12-month follow-up of intensive outpatient treatment for PTSD combining prolonged exposure therapy, EMDR and physical activity.

BACKGROUND: Preliminary evidence shows promising treatment outcomes at short-term follow-up for intensive posttraumatic stress disorder (PTSD) treatment, but long-term follow-up studies are sparse. This study is a sequel to a previous pilot study and open trial, set out to investigate treatment outcomes at 12-month follow-up for outpatients completing an 8-day intensive treatment for PTSD. METHODS: All patients were diagnosed with PTSD and had multiple previous psychotherapy attempts (M = 3.1). Patients were assessed at pre-treatment, post-treatment, 3- and 12-month follow-up. Of 35 treated patients, 32 (91.4%) attended the long-term follow-up assessment. The treatment programme combined prolonged exposure therapy, eye movement desensitization and reprocessing, and physical activity. RESULTS: The effect sizes indicated large reductions in symptoms of PTSD, depression, anxiety, interpersonal problems, and well-being. Changes in functioning showed a small-medium effect. Results were stable across the follow-up period. The treatment response rates showed that 46-60% of patients achieved recovery with respect to PTSD symptoms, and that 44-48% no longer met diagnostic criteria for PTSD. CONCLUSIONS: Time-limited and concentrated outpatient treatment for PTSD can yield large and enduring positive outcomes. Controlled trials are needed to establish relative efficacy. TRIAL REGISTRATION: The study was registered in Current Research Information System In Norway (Cristin). Cristin-project-ID: 654,790. Date of registration: 18.03.2019.

Ginkgo biloba L. exocarp petroleum ether extract inhibits methicillin-resistant Staphylococcus aureus by modulating ion transport, virulence, and biofilm formation in vitro and in vivo.

ETHNOPHARMACOLOGICAL RELEVANCE: As reported in the Ancient Chinese Medicinal Books, Ginkgo biloba L. fruit has been used as a traditional Chinese medicine for the treatment asthma and cough or as a disinfectant. Our previous study demonstrated that G. biloba exocarp extract (GBEE), an extract of a traditional Chinese herb, inhibits the formation of methicillin-resistant Staphylococcus aureus (MRSA) biofilms. However, GBEE is a crude extract that contains many components, and the underlying mechanisms of purified GBEE fractions extracted with solvents of different polarities are unknown. AIM OF THE STUDY: This study aimed to investigate the different components in GBEE fractions extracted with solvents of different polarities and their antibacterial effects and mechanisms against MRSA and Staphylococcus haemolyticus biofilms both in vitro and in vivo. METHODS: The components in different fractions were detected by high-performance liquid chromatography-high resolution mass spectrometry (HPLC-HRMS). Microbroth dilution assays and time growth curves were used to determine the antibacterial effects of the fractions on 15 clinical bacterial isolates. Crystal violet staining, scanning electron microscopy (SEM) and transmission electron microscopy (TEM) were utilized to identify the fractions that affected bacterial biofilm formation. The potential MRSA targets of the GBEE fraction obtained with petroleum ether (PE), denoted GBEE-PE, were screened by transcriptome sequencing, and the gene expression profile was verified by quantitative polymerase chain reaction (qPCR). RESULTS: HPLC-HRMS analysis revealed that the four GBEE fractions (extracted with petroleum ether, ethyl acetate, n-butanol, and water) contained different ginkgo components, and the antibacterial effects decreased as the polarity of the extraction solvent increased. The antibacterial activity of GBEE-PE was greater than that of the GBEE fraction extracted with ethyl acetate (EA). GBEE-PE improved H. illucens survival and reduced MRSA colonization in model mouse organs. Crystal violet staining and SEM and TEM analyses revealed that GBEE-PE inhibited MRSA and S. haemolyticus biofilm formation. Transcriptional analysis revealed that GBEE-PE inhibits MRSA biofilms by altering ion transport, cell wall metabolism and virulence-related gene expression. In addition, the LO2 cell viability and H. illucens toxicity assay data showed that GBEE-PE at 20 mg/kg was nontoxic. CONCLUSION: The GBEE fractions contained different components, and their antibacterial effects decreased with increases in the polarity of the extraction solvent. GBEE-PE limited MRSA growth and biofilm formation by affecting ion transport, cell wall synthesis, and virulence-related pathways. This research provides a more detailed overview of the mechanism by which GBEE-PE inhibits MRSA both in vitro and in vivo and suggests that GBEE-PE is a new prospective antimicrobial with the potential to be used in MRSA therapeutics in the future.

Effects of Five Coumarins and Standardized Extracts from Tagetes lucida Cav. on Motor Impairment and Neuroinflammation Induced with Cuprizone.

