Urinary L-FABP as an Early Biomarker for Pediatric Acute Kidney Injury Following Cardiac Surgery with Cardiopulmonary Bypass: A Systematic Review and Meta-Analysis.

Acute kidney injury (AKI) following surgery with cardiopulmonary bypass (CPB-AKI) is common in pediatrics. Urinary liver-type fatty acid binding protein (uL-FABP) increases in some kidney diseases and may indicate CPB-AKI earlier than current methods. The aim of this systematic review with meta-analysis was to evaluate the potential role of uL-FABP in the early diagnosis and prediction of CPB-AKI. Databases Pubmed/MEDLINE, Scopus, and Web of Science were searched on 12 November 2023, using the MeSH terms "Children", "CPB", "L-FABP", and "Acute Kidney Injury". Included papers were revised. AUC values from similar studies were pooled by meta-analysis, performed using random- and fixed-effect models, with p < 0.05. Of 508 studies assessed, nine were included, comprising 1658 children, of whom 561 (33.8%) developed CPB-AKI. Significantly higher uL-FABP levels in AKI versus non-AKI patients first manifested at baseline to 6 h post-CPB. At 6 h, uL-FABP correlated with CPB duration (r = 0.498, p = 0.036), postoperative serum creatinine (r = 0.567, p < 0.010), and length of hospital stay (r = 0.722, p < 0.0001). Importantly, uL-FABP at baseline (AUC = 0.77, 95% CI: 0.64-0.89, n = 365), 2 h (AUC = 0.71, 95% CI: 0.52-0.90, n = 509), and 6 h (AUC = 0.76, 95% CI: 0.72-0.80, n = 509) diagnosed CPB-AKI earlier. Hence, higher uL-FABP levels associate with worse clinical parameters and may diagnose and predict CPB-AKI earlier.

Continuous flow reactions in the preparation of active pharmaceutical ingredients and fine chemicals.

Herein, we present an overview of continuous flow chemistry, including photoflow and electroflow technologies in the preparation of active pharmaceutical ingredients (APIs) and fine chemical intermediates. Examples highlighting the benefits and challenges associated with continuous flow processes, mainly involving continuous thermal, photo- and electrochemical transformations, are drawn from the relevant literature, especially our experience and collaborations in this area, with emphasis on the synthesis and prospective scale-up.

Examining the association between serum galactose-deficient IgA1 and primary IgA nephropathy: a systematic review and meta-analysis.

BACKGROUND: IgA nephropathy (IgAN) is a common primary glomerular disease. The O-glycosylation status of IgA1 plays a crucial role in disease pathophysiology. The level of poorly-O-galactosylated IgA1, or galactose-deficient IgA1 (Gd-IgA1), has also been identified as a potential biomarker in IgAN. We sought to examine the value of serum Gd-IgA1 as a biomarker in IgAN, by investigating its association with clinical, laboratory, and histopathological features of IgAN. METHODS: The review followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations and was registered in PROSPERO (CRD42021287423). The literature search was conducted in PubMed, Web of Science, Cochrane, and Scopus, and the selected articles were evaluated for eligibility based on predefined criteria. The methodological quality of the studies was assessed using the Newcastle-Ottawa Scale. Statistical analysis was performed to calculate effect sizes and assess heterogeneity among the studies. RESULTS: This review analyzed 29 out of 1,986 studies, conducted between 2005 and 2022, with participants from multiple countries. Gd-IgA1 levels were not associated with age and gender, while associations with hypertension, hematuria, and proteinuria were inconsistent. In the meta-analyses, a correlation between serum Gd-IgA1 and estimated glomerular filtration rate was identified, however, the relationships between Gd-IgA1 levels and chronic kidney disease (CKD) stage and progression to kidney failure were inconsistent. CONCLUSIONS: Serum Gd-IgA1 levels were not associated with validated prognostic risk factors, but were negatively correlated with kidney function. Further research in larger studies using standardized assays are needed to establish the value of Gd-IgA1 as a prognostic risk factor in IgAN.

Deciphering the role of PGRMC2 in the human endometrium during the menstrual cycle and in vitro decidualization using an in vitro approach.

