Less Favorable Nutri-Score Consumption Ratings Are Prospectively Associated with Abdominal Obesity in Older Adults.

Nutri-Score is a front-of-package (FOP) labeling designed to assist consumers in selecting healthier options at the point of purchase and ultimately enhance their health. This study aims to evaluate the association between the Nutri-Score system and incident abdominal obesity (AO) in community-dwelling older adults. A prospective cohort of 628 individuals aged ≥ 60 were recruited in Spain between 2008-2010 and were reexamined between 2015-2017. Dietary intake was evaluated utilizing a validated computerized dietary history. Food was categorized based on the Nutri-Score system into five levels from A (green, representing the best quality) to E (red, representing the poorest quality). A five-color Nutri-Score dietary index (5-CNS DI) in g/day/kg was calculated for each participant. AO was determined by a waist circumference (WC) of ≥102 cm for men and ≥88 cm for women. Logistic regression models were adjusted for the main potential confounders. During a mean six-year follow-up, 184 incident cases of AO occurred. The odds ratio (OR) and 95% confidence interval (CI) for AO, when comparing the highest and lowest quartiles of the 5-CNS DI, were 2.45 (1.17-5.14), with a p-value for trend of 0.035. In sensitivity analyses, the OR was 2.59 (1.22-5.52, p-trend: 0.032) after adjustment for WC at baseline, and 1.75 (0.74-4.18, p-trend: 0.316) after adjustment for ultra-processed food consumption. In conclusion, less favorable food-consumption ratings in the Nutri-Score are associated with incident AO in the elderly. These findings support the use of this FOP system to potentially improve metabolic health.

[Lichenoid drug eruption with unfavorable evolution. Difficulties in diagnosis]. / Erupción liquenoide medicamentosa con evolución desfavorable. Dificultades en el diagnóstico.

We report the case of a woman who started with a lichenoid eruption, unfavorable evolution, for which a drug reaction was suspected. The final diagnosis was paraneoplastic pemphigus. Multidisciplinary care and evaluation by an Allergist is important in patients with severe skin reactions, suspected of drug reactions, due to the difficulty in establishing the diagnosis.

Se reporta el caso de una mujer que inició con erupción liquenoide, con evolución desfavorable, por lo que se sospechó una reacción medicamentosa. El diagnóstico final fue pénfigo paraneoplásico. Es importante la atención multidisciplinaria y la evaluación de un alergólogo en pacientes con reacciones cutáneas graves, por sospecha de reacciones farmacológicas, debido a la dificultad para establecer el diagnóstico.

Less favourable food consumption ratings in the Five-Color Nutri-Score are associated with incident frailty in older adults.

BACKGROUND: The Nutri-Score front-of-package labelling classifies food products according to their nutritional quality, so healthier food choices are easier when shopping. This study prospectively assesses the association of a diet rated according to the Nutri-Score system and incident frailty in community-dwelling older adults. METHODS: Cohort study with 1,875 individuals aged ≥60 recruited during 2008-2010 in Spain. At baseline, food consumption was assessed using a validated dietary history. Food was categorised into five Nutri-Score labels (A/green-best quality; B, C, D, E/red-worst quality) utilising an algorithm established in 2017 and currently in use. For each participant, a Five-Color Nutri-Score Dietary Index (5-CNS DI) in grams per day per kilogram was calculated. The 5-CNS DI sums up the grams per day of food consumed times their corresponding nutritional quality value (from A rated as 1 to E rated as 5) and divided by weight in kilograms. From baseline to December 2012, incident frailty was ascertained based on Fried's criteria. Statistical analyses were performed with logistic regression adjusted for main confounders. RESULTS: After a mean follow-up of 3.5 years, 136 cases of frailty were identified. The multivariable-adjusted odds ratios (95% confidence interval) of incident frailty across increasing quartiles of the 5-CNS DI were 1, 1.51 (0.86-2.68), 1.56 (0.82-2.98) and 2.32 (1.12-4.79); P-trend = 0.033. The risk of frailty increased by 28% (3-58%) with a 10-unit increment in this dietary index. Similar results were found with the Nutri-Score algorithm modified in 2022. CONCLUSIONS: consumption of a diet with less favourable Nutri-Score ratings doubles the risk of frailty among community-dwelling older adults.

