Miracle-dz/UniFAR-FTUs huggingface dataset:
Iron dysregulation in Huntington's disease

Huntington's disease (HD) is one of many neurodegenerative diseases with reported alterations in brain iron homeostasis that may contribute to neuropathogenesis. Iron accumulation in the specific brain areas of neurodegeneration in HD has been proposed based on observations in post‐mortem tissue and magnetic resonance imaging studies. Altered magnetic resonance imaging signal within specific brain regions undergoing neurodegeneration has been consistently reported and interpreted as altered levels of brain iron. Biochemical studies using various techniques to measure iron species in human samples, mouse tissue, or in vitro has generated equivocal data to support such an association. Whether elevated brain iron occurs in HD, plays a significant contributing role in HD pathogenesis, or is a secondary effect remains currently unclear.
Overview of current surgical management of fibroids: ‘Organ-preserving modalities’

Summary Uterine fibroids are the most common solid tumours occurring in female pelvis and frequently encountered by gynaecologists. Generally about 50% remain asymptomatic and can be monitored through regular follow-up visits but symptomatic fibroids require surgical intervention at some stage. They occur in 25 – 50% of women over the age of 30 years, increasing with age and being more common in certain ethnic populations, especially the Afro-Caribbean. They have a major impact on women's health and were the most common indication for hysterectomy in England in 1993 – 1994.They have significant cost implications, the 72,362 hysterectomies performed in 1993 – 1994 costing the NHS an estimated £70 million. Although hysterectomy is the most certain cure for women with symptomatic fibroids who do not wish to preserve fertility, an increasing number of women are choosing and looking for the options of organ-conserving surgery. The surgery can be carried out abdominally, laparoscopically and vaginally although all routes are associated with an appreciable rate of morbidity. The discussion of organ-preserving surgery includes mainly myomectomy, transcervical resection of fibroid, uterine artery embolisation (UAE) and MRI-guided laser ablation. Hysterectomy is associated with a high rate of satisfaction and is likely to relieve menstrual problems in almost all women. Much work has been undertaken on this subject so far, with a view to safe and effective surgical approaches.
Clinical Course and Outcomes of Single-Organism Enterococcus Peritonitis in Peritoneal Dialysis Patients

♦ Background and Objectives: Enterococci are part of the normal flora of the gastrointestinal tract. They can cause enteric peritonitis, which is a serious complication of peritoneal dialysis (PD). However, the clinical course and outcome of PD-related Enterococcus peritonitis remains unclear. ♦ Methods: We reviewed all Enterococcus peritonitis episodes occurring in our dialysis unit from 1995 to 2009. ♦ Results: During the study period, 1421 episodes of peritonitis were recorded. Of 29 episodes (2.0%) that were attributable to single-organism Enterococcus, 12 episodes were caused by E. faecalis; 9, by E. faecium; and the remaining 8, by other Enterococcus species. The overall rate of ampicillin resistance was 41.4%. Recent use of antibiotics was associated with the development of ampicillin-resistant Enterococcus (ARE) peritonitis (hazard ratio: 12.53; p = 0.04). The primary response rate of Enterococcus peritonitis was significantly higher than that of Escherichia coli peritonitis (89.7% vs. 69.9%, p = 0.038), but the primary response rate was not significantly lower for ARE peritonitis than for ampicillin-susceptible Enterococcus (ASE) peritonitis (83.3% vs. 94.1%, p = 0.553). However, significantly more patients with ARE had received vancomycin (83.3% vs. 23.5%, p = 0.003), with a longer mean duration of vancomycin treatment (11.8 ± 6.9 days vs. 3.7 ± 6.8 days, p = 0.005). ♦ Conclusions: Recent use of antibiotics was a risk factor for the development of ARE peritonitis. Outcomes in ASE and ARE peritonitis were similar, but vancomycin was required during treatment for ARE peritonitis, in turn possibly predisposing the patients to infections caused by vancomycin-resistant organisms.
Occupation, Lifestyle Factors and Health-Related Quality Of Life: The Hordaland Health Study

