Case report: two novel PPARG pathogenic variants associated with type 3 familial partial lipodystrophy in Brazil.

INTRODUCTION AND AIM: Type 3 Familial Partial Lipodystrophy (FPLD3) is a rare metabolic disease related to pathogenic PPARG gene variants. FPLD3 is characterized by a loss of fatty tissue in the upper and lower limbs, hips, and face. FPLD3 pathophysiology is usually associated with metabolic comorbidities such as type 2 diabetes, insulin resistance, hypertriglyceridemia, and liver dysfunction. Here, we clinically and molecularly characterized FPLD3 patients harboring novel PPARG pathogenic variants. MATERIALS AND METHODS: Lipodystrophy-suspected patients were recruited by clinicians from an Endocrinology Reference Center. Clinical evaluation was performed, biological samples were collected for biochemical analysis, and DNA sequencing was performed to define the pathogenic variants associated with the lipodystrophic phenotype found in our clinically diagnosed FPLD subjects. Bioinformatics predictions were conducted to characterize the novel mutated PPARγ proteins. RESULTS: We clinically described FPLD patients harboring two novel heterozygous PPARG variants in Brazil. Case 1 had the c.533T > C variant, which promotes the substitution of leucine to proline in position 178 (p.Leu178Pro), and cases 2 and 3 had the c.641 C > T variant, which results in the substitution of proline to leucine in the position 214 (p.Pro214Leu) at the PPARγ2 protein. These variants result in substantial conformational changes in the PPARγ2 protein. CONCLUSION: Two novel PPARG pathogenic variants related to FPLD3 were identified in a Brazilian FPLD cohort. These data will provide new epidemiologic data concerning FPLD3 and help understand the genotype-phenotype relationships related to the PPARG gene.

Hemophagocytic lymphohistiocytosis and macrophage activation syndrome: two rare sides of the same devastating coin.

Hemophagocytic lymphohistiocytosis (HLH) is a rare genetic hyperinflammatory syndrome that occurs early in life. Macrophage activation syndrome (MAS) usually refers to a secondary form of HLH associated with autoimmunity, although there are other causes of secondary HLH, such as infections and malignancy. In this article, we reviewed the concepts, epidemiology, clinical and laboratory features, diagnosis, differential diagnosis, prognosis, and treatment of HLH and MAS. We also reviewed the presence of MAS in the most common autoimmune diseases that affect children. Both are severe diseases that require prompt diagnosis and treatment to avoid morbidity and mortality.

Bridge: A New Algorithm for Rooting Orthologous Genes in Large-Scale Evolutionary Analyses.

Orthology information has been used for searching patterns in high-dimensional data, allowing transferring functional information between species. The key concept behind this strategy is that orthologous genes share ancestry to some extent. While reconstructing the history of a single gene is feasible with the existing computational resources, the reconstruction of entire biological systems remains challenging. In this study, we present Bridge, a new algorithm designed to infer the evolutionary root of orthologous genes in large-scale evolutionary analyses. The Bridge algorithm infers the evolutionary root of a given gene based on the distribution of its orthologs in a species tree. The Bridge algorithm is implemented in R and can be used either to assess genetic changes across the evolutionary history of orthologous groups or to infer the onset of specific traits in a biological system.

Hemophagocytic lymphohistiocytosis and macrophage activation syndrome: two rare sides of the same devastating coin

Abstract Hemophagocytic lymphohistiocytosis (HLH) is a rare genetic hyperinflammatory syndrome that occurs early in life. Macrophage activation syndrome (MAS) usually refers to a secondary form of HLH associated with autoimmunity, although there are other causes of secondary HLH, such as infections and malignancy. In this article, we reviewed the concepts, epidemiology, clinical and laboratory features, diagnosis, differential diagnosis, prognosis, and treatment of HLH and MAS. We also reviewed the presence of MAS in the most common autoimmune diseases that affect children. Both are severe diseases that require prompt diagnosis and treatment to avoid morbidity and mortality.

Sex differences in the biomechanical and biochemical responses of caudal rat intervertebral discs to injury.

