Multicentric Longitudinal Prospective Study in a European Cohort of MYO7A Patients: Disease Course and Implications for Gene Therapy.

Purpose: We investigated the natural history of retinal dystrophy owing to variants in the MYO7A gene. Methods: Fifty-three patients (mean age, 33.6 ± 16.7 years) with Usher syndrome owing to biallelic, mostly pathogenic, variants in MYO7A underwent baseline and two annual follow-up visits. Best-corrected visual acuity (BCVA), semiautomatic kinetic visual field, full-field electroretinogram, color fundus imaging, microperimetry, spectral-domain optical coherence tomography, and fundus autofluorescence were assessed. Results: At baseline, all patients presented with decreased BCVA (66.4 ± 17.9 Early Treatment Diabetic Retinopathy score and 59.5 ± 21.7 Early Treatment Diabetic Retinopathy score, in the better- and worse-seeing eyes, respectively), restricted semiautomatic kinetic visual field (III4e area, 3365.8 ± 4142.1°2; 4176.4 ± 4400.3°2) and decreased macular sensitivity (9.7 ± 9.9 dB; 9.0 ± 10.2 dB). Spectral-domain optical coherence tomography revealed reduced central macular thickness (259.6 ± 63.0 µm; 250.7 ± 63.3 µm) and narrowed ellipsoid zone band width (2807.5 ± 2374.6 µm; 2615.5 ± 2370.4 µm). Longitudinal analyses (50 patients) showed a significant decrease of BCVA in better-seeing eyes, whereas no changes were observed in worse-seeing eyes for any parameter. BCVA, semiautomatic kinetic visual field (III4e and V4e) and macular sensitivity were related significantly to age at baseline. Hyperautofluorescent foveal patch (16 eyes [31.4%]) and abnormal central hypoautofluorescence (9 eyes [17.6%]) were significantly associated with worse morphological and functional read-outs compared with the hyperautofluorescent ring pattern (22 eyes [43.1%]). Conclusions: Our European multicentric study offers the first prospective longitudinal analysis in one of the largest cohorts of MYO7A patients described to date, confirming the slow disease progression. More important, this study emphasizes the key role of fundus autofluorescence patterns in retinal impairment staging and advocates its adoption as an objective biomarker in patient selection for future gene therapy clinical trials.

Antibodies Against ZSCAN1 in Pediatric and Adult Patients With Non-Paraneoplastic ROHHAD Syndrome.

OBJECTIVES: To report the association of zinc finger and SCAN domain containing 1 antibodies (ZSCAN1-abs) with rapid-onset obesity, hypothalamic dysfunction, hypoventilation, and autonomic dysregulation (ROHHAD) syndrome in patients without tumor. METHODS: Patients with symptoms compatible with ROHHAD syndrome but without an associated tumor were selected from our database. Serum and CSF samples were examined for the presence of ZSCAN1-abs by an in-house cell-based assay. In addition, samples from 149 patients with several inflammatory and noninflammatory disorders and 50 healthy participants served as controls. RESULTS: Thirteen patients with ROHHAD syndrome were identified. Of these, we had paired serum/CSF samples from 6 patients and only serum from the other 7. Five of 6 patients (83.3%) with paired serum/CSF (4 children, 1 adult) had ZSCAN-abs only in CSF and 1 had antibodies in serum and CSF. ZSCAN1-abs were not detected in the remaining 7 patients with ROHHAD with only serum available or in any of the 199 control samples. DISCUSSION: Patients with ROHHAD syndrome should be investigated for the presence of ZSCAN1-abs in CSF. The antibodies do not necessarily predict the presence of a tumor. The detection of ZSCAN1-abs in an adult patient suggests that this condition also occurs beyond the pediatric age.

Vitamin D Status in an Italian Pediatric Cohort: Is There a Role for Tobacco Smoking Exposure?

