A multicenter evaluation of external outflow graft obstruction with a fully magnetically levitated left ventricular assist device.

BACKGROUND: The HeartMate 3 (HM 3; Abbott) left ventricular assist device (LVAD) has improved hemocompatibility-related adverse outcomes. In sporadic cases, external compression of the outflow graft causing obstruction (eOGO) can result from substance accumulation between the outflow graft and its bend relief. We sought to evaluate the prevalence, course, and clinical implications of eOGO in an international study. METHODS: A multicenter retrospective analysis of HM 3 LVADs implanted between November 2014 and April 2021 (n = 2108) was conducted across 17 cardiac centers in 8 countries. We defined eOGO as obstruction >25% in the cross-sectional area in imaging (percutaneous angiography, computed tomography, or intravascular ultrasound). The prevalence and annual incidence were calculated. Serious adverse events and outcomes (death, transplantation, or device exchange) were analyzed for eOGO cases. RESULTS: Of 2108 patients, 62 were diagnosed with eOGO at a median LVAD support duration of 953 (interquartile range, 600-1267) days. The prevalence of eOGO was 3.0% and the incidence at 1, 2, 3, 4, and 5 years of support was 0.6%, 2.8%, 4.0%, 5.2%, and 9.1%, respectively. Of 62 patients, 9 were observed, 27 underwent surgical revision, 15 underwent percutaneous stent implantation, 8 received a heart transplant, and 2 died before intervention. One patient underwent surgical revision and later stent implantation. The mortality with therapeutic intervention was 9/53 (17.0%). CONCLUSIONS: Although uncommon, HM 3 LVAD-supported patients might develop eOGO with an increasing incidence after 1 year of support. Although engineering efforts to reduce this complication are under way, clinicians must maintain a focus on early detection and remain vigilant.

Polymorphisms of the Proinflammatory Cytokine Genes Modulate the Response to NSAIDs but Not to Triptans in Migraine Attacks.

Migraine is a common neurovascular disorder characterized by recurrent episodes of headache and associated neurological symptoms. At present, a significant portion of patients do not obtain a satisfactory response to acute pain-relieving therapies, including NSAIDs and triptans. In this context, pharmacogenetics plays a key role in the understanding of such a diverse response. In order to investigate whether functional polymorphisms in proinflammatory cytokine genes (IL-1α, IL-1ß, IL-1RN; IL-6 and TNF-α) may influence the response to acute treatment, 313 consecutive patients with episodic migraine without aura were enrolled. Pain relief by administration of NSAIDs or triptans for three consecutive migraine attacks was evaluated. We found a significant association between A allele of the TNF-α promoter (−308 A/G) and a lack of efficacy after NSAID administration (p < 0.01, OR 2.51, 95% CI: 1.33 < OR < 4.75 compared to the G allele). Remaining polymorphisms had no significant effect on pain relief. Our study showed that a functional polymorphism in the TNF-α gene significantly modulates the clinical response to NSAID administration in acute attacks. Patients with higher production of the active cytokine during stress showed a significantly lower anti-migraine effect. Our results further support a role for TNF-α in the pathophysiological mechanisms of migraine attack.

Alteration of Iron Concentration in Alzheimer's Disease as a Possible Diagnostic Biomarker Unveiling Ferroptosis.

Proper functioning of all organs, including the brain, requires iron. It is present in different forms in biological fluids, and alterations in its distribution can induce oxidative stress and neurodegeneration. However, the clinical parameters normally used for monitoring iron concentration in biological fluids (i.e., serum and cerebrospinal fluid) can hardly detect the quantity of circulating iron, while indirect measurements, e.g., magnetic resonance imaging, require further validation. This review summarizes the mechanisms involved in brain iron metabolism, homeostasis, and iron imbalance caused by alterations detectable by standard and non-standard indicators of iron status. These indicators for iron transport, storage, and metabolism can help to understand which biomarkers can better detect iron imbalances responsible for neurodegenerative diseases.

Machine Learning Profiling of Alzheimer's Disease Patients Based on Current Cerebrospinal Fluid Markers and Iron Content in Biofluids.

Alzheimer's disease (AD) is the most common form of dementia, characterized by a complex etiology that makes therapeutic strategies still not effective. A true understanding of key pathological mechanisms and new biomarkers are needed, to identify alternative disease-modifying therapies counteracting the disease progression. Iron is an essential element for brain metabolism and its imbalance is implicated in neurodegeneration, due to its potential neurotoxic effect. However, the role of iron in different stages of dementia is not clearly established. This study aimed to investigate the potential impact of iron both in cerebrospinal fluid (CSF) and in serum to improve early diagnosis and the related therapeutic possibility. In addition to standard clinical method to detect iron in serum, a precise quantification of total iron in CSF was performed using graphite-furnace atomic absorption spectrometry in patients affected by AD, mild cognitive impairment, frontotemporal dementia, and non-demented neurological controls. The application of machine learning techniques, such as clustering analysis and multiclassification algorithms, showed a new potential stratification of patients exploiting iron-related data. The results support the involvement of iron dysregulation and its potential interaction with biomarkers (Tau protein and Amyloid-beta) in the pathophysiology and progression of dementia.