STUDY QUESTION: What is the human endometrial non-classical progesterone receptor (PGR) membrane component 2 (PGRMC2) expression pattern throughout the menstrual cycle and what role does it play during decidualization? SUMMARY ANSWER: Endometrial PGRMC2 expression fluctuates during the human menstrual cycle and is abundantly expressed in human endometrial stromal cells (hEnSCs) during in vitro decidualization, process where PGRMC2 is involved in embryo implantation-related pathways. WHAT IS KNOWN ALREADY: The endometrial response to progesterone is mediated by the classical and non-classical PGRs. We previously demonstrated that PGR membrane component 1 (PGRMC1) is critical for endometrial function, embryo implantation, and future placentation, however, the role(s) of PGRMC2, which is structurally similar to PGRMC1, have not been studied in the human endometrium. STUDY DESIGN, SIZE, DURATION: This prospective study comprehensively evaluated the endometrial expression of PGRMC2 throughout the human menstrual cycle and during in vitro decidualization of hEnSCs (isolated from 77 endometrial biopsies that were collected from 66 oocyte donors), using immunohistochemistry, RT-qPCR, western blot, transcriptomic, and proteomic analyses. In addition, functional analysis was carried out to validate the implication of PGRMC2 in hEnSCs during embryo invasion using an in vitro outgrowth model. PARTICIPANTS/MATERIALS, SETTING, METHODS: In vitro decidualization of hEnSCs was induced using co-treatment with cAMP and medroxyprogesterone 17-acetate progestin, and evaluated by measuring prolactin by ELISA and F-actin immunostaining. RT-qPCR was employed to compare expression with other PGRs. To reveal the function of PGRMC2 during the decidualization process, we specifically knocked down PGRMC2 with siRNAs and performed RNA-seq and quantitative proteomics techniques (SWATH-MS). The common differentially expressed genes (DEGs) and proteins (DEPs) were considered for downstream functional enrichment analysis. Finally, to verify its implication in the trophoblast invasion, an outgrowth model was carried out where hEnSCs with silenced PGRMC2 were co-cultured with human trophoblastic spheroids (JEG-3) following in vitro decidualization. MAIN RESULTS AND THE ROLE OF CHANCE: In contrast to PGRMC1 and classical PGRs, endometrial PGRMC2 gene expression was significantly lower during the late- versus mid-secretory phase (P < 0.05). Accordingly, the elevated PGRMC2 protein abundance observed in the endometrial epithelial glands throughout the menstrual cycle dropped in the late secretory phase, when abundance decreased in all endometrial compartments. Nevertheless, PGRMC2 protein increased during the mid-secretory phase in stromal and glandular cells, and PGRMC2 mRNA (P < 0.0001) and protein (P < 0.001) levels were significantly enhanced in the membranes/organelles of decidualized hEnSCs, compared to non-decidualized hEnSCs. Notably, PGRMC1 and PGRMC2 mRNA were significantly more abundant than classical PGRs throughout menstrual cycle phases and in decidualized and non-decidualized hEnSCs (P < 0.05). RNA-seq and proteomics data revealed 4687 DEGs and 28 DEPs, respectively, in decidualized hEnSCs after PGRMC2 silencing. While functional enrichment analysis showed that the 2420 upregulated genes were mainly associated with endoplasmic reticulum function, vesicular transport, morphogenesis, angiogenesis, cell migration, and cell adhesion, the 2267 downregulated genes were associated with aerobic respiration and protein biosynthesis. The protein enrichment analysis showed that 4 upregulated and 24 downregulated proteins were related to aerobic respiration, cellular response, metabolism, localization of endoplasmic reticulum proteins, and ribonucleoside biosynthesis routes. Finally, PGRMC2 knockdown significantly compromised the ability of the decidualized hEnSCs to support trophoblast expansion in an outgrowth model (P < 0.05). LARGE-SCALE DATA: Transcriptomic data are available via NCBI's Gene Expression Omnibus (GEO) under GEO Series accession number GSE251843 and proteomic data via ProteomeXchange with identifier PXD048494. LIMITATIONS, REASONS FOR CAUTION: The functional analyses were limited by the discrete number of human endometrial biopsies. A larger sample size is required to further investigate the potential role(s) of PGRMC2 during embryo implantation and maintenance of pregnancy. Further, the results obtained in the present work should be taken with caution, as the use of a pure primary endometrial stromal population differentiated in vitro does not fully represent the heterogeneity of the endometrium in vivo, nor the paracrine communications occurring between the distinct endometrial cell types. WIDER IMPLICATIONS OF THE FINDINGS: The repression of endometrial PGRMC2 during the late- versus mid-secretory phase, together with its overexpression during decidualization and multiple implications with embryo implantation not only highlighted the unknown roles of PGRMC2 in female reproduction but also the potential to exploit PGRMC2 signaling pathways to improve assisted reproduction treatments in the future. STUDY FUNDING/COMPETING INTEREST(S): This research was funded by Instituto de Salud Carlos III (ISCIII) granted to F.D. (PI20/00405 and PI23/00860), co-funded by the European Union. Y.M.-L. was supported by a predoctoral research grant from Generalitat Valenciana (ACIF/2019/262). R.G.-M. was supported by Generalitat Valenciana (CIAPOT/2022/15). P.d.C. was supported by a predoctoral grant for training in research into health (PFIS FI20/00086) from the Instituto de Salud Carlos III. I.D.-H. was supported by the Spanish Ministry of Science, Innovation and Universities (FPU18/01550). A.P. was supported by the Instituto de Salud Carlos III (PFIS FI18/00009). This research was also supported by IVI Foundation-RMA Global (1911-FIVI-103-FD). The authors declare no conflict of interest.

