Miracle-dz/UniFAR-FTUs huggingface dataset:
Abnormalities of tear function in patients with pseudoexfoliation

Background and Aim: Pseudoexfoliation (PEX) seems to affect the tear secretion and tear film stability by altering cell morphology in conjunctiva. We aimed to study the abnormalities of tear secretion and tear film that can occur in patients with PEX material on lens. Methods: In this prospective non-randomized study, Group 1 consisted of 30 eyes of 15 normal subjects without PEX material on lens serving as controls and Group 2 consisted of 43 eyes of 30 patients with PEX at least in one eye. Patients with ocular surface disorder, PEX glaucoma, previous ocular surgeries and adnexal abnormalities were excluded. To study the tear function, Schirmer's two and tear film break-up time (TBUT) were performed in all eyes. Results: Average Schirmer's and TBUT in Group 1 were 22.05 ± 4.4 mm and 14.75 ± 2.5 s respectively, whereas in Group 2 they were 10.6 ± 7 mm and 5.6 ± 2.8 s and the differences were clinically significant ( P P = 0.065). Conclusion: PEX syndrome causes unstable tear film and reduced tear secretion.
Genetic evidence for Dnmt3a‐dependent imprinting during oocyte growth obtained by conditional knockout with Zp3‐Cre and complete exclusion of Dnmt3b by chimera formation

In the male and female germ‐lines of mice, both of the two de novo DNA methyltransferases Dnmt3a and Dnmt3b are expressed. By the conditional knockout experiments using the Tnap‐Cre gene, we previously showed that deletion of Dnmt3a in primordial germ cells disrupts paternal and maternal imprinting, however, Dnmt3b mutants did not show any defect. Here, we have knocked out Dnmt3a after birth in growing oocytes by using the Zp3‐Cre gene and obtained genetic evidence that de novo methylation by Dnmt3a during the oocyte growth stage is indispensable for maternal imprinting. We also carried out DNA methylation analysis in the mutant oocytes and embryos and found that hypomethylation of imprinted genes in Dnmt3a‐deficient oocytes was directly inherited to the embryos, but repetitive elements were re‐methylated during development. Furthermore, we show that Dnmt3b‐deficient cells can contribute to the male and female germ‐lines in chimeric mice and can produce normal progeny, establishing that Dnmt3b is dispensable for mouse gametogenesis and imprinting. Finally, Dnmt3‐related protein Dnmt3L is not only essential for methylation of imprinted genes but also enhances de novo methylation of repetitive elements in growing oocytes.
Megestrol acetate in cancer patients with anorexia-cachexia syndrome: a meta-analysis

Background: Anorexia-cachexia syndrome (ACS) often occurs in patients with advanced cancer. To evaluate the effect of megestrol acetate (MA) in cancer patients with ACS, a meta-analysis of published randomized controlled trials (RCT) was performed. Methods: The databases of PubMed and Web of Science were searched from January 1966 until April 2013 and abstracts presented at American Society of Clinical Oncology conferences were searched to identify relevant clinical trials. Summary relative risks (RRs) and 95% confidence intervals (CIs) were calculated. Results: Data from a total of 1,142 cancer patients with ACS in 11 RCTs were identified and included for meta-analysis. Cancer patients with ACS who received MA had increased weight gain (179 events among 534 patients treated with MA vs . 83 events among 447 control patients; RR 2.17; 95% CI: 1.59-2.97), and increased appetite improvement (174 events among 321 patients treated with MA vs . 53 events among 280 control patients; RR 4.68; 95% CI: 3.25-6.76). Conclusions: The use of MA can improve appetite and is associated with weight gain in cancer patients with ACS. Despite the fact that these patients are receiving palliative care they should be informed of the risks involved in taking MA.
Analysis of alpha hemoglobin stabilizing protein overexpression in murine β‐thalassemia

