A holistic picture of spatial distribution of river polluting loads in a highly anthropized area.

For many years, there has been a debate on the polluting loads affecting the Gulf of Naples, one of Italy's most spectacular and iconic landscape. The wide territory bordering the Gulf includes the Sarno river basin (SRB) managed by the Southern Apennines River Basin District Authority in the framework of Unit of Management Sarno (UoM-Sarno). The paper investigated the anthropogenic pressures and their spatial distribution in the UoM-Sarno, revealing as SRB represents a hotspot of pollution mainly due to the high population density and widespread hydro-demanding activities which are responsible of high organic and eutrophication loads. The pollution sources, variably distributed on the area, and potentially conveyed to the wastewater treatment plants (WWTPs) located into SRB, were estimated considering the WWTPs treatment capacity as well. Results revealed a holistic picture of UoM-Sarno area allowing to establish the priorities of the interventions aimed at safeguarding the coastal marine resources. In particular, 2590 tons BOD/year were directly discharged into the Gulf of Naples due to the missing of sewers, and other 10,600 tons BOD/year are potentially discharged in the Sarno river reaching the sea, considering the contribution of population, industrial activity, and livestock.

Prevalence of exercise-induced oxygen desaturation after recovery from SARS-CoV-2 pneumonia and use of lung ultrasound to predict need for pulmonary rehabilitation.

BACKGROUND: Persistence of breathlessness after recovery from SARS-CoV-2 pneumonia is frequent. Recovery from acute respiratory failure (ARF) is usually determined by normalized arterial blood gases (ABGs), but the prevalence of persistent exercise-induced desaturation (EID) and dyspnea is still unknown. METHODS: We investigated the prevalence of EID in 70 patients with normal arterial oxygen at rest after recovery from ARF due to COVID-19 pneumonia. Patients underwent a 6-min walking test (6MWT) before discharge from hospital. We recorded dyspnea score and heart rate during 6MWT. We also investigated the possible role of lung ultrasound (LU) in predicting EID. Patients underwent a LU scan and scores for each explored area were summed to give a total LU score. RESULTS: In 30 patients (43%), oxygen desaturation was >4% during 6MWT. These patients had significantly higher dyspnea and heart rate compared to non-desaturators. LU score >8.5 was significantly able to discriminate patients with EID. CONCLUSION: In SARS-CoV-2 pneumonia, ABGs at discharge cannot predict the persistence of EID, which is frequent. LU may be useful to identify patients at risk who could benefit from a rehabilitation program.

Disinfection of roof harvested rainwater inoculated with E. coli and Enterococcus and post-treatment bacterial regrowth: Conventional vs solar driven advanced oxidation processes.

Solar driven advanced oxidation processes (AOPs) (an alternative solar photo Fenton like process (SPF), sunlight/H2O2 (SHP) and sunlight/chlorine (SCL)) and respective dark conditions, were compared for the first time to conventional (chlorination and UV-C radiation) disinfection processes, in the inactivation of E. coli and Entero strains inoculated in real roof-harvested rainwater (RHRW), to evaluate their possible safe use for crop irrigation. In this regard, bacterial regrowth was also evaluated 6, 12, 24 and 48 h after disinfection treatment. The SPF, using iminodisuccinic acid (IDS)-Cu complex as catalyst, was optimized (H2O2/IDS-Cu 55/1 best molar ratio) under mild conditions (spontaneous pH) and sunlight. The faster inactivation kinetics were observed for the SCL process (k = 1.473 min-1, t1/2 = 0.47 min for E. coli and k = 1.193 min-1, t1/2 = 0.57 min for Entero), while the most effective processes in controlling bacterial regrowth were SPF and SCL. Although UV-C radiation (0-1.3 × 104 µW s cm-2 dose range) was the second faster disinfection process (k = 1.242 min-1, t1/2 = 0.55 min for E. coli and k = 1.150 min-1, t1/2 = 0.60 min for Entero), it was the less effective process in controlling bacterial regrowth (>10 CFU 100 mL-1 already after 6 h post-treatment incubation). According to the bacterial inactivation and regrowth tests carried out in this work, SPF and SCL are interesting options for RHRW disinfection, in case of effluent use for crop irrigation.

