COVID-19 and Pregnancy: A Dangerous Mix for Bone Turnover and Metabolism Biomarkers in Placenta and Colostrum.

Background: In pregnant women, COVID-19 can alter the metabolic environment, cell metabolism, and oxygen supply of trophoblastic cells and, therefore, have a negative influence on essential mechanisms of fetal development. The purpose of this study was to investigate, for the first time, the effects of COVID-19 infection during pregnancy with regard to the bone turnover and endocrine function of several metabolic biomarkers in colostrum and placenta. Methods: One hundred and twenty-four pregnant mothers were recruited from three hospitals between June 2020 and August 2021 and assigned to two groups: Control group and COVID-19 group. Metabolism biomarkers were addressed in placental tissue and colostrum. Results: Lipocalin-2 and resistin levels were higher in the placenta, revealing an underlying pro-inflammatory status in the gestation period for mothers suffering from COVID-19; a decrease in GLP-1 and leptin was also observed in this group. As for adiponectin, resistin, and insulin, their concentrations showed an increase; a decrease in GLP-1, leptin, and PYY was also reported in the colostrum of mothers suffering from COVID-19 compared with the control group. Conclusions: As for bone turnover, placental samples from mothers with COVID-19 showed lower levels of OPG, while DKK-1 increased compared with the control group. Colostrum samples showed higher levels of OPG, SOST, and PTH in the COVID-19 group, a fact that could have noteworthy implications for energy metabolism, fetal skeletal development, and postnatal bone density and mineralization. Further research is needed to explain the pathogenic mechanism of COVID-19 that may affect pregnancy, so as to assess the short-term and long-term outcomes in infants' health.

Multiple scale assessment of habitat, landscape, and geographic-specific attributes driving decapod assemblages in Posidonia oceanica seagrass meadows.

Seagrass meadows are biodiversity hotspots for invertebrate species including decapods. Understanding the drivers of species abundance, richness and diversity of decapod assemblages is crucial for the conservation of such hotspots, but how drivers act across multiple spatial scales remains unexplored. Here we describe the decapod assemblages of Posidonia oceanica seagrass meadows and assess the influence of attributes from three increasing spatial scales (habitat, landscape, and geographical levels) on the assemblages' structure and composition, as well as the variability partitioning among each one of these levels. Overall, geographical level attributes (i.e., inlet aperture, confinement) affected the most the decapod assemblages, while we only found a modest contribution from habitat (e.g., detritus biomass, sediment organic matter) and landscape attributes (e.g., fragmentation). We suggest that decapod assemblages are driven by the interaction of multiple processes occurring at different scales and other highly stochastic phenomena such as larval dispersion and recruitment.

Post-publication research integrity concerns in randomized clinical trials: A scoping review of the literature.

BACKGROUND: Post-publication handling of integrity concerns in randomized clinical trials (RCTs) is a contentious matter. OBJECTIVES: We undertook a scoping systematic review to map the literature regarding post-publication integrity issues in RCTs. SEARCH STRATEGY AND SELECTION CRITERIA: Following prospective registration (https://osf.io/pgxd8) we initially searched PubMed and Scopus but subsequently extended it to include the Cochrane Library, and Google Scholar databases without language, article type or publication time restriction until November 2022. Reviewers independently selected published articles covering any aspect of post-publication research integrity concerns in RCTs. DATA COLLECTION AND ANALYSIS: The study findings grouped within domains relating to issues concerning post-publication integrity were extracted in duplicate, verified by a third reviewer, and then tabulated. MAIN RESULTS: The initial search captured 3159 citations, of which 89 studies were included in the review. Cross-sectional studies constituted the majority of included studies (n = 34, 38.2%), followed by systematic reviews (n = 10, 11.2%), methodology reviews/studies (n = 9, 10.1%) and other types of descriptive studies (n = 8, 9.0%). A total of 21 articles (23.6%) covered the domain on general issues, 25 (28.1%) in the journal's instructions and policies domain, eight (9.0%) in the editorial and peer review domain, one (1.1%) in the correspondence and complaints (post-publication peer review) domain, 12 (13.5%) in the investigation for concerns domain, six (6.7%) in the post-investigation decisions and sanctions domain, none in the critical appraisal guidance domain, five (5.6%) in the integrity assessment in systematic reviews domain, and 26 (29.2%) in the recommendations for future research domain. A total of 12 of the selected articles (13.5%) covered two (n = 9) or three (n = 3) different domains. CONCLUSIONS: Various research integrity domains and issues covering post-publication aspects of RCT integrity were captured and gaps were identified, mostly related with the necessary implications for all stakeholders to improve research transparency. There is an urgent need for a multistakeholder consensus towards creating specific statements for addressing post-publication integrity concerns in RCTs.

