Arterial Hypertension, Structural Damage of the Brain and Cognitive Test / Hipertensión arterial, daño estructural del cerebro y test cognitivos.

Introduction: The arterial hypertension cause brain vascular damage (white matter lesion) and the burden and progression determine their cognitive consequences. Therefore, arterial hypertension is considered the main modifiable vascular risk factor for cognitive impairment and dementia. Therefore, the aim of the current study was to evaluate the results of cognitive tests in a sample of hypertensive patients and to establish possible associations with structural brain lesions (atrophy, white matter lesions) identified by magnetic resonance imaging Methods: Were included 70 hypertensive patients from Heart-Brain study in Argentina with magnetic resonance imaging and cognitive test. Fazekas scale and the Global Cortical Atrophy were used to quantify the white matter lesions and the brain atrophy, respectively. The Mini-Mental Status Examination, Clock Drawing test and Mini-Boston Naming test were used to evaluate the cognitive status. Results: average age 69.7 ± 10.6 years, 55.7% female). Based on the linear regression analysis, Fazekas scale and cognitive tests were inversely associated. For each grade of increase in Fazekas scale, the clock drawing test (Coef -0.56, CI 95% -1.01 -0.10, p=0.01) and the Mini-mental Status Examination (Coef -0.7, CI 95% -1.27 -0.13, p=0.01) scores decreased. The subcortical atrophy was significantly associated with the clock drawing test (OR 3.29, CI 95% 1.25-8.63; p=0.016). Conclusion: The cognitive tests, particularly the clock drawing test could be used (in the clinical routine practice) as "subrrogate" of the brain structural hypertension-mediated damage.

Introducción: La hipertensión arterial causa daño vascular cerebral (lesiones de sustancia blanca) y su carga y progresión determinan las consecuencias cognitivas. Así, la hipertensión es considerada el principal factor de riesgo vascular modificable para desarrollar deterioro cognitivo y demencia. Por lo tanto el objetivo de la presente investigación fue evaluar el resultado de los test cognitivos en una muestra de pacientes hipertensos y establecer las posibles asociaciones con las lesiones estructurales del cerebro (atrofia, lesiones de sustancia blanca) identificadas mediante resonancia magnética. Métodos: Se incluyeron 70 pacientes hipertensos pertenecientes al estudio Corazón-Cerebro en Argentina a los que se les realizó resonancia magnética y evaluación cognitiva. Se utilizaron las escalas de Fazekas y la Global Cortico Atrophy para evaluar las lesiones de sustancia blanca y la atrofia cerebral, respectivamente y el Mini-mental test, el test del reloj y el test de denominación Mini-Boston para conocer el estatus cognitivo. Resultados: Edad promedio 69.7 ± 10.6 años, 55.7% mujeres. Basados en el análisis de regresión lineal, la escala de Fazekas se asoció en forma inversa con los test cognitivos. Por cada punto de aumento en la escala de Fazekas el puntaje del test del reloj descendió -0.56 (IC 95% -1.01 -0.10, p=0.01) y el Mini-mental test -0.7 (IC95% -1.27 -0.13, p=0.01). La atrofia subcortical se asoció en forma inversa solo con el test del reloj (OR 3.29, IC 95% 1.25-8.63; p=0.016). Conclusión: Los test cognitivos, en especial el test del reloj, podrían ser utilizados, en la práctica clínica asistencial, como un subrogado del daño estructural del cerebro mediado por la hipertensión arterial.

Nucleophilic catalysis of p-substituted aniline derivatives in acylhydrazone formation and exchange.

Hydrazone bond formation is a versatile reaction employed in several research fields. It is one of the most popular reversible reactions in dynamic combinatorial chemistry. Under physiological conditions, hydrazone exchange benefits from the addition of a nucleophilic catalyst. We report a mechanistic study and superior performance of electron-rich p-substituted aniline derivatives as catalysts for efficient hydrazone formation and exchange in both protic and aprotic solvents. Rigorous kinetic analyses demonstrate that imine formation with 3-hydroxy-4-nitrobenzaldehyde and aniline derivatives proceeds with unprecedented third-order kinetics in which the aldehyde consistently shows a partial order of two. Computational investigations provide insights into the mechanisms of these transformations.

