Subtemporal Approach for the Treatment of Ruptured and Unruptured Distal Basilar Artery Aneurysms: Is There a Contemporary Use?

BACKGROUND AND OBJECTIVES: Distal basilar artery aneurysms (DBAs) are high-risk lesions for which endovascular treatment is preferred because of their deep location, yet indications for open clipping nonetheless remain. The subtemporal approach allows for early proximal control and direct visualization of critical posterior perforating arteries, especially for posterior-projecting aneurysms. Our objective was to describe our clinical experience with the subtemporal approach for clipping DBAs in the evolving endovascular era. METHODS: This was a retrospective, single-institution case series of patients with DBAs treated with microsurgery over a 21-year period (2002-2023). Demographic, clinical, and surgical data were collected for analysis. RESULTS: Twenty-seven patients underwent clipping of 11 ruptured and 16 unruptured DBAs with a subtemporal approach (24 female; mean age 53 years). Ten patients had expanded craniotomies for treatment of additional aneurysms. The aneurysm occlusion rate was 100%. Good neurological outcomes as defined by the modified Rankin Scale score ≤2 and Glasgow Outcome Scale score ≥4 were achieved in 21/27 patients (78%). Two patients died before hospital discharge, one from vasospasm-induced strokes and another from an intraoperative myocardial infarction. CONCLUSION: These results demonstrate that microsurgical clip ligation of DBAs using the subtemporal approach remains a viable option for complex lesions not amenable to endovascular management.

Higher Doses of Calcium Associated With Survival in Trauma Patients.

INTRODUCTION: Calcium is required for coagulation, cardiac output, and peripheral vascular resistance. Between 85% and 94% of trauma patients treated with massive blood transfusion develop hypocalcemia.1 The aim of this study is to evaluate the relationship between increased intravenous calcium administration during massive transfusion and improved survival of trauma patients. METHODS: We performed a retrospective analysis of trauma patients who received massive transfusion over a 2-y period. Doses of elemental calcium administered per unit of blood product transfused were calculated by calcium to blood product ratio (CBR). Chi-square test evaluated association between coagulopathy and 30-d mortality. Two-sample t-test evaluated association between CBR and coagulopathy. Bivariate regression analysis evaluated association between CBR and blood products transfused per patient. Multivariable logistic regression analysis, controlling for age, sex, coagulopathy, and Injury Severity Score evaluated the association between CBR and mortality. RESULTS: The study included 77 patients. Coagulopathy was associated with increased 30-d mortality (P < 0.05). Patients who survived had higher CBR than those who died (P < 0.05). CBR was associated with a significant reduction in total blood products transfused per patient (P < 0.05). CBR was not associated with coagulopathy (P = 0.24). Multivariable logistic regression analysis demonstrated that Injury Severity Score ≥16, coagulopathy and decreased CBR were significant predictors of mortality (P < 0.05). CBR above 50 mg was a predictor of survival (P < 0.05). CONCLUSIONS: Higher doses of calcium given per blood product transfused were associated with improved 30-d survival and decreased blood product transfusions.

Impact of weight loss and weight gain trajectories on body composition in a population at high risk of type 2 diabetes: A prospective cohort analysis.

AIM: In a primary care population at high risk of type 2 diabetes, 24-month weight change trajectories were used to investigate the impact of weight cycling on fat mass (FM) and fat-free mass (FFM). MATERIALS AND METHODS: Cohort data from the Walking Away from Type 2 Diabetes trial was used, which recruited adults at-risk of type 2 diabetes from primary care in 2009/10. Annual weight change trajectories based on weight loss/gain of ≥5% were assessed over two 24-month periods. Body composition was measured by bioelectrical impedance analysis. Repeated measures were analysed using generalized estimating equations with participants contributing up to two 24-month observation periods. RESULTS: In total, 622 participants were included (average age = 63.6 years, body mass index = 32.0 kg/m2 , 35.4% women), contributing 1163 observations. Most observations (69.2%) were from those that maintained their body weight, with no change to FM or FFM. A minority (4.6% of observations) lost over 5% of body weight between baseline and 12 months, which was then regained between 12 and 24 months. These individuals regained FM to baseline levels, but lost 1.50 (0.66, 2.35) kg FFM, adjusted for confounders. In contrast, those that gained weight between baseline and 12 months but lost weight between 12 and 24 months (5.5% of observations) had a net gain in FM of 1.70 (0.27, 3.12) kg with no change to FFM. CONCLUSION: Weight cycling may be associated with a progressive loss in FFM and/or gain in FM in those with overweight and obesity at-risk of type 2 diabetes.