Recurrent C3 glomerulopathy after kidney transplantation.

The complement system is part of innate immunity and is pivotal in protecting the body against pathogens and maintaining host homeostasis. Activation of the complement system is triggered through multiple pathways, including antibody deposition, a mannan-binding lectin, or activated complement deposition. C3 glomerulopathy (C3G) is a rare glomerular disease driven by complement dysregulation with high post-transplantation recurrence rates. Its treatment is mainly based on immunosuppressive therapies, specifically mycophenolate mofetil and glucocorticoids. Recent years have seen significant progress in understanding complement biology and its role in C3G pathophysiology. New complement-tergeting treatments have been developed and initial trials have shown promising results. However, challenges persist in C3G, with recurrent post-transplantation cases leading to suboptimal outcomes. This review discusses the pathophysiology and management of C3G, with a focus on its recurrence after kidney transplantation.

Potential Role of Bone Metabolism Markers in Kidney Transplant Recipients.

BACKGROUND: The impact of treatments, suppressing the immune system, persistent hyperparathyroidism, and other risk factors on mineral and bone disorder (MBD) after kidney transplantation is well-known. However, there is limited knowledge about their effect on bone metabolism biomarkers. This study aimed to investigate the influence of kidney transplant on these markers, comparing them to patients undergoing hemodialysis and healthy individuals. METHODS: In this cross-sectional study, three groups were included: kidney transplant patients (n = 57), hemodialysis patients (n = 26), and healthy controls (n = 31). Plasma concentrations of various bone metabolism biomarkers, including Dickkopf-related protein 1, osteoprotegerin, osteocalcin, osteopontin, sclerostin, and fibroblast growth factor 23, were measured. Associations between these biomarkers and clinical and laboratory data were evaluated. RESULTS: A total of 114 patients participated. Transplant recipients had significantly lower levels of Dickkopf-related protein 1, osteoprotegerin, osteocalcin, osteopontin, sclerostin, and fibroblast growth factor 23 compared to hemodialysis patients. Alkaline phosphatase levels positively correlated with osteopontin (r = 0.572, p < 0.001), while fibroblast growth factor 23 negatively correlated with 25-hydroxyvitamin D (r = -0.531, p = 0.019). The panel of bone biomarkers successfully predicted hypercalcemia (area under the curve [AUC] = 0.852, 95% confidence interval [CI] = 0.679-1.000) and dyslipidemia (AUC = 0.811, 95% CI 0.640-0.982) in transplant recipients. CONCLUSION: Kidney transplantation significantly improves mineral and bone disorders associated with end-stage kidney disease by modulating MBD markers and reducing bone metabolism markers, such as Dickkopf-related protein 1, osteoprotegerin, osteocalcin, osteopontin, and sclerostin. Moreover, the panel of bone biomarkers effectively predicted hypercalcemia and dyslipidemia in transplant recipients.

Proteomic Profiling Identifies Candidate Diagnostic Biomarkers of Hydrosalpinx in Endometrial Fluid: A Pilot Study.

Hydrosalpinx is a fluid occlusion and distension of the fallopian tubes, often resulting from pelvic inflammatory disease, which reduces the success of artificial reproductive technologies (ARTs) by 50%. Tubal factors account for approximately 25% of infertility cases, but their underlying molecular mechanisms and functional impact on other reproductive tissues remain poorly understood. This proteomic profiling study applied sequential window acquisition of all theoretical fragment ion spectra mass spectrometry (SWATH-MS) to study hydrosalpinx cyst fluid and pre- and post-salpingectomy endometrial fluid. Among the 967 proteins identified, we found 19 and 17 candidate biomarkers for hydrosalpinx in pre- and post-salpingectomy endometrial fluid, respectively. Salpingectomy significantly affected 76 endometrial proteins, providing insights into the enhanced immune response and inflammation present prior to intervention, and enhanced coagulation cascades and wound healing processes occurring one month after intervention. These findings confirmed that salpingectomy reverses the hydrosalpinx-related functional impairments in the endometrium and set a foundation for further biomarker validation and the development of less-invasive diagnostic strategies for hydrosalpinx.