Net-like superficial lymphatic malformation.

The net-like superficial lymphatic malformation (LM) is a newly described entity with distinctive clinical, dermoscopic, and histologic characteristics. Clinical picture consists of red to purplish macules with a finely reticulated pattern of vascular structures. Dermoscopy shows arborizing telangiectatic vessels. Histology is characterized by a vascular proliferation composed of thin-walled vessels, located in the upper dermis, that stains positive with podoplanin (D2-40). We report a new case of LM with an additional clinical feature, hypopigmented areas.

A Novel NFIX-STAT6 Gene Fusion in Solitary Fibrous Tumor: A Case Report.

Solitary fibrous tumor is a rare subtype of soft-tissue sarcoma with a wide spectrum of histopathological features and clinical behaviors, ranging from mildly to highly aggressive tumors. The defining genetic driver alteration is the gene fusion NAB2-STAT6, resulting from a paracentric inversion within chromosome 12q, and involving several different exons in each gene. STAT6 (signal transducer and activator of transcription 6) nuclear immunostaining and/or the identification of NAB2-STAT6 gene fusion is required for the diagnostic confirmation of solitary fibrous tumor. In the present study, a new gene fusion consisting of Nuclear Factor I X (NFIX), mapping to 19p13.2 and STAT6, mapping to 12q13.3 was identified by targeted RNA-Seq in a 74-year-old female patient diagnosed with a deep-seated solitary fibrous tumor in the pelvis. Histopathologically, the neoplasm did not display nuclear pleomorphism or tumor necrosis and had a low proliferative index. A total of 378 unique reads spanning the NFIXexon8-STAT6exon2 breakpoint with 55 different start sites were detected in the bioinformatic analysis, which represented 59.5% of the reads intersecting the genomic location on either side of the breakpoint. Targeted RNA-Seq results were validated by RT-PCR/ Sanger sequencing. The identification of a new gene fusion partner for STAT6 in solitary fibrous tumor opens intriguing new hypotheses to refine the role of STAT6 in the sarcomatogenesis of this entity.

Usefulness of carotid ultrasonography in the assessment of coronary artery disease extension in patients undergoing exercise echocardiography.

OBJECTIVES: To evaluate whether carotid disease is associated with coronary artery disease (CAD) extension in patients undergoing treadmill exercise stress echocardiography (EE). METHODS: We retrospectively studied 156 patients without previous vascular disease who underwent EE, carotid ultrasonography, and coronary angiography between 2002 and 2013. Low-, intermediate-, and high-risk EE were defined as negative, localized ischemia, and multivessel/extensive ischemia EE respectively; carotid disease according to Mannheim and American Society of Echocardiography Consensus and CAD extension from zero to three vessel disease as stenosis ≥50% by visual assessment. RESULTS: Of the 156 patients, 67 (42.9%), 43 (27.6%), 22 (14.1%), and 24 (15.4%) had zero, one, two, and three vessel disease respectively. Age (P = 0.047), male sex (P = 0.010), diabetes mellitus (P = 0.039), smoking habit (P = 0.015), fasting plasma glucose (P = 0.021), European Systematic COronary Risk Evaluation (P = 0.003), pretest CAD probability (P = 0.003), high-risk EE (P < 0.001), and carotid plaque presence (CP) (P < 0.001) were associated in univariate analysis with more extensive CAD. Predictors of CAD extension in multivariate analysis were high-risk EE (odds ratio [OR] 2.42, P < 0.001), CP presence (OR 1.75, P = 0.004), and pretest CAD probability >65% (OR 1.49, P = 0.023). CP was also associated with multivessel CAD in the 53 patients with low- or intermediate-risk EE (P = 0.001). CONCLUSIONS: CP is associated with CAD extension in patients with ischemic heart disease suspicion undergoing EE. Patients with CP could benefit from a more aggressive therapeutic strategy regarding patients without carotid disease and similar risk EE, especially in intermediate- and/or low-risk test where guidelines recommend initially optimal medical treatment.

Mitochondrial Genetic Diversity of Eurasian Red Squirrels (Sciurus vulgaris) from Denmark.

