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Endoscopic drainage requires transpapillary access to the pancreatic duct during ERCP. When ERCP failed, EUS-guided pancreatico-gastro or bulbostomy and/or rendez-vous technique offers an alternative to surgery. Although data has demonstrated that the procedure can be safe and effective, EUS-guided PD drainage remains one of the most technically challenging therapeutic EUS interventions, as evidenced by the multiple considerations on device selection and the risk of severe complications.
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Endossonografia , Ultrassonografia de Intervenção , Humanos , Endossonografia/métodos , Ultrassonografia de Intervenção/métodos , Ductos Pancreáticos/diagnóstico por imagem , Ductos Pancreáticos/cirurgia , Colangiopancreatografia Retrógrada Endoscópica , Drenagem/métodosRESUMO
Most common congenital malformation of the thorax, Pectus Excavatum affects about one in 500 people. Several surgical or medical techniques have been proposed. Some are followed by complications or insufficient results even though their constant functional value is highly controversial. Secondary surgery with a deep customized 3D elastomer implant, may be an elegant effective and safe solution compared to others; it allows a good aesthetic result expected by patients in the absence of any respiratory or cardio-vascular functional context.
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Tórax em Funil , Elastômeros , Estética , Tórax em Funil/cirurgia , Humanos , Próteses e ImplantesRESUMO
BACKGROUND AND AIMS: To evaluate the long-term effect of simultaneous treatment of hypertension and hypercholesterolemia with angiotensin-converting enzyme (ACE) inhibitors and statins on the incidence of major cardiovascular events (MACE) and other clinical outcomes. METHODS AND RESULTS: We considered data from a subset of Brisighella Heart Study (BHS) participants who were consecutively evaluated in three epidemiological surveys between 2012 and 2020. We excluded normotensive subjects and individuals with a low calculated 10-year CVD risk, hypertensive patients treated with antihypertensive drugs different from ACE inhibitors and patients who changed antihypertensive medications during follow-up. The remaining participants were divided into four groups depending on whether they were treated with (I) perindopril ± amlodipine without statin treatment (N. 132), (II) perindopril ± amlodipine and atorvastatin (N. 132), (III) an ACE inhibitor other than perindopril ± a calcium-channel blocker without statin therapy (N. 133), (IV) an ACE inhibitor other than perindopril ± a calcium-channel blocker and statin therapy (N. 145). The long-term (8 years) effects of the different combined treatment were compared among the pre-defined groups. Over the follow-up period of 8 years, the proportion of subjects who developed MACE, type 2 diabetes mellitus and hyperuricemia, and the proportion of subjects needing for the intensification of antihypertensive treatment to improve blood pressure control were statistically different among the predefined groups (P < 0.05). CONCLUSION: Combined treatment with ACE inhibitors and statins (especially atorvastatin) in hypertensive patients seems to significantly reduce the risk of developing CVD in comparison with treatment with ACE inhibitors alone.
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Diabetes Mellitus Tipo 2 , Inibidores de Hidroximetilglutaril-CoA Redutases , Hipercolesterolemia , Hipertensão , Anlodipino , Inibidores da Enzima Conversora de Angiotensina , Anti-Hipertensivos , Atorvastatina , Pressão Sanguínea , Cálcio , Bloqueadores dos Canais de Cálcio , Seguimentos , Humanos , PerindoprilRESUMO
Background: Zellweger syndrome (ZS) is a congenital autosomal recessive disease within the spectrum of peroxisome biogenesis disorders, characterized by the impairment of peroxisome assembly. The presence of peroxisome enzyme deficiencies leads to complex developmental sequelae, progressive disabilities, and multiorgan damage, due to intracellular accumulation of very-long-chain fatty acids (VLCFAs). Case Presentation: We report the case of an infant affected by ZS in which agammaglobulinemia, detected through neonatal screening of congenital immunodeficiencies, appeared as a peculiar trait standing out among all the other classical characteristics of the syndrome. The exome analysis through next-generation sequencing (NGS), which had previously confirmed the diagnostic suspicion of ZS, was repeated, but no mutations causative of inborn error of immunity (humoral defect) were detected. Conclusion: In this case, no genetic variants accountable for the abovementioned agammaglobulinemia were detected. Given that the scientific literature reports the involvement of peroxisomes in the activation of Nuclear Factor κ-light-chain-enhancer of activated B cells (NF-κB) pathway, which is crucial for B-cell survival, with this work, we hypothesize the existence of a link between ZS and humoral immunodeficiencies. Further studies are required to confirm this hypothesis.
