MR Imaging of Adverse Effects and Ocular Growth Decline after Selective Intra-Arterial Chemotherapy for Retinoblastoma.

This retrospective multicenter study examines therapy-induced orbital and ocular MRI findings in retinoblastoma patients following selective intra-arterial chemotherapy (SIAC) and quantifies the impact of SIAC on ocular and optic nerve growth. Patients were selected based on medical chart review, with inclusion criteria requiring the availability of posttreatment MR imaging encompassing T2-weighted and T1-weighted images (pre- and post-intravenous gadolinium administration). Qualitative features and quantitative measurements were independently scored by experienced radiologists, with deep learning segmentation aiding total eye volume assessment. Eyes were categorized into three groups: eyes receiving SIAC (Rb-SIAC), eyes treated with other eye-saving methods (Rb-control), and healthy eyes. The most prevalent adverse effects post-SIAC were inflammatory and vascular features, with therapy-induced contrast enhancement observed in the intraorbital optic nerve segment in 6% of patients. Quantitative analysis revealed significant growth arrest in Rb-SIAC eyes, particularly when treatment commenced ≤ 12 months of age. Optic nerve atrophy was a significant complication in Rb-SIAC eyes. In conclusion, this study highlights the vascular and inflammatory adverse effects observed post-SIAC in retinoblastoma patients and demonstrates a negative impact on eye and optic nerve growth, particularly in children treated ≤ 12 months of age, providing crucial insights for clinical management and future research.

Regression discontinuity design for the study of health effects of exposures acting early in life.

Regression discontinuity design (RDD) is a quasi-experimental approach to study the causal effect of an exposure on later outcomes by exploiting the discontinuity in the exposure probability at an assignment variable cut-off. With the intent of facilitating the use of RDD in the Developmental Origins of Health and Disease (DOHaD) research, we describe the main aspects of the study design and review the studies, assignment variables and exposures that have been investigated to identify short- and long-term health effects of early life exposures. We also provide a brief overview of some of the methodological considerations for the RDD identification using an example of a DOHaD study. An increasing number of studies investigating the effects of early life environmental stressors on health outcomes use RDD, mostly in the context of education, social and welfare policies, healthcare organization and insurance, and clinical management. Age and calendar time are the mostly used assignment variables to study the effects of various early life policies and programs, shock events and guidelines. Maternal and newborn characteristics, such as age, birth weight and gestational age are frequently used assignment variables to study the effects of the type of neonatal care, health insurance, and newborn benefits, while socioeconomic measures have been used to study the effects of social and welfare programs. RDD has advantages, including intuitive interpretation, and transparent and simple graphical representation. It provides valid causal estimates if the assumptions, relatively weak compared to other non-experimental study designs, are met. Its use to study health effects of exposures acting early in life has been limited to studies based on registries and administrative databases, while birth cohort data has not been exploited so far using this design. Local causal effect around the cut-off, difficulty in reaching high statistical power compared to other study designs, and the rarity of settings outside of policy and program evaluations hamper the widespread use of RDD in the DOHaD research. Still, the assignment variables' cut-offs for exposures applied in previous studies can be used, if appropriate, in other settings and with additional outcomes to address different research questions.

Immunostimulatory and Antibacterial Effects of Cannabis sativa L. Leaves on Broilers.