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) with no curative treatment, and the available therapies aim to modify the course of the disease. It has been demonstrated that extracts of Tagetes lucida have immunomodulatory and neuroprotective effects. This work induced motor damage and neuroinflammation in male BALB/c mice by oral administration of cuprizone (CPZ) (40 mg/kg) for five weeks. In addition, the extracts and coumarins of Tagetes lucida (25 mg/kg) were used to control these damage variables; during the experiment, animals were subject to behavioral tests, and at the end of 5 weeks, mice from each group were used to measure the integrity of biological barriers (brain, kidneys, and spleen) through the extravasation test with blue Evans dye. In another group of animals, the ELISA method measured the brain concentrations of IL-1ß, IL-4, IL-10, and TNF-α. The results presented here allow us to conclude that the extracts and coumarins IC, HN, PE, DF, and SC of Tagetes lucida exert a neuroprotective effect by controlling the motor damage and neuroinflammation by increasing the expression of IL-4 and IL-10 and decreasing IL-1ß and TNF-α; notably, these treatments also protect organs from vascular permeability increase, mainly the BBB, in mice with CPZ-induced experimental encephalomyelitis (VEH * p < 0.05). However, more studies must be carried out to elucidate the molecular mechanisms of the pharmacological effects of this Mexican medicinal plant.

Schisandra lignans ameliorate nonalcoholic steatohepatitis by regulating aberrant metabolism of phosphatidylethanolamines.

Nonalcoholic steatohepatitis (NASH) is a spectrum of chronic liver disease characterized by hepatic lipid metabolism disorder. Recent reports emphasized the contribution of triglyceride and diglyceride accumulation to NASH, while the other lipids associated with the NASH pathogenesis remained unexplored. The specific purpose of our study was to explore a novel pathogenesis and treatment strategy of NASH via profiling the metabolic characteristics of lipids. Herein, multi-omics techniques based on LC-Q-TOF/MS, LC-MS/MS and MS imaging were developed and used to screen the action targets related to NASH progress and treatment. A methionine and choline deficient (MCD) diet-induced mouse model of NASH was then constructed, and Schisandra lignans extract (SLE) was applied to alleviate hepatic damage by regulating the lipid metabolism-related enzymes CES2A and CYP4A14. Hepatic lipidomics indicated that MCD-diet led to aberrant accumulation of phosphatidylethanolamines (PEs), and SLE could significantly reduce the accumulation of intrahepatic PEs. Notably, exogenous PE (18:0/18:1) was proved to significantly aggravate the mitochondrial damage and hepatocyte apoptosis. Supplementing PE (18:0/18:1) also deteriorated the NASH progress by up regulating intrahepatic proinflammatory and fibrotic factors, while PE synthase inhibitor exerted a prominent hepatoprotective role. The current work provides new insights into the relationship between PE metabolism and the pathogenesis of NASH.

Acupuncture for premature ejaculation: a systematic review and meta-analysis.

Background: Although acupuncture is widely used to treat premature ejaculation (PE), its effectiveness remains highly controversial. Aim: To evaluate the efficacy and safety of acupuncture on PE. Methods: According to the relevant keywords, 11 major English and Chinese databases were searched for randomized controlled trials (RCTs) of acupuncture alone or in combination with other treatments for PE. The quality of evidence across studies was assessed by the GRADEpro tool. Outcomes: Study outcome measures included the intravaginal ejaculation latency time (IELT), the Premature Ejaculation Diagnostic Tool (PEDT), the Chinese Index of Premature Ejaculation-5 (CIPE-5), treatment success rate, and adverse events. Results: Seven trials were included in this review for a total of 603 participants. A low quality of evidence suggests that it is not possible to determine whether acupuncture, as compared with a selective serotonin reuptake inhibitor, has an advantage in improving the IELT (standardized mean difference [SMD], -1.75; 95% CI, -6.12 to 2.63; P = .43, I2 = 98%), PEDT scores (SMD, 0.32; 95% CI, -0.68 to 1.32; P = .53, I2 = 85%), and treatment success rate (risk ratio, 0.69; 95% CI, 0.41-1.14; P = .15). However, participants receiving acupuncture had a lower CIPE-5 (SMD, -1.06; 95% CI, -1.68 to -0.44; P < .01). As compared with sham acupuncture, acupuncture significantly improved the IELT (SMD, 1.47; 95% CI, 1.01-1.92; P < .01, I2 = 0%) and PEDT scores (SMD, -1.23; 95% CI, -1.78 to -0.67; P < .01, I2 = 37%). When compared with other treatments alone, a combined treatment with acupuncture can significantly improve the IELT (SMD, 7.06; 95% CI, 2.53-11.59; P < .01, I2 = 97%), CIPE-5 (SMD, 0.84; 95% CI, 0.45-1.22; P < .01, I2 = 0%), and treatment success rate (SMD, 1.60; 95% CI, 1.18-2.16; P < .01, I2 = 53). Clinical Implications: The results suggest a significant effect of acupuncture in the treatment of certain important indicators of PE; however, this finding needs to be treated with caution because of the quality of the RCTs included. Strengths and Limitations: Comprehensive inclusion of available RCTs has been performed. However, limitations include a low number of studies and a lack of detailed information to allow subgroup analysis. Conclusion: The present systematic review and meta-analysis show that acupuncture has a significant effect on several subjective PE parameters, such as improving the feeling of control over ejaculation and distress, particularly when used in an integrated way. However, due to the low quality of evidence, acupuncture still needs larger well-designed RCTs to be confirmed.

Biochemical and transcriptomic responses of buckwheat to polyethylene microplastics.

