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Crosstalk between the actin and microtubule cytoskeletons is important for many cellular processes. Recent studies have shown that microtubules and F-actin can assemble to form a composite structure where F-actin occupies the microtubule lumen. Whether these cytoskeletal hybrids exist in physiological settings and how they are formed is unclear. Here, we show that the short-crossover Class I actin filament previously identified inside microtubules in human HAP1 cells is cofilin-bound F-actin. Lumenal F-actin can be reconstituted in vitro, but cofilin is not essential. Moreover, actin filaments with both cofilin-bound and canonical morphologies reside within human platelet microtubules under physiological conditions. We propose that stress placed upon the microtubule network during motor-driven microtubule looping and sliding may facilitate the incorporation of actin into microtubules.
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Citoesqueleto de Actina , Actinas , Plaquetas , Microtúbulos , Microtúbulos/metabolismo , Humanos , Citoesqueleto de Actina/metabolismo , Plaquetas/metabolismo , Actinas/metabolismo , Fatores de Despolimerização de Actina/metabolismo , Microscopia CrioeletrônicaRESUMO
Inadequate care within Tanzania's primary health system contributes to thousands of preventable maternal and child deaths, and unwanted pregnancies each year. A key contributor is lack of coordination between three primary healthcare actors: public sector Community Health Workers (CHWs) and health facilities, and private sector Accredited Drug Dispensing Outlets (ADDOs). The Afya-Tek program aims to improve the continuity of care amongst these actors in Kibaha district, through a mobile-application based digital referral system that focuses on improving maternal, child and adolescent health. The digital system called Afya-Tek was co-created with users and beneficiaries, and utilises open-source technology in-line with existing government systems. The system guides healthcare actors with individualised decision support during client visits and recommends accurate next steps (education, treatment, or referral). From July 2020 to June 2023, a total of 241,000 individuals were enrolled in the Afya-Tek program covering 7,557 pregnant women, 6,582 postpartum women, 45,900 children, and 25,700 adolescents. CHWs have conducted a total of 626,000 home visits to provide health services, including screening clients for danger signs. This has resulted in 38,100 referrals to health facilities and 24,300 linkages to ADDOs. At the ADDO level, 48,552 clients self-presented; 33% of children with pneumonia symptoms received Amoxicillin; 34% of children with diarrhoea symptoms received ORS and zinc; and 4,203 referrals were made to nearest health facilities. Adolescents preferred services at ADDOs as a result of increased perceived privacy and confidentiality. In total, 89% of all referrals were attended by health facilities. As the first digital health program in Tanzania to demonstrate the linkage among public and private sector primary healthcare actors, Afya-Tek holds promise to improve maternal, child and adolescent health as well as for scale-up and sustainability, through incorporation of other disease conditions and integration with government's Unified Community System (UCS).
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Continuidade da Assistência ao Paciente , Humanos , Tanzânia , Adolescente , Feminino , Criança , Continuidade da Assistência ao Paciente/organização & administração , Gravidez , Agentes Comunitários de Saúde , Tecnologia Digital , Saúde da Criança , Encaminhamento e Consulta , Adulto , Pré-Escolar , Saúde do Adolescente , MasculinoRESUMO
IMPORTANCE: Women are a growing cohort within the U.S. military. Pelvic floor health is a component of health maintenance for which support needs vary by sex. The American Journal of Obstetrics & Gynecology reports that 1 in 4 women is affected by moderate to severe pelvic floor dysfunction (PFD). Understanding the specific experience of female service members is warranted for health care optimization and preservation of force readiness. OBJECTIVE: We aimed to identify the prevalence, incidence, and risk factors associated with incident PFD in active-duty females during an 11-year window. STUDY DESIGN: We used the Medical Assessment and Readiness System at Womack Army Medical Center, which includes medical record and personnel data from 2011 to 2022. Pelvic floor dysfunction diagnoses were identified using diagnosis codes and analyzed with respect to demographic parameters. RESULTS: Between 2011 and 2022, 32,996 of 550,303 active-duty females were diagnosed with PFD (period prevalence: 6.00%). Using 2011-2012 as a washout period, 27,046 of 486,558 participants were diagnosed during 1,879,990.90 person-years of follow-up (incidence rate: 14.39 cases per 1,000 person-years). The incidence rate of PFD increased in both new and established active-duty females. Increasing time since service entry was the strongest, statistically significant independent predictor of PFD. Three or more deployments and specific physical fitness scoring were also predictors of PFD. CONCLUSIONS: The incidence rate of PFD among female service members is increasing, and multiple military-specific factors predict PFD. As the percentage of women in active-duty service continues to grow, additional investigation is needed to confirm PFD trends, illuminate other predictors, and prevent adverse outcomes.
