Autophagy initiation triggers p150Glued-AP-2ß interaction on the lysosomes and facilitates their transport.

The endocytic adaptor protein 2 (AP-2) complex binds dynactin as part of its noncanonical function, which is necessary for dynein-driven autophagosome transport along microtubules in neuronal axons. The absence of this AP-2-dependent transport causes neuronal morphology simplification and neurodegeneration. The mechanisms that lead to formation of the AP-2-dynactin complex have not been studied to date. However, the inhibition of mammalian/mechanistic target of rapamycin complex 1 (mTORC1) enhances the transport of newly formed autophagosomes by influencing the biogenesis and protein interactions of Rab-interacting lysosomal protein (RILP), another dynein cargo adaptor. We tested effects of mTORC1 inhibition on interactions between the AP-2 and dynactin complexes, with a focus on their two essential subunits, AP-2ß and p150Glued. We found that the mTORC1 inhibitor rapamycin enhanced p150Glued-AP-2ß complex formation in both neurons and non-neuronal cells. Additional analysis revealed that the p150Glued-AP-2ß interaction was indirect and required integrity of the dynactin complex. In non-neuronal cells rapamycin-driven enhancement of the p150Glued-AP-2ß interaction also required the presence of cytoplasmic linker protein 170 (CLIP-170), the activation of autophagy, and an undisturbed endolysosomal system. The rapamycin-dependent p150Glued-AP-2ß interaction occurred on lysosomal-associated membrane protein 1 (Lamp-1)-positive organelles but without the need for autolysosome formation. Rapamycin treatment also increased the acidification and number of acidic organelles and increased speed of the long-distance retrograde movement of Lamp-1-positive organelles. Altogether, our results indicate that autophagy regulates the p150Glued-AP-2ß interaction, possibly to coordinate sufficient motor-adaptor complex availability for effective lysosome transport.

Elaborate Evaluation of Farnsworth Dichotomous D-15 Panel Test Can Help Differentiate between Best Vitelliform Macular Dystrophy and Autosomal Recessive Bestrophinopathy.

INTRODUCTION: The colour vision in bestrophinopathies has not been assessed in detail so far. The aim of this study was to explore the extent to which distinct types of bestrophinopathies differ in regard to colour vision deficiencies using Farnsworth Dichotomous D-15 and Lanthony Desaturated D-15 panel tests. METHODS: Both D-15 tests were performed in 52 eyes of 26 patients with Best vitelliform macular dystrophy (BVMD) and 10 eyes of 5 patients with autosomal recessive bestrophinopathy (ARB). Two methods were used for a quantitative assessment of the colour vision deficiencies: moment of inertia method and Bowman method. The following parameters were calculated: confusion angle, confusion index (C-index), selectivity index (S-index), total error score (TES), and colour confusion index (CCI). RESULTS: The median value of confusion angle for all stages of BVMD fell into a narrow range around 62, indicating normal results. The median confusion angle value was 57 in ARB patients within a very wide range down to -82, indicating non-specific deficits. These differences were statistically significant. Significantly abnormal C-index and CCI values were found only in ARB patients, being 2.0 and 1.49, respectively. The majority of parameters of D-15 tests were independent of the visual acuity in both bestrophinopathies. CONCLUSIONS: Elaborate evaluation of the D-15 panel tests might help establish a differential diagnosis between different bestrophinopathies, as the pattern of the colour vision loss is different between BVMD and ARB. The quantitative parameters of colour vision tests in bestrophinopathies are independent of the visual acuity.

Maternal diet during pregnancy and risk of allergic diseases in children up to 7-9 years old from Polish Mother and Child Cohort study.

