Arthrodesis in Acute and Chronic Lisfranc's Patients: A Retrospective Cohort Study.

Injury to Lisfranc's joint complex affects the longitudinal and transverse arches of the foot and can significantly alter its biomechanics. Some of the previous studies have suggested primary arthrodesis to be superior to open reduction and internal fixation for treating primarily ligamentous Lisfranc injuries. Additionally, arthrodesis is often used for treating chronic Lisfranc injuries, including those which previously underwent open reduction and internal fixation and subsequently developed arthrosis. The purpose of this study was to retrospectively evaluate the outcomes of arthrodesis at the level of Lisfranc's articulation for both acute and chronic injuries. Patients who underwent midfoot arthrodesis surgical procedures between years 2001 and 2017 were retrospectively reviewed. About 187 patients with an average age of 55.9 ± 13.2 years old and a minimum follow-up of 1 year were included in the study. Median time to return to preoperative activities was 11 weeks. Overall successful joint fusion rate was 81.4%. However, concomitantly fused joints of the midfoot and hindfoot, in addition to the tarsometatarsal joints (TMTJ), were included in the overall fusion rate. Fusion rate at the first TMTJ was 90.2% (101 out of 112), second TMTJ was 94.4% (67 out of 71), and third TMTJ was 97.8% (45 out of 46). The present study demonstrates that patients who undergo arthrodesis for both acute and chronic Lisfranc injuries typically can return to activity in under approximately 3 months postoperatively (acute patients significantly faster) with a high union rate at the TMTJs. However, the overall union rate is significantly lower when concomitant proximal midfoot and rearfoot arthrodesis procedures are performed.

Insertional Achilles Tendinopathy: Analysis of 166 Procedures and Return to Activity.

The surgical procedure for Insertional Achilles tendinopathy (IAT) varies widely with no consensus as to approach and documenting return to activity (RTA). This study presents outcomes of surgery for IAT by a single surgeon, documenting activity level and return to activity. From January 2001 through January 2018, 166 procedures were reviewed. Surgery included debridement of the Achilles insertion, resection of the superior calcaneus and bursa, and re-attachment with suture anchors. There were 110 males and 56 females. The majority of patients in the entire cohort were runners (n = 54). The average age of the cohort was 50.3 ± 12.1 years (range 20-80). Average follow-up was 114.0 ± 63.5 months (range 6-222 months). Average RTA for males and females were 6.43 months and 7.22 months, (p = .2), respectively. There was no difference in RTA between patients who had calcific tendinosis (n = 84) and noncalcific tendinosis (n = 82). Complications were 2 infections, 2 DVTs, and 17 deep suture reactions with a total complication rate of 12.6%; there were no re-ruptures postoperatively. There was no significant difference in number of complications between absorbable and nonabsorbable suture in the anchors (p = .41). The average RM score was 1.5 ± 0.7. The RM scores were better for males (p = .002), but there were no differences in RTA or complications between sexes. Overall, 95.8% of the procedures resulted in improved outcome and ability to return to activity including sports. This retrospective investigation shows surgical intervention for IAT yields good results with an average return to activity including sports in approximately 7 months.

Acute Achilles Tendon Rupture Repair in Athletically Active Patients: Results on 188 Tendons.

We report on the outcome of acute Achilles tendon ruptures by a single surgeon using open and percutaneous techniques was performed. This prospective study included 186 patients with 188 ruptured Achilles tendons. A traditional open technique was primarily performed on patients from January 2001 to December 2011. From January 2012 to January 2018, a percutaneous repair was primarily performed. Outcome measures included the Roles and Maudsley (RM) score, ability to perform a single leg heel raise, calf atrophy and return to activity. There were 149 males (average age 42.5 ± 12.7 years) and 39 females (average age 41.7 ± 11.4 years). Of the 188 ruptured tendons (92 repairs on the right Achilles and 96 on the left), 103 were repaired percutaneously and 85 had open repairs. There were 18 (9.6%) complications. Three re-ruptures occurred, one following open and two following percutaneous repairs, all within 12 weeks of the original repair. Two patients developed a Venousthromboembolism (1.0%). Thirteen patients had suture reactions; three infections (1.6%), 11 wound complications (5.8%), and 3 required surgical excision of the suture material (1.6%). Non-absorbable sutures were associated with more wound complications and were more frequently used in open repairs (p = .003). Patients who underwent open repair experienced more wound complications (p = .0001). Patients who underwent percutaneous repair using absorbable suture experienced a lower rate of overall complications (p = .0007). Basketball (n = 29) was the most common sport during which ruptures occurred. Return to activity (RTA) was 8.2 ± 2.9 months. There was no difference for RTA between males and females (p = .54) and RM scores (p= .69), nor surgical technique, and no difference for RTA based on the desired activity (p = .47). 123 of the 188 patients returned to their desired activity (65.5%). There was a statistically significant evidence of a positive association between inability to perform heel-raises and decreased activity (p = .01).

