Exploring food system resilience to the global polycrisis in six Asian countries.

The world is currently in the midst of a global food crisis brought about and exacerbated by a series of mutually reinforcing shocks to food systems This study investigated the resilience of food systems in six Asian countries (Bangladesh, Kyrgyz Republic, Lao PDR, Pakistan, Philippines, and Sri Lanka) amidst the global 'polycrisis' caused by COVID-19, geopolitical conflicts, and climate change. Trend analyses were performed for 19 indicators sourced from global databases and World Food Programme national data, representing the four domains of food system resilience: exposure to shocks; resilience capacities and agro- and food diversity, resilience responses and strategies; and long-term resilience outcomes. The analysis revealed that all six countries experienced the effects of the 'polycrisis', leading to diverse impacts on exchange rates, with Sri Lanka, Pakistan, and Lao PDR facing significant currency depreciation. While most countries increased crop production and decreased food imports during the crisis, government economic support during the pandemic varied widely. Resilience outcomes, including national food price inflation and the proportion of populations facing food insecurity, witnessed upward variations. Overall, countries with higher resilience capacities at the start of the 'polycrisis' showed less severe long-term resilience outcomes. Our findings highlight the varied challenges and resilience capacities across each country, influenced by a complex interplay of economic, political, agricultural, and food affordability factors crucial for determining long-term resilience in their food systems. Recommendations for future research include focusing on resilience assessment in food systems, integrating climate change adaptation measures, and developing early intervention strategies.

Intra-rater reliability and feasibility of the HexCom advanced disease complexity assessment model / Fiabilidad intraobservador y viabilidad del modelo de valoración de la complejidad en enfermedad avanzada HexCom®

Aim: To study the intra-rater reliability and feasibility of the HexCom complexity assessment model by analyzing internal consistency, intra-rater reliability and response time. Design: Test–retest study with a selection of 11 clinical situations that cover the full scope of situations assessed by the HexCom model and which are responded to individually. Location: Home care, primary care, hospital and sociosanitary care. Two specialized palliative home care teams (PADES). Participants: A total of 20 professionals comprising 10 experts in palliative home care (PADES) and 10 professionals from general palliative care (primary care, hospital and sociosanitary care). These professionals came from the fields of family medicine (5), internal medicine (2), geriatrics (2), nursing (9), psychology (1) and social work (1). Main measurements: Cronbach's alpha, weighted kappa, response time. Results: Cronbach's alpha of 0.91 for HexCom-Red and 0.87 for HexCom-Clin. Intra-rater reliability ranging from good to very good for HexCom-Red (kappa: 0.78–1) and from moderate to very good for HexCom-Clin (kappa: 0.58–0.91). Average response time of 0:57 for HexCom-Red and 3:80min for HexComClin. Conclusions: HexCom-Red and HexCom-Clin are reliable tools and feasible for use by all professionals involved in both general and specialized palliative care at different levels.(AU)

Objetivo: Estudiar la fiabilidad intraobservador y la viabilidad del modelo de valoración de la complejidad HexCom®, a través del análisis de la consistencia interna, la concordancia intraobservador y el tiempo de respuesta. Diseño: Estudio test-retest con un panel de 11 situaciones clínicas que incluyen todo el abanico de situaciones valoradas por el modelo HexCom® y que son respuestas individualmente. Emplazamiento: Atención domiciliaria, primaria, hospitalaria y sociosanitaria. Dos equipos de atención domiciliaria paliativa especializada (PADES). Participantes: Veinte profesionales, 10 expertos en atención domiciliaria paliativa (PADES) y 10 de atención paliativa generalista (atención primaria, hospitalaria y sociosanitaria). Incluye medicina de familia (5), medicina interna (2) y geriatría (2), enfermería (9), psicología (1) y trabajo social (1). Medidas principales: Alfa de Cronbach, Kappa ponderado, tiempo de respuesta. Resultados: Alfa de Cronbach de 0,91 por HexCom-Red® y de 0,87 por HexCom-Clin®. Fiabilidad intraobservador entre buena y muy buena por HexCom-Red® (Kappa: 0,78-1) y entre moderada y muy buena por HexCom-Clin® (Kappa: 0,58-0,91). Tiempo de respuesta de 0:57min de media por el HexCom-Red y de 3:80min por HexCom-Clin®. Conclusiones: Los instrumentos HexCom-Red® y HexCom-Clin® son fiables y su uso factible para todas las profesiones implicadas en la atención paliativa, tanto generalista como especializada y de los diferentes niveles asistenciales.(AU)

Intra-rater reliability and feasibility of the HexCom advanced disease complexity assessment model.