The aim of this study was to evaluate the effect of dried Cannabis sativa L. leaves as a phytogenic mixture added to broiler feed on CD4+ and CD8+ T lymphocyte subpopulations, Newcastle disease virus (NDV) antibody titres, and the presence of E. coli in faecal samples. The study was conducted on 100 male Ross 308 broilers, divided into four groups of 25 broilers, for a 42-day research period. The groups were housed separately in boxes on a litter of softwood shavings and were fed starter mixture from day 1 to day 21 and finisher mixture from day 22 to day 42. Industrial hemp (C. sativa) was grown in the Crkvina area, Croatia (latitude: 45°18'46.8″ N; longitude: 15°31'30″ E). The hemp leaves were manually separated, sun-dried, and ground to a powder. The mixture offered to the control group did not contain cannabis leaves, whereas the three experimental groups received mixtures containing mixed cannabis leaves in a quantity of 10 g/kg, 20 g/kg, or 30 g/kg (E_10, E_20, and E_30, respectively). The mean NDV antibody level was uniform in all study groups until post-vaccination day 14 and increased comparably with time. The percentage of CD4+ and CD8+ lymphocytes in the peripheral blood subpopulation showed statistically significant differences (p < 0.001) in the E_20 group as compared with the control group and both the E_10 and E_30 groups throughout the study period. As the broiler age increased, the CD4+-to-CD8+ ratios also increased and were statistically significant (p < 0.0001) on day 42 in all experimental groups as compared to the control group. Comparing the control group with the experimental groups indicated that the bacterial count was lower in broiler groups having received feed with the addition of 20 g/kg and 30 g/kg C. sativa leaves. In conclusion, the C. sativa leaves were found to elicit a favourable immunomodulatory effect on cell-mediated and humoral immune responses in broilers via increased CD4+ and CD8+ lymphocyte subpopulations and higher CD4+:CD8+ cell ratios, thus indicating enhanced immune function capacity. In addition, C. sativa leaves may have complementary effects on the broiler post-vaccination immune response, increase broilers' resistance to infectious diseases, reduce the effect of stress associated with vaccination, and improve broiler health and welfare.

Maternal antenatal mental health and its associations with perinatal outcomes and the use of healthcare services in children from the NINFEA birth cohort study.

To investigate the associations between maternal mental health disorders before and during pregnancy and perinatal outcomes and child healthcare utilization between 6 and 18 months of age. Among the 6814 mother-child pairs from the Italian Internet-based NINFEA birth cohort, maternal depression, anxiety, and sleep disorders diagnosed by a physician before and during pregnancy were assessed through self-reported questionnaires completed during pregnancy and 6 months after delivery. Perinatal outcomes (preterm birth, birth weight, small for gestational age, congenital anomalies, and neonatal intensive care unit (NICU)) and children's healthcare utilization (emergency department (ED) visits, hospitalizations, and outpatient visits) were reported by mothers at 6 and 18 months postpartum. We used regression models adjusted for maternal age, education, parity, country of birth, region of delivery, and household income. Maternal mental health disorders were not associated with perinatal outcomes, except for depression, which increased the risk of offspring admission to NICU, and anxiety disorders during pregnancy, which were associated with preterm birth and lower birth weight. Children born to mothers with depression/anxiety disorders before pregnancy, compared to children of mothers without these disorders, had an increased odds of a visit to ED for any reason (odds ratio (ORadj) = 1.26, 95% confidence interval (CI): 1.02-1.54), of an ED visit resulting in hospitalization (ORadj = 1.75, 95%CI: 1.27-2.42), and of planned hospital admissions (ORadj = 1.55, 95%CI: 1.01-2.40). These associations with healthcare utilization were similar for mental disorders also during pregnancy. The association pattern of maternal sleep disorders with perinatal outcomes and child healthcare utilization resembled that of maternal depression and/or anxiety disorders with these outcomes.   Conclusion: Antenatal maternal mental health is a potential risk factor for child-health outcomes and healthcare use. Early maternal mental health interventions may help to promote child health and reduce healthcare costs. What is Known: • Poor maternal mental health affects pregnancy outcomes and child health, and children of mothers with mental health conditions tend to have increased healtcare utilization. • Parents with poor mental health often face challenges in caring for their children and have less parenting self-efficacy, which could potentially lead to frequent medical consultations for minor health issues. What is New: • Maternal pre-pregnancy mental disorders were not associated with preterm birth, low birth weight, SGA, and congenital anomalies, except for depression, which increased the risk of offspring admission to NICU. Anxiety disorders during pregnancy were associated with lower birth weight and an increased odds of preterm birth. • Maternal depression and/or anxiety and sleep disorders, both before and during pregnancy, were associated with an increase in children's healthcare utilization between 6 and 18 months of life.

Socioeconomic position, family context, and child cognitive development.