Predictive value of non-specific bronchial challenge testing for respiratory symptoms and lung function in aluminium smelter workers.

OBJECTIVE: To assess the predictive value of bronchial hyper-responsiveness (BHR) for the subsequent development of respiratory symptoms, airflow limitation and decline in lung function among aluminium smelter workers. METHODS: An inception cohort study of new employees at two Australian aluminium smelters was conducted. Participants completed a modified British Medical Research Council respiratory questionnaire, spirometry and a methacholine bronchial challenge test at baseline and at annual follow-up reviews. BHR was defined as PD20 ≤4000 µg. Poisson and mixed effects models were fitted to respiratory symptoms and lung function (forced expiratory volume in 1 s (FEV1) and FEV1/forced vital capacity (FVC)). RESULTS: Baseline interview and lung function testing were completed by 278 workers, who were followed for a median of 4 years. BHR at baseline, present in 82 workers, was not associated with incident wheeze risk ratio (RR)=1.07 (95% CI 0.74 to 1.55) and cough RR=0.78 (95% CI 0.45, 1.35), but there was some increased risk of chest tightness RR=1.40 (95% CI 0.99, 1.98) after adjustment for age, sex, smoking and atopy. BHR at baseline was associated with lower FEV1 and FVC, although the rate of annual decline in FEV1 or FVC was similar between those with or without BHR. The specificity of BHR was 77% for wheeze, 70% for cough and 77% for chest tightness, but the sensitivity was poor, at 33%, 24% and 39%, respectively. CONCLUSION: Methacholine challenge testing at entry to employment was not sufficiently predictive of later adverse respiratory outcomes, and notwithstanding the study limitations is unlikely to be a useful pre-employment or preplacement screening test in the aluminium smelting industry.

USP6 oncogene promotes Wnt signaling by deubiquitylating Frizzleds.

The Wnt signaling pathways play pivotal roles in carcinogenesis. Modulation of the cell-surface abundance of Wnt receptors is emerging as an important mechanism for regulating sensitivity to Wnt ligands. Endocytosis and degradation of the Wnt receptors Frizzled (Fzd) and lipoprotein-related protein 6 (LRP6) are regulated by the E3 ubiquitin ligases zinc and ring finger 3 (ZNRF3) and ring finger protein 43 (RNF43), which are disrupted in cancer. In a genome-wide small interfering RNA screen, we identified the deubiquitylase ubiquitin-specific protease 6 (USP6) as a potent activator of Wnt signaling. USP6 enhances Wnt signaling by deubiquitylating Fzds, thereby increasing their cell-surface abundance. Chromosomal translocations in nodular fasciitis result in USP6 overexpression, leading to transcriptional activation of the Wnt/ß-catenin pathway. Inhibition of Wnt signaling using Dickkopf-1 (DKK1) or a Porcupine (PORCN) inhibitor significantly decreased the growth of USP6-driven xenograft tumors, indicating that Wnt signaling is a key target of USP6 during tumorigenesis. Our study defines an additional route to ectopic Wnt pathway activation in human disease, and identifies a potential approach to modulate Wnt signaling for therapeutic benefit.

Are children more vulnerable to mesothelioma than adults? A comparison of mesothelioma risk among children and adults exposed non-occupationally to blue asbestos at Wittenoom.

