Plastic debris in lakes and reservoirs.

Plastic debris is thought to be widespread in freshwater ecosystems globally1. However, a lack of comprehensive and comparable data makes rigorous assessment of its distribution challenging2,3. Here we present a standardized cross-national survey that assesses the abundance and type of plastic debris (>250 µm) in freshwater ecosystems. We sample surface waters of 38 lakes and reservoirs, distributed across gradients of geographical position and limnological attributes, with the aim to identify factors associated with an increased observation of plastics. We find plastic debris in all studied lakes and reservoirs, suggesting that these ecosystems play a key role in the plastic-pollution cycle. Our results indicate that two types of lakes are particularly vulnerable to plastic contamination: lakes and reservoirs in densely populated and urbanized areas and large lakes and reservoirs with elevated deposition areas, long water-retention times and high levels of anthropogenic influence. Plastic concentrations vary widely among lakes; in the most polluted, concentrations reach or even exceed those reported in the subtropical oceanic gyres, marine areas collecting large amounts of debris4. Our findings highlight the importance of including lakes and reservoirs when addressing plastic pollution, in the context of pollution management and for the continued provision of lake ecosystem services.

The differential effects of palmitic acid and oleic acid on the metabolic response of hypothalamic astrocytes from male and female mice.

Diets rich in saturated fats are more detrimental to health than those containing mono- or unsaturated fats. Fatty acids are an important source of energy, but they also relay information regarding nutritional status to hypothalamic metabolic circuits and when in excess can be detrimental to these circuits. Astrocytes are the main site of central fatty acid ß-oxidation, and hypothalamic astrocytes participate in energy homeostasis, in part by modulating hormonal and nutritional signals reaching metabolic neurons, as well as in the inflammatory response to high-fat diets. Thus, we hypothesized that how hypothalamic astrocytes process-specific fatty acids participates in determining the differential metabolic response and that this is sex dependent as males and females respond differently to high-fat diets. Male and female primary hypothalamic astrocyte cultures were treated with oleic acid (OA) or palmitic acid (PA) for 24 h, and an untargeted metabolomics study was performed. A clear predictive model for PA exposure was obtained, while the metabolome after OA exposure was not different from controls. The observed modifications in metabolites, as well as the expression levels of key metabolic enzymes, indicate a reduction in the activity of the Krebs and glutamate/glutamine cycles in response to PA. In addition, there were specific differences between the response of astrocytes from male and female mice, as well as between hypothalamic and cerebral cortical astrocytes. Thus, the response of hypothalamic astrocytes to specific fatty acids could result in differential impacts on surrounding metabolic neurons and resulting in varied systemic metabolic outcomes.

High Cardiac Troponin Levels in Infants with Acute SARS-CoV-2 Infection: A Prospective Comparative Study.

OBJECTIVE: To investigate the specific role of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in inducing elevation of marker of myocardial injury in infants with acute coronavirus disease 2019 (COVID-19). STUDY DESIGN: A prospective, multicentric 3-arm comparative study (March 2020 through March 2022) enrolling 152 infants hospitalized for COVID-19, 79 children with acute infections other than SARS-CoV-2, and 71 healthy controls. Determination of high-sensitivity cardiac troponin (hs-cTn) levels was the primary outcome. RESULTS: The proportion of children with hs-cTn values above the upper limit of normal (44 [28.9%]), as well as with a 3-fold increased value (20 [13.2%]) were significantly higher in the COVID-19 group than those in both control groups. The risk of presenting a 3-fold increased hs-cTn value was higher in children with SARS-CoV-2 infection compared with either healthy children (OR, 5.23; 95% CI, 1.19-23.02) or those with other infections (OR, 11.89; 95% CI, 1.56-89.79). In children with COVID-19, hs-cTn elevation was associated with neither clinical nor biochemical characteristics, nor perinatal risk factors, but with an age of <3 months (P < .001). After adjustment for age, sex, and underlying clinical conditions, elevated hs-cTn was independently associated with COVID-19 in a multivariable regression model. All children showed a progressive reduction of hs-cTn until normalization over time, without clinical, ECG, or echocardiographic manifestations up to 1 year of follow-up. CONCLUSIONS: Infants with acute SARS-CoV-2 infection may show a subclinical and transient alteration of myocardial injury markers, especially in the first months of life. hs-cTn levels normalized during follow-up and were not associated with cardiac functional impairment; nevertheless, long-term consequences are unknown and should be followed carefully.

