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Maria Serra,1 Anna Presicci,2 Luigi Quaranta,3 Mariaclara Achille,4 Elvita Caputo,4 Silvia Medicamento,4 Francesco Margari,5 Federica Croce,5 Lucia Margari4 1Department of Pharmacy-Pharmaceutical Sciences, University of Bari “Aldo Moro”, Bari, Italy; 2Department of Neuroscience, Sense Organs and Locomotor System, University Hospital “Policlinico”, Bari, Italy; 3Department of Computer Science, University of Bari “Aldo Moro”, Bari, Italy; 4Department of Biomedical Sciences and Human Oncology, University of Bari “Aldo Moro”, Bari, Italy; 5Department of Basic Medical Science, Neuroscience and Sensory Organs, University of Bari “Aldo Moro”, Bari, ItalyCorrespondence: Maria Serra, Department of Pharmacy-Pharmaceutical Sciences, University of Bari “Aldo Moro”, Via Edoardo Orabona 4, Bari, 70125, Italy, Tel +39 080 5592829, Fax +39 080 5595260, Email maria.serra.13@gmail.comIntroduction: Many studies highlighted the role of inflammation in the pathogenesis of depression, although not for every patient nor for every symptom. It is widely shared that stressors can increase inflammation and lead to depressive symptoms. Little is known about the symptom-specificity of the inflammation-depression link in adolescence, which we aimed to explore. The single symptom analysis is a core feature of the recent network approach to depression, supposing that psychiatric disorders consist of co-occurring symptoms and their tendency to cause each other.Patients and Methods: We recruited 52 adolescents diagnosed with a Depressive Disorder during the COVID-19 stressful period. We used regression analysis to measure associations between high sensitivity C-Reactive Protein (hs-CRP) and Interleukin-6 (IL-6) and depressive symptoms assessed by the Children’s Depression Inventory 2 (CDI 2). For the study of symptom specificity, we selected 13 items from the CDI 2 Self Report corresponding with the DSM-5 diagnostic criteria for Major Depressive Disorder and we coded them as dichotomous variables to perform a regression analysis.Results: We found that a higher CDI 2-Parent Version total score was significantly predicted by higher hs-CRP (coefficient 3.393; p 0.0128) and IL-6 (coefficient 3.128; p 0.0398). The endorsement of the symptom self-hatred, measuring the DSM-5 symptom “feelings of worthlessness”, was significantly predicted by hs-CRP (OR 10.97; 95% CI 1.29– 93.08; p 0.0282).Conclusion: A novel symptom-specificity emerged, with hs-CRP significantly predicting the endorsement of the symptom self-hatred, recognized as a core feature of adolescent depression, following the network theory. We considered it a possible phenotypic expression of one depression endophenotype previously causally linked to inflammation. Due to the limited sample size, these preliminary findings require confirmation with future research focusing on the relationship between inflammation and self-hatred and other central nodes of the depression network, representing an opportunity for targeting interventions on crucial symptoms.Keywords: endophenotype, inflammation, network, self-hatred, stress

One of the major problems related to climate change is the increase in land area affected by higher salt concentrations and desertification. Finding economically and environmentally friendly sustainable solutions that effectively mitigate salt stress damage to plants is of great importance. In our work, some natural products and microbial biocontrol agents were evaluated for their long-term effectiveness in reducing salt stress in lettuce ( Lactuca sativa L. var. romana ) plants. Fourteen different treatments applied to soil pots, with and without salt stress, were analyzed using biometric (leaf and root length and width), physiological (chlorophyll and proline content), and morphological (microscopic preparations) techniques and NGS to study the microbial communities in the soil of plants subjected to different treatments. Under our long-term experimental conditions (90 days), the results showed that salt stress negatively affected plant growth. The statistical analysis showed a high variability in the responses of the different biostimulant treatments. Notably, the biocontrol agents Papiliotrema terrestris (strain PT22AV), Bacillus amyloliquefaciens (strain B07), and Rahnella aquatilis (strain 36) can act as salt stress mitigators in L. sativa . These findings suggest that both microbial biocontrol agents and certain natural products hold promise for reducing the adverse effects of salt stress on plants.

