Pregnancy in women with dilated cardiomyopathy genetic variants.

INTRODUCTION AND OBJECTIVES: Limited information is available on the safety of pregnancy in patients with genetic dilated cardiomyopathy (DCM) and in carriers of DCM-causing genetic variants without the DCM phenotype. We assessed cardiac, obstetric, and fetal or neonatal outcomes in this group of patients. METHODS: We studied 48 women carrying pathogenic or likely pathogenic DCM-associated variants (30 with DCM and 18 without DCM) who had 83 pregnancies. Adverse cardiac events were defined as heart failure (HF), sustained ventricular tachycardia, ventricular assist device implantation, heart transplant, and/or maternal cardiac death during pregnancy, or labor and delivery, and up to the sixth postpartum month. RESULTS: A total of 15 patients, all with DCM (31% of the total cohort and 50% of women with DCM) experienced adverse cardiac events. Obstetric and fetal or neonatal complications were observed in 14% of pregnancies (10 in DCM patients and 2 in genetic carriers). We analyzed the 30 women who had been evaluated before their first pregnancy (12 with overt DCM and 18 without the phenotype). Five of the 12 (42%) women with DCM had adverse cardiac events despite showing NYHA class I or II before pregnancy. Most of these women had a history of cardiac events before pregnancy (80%). Among the 18 women without phenotype, 3 (17%) developed DCM toward the end of pregnancy. CONCLUSIONS: Cardiac complications during pregnancy and postpartum were common in patients with genetic DCM and were primarily related to HF. Despite apparently good tolerance of pregnancy in unaffected genetic carriers, pregnancy may act as a trigger for DCM onset in a subset of these women.

Next-generation sequencing reveals remarkable genetic stability in primary and corresponding recurrent intestinal-type sinonasal adenocarcinoma.

BACKGROUND: Recurrent intestinal-type sinonasal adenocarcinoma (ITAC) can occur several years after primary treatment and with different histology. We aimed to clarify if such recurrences could be second primary tumors and to identify actionable mutations as targets for personalized treatment of recurrent ITAC. METHODS: Twelve pairs of primary and recurrent ITAC were histologically examined and analyzed by next-generation sequencing. RESULTS: Histological differences between primary and recurrent tumor pairs were observed in five cases. Frequent mutations included TP53, APC, TSC2, ATM, EPHA2, BRCA2, LRP1B, KRAS, and KMT2B. There was 86% concordance of somatic mutations between the tumor pairs, while four cases carried additional mutations in the recurrence. CONCLUSIONS: We found all cases to be clonal recurrences and not second primary tumors. Moreover, tumor pairs showed a remarkable genomic stability, suggesting that personalized treatment of a recurrence may be based on actionable molecular genetic targets observed in the primary tumor.

Gut Microbiota and Derived Short-Chain Fatty Acids Are Linked to Evolution of Heart Failure Patients.

There is a lack of direct evidence regarding gut microbiota dysbiosis and changes in short-chain fatty acids (SCFAs) in heart failure (HF) patients. We sought to assess any association between gut microbiota composition, SCFA production, clinical parameters, and the inflammatory profile in a cohort of newly diagnosed HF patients. In this longitudinal prospective study, we enrolled eighteen newly diagnosed HF patients. At admission and after 12 months, blood samples were collected for the assessment of proinflammatory cytokines, monocyte populations, and endothelial dysfunction, and stool samples were collected for analysis of gut microbiota composition and quantification of SCFAs. Twelve months after the initial HF episode, patients demonstrated improved clinical parameters and reduced inflammatory state and endothelial dysfunction. This favorable evolution was associated with a reversal of microbiota dysbiosis, consisting of the increment of health-related bacteria, such as genus Bifidobacterium, and levels of SCFAs, mainly butyrate. Furthermore, there was a decrease in the abundance of pathogenic bacteria. In vitro, fecal samples collected after 12 months of follow-up exhibited lower inflammation than samples collected at admission. In conclusion, the favorable progression of HF patients after the initial episode was linked to the reversal of gut microbiota dysbiosis and increased SCFA production, particularly butyrate. Whether restoring butyrate levels or promoting the growth of butyrate-producing bacteria could serve as a complementary treatment for these patients deserves further studies.

Achyrocline satureioides Hydroalcoholic Extract as a Hypoallergenic Antimicrobial Substitute of Natural Origin for Commonly Used Preservatives in Cosmetic Emulsions.

