Miracle-dz/UniFAR-FTUs huggingface dataset:
Gata2 Is Required for Migration and Differentiation of Retinorecipient Neurons in the Superior Colliculus

The superior colliculus (SC)/optic tectum of the dorsal mesencephalon plays a major role in responses to visual input, yet regulation of neuronal differentiation within this layered structure is only partially understood. Here, we show that the zinc finger transcription factor Gata2 is required for normal SC development. Starting at embryonic day 15 (E15) (corresponding to the times at which neurons of the outer and intermediate layers of the SC are generated), Gata2 is transiently expressed in the rat embryonic dorsal mesencephalon within a restricted region between proliferating cells of the ventricular zone and the deepest neuronal layers of the developing SC. The Gata2-positive cells are postmitotic and lack markers of differentiated neurons, but express markers for immature neuronal precursors including Ascl1 and Pax3/7. In utero electroporation with Gata2 small hairpin RNAs at E16 into cells along the dorsal mesencephalic ventricle interferes with their normal migration into the SC and maintains them in a state characterized by retention of Pax3 expression and the absence of mature neuronal markers. Collectively, these findings indicate that Gata2 plays a required role in the transition of postmitotic neuronal precursor cells of the retinorecipient layers of the SC into mature neurons and that loss of Gata2 arrests them at an intermediate stage of differentiation.
The role of microbiota in hepatic encephalopathy

Hepatic encephalopathy (HE), which consists of minimal (MHE) and overt (OHE) stages, is a model for impaired gut-liver-brain axis in cirrhosis. Microbiota changes in both stages have been associated with impaired cognition, endotoxemia, and inflammation. There is dysbiosis (reduced autochthonous taxa [Lachnospiraceae, Ruminococcaceae, and Clostridiales XIV] and increased Enterobacteriaceae and Streptococcaceae) with disease progression. In MHE, there is an increased abundance of Streptococcus salivarius linked to cognition and ammonia. In OHE, stool Alcaligenaceae and Porphyromonadaceae are associated with poor cognition. Colonic mucosal microbiome in cirrhosis is significantly different compared with stool and independently related to cognition. HE treatment can affect microbial composition and function; cognitive improvement in MHE after rifaximin, a non-absorbable antibiotic, occurred without significant stool microbiota composition change but improved metabolic linkages. Similarly, there are only modest lactulose and rifaximin-associated changes on microbiota composition in OHE. HE represents an important model to study microbiome-brain interactions.
Aneurysmal Bone Cyst of Maxilla-A Rare Case Report and Review

An Aneurysmal bone cyst (ABC) is a rare benign lesion seen as a locally destructive, rapidly expansile, mostly affecting long bones and vertebrae. The association of ABC with Cementoossifying fibroma (COF) is extremely rare with only few cases reported so far in maxilla. We are herewith reporting one such case of hybrid lesion in a 15-year old boy, who came with a solitary swelling of right maxilla and showing partial obliteration of buccal vestibular sulcus and paraesthesia over right cheek region. Coronal Computed tomography (CT) of Para nasal sinus (PNS) view revealed large expansile lesion with thinning of cortex in right maxillary sinus involving hard palate and right alveolar process. Histological features were confirmative of the diagnosis of Aneurysmal Bone Cyst of Maxilla secondary to Cemento-ossifying fibroma. Treatment consisted of the enucleation of the lesion with surgical curettage through an intraoral approach under general anaesthesia. Case report & Review (J Int Dent Med Res 2013; 6: (1), pp. 49-53)
Posterior Parietal Cortex Encoding of Dynamic Hand Force Underlying Hand–Object Interaction

