Associations of neighborhood greenspace, and active living environments with autism spectrum disorders: A matched case-control study in Ontario, Canada.

BACKGROUND: Increasing evidence links early life residential exposure to natural urban environmental attributes and positive health outcomes in children. However, few studies have focused on their protective effects on the risk of autism spectrum disorder (ASD). The aim of this study was to investigate the associations of neighborhood greenspace, and active living environments during pregnancy with ASD in young children (≤6 years). METHODS: We conducted a population-based matched case-control study of singleton term births in Ontario, Canada for 2012-2016. The ASD and environmental data was generated using the Ontario Autism Spectrum Profile, the Better Outcomes Registry & Network Ontario, and Canadian Urban Environmental Health Research Consortium. We employed conditional logistic regressions to estimate the odds ratio (OR) between ASD and environmental factors characterizing selected greenspace metrics and neighborhoods conducive to active living (i.e., green view index (GVI), normalized difference vegetation index (NDVI), tree canopy, park proximity and active living environments index (ALE)). RESULTS: We linked 8643 mother-child pairs, including 1554 cases (18%). NDVI (OR 1.034, 0.944-1.024, per Inter Quartile Range [IQR] = 0.08), GVI (OR 1.025, 95% CI 0.953-1.087, per IQR = 9.45%), tree canopy (OR 0.992, 95% CI 0.903-1.089, per IQR = 6.24%) and the different categories of ALE were not associated with ASD in adjusted models for air pollution. In contrast, living closer to a park was protective (OR 0.888, 0.833-0.948, per 0.06 increase in park proximity index), when adjusted for air pollution. CONCLUSIONS: This study reported mixed findings showing both null and beneficial effects of green spaces and active living environments on ASD. Further investigations are warranted to elucidate the role of exposure to greenspaces and active living environments on the development of ASD.

Bioactive Potential of Carrot-Based Products Enriched with Lactobacillus plantarum.

The primary goal of this study was to generate different kinds of functional products based on carrots that were supplemented with lactic acid bacteria. The fact that carrots (Daucus carota sp.) rank among the most popular vegetables in our country led to the convergence of the research aim. Their abundance of bioactive compounds, primarily polyphenols, flavonoids, and carotenoids, offers numerous health benefits. Among the obtained products, the freeze-dried carrot powder (FDCP) variation presented the highest concentrations of total carotenoids (TCs) and ß-carotene (BC) of 26.977 ± 0.13 mg/g DW and 22.075 ± 0.14 mg/g DW, respectively. The amount of total carotenoids and ß-carotene significantly increased with the addition of the selected lactic acid bacteria (LAB) for most of the samples. In addition, a slight increase in the antioxidant activity compared with the control sample for the FDCP variant, with the highest value of 91.74%, was observed in these functional food products. The content of polyphenolic compounds varied from 0.044 to 0.091 mg/g DW, while the content of total flavonoids varied from 0.03 to 0.66 mg/g DW. The processing method had an impact on the population of L. plantarum that survived, as indicated by the viability of bacterial cells in all the analyzed products. The chromatographic analysis through UHPLC-MS/MS further confirmed the abundance of the bioactive compounds and their corresponding derivatives by revealing 19 different compounds. The digestibility study indicated that carotenoid compounds from carrots followed a rather controlled release. The carrot-based products enriched with Lactobacillus plantarum can be considered newly functional developed products based on their high content of biologically active compounds with beneficial effects upon the human body. Furthermore, these types of products could represent innovative products for every related industry such as the food, pharmaceutical, and cosmeceutical industries, thus converging a new strategy to improve the health of consumers or patients.

Critical windows of exposure to air pollution and gestational diabetes: assessing effect modification by maternal pre-existing conditions and environmental factors.