OBJECTIVES: The presence of asbestos in public buildings is a legacy of past asbestos use in many developed countries. Of particular concern is the amount and current condition in schools and the vulnerability of children to mesothelioma. Our aim was to compare the risk of mesothelioma between those exposed to blue asbestos as children and as adults at Wittenoom. METHODS: Public sources were used to establish the Wittenoom residents' cohort. Mesothelioma incidence rates per 100 000 person-years at risk were derived for those first exposed to asbestos at Wittenoom as children (<15 years) or adults separately. Proportional hazards survival models examined the slope of the exposure-response relationship between asbestos exposure and incidence of mesothelioma in different sex and age groups. RESULTS: The mesothelioma rate was lower among those first exposed as children (76.8 per 100 000) than those first exposed as adults (121.3 per 100 000). Adjusting for cumulative exposure to asbestos and sex, those exposed as adults had a greater risk of mesothelioma (adjusted HR 2.5, 95% CI 1.7 to 3.7). The slope of the exposure-response relationship did not differ between those exposed as children and those exposed as adults. CONCLUSION: We found no greater susceptibility to mesothelioma among those first exposed to asbestos as children than those first exposed as adults. However, given the long latency of mesothelioma, and the greater years of life yet to be lived by the Wittenoom children, it is likely that there will be more cases of mesothelioma in the future among those first exposed as children.

Is size the only determinant of delayed abdominal closure in pediatric liver transplant?

The aim was to determine the factors associated with the use of delayed abdominal closure in pediatric liver transplantation (LT) and whether this affected outcome. From a prospectively maintained database, transplants performed in children (≤18 years) were identified (October 2010 to March 2015). Primary abdominal closure was defined as mass closure performed at time of transplant. Delayed abdominal closure was defined as mass closure not initially performed at the same time as transplant; 230 children underwent LT. Of these, 176 (76.5%) had primary closure. Age was similar between the primary and delayed groups (5.0 ± 4.9 versus 3.9 ± 5.0 years; P = 0.13). There was no difference in the graft-to-recipient weight ratio (GRWR) in the primary and delayed groups (3.4 ± 2.8 versus 4.1 ± 2.1; P = 0.12). Children with acute liver failure (ALF) were more likely to experience delayed closure then those with chronic liver disease (CLD; P < 0.001). GRWR was similar between the ALF and CLD (3.4 ± 2.4 versus 3.6 ± 2.7; P = 0.68). Primary closure children had a shorter hospital stay (P < 0.001), spent fewer days in pediatric intensive care unit (PICU; P = 0.001), and required a shorter duration of ventilation (P < 0.001). Vascular complications (arterial and venous) were similar (primary 8.2% versus delayed 5.6%; P = 0.52). Graft (P = 0.42) and child survival (P = 0.65) in the primary and delayed groups were similar. Considering timing of mass closure after transplant, patients in the early delayed closure group (<6 weeks) were found to experience a shorter time of ventilation (P = 0.03) and in PICU (P = 0.003). In conclusion, ALF was the main determinant of delayed abdominal closure rather than GRWR. The optimal time for delayed closure is within 6 weeks. The use of delayed abdominal closure does not adversely affect graft/child survival. Liver Transplantation 23 352-360 2017 AASLD.

Longitudinal analysis of respiratory outcomes among bauxite exposed workers in Western Australia.

INTRODUCTION: Occupational exposure to bauxite is common in the aluminium industry but little is known about the associated health effects. This study investigates respiratory health in relation to respirable bauxite dust exposure longitudinally over a 13 year period. METHODS: An inception cohort study recruited 91 male bauxite miners and 363 male alumina refinery workers. Annual measurements of respiratory symptoms and lung function were made. Cumulative exposure to bauxite was derived from job histories and air monitoring data. Mixed-effects modeling was used. RESULTS: No associations were found between cumulative bauxite exposure and respiratory symptoms or lung function. However, when analysis was restricted to the first three rounds, FEV1 was significantly lower in all exposure groups than in those unexposed but with no significant trend. CONCLUSION: Increasing exposure to bauxite dust in the aluminum industry was not associated with respiratory symptoms or consistent decrements in lung function.

