Determinants of Intention to Use HIV Pre-exposure Prophylaxis and Condom Use Among a Sample of Cisgender Female Sex Workers Working Mostly Outdoors in Madrid, Spain.

There is scant knowledge regarding pre-exposure prophylaxis (PrEP) use among female sex workers (FSWs) in Europe. Spain recognized FSWs as a population at high risk of acquiring HIV and granted them subsidized access to PrEP when the medication first became nationally available in 2019. Nevertheless, FSWs represented just 0.2% of PrEP users in 2022. A total of 102 HIV-negative FSWs reached through field activities of local NGOs located in Madrid were interviewed between January and March 2022. Participants were selected through convenience sampling over a fixed recruitment period. FSWs completed a 73-item survey with questions about individual, occupational, social, and structural determinants. The objective of this study was to identify (1) the prevalence of intention to use oral PrEP and its determinants, and (2) the prevalence of inconsistent condom use, which is the risk factor that qualifies FSWs for subsidized PrEP in the national health system, and its determinants. Importantly, the study sample overrepresented street-based FSWs (71.6%). A quarter (25.5%) of the study participants used condoms inconsistently. PrEP awareness was low (9.8%), but intention to use PrEP was high (72.5%). Intention to use oral PrEP was significantly associated with feeling protected against HIV by taking PrEP and perceiving insufficient protection by condom use alone. Inconsistent condom use was significantly associated with frequent heroin/cocaine use, having clients who inject drugs, and willingness to take PrEP despite it not protecting 100% against HIV infection. FSWs, in this specific sample, are likely to benefit from targeted PrEP awareness campaigns and implementation projects that prioritize those who use drugs and are more likely to engage in condomless sex.

Emerging and multifaceted potential contributions of polyphenols in the management of type 2 diabetes mellitus.

Type 2 diabetes mellitus (T2DM) is recognized as a serious public health concern with a considerable impact on human life, long-term health expenditures, and substantial health losses. In this context, the use of dietary polyphenols to prevent and manage T2DM is widely documented. These dietary compounds exert their beneficial effects through several actions, including the protection of pancreatic islet ß-cell, the antioxidant capacities of these molecules, their effects on insulin secretion and actions, the regulation of intestinal microbiota, and their contribution to ameliorate diabetic complications, particularly those of vascular origin. In the present review, we intend to highlight these multifaceted actions and the molecular mechanisms by which these plant-derived secondary metabolites exert their beneficial effects on type 2 diabetes patients.

Age-Dependent Changes in the Occurrence and Segregation of GABA and Acetylcholine in the Rat Superior Cervical Ganglia.

The occurrence, inhibitory modulation, and trophic effects of GABA have been identified in the peripheral sympathetic nervous system. We have demonstrated that GABA and acetylcholine (ACh) may colocalize in the same axonal varicosities or be segregated into separate ones in the rat superior cervical ganglia (SCG). Neurotransmitter segregation varies with age and the presence of neurotrophic factors. Here, we explored age-dependent changes in the occurrence and segregation of GABA and ACh in rats ranging from 2 weeks old (wo) to 12 months old or older. Using immunohistochemistry, we characterized the expression of L-glutamic acid decarboxylase of 67 kDa (GAD67) and vesicular acetylcholine transporter (VAChT) in the rat SCG at 2, 4, 8, 12 wo and 12 months old or older. Our findings revealed that GAD67 was greater at 2 wo compared with the other ages, whereas VAChT levels were greater at 4 wo than at 12 wo and 12 months old or older. The segregation of these neurotransmitters was more pronounced at 2 and 4 wo. We observed a caudo-rostral gradient of segregation degree at 8 and 12 wo. Data point out that the occurrence and segregation of GABA and ACh exhibit developmental adaptative changes throughout the lifetime of rats. We hypothesize that during the early postnatal period, the increase in GABA and GABA-ACh segregation promotes the release of GABA alone which might play a role in trophic actions.

Rapid generation of an RBL cellular model to study proteins that cause allergenic reactions in vitro.