What Have We Learned about the Prevention of NMSC from Albino Patients from Malawi? Secondary Prevention Maintained over Time.

BACKGROUND: We have conducted cooperative campaigns focusing on albino patients in a rural area of Malawi. What have we learned? METHODS: Three surgical campaigns were performed in Nkhotakota district (2019-2023). Albino clinical and tumor characteristics were collected. RESULTS: Between 22 and 75 albinos were evaluated in each campaign (mean age < 28 years old). Most patients did not use sunscreen in a way that provided optimal photoprotection. Regarding tumors, the proportion of basal and squamous cell carcinomas ranged from 1:1 to almost 2:1. Of 156 albino patients, 34 attended more than once. However, of the 19 patients with 30 tumors operated on in 2021, only seven were assessed the following year (12 were lost to follow-up). At least 14 albinos with locally advanced tumors were evaluated. CONCLUSIONS: Distributing photoprotective clothing could be more efficient or perhaps an earlier measure of sunscreen in rural Africa as it does not require permanent repositioning. Very-high-risk patients (previous interventions with positive margins or high-risk tumors, intense actinic damage, and new tumors constantly appearing, especially those presenting SCCs) require close follow-up and treatment and represent our main target. Secondary prevention with Malawian collaboration and the use of teledermatology is essential for patient tracking, as they are able to offer curative treatments.

Adenosine receptors are the on-and-off switch of astrocytic cannabinoid type 1 (CB1) receptor effect upon synaptic plasticity in the medial prefrontal cortex.

The medial prefrontal cortex (mPFC) is involved in cognitive functions such as working memory. Astrocytic cannabinoid type 1 receptor (CB1R) induces cytosolic calcium (Ca2+) concentration changes with an impact on neuronal function. mPFC astrocytes also express adenosine A1 and A2A receptors (A1R, A2AR), being unknown the crosstalk between CB1R and adenosine receptors in these cells. We show here that a further level of regulation of astrocyte Ca2+ signaling occurs through CB1R-A2AR or CB1R-A1R heteromers that ultimately impact mPFC synaptic plasticity. CB1R-mediated Ca2+ transients increased and decreased when A1R and A2AR were activated, respectively, unveiling adenosine receptors as modulators of astrocytic CB1R. CB1R activation leads to an enhancement of long-term potentiation (LTP) in the mPFC, under the control of A1R but not of A2AR. Notably, in IP3R2KO mice, that do not show astrocytic Ca2+ level elevations, CB1R activation decreases LTP, which is not modified by A1R or A2AR. The present work suggests that CB1R has a homeostatic role on mPFC LTP, under the control of A1R, probably due to physical crosstalk between these receptors in astrocytes that ultimately alters CB1R Ca2+ signaling.

PGI1-mediated vascular oxidative pentose phosphate pathway modulates photosynthesis via long-distance cytokinin signaling.