BACKGROUND: The impact of maternal diet during pregnancy on the risk of allergic diseases in childhood is an increasing scientific and public health concern. We evaluated the associations of maternal type of diet and essential elements and vitamins intake during pregnancy with offspring allergic and respiratory outcomes. METHODS: The study population included 557 mother-child pairs from Polish Mother and Child Cohort (REPRO_PL). Based on the Food Frequency Questionnaire filled in between the 20th-24th week of pregnancy, overall maternal diet was evaluated as the difference between the Prudent Dietary Pattern (PDP) score and Western Dietary Pattern (WDP) score ((PDP-WDP) score) and maternal achievement of dietary recommendations (estimated average requirement, EAR) for essential elements and vitamins was assessed. Children's health examination at age of 1, 2, and 7-9 years covered the following symptoms: infections, wheezing/asthma, food allergy, allergic rhinitis, and atopic dermatitis. At age of 7-9 years, children underwent spirometry and skin-prick tests. RESULTS: Children of the mothers who were not achieving adequate intake of vitamin C during pregnancy had a higher risk of wheezing and having more than two infections within the first two years of life comparing to those who met EAR (OR = 2.6, p = 0.05, and OR = 2.3, p = 0.04, respectively). Inadequate intake of vitamin E during pregnancy was related to a higher risk of atopic dermatitis (OR = 2.7, p = 0.04), whereas inadequate intake of magnesium during pregnancy was associated with the risk of wheezing in the offspring at age of two years (OR = 3.7, p = 0.03). A lower (PDP-WDP) score during pregnancy (indicating unhealthier diet) was associated with a higher risk of infections (OR = 1.5, p = 0.007) but a lower risk of atopic dermatitis (OR = 0.7, p = 0.02) at age of 7-9 years. CONCLUSIONS: These results may contribute to the body of evidence for the impact of maternal diet during pregnancy for children's optimal health, however further studies are needed before drawing conclusions and recommendations for clinical practice.

Testicular torsion: its effect on autoimmunisation, pituitary-testis axis and correlation with primary gonadal dysfunction in boys.

BACKGROUND: Torsion of the testis is an urgent surgical condition that endangers the viability of the gonad and the fertility of the patient. Our aim was to assess potential autoimmune processes and hormonal abnormalities in boys operated on due to that illness. METHODS: The authors evaluated the levels of antibodies against sperm and Leydig cells, concentrations of follicle-stimulating, luteinizing and anti-Müllerian hormone, testosterone, oestradiol and vascular endothelial growth factor in the serum in 28 boys operated on due to torsion of the testis. Patients' sexual maturity was assessed according the Tanner scale (group G1, G4 and G5). RESULTS: No antibodies against sperm or Leydig cells were found in the serum. Statistically significant differences in follicle-stimulating and anti-Müllerian hormone concentrations were observed in the G1, and they were higher in the study than in the control group. There were no statistically significant differences in luteinizing hormone, testosterone, oestradiol and vascular endothelial growth factor concentrations in the study group or control group. Testosterone concentration was unrelated to total testicular volume. CONCLUSIONS: Results did not confirm the autoimmune process in boys with torsion of the testis. The pituitary-testis axis seems to have sufficient compensation capabilities. However, study results suggest that primary gonadal dysfunction may predispose to torsion. IMPACT: Significant differences exist between the literature data and own results on the formation of antibodies and hormonal changes due to testicular torsion in boys. It is a novel, prospective study on antibodies against sperms and Leydig cells in the serum and on hormonal processes occurring as a result of the testicular torsion from the prenatal period to the adolescence with division into pubertal groups. The study has revealed sufficient compensation capabilities of the pituitary-testis axis and no autoimmune process in boys with torsion of the testis.

Sensitization to cat and dog components and prediction of symptoms in cat-sensitized children.