Major achievements of primate evolution are skilled hand–object interaction and tool use, both in part dependent on parietal cortex expansion. We recorded spiking activity from macaque inferior parietal cortex during directional manipulation of an isometric tool, which required the application of hand forces to control a cursor's motion on a screen. In areas PFG/PF, the activity of ∼70% neurons was modulated by the hand force necessary to implement the desired target motion, reflecting an inverse model, rather than by the intended motion of the visual cursor (forward model). The population vector matched the direction and amplitude of the instantaneous force increments over time. When exposed to a new force condition, that obliged the monkey to change the force output to successfully bring the cursor to the final target, the activity of a consistent subpopulation of neurons changed in an orderly fashion and, at the end of a “Wash-out” session, retained memory of the new learned association, at the service of predictive control of force. Our findings suggest that areas PFG/PF represent a crucial node of the distributed control of hand force, by encoding instantaneous force variations and serving as a memory reservoir of hand dynamics required for object manipulation and tool use. This is coherent with previous studies in humans showing the following: (1) impaired adaptation to a new force field under TMS parietal perturbation; (2) defective control of direction of hand force after parietal lesion; and (3) fMRI activation of parietal cortex during object manipulation requiring control of fine hand forces. SIGNIFICANCE STATEMENT Skilled object manipulation and tool use are major achievements of primate evolution, both largely dependent on posterior parietal cortex (PPC) expansion. Neurophysiological and fMRI studies in macaque and humans had documented a crucial role of PPC in encoding the hand kinematics underlying these functions, leaving to premotor and motor areas the role of specifying the underlying hand forces. We recorded spiking activity from macaque PPC during manipulation of an isometric tool and found that population activity is not only modulated by the dynamic hand force and its change over time, but also retains memory of the exerted force, as a reservoir to guide of future hand action. This suggests parallel parietal encoding of hand dynamics and kinematics during object manipulation.
Heterogeneity of Hemodynamic Parameters in Untreated Primary Hypertension, and Individualization of Antihypertensive Therapy Based on Noninvasive Hemodynamic Measurements

Noninvasive measurement of hemodynamic parameter was undertaken in 240 patients with untreated primary hypertension using impedance cardiography (ICG) in outpatient clinics. High output was defined as a cardiac index (CI) >3.6 L/minute/m2 and high resistance was defined as the total peripheral resistance index (TPRI) >2700 dyne·s·m2/cm5. Of all patients, 67% had high-resistance hypertension (high TPRI with normal or low CI), and 16% had high-output hypertension (high CI with normal TPRI). Treatment with β-blockers for high-output hypertension and with calcium channel blockers for high-resistance hypertension reduced blood pressure equally, and restored normal hemodynamic balance, as reported in studies using invasive monitoring methods. These findings suggest that it is appropriate to use noninvasive ICG measurements to guide antihypertensive therapy. Multivariate analysis showed that female gender, tachycardia, and low body mass index (BMI) were associated with high-output hypertension, but age was not. Heterogeneity of hemodynamic parameters is thought to be one of the reasons why the efficacies of antihypertensive agents differ between patients. It may be feasible to predict which antihypertensive agent would be the most effective for a particular patient based on hemodynamic measurements or combination of gender, heart rate, and BMI.
Factors contributing to poor antiretroviral therapy adherence among patients at Jwaneng Mine Hospital MASA Clinic in Botswana

This study establishes factors that contribute to poor ART adherence. It was done at Jwaneng Mine Hospital MASA Clinic in Botswana. A qualitative study was done using a structured questionnaire which included open and close-ended questions. A total of 36 people (17 male and 19 female) who are HIV positive and on ART participated in the study. Participants were aged 21 years and above. Data was analysed using qualitative method. Frequencies were used for analysis of closeended questions. Themes were identified in open-ended questions. The responses given by the patients gave an insight on factors that may be contributing to poor ART adherence among patients at Jwaneng Mine hospital MASA Clinic although the study population was too small to make definite conclusions. In this study it was revealed that the following factors may play a role in poor ART adherence: Transport issues, Forgetfulness and long waiting hours. The main finding in this research was that many factors thought to be contributing to poor adherence do not seem to have influence on ART adherence but the fact of the matter is general ART adherence of patients at Jwaneng Mine Hospital is low. To enhance good adherence, it is of paramount importance that ART be rolled-out even to the lowest level health facilities, more nurses should be trained on prescribing and dispensing of ART, and patients should be given at least two months supply of ART. Lastly, it would be of importance to conduct a similar type of study in the future on a larger scale to verify the results of this study.
Antibody response to Streptococcus pneumoniae proteins PhtD, LytB, PcpA, PhtE and Ply after nasopharyngeal colonization and acute otitis media in children

