Science at the Heart of Psychotherapy: A Review of Three Evidence-Based Treatments

Changes in the U.S. healthcare system over the past fewdecades have led to a transformation of the mental healthfield. The demand for accountability and the need for effective,cost-efficient treatments have spurred the movementtoward evidence-based practices. Today, a number of empiricallybased psychotherapies exist that have proven efficaciousin the treatment of a wide range of physical and psychologicaldisorders. Despite the strong evidence base for these treatments,their dissemination and implementation have beenslow. The intention of the present article is to summarize themajor characteristics of three types of psychotherapy (cognitivebehavioral therapy, acceptance and commitment therapy,and dialectical behavior therapy) that have received muchempirical support and have demonstrated applicability to awide range of both mental and medical problems. For eachtreatment, some background information is provided, alongwith the theoretical underpinnings of the treatment, a summaryof the current state of the evidence, and limitations andcriticisms in the literature

Host tropism determination by convergent evolution of immunological evasion in the Lyme disease system

Pathogens possess the ability to adapt and survive in some host species but not in others-an ecological trait known as host tropism. Transmitted through ticks and carried mainly by mammals and birds, the Lyme disease (LD) bacterium is a well-suited model to study such tropism. Three main causative agents of LD, Borrelia burgdorferi, B. afzelii, and B. garinii, vary in host ranges through mechanisms eluding characterization. By feeding ticks infected with different Borrelia species, utilizing feeding chambers and live mice and quail, we found species-level differences in bacterial transmission. These differences localize on the tick blood meal, and specifically complement, a defense in vertebrate blood, and a polymorphic bacterial protein, CspA, which inactivates complement by binding to a host complement inhibitor, Factor H (FH). CspA selectively confers bacterial transmission to vertebrates that produce FH capable of allele-specific recognition. CspA is the only member of the Pfam54 gene family to exhibit host-specific FH-binding. Phylogenetic analyses revealed convergent evolution as the driver of such uniqueness, and that FH-binding likely emerged during the last glacial maximum. Our results identify a determinant of host tropism in Lyme disease infection, thus defining an evolutionary mechanism that shapes host-pathogen associations

Host tropism determination by convergent evolution of immunological evasion in the Lyme disease system [preprint]

Microparasites selectively adapt in some hosts, known as host tropism. Transmitted through ticks and carried mainly by mammals and birds, the Lyme disease (LD) bacterium is a well-suited model to study such tropism. LD bacteria species vary in host ranges through mechanisms eluding characterization. By feeding ticks infected with different LD bacteria species, utilizing feeding chambers and live mice and quail, we found species-level differences of bacterial transmission. These differences localize on the tick blood meal, and complement, a defense in vertebrate blood, and a bacterial polymorphic protein, CspA, which inactivates complement by binding to a host complement inhibitor, FH. CspA selectively confers bacterial transmission to vertebrates that produce FH capable of allele-specific recognition. Phylogenetic analyses revealed convergent evolution as the driver of such findings, which likely emerged during the last glacial maximum. Our results identify LD bacterial determinants of host tropism, defining an evolutionary mechanism that shapes host-microparasite associations

Patient-reported symptom burden of Charcot-Marie-Tooth Disease Type 1A: findings from an observational digital lifestyle study

Objectives: This study aims to explore the impact of Charcot-Marie-Tooth disease type 1A (CMT1A) and its treatment on patients in European (France, Germany, Italy, Spain, and the United Kingdom) and US real-world practice. Methods: Adults with CMT1A (n = 937) were recruited to an ongoing observational study exploring the impact of CMT. Data were collected via CMT&Me, an app through which participants completed patient-reported outcome measures. Results: Symptoms ranked with highest importance were weakness in the extremities, difficulty in walking, and fatigue. Almost half of participants experienced a worsening of symptom severity since diagnosis. Anxiety and depression were each reported by over one-third of participants. Use of rehabilitative interventions, medications, and orthotics/walking aids was high. Conclusions: Patient-reported burden of CMT1A is high, influenced by difficulties in using limbs, fatigue, pain, and impaired quality of life. Burden severity appears to differ across the population, possibly driven by differences in rehabilitative and prescription-based interventions, and country-specific health care variability

