Miracle-dz/UniFAR-FTUs huggingface dataset:
Association of prenatal phenobarbital and phenytoin exposure with small head size at birth and with learning problems

Small head size has been observed in prenatally anticonvulsant‐exposed neonates. In infancy, cognitive impairments were revealed. It is presently unknown whether these impairments are permanent or disappear after puberty. We studied the link between the prenatal influence of anticonvulsants on brain development and cognitive functioning in adulthood: a retrospective study on head size and a follow‐up assessing cognitive capacities among adults who had been included in the retrospective study. The retrospective study comprised 172 exposed and 168 control neonates, matched with respect to age, sex and their mothers' age. Prenatally phenobarbital + phe‐nytoin‐exposed neonates had a significantly smaller occipitofrontal circumference (OFC) than prenatally phenobarbital‐monotherapy‐exposed and control neonates (mean difference of 0.7 cm). In the follow‐up, no difference in cognitive functioning was found between the exposed and the control groups. Most of the prenatally anticonvulsant‐exposed subjects had normal intellectual capacity. However, 12% of the exposed subjects versus 1% of the controls had persistent learning problems. In addition, more of the exposed subjects were mentally retarded. There was no clear relationship between learning problems and small OFC, maternal epilepsy or unfavourable family climate.
Neural control of the lower urinary and gastrointestinal tracts: Supraspinal CNS mechanisms

Normal urinary function is contingent upon a complex hierarchy of CNS regulation. Lower urinary tract afferents synapse in the dorsal horn of the spinal cord and ascend to the midbrain periaqueductal gray (PAG), with a separate nociception path to the thalamus. A spino‐thalamo‐cortical sensory pathway is present in some primates, including humans. In the brainstem, the pontine micturition center (PMC) is a convergence point of multiple influences, representing a co‐ordinating center for voiding. Many PMC neurones have characteristics necessary to categorize the center as a pre‐motor micturition nucleus. In the lateral pontine brainstem, a separate region has some characteristics to suggest a “continence center. ” Cerebral control determines that voiding is permitted if necessary, socially acceptable and in a safe setting. The frontal cortex is crucial for decision making in an emotional and social context. The anterior cingulate gyrus and insula co‐ordinate processes of autonomic arousal and visceral sensation. The influence of these centers on the PMC is primarily mediated via the PAG, which also integrates bladder sensory information, thereby moderating voiding and storage of urine, and the transition between the two phases. The parabrachial nucleus in the pons is also important in behavioral motivation of waste evacuation. Lower urinary tract afferents can be modulated at multiple levels by corticolimbic centers, determining the interoception of physiological condition and the consequent emotional motor responses. Alterations in cognitive modulation, descending modulation, and hypervigilance are important in functional (symptom‐based) clinical disorders. Neurourol. Urodynam. 29: 119–127, 2010. © 2009 Wiley‐Liss, Inc.
Effectiveness of early intervention in psychosis

Purpose of review Over 15 years, early intervention in psychosis has grown to become a mainstream funded approach to clinical care. This review examines recent developments in evaluating the effectiveness of early intervention. It considers identification and treatment of those at risk of psychosis, as well as interventions in the postonset phase of illness. Recent findings Development of methods identifying those at risk of psychosis continues to evolve. Promising results in the prevention and delay of transition to psychotic disorder from a high-risk state have been found. Psychological and psychosocial interventions are important components of these preventive programmes. Two recent meta-analyses indicate that there is a consistent relationship between duration of untreated psychosis and outcome independent of other factors. Further evidence shows that early intervention reduces the duration of untreated psychosis, produces better outcomes in terms of symptomatic and functional domains, and is cheaper than standard models of care. Summary There is evidence that early intervention is effective for early psychosis. Some challenges remain. These include developing a greater focus on functional recovery and prevention of relapse.
Energy Healing: A Complementary Treatment for Orthopaedic and Other Conditions

