Miracle-dz/UniFAR-FTUs huggingface dataset:
Sex, ageing and resting blood pressure: gaining insights from the integrated balance of neural and haemodynamic factors

Young women tend to have lower blood pressure, and less risk of hypertension, compared to young men. As people age, both blood pressure and the risk of hypertension increase in both sexes; this occurs most strikingly in women after menopause. However, the mechanisms for these influences of sex and age remain incompletely understood. In this review we are specifically interested in the interaction between neural (sympathetic nerve activity; SNA) and haemodynamic factors (cardiac output, blood pressure and vascular resistance) and how these change with sex and age. While peripheral vascular SNA can vary 7‐ to 10–fold among normotensive young men and women, it is reproducible in a given individual. Surprisingly, higher levels of SNA are not associated with higher blood pressures in these groups. In young men, high SNA is associated with higher total peripheral vascular resistance (TPR), and appears to be balanced by lower cardiac output and less peripheral vascular responsiveness to adrenergic stimulation. Young women do not exhibit the SNA–TPR relationship. Recent evidence suggests that β–adrenergic vasodilatation offsets the vasoconstrictor effects of α–adrenergic vasoconstriction in young women, which may contribute to the generally lower blood pressures in this group. Sympathetic nerve activity increases with age, and in groups over 40, levels of SNA are more tightly linked to levels of blood pressure. The potentially protective β–adrenergic effect seen in young women appears to be lost after menopause and probably contributes to the increased blood pressure and increased risk of hypertension seen in older women.
Energy system contribution to 1500- and 3000-metre track running

The aim of the present study was to quantify the contributions of the aerobic and anaerobic energy systems to 1500- and 3000-m track running events during all-out time-trials performed individually on a synthetic athletic track. Ten 3000-m (8 males, 2 females) and fourteen 1500-m (10 males, 4 females) trained track athletes volunteered to participate in the study. The athletes performed a graded exercise test in the laboratory and two time-trials over 1500 or 3000 m. The contributions of the energy systems were calculated by measures of race oxygen uptake, accumulated oxygen deficit (AOD), race blood lactate concentration, estimated phosphocreatine degradation and some individual muscle metabolite data. The relative aerobic energy system contribution (based on AOD measures) for the 3000 m was 86% (male) and 94% (female), while for the 1500 m it was 77% (male) and 86% (female). Estimates of anaerobic energy expenditure based on blood lactate concentrations, while not significantly different (P > 0.05), were generally lower compared with the AOD measures. In conclusion, the results of the present study conform with some recent laboratory-based measures of energy system contributions to these events.
Cannabis for Inflammatory Bowel Disease

The marijuana plant Cannabis sativa has been used for centuries as a treatment for a variety of ailments. It contains over 60 different cannabinoid compounds. Studies have revealed that the endocannabinoid system is involved in almost all major immune events. Cannabinoids may, therefore, be beneficial in inflammatory disorders. In murine colitis, cannabinoids decrease histologic and microscopic inflammation. In humans, cannabis has been used to treat a plethora of gastrointestinal problems, including anorexia, emesis, abdominal pain, diarrhea, and diabetic gastroparesis. Despite anecdotal reports on medical cannabis in inflammatory bowel disease (IBD), there are few controlled studies. In an observational study in 30 patients with Crohn's disease (CD), we found that medical cannabis was associated with improvement in disease activity and reduction in the use of other medications. In a more recent placebo-controlled study in 21 chronic CD patients, we showed a decrease in the CD activity index >100 in 10 of 11 subjects on cannabis compared to 4 of 10 on placebo. Complete remission was achieved in 5 of 11 subjects in the cannabis group and 1 of 10 in the placebo group. Yet, in an additional study, low-dose cannabidiol did not have an effect on CD activity. In summary, evidence is gathering that manipulating the endocannabinoid system can have beneficial effects in IBD, but further research is required to declare cannabinoids a medicine. We need to establish the specific cannabinoids, as well as appropriate medical conditions, optimal dose, and mode of administration, to maximize the beneficial effects while avoiding any potential harmful effects of cannabinoid use.
Impact of high-sensitivity Troponin T on hospital admission, resources utilization, and outcomes

