Pediatric peri-insular hemispherotomy and functional hemispherectomy for severe medically refractory epilepsy: comparison of two techniques.

PURPOSE: Since it was first described in the 1970s, functional hemispherotomy has been an essential tool in treating disabling, medically refractory epilepsy resulting from diffuse unilateral hemispheric disease. We report our experience with 23 patients who underwent hemispherotomy, both using the functional hemispherotomy (FH) as well as a modified peri-insular hemispherotomy (PIH) technique. We present the surgical technique for the latter, review outcomes following disconnection surgery and discuss the differences between the techniques when it comes to complications and postoperative results. METHODS: A retrospective study of 23 patients with refractory seizures who underwent cerebral hemispherectomy. A thorough analysis of the clinical, imaging, surgical features and postoperative results was performed. We also present the surgical technique for a modified PIH technique. RESULTS: Between 2000 and 2020, 23 pediatric patients with refractory seizures underwent hemispherotomy (12 FHs, 11 modified PIHs). 91.3% of patients were seizure free at 6 months, 87% at 1 year, and 78.3% at last follow-up. None of the 23 patients presented Engel IV outcome. FH was found to have statistically longer surgical duration (5 ± 1.5 vs. 3.83 ± 0.5 h; p = <0.001). Neurocognition was improved in two thirds of the patients (66.9%). Our study also shows improvement of motor activity in the majority of the patients, regardless of the pathology and surgical technique. In the present report we modified the Cook et al. technique by implementing an amygdalohippocampectomy with resection of the tail of the hippocampus posteriorly and medially, to achieve temporo-occipital disconnection, instead of a complete temporal lobectomy. CONCLUSION: When patients are wisely selected, the hemispherectomy procedure should be considered as a most attractive and curative treatment for children with refractory seizures, not only giving the patient a high chance of seizure freedom but also providing an improvement in motor and cognitive skills. In our particular case and based on the present study, the modified PIH proves to be a highly effective technique. It not only has a shorter surgical time but also a very low complication rate.

Tumores del sistema nervioso central. Clasificación de la Organización Mundial de la Salud 2021. Hacia un cambio de paradigma / Tumors of the central nervous system. Classification of the World Health Organization 2021. Towards a paradigm shift

El estudio de los tumores del sistema nervioso central (SNC) resulta ser un tema de gran consideración y su conocimiento reviste una alta importancia en la práctica médica. Las clasificaciones de las neoplasias del SNC comenzaron a mediados del siglo XIX hasta que en 1979 la Organización Mundial de la Salud (OMS) publicó la primera edición de una sistemática útil con el objetivo de establecer un lenguaje común para todas las especialidades médicas. Al día de hoy, 5 ediciones actualizaron la taxonomía neoplásica. La quinta edición del año 2021 consolida el cambio de paradigma dado por los avances moleculares, si bien todavía la transición se encuentra en proceso entre la caracterización morfológica y la biológica molecular. En este artículo, se analizan las nuevas modificaciones incorporadas en las diferentes familias tumorales más frecuentes en pediatría haciendo hincapié en aquella información de utilidad para el médico pediatra en su práctica diaria y la consulta multidisciplinaria.

The study of central nervous system (CNS) tumors is a subject of great interest and such knowledge is of great importance in medical practice. The classifications of CNS neoplasms began in the mid-19 th century, until the World Health Organization (WHO) published, in 1979, the first edition of a useful systematic review for the purpose of establishing a common language for all medical specialties. To date, 5 updated editions of neoplastic taxonomy have been published.The fifth edition, from 2021, consolidates the paradigm shift brought about by molecular advances, although the transition between morphological and molecular biological characterization is still in progress. In this article, the new modifications introduced in the different most frequent families of tumors in pediatrics are analyzed, emphasizing useful information for pediatricians in their daily practice and multidisciplinary consultations.

Surgical Anatomy and Technique of Peri-Insular Hemispherotomy in Pediatric Epilepsy.