Socioeconomic position (SEP) may have different effects on cognitive development and family context could play a role in this association. This work aimed to analyse the role of socioeconomic positions, measured via various indicators collected longitudinally, in cognitive development at 7-11 years of age, evaluating the role of family context as a potential mediator. The study sample included 394 and 382 children from the INMA Gipuzkoa and Valencia cohorts, respectively. SEP indicators were assessed during pregnancy (family social class, parental education, employment, and disposable income) and at 7 (Gipuzkoa) and 11 (Valencia) years of age (At Risk of Poverty or Social Exclusion (AROPE)). Family context and cognitive development were measured with the Haezi-Etxadi Family Assessment Scale 7-11 (HEFAS 7-11) and Raven's Coloured Progressive Matrices (Raven's CPM), respectively. Linear regression models were developed to assess the relationships between (a) SEP-family context, (b) SEP-cognitive development, and (c) family context-cognitive development, adjusting for a priori-selected confounders. Simple and multiple mediation analyses were performed to explore the role of family context in the SEP-cognitive development relationship. Lower SEP was related with a lower cognitive score, this association being particularly robust for family social class. SEP indicators were related to subscales of family context, in particular those regarding cognitive stimulation, parental stress, and parenting. A relationship was also found between these three subscales and child cognitive development, mediating the effect of family social class on child cognition by 5.2, 5.5, and 10.8%, respectively, and 12.0% jointly.    Conclusion: Both family SEP and context contribute to a child's cognitive development. Equalising policies and positive parenting programmes could contribute to improving cognitive development in children. What is Known: • Parental social class, education, and employment status have been widely employed to measure socioeconomic position. What is New: • This work focuses on standard measurements of socioeconomic position but also other economic indicators such as the EHII and AROPE, and their effect on child cognitive development and family context. • Promotion of cognitive and linguistic development, parental stress and conflict, and parental profile fostering child development mediated the effect of family social class on cognitive development.

Transporting results in an observational epidemiology setting: purposes, methods, and applied example.

In the medical domain, substantial effort has been invested in generating internally valid estimates in experimental as well as observational studies, but limited effort has been made in testing generalizability, or external validity. Testing the external validity of scientific findings is nevertheless crucial for the application of knowledge across populations. In particular, transporting estimates obtained from observational studies requires the combination of methods for causal inference and methods to transport the effect estimates in order to minimize biases inherent to observational studies and to account for differences between the study and target populations. In this paper, the conceptual framework and assumptions behind transporting results from a population-based study population to a target population is described in an observational setting. An applied example to life-course epidemiology, where internal validity was constructed for illustrative purposes, is shown by using the targeted maximum likelihood estimator.

When the second comes first- rhabdomyosarcoma preceding heritable retinoblastoma- a case report.

BACKGROUND: Retinoblastoma (rb) is the most frequent intraocular tumor, accounting for 3% of all childhood cancers. Heritable rb survivors are germline carriers for an RB1 mutation and have a lifelong risk to develop non-ocular second primary tumors (SPTs) involving multiple other organs like the bones, soft tissues, or skin. These SPTs usually become manifest several years succeeding the diagnosis of rb. In our instance, however, a non-ocular SPT presented prior to the diagnosis of heritable rb. CASE PRESENTATION: We report a rare case of a monozygotic twin who presented with primary rhabdomyosarcoma (RMS) preceding the manifestation of heritable rb. The rb was diagnosed when the child developed strabismus while already on therapy for the RMS. The child underwent therapy for both as per defined treatment protocols. The rb regressed well on treatment, but the RMS relapsed and the child developed multiple refractory metastatic foci and succumbed to his disease. CONCLUSIONS: Non-ocular SPTs like sarcomas are usually known to manifest in heritable rb survivors with a lag of two to three decades (earlier if exposure to radiation is present) from the presentation of the rb. However, in our case, this seemed to be reversed with the RMS being manifest at an unusual early age and the rb being diagnosed at a later point in time.

Association of child neurodevelopmental or behavioural problems with maternal unemployment in a population-based birth cohort.

