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Genetically encoded calcium indicators (GECIs) such as GCaMP are invaluable tools in neuroscience to monitor neuronal activity using optical imaging. The viral transduction of GECIs is commonly used to target expression to specific brain regions, can be conveniently used with any mouse strain of interest without the need for prior crossing with a GECI mouse line, and avoids potential hazards due to the chronic expression of GECIs during development. A key requirement for monitoring neuronal activity with an indicator is that the indicator itself minimally affects activity. Here, using common adeno-associated viral (AAV) transduction procedures, we describe spatially confined aberrant Ca2+ microwaves slowly travelling through the hippocampus following expression of GCaMP6, GCaMP7, or R-CaMP1.07 driven by the synapsin promoter with AAV-dependent gene transfer in a titre-dependent fashion. Ca2+ microwaves developed in hippocampal CA1 and CA3, but not dentate gyrus nor neocortex, were typically first observed at 4 wk after viral transduction, and persisted up to at least 8 wk. The phenomenon was robust and observed across laboratories with various experimenters and setups. Our results indicate that aberrant hippocampal Ca2+ microwaves depend on the promoter and viral titre of the GECI, density of expression, as well as the targeted brain region. We used an alternative viral transduction method of GCaMP which avoids this artefact. The results show that commonly used Ca2+-indicator AAV transduction procedures can produce artefactual Ca2+ responses. Our aim is to raise awareness in the field of these artefactual transduction-induced Ca2+ microwaves, and we provide a potential solution.

Cystic echinococcosis (CE) is a zoonotic disease caused by Echinococcus granulosus sensu lato, the metacestode of a tapeworm parasite of high medical importance. Infection of the parasite leads to the development of echinococcal cysts, and the spleen is a rarely infected organ. A 46-year-old woman who was born and who resides in Sardinia, Italy, was referred to the Echinococcosis outpatient clinic at the University Hospital of Sassari (Sardinia, Italy) for a pain in the left flank. She used to live in the countryside, in contact with several animals, and for 2 years, she had been working in a family garden, growing vegetables as a hobby. Ultrasounds and X-ray were performed, which evidenced a rounded formation in the upper third of the spleen, while a CT scan confirmed a parasitological cyst. Immunological examinations on serum samples did not detect specific antibodies against Echinococcus spp. Following surgical exportation, the whole spleen with the cystic lesion was delivered to the World Organisation for Animal Health (WOAH) and the National Reference Laboratory for Echinococcosis for further laboratory analyses. Moreover, characterization of the cyst fluid resulted dense and shiny. Observation under a light microscope at ×400 magnification revealed the formation of rectangular crystals and aggregates attributable to cholesterol molecules. Subsequently, through parasitological investigation, molecular biology investigations confirmed E. granulosus sensu stricto G1. We describe cholesterol crystals in a splenic echinococcal cyst for the first time. There is no clear explanation of how the cholesterol crystals formed in this case, but this was attributed to multifactorial causes, including atherosclerosis, chronic inflammation, parasite metabolism, and host responses.

Primary pelvic peritoneal masses, not arising from major organs, are uncommon in adults. Leiomyomas are a group of benign smooth muscle tumors, most commonly found in the uterus in premenopausal women (70–80%). Extra-uterine locations are very rare and more frequent in women. We highlighted the role of MRI due to its capability in soft tissue characterization, that may positively impact the therapeutical decision-making process. Herein, we present the case of a 66-year-old man with a peritoneal solid mass suspicious for a leiomyoma at Magnetic Resonance Imaging and confirmed at histologic specimen in order to discuss the crucial imaging findings that could raise suspicion of such a rare pathology in man.

The manuscript provides an overview of the mid-term results of the citizen science campaign activities conducted within the Life CONCEPTU MARIS project (LIFE20 NAT/IT/001371) whose aim is to improve the conservation status of cetaceans and pelagic sea turtles by addressing information gaps, setting up an internationally agreed-upon approach for surveillance, and identifying appropriate conservation measures. It fosters a cooperative effort by engaging the scientific community, stakeholders, policy makers and citizens in a common effort to support biodiversity.