Health-related quality of life was estimated using the physical and mental summary scores of the SF-12 Health Survey in a cross-sectional study of a general population of 23,312 individuals aged 40–47 years in Hordaland County, Norway. The mean scores in the main occupational groups were adjusted for lifestyle factors using a six-way analysis of covariance. The category of legislators, senior officials, and managers scored highest on both the physical and the mental components, whereas the drivers scored lowest on the physical health and agricultural and fishery workers scored lowest on mental health. Smoking showed marked dose-response relationships with reduced physical and mental health, and inverse U-shaped relationships were found for alcohol consumption and the body mass index, with the mental scale for body mass index peaking above the recommended range of 18.5 to 25.0 kg/m2. Although selection bias related to the choice of occupation cannot be ruled out, the low scores of the quality of life measure for the agricultural and fishery workers and the drivers most likely reflect the effect of known health stressors for these occupations.
Putative Activation of the Peroxisome Proliferator-Activated Receptor γ Impairs Androgen and Enhances Progesterone Biosynthesis in Primary Cultures of Porcine Theca Cells1

Abstract Ovarian theca cells are the predominant source of gonadotropin-stimulated androgen biosynthesis in vivo. Troglitazone (TG), a synthetic agonist of the peroxisome proliferator-activated receptor γ (PPARγ) and a thiazolidinedione used to treat insulin resistance, decreases serum androgen concentrations in women with hyperthecosis and/or polycystic ovary syndrome. Using reverse transcription-polymerase chain reaction (RT-PCR), we demonstrated the presence of PPARγ mRNA in the porcine ovary. Since activation of ovarian PPARγ may alter hormone-stimulated steroidogenesis in vitro, we cultured porcine theca cells for 48 h in the presence of two different PPARγ ligands, TG and 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2). Putative TG-mediated activation of PPARγ resulted in a 53%–69% decrease in LH- and/or insulin-stimulated androstenedione and testosterone accumulation. Although TG reduced 3-isobutylmethylxanthine-enhanced LH-stimulated cAMP accumulation by 74%–78%, it did not alter basal cAMP concentrations. Exposure to 8Br-cAMP did not overcome the TG-induced inhibition of androgen accumulation. In contrast, TG administration amplified basal and hormone-stimulated progesterone accumulation, particularly in the presence of insulin, without altering levels of 17α-hydroxyprogesterone. The putative natural PPARγ ligand, 15d-PGJ2, inhibited androgen biosynthesis and stimulated progesterone production. RT-PCR-based amplification of cytochrome P450 cholesterol side-chain cleavage (CYP11A) and cytochrome P450 17α-hydroxylase/C-17,20-lyase (CYP17) transcripts indicated that TG moderately enhanced expression of these genes. However, TG did not affect CYP17 protein expression. We conclude that putative ligand-mediated activation of PPARγ decreases LH- and/or insulin-driven theca cell androgen production by impairing the ability of CYP17 to synthesize androstenedione from available progestins. The corresponding augmentation of progesterone production could suggest that PPARγ activation induces theca cell differentiation toward a progestin-synthesizing phenotype.
Association of Selective Serotonin Reuptake Inhibitors with Transfusion in Surgical Patients

BACKGROUND:The clinical relevance of chronic exposure to selective serotonin reuptake inhibitors (SSRIs) to transfusion in surgical patients is unclear. METHODS:We conducted a prospective cohort study involving patients undergoing cardiac, vascular, spinal, and intracranial surgery at 2 academic medical centers. Medication use, demographics, comorbidities, and laboratory values were determined at baseline by patient interview and review of medical records. The primary outcome was transfusion of any hemostatic allogeneic blood product (i.e., fresh frozen plasma, platelets, and/or cryoprecipitate) through postoperative day 2. RESULTS:The study sample consisted of 767 patients; 364 patients (47.5%) underwent cardiac surgery and the remainder underwent noncardiac surgery. Eighty-eight patients (11.5%) used SSRIs preoperatively. Among cardiac patients, the absolute number of allogeneic transfusions was higher for SSRI users than nonusers (2 [0–6] vs 0 [0–2], median [25%–75%], respectively, P = 0.008), and a similar trend was observed for noncardiac surgery. After adjusting for covariates using ordinal logistic regression, preoperative SSRI use was associated with an approximately 2-fold (odds ratio, 2.2; 95% confidence interval, 1.2–3.98) increase in odds of exposure to allogeneic hemostatic blood products; similar results were observed using propensity score adjustment (odds ratio, 1.85; 95% confidence interval, 1.11–3.07). A significant interaction between SSRI use and surgery type, age, sex, or concurrent antiplatelet therapy was not found; however, heterogeneity in magnitude of effect could not be excluded. CONCLUSIONS:Preoperative use of SSRIs is associated with increased exposure to allogeneic hemostatic blood products in surgical patients at high risk for perioperative bleeding. Determining whether perioperative continuation or withdrawal of SSRIs produces a net clinical benefit requires randomized controlled trials.
Yeast Nfs1p Is Involved in Thio-modification of Both Mitochondrial and Cytoplasmic tRNAs*