BACKGROUND AND OBJECTIVES: Hemispherotomy is a highly complex procedure that demands a steep learning curve. An incomplete brain disconnection often results in failure of seizure control. The purpose of this article was to present a step-by-step guide to the surgical anatomy of this procedure. It is composed of a 7-stage approach, enhancing access to and improving visualization of deep structures. METHODS: A retrospective analysis of 39 pediatric patients with refractory epilepsy who underwent this technique was conducted. Engel scores were assessed 1 year postsurgery. Cadaveric dissections were performed to illustrate the procedure. RESULTS: Between 2015 and 2022, 39 patients were surgically treated using the peri-insular technique. The technique involved 7 stages: patient positioning, operative approach, opercular resection, transventricular callosotomy, fronto-orbital disconnection, anterior temporal disconnection, and posterior temporal disconnection. Most of the patients (92.30%) were seizure-free (Engel class I) at 1 year postoperative, 5.13% were nearly seizure-free (Engel II), and 2.56% showed significant improvement (Engel III). Complications occurred in 8% of cases, including 1 infection, 2 cases of aseptic meningitis, and 1 non-shunt-requiring acute hydrocephalus. CONCLUSION: The peri-insular hemispherotomy technique offers excellent seizure control with a low complication rate. Our visual documentation of surgical anatomy, complemented by detailed descriptions of surgical nuances, significantly contributes to a comprehensive understanding of this technique.

Tumors of the central nervous system. Classification of the World Health Organization 2021. Towards a paradigm shift. / Tumores del sistema nervioso central. Clasificación de la Organización Mundial de la Salud 2021. Hacia un cambio de paradigma.

The study of central nervous system (CNS) tumors is a subject of great interest and such knowledge is of great importance in medical practice. The classifications of CNS neoplasms began in the mid-19th century, until the World Health Organization (WHO) published, in 1979, the first edition of a useful systematic review for the purpose of establishing a common language for all medical specialties. To date, 5 updated editions of neoplastic taxonomy have been published. The fifth edition, from 2021, consolidates the paradigm shift brought about by molecular advances, although the transition between morphological and molecular biological characterization is still in progress. In this article, the new modifications introduced in the different most frequent families of tumors in pediatrics are analyzed, emphasizing useful information for pediatricians in their daily practice and multidisciplinary consultations.

El estudio de los tumores del sistema nervioso central (SNC) resulta ser un tema de gran consideración y su conocimiento reviste una alta importancia en la práctica médica. Las clasificaciones de las neoplasias del SNC comenzaron a mediados del siglo XIX hasta que en 1979 la Organización Mundial de la Salud (OMS) publicó la primera edición de una sistemática útil con el objetivo de establecer un lenguaje común para todas las especialidades médicas. Al día de hoy, 5 ediciones actualizaron la taxonomía neoplásica. La quinta edición del año 2021 consolida el cambio de paradigma dado por los avances moleculares, si bien todavía la transición se encuentra en proceso entre la caracterización morfológica y la biológica molecular. En este artículo, se analizan las nuevas modificaciones incorporadas en las diferentes familias tumorales más frecuentes en pediatría haciendo hincapié en aquella información de utilidad para el médico pediatra en su práctica diaria y la consulta multidisciplinaria.

Bio-based polyester-polyurethane foams: synthesis and degradability by Aspergillus niger and Aspergillus clavatus.