Bisphenol-A Neurotoxic Effects on Basal Forebrain Cholinergic Neurons In Vitro and In Vivo.

The widely used plasticizer bisphenol-A (BPA) is well-known for producing neurodegeneration and cognitive disorders, following acute and long-term exposure. Although some of the BPA actions involved in these effects have been unraveled, they are still incompletely known. Basal forebrain cholinergic neurons (BFCN) regulate memory and learning processes and their selective loss, as observed in Alzheimer's disease and other neurodegenerative diseases, leads to cognitive decline. In order to study the BPA neurotoxic effects on BFCN and the mechanisms through which they are induced, 60-day old Wistar rats were used, and a neuroblastoma cholinergic cell line from the basal forebrain (SN56) was used as a basal forebrain cholinergic neuron model. Acute treatment of rats with BPA (40 µg/kg) induced a more pronounced basal forebrain cholinergic neuronal loss. Exposure to BPA, following 1- or 14-days, produced postsynaptic-density-protein-95 (PSD95), synaptophysin, spinophilin, and N-methyl-D-aspartate-receptor-subunit-1 (NMDAR1) synaptic proteins downregulation, an increase in glutamate content through an increase in glutaminase activity, a downregulation in the vesicular-glutamate-transporter-2 (VGLUT2) and in the WNT/ß-Catenin pathway, and cell death in SN56 cells. These toxic effects observed in SN56 cells were mediated by overexpression of histone-deacetylase-2 (HDAC2). These results may help to explain the synaptic plasticity, cognitive dysfunction, and neurodegeneration induced by the plasticizer BPA, which could contribute to their prevention.

Rationale of the association between Mediterranean diet and the risk of frailty in older adults and systematic review and meta-analysis.

Frailty is a geriatric syndrome whose frequency is increasing in parallel with population aging and is of great interest due to its dire consequences: increased disability, hospitalizations, falls and fractures, institutionalization, and mortality. Frailty is multifactorial but nutritional factors, which are modifiable, play a crucial role in its pathogenesis. Epidemiologic evidence supports that high-quality dietary patterns can prevent, delay or even reverse the occurrence of frailty. In order to add new knowledge bridging the gap as the main purpose of the present article we performed a comprehensive review of the rationale behind the association of MedDiet with frailty and a systematic review and meta-analysis updating the latest ones published in 2018 specifically examining the relationship of Mediterranean diet (MedDiet) and incident frailty. Adding the updated information, our results confirmed a robust association of a higher adherence to MedDiet with reduced incident frailty. Key components of the MedDiet, i.e., abundant consumption of vegetables and fruit as well as the use of olive oil as the main source of fat, all of which have been associated with a lower incidence of frailty, may help explain the observed benefit. Future well-designed and sufficiently large intervention studies are needed to confirm the encouraging findings of the current observational evidence. Meanwhile, based on the existing evidence, the promotion of MedDiet, a high-quality dietary pattern, adapted to the conditions and traditions of each region, and considering lifelong and person-tailored strategies, is an open opportunity to reduced incident frailty. This could also help counteract the worrying trend towards the spread of unhealthy eating and lifestyle models such as those of Western diets that greatly contribute to the genesis of chronic non-communicable diseases and disability.

Introducción al filtrado, análisis y curación de variantes genéticas en pacientes con Discapacidad Intelectual / Introduction to filtering, analysis and curation of genetic variants in patients with Intellectual Disability

Resumen Actualmente la secuenciación del exoma completo (WES; Whole-exome sequencing) mediante la técnica NGS (Next-generation sequencing) es uno de los estudios genéticos más solicitados dentro del abordaje de pacientes con Discapacidad Intelectual con o sin otras anomalías. Al igual que con otros proce dimientos y estudios clínicos, es conveniente que los médicos prescriptores tengan una comprensión clara de los alcances y limitaciones del uso de WES, del proceso de análisis de las variantes genéticas identificadas, así como de aspectos a evaluar acerca de la calidad y estructura de los informes de los estudios de NGS, con el objetivo de que puedan interpretar mejor los resultados de un estudio y plantear de la mejor manera la correlación de los mismos con la clínica observada.

