The effects of aerobic exercise and transcranial direct current stimulation on cognitive function in older adults with and without cognitive impairment: A systematic review and meta-analysis.

BACKGROUND: Aerobic exercise (AE) may slow age-related cognitive decline. However, such cognition-sparing effects are not uniform across cognitive domains and studies. Transcranial direct current stimulation (tDCS) is a form of non-invasive brain stimulation and is also emerging as a potential alternative to pharmaceutical therapies. Like AE, the effectiveness of tDCS is also inconsistent for reducing cognitive impairment in ageing. The unexplored possibility exists that pairing AE and tDCS could produce synergistic effects and reciprocally augment cognition-improving effects in older individuals with and without cognitive impairments. Previous research found such synergistic effects on cognition when cognitive training is paired with tDCS in older individuals with and without mild cognitive impairment (MCI) or dementia. AIM: The purpose of this systematic review with meta-analysis was to explore if pairing AE with tDCS could augment singular effects of AE and tDCS on global cognition (GC), working memory (WM) and executive function (EF) in older individuals with or without MCI and dementia. METHODS: Using a PRISMA-based systematic review, we compiled studies that examined the effects of AE alone, tDCS alone, and AE and tDCS combined on cognitive function in older individuals with and without mild cognitive impairment (MCI) or dementia. Using a PICOS approach, we systematically searched PubMed, Scopus and Web of Science searches up to December 2021, we focused on 'MoCA', 'MMSE', 'Mini-Cog' (measures) and 'cognition', 'cognitive function', 'cognitive', 'cognitive performance', 'executive function', 'executive process', 'attention', 'memory', 'memory performance' (outcome terms). We included only randomized controlled trials (RTC) in humans if available in English full text over the past 20 years, with participants' age over 60. We assessed the methodological quality of the included studies (RTC) by the Physiotherapy Evidence Database (PEDro) scale. RESULTS: Overall, 68 studies were included in the meta-analyses. AE (ES = 0.56 [95% CI: 0.28-0.83], p = 0.01) and tDCS (ES = 0.69 [95% CI: 0.12-1.26], p = 0.02) improved GC in all three groups of older adults combined (healthy, MCI, demented). In healthy population, AE improved GC (ES = 0.46 [95% CI: 0.22-0.69], p = 0.01) and EF (ES = 0.27 [95% CI: 0.05-0.49], p = 0.02). AE improved GC in older adults with MCI (ES = 0.76 [95% CI: 0.21-1.32], p = 0.01). tDCS improved GC (ES = 0.69 [90% CI: 0.12-1.26], p = 0.02), all three cognitive function (GC, WM and EF) combined in older adults with dementia (ES = 1.12 [95% CI: 0.04-2.19], p = 0.04) and improved cognitive function in older adults overall (ES = 0.69 [95% CI: 0.20-1,18], p = 0.01). CONCLUSION: Our systematic review with meta-analysis provided evidence that beyond the cardiovascular and fitness benefits of AE, pairing AE with tDCS may have the potential to slow symptom progression of cognitive decline in MCI and dementia. Future studies will examine the hypothesis of this present review that a potentiating effect would incrementally improve cognition with increasing severity of cognitive impairment.

Sex Differences in Low-Density Lipoprotein Cholesterol Reduction With PCSK9 Inhibitors in Real-world Patients: The LIPID-REAL Registry.

BACKGROUND: Previous evidence supports that monoclonal antibodies that inhibit the proprotein convertase subtilisin/kexin type 9 (PCSK9) reduce low-density lipoprotein cholesterol (LDLc) by 50%-65%, regardless of baseline treatments. We tested possible sex differences in a multicentre registry of real-world patients treated with PCSK9 inhibitors. METHODS: This is a multicentre and retrospective study of 652 patients initiating treatment with any PCSK9 inhibitor in 18 different hospitals. Before-treatment and on-treatment LDLc and medical treatments, clinical indication, and clinical features were recorded. RESULTS: Women represented 24.69% of the cohort. The use of statins was similar in both sexes, but women were receiving most frequently ezetimibe. Before-treatment median LDLc was 135 (interquartile range 115-166) mg, and it was higher in women. The median on-treatment LDLc was 57 (interquartile range 38-84) mg/dL, which represented a mean 54.5% reduction. On-treatment LDLc was higher in women, and the mean LDLc reduction was lower in women (47.4% vs. 56.9%; P = 0.0002) receiving evolocumab or alirocumab. The percentage of patients who achieved ≥50% LDLc reduction was higher in men (71.36% vs. 57.62%; P = 0.002). According to LDLc before-treatment quartiles, LDLc reduction was statistically lower in women in the 2 highest and a significant interaction of women and baseline LDLc >135 mg/dL was observed. Women were negatively associated with lower rates of LDLc treatment target achievement (odds ratio: 0.31). Differences were also observed in women with body mas index >25 kg/m2. Only 14 patients (2.14%) presented side effects. CONCLUSIONS: This multicentre and retrospective registry of real-world patients treated with PCSK9 inhibitors highlights significant gender differences in LDLc reduction.

