Miracle-dz/UniFAR-FTUs huggingface dataset:
Carnitine Insufficiency Caused by Aging and Overnutrition Compromises Mitochondrial Performance and Metabolic Control*

In addition to its essential role in permitting mitochondrial import and oxidation of long chain fatty acids, carnitine also functions as an acyl group acceptor that facilitates mitochondrial export of excess carbons in the form of acylcarnitines. Recent evidence suggests carnitine requirements increase under conditions of sustained metabolic stress. Accordingly, we hypothesized that carnitine insufficiency might contribute to mitochondrial dysfunction and obesity-related impairments in glucose tolerance. Consistent with this prediction whole body carnitine dimunition was identified as a common feature of insulin-resistant states such as advanced age, genetic diabetes, and diet-induced obesity. In rodents fed a lifelong (12 month) high fat diet, compromised carnitine status corresponded with increased skeletal muscle accumulation of acylcarnitine esters and diminished hepatic expression of carnitine biosynthetic genes. Diminished carnitine reserves in muscle of obese rats was accompanied by marked perturbations in mitochondrial fuel metabolism, including low rates of complete fatty acid oxidation, elevated incomplete β-oxidation, and impaired substrate switching from fatty acid to pyruvate. These mitochondrial abnormalities were reversed by 8 weeks of oral carnitine supplementation, in concert with increased tissue efflux and urinary excretion of acetylcarnitine and improvement of whole body glucose tolerance. Acetylcarnitine is produced by the mitochondrial matrix enzyme, carnitine acetyltransferase (CrAT). A role for this enzyme in combating glucose intolerance was further supported by the finding that CrAT overexpression in primary human skeletal myocytes increased glucose uptake and attenuated lipid-induced suppression of glucose oxidation. These results implicate carnitine insufficiency and reduced CrAT activity as reversible components of the metabolic syndrome.
Epidemiology of Streptococcus pneumoniae infection in Malaysia

During a 1-year period from October 1995 to September 1996, 273 isolations of Streptococcus pneumoniae were made from various types of clinical specimens. The majority of the isolates (39·2%) were from sputum whilst 27·5% were from blood, CSF and other body fluids. The organism was isolated from patients of all age groups, 31·1% from children aged 10 years and below, 64·7% of which come from children aged 2 years or below. The majority of the isolates belong to serotypes 1, 6B, 19B, 19F and 23F. Serotypes 1 and 19B were the most common serotypes associated with invasive infection. About 71·9% of the invasive infections were due to serotypes included in the available 23 valent polysaccharide vaccine. The rates of resistance to penicillin and erythromycin were 7·0 and 1·1% respectively. Our findings show that the serotypes of S. pneumoniae causing most invasive infections in Malaysia are similar to those in other parts of the world and the available vaccine may have a useful role in this population.
Prevalence and causes of low birth weight in India.

INTRODUCTION The aims of the study are (i) to understand inter-zone and interstate variation of low birth weight (LBW) and (ii) to determine the key variables to reduce LBW in India. METHODS Using the latest National Family Health Survey (NFHS) data of 2005-06 which showed the percentage distribution of LBW infants, ANOVA and post-hoc test were performed to determine the spatial variation of birth weight. The covariates which influence LBW fell into three categories: (i) social variables which included location, mother's education, religion, access of mothers to newspapers, television and family structure; (ii) economic variable namely, the wealth index, and (iii) biological variables which consisted of sex of the children, birth order, and mother's body mass index (BMI). Three models of Logistic regression were carried out to examine the influence of the combinations of these direct and indirect factors. RESULTS In India, nearly 20% of new borns have LBW. Males have less frequency of LBW than females. The North-east zone has the lowest prevalence of LBW while the north zone has the highest. Mother's education, access to TV and nuclear family, and intake of iron tablets are the most important socio-economic influences on the determination of birth weight in India. CONCLUSION It is essential to provide proper diet and nutritional care of mothers during pregnancy. Increased education of mothers through programmes in TV and newspapers articles have significant roles to play in reducing LBW in India.
Co‐ordinated expression of connexins 26 and 32 in human endometrial glandular epithelium during the reproductive cycle and the influence of hormone replacement therapy

