Miracle-dz/UniFAR-FTUs huggingface dataset:
Pharmacokinetics of Levodopa/Carbidopa Microtablets Versus Levodopa/Benserazide and Levodopa/Carbidopa in Healthy Volunteers

ObjectivesTo compare bioavailability and pharmacokinetics of single doses of 3 different levodopa formulations given orally in healthy volunteers. Two marketed formulations, standard levodopa/carbidopa, 100/25 mg (LC-100), and dispersible levodopa/benserazide, 100/25 mg (LB-100), were used as reference formulations for a newly developed dispersible microtablet formulation of levodopa/carbidopa, 5/1.25 mg (LC-5). The microtablets are intended for individualized dosing of levodopa/carbidopa in Parkinson disease by means of an electronic dose dispenser with a built-in diary for symptom registration. MethodsA single-dose, open, randomized, 3-way crossover study was performed in 19 healthy subjects. Concentrations of levodopa, carbidopa, and the metabolite 3-O-MD in plasma were determined after intake of 100 mg of levodopa, that is, one tablet of reference formulations and 20 microtablets of the new formulation. ResultsThe LC-5 microtablets were bioequivalent to the LC-100 tablets in area under the curve (AUC) and maximum concentration in plasma (Cmax) for levodopa, and to the LB-100 tablets in AUC. The dispersible levodopa/benserazide formulation showed earlier time to Cmax and significantly higher Cmax for levodopa in plasma compared to the microtablets. Carbidopa showed larger interindividual variation in AUC and Cmax than levodopa, and the bioequivalence comparison LC-5/LC-100 for this compound did not reach the target. Nevertheless, comparison of 3-O-MD levels for LC-5/LC-100, assuming proportionality to levodopa levels, demonstrated bioequivalence. ConclusionsThe new levodopa/carbidopa microtablets had a pharmacokinetic profile that would allow for a convenient switch of therapy from standard tablets. Frequent dose administration of levodopa/carbidopa microtablets with an electronic dose dispenser might offer an optimal oral drug delivery in Parkinson disease.
An Olfactory Reference Syndrome Successfully Treated by Aripiprazole Augmentation of Antidepressant Therapy

ObjectiveTo describe a case of a 65-year-old woman with persistent olfactory hallucination and delusional self-reference, successfully treated by aripiprazole augmentation of antidepressant therapy. BackgroundOlfactory reference syndrome is a nosologic entity, which has been assimilated to various Diagnostic and Statistical Manual of Mental Disorder-IV-text revision codified diseases and several pharmacologic treatments have been proposed without a constant clinical response. MethodPsychiatric, neurologic, neuropsychologic, imaging, and electroencephalogram data are reported. ResultsThe patient showed a significant improvement with aripiprazole. ConclusionsWe propose a pathophysiologic model of olfactory reference syndrome to explain the good response of our patient to aripiprazole. We hypothesize a disruption in the top-down regulation of the orbitofrontal cortex on the primary olfactory cortex and the olfactory bulb at the basis of the illness. Aripiprazole acting as a partial agonist of dopamine D2 receptors in the olfactory bulb compensates for the lack of modulation in this site, restoring the correct processing of olfactory information.
Development and validation of a short, easy-to-use questionnaire for diagnosing urinary incontinence and lower urinary tract symptoms in women: the Female Urinary Symptom Score

We have developed the Female Urinary Symptom Score (FUSS), a symptom questionnaire for the evaluation of urinary incontinence and lower urinary tract symptoms in women and their effect on quality of life. The FUSS is a modified version of the International Prostate Symptom Score adapted for use in women. It consists of a simple questionnaire of only eight questions, which patients can answer quickly on a numerical scale. We performed a validation study of the FUSS by comparing it with the King’s Health Questionnaire (KHQ), a well-validated but longer symptom questionnaire. We sent both questionnaires to 220 women between the ages of 45 and 65 years randomly selected from two general practices in the United Kingdom. Urinary symptom status was unknown; 149 (94%) of the FUSS questionnaires and 115 (73%) of the KHQs were completed correctly. Correlation was conducted on the scores of the 115 matched pairs and was high (r = 0.83). We sent another copy of the FUSS questionnaire to the same group of women after four weeks, and found that the test and re-test scores for FUSS were highly correlated (r = 0.88). We conclude that the FUSS is a simple, reliable and reproducible tool for the diagnosis of urinary symptoms in women. As it is brief, we believe that it will be useful in the primary care setting, enabling women to receive appropriate treatment and care as early as possible.
Violence against psychiatrists by patients: survey in a London mental health trust