Effect of a smartphone application (Perx) on medication adherence and clinical outcomes: a 12-month randomised controlled trial.

OBJECTIVE: To determine whether the Perx app improves medication adherence and clinical outcomes over 12 months compared with standard care in patients requiring polypharmacy. DESIGN: Randomised controlled trial with 12-month follow-up. SETTING: Outpatient clinics in three tertiary hospitals in Sydney, Australia. PARTICIPANTS: Eligible participants were aged 18-75 years, with at least one chronic condition, taking ≥3 different medications (oral medications or injections), with smartphone accessibility. Participants were randomised in a 1:1 ratio. INTERVENTIONS: The intervention group used the Perx app that contained customised reminders and gamified interactions to reward verified medication adherence. MAIN OUTCOME MEASURES: The primary outcome was medication adherence over 12 months measured using pill counts. Secondary outcomes included clinical outcomes (haemoglobin A1c (HbA1c), cholesterol, blood glucose, triglycerides, creatinine, thyroid function, blood pressure and weight). RESULTS: Of 1412 participants screened for eligibility, 124 participants were randomised; 45 in the Perx arm and 40 in the control arm completed the study. The average age was 59.5, 58.9% were women, chronic conditions were cardiovascular disease (78%), type 2 diabetes (75%), obesity (65%) or other endocrine disorders (18%). On average, participants were taking six medications daily. The Perx group had greater improvements in adherence at month 2 (Coef. 8%; 95% CI 0.01 to 0.15), month 3 (Coef. 7%; 95% CI 0.00 to 0.14) and month 12 (Coef. 7%; 95% CI 0.00 to 0.13). The probability of HbA1c ≤6.5% was greater in the Perx group at months 9 and 12 and cholesterol (total and low-density lipoprotein cholesterol) was lower in the Perx group at month 3. The intervention was particularly effective for those with obesity, taking medications for diabetes and taking ≤4 medications. CONCLUSIONS: This study provides evidence that app-based behavioural change interventions can increase medication adherence and produce longer-term improvements in some clinical outcomes in adults managing multimorbidity. More trials are needed to build the evidence base. TRIAL REGISTRATION NUMBER: ACTRN12617001285347.

Diferencias de edad en el rendimiento de golpeo de balón en fútbol / Age-Related Differences in Kicking Performance in Soccer

El objetivo de este estudio fue examinar la evolución del rendimiento máximo de golpeo de balón a lo largo de la edad en futbolistas jóvenes de élite. Un total de 175 fueron divididos en 11 grupos edad (U-9 hasta U-19), además del equipo filial del club (U-23). Se registró la velocidad máxima de golpeo con la pierna dominante y no dominante mediante radar. El déficit de golpeo fue calculado para comparar el rendimiento entre ambas piernas. La velocidad máxima de golpeo aumenta progresivamente de forma significativa desde U-9 hasta U-16 con la pierna dominante y hasta U-18 con la no dominante, y sigue aumentando de forma no significativa hasta U-23. La etapa con mayor incremento de la velocidad de golpeo fue entre U-13 y U-16. Existe un déficit de golpeo con la pierna no dominante y sus valores permanecen estables (9.43%-18.18%) sin cambios significativos desde U-9 hasta U-23