The IscS protein is a pyridoxal phosphate-containing cysteine desulfurase involved in iron-sulfur cluster biogenesis. In prokaryotes, IscS is also involved in various metabolic functions, including thio-modification of tRNA. By contrast, the eukaryotic ortholog of IscS (Nfs1) has thus far been shown to be functional only in mitochondrial iron-sulfur cluster biogenesis. We demonstrate here that yeast Nfs1p is also required for the post-transcriptional thio-modification of both mitochondrial (mt) and cytoplasmic (cy) tRNAs in vivo. Depletion of Nfs1p resulted in an immediate impairment of the 2-thio-modification of 5-carboxymethylaminomethyl-2-thiouridine at the wobble positions of \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(\mathrm{mt-tRNA}_{\mathrm{UUU}}^{\mathrm{Lys}}\) \end{document} and \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(\mathrm{mt-tRNA}_{\mathrm{UUG}}^{\mathrm{Gln}}\) \end{document}. In addition, we observed a severe reduction in the 2-thio-modification of 5-methoxycarbonylmethyl-2-thiouridine (mcm5s2U) of \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(\mathrm{cy-tRNA}_{\mathrm{UUU}}^{\mathrm{Lys}2}\) \end{document} and \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(\mathrm{cy-tRNA}_{\mathrm{UUC}}^{\mathrm{Glu}3}\) \end{document}, although the effect was somewhat delayed compared with that seen in mt-tRNAs. Mass spectrometry analysis revealed an increase in 5-methoxycarbonylmethyluridine concomitant with a decrease in mcm5s2U in cy-tRNAs that were prepared from Nfs1p-depleted cells. These results suggest that Nfs1p is involved in the 2-thio-modification of both 5-carboxymethylaminomethyl-2-thiouridine in mt-tRNAs and mcm5s2U in cy-tRNAs.
The effects of oestrogens on linear bone growth

Regulation of linear bone growth in children and adolescents comprises a complex interaction of hormones and growth factors. Growth hormone (GH) is considered to be the key hormone regulator of linear growth in childhood. The pubertal increase in growth velocity associated with GH has traditionally been attributed to testicular androgen secretion in boys, and to oestrogens or adrenal androgen secretion in girls. Research data indicating that oestrogen may be the principal hormone stimulating the pubertal growth spurt in boys as well as girls is reviewed. Such an action is mediated by oestrogen receptors (ER‐α and ER‐β) in the human growth plate, and polymorphisms in the ER gene may influence adult height in healthy subjects. Prepubertal oestradiol concentrations are significantly higher in girls than in boys, explaining sex‐related differences in pubertal onset. Men with a disruptive mutation in the ER gene (oestrogen resistance) or in the CYP19 gene (aromatase deficiency) who have no pubertal growth spurt and continue to grow into adulthood due to lack of epiphyseal fusion supports this notion. Furthermore, phenotypic females with complete androgen insensitivity syndrome have a normal female growth spurt despite lack of androgen action. Oestrogens may also influence linear bone growth indirectly via modulation of the GH‐insuIin‐like growth factor‐I (IGF‐I) axis. Thus, ER blockade diminishes endogenous GH secretion, androgen receptor (AR) blockade increases GH secretion in peripubertal boys, and non‐aromatizable androgens [oxandrolone or dihydrotestosterone (DHT)] have no effect on GH secretion. Treatment with aromatase inhibitors reduces circulating IGF‐I concentrations in healthy males, and reduces growth in boys with testotoxicosis. Taken together, these findings suggest that oestrogens may, in addition to their direct effects, stimulate GH secretion and thereby increase circulating IGF‐I, which in turn may stimulate growth. Thus, oestrogens have important biphasic actions on longitudinal growth in boys as well as in girls. Very low levels of oestrogens may stimulate bone growth without affecting sexual maturation directly at the growth plate as well as through stimulation of the GH‐IGF axis, which in turn may stimulate growth. Conversely, higher levels of oestrogens stimulate secondary sexual characteristics and epiphyseal fusion.
Toll-Like Receptor 2 Regulates CXC Chemokine Production and Neutrophil Recruitment to the Cornea in Onchocerca volvulus/ Wolbachia-Induced Keratitis

