Elexacaftor/tezacaftor/ivacaftor corrects monocyte microbicidal deficiency in cystic fibrosis.

BACKGROUND: Cystic fibrosis (CF), which is caused by mutations in the CF transmembrane conductance regulator (CFTR), is characterised by chronic bacterial lung infection and inflammation. In CF, monocytes and monocyte-derived macrophages have been shown to display defective phagocytosis and antimicrobial activity against relevant lung pathogens, including Pseudomonas aeruginosa. Thus, we addressed the effect of CFTR triple modulator therapy (elexacaftor/tezacaftor/ivacaftor (ETI)) on the activity of CF monocytes against P. aeruginosa. METHODS: Monocytes from people with CF (PWCF) before and after 1 and 6 months of ETI therapy were isolated from blood and infected with P. aeruginosa to assess phagocytic activity and intracellular bacterial killing. The oxidative burst and interleukin-6 secretion were also determined. Monocytes from healthy controls were also included. RESULTS: Longitudinal analysis of the clinical parameters confirmed an improvement of lung function and lung microbiology by ETI. Both the phagocytic and microbicidal deficiencies of CF monocytes also improved significantly, although not completely. Furthermore, we measured an exuberant oxidative burst in CF monocytes before therapy, which was reduced considerably by ETI. This led to an improvement of reactive oxygen species-dependent bactericidal activity. Inflammatory response to bacterial stimuli was also lowered compared with pre-therapy. CONCLUSIONS: PWCF on ETI therapy, in a real-life setting, in addition to clinical recovery, showed significant improvement in monocyte activity against P. aeruginosa, which may have contributed to the overall effect of ETI on pulmonary disease. This also suggests that CF monocyte dysfunctions may be specifically targeted to ameliorate lung function in CF.

Mid-term safety and effectiveness of intravitreal dexamethasone implant to treat persistent cystoid macular edema in vitrectomized eyes for bacterial endophthalmitis.

PURPOSE: To evaluate the mid-term safety and effectiveness of intravitreal dexamethasone implant (DEX-i) for treating unresponsive to medical therapy cystoid macular edema (CME) in vitrectomized eyes for endophthalmitis. METHODS: Retrospective and interventional case series study conducted on vitrectomized eyes for endophthalmitis that developed a CME that did not adequately respond to medical therapy, who underwent 0.7-mg DEX-i. Main outcome measures were changes in central retinal thickness (CRT) and best corrected visual acuity (BCVA). RESULTS: Eleven eyes were included in the study. Microbiological findings of vitreous biopsies were 7 (63.6%) staphylococcus epidermidis; 3 (27.3%) Pseudomonas aeruginosa; and 1 (9.1%) Propionibacterium acnes. Median (interquartile range, IqR) duration of CME was 4.0 (3.0-4.0) months. Median (IqR) time between vitrectomy and DEX-i was 9.0 (9.0-11.0) months. Median CRT was significantly decreased from 548.0 (412.8-572.5) µm at baseline to 308.0 (281.3-365.5) µm at month 6 (p = 0.0009, Friedman test). Median BCVA significantly improved from 38.0 (30.5-44.8) letters at baseline to 50.0 (46.8-53.0) letters at month 6 (p < 0.0001, Friedman), with 9 (81.8%) eyes gaining ≥ 10 letters. Elevation of intraocular pressure was observed in one (9.1%) eye, which was successfully controlled with medical therapy. No recurrence of endophthalmitis or other complications was observed. Eight (72.7%) eyes required an additional DEX-i, while 3 (27.3%) were successfully controlled with only one DEX-i. CME recurrence occurred in 5 (62.5%) Gram-positive and 3 (100.0%) Gram-negative bacteria (p = 0.2357). CONCLUSION: In vitrectomized eyes for endophthalmitis affected by CME unresponsive to medical therapy, DEX-i had an acceptable safety profile and achieved favorable outcomes. The possibility of suppressing mechanisms for infection control should be taken into account, although correct management of endophthalmitis and long time without reactivation before DEX-i reduce the risk.

Design, synthesis and biological evaluation of N-substituted α-hydroxyimides and 1,2,3-oxathiazolidine-4-one-2,2-dioxides with anticonvulsant activity.

