Carvacrol-Loaded Nanoemulsion Promotes Tocolytic and Anti-Dysmenorrhea Effects in Rodents.

INTRODUCTION: Carvacrol is a phenolic constituent of essential oils that has antinociceptive, anti-inflammatory, and antioxidant activities. METHOD: This study aimed to evaluate the in vitro spasmolytic and in vivo anti-dysmenorrhea potential of a nanoemulsion-containing carvacrol (nanoCARV). RESULTS: In isolated rat uterus, nanoCARV reduced spontaneous contractions (pEC50 = 3.91 ± 0.25) and relaxed preparations pre-contracted with oxytocin (pEC50 = 3.78 ± 0.2), carbachol (pEC50 = 4.15 ± 0.4), prostaglandin F2α (pEC50 = 3.00 ± 0.36), and KCl (pEC50 = 3.98 ± 0.32). The investigation of the mechanism of action revealed significant differences (p < 0.05) between the pEC50 values of nanoCARV in the absence or presence of aminophylline or tetraethylammonium. In a primary dysmenorrhea model, treatment with nanoCARV reduced the number of oxytocin-induced abdominal writhes. CONCLUSIONS: These data indicate that the anti-dysmenorrhea effect of nanoCARV may be related to the relaxation of uterine smooth muscle, with participation of the cAMP signaling pathway and potassium channels.

Desmistificando a coleta citopatológica: uma forma de prevenir o câncer de colo do útero / Demystifying cytopathological collection: a way to prevent cervical cancer

Objetivo: Relatar uma ação de Educação em Saúde sobre a prevenção do câncer de colo uterino por meio da citologia. Método: Trata-se de um relato de experiência vivenciado por uma enfermeira durante uma ação a dez mulheres sobre a importância da coleta citopatológica para prevenção desse câncer. Foi realizada em maio de 2023, em uma unidade básica de saúde e dividida em três momentos: no primeiro, foi realizado um Brainstorm, no segundo um pré-teste utilizando uma dinâmica e o terceiro momento foi o pós-teste. Resultado: Foi evidenciado que as mulheres não tinham entendimento correto sobre a coleta citopatológica, as etapas do exame, ou seja, o conhecimento era insuficiente e não se sentiam preparadas para falar sobre o assunto. Conclusão: A ação permitiu um maior conhecimento das usuárias e das suas necessidades de entendimento e esclarecimentos sobre a coleta citopatológica, levando em consideração a sua importância no rastreio precoce de câncer de colo do útero.(AU)

Objective: To report a Health Education action on the prevention of cervical cancer through cytology. Method: This is an experience report lived by a nurse during an action with ten women on the importance of cytopathological collection for the prevention of this cancer. It was carried out in May 2023, in a basic health unit and divided into three moments: in the first, a Brainstorm was performed, in the second, a pre-test using a dynamic and the third moment was the post-test. Result: It was evidenced that the women did not have a correct understanding of the cytopathological collection, the examination steps, that is, the knowledge was insufficient and they did not feel prepared to talk about the subject. Conclusion: The action allowed for a greater knowledge of the users and their needs for understanding and clarification about the cytopathological collection, taking into account its importance in the early screening of cervical cancer.(AU)

Objetivo: Relatar un programa de educación sanitaria sobre la prevención del cáncer de cuello de útero mediante la citología. Método: Este es un informe de la experiencia de una enfermera durante una acción con diez mujeres sobre la importancia de la recolección citopatológica para prevenir este cáncer. Tuvo lugar en mayo de 2023 en una unidad básica de salud y se dividió en tres etapas: la primera fue una lluvia de ideas, la segunda fue un pre-test mediante dinámicas y la tercera fue el post-test. Resultados: Quedó claro que las mujeres no tenían una comprensión correcta de la colecta citopatológica y de las etapas del examen, o sea, sus conocimientos eran insuficientes y no se sentían preparadas para hablar del tema. Conclusión: La acción permitió una mayor concienciación de las usuarias y su necesidad de comprensión y aclaración sobre la colecta citopatológica, teniendo en cuenta su importancia en el cribado precoz del cáncer de cuello uterino.(AU)

Five-Year Outcomes With Pembrolizumab Versus Chemotherapy as First-Line Therapy in Patients With Non-Small-Cell Lung Cancer and Programmed Death Ligand-1 Tumor Proportion Score ≥ 1% in the KEYNOTE-042 Study.