Achyrocline satureioides is a South American herb used in traditional medicine to treat a wide range of ailments. The healing and antimicrobial effects of this plant have already been covered by many studies, which have confirmed its beneficial effects on human health. In this study, the antimicrobial effect of A. satureioides hydroalcoholic extract against Escherichia coli ATCC10536, Staphylococcus aureus ATCC25923, Staphylococcus epidermidis ATCC12228 and Lactobacillus acidophilus INCQS00076 was determined. The cytotoxicity of the extract was tested on human HaCaT keratinocytes showing very favourable effects on the proliferation and renewal of keratinocytes. According to the results of the HPLC and GC-MS analyses, the lyophilized extract contained only a minimal amount of fragrance allergens. The extract was then used in two cosmetic formulations, and one of them showed a significant synergistic interaction with other cosmetic components. We suggest the use of A.satureioides hydroalcoholic extract as a suitable antimicrobial component of natural origin for cosmetic preparations as a substitute for commonly used preservatives that can cause skin irritation and as a material with its own biological activity.

Antimicrobial Properties of Essential Oils Obtained from Autochthonous Aromatic Plants.

The aim of this work was to determine the antimicrobial activity of the essential oils of six plants widely distributed in the Dehesa of Extremadura, such as Calendula officinalis, Cistus ladanifer, Cistus salviifolius, Cistus multiflorus, Lavandula stoechas, and Rosmarinus officinalis. The content of total phenolic compounds (TPC) and the antimicrobial activity of the essential oils against pathogenic and spoilage bacteria and yeasts as well as aflatoxin-producing molds were determined. A great variability was observed in the composition of the essential oils obtained from the six aromatic plants. The Cistus ladanifer essential oil had the highest content of total phenols (287.32 ppm), followed by the Cistus salviifolius essential oil; and the Rosmarinus officinalis essential oil showed the lowest amount of these compounds. The essential oils showed inhibitory effects on the tested bacteria and also yeasts, showing a maximum inhibition diameter of 11.50 mm for Salmonella choleraesuis and Kregervanrija fluxuum in the case of Cistus ladanifer and a maximum diameter of 9 mm for Bacillus cereus and 9.50 mm for Priceomyces carsonii in the case of Cistus salviifolius. The results stated that antibacterial and antiyeast activity is influenced by the concentration and the plant material used for essential oil preparation. In molds, aflatoxin production was inhibited by all the essential oils, especially the essential oils of Cistus ladanifer and Cistus salviifolius. Therefore, it can be concluded that the essential oils of native plants have significant antimicrobial properties against pathogenic and spoilage microorganisms, so they could be studied for their use in the industry as they are cheap, available, and non-toxic plants that favor the sustainability of the environment of the Dehesa of Extremeña.

Improvement of shelf-life of cherry (Prunus avium L.) by combined application of modified-atmosphere packaging and antagonistic yeast for long-distance export.

BACKGROUND: The last decade has seen a growing interest in reducing the use of chemical fungicides for postharvest decay control. In the research for new, safe alternatives, the combined application of biocontrol agents and passive modified-atmosphere packaging (MAP) has been shown to be a promising strategy to extend fruit quality. Therefore, the aim of this work was to evaluate the effect of the combined application of MAP and two antagonistic yeasts, Metschnikowia pulcherrima L672 and Pichia kudriavzevii PK18, on sweet cherry shelf life. RESULTS: Microbiological, physico-chemical, and quality fruit analysis from batches treated with antagonistic yeast were compared with a control batch without yeast application and a batch to which fludioxonil (Scholar®) was applied. The composition of the atmosphere and physico-chemical traits showed similar values among the different batches during cold storage. However, interestingly, the combination of MAP with the antagonistic yeasts M. pulcherrima L672 and P. kudriavzevii PK18 increases the control of microbiological spoilage with results comparable to the application of fludioxonil. In addition, these batches experienced a slight decrease in volatile compounds associated with fresh fruit aroma, whereas in the control batch an increase of altered fruit aromas was observed. The same effect of control of spoilage was observed during the shelf life period. CONCLUSION: These results showed the positive effect of the combination of antagonistic yeasts and MAP, obtaining similar results in terms of control of microbiological spoilage and physico-chemical quality compared with the application of fludioxonil. © 2023 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