In this investigation, we studied a family of compounds with an oxathiazolidine-4-one-2,2-dioxide skeleton and their amide synthetic precursors as new anticonvulsant drugs. The cyclic structures were synthesized using a three-step protocol that include solvent-free reactions and microwave-assisted heating. The compounds were tested in vivo through maximal electroshock seizure test in mice. All the structures showed activity at the lower doses tested (30 mg/Kg) and no signs of neurotoxicity were detected. Compound encoded as 1g displayed strong anticonvulsant effects in comparison with known anticonvulsants (ED50 = 29 mg/Kg). First approximations about the mechanisms of action of the cyclic structures were proposed by docking simulations and in vitro assays against sodium channels (patch clamp methods).

Children sustaining a severe acquired brain lesion before age 3 years: a follow-up study at 1 year from insult.

PURPOSE: To describe the functional and cognitive outcome of acquired brain injury of different aetiologies in children before age 3 years, at initial hospitalization and at a 1-year follow-up, after a rehabilitation programme. METHOD: Data were collected at 6 months and at 12 months from the event; cognitive data were collected as soon as possible at T1. The full sample was divided into three groups according to aetiology. RESULTS: At T0, 74 patients showed so severe a cognitive impairment that they could not be evaluated, others presented with motor, linguistic and cognitive deficits. At T1, the proportion of non-evaluable patients decreased to 58 children. Patients with anoxic lesions showed the most unfavourable motor and visual outcome; patients with infectious lesions showed most frequently a motor global delay. CONCLUSIONS: At 1 year from insult about 50% of patients could undergo a cognitive evaluation. Improvement differed according to aetiology.

Psychological and behavioural difficulties following severe TBI in adolescence: a comparison with a sample of peers with brain lesions of other origin and with a control group.

OBJECTIVE: To describe behavioural and adjustment problems in a group of 57 adolescents with severe traumatic brain injury (TBI) and compare them with a clinical group of peers with brain lesions of other origin (N = 33) and a control group of healthy adolescents (N = 48). METHODS: All subjects received an age-appropriate assessment, including the child behaviour checklist (CBCL) 4/18, the strengths and difficulties questionnaire (SDQ) and the vineland adaptive behaviour scales (VABS). RESULTS: Compared with healthy peers, adolescents with TBI presented with more marked behavioural problems on most CBCL scales (Internalization and Externalization domains were both affected) and on the SDQ Hyperactivity and Peer problems scales. They also showed a more impaired functioning in most VABS domains. Compared with adolescents with brain lesions of other aetiology, patients with TBI showed more conduct problems on the SDQ scale, but no significant differences were found on the CBCL scales. Regarding the VABS, patients with other lesions presented with the worst outcome in the Motor and Daily Living Skills domains. CONCLUSIONS: Adolescents with TBI are exposed at a very high risk to develop behavioural and psychological disturbances with the potential to severely affect their social re-entry. Further knowledge is needed to plan early and well-timed interventions.

A diffusion tensor magnetic resonance imaging study of paediatric patients with severe non-traumatic brain injury.

AIM: In this observational study using 3T magnetic resonance imaging (MRI) and diffusion tensor, we investigated the differential effects of pathology, stage of disease, state of consciousness, and aetiology on the modifications of supra- and infra-tentorial white matter tracts and their correlations with clinical scales in paediatric patients with severe non-traumatic brain injury. METHOD: Diffusion tensor magnetic resonance imaging (DT-MRI) was obtained from seven children with unresponsive wakefulness syndrome (UWS; five males, two females; age at event 5y; standard deviation [SD] 2y 1mo), six children in a minimally conscious state (MCS; three males, three females; age at event 5y 10mo; SD 5y), and 10 healthy children as controls(two males, eight females; age at study 10y 10mo; SD 2y 10mo). Fractional anisotropy, mean, axial, and radial diffusivities were calculated for the corpus callosum, inferior, middle (MCP), and superior cerebellar peduncles (SCP). RESULTS: DT-MRI parameters from corpus callosum and SCP differed between patients and controls. MCP abnormalities were detected in patients presenting non-traumatic composite aetiology (n=4) versus those suffering from pure anoxia (n=9). The supra-tentorial compartment was more damaged (i.e. decreased fractional anisotropy and increased diffusivities) than the infra-tentorial one. Correlations were found between DT-MRI abnormalities and Glasgow Outcome Scale scores. INTERPRETATION: In paediatric UWS/MCS, the severity of clinical disability correlates with white matter tract abnormalities.