Acute care nurse managers' definitions of and barriers to well-being: A thematic analysis of open-ended survey questions.

BACKGROUND: During the COVID-19 pandemic, acute care nurse managers functioned in a critical role by helping to advance the mission and goals of their organization while navigating a rapidly evolving healthcare landscape. This resulted in high levels of ongoing job-related stress which is linked to negative physical, psychological, and job-related outcomes. Little is known about the perceptions regarding their own professional well-being during this time. AIM: The aim of this study was to qualitatively describe acute care nurse managers' perceptions of and barriers to their professional well-being. METHODS: Using a qualitative descriptive approach, nurse managers from a hospital system in the southwestern United States responded to two short-answer, survey-based questions in 2022: (1) "Describe the definition of nurse-manager well-being in your own words" and (2) "What do you feel is your biggest barrier to professional well-being?" Reflexive thematic analysis was utilized to analyze participant responses (N = 80). RESULTS: Professional well-being is a complex concept influenced by the nurse manager's ability to navigate work-life balance; care for their own physical, emotional, and spiritual selves; give and receive support from stakeholders; and manage feelings of thriving vs. struggling in the role. Barriers most cited as influencing well-being included having too little time to get things done coupled with increasing workloads, feeling stuck in the middle among stakeholders, and coping with ongoing staffing challenges. LINKING EVIDENCE TO ACTION: The definition of and barriers to well-being are influenced by the specific needs and experiences of the nurse manager. While not all barriers can be immediately removed, the identification of individual and organization-specific barriers needs to be taken seriously, reviewed by those who can promote change, and evidence-based solutions for improvement piloted or implemented when feasible.

Moderate-intensity stepping in older adults: insights from treadmill walking and daily living.

BACKGROUND: A step cadence of 100 steps/minute is widely used to define moderate-intensity walking. However, the generalizability of this threshold to different populations needs further research. We investigate moderate-intensity step cadence values during treadmill walking and daily living in older adults. METHODS: Older adults (≥ 60 years) were recruited from urban community venues. Data collection included 7 days of physical activity measured by an activPAL3™ thigh worn device, followed by a laboratory visit involving a 60-min assessment of resting metabolic rate, then a treadmill assessment with expired gas measured using a breath-by-breath analyser and steps measured by an activPAL3™. Treadmill stages were undertaken in a random order and lasted 5 min each at speeds of 1, 2, 3, 4 and 5 km/h. Metabolic equivalent values were determined for each stage as standardised values (METSstandard) and as multiples of resting metabolic rate (METSrelative). A value of 3 METSstandard defined moderate-intensity stepping. Segmented generalised estimating equations modelled the association between step cadence and MET values. RESULTS: The study included 53 participants (median age = 75, years, BMI = 28.0 kg/m2, 45.3% women). At 2 km/h, the median METSstandard and METSrelative values were above 3 with a median cadence of 81.00 (IQR 72.00, 88.67) steps/minute. The predicted cadence at 3 METSstandard was 70.3 (95% CI 61.4, 75.8) steps/minute. During free-living, participants undertook median (IQR) of 6988 (5933, 9211) steps/day, of which 2554 (1297, 4456) steps/day were undertaken in continuous stepping bouts lasting ≥ 1 min. For bouted daily steps, 96.4% (90.7%, 98.9%) were undertaken at ≥ 70 steps/minute. CONCLUSION: A threshold as low as 70 steps/minute may be reflective of moderate-intensity stepping in older adults, with the vast majority of all bouted free-living stepping occurring above this threshold.

