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Abstract Introduction To compare the long-term efficacy of navigated subthreshold micropulse laser (NSML) and continuous oral eplerenone (EPL) in chronic central serous chorioretinopathy (cCSC). Methods This retrospective observational study included 44 eyes with cCSC (EPL: n = 26; NSML: n = 18). Best-corrected visual acuity (BCVA), central macular thickness (CMT), subretinal fluid (SRF) height, and subfoveal choroidal thickness (SFCT) were evaluated over 12 months. Results Both groups showed significant improvements in BCVA and CMT (p 0.05). Conclusions Both NSML and EPL improved retinal morphology and visual function in patients with cCSC. NSML achieved faster SRF resolution, while EPL resulted in more significant choroidal thickness reduction. These findings suggest distinct mechanisms of action: NSML primarily affects the retinal pigment epithelium, while EPL modulates choroidal vasculature. Treatment choice may depend on individual patient characteristics and treatment goals.

Abstract Introduction This was a prospective study to investigate the antimicrobial efficacy of a novel ophthalmic solution comprising ozonated sunflower oil in liposomes plus hypromellose in conjunction with liposomal foam (BlefOX), in patients undergoing intravitreal injection, in comparison to povidone iodine 5%. Methods The study employed a paired-eye design with n = 195 patients and a total of n = 390 eyes divided into two groups. Conjunctival swabs were collected from both eyes of each patient at baseline (T0—3 days before the injection). The study group underwent home therapy, which included instilling two drops of an isotonic ophthalmic solution containing 0.5% ozonated sunflower oil in liposomes plus hypromellose (Ozodrop) four times daily and applying liposomal foam twice daily to the eye undergoing intravitreal injections. In contrast, the control group (contralateral eyes) received treatment with povidone iodine 5%. This treatment regimen was maintained for 3 days. At T1 (10 min before injection), all patients instilled one drop of a topical solution of povidone iodine 5% into the conjunctival sac of both eyes. After 30 seconds had elapsed, a conjunctival swab was obtained for each eye in both study groups. Results The results, derived from conjunctival swabs, exhibited a significant reduction in the microbial load of the study group on both chocolate agar and blood agar (p ≤ 0.007). The study demonstrated that the combination of povidone iodine 5% + Ozodrop + BlefOX provides a greater reduction in microbial load than povidone iodine 5% alone on both chocolate agar (141 [72.31%] vs. 98 [50.26%], p

Age-related macular degeneration (AMD) is a multifactorial disease characterized by progressive alterations of different retinal structures ultimately leading to vision loss. Among these, the choriocapillaris (CC) has been found to be affected in different stages of AMD. In this review we provide a discussion on the different stages of AMD, focusing particularly on the alterations involving the CC. This has been possible thanks to the introduction of optical coherence tomography-angiography, a recently developed imaging technique which allows the detection of blood flow in choroidal vessels. Therefore, the aim of this review is to provide a description of the various alterations involving the CC in the different stages of AMD.

Abstract The purpose of the study was to detect Hard Exudates (HE) and classify Disorganization of Retinal Inner Layers (DRIL) implementing a Deep Learning (DL) system on optical coherence tomography (OCT) images of eyes with diabetic macular edema (DME). We collected a dataset composed of 442 OCT images on which we annotated 6847 HE and the presence of DRIL. A complex operational pipeline was defined to implement data cleaning and image transformations, and train two DL models. The state-of-the-art neural network architectures (Yolov7, ConvNeXt, RegNetX) and advanced techniques were exploited to aggregate the results (Ensemble learning, Edge detection) and obtain a final model. The DL approach reached good performance in detecting HE and classifying DRIL. Regarding HE detection the model got an AP@0.5 score equal to 34.4% with Precision of 48.7% and Recall of 43.1%; while for DRIL classification an Accuracy of 91.1% with Sensitivity and Specificity both of 91.1% and AUC and AUPR values equal to 91% were obtained. The P-value was lower than 0.05 and the Kappa coefficient was 0.82. The DL models proved to be able to identify HE and DRIL in eyes with DME with a very good accuracy and all the metrics calculated confirmed the system performance. Our DL approach demonstrated to be a good candidate as a supporting tool for ophthalmologists in OCT images analysis.

Background/objectiveRetinal vein occlusion (RVO) is a common, sight-threatening vascular disorder affecting individuals of all ages, with incidence increasing with age. Due to its complex, multifactorial nature, treating RVO remains a clinical challenge. Currently, treatment strategies include laser photocoagulation (especially for branch RVO), anti-VEGF therapies, and intravitreal corticosteroids. This systematic review (without meta-analysis) aimed to update the evidence on the efficacy and safety of the sustained-release intravitreal dexamethasone implant (DEX-i) in managing macular edema (ME) secondary to central and branch RVO.MethodsA systematic review was conducted to assess current literature on DEX-i for ME secondary to RVO. Relevant studies were analyzed for outcomes related to visual acuity, retinal thickness, and the safety profile of DEX-i in RVO treatment.ResultsEvidence indicates that DEX-i substantially improves best-corrected visual acuity (BCVA) and reduces central retinal thickness (CRT) in ME associated with both branch and central RVO, demonstrating rapid and sustained effects. Common adverse events associated with DEX-i included manageable complications, such as medically controlled intraocular pressure elevation and progression of cataracts.ConclusionDEX-i offers effective and sustained improvements in both visual and anatomical outcomes for patients with ME secondary to RVO. Individualized treatment selection is essential to optimize patient outcomes. Future directions include identifying predictive biomarkers and adopting patient-centered approaches based on individual clinical characteristics, which may enhance treatment success in RVO.

Introdução: A Doença Multicêntrica de Castleman (MCD) é associada ao KSHV, que é mais comum em pessoas que vivem com HIV (PVHA) e apresentam CD4 < 200 cels/mm3. É uma doença que cursa com febre, perda ponderal, prostração, sintomas gastrointestinais e respiratórios inespecíficos, linfonodomegalias, edema, derrames cavitários e hepatoesplenomegalia. Achados laboratoriais incluem elevação de proteína C reativa (PCR), pancitopenia, hiponatremia e hipoalbuminemia. É uma doença que mimetiza outras que podem acometer a PVHA, postergando o diagnóstico e aumentando a morbimortalidade, já que a MCD sem tratamento geralmente é fatal. O diagnóstico se dá pela análise histopatológica do linfonodo ou baço e o tratamento é feito com rituximabe, que em 90% dos casos leva à resolução dos sintomas. Materiais/métodos: Descrever caso de paciente com MCD. Relato: Paciente de 24 anos, negro, sexo masculino, iniciou quadro de tosse produtiva, febre vespertina, emagrecimento e prostração. Teve o diagnóstico de HIV, foi excluída tuberculose pulmonar e iniciou terapia antirretroviral (TARV) com dolutegravir. Cinco semanas após, internou por dispneia, aumento do volume abdominal e edema de membros inferiores. Na ocasião do diagnóstico do HIV apresentava 144973 cópias/mL (log 5,16) e contagem CD4 33 células/mm3 (5,44%) e na admissão, 85 cópias/mL (log 1,9) e CD4 52 células/mm3 (19%). Tinha aumento de PCR, hiponatremia, hipoalbuminemia, pancitopenia. Foram realizadas tomografias que demonstraram linfonodomegalias axilares, inguinais e retroperitoneais e esplenomegalia volumosa. Biópsia de medula óssea excluiu doença linfoproliferativa. As culturas e sorologias para doenças oportunistas foram negativas. A biópsia linfonodos inguinal (1 cm) foi positiva para KSHV e compatível com MCD sem Sarcoma de Kaposi. O paciente foi tratado com rituximabe e paclitaxel por quatro semanas com remissão completa dos sintomas. Sete meses depois teve recidiva, sendo tratado novamente. Segue sem recaídas há 9 meses. Conclusão: Trata-se de um caso de PVHA com MCD, que é rara, porém, com incidência aumentando desde a implementação da TARV4. É subdiagnosticada por mimetizar outras doenças mais comuns, o que faz com que muitos pacientes venham a óbito. Não é doença de notificação compulsória, o que tem impacto negativo no entendimento da real incidência e prevalência na população de PVHA. Esse caso denota a importância da biópsia de linfonodo em pacientes com AIDS. Palavras-chave: Doença Multicêntrica de Castleman, Sarcoma de Kaposi, AIDS. Conflitos de interesse: Não houve conflitos de interesse. Ética e financiamentos: Não houve conflito de interesse.