Allergic diseases affect nearly 30% of people worldwide. There is a wide range of allergen sources, such as animal dander, food, venom, dust mites, and pollen. The skin prick test is the predominant technique used to identify allergenic sensitivity in vivo; the main problem is that it can be imprecise as many of the allergen extracts are made of mixtures of allergic and nonallergic components, making it difficult to identify the disease-eliciting allergen. An alternative to solve this problem is employing cellular models in vitro that may allow allergen identification, allergy diagnosis, and testing of novel potential compounds that can be used in immunotherapeutics. For example, rat basophilic leukemia (RBL) cells are a well-suited model for studying allergies. Unfortunately, cells generated from RBL cells are not commercially available. Therefore, we developed an RBL model with a degranulation gene reporter capable of recognizing human IgE involved in allergenic sensitivity using commercial plasmids. Employing this model, we successfully evaluated the capacity of union between IgE from allergic patients to allergenic proteins from Oleaceae tree pollen. This RBL cell model can be used as a diagnostic method for sensitivity to any allergens from different sources in vitro.

Recurrent Ischemic Strokes due to Monogenic COL4A1 Mutation: The First Case Report from Latin America.

Introduction. Monogenic mutations as the cause of recurrent ischemic cerebral small-vessel disease with leukodystrophy are rare. COL4A1 gene mutations are a relatively new etiology of cerebrovascular lesions in young adults; however, any patient has been reported from Latin America. Case Presentation. We presented a Mexican young female with leukodystrophy and recurrent stroke secondary to COL4A1 monogenic mutation. Discussion/Conclusion. COL4A1 monogenic mutations are associated with cerebral small-vessel disease and other systemic manifestations. To date, there is little evidence to justify the treatment and prevention of recurrent strokes in patients with this mutation.

Perspectives of Proteomics in Respiratory Allergic Diseases.

Proteomics in respiratory allergic diseases has such a battery of techniques and programs that one would almost think there is nothing impossible to find, invent or mold. All the resources that we document here are involved in solving problems in allergic diseases, both diagnostic and prognostic treatment, and immunotherapy development. The main perspectives, according to this version, are in three strands and/or a lockout immunological system: (1) Blocking the diapedesis of the cells involved, (2) Modifications and blocking of paratopes and epitopes being understood by modifications to antibodies, antagonisms, or blocking them, and (3) Blocking FcεRI high-affinity receptors to prevent specific IgEs from sticking to mast cells and basophils. These tools and targets in the allergic landscape are, in our view, the prospects in the field. However, there are still many allergens to identify, including some homologies between allergens and cross-reactions, through the identification of structures and epitopes. The current vision of using proteomics for this purpose remains a constant; this is also true for the basis of diagnostic and controlled systems for immunotherapy. Ours is an open proposal to use this vision for treatment.

In vivo tracing of immunostimulatory raw starch microparticles after mucosal administration.

Raw starch microparticles (SMPs) proved efficient antigen carriers with adjuvant properties when administered via the mucosal route; however, the underlying mechanisms associated with this bioactivity are unknown. In the present study, we explored the mucoadhesion properties, fate, and toxicity of starch microparticles after mucosal administration. Nasally administered microparticles were mainly retained in nasal turbinates, reaching the nasal-associated lymphoid tissue; this step is facilitated by the ability of the microparticles to penetrate through the mucous epithelium. Likewise, we found intraduodenally administered SMPs on the small intestinal villi, follicle-associated epithelium, and Peyer's patches. Furthermore, under simulated gastric and intestinal pH conditions, we detected mucoadhesion between the SMPs and mucins, regardless of microparticle swelling. SMPs' mucoadhesion and translocation to mucosal immune responses induction sites explain the previously reported role of these microparticles as vaccine adjuvants and immunostimulants.

Contributions of the receptor for advanced glycation end products axis activation in gastric cancer.

Compelling shreds of evidence derived from both clinical and experimental research have demonstrated the crucial contribution of receptor for advanced glycation end products (RAGE) axis activation in the development of neoplasms, including gastric cancer (GC). This new actor in tumor biology plays an important role in the onset of a crucial and long-lasting inflammatory milieu, not only by supporting phenotypic changes favoring growth and dissemination of tumor cells, but also by functioning as a pattern-recognition receptor in the inflammatory response to Helicobacter pylori infection. In the present review, we aim to highlight how the overexpression and activation of the RAGE axis contributes to the proliferation and survival of GC cells as and their acquisition of more invasive phenotypes that promote dissemination and metastasis. Finally, the contribution of some single nucleotide polymorphisms in the RAGE gene as susceptibility or poor prognosis factors is also discussed.

