Individualized time windows enhance TMS-EEG signal characterization and improve assessment of cortical function in schizophrenia.

Transcranial magnetic stimulation and electroencephalography (TMS-EEG) recordings are crucial to directly assess cortical excitability and inhibition in a non-invasive and task-free manner. TMS-EEG signals are characterized by TMS-evoked potentials (TEPs), which are employed to evaluate cortical function. Nonetheless, different time windows (TW) have been used to compute them over the years. Moreover, these TWs tend to be the same for all participants omitting the intersubject variability. Therefore, the objective of this study is to assess the effect of using different TWs to compute the TEPs, moving from a common fixed TW to more adaptive individualized TWs. Twenty-nine healthy (HC) controls and twenty schizophrenia patients (SCZ) underwent single-pulse (SP) TMS-EEG protocol. Firstly, only the HC were considered to evaluate the TEPs for three different TWs in terms of amplitude and topographical distribution. Secondly, the SCZ patients were included to determine which TW is better to characterize the brain alterations of SCZ. The results indicate that a more individualized TW provides a better characterization of the SP TMS-EEG signals, although all of them show the same tendency. Regarding the comparison between groups, the individualized TW is the one that provides a better differentiation between populations. They also provide further support to the possible imbalance of cortical excitability/inhibition in the SCZ population due to its reduced activity in the N45 TEP and greater amplitude values in the N100. Results also suggest that the SCZ brain has a baseline hyperactive state since the TEPs of the SCZ appear earlier than those of the HC.

Relation between task-related activity modulation and cortical inhibitory function in schizophrenia and healthy controls: a TMS-EEG study.

Schizophrenia has been associated with a reduced task-related modulation of cortical activity assessed through electroencephalography (EEG). However, to the best of our knowledge, no study so far has assessed the underpinnings of this decreased EEG modulation in schizophrenia. A possible substrate of these findings could be a decreased inhibitory function, a replicated finding in the field. In this pilot study, our aim was to explore the association between EEG modulation during a cognitive task and the inhibitory system function in vivo in a sample including healthy controls and patients with schizophrenia. We hypothesized that the replicated decreased task-related activity modulation during a cognitive task in schizophrenia would be related to a hypofunction of the inhibitory system. For this purpose, 27 healthy controls and 22 patients with schizophrenia (including 13 first episodes) performed a 3-condition auditory oddball task from which the spectral entropy modulation was calculated. In addition, cortical reactivity-as an index of the inhibitory function-was assessed by the administration of 75 monophasic transcranial magnetic stimulation single pulses over the left dorsolateral prefrontal cortex. Our results replicated the task-related cortical activity modulation deficit in schizophrenia patients. Moreover, schizophrenia patients showed higher cortical reactivity following transcranial magnetic stimulation single pulses over the left dorsolateral prefrontal cortex compared to healthy controls. Cortical reactivity was inversely associated with EEG modulation, supporting the idea that a hypofunction of the inhibitory system could hamper the task-related modulation of EEG activity.

Exercise during pregnancy for preventing gestational diabetes mellitus and hypertensive disorders: An umbrella review of randomised controlled trials and an updated meta-analysis.

OBJECTIVE: This study aimed to provide, through an umbrella review, an overview of the effect of single exercise interventions during pregnancy on gestational diabetes mellitus (GDM) and hypertensive disorders of pregnancy (HDP). Also, to update the current evidence through an updated meta-analysis. DESIGN: Umbrella review. SETTING: PubMed, EMBASE, Web of Science, Cochrane database of systematic reviews, Epistemonikos, SPORTDiscus, Clinicaltrials.gov, and PROSPERO register were searched from the database inception until August 2021. POPULATION: Peer-reviewed systematic reviews and meta-analyses of randomised controlled trials (RCTs) and RCTs samples. METHODS: Random-effects model was used to calculate relative risk with 95% confidence interval in the updated meta-analysis. The reference category was the groups that received usual prenatal care. AMSTAR 2 and the Cochrane Collaboration tool were used to assess the quality and GRADE approach was used to assess the overall certainly of evidence. MAIN OUTCOME MEASURES: GDM and HDP relative risk. RESULTS: Twenty-three systematic reviews and meta-analyses; and 63 RCTs were included. Single exercise interventions reduced the incidence of GDM and HDP in most systematic reviews and meta-analyses. Moreover, exercise interventions during pregnancy decrease the incidence of developing GDM and GH, particularly when they are supervised, have a low to moderate intensity level, and are initiated during the first trimester of pregnancy. CONCLUSION: Based on the findings, obstetric and physical exercise professionals could recommend exercise interventions during pregnancy as an effective strategy to improve maternal outcomes.