Removal of carbamazepine, diclofenac and trimethoprim by solar driven advanced oxidation processes in a compound triangular collector based reactor: A comparison between homogeneous and heterogeneous processes.

Contaminants of emerging concern (including pharmaceuticals) are not effectively removed by municipal wastewater treatment plants (WWTPs), so particular concern is related to agricultural wastewater reuse due to their possible uptake in crops irrigated with WWTPs effluents. Advanced oxidation processes (AOPs) and solar AOPs have been demonstrated to effectively remove pharmaceuticals from different aqueous matrices. In this study, an heterogeneous photocatalytic process using powdered nitrogen-doped TiO2 immobilized on polystyrene spheres (sunlight/N-TiO2) was compared to the benchmark homogenous AOP sunlight/H2O2 in a compound triangular collector reactor, to evaluate the degradation of three pharmaceuticals (carbamazepine (CBZ), diclofenac (DCF), trimethoprim (TMP)) in water. The degradation of the contaminants by sunlight and sunlight-AOPs well fit the pseudo-first order kinetic model (but for TMP under sunlight). High removal efficiency by solar photolysis was observed for DCF (up to 100%, half-life sunlight cumulative energy QS,1/2 = 2 kJ L-1, half-life time t1/2 = 32 min), while CBZ (32%, QS,1/2 = 28 kJ L-1, t1/2 = 385 min) and TMP (5% removal after 300 min) removal was poor. The degradation rate of CBZ, TMP and DCF was found to be slower during sunlight/H2O2 (QS,1/2 = 5 kJ L-1, t1/2 = 77 min; QS,1/2 = 20 kJ L-1, t1/2 = 128 min; QS,1/2 = 4 kJ L-1, t1/2 = 27 min, respectively) compared to sunlight/N-TiO2 (QS,1/2 = 4 kJ L-1, t1/2 = 55 min; QS,1/2 = 3 kJ L-1, t1/2 = 42 min; QS,1/2 = 2 kJ L-1, t1/2 = 25 min, respectively). These results are promising in terms of solar technology upscale because the faster degradation kinetics observed for sunlight/N-TiO2 process would result in smaller treatment volume, thus possibly perspective compensating the cost of the photocatalyst.

Effects of ZnO nanoparticles in the Caspian roach (Rutilus rutilus caspicus).

Most studies investigating the toxicity of zinc oxide nanoparticles (ZnO NPs) focused on the effect of size, whereas exposure concentration and duration remained poorly understood. In this study, the effect of acute and sub-acute exposures of ZnO NPs on Zn compartmentalization and biomarkers' expression were investigated in Rutilus rutilus caspicus (Caspian roach) considering various exposure scenarios: i) the assessment of the concentration-response curves and median lethal concentration (LC50); ii) the assessment of the effects of organisms exposed at LC50 value and one tenth of LC50 value of ZnO NPs suspensions for 4 d and 28 d, respectively; iii) the assessment of 14 d depuration period. The same concentrations of ZnSO4 were investigated. The highest Zn accumulation was detected in gill after sub-acute exposure (4.8 mg/L; 28 d) followed by liver, kidney and muscle. In gill, liver and muscle, Zn from Zn NPs accumulated higher concentrations. Depuration (14 d) decreased Zn content in each organ, but no complete removal occurred except for muscle. Biomarkers' activity was significantly over expressed after treatments, but depuration brought back their values to background levels and most effects were related to acute concentrations (48 mg/L; 4 d) and in presence of ZnSO4. Histopathological analyses showed that the exposure to ZnO NPs increased lesions in gill, liver and kidney, with a direct proportionality between alterations and Zn accumulated in the target organs. After depuration, lesions regressed for both ZnO NPs and ZnSO4, but not in a complete way. These data could contribute to increase the knowledge about ZnO NPs risk assessment in aquatic vertebrates, suggesting that the size of ZnO NPs can influence biomarker and histopathological effects.

Electroclinical findings and long-term outcomes in epileptic patients with inv dup (15).