In this article, the degradability by Aspergillus niger and Aspergillus clavatus of three bio-based polyurethane (PU) foams is compared to previous degradability studies involving a Pseudomonas sp. bacterium and similar initial materials (Spontón et al. in Int. Biodet. Biodeg. 85:85-94, 2013, https://doi.org/10.1016/j.ibiod.2013.05.019 ). First, three new polyester-polyurethane foams were prepared from mixtures of castor oil (CO), maleated castor oil (MACO), toluene diisocyanate (TDI), and water. Then, their degradation tests were carried out in an aqueous medium, and employing the two mentioned fungi, after their isolation from the environment. From the degradation tests, the following was observed: (a) the insoluble (and slightly collapsed) foams exhibited free hydroxyl, carboxyl, and amine moieties; and (b) the water soluble (and low molar mass) compounds contained amines, carboxylic acids, and glycerol. The most degraded foam contained the highest amount of MACO, and therefore the highest concentration of hydrolytic bonds. A basic biodegradation mechanism was proposed that involves hydrolysis and oxidation reactions.

Ecophysiological mechanisms and growth of Inga vera Willd. under different water and light availability.

Light and water availability can impact plant survival and growth, making ecophysiological studies crucial for understanding their tolerance and to single and combined stresses. The aimed of this study was to investigate the physiological and growth responses of Inga vera Willd. plants induced by different water regimes and light intensities. Three water regimes were implemented based on substrate water retention capacity (WRC) - 50%, 75%, and 100%, along with shading levels (SH) - 0% (full sun), 30%, and 70%. Evaluations were conducted at 25 and 50 days after applying the water regimes, and during a recovery period of 30 days when all treatments were maintained at 75% of WRC. Photochemical efficiency, gas exchange, chlorophylls indices, growth, quality of the seedlings and content proline amino acid were assessed. Overall, I. vera plants showed greater sensitivity to increased exposure to light than to low water availability. The interaction of SH + WRC was beneficial for the gas exchange and chlorophylls indices characteristics under SH 70% + WRC 75-100% at 25 and 50 days, with higher results, greater plant growth and higher proline contents for leaves and roots under SH 30% and 70% + WRC 50%, 75% and 100% at 25 and 50 days. There was no recovery effect for seedlings grown in full sun. The plants grown under shade during the recovery period maintained their values for most of the characteristics evaluated. SH 30% + WRC 75% contributed to an increase in photosynthetic metabolism and, as a result, to the quality of the seedlings.

PEGylation of Chrysin Improves Its Water Solubility while Preserving the In Vitro Biological Activity.

Chrysin is a natural flavonoid that despite having numerous biological properties, its therapeutic value is limited due to its very low solubility in aqueous media. In this work, chrysin was conjugated with methoxypolyethylene glycols (mPEGs) of different molecular weights (350, 500, 750, and 2000 g/mol), affording PEGylated chrysins with high yields and excellent purities. In all cases, an increase in the water solubility of the conjugates was observed, which was highest when 500 g/mol of mPEG was used in the PEGylation reaction. Furthermore, in aqueous solution, PEGylated chrysins formed aggregates of ellipsoid shape. Electrochemical studies showed that the redox properties were conserved after PEGylation. While in vitro antibacterial and antifungal studies probed that the intrinsic activity was conserved, in vitro antitumor activities against HepG2 (liver carcinoma cells) and PC3 (prostate cancer cell) showed that PEGylated chrysins retained the cytotoxic activity and the ability of induction of apoptosis for the evaluated human cancer cells.

Poly(allylamine)-tripolyphosphate Ionic Assemblies as Nanocarriers: Friend or Foe?

Designing effective drug nanocarriers that are easy to synthesize, robust, and nontoxic is a significant challenge in nanomedicine. Polyamine-multivalent molecule nanocomplexes are promising drug carriers due to their simple and all-aqueous manufacturing process. However, these systems can present issues of colloidal instability over time and cellular toxicity due to the cationic polymer. In this study, we finely modulate the formation parameters of poly(allylamine-tripolyphosphate) complexes to jointly optimize the robustness and safety. Polyallylamine was ionically assembled with tripolyphosphate anions to form liquid-like nanocomplexes with a size of around 200 nm and a zeta potential of -30 mV. We found that nanocomplexes exhibit tremendous long-term stability (9 months of storage) in colloidal dispersion and that they are suitable as protein-loading agents. Moreover, the formation of nanocomplexes induced by tripolyphosphate anions produces a switch-off in the toxicity of the system by altering the overall charge from positive to negative. In addition, we demonstrate that nanocomplexes can be internalized by bone-marrow-derived macrophage cells. Altogether, these nanocomplexes have attractive and promising properties as delivery nanoplatforms for potential therapies based on the immune system activation.