AIM: To study the intra-rater reliability and feasibility of the HexCom complexity assessment model by analyzing internal consistency, intra-rater reliability and response time. DESIGN: Test-retest study with a selection of 11 clinical situations that cover the full scope of situations assessed by the HexCom model and which are responded to individually. LOCATION: Home care, primary care, hospital and sociosanitary care. Two specialized palliative home care teams (PADES). PARTICIPANTS: A total of 20 professionals comprising 10 experts in palliative home care (PADES) and 10 professionals from general palliative care (primary care, hospital and sociosanitary care). These professionals came from the fields of family medicine (5), internal medicine (2), geriatrics (2), nursing (9), psychology (1) and social work (1). MAIN MEASUREMENTS: Cronbach's alpha, weighted kappa, response time. RESULTS: Cronbach's alpha of 0.91 for HexCom-Red and 0.87 for HexCom-Clin. Intra-rater reliability ranging from good to very good for HexCom-Red (kappa: 0.78-1) and from moderate to very good for HexCom-Clin (kappa: 0.58-0.91). Average response time of 0:57 for HexCom-Red and 3:80min for HexComClin. CONCLUSIONS: HexCom-Red and HexCom-Clin are reliable tools and feasible for use by all professionals involved in both general and specialized palliative care at different levels.

Gender and Observed Complexity in Palliative Home Care: A Prospective Multicentre Study Using the HexCom Model.

This study analyses gender differences in the complexity observed in palliative home care through a multicentre longitudinal observational study of patients with advanced disease treated by palliative home care teams in Catalonia (Spain). We used the HexCom model, which includes six dimensions and measures three levels of complexity: high (non-modifiable situation), medium (difficult) and low. Results: N = 1677 people, 44% women. In contrast with men, in women, cancer was less prevalent (64.4% vs. 73.9%) (p < 0.001), cognitive impairment was more prevalent (34.1% vs. 26.6%; p = 0.001) and professional caregivers were much more common (40.3% vs. 24.3%; p < 0.001). Women over 80 showed less complexity in the following subareas: symptom management (41.7% vs. 51,1%; p = 0.011), emotional distress (24.5% vs. 32.8%; p = 0.015), spiritual distress (16.4% vs. 26.4%; p = 0.001), socio-familial distress (62.7% vs. 70.1%; p = 0.036) and location of death (36.0% vs. 49.6%; p < 0.000). Men were more complex in the subareas of "practice" OR = 1.544 (1.25-1.90 p = 0.000) and "transcendence" OR = 1.52 (1.16-1.98 p = 0.002). Observed complexity is related to male gender in people over 80 years of age. Women over the age of 80 are remarkably different from their male counterparts, showing less complexity regarding care for their physical, psycho-emotional, spiritual and socio-familial needs.

[Wish to hasten death in home palliative care. Look for your seven percent.] / El deseo de adelantar la muerte en cuidados paliativos domiciliarios. Busca tu siete por ciento.

OBJECTIVE: The wish to hasten death has been little researched in the area of Mediterranean countries and we are not aware of specific studies on its particularities in home care in our setting. The aim of this work was to investigate the prevalence and evolution of wish to hasten death in home care, analysing its relationship with physical, emotional, spiritual, ethical and social-family unrest. METHODS: Longitudinal observational study in palliative home care in Catalonia. 43 teams agreed on the level of complexity after the first visit and after the discharge of the patient with the HexCom model, which classifies the desire to anticipate death into Low complexity (no or sporadic manifestation); Medium (persistent desire that requires specific treatment); or High (persistent desire that is considered potentially refractory). For the comparison of proportions, Pearson's Chi-squared test was used and a multivariate logistic regression analysis was performed, in which the dependent variable corresponded to the desire to hasten initial death. The level of significance was p≤0.05. RESULTS: The total number of patients included in this study was 1,677, of whom 1,169 (69.7%) were oncologic. The prevalence of desire to hasten death was 6.67%. It was related to spiritual distress, especially lack of meaning (OR 3.25) and lack of connection (OR 3.81), to psychoemotional distress (OR 2.34) and to ethical distress. Protective factors were spiritual distress in relation to transcendence (OR 0.50), the caregiver being a partner (OR 0.50) and being cared for by a team that included psychology and social work (OR 0.34). The desire to anticipate death is stable in 71.6% of patients. CONCLUSIONS: The desire to anticipate death is a changing and complex phenomenon that can emerge at any time. The presence of psycho-emotional, spiritual-existential and ethical discomfort, especially in patients without a partner, should make us take a proactive attitude to identify it early.