Environmental surface surveillance during a COVID-19 outbreak in a school community: implications for controlling indirect transmission.

Environmental surface surveillance is a valuable tool for detecting and controlling infectious diseases. During the COVID-19 pandemic, concerns have been raised regarding the potential for indirect transmission of SARS-CoV-2 via contaminated surfaces. However, few studies have evaluated environmental contamination in non-clinical settings during outbreaks. We conducted a study in a school community during a major outbreak, collecting 35 surface samples from high-traffic areas and testing them for SARS-CoV-2 RNA using RT-qPCR. Our results showed that 31.4% of samples were positive, including high-touch surfaces such as drinking fountains and washbasins. These findings emphasize the importance of environmental monitoring to identify and address specific areas for attention, and implementing such strategies can help prevent the indirect transmission of COVID-19 in various settings.

Anti-Inflammatory Effects of Peripheral Dopamine.

Dopamine is synthesized in the nervous system where it acts as a neurotransmitter. Dopamine is also synthesized in a number of peripheral organs as well as in several types of cells and has organ-specific functions and, as demonstrated more recently, is involved in the regulation of the immune response and inflammatory reaction. In particular, the renal dopaminergic system is very important in the regulation of sodium transport and blood pressure and is particularly sensitive to stimuli that cause oxidative stress and inflammation. This review is focused on how dopamine is synthesized in organs and tissues and the mechanisms by which dopamine and its receptors exert their effects on the inflammatory response.

Selenoneine-inspired selenohydantoins with glutathione peroxidase-like activity.

Chronic diseases such as cystic fibrosis, inflammatory bowel diseases, rheumatoid arthritis, and cardiovascular illness have been linked to a decrease in selenium levels and an increase in oxidative stress. Selenium is an essential trace element that exhibits antioxidant properties, with selenocysteine enzymes like glutathione peroxidase being particularly effective at reducing peroxides. In this study, a series of synthetic organoselenium compounds were synthesized and evaluated for their potential antioxidant activities. The new selenohydantoin molecules were inspired by selenoneine and synthesized using straightforward methods. Their antioxidant potential was evaluated and proven using classical radical scavenging and metal-reducing methods. The selenohydantoin derivatives exhibited glutathione peroxidase-like activity, reducing hydroperoxides. Theoretical calculations using Density Functional Theory (DFT) revealed the selenone isomer to be the only one occurring in solution, with selenolate as a possible tautomeric form in the presence of a basic species. Cytocompatibility assays indicated that the selenohydantoin derivatives were non-toxic to primary human aortic smooth muscle cells, paving the way for further biological evaluations of their antioxidant activity. The results suggest that selenohydantoin derivatives with trifluoro-methyl (-CF3) and chlorine (-Cl) substituents have significant activities and could be potential candidates for further biological trials. These compounds may contribute to the development of effective therapies for chronic diseases such cardiovascular diseases.

Electrochemical reduction of 5-benzylidene thiazolidine-2,4-diones: a greener approach to the preparation of glitazone APIs.

A transition-metal free methodology for the chemoselective reduction of benzylidene thiazolidine-2,4-diones and similar heterocycles is described, allowing the preparation of a broad scope of the corresponding reduced derivatives in up to 90% yield. The protocol has a simple and safe experimental setup, in which water was employed as the hydrogen source. To further demonstrate the synthetic utility of this transformation, the antidiabetic API Pioglitazone was prepared in 81% yield. To the best of our knowledge, this is the first hydride and transition-metal free protocol for the synthesis of Pioglitazone, highlighting its potential utility as a greener alternative in both academic and industrial synthesis.

