Miracle-dz/UniFAR-FTUs huggingface dataset:
Familial aggregation of Alzheimer disease among whites, African Americans, and Caribbean Hispanics in northern Manhattan.

BACKGROUND Alzheimer disease (AD) aggregates in families. OBJECTIVE To compare the familial aggregation and lifetime risk of AD to the age of 90 years in the first-degree relatives of patients with AD and unrelated controls among Caribbean Hispanics, African Americans, and whites in Washington Heights, Manhattan, New York, NY. METHODS Family history of AD and demographic information were obtained from informants of 435 patients with probable or possible AD concerning 1577 siblings and parents and from 1094 controls without dementia concerning 3952 siblings and parents. RESULTS Lifetime risk of AD to the age of 90 years was 25.9% in relatives of patients and 19.1% in relatives of controls. Rate ratio (RR) for AD in relatives of patients compared with relatives of controls was 1.5 overall (95% confidence interval [CI], 1.2-1.9), and was greater for siblings (RR, 1.8; 95% CI, 1.2-2.5) than for parents (RR, 1.2; 95% CI, 0.9-1.8). Within ethnic groups, RR for AD among relatives was significantly elevated in whites (RR, 2.0; 95% CI, 1.2-3.3) and Hispanics (RR, 1.5; 95% CI, 1.1-2.1), but the difference did not reach statistical significance in African Americans (RR, 1.4; 95% CI, 0.7-2.7). Risk of AD was greater among relatives who were women compared with men (RR, 1.5; 95% CI, 1.2-1.9). CONCLUSIONS Familial aggregation of AD was increased among families of patients compared with those of controls in all 3 ethnic groups. Risk of AD was highest among siblings and women relatives.
Dysbacteriosis and squamous (pre)neoplasia of immigrants and Dutch women as established in population‐based cervical screening

We examined the statistical relationships between dysbacteriosis and (pre)neoplasia related to age and ethnicity from the cervical screening of almost half a million smears. Data from 445,080 smears were coded according to KOPAC (the Dutch national cervical smear coding system) with nine grades. Prevalence per 100,000 smears and relative risks (RR) were calculated for dysbacteriosis and for squamous abnormalities. Patients were stratified by their probable country of origin. Dutch women had an RR of 0.92 for dysbacteriosis. Surinamese women had the highest RR for dysbacteriosis (RR = 2.36) and Moroccan women had the lowest (RR = 1.00). The same trends were seen for the risks of squamous abnormalities. The data for Turkish women follow the patterns of those for Surinamese women. The RR of dysbacteriosis is highest at 50 yr (1.28) and lowest at 35 yr (0.86). When dysbacteriotic and non‐dysbacteriotic smears were compared, dysbacteriosis was observed more frequently in smears with squamous abnormalities (4.1% vs. 2.2%). Dysbacteriosis may warrant more intensive cytological surveillance and changes in lifestyle. Diagn. Cytopathol. 2006;34: 377–381. © 2006 Wiley‐Liss, Inc.
Postnatal Changes in Cerebral Oxygen Extraction in the Preterm Infant Are Associated with Intraventricular Hemorrhage and Hemorrhagic Parenchymal Infarction but Not Periventricular Leukomalacia

Fluctuations in cerebral hemodynamics have been implicated in the pathogenesis of acquired brain damage in babies born prematurely. This study examined the changes in cerebral fractional oxygen extraction (FOE) over the first 3 d after birth in 25 very-low-birth-weight preterm infants. Twelve infants had no major cerebral injury and 13 had acquired brain injury; cystic periventricular leukomalacia (PVL) was present in 4 and intraventricular hemorrhage (IVH) in 9, of whom 2 also had hemorrhagic parenchymal infarction (HPI). Normal values (median, 5th–95th centiles) for cerebral FOE in very-low-birth-weight infants with no cerebral injury were 0.38 (0.23–0.53) on d 1, 0.31 (0.18–0.45) on d 2, and 0.28 (0.17–0.38) on d 3. Infants who developed cystic PVL had no significant change in cerebral FOE during the first 3 d after birth. By contrast, cerebral FOE fluctuated in infants with IVH over the 3 d of measurement, decreasing from d 1 to d 2 (p = 0.03) and increasing from d 2 to d 3 (p = 0.02). The highest cerebral FOE values were seen in the two infants with HPI. The different patterns of change in cerebral FOE with HPI and cystic PVL provide additional evidence that the pathogenesis of these two conditions is different. Because high cerebral FOE is likely to be a consequence of low cerebral oxygen delivery, probably because of low cerebral blood flow, our results indicate that fluctuations in cerebral blood flow may occur when there is IVH or HPI.
Identification of Domains of the Human Papillomavirus Type 11 E1 Helicase Involved in Oligomerization and Binding to the Viral Origin