Melanistic Eurasian red squirrels Sciurus vulgaris are commonly found on the Danish island of Funen. They are thought to represent native Danish squirrel types and are presently under threat from admixture with introduced red squirrels. In response, a conservation program was started in 2009 that involves the translocation of melanistic squirrels from Funen to the squirrel-free island of Langeland. Using mitochondrial DNA of 101 historical and modern samples from throughout Denmark, we assess for the first time population structure and mitochondrial genetic diversity of Danish squirrels compared to its larger pan-Eurasian distribution. We find that Danish squirrels have low levels of genetic diversity, especially melanistic individuals. Bayesian skyline reconstructions show that Danish squirrels have most probably experienced a severe bottleneck within the last 200 years. Also, fine-scale genetic structure was found between squirrels from the regions of Funen, Zealand and Jutland, which mimics the insular geography of Denmark. Additional nuclear DNA analyses will be required to determine the precise admixture levels between original Danish and introduced squirrels and to locate unmixed candidate populations for specific conservation efforts.

Predicting cognitive function and dementia risk in patients with hypertension.

In spite of the fact that hypertension stand out as the main vascular risk factor for developing dementia, it is essential to acknowledge the presence of other risk factors, both vascular and non-vascular that contribute to increase this risk. This study stratified the dementia risk using CAIDE (Cardiovascular Risk Factors, Aging, and Incidence of Dementia) dementia risk score in a sample of 1279 hypertensive patients from the Heart-Brain Study in Argentina and to observed the association between the risk factors include in the CAIDE score and the current cognitive status. The average age of the sample was 60.2 ± 13.5 years (71% female) and the average years of education was 9.9 ± 5.1 years. To assess the current cognitive status, we used the Mini-mental test (MMSE), the clock drawing test (CDT) and Mini-Boston test. According to CAIDE score ( ≥9 points) the risk of dementia was 40.4% in the total sample and 28.1% in the middle-life hypertensive patients (between 47 to 53 years). An inverse association was observed between CAIDE score and the results of current cognitive tests (MMSE = R2 0.9128, p < 0.0001; CDT = R2 0.9215, p < 0.0001 y Mini-Boston= R2 0.829, p < 0.0001). The CAIDE score can predict the risk of dementia in hypertensive patients and its result was associated with the current cognitive status (result of cognitive tests).

Regression of Cardiac Lymphoma With Chemotherapy.

A patient was admitted for chest pain with electrocardiographic changes, and cardiac magnetic resonance showed focal myocardial hypertrophy secondary to edema. Combined positron emission tomography and computed tomography corroborated foci of myocardial hypermetabolism, as well as multiple adenopathies consistent with lymphoma in the biopsy. Hypertrophy and edema regressed with chemotherapy.

[Giant cell tumour of bone in the rib cage treated with denosumab. A case report]. / Tumor de células gigantes óseo en arco costal, tratado con denosumab. Reporte de un caso.

Giant cell tumour of bone (GCTOB) accounts for 4-5% of all primary bone tumours and occurs most frequently in females between 20 and 45 years old. It is found in the epiphyses of the long bones, vertebral bodies and flat bones. We report the case of a 31-year-old woman who presented with a one month history of thoracic pain. On examination, a mass was found in the right breast with signs of an ipsilateral pleural effusion. A thoracic CAT scan revealed an infiltrating mass which was subsequently biopsied and a GCTOB was diagnosed. Due to the localization and the morphology, a wide range of differential diagnoses were considered. Genetic studies detected a mutation of the gene H3F3A, supporting the original diagnosis. The patient underwent treatment with denosumab followed by surgical resection of the mass. The histopathology of the tumour revealed various histological changes which were a source of diagnostic pitfalls.

The Phosphorylation of Kv1.3: A Modulatory Mechanism for a Multifunctional Ion Channel.