Carga por mortalidad del cáncer de labio, cavidad bucal y faringe

Fundamento: un análisis de la tendencia al cambio en la mortalidad del cáncer de labio, cavidad bucal y faringe y la cuantificación del impacto sobre la esperanza de vida en la población cubana puede ayudar a los investigadores y a los responsables de la formulación de políticas de Salud Pública a tener una visión integral de este problema. Objetivo: estimar la carga por mortalidad de cáncer de labio, cavidad bucal y faringe, por sexo, en Cuba en el período comprendido de 2005- 2020. Método: se realizó un estudio descriptivo, de corte transversal en el que se utilizaron series de datos quinquenales. El universo estuvo conformado por todas las muertes por cáncer de labio, cavidad bucal y faringe para los años estudiados. Se utilizó, para cada año y causas, el número de defunciones, se calcularon tasas por 100 000 habitantes y los años de vida potencialmente perdidos por mortalidad. Se calculó, el promedio y se estimó del cambio porcentual anual. Resultados: las tasas de mortalidad fueron entre 7,62 y 12,23 en hombres y 2,60 y 3,74 en mujeres, por 100 000 habitantes. En cuanto a los años de vida dejados de vivir temparanamente, por cáncer de labio, cavidad bucal y faringe se observó que en hombres las tasas asciendieron de 131 en el 2005 a 169 en el 2020 y de 40 a 52 en las mujeres. Concluciones: la carga por cáncer de labio, cavidad bucal y faringe en Cuba ha aumentado, fue superior en hombres, la tendencia es creciente en ambos sexos, por cáncer nasofaríngeo tanto hombres como mujeres fallecieron a edades más tempranas que, por otras localizaciones estudiadas, el cambio porcentual fue superior por cáncer faríngeo.

Background: an analysis of the trend of change in the mortality of cancer of the lip, oral cavity and pharynx and the quantification of the impact on life expectancy in the Cuban population can help researchers and those responsible for formulating health policies. Public to have a comprehensive view of this problem. Objective: to estimate the mortality burden of cancer of the lip, oral cavity and pharynx, by sex, in Cuba in the period 2005-2020. Method: a descriptive, cross-sectional study was carried out in which five-year data series were used. The universe was made up of all deaths from cancer of the lip, oral cavity and pharynx for the years studied. For each year and causes, the number of deaths was used; rates per 100,000 inhabitants and the years of life potentially lost due to mortality were calculated. The average was calculated and the annual percentage change was estimated. Results: mortality rates were between 7.62 and 12.23 in men and 2.60 and 3.74 in women, per 100,000 inhabitants. Regarding the years of life lost early, due to cancer of the lip, oral cavity and pharynx, it was observed that in men the rates rose from 131 in 2005 to 169 in 2020 and from 40 to 52 in women. Conclusions: the burden of cancer of the lip, oral cavity and pharynx in Cuba has increased, it was higher in men, the trend is growing in both sexes, both men and women died at younger ages due to nasopharyngeal cancer than, due to other locations studied, the percentage change was higher for pharyngeal cancer.

Receptor of advanced glycation end-products axis and gallbladder cancer: A forgotten connection that we should reconsider.

Compelling evidence derived from clinical and experimental research has demonstrated the crucial contribution of chronic inflammation in the development of neoplasms, including gallbladder cancer. In this regard, data derived from clinical and experimental studies have demonstrated that the receptor of advanced glycation end-products (RAGE)/AGEs axis plays an important role in the onset of a crucial and long-lasting inflammatory milieu, thus supporting tumor growth and development. AGEs are formed in biological systems or foods, and food-derived AGEs, also known as dietary AGEs are known to contribute to the systemic pool of AGEs. Once they bind to RAGE, the activation of multiple and crucial signaling pathways are triggered, thus favoring the secretion of several proinflammatory cytokines also involved in the promotion of gallbladder cancer invasion and migration. In the present review, we aimed to highlight the relevance of the association between high dietary AGEs intakes and high risk for gallbladder cancer, and emerging data supporting that dietary intervention to reduce gallbladder cancer risk is a very attractive approach that deserves much more research efforts.

Educational inequalities and premature mortality: the Cuba Prospective Study.