ABSTRACT The filarial nematode Onchocerca volvulus is the causative organism of river blindness. Our previous studies demonstrated an essential role for endosymbiotic Wolbachia bacteria in corneal disease, which is characterized by neutrophil infiltration into the corneal stroma and the development of corneal haze. To determine the role of Toll-like receptors (TLRs) in neutrophil recruitment and activation, we injected a soluble extract of O. volvulus containing Wolbachia bacteria into the corneal stromata of C57BL/6, TLR2−/−, TLR4−/−, TLR2/4−/−, and TLR9−/− mice. We found an essential role for TLR2, but not TLR4 or TLR9, in neutrophil recruitment to the cornea and development of corneal haze. Furthermore, chimeric mouse bone marrow studies showed that resident bone marrow-derived cells in the cornea can initiate this response. TLR2 expression was also essential for CXC chemokine production by resident cells in the cornea, including corneal fibroblasts, and for neutrophil activation. Taken together, these findings indicate that Wolbachia activates TLR2 on resident bone marrow-derived cells in the corneal stroma to produce CXC chemokines, leading to neutrophil recruitment to the corneal stroma, and that TLR2 mediates O. volvulus/Wolbachia-induced neutrophil activation and development of corneal haze.
Coping with Childbirth: Brain Structural Associations of Personal Growth Initiative

Major life events require psychological adaptations and can be accompanied by brain structural and functional changes. The goal of the current study was to investigate the association of personal growth initiative (PGI) as a form of proactive coping strategy before childbirth, with gray matter volume after delivery. Childbirth is one of the few predictable major life events, which, while being one of the most positive experiences for many, is also accompanied by multidimensional stress for the mother. Previous research has shown that high stress is associated with reductions in gray matter volume in limbic cortices as well as the prefrontal cortex (PFC). We hypothesized that PGI before childbirth is positively related to gray matter volume after delivery, especially in the ventromedial PFC (vmPFC). In a prospective study, 22 first-time mothers answered questionnaires about their PGI level 1 month before birth (T1) and 1 month after delivery (T2). Four months after giving birth, a follow-up assessment was applied with 16 of these mothers (T3). Structural brain data were acquired at both postpartal measurement occasions. Voxel-based morphometry was used to correlate prenatal PGI levels with postpartal gray matter volume. Higher PGI levels before delivery were positively associated with larger gray matter volume in the vmPFC directly after childbirth. Previous structural neuroimaging research in the context of major life events focused primarily on pathological reactions to stress (e.g., post-traumatic stress disorder; PTSD). The current study gives initial indications that proactive coping may be positively associated with gray matter volume in the vmPFC, a brain region which shows volumetric reductions in PTSD patients.
Toward a Person‐centered Medicine: Religious Studies in the Medical Curriculum

Abstract The role of religious studies in the medical curriculum derives from three important aspects of people's engagement with religious belief and practice. These are (1) religion as a source of meaning, (2) religion as a source and frame‐work for values, and (3) religion as an outstanding context for the appreciation of human diversity. By offering separate religious studies courses, or by introducing religious themes and content into students' other learning experiences, the curriculum can foster the student's respect for the individuality of the patient in his or her cultural context; heighten the student's awareness of the patient's—and his or her own—beliefs, values, and faith as resources for dealing with illness, suffering, and death; help students address any of the myriad value‐laden aspects of everyday living that are part of the context of many doctor—patient encounters; and strengthen the student's commitment to a person‐centered medicine that emphasizes the care of the suffering person rather than the biology of disease. The authors discuss the strengths and limitations of several settings for the teaching of religious issues in medicine, and suggest specific pedagogical approaches, readings, and resources. Acad. Med. 70(1995):806–813.
Association between hypertension and variation in the alpha- and beta-adducin genes in a white population.