Introduction: Vitamin D deficiency is a common public health issue worldwide. The purpose of this study was to investigate the vitamin D status and its potential determinants in children residing in Sardinia (40°N), Italy. Methods: A total of 182 children (males: 51.7%; median age: 9 years) were enrolled over a 12-month period. Serum 25(OH)D was measured by an immune-chemiluminescence assay. A questionnaire was used to gather information on other variables, including passive smoke exposure. Results: Mean (SD) serum 25(OH)D was 25.2 (8.3) ng/mL for the whole group. The majority (n=123, 67.6%) of children had vitamin D sufficient values >20 ng/mL, while about 1/3 had vitamin D insufficient/deficient values (≤20 ng/mL (n=59, 32.4%). Among the variables investigated, passive smoke exposure was significantly associated with insufficient 25(OH)D levels (p<0.0001). Conclusion: Our results further prove that hypovitaminosis D is common in the Italian children and documented that passive smoke exposure is a significant risk factor for hypovitaminosis D.

Pituitary macroadenomas in childhood and adolescence: a clinical analysis of 7 patients.

BACKGROUND: Pituitary adenomas (PPAs) are uncommon in childhood and adolescence, accounting for 2-6% of all intracranial neoplasms. Delayed puberty, growth retardation, galactorrhea and weight gain are common features at presentation in pediatric patients. Functional tumors constitute a vast majority (90%) of PPAs, with the most frequent being prolactinomas. CASE PRESENTATION: A retrospective review of the clinical features and outcomes of 7 pediatric patients with pituitary macroadenomas was conducted. We included PPAs in patients under 18 years at diagnosis with diameters larger than 10 mm by magnetic resonance (MRI). Six patients were males (85%), with age at diagnosis ranging from 8 to 15 (median 14 ± 2.8SDS). The primary symptoms that led to medical attention were growth retardation, gigantism and secondary amenorrhea. The visual field was reduced in three cases (42%). Suprasellar extension was present in 3 subjects, and one had a giant adenoma. Adenomas were clinically functioning in 6 patients (85%) (three prolactinomas, two somatropinomas, one secreting FSH and one no-producer). The prolactinomas responded to treatment with cabergoline. For the rest, one required transsphenoidal surgery and the other three both surgery and radiotherapy. All patients undergoing radiotherapy had secondary panhypopituitarism. In relation to the genetic studies, two patients presented a pathogenic mutation of the AIP gene and one of the MEN1. DISCUSION AND CONCLUSION: Pediatric pituitary macroadenomas are a distinct entity, mostly found in males and with a predominance of functional tumors leading to detrimental effects on growth and puberty in addition to neuro-ophthalmological manifestations. It is important to perform genetic studies in patients with macroadenomas appearing under the age of 18 years as genetic and syndromic associations are more frequent in this age group.

Hormonal control during infancy and testicular adrenal rest tumor development in males with congenital adrenal hyperplasia: a retrospective multicenter cohort study.

IMPORTANCE: Testicular adrenal rest tumors (TARTs), often found in male patients with congenital adrenal hyperplasia (CAH), are benign lesions causing testicular damage and infertility. We hypothesize that chronically elevated adrenocorticotropic hormone exposure during early life may promote TART development. OBJECTIVE: This study aimed to examine the association between commencing adequate glucocorticoid treatment early after birth and TART development. DESIGN AND PARTICIPANTS: This retrospective multicenter (n = 22) open cohort study collected longitudinal clinical and biochemical data of the first 4 years of life using the I-CAH registry and included 188 male patients (median age 13 years; interquartile range: 10-17) with 21-hydroxylase deficiency (n = 181) or 11-hydroxylase deficiency (n = 7). All patients underwent at least 1 testicular ultrasound. RESULTS: TART was detected in 72 (38%) of the patients. Prevalence varied between centers. When adjusted for CAH phenotype, a delayed CAH diagnosis of >1 year, compared with a diagnosis within 1 month of life, was associated with a 2.6 times higher risk of TART diagnosis. TART onset was not predicted by biochemical disease control or bone age advancement in the first 4 years of life, but increased height standard deviation scores at the end of the 4-year study period were associated with a 27% higher risk of TART diagnosis. CONCLUSIONS AND RELEVANCE: A delayed CAH diagnosis of >1 year vs CAH diagnosis within 1 month after birth was associated with a higher risk of TART development, which may be attributed to poor disease control in early life.