BACKGROUND: Although socioeconomic status is a major determinant of premature mortality in many populations, the impact of social inequalities on premature mortality in Cuba, a country with universal education and health care, remains unclear. We aimed to assess the association between educational level and premature adult mortality in Cuba. METHODS: The Cuba Prospective Study (a cohort study) enrolled 146 556 adults aged 30 years and older from the general population in five provinces from Jan 1, 1996, to Nov 24, 2002. Participants were followed up until Jan 1, 2017, for cause-specific mortality. Deaths were identified through linkage to the Cuban Public Health Ministry's national mortality records. Cox regression models yielded rate ratios (RRs) for the effect of educational level (a commonly used measure for social status) on mortality at ages 35-74 years, with assessment for the mediating effects of smoking, alcohol consumption, and BMI. FINDINGS: A total of 127 273 participants aged 35-74 years were included in the analyses. There was a strong inverse association between educational level and premature mortality. Compared with a university education, men who did not complete primary education had an approximately 60% higher risk of premature mortality (RR 1·55, 95% CI 1·40-1·72), while the risk was approximately doubled in women (1·96, 1·81-2·13). Overall, 28% of premature deaths could be attributed to lower education levels. Excess mortality in women was primarily due to vascular disease, while vascular disease and cancer were equally important in men. 31% of the association with education in men and 18% in women could be explained by common modifiable risk factors, with smoking having the largest effect. INTERPRETATION: This study highlights the value of understanding the determinants of health inequalities in different populations. Although many major determinants lie outside the health system in Cuba, this study has identified the diseases and risk factors that require targeted public health interventions, particularly smoking. FUNDING: UK Medical Research Council, British Heart Foundation, Cancer Research UK, CDC Foundation (with support from Amgen).

Effect of Hypoxia in the Transcriptomic Profile of Lung Fibroblasts from Idiopathic Pulmonary Fibrosis.

Idiopathic pulmonary fibrosis (IPF) is an aging-associated disease characterized by exacerbated extracellular matrix deposition that disrupts oxygen exchange. Hypoxia and its transcription factors (HIF-1α and 2α) influence numerous circuits that could perpetuate fibrosis by increasing myofibroblasts differentiation and by promoting extracellular matrix accumulation. Therefore, this work aimed to elucidate the signature of hypoxia in the transcriptomic circuitry of IPF-derived fibroblasts. To determine this transcriptomic signature, a gene expression analysis with six lines of lung fibroblasts under normoxia or hypoxia was performed: three cell lines were derived from patients with IPF, and three were from healthy donors, a total of 36 replicates. We used the Clariom D platform, which allows us to evaluate a huge number of transcripts, to analyze the response to hypoxia in both controls and IPF. The control's response is greater by the number of genes and complexity. In the search for specific genes responsible for the IPF fibroblast phenotype, nineteen dysregulated genes were found in lung fibroblasts from IPF patients in hypoxia (nine upregulated and ten downregulated). In this sense, the signaling pathways revealed to be affected in the pulmonary fibroblasts of patients with IPF may represent an adaptation to chronic hypoxia.

Impacto sobre la incidencia de la tuberculosis en Cuba, 1994-2015 / Impact on the incidence of tuberculosis in Cuba, 1994-2015

Introducción: La incidencia es fundamental para evaluar la carga de tuberculosis. Objetivo: Valorar el impacto del Programa Nacional de Control de la Tuberculosis en la incidencia de la tuberculosis en Cuba en el periodo 1994-2015. Métodos: Estudio de series temporales de la incidencia de tuberculosis en el periodo 1994-2015. Se estimó la tendencia exponencial y las variaciones de las tendencias de casos nuevos notificados en Cuba y sus provincias; los totales y medias anuales de los periodos 1994-1999, 1999-2015 y 1994-2015. Se calcularon las diferencias absolutas y relativas entre las provincias cubanas desde 1994-2015. Resultados: La tendencia general de la tasa fue descendente. El periodo de 1994-1999 visualizó una reducción de -0,33x100 000(-505 casos) y entre 1999 y 2015 fue de -0,42(-448 casos). La reducción media anual entre 1994-1999 fue de -0,07 y de 1999-2015 fue de -0,03. En 1994, 1999 y 2015 se notificaron 1616 casos (14,7), 1111(10,0) y 651(5,8), respectivamente. En 1994 la mayor tasa correspondió a la provincia de Cienfuegos (23,1) con riesgo atribuible poblacional porcentual del 65,8 por ciento. En 1999 y 2015 las mayores tasas se presentaron en Ciego de Ávila (18,3) y (9,5), respectivamente (riesgo atribuible poblacional porcentual del 60,7 por ciento en 1999 y del 75,8 por ciento en 2015). En 1994 y 1999 todas las provincias tuvieron tasas > 5,0. En 2015, ocho provincias mostraron tasas < 5,0. En 1999 la provincia con mayor variación de su tasa anual fue Cienfuegos (-0,65) y en 2015 Camagüey (-0,73). Conclusiones: El Programa Nacional de Control de la Tuberculosis en Cuba obtuvo hasta el 2015 una discreta disminución sostenida de la incidencia de la enfermedad en el país; pero no es suficiente para lograr su eliminación, por lo que se requieren nuevas intervenciones diferenciadas y priorizadas(AU)

