Water deficit response in nodulated soybean roots: a comprehensive transcriptome and translatome network analysis.

BACKGROUND: Soybean establishes a mutualistic interaction with nitrogen-fixing rhizobacteria, acquiring most of its nitrogen requirements through symbiotic nitrogen fixation. This crop is susceptible to water deficit; evidence suggests that its nodulation status-whether it is nodulated or not-can influence how it responds to water deficit. The translational control step of gene expression has proven relevant in plants subjected to water deficit. RESULTS: Here, we analyzed soybean roots' differential responses to water deficit at transcriptional, translational, and mixed (transcriptional + translational) levels. Thus, the transcriptome and translatome of four combined-treated soybean roots were analyzed. We found hormone metabolism-related genes among the differentially expressed genes (DEGs) at the translatome level in nodulated and water-restricted plants. Also, weighted gene co-expression network analysis followed by differential expression analysis identified gene modules associated with nodulation and water deficit conditions. Protein-protein interaction network analysis was performed for subsets of mixed DEGs of the modules associated with the plant responses to nodulation, water deficit, or their combination. CONCLUSIONS: Our research reveals that the stand-out processes and pathways in the before-mentioned plant responses partially differ; terms related to glutathione metabolism and hormone signal transduction (2 C protein phosphatases) were associated with the response to water deficit, terms related to transmembrane transport, response to abscisic acid, pigment metabolic process were associated with the response to nodulation plus water deficit. Still, two processes were common: galactose metabolism and branched-chain amino acid catabolism. A comprehensive analysis of these processes could lead to identifying new sources of tolerance to drought in soybean.

Characterization of optical fibers doped with nanoparticles for distributed displacement sensing.

High-scattering optical fibers have emerged as a key component in distributed sensing systems, primarily due to their capacity to enhance signal-to-noise ratio. This paper presents an experimental characterization of optical fibers doped with oxide nanoparticles for displacement sensing. They were manufactured using the phase-separation technique and different doping compounds, including calcium, strontium, lanthanum and magnesium. The Rayleigh backscattering (RBS) signatures in time and frequency domains were acquired using an Optical Backscatter Reflectometer (OBR). The maximum representative length, backscattering gain and strain sensitivity were evaluated. The results indicate that the fiber co-doped with magnesium and erbium chlorides offered the best compromise between strain sensitivity (0.96 pm/µ ϵ) and maximum length (17 m). For conditions of single and multiple perturbations, strain saturation was reached at ≥7000 µm and <1500 µm, respectively. In addition, the results reveal that, under a condition of variable temperature (30-60 °C), the sensor response becomes significantly nonlinear over length, requiring a technique for temperature cross-sensitivity mitigation that accounts for nonlinearities in sensitivity and hysteresis.

Assessing the contributions of an urban population health initiative to shift political priority towards cardiovascular health: three case studies from Brazil, Mongolia and Senegal.

BACKGROUND: The urban population health initiative was designed as a multidisciplinary, multisector programme to address cardiovascular (CV) disease, specifically hypertension and its underlying causes in the cities of Ulaanbaatar, Mongolia; Dakar, Senegal; and São Paulo, Brazil. This article aims to provide an overview of the history and dynamics of CV disease policy making in the three countries, to present the policy reform contributions of the initiative and its role in the policy agenda-setting framework/process in each country and to identify the enablers and challenges to the initiative for doing so. METHODS: A qualitative case study was conducted for each setting from November 2020 to January 2021, comprised of a document review, semi-structured in-depth interviews and unstructured interviews with stakeholders involved in the initiative. The literature review included documents from the initiative and the peer-reviewed and grey literature with a total of 188 documents screened. Interviews were conducted with 21 stakeholders. Data collection and thematic analysis was guided by (i) the Kingdon multiple streams conceptual framework with the main themes being CV disease problems, policy, politics and the role of policy entrepreneurs; and (ii) the study question inquiring on the role of the urban population health initiative at the CV disease policy level and enabling and challenging factors to advancing CV disease policy. Data were thematically analysed using the Framework Method. RESULTS: Each setting was characterized by a high hypertension and CV disease burden combined with an aware and proactive political environment. Policy outcomes attributed to the initiative were updating the guidelines and/or algorithms of care for hypertension and including revised physical and nutritional education in school curricula, in each city. Overall, the urban health initiative's effects in the policy arena, were most prominent in Mongolia and Senegal, where the team effectively acted as policy entrepreneur, promoting the solutions/policies in alignment with the most pressing local problems and in strong involvement with the political actors. The initiative was also involved in improving access to CV disease drugs at primary health levels. Its success was influenced by the local governance structures, the proximity of the initiative to the policy makers and the local needs. In Brazil, needs were expressed predominantly in the clinical practice. CONCLUSIONS: This multi-country experience shows that, although the policy and political environment plays its role in shaping initiatives, often the local priority needs are the driving force behind wider change.

