Comparison of two statistical methodologies for a binary classification problem of two-dimensional images.

The present work intends to compare two statistical classification methods using images as covariates and under the comparison criterion of the ROC curve. The first implemented procedure is based on exploring a mathematical-statistical model using multidimensional arrangements, frequently known as tensors. It is based on the theoretical framework of the high-dimensional generalized linear model. The second methodology is situated in the field of functional data analysis, particularly in the space of functions that have a finite measure of the total variation. A simulation study is carried out to compare both classification methodologies using the area under the ROC curve (AUC). The model based on functional data had better performance than the tensor model. A real data application using medical images is presented.

[Patients hospitalized in the ICU for acute coronary syndrome from 2012 to 2021 : A single-center retrospective study]. / Les patients hospitalisés en réanimation pour un syndrome coronarien aigu de 2012 à 2021 : une étude rétrospective monocentrique.

INTRODUCTION: Acute Coronary Syndrome (ACS) are one of the main causes of mortality in France. Patients presenting with ACS are typically hospitalized in a specialized cardiology ward. The main objective of this study was to describe, characterize and evaluate the outcome of patients hospitalized for ACS in a generalist intensive care unit (rather than a cardiac care unit). METHODS: This was a retrospective study. Our population consisted of ACS patients admitted to an intensive care unit in a hospital center (Centre Hospitalier de Troyes) between 2012 and 2021. All patients admitted for ACS to the intensive care unit and who underwent coronary angiography were included. RESULTS: In 10 years, 104 patients, or 3.8% of ACS patients who underwent coronary angiography were admitted to intensive care. The majority were admitted after recovered cardiac arrest (72%) and were in cardiogenic shock (68%), accounting for a high in-hospital mortality (45.2%). In-hospital mortality was 45.2%. In multivariate analysis, the GRACE score was associated with in-hospital mortality (OR for each additional point = 1.024, 95% confidence interval 1.006-1.045, p = 0.01). Among the survivors, 88% had good neurological function when leaving the hospital. DISCUSSION: Mortality of ACS patients in intensive care was close to 50%. However, the neurological prognosis of the surviving patients was good. This population is rarely mentioned in the literature, and deserves to be evaluated by multicenter, prospective registries, with a view to improving management and prognosis.

Genetic association study of preterm birth and gestational age in a population-based case-control study in Peru.

BACKGROUND: Preterm birth (PTB) affects ∼15 million pregnancies worldwide. Genetic studies have identified several candidate loci for PTB, but results remain inconclusive and limited to European populations. Thus, we conducted a genome-wide association study (GWAS) of PTB and gestational age at delivery (GA) among 2,212 Peruvian women. METHODS: PTB cases delivered≥20 weeks' but < 37 weeks' gestation, while controls delivered at term (≥37 weeks but <42 weeks). Multivariable regressions were used to identify genetic markers for PTB and GA (∼6 million SNPs), adjusting for maternal age and the first two genetic principal components. In silico functional analysis was conducted among top signals detected with an arbitrary P < 1.0×10-5 . We sought to replicate genetic markers for PTB and GA identified in Europeans, and we developed a genetic risk score for GA based on European markers. RESULTS: Mean GA was 30 ± 4 weeks in PTB cases (N = 933) and 39 ± 1 in the controls (N = 1,279). No associatiosn were identified at genome-wide level. Nominal PTB variants were enriched for biological pathways associated with polyketide, progesterone, steroid hormones, and glycosyl metabolism. Nominal GA variants were enriched in intronic regions and cancer pathways. Variants in WNT4 associated with GA in Europeans were replicated in our study. A genetic risk score was associated with a 2-day longer GA (P = 0.002) in our sample. CONCLUSIONS: This study identified various signals suggestively associated with PTB and GA in pregnant Peruvian women. None of these variants overlapped with signals previously identified in Europeans.

Is there a role for intestinal sporobiota in the antimicrobial resistance crisis?