Introduction: Incidence is critical to assess the burden of tuberculosis. Objective: Assess the impact of the National Program of Tuberculosis Control on the incidence of tuberculosis in Cuba in the period 1994-2015. Methods: Study of time series of tuberculosis incidence in the period 1994-2015. The exponential trend and variations in the trends of new cases reported in Cuba and its provinces were estimated; also the annual totals and averages for the periods 1994-1999, 1999-2015 and 1994-2015. The absolute and relative differences between the Cuban provinces from 1994-2015 were calculated. Results: The overall trend of the rate was downward. The period from 1994-1999 had a reduction of -0.33x100 000 (-505 cases) and between 1999 and 2015 it was -0.42 (-448 cases). The average annual reduction between 1994-1999 was -0.07 and from 1999-2015 it was -0.03. In 1994, 1999 and 2015, 1616 cases (14.7), 1111 (10.0) and 651 (5.8) were reported, respectively. In 1994 the highest rate corresponded to the province of Cienfuegos (23.1) with a percentage population attributable risk of 65.8percent. In 1999 and 2015, the highest rates occurred in Ciego de Ávila (18.3) and (9.5), respectively (percentage population attributable risk of 60.7percent in 1999 and 75.8percent in 2015). In 1994 and 1999 all provinces had rates > 5.0. In 2015, eight provinces showed rates < 5.0. In 1999 the province with the greatest variation in its annual rate was Cienfuegos (-0.65) and in 2015 Camagüey (-0.73). Conclusions: The National Program of Tuberculosis Control in Cuba obtained until 2015 a discreet sustained decrease in the incidence of the disease in the country; but it is not enough to achieve its elimination, so new differentiated and prioritized interventions are required(AU)

Current Insights on the Impact of Proteomics in Respiratory Allergies.

Respiratory allergies affect humans worldwide, causing extensive morbidity and mortality. They include allergic rhinitis (AR), asthma, pollen food allergy syndrome (PFAS), aspirin-exacerbated respiratory disease (AERD), and nasal polyps (NPs). The study of respiratory allergic diseases requires new technologies for early and accurate diagnosis and treatment. Omics technologies provide the tools required to investigate DNA, RNA, proteins, and other molecular determinants. These technologies include genomics, transcriptomics, proteomics, and metabolomics. However, proteomics is one of the main approaches to studying allergic disorders' pathophysiology. Proteins are used to indicate normal biological processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention. In this field, the principal goal of proteomics has been to discover new proteins and use them in precision medicine. Multiple technologies have been applied to proteomics, but that most used for identifying, quantifying, and profiling proteins is mass spectrometry (MS). Over the last few years, proteomics has enabled the establishment of several proteins for diagnosing and treating respiratory allergic diseases.

Autopsia y certificados médicos de defunción en fallecidos relacionados con la COVID-19

RESUMEN Introducción: La pandemia de la COVID-19 ha sido la mayor del siglo actual y motivo de numerosos trabajos científicos. En Cuba se ha constituido el Grupo Temporal de Anatomía Patológica para estudiar las autopsias de los fallecidos por la COVID-19 (más de 400). Los certificados médicos de defunción, documentos de inestimable valor, en Cuba se reparan de acuerdo a los resultados de las autopsias, para elevar su calidad. Objetivos: Evaluar los resultados de las autopsias con diagnósticos de COVID-19, comparadas con los certificados médicos de defunción. Métodos: Se evaluaron los diagnósticos de causas de muerte de 65 autopsias del año 2020 con sus certificados médicos de defunción. Los diagnósticos fueron procesados en el Sistema Automatizado de Registro y Control de Anatomía Patológica. Se analizaron las causas directas de muerte, causas básicas de muerte, causas de muerte intermedias y causas de muerte contribuyentes. Se definió la coincidencia total de ambos diagnósticos, coincidencia parcial, no coincidencia o discrepancia diagnóstica y datos insuficientes. Resultados: Las discrepancias diagnósticas de causa básica y directa de muerte son 46,2 % y 60,0 % del total de casos y 19,4 % y 64,5 % cuando la COVID-19 fue causa básica de muerte. Las elevadas cifras de discrepancias diagnósticas, se corresponden con las reportadas en estudios previos, tanto en diagnósticos clínicos como en los certificados médicos de defunción. Conclusiones: Existe elevadas cifras de discrepancias diagnósticas en los resultados de las autopsias con diagnósticos de COVID-19, comparadas con los certificados médicos de defunción.