Direct and indirect effects of physiological, psychological and cognitive variables on academic achievement in children.

BACKGROUND: Associations between cardiorespiratory fitness (CRF), screen time, psychological well-being, executive functions, and academic achievement have been reported, however, few studies have analysed models considering the effect of all these variables on academic achievement. This study aims to analyse the direct and indirect associations of mothers' education level, CRF, screen time, psychological well-being, executive functions, with academic achievement in schoolchildren, by sex. METHODS: This was a cross-sectional analysis of MOVI-daFit! study including 519 schoolchildren (49.52% girls) aged 9-11 years old. Executive functions were assessed with the NIH Toolbox, CRF with the 20-m shuttle run test, academic achievement through the final academic grades in language and mathematics and mother's education level, screen time and well-being by questionnaires. RESULTS: Structural equation modelling revealed that in boys cognitive flexibility had a significant direct effect on academic achievement and screen time a total significant effect on academic achievement. In girls, CRF was associated with inhibition and psychological well-being, and this was associated with academic achievement. CONCLUSIONS: Physiological, psychological, and behavioural variables act together to impact academic achievement, and that differences by sex might exist. Thus, strategies to enhance academic achievement in schoolchildren should consider psychological well-being, CRF, screen time, and sex differences. IMPACT: Physiological, psychological, and behavioural variables, such as cardiorespiratory fitness, screen time, psychological well-being, and cognition all together have an impact on academic achievement, with differences by sex. Previous studies have demonstrated the separate effect of these variables, however, to date, this is the first study that analyses all together in the same model their impact on academic achievement, by sex. This study shows that in boys cognitive flexibility and screen time impact academic achievement. In girls, cardiorespiratory fitness is highly associated with psychological well-being, and this, in turn, was associated with academic achievement.

Image quality of whole-body diffusion MR images comparing deep-learning accelerated and conventional sequences.

OBJECTIVES: To compare the image quality of deep learning accelerated whole-body (WB) with conventional diffusion sequences. METHODS: Fifty consecutive patients with bone marrow cancer underwent WB-MRI. Two experts compared axial b900 s/mm2 and the corresponding maximum intensity projections (MIP) of deep resolve boost (DRB) accelerated diffusion-weighted imaging (DWI) sequences (time of acquisition: 6:42 min) against conventional sequences (time of acquisition: 14 min). Readers assessed paired images for noise, artefacts, signal fat suppression, and lesion conspicuity using Likert scales, also expressing their overall subjective preference. Signal-to-noise and contrast-to-noise ratios (SNR and CNR) and the apparent diffusion coefficient (ADC) values of normal tissues and cancer lesions were statistically compared. RESULTS: Overall, radiologists preferred either axial DRB b900 and/or corresponding MIP images in almost 80% of the patients, particularly in patients with a high body-mass index (BMI > 25 kg/m2). In qualitative assessments, axial DRB images were preferred (preferred/strongly preferred) in 56-100% of cases, whereas DRB MIP images were favoured in 52-96% of cases. DRB-SNR/CNR was higher in all normal tissues (p < 0.05). For cancer lesions, the DRB-SNR was higher (p < 0.001), but the CNR was not different. DRB-ADC values were significantly higher for the brain and psoas muscles, but not for cancer lesions (mean difference: + 53 µm2/s). Inter-class correlation coefficient analysis showed good to excellent agreement (95% CI 0.75-0.93). CONCLUSION: DRB sequences produce higher-quality axial DWI, resulting in improved MIPs and significantly reduced acquisition times. However, differences in the ADC values of normal tissues need to be considered. CLINICAL RELEVANCE STATEMENT: Deep learning accelerated diffusion sequences produce high-quality axial images and MIP at reduced acquisition times. This advancement could enable the increased adoption of Whole Body-MRI for the evaluation of patients with bone marrow cancer. KEY POINTS: Deep learning reconstruction enables a more than 50% reduction in acquisition time for WB diffusion sequences. DRB images were preferred by radiologists in almost 80% of cases due to fewer artefacts, improved background signal suppression, higher signal-to-noise ratio, and increased lesion conspicuity in patients with higher body mass index. Cancer lesion diffusivity from DRB images was not different from conventional sequences.

