Interferon-λ and interleukin 22 act synergistically for the induction of interferon-stimulated genes and control of rotavirus infection.

The epithelium is the main entry point for many viruses, but the processes that protect barrier surfaces against viral infections are incompletely understood. Here we identified interleukin 22 (IL-22) produced by innate lymphoid cell group 3 (ILC3) as an amplifier of signaling via interferon-λ (IFN-λ), a synergism needed to curtail the replication of rotavirus, the leading cause of childhood gastroenteritis. Cooperation between the receptor for IL-22 and the receptor for IFN-λ, both of which were 'preferentially' expressed by intestinal epithelial cells (IECs), was required for optimal activation of the transcription factor STAT1 and expression of interferon-stimulated genes (ISGs). These data suggested that epithelial cells are protected against viral replication by co-option of two evolutionarily related cytokine networks. These data may inform the design of novel immunotherapy for viral infections that are sensitive to interferons.

Interleukin-22 protects intestinal stem cells against genotoxic stress.

Environmental genotoxic factors pose a challenge to the genomic integrity of epithelial cells at barrier surfaces that separate host organisms from the environment. They can induce mutations that, if they occur in epithelial stem cells, contribute to malignant transformation and cancer development1-3. Genome integrity in epithelial stem cells is maintained by an evolutionarily conserved cellular response pathway, the DNA damage response (DDR). The DDR culminates in either transient cell-cycle arrest and DNA repair or elimination of damaged cells by apoptosis4,5. Here we show that the cytokine interleukin-22 (IL-22), produced by group 3 innate lymphoid cells (ILC3) and γδ T cells, is an important regulator of the DDR machinery in intestinal epithelial stem cells. Using a new mouse model that enables sporadic inactivation of the IL-22 receptor in colon epithelial stem cells, we demonstrate that IL-22 is required for effective initiation of the DDR following DNA damage. Stem cells deprived of IL-22 signals and exposed to carcinogens escaped DDR-controlled apoptosis, contained more mutations and were more likely to give rise to colon cancer. We identified metabolites of glucosinolates, a group of phytochemicals contained in cruciferous vegetables, to be a widespread source of genotoxic stress in intestinal epithelial cells. These metabolites are ligands of the aryl hydrocarbon receptor (AhR)6, and AhR-mediated signalling in ILC3 and γδ T cells controlled their production of IL-22. Mice fed with diets depleted of glucosinolates produced only very low levels of IL-22 and, consequently, the DDR in epithelial cells of mice on a glucosinolate-free diet was impaired. This work identifies a homeostatic network protecting stem cells against challenge to their genome integrity by AhR-mediated 'sensing' of genotoxic compounds from the diet. AhR signalling, in turn, ensures on-demand production of IL-22 by innate lymphocytes directly regulating components of the DDR in epithelial stem cells.

Ultra-rapid lispro improved postprandial glucose control compared to insulin lispro in predominantly Chinese patients with type 1 diabetes: A prospective, randomized, double-blind phase 3 study.

AIMS: To investigate the efficacy and safety of ultra-rapid lispro (URLi) versus insulin lispro in predominantly Chinese patients with type 1 diabetes (T1D) in a prospective, randomized, double-blind, treat-to-target, phase 3 study. MATERIALS AND METHODS: Following a lead-in period, during which insulin glargine U-100 or insulin degludec U-100 was optimized, patients were randomly assigned (1:1) to URLi (n = 176) or insulin lispro (n = 178). The primary objective was to test the noninferiority of URLi to insulin lispro in glycaemic control (noninferiority margin = 0.4% for glycated haemoglobin [HbA1c] change from baseline to week 26), with testing for the superiority of URLi to insulin lispro with regard to 1- and 2-hour postprandial glucose (PPG) excursions during a mixed-meal tolerance test and HbA1c change at week 26 as the multiplicity-adjusted objectives. RESULTS: From baseline to week 26, HbA1c decreased by 0.21% and 0.28% with URLi and insulin lispro, respectively, with a least squares mean treatment difference of 0.07% (95% confidence interval -0.11 to 0.24; P = 0.467). URLi demonstrated smaller 1- and 2-hour PPG excursions at week 26 with least squares mean treatment differences of -1.0 mmol/L (-17.8 mg/dL) and -1.4 mmol/L (-25.5 mg/dL), respectively (p < 0.005 for both) versus insulin lispro. The safety profiles of URLi and insulin lispro were similar. CONCLUSIONS: In this study, URLi administered in a basal-bolus regimen demonstrated superiority to insulin lispro in controlling PPG excursions, with noninferiority of HbA1c control in predominantly Chinese patients with T1D.