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BACKGROUND AND PURPOSE: Thromboxane A2 (TXA2) is a prostanoid produced during platelet activaton, important in enhancing platelet reactivity by activation of TP receptors. However, due to the short half-life, studying TXA2 signalling is challenging. To enhance our understanding of TP receptor-mediated platelet biology, we therefore synthesised mono and difluorinated TXA2 analogues and explored their pharmacology on heterologous and endogenously expressed TP receptor function. EXPERIMENTAL APPROACH: Platelet functional and signalling responses were studied using aggregometry, Ca2+ mobilisation experiments and immunoblotting and compared with an analogue of the TXA2 precursor prostaglandin H2, U46619. Gαq/Gαs receptor signalling was determined using a bioluminescence resonance energy transfer (BRET) assay in a cell line overexpression system. KEY RESULTS: BRET studies revealed that F-TXA2 and F2-TXA2 promoted receptor-stimulated TP receptor G-protein activation similarly to U46619. Unexpectedly, F2-TXA2 caused reversible aggregation in platelets, whereas F-TXA2 and U46619 induced sustained aggregation. Blocking the IP receptor switched F2-TXA2-mediated reversible aggregation into sustained aggregation. Further BRET studies confirmed F2-TXA2-mediated IP receptor activation. F2-TXA2 rapidly and potently stimulated platelet TP receptor-mediated protein kinase C/P-pleckstrin, whereas IP-mediated protein kinase A/P-vasodilator-stimulated phosphoprotein was more delayed. CONCLUSION AND IMPLICATIONS: F-TXA2 is a close analogue to TXA2 used as a selective tool for TP receptor platelet activation. In contrast, F2-TXA2 acts on both TP and IP receptors differently over time, resulting in an initial wave of TP receptor-mediated platelet aggregation followed by IP receptor-induced reversibility of aggregation. This study reveals the potential difference in the temporal aspects of stimulatory and inhibitory pathways involved in platelet activation.
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As anaesthesiologists face increasing clinical demands and a limited and competitive funding environment for academic work, the sustainability of academic anaesthesiologists has never been more tenuous. Yet, the speciality needs academic anaesthesiologists in many roles, extending beyond routine clinical duties. Anaesthesiologist educators, researchers, and administrators are required not only to train future generations but also to lead innovation and expansion of anaesthesiology and related specialities, all to improve patient care. This group of early career researchers with geographically distinct training and practice backgrounds aim to highlight the diversity in clinical and academic training and career development pathways for anaesthesiologists globally. Although multiple routes to success exist, one common thread is the need for consistent support of strong mentors and sponsors. Moreover, to address inequitable opportunities, we emphasise the need for diversity and inclusivity through global collaboration and exchange that aims to improve access to research training and participation. We are optimistic that by focusing on these fundamental principles, we can help build a more resilient and sustainable future for academic anaesthesiologists around the world.