OBJECTIVE: To define the electroclinical phenotype and long-term outcomes in a cohort of patients with inv dup (15) syndrome. MATERIAL AND METHODS: The electroclinical data of 45 patients (25 males) affected by inv dup (15) and seizures were retrospectively analysed, and long-term follow-up of epilepsy was evaluated. RESULTS: Epilepsy onset was marked by generalized seizures in 53% of patients, epileptic spasms in 51%, focal seizures in 26%, atypical absences in 11% and epileptic falls in 9%. The epileptic syndromes defined were: generalized epilepsy (26.7%), focal epilepsy (22.3%), epileptic encephalopathy with epileptic spasms as the only seizure type (17.7%) and Lennox-Gastaut syndrome (33.3%). Drug-resistant epilepsy was detected in 55.5% of patients. There was a significant higher prevalence of seizure-free patients in those with seizure onset after the age of 5 years and with focal epilepsy, with respect to those with earlier epilepsy onset because most of these later developed an epileptic encephalopathy (69.2% vs 34.4%; P = .03), usually Lennox-Gastaut Syndrome in type. In fact, among patients with early-onset epilepsy, those presenting with epileptic spasms as the only seizure type associated with classical hypsarrhythmia achieved seizure freedom (P < .001) compared to patients with spasms and other seizure types associated with modified hypsarrhythmia. CONCLUSIONS: Epilepsy in inv dup (15) leads to a more severe burden of disease. Frequently, these patients show drug resistance, in particular when epilepsy onset is before the age of five and features epileptic encephalopathy.

Municipal wastewater spiramycin removal by conventional treatments and heterogeneous photocatalysis.

This study assessed the effects and removal options of the macrolide spiramycin, currently used for both in human and veterinary medicine- with a special focus on advanced oxidation processes based on heterogeneous TiO2_assisted photocatalysis. Spiramycin real concentrations were investigated on a seasonal basis in a municipal wastewater treatment plant (up to 35µgL-1), while its removal kinetics were studied considering both aqueous solutions and real wastewater samples, including by-products toxicity assessment. High variability of spiramycin removal by activated sludge treatments (from 9% (wintertime) to >99.9% (summertime)) was observed on a seasonal basis. Preliminary results showed that a total spiramycin removal (>99.9%) is achieved with 0.1gL-1 of TiO2 in aqueous solution after 80min. Integrated toxicity showed residual slight acute effects in the photocatalytic treated solutions, independently from the amount of TiO2 used, and could be linked to the presence of intermediate compounds. Photolysis of wastewater samples collected after activated sludge treatment during summer season (SPY 5µgL-1) allowed a full SPY removal after 80min. When photocatalysis with 0.1gL-1 of TiO2 was carried out in wastewater samples collected in winter season (SPY 30µgL-1) after AS treatment, SPY removal was up to 91% after 80min.

Emerging Concern from Short-Term Textile Leaching: A Preliminary Ecotoxicological Survey.

Textile dyes and their residues gained growing attention worldwide. Textile industry is a strong water consumer potentially releasing xenobiotics from washing and rinsing procedures during finishing processes. On a decentralised basis, also final consumers generate textile waste streams. Thus, a procedure simulating home washing with tap water screened cotton textiles leachates (n = 28) considering physico-chemical (COD, BOD5, and UV absorbance) and ecotoxicological data (Daphnia magna, Pseudokirchneriella subcapitata and Lepidium sativum). Results evidenced that: (i) leachates presented low biodegradability levels; (ii) toxicity in more than half leachates presented slight acute or acute effects; (iii) the remaining leachates presented "no effect" suggesting the use of green dyes/additives, and/or well established finishing processes; (iv) no specific correlations were found between traditional physico-chemical and ecotoxicological data. Further investigations will be necessary to identify textile residues, and their potential interactions with simulated human sweat in order to evidence potential adverse effects on human health.

Children with developmental dyslexia showed greater sleep disturbances than controls, including problems initiating and maintaining sleep.