The purpose of this current study was to examine the age-related differences in kicking performance with both legs in 175 youth soccer players. Players from the development programme of a professional club were grouped according to their respective under-age team (U-9 to U-18), in addition to the club's second team (U-23). Maximal kicking velocity with the preferred and non-preferred leg was recorded using a Doppler radar gun. Kicking deficit was calculated to compare side-to-side performance. Maximal kicking velocity improved progressively from the U-9 to U-16 age groups for the preferred leg and from U-16 to U-18 for the non-preferred leg, and continued to improve moderately but non-statistically significant until U-23. The stage of greatest kicking velocity development was between 13 and 16 years of age. There is a kicking deficit with the non-preferred leg and its values remain steady (9.43%-18.18%) without significant changes in players from U-9 to U-23 categories

Walking on a treadmill improves the stride length-cadence relationship in individuals with Parkinson's disease.

BACKGROUND: The gait pattern in Parkinson´s disease (PD) is characterized by a deficit in the internal regulation of stride length (SL), while the control of cadence (Cad) remains intact. The use of the treadmill as a gait rehabilitation tool has provided novel options for treatment of gait impairments in PD. However, it remains unclear whether walking on the treadmill changes the stride length-cadence relationship (SLCrel) in PD. The purpose of the present study was to analyze the SLCrel in PD subjects walking on a treadmill vs. overground, and to further compare the SLCrel to that of age-matched healthy subjects. METHODS: Fifteen PD subjects and fifteen age-matched controls walked overground and on a treadmill at five different self-selected speeds. Gait speed, SL and Cad were recorded at each self-selected speed. A linear regression analysis was conducted to explore the SLCrel and to determine the slope and intercept for each participant. RESULTS: PD subjects showed a lower intercept than control subjects when walking both overground and on a treadmill (F = 8.51, p = 0.007). In comparison with walking overground, walking on a treadmill resulted in a significant increase in the intercept in both PD and control groups (F = 12.17, p = 0.002). There were no significant differences in the slope of the SLCrel. CONCLUSION: PD subjects are able to improve the internal regulation of SL when walking on a treadmill. Our results confirm the potential therapeutic effects of treadmill training for gait rehabilitation in PD and suggest that the mechanisms underlying the positive effects of treadmill training on PD subjects are sustained.

Effect of composition and coating on the interparticle interactions and magnetic hardness of MFe2O4 (M = Fe, Co, Zn) nanoparticles.

Single domain superparamagnetic ferrite nanoparticles with the composition MFe2O4 (M = Fe, Co, Zn) have been prepared by thermal decomposition of metal acetylacetonates in diphenyl ether or dibenzyl ether, using oleic acid in the presence of oleylamine as a stabilizing agent. The Fe, Co and Zn ferrite nanoparticles are monodisperse with diameters of 4.9, 4.4 and 4.7 nm, respectively. The TG and IR results indicate that four or six carboxylate groups per nm2 are bonded at the surface of the particles acting as chelating and/or bridging bidentate ligands depending on the composition. The oleate groups minimize the interparticle interactions in Fe and Zn ferrite samples, while in the Co ferrite sample dipolar interactions produce broad maxima in the ZFC and energy barriers distribution curves. The inversion degree has been estimated from the Raman spectra and the obtained x values have been used to calculate the saturation magnetization and compare them with the experimental MS values. Compared to bulk materials, the magnetization value is higher for the Zn ferrite sample due to its mixed spinel cation distribution. For the Co ferrite sample, and probably for the Fe one, the low value of saturation magnetization seems to be due to the surface disordered layer of canted spins. Compared to non-coated nanoparticles with the same composition and similar size, the oleate groups, covalently bonded to the superficial cations, increase the anisotropy field and decrease the magnetization.

177Lu-DOTATATE treatment in neuroendocrine tumours. A preliminary study. / Tratamiento con 177LU-DOTATATE en tumores neuroendocrinos. Estudio preliminar.

