Miracle-dz/UniFAR-FTUs huggingface dataset:
Giving an Older Patient Newer Drugs

Commentary It is often observed that children are not just small adults. They are physiologically different in many ways, including in drug metabolism and susceptibility to idiosyncratic side effects of drugs. At the other end of the life span, similar observations can be made regarding how older adults differ from their younger adult counterparts. These differences at each end of the age spectrum are especially pertinent to the treatment of epilepsy, which has a bimodal distribution of incidence, with peaks in the young and old. The largest and fastest growing peak is in older adults, with one estimate suggesting that half of all epilepsy may be in adults over age 60 by the year 2020 (1). As the pace of new antiepileptic drug (AED) development accelerated in the 1990s, new algorithms for selecting AEDs had to be developed on the basis of relatively few comparative AED trials. A few of these trials focused on determining the optimal choice of AED for older patients. In 1999, Brodie and colleagues reported findings in 150 older adults with new-onset epilepsy who were randomized to treatment with immediate release carbamazepine (CBZ-IR)—the de facto standard for treatment of partial seizures at the time—or lamotrigine (LTG) (2). The primary outcome measure was retention on the randomly selected AED over the 24-week study. The findings were striking—the CBZ-treated subjects were more than twice as likely to come off of therapy, and the greater attrition in the CBZ group was nearly all accounted for by poorer tolerability. The importance of tolerability was emphasized by the larger US Department of Veterans Affairs (VA) cooperative study of epilepsy in the elderly, which compared CBZ-IR, LTG, and also gabapentin (GBP) using a similar survival analysis (3). Although efficacy did not greatly vary among the AEDs studied, there were significant differences in tolerability, again with more dropouts because of adverse effects in the CBZ-IR group than the others. As the use of controlled-release CBZ (CBZ-CR) preparations became more common, many argued that the correct comparison with newer AEDs should be with the better-tolerated CBZ-CR. In 2007, Saetre and colleagues reported findings in 185 adults aged 65 years or older who were randomized to treatment with CBZ-CR or LTG and followed over 40 weeks (4). In this study, the primary measure, retention on AED over the course of the study, did not differ between the two drugs. Similarly, time to withdrawal and proportion of seizure-free paA Randomized, Double-Blind Comparison of Antiepileptic Drug Treatment in the Elderly With New-Onset Focal Epilepsy.
Splenic irradiation as primary therapy for prolymphocytic leukemia

A patient with prolymphocytic leukemia (PLL), a lymphoproliferative disorder that carries a poor prognosis, is presented. The disease was diagnosed at an early stage and treatment could be delayed for four years. When massive, painful splenomegaly developed, splenic irradiation (SI) was chosen as the primary form of therapy and an excellent systemic response could be achieved. Our observation is in agreement with preliminary studies, which advocate SI as the primary form of therapy in PLL. Furthermore, it is emphasized that an early diagnosis of PLL is necessary to establish its true course and that the prognosis may be better than originally thought.
The effect of mebudipine on cardiac function and activity of the myocardial nitric oxide system in ischaemia–reperfusion injury in rats

Objectives Previous studies have suggested that failure of the synthesis of nitric oxide is involved in the pathophysiology of myocardial ischaemia–reperfusion injury. In this study, we investigated the effect of mebudipine, a new dihydropyridine calcium channel blocker, on cardiac function and activity of the myocardial nitric oxide system in ischaemia–reperfusion injury in isolated rat hearts. Methods Forty male Wistar rats (250–300 g) were divided into four groups (n = 10): sham, control, vehicle and drug groups. The animals were anesthetised with sodium pentobarbital (6 mg/kg intraperitoneal). The hearts were quickly removed, mounted on a Longendorff apparatus and perfused with Krebs-Henseleit solution under constant pressure at 37°C. After 20 min stabilisation period, the ischaemic groups received 30 min global ischaemia and 120 min reperfusion. For the drug and vehicle groups, before ischaemia the hearts were perfused with mebudipine (10-3 µM) or ethanol-enriched solution (0.01%) for 25 min, respectively. Myocardial function, and creatine kinase, lactate dehydogenase and total nitric oxide metabolite (nitrite and nitrate) levels were analysed. Results Cardiac functions had recovered significantly in the mebudipine group (p < 0.01). Furthermore, mebudipine remarkably reduced the levels of lactate dehydogenase and creatine kinase in the coronary effluent and increased myocardial nitric oxide metabolite levels compared with the control group. Conclusion Our results indicate that mebudipine reduced the intensity of myocardial ischaemia–reperfusion injury, and that activation of the myocardial nitric oxide system played an important role in this regard.
Effects of Isopropyl Unoprostone Ophthalmic Solution on Cultured Rabbit Corneal Epithelial Cells

