Miracle-dz/UniFAR-FTUs huggingface dataset:
Movement disorders in spinocerebellar ataxias

We read the article by van Gaalen et al. with great interest. These authors reviewed the frequency and main type of movement disorders found in each form of spinocerebellar ataxia (SCA). They also reported unusual movement disorders and noncerebellar manifestations, such as stiff-person syndrome, camptocormia, restless legs syndrome, and periodic limb movements during sleep. One of the key points highlighted by this review is the pattern of extracerebellar degeneration in SCA, supporting previous data describing substantia nigra, pons, pallidum, putamen, caudate nucleus, motor cortex, and thalamus involvement. For instance, the presence of parkinsonism in SCA3 is consistent with nigrostriatal impairment, a finding demonstrated in an early study. Recently, our group reported a case of akathisia in a patient with clinicallyand molecularly-proven SCA3. Akathisia is known to occur frequently in Parkinson’s disease, and striatal dopaminergic dysfunction is postulated to be the pathophysiological etiology of this movement disorder. Similarly, basal ganglia involvement, associated with dopaminergic dysfunction, is the most likely explanation for common movement disorders in SCA3 such as dystonia and bradykinesia. Given the pathophysiological mechanisms outlined, we performed a dopamine transporter (DAT) scan in vivo, using a tropane-derivative dopamine transporter type 1-99m technetium based ligand ([TC]-TRODAT-1), as the radioligand, to elucidate the underlying pathophysiology of the patient’s akathisia. Our results revealed DAT density within normal control ranges, suggesting that akathisia may not be related to presynaptic dopaminergic dysfunction. In line with these results, other pharmacologic studies have also implicated nondopaminergic pathways in the pathophysiology of akathisia. In conclusion, we believe that akathisia should be considered in the context of unusual SCArelated movement disorders, and that future studies will confirm akathisia-related pathophysiology. We also speculate that movement disorders in SCA are more complex than previously thought, involving degeneration in other brain regions.
The Influence of Acute Hypoxia and Carotid Body Denervation on Thermoregulation During Non‐Rapid Eye Movement Sleep in the Developing Lamb

We investigated the influence of ambient temperature on the thermoregulatory response to hypoxia in developing lambs before (at 4 and 14 days of age) and after (17 and 30 days of age) carotid body denervation (CBD). Lambs were studied during non‐rapid eye movement sleep at thermoneutral (23‐15°C) and cool (10‐5°C) ambient temperatures, during normoxia and acute hypoxia (inspired oxygen content of 13%). Measurements of oxygen consumption, arterial partial pressures of O2 and CO2, colonic temperature, incidence of shivering and plasma concentrations of thyroid hormones, cortisol, insulin and glucose were made under each condition. Oxygen consumption was higher at cool compared with thermoneutral ambient temperatures and decreased during hypoxia during cooling at all stages. At 4 days of age, only one lamb shivered during cooling in normoxia, but 4 out of 12 lambs shivered during hypoxia and colonic temperature fell, significantly, by 0.2°C. At 14 days, 8 out of 12 lambs shivered during cooling, of which 6 continued to shiver during hypoxia but colonic temperature did not change significantly. Plasma triiodothyronine concentrations increased on cooling at 4 and 14 days, an affect that was inhibited by hypoxia at 4, but not 14 days of age. At 17 days of age, i.e. post‐CBD, plasma thyroid hormone concentrations and oxygen consumption were lower during cold exposure compared with intact lambs at 14 days of age. In CBD lambs, imposing further hypoxia resulted in colonic temperature falling 0.6°C during cooling, with only 2 out of 10 lambs shivering. Plasma glucose and insulin, but not cortisol, concentrations decreased during hypoxia, irrespective of age or CBD. It is concluded that hypoxia has an important influence on metabolism and thermoregulation, which is modulated by age and environmental conditions. Compromised carotid body function, in lambs older than 2 weeks of age, can result in severe hypoxia and thermoregulatory dysfunction even with modest environmental cooling.
Prevention of Spinal Anesthesia-Induced Hypotension in the Elderly: Comparison Between Preanesthetic Administration of Crystalloids, Colloids, and No Prehydration