El electrocardiograma en la amiloidosis cardíaca: un arma para la sospecha diagnóstica de esta enfermedad / The electrocardiogram in cardiac amyloidosis: a weapon for the diagnosis suspect of this disease / O electrocardiograma na amiloidose cardíaca: uma arma para a suspeita diagnóstica desta doença

La amiloidosis cardíaca (AC) es una enfermedad con mal pronóstico si el tratamiento no se inicia de forma temprana, por lo que una de las asignaturas pendientes en esta enfermedad consiste en realizar un diagnóstico precoz. El electrocardiograma (ECG) es una prueba diagnóstica de bajo costo y amplia disponibilidad que nos permite sospechar esta enfermedad, dado que resulta normal en < 5% de los pacientes. El hallazgo clásico es la presencia de bajos voltajes en relación con la gran hipertrofia que se observa en las pruebas de imagen, así como el conocido patrón de pseudoinfarto. Ambos hallazgos son más frecuentes en el subtipo de amiloidosis por cadenas ligeras, que era el más frecuentemente diagnosticado en el pasado. Sin embargo, con la expansión del diagnóstico no invasivo del subtipo a transtiretina, su identificación ha crecido de forma exponencial y se convirtió en el más diagnosticado con más frecuencia en nuestro medio. Se debe prestar especial atención a todos estos hallazgos electrocardiográficos, con el fin de que esta prueba diagnóstica de sencilla obtención pueda contribuir de forma importante a la sospecha y al diagnóstico precoz de la AC.

Cardiac amyloidosis (CA) is a serious disease with a poor prognosis if treatment is not started early, so one of the pending issues in this condition is to make an early diagnosis. The electrocardiogram (EKG) is an inexpensive and widely available diagnostic test that can offer differential data when suspecting this disease, being normal in < 5% of these patients. The classic EKG finding is the presence of low voltages in relation to the large hypertrophy seen on imaging tests, as well as the well-known pseudoinfarct pattern. Both findings are more frequent in the light chain subtype of CA, which was the most frequently diagnosed in the past. However, with the growth of noninvasive diagnostic tests, the identification of the transtyretin subtype has grown exponentially, becoming the most frequently diagnosed in our setting. Special attention should be paid to all these electrocardiographic findings, so that this simple diagnostic test can make an important contribution to the early suspicion and diagnosis of CA.

A amiloidose cardíaca (AC) é uma doença grave com um mau prognóstico no caso de não se iniciar tratamento de forma precoce, pelo que a necessidade de um pronto diagnóstico é imperiosa. Quando se suspeita desta doença, o eletrocardiograma (ECG) é um teste de diagnóstico pouco dispendioso e disponível em todo o mundo, que pode fornecer dados discriminativos importantes, sendo normal em menos de 5% dos casos. O achado clássico do ECG é a presença de baixas voltagens em relação à grande hipertrofia vista na imagem, bem como o conhecido padrão de pseudoinfarte. Ambos os resultados são mais frequentes no subtipo a cadenas ligeras, o mais frequentemente diagnosticado no passado. No entanto, com o aumento dos testes de diagnóstico não-invasivos, o diagnóstico ddo subtipo a transtirretina, o mais cresceu de forma exponencial, tornando-se o mais frequentemente diagnosticado no nosso meio. Deve ser dada especial atenção a todos estes achados eletrocardiográficos já que esta prova de diagnóstico de fácil obtenção pode contribuir de forma importante para a suspeição de diagnóstico precoce de AC.

Seudoartrosis después de una osteotomía en Chevron: incidencia, tratamiento, seguimiento y evolución / Nonunion after Chevron osteotomy. Incidence, treatment, follow-up, and outcomes