Complementary and alternative therapies continue to grow in popularity among healthcare consumers. Among those modalities is energy healing (EH) (Eisenberg et al., 1998). EH is an adjunctive treatment that is noninvasive and poses little downside risk to patients. Well more than 50 major hospitals and clinics throughout the United States offer EH to patients (DiNucci, research table on healthcare facilities that offer Reiki, unpublished data, 2002). The National Institutes of Health is funding numerous EH studies that are examining its effects on a variety of conditions, including temporomandibular joint disorders, wrist fractures, cardiovascular health, cancer, wound healing, neonatal stress, pain, fibromyalgia, and AIDS (National Institutes of Health, 2004a). Several well-designed studies to date show significant outcomes for such conditions as wound healing (Grad, 1965) and advanced AIDS (Sicher, Targ, Moore, & Smith, 1998), and positive results for pain and anxiety (Aetna Intellihealth, 2003a; Wardell, Weymouth, 2004), among others (Gallob, 2003). It is also suggested that EH may have positive effects on various orthopaedic conditions, including fracture healing, arthritis, and muscle and connective tissue (Prestwood, 2003). Because negative outcomes risk is at or near zero throughout the literature, EH is a candidate for use on many medical conditions.
A Comparison of the Imaging Characteristics and Microregional Distribution of 4 Hypoxia PET Tracers

We compared the imaging characteristics and hypoxia selectivity of 4 hypoxia PET radiotracers (18F-fluoromisonidazole [18F-FMISO], 18F-flortanidazole [18F-HX4], 18F-fluoroazomycin arabinoside [18F-FAZA], and 64Cu-diacetyl-bis(N4-methylsemicarbazone) [64Cu-ATSM]) in a single murine xenograft tumor model condition using small-animal PET imaging and combined ex vivo autoradiography and fluorescence immunohistochemistry. Methods: Nude mice bearing SQ20b xenograft tumors were administered 1 of 4 hypoxia PET tracers and images acquired 80–90 min after injection. Frozen sections from excised tumors were then evaluated for tracer distribution using digital autoradiography and compared with histologic markers of tumor hypoxia (pimonidazole, carbonic anydrase 9 [CA9]) and vascular perfusion (Hoechst 33342). Results: The highest tumor uptake was observed with 64Cu-ATSM (maximum standardized uptake values [SUVmax], 1.26 ± 0.13) and the lowest with 18F-FAZA (SUVmax, 0.41 ± 0.24). 18F-FMISO and 18F-HX4 had similar intermediate tumor uptake (SUVmax, 0.76 ± 0.38 and 0.65 ± 0.19, respectively). Digital autoradiographs of hypoxia tracer distribution were compared pixel by pixel with images of immunohistochemistry stains. The fluorinated nitroimidazoles all showed radiotracer uptake increasing with pimonidazole and CA9 staining. 64Cu-ATSM showed the opposite pattern, with highest radiotracer uptake observed in regions with the lowest pimonidazole and CA9 staining. Conclusion: The fluorinated nitroimidazoles showed similar tumor distributions when compared with immunohistochemistry markers of hypoxia. Variations in tumor standardized uptake value and normal tissue distribution may determine the most appropriate clinical setting for each tracer. 64Cu-ATSM showed the highest tumor accumulation and little renal clearance. However, the lack of correlation between 64Cu-ATSM distribution and immunohistochemistry hypoxia markers casts some doubt on the hypoxia selectivity of 64Cu-ATSM.
Characterization and Modeling of Transistor Variability in Advanced CMOS Technologies

This paper aims at reviewing the results that we have obtained during the last ten years in the characterization and modeling of transistor mismatch in advanced complementary metal-oxide-semiconductor (CMOS) technologies. First, we review the theoretical background and modeling approaches that are generally employed for analyzing and interpreting the mismatch results. Next, we present the experimental procedures and methodologies that we used for characterizing the transistor matching. Then, we discuss typical matching results that were obtained on modern CMOS technologies and analyze the main variability (mismatch) sources. Finally, we conclude by summarizing our findings and giving some recommendations for future technologies.
Electromyographic and Kinetic Analysis of Traditional, Chain, and Elastic Band Squats