Alzheimer Disease: Recent Updates on Apolipoprotein E and Gut Microbiome Mediation of Oxidative Stress, and Prospective Interventional Agents.

Alzheimer's disease (AD) is a current public health challenge and will remain until the development of an effective intervention. However, developing an effective treatment for the disease requires a thorough understanding of its etiology, which is currently lacking. Although several studies have shown the association between oxidative damage and AD, only a few have clarified the specific mechanisms involved. Herein, we reviewed recent preclinical and clinical studies that indicated the significance of oxidative damage in AD, as well as potential antioxidants. Although several factors regulate oxidative stress in AD, we centered our investigation on apolipoprotein E and the gut microbiome. Apolipoprotein E, particularly apolipoprotein E-ε4, can impair the structural facets of the mitochondria. This, in turn, can minimize the mitochondrial functionality and result in the progressive build-up of free radicals, eventually leading to oxidative stress. Similarly, the gut microbiome can influence oxidative stress to a significant degree via its metabolite, trimethylamine N-oxide. Given the various roles of these two factors in modulating oxidative stress, we also discuss the possible relationship between them and provide future research directions.

Respiratory health issues in the Asia-Pacific region: an overview.

The Asia-Pacific region is home to a large heterogeneous population whose respiratory health is influenced by diverse social, economic and environmental factors. Despite this variability, the most prevalent causes of respiratory morbidity and mortality are tobacco smoking, infection, and air pollution. This review aims to summarize current respiratory health issues in the region including smoking-related diseases especially COPD, lung cancer and infectious problems such as pandemic influenza, the severe acute respiratory syndrome coronavirus, bacterial pneumonia and tuberculosis, as well as the contribution of air pollution to respiratory disease. Published data on trends in the epidemiology and management of respiratory diseases and are summarized; finally, the limitations of available data and projections for the future of respiratory health in the region are discussed.

Bone density and quality in patients treated with direct-acting oral anticoagulants versus warfarin.

INTRODUCTION: Direct-acting oral anticoagulants (DOACs) are therapeutic alternatives to warfarin that act independently of vitamin K, thus not affecting bone matrix formation. The aim of this study was to compare bone mineral density (BMD) and microarchitecture in patients treated with DOACs versus warfarin. METHODS: Cross-sectional, observational study in patients using oral anticoagulants for >1 year and a paired control group (CG). Based on the type of anticoagulant used, the patients were grouped into a DOAC (DOACG) or warfarin (WG) group. All patients filled out a questionnaire and underwent BMD evaluation and trabecular bone score (TBS) measurement. RESULTS: In all, 150 patients were included (50 patients in each group). The mean age was 60.49 ± 7.48 years, and most participants were men (64%). The most frequent comorbidities were hypertension, dyslipidemia, and hyperglycemia (comparison between groups p > 0.05). Low bone mass was diagnosed in 42%, 50%, and 66% of the patients in the CG, DOACG, and WG, respectively (p = 0.012). On logistic regression analysis, BMD was associated with body mass index (BMI; odds ratio [OR] 0.846, 95% confidence interval [CI] 0.763-0.926, p = 0.001), creatinine level (OR 0.024, 95%CI 0.001-0.434, p = 0.017), and TBS value (OR 17.777, 95%CI 4.526-96.903, p = 0.000). The mean TBS decreased progressively from the CG to the DOACG and WG (1.328 ± 0.112, 1.264 ± 0.138, and 1.203 ± 0.112, respectively, p < 0.001). On multivariate linear regression, negative predictors of TBS included warfarin use (-0.06, 95%CI -0.11 to -0.02, p = 0.006), BMI (-0.01, 95%CI -0.01 to -0.00, p < 0.001), and hyperglycemia (-0.07, 95%CI -0.11 to -0.03, p = 0.003), while positive predictors were an active IPAQ classification (0.06, 95%CI 0.01-0.11, p = 0.029) and family history of hip fracture (0.07, 95%CI 0.01-0.14, p = 0.029). CONCLUSION: Patients using anticoagulants have lower BMD and TBS values compared with controls. This negative effect on bone was more pronounced with warfarin, but was also seen with DOACs.