Systematic Review of Treatment Options and Therapeutic Responses for Lesions of the Sella and Orbit: Evidence-Based Recommendations.

OBJECTIVE: Inflammatory pathologies of the sella and orbit are rare but require prompt diagnosis to initiate effective treatment. Because uniform recommendations for treatment are currently lacking, we performed an evidence-based review to identify recommendations. METHODS: We performed a literature search of the PubMed, Embase, and Web of Science databases to identify papers evaluating treatment of inflammatory pathologies of the sella and orbit. We used PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines to define recommendations, specifically examining aggregated sample sizes, disease-specific patient follow-up, and clinical trials focused on inflammatory diseases of the sella and orbit. RESULTS: A total of 169 studies were included and organized by disease pathology. Treatments for various pathologies were recorded. Treatment options included surgery, radiation, steroids, targeted treatments, immunomodulators, intravenous immune globulin, and plasmapheresis. Steroids were the most often employed treatment, second-line management options and timing varied. Pathological diagnosis was highly associated with treatment used. Most evidence were level 3 without available control groups, except for 13 trials in neuromyelitis optica with level 1 or 2 evidence. CONCLUSIONS: This is the first evidence-based review to provide recommendations on specific treatments for pathologies of the orbit and sella. The reported data may be useful to help guide randomized clinical trials and provide resource for clinical management decisions based on the available evidence.

Application of Radiomics to the Differential Diagnosis of Temporal Bone Skull Base Lesions: A Pilot Study.

BACKGROUND: Temporal bone skull base pathologies represent a complex differential because they can be radiographically obscure and difficult to diagnose without biopsy. Radiomics involves the use of mathematical quantification of imaging data beyond simple intensity, size, and location to inform diagnosis and prognosis. We examined the feasibility of using radiomic parameters to help predict temporal bone tumor type. METHODS: A total of 117 radiomic parameters were analyzed from 5 magnetic resonance imaging sequences (T1 without contrast, T1 with contrast, T2, fluid-attenuated inversion recovery, apparent diffusion coefficient [ADC]) for each tumor. Statistical analysis was used to delineate known primary, metastatic/secondary, and lymphoma lesions using radiomics. RESULTS: The mean tumor volumes for the 14 primary, 12 secondary, and 8 lymphoma lesions were 2.98 ± 2.11, 3.28 ± 2.31, and 12.16 ± 7.1 cm3, respectively (P = 0.2). No significant differences in mean intensity values for any sequence helped distinguish tumors (P > 0.05), but 6 radiomic parameters were significantly correlated with diagnostic accuracy. Discriminant analysis using a stepwise algorithm generated a model where radiomic parameters for T1 cluster prominence, ADC dependence nonuniformity, T1 with contrast zone percentage, and ADC informational measure of correlation 2 achieved the best predictive model (P = 0.0001). These significant characteristics were often indirect measures of tumor heterogeneity on different magnetic resonance imaging sequences. CONCLUSIONS: These data suggest that quantitative measures of tumor heterogeneity can be discriminatory of pathology and might be integrated into clinical workflow. Although this pilot study requires further validation, these data support the exploration of radiomics in temporal bone radiographic diagnostics.

Immunohistochemical Profiling and Staging in Esthesioneuroblastoma: A Single-Center Cohort Study and Systematic Review.