Antimicrobial resistance (AMR) is a complex issue requiring specific, multi-sectoral measures to slow its spread. When people are exposed to antimicrobial agents, it can cause resistant bacteria to increase. This means that the use, misuse, and excessive use of antimicrobial agents exert selective pressure on bacteria, which can lead to the development of "silent" reservoirs of antimicrobial resistance genes. These genes can later be mobilized into pathogenic bacteria and contribute to the spread of AMR. Many socioeconomic and environmental factors influence the transmission and dissemination of resistance genes, such as the quality of healthcare systems, water sanitation, hygiene infrastructure, and pollution. The sporobiota is an essential part of the gut microbiota that plays a role in maintaining gut homeostasis. However, because spores are highly transmissible and can spread easily, they can be a vector for AMR. The sporobiota resistome, particularly the mobile resistome, is important for tracking, managing, and limiting the spread of antimicrobial resistance genes among pathogenic and commensal bacterial species.

The sensory shark: high-quality morphological, genomic and transcriptomic data for the small-spotted catshark Scyliorhinus canicula reveal the molecular bases of sensory organ evolution in jawed vertebrates.

Cartilaginous fishes (chimaeras and elasmobranchs -sharks, skates and rays) hold a key phylogenetic position to explore the origin and diversifications of jawed vertebrates. Here, we report and integrate reference genomic, transcriptomic and morphological data in the small-spotted catshark Scyliorhinus canicula to shed light on the evolution of sensory organs. We first characterise general aspects of the catshark genome, confirming the high conservation of genome organisation across cartilaginous fishes, and investigate population genomic signatures. Taking advantage of a dense sampling of transcriptomic data, we also identify gene signatures for all major organs, including chondrichthyan specializations, and evaluate expression diversifications between paralogs within major gene families involved in sensory functions. Finally, we combine these data with 3D synchrotron imaging and in situ gene expression analyses to explore chondrichthyan-specific traits and more general evolutionary trends of sensory systems. This approach brings to light, among others, novel markers of the ampullae of Lorenzini electro-sensory cells, a duplication hotspot for crystallin genes conserved in jawed vertebrates, and a new metazoan clade of the Transient-receptor potential (TRP) family. These resources and results, obtained in an experimentally tractable chondrichthyan model, open new avenues to integrate multiomics analyses for the study of elasmobranchs and jawed vertebrates.

Sleep-wake behavior and responses to sleep deprivation and immune challenge of protein kinase RNA-activated knockout mice.

Protein Kinase RNA-activated (PKR) is an enzyme that plays a role in many systemic processes, including modulation of inflammation, and is implicated in neurodegenerative diseases, such as Alzheimer's disease (AD). PKR phosphorylation results in the production of several cytokines involved in the regulation / modulation of sleep, including interleukin-1ß, tumor necrosis factor-α and interferon-γ. We hypothesized targeting PKR would alter spontaneous sleep of mice, attenuate responses to sleep deprivation, and inhibit responses to immune challenge. To test these hypotheses, we determined the sleep-wake phenotype of mice lacking PKR (knockout; PKR-/-) during undisturbed baseline conditions; in responses to six hours of sleep deprivation; and after immune challenge with lipopolysaccharide (LPS). Adult male mice (C57BL/6J, n = 7; PKR-/-, n = 7) were surgically instrumented with EEG recording electrodes and an intraperitoneal microchip to record core body temperature. During undisturbed baseline conditions, PKR -/- mice spent more time in non-rapid eye movement sleep (NREMS) and rapid-eye movement sleep (REMS), and less time awake at the beginning of the dark period of the light:dark cycle. Delta power during NREMS, a measure of sleep depth, was less in PKR-/- mice during the dark period, and core body temperatures were lower during the light period. Both mouse strains responded to sleep deprivation with increased NREMS and REMS, although these changes did not differ substantively between strains. The initial increase in delta power during NREMS after sleep deprivation was greater in PKR-/- mice, suggesting a faster buildup of sleep pressure with prolonged waking. Immune challenge with LPS increased NREMS and inhibited REMS to the same extent in both mouse strains, whereas the initial LPS-induced suppression of delta power during NREMS was greater in PKR-/- mice. Because sleep regulatory and immune responsive systems in brain are redundant and overlapping, other mediators and signaling pathways in addition to PKR are involved in the responses to acute sleep deprivation and LPS immune challenge.

Valorization of steelmaking slag and coal fly ash as amendments in combination with Betula pubescens for the remediation of a highly As- and Hg-polluted mining soil.