PURPOSE: To estimate associations between suspected or diagnosed neurodevelopmental or behavioural problems in 7-year-old children and maternal unemployment at child age 7 and 10, in a Portuguese birth cohort. METHODS: We evaluated 5754 mothers and their children of the population-based birth cohort Generation XXI in Porto, Portugal. Data on suspected and diagnosed child neurodevelopmental and behavioural problems (exposures)-learning, attention and language problems, externalising behaviours, developmental delay, autism spectrum disorders, and other neurodevelopmental problems-were retrieved at 7 years of age by interviewing caregivers. Maternal employment status (outcome) was collected at the 7- and 10-year follow-up waves. Robust Poisson regression models were used to estimate associations. RESULTS: After adjustment for maternal and household characteristics, women were more likely to be unemployed at child age 10 if the child had, up to age 7, any of the following suspected problems: an autism spectrum disorder (PR = 1.73; 95% CI 1.07, 2.79), developmental delay (PR = 1.58; 95% CI 1.20, 2.06), externalising behaviours (PR = 1.29; 95% CI 1.11, 1.50) or learning problems (PR = 1.26; 95% CI 1.07, 1.48). When the exposure was restricted to clinically diagnosed disorders, the magnitude of associations remained similar but estimates were less precise. Associations with unemployment were stronger at child age 10 (prospective analyses), than at child age 7 (cross-sectional). CONCLUSION: Having a child with learning, developmental or behavioural problems, or an autism spectrum disorder up to age 7 was associated with maternal unemployment three years later, even in a less affluent European economy where the dual-earner family structure is often necessary to make ends meet.

Acetamiprid's degradation products and mechanism: Part II - Inert atmosphere and charge storage.

Reuse and/or recycling of spent adsorbents is taking a central role in modern thinking and catalyzed carbonization is the way forward. Herein we explore the carbonization of adsorbed acetamiprid, in an inert atmosphere, as a way of recycling and producing nitrogen-rich carbon material for potential use in supercapacitors. Added value material and the reuse of the adsorbent were achieved by carbonization at 700 °C under argon. The formation of a nitrogen-doped carbon layer as an active material on the adsorbent, bonded through a C-Si linkage, has been conclusively verified through elemental composition quantification using XPS and EDX measurements. Two-stage catalytic decomposition and condensation of the adsorbed pesticide is followed by TGA and TPD-MS. Attained carbon-based materials give stable Faradaic capacitance with a slight dependency on the number of adsorbing cycles. Capacitance calculated with respect to the adlayer carbon material reaches values as high as 610 F g-1. Galvanostatic Charge/Discharge measurement confirmed the stability of explored materials with a slight increase in capacitance over 1000 cycles. The presented results envisage electroactive materials preparation from environmental pollutants, adding value to spent adsorbents.

Gender- and Age-Related Differences of Ocular Biometric Parameters in Patients Undergoing Cataract Surgery in Bosnia and Herzegovina.

Purpose: The aim of the study is to determine the distribution and mutual relationship of ocular biometric parameters, as well as to evaluate gender- and age-related differences in patients undergoing cataract surgery in Bosnia and Herzegovina. Materials and Methods: It was a retrospective cross-sectional study of consecutive patients who underwent cataract surgery between January 2017 and December 2021 in a tertiary care clinic. All biometric measurements were performed using the optical biometer OA-2000 (Tomey, Nagoya, Japan). Results: The study evaluated 1278 eyes from 1278 consecutive cataract patients. The average age of all included patients was 69.4 ± 9.98 (range 40-96). A total of 672 eyes (52.58%) were from females. The mean axial length (AL), anterior chamber depth (ACD), lens thickness (LT), and mean keratometry were 23.46 ± 1.18 mm, 3.17 ± 0.40 mm, 4.54 ± 0.48 mm, and 43.42 ± 1.55D, respectively. Corneal astigmatism of ≥1D, >2D and >3D was found in 33.4%, 7.8% and 2.5% patients, respectively. Females were found to have shorter AL (p < 0.0001), shallower ACD (p < 0.0001) and steeper corneas (p < 0.0001). In both genders, AL, ACD and with the rule astigmatism showed a decreasing trend (p = 0.0001), while keratometry, the average cylinder, and against the rule astigmatism showed an increasing trend (p = 0.0001) with increasing age. Furthermore, in both genders, there was an increasing trend in ACD (p = 0.0001), and a decreasing trend in keratometry (p = 0.0001) and LT (p = 0.0001) with increasing AL. Conclusions: This study provides useful reference data on ocular biometry for cataract surgeons in Bosnia and Herzegovina. Female patients tend to have steeper corneas, shorter AL and shallower AC than males, and these differences are independent of age or AL.