The ubiquity of microplastic is widely recognized as pollution. Microplastic can affect the growth performances of plants. Buckwheat is a potential model crop to investigate plant responses to hazardous materials. Still, little is known about the response of buckwheat to microplastics. Thus, this study investigated the effect and uptake of polyethylene (PE) in buckwheat plant growth by monitoring the morphological and photosynthetic merits, antioxidant systems and transcriptome analysis of gene expression. Results confirmed that the impacts of PE on buckwheat growth were dose-dependent, while the highest concentration (80 mg/L) exposure elicited significantly negative responses of buckwheat. PE can invade buckwheat roots and locate in the vascular tissues. PE exposure disturbed the processes of carbon fixation and the synthesis of ATP from ADP + Pi in buckwheat leaves. The promotion of photosynthesis under PE exposure could generate extra energy for buckwheat leaves to activate antioxidant systems by increasing the antioxidant enzyme activities at an expense of morphological merits under microplastic stresses. Further in-depth study is warranted about figuring out the interactions between microplastics and biochemical responses (i.e., photosynthesis and antioxidant systems), which have great implications for deciphering the defense mechanism of buckwheat to microplastic stresses.

Quantification of Xylanolytic and Cellulolytic Activities of Fungal Strains Isolated from Palmaria palmata to Enhance R-Phycoerythrin Extraction of Palmaria palmata: From Seaweed to Seaweed.

R-phycoerythrin (R-PE) can be enzymatically extracted from red seaweeds such as Palmaria palmata. This pigment has numerous applications and is notably known as an antioxidant, antitumoral or anti-inflammatory agent. Enzymes secreted by P. palmata associated fungal strains were assumed to be efficient and adapted for R-PE extraction from this macroalga. The aim of the present study was to quantify both xylanolytic and cellulolytic activities of enzymatic extracts obtained from six Palmaria palmata derived fungal strains. Degradation of P. palmata biomass by fungal enzymatic extracts was also investigated, focused on soluble protein and R-PE extraction. Enzymatic extracts were obtained by solid state fermentation. Macroalgal degradation abilities were evaluated by measuring reducing sugar release using DNS assays. Soluble proteins and R-PE recovery yields were evaluated through bicinchoninic acid and spectrophotometric assays, respectively. Various enzymatic activities were obtained according to fungal isolates up to 978 U/mL for xylanase and 50 U/mL for cellulase. Enzymatic extract allowed high degrading abilities, with four of the six fungal strains assessed exhibiting at least equal results as the commercial enzymes for the reducing sugar release. Similarly, all six strains allowed the same soluble protein extraction yield and four of them led to an improvement of R-PE extraction. R-PE extraction from P. palamata using marine fungal enzymes appeared particularly promising. To the best of our knowledge, this study is the first on the use of enzymes of P. palmata associated fungi in the degradation of its own biomass for biomolecules recovery.

Dose-Effect Determination of a Neuroprotector Fraction Standardized in Coumarins of Tagetes lucida and Bioavailability.

Neurodegeneration has been associated with chronic inflammation states in the brain. For this reason, attention has been directed to drugs indicated as anti-inflammatory as possible therapies for the treatment of said conditions. Tagetes lucida has been widely used as a folk remedy in illnesses associated with the central nervous system and inflammatory ailments. Among the compounds that stand out in the plant against these conditions are coumarins, such as 7-O-prenyl scopoletin, scoparone, dimethylfraxetin, herniarin, and 7-O-prenylumbelliferone. Therefore, the relationship between the therapeutic effect and the concentration was evaluated through pharmacokinetic and pharmacodynamic studies, including vascular permeability evaluation by blue Evans and pro- and anti-inflammatory cytokines quantification, under a neuroinflammation model induced by lipopolysaccharide by the oral administration of three different doses (5, 10, and 20 mg/kg) of a bioactive fraction of T. lucida. In the present study, it was found that all doses showed a neuroprotective and immunomodulatory effect, although the doses of 10 and 20 mg/kg were able to exert their effect for a longer time and to a greater extent. The protective effects of the fraction may be mainly associated with the DR, HR, and SC coumarins due to their structural profile and plasmatic and brain tissue bioavailability.

Clinical Efficacy of Longbeisan Application at Shenque （CV 8） Combined with Oral Administration of Chinese Medicine in Treatment of Premature Ejaculation / 中国实验方剂学杂志

