Optical coherence tomography (OCT) and OCT angiography allow early identification of sickle cell maculopathy in children and correlate it with systemic risk factors.

PURPOSE: To determine the presence of sickle cell retinopathy and maculopathy and to identify associations between markers of hemolysis and systemic and ocular manifestations in children affected by sickle cell disease. METHODS: Eighteen children with sickle cell disease, aged 5-16 years, underwent complete eye examination including best-corrected visual acuity, slit-lamp biomicroscopy, ophthalmoscopy after pharmacological mydriasis, spectral-domain optical coherence tomography (SD-OCT), and optical coherence tomography angiography (OCTA). Blood test results and clinical history information were collected for each child, including fetal hemoglobin (HbF), hemoglobin (Hb), hematocrit (Htc), mean corpuscular volume (MCV), mean corpuscular hemoglobin concentration (MCHC), reticulocytes percentage (%ret), lactic dehydrogenase (LDH), total and direct bilirubin, glomerular filtration rate, number of painful crises, acute chest syndromes, and splenic sequestration. Therapeutic regimen and transfusion therapy were also evaluated. RESULTS: Sixteen of 36 eyes (44.4%) had non-proliferative sickle cell retinopathy on ophthalmoscopic evaluation. No patients had proliferative sickle cell retinopathy. In 13 of 36 eyes (36.1%), SD-OCT and OCTA detected signs of sickle cell maculopathy. Nine eyes (25%) presented sickle cell retinopathy and maculopathy, 7 eyes (19.4%) sickle cell retinopathy alone, and 4 eyes (11.1%) sickle cell maculopathy alone. A statistically significant association was found between sickle cell retinopathy; lower levels of HbF, Hb, and Htc; and higher MCV and percentage of reticulocytes. Sickle cell maculopathy was associated with lower values of H and Htc and higher levels of reticulocytes and total bilirubin. CONCLUSIONS: We identified early signs of sickle cell retinopathy and maculopathy in a pediatric population with SD-OCT and OCTA. These two retinal complications were more frequent in children with higher hemolytic rates.

Pyrethroid and organophosphate pesticide resistance in field populations of horn fly in Brazil.

Pesticides are used worldwide to control arthropod parasites in cattle herds. The indiscriminate and/or inappropriate use of pesticides without veterinary guidance is a reality in several countries of South America. Improper pesticide use increases the chances of contamination of food and the environment with chemical pesticides and their metabolites. Reduction of these contamination events is an increasing challenge for those involved in livestock production. The horn fly, Haematobia irritans (Linnaeus) (Diptera: Muscidae), is one of the most economically important parasites affecting cattle herds around the world. As such, horn fly control efforts are often required to promote the best productive performance of herds. Pesticide susceptibility bioassays revealed that pyrethroid resistance was widespread and reached high levels in horn fly populations in the Brazilian state of Rondônia. The knockdown resistance (kdr) sodium channel gene mutation was detected in all horn fly populations studied (n = 48), and the super kdr sodium channel gene mutation was found in all homozygous resistant kdr individuals (n = 204). Organophosphate resistance was not identified in any of the fly populations evaluated.

Plantar pain is not always fasciitis.

The case is described of a patient with chronic plantar pain, diagnosed as fasciitis, which was not improved by conventional treatment. Magnetic resonance imaging revealed flexor hallucis longus tenosynovitis, which improved after local glucocorticoid injection.

Interleukin-8 is associated with acute and persistent dysfunction after optic neuritis.