AIM: Although there have been frequent clinical reports about sleep disturbances in children with learning disabilities, no data are available about the prevalence of sleep disturbances in children with developmental dyslexia (DD). This study evaluated sleep disturbances in children with DD referred to a hospital clinic and compared their scores with healthy controls. METHODS: We consecutively enrolled 147 children (66% male) aged 10.26 ± 2.63 years who were referred by clinical paediatricians to the Clinic for Child and Adolescent Neuropsychiatry at the Second University of Naples with DD and 766 children without DD (60% male) aged 10.49 ± 2.39 years recruited from schools in the same urban area. Sleep disturbances were assessed with the Sleep Disturbances Scale for Children (SDSC), which was filled out by the children's main carers. RESULTS: Compared with the controls, the children with DD showed significantly higher rates of above threshold scores on the total SDSC score (p < 0.001) and on the subscales for disorders in initiating and maintaining sleep (p < 0.001), sleep breathing disorders (p < 0.001) and disorders of arousal (p < 0.001). CONCLUSION: Sleep disorders were significantly more frequent in children with DD than in healthy controls. A possible relationship between dyslexia and sleep disorders may have relevant clinical implications.

Migraine and obesity: metabolic parameters and response to a weight loss programme.

BACKGROUND AND OBJECTIVE: Weight loss can determine significant improvement of migraine in obese patients. Herein, we evaluated a clinical sample of adolescent migraineurs with obesity who participated in an interdisciplinary programme for weight loss, in order to identify possible metabolic parameters associated with good migraine control. SUBJECTS AND METHODS: Using a cross-sectional design, we evaluated 112 out of 135 adolescents who previously underwent our intervention programme. Based on persistence of headache, subjects for comparison were 40 migraine-free and 72 not migraine-free adolescents. Participants underwent anthropometric evaluations and biochemical tests. RESULTS: Patients with persistence of migraine had significantly higher weight (P < 0.01), body mass index (P < 0.01), waist circumference (P < 0.01), homeostasis model assessment of insulin resistance (P < 0.001), triglyceride (P < 0.05), total cholesterol (P < 0.05) and low-density lipoprotein cholesterol (P < 0.05) values when compared with those who became migraine-free. Between potential predictors, only insulin resistance (odds ratio = 3.5, 95% confidence interval = 1.4-6.1; P < 0.001) was significantly associated with persistence of migraine after intervention programme. CONCLUSIONS: Among obese adolescents with migraine who underwent an intervention programme for weight loss, patients who did not become migraine-free showed higher adiposity values than those who became migraine-free. Patients with insulin resistance had 3.5 times the odds of having persistence of migraine compared with those without.

Intellectual disabilities and power spectra analysis during sleep: a new perspective on borderline intellectual functioning.

BACKGROUND: The role of sleep in cognitive processes has been confirmed by a growing number of reports for all ages of life. Analysing sleep electroencephalogram (EEG) spectra may be useful to study cortical organisation in individuals with Borderline Intellectual Functioning (BIF), as seen in other disturbances even if it is not considered a disease. The aim of this study was to determine if the sleep EEG power spectra in children with BIF could be different from typically developing children. METHODS: Eighteen BIF (12 males) (mean age 11.04; SD ± 1.07) and 24 typical developing children (14 men) (mean age 10.98; SD ± 1.76; P = 0.899) underwent an overnight polysomnography (PSG) recording in the Sleep Laboratory of the Clinic of Child and Adolescent Neuropsychiatry, after one adaptation night. Sleep was subdivided into 30-s epochs and sleep stages were scored according to the standard criteria and the power spectra were calculated for the Cz-A2 channel using the sleep analysis software Hypnolab 1.2 (SWS Soft, Italy) by means of the Fast Fourier Transform and the power spectrum was calculated for frequencies between 0.5 and 60 Hz with a frequency step of 1 Hz and then averaged across the following bands delta (0.5-4 Hz), theta (5-7 Hz), alpha (8-11 Hz), sigma (11-15 Hz), and beta (16-30 Hz), gamma (30-60 Hz) for S2, SWS and REM (Rapid Eye Movement) sleep stages. RESULTS: BIF have a reduced sleep duration (total sleep time; P < 0.001), and an increased rate of stage shifts (P < 0.001) and awakenings (P < 0.001) and WASO (wakefulness after sleep onset) % (P < 0.001); the stage 2% (P < 0.001), and REM% (P < 0.001) were lower and slow-wave sleep percentage was slightly higher (P < 0.001). All children with BIF had an AHI (apnoea-hypopnea index) less than 1 (mean AHI = 0.691 ± 0.236) with a mean oxygen saturation of 97.6% and a periodic leg movement index (PLMI) less than 5 (mean PLMI = 2.94 ± 1.56). All sleep stages had a significant reduction in gamma frequency (30-60 Hz) (P < 0.001) and an increased delta frequency (0.5-4.0 Hz) (P < 0.001) power in BIF subjects compared with typically developing children. CONCLUSION: Our findings shed light on the importance of sleep for cognition processes particularly in cognitive borderline dysfunction and the role of EEG spectral power analysis to recognize sleep characteristics in BIF children.