Hormones are involved in the regulation of intercellular communication, and gap junction intercellular communication may play an important role in the prevention of endometrial cancer. We have investigated changes in the expression of the gap junction proteins connexin 26 (Cx26) and Cx32 in human endometrial glandular epithelium during the reproductive cycle as well as the influence of hormone replacement therapy. Frozen sections from 71 endometrial tissue samples (53 taken from women who had undergone hysterectomy during the menstrual cycle, 3 early pregnancy deciduae and 15 from menopausal women, some of whom were receiving estrogen alone or estrogen plus progesterone) were analyzed by immunofluorescence and confocal laser scanning microscopy. Cx26 and Cx32 were expressed weakly in the proliferative phase, markedly during ovulation and most strongly in the mid‐secretory phase; by the late secretory phase, they decreased drastically. Cx26 and Cx32 also were expressed in early pregnancy. Women who had received estrogen and progesterone expressed the Cxs, but those who had received estrogen only or no therapy did not. These results were confirmed by Western blot analysis. They indicate that expression of Cx26 and Cx32 is correlated with cell differentiation and with the glandular function of the endometrial epithelium and suggest that expression of Cxs is controlled by serum progesterone. Int. J. Cancer 73:479–485, 1997. © 1997 Wiley‐Liss, Inc.
Patient experience of lung volume reduction procedures for emphysema: a qualitative service improvement project

The aim of this service improvement project was to gain understanding of the patient experience of lung volume reduction surgery (LVRS) and endobronchial valve (EBV) placement, from referral through to post-discharge care. Focus group interviews were carried out in two tertiary centres in London and Leicester, UK. Sixteen patients who had undergone lung volume reduction surgery (LVRS), endobronchial valve (EBV) placement, or both, were recruited. Prior to participation in each focus group, participants completed a questionnaire to guide and focus discussion. Thematic analysis identified common themes to the participant experience of receiving lung volume reduction interventions. Themes included patient focus on declining health and the need to “fight” for a referral; consequences of having procedures and potential unexpected complications; and vulnerability post discharge and limited continuity of care. Participants were clear that the benefits of having had either LVRS or EBV procedures outweighed any difficulties experienced. Participants were keen to have further similar interventions if appropriate. These data confirm the need to develop more systematic lung volume reduction pathways, provide appropriate information, and ensure that post-discharge care is optimal. Patients feel they have to fight to get a lung volume reduction procedure; a more systematic approach is needed http://ow.ly/82Oy30cLORk
Cost-effectiveness of long-acting risperidone injection versus alternative atypical antipsychotic agents in patients with schizophrenia in China.

OBJECTIVES To determine the most cost-effective strategy involving first-line treatment with long-acting risperidone, olanzapine, and quetiapine from the perspective of the Chinese health-care system. METHODS A decision analytical model was applied. The model used a time horizon of 2 years. The probabilities of treatment response of different agents and the relapse and hospitalization rates were estimated by a Delphi panel of 17 senior psychiatrists in China. The unit cost for each medical service was calculated from the price system database built by China National Development and Reform Commission and the medical resource utilization was estimated by the Delphi panel. The principal efficacy measure was the proportion of patients successfully treated. Various sensitivity analyses were carried out to test the robustness of the model. RESULTS The proportion of patients successfully treated over the 2-year period was 46.71% for long-acting risperidone, 39.93% for olanzapine, and 31.28% for quetiapine. The mean cost-effectiveness ratios were RMB189,427, RMB202,432, and RMB233,015 per successfully treated patient for long-acting risperidone, quetiapine and olanzapine, respectively. Results of the sensitivity analyses confirmed that the results were robust. CONCLUSIONS The results showed that long-acting risperidone is more cost-effective than olanzapine and quetiapine for patients with schizophrenia in long-term maintenance treatment.
Autoimmunity‐mediated antitumor immunity: Tumor as an immunoprivileged self

The association of autoimmunity with antitumor immunity challenges a paradigm of selective surveillance against tumors. Aided with well‐characterized models of robust autoimmunity, we show that self‐antigen‐specific effector T (Teff) cell clones could eradicate tumor cells. However, a tumor microenvironment reinforced by Treg cells and myeloid‐derived suppressor cells (MDSCs) presented a barrier to the autoimmune effectors, more so in tumors than in healthy tissues. This barrier required optimal CTLA4 expression in Teff cells. In a spontaneous model of breast cancer, subtle reductions in CTLA4 expression impeded tumor onset and progression, providing the first direct evidence that CTLA4 inhibits spontaneous tumor development. In an adoptive therapy model of lymphoma, self‐antigen‐specific Teff cells were potentiated by even a modest reduction of CTLA4. A subtle reduction of CTLA4 did not curtail Treg‐cell suppression. Thus, Teff cells had an exquisite sensitivity to physiological levels of CTLA4 variations. However, both Treg and Teff cells were impacted by anti‐CTLA4 antibody blockade. Therefore, whether CTLA4 impacts through Treg cells or Teff cells depends on its expression level. Overall, the results suggest that the tumor microenvironment represents an “immunoprivileged self” that could be overcome practically and at least partially by RNAi silencing of CTLA4 in Teff cells.
Treatment of 72 newly diagnosed Waldenström macroglobulinemia cases with oral melphalan, cyclophosphamide, and prednisone

Current treatment regimens for Waldenström macroglobulinemia (WM) are based on the use of oral alkylating agents. Recently, however, other more costly agents have been proposed for the treatment of WM. In the current study, the authors report on results obtained using oral melphalan, cyclophosphamide, and prednisone (MCP) to treat 72 patients with WM, and they compare these results (and the associated costs) with those observed using more aggressive protocols.
Can contrast media increase organ doses in CT examinations? A clinical study.