In Arabidopsis, the plastidial isoform of phosphoglucose isomerase, PGI1, mediates growth and photosynthesis, likely due to its involvement in the vascular production of cytokinins (CK). To examine this hypothesis, we characterized pgi1-2 knockout plants impaired in PGI1 and pgi1-2 plants specifically expressing PGI1 in root tips and vascular tissues. Moreover, to investigate whether the phenotype of pgi1-2 plants is due to impairments in the plastidial oxidative pentose phosphate pathway (OPPP) or the glycolytic pathway, we characterized pgl3-1 plants with reduced OPPP and pfk4pfk5 knockout plants impaired in plastidial glycolysis. Compared with wild-type (WT) leaves, pgi1-2 leaves exhibited weaker expression of photosynthesis- and 2-C-methyl-D-erythritol 4-P (MEP) pathway-related proteins, and stronger expression of oxidative stress protection-related enzymes. Consistently, pgi1-2 leaves accumulated lower levels of chlorophyll, and higher levels of tocopherols, flavonols and anthocyanins than the WT. Vascular- and root tip-specific PGI1 expression countered the reduced photosynthesis, low MEP pathway-derived CK content, dwarf phenotype and the metabolic characteristics of pgi1-2 plants, reverting them to WT-like levels. Moreover, pgl3-1, but not pfk4pfk5 plants phenocopied pgi1-2. Histochemical analyses of plants expressing GUS under the control of promoter regions of genes encoding plastidial OPPP enzymes exhibited strong GUS activity in root tips and vascular tissues. Overall, our findings show that root tip and vascular PGI1-mediated plastidial OPPP activity affects photosynthesis and growth through mechanisms involving long-distance modulation of the leaf proteome by MEP pathway-derived CKs.

Association of aortic stiffness with abdominal vascular and coronary calcifications in patients with stage 3 and 4 chronic kidney disease.

RATIONALE AND OBJECTIVES: Increased central (aortic) arterial stiffness has hemodynamic repercussions that affect the incidence of cardiovascular and renal disease. In chronic kidney disease (CKD) there may be an increase in aortic stiffness secondary to multiple metabolic alterations including calcification of the vascular wall (VC). The objective of this study was to analyze the association of central aortic pressures and aortic stiffness with the presence of VC in abdominal aorta (AAC) and coronary arteries(CAC). MATERIALS AND METHODS: We included 87 pacientes with CKD stage 3 and 4. Using applanation tonometry, central aortic pressures and aortic stiffness were studied. We investigated the association of aortic pulse wave velocity (Pvc-f) and Pvc-f adjusted for age, blood pressure, sex and heart rate (Pvc-f index) with AAC obtained on lumbar lateral radiography and CAC assessed by multidetector computed tomography. AAC and CAC were scored according to Kauppila and Agatston methods, respecti-vely. For the study of the association between Pvc-f index, Kauppila score, Agatston score, central aortic pressures, clinical parameters and laboratory data, multiple and logistic regression were used. We investigated the diagnosis performance of the Pvc-f index for prediction of VC using receiver-operating characteristic (ROC). RESULTS: Pvc-f and Pvc-f index were 11.3 ± 2.6 and 10.6 m/s, respectively. The Pvc-f index was higher when CKD coexisted with diabetes mellitus (DM). AAC and CAC were detected in 77% and 87%, respectively. Albuminuria (ß = 0.13, p = 0.005) and Kauppila score (ß = 0.36, p = 0.001) were independently associated with Pvc-f index. In turn, Pvc-f index (ß = 0.39, p = 0.001), DM (ß = 0.46, p = 0.01), and smoking (ß = 0.53; p = 0.006) were associated with Kauppila score, but only Pvc-f index predicted AAC [OR: 3.33 (95% CI: 1.6-6.9; p = 0.001)]. The Kauppila score was independently associated with the Agatston score (ß = 1.53, p = 0.001). The presence of AAC identified patients with CAC with a sensitivity of 73%, a specificity of 100%, a positive predictive value of 100% and a negative predictive value of 38%. The Vpc-f index predicted the presence of CAC [OR: 3.35 (95% CI: 1.04-10.2, p = 0.04)]. In the ROC curves, using the Vpc-f index, the AUC for AAC and CAC was 0.82 (95%CI: 0.71-0.93, p = 0.001) and 0.81 (95% CI: 0.67-0.96, p = 0.02), respectively. CONCLUSIONS: When stage 3-4 CKD coexists with DM there is an increase in aortic stiffness determined by the Vpc-f index. In stage 3-4 CKD, AAC and CAC are very prevalent and both often coexist. The Vpc-f index is independently associated with AAC and CAC and may be useful in identifying patients with VC in these territories.