Abstract Currently, Whole exome sequencing (WES) using NGS (Next-generation sequencing) technology is one of the most requested genetic studies within the approach of patients with intellectual disability with or without other anomalies. As with other procedures and clinical studies, it is convenient for prescribing physicians to have a clear understanding of the scope and limitations of the use of WES, the analysis process of the genetic variants identified, as well as aspects to be evaluated regarding quality and structure of the reports of the NGS studies, with the aim that they can better interpret the results of a study, evaluate its quality, and propose in the best way the correlation of the same with the observed phenotype.

Cadmium-promoted thyroid hormones disruption mediates ROS, inflammation, Aß and Tau proteins production, gliosis, spongiosis and neurodegeneration in rat basal forebrain.

Cadmium (Cd) produces cognition decline following single and repeated treatment, although the complete mechanisms are still unrevealed. Basal forebrain (BF) cholinergic neurons innervate the cortex and hippocampus, regulating cognition. Cd single and repeated exposure induced BF cholinergic neuronal loss, partly through thyroid hormones (THs) disruption, which may cause the cognition decline observed following Cd exposure. However, the mechanisms through which THs disruption mediate this effect remain unknown. To research the possible mechanisms through which Cd-induced THs deficiency may mediate BF neurodegeneration, Wistar male rats were treated with Cd for 1- (1 mg/kg) or 28-days (0.1 mg/kg) with or without triiodothyronine (T3, 40 µg/kg/day). Cd exposure promoted neurodegeneration, spongiosis, gliosis and several mechanisms related to these alterations (increased H202, malondialdehyde, TNF-α, IL-1ß, IL-6, BACE1, Aß and phosphorylated-Tau levels, and decreased phosphorylated-AKT and phosphorylated-GSK-3ß levels). T3 supplementation partially reversed the effects observed. Our results show that Cd induces several mechanisms that may be responsible for the neurodegeneration, spongiosis and gliosis observed in the rats' BF, which are partially mediated by a reduction in THs levels. These data may help to explain the mechanisms through which Cd induces BF neurodegeneration, possibly leading to the cognitive decline observed, providing new therapeutic tools to prevent and treat these damages.

[Lugol as a rare cause of anaphylactic reaction after colposcopy. Case report]. / Lugol como causa inusual de anafilaxia después de la colposcopia. Reporte de un caso clínico.

INTRODUCTION: Lugol is a solution composed of elemental iodine (5%) and potassium iodide (10%) together with distilled water, used during colposcopic assessment to identify possible cervical cell alterations. CASE REPORT: A 31-year-old female who presents an episode suggestive of anaphylaxis ninety minutes after a colposcopy exploration, successfully treated with intramuscular hydrocortisone and desclorfeniramine. During colposcopy Lugol solution and acetic acid was applied. Skin prick test (SPT) with Lugol solution was positive (papule 9x7 mm). Four control tests were negative. Intradermal tests (IDT) were positive with Lugol and elemental iodine, the last one turned-out irritant. It was ruled out possible cross-reactivity with other iodine preparations (Betadine®) and potassium iodide (Yoduk®). CONCLUSIONS: Our report demonstrates a rare case of allergy to Lugol solution with positive SPT and a clinical suggestive reaction, with tolerance to other iodine preparations and potassium iodide.

INTRODUCCIÓN: El lugol es una solución compuesta por yodo elemental (5%), yoduro de potasio (10%) y agua destilada, utilizada durante las colposcopias para detectar alteraciones celulares en el cérvix. REPORTE DE CASO: Paciente femenina de 31 años, que tuvo un evento de anafilaxia noventa minutos después de la colposcopia, tratada exitosamente con hidrocortisona por vía intramuscular y desclorfeniramina. Durante la colposcopia se aplicó lugol y ácido acético. La prueba de prick con lugol resultó positiva, con formación de una pápula de 9 x 7 mm, al igual que las pruebas intradérmicas para lugol y yodo elemental. Cuatro controles fueron negativos, excepto para yodo elemental, que resultó irritante en intradermorreacción. Se descartó reactividad cruzada con otras soluciones yodadas (Betadine®) y (Yoduk®). CONCLUSIONES: Reportamos un caso raro de alergia a lugol con prick positivo y una reacción clínica sugerente, con tolerancia a otras preparaciones yodadas y a yoduro de potasio.

