Miracle-dz/UniFAR-FTUs huggingface dataset:
Estradiol alters body temperature regulation in the female mouse

ABSTRACT Hot flushes are due to estrogen withdrawal and characterized by the episodic activation of heat dissipation effectors. Recent studies (in humans and rats) have implicated neurokinin 3 (NK3) receptor signaling in the genesis of hot flushes. Although transgenic mice are increasingly used for biomedical research, there is limited information on how 17β-estradiol and NK3 receptor signaling alters thermoregulation in the mouse. In this study, a method was developed to measure tail skin temperature (TSKIN) using a small data-logger attached to the surface of the tail, which, when combined with a telemetry probe for core temperature (TCORE), allowed us to monitor thermoregulation in freely-moving mice over long durations. We report that estradiol treatment of ovariectomized mice reduced TCORE during the light phase (but not the dark phase) while having no effect on TSKIN or activity. Estradiol also lowered TCORE in mice exposed to ambient temperatures ranging from 20 to 36°C. Unlike previous studies in the rat, estradiol treatment of ovariectomized mice did not reduce TSKIN during the dark phase. Subcutaneous injections of an NK3 receptor agonist (senktide) in ovariectomized mice caused an acute increase in TSKIN and a reduction in TCORE, consistent with the activation of heat dissipation effectors. These changes were reduced by estradiol, suggesting that estradiol lowers the sensitivity of central thermoregulatory pathways to NK3 receptor activation. Overall, we show that estradiol treatment of ovariectomized mice decreases TCORE during the light phase, reduces the thermoregulatory effects of senktide and modulates thermoregulation differently than previously described in the rat.
Default mode network connectivity in patients with idiopathic normal pressure hydrocephalus.

OBJECTIVE Idiopathic normal pressure hydrocephalus (iNPH) is a neurological disorder characterized by gait disturbance, cognitive impairment, and incontinence. It is unclear whether the pathophysiology of iNPH is associated with alterations in the default mode network (DMN). The authors investigated alterations in the DMN of patients with iNPH and sought to determine whether a relationship exists between the resting-state functional connectivity of the DMN and a patient's clinical symptoms. METHODS Resting-state functional MRI (rs-fMRI) was performed in 16 preoperative patients with iNPH and 15 neurologically healthy control subjects of a similar age. Independent component and dual-regression analyses were used to quantify DMN connectivity. The patients' clinical symptoms were rated according to the iNPH grading scale (iNPHGS). Each of their specific clinical symptoms were rated according to the cognitive, gait, and urinary continence domains of iNPHGS, and neurocognitive status was assessed using the Mini-Mental State Examination, Frontal Assessment Battery (FAB), and Trail Making Test Part A. The strength of DMN connectivity was compared between patients and controls, and the correlation between DMN connectivity and iNPHGS was examined using both region of interest (ROI)-based analysis and voxel-based analysis. The correlation between DMN connectivity and each of the specific clinical symptoms, as well as neurocognitive status, was examined using voxel-based analysis. RESULTS Both ROI-based and voxel-based analyses revealed reduced DMN connectivity in patients with iNPH. ROI-based analysis showed increased DMN connectivity with worsening clinical symptoms of iNPH. Consistently, voxel-based analyses revealed that DMN connectivity correlated positively with the iNPHGS score, as well as the cognitive and urinary continence domain scores, and negatively with the FAB score. The significant peak in correlation in each case was localized to the precuneus. CONCLUSIONS This is the first study to establish alterations in the DMN of patients with iNPH. DMN connectivity may be a useful indicator of the severity of clinical symptoms in patients with iNPH.
Relationship between outdoor temperature and blood pressure