Accuracy of biomicroscopy, ultrasonography and spectral-domain OCT in detection of complete posterior vitreous detachment.

BACKGROUND: To evaluate the accuracy of preoperative biomicroscopy (BM), ultrasonography (US), and spectral domain optical coherence tomography (SD-OCT) to determine complete posterior vitreous detachment (PVD) confirmed by intraoperative findings of triamcinolone acetonide-assisted pars plana vitrectomy (PPV). METHODS: This prospective study included all consecutive patients admitted for surgical treatment of the epiretinal membrane (ERM) and macular hole (MH). The presence of complete PVD was determined one day before PPV using BM, US, SD-OCT. The preoperative findings were compared to the PVD status determined during PPV. RESULTS: A total of 123 eyes from 123 patients were included in the study. Indications for PPV included ERM in 57 (46.3%), full thickness macular hole in 57 (46.3%) and lamellar macular hole in 9 (7.3%) patients. Complete PVD during PPV was observed in 18 (31.6%; 95%CI:18.7-49.9) patients with ERM and 13 (19.7%; 95%CI:10.4-33.7) patients with MH. The sensitivity of preoperative BM, US, SD-OCT was 48.4% (95%CI:30.2-66.9), 61.3% (95%CI:42.2-78.2) and 54.8% (95%CI:36.0-72.7) respectively. The specificity of preoperative BM, US, SD-OCT was 81.5% (95%CI:72.1-88.9), 90.2% (95%CI:82.2-95.4) and 85.9% (95%CI:77.0-92.3) respectively. With a prevalence of 25.2% of PVD in our sample the positive predictive value of preoperative BM, US, SD-OCT was 46.9% (95%CI:29.1-65.3), 67.9% (95%CI:47.6-84.1) and 56.7% (95%CI:37.4-74.5) respectively. CONCLUSION: Preoperative BM, US, and SD-OCT showed relatively low sensitivity but also good specificity in assessing complete PVD. A combination of all three diagnostic methods can provide a good assessment of the vitreoretinal interface state.

Associations of Maternal Educational Level, Proximity to Greenspace During Pregnancy, and Gestational Diabetes With Body Mass Index From Infancy to Early Adulthood: A Proof-of-Concept Federated Analysis in 18 Birth Cohorts.

International sharing of cohort data for research is important and challenging. We explored the feasibility of multi-cohort federated analyses by examining associations between three pregnancy exposures (maternal education, exposure to green vegetation and gestational diabetes) with offspring BMI from infancy to 17 years. We used data from 18 cohorts (n=206,180 mother-child pairs) from the EU Child Cohort Network and derived BMI at ages 0-1, 2-3, 4-7, 8-13 and 14-17 years. Associations were estimated using linear regression via one-stage IPD meta-analysis using DataSHIELD. Associations between lower maternal education and higher child BMI emerged from age 4 and increased with age (difference in BMI z-score comparing low with high education age 2-3 years = 0.03 [95% CI 0.00, 0.05], 4-7 years = 0.16 [95% CI 0.14, 0.17], 8-13 years = 0.24 [95% CI 0.22, 0.26]). Gestational diabetes was positively associated with BMI from 8 years (BMI z-score difference = 0.18 [CI 0.12, 0.25]) but not at younger ages; however associations attenuated towards the null when restricted to cohorts which measured GDM via universal screening. Exposure to green vegetation was weakly associated with higher BMI up to age one but not at older ages. Opportunities of cross-cohort federated analyses are discussed.

Risk factors for overweight and obesity after childhood acute lymphoblastic leukemia in North America and Switzerland: A comparison of two cohort studies.

