exercise. During recovery, temporal and spectral variables came back to their rest values within about 30 minutes following an exponential pattern. Non-linear analyses revealed that heartbeat dynamics were disorganised at the beginning of recovery, and involved more regulating systems than at rest, even after 50 minutes of recovery. We concluded that, during heavy exercise, heart rate variability was mainly influenced by other factors than autonomous nervous system, and suggest that mechanical or neurological couplings between the cardiac, locomotor and respiratory systems could play an important part in the observed changes.
Evaluating Living Kidney Donors: Relationship Types, Psychosocial Criteria, and Consent Processes at US Transplant Programs

We conducted a survey of 132 US kidney transplant programs to examine how they evaluate and select potential living kidney donors, focusing on donor‐recipient relationships, psychosocial criteria, and consent processes. There is heterogeneity in donor‐recipient relationships that are considered acceptable, although most programs (70%) will not consider publicly solicited donors. Most programs (75%) require a psychosocial evaluation for all potential living donors. Most programs agree that knowledge of financial reward (90%), active substance abuse (86%), and active mental health problems (76%) are absolute contraindications to donation. However, there is greater variability in how other psychosocial issues are considered in the selection process. Consent processes are highly variable across programs: donor and recipient consent for the donor evaluation is presumed in 57% and 76% of programs, respectively. The use of 13 different informed consent elements varied from 65% (alternative donation procedures) to 86% (description of evaluation, surgery and recuperative period) of programs. Forty‐three percent use a ‘cooling off’ period. Findings demonstrate high variability in current practice regarding acceptable donor‐recipient relationships, psychosocial criteria, and consent processes. Whether greater consensus should be reached on these donor evaluation practices, especially in the context of more expansive use of living donor kidney transplantation, is discussed.
Why board chairpersons need to be able to recognise the corporate psychopath CEO

This conceptual paper discusses some of the main reasons why, despite headlines indicating that psychopathy and success somehow go together, board chairpersons need to be informed how to recognize and deal with the psychopathic CEO. The consequences of psychopathic bullying and abusive leadership are explored through the literature. The paper concludes that psychopaths in CEO and other leadership positions are detrimental to the longer term interests of the organisations that employ them and that therefore their leadership needs to be countered by board chairs, as the only people who can realistically undertake this daunting task.
Dendritic spines containing μ‐opioid receptors in rat striatal patches receive asymmetric synapses from prefrontal corticostriatal afferents

Prefrontal corticostriatal afferents to the caudate‐putamen nucleus (CPN) have been implicated in motor and cognitive functions that are subject to opioid modulation through the μ‐opioid receptor (MOR). We examined the cellular basis for this modulation by combining anterograde transport of biotinylated dextran amine (BDA) following injections into the rat prefrontal cortex with immunocytochemical detection of MOR in patch compartments of the CPN. The BDA‐labeled neurons in deep layer V and layer VI of the dorsal part of the anterior cingulate cortex and the medial agranular cortex projected bilaterally, with an ipsilateral predominance, to MOR‐enriched patches in the dorsomedial and dorsocentral CPN, respectively. BDA‐labeled terminals often apposed MOR‐immunoreactive dendrites and perikarya but formed exclusively asymmetric, excitatory‐type synapses mainly with dendritic spines. Of the total anterogradely labeled axon terminals forming asymmetric synapses, 40% (151 of 377) were with MOR‐labeled spines, and 58% (220 of 377) were with unlabeled dendritic spines. In addition, immunogold‐silver particles for MOR were seen in 14% (134 of 938) of all BDA‐labeled axons and axon terminals. These dually labeled axon terminals also formed asymmetric synapses with dendritic spines that contained MOR immunoreactivity. The proportions of BDA‐labeled axon terminals forming asymmetric synapses with MOR‐labeled or unlabeled spines were similar in the CPN ipsilateral and contralateral to the cortical injections. These results suggest that, in patch compartments of the CPN, MOR plays a critical role in postsynaptic response to, but also in presynaptic modulation of, prefrontal corticostriatal excitation. J. Comp. Neurol. 396:223–237, 1998. © 1998 Wiley‐Liss, Inc.
Bronchoscopic lung volume reduction with a dedicated coil: a clinical pilot study

Background: Lung volume reduction aims to improve symptoms by reducing hyperinflation. Endoscopic approaches so far have generally been hampered in their efficacy by collateral ventilation (CV). We sought to determine the safety and feasibility of a new endoscopic lung volume reduction approach independent of the effects of CV. Methods: Patients with severe emphysema were eligible. Inclusion and exclusion criteria were modeled after the National Emphysema Treatment Trial (NETT) study. Homogenous and heterogeneous disease was allowed. Treatment consisted of the placement of coils into the parenchyma of the most diseased area with the intent of achieving parenchymal compression. Primary endpoints were safety and feasibility assessments. Secondary endpoints were efficacy outcomes. Results: Eleven patients underwent 21 procedures. Procedures were performed under general anesthesia and lasted 45±15 minutes and per procedure 4.9±0.6 coils were placed. All procedures were well tolerated. The total follow-up time was 7-11 months and in that time 33 adverse events were reported, none of them severe. No pneumothorax occurred. Efficacy seemed better in heterogeneous rather than homogenous disease. Conclusion: Endoscopic lung volume reduction with coils is safe and feasible. Further studies of the efficacy are indicated.
Effect of low‐intensity laser irradiation (660 nm) on a radiation‐impaired wound‐healing model in murine skin