Abstract Introduction The aims of this work were to evaluate the real-world efficacy and safety of a loading dose of intravitreal faricimab in eyes with active neovascular age-related macular degeneration (n-AMD) or diabetic macular edema (DME) and to analyze the treatment outcome in relation to specific biomarkers. Methods Patients with active n-AMD or DME, treated with four monthly intravitreal injections of faricimab, were enrolled in this retrospective, uncontrolled study. Best-corrected visual acuity (BCVA), central subfield thickness (CST), presence of retinal fluid (RF) on optical coherence tomography (OCT), and adverse events were assessed at baseline and at weeks 4, 8, 12, and 16. Predefined biomarkers were evaluated at baseline (BL) and at last visit. Results Sixteen eyes of 15 patients with n-AMD (n-AMD group) and 15 eyes of 12 patients with DME (DME group) were included. Mean (± standard deviation) logarithm of minimum angle of resolution (logMAR) BL BCVA changed from 0.68 (± 0.43) to 0.53 (± 0.36; P = 0.13) and from 0.51 (± 0.34) to 0.32 (± 0.24; P: 0.048) at week 16 in n-AMD and DME group, respectively. A statistically significant mean CST reduction was reported in both groups at last visit (n-AMD: − 166.5 μm; P = 0.0009/DME: − 110.8 μm; P = 0.0086). Seventy-five and 33% of eyes with n-AMD and DME respectively achieved complete RF resolution at last visit. Subfoveal inner and outer retinal damage correlated with a lower final BCVA in n-AMD group. The presence of large (> 100 μm) juxtafoveal microaneurysms (MAs) was significantly correlated with a higher chance of residual fluid in eyes with DME. Conclusions Both n-AMD and DME groups achieved satisfactory anatomical results after a loading-dose of intravitreal faricimab. BCVA improvement might be hampered by pre-existing retinal damage in eyes with n-AMD. Large, juxtafoveal MAs might represent a hallmark of a slower anatomical response to the treatment in eyes with DME.

Abstract Introduction To assess changes in choriocapillaris (CC) vascular density surrounding macular neovascularization (MNV) in treatment-naïve age-related macular degeneration (AMD) after faricimab application using optical coherence tomography angiography (OCTA). Methods Twenty-five eyes of 25 treatment-naïve individuals who underwent intravitreal faricimab injections for neovascular AMD (nAMD) with type 1 MNV were included. Spectral-domain optical coherence tomography (SD-OCT) images and en-face swept-source OCTA images were analyzed, and the percentage of CC flow deficit (FD%), FD average area (FDa) and FD number (FDn) in five progressive 20.0-μm-wide concentric rings (R1, R2, R3, R4 and R5) surrounding the dark halo around the MNV were calculated. Image acquisition was carried out prior to the first faricimab injection (T0) and 1 month after the injection (T1). Results The topographical sub-analysis revealed noteworthy changes in all rings at T1 compared to T0. There was a notable progressive reduction in FD% at T1 compared to T0 values across all rings, indicating a gradual CC reperfusion following anti-VEGF treatment. Additionally, the average size of FD decreased after the loading phase. Although not reaching statistical significance, there was a progressive reduction in the FDa across all rings. Conclusion Our study highlights a CC FD reduction following the administration of three consecutive faricimab injections. This effect was detected in all rings surrounding the dark halo. These observations suggest a partial CC reperfusion surrounding the MNV, potentially serving as an indicator for disease regression.

Abstract Introduction Optimizing treatment protocols for wet age-related macular degeneration (wAMD) is an ongoing challenge, as it involves a delicate balance between achieving therapeutic efficacy and minimizing invasive procedures' frequency. This study aimed to apply the Lean methodology and evaluate the effectiveness of this new setting on intravitreal therapy for wAMD, employing different anti-vascular endothelial growth factors (VEGF) drugs (bevacizumab, brolucizumab, aflibercept, ranibizumab), drawing data from the Bari Intravitreal Injections Registry (BIVIR). Methods This was a retrospective, monocentric, nonrandomized, comparative study. Lean methodology was employed to design the new setting and the BIVIR collected information from electronic medical records. Clinical data of four groups, stratified based on the first-line anti-VEGF agents used, were compared. Best-corrected visual acuity (BCVA) and central retinal thickness (CRT) changes were compared between the four groups at 3 and 12 months. Results Out of 4990 eyes and 41,323 intravitreal injections (IVs) recorded in BIVIR, 1421 eyes of 1182 patients were included. The mean number of IVs in first year was 6.1 ± 2.5, with no significant differences among the four subgroups. The mean change in BCVA was + 6.2 letters [95% confidence interval (CI) 5.6–6.8] after two IVs, and + 5.9 (95% CI 5.1–6.8) letters after three IVs; at three months, brolucizumab was associated with a greater mean increase in BCVA than bevacizumab (p = 0.050); aflibercept (p = 0.044) and ranibizumab p = 0.047). At the 1-year follow-up, the mean change was + 6.3 letters (95% CI 5.4–7.2), brolucizumab and ranibizumab were associated with a superior improvement in BCVA compared to aflibercept (p = 0.033). Regarding the CRT, a significant reduction was observed in the subgroup treated with brolucizumab at the 3-month follow-up, compared to bevacizumab (p = 0.003), aflibercept (p = 0.015), and ranibizumab (p

Abstract Autism spectrum disorder (ASD) is a complex neurodevelopmental condition with a strong genetic component in which rare variants contribute significantly to risk. We performed whole genome and/or exome sequencing (WGS and WES) and SNP-array analysis to identify both rare sequence and copy number variants (SNVs and CNVs) in 435 individuals from 116 ASD families. We identified 37 rare potentially damaging de novo SNVs (pdSNVs) in the cases (n = 144). Interestingly, two of them (one stop-gain and one missense variant) occurred in the same gene, BRSK2. Moreover, the identification of 8 severe de novo pdSNVs in genes not previously implicated in ASD (AGPAT3, IRX5, MGAT5B, RAB8B, RAP1A, RASAL2, SLC9A1, YME1L1) highlighted promising candidates. Potentially damaging CNVs (pdCNVs) provided support to the involvement of inherited variants in PHF3, NEGR1, TIAM1 and HOMER1 in neurodevelopmental disorders (NDD), although mostly acting as susceptibility factors with incomplete penetrance. Interpretation of identified pdSNVs/pdCNVs according to the ACMG guidelines led to a molecular diagnosis in 19/144 cases, although this figure represents a lower limit and is expected to increase thanks to further clarification of the role of likely pathogenic variants in ASD/NDD candidate genes not yet established. In conclusion, our study highlights promising ASD candidate genes and contributes to characterize the allelic diversity, mode of inheritance and phenotypic impact of de novo and inherited risk variants in ASD/NDD genes.

Mesoscale numerical weather prediction models are frequently utilized for wind speed analysis and forecasting in the planning and support of wind power generation. However, high computational costs only allow for routine use up to a kilometer scale, which is sometimes too coarse to support onshore wind power generation in areas with complex orography. To address this, an algorithm was developed in southern Italy to downscale the wind fields output using the weather research and forecasting (WRF) model for the first 250 m above ground level. The algorithm is based on artificial neural networks (ANNs) and uses the WRF model outputs on a 1.2 km regular grid, and the land surface height and orientation on a 240 m regular grid to downscale wind fields to a 240 m regular grid. To train the ANNs, a WRF simulation dataset in large eddy simulation (LES) mode was developed. Particular attention was paid to defining the ANN architectures and analyzing inputs to mitigate overfitting risk while maintaining manageable computation costs. The evaluation of outcomes conducted using independent test datasets from WRF-LES simulations reveals that the wind speed root-mean-square difference (RMSD) is 0.5 m/s over land and 0.2 m/s over the sea surface, respectively, at a spatial resolution of approximately 800 m. These figures are lower than the RMSD values of 1.6 m/s over land and 1.0 m/s over the sea surface, accompanied by a spatial resolution of 1.8 km, which were obtained through comparison with the spline interpolation method.

