Miracle-dz/UniFAR-FTUs huggingface dataset:
Amino Acid Change in the Carbohydrate Response Element Binding Protein Is Associated With Lower Triglycerides and Myocardial Infarction Incidence Depending on Level of Adherence to the Mediterranean Diet in the PREDIMED Trial

Background—A variant (rs3812316, C771G, and Gln241His) in the MLXIPL (Max-like protein X interacting protein-like) gene encoding the carbohydrate response element binding protein has been associated with lower triglycerides. However, its association with cardiovascular diseases and gene–diet interactions modulating these traits are unknown. Methods and Results—We studied 7166 participants in the PREvención with DIeta MEDiterránea trial testing a Mediterranean diet (MedDiet) intervention versus a control diet for cardiovascular prevention, with a median follow-up of 4.8 years. Diet, lipids, MLXIPL polymorphisms, and cardiovascular events were assessed. Data were analyzed at baseline and longitudinally. We used multivariable-adjusted Cox regression to estimate hazard ratios for cardiovascular outcomes. The MLXIPL-rs3812316 was associated with lower baseline triglycerides (P=5.5×10−5) and lower hypertriglyceridemia (odds ratio, 0.73; 95% confidence interval [CI], 0.63–0.85; P=1.4×10−6 in G-carriers versus CC). This association was modulated by baseline adherence to MedDiet. When adherence to MedDiet was high, the protection was stronger (odds ratio, 0.63; 95% CI, 0.51–0.77; P=8.6×10−6) than when adherence to MedDiet was low (odds ratio, 0.88; 95% CI, 0.70–1.09; P=0.219). Throughout the follow-up, both the MLXIPL-rs3812316 (P=3.8×10−6) and the MedDiet intervention (P=0.030) were significantly associated with decreased triglycerides. Likewise in G-carriers MedDiet intervention was associated with greater total cardiovascular risk reduction and specifically for myocardial infarction. In the MedDiet, but not in the control group, we observed lower myocardial infarction incidence in G-carriers versus CC (hazard ratios, 0.34; 95% CI, 0.12–0.93; P=0.036 and 0.90; 95% CI, 0.35–2.33; P=0.830, respectively). Conclusions—Our novel results suggest that MedDiet enhances the triglyceride-lowering effect of the MLXIPL-rs3812316 variant and strengthens its protective effect on myocardial infarction incidence. Clinical Trial Registration—URL: www.controlled-trials.com. Unique Identifier: ISRCTN35739639.
CYP2C8 Is a Novel Target of Peroxisome Proliferator-Activated Receptor α in Human Liver

Human cytochrome P450 (CYP) 2C enzymes metabolize ∼30% of clinically prescribed drugs and various environmental chemicals. CYP2C8, an important member of this subfamily, metabolizes the anticancer drug paclitaxel, certain antidiabetic drugs, and endogenous substrates, including arachidonic acid, to physiologically active epoxyeicosatrienoic acids. Previous studies from our laboratory showed that microRNA 107 (miR107) and microRNA 103 downregulate CYP2C8 post-transcriptionally. miR107 is located in intron 5 of the pantothenate kinase 1 (PANK1) gene. p53 has been reported to coregulate the induction of PANK1 and miR107. Here, we examine the possible downregulation of CYP2C8 by drugs capable of inducing miR107. Hypolipidemic drugs, such as bezafibrate, known activators of the peroxisome proliferator-activated receptor α (PPARα), induce both the PANK1 gene and miR107 (∼2.5-fold) in primary human hepatocytes. Surprisingly, CYP2C8 mRNA and protein levels were induced by bezafibrate. CYP2C8 promoter activity was increased by ectopic expression of PPARα in HepG2 cells, with a further increase after bezafibrate (∼18-fold), 4-chloro-6-(2,3-xylidino)-2-pyrimidinylthio acetic acid (∼10-fold) treatment, or the antidiabetic drug rosiglitazone, all known PPAR activators. Promoter sequence analyses, deletion studies, mutagenesis studies, and electrophoretic mobility shift assays identified a PPARα response element located at position −2109 base pair relative to the translation start site of CYP2C8. Chromatin immunopreciptation assay analysis confirmed recruitment of PPARα to this PPARα response element after bezafibrate treatment of human hepatocytes. Thus, we show for the first time that CYP2C8 is transcriptionally regulated by PPARα, suggesting the potential for drug-drug interactions due to upregulation of CYP2C8 by PPAR activators.
Motivation and return to work among the long-term sicklisted: an action theory perspective

