Miracle-dz/UniFAR-FTUs huggingface dataset:
Fixed combination therapy of hypertension: focus on valsartan/hydrochlorothiazide combination (Diovan®/HCT)

Hypertension is a major risk factor for cardiovascular morbidity and mortality. Monotherapy of hypertension is often ineffective, since it controls approximately 50% of the blood pressure of hypertensive patients. For lowering blood pressure to less than 140/90 mmHg (or <130/80 mmHg among people with diabetes or chronic renal disease) according to JNC-7 guidelines, combination therapy of two or more drugs is often necessary. The combination of a diuretic with an angiotensin-converting enzyme inhibitor (ACEI) or an angiotensin receptor blocker (ARB) is effective and provides the additional benefit of blocking the effects of angiotensin II, which is responsible for cardiovascular remodeling and its complications. ARBs may have an advantage over the ACEIs because they block the action of all angiotensin II directly, whereas ACEIs are ineffective in blocking angiotensin II generated by nonclassical ACE pathways. Valsartan (Diovan®, Novartis) is one of the seven currently approved ARBs in the USA for the treatment of hypertension, and it has been shown to be very effective in controlling blood pressure given once-daily in doses of 80–160 or 320 mg. Its fixed combination with hydrochlorothiazide (HCT) is even more effective in controlling blood pressure in 70% of the cases. The most commonly used combinations are valsartan/HCT (Diovan/HCT), 80/12.5 and 160/12.5 mg given once-daily.
Identification and Characterization of Nodulation-Signaling Pathway 2, a Gene of Medicago truncatula Involved in Nod Factor Signaling1

Bacterially derived Nod factor is critical in the establishment of the legume/rhizobia symbiosis. Understanding the mechanisms of Nod factor perception and signal transduction in the plant will greatly advance our understanding of this complex interaction. Here, we describe the identification of a new locus, nodulation-signaling pathway 2 (NSP2), of Medicago truncatula that is involved in Nod factor signaling. Mutants at this locus are blocked for Nod factor-induced gene expression and show a reduced root hair deformation response. nsp2 plants also show a complete absence of infection and cortical cell division following Sinorhizobium meliloti inoculation. Nod factor-induced calcium spiking, one of the earliest responses tested, is still functional in these mutant plants. We conclude that the geneNSP2 is a component of the Nod factor signal transduction pathway that lies downstream of the calcium-spiking response.
Hippocampal adult neurogenesis occurs in a microenvironment provided by PSA‐NCAM‐expressing immature neurons

Neurons continue to be generated in the adult hippocampus. In the present study, the early developmental processes of newly generated neurons in the adult rat hippocampus were examined by confocal laser scanning microscopy using a combination of bromodeoxyuridine (BrdU) labeling and immunohistochemistry for highly polysialylated neural cell adhesion molecule (PSA‐NCAM) and NeuroD, which are markers for immature neurons, and glial fibrillary acidic protein (GFAP). Rats were injected with BrdU and 2 hours, 1, 3, and 7 days after the injection, the hippocampus was processed for immunohistochemistry. One day after the injection, BrdU‐labeled cells were found frequently in clusters consisting of dividing cells, putative undifferentiated cells, NeuroD‐positive differentiated neurons, and GFAP‐positive astrocytes. Three days later, BrdU‐labeled cells were loosely aggregated and BrdU‐positive fragmented nuclei were sometimes observed, suggesting that apoptosis occurred in the clusters. These BrdU‐labeled nuclei were frequently associated in various ways with the processes of immature PSA‐positive granule cells. They are positioned along PSA‐positive apical and basal dendrites or surrounded by these processes. By 7 days after the injection, the number of the clusters was reduced and the BrdU‐labeled cells had developed dendrites. These cell‐to‐cell associations support the hypothesis that the clustering and a microenvironment provided by the PSA‐expressing immature neurons contribute to the early developmental events of adult neurogenesis, such as proliferation, differentiation, apoptosis, and neurophilic migration in the adult hippocampus. © 2002 Wiley‐Liss, Inc.
The Effects of Galantamine Hydrobromide Treatment on Dehydroepiandrosterone Sulfate and Cortisol Levels in Patients with Chronic Fatigue Syndrome

