Miracle-dz/UniFAR-FTUs huggingface dataset:
Outcome after mitral valve repair for functional ischemic mitral regurgitation.

BACKGROUND AND AIM OF THE STUDY Functional ischemic mitral regurgitation (MR) can occur secondary to coronary artery disease. Controversy exists regarding management of these patients. Mitral valve annuloplasty in conjunction with coronary artery bypass grafting (CABG), accepted as the best treatment for severe MR, has been disputed for lesser degrees of regurgitation due to higher mortality. The results of a combined procedure approach were reviewed. METHODS Between February 1992 and June 1999, 100 consecutive patients (mean age 67+/-11 years) with functional ischemic MR underwent mitral valve repair + CABG. The repair was limited to a Duran flexible annuloplasty ring. Among patients, 72% had a preoperative myocardial infarction and 51% required perioperative intra-aortic balloon pump. NYHA functional class was III-IV in 72%; preoperative MR by transesophageal echocardiography (TEE) was grade 3-4+ in 80% and grade 2+ in 20%. RESULTS Intraoperative completion TEE indicated 0-1+ MR in 98%. Early mortality was 12% and late mortality 14%, for an overall survival of 74%. The mean follow up was 35.8 months. Follow up TEE on 82% of patients showed zero to trivial MR in 42% of patients, grade 1+ MR in 29%, 2+ MR in 24%, and 3-4+ MR in 5%. Follow up NYHA class was I-II in 81% of patients and III-IV in 19%. A significant correlation was found between recurrent MR and declining left ventricular function on follow up only, as well as the occurrence of preoperative myocardial infarction. CONCLUSION Functional ischemic MR remains a difficult problem to treat, and has a poor long-term outcome. Ring annuloplasty for functional ischemic MR with coronary artery disease achieves immediate valve competence. However, a significant number of patients develop recurrent MR at intermediate follow up.
Five-year blood pressure control and mortality following health education for hypertensive patients.

Three health education interventions for urban poor hypertensive patients were introduced sequentially in a randomized factorial design: 1) an exit interview to increase understanding of and compliance with the prescribed regimen; 2) a home visit to encourage a family member to provide support for the patient's regimen; and 3) invitations to small group sessions to increase the patient's confidence and ability to manage his/her problem. Previous evaluation of the initial two-year experience demonstrated a positive effect of the educational program on compliance with the medical treatment and blood pressure control. Data accumulated over an additional three years, including mortality analysis, are now presented. The study group consisted of the same cohort of 400 ambulatory hypertensive outpatients in the eight experimental and control groups. The five-year analysis shows a continuing positive effect on appointment keeping, weight control, and blood pressure control. All-cause life table mortality rate was 57.3 per cent less for the experimental group compared to the control group (12.9/100 vs 30.2/100, p less than .05), while the hypertension-related mortality rate was 53.2 per cent less (8.9/100 vs 19.0/100, p less than .01). The results from this longitudinal study provide evidence to encourage health practitioners to utilize such educational programs in the long-term management and control of high blood pressure.
Evidence that Stable Retroviral Transduction and Cell Survival following DNA Integration Depend on Components of the Nonhomologous End Joining Repair Pathway

ABSTRACT We have previously reported several lines of evidence that support a role for cellular DNA repair systems in completion of the retroviral DNA integration process. Failure to repair an intermediate in the process of integrating viral DNA into host DNA appears to trigger growth arrest or death of a large percentage of infected cells. Cellular proteins involved in the nonhomologous end joining (NHEJ) pathway (DNA-PKCS) and the damage-signaling kinases (ATM and ATR) have been implicated in this process. However, some studies have suggested that NHEJ proteins may not be required for the completion of lentiviral DNA integration. Here we provide additional evidence that NHEJ proteins are required for stable transduction by human immunodeficiency type 1 (HIV-1)-based vectors. Our analyses with two different reporters show that the number of stably transduced DNA-PKCS-deficient scid fibroblasts was reduced by 80 to 90% compared to the number of control cells. Furthermore, transduction efficiency can be restored to wild-type levels in scid cells that are complemented with a functional DNA-PKCS gene. The efficiency of stable transduction by an HIV-1-based vector is also reduced upon infection of Xrcc4 and ligase IV-deficient cells, implying a role for these components of the NHEJ repair pathway. Finally, we show that cells deficient in ligase IV are killed by infection with an integrase-competent but not an integrase-deficient HIV-1 vector. Results presented in this study lend further support to a general role for the NHEJ DNA repair pathway in completion of the retroviral DNA integration process.
The Actinomyces oris type 2 fimbrial shaft FimA mediates co‐aggregation with oral streptococci, adherence to red blood cells and biofilm development