Exposure to infectious diseases in early life has been linked to increased mortality risk in later life in high-disease settings, such as eighteenth- and nineteenth-century Europe. Less is known about the long-term effects of early-life disease exposure in milder disease environments. This study estimates heterogeneous effects from disease exposure in infancy on later-life mortality in twentieth-century Sweden, by socioeconomic status at birth and sex. Using historical population data for southern Sweden, we study 11,515 individuals who were born in 1905-1929 from age 1 until age 85. We measure exposure to disease using the local post-early neonatal mortality rate in the first 12 months after birth and apply flexible parametric survival models. For females, we find a negative effect on life expectancy (scarring) at ages 1-85 following high disease exposure in infancy, particularly for those born to unskilled workers. For males, we find no negative effect on later-life survival, likely because stronger mortality selection in infancy outweighs scarring. Thus, even as the incidence of infectious diseases declined at the start of the twentieth century, early-life disease exposure generated long-lasting negative but heterogeneous population health effects., (Copyright © 2024 The Authors.)

Introduction: Refractory and super-refractory status epilepticus are medical emergencies that must be promptly treated in consideration of their high mortality and morbidity rate. Nevertheless, the available evidence of effective treatment of these conditions is scarce. Among novel antiseizure medications (ASMs), highly purified cannabidiol (hpCBD) has shown noteworthy efficacy in reducing seizures in Lennox-Gastaut syndrome (LGS), Dravet syndrome (DS), and Tuberous Sclerosis Complex (TSC)., Case Presentation: Here, we present two cases of effective use of hpCBD in both refractory and super- refractory status epilepticus. The administration of the nasogastric tube permitted the resolution of status epilepticus without adverse events. At 6-month follow-up, both patients were on hpCBD treatment, which continued to be efficacious for treating seizures., Conclusion: According to our experience, hpCBD should be taken into consideration as an add-on therapy of RSE and SRSE while also considering the possibility of maintaining this treatment during the follow-up of patients. However, more studies and real-world experiences are needed to better understand its effectiveness in this setting and the interaction with other ASMs., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Ample evidence demonstrates that early-life adversity negatively affects morbidity and survival in late life. We show that disease exposure in infancy also has a continuous impact on reproduction and health across the female life course and even affects early-life health of the next generation. Using Swedish administrative data, obstetric records, and local infant mortality rates as a measure of disease exposure, we follow women's reproductive careers and offspring health 1905-2000, examining a comprehensive set of outcomes. Women exposed to disease in infancy give birth to a lower proportion of boys, consistent with notions that male fetuses are more vulnerable to adverse conditions and are more often miscarried. Sons of exposed mothers are also more likely to be born preterm and have higher birthweight suggesting in utero out-selection. Exposed women have a greater risk of miscarriage and of male stillbirth, but their overall likelihood of giving birth is not affected., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Glaucoma is a group of progressive optic neuropathies characterized by loss of retinal ganglion cells and visual field deterioration. Despite the fact that the underlying pathophysiology of glaucoma remains unknown, elevated intraocular pressure (IOP) is a well-established risk factor, and the only factor that can be modified. Robust evidence from epidemiological studies and clinical trials has clearly demonstrated the benefits of IOP control in reducing the risk of glaucoma progression. IOP-lowering therapy by the means of eye drops remains a first-line treatment option. However, like other chronic and asymptomatic conditions, many patients with glaucoma have difficulties in maintaining high rates of adherence persistence to prescribed medications. On average, patients with chronic medical conditions take 30-70% of the prescribed medication doses, and on average 50% discontinue medications in the first months of therapy. The ophthalmic literature shows similarly low rates of adherence to treatment. Indeed, poor adherence is associated with disease progression and increased complication rates, as well as healthcare costs. The present review analyzes and discusses the causes of variability of the adherence to the prescribed drugs. The education of patients about glaucoma and the potential consequences of insufficient adherence and persistence seems fundamental to maximize the probability of treatment success and therefore prevent visual disability to avoid unnecessary healthcare costs., (© 2023. The Author(s).)