Introducción: El hallux valgus es el trastorno más común del primer dedo del pie. Provoca dolor, discapacidad funcional y altera los patrones de la marcha. Las deformidades leves o moderadas se han corregido con osteotomías distales del primer metatarsiano, como la osteotomía en chevron, un procedimiento seguro, pero no exento de complicaciones. Los objetivos de este estudio fueron determinar la incidencia de seudoartrosis por dicha osteotomía y comunicar nuestro método terapéutico, el seguimiento y la evolución. materiales y métodos: Se realizó un estudio multicéntrico, retrospectivo que incluyó a pacientes operados entre 2009 y 2018. Se evaluaron 1156 osteotomías en chevron como tratamiento del hallux valgus leve o moderado en 1017 pacientes (rango etario 16-83 años; promedio 57.5) realizadas por 4 cirujanos experimentados. El criterio de inclusión fue que el paciente contara con estudios por imágenes compatibles con seudoartrosis a los 6 meses de la cirugía. Resultados: Se evaluó a 5 pacientes con diagnóstico de seudoartrosis después de una osteotomía en chevron para tratar el hallux valgus. Los puntajes promedio de la AOFAS fueron 51 antes del tratamiento del hallux valgus y 87,8 después del tratamiento de la seudoartrosis. Conclusiones: La incidencia de seudoartrosis fue del 0,4% en el posoperatorio alejado. Nuestro abordaje y el tratamiento de la seudoartrosis lograron una excelente mejoría clínica y funcional en todos los pacientes operados. Nivel de Evidencia: III

Introduction: Hallux valgus is the most common disorder of the first toe. It causes pain, functional impairment, and alters gait patterns. Mild to moderate deformities are tipically corrected with distal osteotomies of the first metatarsal, such as the chevron osteotomy, a safe procedure, but not without complications. The objectives of this study were to determine the incidence of pseudarthrosis following this osteotomy and report our therapeutic method, follow-up, and outcomes. Materials and methods: A retrospective multicenter study was carried out, which included patients operated on between 2009 and 2018. A total of 1156 chevron osteotomies were evaluated as a treatment for mild to moderate hallux valgus in 1017 patients (age range 16 -83 years; average 57.5 years) performed by 4 experienced surgeons. The inclusion criterion was that the patient had imaging studies compatible with pseudarthrosis six months after surgery. Results: We evaluated five patients who met our criterion. The average AOFAS (American Orthopedic Foot and Ankle Society) scores were 51 before hallux valgus treatment and 87.8 after pseudarthrosis treatment. Conclusion: The incidence of pseudarthrosis was 0.4% in the distant postoperative period. Our approach and treatment of pseudarthrosis achieved excellent clinical and functional improvements in all operated patients. Level of Evidence: III

Natural History of MYH7-Related Dilated Cardiomyopathy.

BACKGROUND: Variants in myosin heavy chain 7 (MYH7) are responsible for disease in 1% to 5% of patients with dilated cardiomyopathy (DCM); however, the clinical characteristics and natural history of MYH7-related DCM are poorly described. OBJECTIVES: We sought to determine the phenotype and prognosis of MYH7-related DCM. We also evaluated the influence of variant location on phenotypic expression. METHODS: We studied clinical data from 147 individuals with DCM-causing MYH7 variants (47.6% female; 35.6 ± 19.2 years) recruited from 29 international centers. RESULTS: At initial evaluation, 106 (72.1%) patients had DCM (left ventricular ejection fraction: 34.5% ± 11.7%). Median follow-up was 4.5 years (IQR: 1.7-8.0 years), and 23.7% of carriers who were initially phenotype-negative developed DCM. Phenotypic expression by 40 and 60 years was 46% and 88%, respectively, with 18 patients (16%) first diagnosed at <18 years of age. Thirty-six percent of patients with DCM met imaging criteria for LV noncompaction. During follow-up, 28% showed left ventricular reverse remodeling. Incidence of adverse cardiac events among patients with DCM at 5 years was 11.6%, with 5 (4.6%) deaths caused by end-stage heart failure (ESHF) and 5 patients (4.6%) requiring heart transplantation. The major ventricular arrhythmia rate was low (1.0% and 2.1% at 5 years in patients with DCM and in those with LVEF of ≤35%, respectively). ESHF and major ventricular arrhythmia were significantly lower compared with LMNA-related DCM and similar to DCM caused by TTN truncating variants. CONCLUSIONS: MYH7-related DCM is characterized by early age of onset, high phenotypic expression, low left ventricular reverse remodeling, and frequent progression to ESHF. Heart failure complications predominate over ventricular arrhythmias, which are rare.

Cognitive enrichment in a social setting: assessing the use of a novel food maze in sanctuary-housed chimpanzees.