BACKGROUND: Acute optic neuritis is often in association with multiple sclerosis (MS). Proinflammatory cytokines trigger neuronal damage in neuroinflammatory disorders but their role in optic neuritis is poorly investigated. OBJECTIVE: The objective of this work is to investigate the associations of intrathecal contents of proinflammatory cytokines with transient and persistent dysfunctions after optic neuritis. METHODS: In 50 MS patients followed for up to six months, cerebrospinal fluid (CSF) levels of IL-1ß, TNF and IL-8 were determined, along with clinical, neurophysiological and morphological measures of optic neuritis severity. RESULTS: Visual impairment, measured by high- and low-contrast visual acuity, and delayed visual-evoked potential (VEP) latencies were significantly correlated to IL-8 levels during optic neuritis. IL-8 at the time of optic neuritis was also associated with persistent demyelination and final axonal loss, inferred by VEP and optical coherence tomography measures, respectively. Contents of IL-8 were correlated to functional visual outcomes, being higher among patients with incomplete recovery. Multivariate analysis confirmed that IL-8 significantly predicted final visual acuity, at equal values of demographics and baseline visual scores. CONCLUSION: Our study points to IL-8 as the main inflammatory cytokine associated with demyelination and secondary neurodegeneration in the optic nerve after optic neuritis.

Effect of triceps surae and quadriceps muscle fatigue on the mechanics of landing in stepping down in ongoing gait.

The aim of this study was to evaluate the effects of muscle fatigue of triceps surae and quadriceps muscles in stepping down in ongoing gait. We expected that the subjects would compensate for muscle fatigue to prevent potential loss of balance in stepping down. A total of 10 young participants walked over a walkway at a self-selected velocity to step down a height difference of 10-cm halfway. Five trials were performed before and after a muscle fatigue protocol. Participants performed two fatigue protocols: one for ankle muscle fatigue and another for knee muscle fatigue. Kinematics of and ground reaction forces on the leading leg were recorded. Fatigue did not cause a change in the frequency of heel or toe landing. Our results indicate that in stepping down fatigue effects are compensated by redistributing work to unfatigued muscle groups and by gait changes aimed at enhancing balance control, which was however only partially successful.

Effect of glatiramer acetate on disease reactivation in MS patients discontinuing natalizumab.

BACKGROUND AND PURPOSE: Multiple sclerosis (MS) patients discontinuing natalizumab are at risk of rebound of disease activity. METHODS: In the present multi-center, open-label, non-randomized, prospective, pilot study, we tested whether treatment with glatiramer acetate (GA) is safe and effective after natalizumab in MS patients. The study was performed at academic tertiary medical centers. Forty active relapsing-remitting MS patients who never failed GA therapy and who discontinued natalizumab after 12-18 months of therapy were enrolled. GA was initiated 4 weeks after the last dose of natalizumab. RESULTS: 62.5% of patients were relapse-free 12 months after GA initiation. Annualized relapse rate and time to relapse were significantly lower than before natalizumab. Notably, the frequency of relapses was significantly lower amongst those patients who had experienced ≤2 relapses the year before initiation of natalizumab therapy, compared with patients who had had three or more relapses. No evidence of rebound was observed in magnetic resonance imaging scans. Furthermore, Expanded Disability Status Scale and Multiple Sclerosis Functional Composite were stable in our patients, again suggesting that 12 months of post-natalizumab-GA therapy is not associated with clinical deterioration. CONCLUSIONS: Following discontinuation of natalizumab, 12 months of therapy with GA is safe and well tolerated in MS patients. GA can reduce the risk of early reactivation/rebound of disease activity in this setting.

Differential role of EGF and BFGF in human GBM-TIC proliferation: relationship to EGFR-tyrosine kinase inhibitor sensibility.

Glioblastoma multiforme (GBM) is among the most devastating human tumors being rapidly fatal despite aggressive surgery, radiation and chemotherapies. It is characterized by extensive dissemination of tumor cells within the brain that hinders complete surgical resection. GBM tumor initiating-cells (TICs) are a rare subpopulation of cells responsible for tumor development, growth, invasiveness and recurrence after chemotherapy. TICs from human GBM can be selected in vitro using the same conditions permissive for the growth of normal neural cells, of which share some features including marker expression, self-renewal capacity, long-term proliferation, and ability to differentiate into neuronal and glial cells. EGFR overexpression and its constitutive activation is one of the most important signaling alteration identified in GBM, and its pharmacological targeting represents an attractive therapeutic goal. We previously demonstrated that human GBM TICs have different sensitivity to the EGFR kinase inhibitors erlotinib and gefitinib, depending on the differential modulation of downstream signaling cascades. In this work we investigated the mechanisms of resistance to erlotinib in two human GBM TIC cultures, analyzing EGF and bFGF individual contribution to proliferation, clonogenicity, and migration. We demonstrated the presence of a small cell subpopulation whose proliferation is supported by EGF and a larger one mainly dependent on bFGF. Thus, insensitivity to EGFR kinase inhibitors as far as TIC proliferation results from a predominant FGFR activation that hides the inhibitory effects induced on EGFR signaling. Conversely, EGF and bFGF induced cell migration with similar efficacy. In addition, unlike neural stem/progenitors cells, the removal of chondroitin sulphate proteoglycans from cell surface was unable to discern EGF- and bFGF-dependent subpopulations in GBM TICs.