Soil pollution by As and Hg is a pressing environmental issue given their persistence. The intricate removal processes and subsequent accumulation of these elements in soil adversely impact plant growth and pose risks to other organisms in the food chain and to underground aquifers. Here we assessed the effectiveness of non-toxic industrial byproducts, namely coal fly ash and steelmaking slag, as soil amendments, both independently and in conjunction with an organic fertilizer. This approach was coupled with a phytoremediation technique involving Betula pubescens to tackle soil highly contaminated. Greenhouse experiments were conducted to evaluate amendments' impact on the growth, physiology, and biochemistry of the plant. Additionally, a permeable barrier made of byproducts was placed beneath the soil to treat leachates. The application of the byproducts reduced pollutant availability, the production of contaminated leachates, and pollutant accumulation in plants, thereby promoting plant development and survival. Conversely, the addition of the fertilizer alone led to an increase in As accumulation in plants and induced the production of antioxidant compounds such as carotenoids and free proline. Notably, all amendments led to increased thiolic compound production without affecting chlorophyll synthesis. While fertilizer application significantly decreased parameters associated with oxidative stress, such as hydrogen peroxide and malondialdehyde, no substantial reduction was observed after byproduct application. Thermal desorption analysis of the byproducts revealed Hg immobilization mechanisms, thereby indicating retention of this metalloid in the form of Hg chloride. In summary, the revalorization of industrial byproducts in the context of the circular economy holds promise for effectively immobilizing metal(loid)s in heavily polluted soils. Additionally, this approach can be enhanced through synergies with phytoremediation.

De-escalating axillary management after neoadjuvant chemotherapy in breast cancer: The ratio of positive sentinel lymph nodes matters.

BACKGROUND: De-escalation of axillary surgery in breast cancer (BC) patients diminishes sequelae without compromising cancer outcomes. Surgical management of the axilla is challenging after neoadjuvant treatment. We aimed to identify the factors associated with residual axillary disease amenable to lymphadenectomy in patients with positive sentinel lymph node biopsy (SLNB). METHODS: We conducted a retrospective observational study in Hospital 12 de Octubre (Spain). We included BC patients with positive SLNB who underwent axillary dissection after neoadjuvant chemotherapy. Univariate and multivariate logistic regression models were performed to identify independent predictors of residual axillary disease. We estimated the ratio of positive nodes in SLNB and assessed the diagnostic validity of this ratio in relation to residual axillary disease. RESULTS: We included 103 patients in the study. Residual axillary disease was identified in 54 patients (52.4%). Clinically node positive status at diagnosis (OR = 18.3, 95%CI: 4.0-83.6) and a ratio of positive nodes in SLNB ≥0.5 (OR = 6.5, 95%CI 41.7-23.7) were associated with residual axillary disease. The sensitivity and negative predictive value of a ratio of positive nodes in SLNB ≥0.5 were 87% (95%CI 75.1%-94.6%) and 75% (95%CI 55.1%-89.3%), respectively. CONCLUSIONS: In our study, for patients with positive SLNB after neoadjuvant chemotherapy, stage N+ at diagnosis and a ratio of positive nodes in SLNB ≥0.5 were independent risk factors of positive residual axillary disease. This ratio is a feasible measure with a good diagnostic validity for residual axillary disease and could be used as a guiding factor in the surgical management of these patients.

Lower cognitive reserve is related to worse working memory performance in older adults after mTBI. An ERP study.

OBJECTIVE: Older adults (OA) after mild traumatic brain injury (mTBI) have a high risk of developing persistent post-injury cognitive impairments. Lower pre-morbid cognitive reserve (CR) is increasingly investigated as a risk factor for cognitive dysfunction in OA. However, how CR protects against effects of mTBI at the brain level remains largely understudied. METHODS: We examined 22 OA who sustained mTBI (mean 67.69 years, SD 5.11) in the sub-acute phase and 15 age- and CR-matched healthy OA (mean 68 years, SD 5.55) performing a three-level visual N-back task using electroencephalography. We calculated inverse efficiency scores of performance from accuracy and reaction times. Event-related potentials served as neurocognitive correlates of attentional (P2) and working memory (P3) processing. RESULTS: Overall, mTBI OA performed worse than healthy OA (p = 0.031). Lower CR generally decreased performance (p < 0.001). Furthermore, with increasing task difficulty, task performance was more affected by CR (p = 0.004). At the brain level, P2 amplitude was lower in mTBI OA than in healthy OA (p = 0.05). There was no clear effect of CR on P2 or P3 measures. CONCLUSION: As mTBI OA with lower CR performed worse on a working-memory task, lower CR may be a risk factor for worse recovery after mTBI in this group.