Seascape genomics of the pink abalone (Haliotis corrugata): An insight into a cross-border species in the northeast Pacific coast.

Seascape genomics gives insight into the geographic and environmental factors shaping local adaptations. It improves the understanding of the potential effects of climate change, which is relevant to provide the basis for the international management of fishery resources. The pink abalone (Haliotis corrugata) is distributed from California, United States to Baja California Sur, Mexico, exposed to a latitudinal environmental gradient in the California Current System. Management of the pink abalone contrasts between Mexico and the United States; Mexico has an active fishery organized in four administrative areas, while the United States has kept the fishery in permanent closure since 1996. However, the impact of environmental factors on genetic variation along the species distribution remains unknown, and understanding this relationship is crucial for effective spatial management strategies. This study aims to investigate the neutral and adaptive genomic structure of H. corrugata. A total of 203 samples from 13 locations were processed using ddRADseq, and covering the species' distribution. Overall, 2,231 neutral, nine potentially adaptive and three genomic-environmental association loci were detected. The neutral structure identified two groups: 1) California, United States and 2) Baja California Peninsula, México. In addition, the adaptive structure analysis also detected two groups with genetic divergence observed at Punta Eugenia. Notably, the seawater temperature significantly correlated with the northern group (temperate) and the southern (warmer) group. This study is a valuable foundation for future research and conservation initiatives, emphasizing the importance of considering neutral and adaptive genetic factors when developing management strategies for marine species.

Motivational drivers for health professionals in a large quality improvement collaborative project in Brazil: a qualitative study.

BACKGROUND: The success of collaborative quality improvement (QI) projects in healthcare depends on the context and engagement of health teams; however, the factors that modulate teams' motivation to participate in these projects are still unclear. The objective of the current study was to explore the barriers to and facilitators of motivation; the perspective was health professionals in a large project aiming to implement evidence-based infection prevention practices in intensive care units of Brazilian hospitals. METHODS: This qualitative study was based on content analysis of semistructured in-depth interviews held with health professionals who participated in a collaborative QI project named "Improving patient safety on a large scale in Brazil". In accordance with the principle of saturation, we selected a final sample of 12 hospitals located throughout the five regions of Brazil that have implemented QI; then, we conducted videoconference interviews with 28 health professionals from those hospitals. We encoded the interview data with NVivo software, and the interrelations among the data were assessed with the COM-B model. RESULTS: The key barriers identified were belief that improvement increases workload, lack of knowledge about quality improvement, resistance to change, minimal involvement of physicians, lack of supplies, lack support from senior managers and work overload. The primary driver of motivation was tangible outcomes, as evidenced by a decrease in infections. Additionally, factors such as the active participation of senior managers, teamwork, learning in practice and understanding the reason for changes played significant roles in fostering motivation. CONCLUSION: The motivation of health professionals to participate in collaborative QI projects is driven by a variety of barriers and facilitators. The interactions between the senior manager, quality improvement teams, and healthcare professionals generate attitudes that modulate motivation. Thus, these aspects should be considered during the implementation of such projects. Future research could explore the cost-effectiveness of motivational approaches.

Hospital care direct costs due to ambulatory care sensitive conditions related to diabetes mellitus in the Mexican public healthcare system.