ObjectiveTo investigate the clinical value of Longbeisan application at Shenque （CV 8） combined with oral administration of Chinese medicine in the treatment of premature ejaculation （PE）. MethodA total of 98 PE patients treated in the andrology department of the First Affiliated Hospital of Henan University of Chinese Medicine at the same time period were randomly assigned into an observation group and a control group， with 49 patients in each group. The observation group received Longbeisan application at Shenque （CV 8） combined with oral treatment of Chinese medicine according to syndrome differentiation， and the control group was treated with dapoxetine hydrochloride tablets. The treatment in both groups lasted for 8 weeks. The intravaginal ejaculatory latency time （IELT）， Chinese index of premature ejaculation-5 （CIPE-5） score， patient's sexual life satisfaction， spouse's sexual life satisfaction， effective rate， and adverse reaction incidence were compared between the two groups. ResultAfter treatment， the observation group had higher total effective rate than the control group ［（85.71% （42/49） vs. 67.35% （33/49）， χ2=6.262， P<0.05］. The IELT， CIPE-5 score， and patient's and spouse's satisfaction scores after treatment increased compared with those before treatment （P<0.01）， and the increases were more significant in the observation group （P<0.05， P<0.01）. The clinical effect of the observation group was better than that of the control group. During the treatment， 7 （7/49，14.29%） patients in the control group and 2 ，2/49，4.08%） patients in the observation group showed adverse reactions， which indicated the safety of the observation group was better than that of the control group （χ2=9.000， P<0.05）. In the follow-up period， 11 （11/49，22.45%） patients in the control group and 3 （3/49，6.12%） patients in the observation group showed aggravation of symptoms， which meant that the observation group had better lasting effect （χ2=0.317， P<0.05）. ConclusionLongbeisan application at Shenque （CV 8） combined with oral administration of Chinese medicine has better clinical effect， stronger safety， and longer effect than dapoxetine hydrochloride in the treatment of PE.

Uso da fitoterapia no tratamento do pé diabético em pessoas idosas: revisão integrativa / Use of phytotherapy in treating diabetic foot in older adults: an integrative review

RESUMO Objetivo identificar as evidências científicas sobre fitoterápicos utilizados no tratamento de pé diabético em pessoas idosas. Métodos revisão integrativa, realizada nas bases de dados Medical Literature Analysis and Retrieval System, SCOPUS, EMBASE, Web of Science e Latin American and Caribbean Health Sciences Literature. Utilizou-se a plataforma Rayyan, como ferramenta auxiliar para arquivamento, organização e seleção dos artigos. Resultados a busca resultou em 158 artigos. Após a estratégia de identificação, seleção, avaliação da elegibilidade, sistematização e leitura na íntegra, a amostra final foi de 10 artigos. Identificou-se fitoterápicos derivados de Calendula officinalis, Ageratina pichinchensis, Phellodendron chinense, Curcumin phytosome, Capsicum spp., Rehmannia Glutinosa e Astragalus membranaceus. Conclusão predominou a investigação de compostos fitoterápicos derivados de quatro plantas utilizados no tratamento do pé diabético em pessoas idosas. Considerações para a prática amparados pela legislação, os enfermeiros podem orientar usuários interessados em utilizar fitoterapia, como solução acessível e de eficácia comprovada.

ABSTRACT Objective to identify the scientific evidence on herbal medicines used in treating diabetic foot in older adults. Methods an integrative review conducted in the Medical Literature Analysis and Retrieval System, SCOPUS, EMBASE, Web of Science and Latin American and Caribbean Health Sciences Literature databases. The Rayyan platform was used as a supporting tool for archiving, organizing and selecting articles. Results the search resulted in 158 articles. After identifying, selecting, evaluating eligibility, systematization and performing a full reading of the articles, the final sample consisted of 10 articles. We identified herbal medicines derived from Calendula officinalis, Ageratina pichinchensis, Phellodendron chinense, Curcumin phytosome, Capsicum spp., Rehmannia Glutinosa and Astragalus membranaceus. Conclusion investigations of herbal compounds derived from four plants used in treating diabetic foot in older adults predominated. Considerations to practice supported by legislation, nurses can guide users interested in using phytotherapy as an accessible solution with proven efficacy.

Topical interventions for preventing hand-foot syndrome resulting from antineoplastic therapy: A scoping review / Intervenciones tópicas para prevenir el síndrome mano-pie resultante de la terapia antineoplásica: revisión del alcance / Intervenções tópicas para prevenção de síndrome mão-pé decorrente de terapia antineoplásica: revisão de escopo

ABSTRACT Objective: To map topical interventions used to prevent hand-foot syndrome in cancer patients undergoing antineoplastic therapy. Method: This is a scoping review reported in accordance with the recommendations of PRISMA-ScR (extension for scoping review) and the Joanna Briggs Institute Manual. The searches were carried out in the electronic databases CINAHL, Cochrane CENTRAL, EMBASE, LILACS, LIVIVO, PubMed, Scopus, Web of Science; and gray literature (Google Scholar, Pro-Quest). Results: The searches resulted in 12,016 references and the final sample consisted of 45 studies. A total of 42 topical interventions were identified, including: moisturizing creams, corticosteroids, acids, mapisal, silymarin, and henna. However, urea was the most cited intervention (62%). As for the presentations of the interventions, they varied among creams, ointments, gels, hydrocolloids, decoctions, patches, powders, oils, and soaps. Conclusion: The results allowed reviewing topical interventions, with emphasis on the use of urea and moisturizing creams. However, most of the interventions identified in this review require evaluation in future studies for better understanding of their benefits.