Interbacterial interactions between oral streptococci and actinomyces and their adherence to tooth surface and the associated host cells are key early events that promote development of the complex oral biofilm referred to as dental plaque. These interactions depend largely on a lectin‐like activity associated with the Actinomyces oris type 2 fimbria, a surface structure assembled by sortase (SrtC2)‐dependent polymerization of the shaft and tip fimbrillins, FimA and FimB respectively. To dissect the function of specific fimbrillins in various adherence processes, we have developed a convenient new technology for generating unmarked deletion mutants of A. oris. Here, we show that the fimB mutant, which produced type 2 fimbriae composed only of FimA, like the wild type co‐aggregated strongly with receptor‐bearing streptococci, agglutinated with sialidase‐treated red blood cells, and formed monospecies biofilm. In contrast, the fimA and srtC2 mutants lacked type 2 fimbriae and were non‐adherent in each of these assays. Plasmid‐based expression of the deleted gene in respective mutants restored adherence to wild‐type levels. These findings uncover the importance of the lectin‐like activity of the polymeric FimA shaft rather than the tip. The multivalent adhesive function of FimA makes it an ideal molecule for exploring novel intervention strategies to control plaque biofilm formation.
Functional dentate gyrus neurogenesis in a rapid kindling seizure model

Neurogenesis in the adult mammalian hippocampus resulting in long‐term persistence of new neurons with features of capacity for functional activation is recognized. Many stimuli are capable of increasing the rate of neurogenesis, including seizure activity. Whether these insults result in an increased number of new functionally active neurons over and above the baseline rate of neurogenesis is not known. The rapid electrical amygdala kindling (REAK) model of seizures isolates the effects of seizures alone in the absence of neuronal death and the resulting seizures induce expression of c‐Fos in the vast majority of dentate gyrus (DG) granule cells. C57BL/6 mice were exposed to REAK then injected with bromodeoxyuridine (BrDU) to label dividing cells, then re‐exposed to REAK after a delay period to allow detection of functional activation in new neurons by measurement c‐Fos expression in response to seizures. Adult subgranular zone cells migrated into the DG granule cell layer (GCL), assumed a neuronal phenotype and demonstrated seizure‐dependent responsiveness. Larger absolute numbers of new neurons demonstrating seizure‐dependent activation were found in the GCL of previously kindled mice. Seizures are capable of increasing the number of new neurons with the capacity for functional activation laid down in the postseizure period and incorporated into seizure‐activated circuitry.
Intravenous iron therapy in non‐anemic iron‐deficient menstruating adolescent females with fatigue

Menstruating women, with or without underlying bleeding disorders, are at increased risk for developing iron deficiency‐related fatigue, even in the absence of anemia. Oral iron therapy has limitations which include poor absorption and non‐adherence due to gastrointestinal side effects. We performed a prospective clinical trial of post‐menarchal adolescent females with iron‐deficiency with or without mild anemia and fatigue who received a standardized regimen of intravenous iron sucrose. The baseline mean (SD) hemoglobin was 11.96 g dl−1 (1.05) in 20 girls (ages 14–21 years); with a range of 10.3–14.1 g dl−1. In this cohort, intravenous iron was well tolerated and patients demonstrated a sustained increase in ferritin levels with means (SD) of 13.4 ng ml−1 (13.1) at baseline to 141.5 ng ml−1 (104.5) at 6 weeks and 85.2 ng ml−1 (128.4) at 6 months after the infusions. We used a standardized (Peds QLTM Multidimensional) fatigue scale to objectively measure fatigue and proxy scores by parents with mean screening scores (SD) of 35.2 (16.8) and 31.9 (19.6), respectively. We demonstrated a clinically significant improvement both in patient as well as parent fatigue scores (in 19 out of 20 subjects) at 6 weeks (Mean (SD) 58.3 (21.3) [P < 0.0001] and 57 (24.4) [P < 0.0001], respectively); as well as 3 and 6 months after the iron infusions. In nonanemic patients, iron administration did not significantly influence hemoglobin concentration. Therefore, the fatigue‐reducing effects of iron therapy reflect the nonhematological functions of iron. Am. J. Hematol. 91:973–977, 2016. © 2016 Wiley Periodicals, Inc.
Numb Protects Human Renal Tubular Epithelial Cells From Bovine Serum Albumin‐Induced Apoptosis Through Antagonizing CHOP/PERK Pathway