OBJECTIVE The purpose of this article is to quantify the CT radiation dose increment in five organs resulting from the administration of iodinated contrast medium. MATERIALS AND METHODS Forty consecutive patients who underwent both un-enhanced and contrast-enhanced thoracoabdominal CT were included in our retrospective study. The dose increase between CT before and after contrast agent administration was evaluated in the portal phase for the thyroid, liver, spleen, pancreas, and kidneys by applying a previously validated method. RESULTS An increase in radiation dose was noted in all organs studied. Average dose increments were 19% for liver, 71% for kidneys, 33% for spleen and pancreas, and 41% for thyroid. Kidneys exhibited the maximum dose increment, whereas the pancreas showed the widest variance because of the differences in fibro-fatty involution. Finally, thyroids with high attenuation values on unenhanced CT showed a lower Hounsfield unit increase and, thus, a smaller increment in the dose. CONCLUSION Our study showed an increase in radiation dose in several parenchymatous tissues on contrast-enhanced CT. Our method allowed us to evaluate the dose increase from the change in attenuation measured in Hounsfield units. Because diagnostic protocols require multiple acquisitions after the contrast agent administration, such a dose increase should be considered when optimizing these protocols.
Characterization of a novel intraocular drug-delivery system using crystalline lipid antiviral prodrugs of ganciclovir and cyclic cidofovir.

PURPOSE In an earlier study, a novel intraocular drug-delivery system was reported in which hexadecyloxypropyl-phospho-ganciclovir (HDP-P-GCV) was used as a prototype. The hypothesis was that many biologically effective compounds could be modified to crystalline lipid prodrugs and could be delivered directly into the vitreous in a long-lasting, slow-release form. This study was undertaken to characterize this new drug-delivery system further, by using small particles of HDP-P-GCV and hexadecyloxypropyl-cyclic cidofovir (HDP-cCDV). METHODS HDP-P-GCV was microfluidized into 4.4-microm (median) particles, injected into rabbit vitreous. The vitreous drug level was then measured at different time points. Crystalline HDP-cCDV was synthesized, suspended in 5% dextrose, and injected into the rabbit's vitreous at 10, 55, 100, 550, or 1000 microg in 50 microL vehicle per eye, to determine the highest nontoxic dose. The dose, 100 microg, was injected into 24 rabbit eyes, to evaluate pharmacokinetics; into 14 rabbit eyes with established HSV retinitis, to evaluate its efficacy; and into 58 rabbit eyes before herpes simplex virus (HSV) infection to evaluate its intraocular antiviral duration. RESULTS Microfluidized particles of HDP-P-GCV showed an increased drug release rate compared with the large-particle drug formulation, with area under concentration-time curve (AUC) of 219.8 +/- 114.1 (n=3) versus 108.3 +/- 47.2 (n=3) for unmodified HDP-P-GCV during the 12-week period after a 2.8-micromole intravitreal injection. There was a 103% increase of the drug released from the microfluidized formulation of HDP-P-GCV versus the unmodified formulation. Intravitreal injections of HDP-cCDV at doses of 100 microg/eye or lower were not toxic. After the 100 microg/eye injections, HPLC analysis showed a vitreous HDP-cCDV level of 0.05 microM at week 5, which declined to 0.002 microM at week 8. The concentration at week 8 (0.002 microM) remained above the IC50 for cytomegalovirus (0.0003 microM). The pretreatment study demonstrated an antiviral effect that lasted 100 days after a single intravitreal injection. CONCLUSIONS This crystalline lipid prodrug intravitreal delivery system is an effective approach to achieving sustained, therapeutic drug levels in the eye. Small microfluidized particles of HDP-P-GCV provide more rapid dissolution and higher vitreous drug levels.
Prehabilitation Influences Exercise-Related Psychological Constructs Such as Self-efficacy and Outcome Expectations to Exercise