Tratamientos agudos de recanalización en el ictus arterial isquémico pediátrico posnatal. Código ictus pediátrico / Acute recanalization treatments in postnatal paediatric ischaemic arterial strole. Paediatric stroke code

El ictus arterial isquémico infantil es una patología mucho menos conocida que en adultos debido a su menor frecuencia y a su diferente etiología. Sin embargo, es también una patología grave con una alta incidencia de secuelas severas y perennes, que sobrepasan el 50% de los casos. El manejo agudo del ictus arterial isquémico pediátrico posnatal (IAIPP) ha cambiado drásticamente en los últimos años, fundamentalmente en lo referente a los tratamientos de recanalización (trombólisis y terapias endovasculares). Estos tratamientos, que antes no se recomendaban en la edad infantil, se están afianzando cada vez más en la práctica diaria. Aunque los estudios realizados en niños no tienen un grado de evidencia alto por ser retrospectivos y porque el número de casos es bajo, soportan la idea de que dichos tratamientos son igual de seguros y eficaces que en los adultos siempre que se realicen con unos criterios de inclusión y exclusión determinados y dentro de un tiempo determinado desde el inicio de los síntomas (ventana terapéutica). En este artículo se revisa, a la luz de los conocimientos actuales, el manejo agudo del IAIPP. Debido a que la eficacia de estos tratamientos está íntimamente ligada al inicio precoz de los mismos, es necesaria la existencia de un código ictus infantil como ampliación del código ictus que se aplica a los adultos. Ha empezado a implantarse en España desde el año 2019 aunque todavía hay importantes zonas del país donde aún no se aplica. (AU)

In children, arterial ischemic stroke is a much less understood disease compared to in adults due to its lower frequency and different aetiology. However, it is also a serious disease, with a high incidence of severe and permanent sequelae that exceeds 50% of total cases. The acute management of postnatal arterial ischaemic stroke (MNAIS) has changed drastically in recent years, chiefly on account of recanalization treatments (thrombolysis and endovascular therapies). These treatments, which used to not be recommended in childhood, are increasingly implemented in everyday clinical practice. Although the evidence from studies carried out in children is not of high quality due to their retrospective design and the small number of reported cases, they support the hypothesis that these treatments are as safe and effective as they are in adults as long as appropriate eligibility criteria are applied and they are used within a certain time from the onset of symptoms (therapeutic window). This article reviews the MNAIS based on the current scientific evidence. Since the efficacy of these treatments is highly dependent on their early initiation, a paediatric stroke code needs to be in place as an extension of the stroke code applied to adults. It has started to be introduced in Spain since 2019, although there are still large areas of the country where it has yet to be applied. (AU)

Acute recanalization treatments in postnatal paediatric ischaemic arterial stroke. Paediatric stroke code.

In children, arterial ischemic stroke is a much less understood disease compared to in adults due to its lower frequency and different aetiology. However, it is also a serious disease, with a high incidence of severe and permanent sequelae that exceeds 50% of total cases. The acute management of postnatal arterial ischaemic stroke (MNAIS) has changed drastically in recent years, chiefly on account of recanalization treatments (thrombolysis and endovascular therapies). These treatments, which used to not be recommended in childhood, are increasingly implemented in everyday clinical practice. Although the evidence from studies carried out in children is not of high quality due to their retrospective design and the small number of reported cases, they support the hypothesis that these treatments are as safe and effective as they are in adults as long as appropriate eligibility criteria are applied and they are used within a certain time from the onset of symptoms (therapeutic window). This article reviews the MNAIS based on the current scientific evidence. Since the efficacy of these treatments is highly dependent on their early initiation, a paediatric stroke code needs to be in place as an extension of the stroke code applied to adults. It has started to be introduced in Spain since 2019, although there are still large areas of the country where it has yet to be applied.

Sarcopenia in chronic viral hepatitis: From concept to clinical relevance.

Although the frequency of metabolic risk factors for cirrhosis and hepatocellular carcinoma (HCC) is increasing, chronic hepatitis B (CHB) and chronic hepatitis C (CHC) remain the most relevant risk factors for advanced liver disease worldwide. In addition to liver damage, hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are associated with a myriad of extrahepatic manifestations including mixed cryoglobulinaemia, lymphoproliferative disorders, renal disease, insulin resistance, type 2 diabetes, sicca syndrome, rheumatoid arthritis-like polyarthritis, and autoantibody production. Recently, the list has grown to include sarcopenia. Loss of muscle mass or muscle function is a critical feature of malnutrition in cirrhotic patients and has been found in approximately 23.0%-60.0% of patients with advanced liver disease. Nonetheless, among published studies, there is significant heterogeneity in the aetiologies of hepatic diseases and measurement methods used to determine sarcopenia. In particular, the interaction between sarcopenia, CHB and CHC has not been completely clarified in a real-world setting. Sarcopenia can result from a complex and multifaceted virus-host-environment interplay in individuals chronically infected with HBV or HCV. Thus, in the present review, we provide an overview of the concept, prevalence, clinical relevance, and potential mechanisms of sarcopenia in patients with chronic viral hepatitis, with an emphasis on clinical outcomes, which have been associated with skeletal muscle loss in these patients. A comprehensive overview of sarcopenia in individuals chronically infected with HBV or HCV, independent of the stage of the liver disease, will reinforce the necessity of an integrated medical/nutritional/physical education approach in the daily clinical care of patients with CHB and CHC.