The quality of life in developing age children with celiac disease.

AIM: The moments that follow the diagnosis of celiac disease and the early stages of the gluten-free diet are extremely difficult and complex for parents and child, because they face an important change punctuated by self-denial and deprivation. The main objective of this research is to assess the impact of celiac disease on quality of life in subjects in developmental age, taking into account the perceptions of parents about the child's illness, with the aim to highlight the effect of disease on the child and the entire family. METHODS: The study included both parents of 45 children aged between 2 and 10 years, with established celiac disease. To evaluate the effect of celiac disease on the lifestyle of affected children and their families has been used, after having adapted to the Italian context, the Impact Scale of Childhood Diseases of Hoare and Russell (1995). This study shows that celiac disease is a condition that has a significant impact on both the child and his family. RESULTS AND CONCLUSION: The results obtained by administration of Impact Scale of Childhood Diseases to parents showed that subjects in developmental age with celiac disease could have difficulty on emotional level that affect child development and the whole family context. Acceptance of the illness by the child depends mainly by how much and how this has been accepted by parents.

Impact of a weight loss program on migraine in obese adolescents.

BACKGROUND AND PURPOSE: Increased headache frequency and severity have been observed in obese populations, but the real impact of a weight loss treatment on headache has not been studied. We investigated this issue in a sample of obese adolescents. METHODS: In all, 135 migraineurs, aged 14-18 years, with body mass index (BMI) ≥ 97 th percentile, participating in a 12-month-long program, were studied before and after treatment. The program included dietary education, specific physical training, and behavioral treatment. RESULTS: Decreases in weight (P < 0.01), BMI (P < 0.01), waist circumference (P < 0.01), headache frequency (P < 0.01) and intensity (P < 0.01), use of acute medications (P < 0.05), and disability (P < 0.05) were observed at the end of the first 6-month period and were maintained through the second 6 months. Both lower baseline BMI and excess change in BMI were significantly associated with better migraine outcomes 12 months after the intervention program. CONCLUSIONS: Significant improvements in both adiposity and headache data were observed in obese adolescents with migraine who participated in a 12-month-long interdisciplinary intervention program for weight loss. Initial body weight and amount of weight loss may be useful for clinicians to predict migraine outcomes.

Primary nocturnal enuresis and learning disability.

AIM: Primary nocturnal enuresis (PNE) is the most common sleep disorder in developmental age, with a prevalence of 6-10% between 5 and 16 years of age, impacting on normal emotional and relational developing. Assessing the prevalence of mild learning disorders in enuretic children and the role of enuresis as risk factor to develop them. METHODS: Twenty-five patients (14 males) aged 7.59 referred for primary nocturnal enuresis to Sleep Disorder Center for developmental age and Nocturnal Enuresis of Second University of Naples (frequency ≥3/week), were enrolled in study. Reading abilities were evaluated using MT (Memory and Learning Transfer) and cognitive performance was assessed using Wechsler Intelligence Scale for Children-Revised version to excluded the subjects with IQ≤75. The control group consisted in 54 children (23 males) matched for age and sex distribution recruited in Campania region schools. Chi Square test was used to verify the different prevalence of academic problems in group of bedwetters and healthy controls. The P level was set at <0.05 for statistical significance. A logistic regression analysis was performed in order to assess the risk of developing learning disabilities by being enuretic. RESULTS: Learning difficulties were present in 18 enuretic and in 7 healthy children (χ2 24.873; P<0.001). χ2 test showed a statistic relevant difference in prevalence of "Attention request" (χ2 20.058; P<0.001) and "Border-line level" (χ2 12.979, P<0.001) identified in mild reading learning disorders in bedwetters respect of control group. Logistic regression analysis showed a strong increase to have mild academic impairment due to be a enuretic with an odd ratio (OR) of 17.26 (CI95% 5.30-56.19). CONCLUSION: Our study shows the higher pre-valence of mild reading difficulties in enuretic children than controls.