RESUMEN Objetivo: Mapear las intervenciones tópicas utilizadas para prevenir el síndrome mano-pie en pacientes con cáncer sometidos a terapia antineoplásica. Método: Esta es una revisión del alcance reportada de acuerdo con las recomendaciones de PRISMA-ScR (extensión para la revisión del alcance) y el Manual del Instituto Joanna Briggs. Las búsquedas se realizaron en las bases de datos electrónicas CINAHL, Cochrane CENTRAL, EMBASE, LILACS, LIVIVO, PubMed, Scopus, Web of Science; y literatura gris (Google Scholar, Pro-Quest). Resultados: Las búsquedas resultaron en 12.016 referencias y la muestra final estuvo compuesta por 45 estudios. Se identificaron 42 intervenciones tópicas, entre ellas: cremas humectantes, corticoides, ácidos, mapisal, silimarina y henna. Sin embargo, la urea fue la intervención más citada (62%). En cuanto a las presentaciones de las intervenciones, variaron entre cremas, ungüentos, geles, hidrocoloides, decocciones, parches, polvos, aceites y jabones. Conclusión: Los resultados permitieron revisar las intervenciones tópicas, con énfasis en el uso de urea y cremas humectantes. Sin embargo, la mayoría de las intervenciones identificadas en esta revisión deben evaluarse en estudios futuros para mejor comprensión de sus beneficios.

RESUMO Objetivo: Mapear as intervenções tópicas utilizadas para a prevenção da síndrome mão-pé em pacientes com câncer em terapia antineoplásica. Método: Trata-se de uma revisão de escopo reportada de acordo com as recomendações do PRISMA-ScR (extensão para revisão de escopo) e o Manual do Instituto Joanna Briggs. As buscas foram realizadas nas bases eletrônicas CINAHL, Cochrane CENTRAL, EMBASE, LILACS, LIVIVO, PubMed, Scopus, Web of Science; e literatura cinzenta (Google Scholar, Pro-Quest). Resultados: As buscas resultaram em 12.016 referências e a amostra final foi composta por 45 estudos. Um total de 42 intervenções tópicas foram identificadas, dentre elas: cremes hidratantes, corticosteroides, ácidos, mapisal, silimarina e henna. Entretanto, a ureia foi a intervenção mais citada (62%). Quanto às apresentações das intervenções, estas variaram entre cremes, pomadas, géis, hidrocoloides, decocções, adesivos, pós, óleos e sabões. Conclusão: Os resultados possibilitaram uma recensão das intervenções tópicas, com destaque ao uso da ureia e cremes hidratantes. Todavia, grande parte das intervenções identificadas nesta revisão necessitam ser avaliadas, em estudos futuros, para melhor compreensão dos seus benefícios.

Oridonin restores hepatic lipid homeostasis in an LXRα-ATGL/EPT1 axis-dependent manner.

Hepatosteatosis is characterized by abnormal accumulation of triglycerides (TG), leading to prolonged and chronic inflammatory infiltration. To date, there is still a lack of effective and economical therapies for hepatosteatosis. Oridonin (ORI) is a major bioactive component extracted from the traditional Chinese medicinal herb Rabdosia rubescens. In this paper, we showed that ORI exerted significant protective effects against hepatic steatosis, inflammation and fibrosis, which was dependent on LXRα signaling. It is reported that LXRα regulated lipid homeostasis between triglyceride (TG) and phosphatidylethanolamine (PE) by promoting ATGL and EPT1 expression. Therefore, we implemented the lipidomic strategy and luciferase reporter assay to verify that ORI contributed to the homeostasis of lipids via the regulation of the ATGL gene associated with TG hydrolysis and the EPT1 gene related to PE synthesis in a LXRα-dependent manner, and the results showed the TG reduction and PE elevation. In detail, hepatic TG overload and lipotoxicity were reversed after ORI treatment by modulating the ATGL and EPT1 genes, respectively. Taken together, the data provide mechanistic insights to explain the bioactivity of ORI in attenuating TG accumulation and cytotoxicity and introduce exciting opportunities for developing novel natural activators of the LXRα-ATGL/EPT1 axis for pharmacologically treating hepatosteatosis and metabolic disorders.

Exercises and neuromuscular electric stimulation for medial longitudinal arch: clinical trial / Exercícios e estimulação elétrica neuromuscular para arco longitudinal medial: ensaio clínico

ABSTRACT Objective The extrinsic muscles, such as the posterior tibialis and long flexor of the hallux and the intrinsic of the foot, are part of the active subsystem of the central system of the foot and play an essential role in the control of the medial longitudinal arch resulting from difficulty in contracting the muscle, neuromuscular electrostimulation (NMES) becomes a resource combined with strengthening and recommended for rehabilitation. T this work aims to evaluate the effectiveness of NMES associated with exercise in deforming the medial longitudinal arch. Methods This is a randomized blind clinical trial. 60 asymptomatic participants were divided into three groups: NMES, exercise and control. The NMES and exercise group performed seven exercises for the intrinsic and extrinsic muscles twice a week for 6 weeks, and the NMES group used an NMES associated with five exercises. Navicular height and medial longitudinal arch angle were taken before and after the intervention period. Results No statistically significant differences existed between groups for navicular height and medial longitudinal arch angle. Conclusion NMES associated with exercise does not change the characteristics of the medial longitudinal arch in association with asymptomatic. Level of Evidence I; Randomized clinical trial.