The voltage-gated potassium channel Kv1.3 plays a pivotal role in a myriad of biological processes, including cell proliferation, differentiation, and apoptosis. Kv1.3 undergoes fine-tuned regulation, and its altered expression or function correlates with tumorigenesis and cancer progression. Moreover, posttranslational modifications (PTMs), such as phosphorylation, have evolved as rapid switch-like moieties that tightly modulate channel activity. In addition, kinases are promising targets in anticancer therapies. The diverse serine/threonine and tyrosine kinases function on Kv1.3 and the effects of its phosphorylation vary depending on multiple factors. For instance, Kv1.3 regulatory subunits (KCNE4 and Kvß) can be phosphorylated, increasing the complexity of channel modulation. Scaffold proteins allow the Kv1.3 channelosome and kinase to form protein complexes, thereby favoring the attachment of phosphate groups. This review compiles the network triggers and signaling pathways that culminate in Kv1.3 phosphorylation. Alterations to Kv1.3 expression and its phosphorylation are detailed, emphasizing the importance of this channel as an anticancer target. Overall, further research on Kv1.3 kinase-dependent effects should be addressed to develop effective antineoplastic drugs while minimizing side effects. This promising field encourages basic cancer research while inspiring new therapy development.

Characterizing the physical and mental health profile of children, adolescents and adults with autism spectrum disorder in Spain.

Introduction: Autistic men and women are more likely to experience health issues than the general population, although the available epidemiological studies addressing co-occurrence conditions are limited. This is the first Spanish epidemiologic study addressing the health profile and poor-health exacerbating factors in individuals of all ages with autism spectrum disorder (ASD). Methods: We analyzed 2,629 registries extracted from Autism Spain's sociodemographic registry (November 2017-May 2020). A descriptive health data analysis was conducted to assess the prevalence of other conditions associated to ASD in the Spanish population. Nervous system disorders (12.9%), mental health diagnoses (17.8%), and other comorbidities (25.4%) were reported. Men-to-women ratio was 4:1. Results: Women, elder individuals and those with intellectual disability (ID) were at an increased risk of health comorbidities and psychopharmacological exposure. Women were also more prone to severe intellectual and functional impairment. Nearly all individuals had difficulties in their adaptative functioning, especially those with ID (50% of the population). Almost half of the sample received psychopharmacological treatments starting from infancy and early childhood, mostly antipsychotics and anticonvulsants. Discussion: This study represents an important first approach to the health status of autistic people in Spain and can contribute to the development of public policies and innovative health strategies.

Updated Review and Clinical Recommendations for the Diagnosis and Treatment of Patients with Retroperitoneal Sarcoma by the Spanish Sarcoma Research Group (GEIS).

Soft tissue sarcomas (STS) are an uncommon and biologically heterogeneous group of tumors arising from mesenchymal cells. The incidence is estimated at five cases per 100,000 people per year. Retroperitoneal sarcomas (RPS) account for 10-15% of all STS, and their management depends on their anatomical characteristics and histotype. Due to their very low incidence, it is recommended that RPS be treated in reference centers and evaluated by an experienced multidisciplinary team (MDT). In Spain, the Spanish Group for Research in Sarcomas (GEIS) brings together experts from various specialties to promote research on sarcomas and improve treatment results. This paper summarizes the GEIS recommendations for the diagnosis, treatment, and follow-up of patients with RPS.

Non-peptidic cell-penetrating agents: synthesis of oligomeric chiral bicyclic guanidinium vectors.

Polycationic oligo(chiral bicyclic guanidines) constitute useful non-peptidic penetrating agents for cell uptake and protein surface recognition. We report herein improved and selective procedures for the preparation of oligoguanidinium scaffolds linked through thioether bonds, with similar or different groups and functions at both ends of the chain. Two synthetic strategies were developed to obtain these compounds in relatively good yields from a common thioacetate precursor: generation of a disulfide intermediate or thiolate formation. Thus, tetraguanidinium intermediates 8 and 22 are best synthesized by the disulfide route, whereas hexamer 29, octamer 31, and trimer 37 arise from a combination of both the disulfide and the thioacetate routes. Finally, tetramer 28 can be readily obtained from either strategy.

Haemodynamic effects of non-invasive ventilation in patients with obesity-hypoventilation syndrome.