Effect of processing on nutritional value of the mandim fish (Arius spixii)

Com o objetivo de avaliar o efeito do beneficiamento sobre o valor nutricional do peixe mandim (Arius spixii) comercializado em Maceió-AL, determinaram-se nas suas formas in natura e beneficiada (salgado-seco) a composição centesimal, valor calórico, cloretos, perfil de ácidos graxos e colesterol, sendo também analisada a ocorrência de óxidos de colesterol. Os resultados obtidos para o mandim in natura e beneficiado, respectivamente, de umidade (70,13% e 40,31%), proteínas (51,73% e 38,07%, base seca), carboidratos (4,67% e 2,24%, base seca), calorias (486 kcal/100g e 367 kcal/100g, base seca), ácidos graxos (poliinsaturados 14,54% e 15,49%, ômega-3 8,51% e 6,51%), colesterol (82,66 mg/100g e 61,30 mg/100g) e óxidos (7-cetocolesterol 8,31 µg/g e 17,90 µg/g), permitiram concluir que o beneficiamento favoreceu alterações significativas no valor nutricional do mandim.In an attempt to analyze how processing enhances the nutritional value of the mandim fish (Arius spixii) marketed in Maceió-AL, Brazil, the following nutritional components were determined in fresh and processed (salted-dried) fish: centesimal composition, calorie count, chloride, fatty acid and cholesterol profile. The presence of cholesterol oxides was also investigated. Respective results for fresh and processed mandim fish were: moisture (70.13% and 40.31%), proteins (51.73% and 38.07%, dried), carbohyrdrates (4.67% and 2.24%, dried), calories (486 kcal/100g and 367 kcal/100g, dried), fatty acids (polyunsaturared 14,54% and 15,49%, ômega-3 8,51% and 6,51%), cholesterol (82.66 mg/100g and 61.30 mg/100g) and oxides (7-ketocholesterol 8.31 µg/g and 17.90 µg/g). These figures clearly showed that processing led to significant change in the nutritional value of the mandim fish

Retinopatia Diabética: Prevenção e Tratamento: Um exame das medidas de prevenção, monitoramento e opções terapêuticas para pacientes com retinopatia diabética.

Diabetic retinopathy is a prevalent and debilitating eye complication associated with diabetes mellitus. This review article addresses prevention measures, monitoring, and therapeutic options for patients with diabetic retinopathy, emphasizing its clinical importance and impact on patients' quality of life. In prevention, strict glycemic control and blood pressure management play central roles in reducing the risk and progression of diabetic retinopathy. Patient education is also crucial in promoting healthy habits. Regular retinal monitoring through fundus photography, optical coherence tomography (OCT), and OCTA angiography enables early detection of retinal changes, allowing for timely interventions. In the field of therapeutic options, intravitreal injections of anti-angiogenics, such as ranibizumab and bevacizumab, have revolutionized the treatment of diabetic macular edema (DME) and improved patients' vision. Therapies based on vascular growth factors, such as aflibercept, offer promising therapeutic alternatives. Managing diabetic retinopathy requires multidisciplinary approaches involving ophthalmologists, endocrinologists, and health educators. Personalizing treatment based on the disease stage and the individual patient's response is essential. Ongoing advances in clinical and technological research offer hope for better control and treatment of diabetic retinopathy, with the goal of preserving vision and enhancing patients' quality of life.A retinopatia diabética é uma complicação ocular prevalente e debilitante associada ao diabetes mellitus. Este artigo de revisão aborda medidas de prevenção, monitoramento e opções terapêuticas para pacientes com retinopatia diabética, enfatizando sua importância clínica e impacto na qualidade de vida dos pacientes. Na prevenção, o controle glicêmico estrito e o manejo da pressão arterial desempenham papéis centrais na redução do risco e progressão da retinopatia diabética. A educação do paciente também é crucial para promover hábitos saudáveis. O monitoramento regular da retina por meio de fotografia do fundo do olho, tomografia de coerência óptica (OCT) e angiografia por OCTA possibilita a detecção precoce de alterações retinianas, permitindo intervenções oportunas. No campo das opções terapêuticas, as injeções intravítreas de antiangiogênicos, como ranibizumabe e bevacizumabe, têm revolucionado o tratamento do edema macular diabético (EMD) e melhorado a visão dos pacientes. Terapias baseadas em fatores de crescimento vascular, como aflibercept, oferecem promissoras alternativas terapêuticas. A gestão da retinopatia diabética requer abordagens multidisciplinares, envolvendo oftalmologistas, endocrinologistas e educadores de saúde. A personalização do tratamento com base no estágio da doença e resposta individual do paciente é essencial. Avanços contínuos na pesquisa clínica e tecnológica oferecem esperança para um melhor controle e tratamento da retinopatia diabética, com o objetivo de preservar a visão e melhorar a qualidade de vida dos pacientes