ABSTRACT Introduction: The COVID-19 pandemic has been the largest in the current century and the reason for numerous scientific works. In Cuba, the Temporary Group of Pathological Anatomy has been established to study the autopsies of those who died from COVID-19 (more than 400). The medical death certificates, documents of inestimable value, in Cuba are repaired according to the results of the autopsies, to raise their quality. Objectives: To evaluate the results of autopsies with COVID-19 diagnoses, compared to medical death certificates. Methods: The diagnoses of causes of death of 65 autopsies of the year 2020 were evaluated with their medical death certificates. The diagnoses were processed in the Automated System for the Registration and Control of Pathology. Direct causes of death, basic causes of death, intermediate causes of death, and contributing causes of death were analyzed. The total agreement of both diagnoses was defined, partial agreement, diagnostic mismatch or discrepancy, and insufficient data. Results: Diagnostic discrepancies of basic and direct cause of death are 46.2 % and 60.0 % of all cases and 19.4 % and 64.5 % when COVID-19 was basic cause of death. The high figures for diagnostic discrepancies correspond to those reported in previous studies, both in clinical diagnoses and in medical death certificates. Conclusions: There are high numbers of diagnostic discrepancies compared with the results of autopsies with COVID-19 diagnoses, compared to medical death certificates.

Functional Implications of Neurotransmitter Segregation.

Here, we present and discuss the characteristics and properties of neurotransmitter segregation, a subtype of neurotransmitter cotransmission. We review early evidence of segregation and discuss its properties, such as plasticity, while placing special emphasis on its probable functional implications, either in the central nervous system (CNS) or the autonomic nervous system. Neurotransmitter segregation is a process by which neurons separately route transmitters to independent and distant or to neighboring neuronal processes; it is a plastic phenomenon that changes according to synaptic transmission requirements and is regulated by target-derived signals. Distant neurotransmitter segregation in the CNS has been shown to be related to an autocrine/paracrine function of some neurotransmitters. In retinal amacrine cells, segregation of acetylcholine (ACh) and GABA, and glycine and glutamate to neighboring terminals has been related to the regulation of the firing rate of direction-selective ganglion cells. In the rat superior cervical ganglion, segregation of ACh and GABA to neighboring varicosities shows a heterogeneous regional distribution, which is correlated to a similar regional distribution in transmission strength. We propose that greater segregation of ACh and GABA produces less GABAergic inhibition, strengthening ganglionic transmission. Segregation of ACh and GABA varies in different physiopathological conditions; specifically, segregation increases in acute sympathetic hyperactivity that occurs in cold stress, does not vary in chronic hyperactivity that occurs in hypertension, and rises in early ages of normotensive and hypertensive rats. Given this, we propose that variations in the extent of transmitter segregation may contribute to the alteration of neural activity that occurs in some physiopathological conditions and with age.

New Insights into the Role of PD-1 and Its Ligands in Allergic Disease.

Programmed cell death 1 (PD-1) and its ligands PD-L1 and PD-L2 are receptors that act in co-stimulatory and coinhibitory immune responses. Signaling the PD-1/PD-L1 or PD-L2 pathway is essential to regulate the inflammatory responses to infections, autoimmunity, and allergies, and it has been extensively studied in cancer. Allergic diseases include asthma, rhinoconjunctivitis, atopic dermatitis, drug allergy, and anaphylaxis. These overactive immune responses involve IgE-dependent activation and increased CD4+ T helper type 2 (Th2) lymphocytes. Recent studies have shown that PD-L1 and PD-L2 act to regulate T-cell activation and function. However, the main role of PD-1 and its ligands is to balance the immune response; however, the inflammatory process of allergic diseases is poorly understood. These immune checkpoint molecules can function as a brake or a kick-start to regulate the adaptive immune response. These findings suggest that PD-1 and its ligands may be a key factor in studying the exaggerated response in hypersensitivity reactions in allergies. This review summarizes the current understanding of the role of PD-1 and PD-L1 and PD-L2 pathway regulation in allergic diseases and how this immunomodulatory pathway is currently being targeted to develop novel therapeutic immunotherapy.