Onyx®, A New Tool for Intraoperative Localization of Liver Lesions.

BACKGROUND: Precise preoperative localization of liver tumors facilitates successful surgical procedures, Intraoperative ultrasonography is a sensitive imaging modality. However, the presence of small non-palpable isoechoic intraparenchymal lesions may be challenging intraoperatively. METHODOLOGY AND MATERIAL DESCRIPTION: Onyx® is a non-adhesive liquid agent comprised of ethylene-vinyl alcohol usually used dissolved in dimethyl-sulfoxide and suspended micronized tantalum powder to provide contrast for visualization under fluoroscopy and ultrasonography and a macroscopic black shape. This embolization material has been increasingly used for the embolization of intracranial arteriovenous malformations. We present the novel application of Onyx® on liver surgery. CURRENT STATUS: We present the case of a female, 55 years-old, whose medical history revealed an elective sigmoidectomy (pT3N1a). After 17 months of follow up, by PET-CT scan, the patient was diagnosed of a small intraparenchymal hypo-attenuated 13 mm tumor located at segment V consistent with metachronous colorectal liver metastasis. Open metastasectomy was performed, ultrasonography-guided Onyx® infusion was delivered the day after, intraoperative ultrasonography showed a palpable hyperechoic material with a posterior acoustic shadowing artifact around the lesion. Onyx® is a promising new tool, without any previous application on liver surgery, feasible with advantages in small not palpable intraparenchymal liver lesions.

Metabolic disorders across the body mass index spectrum in a Colombian population with nonalcoholic fatty liver disease.

BACKGROUND AND AIMS: The relationship between obesity and nonalcoholic fatty liver disease (NAFLD) has long been established, and the prevalence of both conditions has grown together. Recent interest in NAFLD in nonobese individuals has led to an increasing number of studies, especially in Asia. Despite the fact that the prevalence of NAFLD in Latin America is one of the highest in the world, there is a lack of information on lean NAFLD populations from the region. The aim of the present study was to assess the risk of metabolic comorbidities across the whole body mass index spectrum when nonalcoholic steatohepatitis (NASH) was first diagnosed in a Latin American population. METHODS: A single-center, cross-sectional study on Colombian patients newly diagnosed with NAFLD, within the time frame of 2010-2020, compared their metabolic biochemical profile, liver enzymes, risk of prevalent metabolic abnormalities, and liver disease. RESULTS: Data from 300 patients were collected. Ninety-two percent of the patients were men and the median patient age was 47 (IQR 20) years. We found no significant differences in the biochemical, metabolic profile, or liver enzyme plasma concentration between lean, overweight, and obese individuals. Obese patients had significantly higher LDL cholesterol, and a higher risk of dyslipidemia (OR 1.86, 95% CI 1.14-3.05). Every 1kg increase in body weight increased the risk of having NASH by 2% (95% CI 2-4). CONCLUSIONS: We evaluated the metabolic risk across the entire body mass index spectrum in a Colombian cohort with NAFLD and presented the characteristics of what we believe is the first Latin American lean NAFLD population to be described.

Gut feelings: the relations between depression, anxiety, psychotropic drugs and the gut microbiome.