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.We report 5-year results from the phase III KEYNOTE-042 study (ClinicalTrials.gov identifier: NCT02220894). Eligible patients with locally advanced/metastatic non-small-cell lung cancer (NSCLC) without EGFR/ALK alterations and with programmed death ligand-1 (PD-L1) tumor proportion score (TPS) ≥ 1% received pembrolizumab 200 mg once every 3 weeks for 35 cycles or chemotherapy (carboplatin + paclitaxel or pemetrexed) for 4-6 cycles with optional maintenance pemetrexed. Primary end points were overall survival (OS) in PD-L1 TPS ≥ 50%, ≥ 20%, and ≥ 1% groups. Patients who completed 35 cycles of pembrolizumab with ≥ stable disease could begin second-course pembrolizumab upon progression. One thousand two hundred seventy-four patients were randomly assigned (pembrolizumab, n = 637; chemotherapy, n = 637). Median follow-up time was 61.1 (range, 50.0-76.3) months. OS outcomes favored pembrolizumab (v chemotherapy) regardless of PD-L1 TPS (hazard ratio [95% CI] for TPS ≥ 50%, 0.68 [0.57 to 0.81]; TPS ≥ 20%, 0.75 [0.64 to 0.87]; TPS ≥ 1%, 0.79 [0.70 to 0.89]), with estimated 5-year OS rates with pembrolizumab of 21.9%, 19.4%, and 16.6%, respectively. No new toxicities were identified. Objective response rate was 84.3% among 102 patients who completed 35 cycles of pembrolizumab and 15.2% among 33 patients who received second-course pembrolizumab. First-line pembrolizumab monotherapy continued to show durable clinical benefit versus chemotherapy after 5 years of follow-up in PD-L1-positive, locally advanced/metastatic NSCLC without EGFR/ALK alterations and remains a standard of care.

Rationale and Design of the Phase III KEYLYNK-012 Study of Pembrolizumab and Concurrent Chemoradiotherapy Followed by Pembrolizumab With or Without Olaparib for Stage III Non-Small-Cell Lung Cancer.

BACKGROUND: Concurrent chemoradiotherapy is a standard therapy for patients with stage III non-small-cell lung cancer (NSCLC). Durvalumab is an approved treatment option following concurrent chemoradiotherapy in the absence of disease progression. The multicenter, phase III, randomized, placebo- and active-controlled, double-blind KEYLYNK-012 study evaluates whether initiation of immunotherapy with pembrolizumab concurrently with chemoradiotherapy, followed by post-chemoradiotherapy pembrolizumab with or without olaparib improves outcomes for participants with stage III NSCLC. (ClinicalTrials.gov: NCT04380636) METHODS: Eligible participants are aged ≥18 years with previously untreated, pathologically confirmed, stages IIIA-C, squamous or nonsquamous NSCLC not suitable for surgery with curative intent. Participants will be randomized 1:1:1 to platinum-doublet chemotherapy plus radiotherapy with pembrolizumab (Groups A and B) or concurrent chemoradiotherapy alone (Group C) for 3 cycles. In the absence of disease progression, participants will receive pembrolizumab plus olaparib placebo (Group A), pembrolizumab plus olaparib (Group B), or durvalumab monotherapy (Group C). Dual primary endpoints are progression-free survival per RECIST version 1.1 by independent central review and overall survival. RESULTS: Enrollment began on July 6, 2020, and is ongoing at approximately 190 sites. CONCLUSION: KEYLYNK-012 will provide important information on the efficacy and safety of pembrolizumab combined with concurrent chemoradiotherapy and subsequent pembrolizumab with or without olaparib in participants with unresectable stage III NSCLC.

Mixed laryngocele mimicking thyroid nodule.