Abstract The purpose of this study was to investigate choroidal morphology remodeling in AMD-associated type 1 macular neovascularization using two different anti-VEGF drugs. We registered 73 treatment-naïve eyes with a diagnosis of exudative AMD and type 1 MNV. Patients received 3 monthly intravitreal aflibercept (n = 36, aflibercept group [AG]) or brolucizumab (n = 37, brolucizumab group [BG]). Baseline best-corrected visual acuity (BCVA) and anatomical (structural optical coherence tomography) parameters were collected at “T1 control”, before the loading phase (LP) of intravitreal injection, and at “T2 control”, 1 month after the last injection. The main outcomes measured were choroidal vascularity index (CVI), sub-foveal choroidal thickness (SFCT), and central macular thickness (CMT). Our results displayed significant SFCT reduction in both groups between T1 and T2 (p 0.05) after the loading aflibercept injections. Moreover, only the BG displayed a significant choroidal remodeling (stromal choroidal area [SCA], total choroidal area [TCA] and CVI) at T2 (p

Background and Aim: Despite the abundant literature, internal limiting membrane (ILM) peeling remains a controversial topic, especially in diabetic eyes. We compared the safety and effectiveness of intraoperative optical coherence tomography (iOCT)-assisted selective epiretinal membrane (ERM) peeling with dye-assisted ERM and ILM peeling, for the treatment of tractional diabetic macular edema (tDME). Material and Methods: In this single-center retrospective study, we evaluated consecutive patients with tDME who underwent iOCT-assisted selective ERM peeling (Group A) or “dual blue” dye-assisted ERM and ILM peeling (Group B). Best corrected visual acuity (BCVA) and central macular thickness (CMT) were compared over a 12-month follow-up. A linear mixed model analysis was performed. Results: At baseline, the two groups were comparable in terms of their demographic and clinical outcomes. No significant difference between BCVA and CMT was observed among the groups. Both groups showed significant improvement in outcomes at the last follow-up (p < 0.001), although only iOCT-assisted ERM peeling ensured significant visual gain and macular thinning (p < 0.001) one month after surgery. A significant effect of time on both outcomes (p < 0.001) and of time–treatment interaction on visual change (p = 0.02) were observed. In eight patients, macular edema recurred (Group A: two patients; Group B: six patients) and was managed with an intravitreal dexamethasone implant. In Group A, one patient developed a recurrence of ERM without the need for reoperation. Conclusions: iOCT-assisted ERM removal may be as effective as dye-assisted ERM and ILM peeling to treat tDME. Additionally, it ensures a quicker recovery of visual function and macular thickness. The observed ERM recurrence within the 1-year follow-up was mild and did not necessitate additional surgery.

Different solvents water, ethanol and ethanol/water (6:4 v/v), were compared in the extraction of pomegranate peels and seeds (PPS) in terms of recovery yields, antioxidant properties, and antimicrobial action against typical spoilage bacterial and fungal species. The best performing extract (ethanol/water (6:4 v/v) was shown to contain mostly ellagic acid and punicalagin as phenolic compounds (5% overall) and hydrolysable tannins (16% as ellagic acid equivalents) and was able to inhibit the growth of the acidophilic Alicyclobacillus acidoterrestris at a concentration as low as 1%. The preservation of the organoleptic profile of A. acidoterrestris-inoculated apple juice with extract at 1% over 20 days was also observed thanks to the complete inhibition of bacterial growth, while the extract at 0.1% warranted a significant (40%) inhibition of the enzymatic browning of apple smoothies over the first 30 min. When incorporated in whey proteins’ isolate (WPI) at 5% w/w, the hydroalcoholic extract conferred well appreciable antioxidant properties to the resulting coating-forming hydrogel, comparable to those expected for the pure extract considering the amount present. The WPI coatings loaded with the hydroalcoholic extract at 5% were able to delay the browning of cut fruit by ca. 33% against a 22% inhibition observed with the sole WPI. In addition, the functionalized coating showed an inhibition of lipid peroxidation of Gouda cheese 2-fold higher with respect to that observed with WPI alone. These results open good perspectives toward sustainable food preservation strategies, highlighting the potential of PPS extract for the implementation of WPI-based active packaging.

In this work, the influence of plenum and port geometry on the performance of the intake process in a four-stroke spark ignition engine for ultralight aircraft applications is analyzed. Three intake systems are considered: the so-called “standard plenum”, with a relatively small plenum volume, the “V1 plenum”, with a larger plenum volume, and the “standard plenum” equipped with a large curvature manifold called the “G2 port”. Both measurements and 3D CFD simulations, by using Ansys® Academic Fluent, Release 20.2, are performed to characterize and analyze the steady-flow field in the intake system for selected valve lifts. The experimental data and the numerical results are in excellent agreement with each other. The results show that at the maximum valve lift, i.e., 12 mm, the V1 plenum allows an increase in the air mass flow rate of 9.1% and 9.4% compared to the standard plenum and the standard plenum with the “G2 port”, respectively. In addition, the volumetric efficiency has been estimated under unsteady-flow conditions for all geometries at relatively high engine rpms. The difference between numerical results and measurements is less than 1% for the standard plenum, thus proving the accuracy of the model, which is then used to study the other configurations. The V1 plenum shows a fairly constant volumetric efficiency as the engine speed increases, although such an efficiency is lower than that of the other two geometries considered in this work. Specifically, the use of the “G2 port” leads to an increase of 1.5% in terms of volumetric efficiency with respect to the configuration with the original manifold. Furthermore, for the “G2 port” configuration, higher turbulent kinetic energy and higher swirl and tumble ratios are observed. This is expected to result in an improvement of air–fuel mixing and flame propagation.

BackgroundThe primary aims of our cross-sectional observational study were: (i) to determine the prevalence of depressive symptoms in children and adolescents with epilepsy compared to controls and (ii) to explore the difference in depressive symptoms in patients with epilepsy only and those with epilepsy and primary headache as a comorbidity. The secondary objective was to explore parental stress levels.Methods68 pediatric patients aged 6–18 years (44 with epilepsy only and 24 with epilepsy and headache) and 50 controls were recruited. Depressive profile and parental stress were assessed using Children's Depression Inventory, Second Edition (CDI-2) and Parenting Stress Index-Short Form (PSI-SF).ResultsThe group with epilepsy showed significantly high depressive symptoms and parental stress compared to controls. The patients with headache in comorbidity experienced more depressive symptoms than those with epilepsy only.ConclusionDepressive symptoms are more prevalent in patients who have comorbid epilepsy and primary headache; therefore, the neurological/psychological mechanisms underlying this condition should be further investigated. The simultaneous presence of epilepsy, headache and depressive symptoms impacts the quality of life of patients and their parents, increasing parental stress and family management.