OBJECTIVE: Esthesioneuroblastoma (ENB) is a rare sinonasal malignant neoplasm with 40% 5-year survival. Because of the rarity of the tumor, the optimal treatment and subsequent prediction of prognosis are unclear. We studied a modern series of patients with ENB to evaluate the association of immunohistochemical (IHC) markers and clinical stages/grades with outcomes. METHODS: A single-center retrospective review of patients with ENB treated during a 25-year period was performed. A systematic literature review evaluating the prognostic benefits of current staging systems in evaluating survival outcomes in ENB was undertaken. RESULTS: Among 29 included patients, 25 (85%) were treated surgically at our institution, with 76% of those endoscopically resected; 7 (24.1%) received chemotherapy, and 18 (62.1%) received radiation therapy. The 5-year overall survival (OS) was 91.3%, and 10-year OS was 78.3%. Progression-free survival at 5 and 10 years was 85.6% and 68.2%, respectively. A total of 36 distinct IHC markers were used to diagnose ENB but were inconsistent in predicting survival. A systematic literature review revealed predictive accuracy for OS using the Kadish, TNM, and Hyams staging/grading systems was 68%, 42%, and 50%, respectively. CONCLUSIONS: This study reports the 5- and 10-year OS and progression-free survival in a modern series of patients with ENB. No traditional IHC marker consistently predicted outcome. Some novel reviewed markers show promise but have yet to enter clinical mainstream use. Our systematic review of accepted staging/grading systems also demonstrated a need for further investigation due to limited prognostic accuracy.

Factors associated with hearing outcomes after a middle fossa approach in 131 consecutive patients with vestibular schwannomas.

OBJECTIVE: The middle fossa approach is an effective option for the treatment of small (Koos grade I and II) vestibular schwannomas (VSs) when the goal is hearing preservation. The authors evaluated the rates of hearing preservation and examined the factors associated with improved hearing outcomes after the middle fossa approach for VSs. METHODS: In this retrospective, single-center cohort study evaluating the clinical outcomes after resection of small VSs using the middle fossa approach, consecutive adult patients (> 18 years) who underwent surgery between January 2000 and December 2021 were included. Clinical and imaging characteristics were analyzed, including baseline hearing status, duration of surgery, anesthetic parameters, and imaging characteristics of the surgically treated tumors. RESULTS: Among the 131 included patients, 102 had valid and discoverable pre- and postoperative audiology assessments. The mean follow-up was 26 months (range 1-180 months). There were 85 patients with serviceable hearing preoperatively, defined as American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) class A or B, of whom 78% retained class A or B hearing at the last follow-up. Binary logistic regression demonstrated that preoperative hearing AAO-HNS class (OR 0.19, 95% CI 0.05-0.77; p = 0.02), overlap between fundus and cochlea (OR 0.32, 95% CI 0.11-0.96; p = 0.04), and duration of anesthesia (OR 0.98, 95% CI 0.97-0.99; p = 0.03) were independent predictors of hearing outcomes. Additionally, 75% of patients with high diffusion-weighted imaging signal in the tumor (p = 0.009) and 67% of patients with the tumor originating at the modiolus of the cochlea (p = 0.004) had poor hearing outcomes. CONCLUSIONS: The hearing preservation rates after microsurgical resection of small VSs using the middle fossa approach are high, with 78% of patients maintaining AAO-HNS class A or B hearing. Poor hearing status at baseline, longer duration of anesthesia, and large overlap between the fundus of the internal auditory canal and the cochlea were independently associated with unfavorable hearing outcomes. Imaging characteristics can be used to stratify patients' risk of hearing loss.

Evaluating pituitary adenomas using national research databases: systematic review of the quality of reporting based on the STROBE scale.

The use of national research databases has become more prevalent for studying various neurosurgical diseases. Despite the advantages of using large databases to glean clinical insight, variation remains in the methodology and reporting among studies. Using STROBE and RECORD guidelines, we evaluated the quality of reporting of the database literature investigating surgical management of benign pituitary adenomas. In this systematic review of the PubMed/MEDLINE database, we identified studies employing large national research databases of patients who underwent surgery for benign pituitary adenoma. We evaluated each of these studies using the STROBE-RECORD reporting guideline criteria to assess their quality. A total of 42 studies from 2003 to 2020 were identified for inclusion. The two raters demonstrated a κ = 0.228 with 84% overall agreement. Commonly underreported criteria included bias (discussed in 56% of studies), main result reporting (70%), subgroup analysis (69%), generalizability (68%), and funding (57%). These factors, in addition to the data sources/measurement criteria, also had the largest discrepancies between reviewers. About 20% of administrative database reviews did not accurately address bias or control for confounding variables. We found frequent underreporting of crucial information and criteria that can be challenging to identify may limit large database studies of pituitary adenomas. Improved reporting of certain criteria is critical to optimize reader understanding of large database studies. This would allow better dissemination and implementation of study findings, especially as the use of these research tools increases.