Objectives Cardiovascular mortality has been linked to changes in outdoor temperature. However, the mechanisms behind these effects are not well established. We aimed to study the effect of outdoor temperature on blood pressure, as increased blood pressure is a risk factor for cardiovascular death. Methods The study population consisted of men aged 53–100 years living in the Boston area. We used a mixed effects model to estimate the effect of three temperature variables: ambient, apparent and dew point temperature (DPT), on repeated measures (every 3–5 years) of diastolic (DBP) and systolic blood pressure (SBP). Random intercepts for subjects and several possible confounders were used in the models, including black carbon and barometric pressure. Results We found modest associations between DBP and ambient and apparent temperature. In the basic models, DBP in association with a 5°C decrease in 7-day moving averages of temperatures increased by 1.01% (95% CI −0.06% to 2.09%) and 1.55% (95% CI 0.61% to 2.49%) for ambient and apparent temperature, respectively. Excluding extreme temperatures strengthened these associations (2.13%, 95% CI 0.66% to 3.63%, and 1.65%, 95% CI 0.41% to 2.90%, for ambient and apparent temperature, respectively). Effect estimates for DPT were close to null. The effect of apparent temperature on SBP was similar (1.30% increase (95% CI 0.32% to 2.29%) for a 5°C decrease in 7-day moving average). Conclusions Cumulative exposure to decreasing ambient and apparent temperature may increase blood pressure. These findings suggest that an increase in blood pressure could be a mechanism behind cold-related, but not heat-related, cardiovascular mortality.
Morphological Variations and Biometrics of Ear: An Aid to Personal Identification.

INTRODUCTION The morphological characteristics and dimensions of external ear vary in different human ethnic races which can be utilized in forensics for personal identification of living or deceased. AIM To determine uniqueness of morphological and biometric variations of both ears for individualization among North East (NE) and North West (NW) subpopulation of India. MATERIALS AND METHODS The study was conducted on randomly selected 80 students, 40 from each subgroup. Nine ear parameters were recorded twice using digital Vernier's caliper by single investigator and two indices (Ear Index and Lobule Index) were calculated for both the ears. Morphological ear shapes and lobule attachment were also noted. Pearson's coefficient correlation test was performed on cross-tabulations to evaluate significant relationship between different variables. RESULTS Of the total 35% free and 65% attached ear lobes were noted in both population groups. Oval ear shape was most commonly noted followed by triangular, rectangular and round in both populations. On comparing anthropometric measurements of ears in two populations it was found that except the tragus length and lobule index all other values were noted more in NW population. No statistical difference was found in ear and lobular indices of males and females although the left ear index and lobule index were found to be higher than right in both populations except in NW females where right lobule index was recorded more than left. CONCLUSION The results obtained can be used in anthropological and forensic sciences for the inclusion and exclusion of persons for identification on the basis of ear variations.
Stressful Life Events and Depressive Symptomatology Among Basque Adolescents: The Mediating Role of Attachment Representations

The occurrence of stressful life events is a risk factor for psychopathology in adolescence. Depression is a problem of notable clinical importance that has a negative psychosocial impact on adolescents and which has considerable social, educational, and economic costs. The aim of this study was to examine the relationship between stressful life events and depressive symptomatology in adolescence, taking into account the effect that attachment representations may have on this relation. Participants were 1653 adolescents (951 girls) aged between 13 and 18 years. The sample was selected by means of a random sampling procedure based on the availability of schools to participate. Data were collected at two time points: attachment and stressful life events were assessed first, and symptoms of depression were evaluated eight to nine months later. Two time points were used in order to better analyze the mediating role of attachment security. Stressful life events were recorded using the Inventory of Stressful Life Events, attachment was evaluated by the Inventory of Parent and Peer Attachment (mother, father, and peer versions), and depressive symptomatology was assessed through the Children’s Depression Scale. In all cases, the Basque version of these scales was used. The results indicated that attachment to parents was a mediating variable in the relationship between stressful life events and depressive symptomatology. Contrary to what we expected, the results indicate that stressful life events did not have a negative effect on peer attachment, and neither did the latter variable act as a mediator of the relationship between stressful life events and depressive symptoms. It can be concluded that attachment-based interventions may be especially useful for reducing depression symptoms among adolescents. The findings also suggest a role for interventions that target parent–child attachment relationships.
Epithelial and stromal genetic instability linked to tumor suppressor genes in ulcerative colitis-associated tumorigenesis