AIMS AND METHOD A survey was undertaken to investigate assaults of psychiatrists by patients in a 12-month period. Surveys were sent to 199 psychiatrists representing all sub-specialties and grades in a London mental health trust. RESULTS There were 129 returned responses (response rate 64.8%). In the 12-month study period, 12.4% of all psychiatrists and 32.4% of senior house officers were assaulted. None received or took up offers of formal, as opposed to informal, psychological support. Most assaults occurred on a psychiatric ward. Vulnerability to assaults was not influenced by courses on prevention and management of violence or by the attitudes of psychiatrists to violence by psychiatric patients. CLINICAL IMPLICATIONS Senior house officers are most vulnerable to assaults. Greater attention may need to be given to psychiatric wards where most assaults occurred. Trusts should ensure that those assaulted are identified and offered support.
Contribution of bone marrow‐derived endothelial progenitor cells to neovascularization and astrogliosis following spinal cord injury

Spinal cord injury causes initial mechanical damage, followed by ischemia‐induced, secondary degeneration, worsening the tissue damage. Although endothelial progenitor cells (EPCs) have been reported to play an important role for pathophysiological neovascularization in various ischemic tissues, the EPC kinetics following spinal cord injury have never been elucidated. In this study, we therefore assessed the in vivo kinetics of bone marrow‐derived EPCs by EPC colony‐forming assay and bone marrow transplantation from Tie2/lacZ transgenic mice into wild‐type mice with spinal cord injury. The number of circulating mononuclear cells and EPC colonies formed by the mononuclear cells peaked at day 3 postspinal cord injury. Bone marrow transplantation study revealed that bone marrow‐derived EPCs recruited into the injured spinal cord markedly increased at day 7, when neovascularization and astrogliosis drastically occurred in parallel with axon growth in the damaged tissue. To elucidate further the contribution of EPCs to recovery after spinal cord injury, exogenous EPCs were systemically infused immediately after the injury. The administered EPCs were incorporated into the injured spinal cord and accelerated neovascularization and astrogliosis. These findings suggest that bone marrow‐derived EPCs may contribute to the tissue repair by augmenting neovascularization and astrogliosis following spinal cord injury. © 2012 Wiley Periodicals, Inc.
Role of Endoscopic Skull Base and Keyhole Surgery for Pituitary and Parasellar Tumors Impacting Vision

Abstract: Significant advances over the last 2 decades in imaging technology, instrumentation, anatomical knowledge, and reconstructive techniques have resulted in the endonasal endoscopic approach becoming an integral part of modern skull base surgery. With growing use and greater experience, surgical outcomes continue to incrementally improve across many skull base pathologies, including those tumors that impact vision and ocular motility. The importance of the learning curve and use of a multi-disciplinary approach is critical to maximizing success, minimizing complications, and enhancing quality of life in these patients. Realizing the limits of the endonasal route and reasonable use of transcranial approaches such as the supraorbital eyebrow craniotomy is also critical, as is appropriate use of nonsurgical therapies including various forms of radiotherapy, radiotherapy, and medical treatment options.
Life Events and Personality Trait Change.