Laryngocele is defined as a dilation of the laryngeal saccule forming an air sac. Some differential diagnoses for laryngocele have been reported. The aim of the present paper was to describe a case of a patient referred for the evaluation a suspected thyroid nodule that was subsequently diagnosed as a mixed laryngocele. A 31-year-old male with no clinical manifestations was referred by an endocrinologist to undergo Doppler ultrasonography and fine-needle aspiration biopsy due to a preliminary ultrasonographic diagnosis of a nodule apparently in the thyroid. The diagnosis of laryngocele was raised considering the cytopathological analysis and imaging exam. Computed tomography of the neck confirmed this hypothesis. The patient was counseled to consult a surgeon, but, up to the end of this report, continued asymptomatic and in follow-up. We report a mixed laryngocele with different clinical behavior, showing that laryngocele may appear to be another entity and drawing the attention of clinicians to imaging similarities.

Karate Training Improves Metabolic Health in Overweight and Obese Adolescents: A Randomized Clinical Trial.

PURPOSE: This study evaluated the effects of 12 weeks of karate training on cardiometabolic parameters, oxidative stress, and inflammation in adolescents with overweight and obesity. METHOD: Seventy adolescents were randomized into 2 groups: control received nutritional and psychological interventions once a week for 12 weeks, and treatment received nutritional and psychological interventions once a week, plus 3 karate sessions per week, for 12 weeks. The main outcome measure was improvement in cardiometabolic parameters, oxidative stress, and inflammation. RESULTS: After the intervention period, the treatment group showed a reduction in resting heart rate (77.86 [10.89]), high-density lipoprotein cholesterol (40.86 [8.31]), and triglycerides (75.18 [32.29]) and an increase in low-density lipoprotein cholesterol (95.64 [42.53]) in relation to pretraining. Regarding oxidative stress markers, there was a reduction in protein carbonylation (0.07 [0.06]) and nitric oxide (1.39 [1.11]) and an increase in superoxide dismutase (0.68 [0.31]) and glutathione (0.11 [0.08]) compared with pretraining. With respect to inflammation, adiponectin increased (14.54 [5.36]) after the intervention when compared with preintervention. CONCLUSION: The study concluded that the intervention may improve cardiometabolic parameters, oxidative stress, and inflammation in adolescents with overweight and obesity. Long-term effects need to be evaluated.

Pembrolizumab plus pemetrexed-platinum for metastatic nonsquamous non-small-cell lung cancer: KEYNOTE-189 Japan Study.

Pembrolizumab plus pemetrexed-platinum significantly improved overall survival (OS) and progression-free survival (PFS) with manageable safety compared with placebo plus pemetrexed-platinum in patients with previously untreated metastatic nonsquamous non-small-cell lung cancer (NSCLC) without EGFR/ALK alterations in the global, randomized, double-blind, phase 3 KEYNOTE-189 study. We present results of Japanese patients enrolled in the KEYNOTE-189 global and Japan extension studies. Patients were randomized 2:1 to intravenous pembrolizumab 200 mg or placebo every 3 weeks (Q3W) for up to 35 cycles. All patients received pemetrexed 500 mg/m2 plus the investigator's choice of cisplatin or carboplatin Q3W for four cycles, followed by maintenance pemetrexed 500 mg/m2 Q3W (all intravenous). Co-primary endpoints were OS and PFS. Forty Japanese patients enrolled (pembrolizumab, n = 25; placebo, n = 15). At data cutoff (20 May 2019; median time from randomization to data cutoff, 18.5 [range, 14.7-38.2] months), the median OS was not reached in the pembrolizumab plus pemetrexed-platinum arm; the median OS was 25.9 (95% confidence interval [CI], 11.9-29.0) months in the placebo plus pemetrexed-platinum arm (hazard ratio [HR] .29; 95% CI, .07-1.15). The median (95% CI) PFS was 16.5 (8.8-21.1) compared with 7.1 (4.7-21.4) months (HR, .62; 95% CI, .27-1.42), respectively. There were no grade 5 adverse events (AE). Grade 3/4 AE occurred in 72% vs 60% of patients in the pembrolizumab vs placebo arms; 40% vs 20% had immune-mediated AE, and 4% vs 0% had infusion reactions. Efficacy and safety outcomes were similar to those from the global study and support first-line therapy with pembrolizumab plus pemetrexed-platinum in Japanese patients with nonsquamous NSCLC without EGFR/ALK alterations.