Situational analysis of hypertension management at primary health care level in São Paulo, Brazil: population, healthcare professional and health system perspectives.

BACKGROUND: Government-led, population-wide initiatives are crucial for advancing the management of hypertension - a leading cause of cardiovascular disease (CVD) morbidity and mortality. An urban population health initiative was conducted against this backdrop, focussing on hypertension in the primary health system in São Paulo, Brazil. Within the frame of the initiative and under the supervision and leadership of the municipal health authorities, a situational analysis was conducted on the needs in hypertension management, marking the first phase of a Design Thinking process. This article describes the situational analysis process and presents the identified elements to be strengthened considering hypertension diagnosis, treatment and control. METHODS: First, a mixed-methods approach was used, starting with a literature review of municipal hypertension data followed by meetings (N = 20) with the local public health administration to assess health system level components. To investigate activities on hypertension diagnosis, treatment and control, nine primary healthcare units were selected from two districts of São Paulo city- Itaquera and Penha- which received an online form addressed to managers, participated in conversation circles of staff and patients, and underwent shadowing of community health agents. RESULTS: Data gave rise to two main outputs: (i) a patient care journey map; and (ii) a matrix summarizing the identified needs at patient, healthcare professional and health system level for diagnosis, treatment and control of hypertension. Patient awareness and knowledge of hypertension was found to be insufficient and its management needs to be improved. For health professionals, disease awareness, technical training, more time dedicated to patients, and simplified guidelines and clinical decision-making tools for hypertension management were identified as principal needs. The situational analysis found that the healthcare systems efficiency might be improved by establishing defined treatment and care delivery goals with a focus on outcomes and implemented through action plans. CONCLUSIONS: This situational analysis identified several needs related to hypertension control in São Paulo that are in line with global challenges to improve the control of CVD risk factors. Findings were also confirmed locally in an expansion phase of this situational analysis to additional primary care facilities. As a consequence, solutions were designed, promptly taken up and implemented by the municipal health secretariat.

The Healthy and Diseased Retina Seen through Neuron-Glia Interactions.

The retina is the sensory tissue responsible for the first stages of visual processing, with a conserved anatomy and functional architecture among vertebrates. To date, retinal eye diseases, such as diabetic retinopathy, age-related macular degeneration, retinitis pigmentosa, glaucoma, and others, affect nearly 170 million people worldwide, resulting in vision loss and blindness. To tackle retinal disorders, the developing retina has been explored as a versatile model to study intercellular signaling, as it presents a broad neurochemical repertoire that has been approached in the last decades in terms of signaling and diseases. Retina, dissociated and arranged as typical cultures, as mixed or neuron- and glia-enriched, and/or organized as neurospheres and/or as organoids, are valuable to understand both neuronal and glial compartments, which have contributed to revealing roles and mechanisms between transmitter systems as well as antioxidants, trophic factors, and extracellular matrix proteins. Overall, contributions in understanding neurogenesis, tissue development, differentiation, connectivity, plasticity, and cell death are widely described. A complete access to the genome of several vertebrates, as well as the recent transcriptome at the single cell level at different stages of development, also anticipates future advances in providing cues to target blinding diseases or retinal dysfunctions.

Legume-rhizobia symbiosis: Translatome analysis.

Leguminous plants can establish endosymbiotic relationships with nitrogen-fixing soil rhizobacteria. Bacterial infection and nodule organogenesis are two independent but highly coordinated genetic programs that are active during this interaction. These genetic programs can be regulated along all the stages of gene expression. Most of the studies, for both eukaryotes and prokaryotes, focused on the transcriptional regulation level determining the abundance of mRNAs. However, it has been demonstrated that mRNA levels only sometimes correlate with the abundance or activity of the coded proteins. For this reason, in the past two decades, interest in the role of translational control of gene expression has increased, since the subset of mRNA being actively translated outperforms the information gained only by the transcriptome. In the case of legume-rhizobia interactions, the study of the translatome still needs to be explored further. Therefore, this review aims to discuss the methodologies for analyzing polysome-associated mRNAs at the genome-scale and their contribution to studying translational control to understand the complexity of this symbiotic interaction. Moreover, the Dual RNA-seq approach is discussed for its relevance in the context of a symbiotic nodule, where intricate multi-species gene expression networks occur.