BACKGROUND: Sensitization to cat and/or dog allergens during childhood represents a risk factor for the development of allergic diseases later in life. OBJECTIVE: The study investigated the association of patterns of sensitization to cat and dog allergen components with clinical symptoms of allergy to these furry animals among cat-sensitized children. METHODS: The children were evaluated for the presence of bronchial asthma, atopic dermatitis and allergic rhinitis. Their mothers completed a questionnaire on pet exposure at home. Levels of serum IgE cat epitopes Fel d (1, 2, 4), as well as dog components Can f (1, 2, 3, 5) were measured in all the studied children. RESULTS: Respiratory symptoms following exposure to the cat allergen were most common in children with Fel d 2 epitope (p = 0.041). After contact with a dog, respiratory symptoms were most common in children with Can f 1 epitope (p = 0.042), atopic dermatitis in children with sensitization to both Can f 1 (p = 0.009) and Can f 2 (p = 0.002), whereas eye symptoms occurred mostly in children with Can f 3 (p = 0.039). CONCLUSIONS: Molecular diagnosis in patients with pet allergy may help clinicians to predict clinical symptoms and their severity.

Role of dynein-dynactin complex, kinesins, motor adaptors, and their phosphorylation in dendritogenesis.

One of the characteristic features of different classes of neurons that is vital for their proper functioning within neuronal networks is the shape of their dendritic arbors. To properly develop dendritic trees, neurons need to accurately control the intracellular transport of various cellular cargo (e.g., mRNA, proteins, and organelles). Microtubules and motor proteins (e.g., dynein and kinesins) that move along microtubule tracks play an essential role in cargo sorting and transport to the most distal ends of neurons. Equally important are motor adaptors, which may affect motor activity and specify cargo that is transported by the motor. Such transport undergoes very dynamic fine-tuning in response to changes in the extracellular environment and synaptic transmission. Such regulation is achieved by the phosphorylation of motors, motor adaptors, and cargo, among other mechanisms. This review focuses on the contribution of the dynein-dynactin complex, kinesins, their adaptors, and the phosphorylation of these proteins in the formation of dendritic trees by maturing neurons. We primarily review the effects of the motor activity of these proteins in dendrites on dendritogenesis. We also discuss less anticipated mechanisms that contribute to dendrite growth, such as dynein-driven axonal transport and non-motor functions of kinesins.

Usefulness of sRtot and Rint in bronchodilator testing in the diagnosis of asthma in children.

INTRODUCTION: The usefulness of total specific resistance (sRtot) and interrupter resistance (Rint) as a bronchodilator reversibility test (BT) alternative to forced expiratory volume in 1 s (FEV1) in asthma diagnosis in children has not been established. AIM: To compare different applied definitions of airflow obstruction in children measuring response to the bronchodilator by spirometry, plethysmography and the interrupter technique in asthmatic children. MATERIAL AND METHODS: It was a prospective, real-life, non-interventional study. Children, aged 6-18 with newly diagnosed asthma, able to perform lung function tests were included into the study. Subjects underwent a history taking, physical examination, reversibility test in spirometry, plethysmography, and the interrupter technique. A standard cut-off of 12% from the initial value for reversibility in FEV1 was employed. Improvement in the pre-bronchodilator sRtot and Rint ≥ 25% and ≥ 35% was assessed after administration of salbutamol (400 µg) as well as allergen sensitization were measured. RESULTS: We included 135 children diagnosed with asthma into the analysis. All investigated parameters changed statistically significantly due to the bronchodilator administration in the examined patients. The FEV1 was not as useful in diagnostics of asthma as the sRtot and Rint, taking into consideration the fait accompli that all the study participants had aptly been diagnosed as having asthma (p < 0.001). The differences between the sRtot and Rint were not statistically significant (p = 0.215). CONCLUSIONS: Our results suggest that sRtot and Rint may be useful parameters in BT in clinical practice in the asthma diagnostic process in children.

Functional and morphological results of treatment of macula-on and macula-off rhegmatogenous retinal detachment with pars plana vitrectomy and sulfur hexafluoride gas tamponade.