Objective Mental fatigue, cognitive disorders, and sleep disturbances seen in chronic fatigue syndrome (CFS) may be attributed to cholinergic deficit. A functional deficiency of cholinergic neurotransmission may cause the hypothalamic-pituitary-adrenal axis hypoactivity seen in CFS. Therefore, we investigated the alterations in stress hormones such as cortisol and dehydroepiandrosterone sulfate (DHEAS) in CFS patients before and after 4-week administration of galantamine hydrobromide, a selective acetylcholinesterase inhibitor, and aimed to investigate whether there are any relationships between the probable hormonal changes and cholinergic treatment. Methods Basal levels of cortisol and DHEAS were measured in 29 untreated CFS patients who were diagnosed according to Centers for Disease Control (CDC) criteria and in 20 healthy controls. In the patient group, four weeks after 8 mg/d galantamine hydrobromide treatment, cortisol and DHEAS levels were measured again. After the treatment 22 patients who stayed in study were divided into two subgroups as responders and nonresponders according to the reduction in their Newcastle Research Group ME/CFS Score Card (NRG) scores. Results Important findings of this study are lower pre-and post-treatment cortisol levels and in all CFS patients compared to controls (F=4.129, p=0.049; F=4.803, p=0.035, respectively); higher basal DHEAS values and higher DHEAS/cortisol molar ratios which were normalized following four weeks' treatment with 8 mg/d galantamine hydrobromide in the treatment-respondent group (F=5.382, p=0.029; F=5.722, p=0.025, respectively). Conclusion The findings of the decrease in basal DHEAS levels and DHEAS/cortisol molar ratios normalizing with galantamine treatment may give some support to the cholinergic deficit hypothesis in CFS.
REGIONAL STUDIES OF CATECHOLAMINES IN THE RAT BRAIN–II

A CONSIDERABLE volume of information is now available on the distribution of norepinephrine and dopamine in mammalian brain (VOGT, 1954; BERTLER and ROSENGREN, 1959). Recent histochemical findings have demonstrated the presence of these amines in specific neurons in various parts of the brain (CARLSSON, FALCK and HILLARP, 1962; DAHLSTROM and FUXE, 1964; FUXE, 1965). There have also been many reports of changes in the storage levels of catecholamines in the brain in response to centrally-acting drugs (BRODIE, SPECTOR and SHORE, 1959 ; CARLSSON, 1964; LAVERTY and SHARMAN, 1965). However, little is known of the dynamic aspects of the metabolism of catecholamines in the brain. The storage levels of norepinephrine and dopamine are not static but reflect dynamic equilibria between the rates of formation and the rates of utilization of the amines. The turnover of catecholamines has been estimated by measuring the rate of decline of specific activity of the amines after the introduction of small amounts of radioactively labelled catecholamines into the endogenous pools. This approach was first used by UDENFRIEND and WYNGAARDEN (1956) to measure the rate of turnover of adrenal medullary catecholamines after the administration of radioactive precursors. Similarly, the rate of turnover of catecholamines in peripheral sympathetic nerves and brain was measured after the administration of labelled DOPA or tyrosine (UDENFRIEND and ZALTZMAN-NIRENBERG, 1963 ; BURACK and DRASK~CZY, 1964). The presence of a specific uptake mechanism for norepinephrine in sympathetic nerves (WHITBY, AXELROD and WEIL-MALHERBE, 1961 ; HERTTING and AXELROD, 1961 ; IVERSEN, 1963) also allows the direct labelling of norepinephrine stores by exposure to radioactive norepinephrine. This method was used to estimate the rate of turnover of norepinephrine in peripheral tissues (MONTANIRI, COSTA, BEAVEN and BRODIE, 1963) but has hitherto not been applicable to brain since peripherally administered catecholamines do not enter the brain (WEIL-MALEERBE, WHITBY and AXELROD, 1961). The development of techniques for the administration of radioactive norepinephrine into the lateral ventricle of the rat brain (MILHAUD and GLOWINSKI, 1963; GLOWINSKI, KOPIN and AXELROD, 1965), however, allows a direct labelling of the brain catecholamines. Previous studies showed (GLOWINSKI et aZ., 1965) that the half-life for the major phase of disappearance of [3H]norepinephrine from the whole brain after intraventricular administration agrees well with other estimates of the half-life for
Adult human mesenchymal cells proliferate and migrate in response to chemokines expressed in demyelination