Potential Role of Novel Cardiovascular Biomarkers in Pediatric Patients with Chronic Kidney Disease.

BACKGROUND: Cardiovascular Disease is the leading cause of death in adult and pediatric patients with Chronic Kidney Disease (CKD) and its pathogenesis involves the interaction of multiple pathways. As Inflammatory mechanisms play a critical role in the vascular disease of CKD pediatric patients, there are several biomarkers related to inflammation strongly associated with this comorbidity. OBJECTIVE: This review provides available evidence on the link between several biomarkers and the pathophysiology of heart disease in patients with CKD. METHODS: The data were obtained independently by the authors, who carried out a comprehensive and non-systematic search in PubMed, Cochrane, Scopus, and SciELO databases. The search terms were "Chronic Kidney Disease", "Cardiovascular Disease", "Pediatrics", "Pathophysiology", "Mineral and Bone Disorder (MBD)", "Renin Angiotensin System (RAS)", "Biomarkers", "BNP", "NTproBNP", "CK-MB", "CXCL6", "CXCL16", "Endocan-1 (ESM-1)", "FABP3", "FABP4", h-FABP", "Oncostatin-M (OSM)", "Placental Growth Factor (PlGF)" and "Troponin I". RESULTS: The pathogenesis of CKD-mediated cardiovascular disease is linked to inflammatory biomarkers, which play a critical role in the initiation, maintenance, and progression of cardiovascular disease. There are several biomarkers associated with cardiovascular disease in pediatric patients, including BNP, NTproBNP, CK-MB, CXCL6, CXCL16, Endocan-1 (ESM-1), FABP3, FABP4, Oncostatin-M (OSM), Placental Growth Factor (PlGF), and Troponin I. CONCLUSION: The pathogenesis of CKD-mediated cardiovascular disease is not completely understood, but it is linked to inflammatory biomarkers. Further studies are required to elucidate the pathophysiological and potential role of these novel biomarkers.

Effects of public health emergencies of international concern on disease control: a systematic review.

Objectives: To assess the accumulated knowledge of the effects of public health emergencies of international concern on disease control and local health systems, and contribute to a better understanding of their effects on health programs and systems. Methods: This was a systematic review of published and gray literature (in English, Portuguese, or Spanish). Electronic databases (BVS/LILACS, PubMed, and SciELO) and Google Scholar were searched. Search terms were: COVID-19 OR H1N1 OR Ebola OR Zika OR poliomyelitis AND (outbreaks OR epidemics) AND (public health systems OR public health surveillance). Results: A total of 3 508 studies were retrieved, of which 31 met the inclusion criteria. The studies addressed the effects of the emergencies on: communicable diseases notification systems; malaria, HIV/AIDS, tuberculosis, poliomyelitis, and malaria surveillance, control, and treatment; microcephaly; dengue; and vaccinations. The populations affected by the emergencies experienced reduced health services, which included fewer health visits, failures in the diagnostic chain, decrease in vaccination, and increased incidence or underreporting of notifiable diseases. Conclusions: Socioeconomic inequity is a determinant of the effects of public health emergencies of international concern within affected populations. The diversion of resources and attention from health authorities disproportionately affects vulnerable populations and can lead, over time, to a weakening of health systems. The analysis of the effects of public health emergencies is important for the development of new protocols that can better respond to future crises.

Recent Advances in the Multistep Continuous Preparation of APIs and Fine Chemicals.

Over the last two decades, with the advent of continuous flow technologies, continuous processes have emerged as a major area in organic synthesis. In this context, continuous flow processes have been increasing in the preparation of Active Pharmaceutical Ingredients (APIs) and fine chemicals, such as complex synthetic intermediates, agrochemicals, and fragrances. Thus, the development of multi-step protocols has attracted special interest from the academic and industrial chemistry communities. In addition to the beneficial aspects intrinsically associated with continuous processes (e.g., waste reduction, optimal heat transfer, improved safety, and the possibility to work under harsh reaction conditions and with more dangerous reagents), these protocols also allow a rapid increase in molecular complexity. Moreover, in telescoped multi-step processes, isolation and purification steps are generally avoided or, if necessary, carried out in-line, presenting an important economy of time, solvents, reagents, and labor. Last, important synthetic strategies such as photochemical and electrochemical reactions are compatible with flow processes and are delivering relevant advances to the synthetic approaches. In this review, a general overview of the fundamentals of continuous flow processes is presented. Recent examples of multi-step continuous processes for the preparation of fine chemicals, including telescoped and end-to-end processes, are discussed, pointing out the possible advantages and/or limitations of each of these methodologies.