Urinary excretion of EGF and MCP-1 in children with vesicoureteral reflux.

PURPOSE: The aim of this study was to investigate the urinary concentration of epidermal growth factor (EGF) and monocyte chemotactic protein-1 (MCP-1) as reflux nephropathy (RN) biomarkers before and after endoscopic treatment of moderate to severe vesico-ureteral reflux (VUR). MATERIALS AND METHODS: A prospective study was carried out on 72 children with moderate to severe VUR. All patients underwent endoscopic treatment using Macroplastique ® or Deflux®. Vesico-ureteral reflux resolution was tested by post-operative voiding cystourethrography after 3 months and 2 years. Follow-up urinary samples were collected at that time. Control samples were taken from healthy children with no clinical evidence of renal and bladder disease and no history of UTI. RESULTS: In VUR patients, pre-operative urinary EGF levels had a down-regulation when compared to controls. Following successful VUR repair, urinary EGF levels of VUR children progressively increased only at long term follow-up but without returning to normal levels. Urinary MCP-1 levels were highly expressed in pre-operative samples and decreased markedly during early post-operative measurements. Urinary MCP-1 levels did not further decreased in late post-operative follow-up. In fact, these levels remained significantly higher when compared to controls. CONCLUSIONS: Urinary levels of EGF and MCP-1 may become useful markers for monitoring the response to surgical treatment in VUR patients. Although endoscopic VUR treatment is effective in reducing the inflammatory response, the persistence of significant abnormal levels of inflammatory cytokines (such as urinary MCP-1) at long term follow-up suggests that surgery alone may not completely treat the chronic renal inflammation evidenced in these children.

Psychological problems, self-esteem and body dissatisfaction in a sample of adolescents with brain lesions: A comparison with a control group.

PRIMARY OBJECTIVES: This study aims to describe psychological problems, self-esteem difficulties and body dissatisfaction in a sample of adolescents with acquired brain lesions and to compare them with an age- and gender-matched control group. RESEARCH DESIGN: In an experimental design, the psychological profile of 26 adolescents with brain lesions of traumatic or vascular aetiology, aged 12-18 years, was compared with that of 18 typically-developing subjects. Moreover, within the clinical group, patients with TBI were compared with patients with vascular lesions. METHODS AND PROCEDURES: The psychological and adaptive profile of the adolescents was assessed by a specific protocol, including CBCL, VABS, RSES, EDI-2 and BES. MAIN OUTCOME AND RESULTS: Adolescents with brain lesions showed more marked psychological problems than their healthy peers; they also presented with a greater impairment of adaptive skills and a lower self-esteem. No significant differences were found between patients with traumatic lesions and patients with vascular lesions. CONCLUSIONS: Adolescents with acquired brain lesions were at higher risk to develop psychological and behavioural difficulties. Furthermore, in the clinical sample, some variables such as the long hospitalization and isolation from family and peers were associated to a greater psychological burden than the aetiology of the brain damage.

Cognitive recovery after severe traumatic brain injury in children/adolescents and adults: similar positive outcome but different underlying pathways?

PRIMARY OBJECTIVE: Does younger age at the time of severe traumatic brain injury (STBI) protect from cognitive symptoms? To answer this question, the authors compared the neuropsychological profile of late school-age children/adolescents and young adult patients at mid- and long-term recovery periods (6 and 12 months post-STBI). METHODS AND PROCEDURES: Twenty-eight children/adolescents and 26 clinically matched adults were tested on measures of general intelligence, attention, executive functions, visuoperceptual, visuospatial and visuoconstructive abilities. Coma duration and the post-acute Glasgow Outcome Scale (GOS) score were used as predictor variables in a series of regression analyses. MAIN OUTCOMES AND RESULTS: Children/adolescents and adults similarly improved on most measures, except for visuospatial and visuoconstructive skills, which worsened in time for children/adolescents. Coma duration significantly predicted performance IQ and visuoperceptual scores in children/adolescents. The GOS score significantly predicted performance and verbal IQ, sustained attention, visuoconstructive and long-term memory skills. Coma duration predicted executive function skills in both age groups. CONCLUSIONS: (1) No evidence was found for a neuroprotective effect of younger age at STBI; and (2) Coma duration and GOS score predicted neuropsychological recovery in children/adolescents and adults, respectively. This suggests the existence of underlying age-specific recovery processes after STBI.