Purpose : The purpose of this study is to enlighten motivation and return to work among the long-term sicklisted. Method : Data are from a mail questionnaire answered by 185 people living in the Stockholm metropolitan area in Sweden. All subjects were on long-term sick leave owing to back or neck symptoms, they were 18 - 55 years of age and had an employer. A part of the questionnaire was based on an action theory perspective emphasising the respondent's own view of his or her present and future situation. People answered structured questions about what kind of work they wanted, if they thought they could get such a work and if they thought they could manage this type of work. All three aspects are of importance in the study of motivation. A follow-up of the employment status of the respondents was made about two years after the questionnaire had been answered. The relationships between their plans and employment status were studied. Results : The results show that our questions had good predictive validity, i.e. there were clear correlations between the answers and employment status two years later. It was shown that wanting to return to work is connected to one's view of own possibilities. What a person wants is not an isolated opinion, but clearly connected with the other aspects, particularly own competence ('can manage'). Conclusion : It is concluded that the action theory approach could be developed into an instrument for 'action analysis' that could be used in work with vocational rehabilitation. Such a development is now under way.
Paenibacillus assamensis sp. nov., a novel bacterium isolated from a warm spring in Assam, India.

A polyphasic approach was used to characterize a bacterium, GPTSA 11(T), isolated from a warm spring located in a reserve forest in Assam, India. The cells are Gram-variable, strictly aerobic, sporulating motile rods. The major fatty acids of the strain are C(15 : 0) anteiso (48.42 %), C(16 : 0) iso (11.59 %), C(16 : 1)omega11c (6.16 %), C(15 : 0) iso (6.03 %), C(17 : 0) anteiso (5.68 %) and C(16 : 1)omega7c alcohol (5.01 %). The presence of the fatty acid C(16 : 1)omega7c alcohol distinguishes this strain from other closely related species of the genus Paenibacillus. The strain contains MK-7 as the diagnostic menaquinone. The G+C content of the genomic DNA is 41.2 mol%. Analysis of the 16S rRNA gene sequence (1466 nt) revealed the presence of signature sequences PAEN 515F (5'-GAGTAACTGCTCTCGGAATGACGGTACTTGAGAAGAAAGCCCC-3') and PAEN 862F (5'-TCGATACCCTTGGTGCCGAAGT-3'), which were found in the species of the genus Paenibacillus surveyed by Shida et al. [Shida, O. , Takagi, H. , Kadowaki, K. , Nakamura, L. K. & Komagata, K. (1997). Int J Syst Bacteriol 47, 289-298]. The sequence shows closest similarity (95.85 %) to that of Paenibacillus apiarius, followed by Paenibacillus alvei (94.34 %), Paenibacillus cineris (93.87 %), Paenibacillus favisporus (93.80 %), Paenibacillus chibensis (93.47 %) and Paenibacillus azoreducens (93.40 %). Biochemical, physiological, chemotaxonomic and phylogenetic analyses justify placement of the strain in the genus Paenibacillus but not within any existing species. It should, therefore, be considered as representing a novel species, for which the name Paenibacillus assamensis sp. nov. is proposed. The type strain is GPTSA 11T (=MTCC 6934T=JCM 13186T).
Effect of low-density lipoprotein apheresis on patients with peripheral arterial disease. Peripheral Arterial Disease LDL Apheresis Multicenter Study (P-LAS).