Heterologous versus homologous COVID-19 booster vaccination in previous recipients of two doses of CoronaVac COVID-19 vaccine in Brazil (RHH-001): a phase 4, non-inferiority, single blind, randomised study.

INTRODUCTION: The inactivated whole-virion SARS-CoV-2 vaccine (CoronaVac, Sinovac) has been widely used in a two-dose schedule. We assessed whether a third dose of the homologous or a different vaccine could boost immune responses. METHODS: RHH-001 is a phase 4, participant masked, two centre, safety and immunogenicity study of Brazilian adults (18 years and older) in São Paulo or Salvador who had received two doses of CoronaVac 6 months previously. The third heterologous dose was of either a recombinant adenoviral vectored vaccine (Ad26.COV2-S, Janssen), an mRNA vaccine (BNT162b2, Pfizer-BioNTech), or a recombinant adenoviral-vectored ChAdOx1 nCoV-19 vaccine (AZD1222, AstraZeneca), compared with a third homologous dose of CoronaVac. Participants were randomly assigned (5:6:5:5) by a RedCAP computer randomisation system stratified by site, age group (18-60 years or 61 years and over), and day of randomisation, with a block size of 42. The primary outcome was non-inferiority of anti-spike IgG antibodies 28 days after the booster dose in the heterologous boost groups compared with homologous regimen, using a non-inferiority margin for the geometric mean ratio (heterologous vs homologous) of 0·67. Secondary outcomes included neutralising antibody titres at day 28, local and systemic reactogenicity profiles, adverse events, and serious adverse events. This study was registered with Registro Brasileiro de Ensaios Clínicos, number RBR-9nn3scw. FINDINGS: Between Aug 16, and Sept 1, 2021, 1240 participants were randomly assigned to one of the four groups, of whom 1239 were vaccinated and 1205 were eligible for inclusion in the primary analysis. Antibody concentrations were low before administration of a booster dose with detectable neutralising antibodies of 20·4% (95% CI 12·8-30·1) in adults aged 18-60 years and 8·9% (4·2-16·2) in adults 61 years or older. From baseline to day 28 after the booster vaccine, all groups had a substantial rise in IgG antibody concentrations: the geometric fold-rise was 77 (95% CI 67-88) for Ad26.COV2-S, 152 (134-173) for BNT162b2, 90 (77-104) for ChAdOx1 nCoV-19, and 12 (11-14) for CoronaVac. All heterologous regimens had anti-spike IgG responses at day 28 that were superior to homologous booster responses: geometric mean ratios (heterologous vs homologous) were 6·7 (95% CI 5·8-7·7) for Ad26.COV2-S, 13·4 (11·6-15·3) for BNT162b2, and 7·0 (6·1-8·1) for ChAdOx1 nCoV-19. All heterologous boost regimens induced high concentrations of pseudovirus neutralising antibodies. At day 28, all groups except for the homologous boost in the older adults reached 100% seropositivity: geometric mean ratios (heterologous vs homologous) were 8·7 (95% CI 5·9-12·9) for Ad26.COV2-S vaccine, 21·5 (14·5-31·9) for BNT162b2, and 10·6 (7·2-15·6) for ChAdOx1 nCoV-19. Live virus neutralising antibodies were also boosted against delta (B.1.617.2) and omicron variants (B.1.1.529). There were five serious adverse events. Three of which were considered possibly related to the vaccine received: one in the BNT162b2 group and two in the Ad26.COV2-S group. All participants recovered and were discharged home. INTERPRETATION: Antibody concentrations were low at 6 months after previous immunisation with two doses of CoronaVac. However, all four vaccines administered as a third dose induced a significant increase in binding and neutralising antibodies, which could improve protection against infection. Heterologous boosting resulted in more robust immune responses than homologous boosting and might enhance protection. FUNDING: Ministry of Health, Brazil.

De novo genesis of retinal ganglion cells by targeted expression of Klf4 in vivo.

