Miracle-dz/UniFAR-FTUs huggingface dataset:
Prevalence and impact of risk factors for lower body difficulty among Mexican Americans, African Americans, and whites.

BACKGROUND The purpose of the study was to estimate the prevalence of sociodemographic, health behavior, chronic disease, and impairment factors and their impact on difficulty in lower body function among two age-cohorts (51-61 and 71-81 years) of Mexican Americans, African Americans, and Whites. METHODS Reports from 8,727 and 4,510 self-respondents of the 1992 baseline Health and Retirement Survey and the 1993 baseline Assets and Health Dynamics Study, respectively, were used to estimate prevalence. Multiple linear regression of the 4-item lower body difficulty scale (alpha = .80) was used to estimate the direct effects of the risk factors within the age-cohort and ethnicity groups. RESULTS Overall, the risk factors are more prevalent among both minority groups and the older age-cohort. Lower body deficits are particularly high among Mexican Americans and the younger age-cohort of African Americans. The impact of risk factors does not vary much by ethnicity or age-cohort. Female gender, pain, arthritis, and heart and lung disease are the major risk factors, and they account for about one-third of the variance in lower body difficulty for each group. CONCLUSIONS Efforts to prevent or reduce lower body difficulty should pay particular attention to pain, arthritis, and heart and lung disease. The central role of sociodemographic and behavioral factors in chronic disease argues for their continued inclusion in disability modeling and prevention.
Salivary melatonin response to acute pain stimuli

Evidence for a relationship between melatonin, nociception, and analgesia in humans is based on data that are only linked by association and simultaneous occurrence. Studies have reported inverse correlation of the circadian melatonin rhythm with nociception latency and enhancement of opioid analgesia by simultaneous administration of melatonin in animals. This study examines the response of salivary melatonin to acute pain stimuli in 18 healthy subjects ranging in age from 19 to 50 years. A biphasic melatonin response following an acute pain stimulus of 36 V was observed, F(8, 8)=17.839, P<0.001. Within 5 min of the stimulus, melatonin decreased and reached a plateau of 36 pg/mL below baseline by 20 min. This decrease was followed by an increase of 5 pg/mL. Melatonin levels subsequently decreased until they had reached levels similar to those anticipated for the time of day and did not vary thereafter. The magnitude of the melatonin response was not related to age or gender. There was no association between voltage and magnitude of the melatonin responses observed at 15 min (r=0.185, P=0.51) or at 30 min (r=0.468, P=0.09). This study provides the first evidence of melatonin utilization and subsequent pineal gland synthesis following acute pain episodes in humans.
Age influences the clinical significance of atypical glandular cells on cytology.

AIM To evaluate women with atypical glandular cells (AGC) or adenocarcinoma in situ (AIS) on cytology. PATIENTS AND METHODS Population-based data of cervical smears taken between 2008-2012 were analyzed. RESULTS Cancer was diagnosed in 107 out of 199 patients (54%) with AGC or AIS; 30 with cervical adenocarcinoma and 77 with endometrial cancer. All women with endometrial cancer were 50 years or older. In women younger than 50 years, cervical pre-cancerous lesions were found in 44 (47%) and cervical adenocarcinoma in 24 out of 92 cases (26%). High-risk HPV infection was found in 62 out of 103 women (60%). The detection rate of high-risk HPV at finding histopathological AGC, AIS, low-grade squamous intraepithelial lesions, high-grade squamous intraepithelial lesions or cervical cancer was 98% (95% confidence interval=0.903-1.000) (54/55). CONCLUSION AGC or AIS indicates endometrial neoplasia in women 50 years or older and pre-cancerous or invasive glandular cervical lesions in younger women. HPV testing seems to identify underlying cervical adenocarcinoma and high grade squamous intraepithelial lesions.
Glutamate and Quisqualate Regulate Expression of Metabotropic Glutamate Receptor mRNA in Cultured Cerebellar Granule Cells

