Functional diversity and metabolic response in benthic communities along an ocean acidification gradient.

Altered ocean chemistry caused by ocean acidification (OA) is expected to have negative repercussions at different levels of the ecological hierarchy, starting from the individual and scaling up to the community and ultimately to the ecosystem level. Understanding the effects of OA on benthic organisms is of primary importance given their relevant ecological role in maintaining marine ecosystem functioning. The use of functional traits represents an effective technique to investigate how species adapt to altered environmental conditions and can be used to predict changes in the resilience of communities faced with stresses associated with climate change. Artificial supports were deployed for 1-y along a natural pH gradient in the shallow hydrothermal systems of the Bottaro crater near Panarea (Aeolian Archipelago, southern Tyrrhenian Sea), to explore changes in functional traits and metabolic rates of benthic communities and the repercussions in terms of functional diversity. Changes in community composition due to OA were accompanied by modifications in functional diversity. Altered conditions led to higher oxygen consumption in the acidified site and the selection of species with the functional traits needed to withstand OA. Calcification rate and reproduction were found to be the traits most affected by pH variations. A reduction in a community's functional evenness could potentially reduce its resilience to further environmental or anthropogenic stressors. These findings highlight the ability of the ecosystem to respond to climate change and provide insights into the modifications that can be expected given the predicted future pCO2 scenarios. Understanding the impact of climate change on functional diversity and thus on community functioning and stability is crucial if we are to predict changes in ecosystem vulnerability, especially in a context where OA occurs in combination with other environmental changes and anthropogenic stressors.

Safety and effectiveness of a somatropin biosimilar in children requiring growth hormone treatment: second analysis of the PATRO Children study Italian cohort.

PURPOSE: To investigate the long-term safety (primary endpoint) and effectiveness (secondary endpoint) of the somatropin biosimilar Omnitrope®. METHODS: PATRO Children is an ongoing, multicenter, observational, post-marketing surveillance study. Children who received Omnitrope® for any indication were included. Adverse events (AEs) were evaluated in all study participants. Auxological data, including height standard deviation scores (HSDS) and height velocity standard deviation scores (HVSDS), were used to assess effectiveness. In this snapshot analysis, data from the Italian subpopulation up to August 2017 were reported. RESULTS: A total of 291 patients (mean age 10.0 years, 56.0% male) were enrolled at 19 sites in Italy. The mean duration of Omnitrope® treatment was 33.1 ± 21.7 months. There were 48 AEs with a suspected relationship to the study drug (as reported by the investigator) that occurred in 35 (12.0%) patients, most commonly headache, pyrexia, arthralgia, insulin-like growth factor above normal range, abdominal pain, pain in extremity and acute gastroenteritis. There were no confirmed cases of type 1 or type 2 diabetes; however, two patients (0.7%) had impaired glucose tolerance that was considered Omnitrope® related. The mean HSDS increased from - 2.41 ± 0.73 at baseline (n = 238) to - 0.91 ± 0.68 at 6.5 years (n = 10). The mean HVSDS increased from - 1.77 ± 1.38 at baseline (n = 136) to 0.96 ± 1.13 at 6.5 years (n = 10). CONCLUSIONS: In this sub-analysis of PATRO Children, Omnitrope® appeared to have acceptable safety and effectiveness in the treatment of in Italian children, which was consistent with the earlier findings from controlled clinical trials.

Evaluation of growth hormone response to GHRH plus arginine test in children with idiopathic short stature: role of peak time.