How I Do It: Endonasal transethmoidal, transcribriform approach for resection of giant olfactory groove meningioma.

BACKGROUND: Olfactory groove meningiomas (OGMs) arise from the cribriform plate of the anterior fossa and account for 9-12% of all meningiomas. Giant OGMs are those larger than 6 cm and are technically challenging to resect. METHOD: Here we present the surgical decision-making and intraoperative details regarding the endonasal endoscopic resection of an OGM using a minimally invasive, endonasal approach in a 68-year-old female patient. CONCLUSION: Giant OGMs can be safely and effectively removed using an endonasal, transcribriform approach.

How I do it: endonasal transcribriform approach for resection of esthesioneuroblastoma.

BACKGROUND: Olfactory neuroblastoma, also known as esthesioneuroblastoma, accounts for only 3-6% of sinonasal malignancies but confers a 40% 5-year overall survival. METHOD: The authors describe techniques for the endonasal, minimally invasive resection of an esthesioneuroblastoma in a 69-year-old man who presented with headaches and anosmia and describe surgical nuances and their effect on adjuvant therapy planning. CONCLUSION: This approach, along with microsurgical techniques, helped increase tumor visualization, improved marginal resection, and reduced surgical risk, which may improve patient outcomes. Multilayered reconstruction with a synthetic dural substitute and creation of a nasoseptal flap were performed to reduce postoperative cerebrospinal fluid leak.

PEGylated Gold Nanoparticle Toxicity in Cardiomyocytes: Assessment of Size, Concentration, and Time Dependency.

Gold Nanoparticles (GNPs) have shown promising capabilities for use in many in-vivo applications such as gene and drug delivery, photothermal ablation of tumors, and tracking in many imaging modalities. Yet GNPs have thus far had limited use in cardiovascular medicine. Polyethylene glycol functionalized (PEGylated) GNPs have been extensively studied in a wide array of in vitro and in vivo models with results showing no apparent toxicity, but to our knowledge an investigation has never been performed to determine direct cardiomyocyte toxicity. In this study, we assessed if PEGylated GNPs exhibited direct toxicity to a primary culture of neonatal rat cardiomyocytes in order to establish PEGylated GNPs for potential future use in cardiovascular medicine applications. We present novel results that demonstrate both a particle size and concentration dependent relationship on cell viability. Cell viability was found to be significantly enhanced for many concentrations and sizes as compared to the control and increased linearly as a function of particle diameter. Additionally, viability increased in a parabolically dependent manner as a function of decreasing particle concentration. These new results could advance understanding of nanoparticle-cell interactions and lead to the development of new applications involving the use of gold nanoparticles in cardiovascular medicine.

Unstable ventricular tachycardia requiring defibrillation from rapid ventricular pacing during basilar apex aneurysm clipping.

BACKGROUND: Controlled hypotension is an important tool in the open treatment of complex intracranial aneurysms. Of the available methodologies, rapid ventricular pacing (RVP) provides titratable, sustained hypotension with a relatively safe profile. METHOD: We report the case of a 63-year-old woman who underwent a combined subfrontal and subtemporal approach for clipping of anterior communicating artery and basilar apex aneurysms. RVP was used during initial dissection of the basilar apex aneurysm and perforators but caused uncontrolled ventricular tachycardia requiring synchronized defibrillation. After restoration of hemodynamic stability, the aneurysm was uneventfully clipped. CONCLUSION: Preparation for unstable cardiac arrhythmias is needed with RVP.

Device-measured physical activity and its association with physical function in adults with type 2 diabetes mellitus.

