NGAL as an early biomarker of kidney disease in Joubert syndrome: three brothers compared.

Joubert syndrome (JBTS) is a rare autosomal recessive disorder with an underestimated prevalence due to lack of recognition of clinical signs or failure to diagnose this pathology. JBTS is clinically heterogeneous, and it is characterized by a multiple organ involvement predominantly due to the requirement for Joubert gene function in several tissues. Renal disease affects approximately 30% of patients with JBTS, presenting itself in most cases as nephronophthisis (NPHP), a structural tubulo-interstitial disorder characterized by thickened basal membrane of the tubular epithelium and progressive interstitial fibrosis, associated with cysts at the cortico-medullary junction. We propose three cases concerning three patients with JBTS having different years of illness and degrees of renal impairment, evaluating the parameters of renal function at the time of genetic diagnosis and seen after a follow-up of 7 years. We measured neutrophil gelatinase-associated lipocalin (NGAL), considered as an excellent predictor of kidney injury, to evaluate whether this biomarker might be an early biomarker for JBTS-related kidney disease. NGAL was high in all three cases, but with different levels, indicating a tubular suffering typical of this syndrome, with dissimilar severity in the analyzed subjects. NGAL could represent an early indicator of renal damage useful to start an intensive nephrologic follow-up

Obestatin: a new element for mineral metabolism and inflammation in patients on hemodialysis.

Background: Obestatin plays a key role in the process of energy balance maintenance with an anorectic effect. The main aim of the study was to evaluate obestatin in uremic patients to determine whether it is correlated with nutritional and inflammatory status. Methods: We studied plasma obestatin in uremic patients (n = 50) undergoing hemodialysis therapy and in healthy subjects. Plasma obestatin was measured using an ELISA kit. Results: Obestatin levels in uremic patients were lower than in healthy subjects (p 23 had lower obestatin levels than those with a BMI Conclusions: Based on the present observational data, obestatin might be implicated in the inflammatory state and the disturbances of calcium/phosphate metabolism of hemodialysis patients. However, further studies are warranted to determine whether this hormone plays a key role in contributing to malnutrition and to the chronic inflammatory process

High mobility group box 1 and tumor growth factor β: useful biomarkers in pediatric patients receiving peritoneal dialysis

AbstractBackground: Peritonitis, the most important limitation of peritoneal dialysis (PD), could be detected by biomarkers in dialysate effluent, representing a noninvasive method to indirectly assess the peritoneum status. The aim of our study was to test high mobility group box 1 (HMGB1) in PD patients, evaluating its role as precocious marker of peritoneum damage during peritonitis. Transforming growth factor (TGF)-β was correlated with peritoneal transport characteristics.Methods: Six patients, treated by ambulatory PD, were enrolled. Samples were collected at the onset of peritonitis (T1) and every day until its resolution (T-end). Serum (s) and peritoneal (p) white blood cell (WBC) count was also evaluated. Peritoneal Equilibration Test evaluated the filter activity of peritoneum.Results: In patients with acute peritonitis, the highest serum and peritoneal HMGB1 values (64 ± 3.6 and 70 ± 5.3 ng/mL, respectively) were assessed, with a progressive decrease of their levels at the resolution time (T-en..

Metformin-related lactic acidosis: is it a myth or an underestimated reality?

AbstractMetformin, belonging to a class of drugs called biguanides, is the recommended first-line treatment for overweight patients with type 2 diabetes mellitus. It has multiple mechanisms of action, such as reduction of gluconeogenesis, increases peripheral uptake of glucose, and decreases fatty acid oxidation. However, a potential serious complication, defined metformin-associated lactic acidosis (MALA), is related to increased plasma lactate levels, linked to an elevated plasma metformin concentrations and/or a coexistent condition altering lactate production or clearance. The mortality rate for MALA approaches 50% and metformin has been contraindicated in moderate and severe renal impairment, to minimize its potential toxic levels. Nevertheless, metformin prescription or administration, despite the presence of contraindications or precipitating factors for MALA, was a common topic highlighted in all reviewed papers. Routine assessment of metformin plasma concentration is not easily available in all l..