PURPOSE: To describe the course of growth hormone response to growth hormone releasing hormone (GHRH) plus arginine provocative test in children with idiopathic short stature (ISS) and to evaluate the role of peak time. METHODS: A retrospective study was performed analyzing 344 GHRH plus arginine provocative tests performed in children and adolescents with short stature. Serum GH levels were measured at four-time points (T0', T30', T45' and T60') and GH peak was defined as the maximum value at any time point. Mean (T30'-T60') GH value and area under the curve (AUC) were calculated. RESULTS: When analyzing the time of peak at the provocative test, the most frequent peak time was T45' (53.8%) in the ISS group, with no differences in gender, age, and pubertal stage. Analyzing GHD subjects, the most frequent time of peak was T30 (50%). Analyzing the whole population, the GH T0' levels were significantly lower in subjects with the GH peak at T45' than those with the GH peak at T30' (1.7 ± 2.0 vs. 3.2 ± 4.0, p < 0.001). In subjects with GH peak at T45', the value of GH peak, AUC and mean GH were significantly higher than in those with GH peak at T30' and T60'. A direct correlation was found between the value of GH peak and growth velocity SDS (r = 0.127, p = 0.04) and a negative one between GH peak and GH level at T0' (r = - 0.111, p = 0.04), even when adjusted for gender, age, pubertal stage and BMI Z score. CONCLUSIONS: The time peak at 45 min seems to be associated with a better response to the test considering GH peak, mean and AUC. Patients with a GH peak at 30 min more probably could have a derangement in GH secretion showing worst growth pattern and/or a GH deficiency and should be carefully observed.

Can Type 1 diabetes progression be halted? Possible role of high dose vitamin D and omega 3 fatty acids.

In Type 1 Diabetes (T1D) in children, close to the onset the requirements of insulin are often reduced. This represents a transient recovery of endogenous insulin secretion named "honeymoon" because transient and followed by a progressive decline in C-peptide secretion. This case report describes the effect of administration of high dose vitamin D and Ω-3 fatty acids on T1D progression in a 8-year-old child. At today after one year and a half from the onset of T1D, the subject shows a near-normal blood glucose with the administration of 1.5-2 UI of insulin once a day. Thus this report may be of assistance to design additional studies to determine and validate the effect of administration of vitamin D and Ω-3 fatty acids on the progression of T1D.

A novel treatment of cystic fibrosis acting on-target: cysteamine plus epigallocatechin gallate for the autophagy-dependent rescue of class II-mutated CFTR.

This corrects the article DOI: 10.1038/cdd.2016.22.

A novel treatment of cystic fibrosis acting on-target: cysteamine plus epigallocatechin gallate for the autophagy-dependent rescue of class II-mutated CFTR.

We previously reported that the combination of two safe proteostasis regulators, cysteamine and epigallocatechin gallate (EGCG), can be used to improve deficient expression of the cystic fibrosis transmembrane conductance regulator (CFTR) in patients homozygous for the CFTR Phe508del mutation. Here we provide the proof-of-concept that this combination treatment restored CFTR function and reduced lung inflammation (P<0.001) in Phe508del/Phe508del or Phe508del/null-Cftr (but not in Cftr-null mice), provided that such mice were autophagy-competent. Primary nasal cells from patients bearing different class II CFTR mutations, either in homozygous or compound heterozygous form, responded to the treatment in vitro. We assessed individual responses to cysteamine plus EGCG in a single-centre, open-label phase-2 trial. The combination treatment decreased sweat chloride from baseline, increased both CFTR protein and function in nasal cells, restored autophagy in such cells, decreased CXCL8 and TNF-α in the sputum, and tended to improve respiratory function. These positive effects were particularly strong in patients carrying Phe508del CFTR mutations in homozygosity or heterozygosity. However, a fraction of patients bearing other CFTR mutations failed to respond to therapy. Importantly, the same patients whose primary nasal brushed cells did not respond to cysteamine plus EGCG in vitro also exhibited deficient therapeutic responses in vivo. Altogether, these results suggest that the combination treatment of cysteamine plus EGCG acts 'on-target' because it can only rescue CFTR function when autophagy is functional (in mice) and improves CFTR function when a rescuable protein is expressed (in mice and men). These results should spur the further clinical development of the combination treatment.

Vitamin D status and type 1 diabetes in children: evaluation according to latitude and skin color.

AIM: We aim to investigate vitamin D (25OHD) levels in children with or without type 1 diabetes (T1D) according to latitude and skin color. METHODS: We compared 25OHD levels in children with T1D living in Piedmont, of Caucasian or Moroccan origin, with healthy control subjects matched for age and ethnicity. Data of resident children in Morocco, with and without T1D, were used for comparison. RESULTS: Caucasian (21.4±1.5 vs. 24.0±0.5 ng/mL, P<0.05) and Moroccan children with T1D (12.0±2.6 vs. 17.1±1.7 ng/mL, P<0.05) living in Piedmont had lower 25OHD levels than their counterparts without diabetes. Moroccan children living in Morocco with and without T1D had similar 25OHD levels. Vitamin D deficiency was associated with T1D in Caucasian and Moroccan children living in Piedmont (OR: 1.720, CI95% 1.034-2.860, P<0.03), CONCLUSION: Lower vitamin D levels were associated with T1D in Piedmont. Further studies are necessary to explain a possible relationship between vitamin D and T1D.