ABSTRACT The E1 helicase of papillomavirus is required, in addition to host cell DNA replication factors, during the initiation and elongation phases of viral episome replication. During initiation, the viral E2 protein promotes the assembly of enzymatically active multimeric E1 complexes at the viral origin of DNA replication. In this study we used the two-hybrid system and chemical cross-linking to demonstrate that human papillomavirus type 11 (HPV11) E1 can self-associate in yeast and form hexamers in vitro in a reaction stimulated by single-stranded DNA. Self-association in yeast was most readily detected using constructs spanning the E1 C-terminal domain (amino acids 353 to 649) and was dependent on a minimal E1-E1 interaction region located between amino acids 353 and 431. The E1 C-terminal domain was also able to oligomerize in vitro but, in contrast to wild-type E1, did so efficiently in the absence of single-stranded DNA. Sequences located between amino acids 191 and 353 were necessary for single-stranded DNA to modulate oligomerization of E1 and were also required, together with the rest of the C terminus, for binding of E1 to the origin. Two regions within the C-terminal domain were identified as important for oligomerization: the ATP-binding domain and region A, which is located within the minimal E1-E1 interaction domain and is one of four regions of E1 that is highly conserved with the large T antigens of simian virus 40 and polyomavirus. Amino acid substitutions of highly conserved residues within the ATP-binding domain and region A were identified that reduced the ability of E1 to oligomerize and bind to the origin in vitro and to support transient DNA replication in vivo. These results support the notion that oligomerization of E1 occurs primarily through the C-terminal domain of the protein and is allosterically regulated by DNA and ATP. The bipartite organization of the E1 C-terminal domain is reminiscent of that found in other hexameric proteins and suggests that these proteins may oligomerize by a similar mechanism.
Indoxyl sulfate potentiates endothelial dysfunction via reciprocal role for reactive oxygen species and RhoA/ROCK signaling in 5/6 nephrectomized rats

Abstract Accumulative indoxyl sulfate (IS) retained in chronic kidney disease (CKD) can potentiate vascular endothelial dysfunction, and herein, we aim at elucidating the underlying mechanisms from the perspective of possible association between reactive oxygen species (ROS) and RhoA/ROCK pathway. IS-treated nephrectomized rats are administered with antioxidants including NADPH oxidase inhibitor apocynin, SOD analog tempol, and mitochondrion-targeted SOD mimetic mito-TEMPO to scavenge ROS, or ROCK inhibitor fasudil to obstruct RhoA/ROCK pathway. First, we find in response to IS stimulation, antioxidants treatments suppress increased aortic ROCK activity and expression levels. Additionally, ROCK blockade prevent IS-induced increased NADPH oxidase expression (mainly p22phox and p47phox), mitochondrial and intracellular ROS (superoxide and hydrogen peroxide) generation, and decreased Cu/Zn-SOD expression in thoracic aortas. Apocynin, mito-TEMPO, and tempol also reverse these markers of oxidative stress. These results suggest that IS induces excessive ROS production and ROCK activation involving a circuitous relationship in which ROS activate ROCK and ROCK promotes ROS overproduction. Finally, ROS and ROCK depletion attenuate IS-induced decrease in nitric oxide (NO) production and eNOS expression levels, and alleviate impaired vasomotor responses including increased vasocontraction to phenylephrine and decreased vasorelaxation to acetylcholine, thereby preventing cardiovascular complications accompanied by CKD. Taken together, excessive ROS derived from NADPH oxidase and mitochondria coordinate with RhoA/ROCK activation in a form of positive reciprocal relationship to induce endothelial dysfunction through disturbing endothelium-dependent NO signaling upon IS stimulation in CKD status.
Effect of methanol extract of Ricinus communis seed on reproduction of male rats.