Aims: The use of high-sensitivity cardiac Troponin T (hs-cTnT) assay might lead to overdiagnosis and overtreatment of Acute Coronary Syndromes (ACS). This study assessed the epidemiological, clinical and prognostic impact of introducing hs-cTnT in the everyday clinical practice of an Emergency Department. Methods and Results: We compared all consecutive patients presenting with suspected ACS at the Emergency Department, for whom troponin levels were measured. In particular, we considered 597 patients presenting during March 2010, when standard cardiac Troponin T (cTnT) assay was used, and 629 patients presenting during March 2011, when hs-cTnT test was used. Patients with suspected ACS and troponin levels above the 99th percentile (Upper Reference Limit, URL) significantly increased when using an hs-cTnT assay (17.2% vs. 37.4%, p< 0.001). Accordingly, also the mean GRACE risk score increased (124.2 ± 37.2 vs. 136.7 ± 32.2; p< 0.001). However, the final diagnosis of Acute Myocardial Infarction (AMI) did not change significantly (8.7% vs. 6.8%, p=0.263) by using a rising and/or falling pattern of hs-cTnT (change ≥ 50% or ≥ 20% depending on baseline values). In addition, no significant differences were found between the two study groups with respect to in-hospital (2.7% vs. 1.9%, p=0.366) and 1-year mortality (9.8% vs. 7.6%, p=0.216). Conclusions: We did not observe overdiagnosis and overtreatment issues in presenters with suspected ACS managed by appropriate changes in hs-cTnT levels, despite the increase in the number of patients presenting with abnormal troponin levels. This occurred without a rise in short-term and mid-term mortality.
Significant association between simple renal cysts and arterial blood pressure.

OBJECTIVE To test the hypothesis that there is an association between simple renal cysts and arterial blood pressure (BP). PATIENTS AND METHODS The study comprised a review of the case-notes of 115 patients (mean age 67.7 years, range 31-91) in whom renal cyst(s) was an incidental ultrasonographic finding, and 115 age- and sex-matched control patients. The notes were reviewed without knowledge of the origin or treatment. RESULTS The systolic and diastolic BP were significantly higher in patients with a cyst(s) than in control patients (P = 0.031 and P = 0.0034; mean difference 6.9 mmHg and 5.0 mmHg, respectively). In those aged 30-70 years, the presence of one or more simple renal cysts increased the risk of having a diastolic BP > or = 95 mmHg from seven in 58 to 17 in 58 patients (P = 0.038). CONCLUSION The association between simple renal cysts and higher arterial BP probably arises from underlying renal disease causing both. Occasionally it is possible that renal ischaemia caused by cyst expansion, and therefore increased renin release, generates the elevation in BP. If so, methods to identify such cysts should be developed.
Dictyostelium discoideum SecG interprets cAMP‐mediated chemotactic signals to influence actin organization

Tight control of actin cytoskeletal dynamics is essential for proper cell function and survival. Arf nucleotide binding‐site opener (ARNO), a mammalian guanine nucleotide exchange factor for Arf, has been implicated in actin cytoskeletal regulation but its exact role is still unknown. To explore the role of ARNO in this regulation as well as in actin‐mediated processes, the Dictyostelium discoideum homolog, SecG, was examined. SecG peaks during aggregation and mound formation. The overexpression of SecG arrests development at the mound stage. SecG overexpressing (SecG OE) cells fail to stream during aggregation. Although carA is expressed, SecG OE cells do not chemotax toward cAMP, indicating SecG is involved in the cellular response to cAMP. This chemotactic defect is specific to cAMP‐directed chemotaxis, as SecG OE cells chemotax to folate without impairment and exhibit normal cell motility. The chemotactic defects of the SecG mutants may be due to an impaired cAMP response as evidenced by altered cell polarity and F‐actin polymerization after cAMP stimulation. Cells overexpressing SecG have increased filopodia compared to wild type cells, implying that excess SecG causes abnormal organization of F‐actin. The general function of the cytoskeleton, however, is not disrupted as the SecG OE cells exhibit proper cell‐substrate adhesion. Taken together, the results suggest proper SecG levels are needed for appropriate response to cAMP signaling in order to coordinate F‐actin organization during development. © 2013 Wiley Periodicals, Inc
Mitochondrial STAT3 Supports Ras-Dependent Oncogenic Transformation