[Health consequences of obesity in children and adolescents]. / Conseguenze dell'obesità sulla salute del bambino e dell' adolescente.

Obesity in childhood is associated with the presence of complications that can undermine health immediately or in the long term. Several conditions, such as pulmonary or orthopedic complications are strictly associated with the severity of overweight, since they are directly associated to the mechanic stress of fat tissue on the airways or on the bones. Other conditions, such as metabolic or liver complications, although increasing with the extent of overweight, are associated with insulin resistance, which can be modulated by different other factors (ethnicity, genetics, fat distribution) and can occur in overweight children as well. No less important are psychological correlates, such as depression and stigma, which can seriously affect the health related quality of life. Pediatric services for the care of childhood obesity need to be able to screen overweight and obese children for the presence of physical and psychological complications, which can be still reversed by weight loss. This article provides pediatricians a comprehensive update on the main complications in obese children and adolescents and their treatment.

Vitamin D levels in a paediatric population of normal weight and obese subjects.

BACKGROUND: Vitamin D exerts pleiotropic effects and few studies are available in the Italian population. AIM: Aim of our study was to evaluate vitamin D status in children living in Northern Italy. METHODS: We studied vitamin D levels in a population of 113 normal weight (NW) and 444 obese (OB) children, prepubertal and pubertal. We considered vitamin D levels >20 ng/ml as normal, but also measured percentage of children with vitamin D levels higher than a cutoff of 30 ng/ml. RESULTS: 68.2 % of NW children showed normal levels of vitamin D, while 31.8 % showed a clear vitamin D deficiency. Only 28.3 % showed vitamin D levels higher than 30 ng/ml. Obese children showed 55.6 % of subjects with normal levels of vitamin D and 44.4 % of subjects a status of vitamin D deficiency. Only the 18.9 % showed vitamin D levels higher than 30 ng/ml. Mean vitamin D levels in NW children (27.3 ± 1.2 ng/ml) were higher than in OB children (21.8 ± 0.6 ng/ml). No differences have been found between prepubertal and pubertal children in terms of vitamin D levels. CONCLUSIONS: Our paediatric population demonstrates a low percentage of vitamin D sufficiency. In particular, obese children show only 19 % of subjects with normal levels while almost half of this population shows a clear deficiency. Further studies are needed to support these results and to evaluate the possible metabolic consequences.

[Craniopharyngioma in children: importance of a multidisciplinary approach and therapeutic strategies in the treatment of relapsing]. / Craniofaringioma in età pediatrica: importanza di un approccio multidisciplinare e strategie terapeutiche nel trattamento della forme recidivanti.

The craniopharyngioma is a benign intracranial nonglial tumor derived from a malformation of the embryonic tissue. Represents approximately 6-9% of brain tumors in children. It grows close to the optic nerve, hypothalamus and pituitary. The most frequent histological variety in children is adamantinomatous. The initial symptoms of intracranial hypertension is headache and nausea, followed by visual disturbances, impaired hormonal changes such as the secretion of GH, gonadotropins, TSH and ACTH and central diabetes insipidus. We present the clinical case of MD, 5yrs at age, which shows signs of intracranial hypertension syndrome: neuroradiological findings raise the diagnosis of adamantinomatous craniopharyngioma for which the child underwent to sub-total surgical removal of the lesion and radiosurgery treatment. During the disease develops visual impairment, and secondary diabetes insipidus, hypothyroidism hipocotisolism that takes therapy with desmopressin (Minirin), Cortone acetate and L-tiroxine. For the failure of previous therapies, the child has performed chemotherapy with cisplatin (30 mg/sqm/day) and Etoposide (150 mg/mq/day). A year after the end of the last cycle of chemotherapy was detected new progression of the lesion with the appearance of worsening headache and vomiting in the upright position. TC notes the expansion of the third ventricle and the patient undergoes surgery craniotomy. This clinical case underlines the difficulties in treatment of recurrent craniopharyngioma in situations where the anatomical location do not permit aggressive radical surgery. Anyway, new studies are needed to evaluate the effectiveness of systemic chemotherapy as a method of experimental treatment that could reduce the progression of disease.