Retinal ganglion cell (RGC) degeneration is a hallmark of glaucoma, the most prevalent cause of irreversible blindness. Thus, therapeutic strategies are needed to protect and replace these projection neurons. One innovative approach is to promote de novo genesis of RGCs via manipulation of endogenous cell sources. Here, we demonstrate that the pluripotency regulator gene Krüppel-like factor 4 (Klf4) is sufficient to change the potency of lineage-restricted retinal progenitor cells to generate RGCs in vivo Transcriptome analysis disclosed that the overexpression of Klf4 induces crucial regulators of RGC competence and specification, including Atoh7 and Eya2 In contrast, loss-of-function studies in mice and zebrafish demonstrated that Klf4 is not essential for generation or differentiation of RGCs during retinogenesis. Nevertheless, induced RGCs (iRGCs) generated upon Klf4 overexpression migrate to the proper layer and project axons aligned with endogenous fascicles that reach the optic nerve head. Notably, iRGCs survive for up to 30 days after in vivo generation. We identified Klf4 as a promising candidate for reprogramming retinal cells and regenerating RGCs in the retina.This article has an associated 'The people behind the papers' interview.

Implementing a multisector public-private partnership to improve urban hypertension management in low-and middle- income countries.

BACKGROUND: Cardiovascular disease presents an increasing health burden to low- and middle-income countries. Although ample therapeutic options and care improvement frameworks exist to address its prime risk factor, hypertension, blood pressure control rates remain poor. We describe the results of an effectiveness study of a multisector urban population health initiative that targets hypertension in a real-world implementation setting in cities across three continents. The initiative followed the "CARDIO4Cities" approach (quality of Care, early Access, policy Reform, Data and digital technology, Intersectoral collaboration, and local Ownership). METHOD: The approach was applied in Ulaanbaatar in Mongolia, Dakar in Senegal, and São Paulo in Brazil. In each city, a portfolio of evidence-based practices was implemented, tailored to local priorities and available data. Outcomes were measured by extracting hypertension diagnosis, treatment and control rates from primary health records. Data from 18,997 patients with hypertension in primary health facilities were analyzed. RESULTS: Over one to two years of implementation, blood pressure control rates among enrolled patients receiving medication tripled in São Paulo (from 12·3% to 31·2%) and Dakar (from 6·7% to 19·4%) and increased six-fold in Ulaanbaatar (from 3·1% to 19·7%). CONCLUSIONS: This study provides first evidence that a multisectoral population health approach to implement known best-practices, supported by data and digital technologies, and relying on local buy-in and ownership, can improve hypertension control in high-burden urban primary care settings in low-and middle-income countries.

Deconstructing design thinking as a tool for the implementation of a population health initiative.

BACKGROUND: The translation of evidence-based practices and rapid uptake of innovations into global health practice is challenging. Design thinking is a consultative process involving multiple stakeholders and has been identified as a promising solution to create and apply implementation strategies in complex environments like health systems. METHODS: We conducted a process evaluation of a real-world example, namely an initiative to innovate hypertension screening, diagnosis and care in São Paulo, Brazil. The parameters of the evaluation were informed by a specification rubric and categorization system, recommended for the investigation of implementation strategies, and the double-diamond conceptual framework to describe and examine the strategic architecture and nature of the design thinking approach, with particular emphasis on identifying potential areas of "value-add" particular to the approach. The retrospective evaluation was performed by an independent partner who had not been involved in the setting up and implementation of the design thinking process. RESULTS: The evaluation unveiled a dense catalogue of strategically driven, mostly theoretically based, activities involving all identified health system stakeholders including patients. Narrative reconstruction illuminated the systematic and coherent nature of this approach, with different resulting actions progressively accounting for all relevant layers of the health system to engineer a broad selection of specific implementation solutions. The relevance of the identified features and the mechanics used to promote more successful implementation practices was manifested in several distinct ways: design thinking offered a clear direction on which innovations really mattered and when, as well as several new dimensions for consideration in the development of an innovation mindset amongst stakeholders. It thereby promoted relationship quality in terms of familiarity and trust, and commitment to evidence-based enquiry and action. Design thinking was also able to navigate the territory between the need for intervention "fidelity" versus "adaptation" and provide the operational know-how to face familiar implementation hurdles. Lastly, it brought a new kind of skill set to the public health stakeholders that incorporated diplomacy, multidisciplinary approaches and management sciences-skills that are considered necessary but not yet widely taught as part of public health training. CONCLUSIONS: Design thinking is a sound and viable tool to use as part of an implementation strategy for engaging with health system stakeholders and successfully translating evidence-based practices and new innovations into routine practice, thereby addressing an important knowledge-practice gap and, more broadly, contributing to the strategic repertoire available to implementation science.