Donor Characteristics in Graft Detachment after Posterior Lamellar Keratoplasty for Fuchs Endothelial Dystrophy and Bullous Keratopathy.

Background: Descemet Membrane Endothelial Keratoplasty (DMEK) has been widely adopted to treat Fuchs endothelial dystrophy (FED) and Bullous keratopathy (BK). Graft detachment (GD) is one of the common earliest post-operatory complications, and it is usually recovered by Air Rebubbling (ARB). Methods: Retrospectively, we investigated predictive factors related to GD between January 2016 and March 2020, a pre-COVID era, in 72 patients, 72 eyes, and their donors' lamellar characteristics, focusing on donor's cause of death. The patients were divided according to the posterior lamellar keratoplasty technique adopted. Results: GD and consequent ARB were most common but not significantly prevalent in DMEK (p = 0.11). It was more common in FED for both surgical approaches. Only in BK treated with DSAEK were host steeper mean astigmatism (p = 0.03) and donors with smaller graft pre-cut diameters (p = 0.02) less likely to be related to GD. Regarding donor's cause of death, only cardiovascular accident could be related to GD in BK treated with DMEK (p = 0.04). Conclusions: Our study shows that the conventional match between pathology and corneal lenticule is not sufficient to prevent ARB. Donor's cause of death can impair graft and host attachment. In particular, cardiovascular death may impair the efficiency of donors' endothelial cells, inducing GD after DMEK in BK.

3,3-Dibromoflavanone, a synthetic flavonoid derivative for pain management with antidepressant-like effects and fewer side effects than those of morphine in mice.

In the pursuit of new lead compounds with fewer side effects than opioids, the novel synthetic phytochemical core, 3,3-dibromoflavanone (3,3-DBF), has emerged as a promising candidate for pain management. Acute assays demonstrated dose-dependent central and peripheral antinociceptive activity of 3,3-DBF through the µ-opioid receptor. This study aimed to explore repeated administration effects of 3,3-DBF in mice and compare them with morphine. Mice were treated with 3,3-DBF (30 mg/kg), morphine (6 mg/kg), or vehicle for 10 days, alongside single-treatment groups. Unlike morphine, 3,3-DBF demonstrated antinociceptive effects in the hot plate test without inducing tolerance. Locomotor activity and motor coordination tests (evaluated through the inverted screen and rotarod tests) revealed no significant differences between the 3,3-DBF-treated and control groups. The gastrointestinal transit assay indicated that 3,3-DBF did not induce constipation, in contrast to morphine. Furthermore, withdrawal signs assessed with the Gellert-Holtzman scale were not comparable to morphine. Additionally, 3,3-DBF exhibited antidepressant-like activity, reducing immobility time in the forced swimming and tail suspension tests, akin to imipramine. In summary, 3,3-DBF demonstrated antinociceptive effects without inducing tolerance or dependence and exhibited antidepressant properties. These findings highlight the potential of 3,3-DBF as a promising therapeutic agent for pain management and its comorbidities, offering advantages over morphine by minimizing side effects.

Synthesis and anticonvulsant activity of bioisosteres of trimethadione, N-derivative-1,2,3-oxathiazolidine-4-one-2,2-dioxides from α-hydroxyamides.