BACKGROUND: Hospitalizations for ambulatory care sensitive conditions (ACSC) incur substantial costs on the health system that could be partially avoided with adequate outpatient care. Complications of chronic diseases, such as diabetes mellitus (DM), are considered ACSC. Previous studies have shown that hospitalizations due to diabetes have a significant financial burden. In Mexico, DM is a major health concern and a leading cause of death, but there is limited evidence available. This study aimed to estimate the direct costs of hospitalizations by DM-related ACSC in the Mexican public health system. METHODS: We selected three hospitals from each of Mexico's main public institutions: the Mexican Social Security Institute (IMSS), the Ministry of Health (MoH), and the Institute of Social Security and Services for State Workers (ISSSTE). We employed a bottom-up microcosting approach from the healthcare provider perspective to estimate the total direct costs of hospitalizations for DM-related ACSC. Input data regarding length of stay (LoS), consultations, medications, colloid/crystalloid solutions, procedures, and laboratory/medical imaging studies were obtained from clinical records of a random sample of 532 hospitalizations out of a total of 1,803 DM-related ACSC (ICD-10 codes) discharges during 2016. RESULTS: The average cost per DM-related ACSC hospitalization varies among institutions, ranging from $1,427 in the MoH to $1,677 in the IMSS and $1,754 in the ISSSTE. The three institutions' largest expenses are LoS and procedures. Peripheral circulatory and renal complications were the major drivers of hospitalization costs for patients with DM-related ACSC. Direct costs due to hospitalizations for DM-related ACSC in these three institutions represent 1% of the gross domestic product (GDP) dedicated to health and social services and 2% of total hospital care expenses. CONCLUSIONS: The direct costs of hospitalizations for DM-related ACSC vary considerably across institutions. Disparities in such costs for the same ACSC among different institutions suggest potential disparities in care quality across primary and hospital settings (processes and resource utilization), which should be further investigated to ensure optimal supply utilization. Prioritizing preventive measures for peripheral circulatory and renal complications in DM patients could be highly beneficial.

Adverse Childhood Experiences and Their Relationships with Perceived Stress and Self-Care Behaviors in African American Social Work Students: Insights from a Latent Class Analysis.

Based on stress sensitization theory and stress proliferation theory, this study was designed to identify adverse childhood experience (ACE) classes and their relationships with perceived stress and self-care behaviors. Hypotheses were that (a) there would be diverse ACE classes among African American social work students; (b) the identified classes embedded in high/multiple ACEs would have greater levels of perceived stress than those in low ACEs; and (c) the identified classes embedded in high/multiple ACEs would have lower levels of self-care behaviors than those in low ACEs. Recruited from one of the South's historically Black colleges and universities, 186 African American social work students completed an online survey. Latent class analysis found three classes fit the data best: low ACEs, high divorce/abuse/neglect, and high/multiple ACEs. Students in the high divorce/abuse/neglect class had the greatest levels of perceived stress and significantly greater perceived stress levels than the low ACEs class. The low ACEs class had greater self-care behaviors than students in the other two ACEs classes. The study revealed diverse ACE classes and the effect of more ACEs on greater perceived stress and lower self-care behaviors, supporting the importance of using a range of approaches to support African American social work students with different ACEs.

Human Metapneumovirus Infections during COVID-19 Pandemic, Spain.

We describe an unusual outbreak of respiratory infections caused by human metapneumovirus in children during the sixth wave of COVID-19 in Spain, associated with the Omicron variant. Patients in this outbreak were older than usual and showed more hypoxia and pneumonia, longer length of stay, and greater need for intensive care.

The transcription factor T-bet is induced by IL-15 and thymic agonist selection and controls CD8αα(+) intraepithelial lymphocyte development.

CD8αα(+) intraepithelial lymphocytes (IELs) are instrumental in maintaining the epithelial barrier in the intestine. Similar to natural killer cells and other innate lymphoid cells, CD8αα(+) IELs constitutively express the T-box transcription factor T-bet. However, the precise role of T-bet for the differentiation or function of IELs is unknown. Here we show that mice genetically deficient for T-bet lacked both TCRαß(+) and TCRγδ(+) CD8αα(+) IELs and thus are more susceptible to chemically induced colitis. Although T-bet was induced in thymic IEL precursors (IELPs) as a result of agonist selection and interleukin-15 (IL-15) receptor signaling, it was dispensable for the generation of IELPs. Subsequently, T-bet was required for the IL-15-dependent activation, differentiation, and expansion of IELPs in the periphery. Our study reveals a function of T-bet as a central transcriptional regulator linking agonist selection and IL-15 signaling with the emergence of CD8αα(+) IELs.

[Comparative analysis of the accreditation of medical facilities in Canada, Chile, the Autonomous Community of Andalusia, Denmark, and MexicoAnálise comparativa da acreditação de estabelecimentos de saúde no Canadá, Chile, Comunidade Autônoma da Andaluzia, Dinamarca e México]. / Análisis comparativo de la acreditación de unidades médicas en Canadá, Chile, la Comunidad Autónoma de Andalucía, Dinamarca y México.