Therapy with radiolabelled somatostatin analogue peptides is a promising new therapy to treat neuroendocrine tumours. The aim of this preliminary study is to present our experience with 177Lu-DOTATATE therapy, and evaluate tolerability and short-term efficacy in patients with tumours expressing somatostatin receptors. A total of 7 patients with metastatic neuroendocrine tumours were treated, each with 4 doses of 177Lu-DOTATATE. The treatment response was evaluated in the form of biochemical response (tumour markers), imaging methods (somatostatin receptor scintigraphy, computed tomography, and magnetic resonance), and functional and quality of life responses using the Karnofsky performance status scale. Treatment toxicity was also evaluated. The results obtained were as follows: Biochemical response: 60% of patients showed tumour marker levels returning to normal, while they decreased significantly in the remaining 40%. Imaging response: 85.7% had a partial response, while 14.3% showed stable disease. All (100%) patients showed a significant improvement in quality of life, with increased Karnofsky scale scores. No patient had acute or chronic toxicity, and subacute transient haematological toxicity was observed in 42.8% of patients. Despite being a preliminary study, it was found that treatment with 177Lu-DOTATATE is a safe treatment with few side effects, and an objective response was achieved in most patients.

Hot1 factor recruits co-activator Sub1 and elongation complex Spt4/5 to osmostress genes.

Hyperosmotic stress response involves the adaptative mechanisms needed for cell survival. Under high osmolarity conditions, many stress response genes are activated by several unrelated transcription factors that are controlled by the Hog1 kinase. Osmostress transcription factor Hot1 regulates the expression of several genes involved in glycerol biosynthesis, and the presence of this transcription factor in their promoters is essential for RNApol II recruitment. The physical association between Hog1 and Hot1 activates this transcription factor and directs the RNA polymerase II localization at these promoters. We, herein, demonstrate that physical and genetic interactions exist between Hot1 and several proteins involved in transcriptional and posttranscriptional processes: for example, transcription co-activator Sub1 and elongation complex Spt4/5. The results presented in this work demonstrate that Hot1 enrichment is not detected through the coding regions of its target genes and rule out a direct role in transcription elongation. Instead, other data presented herein indicate a key function of the Hot1 transcription factor in the recruitment of these proteins to the promoter or the 5'-coding region of the genes under its control.

Development of new tolerant strains to hydrophilic and hydrophobic organic solvents by the yeast surface display methodology.

Yeast surface display is a research methodology based on anchoring functional proteins and peptides onto the surface of the cells of this eukaryotic organism. Its development has resulted in the construction of a good number of new whole-cell biocatalysts with diverse applications in biotechnology, pharmacy, and medicine. In this work, we describe the design of new yeast strains in which several proteins and peptides have been introduced at the N-terminal position of protein agglutinin Aga2p. In all cases, proteins were correctly expressed and displayed on the cell surface according to the western blot, fluorescence microscopy, and fluorescence-activated cell sorting (FACS) analyses. The introduction of a glycosylable, Ser/Thr-rich protein (S1) resulted in improved resistance to ethanol, nonane, and dimethyl sulfoxide (DMSO) stress. The protein with a very high hydrophobic content (S2d) proved to confer tolerance to acetonitrile, ethanol, nonane, salt, and sodium dodecyl sulfate (SDS). The introduction of five leucine residues at the N-terminal position of S1 and S2 resulted in similar or increased resistance to the above-mentioned stress conditions. The adverse effects described in a previous work, when these residues were introduced into the N-terminus of Aga2p, with no other protein acting as a spacer, were not observed. Indeed, these strains grew better in the presence of hydrophilic solvents such as acetonitrile and ethanol. The new strains reported in this work have biotechnological potentiality given their behavior under adverse conditions of interest for biocatalytic and industrial processes.

Effect of surface stiffness on the neural control of stretch-shortening cycle movements.

AIM: It is accepted that leg stiffness (Kleg ) increases when surface stiffness decreases, and vice versa. However, little is known how the central nervous system fulfils this task. To understand the effect of surface stiffness on the neural control of stretch-shortening cycle movements, this study aimed to compare modulation of spinal and corticospinal excitability at distinct phases after ground contact during two-legged hopping when changing from solid to elastic ground. METHODS: Motor-evoked potentials (MEPs) induced by transcranial magnetic stimulation (TMS) and H-reflexes were elicited at the time of the short (SLR)-, medium (MLR)- and long (LLR)-latency responses of the soleus muscle (SOL) during two-legged hopping on different stiffness surfaces, elastic and stiff. RESULTS: Soleus H-reflexes during two-legged hopping on the elastic surface were lower at SLR and larger at LLR than on the stiff surface (P < 0.05 for both comparisons). SOL MEP size was higher at the time of SLR during hopping on the elastic surface than on the stiff surface (P < 0.05) although the background EMG was similar. CONCLUSION: It is argued that this phase-specific adaptation in spinal reflex excitability is functionally relevant to adjust leg stiffness to optimally exploit the properties of the elastic surface. Thus, the increased corticospinal excitability on the elastic surface may reflect a more supraspinal control of the ankle muscles to compensate the decrease in reflexive stiffness at the beginning of touchdown and/or counteract the higher postural challenges associated with the elastic surface.