AIM The effectiveness of low-density lipoprotein (LDL) apheresis for patients with peripheral arterial disease (PAD) was investigated to confirm a hypothesis based on subjective evidence that the amelioration of blood rheology would be the most contributing factor for improvement in clinical symptoms. Evaluation of the severity of intermittent claudication is difficult because of the lack of an accurate parameter to assess muscle ischemia during exercise, thus we objectively evaluated by non-invasive near-infrared spectroscopy (NIRS) on a treadmill in this study. METHODS Thirty-one patients with PAD were evaluated for hemostatic function and physiological parameters such as ankle-brachial pressure index (ABI), maximum tolerated walking distance (MTWD) and recovery time (RT) or recovery ability index (RAI) on NIRS. Laboratory tests included plasma assays of total cholesterol, LDL-cholesterol, high-density lipoprotein (HDL) cholesterol, triglyceride, and fibrinogen. The change in red-cell filtration rate was evaluated for the improvement of microcirculation. Statistical analysis was performed using the paired Student's t-test with Bonferroni's correction. RESULTS A significant improvement in ABI and MTWD was observed after average 9.6+/-0.8 sessions of LDL apheresis treatment and the amelioration of microcirculation in ischemic muscle was objectively evaluated as significant improvement in RAI on NIRS. Rest pain was improved in all 5 patients with Fontaine's classification III or IV. A severe ulcer refractory to usual medications was dramatically diminished in the area by 10 sessions of LDL apheresis and fully healed 5 months after the final LDL apheresis treatment followed by medication. No angiographical change was observed in the arterial occlusive lesions in any patients. CONCLUSIONS The effectiveness of LDL apheresis on the improvement in physiological parameters such as ABI, MTWD and clinical symptoms in patients with PAD was confirmed. The severity of intermittent claudication was objectively evaluated using non-invasive NIRS. The RT or RAI was useful parameter to evaluate the improvement in the ischemic symptoms of the extremities.
Clinical evaluation of atypical glandular cells of undetermined significance.

OBJECTIVE This study was undertaken to determine the clinical implications of the finding of atypical glandular cells of undetermined significance in cervical cytologic specimens in our patient population. STUDY DESIGN A retrospective study was performed. All cervical cytologic examinations with the diagnosis of atypical cells of undetermined significance between January 1992 and June 1997 were identified by means of a computerized database. Medical records were reviewed to identify patient demographic characteristics and to determine the presence or absence of associated pathologic conditions of the cervix and endometrium. The chi2 test and analysis of variance were applied to dichotomous and continuous variables, respectively, to determine the implications of a cytologic evaluation of atypical glandular cells of undetermined significance. RESULTS Cytologic results reported as atypical glandular cells of undetermined significance were obtained in a patient cohort of 492. Atypical glandular cells of undetermined significance was the only cytologic diagnosis in 224 patients; 268 patients had both atypical glandular cells of undetermined significance and an additional squamous abnormality, including atypical squamous cells of undetermined significance and cervical intraepithelial neoplasia I, II, or III. Two patients were excluded because of a history of endometrial cancer. A histologic evaluation was obtained within 1 year in 353 cases. Among the 353 patients who had a histologic evaluation performed, 227 (64%) had benign cervical and endometrial findings. There were 18 glandular lesions (5%), including complex hyperplasia with atypia, adenocarcinoma in situ of the cervix, adenocarcinoma of the cervix, and adenocarcinoma of the endometrium. A squamous lesion was present in 108 patients (31%). Most squamous lesions (81%) were found in patients with atypical glandular cells of undetermined significance associated with a squamous abnormality, whereas only 19% were found in patients with atypical glandular cells of undetermined significance as the only diagnosis. Women <35 years old had a much higher frequency of histologic abnormalities than did women >50 years old (P <.0001), with most of these lesions being squamous. Women >50 years old had a much higher frequency of glandular histologic abnormalities (P <.001). CONCLUSION More than a third of women with Papanicolaou smears reported as showing atypical glandular cells of undetermined significance will be found to have a histologic abnormality. Women <35 years old with a cytologic evaluation of atypical glandular cells of undetermined significance have a higher frequency of histopathologic findings, with most being squamous lesions. Women with a cytologic evaluation of atypical glandular cells of undetermined significance who are >50 years old have more glandular lesions than do younger women. The term atypical glandular cells of undetermined significance is a misnomer. The significance of this cytologic finding has been defined and represents a marker for serious pathologic processes.
Alterations in Physiologic Functions and in Brain Monoamine Content in Streptozocin-Diabetic Rats