Analysis of null deletion polymorphism of glutathione S-transferase theta (GSTT-1), associated with anti-GSTT-1 antibodies development in transplantation.

Glutathione S-transferase theta 1 (GSTT1) is an enzyme involved in phase II biotransformation processes and a member of a multigene family of detoxifying and clearing reactive oxygen species. GSTT1 is polymorphic like other biotransforming enzymes, allowing variability in hepatic conjugation processes. Immunological recognition of the GSTT1 alloantigen, as evidenced by donor-specific antibodies formation, has previously been observed in recipients lacking GSTT1 protein (called GSTT1-, GSTT*0, null phenotype or homozygous for the GSTT1 deletion) who receive liver or kidney transplants from GSTT1+ donors and is a risk factor for the development of de novo hepatitis following liver transplants from a GSTT1 expressing donor. Antibodies against GSTT1 are demonstrated in patients who are GSTT1 null and received a transplant from a GSTT1+ donor. Understanding the local population frequency of the GSTT1 deletion is of value in understanding the potential clinical risk of developing post-transplant complications, which can be attributed to the nonexpression of GSTT1. A population of 173 healthy donors of the Murcia Region in Southeast Spain was evaluated for a null allele of GSTT1 (n = 173). DNA was extracted, and GSTT-1 null allele detection was performed by real-time polymerase chain reaction. The frequency of the null GSTT1 genotype (nonexpression or deletion of the homozygous polymorphism of the GSTT1 protein) was 17.9% (n = 31 null allele GSTT1/173 total individuals). Our data suggest that the frequency of null GSTT1 mutations in our population in Southeast Spain is 17.9%, lower than in other Caucasoid populations. This would convert our recipient population into more susceptible to nonlocal potential organ donors and less susceptible to local donors. All recipients bearing this GSTT1 deletion homozygous would be without the protein and triggering an alloantigen in the case of transplantation with a donor without deletion.

The age again in the eye of the COVID-19 storm: evidence-based decision making.

BACKGROUND: One hundred fifty million contagions, more than 3 million deaths and little more than 1 year of COVID-19 have changed our lives and our health management systems forever. Ageing is known to be one of the significant determinants for COVID-19 severity. Two main reasons underlie this: immunosenescence and age correlation with main COVID-19 comorbidities such as hypertension or dyslipidaemia. This study has two aims. The first is to obtain cut-off points for laboratory parameters that can help us in clinical decision-making. The second one is to analyse the effect of pandemic lockdown on epidemiological, clinical, and laboratory parameters concerning the severity of the COVID-19. For these purposes, 257 of SARSCoV2 inpatients during pandemic confinement were included in this study. Moreover, 584 case records from a previously analysed series, were compared with the present study data. RESULTS: Concerning the characteristics of lockdown series, mild cases accounted for 14.4, 54.1% were moderate and 31.5%, severe. There were 32.5% of home contagions, 26.3% community transmissions, 22.5% nursing home contagions, and 8.8% corresponding to frontline worker contagions regarding epidemiological features. Age > 60 and male sex are hereby confirmed as severity determinants. Equally, higher severity was significantly associated with higher IL6, CRP, ferritin, LDH, and leukocyte counts, and a lower percentage of lymphocyte, CD4 and CD8 count. Comparing this cohort with a previous 584-cases series, mild cases were less than those analysed in the first moment of the pandemic and dyslipidaemia became more frequent than before. IL-6, CRP and LDH values above 69 pg/mL, 97 mg/L and 328 U/L respectively, as well as a CD4 T-cell count below 535 cells/µL, were the best cut-offs predicting severity since these parameters offered reliable areas under the curve. CONCLUSION: Age and sex together with selected laboratory parameters on admission can help us predict COVID-19 severity and, therefore, make clinical and resource management decisions. Demographic features associated with lockdown might affect the homogeneity of the data and the robustness of the results.