Multimodal Assessment of the Prognostic Role of Ectopic Inner Foveal Layers on Epiretinal Membrane Surgery.

BACKGROUND: To perform a multimodal assessment of the ectopic inner foveal layers' (EIFL) prognostic role on idiopathic epiretinal membrane (ERM) surgery. METHODS: We retrospectively followed-up for 12 months 27 patients who underwent ERM surgery and stratified them based on EIFL presence (group 1) or absence (group 2) at baseline. Central Retinal Thickness (CRT) and best-corrected visual acuity (BCVA) were compared pre- and post-operatively at 1, 4 and 12 months, whereas fixation stability (FS), macular sensitivity (MS) and multifocal electroretinogram (mfERG) responses were confronted at baseline and 12 months. RESULTS: In group 1, BCVA improved at 4 and 12 months (MD = 0.14 (SE = 0.04); MD = 0.13 (SE = 0.05), respectively) as well as in group 2 (MD = 0.31 (SE = 0.07); MD = 0.41 (SE = 0.08), respectively). CRT did not change in group 1, whereas it decreased in group 2 at 4 and 12 months (MD = -73.13; SE = 23.56; MD = -76.20; SE = 23.56). MS showed no changes in both groups after surgery. FS did not change in group 1, whereas group 2 improved FS 2° (+8.91 ± 13.97) and FS 4° (+4.33 ± 3.84). MfERG P1 wave did not change in group 1, while in group 2 αP1-2, αP1-3 and αP1-4 improved postoperatively (27.97 ± 27.62; 12.51 ± 17.36; 10.49 ± 17.19, respectively). CONCLUSIONS: Multimodal assessment confirmed that EIFL negatively affected ERM surgery outcomes.

Pars Plana Vitrectomy in Inherited Retinal Diseases: A Comprehensive Review of the Literature.

Inherited retinal diseases (IRDs) are a group of clinically and genetically heterogeneous disorders that may be complicated by several vitreoretinal conditions requiring a surgical approach. Pars plana vitrectomy (PPV) stands as a valuable treatment option in these cases, but its application in eyes with such severely impaired chorioretinal architectures remains controversial. Furthermore, the spreading of gene therapy and the increasing use of retinal prostheses will end up in a marked increase in demand for PPV surgery for IRD patients. The retinal degeneration that typically affects patients with hereditary retinal disorders may influence the execution of the surgery and the expected results. Considering the importance of PPV application in IRD-related complications, it is fundamental to try to understand from the literature what is adequate and safe in posterior eye segment surgery. Use of dyes, light toxicity, and risk of wounding scar development have always been themes that discourage the execution of vitreoretinal surgery in already impaired eyes. Therefore, this review aims to comprehensively summarize all PPV applications in different IRDs, highlighting the favorable results as well as the potential precautions to consider when performing vitreoretinal surgery in these eyes.

Genetics and Natural History of Non-pancreatectomized Patients With Congenital Hyperinsulinism Due to Variants in ABCC8.

CONTEXT: Patients with congenital hyperinsulinism due to ABCC8 variants generally present severe hypoglycemia and those who do not respond to medical treatment typically undergo pancreatectomy. Few data exist on the natural history of non-pancreatectomized patients. OBJECTIVE: This work aims to describe the genetic characteristics and natural history in a cohort of non-pancreatectomized patients with congenital hyperinsulinism due to variants in the ABCC8 gene. METHODS: Ambispective study of patients with congenital hyperinsulinism with pathogenic or likely pathogenic variants in ABCC8 treated in the last 48 years and who were not pancreatectomized. Continuous glucose monitoring (CGM) has been periodically performed in all patients since 2003. An oral glucose tolerance test was performed if hyperglycemia was detected in the CGM. RESULTS: Eighteen non-pancreatectomized patients with ABCC8 variants were included. Seven (38.9%) patients were heterozygous, 8 (44.4%) compound heterozygous, 2 (11.1%) homozygous, and 1 patient carried 2 variants with incomplete familial segregation studies. Seventeen patients were followed up and 12 (70.6%) of them evolved to spontaneous resolution (median age 6.0 ± 4 years; range, 1-14). Five of these 12 patients (41.7%) subsequently progressed to diabetes with insufficient insulin secretion. Evolution to diabetes was more frequent in patients with biallelic variants in the ABCC8 gene. CONCLUSION: The high remission rate observed in our cohort makes conservative medical treatment a reliable strategy for the management of patients with congenital hyperinsulinism due to ABCC8 variants. In addition, a periodic follow-up of glucose metabolism after remission is recommended, as a significant proportion of patients evolved to impaired glucose tolerance or diabetes (biphasic phenotype).