[What new fathers know, think and do: a survey about fathering's attitudes, beliefs and behaviors in a sample of 570 men just after the birth of their newborn]. / Cosa sanno, cosa pensano, cosa fanno i neo-papà: indagine su attitudini, conoscenze e comportamenti di 570 uomini rispetto al proprio ruolo paterno a poche ore dalla nascita del loro bambino.

AIM: The aim of this paper was to know and analyze information, attitudes and behaviors related with transformations occurring in men when they become fathers. METHODS: A self-administered questionnaire has been given out to all men whose newborns were born in the Hospitals located into Borgosesia, Ivrea, Novara, Verbania and Vercelli (Piedmont region in north west of the Italy) in the last quarter of 2006. The questionnaire was created ad hoc and filled out on the day of discharge; results underwent statistical analyses through SPSS system. RESULTS: For the duration of the research, out of 870 men who became fathers in the hospitals were involved in this study, 570 responded voluntarily to the self-administered questionnaire (65.6% of the total sample). They showed a lack of information about how to take care of their newborns and the emotional turmoil of women after delivery (58% think children are blind when they are born, 52% think it is better to breastfeed newborns at fixed times and 47% ignore that mothers can enter a depression state). Eighty-eight percent of respondents were in the delivery room to see their child's birth, 56% took a leave from job to stay with mother and child in the hospital and 58% of them report the intention to take an additional 2-3 days leave after coming home from the hospital; 27% had trouble sleeping during pregnancy and are afraid not to be good fathers for their child; 90% believe that their newborn will make them change life habits. Most of the new fathers had difficulties in sharing emotions and feelings related with their status of fathers-to-be with other men. Some of these results are significantly different in older fathers, fathers having their first child and fathers with a lesser level of education. CONCLUSION: During pregnancy and in the first months after their child is born, fathers-to-be and new fathers must be considered a potential target for educational interventions aiming at promoting their parenting information and reinforcing their positive attitudes and beliefs related with their fathering status.

[Update on prevention of infections in patients without spleen or with diminished splenic function]. / Update sulla prevenzione delle infezioni nei pazienti splenectomizzati o con iposplenismo funzionale.

Patients without spleen or with diminished splenic function are at high risk (10-50 times higher than in normal population) of developing life-threatening infections (OPSI). Mortality from OPSI is estimated at 50 to 80% of cases. More frequent causative agents are encapsulated bacteria: Streptococcus Pneumoniae, Haemophilus influenzae type b and Neisseria Meningitidis. The risk of OPSI can be reduced by immunizing patients against these pathogens and by prescribing antibiotic prophylaxis. Continuous antibiotic prophylactic for 2-5 years after splenectomy (longer periods might expose the patients to the risk of antibiotic resistance) with penicillin or amoxicillin/clavulanate acid is mandatory. Asplenic individuals should take empirical antibiotic therapy - so called "self-treatment" - and immediate medical consultation in presence of febrile illness. All patients and their parents should be carefully educated about the risk of infections in order to obtain a good long-term compliance with these recommendations.

The W520X mutation in the TSHR gene brings on subclinical hypothyroidism through an haploinsufficiency mechanism.