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Anestesiologia , Humanos , Mentores , Anestesiologistas , PesquisadoresRESUMO
SIGNIFICANCE: This pilot randomized trial, the first to evaluate a specific base-in relieving prism treatment strategy for childhood intermittent exotropia, did not support proceeding to a full-scale clinical trial. Defining and measuring prism adaptation in children with intermittent exotropia are challenging and need further study. PURPOSE: This study aimed to determine whether to proceed to a full-scale trial of relieving base-in prism spectacles versus refractive correction alone for children with intermittent exotropia. METHODS: Children 3 years old to those younger than 13 years with distance intermittent exotropia control score of ≥2 points on the Intermittent Exotropia Office Control Scale (Strabismus 2006;14:147-150; 0 [phoria] to 5 [constant]), ≥1 episode of spontaneous exotropia, and 16 to 35∆ by prism-and-alternate-cover test, who did not fully prism adapt on a 30-minute in-office prism-adaptation test were randomized to base-in relieving prism (40% of the larger of distance and near exodeviations) or nonprism spectacles for 8 weeks. A priori criteria to conduct a full-scale trial were defined for the adjusted treatment group difference in mean distance control: "proceed" (≥0.75 points favoring prism), "uncertain" (>0 to <0.75 points favoring prism), or "do not proceed" (≥0 points favoring nonprism). RESULTS: Fifty-seven children (mean age, 6.6 ± 2.2 years; mean baseline distance control, 3.5 points) received prism (n = 28) or nonprism (n = 29) spectacles. At 8 weeks, mean control values were 3.6 and 3.3 points in prism (n = 25) and nonprism (n = 25) groups, respectively, with an adjusted difference of 0.3 points (95% confidence interval, -0.5 to 1.1 points) favoring nonprism (meeting our a priori "do not proceed" criterion). CONCLUSIONS: Base-in prism spectacles, equal to 40% of the larger of the exodeviations at distance or near, worn for 8 weeks by 3- to 12-year-old children with intermittent exotropia did not yield better distance control than refractive correction alone, with the confidence interval indicating that a favorable effect of 0.75 points or larger is unlikely. There was insufficient evidence to warrant a full-scale randomized trial.
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Exotropia , Criança , Humanos , Pré-Escolar , Exotropia/terapia , Óculos , Projetos Piloto , Refração Ocular , Testes VisuaisRESUMO
SummaryOpioids are often used to provide postsurgical analgesia but may cause harm if used inappropriately. We introduced an opioid stewardship program in three Melbourne hospitals to reduce the inappropriate use of opioids after patient discharge. The program had four pillars: prescriber education, patient education, a standardised quantity of discharge opioids, and general practitioner (GP) communication. Following introduction of the program, we undertook this prospective cohort study. The study aimed to describe post-program discharge opioid prescribing, patient opioid use and handling, and the impact of patient demographics, pain and surgical treatment factors on discharge prescribing. We also evaluated compliance with the program components. We recruited 884 surgical patients from the three hospitals during the ten-week study period. Discharge opioids were dispensed to 604 (74%) patients, with 20% receiving slow-release opioids. Junior medical staff undertook 95% of discharge opioid prescribing, which was guideline-compliant for 78% of patients. Of the patients discharged with opioids, a GP letter was sent for only 17%. Follow-up at two weeks was successful in 423 (70%) patients and in 404 (67%) at three months. At the three-month follow-up, 9.7% of patients reported ongoing opioid use; in preoperatively opioid naïve patients, the incidence was 5.5%. At the two-week follow-up, only 5% reported disposal of excess opioids, increasing to 26% at three months. Ongoing opioid therapy at three months in our study cohort (9.7%; 39/404) was associated with preoperative opioid consumption and higher pain scores at the three-month follow-up. The introduction of the opioid stewardship program resulted in highly guideline-compliant prescribing, but hospital-to-GP communication was uncommon and opioid disposal rates were low. Our findings suggest that opioid stewardship programs can improve postoperative opioid prescribing, use and handling, but the realisation of these gains will require effective program implementation.
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Analgésicos Opioides , Alta do Paciente , Humanos , Estudos Prospectivos , Dor Pós-Operatória/tratamento farmacológico , Padrões de Prática MédicaRESUMO
BACKGROUND: Emollients are universally recommended for atopic dermatitis/eczema ('eczema'), to improve the skin barrier and reduce symptoms. However, our knowledge of the frequency and nature of adverse effects associated with their use is limited. OBJECTIVES: We sought to determine how well adverse events are reported in randomized controlled trials (RCTs) of emollients for eczema. METHODS: MEDLINE was searched from inception (1946) to May 2022. Inclusion criteria were RCTs of moisturizers or emollients used as a leave-on treatment (as the intervention or control) in adults or children with eczema. Exclusion criteria were non-RCTs; patients with other diagnoses included; use of emollient as bath additives, soap substitutes or as preventative; and not published in English. References of eligible papers were reviewed for any additional, relevant research. Data were extracted into an Excel spreadsheet and analysed descriptively. An assessment of study quality was carried out using the Joanna Briggs Institute tool for RCTs. RESULTS: From 369 potential papers, 35 papers (reporting on 34 studies) were included. Most research was conducted in research centres or hospitals (unclear in 34%). In total, 89% reported collecting data on adverse events related to emollient treatment use but the methods used were poorly reported (40% unclear). Four papers used patient questionnaires/diaries. However, it was unclear how and what was collected as only two studies showed the questionnaires used. CONCLUSIONS: Reporting of adverse events related to emollient use in trials of patients with eczema is poor and inconsistent. Agreement should be reached on how and what adverse events should be collected, to standardize reporting across studies.