BACKGROUND: Ambient air pollution has been associated with gestational diabetes (GD), but critical windows of exposure and whether maternal pre-existing conditions and other environmental factors modify the associations remains inconclusive. METHODS: We conducted a retrospective cohort study of all singleton live birth that occurred between April 1st 2006 and March 31st 2018 in Ontario, Canada. Ambient air pollution data (i.e., fine particulate matter with a diameter ≤ 2.5 µm (PM2.5), nitrogen dioxide (NO2) and ozone (O3)) were assigned to the study population in spatial resolution of approximately 1 km × 1 km. The Normalized Difference Vegetation Index (NDVI) and the Green View Index (GVI) were also used to characterize residential exposure to green space as well as the Active Living Environments (ALE) index to represent the active living friendliness. Multivariable Cox proportional hazards regression models were used to evaluate the associations. RESULTS: Among 1,310,807 pregnant individuals, 68,860 incident cases of GD were identified. We found the strongest associations between PM2.5 and GD in gestational weeks 7 to 18 (HR = 1.07 per IQR (2.7 µg/m3); 95% CI: 1.02 - 1.11)). For O3, we found two sensitive windows of exposure, with increased risk in the preconception period (HR = 1.03 per IQR increase (7.0 ppb) (95% CI: 1.01 - 1.06)) as well as gestational weeks 9 to 28 (HR 1.08 per IQR (95% CI: 1.04 -1.12)). We found that women with asthma were more at risk of GD when exposed to increasing levels of O3 (p- value for effect modification = 0.04). Exposure to air pollutants explained 20.1%, 1.4% and 4.6% of the associations between GVI, NDVI and ALE, respectively. CONCLUSION: An increase of PM2.5 exposure in early pregnancy and of O3 exposure during late first trimester and over the second trimester of pregnancy were associated with gestational diabetes whereas exposure to green space may confer a protective effect.

Incidence and Risk Factors for Acute Kidney Injury after Allogeneic Stem Cell Transplantation: A Prospective Study.

(1) Background: Acute kidney injury (AKI) is a serious complication of hematopoietic stem cell transplantation (HSCT). (2) Methods: The aim was to identify the incidence, severity, and risk factors for AKI during the first 100 days after allo-HSCT; we performed a prospective observational study on 135 consecutive patients. (3) Results: The mean age was 38.3 ± 11.9 years (50.6% females), AKI developed in 93 patients (68.9%), the median time of appearance was 28 days, and the mean serum creatinine at the time of AKI was 1.8 ± 0.8 mg/dL. A total of 36 (38.7%) patients developed stage 1 AKI, 33 (35.5%) patients developed stage 2, and 24 (25.8%) patients developed stage 3; eight (8.6%) patients required temporary hemodialysis, and the mortality rate in these patients was 87.5%. Death was twice as frequent in the AKI subgroup, without statistical significance. Cyclosporine overdose (HR = 2.36, 95% CI: 1.45-3.85, p = 0.001), tacrolimus overdose (HR = 4.72, 95% CI: 2.22-10.01, p < 0.001), acute graft-versus-host disease (aGVHD) (HR = 1.96, 95% CI: 1.13-3.40, p = 0.01), and CRP level (HR = 1.009, 95% CI: 1.007-1.10, p < 0.001) were independent risk factors for AKI. Sepsis (HR = 5.37, 95% CI: 1.75-16.48, p = 0.003) and sinusoidal obstruction syndrome (HR = 5.10, 95% CI: 2.02-12.85, p = 0.001) were found as independent risk factors for AKI stage 3. (4) Conclusions: AKI occurs with high incidence and increased severity after allo-HSCT. Careful monitoring of calcineurin inhibitors and proper management of sepsis may reduce this risk.

Improving flexor tendon gliding by using the combination of carboxymethylcellulose-polyethylene oxide on murine model.

The current approach to flexor tendon injuries is complex and is no longer limited to suturing techniques. Strategies for improving hand function currently include rehabilitation protocols, appropriate suturing materials and techniques, changing the gliding surface by using lubricants and providing growth factors. One product, originally used in spinal surgery, has been shown to be effective in preventing postoperative adhesions. It is a combination of carboxymethylcellulose and polyethylene oxide-Dynavisc® (FzioMed, Inc.). The aim of the present study was to test the effect of Dynavisc® on acute injuries of the intrasynovial flexor tendons in the prevention of postoperative adhesions and the improvement of functional results. The study was performed on 20 Wistar rats distributed in two groups. The control group, represented by 10 rats, in which after the reconstruction of the flexor tendon, the peritendinous area was injected with saline solution and the study group, in which the peritendinous area was injected with a single administration of the lubricating gel, Dynavisc® (carboxymethylcellulose and polyethylene oxide). At 4 and 12 weeks, the rats were sacrificed and tissue biopsy consisted of tendon fragments and adjacent tissue. The evaluation of the results was performed by measuring the adhesion score and observing histological parameters. The presence of important adhesions was found in the control group compared with the group treated with Dynavisc®, where a supple and smooth tendon, with significantly fewer adhesions were found. The differences between the two groups were significant, thus indicating the efficiency of the lubricant in preventing adhesions. This study supported the important role of Dynavisc® in the regeneration of the tendon and the peritendinous structures, by limiting aberrant fibrous proliferation in the regeneration process and helping to build a peritendinous space.