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy from the pediatric perspective.

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a rare autosomal recessive disease caused by mutations of the AutoImmune REgulator gene. The clinical spectrum of the disease encompasses several autoimmune endocrine and non-endocrine manifestations, which may lead to acute metabolic alterations and eventually life-threatening events. The clinical diagnosis is defined by the presence of at least two components of the classic triad including chronic mucocoutaneous candidiasis (CMC), chronic hypoparathyroidism (CH), Addison's disease (AD). Other common features of the disease are hypergonadotropic hypogonadism, alopecia, vitiligo, autoimmune hepatitis, Type 1 diabetes, gastrointestinal dysfunction. APECED usually begins in childhood. CMC is the first manifestation to appear, usually before the age of 5 yr, followed by CH and then by AD. The clinical phenotype may evolve over several years and many components of the disease may not appear until the 4th or 5th decade of life. The phenotypical expression of the syndrome shows a wide variability even between siblings with the same genotype. In view of this heterogeneity, an early diagnosis of APECED can be very challenging often leading to a considerable diagnostic delay. Therefore, clinicians should be aware that the presence of even a minor component of APECED in children should prompt a careful investigation for other signs and symptoms of the disease, thus allowing an early diagnosis and prevention of severe and life-threatening events. Aim of this review is to focus on clinical presentation, diagnosis and management of the major components of APECED in children particularly focusing on endocrine features of the disease.

Treatment with pamidronate for osteoporosis complicating long-term intestinal failure.

Long-term home parenteral nutrition (PN) is a potential risk for developing osteoporosis. Various attempts have been made to treat bone disease both by modifying the composition of PN and by administering hormones, such as calcitonin, parathyroid hormone, and sexual hormones. Bisphosphonates are recognized as a medication useful for the treatment of several bone disorders associated with excessive reabsorption. Nevertheless, there have been no paediatric studies on bisphosphonates use for intestinal failure-associated bone disease. Our study includes 6 paediatric patients receiving extremely long-term home PN (at least 3 years) who showed radiological and clinical signs of osteoporosis. Diagnosis of bone disease was made after a median period of 127.5 PN months. Treatment consisted in 2 cycles of intravenous pamidronate, 30 mg/m once per month for 6 months consecutively. They all showed a significant improvement in bone mineral density, evaluated after 6 and 12 months of pamidronate treatment. In our sample anthropometrical variables (weight, height, and body mass index) are not related with the z-score trend. Our patients had normal levels of calcium, phosphorus, and vitamin D, and proper nutrient intake. At the last follow-up, dual-energy x-ray absorptiometry scan showed that no patients had a z-score lower than -2.5; moreover, nobody developed bone fractures during the 108-month follow-up. The patients did not have any prominent adverse effect. Finally, in our experience, pamidronate is effective for improving bone mineral density and safe in patients with intestinal failure-associated bone disease.

Changes in adhesion ability of Aeromonas hydrophila during long exposure to salt stress conditions.