Phase Behavior and Electrochemical Properties of Highly Asymmetric Redox Coacervates.

This work reports the phase behavior and electrochemical properties of liquid coacervates made of ferricyanide and poly(ethylenimine). In contrast to the typical polyanion/polycation pairs used in liquid coacervates, the ferricyanide/poly(ethylenimine) system is highly asymmetric because poly(ethylenimine) has approximately 170 charges per molecule, while ferricyanide has only 3. Two types of phase diagrams were measured and fitted with a theoretical model. In the first type of diagram, the stability of the coacervate was studied in the plane given by the concentration of poly(ethylenimine) versus the concentration of ferricyanide for a fixed concentration of added monovalent salt (NaCl). The second type of diagram involved the plane given by the concentration of poly(ethylenimine) vs the concentration of the added monovalent salt for a fixed poly(ethyleneimine)/ferricyanide ratio. Interestingly, these phase diagrams displayed qualitative similarities to those of symmetric polyanion/polycation systems, suggesting that coacervates formed by a polyelectrolyte and a small multivalent ion can be treated as a specific case of polyelectrolyte coacervate. The characterization of the electrochemical properties of the coacervate revealed that the addition of monovalent salt greatly enhances charge transport, presumably by breaking ion pairs between ferricyanide and poly(ethylenimine). This finding highlights the significant influence of added salt on the transport properties of coacervates. This study provides the first comprehensive characterization of the phase behavior and transport properties of asymmetric coacervates and places these results within the broader context of the better-known symmetric polyelectrolyte coacervates.

Polyelectrolyte-multivalent molecule complexes: physicochemical properties and applications.

The complexation of polyelectrolytes with other oppositely charged structures gives rise to a great variety of functional materials with potential applications in a wide spectrum of technological fields. Depending on the assembly conditions, polyelectrolyte complexes can acquire different macroscopic configurations such as dense precipitates, nanosized colloids and liquid coacervates. In the past 50 years, much progress has been achieved to understand the principles behind the phase separation induced by the interaction of two oppositely charged polyelectrolytes in aqueous solutions, especially for symmetric systems (systems in which both polyions have similar molecular weight and concentration). However, in recent years, the complexation of polyelectrolytes with alternative building blocks such as small charged molecules (multivalent inorganic species, oligopeptides, and oligoamines, among others) has gained attention in different areas. In this review, we discuss the physicochemical characteristics of the complexes formed by polyelectrolytes and multivalent small molecules, putting a special emphasis on their similarities with the well-known polycation-polyanion complexes. In addition, we analyze the potential of these complexes to act as versatile functional platforms in various technological fields, such as biomedicine and advanced materials engineering.

Sociodemographic and clinical factors associated with poor COVID-19 outcomes in patients with rheumatic diseases: data from the SAR-COVID Registry.