Foraging devices are effective enrichment tools for non-human primates, as they provide both cognitive and manipulative stimulation that may enhance these animals' welfare. We assessed the behavioral effects of a novel tool-based enrichment on 14 chimpanzees (Pan troglodytes) housed at Fundació Mona (Girona, Spain). The device consisted of a vertical maze filled with food rewards, which chimpanzees could extract by using tools. We conducted behavioral observations in two conditions over an approximately 2.5-month period: when the food maze was loaded (12 enrichment days), and when it was empty (12 baseline days). Data were collected using 2-min scan sampling and untimed-event focal sampling during two daily sessions of 80 min each. We expected that the chimpanzees' interest in the enrichment would decrease over time, but that its use would be linked to an increase in the occurrence of species-typical behaviors, a reduction in negative indicators of welfare, and changes in social behaviors. We found that participation widely varied among subjects, being higher in females and decreasing through time. Furthermore, participation was linked to an increase in tool use and a decrease in inactivity, but also to an increase in aggression-related behaviors. In contrast, participation had no effect on the occurrence of abnormal behaviors, social proximity or affiliation-related behaviors. Finally, we detected an increase in self-directed behaviors only when subjects actively interacted with the device. We conclude that, in future studies, these types of devices should be evaluated for longer periods of time and more attention should be paid to individuals' preferences and abilities.

Can You Hear Us Now? Equity in Global Advocacy for Palliative Care.

Evidence-based advocacy underpins the sustainable delivery of quality, publicly guaranteed, and universally available palliative care. More than 60 million people in low- and middle-income countries (LMICs) have no or extremely limited access to either palliative care services or essential palliative care medicines (e.g., opioids) on the World Health Organization Model List. Indeed, only 12% of the global palliative care need is currently being met. Palliative care advocacy works to bring this global public health inequity to light. Despite their expertise, palliative care practitioners in LMICs are rarely invited to health policymaking tables - even in their own countries - and are underrepresented in the academic literature produced largely in the high-income world. In this paper, palliative care experts from Bangladesh, Colombia, Egypt, Sudan, Uganda, and Zambia affiliated with the International Association for Hospice & Palliative Care Advocacy Focal Point Program articulate the urgent need for evidence-based advocacy, focusing on significant barriers such as urban/rural divides, cancer-centeredness, service delivery gaps, opioid formulary limitations, public policy, and education deficits. Their advocacy is situated in the context of an emerging global health narrative that stipulates palliative care provision as an ethical obligation of all health systems. To support advocacy efforts, palliative care evaluation and indicator data should assess the extent to which LMIC practitioners lead and participate in global and regional advocacy. This goal entails investment in transnational advocacy initiatives, research investments in palliative care access and cost-effective models in LMICs, and capacity building for a global community of practice to capture the attention of policymakers at all levels of health system governance.

Development of real-time PCR methods for the quantification of Methanoculleus, Methanosarcina and Methanobacterium in anaerobic digestion.

Anaerobic digestion is a growing technology to manage organic waste and produce bioenergy. To promote this technology, it is essential to know, at the molecular level, the dynamics of microbial communities, specifically the methanogenic community. In the present study, three primer pairs were selected from seven primer pairs which were designed and tested with different concentrations and conditions to detect Methanosarcina, Methanoculleus and Methanobacterium by real-time PCR based on the SYBR Green System. The functionality of the developed methods was demonstrated by the high linear relationship of the standard curves, and the specificity of each primer was empirically verified by testing DNA isolated from methane-producing and non-producing strains. These assays also exhibited good repeatability and reproducibility, which indicates the robustness of the methods. The described primers were successfully used to investigate the methanogenic communities of 10 samples from an anaerobic co-digestion. The genus Methanosarcina was the dominant methanogenic group.

Control of toxigenic Aspergillus spp. in dried figs by volatile organic compounds (VOCs) from antagonistic yeasts.

Aspergillus flavus and Aspergillus niger are fungi which can contaminate dried figs before and after harvest and consequently produce aflatoxins (AFs) and ochratoxin A (OTA). Many approaches have been applied to minimise the growth of these filamentous fungi, mainly involving the use of synthetic fungicides which are limited due to their negative impact on human health and the environment. In this context, biocontrol is a recent approach that needs to be explored. This study evaluated the potential of three volatile organic compounds (VOCs), octanoic acid (OA), 2-phenylethyl acetate (2PEA) and furfuryl acetate (FA), produced by Hanseniaspora uvarum and Hanseniaspora opuntiae yeasts on the growth, germination, gene expression and production of AFs and OTA by A. flavus M144 and A. niger M185 on dried fig-based agar and the incidence rates in dried figs. Two of the three VOCs evaluated (2PEA and FA) effectively controlled A. flavus M144 and A. niger M185 by using at least amounts of 50 µL (715 µL/L in the headspace) for FA and 100 µL (1430 µL/L in the headspace) for 2PEA in dried figs. One of the mode of actions of both compounds consists in early repressing the expression of genes involved in the biosynthesis of AFs (aflR) and OTA (pks) of A. flavus and A. niger, respectively. The results of this study support the application of 2PEA and FA at the early post-harvest stages of dried figs to control mycotoxin accumulation.