A pH-enhanced resolution in benchtop NMR spectroscopy.

NMR spectroscopy is one of the most potent methods in analytical chemistry. NMR titration experiments are particularly useful since they measure molecular binding affinities and other concentration-dependent effects. These experiments, however, require a long series of measurements. An alternative to these serial measurements has recently been presented, exploiting a pH (or generally - a concentration) gradient along the NMR tube. The proposed experiment, although efficient, was based on the sensitivity- and hardware-demanding chemical shift imaging (CSI) method. Thus, it is practically limited to high-resolution NMR spectrometers. This paper proposes modifying and adapting the approach to the popular and cost-efficient benchtop NMR machines. Instead of CSI, we use a device that shifts the NMR tube vertically to measure the spectra of different sample volumes, which have different pH values due to the established gradient along the tube. We demonstrate the potential of the method on the test samples of L-tyrosine and 2,6-lutidine, and two real samples from the food industry - an infant formula and an energy drink. The proposed method boosts spectral resolution and allows for the sampling of a broader range of pH values when compared to the original approach.

Comparative study of ultrasound application versus mechanical agitation on pork belly brining for bacon production.

Pork belly brining is a time-consuming step of bacon production that needs to be studied and enhanced through suitable technologies. In this sense, this study aimed at evaluating the impact of ultrasound (US), mechanical agitation (AG), and static brine (SB) on the kinetics of water loss (WL), solids gain (SG), and salt content (SC) of pork belly during brining under different temperatures. Mathematical models were used to estimate mass transfer rates, equilibrium parameters, and thermodynamic properties. Peleg model was chosen as the most suitable model to predict the kinetics experimental data (Radj2 ≥ 0.979 and RMSE ≤ 0.014). The increase in the brine temperature increased WL, SG, and SC for all treatments. Nonlinear effects of temperature were observed for WL, SG, and SC, following an Arrhenius-type behavior. The assistance of ultrasound significantly enhanced the velocity of WL, SG, and SC by 32-56%, while AG improved by 18-39% both compared to SB. Brining was considered an endothermic and non-spontaneous process through the thermodynamic assessment. The increase in temperature and the AG and US processes accelerated the formation of the activated complex. The application of ultrasound was considered the most suitable technology to reduce the brining time. However, significant improvements can be obtained by mechanical agitation. Therefore, both methods can be used to reduce the time processing of pork belly aiming at accelerating the bacon production process.

Decentralized Mixed Effects Modeling in COINSTAC.

Performing group analysis on magnetic resonance imaging (MRI) data with linear mixed-effects (LME) models is challenging due to its large dimensionality and inherent multi-level covariance structure. In addition, as large-scale collaborative projects become commonplace in neuroimaging, data must increasingly be stored and analyzed from different locations. In such settings, substantial overhead can occur in terms of data transfer and coordination between participating research groups. In some cases, data cannot be pooled together due to privacy or regulatory concerns. In this work, we propose a decentralized LME model to perform a large-scale analysis of data from different collaborations without data pooling. This method is efficient as it overcomes the hurdles of data sharing and has lower bandwidth and memory requirements for analysis than the centralized modeling approach. We evaluate our model using features extracted from structural magnetic resonance imaging (sMRI) data. Results highlight gray matter reductions in the temporal lobe/insula and medial frontal regions in schizophrenia, consistent with prior studies. Our analysis also demonstrates that decentralized LME models achieve similar performance compared to the models trained with all the data in one location. We also implement the decentralized LME approach in COINSTAC, an open source, decentralized platform for federating neuroimaging analysis, providing an easy to use tool for dissemination to the neuroimaging community.