Yellow Subthreshold Micropulse Laser in Retinal Diseases: An In-Depth Analysis and Review of the Literature.

Yellow subthreshold micropulse laser (YSML) is a retinal laser capable of inducing a biologic response without causing thermal damage to the targeted tissue. The 577-nm YSML is delivered to the retina abiding by different protocols in which wavelength, power, duration, spot size and number of spots can be properly set to achieve the most effective and safe treatment response in various chorioretinal disorders. The ultrashort trains of power modulate the activation of the retinal pigment epithelium cells and intraretinal cells, such as Müller cells, causing no visible retinal scars. Subthreshold energy delivered by YSML stimulates the production of the heat-shock proteins, highly conserved molecules that protect cells against any sort of stress by blocking apoptotic and inflammatory pathways that cause cell damage. YSML treatment allows resorption of the subretinal fluid in central serous chorioretinopathy and intraretinal fluid in various conditions including diabetic macular edema, postoperative cystoid macular edema and other miscellaneous conditions. YSML also seems to modulate the development and progression of reticular pseudodrusen in dry age-related macular degeneration. The aim of this review is to discuss and summarize the safety and efficacy of YSML treatment in retinal diseases.

An update on ophthalmological perspectives in oculodermal melanocytosis (Nevus of Ota).

PURPOSE: To provide a review of the literature on oculodermal melanocytosis (ODM) with a focus on the diagnostic and therapeutic implications of multimodal imaging techniques in the management of ophthalmic complications. METHODS: The authors carried out a literature search on PubMed, Medline, and Scopus of English language articles published on ODM through August 2021. This review presents traditional and novel diagnostic methods in the diagnosis and follow-up of patients with particular emphasis on addressing the role of imaging in the management of the ophthalmic complications of the condition towards improving current practice patterns. RESULTS: ODM is a rare, prevalently unilateral, congenital condition that presents with brown or blue/gray flat asymptomatic lesions of the skin, mucosae, episclera/sclera, and uvea localized within the territory of distribution of the ophthalmic and mandibular branches of the trigeminal nerve. Glaucoma and predisposition to uveal melanoma are the main ophthalmic complications. Diagnosis and management are through comprehensive opthalmological examination and traditional imaging methods such as ultrasonography and fluorescein/indocyanine green angiography as pigmentation of the fundus can conceal subtle retinal and choroidal alterations. Anterior segment optical coherence tomography and ultrasound biomicroscopy are used to evaluate the anterior segment and the ciliary body in the presence of glaucoma or melanoma of the anterior uveal tract. Fundus autofluorescence and retinal pigment epithelium (RPE) alterations are of aid in the differential diagnosis between choroidal nevi and melanoma. Enhanced depth imaging spectral domain optical coherence tomography offers outstanding in vivo evaluation of the dimensions and details of tumors or nevi and surrounding choroidal tissues and small choroidal melanomas may show distortions of the retinal and sub-retinal profile, presence of intra and sub-retinal fluid, abnormalities of the RPE, and compression of the choriocapillaris. CONCLUSIONS: Novel multimodal imaging techniques are significant in the diagnosis and management of the ophthalmic complications of ODM. Fundus autofluorescence and enhanced depth spectral domain optical coherence tomography have adjunctive value in the detection of early-stage melanoma and differential diagnosis between nevi and melanoma. Awareness of current and emerging imaging techniques can propagate improved standardized definition and assessment of the complications of ODM.