COVID-19: age, Interleukin-6, C-reactive protein, and lymphocytes as key clues from a multicentre retrospective study.

BACKGROUND: The SARS-CoV-2 infection has widely spread to become the greatest public health challenge to date, the COVID-19 pandemic. Different fatality rates among countries are probably due to non-standardized records being carried out by local health authorities. The Spanish case-fatality rate is 11.22%, far higher than those reported in Asia or by other European countries. A multicentre retrospective study of demographic, clinical, laboratory and immunological features of 584 Spanish COVID-19 hospitalized patients and their outcomes was performed. The use of renin-angiotensin system blockers was also analysed as a risk factor. RESULTS: In this study, 27.4% of cases presented a mild course, 42.1% a moderate one and for 30.5% of cases, the course was severe. Ages ranged from 18 to 98 (average 63). Almost 60 % (59.8%) of patients were male. Interleukin 6 was higher as severity increased. On the other hand, CD8 lymphocyte count was significantly lower as severity grew and subpopulations CD4, CD8, CD19, and NK showed concordant lowering trends. Severity-related natural killer percent descents were evidenced just within aged cases. A significant severity-related decrease of CD4 lymphocytes was found in males. The use of angiotensin-converting enzyme inhibitors was associated with a better prognosis. The angiotensin II receptor blocker use was associated with a more severe course. CONCLUSIONS: Age and age-related comorbidities, such as dyslipidaemia, hypertension or diabetes, determined more frequent severe forms of the disease in this study than in previous literature cohorts. Our cases are older than those so far reported and the clinical course of the disease is found to be impaired by age. Immunosenescence might be therefore a suitable explanation for the hampering of immune system effectors. The adaptive immunity would become exhausted and a strong but ineffective and almost deleterious innate response would account for COVID-19 severity. Angiotensin-converting enzyme inhibitors used by hypertensive patients have a protective effect in regards to COVID-19 severity in our series. Conversely, patients on angiotensin II receptor blockers showed a severer disease.

Effects of exercise-based interventions on postpartum depression: A meta-analysis of randomized controlled trials.

BACKGROUND: There is inconsistent evidence about the effect of physical activity on the prevention and treatment of depression during the postnatal period. The aim of this meta-analysis was to determine the effect of physical activity interventions during pregnancy and the postpartum period for controlling postpartum depressive symptoms. METHODS: We systematically searched Cochrane Library Plus, Science Direct, EMBASE, CINAHL, PubMed, Web of Science, and Scopus, from January 1990 to May 2016, for randomized or nonrandomized controlled trials addressing the effect of physical activity on postpartum depression. The inverse variance-weighted method was used to compute pooled estimates of effect size and respective 95% confidence intervals (95% CI) for physical activity intervention on postpartum depression. Subgroup analyses were performed comparing women with and without postpartum depressive symptoms according to specific scales measuring this construct. Meta-regression and sensitivity analysis were computed to evaluate heterogeneity. RESULTS: Twelve studies were included in the meta-analysis. Effect size for the relationship between physical activity interventions during pregnancy and the postpartum period on postpartum depressive symptoms was 0.41 (95% CI 0.28-0.54). Heterogeneity was I2  = 33.1% (P = .117). When subgroup analyses were done, pooled effect sizes were 0.67 (95% CI 0.44-0.90) for mothers who met postpartum depressive symptoms criteria at baseline based on specific scales, and 0.29 (95% CI 0.14-0.45) for mothers who did not meet those depressive symptoms criteria at baseline. CONCLUSION: Physical exercise during pregnancy and the postpartum period is a safe strategy to achieve better psychological well-being and to reduce postpartum depressive symptoms.

Screen-printed nanoparticles as anti-counterfeiting tags.