Systemic delivery of multipotent mesenchymal stem cells (MSC) may be of benefit in the treatment of neurological diseases, including multiple sclerosis (MS). Certainly, animal studies have demonstrated functional benefits following MSC transplantation, although the mechanisms by which MSCs migrate to lesions and stimulate repair remain unknown. Chemokines stimulate migration in other settings. In this study, we systematically explore the migratory and proliferative responses of human MSCs (hMSC) to chemokines expressed in MS lesions. We demonstrate that these chemokines trigger hMSC migration. In addition, we show that RANTES and IP-10 promote hMSC proliferation.
Illness Behavior in Patients With Chronic Low Back Pain and Activation of the Affective Circuitry of the Brain

Objective Patients with chronic low back pain (cLBP) show a range of behavioral patterns that do not correlate with degree of spinal abnormality found in clinical, radiological, neurophysiological, or laboratory investigations. This may indicate an augmented central pain response, consistent with factors that mediate and maintain psychological distress in this group. Methods Twenty-four cLBP patients were scanned with functional magnetic resonance imaging while receiving noxious thermal stimulation to the right hand. Patients were clinically assessed into those with significant pain-related illness behavior (Waddell signs [WS]-H) or without (WS-L) based on WS. Results Our findings revealed a significant increase in brain activity in WS-H versus WS-L patients in response to noxious heat in the right amygdala/parahippocampal gyrus and ventrolateral prefrontal and insular cortex (at a VoxelPThreshold = 0.01). We found no difference between groups for heat pain thresholds (t(22) = −1.17, p = . 28) or sensory-discriminative pain regions. Conclusions Patients with cLBP displaying major pain behavior have increased activity in the emotional circuitry of the brain. This study is the first to suggest an association between a specific clinical test in cLBP and neurobiology of the brain. Functional magnetic resonance imaging may provide a tool capable of enhancing diagnostic accuracy and affecting treatment decisions in cases where no structural cause can be identified.
Complex Carbohydrate Utilization by the Healthy Human Microbiome

The various ecological habitats in the human body provide microbes a wide array of nutrient sources and survival challenges. Advances in technology such as DNA sequencing have allowed a deeper perspective into the molecular function of the human microbiota than has been achievable in the past. Here we aimed to examine the enzymes that cleave complex carbohydrates (CAZymes) in the human microbiome in order to determine (i) whether the CAZyme profiles of bacterial genomes are more similar within body sites or bacterial families and (ii) the sugar degradation and utilization capabilities of microbial communities inhabiting various human habitats. Upon examination of 493 bacterial references genomes from 12 human habitats, we found that sugar degradation capabilities of taxa are more similar to others in the same bacterial family than to those inhabiting the same habitat. Yet, the analysis of 520 metagenomic samples from five major body sites show that even when the community composition varies the CAZyme profiles are very similar within a body site, suggesting that the observed functional profile and microbial habitation have adapted to the local carbohydrate composition. When broad sugar utilization was compared within the five major body sites, the gastrointestinal track contained the highest potential for total sugar degradation, while dextran and peptidoglycan degradation were highest in oral and vaginal sites respectively. Our analysis suggests that the carbohydrate composition of each body site has a profound influence and probably constitutes one of the major driving forces that shapes the community composition and therefore the CAZyme profile of the local microbial communities, which in turn reflects the microbiome fitness to a body site.
Decoy Receptor 3 Improves Survival in Experimental Sepsis by Suppressing the Inflammatory Response and Lymphocyte Apoptosis