PurposeTo compare radial peripapillary capillary (RPC) vascular plexus parameters and peripapillary retinal nerve fiber layer (pRNFL) thickness between Early-Treated Adults with Phenylketonuria (ETPKU) and controls.MethodsThis observational study was a monocentric, case control study including 36 eyes of 36 participants. Among these, 18 were early-treated PKU (ETPKU) and 18 were controls. A SD-OCTA (XR Avanti AngioVue OCTA; Optovue Inc., Fremont, CA) was employed to assess the OCT and OCTA parameters of all the participants. The main outcome measures were the RPC vessels density (VD) %, and the pRNFL thickness.ResultsThe average pRNFL thickness was significantly reduced in ETPKU (110.78 ± 12.48 μm) compared to controls (113.22 ± 13.95 μm), p = 0.046. The mean VD% of the small vessels of the RPC plexus was 52.31 ± 2.2 in ETPKU and 50.71 ± 3.2 in controls (p = 0.049), while the VD% of all the radial peripapillary capillary plexus (RPCP) was 58.5 ± 2.2 in ETPKU and 55.08 ± 3.4 in controls (p

Abstract The balance of processes affecting electron density drives the dynamics of upper‐atmospheric electrical events, such as sprites. We examine the detachment of electrons from negatively charged atomic oxygen (O−) via collisions with neutral molecular nitrogen (N2) leading to the formation of nitrous oxide (N2O). Past research posited that this process, even without significant vibrational excitation of N2, strongly impacts the dynamics of sprites. We introduce updated rate coefficients derived from recent experimental measurements which suggest a negligible influence of this reaction on sprite dynamics. Given that previous rates were incompatible with the observed decay of the light emissions from sprite glows, our findings support that glows actually result from electron depletion in sprite columns.

This work is an investigation on the influence of both residual gas and ozone on the combustion process in an HCCI engine fuelled with iso-octane/air/ozone mixtures and on how ozone reacts with residual gases. It is well known that ozone releases oxygen atoms mainly through the O3+M⇄O2+O+M reaction and this may lead to an improvement of the engine combustion. Nevertheless, the chemical interaction between ozone and the species in the residual gas has not yet been investigated in the literature. CFD simulations of a closed-valve engine cycle have been carried out by using an axisymmetric domain. The model has been validated against experimental data and a parametric analysis has been carried out to assess different compositions and amounts of residual gases on the engine performance. The results show that during compression ozone enables Low-Temperature Combustion, with a small amount of heat released before the occurrence of auto-ignition. The combustion is faster and advanced with a reduction of UHCs and an increase of NOx. The results show that the influence of ozone is more effective as the mass of residual gases increases. With an ozone concentration of 35 ppm at IVC the gross work per cycle increases by 2.52 %, 3.58 % and 5.7 %, compared to the case without ozone, with 0 %, 5 % and 10 % by mass of residual gases, respectively. It can be concluded that ozone is more beneficial for cases where combustion is slower due to the higher amount of residual gases.

Abstract BackgroundWith the capability to render prediagnoses, consumer wearables have the potential to affect subsequent diagnoses and the level of care in the health care delivery setting. Despite this, postmarket surveillance of consumer wearables has been hindered by the lack of codified terms in electronic health records (EHRs) to capture wearable use. ObjectiveWe sought to develop a weak supervision–based approach to demonstrate the feasibility and efficacy of EHR-based postmarket surveillance on consumer wearables that render atrial fibrillation (AF) prediagnoses. MethodsWe applied data programming, where labeling heuristics are expressed as code-based labeling functions, to detect incidents of AF prediagnoses. A labeler model was then derived from the predictions of the labeling functions using the Snorkel framework. The labeler model was applied to clinical notes to probabilistically label them, and the labeled notes were then used as a training set to fine-tune a classifier called Clinical-Longformer. The resulting classifier identified patients with an AF prediagnosis. A retrospective cohort study was conducted, where the baseline characteristics and subsequent care patterns of patients identified by the classifier were compared against those who did not receive a prediagnosis. ResultsThe labeler model derived from the labeling functions showed high accuracy (0.92; F1F122PPP ConclusionsOur work establishes the feasibility and efficacy of an EHR-based surveillance system for consumer wearables that render AF prediagnoses. Further work is necessary to generalize these findings for patient populations at other sites.

Abstract The transcription factor MYB plays a pivotal role in haematopoietic homoeostasis and its aberrant expression is involved in the genesis and maintenance of acute myeloid leukaemia (AML). We have previously demonstrated that not all AML subtypes display the same dependency on MYB expression and that such variability is dictated by the nature of the driver mutation. However, whether this difference in MYB dependency is a general trend in AML remains to be further elucidated. Here, we investigate the role of MYB in human leukaemia by performing siRNA-mediated knock-down in cell line models of AML with different driver lesions. We show that the characteristic reduction in proliferation and the concomitant induction of myeloid differentiation that is observed in MLL-rearranged and t(8;21) leukaemias upon MYB suppression is not seen in AML cells with a complex karyotype. Transcriptome analyses revealed that MYB ablation produces consensual increase of MAFB expression in MYB-dependent cells and, interestingly, the ectopic expression of MAFB could phenocopy the effect of MYB suppression. Accordingly, in silico stratification analyses of molecular data from AML patients revealed a reciprocal relationship between MYB and MAFB expression, highlighting a novel biological interconnection between these two factors in AML and supporting new rationales of MAFB targeting in MLL-rearranged leukaemias.

As zero-carbon fuels, hydrogen and ammonia are of great interest in the transition toward a climate-neutral transportation system. In order to use these fuels and their blends in reciprocating engines, a characterization of the combustion of NH3/H2/air mixtures at high pressures and temperatures is needed. The aim of this work is to compute the Laminar Flame Speed (LFS) of NH3/H2/air mixtures by varying the thermochemical conditions of the reactants. For this purpose, several simulations have been carried out using different kinetic reaction mechanisms. The accuracy of the model has been assessed by comparing the results with experimental data available in the scientific literature. Finally, the influence of mixture composition and thermodynamic conditions of the reactants on LFS has been assessed by considering temperature and pressure values relevant to automotive applications and not yet explored in the literature. By adding H2 to NH3/air mixtures, LFS increases exponentially. By plotting the logarithm of LFS as a function of the H2 mole fraction, the numerical results are well fitted by using a second-degree polynomial regression. However, a linear regression is accurate enough if the H2 mole fraction does not exceed 0.6. Regarding the effect of pressure, the decrease in LFS with increasing pressure is less important as pressure increases. On the other hand, LFS increases with temperature, and this effect is more pronounced as the H2 mole fraction decreases and pressure increases.

Abstract Introduction The aim of this work is to utilize swept-source optical coherence tomography angiography (SS-OCTA) to assess the long-term changes in the choroidal and choriocapillaris (CC) layers of the fellow unaffected eye of patients with unilateral resolved chronic central serous chorioretinopathy (cCSC) following treatment with continuous oral eplerenone (EPL). Methods The study included 35 patients with cCSC and subretinal fluid (SRF) in one eye. SS-OCTA imaging was performed on the fellow cCSC eyes at baseline, 6 months, and 12 months during eplerenone therapy. CC OCT angiography was analyzed to determine the percentage of choriocapillaris flow deficits (FD%), the number of flow deficits (FDn), and the average area of flow deficits (FDa). Results The results demonstrated significant changes in CC flow deficits from baseline to follow-up visits. Specifically, there was a significant decrease in FD% from 28.9 ± 2.2% at baseline to 26.4 ± 1.9% at 6 months (p = 0.023), and further to 24.9 ± 1.7% at 12 months (p = 0.001). Additionally, the FD area gradually contracted over the follow-up period (p 0.05). Conclusions The findings of this study demonstrated long-term reperfusion of the choriocapillaris in unaffected fellow cCSC eyes during continuous oral eplerenone therapy. The beneficial effects of eplerenone therapy were observed after 6 months and maintained at 1 year. These results suggest that specific mineralocorticoid receptor (MR) antagonists may be effective in promoting choriocapillaris recovery in the unaffected eyes of patients with cCSC.