Objective: To compare and contrast the characteristics of the accreditation process for health care facilities in Canada, Chile, the Autonomous Community of Andalusia (Spain), Denmark, and Mexico, in order to identify shared characteristics, differences, and lessons learned that may be useful for other countries and regions. Methods: An observational, analytical, retrospective study using open-access secondary sources on the accreditation and certification of health care facilities in 2019-2021 in these countries and regions. The general characteristics of the accreditation processes are described and comments are made on key aspects of the design of these programs. Additionally, analytical categories were created for degree of implementation and level of complexity, and the positive and negative results reported are summarized. Results: The operational components of the accreditation processes are country-specific, although they share similarities. The Canadian program is the only one that involves some form of responsive evaluation. There is a wide range in the percentage of establishments accredited from country to country (from 1% in Mexico to 34.7% in Denmark). Notable lessons learned include the complexity of application in a mixed public-private system (Chile), the risk of excessive bureaucratization (Denmark), and the need for clear incentives (Mexico). Conclusions: The accreditation programs operate in a unique way in each country and region, achieve varying degrees of implementation, and have an assortment of problems, from which lessons can be learned. Elements that hinder their implementation should be considered and adjustments made for the health systems of each country and region.

Objetivo: Comparar as características do processo de acreditação de estabelecimentos de saúde no Canadá, Chile, Comunidade Autônoma da Andaluzia, Dinamarca e México, a fim de identificar elementos comuns e diferenças, bem como lições aprendidas que podem ser úteis para outros países e regiões. Métodos: Estudo observacional, analítico e retrospectivo usando fontes secundárias de livre acesso sobre acreditação e certificação de estabelecimentos de saúde durante o período 2019-2021 nos países e regiões supracitados. As características gerais do processo de acreditação e suas respostas a pontos-chave no delineamento de tais programas foram descritas. Além disso, foram geradas categorias de análise para o andamento de sua implantação e seu grau de complexidade, e os desfechos favoráveis e desfavoráveis relatados foram resumidos. Resultados: Os componentes operacionais do processo de acreditação são peculiares a cada país, embora compartilhem certas semelhanças. O programa canadense é o único que contempla algum tipo de avaliação responsiva. Houve grande variação entre países no percentual de estabelecimentos acreditados (de 1% no México a 34,7% na Dinamarca). Entre as lições aprendidas, destacam-se a complexidade da aplicação do sistema misto público-privado (Chile), o risco de burocratização excessiva (Dinamarca) e a necessidade de incentivos claros (México). Conclusões: Os programas de acreditação operam de forma peculiar em cada país ou região, têm diferentes escopos e também apresentam diversos problemas a partir dos quais podemos aprender. É preciso considerar os elementos que dificultam a implementação e realizar as adequações necessárias para os sistemas de saúde de cada país ou região.

A Novel Combination of Sotorasib and Metformin Enhances Cytotoxicity and Apoptosis in KRAS-Mutated Non-Small Cell Lung Cancer Cell Lines through MAPK and P70S6K Inhibition.

Novel inhibitors of KRAS with G12C mutation (sotorasib) have demonstrated short-lasting responses due to resistance mediated by the AKT-mTOR-P70S6K pathway. In this context, metformin is a promising candidate to break this resistance by inhibiting mTOR and P70S6K. Therefore, this project aimed to explore the effects of the combination of sotorasib and metformin on cytotoxicity, apoptosis, and the activity of the MAPK and mTOR pathways. We created dose-effect curves to determine the IC50 concentration of sotorasib, and IC10 of metformin in three lung cancer cell lines; A549 (KRAS G12S), H522 (wild-type KRAS), and H23 (KRAS G12C). Cellular cytotoxicity was evaluated by an MTT assay, apoptosis induction through flow cytometry, and MAPK and mTOR pathways were assessed by Western blot. Our results showed a sensitizing effect of metformin on sotorasib effect in cells with KRAS mutations and a slight sensitizing effect in cells without K-RAS mutations. Furthermore, we observed a synergic effect on cytotoxicity and apoptosis induction, as well as a notable inhibition of the MAPK and AKT-mTOR pathways after treatment with the combination, predominantly in KRAS-mutated cells (H23 and A549). The combination of metformin with sotorasib synergistically enhanced cytotoxicity and apoptosis induction in lung cancer cells, regardless of KRAS mutational status.

Identification and Functional Analysis of APOB Variants in a Cohort of Hypercholesterolemic Patients.

