Comparative toxicity of physiological and biochemical parameters in Euglena gracilis to short-term exposure to potassium sorbate

Ecotoxicology - Potassium sorbate is the potassium salt of sorbic acid, is a widespread and efficient antioxidant that has multiple functions in plants, traditionally associated with the reactions...     

A prospective study of visceral leishmaniasis in an endemic area of Brazil

The epidemiology, clinical patterns, and risk factors for visceral leishmaniasis were prospectively studied in an endemic area of Brazil. The prevalence of disease was 3.1% for children less than 15 years of age, and the annual incidence was 4.3 cases per 1,000 children. The number of children with disease fluctuated yearly and seasonally, and distribution of the disease varied within the endemic area. Risk factors included young age (median, three years) and malnutrition before the onset of disease. Intestinal parasitism, recent migration into the area, and house location within the area did not influence the progression of infection to disease. Serological testing indicated that 7.5% of children were infected with Leishmania each year and that the ratio of disease to infection was 1:18.5 for the whole area and 1:6.5 for the section with the highest prevalence of disease. Early diagnosis and therapy altered clinical patterns of the disease.     

Anomalous origin of the left pulmonary artery from the ascending aorta. Successful surgical correction in an infant with Fallot's tetralogy

We describe the case of a 40-day-old female patient with a history of breathlessness since birth who was referred to our hospital for surgical correction of common arterial trunk. The invasive investigation disclosed a Fallot cent s tetralogy anatomy associated with an anomalous origin of the left pulmonary artery from the ascending aorta. Immediately after diagnosis, the patient underwent a successful total surgical correction of the defect, including simultaneous anastomosis of the left pulmonary artery to the pulmonary trunk.     

Water-based resistance training program with isolated concentric action improves physical functional capacity and muscular strength in older women

Background

Resistance training has proven to be an excellent method for counteracting aging physical dysfunctions. However, its application in the liquid environment is not yet fully elucidated.

Aim

To investigate the effects of water-based resistance training (WBRT) with the concentric phase performed as fast as possible, compared to conventional resistance training (CRT), on physical functional capacity, muscle strength, and body composition in older women.

Methods

Thirteen healthy older women participated in the WBRT and 11 in the CRT. Estimation statistics focused on the effect size of the experiment/intervention were used. We also analyzed the intervention effect based on the percentage delta between WBRT and CRT.

Results

The WBRT group showed a negative large effect (d?=?? 0.922; p?=?0.0274) for the timed up and go, and a large effect for chair rise in 30″ and the elbow flex test (d?=?1.58; p?=?0.0012; d?=?2.8; p?=?0.01) respectively. Intervention comparisons based on the delta percentage between WBRT and CRT presented an intermediate effect (d?=?0.606; p?=?0.157) for the stair climb, a large effect (d?=?0.988; p?=?0.0282) for the timed up and go, and a large negative effect [d?=?? 1.32 (90.0% CI ? 1.92, ? 0.646); p?=?0.0038] for the elbow flex test. Concentric extensor-flexor peak torque (60°/s) showed an intermediate effect (d?=?0.749; p?=?0.0876; d?=?0.65; p?=?0.122 respectively). Body fat (%) demonstrated an intermediate effect (d?=?0.523; p?=?0.234).

Conclusion

WBRT with the concentric phase performed as fast as possible was able to improve physical functional capacity and maximal knee extension strength of older women.

     

Interpretation of liver chemistries in adult donors after living donor liver transplantation

OBJECTIVES: The safety of donors is paramount in adult living donor liver transplantation. Our goal is to compare the pattern of recovery of hepatic synthetic function and aminotransferases in healthy adult donors with and without complications. METHODS: We reviewed 47 consecutive patients undergoing right donor hepatectomy at our center. Laboratory data were collected through the first 2 postoperative weeks and results from donors with and without complications were compared. RESULTS: Donor morbidity was 25% and there were no donor deaths. Total bilirubin peaked on postoperative day 3, whereas aminotransferases and international normalized ratio peaked on postoperative day 1. Peak total bilirubin was higher in patients with fluid collections (n = 7) compared with those without fluid collections (n = 40), 4.6 mg/dL and 2.3 mg/dL, respectively, P = 0.02. On postoperative day 3 the peak total bilirubin was greater than 3.0 mg/dL in 86% of donors with fluid collections and 15% of donors without fluid collections, (P = 0.0005) whereas aminotransferases and alkaline phosphatase were not significantly different between these 2 groups. CONCLUSIONS: After right donor hepatectomy a total bilirubin greater than 3.0 mg/dL on postoperative day 3 should prompt an evaluation for a fluid collection, even if other liver tests are normal or declining.     