Morphofunctional programming of microglia requires distinct roles of type II myosins.

The ramified morphology of microglia and the dynamics of their membrane protrusions are essential for their functions in central nervous system development, homeostasis, and disease. Although their ability to change and control shape critically depends on the actin and actomyosin cytoskeleton, the underlying regulatory mechanisms remain largely unknown. In this study, we systematically analyzed the actomyosin cytoskeleton and regulators downstream of the small GTPase RhoA in the control of microglia shape and function. Our results reveal that (i) Myh9 controls cortical tension levels and affects microglia protrusion formation, (ii) cofilin-mediated maintenance of actin turnover regulates microglia protrusion extension, and (iii) Myh10 influences microglia inflammatory activation. Overall we uncover molecular pathways that regulate microglia morphology and identify type-II myosins as important regulators of microglia biology with differential roles in the control of cell shape (Myh9) and functions (Myh10).

An Optimized Self-Compensated Solution for Temperature and Strain Cross-Sensitivity in FBG Interrogators Based on Edge Filter.

Optical fiber sensors based on fiber Bragg gratings (FBGs) are prone to measurement errors if the cross-sensitivity between temperature and strain is not properly considered. This paper describes a self-compensated technique for canceling the undesired influence of temperature in strain measurement. An edge-filter-based interrogator is proposed and the central peaks of two FBGs (sensor and reference) are matched with the positive and negative slopes of a Fabry-Perot interferometer that acts as an optical filter. A tuning process performed by the grey wolf optimizer (GWO) algorithm is required to determine the optimal spectral characteristics of each FBG. The interrogation range is not compromised by the proposed technique, being determined by the spectral characteristics of the optical filter in accordance with the traditional edge-filtering interrogation. Simulations show that, by employing FBGs with optimal characteristics, temperature variations of 30 °C led to an average relative error of 3.4% for strain measurements up to 700µÏµ. The proposed technique was experimentally tested under non-ideal conditions: two FBGs with spectral characteristics different from the optimized results were used. The temperature sensibility decreased by 50.8% as compared to a temperature uncompensated interrogation system based on an edge filter. The non-ideal experimental conditions were simulated and the maximum error between theoretical and experimental data was 5.79%, proving that the results from simulation and experimentation are compatible.

Energization by multiple substrates and calcium challenge reveal dysfunctions in brain mitochondria in a model related to acute psychosis.

Schizophrenia etiology is unknown, nevertheless imbalances occurring in an acute psychotic episode are important to its development, such as alterations in cellular energetic state, REDOX homeostasis and intracellular Ca2+ management, all of which are controlled primarily by mitochondria. However, mitochondrial function was always evaluated singularly, in the presence of specific respiratory substrates, without considering the plurality of the electron transport system. In this study, mitochondrial function was analyzed under conditions of isolated or multiple respiratory substrates using brain mitochondria isolated from MK-801-exposed mice. Results showed a high H2O2 production in the presence of pyruvate/malate, with no change in oxygen consumption. In the condition of multiple substrates, however, this effect is lost. The analysis of Ca2+ retention capacity revealed a significant change in the uptake kinetics of this ion by mitochondria in MK-801-exposed animals. Futhermore, when mitochondria were exposed to calcium, a total loss of oxidative phosphorylation and an impressive increase in H2O2 production were observed in the condition of multiple substrates. There was no alteration in the activity of the antioxidant enzymes analyzed. The data demonstrate for the first time, in an animal model of psychosis, two important aspects (1) mitochondria may compensate deficiencies in a single mitochondrial complex when they oxidize several substrates simultaneously, (2) Ca2+ handling is compromised in MK-801-exposed mice, resulting in a loss of phosphorylative capacity and an increase in H2O2 production. These data favor the hypothesis that disruption of key physiological roles of mitochondria may be a trigger in acute psychosis and, consequently, schizophrenia.

Impact of early detection of acute invasive fungal rhinosinusitis in immunocompromised patients.