BACKGROUND: To examine morphological and functional results after pars plana vitrectomy (PPV) with sulfur hexafluoride (SF6) gas tamponade due to macula-on and macula-off rhegmatogenous retinal detachment (RRD) during 6 months of the follow-up. METHODS: The study included 62 eyes that underwent successful PPV with SF6 tamponade with macula-on (34 eyes) and macula-off (28 eyes) RRD preoperatively. The best-corrected visual acuity (BCVA), Amsler test, M-charts, optical coherence tomography (OCT) and microperimetry were performed at 1, 3 and 6 months postoperatively. RESULTS: Results of the Amsler test were abnormal postoperatively in 54% of the patients in the group with macula-off and in 32% of the patients with macula-on RRD. Horizontal M-charts improved significantly from 0.33 to 0.2, vertical M-charts- from 0.29 to 0.17 during 6 months of the follow-up. There was a significant increase in the central retinal thickness (CRT) and average thickness (AT) between follow-up examinations only in the macula-off group. 29 of 62 eyes (47%) after surgery (equally with macula-on and macula-off RRD) showed morphological changes in OCT in the macular region, as epiretinal membrane, macular edema, subretinal fluid or alterations of the outer layers of the retina. The average threshold in microperimetry increased significantly within both groups during the follow-up. CONCLUSION: Both horizontal and vertical M-charts scores, as were as microperimetry sensitivity improved significantly during the 6 months of the follow-up both in macula-on and macula-off group. Although PPV with SF6 gas tamponade was successful, almost half of eyes revealed anatomical changes in the macular region in OCT both with macula-on and macula-off group. TRIAL REGISTRATION: Current Controlled Trials NCT03902795 registered on 03/04/2019. Retrospectively registered.

Exhaled nitric oxide correlates with IL-2, MCP-1, PDGF-BB and TIMP-2 in exhaled breath condensate of children with refractory asthma.

INTRODUCTION: There is evidence that parameters obtained from exhaled breath condensate (EBC) reflect changes in the level of the airway lining fluid. The telation between exhaled nitric oxide (NO) and EBC inflammatory markers has not been analyzed in the context of the inflammatory profile in the airways in asthmatic children. AIM: To show the cytokine profile in EBC of children with severe/refractory asthma as well as correlations between the fractional exhaled NO (FeNO) level and cytokine concentrations. MATERIAL AND METHODS: The study population consisted of eight children aged 8 to 17 years with IgE-dependent, severe/refractory asthma with a duration of at least 2 years. This was an observational study, the first consecutive eight patients with asthma symptoms on the day of the study visit, when EBC samples were obtained. RESULTS: The inter-subject variability of study cytokines ranged from 8.6 to 54.6. Cytokines with coefficient of variation < 20% were: interferon-γ, interleukins IL-2, IL-7, IL-15, IL-16, monokine induced by interferon γ (MIG) and tumor necrosis factor α. We showed a significant positive correlation between the FeNO level and crucial mediators in asthma development and progression (IL-2, MCP-1), and potent markers of airway remodeling (PDGFBB, TIMP-2). All correlations between two different variables were controlled for the effects of age, forced expiratory volume in 1 s and number of asthma exacerbations during last 12 months. CONCLUSIONS: The profiling of cytokine expression in EBC can be reproducibly performed in children with severe/refractory asthma. When treating asthma in children, the FeNO level should be monitored as a prevention strategy of the progression of the remodeling leading to refractory/severe asthma. Exhaled breath condensate may be a useful tool to phenotype asthma via a non-invasive approach.

Relationship between the area of isopters and Vigabatrin dosage during two years of observation.