Cosleeping in childhood migraine.

AIM: Cosleeping is the practice of parents and children sleeping together in body contact for all or part of the night. There is a close relationship between sleep habits and headache disorders. Aim of the study was to identify prevalence of cosleeping in children with migraine disorder. METHODS: A total of 181 school-aged children referred to Headache Center for Developmental Age for Migraine without aura (MoA). Sex and age matched control group consists of 729 children recruited in schools in Campania. RESULTS: Cosleeping's prevalence is higher in children with MoA than in the control group (P=0.003) and an OR of 2.32 (95% CI 1.36-3.97). CONCLUSION: At our knowledge, our study is the first specific on prevalence of cosleeping in MoA school-aged children and show the importance of migraine power to invade all aspect of life of children affecting also their family management.

Quality of thermoplasticized and single point root fillings assessed by micro-computed tomography.

AIM: To evaluate ex vivo the quality of root fillings completed by two thermoplasticized gutta-percha techniques (Thermafil and System B) and a cold gutta-percha technique (single point) by µCT analysis. METHODOLOGY: A total of 30 freshly extracted human single-rooted permanent teeth were selected. Root canals were prepared with ProTaper Universal instruments and then randomly divided into three groups (n = 10) depending on the filling technique. In group 1, canals were filled with a single-point technique; group 2 was filled with Thermafil; in group 3 System B was used. In group 1 and group 3, the root filling was performed using ProTaper Universal gutta-percha points, in group 2 Thermafil obturators were used; AH-Plus sealer was used in all groups. Assessment of the root filling was carried out by µCT, using a desktop X-ray micro focus CT scanner. Percentage of root canal filling materials and voids was calculated for each specimen. Data were statistically analysed using Kruskal-Wallis test (P < 0.05). RESULTS: Mean percentages of filling materials were 98.379 ± 1.204 in the single-point group, 99.023 ± 1.457 in Thermafil group, and 98.167 ± 3.432 in System B group. No statistically significant difference was found amongst the groups. CONCLUSION: All techniques produced comparable results in terms of percentage of filling and void distribution.

Migraine and enuresis in children: An unusual correlation?

Several reports in the medical literature suggest the existence of a correlation and/or comorbidity between sleep disorders and headache, linked to probably common pathophysiological substrates. Undoubtedly, migraine and primary nocturnal enuresis (PNE) are different diseases, normally diagnosed and evaluated in independent way even if it is possible to find some common points. The possible consequences of our ideas are that PNE could be considered as migraine equivalent, such as a "periodic syndrome", and the treatment and care of migraine cannot exclude the causal role of sleep disorders.

The insulin gene variable number of tandemrepeats (INS VNTR) genotype and sleep disordered breathing in childhood obesity.

Aim of our study is to verify the association between the genetic predisposition to hyperinsulinism due to the presence of the insulin gene (INS) I/I genotype and the development of sleep-related breathing disorders (SRBD) in obese children and adolescents. Two hundred and fifty-six obese children and adolescents (125 girls) have been investigated. As initial screening all subjects' mothers filled out the Sleep Disturbances Scale for Children (SDSC). The Sleep-Disordered Breathing (SDB) scale has been taken into account. Successively, a subgroup of 34 patients belonging to the first (14 children) and the last (20 children) SDB score quintiles underwent an overnight polysomnography and the apnea-hypopnea index (AHI) was evaluated. All subjects were genotyped for the INS VNTR and fasting insulin levels were evaluated. The population was divided into two groups according to the genotype: the first group was comprehensive of patients homozygotes for class I allele and the second group was composed by class III allele heterozygotes and homozygotes patients. Subjects I/I showed statistically signifIcant higher insulin levels (p<0.001) and SDB scores (p<0.001). Moreover, in the subgroup of patients investigated with polysomnography, class I homozygous subjects showed higher AHI compared to those patients carrying class III allele (p<0.001). Our data support the hypothesis that INS VNTR is associated with the development of SDB among obese children and adolescents.