Abstract: Metabotropic glutamate receptor (type 1; mGluR1) is expressed predominantly in the hippocampus and the cerebellum. Using cultured cerebellar granule cells, we investigated the regulation of the mGluR1 mRNA expression. Levels of mGluR1 mRNA were decreased to less than half by high potassium stimulation and by glutamate and quisqualate. Although these glutamate receptor agonists tested are also known to cause neuronal cell death in culture, the effect of cell death cannot explain the observed reduction in mGluR1 mRNA because of the following reasons: (a) antagonists of N‐methyl‐D‐aspartate and non‐N‐methyl‐D‐aspartate receptors inhibited cell death, but not the reduction of the level of mGluR1 mRNA; (b) mGluR1 mRNA returned to its initial level 48 h after the agonist application; and (c) the mRNA level of one of the α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionate/kainate receptors (GluR1) was not altered by these conditions. Therefore, we conclude that the glutamate or quisqualate stimulation can specifically inhibit the expression of mGluR1 mRNA. The dose response of quisqualate for the reduction in mGluR1 mRNA is consistent with that for inositol phosphate formation stimulated through the cloned mGluR1. The mRNA reduction did not require extracellular calcium. Desensitization of mGluR1 with phorbol ester abolished the mRNA reduction. These results suggest that the reduction in mGluR1 mRNA is mediated by the activation of the metabotropic receptor itself.
Prognostic relevance of baseline and sequential peripheral blood tyrosinase expression in 200 consecutive advanced metastatic melanoma patients

The relationship between the disease course and the prognostic relevance of sequential tyrosinase reverse transcription-PCR assay in the peripheral blood of advanced metastatic melanoma patients was ascertained. The clinical usefulness of tyrosinase in stage IV melanoma patients is still debated, owing to the wide range of variability (positive expression from 30 up to 100% of patients) and the possibility of a transient shedding of melanoma cells into the bloodstream. A total of 200 consecutive stage IV metastatic patients treated at our department were included, 149 with active metastatic disease undergoing systemic therapies (group A), and 51 disease free after surgery (group B). For each patient, a baseline sample was obtained within 3 weeks of either the clinical/radiological demonstration of metastatic disease or the surgical treatment; thereafter, tyrosinase determinations were performed at day 1 of each therapy course before chemotherapy administration or at each follow-up visit. Tyrosinase expression was determined using standard reverse transcription-PCR nested techniques. A baseline positive determination was obtained in 72.5% of the patients with active metastatic disease (group A) but not in any of the patients who were disease free after surgery (group B). Therapy administration induced an early clearance of circulating melanoma cells, from 72.5 to 44.9% at the second down to 29.5% at the third determination. Tyrosinase expression before the third cycle was significantly associated with the clinical response: 56/81 (69.1%) patients with a negative tyrosinase determination obtained a response or a stable disease, whereas 29/34 (85.3%) patients with a positive test developed a progressive disease (P<0.001). A clinical response was observed in all the patients who had a negative tyrosinase at the first three determinations, although all patients whose first three determinations were positive developed a progressive disease. Multivariate analysis showed that baseline tyrosinase status carries an independent prognostic value on both overall survival and time to progression; moreover, tyrosinase results during follow-up were entered as time-dependent covariates in a multivariate analysis and were shown to be the most significant prognostic parameter associated to both overall survival and time to progression. In particular, the presence of a constant positive expression during follow-up was associated with the development of new metastatic sites in 95.6% of patients with active metastatic disease. Our results demonstrate that the discrepancies in the positive tyrosinase rates reported in the literature are related to the disease status at the time of sampling and to chemotherapy administration. Tyrosinase expression in the peripheral blood both at baseline and during follow-up can be considered a reliable prognostic parameter associated with the response to treatment, development of new metastatic sites, time to progression and survival.
Altered norepinephrine turnover in the brain of rats with chronic renal failure.