The use of low‐intensity laser therapy (LILT) as a therapeutic modality has become popular in a variety of clinical applications including the promotion of wound repair. Although the clinical evidence base for such application remains sparse, recent studies have demonstrated a number of quantifiable photobiological effects associated with such therapy. In the present study, the effect of laser irradiation at various radiant exposures on a radiation‐impaired wound‐healing model in murine skin was investigated.
The contribution of trees to ecosystem methane emissions in a temperate forested wetland

Wetland‐adapted trees are known to transport soil‐produced methane (CH4), an important greenhouse gas to the atmosphere, yet seasonal variations and controls on the magnitude of tree‐mediated CH4 emissions remain unknown for mature forests. We examined the spatial and temporal variability in stem CH4 emissions in situ and their controls in two wetland‐adapted tree species (Alnus glutinosa and Betula pubescens) located in a temperate forested wetland. Soil and herbaceous plant‐mediated CH4 emissions from hollows and hummocks also were measured, thus enabling an estimate of contributions from each pathway to total ecosystem flux. Stem CH4 emissions varied significantly between the two tree species, with Alnus glutinosa displaying minimal seasonal variations, while substantial seasonal variations were observed in Betula pubescens. Trees from each species emitted similar quantities of CH4 from their stems regardless of whether they were situated in hollows or hummocks. Soil temperature and pore‐water CH4 concentrations best explained annual variability in stem emissions, while wood‐specific density and pore‐water CH4 concentrations best accounted for between‐species variations in stem CH4 emission. Our study demonstrates that tree‐mediated CH4 emissions contribute up to 27% of seasonal ecosystem CH4 flux in temperate forested wetland, with the largest relative contributions occurring in spring and winter. Tree‐mediated CH4 emissions currently are not included in trace gas budgets of forested wetland. Further work is required to quantify and integrate this transport pathway into CH4 inventories and process‐based models.
Production of granulocyte colony‐stimulating factor and granulocyte/macrophage‐colony‐stimulating factor after interleukin‐1 stimulation of marrow stromal cell cultures from normal or aplastic anemia donors

We have studied stromal cell function in naive or interleukin‐1 (IL‐1)‐stimulated (100 pg/ml) long‐term marrow cultures (LTC) from 12 normal donors and 21 patients with severe aplastic anemia (AA). Conditioned media (CM) from normal LTC contained levels of erythroid burst‐promoting activity (BPA) and granulocyte/macrophage (GM) colony‐stimulating activity (CSA) comparable to those previously described (Migliaccio et al., [1990] Blood, 75:305–312). The addition of IL‐1 to these cultures increased the level of CSA and, specifically, of granulocyte colony‐stimulating factor (G‐CSF) released. Anti‐GM‐CSF antibody neutralized BPA and CSA in normal naive LTC CM but only the CSA in the CM from IL‐1‐stimulated LTC. Since the concentrations of GM‐CSF, as detected with a specific immunoassay, did not increase after IL‐1 treatment, these data suggest that IL‐1‐stimulated cultures contain an unidentified growth factor having BPA. CM from AA stromal cells contained levels of CSA comparable to those observed in normal stromal cell CM but had significantly lower levels of BPA. Neither anti‐GM‐CSF nor anti‐IL‐3 antibodies neutralized the BPA in AA stromal cell CM. This activity may be related to that found in the CM of IL‐1‐treated normal stromal cells. In nearly 50% of stromal cell cultures of AA patients, addition of IL‐1 failed to increase the BPA, CSA, or G‐CSF. The presence of an inhibitor in naive or IL‐1‐treated AA stromal cell CM was excluded by adding the CM to IL‐3‐stimulated cultures. These findings suggest that G‐CSF and GM‐CSF genes are differentially regulated in the marrow microenvironment. Furthermore, a marrow microenvironment, deficient in BPA production and, in some cases, unresponsive to IL‐1 could contribute to marrow failure in some patients with AA. © 1992 Wiley‐Liss, Inc.
Historical Analysis of Participation in 161 km Ultramarathons in North America

Participation trends in 100 m (161 km) ultramarathon running competitions in North America were examined from race results from 1977 through 2008. A total of 32, 352 finishes accounted for by 9815 unique individuals were identified. The annual number of races and number of finishes increased exponentially over the study period. This growth in number of finishes occurred through a combination of (1) an increase in participation among runners ≥40 years of age from less than 40% of the finishes prior to the mid-1980s to 65–70% of the finishes since 1996, (2) a growth (p < 0.0001) in participation among women from virtually none in the late 1970s to nearly 20% since 2004, and (3) an increase in the average annual number of races completed by each individual to 1.3. While there has been considerable growth in participation, the 161 km ultramarathon continues to attract a relatively small number of participants compared with running races of shorter distances.