AIMS: Stressful environmental conditions influence both bacterial growth and expression of virulence factors. In the present study, we evaluated the influence of NaCl on Aeromonas hydrophila adhesiveness at two temperatures. This agent is often involved in clinical cases; however, its pathogenic potential is still not fully understood. METHODS AND RESULTS: Bacteria were grown in presence of 1·7%, 3·4%, 6·0% NaCl over a 188 day period and then reinoculated in fresh Nutrient Broth with incubation at 4 and 24°C. Bacterial adhesiveness was tested on Hep-2 cells, and specimens were processed for light, scanning and transmission electron microscopy. Adhesive capacity decreased over time with an increase in reduction percentages depending on NaCl concentrations. At 1·7% NaCl, the reduction was apparently temporary and adhesiveness rapidly recovered in revitalized bacteria, while 3·4%, 6·0% NaCl seemed to be detrimental. Normal, elongated and filamentous bacteria retained adhesiveness capability, although with reduced expression, while in spherical cells, this property seemed to be lost or dramatically reduced. CONCLUSIONS: Our study shows that high osmolarity plays a significant role in adhesion inhibition, therefore having possible implications in the pathogenesis of the infections by Aer. hydrophila. SIGNIFICANCE AND IMPACT OF THE STUDY: This study intends to give a contribution to a better understanding of the pathogenic role of this bacterium whose pathogenicity is still under debate.

Impact of environmental changes and human-related factors on the potential malaria vector, Anopheles labranchiae (Diptera: Culicidae), in Maremma, Central Italy.

The Maremma Plain (central Italy) was hyper-endemic for malaria until the mid-20th century, when a national campaign for malaria elimination drastically reduced the presence of the main vector Anopheles labranchiae Falleroni. However, the introduction of rice cultivation over 30 yr ago has led to an increase in the An. labranchiae population and concern over possible malaria reemergence. We studied the impact of anthropogenic environmental changes on the abundance and distribution of An. labranchiae in Maremma, focusing on rice fields, the main breeding sites. Adults and larvae were collected in three main areas with diverse ecological characteristics. Data were collected on human activity, land use, and seasonal climatic and demographic variations. We also interviewed residents and tourists regarding their knowledge of malaria. Our findings showed that the most important environmental changes have occurred along the coast; An. labranchiae foci are present throughout the area, with massive reproduction strictly related to rice cultivation in coastal areas. Although the abundance of this species has drastically decreased over the past 30 yr, it remains high and, together with climatic conditions and the potential introduction of gametocyte carriers, it may represent a threat for the occurrence of autochthonous malaria cases. Our findings suggest the need for the continuous monitoring of An. labranchiae in the study area. In addition to entomological surveillance, more detailed knowledge of human-induced environmental changes is needed, so as to have a more complete database that can be used for vector-control plans and for properly managing emergencies related to autochthonous introduced cases.

Update on early cardiovascular and metabolic risk factors in children and adolescents affected with growth hormone deficiency.

Growth hormone (GH), in addition to promote linear growth during childhood, exerts a key role in several processes of substrate metabolism. Adults with untreated GH deficiency and adolescents who discontinued GH therapy at completion of growth, exhibit a cluster of cardiovascular risk factors such as impaired cardiac performance, alteration in body proportion with increased visceral fat, dyslipidemia and hypertension, that could place them at higher risk of cardiovascular morbidity. Although studies on adolescents and children are still scarce, there is evidence that early markers of cardiovascular disease can be already detected in untreated children with GH deficiency and that, as in adults, GH replacement therapy exerts a beneficial role on metabolic alterations. Untreated GH deficiency in childhood and adolescence seems to be associated with reduced cardiac size and impaired cardiac function, dyslipidemia, abnormalities in body composition and in peripheral inflammatory markers. GH replacement therapy exerts a beneficial effects on most of these alterations. Aim of this review is to summarize the current findings on the effects of GH deficiency and GH treatment on early cardiovascular risk factors in children and adolescents.

The effects of experimentally-induced fatigue on gait parameters during obstacle crossing: A systematic review.