Multicomponent Reactions Applied to Total Synthesis of Biologically Active Molecules: A Short Review.

Multicomponent reactions (MCRs) are processes in which three or more starting materials are combined in the same reaction vessel, forming an adduct that contains all or most of the atoms of the starting materials. MCRs are one-pot processes that provide attractive advantages for the total synthesis of target molecules. These reactions allow rapid access to structurally complex adducts from particularly simple starting materials. Moreover, MCRs are generally intrinsically associated with principles of green syntheses, such as atom economy, minimization of isolation, and purification of synthetic intermediates, leading to large solvent economies and avoiding the production of large amounts of reaction waste. Thus, synthetic routes employing multicomponent reactions are generally more convergent, economical and often allow higher overall yields. In total synthesis, the use of MCRs has been mainly applied in the preparation of key advanced intermediates. Progress in the use of MCRs in total synthesis has been described over the last decades, including not only classical MCRs reactions (e.g. isocyanide-based transformations), but also non-traditional multicomponent reactions. Furthermore, reports concerning stereoselective multicomponent transformations are still scarce and present further development opportunities. This review aims to provide a general overview of the application of MCRs as key steps in the rapid preparation of structurally complex derivatives and fine chemicals. In special, some selected examples have been successfully applied for medicinal purposes. Finally, in some representative cases, either key intermediates formed during the reaction vessel or corresponding transition states have been disclosed in order to provide insights into the reaction mechanisms.

Effects of public health emergencies of international con- cern on disease control: a systematic review

[ABSTRACT]. Objectives. To assess the accumulated knowledge of the effects of public health emergencies of international concern on disease control and local health systems, and contribute to a better understanding of their effects on health programs and systems. Methods. This was a systematic review of published and gray literature (in English, Portuguese, or Spanish). Electronic databases (BVS/LILACS, PubMed, and SciELO) and Google Scholar were searched. Search terms were: COVID-19 OR H1N1 OR Ebola OR Zika OR poliomyelitis AND (outbreaks OR epidemics) AND (public health systems OR public health surveillance). Results. A total of 3 508 studies were retrieved, of which 31 met the inclusion criteria. The studies addressed the effects of the emergencies on: communicable diseases notification systems; malaria, HIV/AIDS, tubercu- losis, poliomyelitis, and malaria surveillance, control, and treatment; microcephaly; dengue; and vaccinations. The populations affected by the emergencies experienced reduced health services, which included fewer health visits, failures in the diagnostic chain, decrease in vaccination, and increased incidence or underreport- ing of notifiable diseases. Conclusions. Socioeconomic inequity is a determinant of the effects of public health emergencies of inter- national concern within affected populations. The diversion of resources and attention from health authorities disproportionately affects vulnerable populations and can lead, over time, to a weakening of health systems. The analysis of the effects of public health emergencies is important for the development of new protocols that can better respond to future crises.

[RESUMEN]. Objetivos. Evaluar el conocimiento acumulado acerca de los efectos de las emergencias de salud pública de importancia internacional en el control de enfermedades y en los sistemas de salud locales, y contribuir a una mejor comprensión de estos efectos en los programas y sistemas de salud. Métodos. Se hizo una revisión sistemática de bibliografía gris y publicada (en español, inglés o portugués) para la que se realizaron búsquedas en bases de datos electrónicas (BVS/LILACS, PubMed y SciELO) y en Google Scholar. Los términos de búsqueda fueron: COVID-19 OR H1N1 OR Ebola OR Zika OR poliomyelitis AND (Outbreaks OR epidemics) AND (public health systems OR public health surveillance). Resultados. Se encontraron 3 508 estudios, de los cuales 31 cumplieron los criterios de inclusión. En los estudios se abordaban los efectos de las emergencias en: los sistemas de notificación de enfermedades transmisibles; la vigilancia, el control y el tratamiento de la malaria, el VIH/sida, la tuberculosis y la poliomielitis; la microcefalia; el dengue; y las vacunas. Las poblaciones afectadas por las emergencias experimentaron una reducción de los servicios de salud, incluida una reducción de las consultas de salud, errores en la cadena de diagnóstico, una disminución de la vacunación y el aumento de la incidencia o subnotificación de enfermedades de notificación obligatoria. Conclusiones. La inequidad socioeconómica es un determinante de los efectos de las emergencias de salud pública de importancia internacional en los grupos poblacionales afectados. El desvío de recursos y atención de las autoridades de salud afecta desproporcionadamente a los grupos vulnerables y puede suponer, con el tiempo, un debilitamiento de los sistemas de salud. El análisis de los efectos de las emergencias de salud pública es crucial para la elaboración de nuevos protocolos que puedan mejorar la respuesta ante futuras crisis.