Background: Intervertebral disc degeneration (IDD) is a major cause of low back pain (LBP) worldwide. Sexual dimorphism, or sex-based differences, appear to exist in the severity of LBP. However, it is unknown if there are sex-based differences in the inflammatory, biomechanical, biochemical, and histological responses of intervertebral discs (IVDs). Methods: Caudal (Coccygeal/Co) bone-disc-bone motion segments were isolated from multiple spinal levels (Co8 to Co14) of male and female Sprague-Dawley rats. Changes in motion segment biomechanics and extracellular matrix (ECM) biochemistry (glycosaminoglycan [GAG], collagen [COL], water, and DNA content) were evaluated at baseline and in response to chemical insult (lipopolysaccharide [LPS]) or puncture injury ex vivo. We also investigated the contributions of Toll-like receptor (TLR4) signaling on responses to LPS or puncture injury ex vivo, using a small molecule TLR4 inhibitor, TAK-242. Results: Findings indicate that IVD motion segments from female donors had greater nitric oxide (NO) release in LPS groups compared to male donors. HMGB1 release was increased in punctured discs, but not LPS injured discs, with no sex effect. Although both male and female discs exhibited reductions in dynamic moduli in response to LPS and puncture injuries, dynamic moduli from female donors were higher than male donors across all groups. In uninjured (baseline) samples, a significant sex effect was observed in nucleus pulposus (NP) DNA and water content. Female annulus fibrosus (AF) also had higher DNA, GAG, and COL content (normalized by dry weight), but lower water content than male AF. Additional injury- and sex-dependent effects were observed in AF GAG/DNA and COL/DNA content. Finally, TAK-242 improved the dynamic modulus of female but not male punctured discs. Conclusions: Our findings demonstrate that there are differences in rat IVD motion segments based on sex, and that the response to injury in inflammatory, biomechanical, biochemical, and histological outcomes also exhibit sex differences. TLR4 inhibition protected against loss of mechanical integrity of puncture-injured IVD motion segments, with differences responses based on donor sex.

Protein-Mediated Electroporation in a Cardiac Voltage-Sensing Domain Due to an nsPEF Stimulus.

This study takes a step in understanding the physiological implications of the nanosecond pulsed electric field (nsPEF) by integrating molecular dynamics simulations and machine learning techniques. nsPEF, a state-of-the-art technology, uses high-voltage electric field pulses with a nanosecond duration to modulate cellular activity. This investigation reveals a relatively new and underexplored phenomenon: protein-mediated electroporation. Our research focused on the voltage-sensing domain (VSD) of the NaV1.5 sodium cardiac channel in response to nsPEF stimulation. We scrutinized the VSD structures that form pores and thereby contribute to the physical chemistry that governs the defibrillation effect of nsPEF. To do so, we conducted a comprehensive analysis involving the clustering of 142 replicas simulated for 50 ns under nsPEF stimuli. We subsequently pinpointed the representative structures of each cluster and computed the free energy between them. We find that the selected VSD of NaV1.5 forms pores under nsPEF stimulation, but in a way that significant differs from the traditional VSD opening. This study not only extends our understanding of nsPEF and its interaction with protein channels but also adds a new effect to further study.

Spatially Coherent Tip-Enhanced Raman Spectroscopy Measurements of Electron-Phonon Interaction in a Graphene Device.

Coherence length (Lc) of the Raman scattering process in graphene as a function of Fermi energy is obtained with spatially coherent tip-enhanced Raman spectroscopy. Lc decreases when the Fermi energy is moved into the neutrality point, consistent with the concept of the Kohn anomaly within a ballistic transport regime. Since the Raman scattering involves electrons and phonons, the observed results can be rationalized either as due to unusually large variation of the longitudinal optical phonon group velocity vg, reaching twice the value for the longitudinal acoustic phonon, or due to changes in the electron energy uncertainty, both properties being important for optical and transport phenomena that might not be observable by any other technique.

Coaxial Placement of Balloon-Expandable and Self-Expanding Stents: Impact on Crush Resistance and Luminal Recovery in a Benchtop Model.

During endovascular interventions, coaxial deployment of stents may be required to preserve luminal gain. This study characterized in vitro the effect on crush resistance and postcompression recovery when 316L stainless steel balloon-expandable (BE) and laser-cut nitinol self-expanding (SE) venous stents were deployed coaxially. Various stent configurations were parallel-plate compressed from a fully expanded state to 50% diameter reduction (Criterion, Model 42; MTS, Eden Prairie, Minnesota) in a 37 °C ± 1 water bath. Coaxial deployments of SE stent inside BE stent and BE stent inside SE stent demonstrated higher crush resistances compared with each stent individually or their mathematical summation (analysis of variance P < .0001; pairwise comparison P < .01). The configuration of SE stent inside BE stent showed higher postcompression luminal recovery at 48.7% compared with that of BE stent inside SE stent at 27.5% (P = .0001). Coaxial deployment of SE stent inside BE stent may improve crush resistance and luminal recovery after compression in the appropriate clinical context.