The efficacy of low molecular weight heparin (LMWH) is well-established in patients with obstetric antiphospholipid syndrome (O-APS). Their role in women with unexplained recurrent pregnancy loss (U-RPL) and late obstetrical complications (intrauterine growth restriction, IUGR and preeclampsia) is controversial. Here we compared rates of miscarriage and late obstetrical complications in RPL patients diagnosed with O-APS (n = 57) or hereditary thrombophilia (n = 25) (both assuming LMWH from the beginning of pregnancy) and in patients with a history of U-RPL (n = 118), assuming or not LMWH, followed at the 'Pregnancy at risk' and 'Recurrent pregnancy loss' outpatient clinics at the San Raffaele Hospital from April 2010 to April 2020. Patients with systemic autoimmune diseases other than primary O-APS were excluded. We tested for bivariate or multivariate associations among adverse pregnancy outcomes, the presence of thrombophilia and LMWH use by using chi-square test, Anova, propensity score adjusted univariate logistic regression and multivariate analysis as appropriate. U-RPL patients assuming LMWH from the beginning of pregnancy (group A) had a significantly lower rate of miscarriage compared to U-RPL patients who were not treated with LMWH (group B) (13 % vs. 41 % respectively, p 0.001) and similar pregnancy rates compared to both O-APS patients with a history of RPL taking LMWH (group C, 18 %) and RPL patients with thrombophilia and treated with LMWH (group D, 16 %). Our data highlight a protective effect of LMWH on miscarriage in patients with a history of U-RPL. In these patients, LMWH seems as effective as in O-APS and hereditary thrombophilia in reducing RPL., Competing Interests: Declarations of Competing Interest None., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Increased population longevity could be influenced by early life factors. Some areas have long-lived populations, also in a historical perspective. We aimed to study these factors in Halland, an area with the highest life expectancy in Sweden. We collected archival data on gestational age and birth characteristics from 995 live singleton full-term births at the Halmstad Hospital, Halland, from the period 1936 to 1938 and compared these to 3364 births from three hospitals in nearby Scania for the period 1935-1945. In addition, data were obtained on maternal and offspring characteristics from the national Swedish Medical Birth Register during 1973-2013. The results show that when controlling for background maternal and offspring characteristics, mean birth weight (BW) and mean birth length were higher in Halland than in Scania, but the proportion of low birth weight (LBW) and small for gestational age (SGA) was lower. However, mean BW for Halland did not differ from the rest of Sweden in recent years 2004-2013. We also conducted a mortality follow-up for children born in Scania, which showed that LBW, being born SGA, or short birth length reduced survival. In conclusion, the high mean life expectancy in Halland compared to the rest of Sweden could have been associated with beneficial early life factors influencing birth size in the past. In more recent decades the mean BW of Halland is not different from the national mean. Thus, longevity could be expected to become more equal to the national mean in the future.

Purpose: To report a case of neurotrophic keratopathy (NK) in a patient affected by primary congenital glaucoma (PCG) who undergone glaucoma drainage implant surgery. NK was successfully treated with human recombinant Nerve Growth Factor (Cenegermin) eye drops., Case Report Description: A 46-years-old patient affected by primary congenital glaucoma underwent Ahmed glaucoma valve implantation in the right eye, after several unsuccessful surgeries to control intraocular pressure (IOP) since the age of three. Surgical intervention was performed without complications, and IOP was well-controlled post-operatively. However, 1 month after surgery, he developed NK with stromal ulceration, initially treated with a topical combination of preservative-free artificial tears and antibiotic ointment. As NK did not resolve, a new treatment with Cenegermin 20 µg/ml eye drops, 6 times daily, was started., Outcome: NK completely resolved after 8 weeks of Cenegermin treatment, with complete restoration of corneal integrity and improvement of corneal sensitivity and transparency. Visual acuity in the operated eye reverted to the pre-operative value., Conclusion: Cenegermin was extremely effective in restoring corneal integrity in this PCG patient with NK.

Purpose: To evaluate morphological differences in retinal nerve fibers layers (RNFL), optic nerve head (ONH), ganglion cell complex (GCC), and macular thickness between amblyopic and normal eyes from spectral domain optical coherence tomography (SD-OCT)., Methods: Of 234 eyes of 117 children, four groups emerged: group A (162 eyes of 81 non-amblyopic subjects); group B (32 fellow eyes of 32 subjects with monolateral amblyopia); group C (32 amblyopic eyes of 32 subjects affected by monolateral amblyopia); group D (8 amblyopic eyes of 4 subjects with bilateral amblyopia). Patients underwent SD-OCT for ONH parameters, RNFL, GCC and macular thickness, retina map, and ONH scan quality index (SQI). Two-sided p values <0.05 were taken as statistically significant. (Analysis: STATA v.13)., Results: Parameters with a significant difference between groups ( p  < 0.005) with their Standard Deviation (SD) are presented: rim area, 2.08 (0.49) mm 2 in group A and 1.76 (0.68) mm 2 in group C; disk area, 2.43 (0.45) mm 2 in group A and 2.02 (0.71) mm 2 in group C; central macular thickness, 250.99 (19.74) µm in group A and 267.16 (23.52) µm in group C; nerve fiber ONH SQI, 62.82 (13.15) in group A, 51.26 (15.55) in group C, 48.29 (14.37) in group D; retina map SQI, 63.34 (10.34) in group A and 57.34 (9.84) in group C. For other parameters no significant difference was observed ( p  > 0.005)., Conclusions: Amblyopia may influence optic nerve morphology, central macular thickness, and OCT scan quality. RNFL and GCC are not affected by monolateral amblyopia.