OBJETIVO: El deseo de adelantar la muerte ha sido poco investigado en el área de los países mediterráneos y no conocemos estudios específicos sobre sus particularidades en atención domiciliaria en nuestro entorno. El objetivo de este trabajo fue investigar la prevalencia y la evolución del deseo de anticipar la muerte en atención domiciliaria, analizando su relación con el malestar físico, emocional, espiritual, ético y sociofamiliar. METODOS: Estudio observacional longitudinal en el ámbito de la atención domiciliaria paliativa en Catalunya. 43 equipos acordaron el nivel de complejidad tras la primera visita y tras el alta del paciente con el modelo HexCom, el cual clasifica el deseo de anticipar la muerte en complejidad Baja (manifestación nula o esporádica); Media (Deseo persistente que requiere tratamiento específico); o Alta (Deseo persistente que se considera potencialmente refractario). Para la comparación de proporciones se utilizó la prueba de Ji cuadrado de Pearson y se realizó un análisis de regresión logística multivariante, en el que la variable dependiente correspondía con el deseo de adelantar la muerte inicial. El nivel de significación fue p≤0,05. RESULTADOS: El número total de pacientes incluidos en este estudio fue de 1.677, de los cuales 1.169 (69,7%) eran oncológicos. La prevalencia de deseo de anticipar la muerte fue del 6,67%. Se relacionó con el malestar espiritual, ante todo con la falta de sentido (OR 3,25) y de conexión (OR 3,81), con el malestar psicoemocional (OR 2,34) y con el malestar ético. Fueron factores protectores el malestar espiritual en relación con la transcendencia (OR 0,50), que el cuidador fuese la pareja (OR 0,50) y ser atendido por un equipo en el que se incluyese psicología y trabajo social (OR 0,34). El deseo de anticipar la muerte fue estable en el 71,6% de los pacientes. CONCLUSIONES: El deseo de anticipar la muerte es un fenómeno cambiante y complejo que puede emerger en cualquier momento. La presencia de malestar psicoemocional, espiritual-existencial y ético, sobre todo en pacientes sin pareja, nos han de hacer tomar una actitud proactiva para identificarlo precozmente.

Null cyp1b1 Activity in Zebrafish Leads to Variable Craniofacial Defects Associated with Altered Expression of Extracellular Matrix and Lipid Metabolism Genes.

CYP1B1 loss of function (LoF) is the main known genetic alteration present in recessive primary congenital glaucoma (PCG), an infrequent disease characterized by delayed embryonic development of the ocular iridocorneal angle; however, the underlying molecular mechanisms are poorly understood. To model CYP1B1 LoF underlying PCG, we developed a cyp1b1 knockout (KO) zebrafish line using CRISPR/Cas9 genome editing. This line carries the c.535_667del frameshift mutation that results in the 72% mRNA reduction with the residual mRNA predicted to produce an inactive truncated protein (p.(His179Glyfs*6)). Microphthalmia and jaw maldevelopment were observed in 23% of F0 somatic mosaic mutant larvae (144 hpf). These early phenotypes were not detected in cyp1b1-KO F3 larvae (144 hpf), but 27% of adult (four months) zebrafish exhibited uni- or bilateral craniofacial alterations, indicating the existence of incomplete penetrance and variable expressivity. These phenotypes increased to 86% in the adult offspring of inbred progenitors with craniofacial defects. No glaucoma-related phenotypes were observed in cyp1b1 mutants. Transcriptomic analyses of the offspring (seven dpf) of cyp1b1-KO progenitors with adult-onset craniofacial defects revealed functionally enriched differentially expressed genes related to extracellular matrix and cell adhesion, cell growth and proliferation, lipid metabolism (retinoids, steroids and fatty acids and oxidation-reduction processes that include several cytochrome P450 genes) and inflammation. In summary, this study shows the complexity of the phenotypes and molecular pathways associated with cyp1b1 LoF, with species dependency, and provides evidence for the dysregulation of extracellular matrix gene expression as one of the mechanisms underlying the pathogenicity associated with cyp1b1 disruption.

Identification of the Active Principle Conferring Anti-Inflammatory and Antinociceptive Properties in Bamboo Plant.