Double-Barrel Nitinol Stent Placement for Iliocaval Reconstruction: The Effect of Deployment Sequence and Direction on Final Configuration.

Double-barrel stent placement across the iliocaval confluence is commonly used for the treatment of chronic bilateral iliocaval occlusion. The difference in the deployment outcomes of synchronous parallel stent deployment versus asynchronous or antiparallel deployment and the underlying stent interactions are poorly understood. In this study, 3 strategies of double-barrel nitinol self-expanding stent deployment across the iliocaval confluence (synchronous parallel, asynchronous parallel, and synchronous antiparallel) were contrasted in vivo in 3 swine followed by assessment of the explanted stent construct. Synchronous parallel stent deployment achieved a desired double-barrel configuration. The asynchronous parallel and antiparallel deployment strategies both resulted in a crushed stent despite subsequent simultaneous balloon angioplasty. These animal model results suggested that in patients who undergo double-barrel iliocaval reconstruction, synchronous parallel stent deployment may provide the desired stent conformation and increase the chance for clinical success.

DNA repair-related genes and adipogenesis: Lessons from congenital lipodystrophies.

Classical and progeroid congenital lipodystrophies are a collection of rare diseases displaying a large genetic heterogeneity. They occur due to pathogenic variants in genes associated with adipogenesis, DNA repair pathways, and genome stability. Subjects with lipodystrophy exhibit an impairment in the homeostasis of subcutaneous white adipose tissue (sWAT), resulting in low leptin and adiponectin levels, insulin resistance (IR), diabetes, dyslipidemia, ectopic fat deposition, inflammation, mitochondrial and endoplasmic reticulum commitments, among others. However, how pathogenic variants in adipogenesis-related genes modulate DNA repair in some classical congenital lipodystrophies has not been elucidated. In the same way, no data is clarifying how pathogenic variants in DNA repair genes result in sWAT loss in different types of progeroid lipodystrophies. This review will concentrate on the main molecular findings to understand the link between DNA damage/repair and adipogenesis in human and animal models of congenital lipodystrophies. We will focus on classical and progeroid congenital lipodystrophies directly or indirectly related to DNA repair pathways, highlighting the role of DNA repair-related proteins in maintaining sWAT homeostasis.

An Advanced Thermal Decomposition Method to Produce Magnetic Nanoparticles with Ultrahigh Heating Efficiency for Systemic Magnetic Hyperthermia.

Due to the limited heating efficiency of available magnetic nanoparticles, it is difficult to achieve therapeutic temperatures above 44 °C in relatively inaccessible tumors during magnetic hyperthermia following systemic administration of nanoparticles at clinical dosage (≤10 mg kg-1 ). To address this, a method for the preparation of magnetic nanoparticles with ultrahigh heating capacity in the presence of an alternating magnetic field (AMF) is presented. The low nitrogen flow rate of 10 mL min-1 during the thermal decomposition reaction results in cobalt-doped nanoparticles with a magnetite (Fe3 O4 ) core and a maghemite (γ-Fe2 O3 ) shell that exhibit the highest intrinsic loss power reported to date of 47.5 nH m2 kg-1 . The heating efficiency of these nanoparticles correlates positively with increasing shell thickness, which can be controlled by the flow rate of nitrogen. Intravenous injection of nanoparticles at a low dose of 4 mg kg-1 elevates intratumoral temperatures to 50 °C in mice-bearing subcutaneous and metastatic cancer grafts during exposure to AMF. This approach can also be applied to the synthesis of other metal-doped nanoparticles with core-shell structures. Consequently, this method can potentially be used for the development of novel nanoparticles with high heating performance, further advancing systemic magnetic hyperthermia for cancer treatment.

The Quality Index for Nutrition in Nursing Homes (QUINN). A new tool for evaluating diet quality in long-term care homes.