Purpose: To investigate the effects of isopropyl unoprostone (referred to as unoprostone) ophthalmic solution on the barrier function of cultured rabbit corneal epithelium grown on permeable supports. Methods: Rabbit corneal epithelial cells cultured on collagen-coated filter inserts were administered one of the following for 30 min: unoprostone in vehicle solution (polysorbate 80), unoprostone in vehicle solution with a preservative (benzalkonium chloride), preservative only or vehicle only. For a control, no chemicals were added to the medium. After administration, the transepithelial electrical resistance (TER) measurement, a sensitive method by which to investigate the barrier function, and morphological observation using phase-contrast microscopy were performed before exposure and at 0.5, 1, 3, 6, 12, 24, 48 and 72 h after exposure. The transmission electron-microscopic observation was performed before and 72 h after exposure in all experimental conditions. Results: The cells exposed to unoprostone with the preservative showed a significant decrease in the TER, although no morphological changes were observed. The corneal epithelial cells exposed to unoprostone without preservative, the vehicle only or the preservative only did not show any differences from the control group at any measurements. Conclusion: The corneal barrier function is damaged by a combined solution of unoprostone and preservative, but not by a single solution of unoprostone, in vitro.
The implementation of a kidney exchange program does not induce a need for additional psychosocial support

The Dutch kidney exchange donation program started in January 2004. A literature review has shown that several factors of the exchange program could influence the psychological well being of participants, such as the loss of the possibility of a ‘medical excuse’ for unwilling donors and the issue of anonymity. However, these factors have not been the subject of empirical study yet. We therefore studied these factors to determine whether additional psychosocial support is necessary for donors and recipients in the Dutch kidney exchange program. We used structured interviews for all 48 donors and recipients that had undergone exchange donation/transplantation in 2004. A psychologist interviewed the participants before and 3 months after transplantation. We included a comparison group of 48 donors and recipients participating in the regular living kidney donation program. Donors did not experience additional pressure to donate due to the exchange donation. Most participants (69%) preferred anonymity between the couples. Ten percentage needed additional emotional support. In this respect the exchange group did not differ from the comparison group. We conclude that the psychosocial support offered to exchange couples can be comparable with the support normally offered to participants in the regular living kidney donation program.
Distribution of volumes of individual glomeruli in kidneys at autopsy: association with age, nephron number, birth weight and body mass index.

BACKGROUND Glomerular hypertrophy occurs in a number of normal and pathological states. Glomerular volume in kidneys at autopsy is usually indirectly derived from estimates of total glomerular mass and nephron number, and provides only a single value per kidney, with no indication of the range of volumes of glomeruli within the kidney of any given subject. We review findings of the distribution of volumes of different glomeruli within subjects without kidney disease, and their correlations with age, nephron number, birth weight and body mass index (BMI). METHODS The study describes findings from autopsy kidneys of selected adult white males from the Southeast USA who had unexpected deaths, and who did not have renal scarring or renal disease. Total glomerular (nephron) number and total glomerular volume were estimated using the disector/fractionator combination, and mean glomerular volume (Vglom) was derived. The volumes of 30 individual glomeruli (IGV) in each subject were determined using the disector/Cavalieri method. IGV values were compared by categories of age, nephron number, birth weight and BMI. RESULTS There was substantial variation in IGV within subjects. Older age, lower nephron number, lower birth weight and gross obesity were associated with higher mean IGV and with greater IGV heterogeneity. High Vglom and high IGVs were associated with more glomerulosclerosis. However, amongst the generally modest numbers of sclerosed glomeruli, the pattern was uniformly of ischemic collapse of the glomerular tuft. There was no detectable focal segmental glomerular tuft injury. DISCUSSION In this series of people without overt renal disease, greater age, nephron deficit, lower birth weight and obesity were marked by glomerular enlargement and greater glomerular volume heterogeneity within individuals.
Scalable and Power-Efficient Implementation of an Asynchronous Router with Buffer Sharing