Metallic nanoparticles with different physical properties have been screen printed as authentication tags on different types of paper. Gold and silver nanoparticles show unique optical signatures, including sharp emission bandwidths and long lifetimes of the printed label, even under accelerated weathering conditions. Magnetic nanoparticles show distinct physical signals that depend on the size of the nanoparticle itself. They were also screen printed on different substrates and their magnetic signals read out using a magnetic pattern recognition sensor and a vibrating sample magnetometer. The novelty of our work lies in the demonstration that the combination of nanomaterials with optical and magnetic properties on the same printed support is possible, and the resulting combined signals can be used to obtain a user-configurable label, providing a high degree of security in anti-counterfeiting applications using simple commercially-available sensors.

A follow-up study to assess the determinants and consequences of physical activity in pregnant women of Cuenca, Spain.

BACKGROUND: In recent years, the influence of physical exercise on pregnancy outcomes has been widely debated. Despite the numerous studies addressing the relationship between maternal physical activity and pregnancy outcomes, the evidence for consistent and significant impact of regular exercise during pregnancy on fetal growth remains lacking. The aims of this study were, first, to assess the level of physical activity performed throughout the pregnancy by objective (accelerometer) and self-reported (questionnaire) measurements, and, second, to ascertain pre-pregnancy physical activity levels, to estimate the relationship between levels of physical activity and some pregnancy and neonatal outcomes. METHODS/DESIGN: This was a prospective cohort study. Participants were pregnant women (n = 194) aged 18 to 40 years who attended for three quarterly appointments for pregnancy ultrasound scans at the Virgen de la Luz Hospital in Cuenca, Spain. All participants provided written informed consents to participate in the study. Physical activity during the pregnancy follow-up was assessed by a self-reported Pregnancy Physical Activity Questionnaire and sleep log; also objectively by a GT3X accelerometer (ActiGraph). Furthermore, pregnancy symptoms inventory, nutritional behavioural assessment, socio-demographic characteristics, and anthropometry and body composition were measured. At the end of the follow up, the following main outcomes were determined: pregnancy outcomes (incidence of gestational diabetes mellitus, pre-eclampsia, pregnancy-induced hypertension, weight gain during pregnancy, type of delivery, and neonatal outcomes (gestational age, birth weight, gender, Apgar score 1 min/5 min, type of resuscitation (I/II/III/IV), and pH of umbilical cord blood). Descriptive statistics for cross-sectional data, linear mixed regression models for absolute differences in changes baseline-final measurements were used as statistical analyses. DISCUSSION: Although the effectiveness of physical activity programmes on improving maternal and neonatal outcomes has heretofore been studied, the impact of free time physical activity during pregnancy has not been assessed using objective measures. This paper reports the design of a prospective cohort study that aims to assess the physical activity levels of pregnant women, and to estimate the relationship between those physical activity levels with maternal and neonatal outcomes. This study could contribute to providing evidence for the formulation of recommendations for physical activity for pregnant women.

Cryo-electron tomography of plunge-frozen whole bacteria and vitreous sections to analyze the recently described bacterial cytoplasmic structure, the Stack.

Cryo-electron tomography (CET) of plunge-frozen whole bacteria and vitreous sections (CETOVIS) were used to revise and expand the structural knowledge of the "Stack", a recently described cytoplasmic structure in the Antarctic bacterium Pseudomonas deceptionensis M1(T). The advantages of both techniques can be complementarily combined to obtain more reliable insights into cells and their components with three-dimensional imaging at different resolutions. Cryo-electron microscopy (Cryo-EM) and CET of frozen-hydrated P. deceptionensis M1(T) cells confirmed that Stacks are found at different locations within the cell cytoplasm, in variable number, separately or grouped together, very close to the plasma membrane (PM) and oriented at different angles (from 35° to 90°) to the PM, thus establishing that they were not artifacts of the previous sample preparation methods. CET of plunge-frozen whole bacteria and vitreous sections verified that each Stack consisted of a pile of oval disc-like subunits, each disc being surrounded by a lipid bilayer membrane and separated from each other by a constant distance with a mean value of 5.2±1.3nm. FM4-64 staining and confocal microscopy corroborated the lipid nature of the membrane of the Stacked discs. Stacks did not appear to be invaginations of the PM because no continuity between both membranes was visible when whole bacteria were analyzed. We are still far from deciphering the function of these new structures, but a first experimental attempt links the Stacks with a given phase of the cell replication process.

