Oreoch-1: A broad-spectrum virus and host-targeting peptide against animal infections.

In recent decades, the global rise of viral emerging infectious diseases has posed a substantial threat to both human and animal health worldwide. The rapid spread and accumulation of mutations into viruses, and the limited availability of antiviral drugs and vaccines, stress the urgent need for alternative therapeutic strategies. Antimicrobial peptides (AMPs) derived from natural sources present a promising avenue due to their specificity and effectiveness against a broad spectrum of pathogens. The present study focuses on investigating the antiviral potential of oreochromicin-1 (oreoch-1), a fish-derived AMP obtained from Nile tilapia, against a wide panel of animal viruses including canine distemper virus (CDV), Schmallenberg virus (SBV), caprine herpesvirus 1 (CpHV-1), and bovine herpesvirus 1 (BoHV-1). Oreoch-1 exhibited a strong antiviral effect, demonstrating an inhibition of infection at concentrations in the micromolar range. The mechanism of action involves the interference with viral entry into host cells and a direct interaction between oreoch-1 and the viral envelope. In addition, we observed that the peptide could also interact with the cell during the CDV infection. These findings not only highlight the efficacy of oreoch-1 in inhibiting viral infection but also emphasize the potential of fish-derived peptides, specifically oreoch-1, as effective antiviral agents against viral infections affecting animals, whose potential to spill into humans is high. This research contributes valuable insights to the ongoing quest for novel antiviral drugs with the potential to mitigate the impact of infectious diseases on a global scale.

Ultra-late response (> 24 weeks) to anti-CGRP monoclonal antibodies in migraine: a multicenter, prospective, observational study.

OBJECTIVE: Nearly 60% of migraine patients treated with monoclonal antibodies (mAbs) targeting the calcitonin gene-related peptide (CGRP) pathway experience a ≥ 50% reduction in monthly migraine days (MMD) at 12 weeks compared to baseline (responders). However, approximately half of the patients not responding to anti-CGRP mAbs ≤ 12 weeks do respond ≤ 24 weeks (late responders). We assessed frequency and characteristics of patients responding to anti-CGRP mAbs only > 24 weeks (ultra-late responders). METHODS: In this multicenter (n = 16), prospective, observational, real-life study, we enrolled all consecutive adults affected by high-frequency episodic migraine (HFEM: ≥ 8 days/month) or chronic migraine (CM), with ≥ 3 prior therapeutic failures, treated with any anti-CGRP mAbs for ≥ 48 weeks. We defined responders patients with a ≥ 50% response rate ≤ 12 weeks, late responders those with a ≥ 50% response rate ≤ 24 weeks, and ultra-late responders those achieving a ≥ 50% response only > 24 weeks. RESULTS: A total of 572 migraine patients completed ≥ 48 weeks of anti-CGRP mAbs treatment. Responders accounted for 60.5% (346/572), late responders for 15% (86/572), and ultra-late responders for 15.7% (90/572). Among ultra-late responders, 7.3% (42/572) maintained the ≥ 50% response rate across all subsequent time intervals (weeks 28, 32, 36, 40, 44, and 48) and were considered persistent ultra-late responders, while 8.4% (48/572) missed the ≥ 50% response rate at ≥ 1 subsequent time interval and were classified as fluctuating ultra-late responders. Fifty patients (8.7%) did not respond at any time interval ≤ 48 weeks. Ultra-late responders differed from responders for higher BMI (p = 0.033), longer duration of medication overuse (p < 0.001), lower NRS (p = 0.017) and HIT-6 scores (p = 0.002), higher frequency of dopaminergic symptoms (p = 0.002), less common unilateral pain-either alone (p = 0.010) or in combination with UAS (p = 0.023), allodynia (p = 0.043), or UAS and allodynia (p = 0.012)-a higher number of comorbidities (p = 0.012), psychiatric comorbidities (p = 0.010) and a higher proportion of patients with ≥ 1 comorbidity (p = 0.020). CONCLUSION: Two-thirds of patients not responding to anti-CGRP mAbs ≤ 24 weeks do respond later, while non-responders ≤ 48 weeks are quite rare (8.7%). These findings suggest to rethink the duration of migraine prophylaxis and the definition of resistant and refractory migraine, currently based on the response after 2-3 months of treatment.

Assessing the Long-Term (48-Week) Effectiveness, Safety, and Tolerability of Fremanezumab in Migraine in Real Life: Insights from the Multicenter, Prospective, FRIEND3 Study.