Network-on-Chip provides scalable communication in Systems-on-Chip with many Intellectual Property cores. Studies have shown that unutilized router buffers lead to significant network performance degradation. This work presents Roundabout, a new asynchronous router architecture with inherent and effective buffer utilization. Inspired by real-life multi-lane roundabouts, it consists of lanes shared by input and output ports. A prototype of Roundabout is evaluated using 45nm CMOS technology. The router is able to achieve a throughput of 465 Mflit/sec. It achieves a network saturation threshold of 129 Gbps on a 4x4 Mesh topology network. Roundabout performance, area and power results are competitive with existing synchronous and asynchronous solutions. It provides good topological tradeoffs for significantly improving network performance without corresponding area overhead.
The Link Between Everyday Discrimination, Healthcare Utilization, and Health Status Among a National Sample of Women.

BACKGROUND Research has not adequately examined the potential negative effects of perceiving routine discrimination on general healthcare utilization or health status, especially among reproductive-aged women. We sought to evaluate the association between everyday discrimination, health service use, and perceived health among a national sample of women in the United States. MATERIALS AND METHODS Data were drawn from the Women's Healthcare Experiences and Preferences survey, a randomly selected, national probability sample of 1078 U.S. women aged 18-55 years. We examined associations between everyday discrimination (via a standardized scale) on frequency of health service utilization and perceived general health status using chi-square and multivariable logistic regression modeling. RESULTS Compared with women who reported healthcare visits every 3 years or less (reference group), each one-point increase in discrimination score was associated with higher odds of having healthcare visits annually or more often (odds ratio [OR] = 1.36, confidence interval [95% CI] = 1.01-1.83). Additionally, each one-point increase in discrimination score was significantly associated with lower odds of having excellent/very good perceived health (OR = 0.65; 95% CI = 0.54-0.80). CONCLUSION Perceived discrimination was associated with increased exposure to the healthcare setting among this national sample of women. Perceived discrimination was also inversely associated with excellent/very good perceived health status.
Malignant peripheral nerve sheath tumors with high and low Ras‐GTP are permissive for oncolytic herpes simplex virus mutants

Malignant peripheral nerve sheath tumors (MPNSTs) occur most frequently in patients with neurofibromatosis type 1 and are often fatal. Current therapy relies upon radical surgical resection, which often fails to completely remove the tumor. To address the need for novel treatment approaches for this disease, we sought to determine if human MPNST‐derived cell lines are sensitive to oncolytic Herpes simplex virus (oHSV) infection. Activation of the Ras pathway and its inhibitory effects on protein kinase R (PKR) activation have been shown to dictate cellular permissivity to oHSV mutants. Because NF‐1‐associated MPNSTs possess inherent hyperactive Ras, we hypothesized these tumors would be ideal therapeutic targets for oHSVs.
Sleep in midlife women: effects of menopause, vasomotor symptoms, and depressive symptoms

ObjectiveThis study aims to evaluate subjective sleep quality in premenopausal and postmenopausal women and to study its association with night sweats, hot flashes, and depressive symptoms. MethodsA total of 158 healthy women were recruited; 107 were premenopausal (44-48 y) and 51 were postmenopausal (53-58 y). Sleep quality was evaluated with the Basic Nordic Sleep Questionnaire, night sweats and hot flashes were evaluated with a specific symptom questionnaire, and depressive symptoms were evaluated with the Beck Depression Inventory. ResultsPostmenopausal women had poorer general sleep quality (P < 0.001), slept more restlessly (P = 0.020), and had more nocturnal awakenings (P = 0.015). However, the frequency of difficulty falling asleep, snoring, witnessed apnea, or use of sleep medication was similar between the groups. Furthermore, sleep latency, morning tiredness, or daytime tiredness did not differ between the groups. Postmenopausal women did not report more unintentional falling asleep at work or during leisure time; however, when not active, they dozed off more easily than premenopausal women (P < 0.001). Postmenopausal women had more night sweats (P < 0.001), hot flashes (P < 0.001), and depressive symptoms (P < 0.001). Even a low frequency of night sweats disturbed sleep in postmenopausal women, whereas only frequent night sweats were disturbing in premenopausal women. Depressive symptoms disturbed sleep regardless of menopause status. ConclusionsMaintenance insomnia, most evidently because of night sweats and hot flashes, seems to be the major type of insomnia in postmenopausal women and has to be considered when choosing insomnia treatment for this group. Initiation of sleep and daytime vitality are not, in general, affected by menopause.
Transtheoretical Model and substance use in HIV-positive youth