Early plants began colonizing earth about 450 million years ago. During the process of coevolution, their metabolic cellular pathways produced a myriad of natural chemicals, many of which remain uncharacterized biologically. Popular preparations containing some of these molecules have been used medicinally for thousands of years. In Brazilian folk medicine, plant extracts from the bamboo plant Guadua paniculata Munro have been used for the treatment of infections and pain. However, the chemical basis of these therapeutic effects has not yet been identified. Here, we performed protein biochemistry and downstream pharmacological assays to determine the mechanisms underlying the anti-inflammatory and antinociceptive effects of an aqueous extract of the G. paniculata rhizome, which we termed AqGP. The anti-inflammatory and antinociceptive effects of AqGP were assessed in mice. We identified and purified a protein (AgGP), with an amino acid sequence similar to that of thaumatins (~20 kDa), capable of repressing inflammation through downregulation of neutrophil recruitment and of decreasing hyperalgesia in mice. In conclusion, we have identified the molecule and the molecular mechanism responsible for the anti-inflammatory and antinociceptive properties of a plant commonly used in Brazilian folk medicine.

Assessing Face Validity of the HexCom Model for Capturing Complexity in Clinical Practice: A Delphi Study.

Capturing complexity is both a conceptual and a practical challenge in palliative care. The HexCom model has proved to be an instrument with strong reliability and to be valid for describing the needs and strengths of patients in home care. In order to explore whether it is also perceived to be helpful in enhancing coordinated and patient-centred care at a practical level, a methodological study was carried out to assess the face validity of the model. In particular, a Delphi method involving a group of 14 experts representing the full spectrum of healthcare professionals involved in palliative care was carried out. The results show that there is a high level of agreement, with a content validity index-item greater than 0.92 both with regard to the complexity model and the HexCom-Red, HexCom-Basic, and the HexCom-Clin instruments, and higher than 0.85 regarding the HexCom-Figure and the HexCom-Patient instruments. This consensus confirms that the HexCom model and the different instruments that are derived from it are valued as useful tools for a broad range of healthcare professional in coordinately capturing complexity in healthcare practice.

Knockout of myoc Provides Evidence for the Role of Myocilin in Zebrafish Sex Determination Associated with Wnt Signalling Downregulation.

Myocilin is a secreted glycoprotein with a poorly understood biological function and it is mainly known as the first glaucoma gene. To explore the normal role of this protein in vivo we developed a myoc knockout (KO) zebrafish line using CRISPR/Cas9 genome editing. This line carries a homozygous variant (c.236_239delinsAAAGGGGAAGGGGA) that is predicted to result in a loss-of-function of the protein because of a premature termination codon p.(V75EfsX60) that resulted in a significant reduction of myoc mRNA levels. Immunohistochemistry showed the presence of myocilin in wild-type embryonic (96 h post-fertilization) anterior segment eye structures and caudal muscles. The protein was also detected in different adult ocular and non-ocular tissues. No gross macroscopic or microscopic alterations were identified in the KO zebrafish, but, remarkably, we observed absence of females among the adult KO animals and apoptosis in the immature juvenile gonad (28 dpf) of these animals, which is characteristic of male development. Transcriptomic analysis showed that adult KO males overexpressed key genes involved in male sex determination and presented differentially expressed Wnt signalling genes. These results show that myocilin is required for ovary differentiation in zebrafish and provides in vivo support for the role of myocilin as a Wnt signalling pathway modulator. In summary, this myoc KO zebrafish line can be useful to investigate the elusive function of this protein, and it provides evidence for the unexpected function of myocilin as a key factor in zebrafish sex determination.

Role of GUCA1C in Primary Congenital Glaucoma and in the Retina: Functional Evaluation in Zebrafish.

Primary congenital glaucoma (PCG) is a heterogeneous, inherited, and severe optical neuropathy caused by apoptotic degeneration of the retinal ganglion cell layer. Whole-exome sequencing analysis of one PCG family identified two affected siblings who carried a low-frequency homozygous nonsense GUCA1C variant (c.52G > T/p.Glu18Ter/rs143174402). This gene encodes GCAP3, a member of the guanylate cyclase activating protein family, involved in phototransduction and with a potential role in intraocular pressure regulation. Segregation analysis supported the notion that the variant was coinherited with the disease in an autosomal recessive fashion. GCAP3 was detected immunohistochemically in the adult human ocular ciliary epithelium and retina. To evaluate the ocular effect of GUCA1C loss-of-function, a guca1c knockout zebrafish line was generated by CRISPR/Cas9 genome editing. Immunohistochemistry demonstrated the presence of GCAP3 in the non-pigmented ciliary epithelium and retina of adult wild-type fishes. Knockout animals presented up-regulation of the glial fibrillary acidic protein in Müller cells and evidence of retinal ganglion cell apoptosis, indicating the existence of gliosis and glaucoma-like retinal damage. In summary, our data provide evidence for the role of GUCA1C as a candidate gene in PCG and offer new insights into the function of this gene in the ocular anterior segment and the retina.