Long non-coding RNAs: spatial amplifiers that control nuclear structure and gene expression

Over the past decade, it has become clear that mammalian genomes encode thousands of long non-coding RNAs (lncRNAs), many of which are now implicated in diverse biological processes. Recent work studying the molecular mechanisms of several key examples — including Xist, which orchestrates X chromosome inactivation — has provided new insights into how lncRNAs can control cellular functions by acting in the nucleus. Here we discuss emerging mechanistic insights into how lncRNAs can regulate gene expression by coordinating regulatory proteins, localizing to target loci and shaping three-dimensional (3D) nuclear organization. We explore these principles to highlight biological challenges in gene regulation, in which lncRNAs are well-suited to perform roles that cannot be carried out by DNA elements or protein regulators alone, such as acting as spatial amplifiers of regulatory signals in the nucleus

Phenotypic spectrum and transcriptomic profile associated with germline variants in TRAF7

PURPOSE: Somatic variants in tumor necrosis factor receptor-associated factor 7 (TRAF7) cause meningioma, while germline variants have recently been identified in seven patients with developmental delay and cardiac, facial, and digital anomalies. We aimed to define the clinical and mutational spectrum associated with TRAF7 germline variants in a large series of patients, and to determine the molecular effects of the variants through transcriptomic analysis of patient fibroblasts. METHODS: We performed exome, targeted capture, and Sanger sequencing of patients with undiagnosed developmental disorders, in multiple independent diagnostic or research centers. Phenotypic and mutational comparisons were facilitated through data exchange platforms. Whole-transcriptome sequencing was performed on RNA from patient- and control-derived fibroblasts. RESULTS: We identified heterozygous missense variants in TRAF7 as the cause of a developmental delay-malformation syndrome in 45 patients. Major features include a recognizable facial gestalt (characterized in particular by blepharophimosis), short neck, pectus carinatum, digital deviations, and patent ductus arteriosus. Almost all variants occur in the WD40 repeats and most are recurrent. Several differentially expressed genes were identified in patient fibroblasts. CONCLUSION: We provide the first large-scale analysis of the clinical and mutational spectrum associated with the TRAF7 developmental syndrome, and we shed light on its molecular etiology through transcriptome studies

Evolutionary diversity and developmental regulation of X-chromosome inactivation

X-chromosome inactivation (XCI) results in the transcriptional silencing of one X-chromosome in females to attain gene dosage parity between XX female and XY male mammals. Mammals appear to have developed rather diverse strategies to initiate XCI in early development. In placental mammals XCI depends on the regulatory noncoding RNA X-inactive specific transcript (Xist), which is absent in marsupials and monotremes. Surprisingly, even placental mammals show differences in the initiation of XCI in terms of Xist regulation and the timing to acquire dosage compensation. Despite this, all placental mammals achieve chromosome-wide gene silencing at some point in development, and this is maintained by epigenetic marks such as chromatin modifications and DNA methylation. In this review, we will summarise recent findings concerning the events that occur downstream of Xist RNA coating of the inactive X-chromosome (Xi) to ensure its heterochromatinization and the maintenance of the inactive state in the mouse and highlight similarities and differences between mammals