The synthesis and anticonvulsant activity of novel heterocycles N-derivative-1,2,3-oxathiazolidine-4-one-2,2-dioxides, bioisosteres of trimethadione (TMD, oxazolidine-2,4-dione) and phenytoin (PHE), are described. TMD is an anticonvulsant drug widely used against absences seizures in the early 80's and PHE is an antiepileptic drug with a wide spectrum activity. The intermediates of synthesis of N-derivative-1,2,3-oxathiazolidine-4-one-2,2-dioxides, α-hydroxyamides, were obtained using microwave assisted synthesis. Anticonvulsant screening was performed in mice after intraperitoneal administration in the maximal electroshock seizure test (MES) and subcutaneous pentylenetetrazole seizures test (scPTZ). These new compounds showed a wide spectrum activity and were no neurotoxic in the RotoRod test. α-Hydroxyamides and N-derivative-1,2,3-oxathiazolidine-4-one-2,2-dioxides were 3-4700 times more potent than valproic acid in the MES test. Quantification of anticonvulsant protection was calculated (ED(50)) for the most active candidates; α-hydroxyamides 3a-c and 3e, and N-derivative-oxathiazolidine-4-one-2,2-dioxides 5a-c with ED(50) values of 9.1, 53.9, 44.6, 25.2, 15.1, 91.1 and 0.06mg/kg, respectively, in the MES test.

Evolution of the cognitive profile in school-aged patients with severe TBI during the first 2 years of neurorehabilitation.

OBJECTIVE: Persistent post-injury cognitive, academic and behavioural deficits have been documented in children who sustained severe TBI during the school-age years. The major aim of this study was to examine and follow-up for 2 years the cognitive profile of a sample of post-injured patients (aged 6-16.11), in order to verify to what extent they recovered their intellectual functions after rehabilitation. METHOD: Twenty-six patients who received a specific neuropsychological treatment and three cognitive evaluations with WISC-III were selected from a pool of 77. RESULTS: This group of patients showed a mild cognitive deficit at baseline, which improved over the 2 years to a borderline level. Despite the improvement in intellectual quotients and single sub-test scores achieved through rehabilitation, different recovery times were seen according to the function under study. The most common deficits are in processing speed, inferential and lexical-semantic skills. CONCLUSIONS: Detailed analysis of the WISC-III sub-tests allows for an accurate description of single cognitive functions after TBI. This allows one to make differential diagnoses between functional profiles and plan individualized rehabilitation treatments. Post-injured school-aged patients should receive rehabilitation for a period of at least 2 years, which is the time necessary for an at-least partial reorganization of basic cognitive functions.

Cognitive and adaptive functioning after severe TBI in school-aged children.

OBJECTIVE: Persistent cognitive and behavioural deficits have been documented in children suffering severe TBI. The aim of the present study was to examine the cognitive and adaptive profile of children of school age with severe TBI. METHODS: This study selected 118 patients and divided them into three groups according to the severity of their clinical-functional picture. All the patients received a functional assessment using the Wee-FIM. Subjects with reduced responsiveness were evaluated by LOCFAS. Last, the cognitive profile children with a better recovery were described with WISC-III and Leiter-R and their adaptive behaviour with VABS. RESULTS: Group 1 (n = 77) showed a borderline cognitive level with a disharmonious profile between VIQ and PIQ, significant deficits in the Processing Speed and Perceptual Organization Indices, lastly specific adaptive behavioural deficits. Length of coma correlated with their cognitive and adaptive profile. Group 2 (n = 14) included subjects with severe language and/or motor disabilities presenting with a partial cognitive functioning level moderately impaired. Group 3 (n = 27) included patients with reduced responsiveness (LOCFAS ≤ 3). CONCLUSIONS: In the first 12 months following severe TBI, 22.9% children stayed in minimal responsiveness, 11.9% showed debilitating language and motor deficits and 65.2% showed a more favourable cognitive recovery and could be assessed by WISC-III.

Psychological and adjustment problems due to acquired brain lesions in pre-school-aged patients.