Glycine max (soy) based diet improves antioxidant defenses and prevents cell death in cadmium intoxicated lungs.

Cadmium (Cd) is a toxic metal and an important environmental contaminant. We analyzed its effects on oligoelements, oxidative stress, cell death, Hsp expression and the histoarchitecture of rat lung under different diets, using animal models of subchronic cadmium intoxication. We found that Cd lung content augmented in intoxicated groups: Zn, Mn and Se levels showed modifications among the different diets, while Cu showed no differences. Lipoperoxidation was higher in both intoxicated groups. Expression of Nrf-2 and SOD-2 increased only in SoCd. GPx levels showed a trend to increase in Cd groups. CAT activity was higher in intoxicated groups, and it was higher in Soy groups vs. Casein. LDH activity in BAL increased in CasCd and decreased in both soy-fed groups. BAX/Bcl-2 semiquantitative ratio showed similar results than LDH activity, confirmed by Caspase 3 immunofluorescence. The histological analysis revealed an infiltration process in CasCd lungs, with increased connective tissue, fused alveoli and capillary fragility. Histoarchitectural changes were less severe in soy groups. Hsp27 expression increased in both intoxicated groups, while Hsp70 only augmented in SoCd. This show that a soy-diet has a positive impact upon oxidative unbalance, cell death and morphological changes induced by Cd and it could be a good alternative strategy against Cd exposure.

Evaluation of fungal hazards associated with dried fig processing.

The processing of dried figs in the industry involves a number of stages that present a significant risk of filamentous fungal infection of the fruit and subsequent mycotoxin contamination, due to the changes in temperature and water activity (aw) to which dried figs are exposed. In this study, the environmental conditions and the physicochemical parameters of dried figs at different processing stages were evaluated in 3 different industries, and were associated with fungal counts and the presence of toxigenic moulds and their mycotoxins. For this, dried figs at 5 relevant stages of industrial processing (curing, sizing, blanching, storage, and final product) in 3 industries located in Extremadura (Spain) were sampled. Changes in moisture content and aw of dried figs during processing were observed and they influenced the mycological quality of figs. Among the fungal genera, Aspergillus spp. predominated in most stages except blanching, where Penicillium spp. prevailed. About 10% of the dried fig samples were contaminated with aflatoxins (AFs) and 6% with ochratoxin A (OTA). Based on findings, longer drying times are necessary after blanching to reduce aw and to avoid the development of toxigenic moulds. In addition, all stages covering industry processing, final storage, and retailing of dried figs are advisable to be conducted at refrigeration conditions and controlled relative humidity to avoid mycotoxin production. The enumeration of AFs- and OTA- producing moulds by real-time PCR seems to be a good indicator for integration into prevention strategies to control filamentous fungal hazards and subsequent mycotoxin synthesis during the processing of dried figs.

Retinol and α-Tocopherol Contents, Fat Color, and Lipid Oxidation as Traceability Tools of the Feeding System in Suckling Payoya Kids.

The effects of Payoya kid feeding systems on the fat-soluble vitamin (retinol/α-tocopherol) contents, fat content, fat color, and the oxidation index were evaluated to determine their potential for use as feeding system traceability tools. Four groups of Payoya kids (55 animals in total) fed milk exclusively were studied: a group fed a milk replacer (MR) and three groups fed natural milk from dams reared with different management systems (mountain grazing (MG), cultivated meadow (CM) and total mixed ration (TMR)). Kids were slaughtered around one month of age and 8 kg of live weight. Kids from the MG and CM groups presented lower retinol (5.56 and 3.72 µg/mL) and higher α-tocopherol plasma (11.43 and 8.85 µg/mL) concentrations than those from the TMR and MR groups (14.98 and 22.47 µg/mL of retinol; 2.49 and 0.52 µg/mL of α-tocopherol, respectively) (p < 0.001). With respect to fat, kids with a higher intramuscular fat percentage (CM and TMR groups) had lower retinol contents (16.52 and 15.99 µg/mL, respectively) than kids from the MG and MR groups (26.81 and 22.63 µg/mL, respectively) (p < 0.001). A dilution effect of vitamins on fat was shown: the higher the amount of fat, the lower the vitamin concentrations, the higher the lipid oxidation index (MDA), and the lower the SUM (absolute value of the integral of the translated spectra between 450 and 510 nm). A discriminant analysis that included all studied variables showed that 94.4% of the kids were classified correctly according to their feeding system and could allow traceability to the consumer.