A Simple Method of Transoperative Maxillomandibular Fixation in Pediatric Facial Fractures.

ABSTRACT: Maxillomandibular fixation in pediatric facial fractures is quite challenging to be achieved, especially in mid-mixed dentition. Traditional well established intermaxillary devices have a lot of limitations in these patients. This article presents a case of a 9-year-old female patient with a displaced mandibular fracture in which orthodontic buttons were used for transoperative maxillomandibular fixation followed by internal fixation after adequate occlusion reestablishment and fracture reduction. The method showed high efficacy and celerity, allowing the success of treatment, with satisfactory evolution of the patient.

Effectiveness of martial arts exercise on anthropometric and body composition parameters of overweight and obese subjects: a systematic review and meta-analysis.

BACKGROUND: Obesity is considered a top public health concern, and its prevalence is growing every day. Thus, interventions to address this problem should be encouraged and further studied. In this regard, the aim of this review was to summarize the evidence of martial arts interventions to evaluate their effectiveness on the anthropometric and body composition parameters of overweight and obese subjects. METHODS: A systematic literature search was conducted on January 26, 2020 using the PubMed, Medline, Lilacs, Cochrane, and Scielo databases. Reference lists of eligible articles and relevant reviews have also been examined. All randomized clinical trials on martial arts that evaluated the anthropometric and body composition parameters of overweight and obese subjects were included, and a narrative synthesis of eligible studies was conducted in accordance with PRISMA guidelines. The Downs & Black checklist was used to assess the quality of the studies. This review was registered in the International Prospective Register of Systematic Reviews (PROSPERO) (identifier CRD42018086116). RESULTS: A total of 82 articles were identified from the initial search strategy. A further 2 articles were identified from the review of relevant bibliographies. Six studies encompassing 258 participants who were overweight or obese were included. Four studies reported Tai Chi practice, one study reported Kung Fu exercise, and another study reported martial arts exercise. The examined meta-analyses did not reveal significant benefits from martial arts practice over control groups after the experiment period for body mass index (- 1.34 kg/m2; 95% CI: - 2.72, 0.05), waist circumference (1.41 cm; 95% CI: - 0.72, 3.54) and percentage of body fat (- 0.75%; 95% CI: - 5.58, 4.08). CONCLUSION: The scarcity, heterogeneity, short intervention time, small sample size, and significant methodological limitations of the available studies do not allow to conclude whether martial arts are effective in the anthropometric and body composition parameters of overweight and obese individuals. This study highlights the need for more research to assess the benefits of martial arts for overweight and obese individuals.

Mass spectrometry imaging as a potential technique for diagnostic of Huanglongbing disease using fast and simple sample preparation.

Huanglongbing (HLB) is a disease of worldwide incidence that affects orange trees, among other commercial varieties, implicating in great losses to the citrus industry. The disease is transmitted through Diaphorina citri vector, which inoculates Candidatus Liberibacter spp. in the plant sap. HLB disease lead to blotchy mottle and fruit deformation, among other characteristic symptoms, which induce fruit drop and affect negatively the juice quality. Nowadays, the disease is controlled by eradication of sick, symptomatic plants, coupled with psyllid control. Polymerase chain reaction (PCR) is the technique most used to diagnose the disease; however, this methodology involves high cost and extensive sample preparation. Mass spectrometry imaging (MSI) technique is a fast and easily handled sample analysis that, in the case of Huanglongbing allows the detection of increased concentration of metabolites associated to the disease, including quinic acid, phenylalanine, nobiletin and sucrose. The metabolites abieta-8,11,13-trien-18-oic acid, suggested by global natural product social molecular networking (GNPS) analysis, and 4-acetyl-1-methylcyclohexene showed a higher distribution in symptomatic leaves and have been directly associated to HLB disease. Desorption electrospray ionization coupled to mass spectrometry imaging (DESI-MSI) allows the rapid and efficient detection of biomarkers in sweet oranges infected with Candidatus Liberibacter asiaticus and can be developed into a real-time, fast-diagnostic technique.