Abstract The purpose of this study was to investigate the effect of diabetic retinopathy (DR) on longitudinal morphological changes in AMD-associated type 1 macular neovascularization using optical coherence tomography angiography (OCTA). We enrolled fifty treatment-naïve eyes with a diagnosis of exudative AMD and type 1 MNV. Twenty of 50 eyes were affected by mild DR. En face OCT angiography were examined for the MNV lesion area (mm2), the MNV flow area (mm2), the central macular thickness (CMT) and the BCVA. The OCTA acquisition was performed at the following visits: (i) before the loading phase (LP) of intravitreal injection of aflibercept (T1), and (ii) 1 month after the last intravitreal injection of loading phase comprising 3 monthly injections (T2). All morpho-functional parameters showed a significantly change at T2 compared to T1 values in both groups. Furthermore, we found a greater MNV area reduction after LP in eyes without DR (P = 0.023). With regard to the remaining parameters, no significant changes were found between two groups (P > 0.05). Our analysis revealed a less MNV area reduction after loading dose of anti-VEGF therapy in eyes affected by diabetic retinopathy.

Giacomo Boscia,1,&ast; Pasquale Viggiano,1,&ast; Federica Marzulli,1 Maria Oliva Grassi,1 Pasquale Puzo,1 Stefano Dore,2 Antonio Pinna,2 Giovanni Alessio,1 Francesco Boscia1 1Department of Translational Biomedicine Neuroscience, University of Bari “Aldo Moro”, Bari, Italy; 2Department of Medicine, Surgery and Pharmacy, University of Sassari, Sassari, Italy&ast;These authors contributed equally to this workCorrespondence: Pasquale Viggiano, Department of Translational Biomedicine Neuroscience, University of Bari “Aldo Moro”, Piazza Giulio Cesare, 11, Bari, Italy, Tel +390805593728, Email pasquale.viggiano90@gmail.comPurpose: To assess the long-term morpho-functional retinal and choroidal changes in chronic central serous chorioretinopathy (cCSC) pachychoroid eyes in response to continuous oral eplerenone (EPL) treatment.Methods: This pilot study was conducted on patients with unilateral exudative cCSC. We enrolled a total of 17 exudative cCSC and 17 non-exudative fellow eyes of 17 patients. Baseline best-corrected visual acuity (BCVA) and anatomical (structural optical coherence tomography [OCT] and OCT angiography) parameters in both eyes were collected at baseline. Follow-up data were collected at 6, 12, and 48 months after initiation of EPL treatment.Results: (i) Exudative cCSC eyes: Compared with baseline (0.34± 0.13 LogMAR), BCVA significantly improved at follow-up examinations (6 months: 0.28± 0.13 LogMAR, p=0.039; 12 months: 0.22± 0.11 LogMAR, p=0.025; 48 months: 0.21± 0.08 LogMAR, p=0.028). Furthermore, there was a significant reduction from baseline in all structural OCT parameters (subretinal fluid and subfoveal choroidal thickness [SFCT]; p< 0.05). (ii) Non-exudative fellow eyes: There was no significant change in BCVA. There was a significant reduction from baseline in SFCT and choriocapillaris flow deficit percentage (p< 0.05).Conclusion: In this pilot study, continuous oral EPL therapy in cCSC pachychoroid eyes resulted in long-term morpho-functional improvement. The beneficial effect of EPL occurred within the first year and was maintained after four years. Based on these preliminary observations, EPL may be effective in the exudative forms of CSC.Keywords: central serous chorioretinopathy, choriocapillaris reperfusion, OCT and OCTA

While there has been a recent onslaught of traditional lab-based fitness measures in immersive virtual reality (IVR) exergaming research, there remains a paucity in the field-based fitness domain, which refers to assessments made outside a formal laboratory setting which are easier, cheaper, and have more practical application. This study aimed to assess changes in field-based fitness tests including the 1-mile run, 20-m dash, multiple single-leg hop-stabilization test, Abalakov jump, and 5-10-5 Pro Agility test during a 1-month workout protocol and to compare differences between groups assigned to either an IVR machine-directed exergaming platform or a traditional, self-directed cable-resistance training control (SELF). Eighteen (7 females) college-aged participants with little resistance training experience were randomized to IVR or SELF and worked out thrice weekly for 4 weeks (12 sessions). Wilcoxon rank-sum tests were performed for continuous variables to assess significance. Compared to SELF, the IVR group had significantly better performance improvements in 20 m dash (−0.1s vs. 0.0s, p = 0.022), 5-10-5 Pro Agility Test (−0.1s vs. −0.0s, p = 0.003), Abalakov Jump (5.8 cm vs. 2.0 cm, p = 0.0013), 1-Mile Run (−11.0s vs. −2.0s, p = 0.008), and Multiple Single-Leg Hop-Stabilization Test with their dominant (−9.0s vs. 1.0s, p = 0.0015) and non-dominant (−8.0s vs. 1.0s, p = 0.003) legs. This training study demonstrates that IVR exergaming, more so than those that traditionally resistance train (SELF), can improve many field-based fitness components including agility, balance and stability, speed/acceleration, cardiovascular endurance, and lower-body power.

Objective: to map scientific knowledge on nursing students’ attitudes and perceptions regarding ageism. Method: scoping review according to the recommendations of the Joanna Briggs Institute. The study question was: What are scientific evidence available on the attitudes and perceptions of nursing students regarding ageism? The search was conducted in 12 databases using the Rayyan application and the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews. The studies were selected by two reviewers using a data extraction tool. Results: of the 4,595 files, 46 that were published between 1984 and 2022 were selected, and the quantitative method was the most used. The most commonly used instrument was the Kogan’s Attitudes Toward Old People Scale. Positive, negative, mixed, neutral, and inconclusive attitudes and perceptions were identified. Conclusion: attitudes and perceptions about ageism are diverse and not conclusive. Future intervention studies are recommended to detect changes in the behavior of nursing students in the face of ageism.

Carinal and tracheobronchial angle tumors have long been a contraindication for surgical removal; the technique of tracheal sleeve pneumonectomy makes it possible to approach this malignancy but still represents a surgical challenge. Left sleeve pneumonectomy is less common compared with right sleeve pneumonectomy and represents a minority component in the literature’s case series due to the complexity of the anatomy. In addition, there is no standard for treatment strategy, and it must be assessed on a case-by-case basis. From 2020 to 2023, we performed three left tracheal sleeve pneumonectomies and one neocarina reconstruction surgery for benign lesions without lung resections. All cases were performed without cardiovascular support such as cardiopulmonary bypass and via median sternotomy. With a median length of stay of 21.5 days (between 14 days and 40 days), all patients were transferred to a physiotherapeutic rehabilitation facility for functional reactivation, where they received physiotherapeutic respiratory therapy given the slow functional recovery. The recorded 30-day mortality was 0. There is no standardized approach for left-sided sleeve pneumonectomy, and it is still a surgical challenge due to intraoperative and postoperative difficulties.

Abstract This study aimed to estimate the risks of adverse infant outcomes in the first year of life related to prenatal Zika virus (ZIKV) exposure. A prospective cohort of pregnant women with rash was recruited in Central-West Brazil in a post-epidemic period (January 2017 to April 2019). We evaluated participants’ medical histories and performed ZIKV diagnostic testing using molecular (reverse transcription polymerase chain reaction [RT-PCR]) and serologic (immunoglobulin [Ig]M and plaque reduction neutralization tests [PRNT90]) assays. The ZIKV-positive group included both RT-PCR-confirmed cases as well as IgM and/or PRNT90-positive probable cases. Children were evaluated at birth and in the first 12 months of life. Transfontanellar ultrasound, central nervous system computed tomography, eye fundoscopy and retinography were performed. We estimated the absolute risk and 95% confidence interval (95% CI) of adverse infant outcomes among confirmed prenatally ZIKV-exposed children. Among 81 pregnant women with rash, 43 (53.1%) were ZIKV infected. The absolute risk of microcephaly among offspring of ZIKV-infected pregnant women was 7.0% (95% CI: 1.5–19.1), including the two cases of microcephaly detected prenatally and one detected postnatally. In total, 54.5% (95% CI: 39.8–68.7) of children in the ZIKV-exposed group had at least one ophthalmic abnormality, with the most frequent abnormalities being focal pigmentary mottling and chorioretinal atrophy or scarring. Our findings reinforce the importance of long-term monitoring of prenatally ZIKV-exposed children born apparently asymptomatic for Congenital Zika Syndrome.