OBJECTIVE Theory and research have emphasized the impact of life events on personality trait change. In this article, we review prospective research on personality trait change in response to nine major life events in the broader domains of love and work. METHOD We expected to find that life events lead to personality trait change to the extent that they have a lasting influence on individuals' thoughts, feelings, and behavior. Moreover, we predicted that love-related life events such as marriage or parenthood would be more strongly related to changes in traits that emphasize affective content, whereas work-related life events would be more likely to lead to change in traits that reflect behavioral or cognitive content. RESULTS The current state of research provided some evidence that life events can lead to changes in personality traits and that different life events may be differently related to specific trait domains. CONCLUSIONS A more general conclusion emerging from this review is that the evidence for the nature, shape, and timing of personality trait change in response to life events is still preliminary. We discuss the implications of the results for theory and research and provide directions for future studies on life events and personality trait change.
Acute inflammation alters adult hippocampal neurogenesis in a multiple sclerosis mouse model

Neural precursor cells (NPCs) located in the subgranular zone (SGZ) of the dentate gyrus (DG) give rise to thousands of new cells every day, mainly hippocampal neurons, which are integrated into existing neuronal circuits. Aging and chronic degenerative disorders have been shown to impair hippocampal neurogenesis, but the consequence of inflammation is somewhat controversial. The present study demonstrates that the inflammatory environment prevailing in the brain of experimental autoimmune encephalomyelitis (EAE) mice enhances the proliferation of NPCs in SGZ of the dorsal DG and alters the proportion between radial glial cells and newborn neuroblasts. The injection protocol of the cell cycle marker bromodeoxyuridine and the immunohistochemical techniques that were employed revealed that the proliferation of NPCs is increased approximately twofold in the SGZ of the dorsal DG of EAE mice, at the acute phase of the disease. However, although EAE animals exhibited significant higher percentage of newborn radial‐glia‐like NPCs, the mean percentage of newborn neuroblasts rather was decreased, indicating that the robust NPCs proliferation is not followed by a proportional production of newborn neurons. Significant positive correlations were detected between the number of proliferating cells in the SGZ and the clinical score or degree of brain inflammation of diseased animals. Finally, enhanced neuroproliferation in the acute phase of EAE was not found to trigger compensatory apoptotic mechanisms. The possible causes of altered neurogenesis observed in this study emphasize the need to understand more precisely the mechanisms regulating adult neurogenesis under both normal and pathological conditions. © 2013 Wiley Periodicals, Inc.
Falls among community‐dwelling psychogeriatric patients

Although increasing interest has been focused on falling in the elderly, little is known about the incidence and consequence of falls in psychogeriatric outpatients. We conducted a 1‐year prospective study of falling in 102 community‐dwelling elderly patients with psychiatric morbidity (mean age: 70 years) and 100 mentally intact elderly patients (controls, mean age: 74 years). The subject group comprised 79 patients with depression, 14 with dementia and nine with combined disease based on DSM‐III‐R criteria. Overall, 216 falls in the subject group and 54 in the controls were reported. At the end of the study, recurrent fallers aged 75 years and older showed significant physical deterioration. Multiple logistic regression analysis of selected medical and demographic variables indicated that the most influential variable regarding falling of the subjects was severity of depression rated using the Hamilton scale. Unexpectedly, the analysis revealed that the use of antidepressants was associated with a lower likelihood of falling. On the basis of the two variables, 75% of all respondents were correctly classified as fallers or non‐fallers.
Barriers and Facilitators to Providing HIV-Related Services in Bostonian African American Churches: A Focus Group Study of Clergy and Community Members

African American churches are potential sites of culturally relevant HIV prevention and service provision. A coalition including an ecumenical group of Christian clergy and lay leaders in the African American church community, a minority AIDS service organization, and an academic medical center, was funded to develop faith-based HIV education, prevention, and testing services. Before service implementation, coalition leaders conducted six focus groups with 46 different religious leaders and community members at risk for or living with HIV/AIDS, to understand program needs and collaboration strategies. Study participants identified key barriers and facilitators that are critical to the success of faith-based HIV/AIDS services.
Dopamine and Cu+/2+ can induce oligomerization of α‐synuclein in the absence of oxygen: Two types of oligomerization mechanisms for α‐synuclein and related cell toxicity studies