AIM: To quantify how differences in metrics characterizing physical activity and sedentary behaviour in type 2 diabetes are associated with physical function. METHODS: This analysis included participants' data from the Chronotype of Patients with Type 2 Diabetes and Effect on Glycaemic Control (CODEC) cross-sectional study. Data were stratified into two groups according to their short physical performance battery (SPPB) score (impaired physical function = SPPB < 10 and normal physical function = SPPB ≥ 10). Hand-grip strength, sit-to-stand 60 (STS-60) and the Duke Activity Status Index (DASI) score were used to assess functional capacity, while physical activity metrics were measured with a wrist-worn accelerometer. The associations between physical activity metrics and measures of functional capacity were analysed using generalized linear modelling. RESULTS: Some 635 adults (median age 66 years, 34% female) were included in this analysis. Overall, 29% of the cohort scored < 10 in the SPPB test indicating impaired physical function. This group spent more time in prolonged sedentary behaviour (600.7 vs. 572.5 min) and undertook less-intense physical activity. Each sd increase in physical activity volume and intensity gradients for those with impaired physical function was associated with 17% more repetitions for STS-60 with similar associations seen for DASI score. Each sd in sedentary time was associated with 15% fewer repetitions in STS-60 and 16% lower DASI score in those with impaired physical function, whereas in normal physical function group it was 2% and 1%, respectively. CONCLUSIONS: The strength of the associations for physical activity measures and functional capacity were modified by physical function status, with the strongest association seen in those with impaired physical function.

Association of depression and anxiety with clinical, sociodemographic, lifestyle and environmental factors in South Asian and white European individuals at high risk of diabetes.

AIM: To investigate the prevalence and correlates of depressive and anxiety symptoms within South Asian and white European populations at high risk of developing Type 2 diabetes. METHODS: Data were collected at baseline, and at 12, 24 and 36 months from 1429 white European individuals (age 64±7 years, 35.8% women) and 160 South Asian individuals (age 59±9 years, 30.6% women) who were at high risk of Type 2 diabetes and who took part in two Type 2 diabetes prevention trials in Leicestershire, UK. The Hospital Anxiety and Depression Scale was administered during each study visit. Clinical, sociodemographic, lifestyle and environmental data were collected. RESULTS: At baseline, the burden of depressive symptoms varied by ethnic group and gender, with 9.9% of white European men, 14.9% of white European women, 23.6% of South Asian men and 29.2% of South Asian women exceeding the cut-off score for mild-to-severe depression. During the course of the study and after adjustment for clinical, sociodemographic, lifestyle and environmental factors, depressive symptoms remained higher in the South Asian compared to the white European participants [score higher by 1.5, 95% CI 0.9-2.1]. Levels of anxiety were also higher in the South Asian participants, although associations were attenuated after adjustment. Social deprivation, BMI, proximity to fast-food outlets and physical activity were correlates for depression in both the South Asian and white European participants. CONCLUSIONS: A higher burden of depressive symptoms was consistently evident among the South Asian individuals, even after adjustment for multiple covariates. It is important to understand both the reasons why these differences are present, to help reduce health inequalities, and whether higher levels of depressive symptoms affect the uptake of and retention rates in diabetes prevention programmes in South Asian communities.

High resolution imaging of the cortex isolated from sea urchin eggs and embryos.

The cellular cortex-consisting of the plasma membrane and the adjacent outer few microns of the cytoplasm-is a critically important, dynamic and complex region in the sea urchin egg and embryo. Some 40 years ago it was discovered that isolated cortices could be obtained from eggs adhered to glass coverslips and since that time this preparation has been used in a wide range of studies, including seminal research on fertilization, exocytosis, the cytoskeleton, and cytokinesis. In this chapter, we discuss methods for isolating cortices from eggs and embryos, including those undergoing cell division. We also provide protocols for analyzing cortical architecture and dynamics using specific localization methods combined with super-resolution Structured Illumination and Stimulated Emission Depletion light microscopy and platinum replica transmission electron microscopy.

In-situ electrochemical analysis of microbial activity.