[RESUMO]. Objetivos. Avaliar o conhecimento acumulado sobre os efeitos das emergências de saúde pública de importância internacional no controle de doenças e nos sistemas de saúde locais e contribuir para uma melhor compreensão desses efeitos sobre os programas e sistemas de saúde. Métodos. Trata-se de uma revisão sistemática da literatura branca e cinzenta (em inglês, português ou espanhol) realizada por meio de pesquisas nos bancos de dados eletrônicos BVS/LILACS, PubMed e SciELO e no Google Scholar. Foram utilizados os seguintes termos de busca: COVID-19 OR H1N1 OR Ebola OR Zika OR poliomyelitis AND (outbreaks OR epidemics) AND (public health systems OR public health surveillance). Resultados. Foi identificado um total de 3 508 estudos, dos quais 31 preencheram os critérios de inclusão. Os estudos abordavam os efeitos das emergências sobre: sistemas de notificação de doenças transmissíveis; vigilância, controle e tratamento de HIV/AIDS, tuberculose, poliomielite e malária; microcefalia; dengue; e vacinações. As populações afetadas pelas emergências enfrentaram uma redução nos serviços de saúde, como menos consultas médicas, problemas na cadeia de diagnóstico, diminuição da vacinação e maior incidência ou subnotificação de doenças de notificação compulsória. Conclusões. A desigualdade socioeconômica é um fator determinante dos efeitos das emergências de saúde pública de importância internacional nas populações afetadas. O desvio dos recursos e da atenção das autoridades sanitárias afeta desproporcionalmente as populações vulneráveis e pode levar, com o passar do tempo, a um enfraquecimento dos sistemas de saúde. A análise dos efeitos das emergências de saúde pública é importante para a elaboração de novos protocolos que possam enfrentar melhor futuras crises.

Prevalence and epidemiological aspects of Chikungunya fever in states of the Northeast region of Brazil: A systematic review.

Chikungunya fever is a disease caused by the Chikungunya virus (CHIKV), which is transmitted through the bite of infected female hematophagous mosquitoes of the genus Aedes (Diptera: Culicidae). In the Americas, the first autochthonous cases of the disease were recorded in 2013. A year later, in 2014, the first records of the disease were acquired locally in Brazil, in the states of Bahia and Amapá. The present study aimed to carry out a systematic review of the literature on the prevalence and epidemiological aspects of Chikungunya fever in states of the Northeast region of Brazil, between the years 2018 to 2022. This study was registered in the Open Science Framework (OSF) and in the International Prospective Register of Systemactic Reviews (PROSPERO) and followed the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). The searches were carried out in the scientific electronic databases Literatura Latino-Americana e do Caribe em Ciências da Saúde (LILACS), U. S. National Library of Medicine (PubMed) and Scientific Electronic Library Online (SciELO), using descriptors cataloged in Descritores em Ciências da Saúde (DeCS) and Medical Subject Headings (MeSH) in Portuguese, English and Spanish. Gray literature was also searched by accessing Google Scholar to search for additional publications not captured in the selected electronic databases. Of the 19 studies included in the present systematic review, seven referred to the state of Ceará. Most cases of Chikungunya fever corresponded to the female gender (ranging from 7.5% to 100.0%), to the age group younger than 60 years (84.2%), to literate individuals (93.3%), belonging to the non-white race/color (95.21%) and blacks (100.0%), and residents of the urban area (range from 51.95% to 100.0%). As for laboratory characteristics, most notifications were diagnosed using clinical-epidemiological criteria (ranging from 71.21% to 90.35%). The epidemiological information about Chikungunya fever in the Northeast region of Brazil presented in this systematic review is useful to better understand the characteristics of the disease introduction process in the country. To this end, prevention and control strategies must be adopted, especially in the Northeast, as this region is most responsible for the number of cases of the disease in the country.