BACKGROUND AND OBJECTIVE: Although it has been reported that pulmonary hypertension is more frequent in patients with obesity-hypoventilation syndrome than in patients with 'pure' obstructive sleep apnoea syndrome, little is known about the haemodynamic repercussions of this entity. The aim was to describe the haemodynamic status, as assessed by echocardiography and 6-min walk test (6MWT), of patients with a newly diagnosed, most severe form of obesity-hypoventilation syndrome, and to evaluate the impact of non-invasive ventilation in these patients. METHODS: A prospective, descriptive, and single-centre follow-up study was conducted. At baseline, patients underwent echocardiography, spirometry, static lung volume measurement, 6MWT, overnight pulse-oximetry and polygraphic recording. Changes in echocardiography and 6MWT were assessed after 6 months of non-invasive ventilation. Right ventricular overload was defined on the basis of right ventricular dilatation, hypokinesis, paradoxical septal motion and/or pulmonary hypertension. RESULTS: Thirty patients (20 women; mean age 69 ± 11) were tested. The percentage of patients with right ventricular overload did not change significantly after non-invasive ventilation (43.3-41.6%; P = 0.24). In patients with right ventricular overload at diagnosis, pulmonary artery systolic pressure decreased significantly at six months (58 ± 11 to 44 ± 12 mm Hg; P = 0.014), and mean distance on 6MWT increased from 350 ± 110 to 426 ± 78 m (P = 0.006), without significant changes in body mass index. CONCLUSIONS: Right ventricular overload is a frequent finding in patients with the most severe form of obesity-hypoventilation syndrome. Treatment with non-invasive ventilation is associated with a decrease in pulmonary artery systolic pressure at six months and an increase in the distance covered during the 6MWT.

The quality of life of people with ASD through physical activity and sports.

Among the factors that influence the quality of life of people with Autism Spectrum Disorder (ASD), physical activity and sport are key dimensions of physical well-being. Few studies take into account the perspectives of people with ASD in order to understand the extent of physical well-being and their subjective perception of it. The development of a system of quality of life indicators related to physical activity and sport for people with ASD and their analysis is the aim of this study, providing guidelines for improvement. A study was carried out with a sample of 276 people, professionals (n = 143), family members (n = 73) and people with ASD (n = 60). The people with ASD in the sample belonged to three age categories: children aged 8-12 years, adolescents aged 12-18 years and adults over 18 years. The research team used a qualitative methodology in the collection of information. They adapted three questionnaires, with validated quality of life scales, to guide the interviews and also applied them in the design of the focus group protocols. Subsequently, the research team analysed the information collected in the focus groups with families and professionals using a DELPHI method. A system for coding the responses and qualitative analysis of the responses was also prepared for the analysis of the data by the research team. Finally, the information obtained was compared with a group of representative experts. The results concluded with the elaboration of a system of quality of life indicators related to the dimension of physical well-being, as well as guidelines and proposals that bring together the perspectives of people with ASD in relation to the practice of sport and physical activity. There is a need to increase the practice of sport among people with ASD in order to promote their health, social participation and personal satisfaction. It is concluded that it is not possible to obtain a broad picture of the quality of life of people with ASD and their families due to lack of information. However, the method and the results obtained represent a first approach at national level to increase knowledge about the quality of life of people with ASD.

Long-term clinical outcome of patients with persistent right ventricle dysfunction or pulmonary hypertension after acute pulmonary embolism.

AIMS: Persistent, echocardiography-assessed right ventricle dysfunction (RVD) and/or pulmonary hypertension (PHT) are relatively frequent findings after an acute pulmonary embolism (PE). It has been suggested that echocardiography might predict long-term adverse events. Our objectives were to evaluate the prognostic value of RVD or isolated PHT 6 months after an acute PE with regard to all-cause mortality or venous thromboembolism (VTE) recurrence. METHODS AND RESULTS: In a previous study, echocardiography was used to assess RVD or PHT on admission and 6 months after an acute PE in 101 consecutive, haemodynamically stable pulmonary patients. We assessed the subsequent vital status and incidence of recurrent VTE in these patients. Six patients were lost for follow-up. The other 95 patients were categorized as those (i) with RVD or PHT 6 months after PE (17 cases, 17.8%) and (ii) patients with neither RVD nor PHT (78 cases, 82.1%). After a mean±SD of 2.8±1.06 years, there were 9 (9.4%) deaths and 12 (12.6%) VTE recurrences. At multivariate analysis, only age predicted all-cause mortality [hazard ratio (HR): 1.081, 95% confidence interval (CI): 1.003-1.166, P=0.004]. RVD or PHT persistence did not appear to increase the risk of mortality or recurrent VTE. CONCLUSION: Persistent echocardiographic signs of right ventricular pressure overload 6 months after an acute PE did not predict long-term adverse outcome events in this study.