New insights into the toxicity mechanism of octanoic and decanoic acids on Saccharomyces cerevisiae.

Octanoic (C8) and decanoic (C10) acids are produced in hypoxic conditions by the yeast Saccharomyces cerevisiae as by-products of its metabolism and are considered fermentation inhibitors in the presence of ethanol at acidic pH. This study aims to broaden our understanding of the physiological limits between toxicity and ester production in yeast cells. To this end, the non-inhibitory concentration (NIC) and maximum inhibitory concentration (MIC) values were first established for C8 and C10 at physiological pH (5.8) without ethanol. The results showed that when these acids were added to culture medium at these values, they tended to accumulate in different cellular fractions of the yeast. While C8 was almost entirely located in the cell wall fraction, C10 was found in the endocellular fraction. Cell fatty acid detoxification was also different; while the esterification of fatty acids was more efficient in the case of C10, the peroxisome was activated regardless of which fatty acid was added. Furthermore, the study of the Pdr12 and Tpo1 transporters that evolved during the detoxification process revealed that C8 was mostly expelled by the Pdr12 carrier, which was related to higher ß-oxidative damage in the presence of endocellular C10. C10 is more toxic at lower concentrations than C8. Although they are produced by yeast, the resulting intracellular medium-chain fatty acids (MCFAs) caused a level of toxicity which promoted cell death. However, MCFAs are involved in the production of beverage flavours.

Effects of exercise during pregnancy on mode of delivery: a meta-analysis.

INTRODUCTION: We conducted a systematic review and meta-analysis to examine the influence of physical exercise interventions on the mode of delivery of healthy pregnant women with low to moderate levels of physical activity. MATERIAL AND METHODS: Key words were used to conduct a computerized search for articles on the topic in six databases: Cochrane Library Plus, Science Direct, EMBASE, PubMed, Web of Science and ClinicalTrials.gov. Ten randomized controlled trials were identified and included in the meta-analysis. Main outcome measures were mode of delivery (normal, instrumental vaginal, or cesarean delivery) and physical activity. RESULTS: Relative risk reductions and their 95% confidence interval were calculated for each study, and the heterogeneity of the studies was estimated using Cochran's Q statistic. The evidence suggests that physical exercise during pregnancy may increase the likelihood of normal delivery (relative risk = 1.12, 95% confidence interval 1.01-1.24; p = 0.041), in particular when exercise takes place during the second and third trimesters (relative risk = 1.14, 95% confidence interval 1.01-1.32; p = 0.048), even reducing the risk of cesarean delivery (relative risk = 0.66, 95% confidence interval 0.46-0.96; p = 0.028). CONCLUSIONS: Regular exercise during pregnancy appears to modestly increase the chance for normal delivery among healthy pregnant women. This applies to women with low to moderate levels of physical activity, but studies are needed to understand better the effect of physical exercise of moderate to vigorous intensity in the different trimesters.

Effect of hydroxytyrosol, Moringa, and spirulina on the physicochemical properties and nutritional characteristics of gluten-free brownies.