Adherence to the Mediterranean diet and depressive, anxiety, and stress symptoms in Spanish adolescents: results from the EHDLA study.

Depression and anxiety are prevalent and disabling conditions among adolescents. The aim of this study was to examine the relationship between adherence to the Mediterranean diet (MD) and depressive, anxiety, and stress symptoms in adolescents. This cross-sectional study included a sample of 698 adolescent students from a region of Spain (mean age of 13.9 ± 1.5 years; 56.2% girls). Adherence to the MD was evaluated with the Mediterranean Diet Quality Index in children and adolescents (KIDMED). Mental health symptoms were measured with the Depression, Anxiety, and Stress Scale (DASS-21). Logistic regression models were performed, including a wide range of potential confounders. Compared to individuals with low adherence to the MD, those with moderate and high adherence had lower odds of experiencing depressive symptoms (odds ratio [OR] = 0.40, 95% confidence interval [CI] 0.24-0.65 and OR = 0.33, 95% CI 0.20-0.55, respectively), which were statistically significant even after adjustment. No significant associations were found regarding anxiety or stress symptoms. Therefore, according to our results, higher adherence to the MD is inversely related to having depressive symptoms among adolescents, regardless of socioeconomic, anthropometric, and lifestyle factors. Considering the deleterious effects of mental health problems in youths, further research on the role of nonpharmacological strategies for the prevention and treatment of depressive symptoms in adolescence is essential.

HCV spontaneous clearers showed low senescence profile in people living with HIV under long ART.

Coinfection with hepatitis C virus (HCV) and human immunodeficiency virus (HIV) increases immune activation, inflammation, and oxidative stress that could lead to premature senescence. Different HCV infections, either acute or chronic infection, could lead to distinct premature cellular senescence in people living with HIV (PLWHIV). Observational study in 116 PLWHIV under antiretroviral treatment with different HCV status: (i) n = 45 chronically infected with HCV (CHC); (ii) n = 36 individuals who spontaneously clarify HCV (SC); (iii) n = 35 HIV controls. Oxidative stress biomarkers were analyzed at lipid, DNA, protein, and nitrates levels, as well as antioxidant capacity and glutathione reductase enzyme. Replicative senescence was evaluated by relative telomere length (RTL) measurement. Additionally, 26 markers of Senescence-Associated Secretory Phenotype (SASP) were analyzed by multiplex immunoassays (Luminex xMAP technology). Differences were evaluated by generalized linear model (GLMs) adjusted by most significant covariates. The SC group had a senescence signature similar to the HIV control group and slightly lower SASP levels. However, significant differences were observed with respect to the CHC group, where an increase in the nitrate concentration [adjusted arithmetic mean ratio, aAMR = 1.73 (1.27-2.35), p < 0.001, q = 0.009] and the secretion of 13 SASP-associated factors [granulocyte macrophage colony-stimulating factor (GM-CSF), interferon-ß, interleukin (IL)-1ß, IL-2, IL-8, IL-13, tumor necrosis factor (TNF)-α, IL-1α, IL-1RA, IL-7, IL-15, C-X-C motif chemokine ligand 10 (IP-10), stem cell factor (SCF); q < 0.1)] was detected. The CHC group also showed higher values of IL-1α, IP-10, and placental growth factor 1 (PIGF-1) than HIV controls. The SC group showed a slightly lower senescence profile than the HIV group, which could indicate a more efficient control of viral-induced senescence due to their immune strengths. Chronic HCV infection in PLWHIV led to an increase in nitrate and elevated SASP biomarkers favoring the establishment of viral persistence.

Intelligence quotient-genotype association in dystrophinopathies: A systematic review and meta-analysis.