Effects of aging on DNA hydroxymethylation and methylation in human dental follicles.

OBJECTIVE: Despite the high frequency of impacted teeth and increased frequency of lesions in dental follicles (DF) with aging, DF age-changes remain unclear. We compared the global methylation and hydroxymethylation profiles in DF in relation to age. DESIGN: DF associated with impacted lower third molars were obtained from 59 individuals. Global DNA methylation (5mC content) and hydroxymethylation (5hmC) were evaluated by ELISA. We tested the correlation between 5mC and 5hmC content, and the correlation of each with patients' age. The differences in age, 5mC, and 5hmC in DF from men/women, and location (left/right mandible) was tested. RESULTS: The mean age of the 59 individuals was 19.56 ±â€¯3.92, ranging from 13 to 31 years, and most were women (n = 39). 5hmC content and age up to 19 years were inversely correlated (Spearman's correlation coefficient=-0.552, p = 0.0003, n = 38). There was no relationship between 5hmC and 5mC content. There was no difference in the medians of age (p = 0.25), 5hmC (p = 0.33) and 5mC (p = 0.86) between men/women, nor in the medians of age (p = 0.39), 5hmC (p = 0.99) and 5mC (p = 0.22) between the left/right side of the tooth extraction. CONCLUSION: An inverse correlation between 5hmC and age was established, with no correlation between 5mC and 5hmC content in DF. The biological meaning of such a decrease of global DNA hydroxymethylation with age in DF remains to be clarified.

Inexpensive and nonconventional fabrication of microfluidic devices in PMMA based on a soft-embossing protocol.

This study describes an inexpensive and nonconventional soft-embossing protocol to produce microfluidic devices in poly(methyl methacrylate) (PMMA). The desirable microfluidic structure was photo-patterned in a poly(vinyl acetate) (PVAc) film deposited on glass substrate to produce a low-relief master. Then, this template was used to generate a high-relief pattern in stiffened PDMS by increasing of curing agent /monomer ratio (1:5) followed by thermal aging in a laboratory oven (200°C for 24 h). The stiffened PDMS masters were used to replicate microfluidic devices in PMMA based on soft embossing at 220-230°C and thermal sealing at 140°C. Both embossing and sealing stages were performed by using binder clips. The proposed protocol has ensured the replication of microfluidic devices in PMMA with great fidelity (>94%). Examples of MCE devices, droplet generator devices and spot test array were successfully demonstrated. For testing MCE devices, a mixture containing inorganic cations was selected as model and the achieved analytical performance did not reveal significant difference from commercial PMMA devices. Water droplets were successfully generated in an oil phase at rate of ca. 60 droplets/min (fixing the continuous phase flow rate at 100 µL/h) with size of ca. 322 ± 6 µm. Glucose colorimetric assay was performed on spot test devices and good detectability level (5 µmol/L) was achieved. The obtained results for two artificial serum samples revealed good agreement with the certified concentrations. Based on the fabrication simplicity and great analytical performance, the proposed soft-embossing protocol may emerge as promising approach for manufacturing PMMA devices.

Efficacy and safety of chloroquine plus prednisone for the treatment of autoimmune hepatitis in a randomized trial.

BACKGROUND AND AIM: Standard treatment for autoimmune hepatitis (AIH) consists of predniso(lo)ne and azathioprine. However, alternative therapy is required for non- or partial responders and in cases of side effects. The aim of this study was to evaluate the treatment outcomes associated with chloroquine plus prednisone in AIH patients. METHODS: Fifty-seven patients were recruited to receive either azathioprine or chloroquine, both with prednisone, in a randomized trial. The primary end-point was complete remission, based on normalization of aminotransferase levels in the first 6 months of treatment plus maintenance for at least 18 months, with minimal or no inflammatory activity in the liver biopsy. Secondary end-points were partial and nonresponse, severe side effects, and treatment withdrawal. RESULTS: There were no differences between groups regarding clinical, serological, histological, and treatment characteristics at baseline. There were no significant differences in the biochemical response rate (67.7 vs 53.8%, P = 0.41) or the complete remission rate (32.26 vs 15.38%, P = 0.217). However, despite the long study period, the sample size was smaller than that required for a noninferiority study. The mean prednisone dose was similar in both groups. There was a nonsignificantly higher rate of adverse effects and a tendency toward improvement in glycemic and cholesterol profiles in the chloroquine group (P = 0.09 and P = 0.07, respectively). CONCLUSIONS: The combination of chloroquine and prednisone exhibited potentially beneficial effects in AIH patients (https://ClinicalTrials.gov: NCT02463331).