BACKGROUND: The aim of the study was to evaluate the relationship between the area of isopters obtained using semi-automated kinetic perimetry (SKP) and Vigabatrin dosage in epilepsy patients with pretreatment baseline examination during 2-years of the follow-up. METHODS: 29 epilepsy patients were included into the study, but 15 individuals were excluded due to cognitive impairment, intracranial pathologies or eye diseases. Finally, 14 patients were examined with SKP before VGB treatment and after 6, 12, 18, and 24 months. Reaction time (RT)-corrected areas of three isopters (III4e, I4e and I2e) were measured for each of five examinations and compared intra-individually during 2-years period. Additionally, six epilepsy patients on other antiepileptic drugs were examined five times with SKP as a control. RESULTS: There was a significant decrease of I2e, I4e and III4e isopters' area during the follow-up of two years. Correlation was found between the I2e isopter's area and both cumulative dose and mean daily dose of VGB. With increasing RT, there was decreasing of all isopters' area in patients receiving VGB. In epilepsy patients who were not receiving VGB, there were no significance differences in isopters' area during follow-up. CONCLUSION: There was attenuation of area of III4e, I4e and I2e isopters obtained with SKP during a period of 2 years. RT, the cumulative dose and the mean daily dose of VGB influenced isopters' area obtained with SKP.

[Anatomical and functional results of pars plana vitrectomy with the internal limiting membrane removal in patients with rhegmatogenous retinal detachment]. / Ocena anatomiczna i funkcjonalna wyników leczenia przedarciowego odwarstwienia siatkówki metoda witrektomii przez czesc plaskqa ciala rzeskowego z usunieciem blony granicznej wewnetrznej.

AIM: To evaluate the benefits of the internal limiting membrane removal in patients with rhegmatogenous retinal detachment who underwent pars plana vitrectomy. MATERIAL AND METHODS: The first study group (B) consisted of 26 patients who underwent vitrectomy with the internal limiting membrane peeling. The second control group (K) consisted of 15 patients, in whom vitrectomy was performed without he internal limiting membrane peeling. Macular detachment was confirmed preoperatively in all patients. Ophthalmic examination was performed 6 months after surgery. This included the best corrected visual acuity for distance and near, M-Charts, fundus examination and spectral domain--optical coherent tomography. RESULTS: The results were statistically analyzed using the Shapiro-Wilk test and the Ch2 test of homogeneity. In the study group (B), the mean postoperative best corrected visual acuity for distance was 0.46, while in the control group (K) it was 0.35 (p = 0.35). The best corrected visual acuity for near in group B was 0.83 and 1.01 (p = 0.63) in group K. Central retinal thickness in group B was 268.64 µm, while in group K it was 335.07 µm (p = 0.20). The statistical analysis revealed significant differences between the two groups regarding the prevalence of defects in the ellipsoidal layer (p = 0.004). They were found to occur more frequently in group K (64.29%) than in group B (20.00%). The prevalence of epiretinal membrane was higher in group K (28.57%) than in group B (3.85%) (p = 0.02). CONCLUSIONS: The internal limiting membrane peeling reduces the risk of secondary epiretinal membrane, restores the ellipsoidal layer integrity and does not affect the visual acuity for distance and near.

HDR brachytherapy versus robotic-based and linac-based stereotactic ablative body radiotherapy in the treatment of liver metastases - A dosimetric comparison study of three radioablative techniques.