Analysis of therapy monitoring in the International Congenital Adrenal Hyperplasia Registry.

OBJECTIVE: Congenital adrenal hyperplasia (CAH) requires exogenous steroid replacement. Treatment is commonly monitored by measuring 17-OH progesterone (17OHP) and androstenedione (D4). DESIGN: Retrospective cohort study using real-world data to evaluate 17OHP and D4 in relation to hydrocortisone (HC) dose in CAH patients treated in 14 countries. PATIENTS: Pseudonymized data from children with 21-hydroxylase deficiency (21OHD) recorded in the International CAH Registry. MEASUREMENTS: Assessments between January 2000 and October 2020 in patients prescribed HC were reviewed to summarise biomarkers 17OHP and D4 and HC dose. Longitudinal assessment of measures was carried out using linear mixed-effects models (LMEM). RESULTS: Cohort of 345 patients, 52.2% female, median age 4.3 years (interquartile range: 3.1-9.2) were taking a median 11.3 mg/m2 /day (8.6-14.4) of HC. Median 17OHP was 35.7 nmol/l (3.0-104.0). Median D4 under 12 years was 0 nmol/L (0-2.0) and above 12 years was 10.5 nmol/L (3.9-21.0). There were significant differences in biomarker values between centres (p < 0.05). Correlation between D4 and 17OHP was good in multiple regression with age (p < 0.001, R2 = 0.29). In longitudinal assessment, 17OHP levels did not change with age, whereas D4 levels increased with age (p < 0.001, R2 = 0.08). Neither biomarker varied directly with dose or weight (p > 0.05). Multivariate LMEM showed HC dose decreasing by 1.0 mg/m2 /day for every 1 point increase in weight standard deviation score. DISCUSSION: Registry data show large variability in 17OHP and D4 between centres. 17OHP correlates with D4 well when accounting for age. Prescribed HC dose per body surface area decreased with weight gain.

Lung ultrasound in Italian neonatal intensive care units: A national survey.

INTRODUCTION: Lung ultrasound (LU) is a noninvasive, bedside imaging technique that is attracting growing interest in the evaluation of neonatal respiratory diseases. We conducted a nationwide survey of LU usage in Italian neonatal intensive care units (NICUs). METHODS: A structured questionnaire was developed and sent online to 114 Italian NICUs from June to September 2021. RESULTS: The response rate was 79%. In the past 4 years (range: 2-6), LU has been adopted in 82% of Italian NICUs. It is the first-choice diagnostic test in 23% of the centers surveyed. The main LU diagnostic applications reported were: pneumothorax (95%), respiratory distress syndrome (89%), transient tachypnea of the newborn (89%), plural effusion (88%), atelectasis (66%), pneumonia (64%), bronchopulmonary dysplasia (43%), congenital pulmonary airway malformation (41%), and congenital diaphragmatic hernia (34%). Thirty percent of participating centers calculated LU score routinely, but only seven units used it to predict the need for surfactant replacement. Sixty-six percent of respondents learned the LU technique via a self-training process, while 34% of them visited an expert in the field for one-to-one tuition. CONCLUSIONS: LU has a widespread use in Italian NICUs. However, the use of LU is extremely heterogeneous among centers. There is an urgent need to ensure standardization of clinical practice guidelines and to design and implement a formalized and accredited training program.

Safety and Efficacy of the New Combination Iron Chelation Regimens in Patients with Transfusion-Dependent Thalassemia and Severe Iron Overload.