Introduction: Background: the assessment of diet quality (DQ) is fundamental to the study of disease-diet associations, and it is necesary to implement an easy to-apply tool in nursing homes (NHs). Our objective was to propose and apply a novel diet quality indicator (DQIn) using an a priori approach for NHs. Methods: the QUality Index for Nutrition in Nursing homes (QUINN) was implemented in a public NH located in Valladolid, Spain, during a 5-week period (n = 137 subjects). The choice of the QUINN components was based on a rapid review. The QUINN was based on 15 dietary components - 12 were basic (vegetables, fruits, legumes, olive oil, cereals, dairy, white fish and seafood, white-meat, eggs/positive; other fats, red and processed meat, and sweets/negative), and 3 were supplementary (fruits and vegetables variety, oily-fish, and whole-grains/positive). Each component was classified into 4-categories (0, 1, 2 o 3 points; range: 0-45 points). Results: the QUINN was tested on a menu offered by a NH giving a result of 34 points (good diet). The components with the highest scores were related to the Mediterranean diet (high consumption of legumes, olive oil, white fish and shellfish; low intake of other fats; and a wide variety of fruits and vegetables), together with cereals, white meat, dairy, and eggs. The components that required a major change were red- and processed-meats, sweets, and whole grains. Conclusion: the menu of this Spanish NH showed a good DQ according to the QUINN. The assessment of the DQ in NHs using QUINN will allow the proposal of interventions aimed at improving their diet.

Introducción: Antecedentes: la valoración de la calidad de la dieta es fundamental para el estudio de las asociaciones enfermedad-dieta, y es necesario implantar una herramienta de fácil aplicación en las residencias de ancianos. Nuestro objetivo fue proponer y aplicar un nuevo indicador de calidad de la dieta (diet quality indicator, DQIn) utilizando un enfoque a priori para su utilización en residencias de ancianos. Métodos: el Índice de Calidad Nutricional en Residencias de Ancianos (QUality Index for Nutrition in Nursing homes, QUINN) se aplicó en una residencia pública de Valladolid durante un periodo de 5 semanas (n = 137 sujetos). La elección de los componentes del QUINN se basó en una revisión rápida. En el QUINN se consideraron 15 componentes dietéticos, 12 básicos (verduras, frutas, legumbres, aceite de oliva, cereales, lácteos, pescado blanco y marisco, carnes blancas, huevos/positivos; otras grasas, carnes rojas y procesadas, y dulces/negativos) y 3 adicionales (variedad de frutas y verduras, pescado azul, y cereales integrales/positivos). Cada componente se clasificó en 4 categorías (0, 1, 2 o 3 puntos; rango: 0-45 puntos). Resultados: el QUINN se aplicó en el menú ofertado por una residencia de ancianos dando un resultado de 34 puntos (dieta de buena calidad). Los componentes con mayor puntuación estaban relacionados con la dieta mediterránea (alto consumo de legumbres, aceite de oliva, pescado blanco y marisco, bajo consumo de otras grasas y variedad de frutas y verduras), junto con los cereales, las carnes blancas, los lácteos y los huevos. Los componentes que requerían un cambio importante fueron las carnes rojas y procesadas, los dulces y los cereales integrales. Conclusión: el menú de esta residencia de ancianos situada en España mostró una calidad de la dieta buena según el QUINN. La evaluación de la calidad de la dieta en las residencias de ancianos mediante el QUINN permitirá proponer intervenciones para mejorar la dieta.

The Quality Index for Nutrition in Nursing Homes (QUINN). A new tool for evaluating diet quality in long-term care homes / El índice de calidad de la nutrición en las residencias de ancianos (QUINN). Una nueva herramienta para evaluar la calidad de la dieta en las residencias de ancianos