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Dermatite Atópica , Eczema , Adulto , Criança , Humanos , Dermatite Atópica/tratamento farmacológico , Eczema/tratamento farmacológico , Emolientes/efeitos adversos , Projetos de Pesquisa , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
The cellular mechanisms of autism spectrum disorder (ASD) are poorly understood. Cumulative evidence suggests that abnormal synapse function underlies many features of this disease. Astrocytes regulate several key neuronal processes, including the formation of synapses and the modulation of synaptic plasticity. Astrocyte abnormalities have also been identified in the postmortem brain tissue of ASD individuals. However, it remains unclear whether astrocyte pathology plays a mechanistic role in ASD, as opposed to a compensatory response. To address this, we combined stem cell culturing with transplantation techniques to determine disease-specific properties inherent to ASD astrocytes. We demonstrate that ASD astrocytes induce repetitive behavior as well as impair memory and long-term potentiation when transplanted into the healthy mouse brain. These in vivo phenotypes were accompanied by reduced neuronal network activity and spine density caused by ASD astrocytes in hippocampal neurons in vitro. Transplanted ASD astrocytes also exhibit exaggerated Ca2+ fluctuations in chimeric brains. Genetic modulation of evoked Ca2+ responses in ASD astrocytes modulates behavior and neuronal activity deficits. Thus, this study determines that astrocytes derived from ASD iPSCs are sufficient to induce repetitive behavior as well as cognitive deficit, suggesting a previously unrecognized primary role for astrocytes in ASD.
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Astrócitos , Transtorno do Espectro Autista , Animais , Astrócitos/fisiologia , Transtorno do Espectro Autista/genética , Hipocampo/patologia , Camundongos , Plasticidade Neuronal/fisiologia , Neurônios/fisiologia , Sinapses/fisiologiaRESUMO
Purpose The purpose of this study was to compare radiographic outcomes in patients treated with the traditional method of open reduction, internal fixation (ORIF) and casting as compared with those treated with ORIF and dorsal spanning plate (DSP) fixation. We hypothesized that the application of a DSP to augment the repair of perilunate dislocations would maintain carpal stability while also allowing early loadbearing through the carpus. Materials and Methods This is a retrospective radiographic review of patients with a perilunate dislocation, who were treated with ORIF and casting or ORIF with a dorsal spanning plate between 2012-2018. Scapholunate (SL) and lunotriquetral (LT) intervals were measured immediately after the index surgery and after scheduled hardware removal. A total of 28 patients met inclusion criteria, including 13 cases with traditional treatment and 15 cases with dorsal spanning plate fixation. Results Comparison of the change in SL interval and LT interval between the 13 patients in the traditional treatment group and the 15 patients in the DSP group did not yield any clinically relevant variation after statistical analysis. Both groups demonstrated minimal change in the radiographic markers of carpal stability from postoperative radiographs obtained immediately after the index repair and after the removal of hardware. Conclusion DSP fixation placed at the index surgery with early loadbearing for the treatment of perilunate dislocation is not inferior to the current mainstay of treatment consisting of cast immobilization without loadbearing and does not confer any increased carpal instability in comparison to ORIF and casting.
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Fungal communities (the mycobiota) are an integral part of the gut microbiota, and the disruption of their integrity contributes to local and gut-distal pathologies. Yet, the mechanisms by which intestinal fungi promote homeostasis remain unclear. We characterized the mycobiota biogeography along the gastrointestinal tract and identified a subset of fungi associated with the intestinal mucosa of mice and humans. Mucosa-associated fungi (MAF) reinforced intestinal epithelial function and protected mice against intestinal injury and bacterial infection. Notably, intestinal colonization with a defined consortium of MAF promoted social behavior in mice. The gut-local effects on barrier function were dependent on IL-22 production by CD4+ T helper cells, whereas the effects on social behavior were mediated through IL-17R-dependent signaling in neurons. Thus, the spatial organization of the gut mycobiota is associated with host-protective immunity and epithelial barrier function and might be a driver of the neuroimmune modulation of mouse behavior through complementary Type 17 immune mechanisms.