BACKGROUND: After childhood acute lymphoblastic leukemia (ALL), sequelae include overweight and obesity, yet with conflicting evidence. We compared the prevalence of overweight and obesity between ≥5-year ALL survivors from the North American Childhood Cancer Survivor Study (CCSS) and the Swiss Childhood Cancer Survivor Study (SCCSS) and described risk factors. METHODS: We included adult childhood ALL survivors diagnosed between 1976 and 1999. We matched CCSS participants (3:1) to SCCSS participants by sex and attained age. We calculated body mass index (BMI) from self-reported height and weight for 1287 CCSS and 429 SCCSS participants; we then compared those with siblings (2034) in North America and Switzerland (678) siblings. We assessed risk factors for overweight (BMI 25-29.9 kg/m2 ) and obesity (≥30 kg/m2 ) using multinomial regression. RESULTS: We found overweight and obesity significantly more common among survivors in North America when compared with survivors in Switzerland [overweight: 30%, 95% confidence interval (CI): 27-32 vs. 24%, 21-29; obesity: 29%, 27-32 vs. 7%, 5-10] and siblings (overweight: 30%, 27-32 vs. 25%, 22-29; obesity: 24%, 22-26 vs. 6%, 4-8). Survivors in North America [odds ratio (OR) = 1.24, 1.01-1.53] and Switzerland (1.27, 0.74-2.21) were slightly more often obese than siblings. Among survivors, risk factors for obesity included residency in North America (5.8, 3.7-9.0); male (1.7, 1.3-2.3); attained age (≥45 years: 5.1, 2.4-10.8); Non-Hispanic Black (3.4, 1.6-7.0); low household income (2.3, 1.4-3.5); young age at diagnosis (1.6, 1.1-2.2). Cranial radiotherapy ≥18 Gray was only a risk factor for overweight (1.4, 1.0-1.8); steroids were not associated with overweight or obesity. Interaction tests found no evidence of difference in risk factors between cohorts. CONCLUSIONS: Although treatment-related risk for overweight and obesity were similar between regions, higher prevalence among survivors in North America identifies important sociodemographic drivers for informing health policy and targeted intervention trials.

CUDC-907, a dual PI3K/histone deacetylase inhibitor, increases meta-iodobenzylguanidine uptake (123/131I-mIBG) in vitro and in vivo: a promising candidate for advancing theranostics in neuroendocrine tumors.

BACKGROUND: Neuroblastoma (NB) and pheochromocytoma/paraganglioma (PHEO/PGL) are neuroendocrine tumors. Imaging of these neoplasms is performed by scintigraphy after injection of radiolabeled meta-iodobenzylguanidine (mIBG), a norepinephrine analog taken up by tumoral cells through monoamine transporters. The pharmacological induction of these transporters is a promising approach to improve the imaging and therapy (theranostics) of these tumors. METHODS: Transporters involved in mIBG internalization were identified by using transfected Human Embryonic Kidney (HEK) cells. Histone deacetylase inhibitors (HDACi) and inhibitors of the PI3K/AKT/mTOR pathway were tested in cell lines to study their effect on mIBG internalization. Studies in xenografted mice were performed to assess the effect of the most promising HDACi on 123I-mIBG uptake. RESULTS: Transfected HEK cells demonstrated that the norepinephrine and dopamine transporter (NET and DAT) avidly internalizes mIBG. Sodium-4-phenylbutyrate (an HDACi), CUDC-907 (a dual HDACi and PI3K inhibitor), BGT226 (a PI3K inhibitor) and VS-5584 and rapamycin (two inhibitors of mTOR) increased mIBG internalization in a neuroblastoma cell line (IGR-NB8) by 2.9-, 2.1-, 2.5-, 1.5- and 1.3-fold, respectively, compared with untreated cells. CUDC-907 also increased mIBG internalization in two other NB cell lines and in one PHEO cell line. We demonstrated that mIBG internalization occurs primarily through the NET. In xenografted mice with IGR-NB8 cells, oral treatment with 5 mg/kg of CUDC-907 increased the tumor uptake of 123I-mIBG by 2.3- and 1.9-fold at 4 and 24 h post-injection, respectively, compared to the untreated group. CONCLUSIONS: Upregulation of the NET by CUDC-907 lead to a better internalization of mIBG in vitro and in vivo.

Physiological variations in hypovirus-infected wild and model long-term laboratory strains of Cryphonectria parasitica.