The practice of routinely prehydrating patients by infusing a crystalloid or colloid solution (up to 1.0 L/70 kg) for prevention of spinal anesthesia-induced hypotension has been challenged recently, after several reports of failure to demonstrate its efficacy in young women. We compared the incidence and frequency of hypotension and vasopressor therapy after spinal anesthesia and no prehydration with crystalloid and colloid prehydration in elderly patients. Eighty-five ASA grade I or II patients (aged 60-89 yr) for elective total hip replacement were randomized to receive 500 mL crystalloid solution (Hartmanns' [TM], n = 29), 500 mL colloid (Haemaccel [TM], n = 28), or no prehydration (n = 28) over 10 min prior to spinal anesthesia. Hypotension was defined as a 30% decrease from baseline systolic blood pressure (BP) or systolic <90 mm Hg, and was treated with ephedrine 3-mg boluses. Although absolute systolic BP readings were significantly higher in the colloid group between 6 and 30 min (P < 0.05), the incidence of hypotension was not significantly different between the groups. The incidence of ephedrine use, incidence of nausea/vomiting, and median total dose of ephedrine were similar in all groups. We conclude that, in elderly patients undergoing elective procedures, withholding prehydration is not associated with any greater degree of hypotension or need for vasopressor therapy compared with crystalloid or colloid prehydration. (Anesth Analg 1997;84:106-10)
On the mechanism of action of picrotoxin on GABA receptor channels in dissociated sympathetic neurones of the rat.

1. The mechanism of action of picrotoxin on GABA receptor channels in rat sympathetic neurones has been investigated with whole‐cell clamp. In addition, the action of picrotoxin on single GABA channels has been examined in outside‐out membrane patches from these cells. 2. Picrotoxin, at concentrations which dramatically reduced the amplitude of whole‐cell GABA currents, did not alter the spectral time constants or single‐channel conductance estimated by analysis of GABA‐activated current noise. This was observed at potentials both negative and positive to the GABA reversal potential (i.e. for both inward and outward GABA currents). In control conditions, the slow and fast time constants from GABA noise were 40 +/‐ 14 ms and 2 +/‐ 0.4 ms, while the estimated single‐channel conductance was 14 +/‐ 2 pS. In the presence of picrotoxin, the time constants and estimated single‐channel conductance were 41 +/‐ 5 ms, 2.7 +/‐ 0.6 ms and 15 +/‐ 2.3 pS. 3. Picrotoxin did not alter the shape of the whole‐cell GABA current‐voltage relationship, indicating that the steady‐state block was not voltage dependent. The lack of effect of picrotoxin on the GABA noise spectra and the lack of outward rectification makes it unlikely that picrotoxin acts by a simple voltage‐dependent (or voltage‐independent) channel blocking mechanism. In the presence of picrotoxin the reversal potential for GABA remained at approximately 0 mV in symmetrical chloride. 4. Distributions of total burst durations, obtained from single‐channel records with low concentrations of GABA, were fitted with three or four exponential components. Picrotoxin had no consistent effect on the time constants of the total burst length distributions. It also did not alter the amplitude of the main conductance state. However, picrotoxin did reduce the frequency of channel openings. 5. The application of brief ionophoretic pulses of GABA, to cells under whole‐cell voltage clamp, revealed that the rate of onset of block by picrotoxin was accelerated in the presence of GABA. In the absence of agonist, picrotoxin produced a more slowly equilibrating block. 6. Our data are consistent with a mechanism whereby picrotoxin binds preferentially to an agonist bound form of the receptor and stabilizes an agonist‐bound shut state. This could, for example, mean that picrotoxin enhances the occurrence of a desensitized state or an allosterically blocked state.
Rationally designed ligand‐independent peptide inhibitors of TREM‐1 ameliorate collagen‐induced arthritis