Mutations in APOB are the second most frequent cause of familial hypercholesterolemia (FH). APOB is highly polymorphic, and many variants are benign or of uncertain significance, so functional analysis is necessary to ascertain their pathogenicity. Our aim was to identify and characterize APOB variants in patients with hypercholesterolemia. Index patients (n = 825) with clinically suspected FH were analyzed using next-generation sequencing. In total, 40% of the patients presented a variant in LDLR, APOB, PCSK9 or LDLRAP1, with 12% of the variants in APOB. These variants showed frequencies in the general population lower than 0.5% and were classified as damaging and/or probably damaging by 3 or more predictors of pathogenicity. The variants c.10030A>G;p.(Lys3344Glu) and c.11401T>A;p.(Ser3801Thr) were characterized. The p.(Lys3344Glu) variant co-segregated with high low-density lipoprotein (LDL)-cholesterol in 2 families studied. LDL isolated from apoB p.(Lys3344Glu) heterozygous patients showed reduced ability to compete with fluorescently-labelled LDL for cellular binding and uptake compared with control LDL and was markedly deficient in supporting U937 cell proliferation. LDL that was carrying apoB p.(Ser3801Thr) was not defective in competing with control LDL for cellular binding and uptake. We conclude that the apoB p.(Lys3344Glu) variant is defective in the interaction with the LDL receptor and is causative of FH, whereas the apoB p.(Ser3801Thr) variant is benign.

Robot-assisted radical cystectomy and ileal conduit with HugoTM RAS system: feasibility, setting and perioperative outcomes.

INTRODUCTION: Robotic approach has shown its feasibility and safety with respect to open approach for radical cystectomy (1). The performances of HugoTM RAS system (Medtronic, Minneapolis, USA) have been demonstrated in several clinical scenarios (2-5). We report the feasibility and surgical settings of the first series of robot-assisted radical cystectomy (RARC) with intracorporeal ileal-conduit performed with HugoTM RAS system. METHODS: Two patients were submitted to RARC with ileal conduit at our institution. The trocar placement scheme and the operating room setting with docking angles of the four arms were already described (6). A 12-mm and a 5-mm trocar for the assistant were placed. In both cases, an ileal-conduit with a Wallace type-1 uretero-enteric derivation was performed intra-corporeally. RESULTS: The first patient was a 71-year-old male with a very-high risk non-muscle invasive bladder cancer(BC), and the second patient was a 64-year-old male with a diagnosis of T2 high-grade BC. Operative times were 360 and 420 minutes with a docking time of 12 and 9 minutes, respectively. No intraoperative complications occurred. The estimated blood loss was 200ml and 400ml, respectively. The second patient developed an ileus on postoperative day 4 (Clavien-Dindo grade 2). No positive surgical margins were recorded. No recurrence nor progression occurred during follow-up. CONCLUSION: RARC with intracorporeal ileal conduit urinary diversion is feasible with HugoTM RAS system. We provided insight into the surgical setting using this novel robotic platform to help new adopters to face this challenging procedure. These findings may help a wider distribution of robotic programs for BC treatment.

Micro-CT analysis of the mandibular bone microarchitecture of rats after radiotherapy and low-power laser therapy.

To investigate whether low-level laser therapy (LLLT), at different times of application (immediate and late) in the region of the parotid glands, has a distance effect on the microarchitecture of the trabecular bone in mandible of rats irradiated by volumetric modular arc therapy (VMAT). Thirty adult Wistar rats were randomly divided into placebo control groups (CG, n = 2), only radiotherapy (RG, n = 2), only LPLT (LG, n = 2), and two other groups using LLLT in the immediate time (24 h) (ILG, n = 12) and late (120 h) (LLG, n = 12) to radiotherapy by VMAT in a single dose of 12 Gy. LLLT with AsGaAl laser (660 nm, 100 mW), a spot size of 0.0028 cm2, was applied in three points in the region of the right parotid gland, with energy of 2 J/cm2, 20 s per point, for 10 consecutive days. After euthanasia, the right hemimandibles of each animal were dissected, prepared, and analyzed by computerized microtomography (micro-CT) and histomorphometry. The different groups were analyzed by the Tukey and Bonferroni multiple comparison tests. The micro-CT analysis found statistically significant differences between the groups, especially in the LLG, which had the highest average bone volume compared to the CG (p = 0.001) and ILG (p = 0.002) and a greater number of trabeculae than the CG (p = 0.000) and ILG (p = 0.031). The ILG also had a higher number of trabeculae than the CG (p = 0.005). Trabecula separation (Tb.Sp) was lower in the LLG (p = 0.000) and ILG (p = 0.002) when compared to the CG. In the histomorphometry, there was no statistical difference between the groups in relation to all the analyzed variables. Micro-CT analysis showed that the LLLT, even applied at a distance, both in the immediate and late VMAT times, has an effect on the mandibular bone microarchitecture by increasing the volume and number of trabeculae and decreasing the spaces between them.