AIM To investigate the effect of methanol extract of Ricinus communis seed (RCE) on male rats reproductive functions. METHODS Thirty-two male albino rats were divided into four groups. Groups 1, 2 and 3 were gavaged with 0.2 mL of 2.5% tween 80 (RCE vehicle; control) or 20 mg/(kg x d) and 40 mg/(kg x d) of RCE, respectively, for 30 days, and group 4 was also gavaged with 40 mg/(kg x d) of RCE, but was allowed a recovery period of 30 days. Five untreated female rats were cohabited with male rats in each group from day 25 of RCE treatment for 5 days, except group 4, where cohabitation began on day 25 of the recovery period. All male rats were sacrificed 24 h after the experiments. The female rats were laparotomized on day 19 of pregnancy and the number and weight of litters were recorded. RESULTS There was a significant decrease (P<0.01) in the weight of the reproductive organs, sperm functions and serum levels of testosterone in RCE treated rats. There was disorganization in the cytoarchitecture of the testes, disruption of the seminiferous tubules and erosion of the germinal epithelium. The number and weight of litters of rats in groups 2 and 4 decreased significantly (P<0.05) but no changes were observed in group 3. RCE caused no changes in liver, kidney, heart or body weights in male rats. CONCLUSION RCE has a reversible negative impact on male reproductive functions, which appears to be mediated via gonadal disruption in testosterone secretion.
Repeat head computed tomography after minimal brain injury identifies the need for craniotomy in the absence of neurologic change

BACKGROUND In this era of cost containment, the value of routine repeat head computed tomography (CT) in patients with mild TBI (mTBI) and no interval neurologic change has been challenged. The purpose of this study was to test the hypothesis that routine repeat head CT provides critical information after mTBI even with no neurologic change. METHODS From January 1996 to May 2010, records from all patients admitted to our Level I trauma center with an arrival Glasgow Coma Scale (GCS) score of 13 to 15 and at least one head CT were retrospectively reviewed. RESULTS In 360 patients with mTBI and positive initial head CT finding, the most common abnormalities were subarachnoid hemorrhage (64%), intraparenchymal hemorrhage (57%), and subdural hemorrhage (40%). Scans were repeated in 8 ± 6 hours; 11% were recalled, 59% remained stable, but 30% showed injury progression. Those patients with worsening repeat head CT finding had higher Injury Severity Score (ISS), were more likely to be intubated and require craniotomy, had longer stay, and had higher mortality (all p < 0.001). On multiple logistic regression, altered GCS score (odds ratio, 3.1–4.0), ISS (odds ratio, 1.1), and presence of mass effect (odds ratio, 2.0) were independently associated with worsening repeat head CT finding. In patients receiving a neurosurgical operative intervention, 32% to 59% had no clinical decline before the worsening repeat CT finding. CONCLUSION After mTBI, worsening of repeat head CT finding is seen in a third of patients and is associated with worse outcomes. A substantial fraction of patients who require operative intervention will have no clinical changes in the first 8 hours, supporting the value of repeat head CT within this time frame. LEVEL OF EVIDENCE Care management study, level III.
Activity of exemestane in metastatic breast cancer after failure of nonsteroidal aromatase inhibitors: a phase II trial.

PURPOSE To evaluate the antitumor activity and toxicity of a new steroidal aromatase inactivator, exemestane, in postmenopausal women with metastatic breast cancer who had progressive disease (PD) after treatment with a nonsteroidal aromatase inhibitor. PATIENTS AND METHODS In this phase II trial, eligible patients were treated with exemestane 25 mg daily (n = 241) followed, at the time PD was determined, by exemestane 100 mg daily (n = 58). RESULTS On the basis of the intent-to-treat analysis by independent review, exemestane 25 mg produced objective responses in 6.6% of patients (95% confidence interval [CI], 3.8% to 10.6%) and overall success (complete response + partial response + no change for 24 weeks or longer) in 24.3% (95% CI, 19.0% to 30.2%). The median durations of objective response and overall success were 58.4 weeks (95% CI, 49.7 to 71.1 weeks) and 37.0 weeks (95% CI, 35.0 to 39.4 weeks), respectively. Increasing the dose of exemestane to 100 mg upon the development of PD produced one partial response (1.7%; 95% CI, 0.0% to 9.2%). Both dosages were well tolerated and were discontinued because of adverse events in only 1.7% of patients. CONCLUSION Exemestane 25 mg once daily seems to be an attractive alternative to chemotherapy for the treatment of patients with metastatic breast cancer after multiple hormonal therapies have failed.
Effect of Withinia Somnifera and Shilajit on Alcohol Addiction in Mice