The aim of this study is the evaluation of the safety and the efficacy of long-term combination therapy deferasirox plus desferrioxamine and deferasirox plus deferiprone in a large group of transfusion-dependent thalassemia patients with high values of serum ferritin and/or magnetic resonance, indicative of severe liver and cardiac iron accumulation. Sixteen adults with transfusion-dependent thalassemia were treated simultaneously with deferasirox plus desferrioxamine, while another 42 patients (seven children) were treated with deferasirox plus deferiprone. The hepatic and cardiac iron overload was assessed prior to treatment and then annually with magnetic resonance imaging, and the serum ferritin was measured monthly. Adverse events were checked at each transfusion visit. The safety of both the combinations was consistent with established monotherapies. Both treatments were able to decrease the serum ferritin and liver iron concentration over time, depending on the level of compliance with therapy. Cardiac iron measured as R2* did not significantly change in patients treated with deferasirox plus desferrioxamine. Most patients with MRI indicative of myocardial siderosis at the beginning of treatment reached normal values of cardiac iron at the last determination if treated with deferasirox plus desferrioxamine. The greatest limitation of these therapies was low patient adherence to the two drugs, which is not surprising considering that the need for an intensive chelation is generally linked to previous issues of compliance.

Lung ultrasound scores in neonatal clinical practice: A narrative review of the literature.

Lung ultrasound (LU) has in recent years increasingly been used as a point-of-care method. Initially, LU was used as a so-called descriptive diagnostic method for neonatal respiratory diseases. Instead, this review article focuses on the use of LU as a "functional" tool using classification of findings in patterns or using semiquantitative scores. We review and describe the evidence that led to the implementation of LU in predicting the need for surfactant replacement therapy in preterm infants and in the identification of newborns at risk of developing bronchopulmonary dysplasia. LU appears to be a very promising method for the future of clinical management of newborns in both acute and chronic phases of pulmonary pathologies related to prematurity. However, further studies are needed to define its role before full implementation.

Impact of Aortic Diameter Measurements at Three Anatomical Landmarks on Left Ventricular Output Calculation in Neonates.

OBJECTIVES: To assess reproducibility and accuracy of left ventricular output (LVO) quantifications in neonates, when left ventricular outflow tract diameter (LVOTD) was measured at the hinges of the aortic valve (AV), at the aortic sinus (AS), and at the sinotubular junction (STJ). METHODS: This was an observational study. In the first cohort of very preterm neonates, we assessed intraobserver and interobserver repeatability of LVOTD measured at the AV, AS, and STJ and of the corresponding LVO. In the second cohort of older neonates, we compared paired LVO measurements by echo and magnetic resonance imaging (MRI). RESULTS: In the first cohort of 48 neonates, mean (standard deviation) weight and age at scan were 1046 (302) g and 28.1 (2.7) weeks. Interobserver bias (95% limits of agreement [LOA]) for LVOTD at the AV, AS, and STJ was 0 (-0.3 to 0.3) mm, 0 (-0.7 to 0.7) mm, and 0 (-0.8 to 0.7) mm, respectively. Interobserver bias (95% LOA) for the corresponding LVO was -1.3 (-31 to 33) ml/kg/min, -0.5 (-88 to 87) ml/kg/min, and -7.2 (-83 to 69) ml/kg/min, respectively. In the second cohort of 10 neonates, median (range) weight and age at scan were 1942 (970-3640) g and 37.2 (31.7-39.8) weeks. LVO measured at the AV showed stronger agreement with MRI: bias (LOA) -10.6 (-74 to 52) ml/kg/min, compared to LVO measured at AS and STJ: 194 (-0.5 to 388) ml/kg/min and 43 (-72 to 159) ml/kg/min respectively. CONCLUSIONS: Reproducibility and accuracy of LVO quantification by echo were better when aortic diameter was measured at AV.

Therapy options for adrenal insufficiency and recommendations for the management of adrenal crisis.

Adrenal insufficiency (AI) is a life-threatening condition requiring life-long glucocorticoid (GC) substitution therapy, as well as stress adaptation to prevent adrenal crises. The number of individuals with primary and secondary adrenal insufficiency in Europe is estimated to be 20-50/100.000. A growing number of AI cases are due to side effects of GC treatment used in different treatment strategies for cancer and to immunotherapy in cancer treatment. The benefit of hormone replacement therapy is evident but long-term adverse effects may arise due to the non-physiological GC doses and treatment regimens used. Given multiple GC replacement formulations available comprising short-acting, intermediate, long-acting and novel modified-release hydrocortisone as well as subcutaneous formulations, this review offers a concise summary on the latest therapeutic improvements for treatment of AI and prevention of adrenal crises. As availability of various glucocorticoid formulations and access to expert centers across Europe varies widely, European Reference Networks on rare endocrine conditions aim at harmonizing treatment and ensure access to specialized patient care for individual case-by-case treatment decisions. To improve the availability across Europe to cost effective oral and parenteral formulations of hydrocortisone will save lives.