[Introduction to filtering, analysis and curation of genetic variants in patients with intellectual disability]. / Introducción al filtrado, análisis y curación de variantes genéticas en pacientes con discapacidad intelectual.

Currently, Whole exome sequencing (WES) using NGS (Next-generation sequencing) technology is one of the most requested genetic studies within the approach of patients with intellectual disability with or without other anomalies. As with other procedures and clinical studies, it is convenient for prescribing physicians to have a clear understanding of the scope and limitations of the use of WES, the analysis process of the genetic variants identified, as well as aspects to be evaluated regarding quality and structure of the reports of the NGS studies, with the aim that they can better interpret the results of a study, evaluate its quality, and propose in the best way the correlation of the same with the observed phenotype.

Actualmente la secuenciación del exoma completo (WES; Whole-exome sequencing) mediante la técnica NGS (Next-generation sequencing) es uno de los estudios genéticos más solicitados dentro del abordaje de pacientes con Discapacidad Intelectual con o sin otras anomalías. Al igual que con otros procedimientos y estudios clínicos, es conveniente que los médicos prescriptores tengan una comprensión clara de los alcances y limitaciones del uso de WES, del proceso de análisis de las variantes genéticas identificadas, así como de aspectos a evaluar acerca de la calidad y estructura de los informes de los estudios de NGS, con el objetivo de que puedan interpretar mejor los resultados de un estudio y plantear de la mejor manera la correlación de los mismos con la clínica observada.

Off-label Use of Oral Immunotherapy for Rhinoconjunctivitis and Asthma due to Grass Pollen: A Safe and Effective Alternative in Patients over 65 Years Old: A Series of Case Reports.

INTRODUCTION: Allergic rhinoconjunctivitis and asthma are the most common IgE-mediated diseases worldwide. Allergen-specific immunotherapy (AIT) is currently the only modifying treatment for these IgE-mediated diseases in both children and adults. Subcutaneous immunotherapy is widely used, but in patients over 65 years old, there may be an increased risk of adverse reactions and a worse response to treatment. Oral immunotherapy (OIT) has been proven to be effective and safe, but currently, in most countries, it has been licensed only for patients up to 65 years old based on its technical datasheet. So far, no studies on the efficacy and safety of this type of immunotherapy in patients older than 65 years old have been published. CASE PRESENTATION: We present four patients older than 65 years old with a diagnosis of moderate seasonal rhinoconjunctivitis and moderate-persistent seasonal pollen-induced asthma. Off-label use of oral immunotherapy (OIT) for grass pollen was prescribed due to the severity of their rhinoconjunctivitis symptoms and the worsening of asthma symptoms during the spring. Improvement in the rhinoconjunctivitis and asthma symptoms was reported by all patients since the first spring season and was maintained during the following two years of follow-up. There were no systemic reactions, and only two patients initially had self-limiting oral pruritus. CONCLUSION: Oral immunotherapy for pollens appears to be a convenient, effective, and safe option in older patients (>65 years) with comorbidities after a three-year treatment. This is, to the best of our knowledge, the first report on the off-label use of OIT in patients over 65 years old with symptoms of allergic rhinoconjunctivitis and asthma.

Insulin Signaling Disruption and INF-γ Upregulation Induce Aß1-42 and Hyperphosphorylated-Tau Proteins Synthesis and Cell Death after Paraquat Treatment of Primary Hippocampal Cells.