Peripheral device to quantify grip and pinch capacity of children

Abstract Introduction Grip and pinch movements are important to perform daily activities and to manipulate objects. In this paper we describe the development and evaluation of a peripheral device to quantify cylindrical grip, pulp-to-pulp pinch, pulp-to-side pinch strength and range of motion of children. Methods Three objects were selected: a door handle, a switch, and a key, which were instrumented with force sensing resistors to analyse the strength. Potentiometers were used to verify the range of motion and micro switches to assure the correct position of the fingers during the movement execution. Thirty volunteers (8.77 ± 1.28), both male and female, were selected to test the peripheral device functionality. Results The results determined the minimum necessary strength values for the object activation and maximum displacement, in which the values are 2.5N, 40°; 2.7N, 55°; and 2.8N, 100%, for door handle object, key object, and switch object, respectively. In the functionally tests, volunteers have shown a superior strength for activating each object and 73.33% of them have completed the range movement in the key object, 86.67% in the switch object, and 93.33% in the door handle object. Conclusion The developed peripheral device enabled the measurement of range and static and dynamic strength of grip and pinch movements of children.

Mutation analysis of CHCHD2 and CHCHD10 in Italian patients with mitochondrial myopathy.

Mutations in CHCHD2 and CHCHD10 were recently reported in a broad spectrum of neurodegenerative diseases, for example, Parkinson's disease, amyotrophic lateral sclerosis, frontotemporal dementia, or mitochondrial myopathy (MM). The aim of the study was to evaluate the prevalence of CHCHD2 and CHCHD10 mutations in Italian MM patients without mitochondrial DNA mutations. The coding regions of CHCHD2 and CHCHD10 were sequenced in 62 MM patients. None of the patients showed CHCHD2 mutations, whereas 1 sporadic MM patient carried a homozygous Pro96Thr substitution in CHCHD10. Muscle biopsy of this patient showed intracellular glycogen accumulation with cytochrome c oxidase negative and ragged red fibers. Our study suggests that the homozygous Pro96Thr mutation in CHCHD10 might be pathogenic but does not support a major role for CHCHD2 in MM pathogenesis.

Differential diagnosis of vacuolar muscle biopsies: use of p62, LC3 and LAMP2 immunohistochemistry.

Intrafibral vacuoles are the morphological hallmark in a wide variety of human skeletal muscle disorders with different etiology. In most cases, differential diagnosis is feasible with a routine histochemical work up of muscle biopsy. Ultrastructural analysis is an important confirmatory tool, but it is not widely available. Immunohistochemical stainings for p62, LAMP2 and LC3 are commonly available as tissutal marker for autophagy. We compared the immunohistochemical patterns for autophagic markers p62, LC3 and LAMP2 with routine histochemical markers in 39 biopsies from patients with definite diagnoses of glycogen storage disease type 2 (LOPD or Pompe disease, PD), sporadic inclusion body myositis (sIBM), oculo-pharyngeal muscular dystrophy (OPMD) and necrotizing myopathy (NM). Moreover, we also analyzed muscles of 10 normal controls. In PD group, LC3 and LAMP2 showed an higher percentage of positive fibers, whereas p62 was limited to a minority of fibers, thus paralleling the results of histochemical stainings; in NM group, LAMP2 and LC-3 were diffusely and unspecifically expressed in necrotic fibers, with p62 significantly expressed only in two cases. OPMD biopsies did not reveal any significant positivity. The most interesting results were observed in sIBM group, where p62 was expressed in all cases, even in fibers without other markers positivity. There results, although limited to a small number of cases, suggest that the contemporary use of p62, LAMP2 and LC-3 staining may have an adjunctive role in characterizing muscle fiber vacuoles, revealing autophagic pathway activation and providing further clues for the understanding of pathogenetic mechanisms.s.

Investigating the role of adipokines in chronic migraine.

Background and aims Adiponectin, leptin, and resistin are adipocyte-derived secretory factors involved in endothelial function, weight, inflammation, and insulin resistance. Recent studies suggested a role for adipokines in episodic migraine as mediators of inflammatory processes. The aim of this study was to investigate plasma concentrations of adiponectin, leptin, and resistin in patients with chronic migraine. Materials and methods Twenty-seven chronic migraineurs (20 females, 7 males; mean age 49.0 ± 9.0 yrs) and 37 healthy controls (23 females, 14 males; mean age 49.8 ± 15.0 yrs) were selected for the study. Fasting plasmatic levels of total adiponectin, leptin, and resistin were measured using ELISA kits during a pain-free period. Fasting glucose, insulin, total and HDL-cholesterol, triglycerides, and ESR were also determined. Results Serum levels of adiponectin and resistin were significantly increased in chronic migraineurs in comparison with controls ( p = 0.001 and p = 0.032, respectively). After correction for BMI, sex and age, leptin levels were significantly increased in chronic migraineurs ( p = 0.007). A positive correlation between leptin concentrations and both indices of insulin resistance and markers of inflammation was found. Discussion Our data suggest that adiponectin and resistin are altered in non-obese chronic migraineurs. Further studies are needed to elucidate the neurobiological mechanisms underlying adipokine dysfunction in migraine.