Biomimetic selenocystine based dynamic combinatorial chemistry for thiol-disulfide exchange.

Dynamic combinatorial chemistry applied to biological environments requires the exchange chemistry of choice to take place under physiological conditions. Thiol-disulfide exchange, one of the most popular dynamic combinatorial chemistries, usually needs long equilibration times to reach the required equilibrium composition. Here we report selenocystine as a catalyst mimicking Nature's strategy to accelerate thiol-disulfide exchange at physiological pH and low temperatures. Selenocystine is able to accelerate slow thiol-disulfide systems and to promote the correct folding of an scrambled RNase A enzyme, thus broadening the practical range of pH conditions for oxidative folding. Additionally, dynamic combinatorial chemistry target-driven self-assembly processes are tested using spermine, spermidine and NADPH (casting) and glucose oxidase (molding). A non-competitive inhibitor is identified in the glucose oxidase directed dynamic combinatorial library.

Design and optimization of broadband tapered optical fibers with a nanofiber waist.

The control over the transmission properties of tapered optical fibers (TOFs) is an important requirement for a whole range of applications. Using a carefully designed flame pulling process that allows us to realize preset fiber radius profiles, we fabricate TOFs with a nanofiber waist. We study the spectral transmission properties of these TOFs as a function of the taper profile and the waist length and show how the transmission band of the TOF can be tuned via different fiber profile parameters. Based on these results, we have designed a nanofiber-waist TOF with broadband transmission for surface spectroscopy of organic molecules. Moreover, our method allows us to analyze the loss mechanisms of optical nanofibers.

Efficacy of a brief multifactorial adherence-based intervention on reducing the blood pressure of patients with poor adherence: protocol for a randomized clinical trial.

BACKGROUND: Lowering of blood pressure by antihypertensive drugs reduces the risks of cardiovascular events, stroke, and total mortality. However, poor adherence to antihypertensive medications reduces their effectiveness and increases the risk of adverse events. In terms of relative risk reduction, an improvement in medication adherence could be as effective as the development of a new drug. METHODS/DESIGN: The proposed randomized controlled trial will include patients with a low adherence to medication and uncontrolled blood pressure. The intervention group will receive a multifactorial intervention during the first, third, and ninth months, to improve adherence. This intervention will include motivational interviews, pill reminders, family support, blood pressure self-recording, and simplification of the dosing regimen. MEASUREMENT: The primary outcome is systolic blood pressure. The secondary outcomes are diastolic blood pressure, proportion of patients with adequately controlled blood pressure, and total cost. DISCUSSION: The trial will evaluate the impact of a multifactorial adherence intervention in routine clinical practice. Ethical approval was given by the Ethical Committee on Human Research of Balearic islands, Spain (approval number IB 969/08 PI).

[Analysis of the frequency of experimentation with and consumption of drugs in high-school students]. / Análisis de la frecuencia de experimentación y consumo de drogas de alumnos de escuelas de nivel medio.

The aim of this study was to survey the frequency of experimentation and consumption of drugs in high-school students in Cordoba, Argentina, relating it to socio-demographic variables. An observational-analytical method was employed, on the basis of the records of the Secretary for the Planning of Drug-Addiction Prevention and Fighting of Drug-Trafficking. Statistical. Bivariate analysis, odds ratio and confidence interval were applied in the processing of each variable. Alcohol consumption was found to be more frequent among males. Of the subjects 12.2% had tried some type of illicit substance. Tranquilizers were the most commonly used psycho-medicine. Drug consumption increased with age, years of schooling and availability of money. Our detection of an epidemiological situation is deemed useful for prevention strategies for drug addiction among teenagers.