In recent studies, we found that Numb is involved in oxidative stress‐induced apoptosis of renal proximal tubular cells; however, its function on ER stress‐induced apoptosis in proteinuric kidney disease remains unknown. The objective of the present study is to explore the role of Numb in urinary albumin‐induced apoptosis of human renal tubular epithelial cells (HKCs). In this study, we demonstrate that incubation of HKCs with bovine serum albumin (BSA) resulted in caspase three‐dependent cell death. Numb expression was down‐regulated by BSA in a time‐ and dose‐dependent manner. Knockdown of Numb by siRNA sensitized HKCs to BSA‐induced apoptosis, whereas overexpression of Numb protected HKCs from BSA‐induced apoptosis. Moreover, BSA activated CHOP/PERK signaling pathway in a time‐ and dose‐dependent manner as indicated by increased expression of CHOP, PERK, and P‐PERK. Furthermore, knockdown of CHOP or PERK significantly attenuated the promoting effect of Numb on BSA‐induced apoptosis, while overexpression of CHOP impaired the protective effect of Numb on BSA‐induced apoptosis. Taken together, our findings demonstrate that Numb plays a protective role on BSA‐induced apoptosis through inhibiting CHOP/PERK signaling pathway in human renal tubular epithelial cells. Therefore, the results from this study provides evidence that Numb is a new target of ER‐associated apoptotic signaling networks and Numb may serve as a promising therapeutic target for proteinuric diseases. J. Cell. Biochem. 117: 163–171, 2016. © 2015 Wiley Periodicals, Inc.
Vasodilator-derived nitric oxide inhibits fetal calf serum- and angiotensin-II-induced growth of renal arteriolar smooth muscle cells.

Chemically derived nitric oxide (NO) and 8-bromo-cyclic-GMP (cGMP) have been shown to inhibit the growth of cultured aortic smooth muscle cells. However, their effects on growth of smooth muscle cells of resistance arteries have not been studied, although abnormalities in the control of such growth are related to the elevated vascular resistance in hypertension. This study evaluated the effects of three chemically dissimilar nitrovasodilators and cGMP on fetal calf serum (FCS)-induced growth of renal arteriolar smooth muscle cells (ASMCs). The compounds used were S-nitroso-N-acetylpencillamine (SNAP), sodium nitroprusside (SNP) and isosorbide-dinitrate (ISDN) and cell growth was evaluated in terms of DNA synthesis and cell number. In addition, the effects of vasodilator-derived NO on Angiotensin-II (Ang-II)-induced ASMC growth and contraction were studied. Treatment with 10(-7) to 10(-3) M SNAP, SNP or ISDN, as well as cGMP, inhibited FCS (5%)-induced DNA synthesis in a concentration-dependent manner (P < .01). These antimitogenic effects of SNAP, SNP and ISDN were inhibited by Hb (50 microM) and potentiated by superoxide dismutase (100 U/ml; P < .05). All compounds tested also inhibited FCS (5%)-induced proliferation of ASMCs (P < .01), with the order of potency being SNAP > SNP > ISDN > cGMP. SNAP (10(-6) M) inhibited cell proliferation induced by 10(-6) M Ang-II, but higher concentrations were required to inhibit ASMC proliferation induced by 5 and 10% FCS. Furthermore, NO generated from SNAP (10(-6) M) inhibited Ang-II (10(-6) M)-induced ASMC contraction. (ABSTRACT TRUNCATED AT 250 WORDS)
Perinatal Cocaine Exposure Stimulates the Expression and Activation of CREB in the Neonatal Rat Heart