Introduction: Forest ecosystems are highly threatened by the simultaneous effects of climate change and invasive pathogens. Chestnut blight, caused by the invasive phytopathogenic fungus Cryphonectria parasitica, has caused severe damage to European chestnut groves and catastrophic dieback of American chestnut in North America. Within Europe, the impacts of the fungus are widely mitigated through biological control that utilizes the RNA mycovirus: Cryphonectria hypovirus 1 (CHV1). Viral infections, similarly to abiotic factors, can cause oxidative stress in their hosts leading to physiological attrition through stimulating ROS (reactive oxygen species) and NOx production. Methods: To fully understand the interactions leading to the biocontrol of chestnut blight, it is vital to determine oxidative stress damage arising during CHV1 infection, especially considering that other abiotic factors, like long-term cultivation of model fungal strains, can also impact oxidative stress. Our study compared CHV1-infected C. parasitica isolates from two Croatian wild populations with CHV1-infected model strains (EP713, Euro7 and CR23) that have experienced long-term laboratory cultivation. Results and Discussion: We determined the level of oxidative stress in the samples by measuring stress enzymes' activity and oxidative stress biomarkers. Furthermore, for the wild populations, we studied the activity of fungal laccases, expression of the laccase gene lac1, and a possible effect of CHV1 intra-host diversity on the observed biochemical responses. Relative to the wild isolates, the long-term model strains had lower enzymatic activities of superoxide dismutase (SOD) and glutathione S-transferase (GST), and higher content of malondialdehyde (MDA) and total non-protein thiols. This indicated generally higher oxidative stress, likely arising from their decades-long history of subculturing and freeze-thaw cycles. When comparing the two wild populations, differences between them in stress resilience and levels of oxidative stress were also observed, as evident from the different MDA content. The intra-host genetic diversity of the CHV1 had no discernible effect on the stress levels of the virus-infected fungal cultures. Our research indicated that an important determinant modulating both lac1 expression and laccase enzyme activity is intrinsic to the fungus itself, possibly related to the vc type of the fungus, i.e., vegetative incompatibility genotype.

Impact of Complete Revascularization on Development of Heart Failure in Patients With Acute Coronary Syndrome and Multivessel Disease: A Subanalysis of the CORALYS Registry.

Background The impact of complete revascularization (CR) on the development of heart failure (HF) in patients with acute coronary syndrome and multivessel coronary artery disease undergoing percutaneous coronary intervention remains to be elucidated. Methods and Results Consecutive patients with acute coronary syndrome with multivessel coronary artery disease from the CORALYS (Incidence and Predictors of Heart Failure After Acute Coronary Syndrome) registry were included. Incidence of first hospitalization for HF or cardiovascular death was the primary end point. Patients were stratified according to completeness of coronary revascularization. Of 14 699 patients in the CORALYS registry, 5054 presented with multivessel disease. One thousand four hundred seventy-three (29.2%) underwent CR, while 3581 (70.8%) did not. Over 5 years follow-up, CR was associated with a reduced incidence of the primary end point (adjusted hazard ratio [HR], 0.66 [95% CI, 0.51-0.85]), first HF hospitalization (adjusted HR, 0.67 [95% CI, 0.49-0.90]) along with all-cause death and cardiovascular death alone (adjusted HR, 0.74 [95% CI, 0.56-0.97] and HR, 0.56 [95% CI, 0.38-0.84], respectively). The results were consistent in the propensity-score matching population and in inverse probability treatment weighting analysis. The benefit of CR was consistent across acute coronary syndrome presentations (HR, 0.59 [95% CI, 0.39-0.89] for ST-segment elevation myocardial infarction and HR, 0.71 [95% CI, 0.50-0.99] for non-ST-elevation acute coronary syndrome) and in patients with left ventricular ejection fraction >40% (HR, 0.52 [95% CI, 0.37-0.72]), while no benefit was observed in patients with left ventricular ejection fraction ≤40% (HR, 0.77 [95% CI, 0.37-1.10], P for interaction 0.04). Conclusions CR after acute coronary syndrome reduced the risk of first hospitalization for HF and cardiovascular death, as well as first HF hospitalization, and cardiovascular and overall death both in patients with ST-segment elevation myocardial infarction and non-ST-elevation acute coronary syndrome. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT04895176.

Family socioeconomic position and changes in planned health care for children with chronic diseases during the COVID-19 pandemic in Italy.