CDKL5 mutations in boys with severe encephalopathy and early-onset intractable epilepsy.

OBJECTIVE: To search for CDKL5 gene mutations in boys presenting with severe early-onset encephalopathy and intractable epilepsy, a clinical picture very similar to that already described in girls with CDKL5 mutations. METHODS: Eight boys (age range 3-16 years, mean age 8.5 years, SD 4.38) with severe or profound mental retardation and early-onset intractable seizures were selected for CDKL5 gene mutation screening by denaturing high-performance liquid chromatography analysis. RESULTS: We found three unrelated boys carrying three different missense mutations of the CDKL5 gene: c.872G>A (p.C291Y), c.863C>T (p.T288I), and c.533G>C (p.R178P). They presented early-onset, polymorphous, and drug-resistant seizures, mostly myoclonic and tonic or spasms. EEG showed epileptiform abnormalities which were multifocal during wakefulness, and pseudoperiodic bisynchronous during sleep. CONCLUSIONS: This study describes three boys carrying CDKL5 missense mutations and their detailed clinical and EEG data, and indicates that CDKL5 gene mutations may represent a cause of severe or profound mental retardation and early-onset intractable seizures, also in boys. Screening for CDKL5 mutations is strongly recommended in individuals with these clinical features.

[Increased in vitro and ex vivo proliferation of erythroid precursors induced by calcitriol in chronic renal failure. Synergistic effect with rHuEPO]. / Aumentata proliferazione dei precursori eritroidi indotta in vitro ed ex vivo dal calcitriolo in corso di uremia cronica.Effetto sinergico con rHuEPO.

BACKGROUND: Calcitriol (C) improves anemia in chronic renal failure. This improvement may be related to the suppression of iPTH release, but also to a direct effect on erythropoiesis. MATERIALS AND METHODS: In order to verify this hypothesis, 33 patients with chronic renal failure were enrolled: 24 were undergoing hemodialysis, 9 managed conservatively. All patients were free from other chronic or hematological disease, had a negative DFO test and aluminum levels below 20 mcg/l. iPTH range was 250-480 pg/l. None had yet been treated with C. In vitro study- Samples were drawn for a basal erythroid precursors (Burst Forming Unit-Erythroid BFU-E) study. After mononuclear cells were isolated by centrifugation with Ficoll-Hypaque, they were incubated for 15 days with rHuEPO 3U/ml (A), rHuEPO 3U/l + C 30 pg (B), rHuEPO 3U/ml + C 300 pg (C), rHuEPO 30 U/ml + C 300 pg (D) was performed. Ex vivo study- After the basal evaluation, 10 pts on dialysis were treated with C (Calcijex-Abbott) 1 g three times a week. BFU-E studies were performed after 1,2 and 4 months. RESULTS: In vitro, culture B showed an increased BFU-E proliferation vs A (41+/- 23 vs 27+/-15, p less than 0.02); in C and D cultures proliferation was 61+/-31 and 78+/- 42 respectively, p less than 0.01 vs A. There was no difference among pts with renal failure and pts treated conservatively. During the in vivo study all cultures showed a progressive proliferation increase, without a plateau level (basal, after 1, 2, 4 months respectively): in A: 17+/-8, 22+/-13, 30.9+/-14.9, 41.4+/-20; in B: 27.3+/-15, 35.6+/-20, 45.5+/-21, 57+/-26; in C: 48.2+/-20.6, 63.7+/-32, 75.7+/-37, 83+/-40; in D: 72+/-24, 91+/-42, 106+/-42, 110+/-42.3 (always p less than 0.001). The hematocrit and hemoglobin increase was constant but not significant. The iPTH decrease was not related to BFU-E proliferation. CONCLUSIONS: In chronic uremia C has a direct effect on erythroid precursor proliferation, both in vitro and ex vivo, with a sinergystic effect with rHuEPO. This effect is not related to iPTH suppression. C may be a useful adjuvant therapy for rHuEPO treatment.