cAMP response binding protein (CREB) is a transcriptional factor known to regulate gene expression. Phosphorylation of CREB at serine 133 is necessary for CREB activation, and quantification of phospho-CREB (p-CREB) expression is an index of CREB activation. Because CREB expression and activation in specific brain regions are modified after chronic cocaine administration, we sought to determine whether chronic perinatal cocaine exposure affects the expression of CREB and p-CREB in the postnatal rat heart. Pregnant rats were treated daily with saline (control) or cocaine at 20 mg/kg (C20) or 60 mg/kg (C60) by intragastric administration throughout gestation. The expression of total CREB and p-CREB was quantified in nuclear extracts isolated from 1- and 7-d-old neonatal rat hearts. Cardiac nuclear p-CREB was increased in the C20 and C60 groups on d 1 and 7 of age compared with their respective age-matched control groups. The increase in p-CREB expression corresponded to an increase in cAMP response element binding activity. We also assayed nuclear protein kinase A activity, which was up-regulated in d 1 animals with prenatal cocaine exposure, but was comparable in all groups at d 7. Our results suggest that perinatal cocaine exposure stimulates CREB activation in the neonatal heart, and it may be mediated by different mechanisms at d 1 and d 7. The changes in myocardial CREB activation induced by perinatal cocaine exposure are likely to result in modified gene expression in the neonatal heart that may account for the cardiac dysfunction reported in human neonates born to cocaine-abusing mothers.
Procalcitonin levels during pregnancy, delivery and postpartum

Abstract Aims: To determine the normal value ranges of procalcitonin (PCT) in women with uncomplicated pregnancies. Methods: This prospective cohort study was conducted between May 2009 and February 2010 among 60 women without signs of clinical infection (31 vaginal deliveries, 29 cesarean sections) attending the maternity unit of the University of Geneva Hospitals. Sequential follow-up of PCT levels was performed at 24–28 weeks (n=7), 36–40 weeks (n=60), at delivery (n=59), and at days 2–3 (n=58) and 10 (n=53) postpartum using a sensitive PCT assay with a functional sensitivity of 0.06 μg/L. Results: Median levels of PCT were: 24–28 weeks: 0.043 μg/L (range 0.010–0.080); 36–40 weeks: 0.061 μg/L (range 0.010–0.110); at delivery: 0.068 μg/L (range 0.010–0.170); days 2–3: 0.200 μg/L (range 0.030–5.00); and day 10: 0.060 μg/L (range 0.020–0.120). At days 2–3 postpartum, three women had a PCT level between 0.25 μg/L and 0.5 μg/L and two women had a level higher than 0.5 μg/L. Conclusions: This study provides reference values for PCT during the third trimester, at delivery and at the immediate postpartum period. A cut-off PCT level of 0.25 μg/L can be used during the third trimester, at delivery, and at the immediate postpartum period to rule out infection.
Glutathione concentration may be a useful predictor of response to second‐line chemotherapy in patients with ovarian cancer

No useful predictor of resistance or sensitivity to second‐line chemotherapy is known for ovarian cancer. The objective of this prospective study was to determine the utility of tumor glutathione S‐transferase‐π (GST‐π) expression or glutathione (GSH) concentration in predicting ovarian cancer patients' responses to second‐line chemotherapy.
Cellular kinetics of the bone remodeling sequence in the rat

The kinetics of the bone remodeling sequence in the rat has been studied using a system in which well‐synchronized remodeling units were induced along the periosteum of rat mandibles. Remodeling of the periosteal surface of the mandibles was induced according to Tran Van (1979) by extraction of the opposing row of teeth; namely, the right maxillary molars were extracted under light ether anesthesia, therefore allowing the right mandibular molars to egress; this, in turn, induced a wave of remodeling activity on the buccal side of the periosteal surface of the alveolar bone. The quantification of the different cellular activities involved in bone remodeling has been performed up to 16 days after induction. This allowed us to demonstrate the sequential activity of the different cell types involved in bone remodeling, to study the cellular kinetics of this sequence of events, and to directly measure the duration of each phase of the bone remodeling sequence. A single wave of osteoclasts appeared 3 days after induction, reached a peak at 4–5 days, and then decreased sharply. This was followed by a single wave of mononuclear cells (Baron et al., 1980) within remodeling sites during the reversal phase; they appeared 4 days after induction, reached a peak by day 7, and then decreased sharply. This reversal activity was then followed by osteoblasts forming new bone on top of a reversal cement line in the remodeling sites, starting 6 days after induction and increasing until the end of the experiment. In addition, the synchronization of the system used in this study allowed direct measurement of the duration of the successive steps of the remodeling sequence. The directly measured values have then been compared to previous data calculated from other systems.
Spectrum of clinical presentations and endocrinological findings of patients with septo-optic dysplasia: a retrospective study