Objective: The aim of the study is to evaluate early and long-term results of chest wall primary Ewing’s sarcoma patients treated in the time period February 2000–February 2023 by a multidisciplinary approach. Methods: We retrospectively reviewed the medical records of patients who underwent chest wall resection for a primary tumor. Treatment approach, extent of resection, 30-day mortality, overall survival (OS), local recurrence-free survival (LRFS), and metastasis-free survival (MFS) were analyzed. Results: Overall, n = 15 consecutive patients were treated for chest wall primary Ewing’s sarcoma. A median of n = 3 ribs was resected with a median of n = 2 ribs adjacent to the lesion. Resections were extended to the adjacent structures in n = 5 patients (33.3%). In all cases, we performed a prosthetic reconstruction, associated with muscle flap (n = 10, 66.6%) or with rigid titanium bars and muscle flap (n = 6, 40%). A radical resection was accomplished in n = 13 patients (84.6%). The median surgical time was 310 ± 120 min; median hospitalization was 7.8 ± 1.9 days. Post-operative mortality was zero. We recorded n = 4 (30.7%) post-operative complication. The median follow-up (FU) was 26 months. Moreover, 5-year overall and event-free survival were 52% and 48%, respectively. Conclusions: This case series confirms the benefit of the multidisciplinary approach for Ewing sarcomas in early and long-term results.

Purpose: To evaluate the immediate alterations in the thickness of the macular ganglion cell–inner plexiform layer (mGCIPL), peripapillary retinal nerve fiber layer (RNFL), inner retinal layer (IRL), and outer retinal layer (ORL) using spectral domain optical coherence tomography (SD-OCT) subsequent to strabismus surgery in pediatric patients diagnosed with horizontal esotropia. Methods: Twenty-eight eyes from twenty-one child patients who had undergone uncomplicated horizontal rectus muscle surgery due to strabismus were included. Measurements of RNFL, mGCL-IPL, IRL, and ORL using structural OCT were conducted both before the surgery and one month after the surgical procedure. Importantly, a control group comprising 14 healthy eyes, matched for age and significant refractive error (p = 0.026). Notably, comparison between the strabismus group at baseline and the healthy group revealed a significant reduction in mGCL-IPL in the strabismus group (60.8 ± 9.2) compared to the healthy control group (68.3 ± 7.2; p = 0.014). Conclusions: Following strabismus surgery, our observations pointed towards a thickening of the mGCL-IPL layer, which is likely attributable to transient local inflammation. Additionally, we identified a significant differentiation in the mGCL-IPL complex between the pediatric patient group with strabismus and the control group.

To assess changes in choriocapillaris (CC) vascular density surrounding macular neovascularization (MNV) in age-related macular degeneration (AMD) when transitioning from various anti-VEGF treatments to faricimab, using optical coherence tomography angiography (OCTA). 25 eyes of 22 individuals who underwent intravitreal faricimab injections for neovascular AMD with type 1 MNV were included. OCTA images were obtained prior to (T0), after one (T1), and after three faricimab injections (T2); Noteworthy changes occurred in the first ring at T2 in comparison to T0. The percentage of CC flow deficit (FD%), FD average area (FDa), and FD number (FDn) in 5 rings (R1-R5) surrounding the dark halo around the MNV were calculated. A reduction in FD% at T2 compared to T0 (50.5 ± 10.2% at T0, 46.4 ± 10.6% at T2; p = 0.020) was seen, indicating CC reperfusion. Additionally, we observed a reduction in the average FDa (140.2 ± 172.1% at T0, 93.7 ± 101.8% at T2; p = 0.029). Our study highlights an FD% after three consecutive faricimab injections. The most pronounced effect was observed in the first ring, directly adjacent to the dark halo, suggesting a partial CC reperfusion surrounding the MNV, potentially indicating disease regression.

Inhibitory control performance may differ greatly as a function of individual differences such as anxiety. Nonetheless, how cognitive control proficiency might be influenced by exposure to various environments and how anxiety traits might impact these effects remain unexplored. A cohort of thirty healthy volunteers participated in the study. Participants performed a Go/No-Go task before exposure to a ‘forest’ and ‘urban’ virtual environment, in a counterbalanced design, before repeating the GNG task. The State-Trait Anxiety Inventory (STAI) was finally filled-in. Our findings unveiled an initial negative correlation between anxiety trait levels and GNG task performance, consistent with the established literature attributing difficulties in inhibitory functionality to anxiety. Additionally, different environmental exposures reported opposite trends. Exposure to the ‘forest’ environment distinctly improved the GNG performance in relation to anxiety traits, while the ‘urban’ setting demonstrated adverse effects on task performance. These results underscore the intricate relationship among cognitive control, environmental exposure, and trait anxiety. In particular, our findings highlight the potential of natural settings, such as forests, to mitigate the impact of anxiety on inhibition. This might have implications for interventions aimed at improving cognitive control.

Virtual reality (VR) can be a promising tool to simulate reality in various settings but the real impact of this technology on the human mental system is still unclear as to how VR might (if at all) interfere with cognitive functioning. Using a computer, we can concentrate, enter a state of flow, and still maintain control over our surrounding world. Differently, VR is a very immersive experience which could be a challenge for our ability to allocate divided attention to the environment to perform executive functioning tasks. This may also have a different impact on women and men since gender differences in both executive functioning and the immersivity experience have been referred to by the literature. The present study aims to investigate cognitive multitasking performance as a function of (1) virtual reality and computer administration and (2) gender differences. To explore this issue, subjects were asked to perform simultaneous tasks (span forward and backward, logical–arithmetic reasoning, and visuospatial reasoning) in virtual reality via a head-mounted display system (HDMS) and on a personal computer (PC). Our results showed in virtual reality an overall impairment of executive functioning but a better performance of women, compared to men, in visuospatial reasoning. These findings are consistent with previous studies showing a detrimental effect of virtual reality on cognitive functioning.

Este trabalho teve por objetivo discutir um produto educacional, seus conhecimentos científicos e sobre Ciência utilizando obras de Cultura Pop. Espera-se contribuir com a área sobre as possibilidades e limitações de elementos da cultura pop no aprendizado de conhecimentos científicos. Foi elaborada uma sequência didática utilizando os Três Momentos Pedagógicos e o modelo OHERIC (observação, hipótese, experiência, resultados, interpretação e conclusão). Buscou-se, a partir da cultura vivenciada pelos estudantes, problematizar conhecimentos químicos, provocar engajamento e inspirar o envolvimento dos estudantes nas atividades propostas.A atividade foi realizada com estudantes do primeiro ano do ensino médio de uma escola pública, no âmbito do Programa Residência Pedagógica, em uma cidade de médio porte do interior de Minas Gerais. No geral, os resultados foram positivos, indicando que a utilização de obras artísticas da cultura pop pode provocar o envolvimento dos alunos na aprendizagem de conhecimento de química. Ademais, o produto educacional se mostra versátil para adaptação a outros contextos sociais, inclusive, com a introdução de obras regionais.

Water, energy, and minerals are fundamental pillars for the future of humankind. Sustainable and renewable productive processes and resources are the only possibility to face the continuously growing global population and high living standards requirements. The present work introduces a proof of concept for the pilot scale production of magnesium hydroxide, Mg(OH)2, from waste saltworks bitterns located in the district of Trapani, Italy. Mg(OH)2 was produced by adopting a proprietary “Magnesium Crystals Granulometry Controlled Reactor”, Mg-CGCR. The influence of several parameters was investigated on Mg(OH)2 suspensions and powders characteristics: (i) the bittern flow rate, (ii) alkaline sodium hydroxide, NaOH, concentrations solutions (adopted as the precipitant agent) and (iii) the final suspension pH value (stoichiometric or OH- excess amounts). A Mg2+ recovery >99 % can be achieved thanks to the adoption of a product recycling strategy in the reactor. Furthermore, highly pure Mg(OH)2 powders, addressed by cationic purity, were synthesized. Results demonstrate the possibility of producing highly pure Mg(OH)2 products from waste-concentrated saline solutions, thus turning waste into valuable compounds.