Caustic Mist Exposure and Respiratory Outcomes in a Cohort Study of Alumina Refinery Workers.

A common chemical exposure in alumina refining is caustic mist. Although recognized as a strong airways irritant, little is known of the chronic respiratory effects of caustic mist in alumina refining. A suitable metric for caustic mist exposure assessment in alumina refining for epidemiological purposes has not been identified. Peak exposure is likely to be important, but is difficult to assess in epidemiological studies. In this study, we investigate the respiratory effects of caustic mist in an inception cohort (n = 416) of alumina refinery workers and describe the development and use of a peak exposure metric for caustic mist. We then compare the results with a metric based on duration of exposure. Participants were interviewed annually about respiratory symptoms and had a lung function test. Job history data were collected from each interview and levels of caustic mist were measured periodically by air monitoring. We found a weak association between the caustic mist peak exposure metric and reported cough (P for linear trend = 0.079) with the highest peak exposure group odds ratio = 2.32 (95% confidence interval: 1.27, 4.22). For lung function, we found declines in the forced expiratory volume in 1 second and forced vital capacity for changes in annual and absolute lung function for both metrics of exposure, but only the ratio of absolute lung function was statistically associated with an increasing duration of caustic exposure (P for linear trend = 0.011). In this cohort, we did not observe an association with respiratory symptoms or consistent decrements in lung function. There was little difference between the exposure metrics used for investigation of the chronic effects from caustic mist.

Is potroom asthma due more to sulphur dioxide than fluoride? An inception cohort study in the Australian aluminium industry.

OBJECTIVES: Although an asthma-like syndrome has been recognised in aluminium smelter workers for over 70 years, the causal agent has been difficult to identify. METHODS: An inception cohort study was conducted at two Australian aluminium smelters where 446 employees participated over a period of 9 years. Cumulative exposures between interviews were estimated from job histories using a task exposure matrix based on measurements in the smelters. Participants completed an MRC respiratory questionnaire, spirometry and methacholine challenge test. Data were analysed with generalised estimating equations to allow for repeated measurements of each participant. RESULTS: Wheeze and chest tightness, the two symptoms most closely related to asthma, showed associations with occupational exposures. SO(2) exposure was significantly associated with these symptoms, bronchial hyper-responsiveness (BHR) to methacholine (a feature of asthma), airflow limitation (reduced forced expiratory volume in 1 second/forced vital capacity ratio) and longitudinal decline in lung function. Fluoride exposure was associated with the same outcomes, but less strongly. Inhalable dust and the benzene soluble fraction (BSF) were associated with symptoms of asthma and BHR. Although many of the exposures were highly correlated, further modelling suggested that of the known respiratory irritants, SO(2) was more likely than fluoride to be primarily responsible for the symptoms observed. Fluoride, inhalable dust and SO(2) were the most important airborne contaminants associated with effects on lung function. CONCLUSIONS: The observed effects were detected at contaminant levels within occupational exposure standards, so further reductions are required, particularly in SO(2) exposures.

Physiological and functional responses of water-cooled versus traditional radiofrequency ablation of peripheral nerves in rats.

BACKGROUND AND OBJECTIVES: Several clinical studies have focused on assessing the effectiveness of different radiofrequency ablation (RFA) modalities in pain management. While a direct head-to-head clinical study is needed, results from independent studies suggest that water-cooled RFA (CRFA) may result in longer lasting pain relief than traditional RFA (TRFA). The primary purpose of this study was, therefore, to investigate in a preclinical model, head-to-head differences between the two RFA technologies. METHODS: RFA was performed in a rat sciatic nerve model (n=66) in two groups: (1) TRFA or (2) CRFA. The surgeon was not blinded to the treatment; however, all the physiological endpoints were assessed in a blinded fashion which include histological, MRI, and nerve function assessment via electromyography. RESULTS: The energy delivered by the generator for CRFA was significantly higher compared with TRFA. Histological staining of nerves harvested immediately following CRFA exhibited extended length and multiple zones of thermal damage compared with TRFA-treated nerves. MRI scans across 4 weeks following treatment showed edematous/inflammatory zones present for longer times following CRFA. Finally, there was greater attenuation and prolonged loss of nerve function measured via electromyography in the CRFA group. CONCLUSIONS: This study shows that CRFA has greater energy output, as well as more pronounced structural and functional changes elicited on the peripheral nerves compared with TRFA. While these preclinical data will need to be confirmed with a large clinical randomized controlled trial, we are encouraged by the direction that they may have set for those trials.