The gut microbiome is involved in the bi-directional relationship of the gut - brain axis. As most studies of this relationship are small and do not account for use of psychotropic drugs (PTDs), we explored the relations of the gut microbiome with several internalizing disorders, while adjusting for PTDs and other relevant medications, in 7,656 Lifelines participants from the Northern Netherlands (5,522 controls and 491 participants with at least one internalizing disorder). Disorders included dysthymia, major depressive disorder (MDD), any depressive disorder (AnyDep: dysthymia or MDD), generalized anxiety disorder (GAD) and any anxiety disorder (AnyAnx: GAD, social phobia and panic disorder). Compared to controls, 17 species were associated with depressive disorders and 3 were associated with anxiety disorders. Around 90% of these associations remained significant (FDR <0.05) after adjustment for PTD use, suggesting that the disorders, not PTD use, drove these associations. Negative associations were observed for the butyrate-producing bacteria Ruminococcus bromii in participants with AnyDep and for Bifidobacterium bifidum in AnyAnx participants, along with many others. Tryptophan and glutamate synthesis modules and the 3,4-Dihydroxyphenylacetic acid synthesis module (related to dopamine metabolism) were negatively associated with MDD and/or dysthymia. After additional adjustment for functional gastrointestinal disorders and irritable bowel syndrome, these relations remained either statistically (FDR <0.05) or nominally (P < 0.05) significant. Overall, multiple bacterial species and functional modules were associated with internalizing disorders, including gut - brain relevant components, while associations to PTD use were moderate. These findings suggest that internalizing disorders rather than PTDs are associated with gut microbiome differences relative to controls.

Serie de 22 casos de ictus isquémico arterial perinatal: factores de riesgo, manejo clínico y secuelas neurológicas / A series of 22 cases of perinatal arterial ischaemic stroke: risk factors, clinical management and neurological sequelae

Introduction. Perinatal arterial ischaemic stroke (PAIS) is almost as common as in adulthood and causes significant neurological sequelae. Aim. The aim is to describe the risk situations surrounding these neonates, the clinical manifestations, the management, the cost-effectiveness of diagnostic tests and the neurological sequelae. Patients and methods. We conducted an observational study of a cohort of patients consisting of neonates with a gestational age = 35 weeks diagnosed with PAIS in our hospital between 2010 and 2021. Results. Twenty-two cases of PAIS were included, and the incidence in our centre was 1/1,869 live newborns. The data showed that 81.8% had some intrapartum risk factor and 40.9% had a combination of several risk factors. It started with seizures (mean age 27.3 hours) in 77.3% of cases. Patients with a stroke in the left hemisphere had more sequelae (77.8%) than those with a stroke on the right-hand side (16.6%) (p = 0.041), with the exception of infantile cerebral palsy (p = 0.04), while we found no difference between hemispheres in the frequency of language impairment (p = 0.06). The mean follow-up time was 6.13 ± 3.06 years. A total of 63.6% of infants had neurological sequelae: infantile cerebral palsy (40.9%), language disorders (22.7%) and intellectual disability (9%). Moreover, 18.2% developed epilepsy (between 0.25 and 1.8 years) and antiseizure treatment was maintained after discharge in 37.5% of cases in the last years of the study. Conclusions. If a newborn infant presents seizures, it is necessary to rule out the possibility of a stroke. PAIS causes neurological sequelae in over 60% of cases. Early identification is essential to improve the neurological prognosis and avoid the prolonged use of antiseizure drugs where possible. (AU)

Introducción: El ictus cerebral isquémico arterial perinatal (IIAP) es una entidad casi tan frecuente como en la época adulta, que ocasiona secuelas neurológicas importantes.ObjetivoDescribir las situaciones de riesgo que rodean a estos neonatos, la clínica que manifiestan, el manejo, la rentabilidad de las pruebas diagnósticas y las secuelas neurológicas.Pacientes y métodosEstudio observacional de una cohorte de pacientes formada por neonatos = 35 semanas de edad gestacional diagnosticados de IIAP entre 2010 y 2021 en nuestro hospital.ResultadosSe incluyeron 22 casos de IIAP, y su incidencia en nuestro centro fue de 1/1.869 recién nacidos vivos. El 81,8% tuvo algún factor de riesgo intraparto y en el 40,9% se aglutinaron varios. Comenzó con convulsiones (edad media 27,3 horas) el 77,3% de casos. Los pacientes con ictus del hemisferio izquierdo tuvieron más secuelas (77,8%) en comparación con los derechos (16,6%) (p = 0,041), a expensas de la parálisis cerebral infantil (p = 0,04), mientras no encontramos diferencia en la frecuencia de alteraciones del lenguaje (p = 0,06) entre hemisferios. El tiempo medio de seguimiento fue de 6,13 años ± 3,06. El 63,6% de los neonatos tuvo secuelas neurológicas: parálisis cerebral infantil (40,9%), trastornos del lenguaje (22,7%) y discapacidad intelectual (9%). Desarrolló epilepsia el 18,2% (entre 0,25 y 1,8 años) y se mantuvo el tratamiento anticrisis tras el alta en el 37,5% de los casos en los últimos años del estudio.ConclusionesAnte un neonato con convulsiones hay que descartar un ictus cerebral. El IIAP ocasiona secuelas neurológicas en más del 60% de los casos. Su identificación precoz es fundamental para mejorar el pronóstico neurológico y evitar el uso prolongado de fármacos anticrisis cuando resulte posible. (AU)