Triggering receptor expressed on myeloid cells 1 (TREM‐1) is critically involved in the pathogenesis of rheumatoid arthritis (RA). In contrast to cytokine blockers, therapeutic blockade of TREM‐1 can blunt excessive inflammation while preserving the capacity for microbial control. However, the nature of the TREM‐1 ligand(s) and mechanisms of TREM‐1 signalling are still not yet well understood, impeding the development of clinically relevant inhibitors of TREM‐1. The aim of this study was to evaluate the anti‐arthritic activity of a novel, ligand‐independent TREM‐1 inhibitory nonapeptide GF9 that was rationally designed using the signalling chain homo oligomerization (SCHOOL) model of cell signalling. Free GF9 and GF9 bound to macrophage‐targeted nanoparticles that mimic human high‐density lipoproteins (GF9‐HDL) were used to treat collagen‐induced arthritis (CIA). We also tested if 31‐mer peptides with sequences from GF9 and helices 4 (GE31) and 6 (GA31) of the major HDL protein, apolipoprotein A‐I, are able to perform three functions: assist in the self‐assembly of GA/E31‐HDL, target these particles to macrophages and block TREM‐1 signalling. We showed that GF9, but not control peptide, ameliorated CIA and protected against bone and cartilage damage. The therapeutic effect of GF9 was accompanied by a reduction in the plasma levels of macrophage colony‐stimulating factor and pro‐inflammatory cytokines such as tumour necrosis factor‐α, interleukin (IL)‐1 and IL‐6. Incorporation of GF9 alone or as a part of GE31 and GA31 peptides into HDL significantly increased its therapeutic efficacy. Collectively, our findings suggest that TREM‐1 inhibitory SCHOOL sequences may be promising alternatives for the treatment of RA.
Inmate responses to lengthy death row confinement.

Psychiatric interview and psychological testing were used to ascertain the effects of extended confinement on "death row" of eight men who were evaluated upon admission to prison and periodically thereafter for at least two years. Five appeared to adjust adequately over time, three to become significantly less functional. As a group they were more likely with increased confinement to utilize projection, to identify with each other and to an antisocial life-style, and to complain about health. While their ego strength was improved, their potential for adjustment in a new environment was felt to be diminished.
Case Report : A Patient with Severe Graves ’ Ophthalmopathy and Follicular Carcinoma

Graves’ disease is the most common form of thyrotoxicosis and may occur at any age, more commonly in females. It is currently viewed as an autoimmune disease of unknown cause. Thyroid carcinoma is a relatively rare tumor, but it represents the most frequent form of cancer of the endocrine glands. The coexistence of hyperthyroidism and thyroid cancer is considered a rare event. In the present case report we describe an unusual patient with severe Graves’ ophthalmopathy and after total thyroidectomy histological examination revealed the presence of follicular carcinoma. Turk Jem 2007; 11: 101-4
[Perceptions of hepatitis B vaccination in France. Analysis of three surveys].

BACKGROUND The main target for hepatitis B vaccination has never been reached, since less than 30% of infants were immunized in 2000. We wished to examine what might explain this situation by surveying attitudes within the general public and among vaccinators. METHODS We analyzed and compared the data on hepatitis B vaccination from three quantitative surveys conducted by the National Institute of Prevention and Health Education in 2003-2005. RESULTS Even those physicians (especially pediatricians) who are favorable to hepatitis B immunization do not always apply recommendations; 95% of physicians stated their patients are rather reticent to participate. Regarding the general public, less than half of French adults would be prepared to have their infant immunized against hepatitis B. CONCLUSION The usefulness of immunizing infants, rather than the absence of adverse events, should be put forth as the main argument in favour of hepatitis B immunization, both for physicians and the larger public.
Transition to adult care: experiences and expectations of adolescents with a chronic illness.

BACKGROUND Effective means of transitioning adolescent patients with chronic illness from paediatric to adult medical care are poorly documented and supported by limited evidence. The purpose of this study is to describe expectations and concerns of adolescents with chronic illness regarding transition from subspecialty paediatric to adult-centred care during the transition process in order guide effective programme design and implementation. METHODS Qualitative content and thematic analysis of semi-structured individual interviews with 22 adolescents with chronic illness, including cystic fibrosis, sickle cell disease, juvenile rheumatoid arthritis, and inflammatory bowel disease. Interviews took place at 1-3 time points over an 18-month study period. RESULTS Transition topics included: timing of transfer to adult care, the transition process, attitudes about transition, and factors that might aid transition. During the study period, one-third of participants made the transition to adult-oriented health care. All participants who had transitioned to adult-oriented care reported participating in a structured transition programme. Concerns of those who had not initiated the transition process centred on re-establishing relationships and bringing a new team 'up to speed'. Most adolescents anticipating transfer to adult care identified only downsides and felt unprepared to transition at the time of the interview. Subjects who had transitioned noted benefits of the adult-oriented system, even if they had been ambivalent prior to transfer of care. Participants suggested that earlier discussions about transition, opportunities to meet new healthcare teams and visits to adult-oriented venues prior to transition might aid in the transition process. CONCLUSIONS Subspecialty paediatric providers should anticipate common fears and concerns of adolescents and discuss the benefits of transfer to adult-oriented care. Further evaluation of existing transition programmes is an area for future study and is necessary for improvement of the continuum of care for adolescents with chronic medical conditions.
Menarcheal age in Turkey: Secular trend and socio-demographic correlates