OBJECTIVE: To describe and compare psychological, behavioural and adjustment problems in pre-school patients with acquired brain lesions of different aetiology. METHODS: Three groups of patients with acquired brain lesions (14 patients post-TBI, 18 brain tumour survivors and 23 patients with vascular or infectious brain lesions), ranging in age between 24-47 months, received a psychological evaluation, including the Child Behavior Checklist for Ages 2-3 (CBCL) and the Vineland Adaptive Behavior Scales (VABS). RESULTS: About half of the total sample (47.2%) showed psychological and behavioural problems. Difficulties vary according to the aetiology of the brain lesions. Brain tumour survivors showed more marked internalizing problems, whereas children with vascular or infectious brain lesions scored higher on the CBCL externalizing scales. Children with traumatic brain injury reported intermediate scores on most of the CBCL scales. CONCLUSIONS: Psychological and behavioural difficulties are very common, not only among school-aged children and adolescents, but also among pre-schoolers with acquired brain lesions. The relevance and the impact of these difficulties must necessarily be considered when developing psychological treatment and rehabilitation plans and planning for social re-entry.

Neuropsychological assessment through Coma Recovery Scale-Revised and Coma/Near Coma Scale in a sample of pediatric patients with disorder of consciousness.

BACKGROUND: The Coma Recovery Scale-Revised (CRS-R) has become a standard tool in assessing Disorders of consciousness (DoC) in adults. However, its measurement validity in pediatrics has only been ascertained in healthy cases. Increasing use of CRS-R in children with DoC imposes appropriate comparison against previously validated tools. The aims of the study were to describe the emergence to a conscious state (eMCS) in pediatric acquired brain injury (ABI); to explore the agreement between the CRS-R and Coma Near Coma Scale (CNCS) and to discuss the advantage of administering the CRS-R in pediatric age. MATERIALS AND METHODS: In this observational prospective study, 40 patients were recruited. Inclusion criteria were age 5 to 18 years, Glasgow Coma Scale (GCS) score ≤ 8 at the insult, and unresponsive wakefulness syndrome (UWS) or minimally conscious state (MCS) at admission. Patients were assessed with CRS-R, and CNCS was used as standard. RESULTS: The agreement between scales was moderate (r = - 0.71). The analysis of the CRS-R domain scores also confirmed that decreasing CNCS levels (from a coma to eMCS) corresponded to concurrent increas of CRS-R scores in all domains. Moreover, CRS-R better defined patients' status in the emergency phase from MCS. Conversely, CRS-R had lower DoC scoring ability in the presence of severe motor impairment. CONCLUSION: We show that CRS-R can track changes in DoC in children as young as 5 years old, and we provide evidence that the agreement with CNCS scores is good.

Long-Term Vocational Outcome at 15 Years from Severe Traumatic and Non-Traumatic Brain Injury in Pediatric Age.

BACKGROUND: Recent studies suggest that acquired brain injury with impaired consciousness in infancy is related to more severe and persistent effects and may have a cumulative effect on ongoing development. In this work, we aim to describe vocational outcome in a group of patients at 15 years from a severe brain lesion they suffered in developmental age. METHODS: This study included a total of 147 patients aged 1.5 to 14 years with acquired brain lesion. Clinical and functional details ("Glasgow Outcome Scale", "Functional Independent Measure" and Intelligence Quotient) were collected at the time of their first hospitalization and vocational outcome was determined after 15 years. RESULTS: 94 patients (63.9%) presented with traumatic brain injury, while 53 patients (36.1%) presented with a brain lesion of other origin. Traumatic patients had a higher probability of being partly or fully productive than non-traumatic ones: 75.5% of traumatic subjects were working-taking into account limitations due to the traumatic event-versus 62.3% of non-traumatic ones. A relationship between some clinical variables and the vocational outcome was found. CONCLUSIONS: Rehabilitation should adequately emphasize "vocational rehabilitation" because a significant proportion of people experiencing a disorder of consciousness in childhood may show good social integration in adult age.

Use of electronic devices by people attending vision rehabilitation services in Italy: A study based on the device and aids registry (D.A.Re).