Successful Treatment of Catastrophic Antiphospholipid Syndrome Using Rituximab: Case Report and Review of the Literature.

BACKGROUND: Kidney involvement is a frequent complication of systemic lupus erythematosus (SLE) and kidney biopsy is essential in differentiating lupus nephritis (LN) from thrombotic microangiopathy (TMA) secondary to antiphospholipid autoantibodies (aPL). Association between antiphospholipid syndrome (APS) and acquired hemophilia due to inhibitors was very rarely described in SLE patients. CASE PRESENTATION: We present the case of a 61-year-old male diagnosed with SLE who acquired deficiency of clotting factor VIII due to circulating inhibitors, admitted for acute kidney injury (AKI), microangiopathic hemolytic anemia, thrombocytopenia, and diplopia. Kidney biopsy showed TMA due to APS, but no signs of LN. Head computed tomography identified low dense areas in the white matter, suggesting small blood vessels' involvement. A diagnosis of probable catastrophic antiphospholipid syndrome (CAPS) was established and treatment with low molecular weight heparin, intravenous methylprednisolone, plasmapheresis, and rituximab was initiated, followed by resolution of AKI, diplopia, and TMA with complete depletion of CD19+B-lymphocytes (CD19+B-Ly) after one month. We further review the current knowledge regarding pathogenesis and management of CAPS in SLE patients. CONCLUSIONS: Targeted therapy was possible after kidney biopsy, improving renal and general prognosis. CD19+B-Ly repopulation preceded biological relapse, so monitoring of CD19+B-Ly may serve as a tool to predict relapses and guide rituximab therapy.

Body composition in patients with chronic obstructive pulmonary disease.

OBJECTIVES: Body composition assessment in chronic obstructive pulmonary disease (COPD) is important, as weight loss and muscular wasting are responsible for low exercise capacity in these patients, and low body mass index (BMI) and fat free mass index (FFMI) are important prognostic factors. Our study aims were: (a) to describe body composition in COPD patients referred to a pulmonary rehabilitation center in Bucharest; (b) to examine the relationships between body composition and disease severity (bronchial obstruction, exercise capacity, quality of life); (c) to test if segmental wasting of lower limbs muscle mass (measured by segmental body composition analysis) correlates with decreased exercise capacity. MATERIAL AND METHODS: We studied 36 consecutive COPD patients referred to our clinic for pulmonary rehabilitation. Patients performed pulmonary function tests, six minutes walking test (6MWT), and health status was evaluated with COPD Assessment Test (CAT). Body composition measurements were performed by direct segmental multi-frequency bioelectrical impedance analysis (BIA). OUTCOMES: This study offers the first data on body composition of Romanian COPD patientsThe prevalence of nutritional depletion (defined by low BMI and/or low FFMI) among our COPD patients was 22.2%. Mean FFMI was significantly lower in normal or underweight patients versus overweight or obese patients. Patients with low FFMI had lower exercise capacity at the 6MWT and higher CAT scores than patients with normal FFMI.Depending on the BMI and FFMI values the patients were divided in four categories: normal, semistarvation, sarcopenia and cachexia. The group of patients with sarcopenia (low FFMI and normal BMI) had the lowest mean MIP (Maximal Inspiratory Pressure), the lowest mean 6MWD (six minutes walking distance) and the higher CAT mean scores among all groups. Exercise capacity was significantly lower in muscular depleted patients (with low skeletal muscle mass index - SSMI). MIP correlated significantly with FFMI and SMMI. No correlations were found between parameters of body composition and FEV1 or CAT. Segmental body composition assessment revealed that unbalanced upper/lower skeletal muscle mass is associated with a lower exercise capacity as measured by 6WMT. CONCLUSIONS: This study offers the first data on body composition of Romanian COPD patients. The prevalence of nutritional depletion is similar to that found in other European studies. No significant correlations were found between FFMI and severity of the disease (bronchial obstruction, distance walked, CAT score). FFMI and SSMI correlated significantly with MIP. Sarcopenic patients had the lowest mean 6MWD, the lowest mean MIP and the highest CAT mean scores. SMMI significantly correlated with 6MWD. Segmental body composition assessment of revealed that "unbalanced" patients had lower results at 6MWT. These results show that body composition evaluation is useful for the assessment of COPD patients referred to pulmonary rehabilitation and should be routinely performed.