Antecedentes: la valoración de la calidad de la dieta es fundamental para el estudio de las asociaciones enfermedad-dieta, y es necesario implantar una herramienta de fácil aplicación en las residencias de ancianos. Nuestro objetivo fue proponer y aplicar un nuevo indicador de calidad de la dieta (diet QUALITY indicator, DQIn) utilizando un enfoque a priori para su utilización en residencias de ancianos. Métodos: el Índice de Calidad Nutricional en Residencias de Ancianos (QUALITY Index for NUTRITION in NURSING homes, QUINN) se aplicó en una residencia pública de Valladolid durante un periodo de 5 semanas (n = 137 sujetos). La elección de los componentes del QUINN se basó en una revisión rápida. En el QUINN se consideraron 15 componentes dietéticos, 12 básicos (verduras, frutas, legumbres, aceite de oliva, cereales, lácteos, pescado blanco y marisco, carnes blancas, huevos/positivos; otras grasas, carnes rojas y procesadas, y dulces/negativos) y 3 adicionales (variedad de frutas y verduras, pescado azul, y cereales integrales/positivos). Cada componente se clasificó en 4 categorías (0, 1, 2 o 3 puntos; rango: 0-45 puntos). Resultados: el QUINN se aplicó en el menú ofertado por una residencia de ancianos dando un resultado de 34 puntos (dieta de buena calidad). Los componentes con mayor puntuación estaban relacionados con la dieta mediterránea (alto consumo de legumbres, aceite de oliva, pescado blanco y marisco, bajo consumo de otras grasas y variedad de frutas y verduras), junto con los cereales, las carnes blancas, los lácteos y los huevos. Los componentes que requerían un cambio importante fueron las carnes rojas y procesadas, los dulces y los cereales integrales. Conclusión: el menú de esta residencia de ancianos situada en España mostró una calidad de la dieta buena según el QUINN. La evaluación de la calidad de la dieta en las residencias de ancianos mediante el QUINN permitirá proponer intervenciones para mejorar la dieta. (AU)

Background: the assessment of diet QUALITY (DQ) is fundamental to the study of disease-diet associations, and it is necesary to implement an easy to-apply tool in NURSING homes (NHs). Our objective was to propose and apply a novel diet QUALITY indicator (DQIn) using an a priori approach for NHs. Methods: the QUALITY Index for NUTRITION in NURSING homes (QUINN) was implemented in a public NH located in Valladolid, Spain, during a 5-week period (n = 137 subjects). The choice of the QUINN components was based on a rapid review. The QUINN was based on 15 dietary components — 12 were basic (vegetables, fruits, legumes, olive oil, cereals, dairy, white fish and seafood, white-meat, eggs/positive; other fats, red and processed meat, and sweets/negative), and 3 were supplementary (fruits and vegetables variety, oily-fish, and whole-grains/positive). Each component was classified into 4-categories (0, 1, 2 o 3 points; range: 0-45 points). Results: the QUINN was tested on a menu offered by a NH giving a result of 34 points (good diet). The components with the highest scores were related to the Mediterranean diet (high consumption of legumes, olive oil, white fish and shellfish; low intake of other fats; and a wide variety of fruits and vegetables), together with cereals, white meat, dairy, and eggs. The components that required a major change were red- and processed-meats, sweets, and whole grains. Conclusion: the menu of this Spanish NH showed a good DQ according to the QUINN. The assessment of the DQ in NHs using QUINN will allow the proposal of interventions aimed at improving their diet. (AU)

Proton Magnetic Resonance Spectroscopy in Post-Traumatic Stress Disorder-Updated Systematic Review and Meta-Analysis.

A stressor-related disorder wherein traumatic experience precipitates protracted disruptions to mood and cognition, post-traumatic stress disorder (PTSD) is associated with wide-ranging abnormalities across the body. While various methods have investigated these deviations, only proton magnetic resonance spectroscopy (1H MRS) enables noninvasive measurement of small-molecule metabolites in the living human. 1H MRS has correspondingly been employed to test hypotheses about the composition and function of multiple brain regions putatively involved in PTSD. Here we systematically review methodological considerations and reported findings, both positive and negative, of the current 1H-MRS literature in PTSD (N = 32 studies) to communicate the brain regional metabolite alterations heretofore observed, providing random-effects model meta-analyses for those most extensively studied. Our review suggests significant PTSD-associated decreases in N-acetyl aspartate in bilateral hippocampus and anterior cingulate cortex with less evident effect in other metabolites and regions. Model heterogeneities diverged widely by analysis (I2 < 0.01% to 90.1%) and suggested regional dependence on quantification reference (creatine or otherwise). While observed variabilities in methods and reported findings suggest that 1H-MRS explorations of PTSD could benefit from methodological standardization, informing this standardization by quantitative assessment of the existing literature is currently hampered by its small size and limited scope.

The Pivotal Role of NF-kB in the Pathogenesis and Therapeutics of Alzheimer's Disease.