BACKGROUND: TSHR is a G-protein-coupled seven transmembrane domain receptor that activates the two major signal transduction pathways: the Gαs/adenylate cyclase and the Gαq/11/phospholipase C pathways. Inactivating mutations in the TSHR gene have been demonstrated to be responsible for subclinical hypothyroidism, a disorder characterized by elevated serum TSH concentrations despite normal thyroid hormones levels. AIM: We identified in a child a nonsense mutation (W520X) in the third transmembrane domain of the TSHR that causes the lack of the C-terminus portion of the receptor. The functional significance of this variation was assessed in vitro. MATERIAL/SUBJECT AND METHODS: The W520X mutation was introduced into the pSVL vector containing the wild-type sequence of TSHR gene. Wild-type and mutated vectors were expressed in Chinese Hamster Ovary (CHO) cells, and cAMP, inositol phosphate (IP), immunofluorescence and FACS analyses were performed. RESULTS: Transfection with pSVL-TSHR vector induced basal cAMP and IP production in the absence of TSH stimulation, indicating a constitutive activity for the TSHR. An impairment of receptor function was demonstrated by the observation that cells expressing the mutant TSHR exhibited a lower second messenger production with respect to the wild-type, despite a normal expression of the receptor at the cell surface. CONCLUSIONS: The mechanism through which the W520X mutation exerts its effect is more likely haploinsufficiency rather than a dominant-negative effect. This could explain the phenotype of our patient, who has a hormonal pattern in the range of a mild subclinical hypothyroidism, without an overt disease phenotype.

Epistaxis in children under the age of two: possible marker of abuse/neglect? A retrospective study in North-Eastern Piedmont hospitals.

AIM: Epistaxis is an extremely common event at all ages; however, under two years of age epistaxis is a very rare event and recent studies carried out in Great Britain concern this event as related to possible non-accidental trauma. To date, no other studies carried out in Italy are available on this topic. METHODS: A file review of all cases of epistaxis occurred in children under the age of 2 who were admitted into the ED in our area over a period of two years was carried out. RESULTS: We have collected data concerning 10 cases of epistaxis occurred in children under 2 years of age with an incidence of 10.4 cases per 10000 accessions to the ED of children under the age of 2. Four of the cases had attendances for head injury or facial trauma. CONCLUSION: The results obtained are higher than the results of the British studies adopting the same methodology, but comparable to their surveillance data on the general population. Through the analysis of the collected data, two correlated assumptions have been made: a possible relationship between epistaxis and neglect, and a relation between epistaxis and domestic accidents.

DNA bacterial load in children with bacteremic pneumococcal community-acquired pneumonia.

This study was conducted to evaluate the association between pneumococcal DNA load and parapneumonic pleural effusion (PPE) in children with community-acquired pneumonia. Bacterial load was quantified and related to the presence of PPE with or without empyema in 72 otherwise healthy children aged ≤5 years who were hospitalised because of radiographically confirmed CAP and showed a real-time polymerase chain reaction that was positive for Streptococcus pneumoniae. The proportion of children with a high bacterial load (i.e. ≥265 DNA copies/mL) was larger among the subjects with PPE than those without it. Multivariate analysis showed that a high bacterial load was significantly associated with PPE (OR 8.65; 95% CI 1.10-67.8 vs a bacterial load of <125 copies/mL). Children with infection due to pneumococcal serotype 19A were at highest risk of developing PPE (OR 7.44; 95% CI 1.10-50.4 vs all other typeable serotypes). The patients with CAP due to pneumococcal serotypes that are not included in the 13-valent conjugate vaccine (PCV13) were more frequently affected by PPE than those with infections associated with serotypes included in the vaccine, except for serotype 19A. Bacterial loads of ≥265 DNA copies/mL are significantly associated with PPE, and serotype 19A is significantly associated with a high bacterial load and the development of PPE. The mean bacterial load of the patients with empyema was higher than that of patients with simple PPE. Although further studies are required, it seems that serotypes not included in PCV13 can play a major role in causing a higher bacterial load and PPE.

Comparison of two classifications of metabolic syndrome in the pediatric population and the impact of cholesterol.