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Microbioma Gastrointestinal , Micobioma , Receptores de Interleucina-17/metabolismo , Comportamento Social , Animais , Fungos , Imunidade nas Mucosas , Mucosa Intestinal , Camundongos , MucosaRESUMO
BACKGROUND: Motor vehicle collisions (MVCs) are the leading cause of unintentional death among children and adolescents; however, public awareness and use of appropriate restraint recommendations are perceived as deficient. We aimed to investigate the use of child safety restraints and examine outcomes in our community. METHODS: We retrospectively queried a level 1 trauma registry for pediatric (0-18 y) MVC patients from October 2013 to December 2018. Demographic and clinical variables were recorded. Data regarding appropriate restraint use by age group were examined. RESULTS: Four hundred thirty-four cases of pediatric MVC were identified. Overall, 53% were improperly restrained or unrestrained. Sixty-two percent of car seat age and 51% of booster age children were improperly restrained or unrestrained altogether. Fifty-nine percent of back seat riding, seatbelt age were improperly restrained/unrestrained, with 26% riding in the front. Fifty-one percent of seatbelt-only adolescents were not belted. Black, non-Hispanic children were more often improperly restrained/unrestrained compared to Hispanics (63% versus 48%, P = 0.001). Improperly restrained/unrestrained children had higher injury severity (10% versus 4% Injury Severity Score > 25, P = 0.021), require operative/interventional radiology (33% versus 19%, P = 0.001), and be discharged to rehabilitation or skilled nursing facility (5.2% versus 1.5%, P = 0.033). Mortality in adolescents was higher among those unrestrained (5.2% versus 0.8%, P = 0.034). CONCLUSIONS: Although efforts to improve adherence to restraint regulations have greatly increased in the last decade, more than half of children in MVC are still improperly restrained. Injury prevention services and community outreach is essential to educate the most vulnerable populations, especially those with infants and toddlers, on adequate motor vehicle safety measures in our community.
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Sistemas de Proteção para Crianças , Ferimentos e Lesões , Acidentes de Trânsito , Adolescente , Criança , Humanos , Lactente , Veículos Automotores , Estudos Retrospectivos , Cintos de SegurançaRESUMO
Gastroesophageal reflux (GER) is a functional self-limiting condition in neonates. When pathologic, it is called GER disease (GERD). There are wide variations in the management of signs, symptoms, and complications associated with GERD in the neonatal intensive care unit (NICU). Evidence does not support an empiric trial of GERD medications as a diagnostic tool or therapy in premature infants. METHODS: A multidisciplinary team developed evidence-based clinical practice guidelines (CPG) for GERD management. Process improvement included developing a GERD management algorithm, electronic order sets, and education for all providers. Multiple plan-do-study-act cycles done. RESULTS: Implementation of standardized GERD management guideline, decreased the overall use of antireflux medications from baseline, 15.1%-6.8% [χ2 (1, N = 1259) = 12.98, P < 0.001]. There was elimination of GERD medication use in preterm from baseline of 19.3% [χ2 (1, N = 220) = 12.18, P < 0.001]. The most frequently used GERD medication was lansoprazole, with an incorrect initial dosing rate of 55.0% that deceased to zero [χ2 (1, N = 33) = 10.73, P = 0.001]. Appropriate testing with PH probe with 24-hour multichannel impedance was observed (17.1%-28.0%) identifying patients with correct GERD diagnosis [χ2 (1, N = 101) = 1.41, P = 0.236]. Length of stay for GERD patient's improved from a median of 89-53 days. CONCLUSION: Standardizing clinical management leads to best practices for GERD management with appropriate diagnostic testing, eliminating incorrect medication dosing, and improved patient safety with value-based outcomes.