Purpose: The aim of our study was to compare dosimetric aspects of three radioablation modalities - direct high-dose-rate brachytherapy (HDR-BT) and virtually planned stereotactic body radiation therapy performed on CyberKnife (SBRTck) and Elekta Versa HD LINAC (SBRTe) applied in patients with liver metastases. Material and methods: We selected 30 patients with liver metastases, who received liver interstitial HDR-BT and virtually prepared plans for SBRTck and SBRTe. In all the cases, the prescribed dose was a single fraction of 25 Gy. Treatment delivery time, doses delivered to PTV and organs at risk, as well as conformity indices, were calculated and compared. Results: The longest median treatment delivery time was observed in SBRTck in contrast to HDR-BT and SBRTe which were significantly shorter and comparable. HDR-BT plans achieved better coverage of PTV (except for D98%) in contrast to SBRT modalities. Between both SBRT modalities, SBRTck plans resulted in better dose coverage in Dmean, D50%, and D90% values compared to SBRTe without difference in D98%. The SBRTe was the most advantageous considering the PCI and R100%. SBRTck plans achieved the best HI, while R50% value was comparable between SBRTe and SBRTck. The lowest median doses delivered to uninvolved liver volume (V5Gy, V9.1Gy) were achieved with HDR-BT, while the difference between SBRT modalities was insignificant. SBRT plans were better regarding more favourable dose distribution in the duodenum and right kidney, while HDR-BT achieved lower doses in the stomach, heart, great vessels, ribs, skin and spinal cord. There were no significant differences in bowel and biliary tract dose distribution between all selected modalities. Conclusions: HDR-BT resulted in more favourable dose distribution within PTVs and lower doses in organs at risk, which suggests that this treatment modality could be regarded as an alternative to other local ablative therapies in carefully selected patients' with liver malignancies. Future studies should further address the issue of comparing treatment modalities in different liver locations and clinical scenarios.

Rab11 regulates autophagy at dendritic spines in an mTOR- and NMDA-dependent manner.

Synaptic plasticity is a process that shapes neuronal connections during neurodevelopment and learning and memory. Autophagy is a mechanism that allows the cell to degrade its unnecessary or dysfunctional components. Autophagosomes appear at dendritic spines in response to plasticity-inducing stimuli. Autophagy defects contribute to altered dendritic spine development, autistic-like behavior in mice, and neurological disease. While several studies have explored the involvement of autophagy in synaptic plasticity, the initial steps of the emergence of autophagosomes at the postsynapse remain unknown. Here, we demonstrate a postsynaptic association of autophagy-related protein 9A (Atg9A), known to be involved in the early stages of autophagosome formation, with Rab11, a small GTPase that regulates endosomal trafficking. Rab11 activity was necessary to maintain Atg9A-positive structures at dendritic spines. Inhibition of mTOR increased Rab11 and Atg9A interaction and increased the emergence of LC3 positive vesicles, an autophagosome membrane-associated protein marker, in dendritic spines when coupled to NMDA receptor stimulation. Dendritic spines with newly formed LC3+ vesicles were more resistant to NMDA-induced morphologic change. Rab11 DN overexpression suppressed appearance of LC3+ vesicles. Collectively, these results suggest that initiation of autophagy in dendritic spines depends on neuronal activity and Rab11a-dependent Atg9A interaction that is regulated by mTOR activity.

M-charts as a tool for quantifying metamorphopsia in age-related macular degeneration treated with the bevacizumab injections.

BACKGROUND: This article is aimed to assess quantitatively metamorphopsia using M-charts in patients suffering from wet age-related macular degeneration (AMD) treated with the intravitreal bevacizumab injections and to compare the results with traditional Amsler grid and ocular coherence tomography (OCT). METHODS: Thirty-six patients diagnosed with wet AMD were examined one day before and one month after the intraocular injection of bevacizumab. Horizontal and vertical metamorphopsia scores using M-charts, distance visual acuity, Amsler test and OCT were performed at each visit. Additionally, 23 healthy subjects were examined as a control group. RESULTS: The rate of metamorphopsia detection was 89% with M-charts and 69% with Amsler test. The horizontal metamorphopsia score improved in 22 patients, the vertical metamorphopsia score improved in 16 patients, the Amsler grid results improved in 6 patients, visual acuity improved in 17 patients. There was no correlation between the degree of metamorphopsia and the visual acuity or the central retinal thickness (CRT). The specificity of both the M-charts and Amsler grid was 100%. CONCLUSIONS: The rate of metamorphopsia detection in wet AMD patients was better with M-charts than with Amsler grid. M-charts may be used in the assessment of efficacy of treatment with intravitreal bevacizumab injections as another outcome measure, moreover they can be used even at home for the self-assessment. M-charts provide additional information concerning the visual function, independent of the visual acuity, CRT and morphological changes in OCT.