In the present study, we used streptozocin (STZ) to induce diabetes in rats and observed alterations in several physiologic functions and in monoamine content of different brain regions. Rats with STZ diabetes displayed a thermoregulatory deficit in the cold. Both the body temperature and metabolic rate of the diabetic animals were reduced at ambient temperatures below 22°C. These diabetic animals had a higher level of the spontaneous pain threshold, but displayed a reduced sensitivity of analgesic responses to morphine injection. In addition, these diabetic animals had a lower level of spontaneous motor activity, but displayed an increased sensitivity of locomotor stimulant responses to amphetamine administration. Biochemical examination revealed that the diabetic animals had a lower serotonin level in both the hypothalamus and the brainstem without changes in the serotonin levels of the corpus striatum. These diabetic animals also had a lower catecholamine level in the hypothalamus, but a higher catecholamine level in the corpus striatum. The alterations in brain monoamine content and in the above-mentioned physiologic parameters were reversed after insulin replacement therapy. The data suggest that alterations in various autonomic, somatosensory, and motor neural functions of untreated STZ-diabetic rats correlated with a reproducible pattern of monoamine content in various brain regions (a pattern that differed from that observed in healthy control rats), and that both the altered neural function and the altered brain monoamine pattern were reversed after insulin therapy.
Mapping epitopes on the insulin molecule using monoclonal antibodies

A panel of 18 monoclonal antibodies (mAb)Δ to insulin have been prepared and used to begin to map antigenic determinants on the insulin molecule. All 18 mAb were of the IgG class, with 14 IgG1, 2 IgG2a and 2 IgG2b. The affinities of these mAb for their immunizing insulin ranged from 1 × 106 to 3 × 108 1/M. The epitope recognized by three of the mAb, 1, 7 and 16 involves the three residues of the A chain, A 8‐10, the so called A chain‐loop determinant. This A chain loop is one of the most evolutionarily diverse regions of insulins from different species. Another mAb, 10, has been hypothesized to recognize a nearby epitope composed of the A chain residues, A4 and A8 and a B chain residue, B29, that are adjacent on the surface of the insulin molecule. Four of the mAb bind to synthetic B chain. The epitopes recognized by these 4 mAb and the last 10 mAb are unknown but the mAb are grouped according to their ability to bind to different species of insulin or proinsulin. The results of an 18 × 18 matrix analysis of pairs of mAb binding simultaneously to insulin indicate that, despite the finding that some mAb see similar antigenic sites on the insulin molecule, each of the mAb recognizes a unique site on the insulin molecule. Finally, a lower estimate of the number of possible antibodies made to insulin has been calculated to be ≧ 115, a number only 10‐fold lower than the lower limit of antibodies made to dinitrophenyl (DNP) or (4‐hydroxy‐5‐iodo‐3‐nitrophenyl)acetyl (NIP), following hapten protein immunization.
Characterization of an Enhancer Element in the Human Apolipoprotein C-III Gene That Regulates Human Apolipoprotein A-I Gene Expression in the Intestinal Epithelium (*)

Studies using transgenic mice indicate that expression of the human apolipoprotein (apo) A-I gene in the liver and small intestine is controlled by spatially distinct cis-acting DNA elements; hepatic expression is controlled by a domain defined by nucleotides −256 to −1, while small intestinal expression requires elements positioned 9 kilobases 3′ to the gene, between nucleotides −1300 and −200 of the convergently transcribed apoC-III gene. In this report we have mapped this enhancer to a 260-base pair (bp) region of the apoC-III promoter spanning nucleotides −780 to −520. The elements contained within this 260-bp apoC-III domain are sufficient to direct a pattern of expression in villus-associated enterocytes distributed along the duodenal-to-ileal axis that resembles that of mouse and human apoA-I. However, the elements produce inappropriate activation of apoA-I expression in proliferating and nonproliferating crypt epithelial cells, and in subpopulations of cholecystokinin- and serotonin-producing enteroendocrine cells. Cis-acting suppressors of these inappropriate patterns of expression are located outside of nucleotides −1300 to −200 of the human apoC-III gene. DNase I protection and gel mobility gel shift assays identified two 21-bp sequences, nucleotides −745 to −725 and −700 to −680 of human apoC-III, which bind nuclear proteins present in a human enterocyte-like cell line (Caco-2). These sequences are conserved in the orthologous mouse apoC-III gene. The 260-bp apoC-III element is the first intestinal enhancer that has been identified in an in vivo system and should provide insights about how cell lineage-specific, differentiation-dependent, and cephalocaudal patterns of gene expression are established and maintained in the perpetually renewing gut epithelium. In addition, novel intestinal transcription factors may bind to the enhancer and regulate its activity.
Interrelationships between mechanical power, energy transfers, and walking and running economy.