BackgroundThe higher incidence of non-Hodgkin lymphoma (NHL) in males is not well understood. Although reactive oxygen species (ROS) have been implicated as causes of NHL, they cannot be measured directly in archived blood.MethodsWe performed untargeted adductomics of stable ROS adducts in human serum albumin (HSA) from 67 incident NHL cases and 82 matched controls from the European Prospective Investigation into Cancer and Nutrition-Italy cohort. Regression and classification methods were employed to select features associated with NHL in all subjects and in males and females separately.ResultsSixty seven HSA-adduct features were quantified by liquid chromatography-high-resolution mass spectrometry at Cys34 (n = 55) and Lys525 (n = 12). Three features were selected for association with NHL in all subjects, while seven were selected for males and five for females with minimal overlap. Two selected features were more abundant in cases and seven in controls, suggesting that altered homeostasis of ROS may affect NHL incidence. Heat maps revealed differential clustering of features between sexes, suggesting differences in operative pathways.ConclusionsAdduct clusters dominated by Cys34 oxidation products and disulfides further implicate ROS and redox biology in the etiology of NHL. Sex differences in dietary and alcohol consumption also help to explain the limited overlap of feature selection between sexes. Intriguingly, a disulfide of methanethiol from enteric microbial metabolism was more abundant in male cases, thereby implicating microbial translocation as a potential contributor to NHL in males.ImpactOnly two of the ROS adducts associated with NHL overlapped between sexes and one adduct implicates microbial translocation as a risk factor.

Summary: Background: Previous prediction models for adiposity gain have not yet achieved sufficient predictive ability for clinical relevance. We investigated whether traditional and genetic factors accurately predict adiposity gain. Methods: A 5-year gain of ≥5% in body mass index (BMI) and waist-to-hip ratio (WHR) from baseline were predicted in mid-late adulthood individuals (median of 55 years old at baseline). Proportional hazards models were fitted in 245,699 participants from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort to identify robust environmental predictors. Polygenic risk scores (PRS) of 5 proxies of adiposity [BMI, WHR, and three body shape phenotypes (PCs)] were computed using genetic weights from an independent cohort (UK Biobank). Environmental and genetic models were validated in 29,953 EPIC participants. Findings: Environmental models presented a remarkable predictive ability (AUCBMI: 0.69, 95% CI: 0.68–0.70; AUCWHR: 0.75, 95% CI: 0.74–0.77). The genetic geographic distribution for WHR and PC1 (overall adiposity) showed higher predisposition in North than South Europe. Predictive ability of PRSs was null (AUC: ∼0.52) and did not improve when combined with environmental models. However, PRSs of BMI and PC1 showed some prediction ability for BMI gain from self-reported BMI at 20 years old to baseline observation (early adulthood) (AUC: 0.60–0.62). Interpretation: Our study indicates that environmental models to discriminate European individuals at higher risk of adiposity gain can be integrated in standard prevention protocols. PRSs may play a robust role in predicting adiposity gain at early rather than mid-late adulthood suggesting a more important role of genetic factors in this life period. Funding: French National Cancer Institute (INCA_N°2019-176) 1220, German Research Foundation (BA 5459/2-1), Instituto de Salud Carlos III (Miguel Servet Program CP21/00058).