The Role of Attitudes Toward Medication and Treatment Adherence in the Clinical Response to LAIs: Findings From the STAR Network Depot Study

Background: Long-acting injectable (LAI) antipsychotics are efficacious in managing psychotic symptoms in people affected by severe mental disorders, such as schizophrenia and bipolar disorder. The present study aimed to investigate whether attitude toward treatment and treatment adherence represent predictors of symptoms changes over time. Methods: The STAR Network \u201cDepot Study\u201d was a naturalistic, multicenter, observational, prospective study that enrolled people initiating a LAI without restrictions on diagnosis, clinical severity or setting. Participants from 32 Italian centers were assessed at three time points: baseline, 6-month, and 12-month follow-up. Psychopathological symptoms, attitude toward medication and treatment adherence were measured using the Brief Psychiatric Rating Scale (BPRS), the Drug Attitude Inventory (DAI-10) and the Kemp's 7-point scale, respectively. Linear mixed-effects models were used to evaluate whether attitude toward medication and treatment adherence independently predicted symptoms changes over time. Analyses were conducted on the overall sample and then stratified according to the baseline severity (BPRS < 41 or BPRS 65 41). Results: We included 461 participants of which 276 were males. The majority of participants had received a primary diagnosis of a schizophrenia spectrum disorder (71.80%) and initiated a treatment with a second-generation LAI (69.63%). BPRS, DAI-10, and Kemp's scale scores improved over time. Six linear regressions\u2014conducted considering the outcome and predictors at baseline, 6-month, and 12-month follow-up independently\u2014showed that both DAI-10 and Kemp's scale negatively associated with BPRS scores at the three considered time points. Linear mixed-effects models conducted on the overall sample did not show any significant association between attitude toward medication or treatment adherence and changes in psychiatric symptoms over time. However, after stratification according to baseline severity, we found that both DAI-10 and Kemp's scale negatively predicted changes in BPRS scores at 12-month follow-up regardless of baseline severity. The association at 6-month follow-up was confirmed only in the group with moderate or severe symptoms at baseline. Conclusion: Our findings corroborate the importance of improving the quality of relationship between clinicians and patients. Shared decision making and thorough discussions about benefits and side effects may improve the outcome in patients with severe mental disorders

El aprendizaje del inglés en un contexto plurilingüe. El método CLIL en el segundo ciclo de Educación Infantil

La globalización hace que la educación ponga cada vez más énfasis en el desarrollo de habilidades plurilingües. En este contexto, hay que incentivar el aprendizaje de las lenguas que, en el contexto educativo español, llevan al fenómeno del bilingüismo o plurilingüismo. Para llegar al aprendizaje de diversas lenguas, se debe entender primero el funcionamiento del aprendizaje de una lengua y conocer las diversas teorías sobre su desarrollo, así como el concepto de “bilingüismo” y sus derivados. El presente trabajo pretende mostrar una propuesta de intervención utilizando el método CLIL en un contexto plurilingüe centrado en el Segundo Ciclo de Educación Infantil, con un conjunto de actividades relacionadas con la temática de “el reciclaje” en las que se fomenta el uso de la lengua extranjera inglesa.La globalització fa que l'educació pose cada vegada més èmfasi en el desenvolupament d'habilitats plurilingües. En aquest context, cal incentivar l'aprenentatge de les llengües que, en el context educatiu espanyol, porten al fenomen del bilingüisme o plurilingüisme. Per a arribar a l'aprenentatge de diverses llengües, s'ha d'entendre primer el funcionament de l'aprenentatge d'una llengua i conéixer les diverses teories sobre el seu desenvolupament, així com el concepte de “bilingüisme” i els seus derivats. El present treball pretén mostrar una proposta d'intervenció utilitzant el mètode CLIL en un context plurilingüe centrat en el Segon Cicle d'Educació Infantil, amb un conjunt d'activitats relacionades amb la temàtica de “el reciclatge” en les quals es fomenta l'ús de la llengua estrangera anglesa.Globalisation means that education is placing increasing emphasis on the development of multilingual skills. In this context, it is necessary to encourage the learning of languages which, in the Spanish educational context, leads to the phenomenon of bilingualism or plurilingualism. In order to achieve the learning of several languages, we need first understand how language learning works and be familiar with the various theories on its development, as well as the concept of "bilingualism" and its derivatives. This paper aims to show a proposal for intervention using the CLIL method in a plurilingual context focused in the Early Childhood Educationon, with a set of activities related to the theme of "recycling" in which the use of the foreign language English is encouraged.Educació