BACKGROUND/OBJECTIVE: This study aims to describe the course and to identify poor prognostic factors of SARS-CoV-2 infection in patients with rheumatic diseases. METHODS: Patients ≥ 18 years of age, with a rheumatic disease, who had confirmed SARS-CoV-2 infection were consecutively included by major rheumatology centers from Argentina, in the national, observational SAR-COVID registry between August 13, 2020 and July 31, 2021. Hospitalization, oxygen requirement, and death were considered poor COVID-19 outcomes. RESULTS: A total of 1915 patients were included. The most frequent rheumatic diseases were rheumatoid arthritis (42%) and systemic lupus erythematosus (16%). Comorbidities were reported in half of them (48%). Symptoms were reported by 95% of the patients, 28% were hospitalized, 8% were admitted to the intensive care unit (ICU), and 4% died due to COVID-19. During hospitalization, 9% required non-invasive mechanical ventilation (NIMV) or high flow oxygen devices and 17% invasive mechanical ventilation (IMV). In multivariate analysis models, using poor COVID-19 outcomes as dependent variables, older age, male gender, higher disease activity, treatment with glucocorticoids or rituximab, and the presence of at least one comorbidity and a greater number of them were associated with worse prognosis. In addition, patients with public health insurance and Mestizos were more likely to require hospitalization. CONCLUSIONS: In addition to the known poor prognostic factors, in this cohort of patients with rheumatic diseases, high disease activity, and treatment with glucocorticoids and rituximab were associated with worse COVID-19 outcomes. Furthermore, patients with public health insurance and Mestizos were 44% and 39% more likely to be hospitalized, respectively. STUDY REGISTRATION: This study has been registered in ClinicalTrials.gov under the number NCT04568421. Key Points • High disease activity, and treatment with glucocorticoids and rituximab were associated with poor COVID-19 outcome in patients with rheumatic diseases. • Some socioeconomic factors related to social inequality, including non-Caucasian ethnicity and public health insurance, were associated with hospitalization due to COVID-19.

Infección por COVID-19 en pacientes oncológicos y asociación con el tratamiento recibido / COVID-19 infection in cancer patients and association with the antineoplastic treatment

Resumen La evidencia que relaciona la terapia oncológica con la incidencia por COVID-19 varía según el tipo de terapia administrada. La incidencia informada en pacientes que reciben tratamiento oncológico varía entre 1 y 4%. El objetivo del presente estudio fue determinar la incidencia por COVID-19 en pacientes oncológicos en tratamiento activo y evaluar si existe asociación con el esquema recibido. Se utilizó una cohorte retrospectiva que incluyó de forma consecutiva a los pacientes adultos que realizaron tratamiento ambulatorio desde marzo/2020 hasta abril/2021 en un Hospital Público de referencia. El evento principal fue el diagnóstico confirmado de COVID-19. La asociación con los tratamientos oncológicos fue evaluada mediante regresión logís tica multivariada ajustando por edad, sexo, localización del tumor, cobertura de salud y localidad de residencia. Se incluyeron 463 pacientes, mediana de edad 58 años (RIC = 47-66), 73.3% (n = 337) mujeres. La incidencia de COVID-19 fue 5.6% (n = 26) con una tasa de mortalidad del 12% (n = 3). El riesgo de infección fue mayor en los que estaban realizando tratamiento únicamente con anticuerpos monoclonales, 14.3% vs. 4.9% (OR-ajustado = 3.3, p = 0.03) y aquellos en tratamiento con inhibidores de puntos de control inmunológicos, 23.1% vs. 5.1% (OR-ajustado = 5.8, p = 0.03). La quimioterapia citotóxica, sola o en combinación con anticuerpos mo noclonales, no presentó mayor riesgo de infección. La edad, sexo, sitio tumoral, cobertura de salud y localidad de residencia no se asoció con la incidencia de COVID-19. En base a nuestros resultados, el tratamiento con anticuerpos monoclonales o inhibidores de puntos de control inmunológicos se asoció con mayor incidencia de infección por COVID-19.