Fabrication of microwell plates and microfluidic devices in polyester films using a cutting printer.

This study reports, for the first time, the possibility to manufacture analytical devices on polyester substrates using a cutting printer. The protocol involves the design of a layout in a graphical software, the cut into polyester films and the lamination against one or multiple polyester films coated with a thermosensitive layer. The feasibility of the proposed approach was demonstrated through the fabrication of 96-microwell plates, 3D microfluidic mixing and distance-based microfluidic devices. The printer has enabled cutting microchannels wider than 300 µm on polyester films and a thickness of 250 µm. Urea and glucose assays were performed on microwell plates aiming for their quantification in artificial urine and serum samples. The presented results revealed good agreement with the expected values. The complexation reaction between Fe2+ and o-phenanthroline was selected as model to investigate the feasibility of the 3D mixing device. Absorbance measurements were recorded for the reaction product performed in both on and off-chip modes. Considering the achieved data, the on-chip mixing exhibited similar behavior when compared to off-chip reaction, thus demonstrating to be efficient to perform mixtures due to the turbulence generated inside three-dimensional channels. Lastly, a distance-based device was designed to detect H2O2 based on the displacement of a dye plug promoted by the oxygen generation using a copper-modified paper sheet. The distance-based peroxymeter revealed a linear behavior in the concentration range between 1 and 5% (v/v) and a LOD equal to 0.5% (65.2 mM). Based on the results herein reported, the proposed method represents a simple and alternative protocol to produce microdevices, using affordable and inexpensive raw materials, within 10 min, and at a cost lower than US$ 0.10 per unit.

The long noncoding RNA KIAA0125 is upregulated in ameloblastomas.

Ameloblastoma and adenomatoid odontogenic tumor (AOT) are jaw tumors derived from the teeth forming apparatus. While ameloblastoma is a destructive, debilitating lesion, with conventional surgical treatment leading to facial deformity and morbodities, AOT shows indolent clinical behavior. The underlying molecular mechanisms associated with their biological behavior are unknown. The use of high-density whole-genome microarray analysis in ameloblastomas and AOT revealed high frequency of genomic gain at 14q32.33, which encompasses the long noncoding RNA (lncRNA) gene KIAA0125. In the present study, we aimed to investigate the expression profile of KIAA0125 in these tumors. Thirteen samples were included (five solid/multicystic ameloblastomas, four AOT, and four dental follicles). The relative quantification of KIAA0125 expression was obtained by qPCR and interactions of KIAA0125 were in silico predicted. We detected higher levels of KIAA0125 transcripts in the ameloblastoma group compared to dental follicles (p = 0.042). The expression levels of KIAA0125 in AOT were not different from that of dental follicles. KIAA0125 was predicted to interact with 41 miRNA families. Four miRNAs of these families have been previously reported differentially expressed in ameloblastoma, being miR-135a-5p, miR-204-5p and miR-205-5p upregulated, and miR-150-5p downregulated. The lncRNA KIAA0125 is likely involved in the ameloblastoma pathobiology. LncRNAs hold strong promise as therapeutic targets and experimental validation of this lncRNA functions may lead to tailored therapies targeting KIAA0125 in extensive and recurrent ameloblastoma cases.

Radium-223 in combination with paclitaxel in cancer patients with bone metastases: safety results from an open-label, multicenter phase Ib study.