Background: Menarche is an important indicator for assessing the developmental status of pubertal girls. Despite its importance, there is no nationwide information on menarcheal age in Turkey. Aim: This paper is the first attempt to examine age at menarche for Turkey as a whole. The aim is to present the secular trend of menarcheal age and variations across different socio-demographic groups. Methods: Data were employed from the Turkey Demographic and Health Survey, 2008. Mean menarcheal ages were estimated for birth cohorts and socio-demographic sub-groups. The pace of decline in menarcheal age has been estimated using multiple linear regression analysis, controlling for year of birth and other variables. Results: Mean age at menarche was estimated as 13.30 (95% CI = 13.26–13.35). It was estimated as 13.17 years (95% CI 12.95–13.38) for the youngest birth cohort (1989–1993), as opposed to 13.44 (95% CI 13.37–13.52) years for the cohort born in 1959–1968. Conclusion: Regression analysis indicated a decrease of 1.44 months per decade, providing evidence of a secular trend in menarcheal age in Turkey. Further results suggested childhood place of residence, education, welfare status and number of siblings to be significantly associated with menarcheal age.
Patient navigation: improving timeliness in the diagnosis of breast abnormalities.

OBJECTIVE Patient navigation is a process that provides assistance to referring physicians in arranging further investigations and consultation for defined patient groups. This can facilitate timely investigations and potentially minimize delays. The purpose of this study was to determine the impact of patient navigation on timeliness in the diagnosis of breast abnormalities. METHODS We retrospectively studied a cohort of 536 women who underwent breast core biopsy at our institution during comparable 6-month periods in 1999 and 2000 to determine the effects of patient navigation, age, and biopsy result on the wait for a biopsy after diagnostic imaging. Patient navigation was used for all women referred through the provincial breast cancer screening program. Navigation was unavailable to patients directly referred by physicians in 1999. In 2000, the program was expanded to encompass all patients. RESULTS From 1999 to 2000, the median wait for a biopsy remained relatively stable for "navigated" screening patients at 12 days (n = 97) and 13 days (n = 133), respectively. The introduction of patient navigation for directly referred patients resulted in a statistically significant decrease in waiting times, from 20 days (n = 144) in 1999 to 14 days (n = 162) in 2000. Age and biopsy results were statistically significant variables, but their effect on the group data was negligible relative to that of navigation. CONCLUSIONS Patient navigation significantly improves timeliness in the diagnosis of breast abnormalities and can potentially improve quality of life with more timely reassurance for women with benign conditions and earlier treatment for those with malignancy.
Tyrosine kinase/p21ras/MAP‐kinase pathway activation by estradiol‐receptor complex in MCF‐7 cells.

The mechanism by which estradiol acts on cell multiplication is still unclear. Under conditions of estradiol‐dependent growth, estradiol treatment of human mammary cancer MCF‐7 cells triggers rapid and transient activation of the mitogen‐activated (MAP) kinases, erk‐1 and erk‐2, increases the active form of p21ras, tyrosine phosphorylation of Shc and p190 protein and induces association of p190 to p21ras‐GAP. Both Shc and p190 are substrates of activated src and once phosphorylated, they interact with other proteins and upregulate p21ras. Estradiol activates the tyrosine kinase/p21ras/MAP‐kinase pathway in MCF‐7 cells with kinetics which are similar to those of peptide mitogens. It is only after introduction of the human wild‐type 67 kDa estradiol receptor cDNA that Cos cells become estradiol‐responsive in terms of erk‐2 activity. This finding, together with the inhibition by the pure anti‐estrogen ICI 182 780 of the stimulatory effect of estradiol on each step of the pathway in MCF‐7 cells proves that the classic estradiol receptor is responsible for the transduction pathway activation. Transfection experiments of Cos cells with the estradiol receptor cDNA and in vitro experiments with c‐src show that the estradiol receptor activates c‐src and this activation requires occupancy of the receptor by hormone. Our experiments suggest that c‐src is an initial and integral part of the signaling events mediated by the estradiol receptor.
The Determinants of Health Expenditures in Tunisia: An ARDL Bounds Testing Approach