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BACKGROUND: Ankle fractures are common and may require open reduction and internal fixation (ORIF). Literature is scarce evaluating the associations of opioid use disorder (OUD) with ORIF postoperative outcomes. This study investigates whether OUD patients have increased (1) costs of care, (2) emergency room visits, and (3) readmission rates. METHODS: ORIF patients with a 90-day history of OUD were identified using an administrative claims database. OUD patients were matched (1:4) to controls by age, sex, and medical comorbidities. The Welch t-test determined the significance of cost of care. Logistic regression yielded odds ratios (ORs) for emergency room visits and 90-day readmission rates. RESULTS: A total of 2183 patients underwent ORIF (n = 485 with OUD vs n = 1698 without OUD). OUD patients incurred significantly higher costs of care compared with controls ($5921.59 vs $5128.22, P < .0001). OUD patients had a higher incidence and odds of emergency room visits compared with controls (3.50% vs 0.64%; OR = 5.57, 95% CI = 2.59-11.97, P < .0001). The 90-day readmission rates were not significantly different between patients with and without OUD (8.65% vs 7.30%; OR = 1.20, 95% CI = 0.83-1.73, P = .320). CONCLUSION: OUD patients have greater costs of care and odds of emergency room visits within 90 days following ORIF.Levels of Evidence: Level III: Retrospective cohort study.
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Analgésicos Opioides/efeitos adversos , Analgésicos Opioides/economia , Fraturas do Tornozelo/cirurgia , Fixação Interna de Fraturas/economia , Fixação Interna de Fraturas/métodos , Custos de Cuidados de Saúde , Redução Aberta/economia , Redução Aberta/métodos , Transtornos Relacionados ao Uso de Opioides/economia , Dor Pós-Operatória/economia , Dor Pós-Operatória/prevenção & controle , Fraturas do Tornozelo/economia , Bases de Dados Factuais , Serviço Hospitalar de Emergência/economia , Feminino , Humanos , Modelos Logísticos , Masculino , Transtornos Relacionados ao Uso de Opioides/etiologia , Readmissão do Paciente/economia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Recent reports of acetic acid-induced drought tolerance and avoidance across a diverse range of plant species encourage consideration of this low-cost commodity organic acid as a biostimulant. These results are surprising as they contrast with earlier studies showing pH-dependent root growth inhibition at similar concentrations. We test the hypothesis that the concentration of the membrane permeable undissociated form of acetic acid (CH3COOH) selectively inhibits maize root growth, and subsequently evaluate its impact on seedling water use and growth under deficit irrigation. We demonstrate conclusively for the first time that when germinating maize on filter paper, low pH exacerbates, and high pH mitigates, this inhibition of root growth in a predictable manner based on the dissociation constant of acetic acid. The buffering capacity of potting media can reduce this root damage through keeping the acetic acid primarily in the membrane impermeable dissociated form (CH3COO-) at near neutral pH, but peat substrates appear to offer some protection, even at low pH. While both deficit irrigation and acetic acid reduced water use and growth of maize seedlings outdoors, there was no significant interaction between the treatments. Twenty nine millimolar total acetic acid (CH3COOH + CH3COO-) reduced transpiration, compared to lower and higher concentrations, but this did not specifically improve performance under reduced water availability, with parallel declines in shoot biomass leading to relatively consistent water use efficiency. Any acetic acid biostimulant claims under water stress should characterize its dissociation level, and exclude root damage as a primary cause.
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BACKGROUND: International normalized ratio (INR) is used as a marker of the haemostatic status following liver resection. However, the impact of liver resection on haemostasis is complex and beyond what can be measured by INR. This study aimed to prospectively assess haemostatic profile following liver resection and determine if INR measurement can safely guide post-operative thromboprophylaxis. METHODS: In this prospective cohort study, patients undergoing liver resection had coagulation parameters (International normalised ratio (INR), prothrombin time (PT), activated partial thromboplastin time, fibrinogen, d-dimer, von Willebrand factor antigen, procoagulant activity of phospholipids and clotting factors II, VII, VIIIc, IX and X) and thromboelastogram parameters assessed perioperatively. Clinical follow-up assessed for thromboembolism and haemorrhage. RESULTS: In the 41 patients included, INR was significantly (P < 0.0001) elevated post-operatively, and INR >1.5 was observed in seven of 41 (17.1%) on post-operative day 1 and one of 41 (2.4%) patients on post-operative day 3, respectively. Factor VII levels showed transient reduction but other factors, especially factors II and X, remained within normal range following liver resection. Thromboelastogram parameters remained normal or supranormal for all patients at all time points. One incident of post-hepatectomy haemorrhage occurred, despite a normal coagulation profile. Two patients suffered late pulmonary embolic episodes. CONCLUSION: Post liver resection haemostasis is complex and poorly reflected by INR, which should not guide initiation of chemical thromboprophylaxis in the immediate post-operative period.