AIMS: Becker muscular dystrophy (BMD) and Duchenne muscular dystrophy (DMD) are associated with intelligence quotients (IQs) lower than the normative values, and it is suggested that IQ is negatively correlated with the number of affected isoforms (i.e., Dp427, Dp140 and Dp71). Therefore, the objective of this meta-analysis was to estimate the IQ, and the IQ-genotype association according to the altered dystrophin isoforms, in the population with BMD or DMD. METHODS: A systematic search in Medline, Web of Science, Scopus and the Cochrane Library was conducted from inception to March 2023. Observational studies that determined the IQ and/or the IQ by genotype in the population with BMD or DMD were included. Meta-analyses of IQ, IQ by genotype and IQ-genotype association by comparing IQ according to the genotype were conducted. The results are shown as the mean/mean differences and 95% confidence intervals. RESULTS: Fifty-one studies were included. The IQ in BMD was 89.92 (85.84, 94.01) and in DMD was 84.61 (82.97, 86.26). Moreover, the IQ for Dp427-/Dp140+/Dp71+ and Dp427-/Dp140-/Dp71+ was 90.62 (86.72, 94.53) and 80.73 (67.49, 93.98) in BMD, while the IQ for Dp427-/Dp140+/Dp71+, Dp427-/Dp140-/Dp71+ and Dp427-/Dp140-/Dp71- was 93.05 (89.42, 96.67), 81.78 (77.23, 86.32) and 49.19 (40.47, 57.90) in DMD. Finally, in DMD, Dp427-/Dp140-/Dp71+ vs Dp427-/Dp140+/Dp71+ and Dp427-/Dp140-/Dp71- vs Dp427-/Dp140-/Dp71+ were associated with -10.73 (-14.66, -6.81) and -36.14 (-48.87, -23.41) points, respectively. CONCLUSIONS: The IQ in BMD and DMD was lower than the normative values. Moreover, in DMD, there is a synergistic association between the number of affected isoforms and IQ.

Diabetes and erectile dysfunction: The relationships with health literacy, treatment adherence, unrealistic optimism, and glycaemic control.

PURPOSE: The aim of this study was to evaluate the relationships between health literacy, unrealistic optimism, and adherence to glycometabolic disease management related to erectile dysfunction (ED) in male patients with type 2 diabetes (T2D) or preDM. MATERIALS AND METHODS: This prospective observational study enroled 167 consecutive patients with T2D and ED. All patients underwent the following examinations: (a) medical history collection; (b) Body Mass Index (BMI) determination; (c) hormonal and biochemical assessment; (d) duration of T2D, complications and treatment; (e) International Index of Erectile Function-5 questionnaire to assess ED; and (f) validated questionnaire to evaluate health literacy, unrealistic optimism, and treatment adherence. RESULTS: Overall, mean age was 62.5 ± 9.4 years (range: 20-75) and mean BMI was 28.4 ± 4.8 kg/m2 (range: 18.4-46.6). The mean IIEF-5 score was 15.4 ± 5.2 (range: 5-25). The majority of patients showed high health literacy. However, low health literacy was found in patients with higher IIEF-5 scores and high BMI. Unrealistic optimism was low in most patients. Higher adherence to treatment was found in patients who reported regular physical activity, who followed a diet, and in patients with a family history of T2D. Regarding anti-diabetic treatment, patients treated with insulin showed higher health literacy than patients not treated with other medications, whereas higher adherence was found in patients using SGLT2-i. CONCLUSIONS: This study highlighted the close relationship between metabolic compensation, BMI, ED, and psychological attitudes, including health literacy and unrealistic optimism.

Effects of saturated versus unsaturated fatty acids on metabolism, gliosis, and hypothalamic leptin sensitivity in male mice.