Alzheimer's Disease (AD) is the most common neurodegenerative disease worldwide, with a high prevalence that is expected to double every 20 years. Besides the formation of Aß plaques and neurofibrillary tangles, neuroinflammation is one the major phenotypes that worsens AD progression. Indeed, the nuclear factor-κB (NF-κB) is a well-established inflammatory transcription factor that fuels neurodegeneration. Thus, in this review, we provide an overview of the NF-κB role in the pathogenesis of AD, including its interaction with various molecular factors in AD mice models, neurons, and glial cells. Some of these cell types and molecules include reactive microglia and astrocytes, ß-secretase, APOE, glutamate, miRNA, and tau protein, among others. Due to the multifactorial nature of AD development and the failure of many drugs designed to dampen AD progression, the pursuit of novel targets for AD therapeutics, including the NF-κB signaling pathway, is rising. Herein, we provide a synopsis of the drug development landscape for AD treatment, offering the perspective that NF-κB inhibitors may generate widespread interest in AD research in the future. Ultimately, the additional investigation of compounds and small molecules that target NF-κB signaling and the complete understanding of NF-κB mechanistic activation in different cell types will broaden and provide more therapeutic options for AD patients.

Nanosecond Pulsed Electric Field (nsPEF): Opening the Biotechnological Pandora's Box.

Nanosecond Pulsed Electric Field (nsPEF) is an electrostimulation technique first developed in 1995; nsPEF requires the delivery of a series of pulses of high electric fields in the order of nanoseconds into biological tissues or cells. They primary effects in cells is the formation of membrane nanopores and the activation of ionic channels, leading to an incremental increase in cytoplasmic Ca2+ concentration, which triggers a signaling cascade producing a variety of effects: from apoptosis up to cell differentiation and proliferation. Further, nsPEF may affect organelles, making nsPEF a unique tool to manipulate and study cells. This technique is exploited in a broad spectrum of applications, such as: sterilization in the food industry, seed germination, anti-parasitic effects, wound healing, increased immune response, activation of neurons and myocites, cell proliferation, cellular phenotype manipulation, modulation of gene expression, and as a novel cancer treatment. This review thoroughly explores both nsPEF's history and applications, with emphasis on the cellular effects from a biophysics perspective, highlighting the role of ionic channels as a mechanistic driver of the increase in cytoplasmic Ca2+ concentration.

Radiographic Imaging as a Quality Index Proxy for Brachiaria brizantha Seeds.

Efficient methodologies for automated seed quality evaluations are important for the seed industry. Advanced seed technology research requires the use of adequate methods to ensure good seed performance under adverse environmental conditions; thus, providing producers with detailed, quick, and accurate information on structural seed integrity and ensuring vigorous production. To address this problem, this study aimed to determine Brachiaria brizantha (Marandu cv., Piatã cv. and Xaraés cv.) seed quality through radiographic imaging analyses associated with vigor tests and anatomical characterizations. Brachiaria seed cultivars displaying different physical and physiological attributes were selected and subjected to the 1000-seed weight test, water content determinations, X-ray analyses, germination tests, and anatomical characterizations. The X-ray analyses made it possible to establish a relationship between the X-ray images and other determined variables. Furthermore, the X-ray images can indicate evidence of internal and external damage that could later compromise germination. The Marandu and Piatã cultivars presented the highest germination percentages, germination speed indices, normal seedling development, and cellular structure preservation compared to the Xaraés cultivar. To summarize, X-ray analyses are efficient methods used for the selection of higher physical quality cultivars and can aid in the decision-making processes of companies and seed producers worldwide.

Targeted Nanoparticles with High Heating Efficiency for the Treatment of Endometriosis with Systemically Delivered Magnetic Hyperthermia.