Abstract The purpose of the study was to test constructs of the Transtheoretical Model (TTM) for predicting alcohol and other drug use in HIV-positive youth (ages 16–25). Questionnaires and interviews about alcohol and other drug use, stage of change, self-efficacy, emotional distress and social support were obtained from 64 HIV-positive youth. Structural equation modeling with standard errors determined by methods appropriate to small samples, demonstrated that self-efficacy mediated the relationship between stage of change and alcohol use and between social support and alcohol use. The same pattern of results emerged for marijuana use. The models predicted 47% of the variance in alcohol use and 69% of the variance in marijuana use. Results supported the TTM and highlight the potential of interventions that seek to boost self-efficacy and social support specific to reducing substance use.
Postoperative titration of intravenous morphine

Background and objective Intravenous morphine titration is used to obtain postoperative pain relief, but few studies have assessed the appropriate regimen. In a quality programme, we performed a prospective non-randomized study of morphine titration in a postanaesthesia care unit (PACU). Methods Four regimens of morphine titration were studied: every 10 (group 1, n = 400) or 5 min (group 2, n = 400) with a maximum of five intravenous boluses; every 5 min, without any limitation in the number of boluses (groups 3 and 4, n = 400 each); in groups 1, 2, and 3, subcutaneous morphine was administered 4 h after titration. In group 4, administration of subcutaneous morphine was allowed only 2 h after titration. A visual analogue pain scale (VAPS) > 30 mm was required to administer morphine and pain relief was defined as a VAPS ≤ 30 mm. Results After morphine titration, VAPS was lower and the number of patients with pain relief was greater in patients from groups 3 and 4. Patients from group 4 had the lowest VAPS (26 ± 17 mm) and the highest percentage of pain relief (73%) at the end of the PACU period. The number of sedated patients increased in groups 3 (62%) and 4 (61%) compared with group 1 (27%). No significant differences in morphine-related adverse effects were observed. Conclusion Intravenous morphine titration every 5 min with an unlimited number of boluses and early subcutaneous administration provided the best analgesic regimen.
Efficient Lattice-Reduction-Aided Successive Interference Cancellation for Clustered Multiuser MIMO System

The lattice-reduction (LR)-aided successive interference cancellation (SIC) is a well-known detection technique achieving near-maximum-likelihood (ML) performance in the multiuser system. However, the LR algorithm and the computation of sequential nulling vectors still incur considerable computational complexity overhead for a large number of mobile stations (MSs). To overcome it, we propose a decoupled LR-aided SIC for clustered MSs, in which the entire system is linearly decoupled into multiple lower dimensional subsystems before the LR-aided SIC is applied. In addition, efficient MS grouping algorithms are proposed to optimize the detection performance of the decoupled LR-aided SIC. The proposed LR-aided SIC with linear preprocessing exhibits a full diversity order, compared with the conventional LR-aided SIC, with considerable computational savings. Finally, to further improve the system performance, a nested LR-aided SIC with preprocessing is also developed.
Anaerobic Production of a Biosurfactant by Bacillus licheniformis JF-2

Bacillus licheniformis JF-2 anaerobically produced a biosurfactant when grown in a glucose-mineral salts medium containing yeast extract and NaNO3. Surface tension of the medium was reduced from 70 to 74 mN/m to as low as 28 mN/m due to the production of an anionic biosurfactant.
Estudo do potencial eólico e previsão de ventos para geração de eletricidade em Santa Catarina