Don't we overestimate drug allergies in children?

OBJECTIVES: On average about 10% of parents report hypersensitivity to at least 1 drug in their children. After diagnosis process a few of these reactions are being confirmed as drug hypersensitivity reactions. The aim of the study was to assess the real-life prevalence of drug hypersensitivity in children based on drug provocation tests. MATERIAL AND METHODS: The authors included 113 children, aged 4-18 years, referred to Pediatrics and Allergy Clinic in Lódz, Poland, due to incidence of adverse reaction during treatment. Medical history regarding allergies to drugs was taken in accordance to the form developed by the United States Food and Drug Administration Adverse Event Reporting System. Skin prick tests, intradermal test and drug provocation test were performed in all patients. RESULTS: In all 113 patients suspected of drug allergy, after all diagnostic procedures, the authors proved IgE-mediated allergy to ß-lactams, nonsteroid anti-inflammatory drugs, local anesthetics in 19 patients (16.8%). Previous history of allergy was a risk factor for drug allergy in studied patients (p = 0.001). The most frequent symptoms of allergy were urticaria and erythematous papular rash. CONCLUSIONS: Drug allergy is a difficult problem in the practice of a doctor and is difficult to diagnose, especially in the pediatric population. It seems that too often isolated symptoms reported during infection or disease are taken as a symptom of drug allergy, and not as a symptom resulting from the course of the disease. Int J Occup Med Environ Health. 2023;36(5):632-42.

Prenatal polyunsaturated fatty acids and atopic dermatitis and food allergy in children from Polish Mother and Child Cohort study.

OBJECTIVES: Polyunsaturated fatty acids (PUFAs) are involved both in immune system regulation and inflammation. The aim of this prospective study was to evaluate the association between maternal dietary intake of PUFAs during pregnancy and atopic dermatitis (AD) and food allergy (FA) in their children up to 7-9 years of age. MATERIAL AND METHODS: The study population consists of 557 mother-child pairs from the Polish Mother and Child Cohort (REPRO_PL). Based on the Food Frequency Questionnaire completed between the 20-24th weeks of pregnancy, n-3 and n-6 PUFAs as well as n-6:n-3 fatty acid ratio were estimated using food composition tables. Children's health examinations at the age of 1, 2, and 7-9 years were performed by an allergist. Generalized estimating equations were performed in order to assess the prevalence of AD and FA at 3 time points. Independent variables in the equation were n-3, n-6 PUFAs and n-6:n-3 PUFAs ratio. In addition multivariate models were performed to assess the association of PUFAs with AD and FA. RESULTS: The prevalence of AD was 37%, 26% and 21% and FA 26%, 22% and 22% at age of 1, 2 and 7-9 years, respectively. Higher n-6:n-3 fatty acid ratio correlated with higher prevalence of AD at age of 7-9 years (p < 0.07). In multivariate model n-6 PUFAs were significantly associated with increased risk of persistent FA (OR = 1.5, 95% CI: 1.1-2.1). CONCLUSIONS: These results may contribute to the existing knowledge on the impact of maternal diet during pregnancy on children's optimal health, however further studies are needed before drawing conclusions and creating clinical practice guidelines. Int J Occup Med Environ Health. 2023;36(3):428-36.

Practical Approach to Hypersensitivity to Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) in Children.