Striking an obstacle while walking can be dangerous, reflecting the higher risks of losing one's balance, tripping and falling. Particular situations during which internal resources are limited, such as in a fatigued state, may impair performance when crossing obstacles, enhancing the risks of falls or accidents. Our goal was thus to review the effects of experimentally-induced fatigue (EIF) on gait parameters during obstacle crossing by healthy individuals. We systematically searched PubMed and Web of Science databases using 'fatigue', 'obstacle crossing' and their equivalent terms to extract data from studies investigating this domain. Nine studies were found. First, EIF-related effects on kinetics, EMG and obstacle contacts have been poorly studied. Second, consistent and inconsistent results were found in the kinematic outcomes after EIF. Consistent results included reductions in stride duration and increased step width. Inconsistent results included gait velocity (no-effect vs increased), leading and trailing-foot vertical clearance (reduced vs increased) and horizontal distance from foot to the obstacle before obstacle avoidance (no-effect vs increased). These findings should be interpreted cautiously, however, due to the heterogeneity of the obstacle crossing and EIF protocols.

The lung immuno-oncology prognostic score (LIPS-3): a prognostic classification of patients receiving first-line pembrolizumab for PD-L1 ≥ 50% advanced non-small-cell lung cancer.

BACKGROUND: To stratify the prognosis of patients with programmed cell death-ligand 1 (PD-L1) ≥ 50% advanced non-small-cell lung cancer (aNSCLC) treated with first-line immunotherapy. METHODS: Baseline clinical prognostic factors, the neutrophil-to-lymphocyte ratio (NLR), PD-L1 tumour cell expression level, lactate dehydrogenase (LDH) and their combination were investigated by a retrospective analysis of 784 patients divided between statistically powered training (n = 201) and validation (n = 583) cohorts. Cut-offs were explored by receiver operating characteristic (ROC) curves and a risk model built with validated independent factors by multivariate analysis. RESULTS: NLR < 4 was a significant prognostic factor in both cohorts (P < 0.001). It represented 53% of patients in the validation cohort, with 1-year overall survival (OS) of 76.6% versus 44.8% with NLR > 4, in the validation series. The addition of PD-L1 ≥ 80% (21% of patients) or LDH < 252 U/l (25%) to NLR < 4 did not result in better 1-year OS (of 72.6% and 74.1%, respectively, in the validation cohort). Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 2 [P < 0.001, hazard ratio (HR) 2.04], pretreatment steroids (P < 0.001, HR 1.67) and NLR < 4 (P < 0.001, HR 2.29) resulted in independent prognostic factors. A risk model with these three factors, namely, the lung immuno-oncology prognostic score (LIPS)-3, accurately stratified three OS risk-validated categories of patients: favourable (0 risk factors, 40%, 1-year OS of 78.2% in the whole series), intermediate (1 or 2 risk factors, 54%, 1-year OS 53.8%) and poor (>2 risk factors, 5%, 1-year OS 10.7%) prognosis. CONCLUSIONS: We advocate the use of LIPS-3 as an easy-to-assess and inexpensive adjuvant prognostic tool for patients with PD-L1 ≥ 50% aNSCLC.

Is dental general anaesthesia in children an outdated concept? A retrospective analysis.

AIM: The aim of this retrospective study was to determine the prevalence of caries and treatment needs in the collective of patients ?16 years of age, who underwent scheduled dental general anaesthesia (DGA) at the University Clinic of Innsbruck from January 2015 to June 2019, with respect to demographic factors. MATERIALS AND METHODS: A retrospective analysis of children's diagnoses, demographics, and dental treatment under general anaesthesia in Innsbruck, Austria, from 2015 to 2019 was performed. Anonymised demographic data (age; gender; the presence or absence of general disease or disablement; parents' first language (German- (GS) or non-German-speaking (non-GS), reflecting ethnicity; and the number of teeth restored and extracted under DGA were collected from patients' files. Data was analysed by means of descriptive and comparative statistics. RESULTS: The main group consisted of 545 subjects at a median age of 5.3 (IQR 4.4-6.6) years, who had exclusively primary teeth and or first molars that received restorations or were extracted. Of the subjects, 84.4% were classified with uncooperativeness due to dental anxiety and 15.6% with systemic diseases or intellectual and or physical disablement. In this group, 47.9% were GS and 52.1% were non-GS or had GS or non- GS parents. In the total sample, 5 (IQR 3-7) primary teeth were restored and 4 (IQR 4-7) extracted. Subgroup analysis revealed statistically significant differences in the number of extracted primary teeth between children with and without systemic diseases or disablement - 3 (IQR 1-5) versus 4 (IQR 2-7) - and between children of GS and non-GS parents - 4 (IQR 2-6) versus 5 (IQR 3-7.8). Zero (IQR 0-0) first molars were filled and extracted. CONCLUSION: Within the study collective of children in poor oral health, the offspring of non-GS families were overrepresented (compared to their prevalence in the total population) and displayed a higher prevalence of deep caries than those of GS parents. By intensifying and special gearing of prophylactic measures to the non-GS population and promoting the parents' insight into the importance of oral hygiene and regular dental attendance, the demand for scheduled DGA might be greatly reduced. In the small share of children who suffer from severe diseases or disablement and are thus unable to cooperate with home care or dental treatment, DGA will remain the treatment of choice.