PURPOSE: Concomitant treatment with radium-223 and paclitaxel is a potential option for cancer patients with bone metastases; however, myelosuppression risk during coadministration is unknown. This phase Ib study in cancer patients with bone metastases evaluated the safety of radium-223 and paclitaxel. METHODS: Eligible patients had solid tumor malignancies with ≥2 bone metastases and were candidates for paclitaxel. Treatment included seven paclitaxel cycles (90 mg/m2 per week intravenously per local standard of care; 3 weeks on/1 week off) plus six radium-223 cycles (55 kBq/kg intravenously; one injection every 4 weeks, starting at paclitaxel cycle 2). The primary end point was percentage of patients with grade 3/4 neutropenia or thrombocytopenia during coadministration of radium-223 and paclitaxel (cycles 2, 3) versus paclitaxel alone (cycle 1). RESULTS: Of 22 enrolled patients, 15 were treated (safety population), with 7 completing all six radium-223 cycles. Treated patients had primary cancers of breast (n = 7), prostate (n = 4), bladder (n = 1), non-small cell lung (n = 1), myxofibrosarcoma (n = 1), and neuroendocrine (n = 1). No patients discontinued treatment from toxicity of the combination. In the 13 patients who completed cycle 3, the rates of grade 3 neutropenia in cycles 2 and 3 were 31% and 8%, respectively, versus 23% in cycle 1; there were no cases of grade 4 neutropenia or grade 3/4 thrombocytopenia. Breast cancer subgroup safety results were similar to the overall safety population. CONCLUSION: Radium-223 was tolerated when combined with weekly paclitaxel, with no clinically relevant additive toxicities. This combination should be explored further in patients with bone metastases.

Relationships between physical activity, quality of life, and age in women attending social groups for the elderly / Relações entre atividade física, qualidade de vida e idade em mulheres que frequentam grupos sociais de idosos

AIMS: To analyze factors associated with physical activity levels among older women attending social groups for the elderly. METHODS: A cross-sectional study was conducted with elderly women enrolled in the Municipal Social Development Foundation in the city of Tubarão, in south Brazil. Sociodemographic and health status variables were evaluated through questionnaires administered during interviews, and by anthropometric evaluation. The level of physical activity was assessed using the Modified Baecke Questionnaire for the Elderly. Quality of life was assessed using the World Health Organization Quality of Life Assessment for older adults. RESULTS: Out of 306 elderly women included in the study, 214 (69.9%) were defined as physically inactive and 92 (30.1%) were active. The proportion of physically active participants between 60-69 years of age was 52.2%, between 70-79 years was 40.2% and equal or more than 80 years was 7.6% (p=0.011). No other sociodemographic or anthropometric characteristics were associated with physical activity. In the non-adjusted analysis there was association between physical activity and better quality of life, as well as with fewer diseases. There was a weak negative correlation between physical activity and number of diseases (correlation coefficient=0.215) and a weak positive correlation between physical activity and quality of life scores (correlation coefficient=0.284). In the adjusted analysis, physical activity remained as a protection factor for loss of quality of life: prevalence ratio=0.88 (95% confidence interval=0.81-0.96), p=0.003. CONCLUSIONS: The study concluded that physical activity in elderly women was associated with better quality of life, even when adjusted for age

OBJETIVOS: Analisar os fatores associados aos níveis de atividade física em mulheres idosas que frequentam grupos sociais para idosos. MÉTODOS: Estudo transversal, realizado com mulheres idosas cadastradas na Fundação Municipal de Desenvolvimento Social, na cidade de Tubarão, no sul do Brasil. As variáveis sociodemográficas e de estado de saúde foram avaliadas por meio de questionários aplicados durante as entrevistas e por avaliação antropométrica. O nível de atividade física foi avaliado pelo Questionário Baecke Modificado para Idosos. A qualidade de vida foi avaliada pelo questionário World Health Organization Quality of Life assessment for older adults. RESULTADOS: Das 306 idosas incluídas no estudo, 214 (69,9%) foram definidas como fisicamente inativas e 92 (30,1%) como ativas. A proporção de participantes fisicamente ativas entre 60-69 anos de idade foi de 52,2%, entre 70-79 anos foi de 40,2% e igual ou maior que 80 anos foi de 7,6% (p=0,011). Nenhuma outra característica sociodemográfica ou antropométrica foi associada à atividade física. Na análise não ajustada houve associação entre atividade física e melhor qualidade de vida, assim como com menos doenças. Houve correlação negativa fraca entre atividade física e número de doenças (coeficiente de correlação= ­0.215) e positiva fraca entre atividade física e nível de qualidade de vida (coeficiente de correlação=0.284). Na análise ajustada, a atividade física permaneceu como fator de proteção para perda de qualidade de vida: razão de prevalência=0,88 (intervalo de confiança 95%=0,81-0,96), p=0,003. CONCLUSÕES: O estudo concluiu que a atividade física em mulheres idosas foi associada à melhor qualidade de vida, mesmo na análise ajustada por idade.