Identification of genuine and novel miRNAs in Amaranthus hypochondriacus from high-throughput sequencing data.

Amaranth has been proposed as an exceptional alternative for food security and climate change mitigation. Information about the distribution, abundance, or specificity of miRNAs in amaranth species is scare. Here, small RNAs from seedlings under control, drought, heat, and cold stress conditions of the Amaranthus hypocondriacus variety "Gabriela" were sequenced and miRNA loci identified in the amaranth genome using the ShortStack software. Fifty-three genuine miRNA clustersthirty-nine belonging to conserved families, and fourteen novel, were identified. Identification of their target genes suggests that conserved amaranth miRNAs are involved in growth and developmental processes, as well as stress responses. MiR0005, an amaranth-specific miRNA, exhibited an unusual high level of expression, akin to that of conserved miRNAs. Overall, our results broaden our knowledge regarding the distribution, abundance and expression of miRNAs in amaranth, providing the basis for future research on miRNAs and their functions in this important species.

Acreditación de servicios y calidad de la atención a neonatos en hospitales mexicanos.

OBJETIVO: Comparar la calidad de atención a neonatos con sepsis neonatal, hipoxia intrauterina, prematuridad y asfixia perinatal en hospitales acreditados (HA) y no acreditados (HNA). Material y métodos. Se evaluaron 28 hospi-tales de la Secretaría de Salud en 11 estados de México; la evaluación incluyó infraestructura, equipamiento e insumos, procesos de gestión de calidad e indicadores de calidad clínica. Se utilizó LQAS y se estimó el cumplimiento promedio de criterios e indicadores en HA y HNA. RESULTADOS: Hubo diferencias significativas en favor de HA en equipamiento e insumos y no significativas en existencia y funcionamiento de los comités hospitalarios. No hubo diferencias consistentes ni significativas en cumplimiento de indicadores clínicos entre los HA y HNA. CONCLUSIONES: La acreditación para la atención de neonatos con los diagnósticos seleccionados no se asocia a diferencias en la calidad de la atención.

S-allylcysteine induces cytotoxic effects in two human lung cancer cell lines via induction of oxidative damage, downregulation of Nrf2 and NF-κB, and apoptosis.

In this study, we investigated the putative cytotoxic effect elicited by the garlic-derived compound S-allylcysteine (SAC) in two human cancer cell lines (HCC827 and NCI-H1975) in order to develop an experimental approach to the therapeutic potential of this molecule for lung cancer. Cells were incubated for 24, 48 and 72 h in the presence of SAC (10 or 20 mM), which resulted in a concentration- and time-dependent decrease in cell viability and culture confluence in both cell lines. These effects were contrasted with - and validated through - those observed in an immortalized but nontumorigenic epithelial cell line from human bronchial epithelium (BEAS-2B, negative control) and an adenocarcinoma human alveolar basal epithelial cell line (A549, positive control). SAC (20 mM at 72 h) also increased the oxidative damage to lipids, augmented apoptosis, and decreased the expression of the nuclear factor erythroid 2-related factor 2 (Nrf2) and the nuclear factor kappa B (NF-κB) proteins in HCC827 and NCI-H1975 cells. Our results establish the efficacy of SAC in reducing malignant growth and proliferation of lung tumor cells. This effect is mediated by the induction of oxidative damage associated with the downregulation of Nrf2 and NF-κB and their corresponding signaling pathways.

Arterial blood stealing as a mechanism of negative BOLD response: From the steady-flow with nonlinear phase separation to a windkessel-based model.