Endometriosis is a devastating disease in which endometrial-like tissue forms lesions outside the uterus. It causes infertility and severe pelvic pain in ≈176 million women worldwide, and there is currently no cure for this disease. Magnetic hyperthermia could potentially eliminate widespread endometriotic lesions but has not previously been considered for treatment because conventional magnetic nanoparticles have relatively low heating efficiency and can only provide ablation temperatures (>46 °C) following direct intralesional injection. This study is the first to describe nanoparticles that enable systemically delivered magnetic hyperthermia for endometriosis treatment. When subjected to an alternating magnetic field (AMF), these hexagonal iron-oxide nanoparticles exhibit extraordinary heating efficiency that is 6.4× greater than their spherical counterparts. Modifying nanoparticles with a peptide targeted to vascular endothelial growth factor receptor 2 (VEGFR-2) enhances their endometriosis specificity. Studies in mice bearing transplants of macaque endometriotic tissue reveal that, following intravenous injection at a low dose (3 mg per kg), these nanoparticles efficiently accumulate in endometriotic lesions, selectively elevate intralesional temperature above 50 °C upon exposure to external AMF, and completely eradicate them with a single treatment. These nanoparticles also demonstrate promising potential as magnetic resonance imaging (MRI) contrast agents for precise detection of endometriotic tissue before AMF application.

Descrição do seguimento farmacoterapêutico de pacientes com hanseníase em município hiperendêmico do estado de Mato Grosso / Pharmacotherapy follow-up of patients with leprosy in a hyperendemic city in the state of Mato Grosso

Introdução: A hanseníase é uma doença crônica, infectocontagiosa e considerada um problema de saúde pública no Brasil. O objetivo deste estudo foi descrever o seguimento farmacoterapêutico de pacientes com diagnóstico de hanseníase. Métodos: Estudo descritivo, com pacientes com hanseníase multibacilar do município de Rondonópolis, Mato Grosso. O seguimento farmacoterapêutico foi realizado a partir de uma versão adaptada do Método Dáder. Para análise de dados aplicou-se a estatística descritiva e o teste Qui-quadrado de Pearson.Resultados: Uma frequência de 95,6% dos participantes apresentou problemas relacionados aos medicamentos, 59,1% apresentaram 3 ou mais problemas, os mais frequentes foram administração errada do medicamento e interação medicamento/nutriente. A inefetividade não quantitativa foi o resultado negativo associado ao medicamento mais evidenciado. Os indivíduos acompanhados em um serviço especializado apresentaram menor número de problemas relacionados aos medicamentos quando comparados àqueles da Estratégia Saúde da Família (p = 0,027).Conclusão: A maioria dos pacientes acompanhados apresentou problemas relacionados ao uso de medicamentos. O método Dáder possibilitou realizar o seguimento farmacoterapêutico de indivíduos com hanseníase.

Introduction: Leprosy is a chronic, infectious, and contagious disease considered a public health problem in Brazil. The objective of this study was to describe the pharmacotherapy follow-up of patients diagnosed with leprosy. Methods: We conducted a descriptive study of patients with multibacillary leprosy in the city of Rondonópolis, state of Mato Grosso, Brazil. Pharmacotherapy follow-up was conducted based on an adapted version of the Dáder method. Data were analyzed using descriptive statistics and Pearson's chi-square test. Results: Drug-related problems (DRP) were reported in 95.6% of patients, among whom 59.1% had 3 or more problems DRPs. The most common DRPs were incorrect drug administration and drug-nutrient interaction. Nonquantitative ineffectiveness was the most common drug-related negative outcome. Patients monitored in a leprosy treatment center had fewer DRPs than those monitored by a Family Health Strategy team (p = 0.027). Conclusion: Most patients had DRPs. The Dáder method allowed pharmacotherapy follow-up of patients with leprosy.

Cost-analysis and cost-effectiveness of physical activity interventions in Brazilian primary health care: a randomised feasibility study.

Physical exercise programs have been carried out in primary health care in Brazil and have provided good results in terms of effectiveness, their economic contribution has not been investigated yet. The aim of the study is to verify the feasibility of brief counseling physical activity intervention and to compare its economic cost and cost-effectiveness with supervised physical exercise intervention in primary care. A multi-arm parallel feasibility trial, with equal randomization [1:1:1] was conducted in Basic Health Units in Brazil. 61 participants were randomized in Brief Counseling Intervention (BCI), Supervised Physical Exercise Intervention (SPEI) and Control Group (CG). Interventions lasted one year. The BCI is more economical than the SPEI, costing around 50% less in the economic comparisons (session cost, annual cost and cost per participant annually). At leisure time, the cost to move one person to the physically active category at 12 months is estimated in R$369.00 for BCI and R$426.21 for the SPEI. The Incremental Cost-effectiveness Ratio (ICER) is R$310.32. The BCI is feasible and more economic, however, the cost effective is not that different. Thus, it is strongly recommended that the two interventions be offered at primary care in Brazil.