Benefits of cardiac pacing in ICD recipients with hypertrophic cardiomyopathy.

PURPOSE: Implantable cardiac defibrillator (ICD) is the only definitive therapy for prevention of sudden cardiac death in hypertrophic cardiomyopathy (HCM). Conventional transvenous ICDs can provide cardiac pacing unlike new subcutaneous ICD, but the usefulness of cardiac pacing in HCM patients is not well defined. We sought to assess the usefulness of ICD pacing in HCM. METHODS: We retrospectively analyzed 93 HCM patients who had undergone ICD implantation at our center. Usefulness of pacing was defined as follows: 1) need of pacing due to bradycardia or AV conduction disturbances, 2) improvement of LV outflow tract obstruction by sequential AV pacing, 3) need for CRT pacing, or 4) successful antitachycardia pacing without a subsequent shock. Independent predictors of useful pacing were investigated by multivariable analysis. RESULTS: During a mean follow-up of 91.3 ± 5.5 months, 43 patients (46.2%) reached the composite endpoint. Independent predictors of pacing usefulness were older age (HR 1.36; 95%CI: 1.088-1.709; p=0.007) and NYHA functional class ≥ II (HR 2.15; 95%CI: 1.083-4.301; p=0.029). Twenty-eight (30.1%) patients had appropriate ICD interventions, triggered by a monomorphic ventricular tachycardia (MVT) in 22 of them (78.5%). In 17 individuals with MVT (77%), antitachycardia pacing successfully treated MVT. CONCLUSIONS: In our HCM series of patients with ICD, 46% of individuals benefitted from cardiac pacing. MVT were documented in nearly 80% of the patients with ventricular arrhythmias and antitachycardia pacing successfully treated them in 77% of cases.

Genotype-phenotype correlations in hypertrophic cardiomyopathy: a multicenter study in Portugal and Spain of the TPM1 p.Arg21Leu variant.

INTRODUCTION AND OBJECTIVES: TPM1 is one of the main hypertrophic cardiomyopathy (HCM) genes. Clinical information on carriers is relatively scarce, limiting the interpretation of genetic findings in individual patients. Our aim was to establish genotype-phenotype correlations of the TPM1 p.Arg21Leu variant in a serie of pedigrees. METHODS: TPM1 was evaluated by next-generation sequencing in 10 561 unrelated probands with inherited heart diseases. Familial genetic screening was performed by the Sanger method. We analyzed TPM1 p.Arg21Leu pedigrees for cosegregation, clinical characteristics, and outcomes. We also estimated the geographical distribution of the carrier families in Portugal and Spain. RESULTS: The TPM1 p.Arg21Leu variant was identified in 25/4099 (0.61%) HCM-cases, and was absent in 6462 control individuals with other inherited cardiac phenotypes (P<.0001). In total, 83 carriers (31 probands) were identified. The combined LOD score for familial cosegregation was 3.95. The cumulative probability of diagnosis in carriers was 50% at the age of 50 years for males, and was 25% in female carriers. At the age of 70 years, 17% of males and 46% of female carriers were unaffected. Mean maximal left ventricular wall thickness was 21.4 ±7.65mm. Calculated HCM sudden death risk was low in 34 carriers (77.5%), intermediated in 8 (18%), and high in only 2 (4.5%). Survival free of cardiovascular death or heart transplant was 87.5% at 50 years. Six percent of carriers were homozygous and 18% had an additional variant. Family origin was concentrated in Galicia, Extremadura, and northern Portugal, suggesting a founder effect. CONCLUSIONS: TPM1 p.Arg21Leu is a pathogenic HCM variant associated with late-onset/incomplete penetrance and a generally favorable prognosis.