BACKGROUND: Development of obesity and its comorbidities is not only the result of excess energy intake, but also of dietary composition. Understanding how hypothalamic metabolic circuits interpret nutritional signals is fundamental to advance towards effective dietary interventions. OBJECTIVE: We aimed to determine the metabolic response to diets enriched in specific fatty acids. METHODS: Male mice received a diet enriched in unsaturated fatty acids (UOLF) or saturated fatty acids (SOLF) for 8 weeks. RESULTS: UOLF and SOLF mice gained more weight and adiposity, but with no difference between these two groups. Circulating leptin levels increased on both fatty acid-enriched diet, but were higher in UOLF mice, as were leptin mRNA levels in visceral adipose tissue. In contrast, serum non-esterified fatty acid levels only rose in SOLF mice. Hypothalamic mRNA levels of NPY decreased and of POMC increased in both UOLF and SOLF mice, but only SOLF mice showed signs of hypothalamic astrogliosis and affectation of central fatty acid metabolism. Exogenous leptin activated STAT3 in the hypothalamus of all groups, but the activation of AKT and mTOR and the decrease in AMPK activation in observed in controls and UOLF mice was not found in SOLF mice. CONCLUSIONS: Diets rich in fatty acids increase body weight and adiposity even if energy intake is not increased, while increased intake of saturated and unsaturated fatty acids differentially modify metabolic parameters that could underlie more long-term comorbidities. Thus, more understanding of how specific nutrients affect metabolism, weight gain, and obesity associated complications is necessary.

Imaging of Anatomical Variants of the Long Head Biceps Tendon.

Anatomical variants of the long head of biceps (LHB) tendon are widely discussed in the literature. As one of the few intra-articular tendons, magnetic resonance arthroscopy can quickly evaluate the proximal part of LHB morphology. It provides good assessment of both intra-articular and extra-articular portions of the tendons. In-depth knowledge about imaging of the anatomical LHB variants discussed in this article is useful preoperatively for orthopaedists and also helps avoid potential diagnostic misinterpretations.

High degree of consensus on diagnosis and management of rotator cuff tears: a Delphi approach.

PURPOSE: To develop a consensus on diagnosis and treatment of rotator cuff tears. The study focused on selected areas: imaging, prognostic factors, treatment options, surgical techniques. METHODS: Panel was composed of all members of the shoulder committee of the Italian Society of Arthroscopy, Knee, Upper arm, Sport, Cartilage and Orthopedic techniques (SIAGASCOT). Four rounds were performed. The first round consisted of gathering questions which were then divided into seven blocks referring to: imaging, patient-related prognostic factors, treatment options, surgical steps, reparative techniques, surgical predictive factors, advanced techniques. Subsequent rounds consisted of condensation by means of online questionnaire and debates. Consensus was defined as two-thirds agreement on one answer. Descriptive statistic was used to summarize the data. RESULTS: Forty-one shoulder experts were involved. Fifty-six statements were finally formulated. A consensus could be achieved on 51. Experts agreed that preoperative magnetic resonance imaging is strongly recommended because it allows a careful evaluation of tear characteristics, while the role of US remains debatable. Controversial patient-related factors such as age, comorbidities, smoking and stiffness do not contraindicate the repair. From a surgical standpoint, the experts highlighted that pseudo-paralysis is not a contraindication to rotator cuff repair. Consensus on specific surgical steps was also achieved: capsular release should be performed only in stiff shoulders; footprint preparation is mandatory, while debridement of tendon edges is not essential. If necessary, a rotator interval release could be performed without interrupting the continuity between subscapularis and supraspinatus tendon; posterior delamination should be always included in the repair. Advanced techniques such as tendon transfers should be selected based on the main clinical deficit, while the superior capsule reconstruction plays a role only in combination with a functional repair. CONCLUSION: A consensus was achieved almost on every topic of controversy explored. Particularly, MRI was deemed necessary to determine tear characteristics, while radiographs remain important for differential diagnosis; age should not be considered a contraindication to surgery; pseudo-paralysis does not represent a contraindication to arthroscopic rotator cuff repair, but superior capsule reconstruction plays a role only in combination with a functional repair. Latissimus dorsi transfer plays a role when the main functional deficit is in elevation, while the lower trapezius transfer plays a role when the main functional deficit is the external-rotation. LEVEL OF EVIDENCE: V.

Impact of the Number of Needle Tip Bevels on the Exerted Forces and Energy in Insulin Pen Injections.