Trabecular bone score (TBS) and bone mineral density in patients with long-term therapy with warfarin.

In this study, we compared patients using the anticoagulant warfarin for more than a year with a control group with similar characteristics but without using the drug. We demonstrated worse BMD and bone quality by trabecular bone score (TBS) in patients using warfarin for more than 1 year. PURPOSE: Evaluate the bone mineral density (BMD) and the trabecular bone score (TBS) of patients taking warfarin for more than 1 year compared with a control group. METHODS: Male patients aged 25-65 years in warfarin use for more than 1 year were included. Patients answered a questionnaire regarding lifestyle habits and realized a dual X-ray densitometry (DXA) (lumbar spine and hip), and TBS was evaluated. RESULTS: From the 96 patients invited, 33 patients accepted to participate and comprised the warfarin group (WG), and 3 were excluded. The control group (CG) was composed of 21 individuals matched by age and race. The mean age of WG was 57.0 ± 7.6 and in the CG 54.0 ± 10.6 years (p = 0.095). The BMD in WG was lower than that in the CG in all sites (spine p < 0.001, total hip p = 0.001, and femoral neck p = 0.005). A longer time of warfarin use increased the likelihood of having low BMD (OR = 1.239, CI 1.064-1.674, p = 0.01), whereas high BMI decreased it (OR = 0.732, CI 0.533-0.918, p = 0.03). The TBS was lower in WG than the CG (p = 0.04). Lower TBS was associated with hypertension in both groups and to the hip BMD (neck and total) (p < 0.005) in the WG. In the multivariate analysis, only hypertension (- 0.10, CI - 0.17 to - 0.03, p = 0.008) and total hip BMD ( 0.26, CI 0.07-0.46, p = 0.009) influenced TBS. CONCLUSION: We demonstrated an association between worsening of BMD and bone quality in patients taking warfarin for more than 1 year.

Asthma and genes encoding components of the vitamin D pathway.

BACKGROUND: Genetic variants at the vitamin D receptor (VDR) locus are associated with asthma and atopy. We hypothesized that polymorphisms in other genes of the vitamin D pathway are associated with asthma or atopy. METHODS: Eleven candidate genes were chosen for this study, five of which code for proteins in the vitamin D metabolism pathway (CYP27A1, CYP27B1, CYP2R1, CYP24A1, GC) and six that are known to be transcriptionally regulated by vitamin D (IL10, IL1RL1, CD28, CD86, IL8, SKIIP). For each gene, we selected a maximally informative set of common SNPs (tagSNPs) using the European-derived (CEU) HapMap dataset. A total of 87 SNPs were genotyped in a French-Canadian family sample ascertained through asthmatic probands (388 nuclear families, 1064 individuals) and evaluated using the Family Based Association Test (FBAT) program. We then sought to replicate the positive findings in four independent samples: two from Western Canada, one from Australia and one from the USA (CAMP). RESULTS: A number of SNPs in the IL10, CYP24A1, CYP2R1, IL1RL1 and CD86 genes were modestly associated with asthma and atopy (p < 0.05). Two-gene models testing for both main effects and the interaction were then performed using conditional logistic regression. Two-gene models implicating functional variants in the IL10 and VDR genes as well as in the IL10 and IL1RL1 genes were associated with asthma (p < 0.0002). In the replicate samples, SNPs in the IL10 and CYP24A1 genes were again modestly associated with asthma and atopy (p < 0.05). However, the SNPs or the orientation of the risk alleles were different between populations. A two-gene model involving IL10 and VDR was replicated in CAMP, but not in the other populations. CONCLUSION: A number of genes involved in the vitamin D pathway demonstrate modest levels of association with asthma and atopy. Multilocus models testing genes in the same pathway are potentially more effective to evaluate the risk of asthma, but the effects are not uniform across populations.