Summary: Background: Nutri-Score is a scientifically validated 5-color front-of-pack nutrition label reflecting the nutrient profile of foods. It has been implemented in several European countries on a voluntary basis, pending the revision of the European labeling regulation. Hence, scientific evidence is needed regarding the ability of the nutrient profile underlying the Nutri-Score (uNS-NPS, 2023-updated version) to characterize healthier foods. Our objective was therefore to study the prospective association between the nutritional quality of diet characterized by the uNS-NPS and the risk of cardiovascular diseases in a large European population. Methods: Our analyses included 345,533 participants from the European Prospective Investigation into Cancer and Nutrition study (EPIC, 1992–2010, 7 European countries). Food intakes were assessed at baseline using country-specific dietary questionnaires. The uNS-NPS was calculated as a continuous scale for each food, based on its 100 g content of energy, sugars, saturated fatty acids, salt, fibre, and protein and percentage content of fruit, vegetables, and pulses. A dietary index was derived at the individual level (uNS-NPS DI: energy-weighted mean of uNS-NPS scores of all foods consumed by a participant). Cardiovascular events during follow-up were retrieved using country-specific methods (self-report, registry data). Multi-adjusted Cox models were computed. Findings: Overall, 16,214 first cardiovascular events were reported (median follow-up: 12.3 years; 4,103,133 person-years). The consumption of foods with a higher uNS-NPS score (reflecting a lower overall nutritional quality of diet) was associated with higher risks of total cardiovascular events (Hazards Ratio (HR) for an increment of 1 standard deviation: 1.03 (95% Confidence Interval 1.01–1.05)), especially myocardial infarction (HR = 1.03 (1.01–1.07)), and stroke (HR = 1.04 (1.01–1.07)). Interpretation: In this large prospective study among European adults, a higher risk of cardiovascular diseases (total and several subtypes) was observed in individuals consuming a diet with a lower nutritional value, as graded by the uNS-NPS score. This brings new evidence on the relevance of the updated nutrient profile underlying the Nutri-Score to characterize foods with a healthier nutrient profile. Funding: EPIC-CVD was supported by EU FP7, ERC, UK MRC, British Heart Foundation, and UK NIHR.

Memory deficits are a debilitating symptom of epilepsy, but little is known about mechanisms underlying cognitive deficits. Here, we describe a Na+ channel-dependent mechanism underlying altered hippocampal dendritic integration, degraded place coding and deficits in spatial memory. Two-photon glutamate uncaging experiments revealed a marked increase in the fraction of hippocampal first-order CA1 pyramidal cell dendrites capable of generating dendritic spikes in the kainate model of chronic epilepsy. Moreover, in epileptic mice dendritic spikes were generated with lower input synchrony, and with a lower threshold. The Nav1.3/1.1 selective Na+ channel blocker ICA-121431 reversed dendritic hyperexcitability in epileptic mice, while the Nav1.2/1.6 preferring anticonvulsant S-Lic did not. We used in vivo two-photon imaging to determine if aberrant dendritic excitability is associated with altered place-related firing of CA1 neurons. We show that ICA-121431 improves degraded hippocampal spatial representations in epileptic mice. Finally, behavioural experiments show that reversing aberrant dendritic excitability with ICA-121431 reverses hippocampal memory deficits. Thus, a dendritic channelopathy may underlie cognitive deficits in epilepsy and targeting it pharmacologically may constitute a new avenue to enhance cognition.

The aim of this study was to economically estimate the effect of inoculation with Azospirillum brasilense (A. brasilense) associated with enhanced efficiency nitrogen fertilizers on corn yield cultivated in the Brazilian Amazon. The experimental design used was completely randomized, in a 2 × 3 × 5 factorial scheme, resulting from the combination of the presence and absence of seeds inoculated with A. brasilense, three sources of N (conventional urea, urea with NBPT, N-(n-butyl)thiophosphoric triamide, and polymer-coated urea), and five doses of N (0; 50; 100; 150; and 200 kg ha−1 of N), with six replications. Inoculation with A. brasilense promoted profit in corn, regardless of dose and the source of N applied. The urea with NBPT provided better economic return compared to polymer-coated urea and conventional urea sources, and doses of N applied in topdressing that promoted the highest economic return were 100 and 150 kg ha−1 of N, with an estimated increase of 62.33 and 135.53 bags ha−1 and increase of BRL 3253.76 and BRL 7074.88 respectively, compared to the control treatment.