Ras, STAT3, and Transformation The STAT (signal transducer and activator of transcription) proteins are activated in response to receptor stimulation and act in the nucleus to regulate gene expression. Gough et al. (p. 1713) found that STAT3 functioned in transformation of cells by the oncogene Ras. However, this activity was maintained in mutants of STAT that fail to activate transcription. Instead, the active STAT3 appeared to be associated with mitochondria. Furthermore, modified STAT3 targeted to the mitochondria promoted transformation by Ras, and mitochondrial function was disrupted in Ras-transformed cells lacking STAT3. Such transformation-specific effects of STAT3 could be a useful target in developing anticancer therapies. A transcription factor promotes the transformation of cells by the Ras oncogene only when present in the mitochondrion. Signal transducer and activator of transcription 3 (STAT3) is a latent cytoplasmic transcription factor responsive to cytokine signaling and tyrosine kinase oncoproteins by nuclear translocation when it is tyrosine-phosphorylated. We report that malignant transformation by activated Ras is impaired without STAT3, in spite of the inability of Ras to drive STAT3 tyrosine phosphorylation or nuclear translocation. Moreover, STAT3 mutants that cannot be tyrosine-phosphorylated, that are retained in the cytoplasm, or that cannot bind DNA nonetheless supported Ras-mediated transformation. Unexpectedly, STAT3 was detected within mitochondria, and exclusive targeting of STAT3 to mitochondria without nuclear accumulation facilitated Ras transformation. Mitochondrial STAT3 sustained altered glycolytic and oxidative phosphorylation activities characteristic of cancer cells. Thus, in addition to its nuclear transcriptional role, STAT3 regulates a metabolic function in mitochondria, supporting Ras-dependent malignant transformation.
Control of differentiation in human colorectal carcinoma cell lines: Epithelial—mesenchymal interactions

Mesenchymal elements have been investigated for their effects on the growth and differentiation of seven human colorectal carcinoma‐derived cell lines. Epithelial cells were cultured as monolayers on plastic; they were also grown on fibroblast lawns and in collagen matrices, with and without fibroblasts. In each case, differentiation was assessed morphologically with monoclonal antibodies directed against components of normal goblet and columnar cells. The results were compared with those obtained when the cell lines were grown in vivo as xenografts in athymic mice.
Microsatellite markers for the Triticum timopheevi-derived leaf rust resistance gene Lr18 on wheat 5BL chromosome

Leaf rust, caused by Puccinia triticina, is a common wheat disease worldwide. Developing resistant cultivars through deploying new or pyramiding resistance genes in a suitable line, is the most effective approach to control this disease. However, to stack genes in a genotype, efficient and reliable markers are required. In the present study, F2 plants and their corresponding F3 families from a cross between the resistant line; Thatcher (Tc) Lr18, and the susceptible cultivar ‘Boolani’ were used to map rust resistance gene, Lr18 using SSR markers on chromosome 5BL of hexaploid wheat. The P. triticina pathotype no 15 was used to inoculate plants. Out of 20 primers tested, eight showed polymorphism between the two parents and were subsequently genotyped in the entire F2 population. The markers Xgpw7425 and Xwmc75 flanked the locus at a distance of 0.3 and 1.2 cM, respectively. Analysis of 81 genotypes from different backgrounds with these two markers confirmed their usefulness in screening absence or presence of Lr18. Therefore, these markers can be used for gene postulation and marker-assisted selection (MAS) of this gene in wheat breeding programs in future.
RC3/Neurogranin and Ca2+/Calmodulin-dependent Protein Kinase II Produce Opposing Effects on the Affinity of Calmodulin for Calcium*

The interaction of calmodulin with its target proteins is known to affect the kinetics and affinity of Ca2+ binding to calmodulin. Based on thermodynamic principles, proteins that bind to Ca2+-calmodulin should increase the affinity of calmodulin for Ca2+, while proteins that bind to apo-calmodulin should decrease its affinity for Ca2+. We quantified the effects on Ca2+-calmodulin interaction of two neuronal calmodulin targets: RC3, which binds both Ca2+- and apo-calmodulin, and αCaM kinase II, which binds selectively to Ca2+-calmodulin. RC3 was found to decrease the affinity of calmodulin for Ca2+, whereas CaM kinase II increases the calmodulin affinity for Ca2+. Specifically, RC3 increases the rate of Ca2+ dissociation from the C-terminal sites of calmodulin up to 60-fold while having little effect on the rate of Ca2+ association. Conversely, CaM kinase II decreases the rates of dissociation of Ca2+ from both lobes of calmodulin and autophosphorylation of CaM kinase II at Thr286 induces a further decrease in the rates of Ca2+ dissociation. RC3 dampens the effects of CaM kinase II on Ca2+ dissociation by increasing the rate of dissociation from the C-terminal lobe of calmodulin when in the presence of CaM kinase II. This effect is not seen with phosphorylated CaM kinase II. The results are interpreted according to a kinetic scheme in which there are competing pathways for dissociation of the Ca2+-calmodulin target complex. This work indicates that the Ca2+ binding properties of calmodulin are highly regulated and reveals a role for RC3 in accelerating the dissociation of Ca2+-calmodulin target complexes at the end of a Ca2+ signal.
Insufficient nitric oxide bioavailability: a hypothesis to explain adverse effects of red blood cell transfusion