Brownies, enriched with fiber and Moringa oleifera, hydroxytyrosol (HXT), and spirulina (encapsulated and nonencapsulated), and dietary fiber using psyllium were elaborated. For that, a commercial control (CTRL) and an experimental control (CTRL) (without antioxidants) were compared. Color, nutritional composition, pH, antioxidant capacity, total phenolic compounds, as well as sensory properties were evaluated. The results showed the brownies developed with psyllium and the different extracts increased total dietary fiber compared to CTRL Commercial and CTRL, with E-spirulina (14.93 g/100 g) and Moringa (11.91 g/100 g) being the most prominent samples. However, with regard to soluble fiber, the highest content of NE-spirulina and the lowest content of HXT were observed. In addition, brownies enriched with extracts showed higher antioxidant capacity and higher phenolic compounds than controls, with HXT standing out at 299.25 µM Trolox/g in ABTS, 1470.08 µM Trolox/g in DPPH, and 18.15 µM Trolox/g in FRAP. However, a high level of phenolic compounds was found in E-Spirulina (604.71 mg/L). In reference to fatty acids, monounsaturated fatty acids (MUFA) (70%) were the predominant fatty acids, followed by polyunsaturated fatty acids (PUFA) (19%) and saturated fatty acids (SFA) (10%). Glutamic acid and asparagine were the predominant amino acids. As for mineral content, N-spirulina and E-spirulina were the brownies with the highest iron bioaccessibility; Si, Na, B, Al, P, Fe, Zn, Bi, Ca, Cu, Mg, Mn, Rb, S, and Sr being the most abundant elements in the brownies of this study. In addition, the HXT and Moringa samples scored higher in overall acceptability compared to the controls. The findings suggest that the incorporation of psyllium, quinoa flour, and antioxidant extracts in brownies could be a viable approach to produce a healthy brownie enriched with fiber, antioxidants and, therefore, considering the nutritional, physicochemical, and organoleptic characteristics, HTX is the ideal compound to enrich bakery products.

Genetic improvement of Saccharomyces cerevisiae wine strains for enhancing cell viability after desiccation stress.

In the last few decades spontaneous grape must fermentations have been replaced by inoculated fermentation with Saccharomyces cerevisiae strains as active dry yeast (ADY). Among the essential genes previously characterized to overcome the cell-drying/rehydration process, six belong to the group of very hydrophilic proteins known as hydrophilins. Among them, only SIP18 has shown early transcriptional response during dehydration stress. In fact, the overexpression in S. cerevisiae of gene SIP18 increases cell viability after the dehydration process. The purpose of this study was to characterize dehydration stress tolerance of three wild and one commercial S. cerevisiae strains of wine origin. The four strains were submitted to transformation by insertion of the gene SIP18. Selected transformants were submitted to the cell-drying-rehydration process and yeast viability was evaluated by both viable cell count and flow cytometry. The antioxidant capacity of SIP18p was illustrated by ROS accumulation reduction after H2 O2 attack. Growth data as cellular duplication times and lag times were calculated to estimate cell vitality after the cell rehydration process. The overexpressing SIP18 strains showed significantly longer time of lag phase despite less time needed to stop the leakage of intracellular compounds during the rehydration process. Subsequently, the transformants were tested in inoculated grape must fermentation at laboratory scale in comparison to untransformed strains. Chemical analyses of the resultant wines indicated that no significant change for the content of secondary compounds was detected. The obtained data showed that the transformation enhances the viability of ADY without affecting fermentation efficiency and metabolic behaviour.

Clinical Significance of the Pre-Transplant CXCR3 and CCR6 Expression on T Cells In Kidney Graft Recipients.

BACKGROUND: T cells play a fundamental role in the processes that mediate graft rejection, tolerance, and defense against infections. The CXCR3 and CCR6 receptors, highly expressed in Th1 (type 1 T helper cells)/Tc1 (T cytotoxic cells, type 1), Th1-Tc1, and Th17-Tc17 lymphocytes, respectively, participate in cell migration toward inflamed tissues. The altered expression level of CXCR3 and CCR6 has been associated with different clinical events after renal transplantation, such as acute rejection (AR) and chronic graft dysfunction, but data are still limited. In this study, we evaluated the expression of the receptor CXCR3 and CCR6 in peripheral blood T lymphocytes from kidney transplant recipients (KTR) and their association with viral infections, AR, and allograft function. METHODS: Through flow cytometry, the peripheral blood expression of CXCR3 and CCR6 in T cells was evaluated in a pretransplant collection of KTR. The levels of these T subpopulations and their association with the incidence of AR, kidney graft function, viral infections, cytomegalovirus, and BK virus were studied. Adverse clinical events and graft function were monitored during the first year post transplant. RESULTS: KTRs with low pretransplantation levels of Th17 (CD4+CXCR3-CCR6+) (tertile 1, Th17<16.4%) had a higher risk of suffering AR during the first year post transplantation (P = .033). KTRs with viral infections or reactivations during the first 3 months post transplantation had significantly lower levels of Tc17 (CD8+CXCR3-CCR6+) and higher levels of Th1 (CD4+CXCR3+CCR6-). In patients with cytomegalovirus reactivations, the viral peak correlates negatively with the pretransplant levels of Th1 (r = -0.606, P = .037). CONCLUSIONS: Pretransplantation assessment of Th1-Th17 and Tc1-Tc17 levels may help predict post-transplant clinical events such as AR and reactivation of viral infections.