Background: Alcohol addiction is a social problem leading to both loss of health and economic prosperity among addicted individuals. Common properties of anti-addictive compounds include anti-anxiety, anticonvulsants, anti-depressant, and nootropic actions primarily through modulation of gamma-aminobutyric acid (GABA) and serotonergic systems. Objective: Here, we screen ashwagandha and shilajit known ethnopharmacologically as nervine tonic and adaptogenic herbs for possible anti-addictive potential. Materials and Methods: Effect of ashwagandha churna and shilajit was measured on ethanol withdrawal anxiety using elevated plus maze. Role of ashwagandha and shilajit on chronic ethanol consumption (21 days) was measured using two bottle choice protocol of voluntary drinking. We also measured the effect of the above herbs on corticohippocampal GABA, dopamine, and serotonin levels. Results: Both ashwagandha and shilajit were found to reduce alcohol withdrawal anxiety in a dose-dependent manner. These herbs alone or in combination also decreased ethanol intake and increased water intake significantly after 21 days of chronic administration. Chronic administration of ashwagandha was found to significantly increase GABA and serotonin levels whereas shilajit altered cortico-hippocampal dopamine in mice. Conclusion: These central nervous system active herbs alone or in combination reduced both alcohol dependence and withdrawal thus showing promising anti-addictive potential. SUMMARY Withinia Somnifera alone and in combination with Shilajeet prevented ethanol withdrawal and alcohol addiction Abbreviations used: GABA: Gama aminobutyric acid, CNS: Central Nervous System, CPP:Condition place preference, DA: Dopamine, 5-HT: 5-hydroxytryptamine, NMDA:N-methyl-D-aspartate Sugato Banerjee
Psychosocial concomitants to dental fear and behaviour management problems.

BACKGROUND Children with dental behavioural management problems (DBMP) form a heterogeneous group, where personal characteristics play significant roles. Attention to everyday life and family situation as additional background facets may help to better understand and treat these patients. AIM This study describes everyday life and family situation in child/adolescent patients referred because of DBMP, as compared to patients in ordinary dental care. DESIGN A study group of 230 referred patients (8-19 years old; 118 girls) was compared to a reference group of 248 same-aged patients (142 girls) without DBMP. Patients and parents were interviewed according to a semistructured protocol. RESULTS Patients referred because of DBMP more often lived in low socioeconomic status families, had parents not living together, fewer leisure-time activities, and were assessed as doing worse in social interactions compared to the reference group. Half of the study group had personal professional support, and some had experienced interventions by the social authorities. Whether these findings apply also to children/adolescents with DBMP who are not referred to specialist care remains to study. CONCLUSIONS Many children and adolescents referred because of DBMP have a burdensome life and family situation. This should be paid attention to in research and in clinical care.
A universal two-level changeover circuit of super-capacitor bank for energy storage systems

This paper proposed a universal two-level changeover circuit of super-capacitor bank for energy storage systems. Using the proposed circuit, the energy utilization efficiency can reach a higher level while the bank voltage fluctuation is limited at a smaller level. This reduces the required size of the energy storage systems and hence cost reduces. Furthermore, the circuit is relatively simple for practical engineering applications and the amounts of switches used in the circuit have been limited to the theoretical minimum amounts. At last, an automatic circuit-drawing program was developed. It draws any two-level changeover circuit required for super-capacitor bank with simple operations.
Phosphoproteomic analysis of wild‐type and antimony‐resistant Leishmania braziliensis lines by 2D‐DIGE technology