BACKGROUND The substitution of tryptophan for glycine at amino acid 460 (Gly460Trp polymorphism) of the alpha-subunit of the heterodimeric cytoskeleton protein adducin increases renal sodium reabsorption and may be involved in the pathophysiology of essential hypertension. In the present study, we investigated in multivariate analyses whether the risk of hypertension was associated with the C1797T polymorphism of the beta-adducin gene. METHODS A total of 1848 subjects randomly selected from a white population were genotyped. Study nurses measured blood pressure at the participants' homes. RESULTS The frequencies of the alpha-adducin Trp and beta-adducin T alleles were 0.23 and 0.11, respectively. In men (N = 904), the beta-adducin T allele was not associated with hypertension [adjusted relative risk (RR) vs. CC homozygotes 0.94, P = 0.77], but T allele carriers had lower plasma renin activity (PRA) and 24-hour urinary aldosterone excretion (P < 0.04). In all women (N = 944), beta-adducin T allele carriers had a higher risk of hypertension than CC homozygotes (RR 1.81, CI 1.18-2.77, P = 0.007), but similar PRA and 24-hour urinary aldosterone excretion (P> 0.29). In 345 post-menopausal women and 190 users of oral contraceptives, the RRs of hypertension were 2.47 (CI 1.34-4.64, P = 0.003) and 2.56 (CI 0.83-7.86, P = 0.10), respectively. For systolic pressure in women, there was a significant interaction (P = 0.02) between the alpha- and beta-adducin polymorphisms. Only in female carriers of the mutated alpha-adducin Trp allele was the systolic pressure significantly higher in beta-adducin T allele carriers compared with CC homozygotes (+3.8 mm Hg, P = 0.02). Furthermore, in the presence of the mutated alpha-adducin Trp allele, the RRs associated with the beta-adducin T allele were 2.35 (P = 0.01) in all women, 2.92 (P = 0.03) in post-menopausal subjects, and 3.79 (P = 0.09) in users of oral contraceptives. CONCLUSIONS The 1797T allele of the beta-adducin gene is associated with increased risk of hypertension in post-menopausal women and in users of oral contraceptives, particularly in the presence of the mutated alpha-adducin Trp allele. We hypothesize that inhibition of the renin-aldosterone system in men and absence of such a compensatory mechanism in women may explain, at least to some extent, the sexual dimorphism of the blood pressure phenotype in relation to the C1797T beta-adducin polymorphism.
Long‐term hormone therapy and radiation is cost‐effective for patients with locally advanced prostate carcinoma

In Radiation Therapy Oncology Group (RTOG) trial 92‐02, after men received neoadjuvant hormone cytoreduction and radiotherapy for locally advanced prostate carcinoma, they were randomized to receive either 2 years of long‐term androgen‐deprivation (LTAD) or no further treatment (short‐term androgen‐deprivation [STAD]). The specific objective of the current study was to determine whether LTAD was a cost‐effective treatment for patients with locally advanced prostate carcinoma.
Dimensions of Personality Disorder: The DSM-III-R Cluster A Diagnoses

The authors adopt a construct validity approach to examine the structural validity of diagnoses of paranoid, schizoid, and schizotypal personality disorders. Systematic descriptions of these diagnoses were developed based on features identified from the literature that were organized using the clinicians' ratings. Each diagnosis was described in terms of a series of behavioral dimensions. Sets of behavioral exemplars were developed to assess each dimension. Dimensions and diagnoses were found to exhibit satisfactory levels of internal consistency that were cross-validated in a general population sample of 274 subjects and a clinical sample of 133 patients with a diagnosis of personality disorder. Some dimensions did not correlate highly with the total diagnosis score. Diagnoses could probably be refined by eliminating these dimensions. The structural relationships between dimensions delineating each diagnosis were explored using factor analysis. Diagnoses were not unifactorial. Instead, each diagnosis was found to be composed of two factors. The factorial structure of each diagnosis was found to be similar in the general population and clinical sample. It is suggested that the results support a dimensional representation of these diagnoses using three dimensions: paranoid behaviors, social avoidance, and perceptual cognitive distortion