Microbes have a wide range of metabolic capabilities available that makes them industrially useful organisms. Monitoring these metabolic processes is a crucial component in efficient industrial application. Unfortunately, monitoring these metabolic processes can often be invasive and time consuming and expensive, especially within an anaerobic environment. Electrochemical techniques, such as cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) offer a non-invasive approach to monitor microbial activity and growth. EIS and CV were used to monitor Clostridium phytofermentans, an anaerobic and endospore-forming bacterium. C. phytofermentans ferments a wide range of sugars into hydrogen, acetate, and ethanol as fermentation by-products. For this study, both traditional microbiological and electrochemical techniques were used to monitor the growth of C. phytofermentans and the formation of fermentation products. An irreversible reduction peak was observed using CV beginning at mid-logarithmic phase of growth. This peak was associated with C. phytofermentans and not the spent medium and was indicative of a decrease in carbon and energy sources to the cells. Additionally, EIS analysis during growth provided information related to increased charge transfer resistance of the culture also as a function of carbon and energy source depletion. Results demonstrate that CV and EIS are useful tools in the monitoring the physiological status of bioprocesses.

The impact of neighbourhood walkability on the effectiveness of a structured education programme to increase objectively measured walking.

Background: Incorporating physical activity into daily activities is key for the effectiveness of lifestyle education interventions aimed at improving health outcomes; however, consideration of the environmental context in which individuals live is not always made. Walkability is a characteristic of the physical environment, and may be a potential facilitator to changing physical activity levels. Methods: Using data collected during the Walking Away from Diabetes randomized controlled trial, we examined the association between the walkability of the home neighbourhood and physical activity of participants. We also determined whether home neighbourhood walkability of participants was associated with the intervention effect of the education programme. Results: Data from 706 participants were available for analysis. Neighbourhood walkability was not significantly associated with any of the physical activity measures at baseline, or at 12, 24 or 36 months following the intervention (P > 0.05 for all). There was no association between walkability and change in purposeful steps/day from baseline to 36 months in the usual care or intervention arm; 25.77 (-99.04, 150.58) and 42.97 (-327.63, 413.45), respectively. Conclusion: Neighbourhood walkability appeared to have no association with objectively measured physical activity in this population. Furthermore, the walkability of participant's neighbourhood did not influence the effectiveness of a lifestyle programme.

Early pregnancy immune biomarkers in peripheral blood may predict preeclampsia.

We performed a prospective cohort study in 197 pregnant women. Peripheral blood was collected between 5 and 16 weeks of gestation. Intracellular cytokine analysis and immunophenotype were performed by flow-cytometry. Serum levels of cytokines and chemokines were analyzed by multiplex assay. 86 patients were eligible for the analysis and 10.5% (n=9) developed preeclampsia. Patients with preeclampsia had significantly higher percentage of CD3+CD4+TNFα+ T helper (Th) 1 cells (45.4±10.3 vs 37.1±8.5, P=0.032) and CD3+CD4+IL17+ Th 17 cells (2.4±1.3 vs 1.6±1.1, P=0.029) when compared to those of patients without preeclampsia. CD3+CD4+CD25+CD127dim/- T regulatory cells (Treg) cells (5.7±1.2% vs 7.0±1.6%, P=0.015) were significantly lower in patients with preeclampsia when compared to those without preeclampsia. Patients with preeclampsia had significantly higher TNFα/IL-10 cell ratio (43.8±10.3 vs 34.3±7.9, P=0.005) and Th17/Treg cell ratio (0.5±0.3 vs 0.2±0.2, P=0.011) when compared to those of patients without preeclampsia. IL-8 and Macrophage inflammatory protein (MIP)-1α serum levels were significantly higher in patients with preeclampsia when compared with patients without preeclampsia (Median=341.0 vs 87.6, U=152, P=0.020 and Median=35.7 vs 17.7, U=120, P=0.029 respectively). Serum MCP-1 levels were significantly lower in patients with preeclampsia when compared with patients without preeclampsia (Median=233.8 vs 390.9, U=183, P=0.021). The logistic regression predictive model combining TNFα/IL-10 ratios, IL-8 and MCP-1 serum levels had the best performance (AUC=0.886, 95%CI 0.8-0.9). We concluded that elevated Th1 and Th17 cell percentages, elevated TNFα/IL-10 and Th17/Treg cell ratios and decreased Treg cell percentages in early pregnancy are associated with preeclampsia.