Protein phosphorylation is one of the most studied post‐translational modifications that is involved in different cellular events in Leishmania. In this study, we performed a comparative phosphoproteomics analysis of potassium antimonyl tartrate (SbIII)‐resistant and ‐susceptible lines of Leishmania braziliensis using a 2D‐DIGE approach followed by MS. In order to investigate the differential phosphoprotein abundance associated with the drug‐induced stress response and SbIII‐resistance mechanisms, we compared nontreated and SbIII‐treated samples of each line. Pair wise comparisons revealed a total of 116 spots that showed a statistically significant difference in phosphoprotein abundance, including 11 and 34 spots specifically correlated with drug treatment and resistance, respectively. We identified 48 different proteins distributed into seven biological process categories. The category “protein folding/chaperones and stress response” is mainly implicated in response to SbIII treatment, while the categories “antioxidant/detoxification,” “metabolic process,” “RNA/DNA processing,” and “protein biosynthesis” are modulated in the case of antimony resistance. Multiple sequence alignments were performed to validate the conservation of phosphorylated residues in nine proteins identified here. Western blot assays were carried out to validate the quantitative phosphoproteome analysis. The results revealed differential expression level of three phosphoproteins in the lines analyzed. This novel study allowed us to profile the L. braziliensis phosphoproteome, identifying several potential candidates for biochemical or signaling networks associated with antimony resistance phenotype in this parasite.
Oxidant Stress during Simulated Ischemia Primes Cardiomyocytes for Cell Death during Reperfusion*

Ischemia-reperfusion injury induces oxidant stress, and the burst of reactive oxygen species (ROS) production after reperfusion of ischemic myocardium is sufficient to induce cell death. Mitochondrial oxidant production may begin during ischemia prior to reperfusion because reducing equivalents accumulate and promote superoxide production. We utilized a ratiometric redox-sensitive protein sensor (heat shock protein 33 fluorescence resonance energy transfer (HSP-FRET)) to assess oxidant stress in cardiomyocytes during simulated ischemia. HSP-FRET consists of the cyan and yellow fluorescent protein fluorophores linked by the cysteine-containing regulatory domain from bacterial HSP-33. During ischemia, ROS-mediated oxidation of HSP-FRET was observed, along with a decrease in cellular reduced glutathione levels. These findings were corroborated by measurements using redox-sensitive green fluorescent protein, another protein thiol ratiometric sensor, which became 93% oxidized by the end of simulated ischemia. However, cell death did not occur during ischemia, indicating that this oxidant stress is not sufficient to induce death before reperfusion. However, interventions that attenuate ischemic oxidant stress, including antioxidants or scavengers of residual O2 that attenuate/prevent ROS generation during ischemia, abrogated cell death during simulated reperfusion. These findings reveal that, in isolated cardiomyocytes, sublethal H2O2 generation during simulated ischemia regulates cell death during simulated reperfusion, which is mediated by the reperfusion oxidant burst.
Impact of pharmacists' directive guidance behaviors on patient satisfaction.

OBJECTIVE To determine the impact of directive guidance (DG) behaviors by pharmacists on patient satisfaction with pharmaceutical care services. DG behaviors are social support behaviors and include such activities as supplying information about medications and providing encouragement and feedback regarding drug therapy. DESIGN Cross-sectional observational study using a self-administered survey. SETTING Two university-affiliated ambulatory care clinics, two chain pharmacies, and one independent pharmacy. PATIENTS One hundred sixty patients with a chronic disease (e.g., asthma, hypertension, diabetes). MAIN OUTCOME MEASURE Patient satisfaction with pharmaceutical care services. RESULTS A total of 160 completed questionnaires were collected from patients at 5 sites. Overall, patients patronizing ambulatory care clinics perceived higher rates of DG behaviors and were more satisfied with pharmaceutical care services, compared with patients in community pharmacies (P < .05). The hierarchical regression model was significant (F(13,112) = 4.9091, P < . 001). DG behaviors explained 32.4% (P < .001) of the variance in patient satisfaction with pharmaceutical care services. CONCLUSION Higher rates of DG behaviors by pharmacists are associated with greater patient satisfaction with pharmaceutical care services.