Abstract Evidence linking anticancer therapy with the incidence of COVID-19 varies according to the type of therapy administered. The reported COVID-19 incidence in patients receiving antineoplastic treatment varies between 1 and 4%. The aim of this study was to determine the incidence of COVID-19 in cancer patients under active treatment and to assess whether there is an association with the received anticancer therapy. It was a retrospective cohort that consecutively included adult outpatients who underwent treatment in a referral center from March 2020 to April 2021. The primary endpoint was the confirmed diagnosis of COVID-19. The association with anticancer treatments was evaluated using multivariate logistic regression adjusting for age, sex, tumor site, health coverage status, and place of residence. The sample included 463 patients, the median age was 58 years (IQR = 47-66), 73.3% (n = 337) were women. The incidence of COVID-19 was 5.6% (n = 26) with a mortality rate of 12% (n = 3). The risk of infection was higher in patients undergoing treatment only with monoclonal antibod ies, 14.3% vs. 4.9% (adjusted OR = 3.3, p = 0.03) and those in treatment with immunotherapy, 23.1% vs. 5.1% (adjusted OR = 5.8, p = 0.03). Cytotoxic chemotherapy, alone or in combination with monoclonal antibodies, did not present an increased risk of infection. Age, sex, tumor site, health coverage, and place of residence did not show association with the incidence of COVID-19. Based on our results, treatment with monoclonal antibodies or immunotherapy was associated with a higher rate of COVID-19 infection while chemotherapy did not modify the incidence of COVID-19.

[COVID-19 infection in cancer patients and association with the antineoplastic treatment]. / Infección por COVID-19 en pacientes oncológicos y asociación con el tratamiento recibido.

Evidence linking anticancer therapy with the incidence of COVID-19 varies according to the type of therapy administered. The reported COVID-19 incidence in patients receiving antineoplastic treatment varies between 1 and 4%. The aim of this study was to determine the incidence of COVID-19 in cancer patients under active treatment and to assess whether there is an association with the received anticancer therapy. It was a retrospective cohort that consecutively included adult outpatients who underwent treatment in a referral center from March 2020 to April 2021. The primary endpoint was the confirmed diagnosis of COVID-19. The association with anticancer treatments was evaluated using multivariate logistic regression adjusting for age, sex, tumor site, health coverage status, and place of residence. The sample included 463 patients, the median age was 58 years (IQR = 47-66), 73.3% (n = 337) were women. The incidence of COVID-19 was 5.6% (n = 26) with a mortality rate of 12% (n = 3). The risk of infection was higher in patients undergoing treatment only with monoclonal antibodies, 14.3% vs. 4.9% (adjusted OR = 3.3, p = 0.03) and those in treatment with immunotherapy, 23.1% vs. 5.1% (adjusted OR = 5.8, p = 0.03). Cytotoxic chemotherapy, alone or in combination with monoclonal antibodies, did not present an increased risk of infection. Age, sex, tumor site, health coverage, and place of residence did not show association with the incidence of COVID-19. Based on our results, treatment with monoclonal antibodies or immunotherapy was associated with a higher rate of COVID-19 infection while chemotherapy did not modify the incidence of COVID-19.

La evidencia que relaciona la terapia oncológica con la incidencia por COVID-19 varía según el tipo de terapia administrada. La incidencia informada en pacientes que reciben tratamiento oncológico varía entre 1 y 4%. El objetivo del presente estudio fue determinar la incidencia por COVID-19 en pacientes oncológicos en tratamiento activo y evaluar si existe asociación con el esquema recibido. Se utilizó una cohorte retrospectiva que incluyó de forma consecutiva a los pacientes adultos que realizaron tratamiento ambulatorio desde marzo/2020 hasta abril/2021 en un Hospital Público de referencia. El evento principal fue el diagnóstico confirmado de COVID-19. La asociación con los tratamientos oncológicos fue evaluada mediante regresión logística multivariada ajustando por edad, sexo, localización del tumor, cobertura de salud y localidad de residencia. Se incluyeron 463 pacientes, mediana de edad 58 años (RIC = 47-66), 73.3% (n = 337) mujeres. La incidencia de COVID-19 fue 5.6% (n = 26) con una tasa de mortalidad del 12% (n = 3). El riesgo de infección fue mayor en los que estaban realizando tratamiento únicamente con anticuerpos monoclonales, 14.3% vs. 4.9% (ORajustado = 3.3, p = 0.03) y aquellos en tratamiento con inhibidores de puntos de control inmunológicos, 23.1% vs. 5.1% (OR-ajustado = 5.8, p = 0.03). La quimioterapia citotóxica, sola o en combinación con anticuerpos monoclonales, no presentó mayor riesgo de infección. La edad, sexo, sitio tumoral, cobertura de salud y localidad de residencia no se asoció con la incidencia de COVID-19. En base a nuestros resultados, el tratamiento con anticuerpos monoclonales o inhibidores de puntos de control inmunológicos se asoció con mayor incidencia de infección por COVID-19.