This study examined mean integrated electromyography (I-EMG) for the quadriceps and hamstring muscle groups, as well as mean and peak vertical ground reaction forces (GRFs), for 3 conditions of the back squat. Conditions included (a) squat with barbell and weight plates, (b) squat with barbell and weight plates plus chains hung on each end of the barbell to replace approximately 10% of the squat load, and (c) squat with barbell and weight plates plus elastic bands offering resistance equivalent to approximately 10% of the squat load. Weight plates equal to the load added by either the chains or elastic bands were removed for the latter 2 squat conditions. Vertical GRFs were obtained during a single testing session for all 3 squat conditions. The tests were performed on a 2-cm thick aluminum platform (0.76 × 1.0 m) bolted directly to a force plate (OR6–5–2000, AMTI, Watertown, MA). Surface electrode I-EMG data from the quadriceps and hamstrings were recorded at 500 Hz. The exercise order was randomly determined for 11 NCAA Division I athletes who had experience using these types of squats. A repeated measures analysis of covariance revealed no differences in I-EMG and GRF during the eccentric or concentric phase for any of the 3 squat conditions. Analyses showed that mean GRF and I-EMG was significantly different between eccentric and concentric phases for all groups. The results question the usefulness of performing squats combining barbell and weight plates with chain and elastic resistance.
The Yeast Mitochondrial Carrier Leu5p and Its Human Homologue Graves' Disease Protein Are Required for Accumulation of Coenzyme A in the Matrix

ABSTRACT The transport of metabolites, coenzymes, and ions across the mitochondrial inner membrane is still poorly understood. In most cases, membrane transport is facilitated by the so-called mitochondrial carrier proteins. The yeast Saccharomyces cerevisiaecontains 35 members of the carrier family, but a function has been identified for only 13 proteins. Here, we investigated the yeast carrier Leu5p (encoded by the gene YHR002w) and its close human homologue Graves' disease protein. Leu5p is inserted into the mitochondrial inner membrane along the specialized import pathway used by carrier proteins. Deletion of LEU5 (strain Δleu5) was accompanied by a 15-fold reduction of mitochondrial coenzyme A (CoA) levels but did not affect the cytosolic CoA content. As a consequence, the activities of several mitochondrial CoA-dependent enzymes were strongly decreased in Δleu5 cells. Our in vitro and in vivo analyses assign a function to Leu5p in the accumulation of CoA in mitochondria, presumably by serving as a transporter of CoA or a precursor thereof. Expression of the Graves' disease protein in Δleu5 cells can replace the function of Leu5p, demonstrating that the human protein represents the orthologue of yeast Leu5p. The function of the human protein might not be directly linked to the disease, as antisera derived from patients with active Graves' disease do not recognize the protein after expression in yeast, suggesting that it does not represent a major autoantigen. The two carrier proteins characterized herein are the first components for which a role in the subcellular distribution of CoA has been identified.
Dolutegravir plus abacavir-lamivudine for the treatment of HIV-1 infection.

BACKGROUND Dolutegravir (S/GSK1349572), a once-daily, unboosted integrase inhibitor, was recently approved in the United States for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in combination with other antiretroviral agents. Dolutegravir, in combination with abacavir-lamivudine, may provide a simplified regimen. METHODS We conducted a randomized, double-blind, phase 3 study involving adult participants who had not received previous therapy for HIV-1 infection and who had an HIV-1 RNA level of 1000 copies per milliliter or more. Participants were randomly assigned to dolutegravir at a dose of 50 mg plus abacavir-lamivudine once daily (DTG-ABC-3TC group) or combination therapy with efavirenz-tenofovir disoproxil fumarate (DF)-emtricitabine once daily (EFV-TDF-FTC group). The primary end point was the proportion of participants with an HIV-1 RNA level of less than 50 copies per milliliter at week 48. Secondary end points included the time to viral suppression, the change from baseline in CD4+ T-cell count, safety, and viral resistance. RESULTS A total of 833 participants received at least one dose of study drug. At week 48, the proportion of participants with an HIV-1 RNA level of less than 50 copies per milliliter was significantly higher in the DTG-ABC-3TC group than in the EFV-TDF-FTC group (88% vs. 81%, P=0.003), thus meeting the criterion for superiority. The DTG-ABC-3TC group had a shorter median time to viral suppression than did the EFV-TDF-FTC group (28 vs. 84 days, P<0.001), as well as greater increases in CD4+ T-cell count (267 vs. 208 per cubic millimeter, P<0.001). The proportion of participants who discontinued therapy owing to adverse events was lower in the DTG-ABC-3TC group than in the EFV-TDF-FTC group (2% vs. 10%); rash and neuropsychiatric events (including abnormal dreams, anxiety, dizziness, and somnolence) were significantly more common in the EFV-TDF-FTC group, whereas insomnia was reported more frequently in the DTG-ABC-3TC group. No participants in the DTG-ABC-3TC group had detectable antiviral resistance; one tenofovir DF-associated mutation and four efavirenz-associated mutations were detected in participants with virologic failure in the EFV-TDF-FTC group. CONCLUSIONS Dolutegravir plus abacavir-lamivudine had a better safety profile and was more effective through 48 weeks than the regimen with efavirenz-tenofovir DF-emtricitabine. (Funded by ViiV Healthcare; SINGLE ClinicalTrials.gov number, NCT01263015 .).
Primary care Randomised controlled trial of prevention of falls in people aged ≥ 75 with severe visual impairment: the VIP trial