CPAMD8 loss-of-function underlies non-dominant congenital glaucoma with variable anterior segment dysgenesis and abnormal extracellular matrix.

Abnormal development of the ocular anterior segment may lead to a spectrum of clinical phenotypes ranging from primary congenital glaucoma (PCG) to variable anterior segment dysgenesis (ASD). The main objective of this study was to identify the genetic alterations underlying recessive congenital glaucoma with ASD (CG-ASD). Next-generation DNA sequencing identified rare biallelic CPAMD8 variants in four patients with CG-ASD and in one case with PCG. CPAMD8 is a gene of unknown function and recently associated with ASD. Bioinformatic and in vitro functional evaluation of the variants using quantitative reverse transcription PCR and minigene analysis supported a loss-of-function pathogenic mechanism. Optical and electron microscopy of the trabeculectomy specimen from one of the CG-ASD cases revealed an abnormal anterior chamber angle, with altered extracellular matrix, and apoptotic trabecular meshwork cells. The CPAMD8 protein was immunodetected in adult human ocular fluids and anterior segment tissues involved in glaucoma and ASD (i.e., aqueous humor, non-pigmented ciliary epithelium, and iris muscles), as well as in periocular mesenchyme-like cells of zebrafish embryos. CRISPR/Cas9 disruption of this gene in F0 zebrafish embryos (96 hpf) resulted in varying degrees of gross developmental abnormalities, including microphthalmia, pharyngeal maldevelopment, and pericardial and periocular edemas. Optical and electron microscopy examination of these embryos showed iridocorneal angle hypoplasia (characterized by altered iris stroma cells, reduced anterior chamber, and collagen disorganized corneal stroma extracellular matrix), recapitulating some patients' features. Our data support the notion that CPAMD8 loss-of-function underlies a spectrum of recessive CG-ASD phenotypes associated with extracellular matrix disorganization and provide new insights into the normal and disease roles of this gene.

Describing Complexity in Palliative Home Care Through HexCom: A Cross-Sectional, Multicenter Study.

BACKGROUND: Complexity has become a core issue in caring for patients with advanced disease and/or at the end-of-life. The Hexagon of Complexity (HexCom) is a complexity assessment model in the process of validation in health-care settings. Our objective is to use the instrument to describe differences in complexity across disease groups in specific home care for advanced disease and/or at the end-of-life patients, both in general and as relates to each domain and subdomain. METHODS: Cross-sectional study of home care was conducted in Catalonia. The instrument includes 6 domains of needs (clinical, psychological/emotional, social/family, spiritual, ethical, and death-related), 4 domains of resources (intrapersonal, interpersonal, transpersonal, and practical), and 3 levels of complexity (High (H), Moderate (M), and Low (L)). Interdisciplinary home care teams assessed and agreed on the level of complexity for each patient. RESULTS: Forty-three teams participated (74.1% of those invited). A total of 832 patients were assessed, 61.4% of which were cancer patients. Moderate complexity was observed in 385 (47.0%) cases and high complexity in 347 (42.4%). The median complexity score was 51 for cancer patients and 23 for patients with dementia (p<0.001). We observed the highest level of complexity in the social/family domain. Patients/families most frequently used interpersonal resources (80.5%). CONCLUSIONS: This study sheds light on the high-intensity work of support teams, the importance of the social/family domain and planning the place of death, substantial differences in needs and resources across disease groups, and the importance of relationship wellbeing at the end-of-life.

Neuroinflammation: An overview of neurodegenerative and metabolic diseases and of biotechnological studies.

Neuroinflammation is an important factor contributing to cognitive impairment and neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), Amyotrophic lateral sclerosis (ALS), ischemic injury, and multiple sclerosis (MS). These diseases are characterized by inexorable progressive injury of neuron cells, and loss of motor or cognitive functions. Microglia, which are the resident macrophages in the brain, play an important role in both physiological and pathological conditions. In this review, we provide an updated discussion on the role of ROS and metabolic disease in the pathological mechanisms of activation of the microglial cells and release of cytotoxins, leading to the neurodegenerative process. In addition, we also discuss in vivo models, such as zebrafish and Caenorhabditis elegans, and provide new insights into therapeutics bioinspired by neuropeptides from venomous animals, supporting high throughput drug screening in the near future, searching for a complementary approach to elucidating crucial mechanisms associated with neurodegenerative disorders.