Prevalence and Characteristics of Pulmonary Hypertension Associated with COPD - A Pilot Study in Patients Referred to a Pulmonary Rehabilitation Program Clinic.

OBJECTIVES: Pulmonary hypertension (PH) is a common complication of chronic obstructive pulmo-nary disease (COPD); its prevalence is currently unknown. The objectives of the study were: (a) to provide data on the prevalence of PH among the COPD patients referred to a pulmonary rehabilitation program; (b) to evaluate possible correlations of PH with the severity of COPD, the presence of hypoxemia and polycythemia. MATERIAL AND METHODS: We retrospectively studied 31 consecutive patients with the diagnosis of COPD hospitalised in our clinic in which echocardiography was performed. Spirometry, peripheral oxygen saturation, haematocrit, echocardiography data, history of exacerbations and cardiac comorbidities were obtained from patients records. PH was defined as systolic pulmonary arterial pressure (sPAP) greater than 35 mmHg or by the presence of right ventricle (RV) abnormalities. OUTCOMES: The prevalence of PH was 38.7%. Resting hypoxemia was significantly more frequent in the PH group than in the non PH patients (p=0.019). Other differences were not statistically significant (severity of bronchial obstruction and polycythemia, cardiac comorbidities). The impact of PH on RV was found in only 5 patients with RV enlargement; no patient had RV hypertrophy or RV systolic dysfunction. Suspected "out of proportion" PH (sPAP greater than 50 mmHg) was encountered in 2 out of 12 patients with PH. CONCLUSIONS: The prevalence of PH in patients with COPD was 38.7%. Resting hypoxemia was significantly more frequent in PH patients. As PH has an important role in the prognosis of COPD patients, it should be evaluated in as many COPD patients as possible.

Pulmonary hypertension secondary to chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is the most common cause of secondary pulmonary hypertension (PH). PH secondary to COPD is associated with a worse prognosis of the disease, a low quality of life, as well as with a higher exacerbation frequency, and consequently with an increase in the healthcare cost of COPD patients. Prevalence of PH in COPD patients is currently unknown. The most important mechanisms leading to PH are hypoxic vasoconstriction, pulmonary hyperinflation and endothelial dysfunction. PH should be suspected in COPD patients in the presence of severe dyspnoea, disproportionate from the decline in lung function, or of severe hypoxemia. Exercise induced PH is an independent predictor of the development of resting PH in patients with COPD. Echocardiography is the first screening method for PH in patients with COPD and it should be widely used, as it can also appreciate the cardiac consequences of PH, especially on the right ventricle. Given the high negative predictive value of the echocardiographic estimation of systolic pulmonary arterial pressure (sPAP) in the diagnosis of PH, the absence of a high sPAP excludes important PH and further unnecessary invasive evaluation. Right cardiac catheterization remains the "gold standard" method in assessing PH, but it is less accessible and cannot be used in routine evaluation of patients with COPD. PH secondary to COPD is usually mild, but a small proportion of patients have severe PH, with specific characteristics, worse prognosis and a specific therapeutic approach.

Endocarditis in the 21(st) Century.

Endocarditis still carries a poor prognosis despite improvement in preventive strategies and advances in diagnosis and also in treatment. Epidemiology of infective endocarditis (IE) has changed in late years. Contemporary antibiotic overuse determines antibiotic resistance against microorganisms involved in IE. Prophylaxis principles have been changed and restricted in order to avoid excessive antibiotic use and unfounded costs. Current guidelines are often based on expert opinion because of the low incidence of the disease, the absence of randomized trials, and the limited number of meta-analyses. The present review will focus on current changes in epidemiology, prophylaxis, diagnosis and treatment options.

A case of 75-year-old survivor of unrepaired tetralogy of Fallot and quadricuspid aortic valve.