INTRODUCTION: Long-term (1-year) fremanezumab treatment proved to be effective, safe, and well tolerated in individuals with migraine and < 2 medication clusters in a randomized controlled trial (RCT). We aimed to assess real-world evidence (RWE), long-term effectiveness, tolerability, and safety of fremanezumab in people with high-frequency episodic migraine (HFEM) or chronic migraine (CM) with > 3 treatment failures and various comorbidities. METHODS: A 48-week, prospective, multicenter (n = 26), cohort study assessed fremanezumab's effectiveness, safety, and tolerability in consecutive adults with HFEM or CM with > 3 treatment failures. Primary endpoint was variation from baseline in monthly migraine days (MMD) in HFEM and monthly headache days (MHD) in CM at weeks 45-48. Secondary endpoints were changes in monthly analgesic medications, Numerical Rating Scale (NRS), Headache Impact Test (HIT-6), and the Migraine Disability Assessment Scale (MIDAS) scores and ≥ 50%, ≥ 75%, and 100% responder rates. RESULTS: Of 533 participants who had received ≥ 1 fremanezumab dose, 130 were treated for ≥ 48 weeks and considered for effectiveness analysis. No participant missed any treatment dosage every other consecutive month during the 12-month period. PRIMARY ENDPOINT: fremanezumab significantly (p < 0.001) reduced both MMD (- 6.4) in HFEM and MHD (- 14.5) in CM. Secondary endpoints: a significant reduction (p < 0.001) was observed in monthly analgesic medications (HFEM - 6.0; CM -16.5), NRS (HFEM - 3.4; CM - 3.4), HIT-6 (HFEM - 16.9; CM - 17.9) and MIDAS score (HFEM - 50.4; CM - 76.6). The ≥ 50%, ≥ 75%, and 100% response rates to fremanezumab were 75.5%, 36.7%, and 2% in HFEM and 71.6%, 44.4%, and 3.7% in CM. Corresponding response rates were 60.5%, 37.2%, and 2.3% in individuals with psychiatric comorbidities, 74.2%, 50%, and 4.8% in CM with medication overuse, and 60.9%, 39.1%, and 4.3% in CM with medication overuse and psychiatric comorbidities. Mild and transient treatment-emergent adverse events occurred in 7.8% of the participants. No subject discontinued the treatment for any reason. CONCLUSION: This RWE study documents that long-term fremanezumab treatment is highly effective and remarkably well tolerated in subjects with HFEM or CM with multiple (> 3) therapeutic failures, even in the presence of concomitant medication overuse, psychiatric comorbidities, or both. The effectiveness-to-tolerability ratio appears to be better in RWE than in RCTs.

Características sociodemográficas, psicológicas y clínicas de una cohorte de personas transgénero de mediana y avanzada edad: importancia de la atención primaria en la asistencia a la transexualidad y diversidad de género / Socio-demographic, psychological and clinical characteristics of a cohort of middle-aged and older transgender persons: the importance of primary health care in supporting transsexuality and gender diversity. Characteristics of a cohort of older transgen

Objetivo: describir la proporción de las personas transgénero mayores de 45 años que solicitan acompañamiento médico o psicológico, así como sus características sociales, historia identitaria, presencia de factores de riesgo cardiovascular, tratamiento hormonal o quirúrgico afirmativo y comorbilidades psiquiátricas.Métodos: estudio transversal descriptivo. Se incluyeron 567 pacientes con incongruencia de género que demandaron atención por la Unidad de Identidad de Género (UIG) del Hospital Universitario Doctor Peset de Valencia en el entre 2012 y 2019 (inclusive).Resultados: un 4,2% de la muestra correspondía a personas mayores de 45 años con una mediana de edad de 52 (RIQ: 50,25-60,25) años. La gran mayoría había experimentado un sentimiento de incongruencia identitaria en la etapa prepuberal o adolescente e hizo el tránsito social durante la edad adulta. Un 25% de las mujeres transgénero se automedicaban antes de acudir a la UIG. Un 29,1% tenía antecedentes de ideación suicida y el 25% había llevado a cabo intentos suicidas. Más de la mitad presentaban al menos dos factores de riesgo cardiovascular y no recibían tratamiento farmacológico específico.Conclusiones: en nuestra muestra, existió una baja proporción de personas trans mayores de 45 años que consultaban en la UIG en comparación con el resto de las franjas etarias más jóvenes. Dicho colectivo se caracterizó por presentar altas tasas de factores de riesgo cardiovascular y comorbilidades psicológicas.(AU)

Aim: to report the proportion of transgender persons aged over 45 who requested medical or psychological care, as well as social characteristics, identity history, cardiovascular risk factors, hormonal or affirmative surgical treatment and psychiatric comorbidities.Methods: cross-sectional, descriptive study. We included 567 patients with gender incongruence who requested care at the Gender Identity Unit (UIG), at Doctor Peset University Hospital (Valencia), from 2012 to 2019.Results: a total of 4.2% of sample corresponded to persons aged over 45, with a median age of 52 [IQR 50.25-60.25]. The vast majority had experienced a feeling of identity incongruity in the prepubertal or adolescent stage and made the social transition during adulthood. A total of 25% of transgender women self-medicated before visiting the UIG; 29.1% had a history of suicidal ideation (IS) and 25% had attempted suicide. More than half presented at least two cardiovascular risk factors and did not receive specific pharmacological treatment.Conclusions: In our sample, there was a low proportion of transgender individuals over the age of 45 who sought care at the IUG compared to younger age groups. This particular group was characterized by high rates of cardiovascular risk factors and psychological comorbidities.(AU)