Carga por mortalidad relacionada con el embarazo, parto y puerperio. Cuba 2005-2018 / Burden of mortality related to pregnancy, childbirth and the puerperium. Cuba 2005-2018

RESUMEN Fundamento la muerte materna representa uno de los acontecimientos más notables dentro de los conflictos de la salud sexual y reproductiva en el mundo. La elevada mortalidad por esta causa en el mundo es inadmisible. Sin embargo, las estimaciones para determinar la carga de morbilidad y mortalidad maternas aún son limitadas. Objetivo determinar la carga por mortalidad relacionada con el embarazo, parto y puerperio en Cuba entre los años 2005 y 2018. Métodos se realizó un estudio descriptivo, de datos transversales nacionales y periodicidad anual. El universo de estudio estuvo conformado por todas las muertes ocurridas durante el embarazo, parto y puerperio en el periodo 2005-2018, en Cuba (N=831). Se calcularon la razón de mortalidad, años de vida potencialmente perdidos por mortalidad, el porcentaje, el promedio y la tendencia. Resultados del total de fallecidas por muertes ocurridas durante el embarazo, parto y puerperio, 463 fueron por muerte directa; 247 por muerte indirecta; y 247, por otras muertes 121. La razón promedió 48,8 fallecidas por cada 100 000 nacidos vivos. Los años de vida potencialmente perdidos fueron 42582: 23433 por muertes directas, 12724 por indirectas, y 6425 por otras muertes. Conclusión las muertes obstétricas directas fueron las más frecuentes, y las de mayor impacto sobre la esperanza de vida; mientras que las obstétricas indirectas mostraron una tendencia a aumentar en el tiempo. Por otras muertes, las mujeres fallecieron en edades más tempranas.

ABSTRACT Background maternal death represents one of the most notable events in the conflicts of sexual and reproductive health in the world. The high mortality from this cause in the world is unacceptable. However, estimates for determining the burden of maternal morbidity and mortality health are still limited. Objective to determine the burden of mortality related to pregnancy, childbirth and the puerperium in Cuba between 2005 and 2018. Methods a descriptive study was carried out, with national cross-sectional data and annual periodicity. The universe of study was made up of all the deaths that occurred during pregnancy, childbirth and the puerperium in the period 2005-2018, in Cuba (N = 831). The mortality ratio, years of life potentially lost due to mortality, the percentage, the average and the trend were calculated. Results of the total number of deceased due to deaths that occurred during pregnancy, childbirth and the puerperium, 463 were due to direct death; 247 for indirect death; and 247, due to other deaths 121. The ratio averaged 48.8 deaths for every 100 000 live births. Years of life potentially lost were 42,582: 23,433 for direct deaths, 12,724 for indirect deaths, and 6,425 for other deaths. Conclusion direct obstetric deaths were the most frequent and those with the greatest impact on life expectancy; while indirect obstetrician women showed a tendency to increase over time. For other deaths, women died at an earlier age.

Características y causas de muerte de pacientes fallecidos con enfermedad renal crónica. Cuba 2011-2016 / Deceased patients with chronic kidney disease. Characteristics and causes in Cuba during 2011-2016

Introducción: La morbimortalidad por enfermedad renal crónica (ERC) ha presentado en las dos últimas décadas un incremento desconcertante. En Cuba, aunque la mortalidad por esta causa ha tenido un comportamiento estable, la incidencia y la prevalencia se mantienen elevadas. Objetivo: Caracterizar los pacientes fallecidos con ERC según variables demográficas, causas de muerte y otras variables seleccionadas. Material y Métodos: Estudio descriptivo, transversal. El universo de estudio estuvo constituido por todos los fallecidos del país en el período, en cuyos certificados de defunción se incluyó entre una de las causas, la ERC. La información fue obtenida de las bases de datos de mortalidad de la Dirección Nacional de Registros Médicos y Estadísticos de Salud del MINSAP. Procesamiento de forma automatizada (SPSS versión 22.0). Fueron calculadas las frecuencias absolutas y relativas. Resultados: La frecuencia global de pacientes fallecidos se incrementó de forma mantenida y resultó mayor en la provincia La Habana (23,6 por ciento). La media de la edad fue de 70 años. Prevaleció el sexo masculino, el color de piel blanco y el grupo de edad de 80 años y más. Los porcentajes más altos según la causa básica de muerte correspondieron a enfermedad renal hipertensiva y Diabetes Mellitus. Conclusiones: Los fallecidos con ERC son mayormente hombres, de piel blanca, y con edades avanzadas. Las principales causas de muerte son la enfermedad hipertensiva y la Diabetes Mellitus(AU)