Electrical Stimulation Induced Current Distribution in Peripheral Nerves Varies Significantly with the Extent of Nerve Damage: A Computational Study Utilizing Convolutional Neural Network and Realistic Nerve Models.

Although electrical stimulation is an established treatment option for multiple central nervous and peripheral nervous system diseases, its effects on the tissue and subsequent safety of the stimulation are not well understood. Therefore, it is crucial to design stimulation protocols that maximize therapeutic efficacy while avoiding any potential tissue damage. Further, the stimulation levels need to be adjusted regularly to ensure that they are safe even with the changes to the nerve due to long-term stimulation. Using the latest advances in computing capabilities and machine learning approaches, we developed computational models of peripheral nerve stimulation based on very high-resolution cross-sectional images of the nerves. We generated nerve models constructed from non-stimulated (healthy) and over-stimulated (damaged) rat sciatic nerves to examine how the current density distribution is affected by nerve damage. Using our in-house numerical solver, the Admittance Method (AM), we computed the induced current distribution inside the nerves and compared the current penetration for healthy and damaged nerves. Our computational results indicate that when the nerve is damaged, primarily evidenced by the decreased nerve fiber packing, the current penetrates deeper inside the nerve than in the healthy case. As safety limits for electrical stimulation of biological tissue are still debated, we ultimately aim to utilize our computational models to determine refined safety criteria and help design safer and more efficacious electrical stimulation protocols.

Block Copolymer-Based Magnetic Mixed Matrix Membranes-Effect of Magnetic Field on Protein Permeation and Membrane Fouling.

In this study, we report the impact of the magnetic field on protein permeability through magnetic-responsive, block copolymer, nanocomposite membranes with hydrophilic and hydrophobic characters. The hydrophilic nanocomposite membranes were composed of spherical polymeric nanoparticles (NPs) synthesized through polymerization-induced self-assembly (PISA) with iron oxide NPs coated with quaternized poly(2-dimethylamino)ethyl methacrylate. The hydrophobic nanocomposite membranes were prepared via nonsolvent-induced phase separation (NIPS) containing poly (methacrylic acid) and meso-2,3-dimercaptosuccinic acid-coated superparamagnetic nanoparticles (SPNPs). The permeation experiments were carried out using bovine serum albumin (BSA) as the model solute, in the absence of the magnetic field and under permanent and cyclic magnetic field conditions OFF/ON (strategy 1) and ON/OFF (strategy 2). It was observed that the magnetic field led to a lower reduction in the permeate fluxes of magnetic-responsive membranes during BSA permeation, regardless of the magnetic field strategy used, than that obtained in the absence of the magnetic field. Nevertheless, a comparative analysis of the effect caused by the two cyclic magnetic field strategies showed that strategy 2 allowed for a lower reduction of the original permeate fluxes during BSA permeation and higher protein sieving coefficients. Overall, these novel magneto-responsive block copolymer nanocomposite membranes proved to be competent in mitigating biofouling phenomena in bioseparation processes.

Exercise versus Metformin to Improve Pregnancy Outcomes among Overweight Pregnant Women: A Systematic Review and Network Meta-Analysis.