BACKGROUND: Early diagnosis of acute invasive fungal rhinosinusitis (AIFRS) is vital to improving outcomes in immunocompromised patients. This study evaluated the impact of a systematic protocol with nasal endoscopy and biopsies to early detect AIFRS in immunocompromised patients. Additionally, we compared the accuracy of frozen-section biopsy and culture with formalin-fixed paraffin-embedded (FFPE) biopsy. METHODS: Retrospective cohort in a Tertiary Referral Hospital. Patients with the suspected diagnosis of AIFRS were evaluated following a standardized protocol, including serial nasal endoscopies and biopsies when necessary. The sensitivity and specificity of frozen-section biopsy and culture were also compared with FFPE. RESULTS: The mortality rate related to AIFRS of this standardized cohort (13/43) was 30.2%. Better outcomes were observed in patients with disease limited to the turbinates and in those with higher peripheral neutrophils count. Frozen-section biopsy positivity correlated with FFPE findings for fungi detection (p-value < 0.0001), with a sensitivity of 90.6%, specificity of 72.7%, and accuracy of 86.0%. CONCLUSION: Implementation of this standardized protocol was related to a considerably low mortality rate among patients with suspected AIFRS at our Institution. Frozen-section biopsy revealed high accuracy to diagnose AIFRS. The current protocol including frozen-tissue biopsy improved the evaluation and survival rates of immunocompromised patients with presumed AIFRS.

Gender Dysphoria in a 62-Year-Old Genetic Female With Congenital Adrenal Hyperplasia.

We report a case of gender dysphoria (GD) in a 62-year-old genetic female patient, raising the pros and cons of performing corrective surgery later in life. This 46,XX DSD patient was registered and reared as a girl; CAH was diagnosed late in childhood. Poor adherence to treatment and lack of proper psychological management contributed to evident GD. Living for years as a male, the patient applied for a legitimate male identification document in his late 50s; thereafter, he requested a sex-reassignment surgery "to disguise his female body upon his death." We informed the patient and family about surgery hazards, while analytical therapy allowed the group to evaluate the actual wish for surgery. When the wish was brought up, the role of death urged the group to rethink the course of treatment. During the process, it became clear that the patient's desire for surgery, more than a wish for changing the genitalia, expressed an impulse related to issues of endorsement and acceptance of his male identity. This report raises interesting questions about sexuality in a social context and prompts the idea that sexuality is broader than sex itself, raising new questions on the psychological risks faced when considering a body change after years of living with a disorder of sex development.

Unraveling the signal scenario of fruit set.

Long-term goals to impact or modify fruit quality and yield have been the target of researchers for many years. Different approaches such as traditional breeding,mutation breeding, and transgenic approaches have revealed a regulatory network where several hormones concur in a complex way to regulate fruit set and development,and these networks are shared in some way among species with different kinds of fruits. Understanding the molecular and biochemical networks of fruit set and development could be very useful for breeders to meet the current and future challenges of agricultural problems.

Cytochrome P450 CYP78A9 is involved in Arabidopsis reproductive development.

Synchronized communication between gametophytic and sporophytic tissue is crucial for successful reproduction, and hormones seem to have a prominent role in it. Here, we studied the role of the Arabidopsis (Arabidopsis thaliana) cytochrome P450 CYP78A9 enzyme during reproductive development. First, controlled pollination experiments indicate that CYP78A9 responds to fertilization. Second, while CYP78A9 overexpression can uncouple fruit development from fertilization, the cyp78a8 cyp78a9 loss-of-function mutant has reduced seed set due to outer ovule integument development arrest, leading to female sterility. Moreover, CYP78A9 has a specific expression pattern in inner integuments in early steps of ovule development as well as in the funiculus, embryo, and integuments of developing seeds. CYP78A9 overexpression did not change the response to the known hormones involved in flower development and fruit set, and it did not seem to have much effect on the major known hormonal pathways. Furthermore, according to previous predictions, perturbations in the flavonol biosynthesis pathway were detected in cyp78a9, cyp78a8 cyp78a9, and empty siliques (es1-D) mutants. However, it appeared that they do not cause the observed phenotypes. In summary, these results add new insights into the role of CYP78A9 in plant reproduction and present, to our knowledge, the first characterization of metabolite differences between mutants in this gene family.

In vivo embryo production in cows superovulated 1 or 2 days after ovum pick-up.