Objective. We have previously documented not only epithelial but also stromal genetic instability in ulcerative colitis (UC)-associated lesions, including adenocarcinomas, using microsatellite markers close to the p53 gene on chromosome 17 (Chr.17). However, about half of the UC-associated tumors do not have p53 gene alterations. The purpose of this study was to detect early genetic instability (loss of heterozygosity (LOH) and microsatellite instability (MSI)) of both epithelial and stromal cells in UC-associated tumorigenesis, using different microsatellite markers from the p53 gene. Material and methods. The laser-captured microdissection-PCR-GeneScan method was applied to investigate genetic instability in both the epithelial and stromal elements of early UC-associated lesions (regenerative mucosa and dysplasia) and carcinomas using multiple microsatellite markers, chiefly close to tumor suppressor genes (TSGs: p16INK4A, Rb, Smad4 and fragile histidine triad (FHIT)). Furthermore, expression of their gene products was analyzed by immunohistochemistry. Results. In epithelium, although LOH for Chr.17 markers increased along with histological progression, the frequencies of LOH or MSI for TSG markers were found to be almost constantly increased in both stromal and epithelial components of all lesion types. In contrast, genetic instability of National Cancer Institute (NCI)-recommended standard markers was not found to be significantly correlated with UC-associated tumorigenesis. Immunohistochemically, epithelial p16INK4A expression tended to be decreased in LOH-positive lesions (p=0.0780) and Smad4 expression was significantly decreased (p<0.05). Conclusions. These results suggest that genetic instability in the stroma, especially regarding TSG markers, may play an important role in early-phase, UC-associated tumorigenesis. In addition, decreased expression of TSG due to genetic alteration might contribute to tumorigenesis.
The epidemiology of biopsy-positive giant cell arteritis: special reference to cyclic fluctuations.

OBJECTIVE The aim of this work was to study changes in the incidence of biopsy-proven giant cell arteritis (GCA) over a period of 20 yr in Göteborg, Sweden. METHODS All cases of biopsy-verified GCA between 1976 and 1995 were included in the study. The annual incidence was calculated for the whole material, for women and men separately, and its fluctuations were tested statistically. In addition, the monthly variation during the last 9 yr could be statistically analysed for the whole material. RESULTS In total, 665 patients were diagnosed with biopsy-verified GCA during the 20 yr period. The average annual incidence was 22.2/100000 inhabitants over 50 yr of age (women 29.8, men 12.5). The annual incidence increased significantly with time (P<0.001) for both men and women. Statistical analysis did not reveal any cyclic fluctuation in the annual incidence (P=0.26), while the monthly number of positive biopsies showed significant fluctuation with peaks in late winter and autumn (P=0.041). CONCLUSIONS The annual incidence of biopsy-positive GCA increased during the years 1976 through 1995. The significant seasonal variation, as well as considerable variation in annual incidence, might be due to the influence of exogenous triggering factors, such as infections. Further support for an exogenous aetiology, in terms of a statistically significant cyclic fluctuation of the annual incidence, was not found, however.
Atypical Forms of Hand, Foot, and Mouth Disease: A Prospective Study of 47 Italian Children

Atypical forms of hand, foot, and mouth disease (HFMD) caused by coxsackievirus A6 have been reported in recent years. High fever and severe cutaneous lesions are common, whereas neurologic complications are rare. Eczematous areas of patients with atopic dermatitis show more lesions. The goal of the current study was to describe the clinical characteristics of children with atypical HFMD and to investigate the involvement of the different enterovirus serotypes associated.
Class II-Restricted Protective Immunity Induced by Malaria Sporozoites