Patients affected with type 1 diabetes and a non-negligible number of patients with type 2 diabetes are insulin dependent. Both the injection technique and the choice of the most suitable needle are fundamental for allowing them to have a good injection experience. The needles may differ in several parameters, from the length and diameter, up to the forces required to perform the injection and to some geometrical parameters of the needle tip (e.g., number of facets or bevels). The aim of the research is to investigate whether an increased number of bevels could decrease forces and energy involved in the insertion-extraction cycle, thus potentially allowing patients to experience lower pain. Two needle variants, namely, 31 G × 5 mm and 32 G × 4 mm, are considered, and experimental tests are carried out to compare 3-bevels with 5-bevels needles for both the variants. The analysis of the forces and energy for both variants show that the needles with 5 bevels require a statistically significant lower drag or sliding force (p-value = 0.040 for the 31 G × 5 mm needle and p-value < 0.001 for 32 G × 4 mm), extraction force (p-value < 0.001 for both variants), and energy (p-value < 0.001 for both variants) during the insertion-extraction cycle. As a result, 3-bevels needles do not have the same functionality of 5-bevels needles, show lower capacity of drag and extraction, and can potentially be related to more painful injection experience for patients.

Glenoid bone loss in anterior shoulder dislocation: a multicentric study to assess the most reliable imaging method.

PURPOSE: The aim of this multicentric study was to assess which imaging method has the best inter-reader agreement for glenoid bone loss quantification in anterior shoulder instability. A further aim was to calculate the inter-method agreement comparing bilateral CT with unilateral CT and MR arthrography (MRA) with CT measurements. Finally, calculations were carried out to find the least time-consuming method. METHOD: A retrospective evaluation was performed by 9 readers (or pairs of readers) on a consecutive series of 110 patients with MRA and bilateral shoulder CT. Each reader was asked to calculate the glenoid bone loss of all patients using the following methods: best fit circle area on both MRA and CT images, maximum transverse glenoid width on MRA and CT, CT PICO technique, ratio of the maximum glenoid width to height on MRA and CT, and length of flattening of the anterior glenoid curvature on MRA and CT. Using Pearson's correlation coefficient (PCC), the following agreement values were calculated: the inter-reader for each method, the inter-method for MRA with CT quantifications and the inter-method for CT best-fit circle area and CT PICO. Statistical analysis was carried out to compare the time employed by the readers for each method. RESULTS: Inter-reader agreement PCC mean values were the following: 0.70 for MRA and 0.77 for CT using best fit circle diameter, 0.68 for MRA and 0.72 for CT using best fit circle area, 0.75 for CT PICO, 0.64 for MRA and 0.62 for CT anterior straight line and 0.49 for MRA and 0.43 for CT using length-to-width ratio. CT-MRA inter-modality PCC mean values were 0.9 for best fit circle diameter, 0.9 for best fit circle area, 0.62 for anterior straight line and 0.94 for length-to-width methods. PCC mean value comparing unilateral CT with PICO CT methods was 0.8. MRA best fit circle area method was significantly faster than the same method performed on CT (p = 0.031), while no significant difference was seen between CT and MRA for remaining measurements. CONCLUSIONS: CT PICO is the most reliable imaging method, but both CT and MRA can be reliably used to assess glenoid bone loss. Best fit circle area CT and MRA methods are valuable alternative measurement techniques.

Upregulation in Inflammation and Collagen Expression in Perirenal but Not in Mesenteric Adipose Tissue from Diabetic Munich Wistar Frömter Rats.

Perirenal adipose tissue (PRAT) surrounding the kidney is emerging as a player and novel independent risk factor in diabetic kidney disease (DKD); DKD is a complication of diabetes and is a major cause of increased cardiovascular (CV) risk and CV mortality in affected patients. We determined the effect of diabetes induction on (i) kidney and CV damage and (ii) on the expression of proinflammatory and profibrotic factors in both the PRAT and the mesenteric adipose tissue (MAT) of Munich Wistar Frömter (MWF) rats. The 16-week-old male MWF rats (n = 10 rats/group) were fed standard chow (MWF-C) or a high-fat/high-sucrose diet for 6 weeks together with low-dose streptozotocin (15 mg/kg i.p.) at the start of dietary exposure (MWF-D). Phenotyping was performed at the end of treatment through determining water intake, urine excretion, and oral glucose tolerance; use of the homeostatic model assessment-insulin resistance index (HOMA-IR) evidenced the development of overt diabetes manifestation in MWF-D rats. The kidney damage markers Kim-1 and Ngal were significantly higher in MWF-D rats, as were the amounts of PRAT and MAT. A diabetes-induced upregulation in IL-1, IL-6, Tnf-α, and Tgf-ß was observed in both the PRAT and the MAT. Col1A1 was increased in the PRAT but not in the MAT of MWF-D, whereas IL-10 was lower and higher in the PRAT and the MAT, respectively. Urinary albumin excretion and blood pressure were not further increased by diabetes induction, while heart weight was higher in the MWF-D. In conclusion, our results show a proinflammatory and profibrotic in vivo environment in PRAT induced by diabetes which might be associated with kidney damage progression in the MWF strain.