Introduction: In this study, we aimed at evaluating whether, during the COVID-19 pandemic, children affected by chronic diseases were impacted by the deferral of planned healthcare caused by the restriction measures. Design: This study was conducted using data from the Italian NINFEA birth cohort, which include children born between 2005 and 2016. Women who completed the 4-year NINFEA follow-up questionnaire before November 2020 (N = 5,307) were invited to complete a questionnaire targeted at evaluating the impacts of the pandemic on their children's health. The questionnaire asked mothers to report whether their children had a chronic disease or condition that required one or more regular health checks by a doctor in 2019 (used as a reference period) and whether the children had problems getting routine health checks after March 2020. Results: We obtained information on 3,721 children. Out of 353 children with a chronic disease that required at least one medical visit in 2019, 130 (36.8%) experienced problems during the pandemic. Lower family income was associated with a higher risk of experiencing health access problems. We observed that children living in families at lower income tertiles had more chance of experiencing healthcare access problems than children living in families at the highest income tertiles (prevalence rate ratio for a tertile decrease in family income: 1.22; 95% CIs: 1.02-1.49). Conclusion: Our study underlines that the COVID-19 pandemic may have caused healthcare access problems for children with prevalent chronic diseases, especially among those living in households with a low socioeconomic position.

Targeting triple-negative breast cancer: A clinical perspective.

Triple-negative breast cancer (TNBC) is a disease with often an aggressive course and a poor prognosis compared to other subtypes of breast cancer. TNBC accounts for approximately 10%-15% of all diagnosed breast cancer cases and represents a high unmet need in the field. Up to just a few years ago, chemotherapy was the only systemic treatment option for this subtype (1). To date, TNBC is considered a heterogeneous disease. One of the existing classifications is based on the analysis of mRNA expression in 587 TNBC cases, in which Lehman et al. proposed six subtypes of TNBC as follows: two basal-like (BL1 and BL2) subtypes, a mesenchymal (M) subtype, a mesenchymal stem-like (MSL) subtype, an immunomodulatory (IM) subtype, and a luminal androgen receptor (LAR) subtype (2). Later studies have demonstrated that the IM and MSL subtypes do not correlate with independent subtypes but reflect background expression by dense infiltration of tumor-infiltrating lymphocytes (TILs) or stromal cells. According to this finding, the classification of TNBC has been revised into the following four subtypes: basal 1, basal 2, LAR, and mesenchymal subtypes (3). Over the last years, several new strategies have been investigated for the treatment of patients with TNBC. Among them, immunotherapy, antibody drug conjugates, new chemotherapy agents, and targeted therapy have been and are currently being developed. The present article aims to provide an updated overview on the different treatment options that are now available or are still under investigation for patients with TNBC.

[Exposome: from definition to future challenges.] / Esposoma: dalla definizione alle sfide future.

The exposome concept arises from the need to integrate different disciplines of public health and environmental sciences, mainly including environmental epidemiology, exposure science, and toxicology. The role of the exposome is to understand how the totality of an individual's exposures throughout the lifetime can impact human health. The etiology of a health condition is rarely explained by a single exposure. Therefore, examining the human exposome as a whole becomes relevant to simultaneously consider multiple risk factors and more accurately estimate concurrent causes of different health outcomes. Generally, the exposome is explained through three domains: general external exposome, specific external exposome, and internal exposome. The general external exposome includes measurable population-level exposures such as air pollution or meteorological factors. The specific external exposome includes information on individual exposures, such as lifestyle factors, typically obtained from questionnaires. Meanwhile, the internal exposome encompasses multiple biological responses to external factors, detected through molecular and omics analyses. Additionally, in recent decades, the socio-exposome theory has emerged, where all exposures are studied as a phenomenon dependent on the interaction between socioeconomic factors that vary depending on the context, allowing the identification of mechanisms that lead to health inequalities. The considerable production of data in exposome studies has led researchers to face new methodological and statistical challenges, introducing various approaches to estimate the effect of the exposome on health. Among the most common are regression models (Exposome-Wide Association Study - ExWAS), dimensionality reduction and exposure grouping techniques, and machine learning methods. The significant conceptual and methodological innovation of the exposome for a more holistic evaluation of the risks associated with human health is continuously expanding and will require further investigations related to the application of information obtained from studies into prevention and public health policies.