Acute and long-term paraquat (PQ) exposure produces hippocampal neurodegeneration and cognition decline. Although some mechanisms involved in these effects were found, the rest are unknown. PQ treatment, for 1 and 14 days, upregulated interferon-gamma signaling, which reduced insulin levels and downregulated the insulin pathway through phosphorylated-c-Jun N-terminal-kinase upregulation, increasing glucose levels and the production of Aß1-42 and phosphorylated-tau, by beta-site amyloid precursor protein cleaving enzyme 1 (BACE1) overexpression and phosphorylated-GSK3ß (p-GSK3ß; ser9) level reduction, respectively, which induced primary hippocampal neuronal loss. This novel information on the PQ mechanisms leading to hippocampal neurodegeneration could help reveal the PQ actions that lead to cognition dysfunction.

Single and repeated bisphenol A treatment induces ROS, Aß and hyperphosphorylated-tau accumulation, and insulin pathways disruption, through HDAC2 and PTP1B overexpression, leading to SN56 cholinergic apoptotic cell death.

Bisphenol-A (BPA), a polymer component extensively used, produces memory and learning alterations after acute and long-term exposure. However, the mechanisms are not well known. Cortex and hippocampus neuronal networks control cognitive functions, which are innervated by basal forebrain cholinergic neurons (BFCN), and their neurodegeneration induces cognitive dysfunctions. Wild type or protein tyrosine phosphatase 1B (PTP1B), histone deacetylase 2 (HDAC2), tau or ß amyloid precursor protein (ßAPP) silenced SN56 cells treated with BPA (0.001 µM-100 µM) with or without N-acetylcysteine (NAC; 1 mM), following 1 and 14 days, were used, as a model of BFCN to determine the insulin pathway dysfunction, oxidative stress (OS) generation and amyloid-ß (Aß) and tau proteins accumulation involvement in the BCFN cell death induction, as a possible mechanism that could produce the cognitive disorders reported. BPA-induced BFCN cell death, after 24 h and 14 days of treatment, through insulin pathway dysfunction, OS generation, mediated by NRF2 pathway downregulation, and Aß and tau proteins accumulation, which were in turn induced by HDAC2 and PTP1B overexpression. This is relevant information to explain the BFCN neurodegeneration mechanisms that could trigger the neurodegeneration in the rest of the regions innerved by them, leading to cognitive disorders.

Food consumption based on the nutrient profile system underlying the Nutri-Score and renal function in older adults.

BACKGROUND: The impact of the Nutri-Score labelling system on renal function is unknown. OBJECTIVE: To assess the association between food consumption based on the nutrient profile system underlying the Nutri-Score and renal function decline in older adults. METHODS: We used data from the Spain-based Seniors-ENRICA cohort, a study with 1312 community-dwelling adults aged ≥60 years recruited during 2008-2010 and followed up to December 2015. At baseline, a validated dietary history was obtained. Based on their nutritional quality, foods consumed were categorized into five labels (A/Green-best quality, B, C, D, E/Red-worst quality) using the established Nutri-Score algorithm. For each participant, a Nutri-Score dietary index (DI) was calculated in g/day/kg of weight. At baseline and at follow-up, measured serum creatinine (SCr) and estimated glomerular filtration rate (eGFR) levels were obtained, and time changes were calculated. A combined outcome for renal decline was defined as: any increase in SCr or any decrease in eGFR beyond expected-for-age. Statistical analyses were performed with logistic regression adjusting for socioeconomic, lifestyle, total energy intake, fresh foods, and comorbidity confounders. RESULTS: A total of 183 cases of renal-function decline occurred over a mean 6-year follow-up. Participants with a higher (less favorable) Nutri-Score DI (interquartile range (IQR)13.2-17.7 (g/day/kg of weight); 46 cases) had higher probability of renal decline than those with a lower Nutri-Score DI (IQR 36.6-46.2; 44 cases); the corresponding odds ratios (95% confidence interval) across increasing quartiles of Nutri-Score DI were 1 (reference), 1.26 (0.78-2.04), 1.55 (0.92-2.62), and 1.82 (1.01-3.30), P-trend = 0.045. Per each 10-point increase in the Nutri-Score DI the odds of renal decline increased by 27% (6%-52%). CONCLUSIONS: Higher Nutri-Score DI, reflecting the consumption of foods with less favourable Nutri-Score rating, was associated with higher kidney function decline in older adults. Consequently, Nutri-Score labeling might be a useful policy tool for preventing kidney function decline, adding to the potential health benefits of this front-of-pack labelling system.