Background: Children and adolescents and low-income individuals are considered particularly vulnerable for mental health implications during the current COVID-19 pandemic. Depression is a frequent negative emotional response during an epidemic outbreak and is also prone importantly to environmental risk like stressors derived from income inequality. We aimed to assess depressive symptomatology in a sample of Italian low-income minors during the COVID-19 outbreak. We hypothesized that the stronger were the negative effects of the pandemic on socioeconomic conditions, the higher would have been the risk for showing depressive symptoms., Methods: We performed a cross-sectional study during July 2020, at the end of the Italian first wave of COVID-19 pandemic. We recruited 109 Italian socioeconomically disadvantaged children and adolescents from 7 to 17 years. We used an online survey to collect socio-demographic and clinical data and information about pandemic-related stressors and to assess depressive symptoms with the Children's Depression Inventory 2 (CDI 2), Parent Version (Emotional Problems subscale) and Self-Report Short Form. We performed logistic regression analysis to assess the association between depressive symptoms and potential risk factors for mental health., Results: 22% and 14% of participants showed depressive symptoms at the CDI 2 Parent Version and Self-Report, respectively. Participants coming from families experiencing a lack of basic supplies during the pandemic (34.9%) were more expected to show depressive symptoms at CDI 2 Parent Version. Participants with a pre-existing neuropsychiatric diagnosis (26.6%) were more likely to exhibit depressive symptoms measured by CDI 2 Parent Version., Conclusions: The results of our study showed that a group of Italian socioeconomically disadvantaged children and adolescents were more vulnerable to depressive symptoms if they suffered from a paucity of essential supplies during the pandemic or had pre-existing neurodevelopmental disorders. The promotion of educational and child-care programs and activities could be crucial in sustaining the prevention of mental distress in those frail subjects who particularly need support outside the family. Further studies are needed to detect effective preventive and therapeutic strategies to adopt promptly in the case of another pandemic wave., (© 2022. The Author(s).)

Introduction: In the last 25 years, topical prostaglandin analogues (PGAs) have emerged to become first line and first choice therapeutic options in the management of glaucoma and ocular hypertension (OHT). Although the short-term efficacy and safety of PGAs has been extensively investigated, less is known about their long term safety and tolerability. This gap in current knowledge is clinically relevant, because treatment-related adverse events and long-term tolerability issues are key determinants of the overall success of long-term therapy and the final outcome of a lifelong, symptomless disease like glaucoma., Areas Covered: We include selected evidence pertaining to the safety and tolerability of available and emerging PGA formulations. We also outline PGA formulations with different concentrations of the active ingredient, different preservatives, and preservative-free (PF) options., Expert Opinion: Undoubtedly PGAs will continue to play a major role in the medical therapy of glaucoma and OHT. Despite extensive literature and prolonged clinical experience with these agents worldwide, a number of areas that warrant further research have been identified in the present review. Recently launched novel PGAs, or those still in development offer new opportunities and future challenges.

Altitude affects intraocular pressure (IOP); however, the underlying mechanisms involved and its relationship with ocular hemodynamics remain unknown. Herein, a validated mathematical modeling approach was used for a physiology-enhanced ( pe- ) analysis of the Mont Blanc study (MBS), estimating the effects of altitude on IOP, blood pressure (BP), and retinal hemodynamics. In the MBS, IOP and BP were measured in 33 healthy volunteers at 77 and 3466 m above sea level. Pe-retinal hemodynamics analysis predicted a statistically significant increase ( p < 0.001) in the model predicted blood flow and pressure within the retinal vasculature following increases in systemic BP with altitude measured in the MBS. Decreased IOP with altitude led to a non-monotonic behavior of the model predicted retinal vascular resistances, with significant decreases in the resistance of the central retinal artery ( p < 0.001) and retinal venules ( p = 0.003) and a non-significant increase in the resistance in the central retinal vein ( p = 0.253). Pe-aqueous humor analysis showed that a decrease in osmotic pressure difference (OPD) may underlie the difference in IOP measured at different altitudes in the MBS. Our analysis suggests that venules bear the significant portion of the IOP pressure load within the ocular vasculature, and that OPD plays an important role in regulating IOP with changes in altitude.