We prospectively compared serum antibody levels of 5 Streptococcus pneumoniae (Spn) proteins: PcpA PhtD, PhtE Ply and LytB associated with nasopharyngeal (NP) colonization and acute otitis media (AOM) infection in a cohort of 6–30 mo old children. Antigen-specific antibody titers were determined by ELISA. A total of 731 visits among 168 children were studied. There were 301 Spn NP colonization episodes documented in 109 (65%) children and 42 Spn AOM episodes in 34 (20%) children. IgG antibody titers to the 5 proteins were significantly different among children over time (p < 0.001), with a rank order as follows: PcpA > PhtE = PhtD > Ply > LytB Characterization of IgG and IgM acute and convalescent serum antibody levels of Spn AOM infection showed the kinetics of the response differed among children, with the same rank order of antibody levels over time. Individual data showed that some children responded to AOM with an antibody increase to one or more of these Spn proteins but some children failed to respond. We conclude that antibody levels to Spn proteins PcpA PhtD, PhtE, Ply and LytB, all rise over time in children age 6 to 30 mo following natural exposure to Spn after NP colonization and AOM; however, there were significant differences in quantity of antibody elicited among these potential vaccine antigens.
Study on self-medication among 2nd year medical students -

Background: Self-medication is use of medicines by individuals to treat self-recognized symptoms and illness. Self-medication is a common type of self-care behavior in the general public, but medical students differ in such practice, as they have knowledge about drugs and diseases. Methods: The present study involved 100 2 nd year final term medical students in “Shivamogga Institute of Medical Sciences,” Shivamogga, Karnataka. Study was questionnaire based, and the results were analyzed by descriptive statistical methods. Results: In our study, 57% were female, and 43% were male. About 60% had knowledge about over the counter (OTC) drugs and considered Ayurveda drugs also OTC drugs. 25% considered self-medication entirely safe, whereas 61% considered self-medication have advantages. Self-medication was preferred by 72% as they felt that there is no need to consult health care professionals for a simple ailment. Self-medication was practiced by 62% students, among which 86% were appropriate, and 48% among them utilized knowledge from previous consultation. In 28% fever was the most common condition and paracetamol was the most commonly used drug. Conclusions: Self-medication was widely practiced among the students. They had good knowledge of OTC drugs. The practice of self-medication was almost appropriate. In general self-medication must be accompanied by appropriate information. Educating benefits and risks of self-medication is very much needed for medical students and the public now a day.
N-Terminal pro-brain natriuretic peptide levels and abnormal geometric patterns of left ventricle in untreated hypertensive patients

Abstract N-terminal pro-brain natriuretic peptide (NT-proBNP) predicts cardiovascular events and mortality in hypertensive patients. Relationship between NT-proBNP level and left ventricular (LV) hypertrophy is well known in hypertensive patients. However, the studies investigating relationship between LV geometric patterns and serum NT-proBNP level have conflicting results and are in a limited number. The goal of the present study is to investigate relation between NT-proBNP and abnormal LV geometric patterns in untreated hypertensive patients. Measurements were obtained from 273 patients with untreated essential hypertension (mean age = 51.7 ± 5.8 years) and 44 healthy control subjects (mean age; 51.3 ± 4.7). Four different geometric patterns (NG: normal geometry; CR: concentric remodelling; EH: eccentric hypertrophy; CH: concentric hypertrophy) were determined according to LV mass index (LVMI) and relative wall thickness. NT-proBNP and other biochemical markers were measured in all subjects. The highest NT-proBNP levels were determined in the CH group compared with the control group and other geometric patterns (p < 0.05). NT-proBNP levels of all geometric patterns were higher than the control group (p < 0.05, for all). NT-proBNP levels were similar between CR and NG groups (p > 0.05). NT-proBNP was independently associated with LV geometry (β = 0.304, p = 0.003) and LVMI (β = 0.266, p = 0.007) in multiple linear regression analysis. Serum NT-proBNP level was independently associated with LVMI and LV geometry in untreated hypertensive patients with preserved ejection fraction.
The impact of metabolic syndrome, recently diagnosed diabetes and hypertension on right ventricular remodeling. Is there difference between risk factors?