The present study evaluated superovulatory responses and in vivo embryo production in cows treated with FSH starting 1 or 2 days after ovum pick-up (OPU). Thirty-three non-lactating Nelore cows were subjected to aspiration of all follicles ≥3mm for OPU. After OPU, cows were randomly divided into two groups in which the follicle superstimulatory treatments with FSH started 1 or 2 days after OPU (Groups D1 and D2, respectively). Data are presented as the least squares mean±s.e.m. The number of follicles ≥3mm before OPU was similar between groups (~34); however, cows in Group D2 had more follicles ≥3mm on the first day of FSH (15.2±2.3 vs 7.6±1.7; P=0.04) and a higher ratio of the number of follicles at first FSH/number of follicles before OPU (0.41±0.04 vs 0.24±0.02; P=0.01). In addition, Group D2 cows had a greater superovulatory response than did cows in Group D1 (18.9±2.8 vs 9.1±1.9 corpora lutea, respectively; P<0.03). However, there was no difference in the total number of recovered ova and embryos from cows in Groups D2 and D1 (5.1±1.4 vs 4.9±1.3, respectively; P>0.10). Nevertheless Group D2 cows had more freezable embryos than Group D1 cows (3.2±1.1 vs 1.3±0.5, respectively; P<0.05). Cows from Group D2 had a much higher proportion (P<0.001) of follicles ≥8mm compared with follicles ≥6mm and <8mm at the time of the last treatment with FSH. In conclusion, to obtain a greater production of viable embryos in superovulated cows after OPU, it is recommended to wait at least 2 days before starting FSH treatment.

Epidemiological Assessment of a Pediatric Palliative Care Clinic at a Brazilian Quaternary Hospital: 20 Years of Experience.

Background: The pediatric palliative care (PPC) sets up an interdisciplinary approach of chronic complex diseases throughout birth to adolescence. It encompasses countless contrasts in development and diagnosis scopes, which make this area a challenge to nonpediatric practitioners. Objective: We sought to assess the most prevalent diseases in follow-up of the PPC team. Methods: We analyzed the medical records of PPC clinic during the years 2001 and 2021 and the diagnosis of outpatients. We established a parallel with the world scientific literature concerning the epidemiology of PPC. Results: The most prevalent diseases were epidermolysis bullosa (36.9%), followed by neurological Inherited Errors of Metabolism (IEM) diseases (19.0%), IEM diseases (14.3%), dysmorphological and chromosomal disorders (8.5%), skeletal disorders mainly osteogenesis imperfecta (6.9%), and liver transplantation conditions (5.5%) (p < 0.001). The less frequent conditions were external causes, such as neonatal insults or traffic accidents (2.8%), cancer (1.7%), congenital cardiopathies (1.4%), congenital infectious diseases (1.1%), gastrointestinal and hepatic conditions (0.8%), and rheumatological conditions (0.3%). The patients were older at diagnosis (6.9 years) and at PPC referral (13.2 years) than patients with epidermolysis bullosa and skeletal disorders and dysmorphological and chromosomal disorders were younger on referral. Conclusion: There are a lot of complex chronic conditions which could benefit from palliative care in pediatric setting. However, epidemiological and symptomatological assessment of the health service is necessary to provide an appropriate care to the country's reality.

An Intersectoral Approach to Hypertension Care: Solutions for Improving Blood Pressure Control in São Paulo, Brazil.

BACKGROUND: Hypertension is the leading risk factor for cardiovascular diseases (CVDs) and a major public health issue worldwide. In Brazil, it affects approximately 52.5% of the adult population. We describe the solutions package and the impact of a population health initiative in São Paulo city, following the CARDIO4Cities approach for the management of cardiovascular risk. METHODS: Using a design thinking approach, interventions were developed with a coalition of local and international stakeholders to address needs of patients, healthcare professionals, and the health system. The resulting solution package was checked to comply with guidelines for non-communicable disease and hypertension management. Clinical impact was measured by extracting the hypertension cascade of care-monitored, diagnosis, treatment, and control-from medical records. RESULTS: Under the leadership of the municipal health authorities, nine solutions were piloted and scaled across the city. Solutions conform with local and international best-practices. Between October 2017 and December 2021, 11,406 patient records were analyzed. Results showed a 40% increase in monitored patients (patients with at least one blood pressure, BP, measurement); reduced proportions of patients diagnosed among those with available BP measurements (72%-53%) and treated among diagnosed (93%-85%); and an improvement in controlled patients among those receiving treatment (16%-27%). CONCLUSIONS: The solution package described in this study was correlated with increased BP control. The implementation methodology and results add to the body of real-world evidence supporting population health implementation science in Brazil and beyond.