ABSTRACT The irradiated-sporozoite vaccine elicits sterile immunity against Plasmodium parasites in experimental rodent hosts and human volunteers. Based on rodent malaria models, it has been proposed that CD8+ T cells are the key protective effector mechanism required in sporozoite-induced immunity. To investigate the role of class II-restricted immunity in protective immunity, we immunized β2-microglobulin knockout (β2M−/−) mice with irradiated Plasmodium yoelii or P. berghei sporozoites. Sterile immunity was obtained in the CD8+-T-cell-deficient mice immunized with either P. berghei or P. yoelii sporozoites. β2M−/− mice with the BALB/c (H-2d) genetic background as well as those with the C57BL (H-2b) genetic background were protected. Effector mechanisms included CD4+ T cells, mediated in part through the production of gamma interferon, and neutralizing antibodies that targeted the extracellular sporozoites. We conclude that in the absence of class I-restricted CD8+ T cells, sporozoite-induced protective immunity can be effectively mediated by class II-restricted immune effector mechanisms. These results support efforts to develop subunit vaccines that effectively elicit high levels of antibody and CD4+ T cells to target Plasmodium preerythrocytic stages.
Therapeutic benefit of spironolactone in experimental chronic cyclosporine A nephrotoxicity.

BACKGROUND Cyclosporine A (CsA) is an immunosuppressive drug used to prevent tissue allograft rejection. However, its long-term utilization is limited due to chronic nephrotoxicity for which no prevention is available. This study evaluated the effect of spironolactone on renal functional and structural alterations induced by CsA, and assessed whether the protective effect was associated with a reduction of transforming growth factor-beta (TGF-beta) and the change of extracellular matrix protein mRNA level. METHODS Male Wistar rats fed with low sodium diet were divided in four treatment groups: vehicle, CsA (30 mg/kg), spironolactone (20 mg/kg), or CsA+spironolactone. After 21 days, creatinine clearance (CCr), blood CsA, arteriolopathy in renal tissue, and TGF-beta, collagen I, collagen IV, fibronectin, and epidermal growth factor (EGF) mRNA levels in renal cortex were determined. RESULTS CsA reduced the CCr and up-regulated TGF-beta, collagen I and fibronectin mRNA expression with a significant development of arteriolopathy, and reduced EGF mRNA levels. In contrast, spironolactone administration prevented the fall in renal function and TGF-beta, collagen I, and fibronectin up-regulation, together with a reduction of arteriolopathy and tubulointerstitial fibrosis. CONCLUSION Our data show that aldosterone plays an important role as a mediator of renal injury induced by CsA. Thus, mineralocorticoid receptor blockade may be a potential strategy to prevent CsA nephrotoxicity.
The Role of Soluble Components in Ambient Fine Particles-Induced Changes in Human Lungs and Blood

Normal individuals developed pulmonary neutrophilic inflammation and increased blood fibrinogen following inhalation of concentrated ambient particles (CAPS). In this study, we sought to determine how soluble components in CAPS contributed to these changes. We expanded and reanalyzed data from 37 young healthy volunteers from a previous study (Ghio et al., 2000) who were exposed to either filtered air or CAPS. Postexposure bronchoalveolar lavage (BAL) as well as pre- and postexposure venous blood samples was analyzed for cellular and acute inflammatory endpoints. Nine most abundant components in the water-soluble fraction of CAPS were correlated with these endpoints using principal component analysis. We found that a sulfate/Fe/Se factor was associated with increased BAL percentage of neutrophils and a Cu/Zn/V factor with increased blood fibrinogen. The concentrations of sulfate, Fe, and Se correlated highly with PM mass (R > 0.75) while the correlations between PM and Cu/Zn/V were modest (R = 0.2-0.6). These results from controlled human exposure linked specific PM components to pulmonary neutrolphil influx and blood fibrinogen increase, and indicated the soluble components of pollutant particles may differentially affect pulmonary and hematological systems in humans exposed to PM.
MiR-186 inhibits proliferation, migration, and invasion of non-small cell lung cancer cells by downregulating Yin Yang 1.