Excess free alpha-globin is cytotoxic and contributes to the pathophysiology of b-thalassemia. Alpha hemoglobin stabilizing protein (AHSP) is a molecular chaperone that binds free alpha-globin to promote its folding and inhibit its ability to produce damaging reactive oxygen species. Reduced AHSP levels correlate with increased severity of b-thalassemia in some human cohorts, but causal mechanistic relationships are not established for these associations. We used transgenic and lentiviral gene transfer methods to investigate whether supraphysiologic AHSP levels could mitigate the severity of b-thalassemia intermedia by providing an increased sink for the excess pool of alpha-globin chains. We tested wild-type AHSP and two mutant versions with amino acid substitutions that confer 3- or 13-fold higher affinity for alpha-globin. Erythroid overexpression of these AHSP proteins up to 11-fold beyond endogenous levels had no major effects on hematologic parameters in b-thalassemic animals. Our results demonstrate that endogenous AHSP is not limiting for a-globin detoxification in a murine model of b-thalassemia.
Pediatric burn care in sub-Saharan Africa

Burn injuries in Africa are considered to be a major health care problem. Sub-Saharan Africa has the highest number of pediatric burn admissions in the world. Burn care is complicated by numerous factors such as financial constraints, lack of resources, health care personnel and modern well equipped easily accessible health care facilities. Despite these numerous obstacles, burn care professionals on the continent of Africa have delivered a sterling service. A review of 70 articles published by authors on the African continent revealed information on topics ranging from the management of the HIV + patient, burn prevention strategies and new trends in African burn care.
Reasons behind consumers’ functional food choices

The aim of this study was to examine what reasons consumers give for either choosing or not choosing functional foods. Laddering interviews were used to find out how consumers described their reasons for choosing functional food alternatives in different product categories and how these descriptions are linked with values. Yoghurt, spread, juice, carbonated soft drinks, sweets and ice cream were used as example product categories. In total, five central means‐end chains, describing the product attributes, consequences and values behind respondents’ food choices, were found, which referred to healthiness, taste and pleasure, security and familiarity, convenience and price. They were found to be independent from each other and had different connotations depending on the product category. The results indicate that respondents did not see functional foods as one homogenous group over different product categories. Instead, consumers seemed to perceive functional products as a member of the general product category such as yoghurt or spread and only secondarily as a functional food.
Reduction of Lysyl Hydroxylase 3 Causes Deleterious Changes in the Deposition and Organization of Extracellular Matrix*

Lysyl hydroxylase 3 (LH3) is a multifunctional enzyme possessing lysyl hydroxylase, collagen galactosyltransferase, and glucosyltransferase (GGT) activities. We report here an important role for LH3 in the organization of the extracellular matrix (ECM) and cytoskeleton. Deposition of ECM was affected in heterozygous LH3 knock-out mouse embryonic fibroblasts (MEF+/−) and in skin fibroblasts collected from a member of a Finnish epidermolysis bullosa simplex (EBS) family known to be deficient in GGT activity. We show the GGT deficiency to be due to a transcriptional defect in one LH3 allele. The ECM abnormalities also lead to defects in the arrangement of the cytoskeleton in both cell lines. Ultrastructural abnormalities were observed in the skin of heterozygous LH3 knock-out mice indicating that even a moderate decrease in LH3 has deleterious consequences in vivo. The LH3 null allele in the EBS family member and the resulting abnormalities in the organization of the extracellular matrix, similar to those found in MEF+/−, may explain the correlation between the severity of the phenotype and the decrease in GGT activity reported in this family.
Improvement of the soy formate dehydrogenase properties by rational design.