Optimizing measurements of linear changes of NMR signal parameters.

Serial NMR experiments are commonly applied in variable-temperature studies, reaction monitoring, and other tasks. The resonance frequencies often shift linearly over the series, and the shift rates help to characterize the studied system. They can be determined using a classical fitting of peak positions or a more advanced method of Radon transform. However, the optimal procedure for data collection remains to be determined. In this paper, we discuss how to invest experimental time, i.e., whether to measure more scans at the expense of the number of spectra or vice versa. The results indicate that classical fitting provides slightly less error than the Radon transform, although the latter can be the method of choice for a low signal-to-noise ratio. We demonstrate this fact through theoretical consideration, simulations, and an experiment. Finally, we extend our considerations to the linear fitting of peak amplitudes. Interestingly, the optimal setup for measuring peak height changes differs from the one for resonance frequency changes - fewer spectra with more scans provide better results.

Interval between balloon removal and oxytocin administration in cervical ripening with double-balloon in singleton pregnancies: An observational study.

OBJECTIVE: To analyze the influence of the resting interval after removal of a double-balloon for cervical ripening and oxytocin administration on the time to onset of active labor in singleton pregnancies. METHODS: A retrospective cohort study of women who required a cervical ripening with double-balloon was conducted between January 2019 and December 2022. We collected data for cervical ripening balloon insertion and removal, oxytocin administration, suspicious or pathological cardiotocographic trace, mode of delivery, maternal and neonatal complications, neonatal outcomes. Proportional hazards model comparing resting interval between double-balloon cervical ripening removal and oxytocin administration. RESULTS: A total of 403 singleton pregnancies were recruited and 213 pregnant women experienced a rest of 12 h between cervical balloon removal and oxytocin administration (resting group). Oxytocin was administered immediately after balloon removal in 190 women (non-resting group). Median insertion-to-active labor interval and insertion-to-delivery interval were significantly shorter in the non-resting group: 18.5 versus 24.0 h, HR 2.59 (CI 95%: 1.97-3.41) and 24.0 versus 29.0 h, HR 2.38 (CI 95%: 1.85-3.05) respectively. Bishop score change and mode of delivery between were similar in both groups. No differences in maternal nor neonatal complications between both groups were found. CONCLUSIONS: Oxytocin administration immediately after removal of a double-balloon for cervical ripening compared with 12 h delayed interval resulted in a shortened time from insertion to active labor onset and to delivery interval without increasing maternal or neonatal adverse outcomes.

Lipid-rich particles of processed food waste for microalgae harvest through lipid-enriched floating biomat formation.

Food waste was collected from the campus canteen and lipid-rich particles (LRP) phase was evaluated to harvest Tetradesmus obliquus. Box-Behnken design showed the highest harvest efficiency (HE) of 84.69 % in run#1 (LRP = 30 %; initial OD680 = 1.75; and harvest time = 6 h). Numerical optimization ramps suggested 24.15 % (v/v) LRP ratio, initial OD680 3.00, and harvest time 3.82 h for maximum HE. Two flocs were observed, a precipitate at the bottom (B-Floc) and a floating biomat (F-Floc). Experimental results showed HE of 88.3 %, with 67 % and 33 % of the harvested biomass forming F-Floc and B-Floc, respectively. Pre-heating of LRP in a boiling water bath for 10 min (HFB-T10) promoted F-Floc proportion up to 91.6 %. In addition, HFB-T10 showed the highest FAMEs yield of 11.17 g/L of the total used volume, which was significantly higher than that of the centrifuged cells and heat-untreated biomat. Moreover, HFB-T10 showed better iodine value and cetane number of the produced biodiesel.