Purpose Unbalanced inflammatory response and lymphocyte apoptosis is associated with high mortality in septic patients. Decoy receptor 3 (DcR3), a member of the tumor necrosis factor receptor superfamily, is an anti-inflammatory and anti-apoptotic factor. Recently, DcR3 expression was found to be increased in septic patients. This study evaluated the therapeutic effect and mechanisms of DcR3 on cecal ligation and puncture (CLP)-induced sepsis in mice. Methods C57BL/6 mice were subjected to CLP-induced polymicrobial sepsis. DcR3 Fc was intravenously injected 30 min before and 6 h after CLP. Bacterial clearance, cytokine production, histology, lymphocyte apoptosis and survival were evaluated. Furthermore, we investigated the systemic effects of DcR3 in in vitro lymphocyte apoptosis regulation. Results Our results demonstrated that DcR3 protein treatments significantly improved survival in septic mice (p <0.05). Treatment with DcR3 protein significantly reduced the inflammatory response and decreased lymphocyte apoptosis in the thymus and spleen. Histopathological findings of the lung and liver showed milder impairment after DcR3 administration. In vitro experiments showed that DcR3 Fc inhibited Fas-FasL mediated lymphocyte apoptosis. Conclusions Treatment with the DcR3 protein protects mice from sepsis by suppressing the inflammatory response and lymphocyte apoptosis. DcR3 protein may be useful in treatment of sepsis.
Upregulation of ERG Genes inCandida Species by Azoles and Other Sterol Biosynthesis Inhibitors

ABSTRACT Infections due to Candida albicans are usually treated with azole antifungals such as fluconazole, but treatment failure is not uncommon especially in immunocompromised individuals. Relatedly, in vitro studies demonstrate that azoles are nonfungicidal, with continued growth at strain-dependent rates even at high azole concentrations. We hypothesized that upregulation ofERG11, which encodes the azole target enzyme lanosterol demethylase, contributes to this azole tolerance in Candidaspecies. RNA analysis revealed that ERG11 expression in C. albicans is maximal during logarithmic-phase growth and decreases as the cells approach stationary phase. Incubation with fluconazole, however, resulted in a two- to fivefold increase in ERG11 RNA levels within 2 to 3 h, and this increase was followed by resumption of culture growth.ERG11 upregulation also occurred following treatment with other azoles (itraconazole, ketoconazole, clotrimazole, and miconazole) and was not dependent on the specific medium or pH. Within 1 h of drug removal ERG11 upregulation was reversed. Azole-dependent upregulation was not limited to ERG11: five of five ERG genes tested whose products function upstream and downstream of lanosterol demethylase in the sterol biosynthetic pathway were also upregulated. Similarly, ERG11upregulation occurred following treatment of C. albicanscultures with terbinafine and fenpropimorph, which target other enzymes in the pathway. These data suggest a common mechanism for globalERG upregulation, e.g., in response to ergosterol depletion. Finally, azole-dependent ERG11 upregulation was demonstrated in three additional Candida species (C. tropicalis, C. glabrata, and C. krusei), indicating a conserved response to sterol biosynthesis inhibitors in opportunistic yeasts.
Waveguide germanium photodetector with high bandwidth and high L-band responsivity

We present a waveguide germanium p-i-n photodetector for C and L-band operation. A record-high responsivity of 1.30 A/W for a germanium p-i-n photodetector is achieved at 1611.5 nm, while maintaining a high 27 GHz bandwidth.
Identification of CYP2B6 sequence variants by use of multiplex PCR with allele-specific genotyping.

BACKGROUND Cytochrome P450 2B6 (CYP2B6) has a role in the metabolism of many clinically important substances, but the variation within the CYP2B6 gene has not been fully characterized. The aim of the present study was to develop a reliable and robust assay for determining genotypic variants. METHODS We used a two-stage procedure. An initial multiplex PCR reaction amplified the relevant gene fragments in exonic and regulatory regions to ensure isolation of CYP2B6 from its similar pseudogene (CYP2B7). This product was then genotyped by allele-specific PCR. RESULTS The assay detected the following published single-nucleotide polymorphisms: C64T (Arg22Cys), C78T, G216C, G516T (Gln172His), C777A (Ser259Arg), A785G (Lys262Arg), and C1459T (Arg487Cys), as well as additional loci found within the single-nucleotide polymorphism (SNP) databases: A1190G, C1268A, C1330T, A1382G, A1402T, and an A/T SNP in intron 2 (A12917T). This approach detected all common, previously reported alleles and identified a new allele (CYP2B6*4C) present in 2.2% of a Caucasian population. Genotypic frequencies obtained were consistent with previously published results. CONCLUSIONS This method is simple, reliable, rapid, and amenable to automation and could facilitate the large-scale genotypic analysis of CYP2B6.
Surgically treated incidentally discovered low-grade gliomas are mostly IDH mutated and 1p19q co-deleted with favorable prognosis.