BACKGROUND: To establish the rate of agreement in predicting metabolic syndrome (MS) in different pediatric classifications using percentiles or fixed cut-offs, as well as exploring the influence of cholesterol. SUBJECTS AND METHODS: Cross-sectional study in a tertiary care center. Nine hundred and twenty-three obese children and adolescents were evaluated for metabolic characteristics, cholesterol levels, the agreement rate and prevalence of MS across age subgroups with pediatric National Cholesterol Education Program/ Adult Treatment Panel III (NCEP-ATP III) and International Diabetes Federation (IDF) classifications. RESULTS: The overall prevalence of MS was 36.2% and 56.7% with NCEPATP III and IDF. The overall concordance was fair (k: 0.269), with substantial values observed only in children older than 10 (k: 0.708) and 16 yr (0.694). Concordant subjects for both classifications, ≤6 yr, had higher triglycerides, blood pressure (p<0.05) and lower HDL-cholesterol (p<0.0001), with respect to those found to be discordant. Concordant subjects ranging 6-10 yr had all parameters higher than those discordant for IDF (p<0.01) and insulin resistance (p<0.05) than those discordant for NCEP-ATP III. Concordant subjects ≥10 yr presented more altered parameters than those included only in NCEP-ATP III (p<0.05). Overt glucose alterations were uncommon (7.4%; confidence interval 95% 0.1-14.9%), although glucose was modestly higher in MS subjects (p<0.01). Total and LDL-cholesterol was lower in subjects with MS than in those without (p<0.05), and in concordant rather than discordant subjects (p<0.05). CONCLUSIONS: Classifications of MS do not identify the same pediatric population. Subjects who satisfied any classification were the most compromised. Lipid alterations were precocious in the youngest. Obese youths with MS presented lower total and LDL-cholesterol.

Measurement of height velocity is an useful marker for monitoring pituitary function in patients who had traumatic brain injury.

To assess the incidence of abnormal neuroendocrine function post-traumatic brain injuriy (TBI) in a large group of paediatric patients and its correlations with clinical parameters (Glasgow coma scale-GCS, Glasgow outcome scale-GOS, TC marshall scale, height velocity). We evaluated 70 patients [58 M, 12 F; age at the time of TBI (mean ± SEM) 8.12 ± 4.23 years] previously hospitalized for TBI at the "Regina Margherita" Hospital, in Turin and "Maggiore della Carità Hospital" in Novara, Italy, between 1998 and 2008. All patients included underwent: auxological, clinical, hormonal and biochemical assessments at recall (after at least 1 year from TBI to T0); auxological visit after 6 months (T6) and hormonal assessments at 12 months (T12) in patients with height velocity (HV) below the 25th centile. At T0, 4 cases of hypothalamus-pituitary dysfunction had been diagnosed; At T6 20/70 patients had an HV <25th centile, but no one had HV < the 3rd centile limit. At T12, among the 20 patients with HV <25th centile, in 13 patients the HV was below the 25th centile and GHRH + Arginine test has been performed. Four subjects demonstrated an impaired GH peak and were classified as GH deficiency (GHD). Of these 4 subjects, 3 subjects showed isolated GHD, while one patient showed multiple hypopituitarism presenting also secondary hypocortisolism and hypothyroidism. The GCS at admission and GOS do not correlate with the onset of hypopituitarism. A simple measurement of the height velocity at least 1 year after the TBI, is enough to recognize patients with a pituitary impairment related to GH deficiency. We suggest to follow-up paediatric population who had TBI with auxological evaluations every 6 months, limiting hormonal evaluation in patients with a reduction of height velocity below the 25th centile limit.

Quality of life, mood disturbances and psychological parameters in adult patients with GH deficiency.

An increased prevalence of depression, emotional lability, decreased energy levels, and poor quality of life have been reported in adults with GH deficiency (GHD). The impairment of psychological parameters depends on the aetiology of GHD and the presence of other pituitary hormone deficiencies because of hormonal effects on neural cell metabolism. Cognitive dysfunctions appear to be specifically related to GHD itself, whereas the lower emotional well-being and reduced motor performance are attributed to other pituitary hormone deficiencies. Traumatic Brain Injury causes very often hypopituitarism and GHD as well as other many psychological symptoms: cognitive impairment, sleeping disorders, and depression. Many neurobehavioral symptoms of postconcussion syndrome (PCS) are the same suffered by adult GHD and hypopituitaric patients but there are no data about the occurrence of hypopituitarism in PCS. In some studies treatment with rhGH is reported to have a beneficial effect and GHD could contribute itself to the global impairment of psychological dysfunctions. The link between psychosocial impairments and GHD is not fully understood. The effects of long-term rhGH therapy on cognitive functions are largely unknown. Thus, long-term placebo-controlled double-blind studies are required to investigate whether psychological dysfunctions are reversible on GH substitution.