BACKGROUND Non-small cell lung cancer (NSCLC) is the main type of lung cancer. While miR-186 is significantly reduced in lung cancer tissues and cells, its role in NSCLC has not been completely elucidated. MATERIAL AND METHODS We used qRT-PCR and western blot methods to investigate the levels of miR-186 and YY1 in 21 pairs of NSCLC tissues. Dual luciferase reporter gene assays were performed to detect whether miR-186 directly targets YY1. Next, the roles of miR-186 and its target gene (YY1) in determining the proliferation, apoptosis and migration capabilities of selected cell lines (A549 and HCC827) were investigated by using miR-186 mimics or YY1 siRNA. RESULTS Our results showed that miR-186 was downregulated and YYI was upregulated in NSCLC tissue, and miR-186 expression was negatively associated with YY1. Similarly, miR-186 was also downregulated and YY1 expression also was upregulated in both A549 and HCC827 cells; furthermore, miR-186 was found to directly target YY1. Cell proliferation, invasion, and migration, as well as apoptosis induction were more strongly inhibited by YY1 siRNA than by miR-186. CONCLUSION Our results suggest that miR-186 and its target gene (YY1) could possibly serve as new prognostic biomarkers and therapeutic targets for treating NSCLC in humans.
Rapid Mineralization of Benzo[a]pyrene by a Microbial Consortium Growing on Diesel Fuel

ABSTRACT A microbial consortium which rapidly mineralized the environmentally persistent pollutant benzo[a]pyrene was recovered from soil. The consortium cometabolically converted [7-14C]benzo[a]pyrene to14CO2 when it was grown on diesel fuel, and the extent of benzo[a]pyrene mineralization was dependent on both diesel fuel and benzo[a]pyrene concentrations. Addition of diesel fuel at concentrations ranging from 0.007 to 0.2% (wt/vol) stimulated the mineralization of 10 mg of benzo[a]pyrene per liter 33 to 65% during a 2-week incubation period. When the benzo[a]pyrene concentration was 10 to 100 mg liter−1 and the diesel fuel concentration was 0.1% (wt/vol), an inoculum containing 1 mg of cell protein per liter (small inoculum) resulted in mineralization of up to 17.2 mg of benzo[a]pyrene per liter in 16 days. This corresponded to 35% of the added radiolabel when the concentration of benzo[a]pyrene was 50 mg liter−1. A radiocarbon mass balance analysis recovered 25% of the added benzo[a]pyrene solubilized in the culture suspension prior to mineralization. Populations growing on diesel fuel most likely promoted emulsification of benzo[a]pyrene through the production of surface-active compounds. The consortium was also analyzed by PCR-denaturing gradient gel electrophoresis of 16S rRNA gene fragments, and 12 dominant bands, representing different sequence types, were detected during a 19-day incubation period. The onset of benzo[a]pyrene mineralization was compared to changes in the consortium community structure and was found to correlate with the emergence of at least four sequence types. DNA from 10 sequence types were successfully purified and sequenced, and that data revealed that eight of the consortium members were related to the classProteobacteria but that the consortium also included members which were related to the genera Mycobacterium andSphingobacterium.
Magnetic Resonance Imaging, Scintigraphy, and Arthroscopic Evaluation of Traumatic Hemarthrosis of the Knee

Forty patients with traumatic knee hemarthrosis were examined within 1 week after injury and observations made with magnetic resonance imaging, scintigraphy, arthroscopic evaluation, radiography, and physical ex amination were compared. Thirty-four patients (85%) had anterior cruciate ligament injuries according to the arthroscopic findings and 28 (83%) of these had asso ciated meniscal tears. Magnetic resonance imaging confirmed the arthroscopic findings, especially if only meniscal tears that required surgery were taken into account (sensitivity, 94% for the lateral and 83% for the medial meniscus). However, the specificity of magnetic resonance imaging was only 29% and 27% for the lateral and medial menisci, respectively, and the accu racy was 28% and 50%, respectively. Marrow edemas, or bone bruises, were seen on magnetic resonance imaging in 80% of the patients and were mainly seen in the lateral compartment. Bone scans correlated well with magnetic resonance imaging findings of marrow edemas. Plain radiographs were normal in all but one case. We show that magnetic resonance imaging does not add information on the status of the anterior cruci ate ligament compared with the clinical examination, and that it may be as good as arthroscopic evaluation for the diagnosis of meniscal tears that require surgery.