Abstract The aim of this study was to compare the right ventricular (RV) structure and diastolic function between normotensive and non-diabetic subjects with metabolic syndrome (MS), and new diagnosed diabetic and hypertensive patients. Study included 89 normotensive and non-diabetic subjects with MS which was defined by the presence ≥3 ATP-NCEP-III criteria, 45 diabetic and 117 hypertensive patients, as well as 76 controls with no MS criteria, matched for age and sex. All subjects underwent laboratory blood tests and complete two-dimensional echocardiography including pulsed and tissue Doppler. RV free wall thickness was similar between MS and diabetic patients, but significantly lower than in hypertensive patients (4.6 ± 0.8 versus 4.3 ± 0.7 versus 4.9 ± 0.9 mm; p < 0.01). Tricuspid E/e′ ratio was similar between observed groups (5.3 ± 1.2 versus 5.2 ± 1.1 versus 5.7 ± 1.2, p > 0.05). RV systolic function evaluated by tissue Doppler (st) was similar between MS and diabetic participants, but still worse than in hypertensive patients (13.1 ± 2.2 versus 13.5 ± 2.5 versus 12.5 ± 2.4, p < 0.05). Global RV function estimated by Tei index was similar among MS and diabetic patients, and most impaired in hypertensive patients (0.47 ± 0.09 versus 0.45 ± 0.08 versus 0.52 ± 0.1, p < 0.01). Increased fasting glucose level, abdominal obesity and hypertension were independent predictors of biventricular hypertrophy, diastolic dysfunction and global dysfunction in whole population. RV structure and function gradually deteriorated from diabetic patients, across MS subject, to hypertensive patients. Normotensive and non-diabetic subjects with MS had similar level of RV impairment as diabetic patients which emphasize the synergic effects of MS components on cardiac damage.
Assessment of squalene adjuvanted and non-adjuvanted vaccines against pandemic H1N1 influenza in children 6 months to 17 years of age

Vaccines were urgently needed in 2009 against A/H1N1 pandemic influenza. Based on the H5N1 experience, it was originally thought that 2 doses of an adjuvanted vaccine were needed for adequate immunogenicity. We tested H1N1 vaccines with or without AF03, a squalene-based adjuvant, in children. Two randomized, open-label, trials were conducted. Participants 3–17 y received two injections of 3.8 µg or 7.5 µg hemagglutinin (HA) with adjuvant or 15 µg HA without adjuvant. Participants aged 6–35 mo received two injections of 1.9 µg or 3.8 µg HA with full or half dose adjuvant or 7.5 µg HA without adjuvant. All subjects 3 to 17 y reached seroprotection (hemagglutination inhibition (HI) titer ≥ 40) after the first dose of the adjuvanted vaccine, and 94% and 98% in the 3–8 and 9–17 y groups respectively with the non-adjuvanted vaccine. In children aged 6–35 mo responses were modest after one dose, but after two doses virtually all children were seroprotected regardless of HA or adjuvant dose. In this age group, antibody titers were 5 to 7 times higher after adjuvanted than non-adjuvanted vaccine. The higher responses with the adjuvanted vaccine were also reflected as better antibody persistence. There was no clustering of adverse events that would be suggestive of a safety signal. While a single injection was sufficient in subjects from 3 y, in children aged 6–35 mo two injections of this A/H1N1 pandemic influenza vaccine were required. Formulation of this vaccine with adjuvant provided a significant advantage for immunogenicity in the latter age group.
Copula Regression Analysis of Simultaneously Recorded Frontal Eye Field and Inferotemporal Spiking Activity during Object-Based Working Memory