Rap1 promotes cell spreading by localizing Rac guanine nucleotide exchange factors.

The Ras-related GTPase Rap1 stimulates integrin-mediated adhesion and spreading in various mammalian cell types. Here, we demonstrate that Rap1 regulates cell spreading by localizing guanine nucleotide exchange factors (GEFs) that act via the Rho family GTPase Rac1. Rap1a activates Rac1 and requires Rac1 to enhance spreading, whereas Rac1 induces spreading independently of Rap1. Active Rap1a binds to a subset of Rac GEFs, including VAV2 and Tiam1 but not others such as SWAP-70 or COOL-1. Overexpressed VAV2 and Tiam1 specifically require Rap1 to promote spreading, even though Rac1 is activated independently of Rap1. Rap1 is necessary for the accumulation of VAV2 in membrane protrusions at the cell periphery. In addition, if VAV2 is artificially localized to the cell edge with the subcellular targeting domain of Rap1a, it increases cell spreading independently of Rap1. These results lead us to propose that Rap1 promotes cell spreading by localizing a subset of Rac GEFs to sites of active lamellipodia extension.

A inserção da Medicina Veterinária em uma Residência Multiprofissional em Saúde da Família e Comunidade: um relato de experiência

Objetivou-se com o presente trabalho descrever a experiência vivenciada por residentes da Medicina Veterinária (MV) durante pandemia da COVID-19. Trata-se de um relato de experiência sobre a inserção de residentes da MV no Programa de Residência Multiprofissional em Saúde da Família e Comunidade (PRMSFC) na Atenção Básica (AB) do município de João Pessoa - PB, durante o período de março de 2021 a fevereiro de 2022. Os primeiros desafios encontrados foram atividades concentradas em consultas, testagens e vacinações, e a falta de informação sobre o trabalho da MV. Os territórios das Unidades de Saúde da Família (USF) caracterizaram-se por áreas com desmatamento, urbanização, falta de saneamento básico, acúmulo de lixo, presença de animais de rua, agrícolas, sinantrópicos e peçonhentos. Nas USF foram observados casos de diversas zoonoses, como esporotricose, toxoplasmose e acidentes com animais peçonhentos. Foram realizadas ações de educação em saúde e articulações com outros serviços. Alguns problemas que limitaram a inserção da MV foram ausência de médicos veterinários na AB, dificuldades com a preceptoria e AB centrada no atendimento ambulatorial. A presença da MV na AB mostrou-se importante para o diagnóstico, notificação, promoção e prevenção em saúde de doenças e agravos da interface ambiente-animal-ser humano.

Overexpression of mTOR and p(240-244)S6 in IDH1 Wild-Type Human Glioblastomas Is Predictive of Low Survival.

PI3K/Akt/mTOR pathway activation is a hallmark of high-grade gliomas, which prompted clinical trials for the use of PI3K and mTOR inhibitors. However, the poor results in the original trials suggested that better patient profiling was needed for such drugs. Thus, accurate and reproducible monitoring of mTOR complexes can lead to improved therapeutic strategies. In this work, we evaluated the expression and phosphorylation of mTOR, RAPTOR, and rpS6 in 195 human astrocytomas and 30 normal brain tissue samples. The expression of mTOR increased in glioblastomas, whereas mTOR phosphorylation, expression of RAPTOR, and expression and phosphorylation of rpS6 were similar between grades. Interestingly, the overexpression of total and phosphorylated mTOR as well as phosphorylated rpS6 (residues 240-244) were associated with wild-type IDH1 only glioblastomas. The expression and phosphorylation of mTOR and phosphorylation of rpS6 at residues 240-244 were associated with a worse prognosis in glioblastomas. Our results suggest that mTOR and rpS6 could be used as markers of overactivation of the PI3K-mTOR pathway and are predictive factors for overall survival in glioblastomas. Our study thus suggests that patients who harbor IDH1 wild-type glioblastomas might have increased benefit from targeted therapy against mTOR.