α‐Synuclein oligomers can induce neurotoxicity and are implicated in Parkinson's disease etiology and disease progression. Many studies have reported α‐synuclein oligomerization by dopamine (DA) and transition metal ions, but few studies provide insight into joint influences of DA and Cu2+. In this study, DA and Cu2+ were coadministered aerobically to measure α‐synuclein oligomerization under these conditions. In the presence of oxygen, DA induced α‐synuclein oligomerization in a dose‐dependent manner. Cu+/2+ did not effect oligomerization in such a manner in the presence of DA. By electrophoresis, Cu2+ was found easily to induce oligomerization with DA. This implies that oligomerization invoked by DA is reversible in the presence of Cu2+, which appears to be mediated by noncovalent bond interactions. In the absence of oxygen, DA induced less oligomerization of α‐synuclein, whereas DA/Cu2+ induced aerobic‐level amounts of oligomers, suggesting that DA/Cu2+ induces oligomerization independent of oxygen concentration. Radical species were detected through electron paramagnetic resonance (EPR) spectroscopic analysis arising from coincubation of DA/Cu2+ with α‐synuclein. Redox reactions induced by DA/Cu2+ were observed in multimer regions of α‐synuclein oligomers through NBT assay. Cellular toxicity results confirm that, for normal and hypoxic conditions, copper or DA/Cu2+ can induce cell death, which may arise from copper redox chemistry. From these results, we propose that DA and DA/Cu2+ induce different mechanisms of α‐synuclein oligomerization, cross‐linking with noncovalent (or reversible covalent) bonding vs. likely radical‐mediated covalent modification. © 2013 Wiley Periodicals, Inc.
Targeted opening of the blood brain barrier by ALA-mediated photodynamic therapy

Background and Objective: We have evaluated the ability of ALA-mediated PDT to selectivly open the BBB in rats. This will permit access of chemotherapeutic agents to brain tumor cells remaining in the resection cavity wall, but limit their penetration into normal brain remote from the site of illumination. Study Design/Materials and Methods: ALA-PDT was performed on non-tumor bearing inbred Fischer rats at increasing fluence levels. Contrast T1-weighted high field (3 T) magnetic resonance imaging (MRI) scans were used to monitor the degree of BBB disruption. Results: PDT at increasing fluence levels between 9 and 17 J demonstrated an increasing contrast flow rate. The BBB was found to be disrupted 2 h following PDT and 80 - 100 % restored 72 h later at the lowest fluence level. No effect on the BBB was observed if 26 J of light was given in the absence of ALA. Conclusion: ALA-PDT was highly effective in opening the BBB in a localized region of the brain. The degradation of the BBB was temporary in nature at fluence levels of 9 J, opening rapidly following treatment and significantly restored during the next 72 h. No signs of permanent tissue damage were seen on histological sections at this fluence level.
SIRT1 inhibition by sirtinol aggravates brain edema after experimental subarachnoid hemorrhage

Secondary brain injury following subarachnoid hemorrhage (SAH) is poorly understood. We utilized a rat model of SAH to investigate whether SIRT1 has a protective role against brain edema via the tumor suppressor protein p53 pathway. Experimental SAH was induced in adult male Sprague‐Dawley rats by prechiasmatic cistern injection. Brain SIRT1 protein levels were examined in the sham controls and in rats 6, 12, 24, 48, and 72 hr after SAH induction. The SIRT1 inhibitor sirtinol was administered by intracerebroventricular infusion. Neurological functions, blood–brain barrier (BBB) disruption, and brain water content were assessed. Endothelial cell apoptosis, caspase 3 protein expression, p53 acetylation, and matrix metalloproteinase‐9 (MMP‐9) activity were examined. Compared with the control, SIRT1 protein expression increased remarkably, reaching a maximum at 24 hr after SAH. Sirtinol treatment significantly lowered SIRT1 expression, accompanied by deteriorated neurologic function, BBB disruption, brain edema, increased endothelial cell apoptosis, and increased MMP‐9 gelatinase activity compared with the rats treated with vehicle only. Our results suggest that increased expression of endogenous SIRT1 may play a neuroprotective role against brain edema after SAH. © 2014 Wiley Periodicals, Inc.
Attentional Bias for Academic Stressors and Classroom Climate Predict Adolescents’ Grades and Socioemotional Functioning