Abstract Background: Septo-optic dysplasia (SOD) is a rare condition with variable clinical pictures and spectrum of findings. Objective: To analyze the spectrum of findings, frequency and age of onset of hypothalamic-pituitary dysfunctions in children with SOD. Method: A retrospective electronic medical record (EMR) chart review was done for patients with SOD seen in a tertiary care center’s pediatric endocrinology clinic between January 1, 2012, and March 31, 2014. The diagnostic criteria for SOD included presence of ≥2 of the following: (i) optic nerve hypoplasia, (ii) agenesis/hypoplasia of septum pellucidum and/or corpus callosum and (iii) hypothalamic-pituitary dysfunction. Results: Eighty patients fitting the diagnostic criteria of SOD were included in this study. The majority of patients (96%) had optic nerve hypoplasia on magnetic resonance imaging and were diagnosed due to visual issues including nystagmus (36%) or strabismus (13.8%). Hypothalamic-pituitary dysfunction was most common (51%) when optic nerve hypoplasia was present with (36%) or without (15%) dysgenesis of septum pellucidum and/or corpus callosum compared to dysgenesis of septum pellucidum and/or corpus callosum alone (4%). Hypothalamic-pituitary dysfunction was noted in 55% of patients, and most (86%) were diagnosed ≤2 years of age. Central hypothyroidism and growth hormone deficiency were most common followed by secondary/tertiary adrenal insufficiency and diabetes insipidus. Conclusions: The risk of hypothalamic-pituitary dysfunction in SOD is highest ≤2 years of age and when both optic nerve hypoplasia and dysgenesis of septum pellucidum/corpus callosum are present, suggesting a need for more frequent follow-up and screening tests for hypothalamic-pituitary dysfunction in these patients.
Associations between dietary flavonoid intakes and bone health in a scottish population

Flavonoids are bioactive polyphenols found particularly in fruit and vegetables, but little is known about their role in bone health in humans. The aim of this observational study was to investigate whether dietary flavonoid intake was associated with bone mineral density (BMD) and bone resorption in a large group of perimenopausal Scottish women. Over 3000 women completed a food frequency questionnaire as part of an osteoporosis screening study. The diets were analyzed for flavonoid intake using a food composition database. BMD was measured at the femoral neck (FN) and lumbar spine (LS) by dual‐energy X‐ray absorptiometry (DXA). Free pyridinoline (PYD) and deoxypyridinoline (DPD) were measured by high‐performance liquid chromatography (HPLC) in second early morning fasted urine samples. The mean flavonoid intake of the diet was 307 ±199 mg/d. The catechin family contributed the most to flavonoid intakes (55%), and the flavones the least (<1%). Associations were found between energy‐adjusted total flavonoid intakes and BMD at the FN and LS (FN r = 0.054, LS r = 0.036, p ≤ .05). Annual percent change in BMD was associated with intakes of procyanidins and catechins (p ≤ .05), and flavanones were negatively associated with bone‐resorption markers (PYD r = −0.049, DPD r = –0.057, p ≤ .001). These associations were still seen after adjusting for confounders. It is concluded that dietary flavonoid intakes are associated with BMD, supporting the evidence from animal and cellular studies. © 2011 American Society for Bone and Mineral Research.
Bradykinin B1 Receptor Expression Induced by Tissue Damage in the Rat Portal Vein: A Critical Role for Mitogen-Activated Protein Kinase and Nuclear Factor-κB Signaling Pathways

The bradykinin B1 receptor (B1R) is normally absent under physiological conditions, but is highly inducible during inflammatory conditions or following tissue damage. The present study attempted to determine some of the mechanisms underlying B1R upregulation following tissue injury in rat portal vein. Damage induced by tissue isolation and in vitro incubation caused a significant and time-dependent increase in des-Arg9–bradykinin (des-Arg9–BK) responsiveness that paralleled the B1R mRNA expression, as confirmed by real-time quantitative PCR. In vitro incubation of rat portal vein also induced the activation of some members of the mitogen activated protein kinase (MAPK) family, namely, extracellular signal-regulated kinase (ERK), c-Jun NH2-terminal kinase (JNK), and p38 MAPK, an effect accompanied by degradation of the inhibitory protein IκB&agr; and translocation of nuclear transcription factor-κB (NF-κB) to the nucleus. The blockade of p38 MAPK, JNK or NF-κB, but not ERK pathways with selective inhibitors, resulted in a significant reduction of the upregulated contractile response caused by the selective B1R agonist des-Arg9–BK, and largely prevented the induction of B1R mRNA expression in the rat portal vein. Together, these results demonstrate that in vitro tissue damage induces activation of several intracellular signaling pathways that have a key role in the control of B1R expression. B1R could exert a pivotal role in the development of the cardiovascular response associated with vascular damage.