In tetralogy of Fallot (TOF), the most common form of cyanotic congenital heart disease, only a few patients reach adulthood without surgical correction. We present the case of a man with TOF who survived until the age of 75 years without surgical intervention and had a very unusual combination of TOF and quadricuspid aortic valve (QAV). QAV, complicated by aortic regurgitation, is an uncommon finding in TOF patients. The hemodynamic consequences for both the right and left ventricles are significant. This case provides a rare insight into the late outcome of an elderly patient with uncorrected TOF.

Heart failure and dilated cardiomyopathy associated with severe longstanding untreated hypothyroidism.

Thyroid hormones have many effects on the heart and vascular system. Although cardiac output is reduced in hypothyroidism, heart failure is relatively rare because there is a lower demand for peripheral oxygen delivery. Hypothyroidism may also result in accelerated atherosclerosis and coronary artery disease. We report the case of a 55-year-old man with severe heart failure associated with severe longstanding untreated hypothyroidism. The patient was admitted for shortness of breath and chest pain. On presentation, signs and symptoms of severe hypothyroidism and heart failure were noticed. The electrocardiogram showed sinus bradycardia and ischemia. Thyroid stimulating hormone was extremely elevated and thyroid hormone levels were undetectable. A cardiac ultrasonography exam revealed abnormalities of the left ventricular dimensions and function consistent with dilated cardiomyopathy. Coronary angiography showed severe multivessel disease. Coronary by-pass was deemed necessary, but surgery was postponed because of severe heart failure. After an increasingly downhill clinical course, the patient died, eight month after his initial presentation, owing to severe heart failure. This patient represents an example of an overlooked diagnosis of severe hypothyroidism, rarely encountered nowadays, leading to dramatic consequences.

Takotsubo cardiomyopathy.

Recently, a novel heart syndrome, mimicking acute coronary syndrome, was described. Patients commonly present with chest pain, ST segment elevation, prolonged QT interval and slight elevation of cardiac enzymes and biomarker levels, despite the absence of significant coronary artery disease. Because of the peculiar left ventricular apical ballooning shape, given by characteristic regional wall motion abnormalities consisting in apical akinesis and basal hyperkinesis, this syndrome was named "Takotsubo" cardiomyopathy, after a round Japanese octopus fishing pot. An episode of emotional or physical stress, including a number of noncardiac illnesses, can be often identified as a trigger. Its unique features include also a strong female predominance and a complete rapid resolution. The management of this syndrome consists mainly in supportive and symptomatic therapy. The evolution, although mainly uneventful, can be complicated, rarely, by left ventricular rupture, making thus the takotsubo cardiomyopathy a newly recognized cause of sudden death. We present some data on the epidemiology, pathogenesis, clinical picture and management of this peculiar form of heart disease, which, although easily confounded with an acute coronary syndrome, has emerged as a unique nosologic entity.

Exercise echocardiography in coronary artery disease.

Exercise echocardiography is one of the stress echocardiography modalities, widely used nowadays, mainly in the patients with coronary artery disease. It is a first-line technique for the diagnosis of coronary disease and for prognostication in various patients' subsets, including patients with chronic coronary artery disease, patients with recent revascularization or myocardial infarction and women. This method relies on the fact that in the presence of a significant coronary stenosis, an adequate level of physical exertion produces a mismatch between oxygen demand and supply, resulting in a wall motion abnormality in the area supplied by that stenotic artery. The wall motion abnormalities that develop are detectable by echocardiography and are a marker of the degree of ischemia. The most commonly employed forms of exercise in conjunction with echocardiography are immediate post exercise imaging on a treadmill and exercising during supine or upright bicycle ergometry. Echocardiograms can be interpreted qualitatively, with a description of the recorded wall motion abnormalities, or quantitatively, calculating a wall motion score. The overall accuracy of exercise echocardiography in the diagnosis of coronary artery disease is about 80-90%. Exercise echocardiography has been shown to provide useful information for the purpose of risk stratification and prediction of coronary events after acute myocardial infarction, after angioplasty and after coronary artery bypass grafting. In women, the accuracy of electrocardiographic stress testing is less than in men and stress echocardiography offers a better alternative in the diagnosis of ischemic heart disease. For the patients with an intermediate pre-test probability of having ischemic heart disease and a resting electrocardiogram which precludes an optimal interpretation of the electrocardiographic stress test (digoxin use, left ventricular hypertrophy with repolarization abnormalities, preexcitation, or left bundle-branch block), exercise echocardiography represents a good alternative to radionuclide imaging.