Synthesis and biological activities of a nitro-shiff base compound as a potential anti-inflammatory agent.

In order to discover a new compound having anti-inflammatory activity, a nitro-Schiff base was evaluated. The compound was synthesized and characterized by 1H NMR and 13C NMR. The cytotoxic activity was evaluated in vitro by hemolysis and MTT cell viability assay. To evaluate genotoxicity, the micronucleus assay was performed in vivo. The anti-inflammatory effects of the compound were examined using in vivo models of inflammation such as neutrophil migration assay, paw edema, and exudation assay. The production of NO was also estimated in vivo and in vitro. The data showed that the compound did not induce hemolysis at all the tested concentrations. Similarly, the compound did not induce cytotoxicity and genotoxicity to the cells. The neutrophil migration assay showed that the compound reduced the number of neutrophils recruited to the peritoneal cavity by approximately 60% at all the tested concentrations. In the exudation assay, the compound showed a reduction in extravasation by 24%. The paw edema model demonstrated a significant reduction in the paw volume at all the evaluated time points. The production of NO was decreased both in vitro and in vivo. These results suggest that the nitro-Schiff base compound efficiently inhibited inflammation and might be a good candidate for the treatment of inflammatory-associated conditions.

Clinimetric analysis of heart failure in Mexican patients.

Heart failure (HF) is a syndrome characterized basically by a circulatory deficit to cover the metabolic and energetic demands of the body. This condition has a broad spectrum in its clinical presentation, affects the quality of life significantly, impacts the family/social environment, and generates a great demand for health services. The purpose of this research is to report the situational diagnose of patients with HF in Mexico. We evaluated 292 patients, 70.2% were men. Average age was 56.7 ± 14.3 years. Ischemic heart disease is the main etiology (98 patients, 33.9%) followed by hypertensive (22.6%) and idiopathic (23.3%) heart disease. The associated clinical background was obesity (31.1%), systemic hypertension (36.7%), myocardial infarction (26.4%), and dyslipidemia (15.1%). The most common symptom was stress dyspnea (41.4%) and jugular vein engorgement at physical examination (32.5%). Anemia was observed in 1% of patients. The average left ventricular ejection fraction was 29.2 ± 10.6%. Sinus rhythm was the most frequently detected in 84.9%. 19.9% of patients had an implantable cardioverter-defibrillator or cardiac resynchronization therapy. 13.7% of patients with QRS > 130 ms. In our population, the meta-analysis global group in chronic heart failure risk score calculated was 16.8 ± 5.7 and for EMPHASIS 3.3 ± 1.5. We observed that age at presentation in HF in this analysis is at least 10 years younger than in other reports. The grade of obesity takes relevance in our group. The association of anemia and HF in Mexico is rare.

La insuficiencia cardiaca es un síndrome caracterizado fundamentalmente por un déficit circulatorio para cubrir las demandas metabólicas y energéticas del organismo. Esta entidad tiene un amplio espectro en su presentación clínica, afecta de manera significativa la calidad de vida, impacta en el entorno familiar/social y genera una gran demanda de los servicios de salud. El propósito de esta investigación es reportar el diagnóstico situacional de pacientes con insuficiencia cardiaca (IC) en México. Evaluamos 292 enfermos, 70.2% eran hombres. Con edad promedio 56.7 ± 14.3 años. La principal etiología es la cardiopatía isquémica (33.9%), seguida de la hipertensiva (22.6%) e idiopática (23.3%). Los antecedentes clínicos asociados fueron: obesidad (31.1%), hipertensión arterial sistémica (36.7%), infarto al miocardio (26.4%) y dislipidemia (15.1%). El síntoma con mayor presentación fue la disnea de esfuerzos (41.4%) y a la exploración física la ingurgitación yugular (32.5%). Se observó anemia en 1% de los enfermos. La fracción de expulsión del ventrículo izquierdo (FEVI) promedio fue de 29.2 + 10.6%. El ritmo sinusal fue el más frecuentemente detectado en 84.9%. El 19.9% de los pacientes tenían instalado un desfibrilador automático implantable (DAI) o tratamiento de resincronización cardiaca (TRC). El 13.7% de los enfermos con QRS mayor de 130 ms. El riesgo (MAGGIC) calculado en nuestro grupo poblacional fue de 16.8 ± 5.7 y para EMPHASIS 3.3 ± 1.5. Observamos que la edad de presentación de la IC en el presente análisis es menor por 10 años en comparación con otros reportes. El grado de obesidad toma relevancia en nuestro grupo. La asociación de anemia e IC en México es poco frecuente.