Growth Hormone Treatment and Papilledema: A Prospective Pilot Study

Objective: To investigate the incidence of pseudotumor cerebri syndrome (PTCS) in children treated with growth hormone (GH) in a paediatric hospital and to identify risk factors for this complication. Methods: Prospective pilot study of paediatric patients treated with recombinant human GH, prescribed by the Paediatric Endocrinology Department, between February 2013 and September 2017. In all these patients, a fundus examination was performed before starting treatment and 3-4 months later. Results: Two hundred and eighty-nine patients were included, of whom 244 (84.4%) had GH deficiency, 36 (12.5%) had short stature associated with small for gestational age, six (2.1%) had a mutation in the SHOX gene and three (1.0%) had Prader-Willi syndrome. Five (1.7%) developed papilledema, all were asymptomatic and had GH deficiency due to craniopharyngioma (n=1), polymalformative syndrome associated with hypothalamic-pituitary axis anomalies (n=2), a non-specified genetic disease with hippocampal inversion (n=1) and one with normal magnetic resonance imaging who had developed a primary PTCS years before. Conclusion: GH treatment is a cause of PTCS. In our series, at risk patients had GH deficiency and hypothalamic-pituitary anatomic anomalies or genetic or chromosomal diseases. Fundus examination should be systematically screened in all patients in this at-risk group, irrespective of the presence or not of symptoms.

Niobium on BEA Dealuminated Zeolite for High Selectivity Dehydration Reactions of Ethanol and Xylose into Diethyl Ether and Furfural.

In this work, we investigated the role of solid-state dealumination by (NH4)2SiF6 (25% Al removal and 13% Si insertion), the impregnation of niobium (10, 18, and 25 wt. %) on dealuminated *BEA (DB) zeolite and their catalytic properties in ethanol and xylose transformations. Among all the studied catalysts, 18%Nb-DB showed increased mesoporosity and external areas. A leveling effect in the number and strength of the proposed two sites (Brønsted and Lewis) present in the catalyst (n1 = 0.24 mmol g-1, -ΔH1 = 49 kJ mol-1, and n2 = 0.20 mmol g-1, -ΔH2 = 42 kJ mol-1) in the catalyst 18%Nb-DB, might be responsible for its good activity. This catalyst presented the highest selectivity for diethyl ether, DEE (97%) with 61% conversion after 50 ethanol pulses at 230 °C (turnover number, TON DEE = 1.15). These features allowed catalytically fruitful bonding of the ethanol molecules to the neighboring sites on the channels, facilitating bimolecular ether formation through a possible SN2 mechanism. The same catalyst was active and selective for transformation of xylose at 180 °C, showing 64% conversion and 51% selectivity for furfural (TON Furfural = 24.7) using water as a green solvent.

Dietary Compounds To Reduce In Vivo Inorganic Arsenic Bioavailability.

It is estimated that approximately 200 million people are exposed to arsenic levels above the World Health Organization provisional guideline value, and various agencies have indicated the need to reduce this exposure. In view of the difficulty of removing arsenic from water and food, one alternative is to reduce its bioavailability (the amount that reaches the systemic circulation after ingestion). In this study, dietary components [glutathione, tannic acid, and Fe(III)] were used to achieve this goal. As(III) or As(V) (1 mg/kg body weight) was administered daily to BALB/c mice, along with the dietary components, for 15 days. The results confirm the efficacy of Fe(III) and glutathione as reducers of arsenic bioavailability and tissue accumulation. Also, these treatments did not result in reductions of Ca, K, P, and Fe contents in the liver. These data suggest that use of these two compounds could be part of valid strategies for reducing inorganic arsenic exposure in chronically exposed populations.