Using a dot-probe detection task, this longitudinal study investigated whether adolescents show an attentional bias for academic stressors at the beginning of the school year (T1), and if such allocation of attention interacts with classroom climate (CC) to predict grades and socioemotional functioning at the end of the term (T2). Among 133 eighth-graders, the majority showed a perceptual bias toward academic threats. Regression analyses indicated that a greater bias at T1 predicted lower grades and more socioemotional problems at T2, and that CC moderated these relationships. Students perceiving low CC and displaying greater attentional bias reported lower grades and more socioemotional problems. Teachers may promote a positive CC to prevent the negative effects of a biased attention on youths' school adjustment.
Tracking of Actinobacillus actinomycetemcomitans in subgingival plaque of aggressive periodontitis patients

Background: Actinobacillus actinomycetemcomitans is thought to be one of the etiological agents in aggressive periodontitis as well as indicated in various systemic diseases. Objective: To evaluate the prevalence of A. actinomycetemcomitans in the subgingival plaque of aggressive periodontitis patients. Study Design: Initially, under the selective growth conditions, the isolates were picked from the plaques and their identification was confirmed by polymerase chain reaction using primers specific for A. actinomycetemcomitans subgingival plaque of 15 patients diagnosed clinically and on radiographic criteria as aggressive periodontitis was inoculated on the Tryptic Soy agar with Bacitracin and Vancomycin culture media for 3-5 days under microaerophilic conditions. The positive colonies were selected based on biochemical tests for further analysis using reported primers for A. actinomycetemcomitans. Results: The results showed that 66.67% of aggressive periodontitis patients and 6.67% of control group of normal patients showed evidence of presence of A. actinomycetemcomitans in the subgingival microflora. Conclusion: This is the first study of its kind in an Indian population whereby almost all aggressive periodontitis patients showed evidence of A. actinomycetemcomitans.
Opening the Black Box

Objective: The Taxonomy of Care for Youth was developed to gather information about the care offered to children and adolescents with behavioral and emotional problems in various care settings. The aim was to determine similarities and differences in the content of care and thereby to classify the care offered to these children and youth within and across care organizations. Method: Interventions (N = 56) offered in primary health care, child and youth care, and mental health care were assessed by using descriptors. Professionals scored the degree of applicability of these descriptors and interventions with similar descriptors were merged. Results: As a result, the interventions could be classified into 7 main types of support and the total number of interventions reduced to 27. Conclusion: The descriptors used in this study were able to classify the various kinds of care offered based on their content, thereby creating an overview of distinct interventions.
White matter microstructure in chronic moderate‐to‐severe traumatic brain injury: Impact of acute‐phase injury‐related variables and associations with outcome measures

This study examines how injury mechanisms and early neuroimaging and clinical measures impact white matter (WM) fractional anisotropy (FA), mean diffusivity (MD), and tract volumes in the chronic phase of traumatic brain injury (TBI) and how WM integrity in the chronic phase is associated with different outcome measures obtained at the same time. Diffusion tensor imaging (DTI) at 3 T was acquired more than 1 year after TBI in 49 moderate‐to‐severe‐TBI survivors and 50 matched controls. DTI data were analyzed with tract‐based spatial statistics and automated tractography. Moderate‐to‐severe TBI led to widespread FA decreases, MD increases, and tract volume reductions. In severe TBI and in acceleration/deceleration injuries, a specific FA loss was detected. A particular loss of FA was also present in the thalamus and the brainstem in all grades of diffuse axonal injury. Acute‐phase Glasgow Coma Scale scores, number of microhemorrhages on T2*, lesion volume on fluid‐attenuated inversion recovery, and duration of posttraumatic amnesia were associated with more widespread FA loss and MD increases in chronic TBI. Episodes of cerebral perfusion pressure <70 mmHg were specifically associated with reduced MD. Neither episodes of intracranial pressure >20 mmHg nor acute‐phase Rotterdam CT scores were associated with WM changes. Glasgow Outcome Scale Extended scores and performance‐based cognitive control functioning were associated with FA and MD changes, but self‐reported cognitive control functioning was not. In conclusion, FA loss specifically reflects the primary injury severity and mechanism, whereas FA and MD changes are associated with objective measures of general and cognitive control functioning. © 2014 The Authors. Journal of Neuroscience Research Published by Wiley Periodicals, Inc.