[A series of 22 cases of perinatal arterial ischaemic stroke: risk factors, clinical management and neurological sequelae]. / Serie de 22 casos de ictus isquémico arterial perinatal: factores de riesgo, manejo clínico y secuelas neurológicas.

INTRODUCTION: Perinatal arterial ischaemic stroke (PAIS) is almost as common as in adulthood and causes significant neurological sequelae. AIM: The aim is to describe the risk situations surrounding these neonates, the clinical manifestations, the management, the cost-effectiveness of diagnostic tests and the neurological sequelae. PATIENTS AND METHODS: We conducted an observational study of a cohort of patients consisting of neonates with a gestational age = 35 weeks diagnosed with PAIS in our hospital between 2010 and 2021. RESULTS: Twenty-two cases of PAIS were included, and the incidence in our centre was 1/1,869 live newborns. The data showed that 81.8% had some intrapartum risk factor and 40.9% had a combination of several risk factors. It started with seizures (mean age 27.3 hours) in 77.3% of cases. Patients with a stroke in the left hemisphere had more sequelae (77.8%) than those with a stroke on the right-hand side (16.6%) (p = 0.041), with the exception of infantile cerebral palsy (p = 0.04), while we found no difference between hemispheres in the frequency of language impairment (p = 0.06). The mean follow-up time was 6.13 ± 3.06 years. A total of 63.6% of infants had neurological sequelae: infantile cerebral palsy (40.9%), language disorders (22.7%) and intellectual disability (9%). Moreover, 18.2% developed epilepsy (between 0.25 and 1.8 years) and antiseizure treatment was maintained after discharge in 37.5% of cases in the last years of the study. CONCLUSIONS: If a newborn infant presents seizures, it is necessary to rule out the possibility of a stroke. PAIS causes neurological sequelae in over 60% of cases. Early identification is essential to improve the neurological prognosis and avoid the prolonged use of antiseizure drugs where possible.

TITLE: Serie de 22 casos de ictus isquémico arterial perinatal: factores de riesgo, manejo clínico y secuelas neurológicas.Introducción. El ictus cerebral isquémico arterial perinatal (IIAP) es una entidad casi tan frecuente como en la época adulta, que ocasiona secuelas neurológicas importantes. Objetivo. Describir las situaciones de riesgo que rodean a estos neonatos, la clínica que manifiestan, el manejo, la rentabilidad de las pruebas diagnósticas y las secuelas neurológicas. Pacientes y métodos. Estudio observacional de una cohorte de pacientes formada por neonatos = 35 semanas de edad gestacional diagnosticados de IIAP entre 2010 y 2021 en nuestro hospital. Resultados. Se incluyeron 22 casos de IIAP, y su incidencia en nuestro centro fue de 1/1.869 recién nacidos vivos. El 81,8% tuvo algún factor de riesgo intraparto y en el 40,9% se aglutinaron varios. Comenzó con convulsiones (edad media 27,3 horas) el 77,3% de casos. Los pacientes con ictus del hemisferio izquierdo tuvieron más secuelas (77,8%) en comparación con los derechos (16,6%) (p = 0,041), a expensas de la parálisis cerebral infantil (p = 0,04), mientras no encontramos diferencia en la frecuencia de alteraciones del lenguaje (p = 0,06) entre hemisferios. El tiempo medio de seguimiento fue de 6,13 años ± 3,06. El 63,6% de los neonatos tuvo secuelas neurológicas: parálisis cerebral infantil (40,9%), trastornos del lenguaje (22,7%) y discapacidad intelectual (9%). Desarrolló epilepsia el 18,2% (entre 0,25 y 1,8 años) y se mantuvo el tratamiento anticrisis tras el alta en el 37,5% de los casos en los últimos años del estudio. Conclusiones. Ante un neonato con convulsiones hay que descartar un ictus cerebral. El IIAP ocasiona secuelas neurológicas en más del 60% de los casos. Su identificación precoz es fundamental para mejorar el pronóstico neurológico y evitar el uso prolongado de fármacos anticrisis cuando resulte posible.