Biphasic NMR of Hyperpolarized Suspensions-Real-Time Monitoring of Solute-to-Solid Conversion to Watch Materials Grow.

Nuclear magnetic resonance (NMR) spectroscopy is a key method for the determination of molecular structures. Due to its intrinsically high (i.e., atomistic) resolution and versatility, it has found numerous applications for investigating gases, liquids, and solids. However, liquid-state NMR has found little application for suspensions of solid particles as the resonances of such systems are excessively broadened, typically beyond the detection threshold. Herein, we propose a route to overcoming this critical limitation by enhancing the signals of particle suspensions by >3.000-fold using dissolution dynamic nuclear polarization (d-DNP) coupled with rapid solid precipitation. For the proof-of-concept series of experiments, we employed calcium phosphate (CaP) as a model system. By d-DNP, we boosted the signals of phosphate 31P spins before rapid CaP precipitation inside the NMR spectrometer, leading to the inclusion of the hyperpolarized phosphate into CaP-nucleated solid particles within milliseconds. With our approach, within only 1 s of acquisition time, we obtained spectra of biphasic systems, i.e., micrometer-sized dilute solid CaP particles coexisting with their solution-state precursors. Thus, this work is a step toward real-time characterization of the solid-solution equilibrium. Finally, integrating the hyperpolarized data with molecular dynamics simulations and electron microscopy enabled us to shed light on the CaP formation mechanism in atomistic detail.

Sex differences in muscle protein expression and DNA methylation in response to exercise training.

BACKGROUND: Exercise training elicits changes in muscle physiology, epigenomics, transcriptomics, and proteomics, with males and females exhibiting differing physiological responses to exercise training. However, the molecular mechanisms contributing to the differing adaptations between the sexes are poorly understood. METHODS: We performed a meta-analysis for sex differences in skeletal muscle DNA methylation following an endurance training intervention (Gene SMART cohort and E-MTAB-11282 cohort). We investigated for sex differences in the skeletal muscle proteome following an endurance training intervention (Gene SMART cohort). Lastly, we investigated whether the methylome and proteome are associated with baseline cardiorespiratory fitness (maximal oxygen consumption; VO2max) in a sex-specific manner. RESULTS: Here, we investigated for the first time, DNA methylome and proteome sex differences in response to exercise training in human skeletal muscle (n = 78; 50 males, 28 females). We identified 92 DNA methylation sites (CpGs) associated with exercise training; however, no CpGs changed in a sex-dependent manner. In contrast, we identified 189 proteins that are differentially expressed between the sexes following training, with 82 proteins differentially expressed between the sexes at baseline. Proteins showing the most robust sex-specific response to exercise include SIRT3, MRPL41, and MBP. Irrespective of sex, cardiorespiratory fitness was associated with robust methylome changes (19,257 CpGs) and no proteomic changes. We did not observe sex differences in the association between cardiorespiratory fitness and the DNA methylome. Integrative multi-omic analysis identified sex-specific mitochondrial metabolism pathways associated with exercise responses. Lastly, exercise training and cardiorespiratory fitness shifted the DNA methylomes to be more similar between the sexes. CONCLUSIONS: We identified sex differences in protein expression changes, but not DNA methylation changes, following an endurance exercise training intervention; whereas we identified no sex differences in the DNA methylome or proteome response to lifelong training. Given the delicate interaction between sex and training as well as the limitations of the current study, more studies are required to elucidate whether there is a sex-specific training effect on the DNA methylome. We found that genes involved in mitochondrial metabolism pathways are differentially modulated between the sexes following endurance exercise training. These results shed light on sex differences in molecular adaptations to exercise training in skeletal muscle.

Methylome and proteome integration in human skeletal muscle uncover group and individual responses to high-intensity interval training.