The South African Schools Act 84 of 1996 forbids discrimination against learners based on pregnancy, while the 2007 guideline document, "Measures for Prevention and Management of Learner Pregnancy," stipulates teachers' role in preventing and managing learner pregnancy. Teachers are, therefore, responsible for pregnant learners in the school environment. In the study, which was conducted in primary and secondary schools in Bapong, we aimed to explore and describe the perceptions of teachers regarding pregnancy of school learners. A qualitative exploratory and descriptive approach with purposive sampling was used. In-depth interviews were used for data collection and content analysis was done through Tesch's approach using open coding. The findings suggest that, despite being against learner pregnancy, teachers are more concerned with the educational success of pregnant learners. They view learner pregnancy as a threat to teachers, other learners and the school environment because they are not trained to deal with pregnancy-related problems. The findings also indicate that the Departments of Health and Education should collaborate in order to initiate a partnership between teachers, school health nurses, and midwives regarding learner pregnancy in schools.

Objectives Our study aimed to investigate how physical activity (PA) changes over an 11-year follow-up among adults from different socioeconomic positions (SEP) near retirement age. Moreover, an analysis of different PA types is considered.Methods We used data from the EPIC-Italy cohort. We evaluated PA using the Cambridge Physical Activity Index (CPAI) and the metabolic equivalent of tasks (MET) per hour of activity for recreational PA and household PA. Educational level was assessed using the Relative Index of Inequality (RII). Occupational classes were classified according to LIFEPATH Consortium knowledge. Logistic regression was used to analyse PA among SEP and changes during follow-up. Analyses were also conducted separately for sex.Results The higher educated were more prevalent in the higher quartile of recreational PA than the lower educated both at baseline and follow-up (37% vs 28% and 37% vs 27%, respectively). At the baseline, the lower educated had a higher risk of being physically inactive than the higher educated based on recreational PA (overall OR: 1.50, 95% CI 1.40 to 1.60). Manual workers did not show a higher risk of less PA than professionals/managers (overall OR: 1.03, 95% CI 0.91 to 1.16).At follow-up, the lower educated and manual workers showed a higher risk of being physically inactive (lower educated OR: 1.46, 95% CI 1.37 to 1.56; manual worker OR: 1.33, 95% CI 1.18 to 1.50). The analyses of changes in PA showed that those who were less educated or manual workers had a higher risk of worsening their PA during the follow-up period, particularly women in recreational PA and men in CPAI measurement.Conclusion Individuals who had a disadvantaged SEP showed a higher risk of performing less PA over time.

Dendrites of hippocampal CA1 pyramidal cells amplify clustered glutamatergic input by activation of voltage-gated sodium channels and N-methyl-D-aspartate receptors (NMDARs). NMDAR activity depends on the presence of NMDAR co-agonists such as D-serine, but how co-agonists influence dendritic integration is not well understood. Using combinations of whole-cell patch clamp, iontophoretic glutamate application, two-photon excitation fluorescence microscopy and glutamate uncaging in acute rat and mouse brain slices we found that exogenous D-serine reduced the threshold of dendritic spikes and increased their amplitude. Triggering an astrocytic mechanism controlling endogenous D-serine supply via endocannabinoid receptors (CBRs) also increased dendritic spiking. Unexpectedly, this pathway was activated by pyramidal cell activity primarily in the theta range, which required HCN channels and astrocytic CB1Rs. Therefore, astrocytes close a positive and frequency-dependent feedback loop between pyramidal cell activity and their integration of dendritic input. Its disruption in mice led to an impairment of spatial memory, which demonstrated its behavioral relevance.