Previous experiments on substitution of the residue Phe290 to Asp, Asn and Ser in NAD(+)-dependent formate dehydrogenase from soya Glycine max (SoyFDH) showed important role of the residue in enzyme thermal stability and catalytic properties (Alekseeva et al. Prot. Eng. Des. Sel., 2012a; 25: :781-88). In this work, we continued site-directed mutagenesis experiments of the Phe290 and the residue was changed to Ala, Thr, Tyr, Glu and Gln. All amino acid changes resulted in increase of catalytic constant from 2.9 to 3.5-4.7 s(-1). The substitution Phe290Ala led to KM (NAD+) decrease from 13.3 to 8.6 μM, and substitutions Phe290Tyr and Phe290Glu resulted in decrease and increase of KM (HCOO-) from 1.5 to 0.9 and -2.9 mM, respectively. The highest improvement of catalytic properties was observed for SoyFDH Phe290Ala which showed 2-fold higher catalytic efficiency with both substrates. Stability of mutants was examined by study of thermal inactivation kinetics and differential scanning calorimetry (DSC). All five amino acids provided increase of thermal stability of mutant SoyFDH in comparison with wild-type enzyme. Mutant SoyFDH Phe290Glu showed the highest improvement-the stabilization effect was 43 at 56°C. The DSC data agree with results of thermal inactivation kinetics. Substitutions Phe290Tyr, Phe290Thr, Phe290Gln and Phe290Glu provided Tm value increase 0.6°-6.6°. SoyFDH Phe290Glu and previously prepared SoyFDH Phe290Asp show similar thermal stability as enzymes from Candida boidinii and Mycobacterium vaccae N10 and have higher catalytic efficiency with NAD(+) compared with all described FDHs. Therefore, these mutants are very perspective enzymes for coenzyme regeneration in processes of chiral synthesis with dehydrogenases.
Management of fractures in endurance horses

Summary This paper provides relevant information for veterinarians responsible for treatment of endurance horses, including a retrospective study of fractures in endurance horses presenting to one referral hospital and to treatment clinics at 3 different race venues. Treatment and case outcome were also noted. The information presented provides clinicians working with high level endurance horses increased awareness of common sites of fractures, of prefracture stress related bone injury within this population of athletes and guidelines in order to manage them more effectively. The most common fractures involve the metacarpo-(tarso-)phalangeal joint. Most distal limb fractures can be diagnosed radiographically, but magnetic resonance imaging or scintigraphy may be required in some cases.
Preferential Inhibition of BMAL2-CLOCK Activity by PER2 Reemphasizes Its Negative Role and a Positive Role of BMAL2 in the Circadian Transcription*

In the molecular oscillatory mechanism governing circadian rhythms, positive regulators, including CLOCK and BMAL1, transactivate Per and Cry genes through E-box elements, and translated PER and CRY proteins negatively regulate their own transactivation. Like BMAL1, its paralog BMAL2 dimerizes with CLOCK to activate the E-box-dependent transcription, but the role of BMAL2 in the circadian clockwork is still elusive. Here we characterized BMAL2 function in NIH3T3 cells and found that the cellular rhythms monitored by Bmal1 promoter-driven bioluminescence signals were blunted by RNA interference-mediated suppression of Bmal2 as well as that of Bmal1. Transcription assays with a 2.1-kb mPer1 promoter revealed that CRY2 inhibited the transactivation mediated by BMAL1-CLOCK more strongly than that by BMAL2-CLOCK. In contrast, PER2 showed a stronger inhibitory effect on BMAL2-CLOCK than on BMAL1-CLOCK. The molecular link between BMAL2 and PER2 was further strengthened by the fact that PER2 exhibited a greater affinity for BMAL2 than for BMAL1 in co-immunoprecipitation experiments. These results indicate a functional partnership between BMAL2 and PER2 and reemphasize the negative role of PER2 in the circadian transcription. As a broad spectrum function, BMAL2-CLOCK activated transcription from a variety of SV40-driven reporters harboring various E/E′-box-containing sequences present in the upstream regions of clock and clock-controlled genes. Importantly, the efficiencies of BMAL2-CLOCK-mediated transactivation relative to that achieved by BMAL1-CLOCK were dependent heavily on the E-box-containing sequences, supporting distinguishable roles of the two BMALs. Collectively, it is strongly suggested that BMAL2 plays an active role in the circadian transcription.
Dynamic macroecology and the future for biodiversity