While transfusion of red blood cells (RBCs) is effective at preventing morbidity and mortality in anemic patients, studies have indicated that some RBC components have functional defects (“RBC storage lesions”) that may actually cause adverse events when transfused. For example, in some studies patients transfused with RBCs stored more than 14 days have had statistically worse outcomes than those receiving “fresher” RBC units. Recipient‐specific factors may also contribute to the occurrence of these adverse events. Unfortunately, these events have been difficult to investigate because up to now they have existed primarily as “statistical occurrences” of increased morbidity and mortality in large data sets. There are currently no clinical or laboratory methods to detect or study them in individual transfusion recipients. We propose a unifying hypothesis, centered on insufficient nitric oxide bioavailability (INOBA), to explain the increased morbidity and mortality observed in some patients after RBC transfusion. In this model, variables associated with RBC units (storage time; 2,3‐diphosphoglycerate acid concentration) and transfusion recipients (endothelial dysfunction) collectively lead to changes in nitric oxide (NO) levels in vascular beds. Under certain circumstances, these variables are “aligned” such that NO concentrations are markedly reduced, leading to vasoconstriction, decreased local blood flow, and insufficient O2 delivery to end organs. Under these circumstances, the likelihood of morbidity and mortality escalates. If the key tenets of the INOBA hypothesis are confirmed, it may lead to improved transfusion methods including altered RBC storage and/or processing conditions, novel transfusion recipient screening methods, and improved RBC‐recipient matching.
Characterization of two force sensors to be used in a robotic hand

In this paper, are presented the characterization of two force sensors, in bias to incorporate them to the fingers of a robotic hand. The main goal of this work is to determine as main characteristic, the response of each sensor, in order to decide, which of them is the most effective for manipulation tasks in a mobile robotic platform. Manipulation mobile robot tasks, require to adapt its behavior and fingers configuration depending of the type and form of diverse objects. The first evaluated sensor is a cheap resistive force sensor and second is a piezoelectric force sensor. As robotic hand and then sensors will be incorporate on a mobile platform, sensor signals are sent to the a computer through a data card acquisition; an Arduino card has been used. We show the evaluation, results and conclusions of the experiments done.
A Tai Chi exercise programme improved exercise behaviour and reduced blood pressure in outpatients with hypertension.

This two-group pretest and posttest quasi-experimental study aimed to evaluate the effects of a Tai Chi exercise programme on exercise behaviour and blood pressure (BP) in outpatients with hypertension. The experimental group (n = 27) received the Yang-style Tai Chi exercise programme three times a week for 8 weeks. The control group (n = 31) received routine care with no Tai Chi exercise. Exercise behaviour and exercise time using Routine Health Care Behaviour scale and BP were assessed at baseline and 8 weeks. The experimental group had a significant improvement on exercise behaviour (t = 2.11, P < 0.001) and exercise time (t = 1.44, P = 0.003), and a significant reduction in systolic BP (t = 2.57, P < 0.001) and diastolic BPs (t = 2.86, P < 0.001) compared with those of the control group. Tai Chi is an inexpensive and viable exercise and can improve exercise behaviour and BP control in outpatients with hypertension. Tai Chi exercise might offer outpatients with hypertension additional options, such as an adjunct to formal cardiac rehabilitation or as an exercise alternative in their management of hypertension. Nursing staff can easily learn and incorporate this exercise in patient education or care planning in the care of patients with hypertension in outpatient settings.
Gene Therapy for Restoring Heart Rhythm