Objectives To assess the efficacy and cost effectiveness of a home safety programme and a home exercise programme to reduce falls and injuries in older people with low vision. Design Randomised controlled trial. Setting Dunedin and Auckland, New Zealand. Participants 391 women and men aged ≥ 75 with visual acuity of 6/24 or worse who were living in the community; 92% (361 of 391) completed one year of follow-up. Interventions Participants received a home safety assessment and modification programme delivered by an occupational therapist (n = 100), an exercise programme prescribed at home by a physiotherapist plus vitamin D supplementation (n = 97), both interventions (n = 98), or social visits (n = 96). Main outcome measures Numbers of falls and injuries resulting from falls, costs of implementing the home safety programme. Results Fewer falls occurred in people randomised to the home safety programme but not in those randomised to the exercise programme (incidence rate ratios 0.59 (95% confidence interval 0.42 to 0.83) and 1.15 (0.82 to 1.61), respectively). However, within the exercise programme, stricter adherence was associated with fewer falls (P = 0.001). A conservative analysis showed neither intervention was effective in reducing injuries from falls. Delivering the home safety programme cost $NZ650 (£234, 344 euros, $US432) (at 2004 prices) per fall prevented. Conclusion The home safety programme reduced falls and was more cost effective than an exercise programme in this group of elderly people with poor vision. The Otago exercise programme with vitamin D supplementation was not effective in reducing falls or injuries in this group, possibly due to low levels of adherence.
Cell adhesion controlled by adhesion G protein–coupled receptor GPR124/ADGRA2 is mediated by a protein complex comprising intersectins and Elmo–Dock

Developmental angiogenesis and the maintenance of the blood–brain barrier involve endothelial cell adhesion, which is linked to cytoskeletal dynamics. GPR124 (also known as TEM5/ADGRA2) is an adhesion G protein–coupled receptor family member that plays a pivotal role in brain angiogenesis and in ensuring a tight blood–brain barrier. However, the signaling properties of GPR124 remain poorly defined. Here, we show that ectopic expression of GPR124 promotes cell adhesion, additive to extracellular matrix–dependent effect, coupled with filopodia and lamellipodia formation and an enrichment of a pool of the G protein–coupled receptor at actin-rich cellular protrusions containing VASP, a filopodial marker. Accordingly, GPR124-expressing cells also displayed increased activation of both Rac and Cdc42 GTPases. Mechanistically, we uncover novel direct interactions between endogenous GPR124 and the Rho guanine nucleotide exchange factors Elmo/Dock and intersectin (ITSN). Small fragments of either Elmo or ITSN1 that bind GPR124 blocked GPR124-induced cell adhesion. In addition, Gβγ interacts with the C-terminal tail of GPR124 and promotes the formation of a GPR124–Elmo complex. Furthermore, GPR124 also promotes the activation of the Elmo–Dock complex, as measured by Elmo phosphorylation on a conserved C-terminal tyrosine residue. Interestingly, Elmo and ITSN1 also interact with each other independently of their GPR124-recognition regions. Moreover, endogenous phospho-Elmo and ITSN1 co-localize with GPR124 at lamellipodia of adhering endothelial cells, where GPR124 expression contributes to polarity acquisition during wound healing. Collectively, our results indicate that GPR124 promotes cell adhesion via Elmo–Dock and ITSN. This constitutes a previously unrecognized complex formed of atypical and conventional Rho guanine nucleotide exchange factors for Rac and Cdc42 that is putatively involved in GPR124-dependent angiogenic responses.
How do different tests evaluate sensation in the lower urinary tract?