Protein synthesis modulation as a therapeutic approach for amyotrophic lateral sclerosis and frontotemporal dementia.

Protein synthesis is essential for cells to perform life metabolic processes. Pathological alterations of protein content can lead to particular diseases. Cells have an intrinsic array of mechanisms and pathways that are activated when protein misfolding, accumulation, aggregation or mislocalization occur. Some of them (like the unfolded protein response) represent complex interactions between endoplasmic reticulum sensors and elongation factors that tend to increase expression of chaperone proteins and/or repress translation in order to restore protein homeostasis (also known as proteostasis). This is even more important in neurons, as they are very susceptible to harmful effects associated with protein overload and proteostatic mechanisms are less effective with age. Several neurodegenerative pathologies such as Alzheimer's, Parkinson's, and Huntington's diseases, amyotrophic lateral sclerosis and frontotemporal dementia exhibit a particular molecular signature of distinct, unbalanced protein overload. In amyotrophic lateral sclerosis and frontotemporal dementia, the majority of cases present intracellular inclusions of ubiquitinated transactive response DNA-binding protein of 43 kDa (TDP-43). TDP-43 is an RNA binding protein that participates in RNA metabolism, among other functions. Dysregulation of TDP-43 (e.g. aggregation and mislocalization) can dramatically affect neurons, and this has been linked to disease development. Expression of amyotrophic lateral sclerosis/frontotemporal dementia TDP-43-related mutations in cellular and animal models has been shown to recapitulate key features of the amyotrophic lateral sclerosis/frontotemporal dementia disease spectrum. These variants can be causative of degeneration onset and progression. Most neurodegenerative diseases (including amyotrophic lateral sclerosis and frontotemporal dementia) have no cure at the moment; however, modulating translation has recently emerged as an attractive approach that can be performed at several steps (i.e. regulating activation of initiation and elongation factors, inhibiting unfolded protein response activation or inducing chaperone expression and activity). This review focuses on the features of protein imbalance in neurodegenerative disorders and the relevance of developing therapeutical compounds aiming at restoring proteostasis. We strive to highlight the importance of research on drugs that, not only restore protein imbalance without compromising translational activity of cells, but are also as safe as possible for the patients.

Seasonal dynamics of meroplankton in a sub-Antarctic fjord (Southern Patagonia, Chile).

Knowledge of seasonal dynamics and composition of meroplankton (larvae of benthic invertebrates) is rather limited for sub-Antarctic regions. We studied the seasonal dynamics of meroplankton in a sub-Antarctic proglacial basin (Gallegos Sound, Chile), by examining changes in the meroplankton community in relation to hydrographic variables along four sampling cruises between early winter 2010 and late winter 2011. The local meroplankton community was composed of 39 larval morphotypes distributed among 11 major taxa, being polychaetes the best represented (15 larvae morphotypes), and bivalve the most abundant. We found distinct seasonal differences in terms of meroplanktonic composition and abundance, with higher abundance and larval morphotype number during austral spring and late winter, and lower in summer and early winter. The pattern observed for meroplankton was directly related to seasonal variations of fluorescence of chlorophyll a and temperature. We found meroplankton abundances lower than those of other sub- and Polar environments. However, meroplanktonic temporal dynamics showed a common pattern for sub- and Polar fjords, suggesting a strong link between benthic spawning and the occurrence of phytoplankton blooms. Supplementary Information: The online version contains supplementary material available at 10.1007/s00300-021-02823-6.