Depressive disorders (DDs) and non-suicidal self-injury (NSSI) are important juvenile mental health issues, showing alarming increasing rates. They frequently co-occur, mainly among adolescents, increasing the suicide risk. We aimed to compare the clinical features of two groups of adolescents with DDs, differed by their engagement or not in NSSI ("DD + NSSI" and "DD"). We hypothesized that NSSI would characterize particularly severe forms of DDs suitable for becoming specific phenotypes of adolescent depression. We enrolled 56 adolescents (11-17 years) diagnosed with a DD according to the DSM-5 criteria. They were assessed for NSSI endorsement (Ottawa Self-Injury Inventory), depressive symptoms (Children's Depression Inventory 2), emotional dysregulation (Difficulties in Emotional Regulation Scale), and anxiety symptoms (Screen for Child Anxiety-Related Emotional Disorders). The two groups accounted for 31 ("DD + NSSI") and 25 ("DD") individuals. The "DD + NSSI" group had significantly higher suicidal ideation ( p 0.0039), emotional dysregulation ( p 0.0092), depressive symptoms ( p 0.0138), and anxiety symptoms ( p 0.0153) than the "DD" group. NSSI seemed to characterize more severe phenotypes of adolescent depression, applying for a potential role as a "specifier" of DDs, describing relevant information for their management. Further studies are needed to support this hypothesis and its potential opportunities for prevention and treatment.

Purpose: To investigate the course of inherited retinal degenerations (IRD) due to mutations in the RPE65 gene., Methods: This longitudinal multicentric retrospective chart-review study was designed to collect best corrected visual acuity (BCVA), Goldman visual field, optical coherence tomography (OCT), and electroretinography (ERG) measurements. The data, including imaging, were collected using an electronic clinical research form and were reviewed at a single center to improve consistency., Results: From an overall cohort of 60 Italian patients with RPE65-associated IRD, 43 patients (mean age, 27.8 ± 19.7 years) were included and showed a mean BCVA of 2.0 ± 1.0 logMAR. Time-to-event analysis revealed a median age of 33.8 years and 41.4 years to reach low vision and blindness based on BCVA, respectively. ERG (available for 34 patients) showed undetectable responses in most patients (26; 76.5%). OCT (available for 31 patients) revealed epiretinal membranes in five patients (16.1%). Central foveal thickness significantly decreased with age at a mean annual rate of -0.6%/y (P = 0.044). We identified 43 different variants in the RPE65 gene in the entire cohort. Nine variants were novel. Finally, to assess genotype-phenotype correlations, patients were stratified according to the number of RPE65 loss-of-function (LoF) alleles. Patients without LoF variants showed significantly (P < 0.05) better BCVA compared to patients with one or two LoF alleles., Conclusions: We described the natural course of RPE65-associated IRD in an Italian cohort showing for the first time a specific genotype-phenotype association. Our findings can contribute to a better management of RPE65-associated IRD patients.

Background/objectives: To compare the number of eye surgical procedures performed in Italy in the 2 months following the beginning of lockdown (study period) because of COVID-19 epidemic with those performed in the two earlier months of the same year (intra-year control) and in the period of 2019 corresponding to the lockdown (inter-year control)., Methods: Retrospective analysis of surgical procedures carried out at 39 Academic hospitals. A distinction was made between elective and urgent procedures. Intravitreal injections were also considered. Percentages for all surgical procedures and incidence rate ratios (IRR) for rhegmatogenous retinal detachment (RRD) events were calculated. A p value <0.05 was considered significant., Results: A total of 20,886 versus 55,259 and 56,640 patients underwent surgery during the lockdown versus intra-and inter-year control periods, respectively. During the lockdown, only 70% of patients for whom an operation/intravitreal injection was recommended, finally underwent surgery; the remaining patients did not attend because afraid of getting infected at the hospital (23%), taking public transportation (6.5%), or unavailable swabs (0.5%). Elective surgeries were reduced by 96.2% and 96.4%, urgent surgeries by 49.7% and 50.2%, and intravitreal injections by 48.5% and 48.6% in the lockdown period in comparison to intra-year and inter-year control periods, respectively. IRRs for RRDs during lockdown dropped significantly in comparison with intra- and inter-year control periods (CI: 0.65-0.80 and 0.61-0.75, respectively, p  < 0.001 for both)., Conclusion: This study provides a quantitative analysis of the reduction of eye surgical procedures performed in Italy because of the COVID-19 epidemic.