Disturbances of the sympathetic nervous system have been described in chronic renal failure, but their role in the genesis and maintenance of hypertension frequently associated with this condition has not been established. The neuroadrenergic activity in brain nuclei involved in the regulation of blood pressure in uremic animals has also not been previously evaluated. In these studies, the neuroadrenergic activity was measured in the anterior, lateral, and posterior hypothalamic nuclei, in the locus coeruleus, and in the nucleus tractus solitarius of Sprague Dawley rats 5/6 nephrectomized or sham operated 4 wk before the experiments. Neuroadrenergic activity was determined by calculating norepinephrine (NE) turnover rate (in picograms per milligram per hour), 3, 6 and 12 h after inhibition of NE synthesis with L-methyltyrosine. The endogenous NE concentration was significantly greater in the posterior hypothalamic nuclei (21,501 +/- 1,777 pg/mg wet wt) and in the locus coeruleus (16,152 +/- 1,114 pg/mg wet tissue) of uremic compared with control rats (12,213 +/- 1,404 and 7,991 +/- 622 pg/mg wet wt, respectively). On the other hand, the endogenous NE content of the nucleus tractus solitarius and the anterior hypothalamic nuclei did not differ between uremic and control rats. The turnover rate of NE in the posterior hypothalamic nuclei of uremic rats (2150 +/- 430 pg/mg per hour) was significantly faster (P < 0.05) than in control rats (977 +/- 244 pg/mg per hour). The turnover rate of NE in the locus coeruleus of uremic rats (2,584 +/- 323 pg/mg per hour) was also significantly faster than in control animals (400 +/- 140 pg/mg per hour; P < 0.01). (ABSTRACT TRUNCATED AT 250 WORDS)
Structure-Function Map of the Receptor Site for β-Scorpion Toxins in Domain II of Voltage-gated Sodium Channels*

Voltage-gated sodium (Nav) channels are the molecular targets of β-scorpion toxins, which shift the voltage dependence of activation to more negative membrane potentials by a voltage sensor-trapping mechanism. Molecular determinants of β-scorpion toxin (CssIV) binding and action on rat brain sodium channels are located in the S1-S2 (IIS1-S2) and S3-S4 (IIS3-S4) extracellular linkers of the voltage-sensing module in domain II. In IIS1-S2, mutations of two amino acid residues (Glu779 and Pro782) significantly altered the toxin effect by reducing binding affinity. In IIS3-S4, six positions surrounding the key binding determinant, Gly845, define a hot spot of high-impact residues. Two of these substitutions (A841N and L846A) reduced voltage sensor trapping. The other three substitutions (N842R, V843A, and E844N) increased voltage sensor trapping. These bidirectional effects suggest that the IIS3-S4 loop plays a primary role in determining both toxin affinity and efficacy. A high resolution molecular model constructed with the Rosetta-Membrane modeling system reveals interactions of amino acid residues in sodium channels that are crucial for toxin action with residues in CssIV that are required for its effects. In this model, the wedge-shaped CssIV inserts between the IIS1-S2 and IIS3-S4 loops of the voltage sensor, placing key amino acid residues in position to interact with binding partners in these extracellular loops. These results provide new molecular insights into the voltage sensor-trapping model of toxin action and further define the molecular requirements for the development of antagonists that can prevent or reverse toxicity of scorpion toxins.
The Use of an In Vitro-cultured Porcine Nasal Mucosa Model for the Biocompatibility Assessment of Biodegradable Magnesium

The development of an in vitro-cultured porcine nasal mucosa model is described. The model was subsequently used for the biocompatibility testing of resorbable magnesium-based implants, which are intended for use in the nasal cavity of patients with chronic rhinosinusitis (CRS). Test specimens made from either pure magnesium or titanium were incubated with the mucosal tissue for 48 hours. Afterwards, tissue viability, PGE2, IL-6 and IL-8 release, magnesium ion release, succinate dehydrogenase activity, apoptosis and 14C amino acid incorporation, were determined. The results suggested favourable biocompatibility, even in the case of rapidly-degrading pure magnesium. However, presumed effects on protein synthesis and apoptosis could not be confirmed.
Active Learning-Based Optimized Training Library Generation for Object-Oriented Image Classification