Clinimetric analysis of heart failure in Mexican patients / Análisis clinimétrico de la insuficiencia cardiaca en pacientes mexicanos

Abstract Heart failure (HF) is a syndrome characterized basically by a circulatory deficit to cover the metabolic and energetic demands of the body. This condition has a broad spectrum in its clinical presentation, affects the quality of life significantly, impacts the family/social environment, and generates a great demand for health services. The purpose of this research is to report the situational diagnose of patients with HF in Mexico. We evaluated 292 patients, 70.2% were men. Average age was 56.7 +- 14.3 years. Ischemic heart disease is the main etiology (98 patients, 33.9%) followed by hypertensive (22.6%) and idiopathic (23.3%) heart disease. The associated clinical background was obesity (31.1%), systemic hypertension (36.7%), myocardial infarction (26.4%), and dyslipidemia (15.1%). The most common symptom was stress dyspnea (41.4%) and jugular vein engorgement at physical examination (32.5%). Anemia was observed in 1% of patients. The average left ventricular ejection fraction was 29.2 +- 10.6%. Sinus rhythm was the most frequently detected in 84.9%. 19.9% of patients had an implantable cardioverter-defibrillator or cardiac resynchronization therapy. 13.7% of patients with QRS > 130 ms. In our population, the meta-analysis global group in chronic heart failure risk score calculated was 16.8 +- 5.7 and for EMPHASIS 3.3 +- 1.5. We observed that age at presentation in HF in this analysis is at least 10 years younger than in other reports. The grade of obesity takes relevance in our group. The association of anemia and HF in Mexico is rare.

Resumen La insuficiencia cardiaca es un síndrome caracterizado fundamentalmente por un déficit circulatorio para cubrir las demandas metabólicas y energéticas del organismo. Esta entidad tiene un amplio espectro en su presentación clínica, afecta de manera significativa la calidad de vida, impacta en el entorno familiar/social y genera una gran demanda de los servicios de salud. El propósito de esta investigación es reportar el diagnóstico situacional de pacientes con insuficiencia cardiaca (IC) en México. Evaluamos 292 enfermos, 70.2% eran hombres. Con edad promedio 56.7 +- 14.3 años. La principal etiología es la cardiopatía isquémica (33.9%), seguida de la hipertensiva (22.6%) e idiopática (23.3%). Los antecedentes clínicos asociados fueron: obesidad (31.1%), hipertensión arterial sistémica (36.7%), infarto al miocardio (26.4%) y dislipidemia (15.1%). El síntoma con mayor presentación fue la disnea de esfuerzos (41.4%) y a la exploración física la ingurgitación yugular (32.5%). Se observó anemia en 1% de los enfermos. La fracción de expulsión del ventrículo izquierdo (FEVI) promedio fue de 29.2 + 10.6%. El ritmo sinusal fue el más frecuentemente detectado en 84.9%. El 19.9% de los pacientes tenían instalado un desfibrilador automático implantable (DAI) o tratamiento de resincronización cardiaca (TRC). El 13.7% de los enfermos con QRS mayor de 130 ms. El riesgo (MAGGIC) calculado en nuestro grupo poblacional fue de 16.8 +- 5.7 y para EMPHASIS 3.3 +- 1.5. Observamos que la edad de presentación de la IC en el presente análisis es menor por 10 años en comparación con otros reportes. El grado de obesidad toma relevancia en nuestro grupo. La asociación de anemia e IC en México es poco frecuente.

Role of FOXC2 and PITX2 rare variants associated with mild functional alterations as modifier factors in congenital glaucoma.