Introduction: Chronic kidney disease (CKD) has increased at an alarming rate worldwide over the last two decades. Although mortality due to CKD has registered stable behavior in Cuba, its prevalence and incidence are showing higher rates. Objective: To describe the main demographic features of deceased patients with CKD in Cuba, the causes of death and other variables during the period 2011-2016. Material and Methods: A descriptive cross-sectional study was conducted. The study universe included all deceased patients in Cuba during the period mentioned. CKD was listed on their death certificates as one of the causes of death. The information used was obtained from the mortality database available on the National Directorate of Medical Records and Health Statistics of the Cuban Ministry of Public Health. Data was processed using SPSS version 22.0. Absolute and relative frequencies were calculated. Results: The global frequency of deceased patients showed a steady increase. Havana was the city that presented the highest percentage (23,6 percent). Nonetheless, the rest of the cities showed an increased frequency rate. The median age was 70 years. The male gender prevailed over the female one as well as white ethnicity and the 80 years and over age group. Regarding the cause of death, the highest percentages corresponded to hypertensive kidney disease and Diabetes Mellitus. Conclusions: Most of the deceased patients with CKD are male, white and at advanced ages. The main causes of death are hypertensive disease and Diabetes Mellitus(AU)

Mortalidad de los enfermos renales crónicos en edad laboral en Cuba / Mortality of chronic kidney patients of working ages in Cuba

Introducción: La enfermedad renal crónica constituye un gran problema de salud en el mundo y en Cuba. Para el año 2040 puede convertirse en la quinta causa más común de años de vida potencialmente perdidos a nivel mundial y es una importante causa de gastos para la salud, la economía y el seguro social de los países. Objetivo: Caracterizar la mortalidad en pacientes renales crónicos en edad laboral en Cuba, en los años 2011-2017, según variables sociodemográficas seleccionadas. Métodos: Investigación transversal descriptiva. El universo estuvo constituido por los 5 716 fallecidos con enfermedad renal crónica. La información fue tomada de las bases de datos de mortalidad de la Dirección Nacional de Estadísticas, del Ministerio de Salud Pública. Se estudiaron las variables: edad, sexo, ocupación y principales causas de muerte. Se calcularon tasas brutas, así como tasas de mortalidad específicas. Resultados: En la edad laboral la mortalidad por enfermedad renal crónica presentó oscilaciones del año 2011 al 2017. La edad media al morir fue 53.7 años, los mayores de 61 años, hombres, presentaron el mayor riesgo (16 por 10 000 habitantes). La tasa en la población económicamente activa desocupada fue de 33 por 10 000 habitantes. El riesgo fue mayor en las ocupaciones elementales (9 por 10 000 habitantes). La enfermedad renal hipertensiva fue la principal causa de muerte (17 por 100 000 habitantes). Conclusiones: Existe ligero incremento de la mortalidad, en hombres el riesgo es mayor, la tasa más alta es en población económicamente activa desocupada y en las ocupaciones elementales. La principal causa de muerte es la enfermedad renal hipertensiva(AU)

Introduction: Chronic kidney disease constitutes a major health problem in Cuba and worldwide. By 2040 it may become the fifth most common cause of years of life potentially lost, worldwide, and a major cause of health expenses, economy and social security. Objective: To describe mortality in chronic kidney patients of working ages in Cuba, from 2011to 2017, according to selected sociodemographic variables. Methods: This is descriptive cross-sectional research. The universe consisted of 5,716 deceased subjects with chronic kidney disease. The information was taken from the mortality databases of the National Directorate of Statistics, from the Ministry of Public Health. The variables were studied age, sex, occupation and main causes of death. Gross and specific mortality rates were calculated. Results: In working age, mortality from chronic kidney disease fluctuated from 2011 to 2017. The mean age at death was 53.7 years, those over 61 years of age, men, had the highest risk (16 per 10,000 inhabitants). The rate in the economically active unemployed population was 33 per 10,000 inhabitants. The risk was higher in basic occupations (9 per 10,000 inhabitants). Hypertensive kidney disease was the leading cause of death (17 per 100,000 population). Conclusions: There is a slight increase in mortality, the risk is higher in men, the highest rate is in the economically active unemployed population and in basic occupations. The leading cause of death is hypertensive kidney disease(AU)