RESUMO Objetivo Os músculos extrínsecos, como o tibial posterior e flexor longo do hálux e os intrínsecos do pé fazem parte do subsistema ativo do foot core system e exercem papel essencial no controle do arco longitudinal medial. Devido à dificuldade na contração desses músculos, a eletroestimulação neuromuscular (EENM) torna-se um recurso aliado ao fortalecimento e é recomendada para reabilitação. O objetivo desse trabalho é avaliar a eficácia da EENM associada ao exercício na deformação do arco longitudinal medial. Métodos Este é um ensaio clínico randomizado cego. 60 participantes assintomáticos foram divididos em três grupos: EENM, exercício e controle. O grupo EENM e exercício realizaram sete exercícios para os músculos intrínsecos e extrínsecos duas vezes por semana por seis semanas, sendo o grupo EENM utilizou a EENM associada a cinco exercícios. A altura do navicular e o ângulo do arco longitudinal medial foram medidos antes e após o período de intervenção. Resultados Não houve diferenças estatisticamente significativas entre os grupos para a altura do navicular e ângulo do arco longitudinal medial. Conclusão A EENM associada ao exercício não altera as características do arco longitudinal medial em indivíduos assintomáticos. Nível de Evidência I; Estudo Clínico Randomizado.

LED phototherapy in tissue repair of chronic wounds in people with diabetes: a systematic review / Fototerapia LED en la reparación de tejidos de heridas crónicas en personas con diabetes: una revisión sistemática / Fototerapia com LED no reparo tecidual de feridas crônicas em pessoas com diabetes: revisão sistemática

ABSTRACT Objective: To identify scientific evidence of LED photobiomodulation in the treatment and tissue repair of chronic wounds in people with Diabetes Mellitus, types I and II. Method: Systematic review conducted from September/2021 to April/2022 in PubMed, LILACS, SCIELO, COHRANE, EMBASE and Web of Science. Randomized and observational clinical trials using LED in wound healing in diabetics, published between 2015 and 2022 were included. Data were descriptively analyzed with title/abstract screening, full text articles reading and definitive selection after meeting the predefined inclusion and exclusion criteria. Results: Fromthe total of 840 references, eight articles were selected, that evaluated the effectiveness of LED phototherapy in wounds of diabetic patients. Conclusion: LED light proved to be beneficial in tissue repair, with increased production in collagen and fibroblasts, angiogenesis, reduction of inflammation and, consequently, a decrease in lesion size.

RESUMEN Objetivo: Identificar evidencias científicas de fotobiomodulación con LED en el tratamiento y reparación de tejidos de heridas crónicas en personas con Diabetes Mellitus, tipos I y II. Método: Revisión sistemática realizada de septiembre/2021 a abril/2022 en PubMed, LILACS, SCIELO, COHRANE, EMBASE y Web of Science. Se incluyeron ensayos clínicos aleatorizados y observacionales con uso de LED en la cicatrización de heridas en diabéticos, publicados entre 2015 y 2022. Los datos fueron analizados descriptivamente con selección de título/resumen, lectura de artículos a texto completo y selección definitiva después de cumplir con la inclusión e inclusiones ex - predefinidas. Resultados: Del total de 840 referencias encontradas, se seleccionaron ocho artículos que evaluaron la efectividad de la fototerapia LED en heridas de pacientes diabéticos. Conclusión: La luz LED demostró ser beneficiosa en la reparación de tejidos, con aumento de la producción de colágeno y fibroblastos, angiogénesis, reducción de la inflamación y, en consecuencia, disminución del tamaño de la lesión.

RESUMO Objetivo: Identificar evidências científicas da fotobiomodulação com LED no tratamento e reparo tecidual em feridas crônicas de pessoas com Diabetes Mellitus, tipo I e II. Método: Revisão sistemática realizada de setembro/2021 a abril/2022 na PubMed, LILACS, SCIELO, COHRANE, EMBASE e Web of Science. Incluídos ensaios clínicos randomizados e observacionais utilizando LED na cicatrização de feridas em diabéticos, publicados entre 2015 a 2022. Os dados foram analisados descritivamente com triagem de título/resumo, leitura dos artigos em texto completo e seleção definitiva após atender aos critérios de inclusão e exclusão pré-definidos. Resultados: Do total de 840 referências encontradas, foram selecionados oito artigos que avaliaram a eficácia da fototerapia LED em feridas de pacientes diabéticos. Conclusão: A luz LED mostrou-se benéfica no reparo tecidual, com aumento na produção de colágeno e fibroblastos, angiogênese, redução da inflamação e consequentemente, diminuição no tamanho da lesão.

Intensive outpatient treatment for PTSD: an open trial combining prolonged exposure therapy, EMDR, and physical activity.

Background: Intensive outpatient treatment could be a promising option for patients with post-traumatic stress disorder (PTSD). Objective: The aim of the study was to test the effectiveness of an eight-day (two-week) intensive treatment for PTSD within a public health care setting (open trial design). Method: Eighty-nine patients were offered the choice between intensive treatment and spaced individual treatment, of which 34 (38.2%) chose the intensive format. Patients were assessed with self-report batteries and interviews at pre-treatment, start of treatment, post-treatment and three-month follow-up. Each day consisted of individual Prolonged Exposure therapy, Eye Movement Desensitization and Reprocessing therapy, group psychoeducation, and physical activity. Therapists rotated between patients. Results: Between 55 and 62% of the patients showed a clinically significant change (recovery) in symptoms of PTSD, and the effect sizes were large (d = 1.38-1.52). Patients also showed reduction in symptoms of depression and anxiety, along with improved well-being and interpersonal functioning. Changes in social and work functioning were more ambiguous. There were no dropouts, attendance was high, and patients were highly satisfied with the treatment. Conclusions: The intensive programme was an attractive and effective treatment option for patients with PTSD.