In this paper, we introduce an active learning (AL)-based object training library generation for a multiclassifier object-oriented image analysis (OOIA) system. While several AL approaches do exist for pixel-based training library generation and for hyperspectral image classification, there is no standard training library generation strategy for OOIA of very high spatial resolution images. Given a sufficient number of training samples, supervised classification is the method of choice for image classification. However, this strategy becomes computationally expensive with the increase in the number of classes or the number of images to be classified. The above-mentioned issue is solved in this proposed method, where an optimized training library of objects (superpixels) is generated based on a batch mode AL approach. A softmax classifier is used as a detector in this method, which helps in determining the right samples to be chosen for library updation. To this end, we construct a multiclassifier system with max-voting decision to classify an image at pixel level. This algorithm was applied on three different very high-resolution airborne data sets, each with varying complexity in terms of variations in geographical context, sensors, illumination, and view angles. Our method has empirically outperformed the traditional OOIA by producing equivalent accuracy with a training library that is orders of magnitude smaller. In addition, the most distinctive ability of the algorithm is experienced in the most heterogeneous data set, where its performance in terms of accuracy is around twice the performance of the traditional method in the same situation. The generality of this classification strategy is proved through its performance on multispectral images and for cross-domain application. Finally, the robustness of this method is identified by comparing its performance with an alternative AL approach—self-learning-based semisupervised SVM. The capability of the proposed method to handle highly heterogeneous data is identified as the primary reason for its robustness.
Improvement of acute and chronic renal dysfunction in liver transplant patients after substitution of calcineurin inhibitors by mycophenolate mofetil.

BACKGROUND Renal dysfunction caused by treatment with the calcineurin inhibitors (CNI) is a major problem in the long-term course after liver transplantation. PATIENTS In 22 liver graft recipients with renal dysfunction and stable graft function between 3 weeks and 12 years after transplantation, CNI were substituted by MMF at a final dose of 1.5-3 g/day between October 1996 and October 1998. METHODS In a prospective non-randomized study, the development of renal function, the side effects of MMF medication, and the stability of liver function were analyzed for a mean follow-up of 15 months. Results. (1) MMF was withdrawn in four patients for major side effects between 1 and 7 months after study entry; eight patients had minor side effects. (2) Six months after study entry, renal function had improved in 17 of the 22 study patients; mean serum creatinine +/-SD (micromol/L) was 201+/-77 at entry and 153+/-65 after 3 months (P<0.001). (3) Improvement occurred in 11 of 15 patients with creatinine elevation > or =12 months and in 6 of 6 patients with creatinine elevation < or =6 months. (4) One patient developed transient liver dysfunction and a second required retransplantation for progressive cholestasis but without signs of rejection. CONCLUSIONS In patients who undergo liver transplantation, substitution of CNI by MMF leads to improvement of acute as well as chronic renal dysfunction in most cases. Side effects of MMF may be limiting in some patients, and the immunological consequences remain to be studied.
Attenuated noradrenergic sensitivity during local cooling in aged human skin

Reflex‐mediated cutaneous vasoconstriction (VC) is impaired in older humans; however, it is unclear whether this blunted VC also occurs during local cooling, which mediates VC through different mechanisms. We tested the hypothesis that the sensitization of cutaneous vessels to noradrenaline (NA) during direct skin cooling seen in young skin is blunted in aged skin. In 11 young (18–30 years) and 11 older (62–76 years) men and women, skin blood flow was monitored at two forearm sites with laser Doppler (LD) flowmetry while local skin temperature was cooled and clamped at 24°C. Cutaneous vascular conductance (CVC; LD flux/mean arterial pressure) was expressed as percentage change from baseline (%ΔCVCbase). At one site, five doses of NA (10−10–10−2m) were sequentially infused via intradermal microdialysis during cooling while the other 24°C site served as control (Ringer solution + cooling). At control sites, VC due to cooling alone was similar in young versus older (−54 ± 5 versus−56 ± 3%ΔCVCbase, P= 0.46). In young, NA infusions induced additional dose‐dependent VC (10−8, 10−6, 10−4 and 10−2m: −70 ± 2, −72 ± 3, −78 ± 3 and −79 ± 4%ΔCVCbase; P < 0.05 versus control). In older subjects, further VC did not occur until the highest infused dose of NA (10−2m: −70 ± 5%ΔCVCbase; P < 0.05 versus control). When cutaneous arterioles are sensitized to NA by direct cooling, young skin exhibits the capacity to further constrict to NA in a dose‐dependent manner. However, older skin does not display enhanced VC capacity until treated with saturating doses of NA, possibly due to age‐associated decrements in Ca2+ availability or α2C‐adrenoceptor function.
Six‐color segmentation of multicolor images in the infection studies of Listeria monocytogenes