Renal Denervation: A Review.

Uncontrolled hypertension persists as an important health issue despite the availability of many medications and nondrug therapies that lower blood pressure. Increasingly, nonadherence to medication is found in approximately 2 of every 5 patients with uncontrolled hypertension. In the search for interventions that lower blood pressure that do not rely on adherence to a regimen requiring daily ingestion of medication or repeated physical activity, device-based methods that denervate the renal arteries have emerged as a potential complement to standard antihypertensive treatments. At least 3 different approaches to renal artery denervation are under active investigation, including the use of radiofrequency energy, ultrasound, or the injection of neurolytic agents into the renal perivascular tissue. In this review, we cover what is currently known about the mechanisms of antihypertensive effects of renal denervation, summarize the efficacy and safety of renal denervation using recent controlled trial publications in a number of hypertensive populations, and conclude with some thoughts about challenges in the field, including the optimization of patient selection for the procedure and what the reader can expect in the near future in this rapidly developing field.

Cadmium-induced neurotoxic effects on rat basal forebrain cholinergic system through thyroid hormones disruption.

Cadmium (Cd) single and repeated exposure produces cognitive dysfunctions. Basal forebrain cholinergic neurons (BFCN) regulate cognitive functions. BFCN loss or cholinergic neurotransmission dysfunction leads to cognitive disabilities. Thyroid hormones (THs) maintain BFCN viability and functions, and Cd disrupts their levels. However, Cd-induced BFCN damages and THs disruption involvement was not studied. To research this we treated male Wistar rats intraperitoneally with Cd once (1 mg/kg) or repetitively for 28 days (0.1 mg/kg) with/without triiodothyronine (T3, 40 µg/kg/day). Cd increased thyroid-stimulating-hormone (TSH) and decreased T3 and tetraiodothyronine (T4). Cd altered cholinergic transmission and induced a more pronounced neurodegeneration on BFCN, mediated partially by THs reduction. Additionally, Cd antagonized muscarinic 1 receptor (M1R), overexpressed acetylcholinesterase S variant (AChE-S), downregulated AChE-R, M2R, M3R and M4R, and reduced AChE and choline acetyltransferase activities through THs disruption. These results may assist to discover cadmium mechanisms that induce cognitive disabilities, revealing a new possible therapeutic tool.

Olive oil consumption is associated with lower frailty risk: a prospective cohort study of community-dwelling older adults.

BACKGROUND: There is no evidence on the specific beneficial association of the main types of olive oil consumption with frailty. OBJECTIVE: The aim was to assess the relationship between olive oil consumption and incident frailty in community-dwelling older adults. DESIGN: Prospective cohort. SETTING: Participants were recruited in 2008-10 and follow-up through 2013. SUBJECTS: In total, 1,896 older adults aged 60+. METHODS: At baseline, olive oil and other food consumption was collected using a validated dietary history. Incident frailty was defined as having at least three of the following five Fried-based criteria: low physical activity, fatigue, slow walking, muscle weakness and unintentional weight loss. Analyses were performed with logistic regression and adjusted for the major confounders. RESULTS: Over a mean follow-up of 3.5 years, 135 incident frailty cases were identified. The odds ratio (95% confidence interval) of frailty across sex-specific tertiles of total olive oil consumption (12.7, 20 and 30.8 g/day, respectively) were: 1 (ref.), 0.52 (0.32, 0.83) and 0.47 (0.29, 0.78), P trend 0.003. When differentiating by olive oil types, the results held for virgin but did not for common (refined) olive oil. CONCLUSION: The highest total olive oil consumption (~3 tablespoons), especially if virgin, was associated with half the risk of frailty as the lowest consumption (~1 tablespoon) among older adults. This study suggests that virgin olive oil should be the preferent culinary olive oil type for frailty prevention. If confirmed in other settings, small doses of virgin olive oil could be added as a simple geriatric nutritional advice on the prevention of frailty.