Reliable projections of climate‐change impacts on biodiversity are vital in formulating conservation and management strategies that best retain biodiversity into the future. While recent modelling has focussed largely on individual species, macroecology has the potential to add significant value to these efforts, by incorporating important community‐level constraints and processes. Here we show how a new dynamic macroecological approach can project climate‐change impacts collectively across all species in a diverse taxonomic group, overcoming shortfalls in our knowledge of biodiversity, while incorporating the key processes of dispersal and community assembly. Our approach applies a recently published technique (DynamicFOAM) to predict the present composition of every community, which form the initial conditions for a new metacommunity model (M‐SET) that projects changes in composition over time, under specified climate and habitat scenarios. Applying this approach at fine resolution to plant biodiversity in Tasmania (2,051 species; 1,157,587 communities), we project high average turnover in community composition from 2010 to 2100 (mean Sorensen's dissimilarity = 0.71 (±7.0 × 10−5)), with major reductions in species richness (32.9 (±0.02) species lost per community) and no plant species benefitting from climate change in the long term. We also demonstrate how our modelling approach can identify habitat likely to be of high value for retaining rare and poorly reserved species under climate change. Our analyses highlight the potential value of this dynamic macroecological approach, that incorporates key ecological processes in projecting climate change impacts for all species simultaneously and uses simple macroecological inputs that can be derived even for highly diverse and poorly studied taxa.
ESTUDIO EPIDEMIOLOGICO SOBRE LA INCIDENCIA DE ENFERMEDAD INFLAMATORIA INTESTINAL EN CUATRO AREAS ESPANOLAS

BACKGROUND The incidence of inflammatory bowel disease (IBD) shows marked geographical variations. The aim of this study was to determine and compare the incidence of IBD in four Spanish areas: Sabadell (Northeast), Vigo (Northwest), Mallorca island and Motril (South). PATIENTS AND METHODS Prospective survey based on inception cohorts over a two-years period (1 October 1991 to September 1993). Subjects were the patients resident in these areas and diagnosed of IBD according to a standard protocol for case ascertainment and definition. RESULTS Altogether 328 cases were identified, of whom 191 were diagnosed as ulcerative colitis (UC), 135 as Crohn's disease (CD) and 2 as indeterminate colitis. The overall adjusted incidence rate per 100,000 persons between ages 15-64 years of UC and CD were respectively 9.8 and 5.2 in Sabadell, 7.7 and 5.0 in Vigo, 7.8 and 5.8 in Mallorca and 4.3 and 6.5 in Motril. The Incidence rate ratio showed no significant differences for either conditions among these areas. The global adjusted incidence rate of UC in Spanish areas (8.0; IC 95%: 6.3-9.7) was significantly lower to that of Northern European countries while that of CD (5.5; IC 95%: 4.1-6.9) was between that of Northern and Southern Europe with no significant differences. CONCLUSIONS The incidence of IBD did not show differences among the Spanish areas, and rates are between 2 and 6 times higher than those previously reported. The incidence of UC is significantly lower than that observed in the North of Europe, while for CD the incidence is between that of Northern and Southern Europe.
Treatment of molecular relapse in patients with acute myeloid leukemia using clofarabine monotherapy

Few studies have examined the treatment of molecular relapse in patients with acute myeloid leukemia (AML) using different treatment regimens. We describe for the first time in the literature experiences with administration of clofarabine monotherapy in the treatment of eight patients with AML with molecular relapse of the disease.
Psychosocial Determinants of Diabetic Control and Satisfaction with Diabetes Care

Diabetes mellitus affects 7.8% of the American population. National health statistic data and other research shows that racial/ethnic disparities exist in terms of prevalence and treatment outcomes. The present study investigated the role of patient health beliefs (i.e., locus of control, self-efficacy) and the doctor-patient relationship (e.g., satisfaction and collaboration with health care provider), as relative predictors of diabetic control (i.e., HbA1c levels) and overall satisfaction with diabetes care, in older adult participants with diabetes. Demographic, psychosocial, and diabetes-related data from the Health and Retirement Study (HRS) 2003 Diabetes Study were analyzed to compare treatment outcomes among non-Hispanic White, non-Hispanic Black, and Hispanic individuals with various types of diabetes. Non-Hispanic White individuals exhibited better diabetic control than their minority counterparts (F(2, 592) = 7.60, p < . 001); however, no significant group differences were noted in terms of psychosocial factors. Diabetic control was best predicted by time since diagnosis (β = -.21, p < .001), satisfaction with diabetes self-care (β = .19, p < .001) and age (β = .12, p < .01). In addition, satisfaction with provider care was best predicted by perceived collaboration with provider (β = .44, p < .001), satisfaction with diabetes self-care (β = .22, p < .001) and diabetes self-efficacy (β = .08, p < .05). Recommendations for future research were discussed.
Regulation of Microtubule Dynamics through Phosphorylation on Stathmin by Epstein-Barr Virus Kinase BGLF4*