Antecedentes: El tratamiento ambulatorio intensivo podría ser una opción prometedora para los pacientes con trastorno de estrés postraumático (TEPT).Objetivo: El objetivo del estudio fue probar la efectividad de un tratamiento intensivo de 8 días (2 semanas) para el TEPT dentro de un entorno de atención de salud pública (diseño de ensayo abierto).Método: Se ofreció a 89 pacientes elegir entre tratamiento intensivo y tratamiento individual espaciado, de los cuales 34 (38,2%) eligieron el formato intensivo. Los pacientes fueron evaluados con baterías de autoinforme y entrevistas antes del tratamiento, al inicio del tratamiento, después del tratamiento y a los 3 meses de seguimiento. Cada día consistió en terapia de exposición prolongada individual, terapia de reprocesamiento y desensibilización por movimientos oculares, psicoeducación grupal y actividad física. Los terapeutas rotaron entre los pacientes.Resultados: Entre el 55-62% de los pacientes mostraron un cambio clínicamente significativo (recuperación) en los síntomas del TEPT, y los tamaños del efecto fueron grandes (d = 1,38­1,52). Los pacientes también mostraron una reducción en los síntomas de depresión y ansiedad, junto con mejoría en bienestar y funcionamiento interpersonal. Los cambios en el funcionamiento social y laboral fueron más ambiguos. No hubo abandonos, la asistencia fue alta y los pacientes estaban altamente satisfechos con el tratamiento.Conclusiones: El programa intensivo fue una opción de tratamiento atractiva y efectiva para pacientes con TEPT.

Response of aerobic granular sludge under polyethylene microplastics stress: Physicochemical properties, decontamination performance, and microbial community.

Microplastics are widely detected in sewage and sludge in wastewater treatment plants and can thereby influence biological processes. In this study, the overall impacts of polyethylene microplastics (PE MPs) and their toxicity mechanisms on aerobic granular sludge (AGS) were investigated. Particle structure, settling properties, particle size distribution, and extracellular polymeric substance characteristics of AGS were significantly affected by PE MPs with concentrations of 20 and 200 n/L. Increased relative contents of reactive oxygen species (ROS) (146.34% and 191.43%) and lactate dehydrogenase (LDH) (185.71% and 316.67%) under PE MPs (20 and 200 n/L) exposure resulted in disruption of cellular structure. The activities of enzymes related to denitrification and phosphorus removal were greatly decreased, while ammonia monooxygenase (AMO) was stable, supporting the high efficiency removal of ammonia nitrogen. High-throughput sequencing demonstrated that the relative abundance of nitrifying and denitrifying bacteria (Nitrospira, Thermomonas, Flavobacterium), and PAOs (Comamonas and Rhodocyclus) were significantly reduced from 4.47%, 3.57%, 2.02%, 9.38%, and 5.45%-2.95%, 2.88%, 1.77%, 8.01%, and 4.86% as the concentration of PE MPs increased from 0 to 200 n/L, respectively. Those findings were consistent with the deterioration in decontamination capability.

D-dimer Thresholds to Exclude Pulmonary Embolism among COVID-19 Patients in the Emergency Department: Derivation with Independent Validation.

OBJECTIVE: To derive and validate a D-dimer cutoff for ruling out pulmonary embolism (PE) in COVID-19 patients presenting to the emergency department (ED). METHODS: A retrospective cohort study was performed in an integrated healthcare system including 22 adult ED's between March 1, 2020, and January 31, 2021. Results were validated among patients enrolled in the RECOVER Registry, representing data from 154 ED's from 26 US states. Consecutive ED patients with laboratory confirmed COVID-19, a D-dimer performed within 48 h of ED arrival, and with objectively confirmed PE were compared to those without PE. After identifying a D-dimer threshold at which the 95% confidence lower bound of the negative predictive value for PE was higher than 98% in the derivation cohort, it was validated using RECOVER registry data. RESULTS: Among 3978 patients with a D-dimer result, 3583 with confirmed COVID-19 infection were included in the derivation cohort. Overall, PE incidence was 4.1% and a D-dimer cutoff of <2 µ/mL (2000 ng/mL) was associated with a NPV of 98.5% (95% CI = 98.0%-98.9%). In the validation cohort of 13,091 patients with a D-dimer, 7748 had confirmed COVID-19 infection, and the PE incidence was 1.14%. A D-dimer cutoff of <2 µ/mL was associated with a NPV of 99.5% (95% CI = 99.3%-99.7%). CONCLUSION: A D-dimer cutoff of <2 µ/ml was associated with a high negative predictive value for PE among patients with COVID-19. However, the resultant sensitivity for PE result at that threshold without pre-test probability assessment would be considered clinically unsafe.

Health-related quality of life associated with warfarin and direct oral anticoagulants in venous thromboembolism.