Enhanced purification and production of Müllerian inhibiting substance for therapeutic applications

It is almost 60 years since Prof. Alfred Jost reported the seminal observations regarding Müllerian inhibiting substance (MIS). His experiments clearly showed that a testicular product other than testosterone, a Müllerian inhibitor, was responsible for Müllerian duct regression. Twenty-five years later Dr. Picon established an organ culture assay which paved the way for the initial studies into the biochemistry and biology of Müllerian inhibiting substance, also known as Anti-Müllerian hormone (AMH), undertaken first in Dr. Nathalie Josso's Laboratory in Paris then in our own laboratory in Boston. Purification of MIS led to cloning the human gene and production of recombinant human (rhMIS). MIS is a 140 kDa glycoprotein homodimer which is activated by a biosynthetic protease, cleaving MIS into an aminoterminus (110 kDa) and a carboxyterminus (25 kDa). The latter domain is sufficient for biological activities. MIS functions by interacting with two receptors; a type II binds the hormone and at type I that initiates downstream signaling. The MIS type II receptor has been cloned and functionally confirmed as distinct from that of other members of the TGFbeta superfamily. MIS can employ a number of type I receptors (ALK2, ALK3, ALK6) and BMP receptor specific SMADS 1, 5, and 8 in various tissue specific contexts. Cell lines derived from human ovarian, breast, and prostate tumors, and from rodent Leydig cell tumors, which respond to MIS in growth inhibition assays, all express the MIS type II receptor. A variety of signal transduction pathways are associated with the grown inhibition mediated by MIS. For example, breast and prostate cancer cell lines use a MIS-mediated NFkappaB pathway leading to G1 arrest and apoptosis. The ovarian cancer cell lines employ a pathway which enhances p16, modulates the E2Fs, and induces apoptosis. These signal transduction events can establish new rational treatment strategies to complement the growth inhibitory effects mediated by MIS. These combination strategies are being tested in vitro, and where appropriate will be tested in vivo using the highly purified MIS preparations, prior to use in early human clinical trials.     

Markers of Increased Cardiovascular Risk in Postmenopausal Women: Focus on Oxidized-LDL and HDL Subpopulations

Objective. To evaluate the effect of gender and menopause in cardiovascular risk (CVR) in a healthy population based on both classical and nontraditional markers. Methods. 56 men and 68 women (48 pre- and 20 postmenopause) were enrolled in the study. The following markers were analyzed: blood pressure (BP), body mass index (BMI), waist circumference (WC), glucose, total cholesterol (total-c), triglycerides (TGs), low-density lipoprotein cholesterol (LDL-c), oxidized-LDL (Ox-LDL), HDL-c and subpopulations, paraoxonase-1 activity, hsCRP, uric acid, tumor necrosis factor alpha (TNF-α), adiponectin, vascular endothelial growth factor (VEGF), and intercellular adhesion molecular 1 (ICAM1). Results. Relative to the women, men present significantly increased BMI, WC, BP, glucose, total-c, TGs, LDL-c, Ox-LDL, uric acid, and TNF-α and reduced adiponectin and total and large HDL-c. The protective profile of women is lost after menopause with a significantly increased BMI, WC, BP, glucose, LDL-c, Ox-LDL, hsCRP, and VEGF and decreased total and large HDL-c. Significant correlations were found in women population and in postmenopausal women between Ox-LDL and total, large, and small HDL-c and between TNF-α and total, large, and small HDL-c, LDL-c, and Ox-LDL. Conclusions. Men present higher CVR than women who lost protection after menopause, evidenced by nontraditional markers, including Ox-LDL and HDL subpopulations.     