BACKGROUND: End-stage renal disease is associated with a high risk of cardiovascular events. It is unknown, however, whether mild-to-moderate kidney dysfunction is causally related to coronary heart disease (CHD) and stroke. METHODS: Observational analyses were conducted using individual-level data from 4 population data sources (Emerging Risk Factors Collaboration, EPIC-CVD [European Prospective Investigation into Cancer and Nutrition-Cardiovascular Disease Study], Million Veteran Program, and UK Biobank), comprising 648 135 participants with no history of cardiovascular disease or diabetes at baseline, yielding 42 858 and 15 693 incident CHD and stroke events, respectively, during 6.8 million person-years of follow-up. Using a genetic risk score of 218 variants for estimated glomerular filtration rate (eGFR), we conducted Mendelian randomization analyses involving 413 718 participants (25 917 CHD and 8622 strokes) in EPIC-CVD, Million Veteran Program, and UK Biobank. RESULTS: There were U-shaped observational associations of creatinine-based eGFR with CHD and stroke, with higher risk in participants with eGFR values 105 mL·min-1·1.73 m-2, compared with those with eGFR between 60 and 105 mL·min-1·1.73 m-2. Mendelian randomization analyses for CHD showed an association among participants with eGFR 105 mL·min-1·1.73 m-2. Results were not materially different after adjustment for factors associated with the eGFR genetic risk score, such as lipoprotein(a), triglycerides, hemoglobin A1c, and blood pressure. Mendelian randomization results for stroke were nonsignificant but broadly similar to those for CHD. CONCLUSIONS: In people without manifest cardiovascular disease or diabetes, mild-to-moderate kidney dysfunction is causally related to risk of CHD, highlighting the potential value of preventive approaches that preserve and modulate kidney function.

Hybrid production plants harness diverse climatic sources for electricity generation, playing a crucial role in the transition to renewable energies. This study aims to forecast the profitability of a combined wind–photovoltaic energy system. Here, we develop a model that integrates predicted spot prices and electricity output forecasts, incorporating relevant climatic variables to enhance accuracy. The jointly modeled climatic variables and the spot price constitute one of the innovative aspects of this work. Regarding practical application, we considered a hypothetical wind–photovoltaic plant located in Italy and used the relevant climate series to determine the quantity of energy produced. We forecast the quantity of energy as well as income through machine learning techniques and more traditional statistical and econometric models. We evaluate the results by splitting the dataset into estimation windows and test windows, and using a backtesting technique. In particular, we found evidence that ML regression techniques outperform results obtained with traditional econometric models. Regarding the models used to achieve this goal, the objective is not to propose original models but to verify the effectiveness of the most recent machine learning models for this important application, and to compare them with more classic linear regression techniques.

The aim of this study was to compare the effects of a medetomidine–vatinoxan combination versus medetomidine alone on heart rate (HR) and mean arterial pressure (MAP) in a short-term surgery in dogs. Four groups of 10 dogs were administered as follows: medetomidine and sevoflurane; medetomidine and desflurane; medetomidine–vatinoxan and sevoflurane; and medetomidine–vatinoxan and desflurane. After administration, the increase in MAP soon stopped at 102–104 mmHg in the two groups administered medetomidine–vatinoxan, compared with significantly higher values of 143–126 mmHg achieved in the two groups administered medetomidine alone. The lowest MAPs in the two medetomidine–vatinoxan groups were 46–50 mmHg, while in the medetomidine groups, they were 58–79 mmHg. From 3 min onwards after administration, in the medetomidine–vatinoxan treatments, HR remained at values very close to those of pre-administration, between 83 and 118 beats min−1, while in the medetomidine treatments, it dropped to 36–43 beats min−1 and then slowly rose to reach 71–90 beats min−1. These results encourage the use of vatinoxan in clinical settings, particularly in anesthetic protocols for dogs when bradycardia and an increase in systemic pressure should be avoided. Further clinical studies are needed to manage the short periods of hypotension, as well as the slight reduction in sedative and pain-relieving medetomidine effects found, particularly when vatinoxan is in combination with desflurane rather than sevoflurane.