Exercise is a major beneficial contributor to muscle metabolism, and health benefits acquired by exercise are a result of molecular shifts occurring across multiple molecular layers (i.e., epigenome, transcriptome, and proteome). Identifying robust, across-molecular level targets associated with exercise response, at both group and individual levels, is paramount to develop health guidelines and targeted health interventions. Sixteen, apparently healthy, moderately trained (VO2 max = 51.0 ± 10.6 mL min-1 kg-1 ) males (age range = 18-45 years) from the Gene SMART (Skeletal Muscle Adaptive Responses to Training) study completed a longitudinal study composed of 12-week high-intensity interval training (HIIT) intervention. Vastus lateralis muscle biopsies were collected at baseline and after 4, 8, and 12 weeks of HIIT. DNA methylation (~850 CpG sites) and proteomic (~3000 proteins) analyses were conducted at all time points. Mixed models were applied to estimate group and individual changes, and methylome and proteome integration was conducted using a holistic multilevel approach with the mixOmics package. A total of 461 proteins significantly changed over time (at 4, 8, and 12 weeks), whilst methylome overall shifted with training only one differentially methylated position (DMP) was significant (adj.p-value < .05). K-means analysis revealed cumulative protein changes by clusters of proteins that presented similar changes over time. Individual responses to training were observed in 101 proteins. Seven proteins had large effect-sizes >0.5, among them are two novel exercise-related proteins, LYRM7 and EPN1. Integration analysis showed bidirectional relationships between the methylome and proteome. We showed a significant influence of HIIT on the epigenome and more so on the proteome in human muscle, and uncovered groups of proteins clustering according to similar patterns across the exercise intervention. Individual responses to exercise were observed in the proteome with novel mitochondrial and metabolic proteins consistently changed across individuals. Future work is required to elucidate the role of these proteins in response to exercise.

Consultas médicas per cápita en el sistema de salud del Perú, 2019. Hacia una nueva descripción del sistema de salud peruano

Introducción. El objetivo del estudio es contribuir a una nueva mirada del sistema de salud peruano a partir de la producción de bienes públicos en salud. Métodos. Se calculó el promedio de prestaciones de salud per cápita producidas por el sistema de salud peruano en niveles nacional, regional y provincial, a partir de fuentes de datos abiertos de la Superintendencia Nacional de Salud (SUSALUD), el Seguro Integral de Salud (SIS) y el Seguro Social de Salud (EsSalud) para el año 2019. Se desarrolló un análisis exploratorio de asociación entre las consultas médicas per cápita y variables socio-económicas. Resultados. Se encontró un promedio nacional de consultas médicas per cápita de 1,8, encontrándose una gran variabilidad de valores a nivel regional (2,9 a 0,8). A nivel provincias se encontró un primer cuartil superior, 50 provincias con valores entre 5,52 y 1,75 que concentran el 55% de la población peruana y el 71,3% de todas las prestaciones médicas. Un segundo cuartil agrupa 47 provincias con valores entre 1,73 - 1,33 y dos cuartiles inferiores que agrupan a 95 provincias con valores entre 1,32 y 0,08. El análisis exploratorio mostro asociación entre las consultas médicas per cápita a nivel regional y las variables analizadas, destacando la tasa de médicos por 1000 habitantes (R2: 064, valor p= 0,000) y el producto bruto interno regional per cápita (R2: 0,59, valor p=0,000). Conclusiones. La distribución por cuartiles en la producción de consultas médicas per cápita permiten identificar territorios con mejor atención, con mayor definición que los atributos de estructura del sistema (número de establecimientos, médicos por 1000 habitantes).