Eficacia de los hidroxicinamatos y los beta-glucanos como herramientas dietéticas frente a la obesidad y sus disfunciones asociadas y su aplicación como nutracéutico / Effectiveness of hydroxycinamates and beta-glucans as dietary tools against obesity and its associated dysfunctions, and their application as nutraceuticals

Durante los últimos años se ha incrementado la incidencia de casos de sobrepeso/obesidad entre la población, afectando en ciertas partes del mundo a más de la mitad de la población adulta. La obesidad lleva asociada comorbilidades como la diabetes tipo 2, la esteatosis hepática no alcohólica y las enfermedades cardiovasculares entre otras muchas, que la han convertido en la segunda causa de muerte evitable en el mundo, solo por detrás del tabaquismo. Ante esta nueva realidad se hace necesaria la búsqueda de nuevas estrategias para combatir el sobrepeso/obesidad y sus patologías asociadas. Los nutracéuticos o suplementos dietéticos se han convertido en una herramienta dietética de sumo interés gracias a su contenido en compuestos bioactivos beneficiosos para la salud. De entre estos compuestos bioactivos, este estudio abordará en profundidad dos de ellos: una fibra soluble, los β-glucanos procedentes de la avena, y un tipo de compuesto fenólico, los hidroxicinamatos. Ambos tipos de compuestos presentan efectos complejos y multifactoriales al actuar como agentes hipolipemiantes, hipoglucemiantes, antioxidantes, prebióticos o saciantes. Ejercen su efecto modulando diferentes vías metabólicas que afectan tanto a la absorción como al metabolismo de los lípidos y los glúcidos, reduciendo el daño oxidativo, promoviendo la proliferación de especies bacterianas beneficiosas y reduciendo la ingesta dietética. Se puede concluir que tanto los beta-glucanos como los hidroxicinamatos presentan potencial como herramienta nutricional en el manejo de distintas disfunciones metabólicas asociadas a la obesidad

Over the last few years the prevalence of overweight and obesity has increased, affecting in certain parts of the World to more than half of the adult population. Obesity has been related to disorders such as type-2 diabetes, non-alcoholic fatty liver disease, and cardiovascular diseases, among others, which has made obesity the second cause of preventable death, only behind smoking. Bearing this in mind, it is necessary to find new strategies to overcome overweight/obesity and its associated pathologies. In this context, nutraceuticals and dietary supplements have become interesting tools thanks to their composition, rich in bioactive compounds beneficial to health. Among bioactive compounds, this study will focus on β-glucans, a type of soluble dietary fiber, and hydroxycinnamic acids, a group of phenols. Both types of compounds show complex and multifactorial effects, acting as hypolipemic, hypoglycemic, antioxidant, prebiotic and satiating agents. They act by modulating different metabolic pathways, affecting the absorption and metabolism of lipids and carbohydrates, reducing oxidative damage, promoting the proliferation of beneficial bacterial species, and reducing dietary intake. It may be concluded that both beta-glucans and hydroxycinnamates have potential as nutritional tools for the management of obesity and its associated metabolic dysfunctions

Duelo por la pérdida perinatal / Grief in perinatal loss

En el presente artículo se aborda el tema de la muerte perinatal y el papel de la matrona en la atención a los padres y familiares que sufren la pérdida. Considerando el vínculo emocional de los padres con el niño antes del nacimiento, su muerte constituye un evento muy doloroso, cuya intensidad y duración varía según diversas circunstancias: la edad gestacional, la personalidad de los padres, en particular de la madre, la calidad de la comunicación entre ellos, las circunstancias familiares que rodean la pérdida, las probabilidades de volver a concebir y, de manera especial, el apoyo social percibido, en particular por parte de la matrona y el equipo de atención obstétrica. Se destaca la importancia de que la matrona tenga en cuenta las necesidades de los dolientes, que muestre empatía y una disposición sincera a brindar apoyo informativo y emocional, con vistas a favorecer el curso normal del duelo (AU)

The present article addresses the topic of perinatal loss and the role of the midwife in terms of care for parents and relatives suffering the loss. Considering the emotional link of parents with their child before birth, death represents a very painful event, with different intensity and duration depending on circumstances such as gestational age, personality of the parents (particularly of the mother), the quality of communication between them, the family circumstances surrounding the death, the likelihood of conceiving another child and, most of all, the social support perceived, particularly from the midwife and the obstetrics care team. The article highlights the importance of the fact that the midwife takes into account the needs of those in grief, that she shows empathy and is sincerely willing to provide information and emotional support, with the aim to encourage the normal course of the grieving process (AU)