IntroductionInverted Internal Limiting Membrane (ILM)-flap technique demonstrated its effectiveness, in terms of anatomical closure rate and visual acuity recovery for high myopic macular holes. We evaluated macular function after a successful inverted ILM-flap for macular holes in high myopic eyes (hMMH) using microperimetry to predict visual prognosis.MethodsA retrospective study on 23 eyes of 23 patients after surgical closure of hMMH, was performed. All patients underwent inverted ILM-flap and gas tamponade. Cataract surgery was performed in phakic eyes. Study outcomes including best-corrected visual acuity (BCVA), retinal sensitivity (RS) at central 12°, central retinal sensitivity (CRS) at central 4° and mean deviation (MD), and fixation behavior as bivariate contour ellipse area (BCEA, degrees2) measured by microperimetry, were evaluated over 6 months. A mixed-effects model was used to evaluate and compare the repeated measurements of outcomes between phakic and pseudophakic eyes. A regression model was performed to assess the relationship between BCVA at 6 months and independent variables.ResultsOverall mean BCVA improved from 0.98 ± 0.21 logMAR at baseline to 0.47 ± 0.31 logMAR at the last follow-up (p

IntroductionMale reproduction is under the control of the hypothalamus–pituitary–gonadal (HPG) axis. The endocannabinoid system (ECS) and the kisspeptin system (KS) are two major signaling systems in the central and peripheral control of reproduction, but their possible interaction has been poorly investigated in mammals. This manuscript analyzes their possible reciprocal modulation in the control of the HPG axis.Materials and methodsAdolescent male rats were treated with kisspeptin-10 (Kp10) and endocannabinoid anandamide (AEA), the latter alone or in combination with the type 1 cannabinoid receptor (CB1) antagonist rimonabant (SR141716A). The hypothalamic KS system and GnRH expression, circulating sex steroids and kisspeptin (Kiss1) levels, and intratesticular KS and ECS were evaluated by immunohistochemical and molecular methods. Non-coding RNAs (i.e., miR145-5p, miR-132-3p, let7a-5p, let7b-5p) were also considered.ResultsCirculating hormonal values were not significantly affected by Kp10 or AEA; in the hypothalamus, Kp10 significantly increased GnRH mRNA and aromatase Cyp19, Kiss1, and Kiss1 receptor (Kiss1R) proteins. By contrast, AEA treatment affected the hypothalamic KS at the protein levels, with opposite effects on the ligand and receptor, and SR141716A was capable of attenuating the AEA effects. Among the considered non-coding RNA, only the expression of miR145-5p was positively affected by AEA but not by Kp10 treatment. Localization of Kiss1+/Kiss1R+ neurons in the arcuate nucleus revealed an increase of Kiss1R-expressing neurons in Kp10- and AEA-treated animals associated with enlargement of the lateral ventricles in Kp10-treated animals. In the brain and testis, the selected non-coding RNA was differently modulated by Kp10 or AEA. Lastly, in the testis, AEA treatment affected the KS at the protein levels, whereas Kp10 affected the intragonadal levels of CB1 and FAAH, the main modulator of the AEA tone. Changes in pubertal transition-related miRNAs and the intratesticular distribution of Kiss1, Kiss1R, CB1, and CB2 following KP and AEA treatment corroborate the KS-ECS crosstalk also showing that the CB1 receptor is involved in this interplay.ConclusionFor the first time in mammals, we report the modulation of the KS in both the hypothalamus and testis by AEA and revealed the KP-dependent modulation of CB1 and FAAH in the testis. KP involvement in the progression of spermatogenesis is also suggested.

Old-growth forests have a primary environmental and ecological value, as they closely recall primeval forests and the natural forest landscape that was spread throughout Italy and Europe before man intervention heavily altered the functioning of most natural ecosystems. These ecosystems are more and more recognized as keystones of environmental policies (i.e., the EU Biodiversity Strategy 2030) aimed to preserve biodiversity and mitigate the impacts of climate change. A recent report highlights that Europe’s old-growth forests account for only 3 percent of the overall forest surface. The majority of italian old-growth forests are located along the Apennines, especially in the Pollino, Sila and Aspromonte National Parks, in remote montane areas characterized by irregular topographical conditions (i.e., high slopes and/or shallow soils) which hamper the access and exploitation of these less productive stands, thus allowing the survival of old-growth forests for many centuries. The ongoing climate change is a significant challenge to the conservation of old-growth forests, particularly in areas such as the Mediterranean basin, where an intensification of extreme climate events is expected. Heat waves can exacerbate drought’s negative impacts on tree growth and survival, leading to reduced woody carbon stocks and biodiversity in old-growth forests. To date, there is poor understanding of such highly valuable and extremely fragile natural ecosystems in Italy. Insights are available based on data gathered as part of two research programs, funded by the Italian Ministry of the Environment and Land and Sea Protection, with the purpose of creating a Network of Old Growth Forests in Italy’s National Parks. In this study, we aimed to highlight the role and importance of old-growth forests, focusing on those located within the Pollino National Park. A comprehensive overview of the key strengths and weaknesses, that mark these peculiar forest ecosystems, was followed by a discussion of the future outlook, grounded on strategies that will ensure not only the protection and conservation of these ecosystems, but also their development and promotion.

Introduction The Positive and Negative Affect Schedule (PANAS) is a self-report questionnaire that consists of two scales to measure positive and negative affective states. An unresolved debate exists whether positive and negative affective states can co-exist or are mutually exclusive. Furthermore, it is unclear how the presence of a dysmetabolic state that affects cognition, such as chronic kidney disease (CKD), impacts these states. Aims We approach this problem using a non-linear method of dimensionality reduction, the Uniform Manifold Approximation and Projection (UMAP), which has the advantage of preserving the data’s global structure. Results We show its application in a cohort of 42 CKD patients and 100 age- and gender-matched healthy volunteers (age 57 ± 20 years). UMAP algorithm allowed to identify two mutually exclusive affective states. The presence of CKD impacts both states. Conclusion This new methodology and its exemplificative application to CKD are discussed here for the first time.

Abstract Using exome sequencing for biomarker discovery and precision medicine requires connecting nucleotide-level variation with functional changes in encoded proteins. However, for functionally annotating the thousands of cancer-associated missense mutations, or variants of uncertain significance (VUS), purifying variant proteins for biochemical and functional analysis is cost-prohibitive and inefficient. We describe parallel functional annotation (PFA) of large numbers of VUS using small cultures and crude extracts in 96-well plates. Using members of a histone methyltransferase family, we demonstrate high-throughput structural and functional annotation of cancer-associated mutations. By combining functional annotation of paralogs, we discovered two phylogenetic and clustering parameters that improve the accuracy of sequence-based functional predictions to over 90%. Our results demonstrate the value of PFA for defining oncogenic/tumor suppressor functions of histone methyltransferases as well as enhancing the accuracy of sequence-based algorithms in predicting the effects of cancer-associated mutations.

False memory formation is usually studied using the Deese-Roediger-McDermott paradigm (DRM), in which individuals incorrectly remember words that were not originally presented. In this paper, we systematically investigated how two modes of thinking (analytical vs. intuitive) can influence the tendency to create false memories. The increased propensity of intuitive thinkers to generate more false memories can be explained by one or both of the following hypotheses: a decrease in the inhibition of the lure words that come to mind, or an increased reliance on the familiarity heuristic to determine if the word has been previously studied. In two studies, we conducted tests of both recognition and recall using the DRM paradigm. Our observations indicate that a decrease in inhibitory efficiency plays a larger role in false memory formation compared to the use of the familiarity heuristic.