Decreased processing speed might account for working memory span deficit in schizophrenia, and might mediate the associations between working memory span and clinical symptoms.

OBJECTIVE: Verbal working memory span is decreased in patients with schizophrenia, and this might contribute to impairment in higher cognitive functions as well as to the formation of certain clinical symptoms. Processing speed has been identified as a crucial factor in cognitive efficiency in this population. We tested the hypothesis that decreased processing speed underlies the verbal working memory deficit in patients and mediates the associations between working memory span and clinical symptoms. METHOD: Forty-nine schizophrenia inpatients recruited from units for chronic and acute patients, and forty-five healthy participants, were involved in the study. Verbal working memory span was assessed by means of the letter-number span. The Digit Copy test was used to assess motor speed, and the Digit Symbol Substitution Test to assess cognitive speed. RESULTS: The working memory span was significantly impaired in patients (F(1,90)=4.6, P<0.05). However, the group difference was eliminated when either the motor or the cognitive speed measure was controlled (F(1,89)=0.03, P=0.86, and F(1,89)=0.03, P=0.88). In the patient group, working memory span was significantly correlated with negative symptoms (r=-0.52, P<0.0001) and thought disorganisation (r=-0.34, P<0.025) scores. Regression analyses showed that the association with negative symptoms was no longer significant when the motor speed measure was controlled (ß=-0.12, P=0.20), while the association with thought disorganisation was no longer significant when the cognitive speed measure was controlled (ß=-0.10, P=0.26). CONCLUSIONS: Decrement in motor and cognitive speed plays a significant role in both the verbal working memory impairment observed in patients and the associations between verbal working memory impairment and clinical symptoms.

Yeast arming by the Aga2p system: effect of growth conditions in galactose on the efficiency of the display and influence of expressing leucine-containing peptides.

The amino or carboxy-terminal regions of certain cell wall proteins are capable of anchoring foreign proteins or peptides on the cell wall of the yeast Saccharomyces cerevisiae. This possibility has resulted in the development of a methodology known as yeast display which has powerful applications in biotechnology, pharmacy, and medicine. This work describes the results of experiments in which the agglutinin Aga2p protein is used as an anchor and several leucine-based peptides have been introduced into its N-terminal or C-terminal position. We found that the sequence of these peptides can affect plasmid stability, growth kinetics, and levels of the fusion protein displayed, and we analyzed how the incubation conditions influence these parameters. Besides, we show that the introduction of these small peptides can modify the properties of cell cover; in particular, fusing five or ten leucine residues to the Aga2p protein results in greater hydrophobicity of the cell wall and also in increased resistance to the presence of the organic solvents acetonitrile and ethanol and to high salt concentrations. The introduction of the RLRLL sequence also results in higher resistance to the exposure of yeast cells to NaCl stress.

The effects of treadmill or overground walking training program on gait in Parkinson's disease.

BACKGROUND: Gait impairment in Parkinson's disease (PD) patients is characterized by the inability to generate appropriate stride length. Treadmill training has been proposed as a therapeutic tool for PD patients. However, it remains unknown whether treadmill training effects are different from overground walking training. Thus, our goal was to explore the effects of two training programs, walking on a treadmill and walking overground, in PD patients. METHODS: 22 PD patients were randomly assigned to a treadmill or overground training group. The training program consisted of 5 weeks (3 sessions/week). Before and after the program we evaluated gait kinematics during walking at preferred and maximal speed; Timed Up and Go (TUG); static posturography and knee extensors strength. Gait parameters were reevaluated in the treadmill training group one month after the cessation of the training. RESULTS: Preferred speed walking improved in both groups after the training program. The treadmill training program, but not the overground, led to an improvement in the stride length at the preferred and maximal walking speed in the PD patients. In addition, the treadmill training group showed improvement of the TUG and static posturography tests. The improvement in gait parameters was maintained one month after the cessation of the treadmill training. CONCLUSIONS: This study provides evidence of a specific therapeutic effect of treadmill training on Parkinsonian gait and balance. Walking on a treadmill may be used as an easy, effective and accessible way to improve the stride length and balance in PD patients.