Being overweight is associated with pregnancy-related disorders such as gestational diabetes mellitus (GDM), hypertensive disorders of pregnancy (HDP), and excessive maternal weight gain (MWG). Exercise and metformin reduce the risk of these disorders. This network meta-analysis (NMA) aims to compare the effect of metformin and different types of exercise (aerobic, resistance and combined) on the risk of GDM, HDP, and MWG among overweight/obese pregnant women. Medline, EMBASE, Web of Science and Cochrane Library were searched from inception to June 2021. Meta-analyses and NMAs were performed. Sixteen randomized controlled trials were included. In the NMA, aerobic exercise showed an effect on GDM (RR = 0.51, 95% CI = 0.26, 0.97), and metformin a reduction in MWG (MWG = -2.93 kg, 95% CI = -4.98, -0.87). No intervention showed any effect on the reduction of HDP. Our study suggests that aerobic exercise may have the greatest effect in reducing the risk of GDM, and perhaps, the MWG. Strategies should be developed to increase adherence to this type of intervention among overweight women without contraindications. Although metformin could reduce MWG, medicalization of pregnancy in healthy women is not justified with the present results. More research is needed on the effect of the intensity and frequency of exercise sessions and the length of interventions.

Monitoring of B Cell in Kidney Transplantation: Development of a Novel Clusters Analysis and Role of Transitional B Cells in Transplant Outcome.

BACKGROUND: B lymphocytes (BL) seem to play an important role in transplantation, although the and role of different subpopulations in monitoring and outcome is not clear. Our aim was to monitoring immunological profiles based on BL subpopulations in kidney recipients (KR) with the risk of acute rejection (AR). METHODS: Monitoring of BL subpopulations was performed by flow cytometry in PBLs before transplantation and three and six months after transplantation (PTX). We used two methodological approaches, a traditional analysis, and a novel cluster analysis, to determine the association between BL subpopulations, AR incidence, and graft function. RESULTS: After three months of PTX, KRs with a B phenotype enriched in transitional BL and plasmablasts had better kidney function and lower AR incidence. KRs with decreased transitional BL and plasmablasts were associated with lower kidney function and higher AR PTX. KRs that had an increase in transitional BL PTX had a better clinical outcome. The increase in transitory BL during PTX was also associated with an increase in Tregs. Indeed, KRs receiving thymoglobulin as induction therapy showed a slight decrease in the relative frequency of naive BLs after three months of PTX. CONCLUSION: The monitoring of BL subpopulations may serve as a non-invasive tool to improve immunological follow-up of patients after kidney transplantation. However, further studies are needed to confirm the obtained results, define cut-off values, and standardize more optimal and even custom/customized protocols.

Interpregnancy Weight Change and Hypertension During Pregnancy: A Systematic Review and Meta-analysis.

OBJECTIVE: To synthesize evidence regarding the association between interpregnancy weight change and hypertensive disorders of pregnancy. DATA SOURCES: MEDLINE, EMBASE, Cochrane Library, Web of Science, and ClinicalTrials.gov databases were systematically searched from the databases' interception until April 2019. Search strategy included the terms: "interpregnancy," "intergestational," "hypertension" and "hypertensive disorders." METHODS OF STUDY SELECTION: Studies that assessed the relationship between interpregnancy weight change and hypertensive disorders of pregnancy were included. Twelve studies and 415,605 women were included in this systematic review and meta-analysis. We used Mendeley reference manager during the review process. Odds ratios (ORs) for the most adjusted models reported by the included articles and the corresponding 95% CIs were calculated. The no weight change category defined by each study was used as the reference category. TABULATION, INTEGRATION, AND RESULTS: Overall, there was an increased risk of hypertensive disorders of pregnancy associated with interpregnancy weight gain (OR 1.37; 95% CI 1.21-1.53; I=62.1%; P<.001). Additionally, interpregnancy weight loss was associated with lower risk of developing hypertensive disorders of pregnancy (OR 0.87; 95% CI 0.75-0.99; I=54.9%; P=.01), Finally, meta-regression showed that interpregnancy weight gain was associated with a graded increase in the risk of hypertensive disorders of pregnancy. CONCLUSION: This systematic review and meta-analysis provides evidence that interpregnancy weight gain is associated with an increased risk of hypertensive disorders of pregnancy, gestational hypertension, and preeclampsia. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42018103002.