Abstract Objective. Different tests can be used to evaluate lower urinary tract (LUT) sensation. The purpose of this study is to compare sensory tests in patients with voiding disorders. Material and methods. Seventy patients with various functional disorders of the LUT were admitted for a cystometry and an electrical perception threshold test of the bladder (bEPT) and distal urethra (uEPT). A pudendal EPT (pEPT) and pudendal somatosensory evoked potentials (pSSEP) were also determined. Correlations were calculated for somatosensory (uEPT, pEPT and pSSEP latency) and viscerosensory tests (volumes at filling sensations and bEPT). Results. Fifty of the 70 patients (71%) had normal bladder filling sensations, with abnormal bEPT in 21/50 (41%), including 11 (22%) with no sensation at maximal electrical stimulation. Twenty out of 70 (29%) had an abnormal pattern of filling sensation, with increased bEPT in 13/20 (65%) and no sensation at electrical stimulation in 8/13 (40%). No significant correlation exists between filling sensation and bladder electrical perception thresholds (r < 0.005, p > 0.243). pEPT correlated with uEPT and SSEP (r > 0.035, p < 0.041). Conclusions. In patients with functional voiding disorders, the EPT can be disturbed independently of the bladder filling sensation. No significant correlation exists between volumes of filling sensations and bEPT (r < 0.005, p > 0.243). Therefore, both tests provide complementary information. Somatosensory tests of the pudendal nerve are correlated, so performing SSEP, pEPT and uEPT provides poor additional information to one of these tests alone. Somatosensory pudendal tests cannot be used to quantify filling sensation.
Clearance and disposition of ritodrine in the fluid compartments of the fetal lamb during and after constant rate fetal intravenous infusion.

The disposition of the beta-2 adrenoreceptor agonist, ritodrine, has been examined in the fetal lamb during and after constant rate fetal intravenous infusion (8-24 h). Samples were collected from the fetal femoral artery, umbilical vein, maternal femoral artery, uterine vein, fetal trachea and the amniotic activity for ritodrine quantitation. The amniotic fluid was also analyzed for conjugated metabolites of ritodrine. Ritodrine appears to be cleared across the sheep placenta only to a limited extent (placental clearance 9.2 +/- 2 ml/min/kg; mean +/- S.E.M.). There is, however, significant fetal nonplacental clearance of ritodrine (fetal nonplacental clearance 52.8 +/- 8.0 ml/min/kg). At least part of this clearance appears to be due to fetal drug metabolism, as evidenced by the accumulation of glucuronide conjugates of ritodrine in the amniotic fluid. Ritodrine was also shown to accumulate in the amniotic and fetal tracheal fluids and persist after fetal arterial plasma ritodrine concentrations became undetectable. The accumulation of ritodrine in the tracheal fluid may be of pharmacologic significance, given the well documented, potent effects of beta-2 agonists on fetal lung function and development.
Optomechanical System Design for Dual-Mode Stand-Off Submillimeter Wavelength Imagers

In this paper, the practical tradeoffs for designing submillimeter wavelength imagers based on optomechanical systems combined with focal plane arrays (FPAs) are presented. The architecture of these systems differs for operation at short and long ranges. General formulas to derive the effective field of view of diffraction limited quasi-optical systems in these two scenarios are shown. These formulas can be used to evaluate the performance of a specific optical system implementation. As an application example, we present the design of an optomechanical system that can operate at both ranges in a modular approach. The presented implementation achieves an effective field of view, which is $\hbox{70}\%$ of the canonical one. The proposed solution consists of a linear FPA of eight active transceivers combined with a raster scan technique. The system for short-range scenario is a side-fed dual-reflector Dragonian architecture because of its good scanning performance when illuminated by an FPA. Thanks to the system's small aperture, the scanner is arranged after the primary mirror, without causing additional scan loss. The Dragonian system is then used to illuminate a confocal dual-reflector architecture to magnify its aperture, and can be used in the long-range scenario. The scanner in this case is before the main aperture and it has to be considered in the performance optimization of the optical system since it adds phase aberration loss.