Efforts to use gene therapy to create a biological pacemaker as an adjunct or replacement of electronic pacemakers have been ongoing for about 15 years. For the past decade, most of these efforts have focused on the hyperpolarization-activated cyclic nucleotide gated-(HCN) gene family of channels alone or in combination with other genes. The HCN gene family is the molecular correlate of the cardiac pacemaker current, If. It is a suitable basis for a biological pacemaker because it generates a depolarizing inward current primarily during diastole and is directly regulated by cyclic adenosine monophosphate (cAMP), thereby incorporating autonomic responsiveness. However, biological pacemakers based either on native HCN channels or on mutated HCN channels designed to optimize biophysical characteristics have failed to attain the desired basal and maximal physiological heart rates in large animals. More recent work has explored dual gene therapy approaches, combining an HCN variant with another gene to reduce outward current, increase an additional inward current, or enhance cAMP synthesis. Several of these dual gene therapy approaches have demonstrated appropriate basal and maximal heart rates with little or no reliance on a backup electronic pacemaker during the period of study. Future research, besides examining the efficacy of other gene combinations, will need to consider the additional issues of safety and persistence of the viral vectors often used to deliver these genes to a specific cardiac region.
Filarial Infection Suppresses Malaria-Specific Multifunctional Th1 and Th17 Responses in Malaria and Filarial Coinfections

The mechanisms underlying the modulation of both the malaria-specific immune response and the course of clinical malaria in the context of concomitant helminth infection are poorly understood. We used multiparameter flow cytometry to characterize the quality and the magnitude of malaria-specific T cell responses in filaria-infected and -uninfected individuals with concomitant asymptomatic Plasmodium falciparum malaria in Mali. In comparison with filarial-uninfected subjects, filarial infection was associated with higher ex vivo frequencies of CD4+ cells producing IL-4, IL-10, and IL-17A (p = 0.01, p = 0.001, and p = 0.03, respectively). In response to malaria Ag stimulation, however, filarial infection was associated with lower frequencies of CD4+ T cells producing IFN-γ, TNF-α, and IL-17A (p < 0.001, p = 0.04, and p = 0.04, respectively) and with higher frequencies of CD4+IL10+T cells (p = 0.0005). Importantly, filarial infection was associated with markedly lower frequencies of malaria Ag-specific Th1 (p < 0.0001), Th17 (p = 0.012), and “TNF-α” (p = 0.0008) cells, and a complete absence of malaria-specific multifunctional Th1 cells. Filarial infection was also associated with a marked increase in the frequency of malaria-specific adaptive regulatory T/Tr1 cells (p = 0.024), and the addition of neutralizing anti–IL-10 Ab augmented the amount of Th1-associated cytokine produced per cell. Thus, among malaria-infected individuals, concomitant filarial infection diminishes dramatically the frequencies of malaria-specific Th1 and Th17 T cells, and alters the quality and magnitude of malaria-specific T cell responses.
Penetration of moxifloxacin into the human aqueous humour after oral administration

Aims: To determine the pharmacokinetics of moxifloxacin, a new generation fluoroquinolone, in the anterior chamber of the human uninflamed eye. Methods: 35 patients undergoing cataract surgery received two doses of 400 mg of oral moxifloxacin with a 12 hour interval and were divided into six groups. Moxifloxacin levels in aqueous humour and serum were determined by a microbiological agar well diffusion technique at 2, 4, 6, 8, 10, and 12 hours after the second dose in each group respectively. Results: Mean moxifloxacin levels in the anterior chamber were 1.20 (SD 0.35) μg/ml at the 2 hours group, 1.22 (0.48) μg/ml at the 4 hours group, 1.20 (0.45) μg/ml at the 6 hours group, 1.58 (0.38) μg/ml at the 8 hours group, 1.37 (0.44) μg/ml at the 10 hours group, and 1.23 (0.55) μg/ml at the 12 hours group. The mean ratio of aqueous to serum moxifloxacin level was 38%. Conclusion: Moxifloxacin penetrates well into the anterior chamber of the human uninflamed eye after oral administration, reaching early significant levels, which are maintained for at least 12 hours and are much higher than the MIC90 values of Gram positive and Gram negative pathogens commonly implicated in intraocular infections with the exceptions of fluoroquinolone resistant staphylococci, MRSA, and Pseudomonas aeruginosa.