Multiple immunofluorescent staining is a powerful strategy for visualizing the spatial and temporal relationship between antigens, cell populations, and tissue components in histological sections. To segment different cell populations from the multicolor image generated by immunostaining based on color addition theory, a systems approach is proposed for automatic segmentation of six colors. After image acquisition and processing, images are automatically segmented with the proposed approach and six‐pseudo channels for individual or colocalized fluorescent dye are generated to distinguish different cell types. The principle of this approach is the classification of each pixel into one of six colors (red, green, blue, yellow, magenta, and cyan) by choosing the minimal angular deviation between the RGB vector of the given pixel and six classically defined edge vectors. In the present infection studies of Listeria monocytogenes, the new multicolor staining methods based on the color addition were applied and the proposed color segmentation was performed for multicolor analysis. Multicolor analysis was accomplished to study the migration and interaction of Listeria and different cell subpopulations such as CD4CD25 double positive T regulatory cells; we also visualized simultaneously the B cells, T cells, dendritic cells, macrophages, and Listeria in another experiment. After Listeria infection, ERTR9 macrophages and dendritic cells formed cluster with Listeria in the infection loci. The principle of color addition and the systems approach for segmentation may be widely applicable in infection and immunity studies requiring multicolor imaging and analysis. This approach can also be applied for image analysis in the multicolor in vivo imaging, multicolor FISH or karyotyping or other studies requiring multicolor analysis. Microsc. Res. Tech., 2007. © 2006 Wiley‐Liss, Inc.
On the Control of Lipolysis in Adipocytes

ABSTRACT: The lipolytic reaction in adipocytes is one of the most important reactions in the management of bodily energy reserves, and dysregulation of this reaction may contribute to the symptoms of Type 2 diabetes mellitus. Yet, progress on resolving the molecular details of this reaction has been relatively slow. However, recent developments at the molecular level begin to paint a clearer picture of lipolysis and point to a number of unanswered questions. While HSL has long been known to be the rate‐limiting enzyme of lipolysis, the mechanism by which HSL attacks the droplet lipids is not yet firmly established. Certainly, the immunocytochemical evidence showing the movement of HSL to the lipid droplet upon stimulation leaves little doubt that this translocation is a key aspect of the lipolytic reaction, but whether or not HSL phosphorylation contributes to the translocation, and at which site(s), is as yet unresolved. It will be important to establish whether there is an activation step in addition to the translocation reaction. The participation of perilipin A is indicated by the findings that this protein can protect neutral lipids within droplets from hydrolysis, but active participation in the lipolytic reaction is yet to be proved. Again, it will be important to determine whether mutations of serine residues of PKA phosphorylation sites of perilipins prevent lipolysis, and whether such modifications abolish the physical changes in the droplet surfaces that accompany lipolysis.
Identification of NEEP21 as a β-Amyloid Precursor Protein-Interacting Protein In Vivo That Modulates Amyloidogenic Processing In Vitro

Alzheimer's disease (AD) is an age-related neurodegenerative disease and the most common form of dementia. AD is pathologically characterized by the deposition of pathogenic Aβ peptides that are derived from larger integral membrane proteins, termed β-amyloid precursor proteins (APPs). In an attempt to understand the function of APP, in vitro studies have focused on the identification of interacting proteins. To investigate the APP in vivo interactome in an unbiased manner, we generated mice that harbor a mouse prion protein promoter-driven cDNA encoding human APP-695 fused to a C-terminal affinity tag. Using this tag, we prepared mild detergent lysates from transgenic mouse brain cortical membrane preparations and isolated a number of previously identified APP-interacting proteins. In addition to these factors, mass spectrometric analysis revealed the presence of NEEP21 as a novel interacting protein. We now report that NEEP21 profoundly affects the processing of APP and Aβ production. Thus, this study demonstrates that using proteomic methods on our transgenic model can uncover important in vivo APP-interacting proteins that will provide insights into the biology of APP.