Uncovering the Formation of Color Gradients for Glucose Colorimetric Assays on Microfluidic Paper-Based Analytical Devices by Mass Spectrometry Imaging.

This study describes the use of mass spectrometry imaging with matrix-assisted laser desorption/ionization (MALDI) and desorption electrospray ionization (DESI) to understand the color gradient generation commonly seen in microfluidic paper-based analytical devices (µPADs). The formation of color gradients significantly impacts assay sensitivity and reproducibility with µPADs but the mechanism for formation is poorly understood. The glucose enzymatic assay using potassium iodide (KI) as a chromogenic agent was selected to investigate the color gradient generated across a detection spot. Colorimetric measurements revealed that the relative standard deviation for the recorded pixel intensities ranged between 34 and 40%, compromising the analytical reliability. While a variety of hypotheses have been generated to explain this phenomenon, few studies have attempted to elucidate the mechanisms associated with its formation. Mass spectrometry imaging using MALDI and DESI was applied to understand the nonuniform color distribution on the detection zone. MALDI experiments were first explored to monitor the spatial distribution of the glucose oxidase and horseradish peroxidase mixture, before and after lateral flow assay with and without KI. MALDI(+)-TOF data revealed uniform enzyme distribution on the detection spots. On the other hand, after the complete assay DESI(-) measurements revealed a heterogeneous shape indicating the presence of iodide and triiodide ions at the zone edge. The reaction product (I3-) is transported by lateral flow toward the zone edge, generating the color gradient. Mass spectrometry imaging has been used for the first time to prove that color gradient forms as result of the mobility small molecules and not the enzyme distribution on µPAD surface.

Reliability of the Mechanical Diagnosis and Therapy System in Patients With Spinal Pain: A Systematic Review.

BACKGROUND: An updated summary of the evidence for the reliability of the Mechanical Diagnosis and Therapy (MDT) system in patients with spinal pain is needed. OBJECTIVE: To investigate the evidence on the intrarater and interrater reliability of MDT in patients with spinal pain. METHODS: Searches in MEDLINE, CINAHL, Embase, PEDro, and Scopus were conducted for this systematic review. We included any study design as long as reliability of the MDT method was tested in patients with spinal pain. We collected data on the reliability of MDT to identify main and subsyndromes, directional preference, the centralization phenomenon, and lateral shift. The methodological quality of studies was assessed using the Quality Appraisal of Diagnostic Reliability and the Guidelines for Reporting Reliability and Agreement Studies checklists. RESULTS: Twelve studies were included (8 studies on back pain, pooled n = 2160 patients; 3 studies on neck pain, pooled n = 45 patients; and 3 studies recruited mixed spinal conditions, pooled n = 389 patients). Studies investigating patients with back pain reported kappa estimates ranging from 0.26 to 1.00 (main and subsyndromes), 0.27 to 0.90 (directional preference), and 0.11 to 0.70 (centralization phenomenon). Kappa estimates for studies investigating neck pain ranged from 0.47 to 0.84 (main and subsyndromes) and 0.46 (directional preference). In mixed populations, kappa estimates ranged from 0.56 to 0.96 (main and subsyndromes). CONCLUSION: The MDT system appears to have acceptable interrater reliability for classifying patients with back pain into main and subsyndromes when applied by therapists who have completed the credentialing examination, but unacceptable reliability in other therapists. We found conflicting evidence regarding the reliability of the MDT system in patients with neck pain or mixed pain locations. J Orthop Sports Phys Ther 2018;48(12):923-933. Epub 22 Jun 2018. doi:10.2519/jospt.2018.7876.