Genetic variants in the NOTCH4 gene influence the clinical features of migraine.

BACKGROUND: Recent studies suggested an important role for vascular factors in migraine etiopathogenesis. Notch4 belongs to a family of transmembrane receptors that play an important role in vascular development and maintenance. The aim of this study was to test the hypothesis that polymorphisms of the NOTCH4 gene would modify the occurrence and the clinical features of migraine. FINDINGS: Using a case-control strategy, we genotyped 239 migraine patients and 264 controls for three different non-synonymous polymorphisms (T320A, G835V, R1346P) of the NOTCH4 gene and for the (CTG) n-encoding polyleucine polymorphism in exon 1. Although the analyzed polymorphisms resulted not associated with migraine, the clinical characteristics of our patients were significantly influenced by the different NOTCH4 genotypes. Longer duration of disease and severity of neurovegetative symptoms during headache attacks were associated with the R1346P and G835V polymorphisms, respectively. In female patients, worsening of migraine symptoms at menarche was significantly correlated with T320A polymorphism. CONCLUSIONS: Our study shows that genetic variations within the NOTCH4 gene significantly modify the clinical characteristics of migraine and may have a role in disease pathogenesis.

Exercício resistido, ansiedade e depressão em portadores de esclerose múltipla / Resistance training, anxiety and depression in multiple sclerosis patients

Há muito tempo são conhecidos os benefícios da prática de exercícios físicos resistidos e a realização destes por portadores de Esclerose Múltipla não é contra indicado se orientado e supervisionado corretamente. Porém, a prática destes exercícios e de atividade física de modo geral provoca uma série de medos e inseguranças nesses pacientes. O objetivo desta pesquisa foi verificar o nível de depressão e o grau de ansiedade de pacientes com Esclerose Múltipla em relação à prática de exercícios resistidos; verificar o impacto da ansiedade para a realização do exercício resistido e graduar o fator de insegurança em relação à prática de exercícios reisitidos nos portadores de Esclerose Múltipla. Foram avaliados 30 pacientes com diagnóstico de Esclerose Múltipla, os quais responderam os seguintes questionários: Inventário de Depressão de Beck, Inventário de Ansiedade Traço-Estado e um Questionário adaptado para pesquisa. Os resultados obtidos por meio dos inventários demonstram que 66,6 por cento dos pacientes não apresentam nenhum tipo de depressão, 66 por cento um grau mediano de ansiedade tanto na A-traço quanto na A-estado. Sobre a prática de atividades físicas, observou-se que 86,6 por cento desses pacientes não praticam qualquer tipo de atividade e apenas 13,4 por cento as praticam. Grande parte dos pacientes que não praticam nenhuma atividade física (46,6 por cento) é desaconselhada por um profissional da saúde a não praticarem. Conclui-se que a maioria dos pacientes apresenta grau mediano de ansiedade , nenhum tipo de depressão e insegurança em praticar exercício, principlamente exercício resistido.

Estudio exploratorio sobre el saber que poseen los docentes acerca de los factores que intervienen en el aprendizaje de la lectura y la escritura, y sobre la incidenia de posibles dificultades en dichos procesos de aprendizaje / Exploration stuyd about the know with own the teahcers about of the factors with mediate in the learning of the read and the write, and about the incidence of the same in the determination of possible difficulties in this process of learning

El propósito de esta investigación fue conocer las características del saber docente sobre los aspectos que inlfuyen en el aprendizaje de la lectura y escritura y los que determinan posibles dificultades en dichos procesos, y además analizar el saber docente sobre el rol del Fonoaudiólogo en los problemas de lectura y escritura. Para poder cumplir con dichas finalidades, se realizó este trabajo en una población compuesta por veintiún docentes del primer ciclo del E.G.B de la ciudad de Totoras, provincia de Santa Fe. Los datos se evaluaron y anlizaron utilizando cuadros estadísticos cuyas cifras se trabajaron en valores porcentuales. Las conclusiones permitieron demostrar, según el criterio adoptado en este trabajo de investigación, que 17 docentes (80,9 por ciento) poseen coherencia en el saber acerca de los factores que determinan posibles dificultades cuando se encuentran comprometidos. Esta coherencia revela un saber que, no obstante, puede ser interpelado desde perspectivas teóricas lingüísticas, psicolingüísticas y/o pedagógicas actuales. En referencia al rol del Fonoaudiólogo en los problemas de lectura y escritura, los resultados obtenidos son: 15 docentes (71,4 por ciento) poseen un saber no satisfactorio, o sea el conocimiento sobre el alcance del rol del Fonoaudiólogo, es escaso. Se pudo comprobar que los años de ejercicio profesional y los estudios complementarios, no incidieron en dichos valores