Pharmacological senolysis reduces doxorubicin-induced cardiotoxicity and improves cardiac function in mice.

Many anticancer agents used in clinics induce premature senescence in healthy tissues generating accelerated aging processes and adverse side-effects in patients. Cardiotoxicity is a well-known limiting factor of anticancer treatment with doxorubicin (DOX), a very effective anthracycline widely used as antitumoral therapy in clinical practice, that leads to long-term morbidity and mortality. DOX exposure severely affects the population of cardiac cells in both mice and human hearts by inducing premature senescence, which may represent the molecular basis of DOX-induced cardiomyopathy. Here, we demonstrate that senescence induction in the heart contributes to impaired cardiac function in mice upon DOX treatment. Concomitant elimination of senescent cells with the senolytic Navitoclax in different formulations produces a significant decrease in senescence and cardiotoxicity markers together with the restoration of the cardiac function in mice followed by echocardiography. These results evidence the potential clinical use of senolytic therapies to alleviate cardiotoxicities induced in chemotherapy-treated patients.

Mediators between physical activity and academic achievement: A systematic review.

BACKGROUND: Research has suggested the beneficial effects of physical activity (PA) on academic achievement (AA). However, the mechanisms underlying this influence remain unclear. Some proposed mechanisms include physiological, cognitive, psychological, and behavioral paths. This study aimed to analyze mediators between PA and AA in children and adolescents. METHODS: Systematic search in Medline, SPORTDiscuss, PsycInfo, Scopus, and Web of Science for observational and experimental studies, published up to March 2021. RESULTS: Twenty-eight studies (75237 participants, aged 4-16) were included. The designs of these studies were: 21 studies cross-sectional, 5 longitudinal, and 2 experimental. Eight out of nine studies analyzing fitness as a mediator reported positive results, and one reported null finding. Adiposity was a significant mediator in one study, in two only in girls, and two reported null results. Cognition as a mediator was supported by four studies, whereas two reported null results. Regarding mental well-being, 10 out of 14 studies reported positive effects, and one out of five behavioral studies found positive results. Although studies were too sparse to draw conclusions, overall, the results indicated that self-esteem, self-image, self-efficacy, stress, and health behaviors might be potential mediators in the relationship between PA and AA. All studies were rated as medium-high quality. CONCLUSION: Overall, the available evidence seems to suggest that cardiorespiratory fitness, cognition, mental well-being, and exercise-related behaviors play some role as mediators of the relationship between PA and AA. However, the cross-sectional nature of most of the reviewed studies prevents us from making any statement in terms of causal paths. Thus, well-designed follow-up and randomized controlled studies aimed not only to tests the effect of PA in AA, but also to examine the influence of mediators are required.

Influence of atrial fibrillation subtypes on anticoagulant therapy in a high-risk older population: the FAI project.