Congenital glaucoma (CG) is a severe and inherited childhood optical neuropathy that leads to irreversible visual loss and blindness in children. CG pathogenesis remains largely unexplained in most patients. Herein we have extended our previous studies to evaluate the role of FOXC2 and PITX2 variants in CG. Variants of the proximal promoter and transcribed sequence of these two genes were analyzed by Sanger sequencing in a cohort of 133 CG families. To investigate possible oligogenic inheritance involving FOXC2 or PITX2 and CYP1B1, we also analyzed FOXC2 and PITX2 variants in a group of 25 CG cases who were known to carry CYP1B1 glaucoma-associated genotypes. The functional effect of three identified variants was assessed by transactivation luciferase reporter assays, protein stability and subcellular localization analyses. We found eight probands (6.0%) who carried four rare FOXC2 variants in the heterozygous state. In addition, we found an elevated frequency (8%) of heterozygous and rare PITX2 variants in the group of CG cases who were known to carry CYP1B1 glaucoma-associated genotypes, and one of these PITX2 variants arose de novo. To the best of our knowledge, two of the identified variants (FOXC2: c.1183C>A, p.(H395N); and PITX2: c.535C>A, p.(P179T)) have not been previously identified. Examination of the genotype-phenotype correlation in this group suggests that the presence of the infrequent PITX2 variants increase the severity of the phenotype. Transactivation reporter analyses showed partial functional alteration of three identified amino acid substitutions (FOXC2: p.(C498R) and p.(H395N); PITX2: p.(P179T)). In summary, the increased frequency in PCG patients of rare FOXC2 and PITX2 variants with mild functional alterations, suggests they play a role as putative modifier factors in this disease further supporting that CG is not a simple monogenic disease and provides novel insights into the complex pathological mechanisms that underlie CG.

Assessment of a subset of Slowly Mutating Y-STRs for forensic and evolutionary studies.

Y-specific short tandem repeat (Y-STR) loci display different mutation rates and consequently are suitable for forensic, genealogical, and evolutionary studies that require different levels of timelines and resolution. Recent efforts have focused on implementing Rapidly Mutating (RM) Y-STRs to assess male specific profiles. However, due to their high mutation rate their use in kinship testing or in phylogenetic studies may be less reliable. In the present study, a novel Slowly Mutating Y-STR (SM) panel, including DYS388, DYS426, DYS461 (Y-GATA-A7.2), DYS485, DYS525, and DYS561, has been developed and evaluated in a sample set of 628 unrelated males from different worldwide populations. This panel is reproducible, sensitive, and robust for forensic applications and may be useful in conjunction with the common multiplexes, particularly in exclusion of kinship cases where minimal discrimination is reported employing the rapidly mutating Y-STR systems. Furthermore, SM Y-STR data may be of value in evolutionary studies to optimize the resolution of phylogenetic relationships generated with current Y-STR panel sets. In this study, we provide an extensive Y-STR allele and haplotype reference dataset for future applications.

Systemic Administration of Antipsychotic Asenapine Pre or Postnatal does not Induce Anxiety-like Behaviors in Mice.

BACKGROUND AND OBJECTIVE: Asenapine is an atypical antipsychotic approved by US Food and Drug Administration in 2009 and by European Medicines Agency in 2010 for Schizophrenia and Bipolar Disorder treatment. Currently, many studies have been developed in an attempt to clarify and minimize the risks related to the use of psychotropic during pre/postnatal period on patients with a history of mental disorders. CONCLUSION: The aim of this study was to test the impact of pre and/or postnatal exposition to asenapine on mice offspring behavior. Four groups of animals, previously treated with a dosage equivalent to 50% of the bioavailability obtained with a 20 mg daily use for human treatment, were exposed to the Open Field and Elevated plus Maze test. Only the group exposed to asenapine during both pre and postnatal periods showed response difference in the Elevated Plus Maze test, which was restricted to urination. However, our data suggest that the administration of asenapine does not induce significant anxiety-like behaviors in mice.

Analysis of the R1b-DF27 haplogroup shows that a large fraction of Iberian Y-chromosome lineages originated recently in situ.

Haplogroup R1b-M269 comprises most Western European Y chromosomes; of its main branches, R1b-DF27 is by far the least known, and it appears to be highly prevalent only in Iberia. We have genotyped 1072 R1b-DF27 chromosomes for six additional SNPs and 17 Y-STRs in population samples from Spain, Portugal and France in order to further characterize this lineage and, in particular, to ascertain the time and place where it originated, as well as its subsequent dynamics. We found that R1b-DF27 is present in frequencies ~40% in Iberian populations and up to 70% in Basques, but it drops quickly to 6-20% in France. Overall, the age of R1b-DF27 is estimated at ~4,200 years ago, at the transition between the Neolithic and the Bronze Age, when the Y chromosome landscape of W Europe was thoroughly remodeled. In spite of its high frequency in Basques, Y-STR internal diversity of R1b-DF27 is lower there, and results in more recent age estimates; NE Iberia is the most likely place of origin of DF27. Subhaplogroup frequencies within R1b-DF27 are geographically structured, and show domains that are reminiscent of the pre-Roman Celtic/Iberian division, or of the medieval Christian kingdoms.