Isometric knee extensor fatigue following a Wingate test: peripheral and central mechanisms.

Central and peripheral fatigue have been explored during and after running or cycling exercises. However, the fatigue mechanisms associated with a short maximal cycling exercise (30 s Wingate test) have not been investigated. In this study, 10 volunteer subjects performed several isometric voluntary contractions using the leg muscle extensors before and after two bouts of cycling at 25% of maximal power output and two bouts of Wingate tests. Transcranial magnetic stimulation (TMS) and electrical motor nerve stimulation (NM) were applied at rest and during the voluntary contractions. Maximal voluntary contraction (MVC), voluntary activation (VA), twitch amplitude evoked by electrical nerve stimulation, M wave and motor potential evoked by TMS (MEP) were recorded. MVC, VA and twitch amplitude evoked at rest by NM decreased significantly after the first and second Wingate tests, indicating central and peripheral fatigue. MVC and VA, but not the twitch amplitude evoked by NM, recovered before the second Wingate test. These results suggest that the Wingate test results in a decrease in MVC associated with peripheral and central fatigue. While the peripheral fatigue is associated with an intramuscular impairment, the central fatigue seems to be the main reason for the Wingate test-induced impairment of MVC.

The Saccharomyces cerevisiae Hot1p regulated gene YHR087W (HGI1) has a role in translation upon high glucose concentration stress.

BACKGROUND: While growing in natural environments yeasts can be affected by osmotic stress provoked by high glucose concentrations. The response to this adverse condition requires the HOG pathway and involves transcriptional and posttranscriptional mechanisms initiated by the phosphorylation of this protein, its translocation to the nucleus and activation of transcription factors. One of the genes induced to respond to this injury is YHR087W. It encodes for a protein structurally similar to the N-terminal region of human SBDS whose expression is also induced under other forms of stress and whose deletion determines growth defects at high glucose concentrations. RESULTS: In this work we show that YHR087W expression is regulated by several transcription factors depending on the particular stress condition, and Hot1p is particularly relevant for the induction at high glucose concentrations. In this situation, Hot1p, together to Sko1p, binds to YHR087W promoter in a Hog1p-dependent manner. Several evidences obtained indicate Yhr087wp's role in translation. Firstly, and according to TAP purification experiments, it interacts with proteins involved in translation initiation. Besides, its deletion mutant shows growth defects in the presence of translation inhibitors and displays a slightly slower translation recovery after applying high glucose stress than the wild type strain. Analyses of the association of mRNAs to polysome fractions reveals a lower translation in the mutant strain of the mRNAs corresponding to genes GPD1, HSP78 and HSP104. CONCLUSIONS: The data demonstrates that expression of Yhr087wp under high glucose concentration is controlled by Hot1p and Sko1p transcription factors, which bind to its promoter. Yhr087wp has a role in translation, maybe in the control of the synthesis of several stress response proteins, which could explain the lower levels of some of these proteins found in previous proteomic analyses and the growth defects of the deletion strain.

Detection of glucose abnormalities in patients with acute coronary heart disease: study of reliable tools in clinical practice.