Immune thrombotic thrombocytopenic purpura in older patients: Results from the Spanish TTP Registry (REPTT).

Immune thrombotic thrombocytopenic purpura (iTTP) is an ultra-rare disease that seldom occurs in the elderly. Few reports have studied the clinical course of iTTP in older patients. In this study, we have analysed the clinical characteristics at presentation and response to therapy in a series of 44 patients with iTTP ≥60 years at diagnosis from the Spanish TTP Registry and compared them with 209 patients with <60 years at diagnosis from the same Registry. Similar symptoms and laboratory results were described in both groups, except for a higher incidence of renal dysfunction among older patients (23% vs. 43.1%; p = 0.008). Front-line treatment in patients ≥60 years was like that administered in younger patients. Also, no evidence of a difference in clinical response and overall survival was seen in both groups. Of note, 14 and 25 patients ≥60 years received treatment with caplacizumab and rituximab, respectively, showing a favourable safety and efficacy profile, like that observed in patients <60 years.

Boar sperm motility is modulated by CCK at a low concentration of bicarbonate under capacitation conditions.

In a previous study, our group detected the cholecystokinin (CCK) protein in the porcine oviduct. This fact, together with the involvement of CCK in the regulation of sperm protein tyrosine phosphorylation by the modulation of HCO3 - uptake (in mice and humans) suggests a role for CCK during sperm capacitation. Therefore, on the one hand, the expression of CCK receptors (CCK1R and CCK2R) on boar testes has been investigated and probed; on the other hand, boar spermatozoa (from seminal doses of 1-day and 5-day storage) were exposed to different concentrations of CCK (0-control, 25 or 50 µM) in a medium supporting capacitation supplemented with 0, 5 or 25 mmol/L of HCO3 - for 1 h at 38.5°C. Sperm motion (total and progressive motility), kinetic parameters, viability, acrosome status, and mitochondrial activity were determined. No differences between groups (0, 25 or 50 µM of CCK) were observed when HCO3 - was absent in the media (p > .05). However, the results showed that when the media was supplemented with 5 mmol/L HCO3 - in 1-day seminal dose storage, the linearity index (LIN, %), straightness index (STR, %) and oscillation index (WOB, %) (sperm kinetics parameters) increased in the presence of CCK regardless the concentration (p < .05). Nevertheless, CCK in sperm from 5-day storage only increased the WOB parameter in comparison to the control (p < .05). Furthermore, the average amplitude of the lateral displacement of the sperm head (ALH, µm) and curvilinear velocity (VCL, µm/s) decreased when CCK was present, depending on its concentration and sperm aging (1-day vs. 5-days) (p < .05). In the case of the media supporting capacitation supplemented with 25 mmol/L HCO3 - , any differences were observed except for sperm viability in the 5-day seminal doses, which increased in the 50 µM-CCK group compared to the control (p < .05). In conclusion, these data suggest an implication of CCK protein during sperm capacitation under low bicarbonate concentration increasing the sperm linear trajectory.

Anisotropic behavior of mechanical properties for thea- andc-domains in a (001) BaTiO3single crystal.

Barium titanate (BaTiO3) single crystal with a tetragonal phase was characterized by nanoindentation. Elastic and elastic-plastic deformation regimes were obtained. The main objective was the evaluation of the anisotropic behavior related to mechanical properties associated with the cross-section of the ferroelectrica- andc-domains (In-plane and out-of-plane) in (001) configuration domains. This behavior was evaluated along a line perpendicular to the between domains, which demonstrated that the mechanical properties of the BaTiO3single crystal depend on the distance from due to the effect of the influence of the neighbor domain. A three-dimensional (3D) finite element (FE) model was developed to simulate mechanical effects revealed by the nanoindentations test. The FE simulation demonstrated that there is no simple isotropic mechanical behavior associated with the domain type. Numerical simulations and experiments performed to study ferroelastic switching domains in BaTiO3crystals revealed the interaction of the 90°-cadomain with the indentation position.