Stathmin is an important microtubule (MT)-destabilizing protein, and its activity is differently attenuated by phosphorylation at one or more of its four phosphorylatable serine residues (Ser-16, Ser-25, Ser-38, and Ser-63). This phosphorylation of stathmin plays important roles in mitotic spindle formation. We observed increasing levels of phosphorylated stathmin in Epstein-Barr virus (EBV)-harboring lymphoblastoid cell lines (LCLs) and nasopharyngeal carcinoma (NPC) cell lines during the EBV lytic cycle. These suggest that EBV lytic products may be involved in the regulation of stathmin phosphorylation. BGLF4 is an EBV-encoded kinase and has similar kinase activity to cdc2, an important kinase that phosphorylates serine residues 25 and 38 of stathmin during mitosis. Using an siRNA approach, we demonstrated that BGLF4 contributes to the phosphorylation of stathmin in EBV-harboring NPC. Moreover, we confirmed that BGLF4 interacts with and phosphorylates stathmin using an in vitro kinase assay and an in vivo two-dimensional electrophoresis assay. Interestingly, unlike cdc2, BGLF4 was shown to phosphorylate non-proline directed serine residues of stathmin (Ser-16) and it mediated phosphorylation of stathmin predominantly at serines 16, 25, and 38, indicating that BGLF4 can down-regulate the activity of stathmin. Finally, we demonstrated that the pattern of MT organization was changed in BGLF4-expressing cells, possibly through phosphorylation of stathmin. In conclusion, we have shown that a viral Ser/Thr kinase can directly modulate the activity of stathmin and this contributes to alteration of cellular MT dynamics and then may modulate the associated cellular processes.
Fear of Falling in People With Multiple Sclerosis: Which Clinical Characteristics Are Important?

Background Fear of falling (FOF) is an important risk indicator for health-related outcomes and quality of life in patients with multiple sclerosis (MS). However, factors associated with FOF in MS are not well investigated. Objectives This study was done to explore predictors of FOF in this population. Methods Seventy relapsing remitting patients with MS were evaluated. Fear of falling was assessed using the Fall Efficacy Scale-International (FES-I). Motor outcomes included: 30-second chair stand test (30s-CST), Berg Balance Scale (BBS), 10-Meter Walk Test (10MWT), and 6-Minute Walk Test (6MWT). Cognitive status was determined using the Montréal Cognitive Assessment (MOCA) and Symbol Digit Modalities Test (SDMT). Affective factors including depression, fatigue, and sleep were also assessed using the Beck Depression Inventory (BDI), Modified Fatigue Impact Scale (MFIS), and Pittsburgh Sleep Quality Index (PSQI), respectively. Results Fear of falling was significantly correlated with all motor and affective measures used. However, a stepwise regression found that only BBS from motor measures, MOCA from cognitive measures, and sleep disorders from affective factors were significantly predictive of the FOF. Conclusions Fear of falling in patients with MS is multifactorial and includes motor and nonmotor factors. Thus, therapies that aim to reduce risk of falling in this population should address motor functions, cognitive abilities, and sleep quality.
Advances in laboratory testing for thrombophilia

Testing for hereditary thrombophilia typically includes tests for activated protein C resistance (APC‐R) and/or factor V Leiden, protein C, protein S, antithrombin, and prothrombin G20210A. New options for these assays have become available in recent years, with different advantages and disadvantages among the currently available methods. Potential interferences for each assay type are discussed, including lupus anticoagulants, heparin, warfarin, direct thrombin inhibitors (such as argatroban, dabigatran, hirudin, or bivalirudin), rivaroxaban, factor deficiencies or elevations, factor V Leiden, and specific mutations that the assay(s) might not be able to detect. Causes of acquired deficiencies are also described, as these must be carefully excluded before diagnosing a hereditary deficiency of protein C, protein S, or antithrombin. Am. J. Hematol. 2012. © 2012 Wiley Periodicals, Inc.