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Hemostáticos , Fígado , Tromboelastografia , Tromboembolia Venosa , Anticoagulantes/uso terapêutico , Humanos , Fígado/cirurgia , Estudos ProspectivosRESUMO
BACKGROUND: We reported that in our previous study that wearing intermittent occlusion therapy glasses (IO-therapy) for 4 hours (h) was non-inferior to patching for 2 h in 3 to 8-year-old children with amblyopia. We hypothesize that an intense regimen of 12-h IO-therapy per day for 4 weeks could be as effective as the standard regimen of 4-h IO-therapy per day for 12 weeks in treating moderate amblyopia in 3 to 8-year-old children. METHODS/DESIGN: A total of 56 children between 3 and 8 years of age with amblyopia in association with anisometropia and/or strabismus will be enrolled. All participants will be prescribed IO-therapy glasses (Amblyz™), set at 30-s opaque/transparent intervals (i.e., occluded 50% of wear time). They will be randomized to receive the standard regimen for 12 weeks or the intense regimen for 4 weeks. Adherence to using the IO-therapy glasses will be objectively monitored in each participant by means of a microsensor dose monitor. The primary study objective is to compare the effectiveness of an intense regimen to a standard regimen of IO-therapy in 3 to 8-year-old children with moderate amblyopia. The secondary study objectives are to determine whether adherence differs between an intense regimen and a standard regimen of IO-therapy, and to determine the dose-response relationship of IO-therapy. DISCUSSION: In addition to testing the effectiveness, this study will test for the first time the association between treatment adherence and the visual outcome of IO-therapy, which will enhance our understanding of the dose-response relationship of IO-therapy. If an intense regimen is shown to be effective, it would alter amblyopia treatment strategies and improve visual outcomes. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02767856. Registered on 10 May 2016.
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Ambliopia/terapia , Cristais Líquidos , Privação Sensorial , Criança , Humanos , Monitorização Fisiológica , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento , Acuidade VisualRESUMO
This is a prospective clinical trial comparing Wound Tracker Professional iOS compatible device with Acetate tracing and Aranz medical wound measuring systems. The study compares 3 different wound measurement systems in 20 patients. Wound Tracker Professional device demonstrated statistically significant difference when compared with the acetate tracing; however, there was no statistically significant difference when compared with the Aranz system. Wound Tracker Professional iOS compatible system is an easily accessible and affordable wound measuring system that can easily be implemented by the clinician in a wound care setting.
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Pé Diabético/patologia , Processamento de Imagem Assistida por Computador , Sistemas Automatizados de Assistência Junto ao Leito , Smartphone , Pé Diabético/diagnóstico por imagem , Humanos , Estudos ProspectivosRESUMO
Synaptic plasticity requires a tight control of mRNA levels in dendrites. RNA translation and degradation pathways have been recently linked to neurodevelopmental and neuropsychiatric diseases, suggesting a role for RNA regulation in synaptic plasticity and cognition. While the local translation of specific mRNAs has been implicated in synaptic plasticity, the tightly controlled mechanisms that regulate local quantity of specific mRNAs remain poorly understood. Despite being the only RNA regulatory pathway that is associated with multiple mental illnesses, the nonsense-mediated mRNA decay (NMD) pathway presents an unexplored regulatory mechanism for synaptic function and plasticity. Here, we show that neuron-specific disruption of UPF2, an NMD component, in adulthood attenuates learning, memory, spine density, synaptic plasticity (L-LTP), and potentiates perseverative/repetitive behavior in mice. We report that the NMD pathway operates within dendrites to regulate Glutamate Receptor 1 (GLUR1) surface levels. Specifically, UPF2 modulates the internalization of GLUR1 and promotes its local synthesis in dendrites. We identified neuronal Prkag3 mRNA as a mechanistic substrate for NMD that contributes to the UPF2-mediated regulation of GLUR1 by limiting total GLUR1 levels. These data establish that UPF2 regulates synaptic plasticity, cognition, and local protein synthesis in dendrites, providing fundamental insight into the neuron-specific function of NMD within the brain.