BACKGROUND: We aimed to assess the real-life prevalence, patient profile, and clinical presentation of drug hypersensitivity to NSAIDs in children after an incidence of an adverse event during treatment, verified by a drug challenge test. METHODS: We included 56 children, aged 4-18 years, referred to our allergy clinic due to the incidence of adverse reaction during treatment. Skin prick tests and a drug provocation test were performed in all patients. Diagnostics for persistent urticaria were performed. RESULTS: In 56 patients suspected of drug allergy, we proved NSAID hypersensitivity in 17 patients (30.1%). In 84.9% (n = 47) of patients, the clinical manifestations of hypersensitivity revealed angioedema and urticaria. The most common culprit drug among NSAIDs in children was ibuprofen. Thirty-one (55.4%) reactions were immediate, and 25 (44.6%) were delayed or late. Previous history of allergy was a risk factor for NSAID hypersensitivity (p = 0.001). Vitamin D deficiency in the blood serum was a risk factor for NASID hypersensitivity (OR = 5.76 (95% Cl: 1.42-23.41)). CONCLUSIONS: Hypersensitivity to NSAIDs is a difficult diagnostic problem in pediatric allergy. The most common manifestation of hypersensitivity to ibuprofen in children is acute urticaria and angioedema. Two important problems in the differential diagnosis are cofactors such as vitamin D levels and viral infections, which require further research.

Vascular Changes in the Macula of Patients after Previous Episodes of Vision Loss Due to Leber Hereditary Optic Neuropathy and Non-Arteritic Ischemic Optic Neuropathy.

PURPOSE: to assess the vasculature and thickness of the macula using OCT-A in patients who had experienced a previous episode of Leber hereditary optic neuropathy (LHON) or non-arteritic anterior ischemic optic neuropathy (NA-AION). METHODS: twelve eyes with chronic LHON and ten eyes with chronic NA-AION and eight NA-AION fellow eyes were examined using OCT-A. The vessel density was measured in the superficial and deep plexus of the retina. Moreover, the full and inner thicknesses of the retina were assessed. RESULTS: There were significant differences in all sectors between the groups in regard to the superficial vessel density and the inner and full thicknesses of the retina. The nasal sector of the macular superficial vessel density was affected more in LHON than in NA-AION; the same with the temporal sector of the retinal thickness. There were no significant differences between the groups in the deep vessel plexus. There were no significant differences between the vasculature of the inferior and superior hemifields of the macula in all groups and no correlation with the visual function. CONCLUSIONS: The superficial perfusion and structure of the macula assessed with OCT-A are affected both in chronic LHON and NA-AION, but more in LHON eyes, especially in the nasal and temporal sectors.

Variability in isopter position and fatigue during semi-automated kinetic perimetry.

BACKGROUND: Assessment of factors influencing response variability to repeat presentations of III4e stimuli and the fatigue effect during semi-automated kinetic perimetry (SKP). DESIGN: Prospective case series; setting: university hospital. PARTICIPANTS: 58 patients with severe visual field loss: 21 with glaucoma, 18 with retinitis pigmentosa, and 19 with postchiasmal visual pathway lesions. METHODS: Following initial testing with three isopters (I2e or V4e, I4e and III4e), presentations of the III4e stimulus were repeated four times during the same session along identical vectors. MAIN OUTCOME MEASURES: Variability in III4e-isopter position (scatter of kinetic threshold) and the difference of isopter area between the first and four subsequent sessions (fatigue effect) of SKP were analyzed by diagnosis, age, visual acuity and reaction time (RT). RESULTS: The mean scatter of the kinetic threshold was 2.5 degrees (deg) in the glaucoma group, 1.5 deg in the group with retinitis pigmentosa, and 1.7 deg in the group of patients with postchiasmal lesions. The difference in the isopter area between a single examination and four times repeated examination was 656 square degrees (deg(2)) in the glaucoma group, 104 deg(2) in the retinitis pigmentosa group and 227 deg(2) in the group of patients with postchiasmal lesions. Post-hoc regression analysis revealed that the variability of isopter position increased as the RT increased. CONCLUSION: The variability of III4e-isopter positionand fatiguewere most pronounced among glaucoma patients. RT is the most important factor influencing the variability of responses and fatigue during SKP, thus we propose that it can be used as a reliability indicator of SKP.