OBJECTIVE LGGs (low-grade gliomas) are sometimes encountered by chance during radiological examinations. These incidentally discovered LGGs (IDLGGs) were relatively under-studied in the literature. The purpose of current study is to review a cohort of patients with IDLGGs surgically treated in our institution for their clinical and histological aspects and determine their IDH1 and 1p19q status. METHODS All patients with hemispheric LGGs receiving operation in our institution between 2001 and 2004 were reviewed. Clinical, radiological and treatment data of the patients were collected and IDLGGs were retrieved and compared with symptomatic LGGs. Histological review was carried out and formalin-fixed paraffin embedded (FFPE) tissues of IDLGGs were examined for IDH1/IDH2 mutation and 1p/19q codeletion. RESULTS Twenty three IDLGGs (10.4%) were identified while 196 patients had symptomatic LGGs. The reasons for patients with IDLGGs having radiological examination included trauma (47.8%), dizziness (26.1%), unrelated headache (21.7%), and health checkup (4.4%). Clinically, patients with IDLGGs had higher preoperative KPS (P < 0.001), smaller tumor volume (P = 0.014), lower frequency of eloquent areas involvement (P < 0.001) and higher rate of complete resection (P = 0.037) comparing to those with symptomatic LGGs. Histologically, there is a preponderance of oligodendroglial differentiation with 6 oligodendrogliomas and 11 oligoastrocytomas but there were also 6 astrocytomas. IDH1 mutation and 1p/19q co-deletion were detected in 95.7% (22/23) and 69.6% (16/23) of IDLGGs, respectively. The latter encompassed all but one of the cases of oligodendroglial tumors. Patients with IDLGGs had longer overall survival than those with symptomatic LGGs (P = 0.027). CONCLUSIONS We conclude that the majority of IDLGGs are IDH1 mutated and are predominantly oligodendroglial tumors. With a median follow-up of 9.3 years to our series, we conclude that patients with IDLGGs had better prognosis than those with symptomatic LGGs. The favorable prognosis of IDLGGs may be accounted by the higher practicability of extensive resection, non-eloquent tumor location and smaller tumor volume. Frequent IDH1 mutation and 1p/19q co-deletion in IDLGGs may also contribute to the favorable prognosis of this subgroup of patients.
The Differential Effects of Chaplain Interventions on Patient Satisfaction

There is an acute need to define the specific skills that make chaplains integral to the healthcare team. This prospective study attempts to identify those skills that may be specific to chaplains, for whom no other member of the health care team has similar training, and to examine if these skills have a differential effect on patient satisfaction. A total of 59 interventions were identified and grouped into 10 categories by focus groups comprised of chaplains. Subsequently, Principal Component Analysis yielded two independent variables; Component 1 representing the “Religious/Spiritual” dimension, and Component 2 representing the “Psychosocial” dimension of chaplains’ work. The two components were used in an OLS regression model to measure patient satisfaction. Interventions that comprise the “Religious/Spiritual” dimension may be considered to be specific skills that chaplains contribute to patient care and these have a slightly stronger correlation with patient satisfaction than the interventions of the “Psychosocial” dimension.
Psychotropic medication use and cognition in institutionalized older adults with mild to moderate dementia

ABSTRACT Background: Most studies examining psychotropic medication use on cognition in older persons with dementia include measures of global cognitive function. The present study examined the relationship between different types of psychotropic medication and specific cognitive functions in older people with dementia. Methods: Two hundred and six institutionalized older adults with dementia (180 women, mean age 85 years) were administered neuropsychological tests. Psychotropic medication use was extracted from their medical status and categorized as: sedatives, antidepressants and antipsychotics. Results: Analysis of covariance revealed that psychotropic consumers, and particularly those who used antipsychotics, performed worse on neuropsychological tests of executive/attentional functioning than non-consumers. There were no differences between consumers of other classes of psychotropic drugs and non-consumers. The number of psychotropic drugs used was inversely related to executive/attentional functioning. Conclusions: These findings show that in institutionalized older adults with dementia, specific impairment of cognitive function, i.e. executive/attentional impairments, are associated with antipsychotic medication use. Future longitudinal studies are recommended.