Inferotemporal (IT) neurons are known to exhibit persistent, stimulus-selective activity during the delay period of object-based working memory tasks. Frontal eye field (FEF) neurons show robust, spatially selective delay period activity during memory-guided saccade tasks. We present a copula regression paradigm to examine neural interaction of these two types of signals between areas IT and FEF of the monkey during a working memory task. This paradigm is based on copula models that can account for both marginal distribution over spiking activity of individual neurons within each area and joint distribution over ensemble activity of neurons between areas. Considering the popular GLMs as marginal models, we developed a general and flexible likelihood framework that uses the copula to integrate separate GLMs into a joint regression analysis. Such joint analysis essentially leads to a multivariate analog of the marginal GLM theory and hence efficient model estimation. In addition, we show that Granger causality between spike trains can be readily assessed via the likelihood ratio statistic. The performance of this method is validated by extensive simulations, and compared favorably to the widely used GLMs. When applied to spiking activity of simultaneously recorded FEF and IT neurons during working memory task, we observed significant Granger causality influence from FEF to IT, but not in the opposite direction, suggesting the role of the FEF in the selection and retention of visual information during working memory. The copula model has the potential to provide unique neurophysiological insights about network properties of the brain.
Cortical Hubs Revealed by Intrinsic Functional Connectivity: Mapping, Assessment of Stability, and Relation to Alzheimer's Disease

Recent evidence suggests that some brain areas act as hubs interconnecting distinct, functionally specialized systems. These nexuses are intriguing because of their potential role in integration and also because they may augment metabolic cascades relevant to brain disease. To identify regions of high connectivity in the human cerebral cortex, we applied a computationally efficient approach to map the degree of intrinsic functional connectivity across the brain. Analysis of two separate functional magnetic resonance imaging datasets (each n = 24) demonstrated hubs throughout heteromodal areas of association cortex. Prominent hubs were located within posterior cingulate, lateral temporal, lateral parietal, and medial/lateral prefrontal cortices. Network analysis revealed that many, but not all, hubs were located within regions previously implicated as components of the default network. A third dataset (n = 12) demonstrated that the locations of hubs were present across passive and active task states, suggesting that they reflect a stable property of cortical network architecture. To obtain an accurate reference map, data were combined across 127 participants to yield a consensus estimate of cortical hubs. Using this consensus estimate, we explored whether the topography of hubs could explain the pattern of vulnerability in Alzheimer's disease (AD) because some models suggest that regions of high activity and metabolism accelerate pathology. Positron emission tomography amyloid imaging in AD (n = 10) compared with older controls (n = 29) showed high amyloid-β deposition in the locations of cortical hubs consistent with the possibility that hubs, while acting as critical way stations for information processing, may also augment the underlying pathological cascade in AD.
Blood pressure reduction by Japanese traditional Miso is associated with increased diuresis and natriuresis through dopamine system in Dahl salt-sensitive rats

Abstract Objectives: We investigated the antihypertensive mechanism of long-term Miso soup consumption in Dahl salt-sensitive (Dahl S) rats with salt-induced hypertension. Material and Methods: Female Dahl S rats fed a low-salt (0.3% NaCl) diet were divided into three groups: (1) six rats given water, (2) six rats given 0.65% (w/v) saline solution or (3) eight rats given 5% (w/v) Miso soup containing 0.65% (w/v) saline solution. They were followed for 12 weeks. Variables in the plasma or 24-h urine were determined. Systolic blood pressure (SBP) was measured by the tail-cuff method. Results: The SBP increased in an age-dependent manner in Dahl S rats drinking saline solutions. The elevation of SBP was significantly attenuated in Dahl S rats given Miso soup although the ultimate cumulative salt loading was much greater in the Miso group than those given the saline solutions. This SBP reduction in the Miso group was associated with an increase in fractional excretion of Na (FENa) and free water clearance in the kidney. Urinary dopamine excretions were increased in the Miso group compared with that in the saline group. The increase in urinary dopamine excretions was associated with a decrease in brain oxidative stress. Urinary dopamine excretions were an independent predictor of SBP in the Miso group. Conclusions: Long-term consumption of Miso soup attenuated blood pressure elevation in Dahl salt-sensitive rats with salt-induced hypertension. The blood pressure reduction was due to, at least in part, constituent(s) of the Miso that increase natriuresis and diuresis and enhance dopaminergic nervous activity in the kidney.