Abstract Brown, K, Loprinzi, PD, Brosky, JA, and Topp, R. Prehabilitation influences exercise-related psychological constructs such as self-efficacy and outcome expectations to exercise. J Strength Cond Res 28(1): 201–209, 2014—Osteoarthritis (OA) is a clinical condition affecting more than 27 million Americans. There is no known cure for OA other than replacing the diseased joint with a joint prosthesis, a process called total knee arthroplasty (TKA). The TKA projections for the year 2016 are 1,046,000, and this number is predicted to increase by 600% to more than 3.4 million cases by 2030. The purpose of this study was to determine whether knee OA patients who engage in guided exercise (prehabilitation) before their TKA report higher levels of self-efficacy to exercise (SEE) and higher outcome expectations for exercise (OEE) than those who do not. Thirty-one participants were randomized into 2 groups (16 in prehabilitation group [PRE] and 15 in control group [CON]), all participants completed the protocol (22 women and 9 men). The PRE group participated in an exercise intervention (prehabilitation) 3 times per week for 8 weeks before TKA. One-way repeated measures analysis of variance was used to investigate the effects of group (PRE vs. CON), time (baseline T1, T2, T3, and T4), and the interaction of group and time on the dependent variables of SEE and OEE. This analysis indicated that SEE did not change over time (p = 0.62) or between the groups (p = 0.86). The analysis of the OEE indicated a significant time effect (p = 0.008). Post hoc analysis indicated that the CON group significantly declined between T2 and T4. The PRE group did not significantly change their OEE over the 4 data collection points of the study.
Serum immunoglobulins in psoriatic erythroderma

The cause of psoriatic erythroderma (PE) is still unknown. Elevation of serum IgE has been reported in erythroderma, and as serum hyper‐IgE is Th2 cell dominated it is of interest to investigate the serum IgE level in PE. In this study, the level of immunoglobulins in the sera of PE patients was analysed by a retrospective case–control study using psoriasis vulgaris (PV) patients as controls. The PE and PV patients were matched in a 1 : 3 pattern: the first three age and sex matched PV inpatients were selected. All of the subjects were nonatopic and without allergic history. The serum IgE level was found to be elevated in 81.3% of the PE group, which is much higher than that (6.3%) of the controls (odds ratio, 65.0; 95% CI, 11.7–361.2; P < 0.001; χ2 test). The mean level of serum IgE was much higher in the PE group (272.38 ± 207.63 IU/mL vs. 53.20 ± 86.05 IU/mL, P < 0.001, Student's t‐test). No differences were found for other immunoglobulins. These results suggest that in PE the Th1/Th2 cell imbalance may be switched from Th1 dominant to Th2 dominant. The exact role of serum IgE in PE should be investigated further.
The Saccharomyces cerevisiae ADR1 gene is a positive regulator of transcription of genes encoding peroxisomal proteins

Expression of the CTA1 gene of Saccharomyces cerevisiae, encoding catalase A, the peroxisomal catalase of this yeast, is sensitive to glucose repression. A DNA fragment cloned as a multicopy plasmid suppressing the glucose repression of CTA1 transcription was demonstrated to contain the ADR1 gene. Multiple copies of ADR1 increased catalase A formation not only on 10% glucose, but also on ethanol medium and in the presence of oleic acid, an inducer of peroxisome proliferation. Compared with wild-type cells, adr1 null mutants produced by disruption of the gene exhibit reduced CTA1 expression. This demonstrates that ADR1 is a true positive regulator of CTA1. Further experiments showed that it acts directly on CTA1. Alcohol dehydrogenase II, which is under ADR1 control, was excluded as a mediator of the effect on CTA1; deletion of bases -123 to -168 of CTA1 reduces expression and eliminates the response to the ADR1 multicopy plasmid without eliminating fatty acid induction; and gel retardation experiments demonstrated that ADR1 binds to a CTA1 upstream fragment (-156 to -184) with limited similarity to the ADR1 binding site of ADH2. Northern hybridization experiments further demonstrated that expression of two genes encoding enzymes of peroxisomal beta-oxidation (beta-ketothiolase, trifunctional enzyme) and of a gene involved in peroxisome assembly (PAS1) is also negatively affected by the adr1 null mutation. These findings demonstrate that the ADR1 protein has much broader regulatory functions than previously recognized.
Physical function and health-related quality-of-life in a population-based sample

Background. It is of interest to understand whether impaired physical function is associated with health-related quality-of-life (HRQOL). We examined upper and lower body physical function and its relationship with two domains of HRQOL among men. Methods. We conducted a population-based observational study of musculoskeletal health among Boston, MA residents, the Boston Area Community Health/Bone Survey. Participants were 1219 randomly-selected Black, Hispanic, and White males (30–79 years). Upper body function was measured using hand grip strength, while lower body function was measured by combining a timed walk and a chair stand test. HRQOL was measured using the physical (PCS-12) and mental health (MCS-12) component scores of the SF-12. Multivariate linear regression models were used to estimate the association between poor function and HRQOL. Results. There was a significant association of poor upper body physical function with the MCS-12 (β coefficient: −4.12, p = 0.003) but not the PCS-12 (β coefficient: 0.79, p = 0.30) compared to those without poor function. Those with poor lower body physical function had significantly lower PCS-12 scores (β: −2.95, p = 0.007), compared to those without poor function, but an association was not observed for MCS-12 scores. Conclusions. Domains of physical function were not consistently related to domains of HRQOL.