Blood Oxygen Level Dependent (BOLD) signal indirectly characterizes neuronal activity by measuring hemodynamic and metabolic changes in the nearby microvasculature. A deeper understanding of how localized changes in electrical, metabolic and hemodynamic factors translate into a BOLD signal is crucial for the interpretation of functional brain imaging techniques. While positive BOLD responses (PBR) are widely considered to be linked with neuronal activation, the origins of negative BOLD responses (NBR) have remained largely unknown. As NBRs are sometimes observed in close proximity of regions with PBR, a blood "stealing" effect, i.e., redirection of blood from a passive periphery to the area with high neuronal activity, has been postulated. In this study, we used the Hagen-Poiseuille equation to model hemodynamics in an idealized microvascular network that account for the particulate nature of blood and nonlinearities arising from the red blood cell (RBC) distribution (i.e., the Fåhraeus, Fåhraeus-Lindqvist and the phase separation effects). Using this detailed model, we evaluate determinants driving this "stealing" effect in a microvascular network with geometric parameters within physiological ranges. Model simulations predict that during localized cerebral blood flow (CBF) increases due to neuronal activation-hyperemic response, blood from surrounding vessels is reallocated towards the activated region. This stealing effect depended on the resistance of the microvasculature and the uneven distribution of RBCs at vessel bifurcations. A parsimonious model consisting of two-connected windkessel regions sharing a supplying artery was proposed to simulate the stealing effect with a minimum number of parameters. Comparison with the detailed model showed that the parsimonious model can reproduce the observed response for hematocrit values within the physiological range for different species. Our novel parsimonious model promise to be of use for statistical inference (top-down analysis) from direct blood flow measurements (e.g., arterial spin labeling and laser Doppler/Speckle flowmetry), and when combined with theoretical models for oxygen extraction/diffusion will help account for some types of NBRs.

The health care sector in the economies of the European Union: an overview using an input-output framework.

BACKGROUND: This study aims to analyse the relative importance of the health care sector (health care activities and services), its interrelations with the rest of productive activities, aggregate supply and demand, employment requirements and apparent labour productivity in the European Union (EU) economy as a whole, and in the economies of member countries. METHODS: The methodology used is based on input-output analysis. Data are extracted from National Accounts and, specifically, from the input-output framework for 2010. Data in national currencies are adjusted using as a conversion factor, specific purchasing power parities for health. RESULTS: In the EU, market production predominates in the provision of health care activities, which are financed mainly by public funding. However, there is significant variability among countries, and, in fact, non-market production predominates in most EU countries. The health care sector has direct backward and forward linkages lower than the average for all sectors of the economy and the average for the services sector. Thus, this sector is relatively independent of the rest of the productive structure in the EU. The health care activities industry is key because of its ability to generate value added and employment. Regarding apparent labour productivity, there are significant differences among EU countries, showing that productivity is positively related to the weight of market production in health care activities and negatively related to the number of hours worked per person employed. CONCLUSIONS: Our results provide useful insights for health authorities in the EU, as they analyse the effect of health policies on macroeconomic indicators using an input-output framework, as well as comparing these effects with those in EU member countries. To the best of our knowledge, an analysis of the health care sector in the EU economy and the countries that integrate it using an input-output framework has not been undertaken. In addition, to compare health care expenditure between countries, data in national currencies have been adjusted using specific purchasing power parities for "health", and not ones referring to the total economy (GDP), which is common practice in many previous studies.

Disrespect and Abuse in Obstetric Care in Mexico: An Observational Study of Deliveries in Four Hospitals.

INTRODUCTION: To identify and describe the frequency and characteristics of disrespect and abuse practices towards women during facility-based delivery in four hospitals in two Mexican states in 2017, using a mixed method of direct observation and women's reports of health care experiences. METHODS: A cross-sectional study was performed to describe disrespect and abuse practices in obstetric care (interactions or conditions that are experienced as or intended to be humiliating or undignified) committed by healthcare providers. We included all pregnant women admitted for childbirth (vaginal and cesarean). Semi-structured interviews were also conducted with women, prior to discharge, regarding their experience at delivery. RESULTS: 867 deliveries were observed. 18.8% of women (n = 163) experienced at least one disrespect and abuse event, especially at secondary care facilities. There were a total of 493 disrespect and abuse events, which, on average, represents three events per woman (39.4% were verbal abuse, 32% were physical abuse, and 28.6% were discrimination). In the majority of cases (> 50%), women did not give consent to not recommended invasive procedures and were not provided with adequate information to those procedures. CONCLUSIONS FOR PRACTICE: Direct observation and interviews was a useful tool to identify disrespectful and abusive practices during delivery care. Our findings provide new evidence of the frequency and characteristics of disrespect and abuse during delivery care in Mexico, which can be used to inform maternal health programs. Additionally, these results encourage the creation of surveillance policies and committees in order to guarantee violence-free and dignified treatment of women during delivery care.