The interrelationships between aerobic demand, kinematic and kinetic-based estimates of mechanical power output and energy transfer, and total body angular impulse (summation of net joint moments integrated with respect to time over a stride) were quantified for walking at 1.69 m.s-1 and running at 3.35 m.s-1 to assess the ability of these various biomechanical expressions to explain interin-dividual differences in walking and running economy. Fourteen healthy men participated in the walking study and 16 recreational male runners were subjects for the running analysis. Each subject performed treadmill locomotion for determination of aerobic demand and overground locomotion from which biomechanical measures were quantified. It was expected that mechanical power and angular impulse expressions would correlate positively with aerobic demand while energy transfer expressions would correlate negatively. Correlations between aerobic demand and power estimates primarily were positive, but explained no more than 32% of the variability in walking or running VO2 (center of mass model: 0.22 < r < 0.57; segment-based model: -0.02 < r < 0.20; kinetic model: -0.07 < r < 0.22). Total body angular impulse also correlated positively with aerobic demand (0.32 < r < 0.42). Energy transfer expressions from the various analytical models showed no consistent relationship with aerobic demand, either in terms of magnitude or direction (-0.26 < r < 0.48). It was concluded that mechanical power, energy transfer, and angular impulse expressions frequently used in analyses of gait explain only a small proportion of normal interindividual variability in the aerobic demand at a given speed of walking or running.
Impact of Load Variation on Joint Angle Estimation From Surface EMG Signals

Many studies use surface electromyogram (sEMG) signals to estimate the joint angle, for control of upper-limb exoskeletons and prostheses. However, several practical factors still affect its clinical applicability. One of these factors is the load variation during daily use. This paper demonstrates that the load variation can have a substantial impact on performance of elbow angle estimation. This impact leads an increase in mean RMSE (Root-Mean-Square Error) from 7.86 ° to 20.44 ° in our experimental test. Therefore, we propose three methods to address this issue: 1) pooling the training data from all loads together to form the pooled training data for the training model; 2) adding the measured load value (force sensor) as an additional input; and 3) developing a two-step hybrid estimation approach based on load and sEMG. Experiments are conducted with five subjects to investigate the feasibility of the proposed three methods. The results show that the mean RMSE is reduced from 20.44 ° to 13.54 ° using method one, 10.47 ° using method two, and 8.48 ° using method three, respectively. Our study indicates that 1) the proposed methods can improve performance and stability on joint angle estimation and 2) sensor fusion (sEMG sensor and force sensor) is an efficient way to resolve the adverse effect of load variation.
Pregnancy and Deep Vein Thrombosis

The diagnosis, treatment, and prevention of deep vein thrombosis (DVT) during pregnancy remain problematic. This article reviews the pathophysiology of pregnancy-related DVT and suggests diagnostic strategies, highlighting the pitfalls specific to this patient population. The treatment of DVT in pregnant patients is difficult because unfractionated heparin and low-molecular-weight heparins, the cornerstones of initial therapy, may have significant maternal side effects and warfarin can cause embryopathy and other adverse fetal effects. As well, there are limited data regarding the efficacy of anticoagulant therapy in the treatment and prophylaxis of DVT during pregnancy. This article briefly reviews the areas of controversy and provides recommendations for the treatment of acute DVT and thromboprophylaxis in pregnant patients.
The relationship between self-report and performance-related measures: questioning the content validity of timed tests.

OBJECTIVE To examine the determinants of the modest correlation between self-report and performance-related measures in patients with osteoarthritis of the hip or knee. METHODS Measures included the Lower Extremity Functional Scale (LEFS), the self paced walk, timed up-and-go, and stair test. Each performance measure consisted of 3 domains: time, pain (visual analog scale), and exertion (Borg scale). Activity specificity was assessed by examining correlations between the LEFS with single activity and multiple activity time scores. Domain specificity was examined by comparing correlations between the LEFS and single and multiple domain scores. The impact of measurement error was considered. RESULTS Increasing the number of activity time scores had no effect. Forming a composite performance score based on time, pain, and exertion substantially increased the correlation from 0.44 (composite timed score) to 0.59 (pooled domain and activity score) (P = 0.009). CONCLUSION Performance scores based on time alone appear to inadequately represent the breadth of health concepts associated with functional status.