INTRODUCTION: Venous thromboembolism (VTE) is commonly treated with oral anticoagulants, including warfarin or direct oral anticoagulants (DOACs). Although DOACs are associated with favorable treatment satisfaction, few studies have assessed whether quality of life differs between DOAC and warfarin users. MATERIALS AND METHODS: We invited adults enrolled in two California-based integrated health care delivery systems and with a history of VTE between January 1, 2015 and June 30, 2018 to complete a survey on their experience with anticoagulants. Health-related quality of life (QOL) was assessed using the RAND 36-item Short Form Health Survey (SF-36), which measures QOL in 2 general component scores (physical and mental). We used multivariable linear regression to compare mean QOL component scores between DOAC-users and warfarin-users, adjusting for patient and clinical characteristics. RESULTS: Overall, 2230 patients (43.1 % women and 31.8 % >75 years of age) taking anticoagulants answered at least 1 question on the SF-36, 975 taking DOACs and 1255 taking warfarin. After adjustment for patient-level factors, there were no significant differences in either physical component scores (39.2 v 38.3, p = 0.24) or mental component scores (48.5 v 49.0, p = 0.42) between DOAC and warfarin users. CONCLUSIONS: Health-related QOL did not significantly differ between DOAC and warfarin users with a history of VTE.

Maternal Pyrroloquinoline Quinone Supplementation Improves Offspring Liver Bioactive Lipid Profiles throughout the Lifespan and Protects against the Development of Adult NAFLD.

Maternal obesity and consumption of a high-fat diet significantly elevate risk for pediatric nonalcoholic fatty liver disease (NAFLD), affecting 10% of children in the US. Almost half of these children are diagnosed with nonalcoholic steatohepatitis (NASH), a leading etiology for liver transplant. Animal models show that signs of liver injury and perturbed lipid metabolism associated with NAFLD begin in utero; however, safe dietary therapeutics to blunt developmental programming of NAFLD are unavailable. Using a mouse model of maternal Western-style diet (WD), we previously showed that pyrroloquinoline quinone (PQQ), a potent dietary antioxidant, protected offspring of WD-fed dams from development of NAFLD and NASH. Here, we used untargeted mass spectrometry-based lipidomics to delineate lipotoxic effects of WD on offspring liver and identify lipid targets of PQQ. PQQ exposure during pregnancy altered hepatic lipid profiles of WD-exposed offspring, upregulating peroxisome proliferator-activated receptor (PPAR) α signaling and mitochondrial fatty acid oxidation to markedly attenuate triglyceride accumulation beginning in utero. Surprisingly, the abundance of very long-chain ceramides, important in promoting gut barrier and hepatic function, was significantly elevated in PQQ-treated offspring. PQQ exposure reduced the hepatic phosphatidylcholine/phosphatidylethanolamine (PC/PE) ratio in WD-fed offspring and improved glucose tolerance. Notably, levels of protective n - 3 polyunsaturated fatty acids (PUFAs) were elevated in offspring exposed to PQQ, beginning in utero, and the increase in n - 3 PUFAs persisted into adulthood. Our findings suggest that PQQ supplementation during gestation and lactation augments pathways involved in the biosynthesis of long-chain fatty acids and plays a unique role in modifying specific bioactive lipid species critical for protection against NAFLD risk in later life.

Transcriptome and metabolome changes induced by bitter melon (Momordica charantia)- intake in a high-fat diet induced obesity model.

Background and aim: Metabolic syndrome (MetS) is a complex disease of physiological imbalances interrelated to abnormal metabolic conditions, such as abdominal obesity, type II diabetes, dyslipidemia and hypertension. In the present pilot study, we investigated the nutraceutical bitter melon (Momordica charantia L) -intake induced transcriptome and metabolome changes and the converging metabolic signaling networks underpinning its inhibitory effects against MetS-associated risk factors. Experimental procedure: Metabolic effects of lyophilized bitter melon juice (BMJ) extract (oral gavage 200 mg/kg/body weight-daily for 40 days) intake were evaluated in diet-induced obese C57BL/6J male mice [fed-high fat diet (HFD), 60 kcal% fat]. Changes in a) serum levels of biochemical parameters, b) gene expression in the hepatic transcriptome (microarray analysis using Affymetrix Mouse Exon 1.0 ST arrays), and c) metabolite abundance levels in lipid-phase plasma [liquid chromatography mass spectrometry (LC-MS)-based metabolomics] after BMJ intervention were assessed. Results and conclusion: BMJ-mediated changes showed a positive trend towards enhanced glucose homeostasis, vitamin D metabolism and suppression of glycerophospholipid metabolism. In the liver, nuclear peroxisome proliferator-activated receptor (PPAR) and circadian rhythm signaling, as well as bile acid biosynthesis and glycogen metabolism targets were modulated by BMJ (p < 0.05). Thus, our in-depth transcriptomics and metabolomics analysis suggests that BMJ-intake lowers susceptibility to the onset of high-fat diet associated MetS risk factors partly through modulation of PPAR signaling and its downstream targets in circadian rhythm processes to prevent excessive lipogenesis, maintain glucose homeostasis and modify immune responses signaling.