Enhancing Hyperheuristics for the Knapsack Problem through Fuzzy Logic.

Hyperheuristics rise as powerful techniques that get good results in less computational time than exact methods like dynamic programming or branch and bound. These exact methods promise the global best solution, but with a high computational time. In this matter, hyperheuristics do not promise the global best solution, but they promise a good solution in a lot less computational time. On the contrary, fuzzy logic provides the tools to model complex problems in a more natural way. With this in mind, this paper proposes a fuzzy hyperheuristic approach, which is a combination of a fuzzy inference system with a selection hyperheuristic. The fuzzy system needs the optimization of its fuzzy rules due to the lack of expert knowledge; indeed, traditional hyperheuristics also need an optimization of their rules. The fuzzy rules are optimized by genetic algorithms, and for the rules of the traditional methods, we use particle swarm optimization. The genetic algorithm will also reduce the number of fuzzy rules, in order to find the best minimal fuzzy rules, whereas traditional methods already use very few rules. Experimental results show the advantage of using our approach instead of a traditional selection hyperheuristic in 3200 instances of the 0/1 knapsack problem.

Quantum relaxation in a system of harmonic oscillators with time-dependent coupling.

In the context of the de Broglie-Bohm pilot-wave theory, numerical simulations for simple systems have shown that states that are initially out of quantum equilibrium-thus violating the Born rule-usually relax over time to the expected |ψ|2 distribution on a coarse-grained level. We analyse the relaxation of non-equilibrium initial distributions for a system of coupled one-dimensional harmonic oscillators in which the coupling depends explicitly on time through numerical simulations, focusing on the influence of different parameters such as the number of modes, the coarse-graining length and the coupling constant. We show that in general the system studied here tends to equilibrium, but the relaxation can be retarded depending on the values of the parameters, particularly to the one related to the strength of the interaction. Possible implications on the detection of relic non-equilibrium systems are discussed.

Epidemiology of cutaneous and mucocutaneous leishmaniasis in Nicaragua.

Leishmaniasis is a major neglected tropical disease which contributes a huge economic burden on already meager economic resources. The World Health Organization (WHO) has estimated an annual incidence of 700,000--1,000,000 patients and about 20,000-30,000 deaths per year. Approximately 66,941 patients of cutaneous leishmaniasis are reported annually in the Americas. In recent years, Nicaragua has presented alarmingly high numbers of patients and elevated incidence rates. Unfortunately, there are no detailed spatial descriptions on the epidemiological situation of leishmaniasis in this country. The objective of this study is to present descriptive data about the epidemiology of leishmaniasis in Nicaragua in the context of the distribution of this neglected tropical disease (NTD) in the Americas. This paper also provides an epidemiological update on different forms of leishmaniasis found in the three administrative regions of Nicaragua and its municipalities. Health authorities from the Ministry of Health of Nicaragua (MINSA) provided the entomological and epidemiological information for the different forms of the disease from 2001 to 2018. Prevalence, incidence rates, clinical classification of disease, age groups, sex, and geographic distribution by municipality and department are described in this study. Approximately 90%-95% of the national patients corresponded to CL and 5-10% correspond to MCL. The disease is distributed in the three regions of the country, with a higher burden in the Departments of Jinotega, Matagalpa and Atlántico Norte. The municipalities with the highest proportion of patients were El Cuá (23.92%), Waslala (14.16), Santa Maria de Pantasma (9.62%), Rancho Grande (9.03%) and Siuna (7.67%). There is an expansion of spatial distribution of CL and MCL in the North Central and South Atlantic regions of the country. These results could inform interventional strategies to address the burden of leishmaniasis in Nicaragua, which would improve the likelihood of meeting the goals for the Leishmaniasis Plan of Action for the Americas.