BACKGROUND AND AIM: Benefits of oral anticoagulants (OAC) in atrial fibrillation (AF) patients with moderate-to-high risk of stroke are independent of AF pattern. We evaluated whether AF clinical subtype influenced OAC use in a representative sample of the Italian older population. METHODS: A cross-sectional examination of all subjects aged 65 + years from three general practices in northern, central, and southern Italy started in 2016. A double-screening procedure was followed by clinical and ECG confirmation. Patients were categorized as having paroxysmal, persistent, or permanent AF. OAC use was evaluated in confirmed AF patients. RESULTS: The sample included 6016 subjects. Excluding 235 non-eligible, participation was 78.3%, which left 4528 participants (mean age 74.5 ± 6.8 years, 47.2% men). Overall, 319 AF cases were identified: 43.0% had paroxysmal, 21.3% persistent, and 35.7% permanent AF. Frequency of OAC therapy was 91.2% in permanent, 85.3% in persistent, and only 43.0% in paroxysmal AF (P < 0.001). In multivariate analysis, controlled for baseline variables and risk scales, persistent and permanent AF were associated with a significant increase in the likelihood of receiving OAC compared with paroxysmal AF (P < 0.001). This was confirmed for permanent AF also in multivariate analyses considering separately vitamin K antagonists or direct-acting oral anticoagulants (OR, 4.37, 95% CI, 2.43-7.85; and 1.92, 95% CI, 1.07-3.42, respectively) and for persistent AF and direct-acting oral anticoagulants (OR, 4.33, 95% CI, 2.30-8.15). CONCLUSIONS: In a population-based survey, AF pattern was an independent predictor of OAC treatment. Paroxysmal AF is still perceived as carrying a lower risk of vascular events.

Statistical Analysis and Kinematic Assessment of Upper Limb Reaching Task in Parkinson's Disease.

The impact of neurodegenerative disorders is twofold; they affect both quality of life and healthcare expenditure. In the case of Parkinson's disease, several strategies have been attempted to support the pharmacological treatment with rehabilitation protocols aimed at restoring motor function. In this scenario, the study of upper limb control mechanisms is particularly relevant due to the complexity of the joints involved in the movement of the arm. For these reasons, it is difficult to define proper indicators of the rehabilitation outcome. In this work, we propose a methodology to analyze and extract an ensemble of kinematic parameters from signals acquired during a complex upper limb reaching task. The methodology is tested in both healthy subjects and Parkinson's disease patients (N = 12), and a statistical analysis is carried out to establish the value of the extracted kinematic features in distinguishing between the two groups under study. The parameters with the greatest number of significances across the submovements are duration, mean velocity, maximum velocity, maximum acceleration, and smoothness. Results allowed the identification of a subset of significant kinematic parameters that could serve as a proof-of-concept for a future definition of potential indicators of the rehabilitation outcome in Parkinson's disease.

Imbalance in Bone Morphogenic Proteins 2 and 7 Is Associated with Renal and Cardiovascular Damage in Chronic Kidney Disease.

Arterial stiffness is a major vascular complication of chronic kidney disease (CKD). The development of renal damage, hypertension, and increased pulse wave velocity (PWV) in CKD might be associated with an imbalance in bone morphogenetic proteins (BMP)-2 and BMP-7. Plasma BMP-2 and BMP-7 were determined by ELISA in CKD patients (stages I-III; n = 95) and Munich Wistar Frömter (MWF) rats. Age-matched Wistar rats were used as a control. The expression of BMP-2, BMP-7, and profibrotic and calcification factors was determined in kidney and perivascular adipose tissues (PVAT). BMP-2 was higher in stage III CKD patients compared to control subjects. BMP-7 was lower at any CKD stage compared to controls, with a significant further reduction in stage III patients. A similar imbalance was observed in MWF rats together with the increase in systolic (SBP) and diastolic blood pressure (DBP), or pulse wave velocity (PWV). MWF exhibited elevated urinary albumin excretion (UAE) and renal expression of BMP-2 or kidney damage markers, Kim-1 and Ngal, whereas renal BMP-7 was significantly lower than in Wistar rats. SBP, DBP, PWV, UAE, and plasma creatinine positively correlated with the plasma BMP-2/BMP-7 ratio. Periaortic and mesenteric PVAT from MWF rats showed an increased expression of BMP-2 and profibrotic and calcification markers compared to Wistar rats, together with a reduced BMP-7 expression. BMP-2 and BMP-7 imbalance in plasma, kidney, and PVATs is associated with vascular damage, suggesting a profibrotic/pro-calcifying propensity associated with progressive CKD. Thus, their combined analysis stratified by CKD stages might be of clinical interest to provide information about the degree of renal and vascular damage in CKD.