O trabalho e dividido em duas partes, na primeira delas o objetivo e a analise das principais caracteristicas dos ventos em seis localidades do Estado de Santa Catarina visando a determinar o potencial eolico para geracao de eletricidade, enquanto na segunda parte se faz um estudo sobre previsao de velocidade de ventos e geracao eolica com base em dados de velocidade de vento gerados pelo modelo meteorologico de meso-escala Eta, do CPTEC / INPE. A primeira parte do trabalho refere-se ao tratamento estatistico dos dados de velocidade de vento, atraves da distribuicao de Weibull, medidos nas estacoes anemometricas da CELESC (Centrais Eletricas de Santa Catarina S.A.). Sao determinadas as velocidades medias, a regularidade, a direcao preferencial dos ventos, assim como o fator de capacidade do local e a quantidade esperada de energia a ser gerada. Os dados de potencia gerada pelos aerogeradores em operacao, no Estado, foram comparados aos valores estimados atraves dos calculos com as velocidades medidas em campo. Na segunda parte do estudo, os dados previstos pelo modelo Eta do CPTEC / INPE, serviram de base para o treinamento de redes neurais, a partir da comparacao com os dados de campo da CELESC, possibilitando uma avaliacao da capacidade de previsao de velocidade de vento e de potencia para um horizonte de 6h. A questao da previsao de geracao eletrica por fonte eolica tornar-se-a de grande importância a medida que aumente a sua participacao no balanco energetico do pais. Os resultados mostram que a tecnica de previsao por meio de redes neurais e adequada, apesar de ainda apresentar as limitacoes decorrentes do escasso banco de dados de velocidade e direcao do vento. O estudo sobre o potencial eolico de Santa Catarina indica a existencia de localidades com caracteristicas de ventos adequadas a geracao. Dentre as regioes analisadas, destacam-se Laguna e Urubici, que apresentaram valores de fator de capacidade, FC, de 0,40 e 0,34, respectivamente, com velocidades medias anuais em torno de 8 m/s, apesar do baixo valor do fator de forma, k, em torno de 1,8, e Agua Doce, com valores de FC em torno de 0,24, velocidade media em torno de 6 m/s e k de 2,4, apresentando resultados satisfatorios para geracao de eletricidade. Ainda, nas demais localidades, estimativas feitas com auxilio do programa WAsP mostram que todas apresentam regioes com valores de FC maiores ou iguais a 0,30. A metodologia desenvolvida neste trabalho, embora se restrinja a uma analise de caso para Santa Catarina, podera ser estendida a todo o pais. %%%%This study is divided in two parts, in the first one the objective is the analysis of the main wind characteristics for in six places in the State of Santa Catarina aiming to determine the wind power for energy generation, in the second one, a study about wind speed and wind power forecast is made based on CPTEC / INPE Eta mesoscale meteorological model wind speed data. The first part of this study refers to a statistical treatment of wind speed data collected by CELESC, using the Weibull Distribution. The…
Conformational stability of dimeric proteins: Quantitative studies by equilibrium denaturation

The conformational stability of dimeric globular proteins can be measured by equilibrium denaturation studies in solvents such as guanidine hydrochloride or urea. Many dimeric proteins denature with a 2‐state equilibrium transition, whereas others have stable intermediates in the process. For those proteins showing a single transition of native dimer to denatured monomer, the conformational stabilities, δGu(H2O), range from 10 to 27 kcal/mol, which is significantly greater than the conformational stability found for monomeric proteins. The relative contribution of quaternary interactions to the overall stability of the dimer can be estimated by comparing Gu(H2O) from equilibrium denaturation studies to the free energy associated with simple dissociation in the absence of denaturant. In many cases the large stabilization energy of dimers is primarily due to the intersubunit interactions and thus gives a rationale for the formation of oligomers. The magnitude of the conformational stability is related to the size of the polypeptide in the subunit and depends upon the type of structure in the subunit interface. The practical use, interpretation, and utility of estimation of conformational stability of dimers by equilibrium denaturation methods are discussed.