This article examines the determinants of health expenditures in Tunisia during the period 1961-2008, using the Autoregressive Distributed Lag (ARDL) approach by Pesaran et al. (2001). The results of the bounds test show that there is a stable long-run relationship between per capita health expenditure, GDP, population ageing, medical density and environmental quality. In fact, on the one hand there are the short-run and long-run results which reveal that health care is a necessity, not a luxury good. On the other hand, results of the causality test show that there is a bidirectional causal flow from health expenditures to income, both in the short and in the long run.
Evaluation of Injectable Minerals and Growth Implants to Enhance Weaned Calf Development

Injectable minerals and growth implants were used in a grazing study to evaluate their effect on performance and health status of weaned beef calves. This 56-day study utilized 131 heifers purchased from two middle Tennessee sale barns in fall 2006. Heifers were randomly allotted to one of four treatments including 1) Control, no mineral injection, no implant, 2) injection of MultiMin, no implant, 3) no mineral injection, Ralgro growth promotant and 4) injection of MultiMin, Ralgro growth promotant. Cattle grazed tall fescue dominated pasture and were supplemented with pelleted corn gluten feed at 0.5% average initial body weight. Cattle were weighed on days 0, 1, 28, 55 and 56 and blood was drawn for glutathione peroxidase activity analysis. Additionally, feed, forage and water samples were collected on day 1. All data were analyzed using the mixed procedure of SAS, with differences determined at (P < 0.05). MultiMin injection had no effect on calf performance while Ralgro administration caused higher (P < 0.05) weight gains. Glutathione peroxidase activity was not affected by Ralgro but was increased (P < 0.01) from d-1 to d-56 by MultiMin injection. MultiMin may be useful in beef calf weaning programs for improving health status.
Cost analysis of postmastectomy reconstruction: A comparison of two staged implant reconstruction using tissue expander and acellular dermal matrix with abdominal‐based perforator free flaps

Two staged tissue expander‐implant with acellular dermal matrix (TE/I + ADM) and deep inferior epigastric perforator (DIEP) flap are the most common implant and autologous methods of reconstruction in the U.S. Implant‐based techniques are disproportionally more popular, partially due to its presumed cost effectiveness. We performed a comprehensive cost analysis to compare TE/I + ADM and DIEP flap.
Targeted STIM deletion impairs calcium homeostasis, NFAT activation, and growth of smooth muscle

The Ca2+‐sensing stromal interaction molecule (STIM) proteins are crucial Ca2+ signal coordinators. Cre‐lox technology was used to generate smooth muscle (sm)‐targeted STIM1‐, STIM2‐, and double STIM1/STIM2‐knockout (KO) mouse models, which reveal the essential role of STIM proteins in Ca2+ homeostasis and their crucial role in controlling function, growth, and development of smooth muscle cells (SMCs). Compared to Cre+/– littermates, sm‐STIM1‐KO mice showed high mortality (50% by 30 d) and reduced bodyweight. While sm‐STIM2‐KO was without detectable phenotype, the STIM1/STIM double‐KO was perinatally lethal, revealing an essential role of STIM1 partially rescued by STIM2. Vascular and intestinal smooth muscle tissues from sm‐STIM1‐KO mice developed abnormally with distended, thinned morphology. While depolarization‐induced aortic contraction was unchanged in sm‐STIM1‐KO mice, α1‐adrenergic‐mediated contraction was 26% reduced, and store‐dependent contraction almost eliminated. Neointimal formation induced by carotid artery ligation was suppressed by 54%, and in vitro PDGF‐induced proliferation was greatly reduced (79%) in sm‐STIM1‐KO. Notably, the Ca2+ store‐refilling rate in STIM1‐KO SMCs was substantially reduced, and sustained PDGF‐induced Ca2+ entry was abolished. This defective Ca2+ homeostasis prevents PDGF‐induced NFAT activation in both contractile and proliferating SMCs. We conclude that STIM1‐regulated Ca2+ homeostasis is crucial for NFAT‐mediated transcriptional control required for induction of SMC proliferation, development, and growth responses to injury. —Mancarella, S. , Potireddy, S. , Wang, Y. , Gao, H. , Gandhirajan, K. , Autieri, M. , Scalia, R. , Cheng, Z. , Wang, H. , Madesh, M. , Houser, S. R. , Gill, D. L. Targeted STIM deletion impairs calcium homeostasis, NFAT activation, and growth of smooth muscle. FASEB J. 27, 893–906 (2013). www.fasebj. org