Pseudoneglect, the tendency to display a leftward perceptual bias, is consistently observed in line bisection tasks. Some studies have shown that pseudoneglect is sensitive to emotions. This emotion-related modulation is likely related to valence-dependent hemispheric lateralization, although the results do not converge. A possible explanation for these inconsistencies could be individual differences in emotional tone. Considering that negative and positive emotions produce different basic activations of the two hemispheres, emotional characteristics of the subjects, such as trait anxiety, could in fact modulate the pseudoneglect phenomenon. To verify this, high- and low-anxiety participants were asked to centrally bisect horizontal lines delimited by neutral or emotional (happy and sad) faces. In line with previous studies, results here showed a decrease in the leftward bisection error in the presence of happy faces, indicating a greater involvement of the left hemisphere in processing positive emotional stimuli. In addition, trait anxiety influenced the magnitude of the visual bias. High-anxiety subjects, compared to low-anxiety subjects, showed a general bias in visual attention toward the left space as a function of emotional valence. Results are discussed within the framework of valence-dependent hemispheric specialization and the relative degree of activation. In sum, our data highlight the relevance of considering emotional individual differences in studying the pseudoneglect phenomenon.

High blood pressure, also known as hypertension, is a major risk factor for cardiovascular disease. Salt intake has been shown to have a significant impact on BP, but the mechanisms by which it influences the blood pressure dipping pattern, and 24-h blood pressure remains controversial. This literature review aims to both summarize the current evidence on high salt diet induced hypertension and discuss the epidemiological aspects including socioeconomic issues in the United States and abroad. Our review indicates that a high salt diet is associated with a blunted nocturnal blood pressure dipping pattern, which is characterized by a reduced decrease in blood pressure during the nighttime hours. The mechanisms by which high salt intake affects blood pressure dipping patterns are not fully understood, but it is suggested that it may be related to changes in the sympathetic nervous system. Further, we looked at the association between major blood pressure and circadian rhythm regulatory centers in the brain, including the paraventricular nucleus (PVN), suprachiasmatic nucleus (SCN) and nucleus tractus solitarius (nTS). We also discuss the underlying social and economic issues in the United States and around the world. In conclusion, the evidence suggests that a high salt diet is associated with a blunted, non-dipping, or reverse dipping blood pressure pattern, which has been shown to increase the risk of cardiovascular disease. Further research is needed to better understand the underlying mechanisms by which high salt intake influences changes within the central nervous system.

Coagulase-negative staphylococci (CoNS) are reportedly responsible for 50–60% of bloodstream infections in very preterm (Staphylococcus capitis is an increasingly prevalent pathogen in the neonatal setting, frequently causing central-line-associated bloodstream infections (CLABSIs) that can be difficult to eradicate. Central venous catheter (CVC) removal versus in situ treatment with CoNS CLABSIs is a controversial treatment strategy with no clear consensus. We reviewed all S. capitis CLABSIs in our NICU between 2019 and 2022, focusing on the role of catheter removal in eradication. Among the 25 patients, 17 CVCs were removed after diagnosis, leading to a 76.5% eradication rate in this group. Three infants had a persistently positive blood culture after CVC substitution. A new catheter was then inserted after a 48 h washout period, resulting in resolution of the infection. Only two of the eight patients (25%) who retained their catheter after diagnosis achieved infection eradication with antibiotic therapy alone. When feasible, catheter removal seems to be the most effective strategy for eradicating S. capitis CLABSIs, sometimes even requiring a 48 h washout period before reinsertion. Further studies on this topic are needed to better standardize the management of this type of infection.

A domain-specific perspective to cognitive functioning in stroke patients may predict their cognitive recovery over time and target stroke rehabilitation intervention. However, data about domain-specific cognitive impairment after stroke are still scarce. This study prospectively investigated the domain-specific pattern of cognitive impairments, using the classification proposed by the Montreal Cognitive Assessment (MoCA), in a cohort of 49 stroke patients at admission (T0), discharge (T1), and six-month follow-up (T2) from subacute intensive rehabilitation. The predictive value of T0 cognitive domains cognitive impairment at T1 and T2 was also investigated. Patients’ cognitive functioning at T0, T1, and T2 was assessed through the MoCA domains for executive functioning, attention, language, visuospatial, orientation, and memory. Different evolutionary trends of cognitive domain impairments emerged across time-points. Patients’ impairments in all domains decreased from T0 to T1. Attention and executive impairments decreased from T0 to T2 (42.9% and 26.5% to 10.2% and 18.4%, respectively). Conversely, altered visuospatial, language, and orientation increased between T1 and T2 (16.3%, 36.7%, and 40.8%, respectively). Additionally, patients’ global cognitive functioning at T1 was predicted by the language and executive domains in a subacute phase (p = 0.031 and p = 0.001, respectively), while in the long term, only attention (p = 0.043) and executive (p = 0.019) domains intervened. Overall, these results confirm the importance of a domain-specific approach to target cognitive recovery across time in stroke patients.

The dual-process theory of thought rests on the co-existence of two different thinking modalities: a quick, automatic, and associative process opposed to a slow, thoughtful, and deliberative process. The increasing interest in determining the neural foundation of the dual-process distinction has yielded mixed results, also given the difficulty of applying the fMRI standard approach to tasks usually employed in the cognitive literature. We report an activation likelihood estimation (ALE) meta-analysis to investigate the neural foundation of the dual-process theory of thought. Eligible studies allowed for the identification of cerebral areas associated with dual-process theory-based tasks without differentiating between fast and slow thinking. The ALE algorithm converged on the medial frontal cortex, superior frontal cortex, anterior cingulate cortex, insula, and left inferior frontal gyrus. These structures partially overlap with the cerebral areas recurrently reported in the literature about the neural basis of the dual-process distinction, where the PARCS theory-based interpretation emphasizes the role of the right inferior gyrus. The results confirm the potential (but still almost unexplored) common ground between the dual-process literature and the cognitive control literature.

Abstract Background It is now well established that atherosclerosis begins in childhood and evolves through adolescence and young adulthood, ultimately resulting in myocardial infarction and stroke in adults. Main test Childhood is a critical phase during which atherosclerosis may begin to develop; in the presence of familial hypercholesterolemia, lifelong elevation of Low Density Lipoprotein cholesterol levels greatly accelerates atherosclerosis. These concepts, which have been largely developed from epidemiologic evidence, have not always been simple to implement in the paediatric clinical practice. The purpose of this article is to briefly review but also to highlight the rationale, the motivation and the methods in the process of identifying children and adolescents with familial hypercholesterolemia, an often hidden but very important genetic disease.

BackgroundThere are little data on remote monitoring (RM) of implantable loop recorders (ILRs) in patients with unexplained syncope and whether it confers enhanced diagnostic power.ObjectiveTo evaluate the effect of RM in ILR recipients for unexplained syncope for early detection of clinically relevant arrhythmias by comparison with a historical cohort with no RM.MethodsSyncRM is a propensity score (PS)-matched study prospectively including 133 consecutive patients with unexplained syncope and ILR followed up by RM (RM-ON group). A historical cohort of 108 consecutive ILR patients with biannual in-hospital follow-up visits was used as control group (RM-OFF group). The primary endpoint was the time to the clinician's evaluation of clinically relevant arrhythmias (types 1, 2, and 4 of the ISSUE classification).ResultsThe primary endpoint of arrhythmia evaluation was reached in 38 patients (28.6%) of the RM-ON group after a median time of 46 days (interquartile range, 13–106) and in 22 patients (20.4%) of the RM-OFF group after 92 days (25–368). The PS-matched adjusted ratio of rates of arrhythmia evaluation was 2.53 (95% confidence interval, 1.32–4.86) in the RM-ON vs. RM-OFF group (p = 0.005).ConclusionIn our PS-matched comparison with a historical cohort, RM of ILR patients with unexplained syncope was associated with a 2.5-fold higher chance of evaluations of clinically relevant arrhythmias as compared with biannual in-office follow-up visits.