Reduced Motivation in Perinatal Fluoxetine-Treated Mice: A Hypodopaminergic Phenotype

Early life is a sensitive period, in which enhanced neural plasticity allows the developing brain to adapt to its environment. This plasticity can also be a risk factor in which maladaptive development can lead to long-lasting behavioral deficits. Here, we test how early-life exposure to the selective-serotonin-reuptake-inhibitor (SSRI), fluoxetine, affects motivation, and dopaminergic signaling in adulthood. We show for the first time that mice exposed to fluoxetine in the early postnatal period exhibit a reduction in effort-related motivation. These mice also show blunted responses to amphetamine and reduced dopaminergic activation in a sucrose reward task. Interestingly, we find that the reduction in motivation can be rescued in the adult by administering bupropion, a dopamine-norepinephrine reuptake inhibitor used as an antidepressant and a smoke cessation aid but not by fluoxetine. Taken together, our studies highlight the effects of early postnatal exposure of fluoxetine on motivation and demonstrate the involvement of the dopaminergic system in this process.SIGNIFICANCE STATEMENT The developmental period is characterized by enhanced plasticity. During this period, environmental factors have the potential to lead to enduring behavioral changes. Here, we show that exposure to the SSRI fluoxetine during a restricted period in early life leads to a reduction in adult motivation. We further show that this reduction is associated with decreased dopaminergic responsivity. Finally, we show that motivational deficits induced by early-life fluoxetine exposure can be rescued by adult administration of bupropion but not by fluoxetine.     

Long-term impact of early initiation of enzyme replacement therapy in 34 MPS VI patients: A resurvey study

Patients with mucopolysaccharidosis type VI (MPS VI) present with a wide range of disease severity and clinical manifestations, with significant functional impairment and shortened lifespan. Enzyme replacement therapy (ERT) with galsulfase has been shown to improve clinical and biochemical parameters including patient survival, quality of life and growth. The present study is a resurvey of 34 Brazilian MPS VI patients with rapidly progressive disease (classical phenotype) who initiated ERT with galsulfase under five years of age and had been on ERT until data collection in 2019, with few exceptions (n = 4 patients who died before 2019).Anthropometric measures, urinary glycosaminoglycans, and data regarding cardiac, orthopedic, neurologic, sleep apnea, hearing and ophthalmologic outcomes were filled in by specialists. Pubertal development, clinical complications, hospitalizations, and surgeries were also assessed.In this resurvey study, treatment with galsulfase has shown to be safe and well tolerated in MPS VI patients who initiated ERT under the age of 5 years and who have been undergoing ERT for approximately 10 years. Mortality rate suggests that early initiation of ERT may have a positive impact on patients' survival, improving but not preventing disease progression and death. MPS VI patients on ERT also showed improved growth velocity and the pubertal development was normal in all surviving patients.Follow-up data on pneumonia and hospitalization suggest that early ERT may have a protective effect against major respiratory complications. Cardiac valve disease progressed since their prior evaluation and spinal cord compression was observed in a large number of patients, suggesting that these disease complications were not modified by ERT.     

The H2020 “NoHoW Project”: A Position Statement on Behavioural Approaches to Longer-Term Weight Management

There is substantial evidence documenting the effects of behavioural interventions on weight loss (WL). However, behavioural approaches to initial WL are followed by some degree of longer-term weight regain, and large trials focusing on evidence-based approaches to weight loss maintenance (WLM) have generally only demonstrated small beneficial effects. The current state-of-the-art in behavioural interventions for WL and WLM raises questions of (i) how we define the relationship between WL and WLM, (ii) how energy balance (EB) systems respond to WL and influence behaviours that primarily drive weight regain, (iii) how intervention content, mode of delivery and intensity should be targeted to keep weight off, (iv) which mechanisms of action in complex interventions may prevent weight regain and (v) how to design studies and interventions to maximise effective longer-term weight management. In considering these issues a writing team within the NoHoW Consortium was convened to elaborate a position statement, and behaviour change and obesity experts were invited to discuss these positions and to refine them. At present the evidence suggests that developing the skills to self-manage EB behaviours leads to more effective WLM. However, the effects of behaviour change interventions for WL and WLM are still relatively modest and our understanding of the factors that disrupt and undermine self-management of eating and physical activity is limited. These factors include physiological resistance to weight loss, gradual compensatory changes in eating and physical activity and reactive processes related to stress, emotions, rewards and desires that meet psychological needs. Better matching of evidence-based intervention content to quantitatively tracked EB behaviours and the specific needs of individuals may improve outcomes. Improving objective longitudinal tracking of energy intake and energy expenditure over time would provide a quantitative framework in which to understand the dynamics of behaviour change, mechanisms of action of behaviour change interventions and user engagement with intervention components to potentially improve weight management intervention design and evaluation.