Introduction. The objective of the study is to contribute with a new perspective about the peruvian health system, based on the production of public goods in health. Methods. For this purpose, we calculated the per capita average of health encounters produced by the peruvian health system at the national, regional and provincial levels. Information was collected on the number of medical encounters, registered at the open data sources of the National Health Superintendence (SUSALUD), the Public Health Insurance (SIS), and the Health Social Insurance (EsSalud) for year 2019. Results. The national average of medical encounters per capita was 1.8, with a great variability of values at the regional level (2.9 to 0.8). In the case of the provinces, a first upper quartile was found, which group 50 provinces with values between 5.52 and 1.75 and concentrate 55% of the Peruvian population and 71.3% of all medical encounters produced by the health system. A second quartile groups 47 provinces, with values between 1.73 - 1.33; and two lower quartiles that group 95 provinces with values between 1.32 and 0.08. We showed an association between per capita medical encounters at the regional level and the socio-economic variables analyzed, in particular the Density of Physicians per 1000 population (R2: 0.64, p-value= 0.000) and the regional gross domestic product per capita (R2: 0.59, p-value=0.000). Conclusion. Medical encounters per capita is a useful indicator, that allows us to identify better served territories, with higher definition than other structure indicators (doctors per 1000 people; number of facilities).

Colostrum Features of Active and Recovered COVID-19 Patients Revealed Using Next-Generation Proteomics Technique, SWATH-MS.

Colostrum performs nutritional, anti-inflammatory and anti-infective functions and promotes immune system formation and organ development. The new coronavirus, SARS-CoV-2, has generated concerns about viral transmission through human milk, with a lack of evidence about human milk's protective effects against the infection. This study aimed at analyzing presence of the virus and at identifying the protein expression profile of human colostrum in active and COVID-19-recovered patients. Colostrum samples were collected from women with COVID-19 (n = 3), women recently recovered from the infection (n = 4), and non-infected women (n = 5). The samples were analyzed by means of RT-qPCR to determine presence of the virus and using SWATH-MS for proteomic analysis. Proteomic results were then analyzed using bioinformatic methods. The viral tests were negative for SARS-CoV-2 in the colostrum from COVID-19 patients. The proteomic analysis identified 301 common proteins in all samples analyzed. Nineteen proteins were upregulated and 7 were downregulated in the COVID-19 group versus the control samples, whereas 18 were upregulated and 7 were downregulated when comparing the COVID-19 group to the recovered group. Eleven proteins were biomarkers of active COVID-19 infection. Ten were upregulated: ACTN1, CD36, FAM3B, GPRC5B, IGHA2, IGK, PLTP, RAC1, SDCBP and SERPINF1, and one was downregulated: PSAP. These proteins are mainly related to immunity, inflammatory response and protein transport. In conclusion, the results of this study suggest that colostrum is not a vehicle for mother-to-child SARS-CoV-2 transmission. Moreover, the colostrum's proteome of active and recuperated patients indicate that it could provide immune benefits to infants.

Report from the society of magnetic resonance angiography: clinical applications of 7T neurovascular MR in the assessment of intracranial vascular disease.

In recent years, ultra-high-field magnetic resonance imaging (MRI) applications have been rapidly increasing in both clinical research and practice. Indeed, 7-Tesla (7T) MRI allows improved depiction of smaller structures with high signal-to-noise ratio, and, therefore, may improve lesion visualization, diagnostic capabilities, and thus potentially affect treatment decision-making. Incremental evidence emerging from research over the past two decades has provided a promising prospect of 7T magnetic resonance angiography (MRA) in the evaluation of intracranial vasculature. The ultra-high resolution and excellent image quality of 7T MRA allow us to explore detailed morphological and hemodynamic information, detect subtle pathological changes in early stages, and provide new insights allowing for deeper understanding of pathological mechanisms of various cerebrovascular diseases. However, along with the benefits of ultra-high field strength, some challenges and concerns exist. Despite these, ongoing technical developments and clinical oriented research will facilitate the widespread clinical application of 7T MRA in the near future. In this review article, we summarize technical aspects, clinical applications, and recent advances of 7T MRA in the evaluation of intracranial vascular disease. The aim of this review is to provide a clinical perspective for the potential application of 7T MRA for the assessment of intracranial vascular disease, and to explore possible future research directions implementing this technique.