Adrenal Disorders and the Paediatric Brain: Pathophysiological Considerations and Clinical Implications

Various neurological and psychiatric manifestations have been recorded in children with adrenal disorders. Based on literature review and on personal case-studies and case-series we focused on the pathophysiological and clinical implications of glucocorticoid-related, mineralcorticoid-related, and catecholamine-related paediatric nervous system involvement. Childhood Cushing syndrome can be associated with long-lasting cognitive deficits and abnormal behaviour, even after resolution of the hypercortisolism. Exposure to excessive replacement of exogenous glucocorticoids in the paediatric age group (e.g., during treatments for adrenal insufficiency) has been reported with neurological and magnetic resonance imaging (MRI) abnormalities (e.g., delayed myelination and brain atrophy) due to potential corticosteroid-related myelin damage in the developing brain and the possible impairment of limbic system ontogenesis. Idiopathic intracranial hypertension (IIH), a disorder of unclear pathophysiology characterised by increased cerebrospinal fluid (CSF) pressure, has been described in children with hypercortisolism, adrenal insufficiency, and hyperaldosteronism, reflecting the potential underlying involvement of the adrenal-brain axis in the regulation of CSF pressure homeostasis. Arterial hypertension caused by paediatric adenomas or tumours of the adrenal cortex or medulla has been associated with various hypertension-related neurological manifestations. The development and maturation of the central nervous system (CNS) through childhood is tightly regulated by intrinsic, paracrine, endocrine, and external modulators, and perturbations in any of these factors, including those related to adrenal hormone imbalance, could result in consequences that affect the structure and function of the paediatric brain. Animal experiments and clinical studies demonstrated that the developing (i.e., paediatric) CNS seems to be particularly vulnerable to alterations induced by adrenal disorders and/or supraphysiological doses of corticosteroids. Physicians should be aware of potential neurological manifestations in children with adrenal dysfunction to achieve better prevention and timely diagnosis and treatment of these disorders. Further studies are needed to explore the potential neurological, cognitive, and psychiatric long-term consequences of high doses of prolonged corticosteroid administration in childhood

Does cognitive behaviour therapy for insomnia reduce repetitive negative thinking and sleep-related worry beliefs? A systematic review and meta-analysis

Repetitive negative thinking (RNT), i.e., worry, rumination, and transdiagnostic repetitive thinking, is thought to exacerbate and perpetuate insomnia in cognitive models. Moreover, RNT is a longitudinal precursor of depression and anxiety, which are often co-present alongside insomnia. Whilst accumu- lating evidence supports the efficacy of cognitive behavioural therapy for insomnia (CBT-I) in reducing depression and anxiety symptoms, the literature on the effects of CBT-I on RNT has never been sys- tematically appraised. Importantly, preliminary evidence suggests that reduction of RNT following CBT-I may be associated with reduction of depression and anxiety. Therefore, we aimed to conduct a sys- tematic review and meta-analysis on the effects of CBT-I on RNT. Seven databases were searched, and 15 randomised controlled trials were included. Results showed moderate-to-large effects of CBT-I on worry (Hedge's g range: 0.41 to g 1⁄4 0.71) but small and non-reliable effects on rumination (g 1⁄4 0.13). No clear evidence was found for an association between post-treatment reduction in RNT and post- treatment reduction in depression and anxiety. Although the literature is small and still developing, CBT-I seems to have a stronger impact on sleep-related versus general measures of RNT. We discuss a research agenda aimed at advancing the study of RNT in CBT-I trials

Idiopathic intracranial hypertension: a unifying neuroendocrine hypothesis through the adrenal-brain axis

The clinical syndrome idiopathic intracranial hypertension (IIH), also termed pseudotumor cerebri, consists of symptoms of headache, nausea, vomiting and visual field defects in combination with findings of papilledema. IIH is more commonly seen in overweight women where the rise in intracranial pressure is putatively a consequence of an endocrine-based disturbance of electrolytes. Less frequently, it can also occur in men and in the pediatric age group. Associated risk factors include primary and secondary aldosteronism, pregnancy, recombinant growth hormone (r-GH) therapy, oral contraceptives, obesity, vitamin A intoxication or deficiency, Addison disease, corticosteroid therapy or acute withdrawal of steroid therapy and Cushing disease. Herein, we review the association between these conditions and IIH working toward its having a unifying neuroendocrine hypothesis