AIM: To investigate the prevalence of glucose abnormalities in patients with acute coronary syndrome and to assess the reliability of certain clinical or analytical variables to predict a pathologic result of oral glucose tolerance test (OGTT) at 3 months from discharge. SUBJECTS AND METHODS: Prospective study of 102 patients admitted to the coronary care units. Patients were classified according to the American Diabetes Association criteria. Three months after discharge, an OGTT was performed to non-diabetic patients. RESULTS: Forty-six (45.1%) patients were identified as diabetic (5 previously undiagnosed) and 56 (54.9%) as non-diabetic. OGTT identified 22% of diabetes, 33% of impaired glucose tolerance, and 45% of normal glucose tolerance. Fasting glucose (r=0.55, p<0.001), glycated hemoglobin (HbA1c) (r=0.46, p<0.001), low HDL cholesterol (HDLc) levels (r=-0.34, p<0.02), waist-hip ratio (r=0.45, p<0.01), high systolic blood pressure (r=0.5, p<0.01), and presence of acute myocardial infarction (r=0.46, p<0.001) at admission resulted significant to predict a pathologic result of OGTT. CONCLUSIONS: Glucose abnormalities are frequent in acute coronary syndrome patients. Certain clinical and analytical markers at admission such as fasting glucose, HbA1c, HDL-c<40 mg/dl, waist-hip ratio, and systolic blood pressure, are useful to recognize patients with a higher predisposition to present a pathologic result in OGTT at 3 months from discharge.

Crystallinity assessment and in vitro cytotoxicity of polylactide scaffolds for biomedical applications.

Bioresorbable polylactides are one of the most important materials for tissue engineering applications. In this work we have prepared scaffolds based on the two optically pure stereoisomers: poly(L: -lactide) (PLLA) and poly(D: -lactide) (PDLA). The crystalline structure and morphology were evaluated by DSC, AFM and X-ray diffraction. PLLA and PDLA crystallized in the α form and the equimolar PLLA/PDLA blend, crystallized in the stereocomplex form, were analyzed by a proliferation assay in contact with mouse L-929 and human fibroblasts and neonatal keratinocytes for in vitro cytotoxicity evaluation. SEM analysis was conducted to determine the cell morphology, spreading and adhesion when in contact with the different polymer surfaces. The preserved proliferation rate showed in MTT tests and the high colonization on the surface of polylactides observed by SEM denote that PLLA, PDLA and the equimolar PLLA/PDLA are useful biodegradable materials in which the crystalline characteristics can be tuned for specific biomedical applications.

Molecular response of Saccharomyces cerevisiae wine and laboratory strains to high sugar stress conditions.

One of the stress conditions that can affect Saccharomyces cerevisiae cells during their growth is osmotic stress. Under particular environments (for instance, during the production of alcoholic beverages) yeasts have to cope with osmotic stress caused by high sugar concentrations. Although the molecular changes and pathways involved in the response to saline or sorbitol stress are widely understood, less is known about how cells respond to high sugar concentrations. In this work we present a comprehensive study of the response to this form of stress which indicates important transcriptomic changes, especially in terms of the genes involved in both stress response and respiration, and the implication of the HOG pathway. We also describe several genes of an unknown function which are more highly expressed under 20% (w/v) glucose than under 2% (w/v) glucose. In this work we focus on the YHR087w (RTC3) gene and its encoded protein. Proteomic analysis of the mutant deletion strain reveals lower levels of several yeast Hsp proteins, which establishes a link between this protein and the response to several forms of stress. The relevance of YHR087W for the response to high sugar and other stress conditions and the relationship of the encoded protein with several Hsp proteins suggest applications of this gene in biotechnological processes in which response to stress is important.

Genetic manipulation of HSP26 and YHR087W stress genes may improve fermentative behaviour in wine yeasts under vinification conditions.

Throughout wine production yeast cells are affected by a plethora of stress conditions that compromise their ability to carry out the whole process. In recent years important knowledge about the mechanisms involved in stress response in both laboratory and wine yeast strains has been obtained. Several studies have indicated that a correlation exists between stress resistance, expression of stress response genes and fermentative behaviour. In this work we introduce several genetic manipulations in two genes induced by several stress conditions: HSP26 (which encodes a heat shock protein) and YHR087W (encoding a protein of unknown function) in two different wine yeasts, ICV16 and ICV27. These manipulations include expression in multicopy and centromeric plasmids, and substitution of the promoter in one of the genomic copies of these genes for that of the SPI1 gene, encoding for a cell wall protein of unknown function, or the PGK1 gene, which encodes the phosphoglycerate kinase glycolytic enzyme. Our results indicate that some of these modifications result in strains with higher expression of these genes, better resistance to certain stress conditions, and even improved fermentative behaviour. The modifications of the YHR087W gene are particularly interesting, and suggest an important role of this gene in the vinification process.