PURPOSE: To investigate the characteristics of electronic device users, specifically smartphones and tablets, in the Device & Aids Register (D.A.Re), from several low-vision rehabilitation services in Italy. METHODS: We collected general and clinical information about ocular and systemic diseases, visual function, reading speed and Instrumental Activities of Daily Living (IADL) questionnaire score. Technological details of each optical and electronic device, (including screen size, touch-screen and OCR functions, text-to-speech function) were also collected. RESULTS: 1218 patients (752 females and 466 males) were included in our analysis, mean age 71.5 (±18.8) years. Users of electronic aids (n.237) were slightly younger (67 vs 72 years, p < 0.001) than non-users (n.981), had a worse reading speed (38 vs 65 words/minute), critical print size (43 vs 28 print size, p < 0.001), poorer visual acuity (VA)(1.0 logMAR or less: 30% non-users vs 73% users, p < 0.001) and more commonly visual field restriction within 10° (23% vs 14%, p = 0.001). A similar proportion of users and non-users were retired (about 70%) and about 16-17% were employed. The use of portable electronic devices (5″or less, p < 0.001; 6″ to 18″ screen size, p = 0.017) was associated with better IADL scores, and the use of stand devices with worse IADL score (p < 0.001); Furthermore, using smartphones and tablets (193 subjects) was strongly associated with better IADL scores. CONCLUSION: We found that using electronic devices, and especially smartphone and tablets, were associated with better vision-related quality of life in low-vision people attending rehabilitation services. While this association does not mean causality, these findings seemed robust to confounder adjustment.

A Radiomic-Based Machine Learning System to Diagnose Age-Related Macular Degeneration from Ultra-Widefield Fundus Retinography.

The present study was conducted to investigate the potential of radiomics to develop an explainable AI-based system to be applied to ultra-widefield fundus retinographies (UWF-FRTs) with the objective of predicting the presence of the early signs of Age-related Macular Degeneration (AMD) and stratifying subjects with low- versus high-risk of AMD. The ultimate aim was to provide clinicians with an automatic classifier and a signature of objective quantitative image biomarkers of AMD. The use of Machine Learning (ML) and radiomics was based on intensity and texture analysis in the macular region, detected by a Deep Learning (DL)-based macular detector. Two-hundred and twenty six UWF-FRTs were retrospectively collected from two centres and manually annotated to train and test the algorithms. Notably, the combination of the ML-based radiomics model and the DL-based macular detector reported 93% sensitivity and 74% specificity when applied to the data of the centre used for external testing, capturing explainable features associated with drusen or pigmentary abnormalities. In comparison to the human operator's annotations, the system yielded a 0.79 Cohen κ, demonstrating substantial concordance. To our knowledge, these results are the first provided by a radiomic approach for AMD supporting the suitability of an explainable feature extraction method combined with ML for UWF-FRT.

Biological Evaluation of Valeriana Extracts from Argentina with Potent Cholinesterase Inhibition for the Treatment of Neurodegenerative Disorders and Their Comorbidities-The Case of Valeriana carnosa Sm. (Caprifoliaceae) Studied in Mice.

Alzheimer's disease (AD) is a neurodegenerative disorder whose pathophysiology includes the abnormal accumulation of proteins (e.g., ß-amyloid), oxidative stress, and alterations in neurotransmitter levels, mainly acetylcholine. Here we present a comparative study of the effect of extracts obtained from endemic Argentinian species of valerians, namely V. carnosa Sm., V. clarionifolia Phil. and V. macrorhiza Poepp. ex DC from Patagonia and V. ferax (Griseb.) Höck and V. effusa Griseb., on different AD-related biological targets. Of these anxiolytic, sedative and sleep-inducing valerians, V. carnosa proved the most promising and was assayed in vivo. All valerians inhibited acetylcholinesterase (IC50 between 1.08-12.69 mg/mL) and butyrylcholinesterase (IC50 between 0.0019-1.46 mg/mL). They also inhibited the aggregation of ß-amyloid peptide, were able to chelate Fe2+ ions, and exhibited a direct relationship between antioxidant capacity and phenolic content. Moreover, V. carnosa was able to inhibit human monoamine oxidase A (IC50: 0.286 mg/mL (0.213-0.384)). A daily intake of aqueous V. carnosa extract by male Swiss mice (50 and 150 mg/kg/day) resulted in anxiolytic and antidepressant-like behavior and improved spatial memory. In addition, decreased AChE activity and oxidative stress markers were observed in treated mouse brains. Our studies contribute to the development of indigenous herbal medicines as therapeutic agents for AD.