Laparoscopic excision of endometriosis may require unilateral parametrectomy.

OBJECTIVE: We investigated the effects of laparoscopic excision of endometriosis with unilateral parametrectomy on bladder, rectal, and sexual function as well as patient satisfaction. METHODS: Women who underwent this procedure between February 1, 2006 and November 15, 2007 were enrolled. Patient characteristics, pre- and postoperative findings, and follow-up data were retrospectively collected from a computerized database. RESULTS: Twelve patients were enrolled in the study. All of the symptoms except dysuria improved after surgery, worsening long after the operation. It seems that all parameters including sexuality, micturition, and defecation are equally important in regards to the final judgement of satisfaction, with a trend towards amelioration long after the operation. CONCLUSIONS: Unilateral parametrectomy may offer successful results in terms of patient satisfaction despite some impairment in bladder, bowel, and sexual function. The risk of permanent functional impairment is high; therefore, surgeons need to maintain the integrity of the contralateral nerve pathway. This is highly important, because pain relief seems to be partially involved in the final judgement of postoperation satisfaction.

Prevalence of Autism Spectrum Disorder in a large Italian catchment area: a school-based population study within the ASDEU project.

AIMS: This study aims to estimate Autism Spectrum Disorders (ASD) prevalence in school-aged children in the province of Pisa (Italy) using the strategy of the ASD in the European Union (ASDEU) project. METHODS: A multistage approach was used to identify cases in a community sample (N = 10 138) of 7-9-year-old children attending elementary schools in Pisa - Italy. First, the number of children with a disability certificate was collected from the Local Health Authority and an ASD diagnosis was verified by the ASDEU team. Second, a Teacher Nomination form (TN) to identify children at risk for ASD was filled in by teachers who joined the study and the Social Communication Questionnaire (SCQ) was filled in by the parents of children identified as positive by the TN; a comprehensive assessment, which included the Autism Diagnostic Observation Schedule-Second Edition, was performed for children with positive TN and SCQ⩾9. RESULTS: A total of 81 children who had a disability certificate also had ASD (prevalence: 0.79%, i.e. 1/126). Specifically, 66 children (57 males and nine females; 62% with intellectual disability -ID-) were certified with ASD, whereas another 15 (11 males and four females; 80% with ID) were recognised as having ASD among those certified with another neurodevelopmental disorder. Considering the population of 4417 (children belonging to schools which agreed to participate in the TN/SCQ procedure) and using only the number of children certified with ASD, the prevalence (38 in 4417) was 0.86%, i.e. one in 116. As far as this population is concerned, the prevalence rises to 1% if we consider the eight new cases (six males and two females; no subject had ID) identified among children with no pre-existing diagnoses and to 1.15%, i.e., one in 87, if probabilistic estimation is used. CONCLUSIONS: This is the first population-based ASD prevalence study conducted in Italy so far and its results indicate a prevalence of ASD in children aged 7-9 years of about one in 87. This finding may help regional, national and international health planners to improve ASD policies for ASD children and their families in the public healthcare system.