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Pancreatic ductal adenocarcinoma (PDAC) patients are frequently treated by chemotherapy. Even if personalized therapy based on molecular analysis can be performed for some tumors, PDAC regimens selection is still mainly based on patients' performance status and expected efficacy. Therefore, the establishment of molecular predictors of chemotherapeutic efficacy could potentially improve prognosis by tailoring treatments. We have recently developed an RNA-based signature that predicts the efficacy of adjuvant gemcitabine using 38 PDAC primary cell cultures. While demonstrated its efficiency, a significant association with the classical/basal-like PDAC spectrum was observed. We hypothesized that this flaw was due to the basal-like biased phenotype of cellular models used in our strategy. To overcome this limitation, we generated a prospective cohort of 27 consecutive biopsied derived pancreatic organoids (BDPO) and include them in the signature identification strategy. As BDPO's do not have the same biased phenotype as primary cell cultures we expect they can compensate one with each other and cover a broader range of molecular phenotypes. We then obtained an improved signature predicting gemcitabine sensibility that was validated in a cohort of 300 resected PDAC patients that have or have not received adjuvant gemcitabine. We demonstrated a significant association between the improved signature and the overall and disease-free survival in patients predicted as sensitive and treated with adjuvant gemcitabine. We propose then that including BDPO along primary cell cultures represent a powerful strategy that helps to overcome primary cell cultures limitations producing unbiased RNA-based signatures predictive of adjuvant treatments in PDAC.
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BACKGROUND: Chemotherapy is the only systemic treatment approved for pancreatic ductal adenocarcinoma (PDAC), with a selection of regimens based on patients' performance status and expected efficacy. The establishment of a potent stratification associated with chemotherapeutic efficacy could potentially improve prognosis by tailoring treatments. PATIENTS AND METHODS: Concomitant chemosensitivity and genome-wide RNA profiles were carried out on preclinical models (primary cell cultures and patient-derived xenografts) derived from patients with PDAC included in the PaCaOmics program (NCT01692873). The RNA-based stratification was tested in a monocentric cohort and validated in a multicentric cohort, both retrospectively collected from resected PDAC samples (67 and 368 patients, respectively). Forty-three (65%) and 203 (55%) patients received adjuvant gemcitabine in the monocentric and the multicentric cohorts, respectively. The relationships between predicted gemcitabine sensitivity and patients' overall survival (OS) and disease-free survival were investigated. RESULTS: The GemPred RNA signature was derived from preclinical models, defining gemcitabine sensitive PDAC as GemPred+. Among the patients who received gemcitabine in the test and validation cohorts, the GemPred+ patients had a higher OS than GemPred- (P = 0.046 and P = 0.00216). In both cohorts, the GemPred stratification was not associated with OS among patients who did not receive gemcitabine. Among gemcitabine-treated patients, GemPred+ patients had significantly higher OS than the GemPred-: 91.3 months [95% confidence interval (CI): 61.2-not reached] versus 33 months (95% CI: 24-35.2); hazard ratio 0.403 (95% CI: 0.221-0.735, P = 0.00216). The interaction test for gemcitabine and GemPred+ stratification was significant (P = 0.0245). Multivariate analysis in the gemcitabine-treated population retained an independent predictive value. CONCLUSION: The RNA-based GemPred stratification predicts the benefit of adjuvant gemcitabine in PDAC patients.
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Adenocarcinoma , Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/genética , Carcinoma Ductal Pancreático/tratamento farmacológico , Carcinoma Ductal Pancreático/genética , Quimioterapia Adjuvante , Desoxicitidina/análogos & derivados , Humanos , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/genética , Estudos Retrospectivos , Transcriptoma , GencitabinaRESUMO
Hymenoptera venom allergy (HVA) is one of the most frequent causes of anaphylaxis following a bee, vespid or ant sting. Real-life data regarding the management of HVA in children are lacking. To address this unmet need, we carried out a survey defining the current management of HVA in children among pediatric allergists in Italy. Educational investments on the improvement of the management of pediatric patients with HVA are urgently needed, and our analysis represents a relevant instrument in targeting a roadmap with this aim. The time for pediatric allergists to take action has come, and a task force from the Rare Allergic Diseases Commission of the Italian Society of Pediatric Allergy and Immunology is working on the topic to improve pediatricians' knowledge and optimize the care of these patients.
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Alérgenos/efeitos adversos , Anafilaxia/terapia , Venenos de Artrópodes/efeitos adversos , Dessensibilização Imunológica/estatística & dados numéricos , Mordeduras e Picadas de Insetos/complicações , Alérgenos/administração & dosagem , Alérgenos/imunologia , Alergistas/normas , Alergistas/estatística & dados numéricos , Alergia e Imunologia/normas , Anafilaxia/diagnóstico , Anafilaxia/imunologia , Animais , Venenos de Artrópodes/administração & dosagem , Venenos de Artrópodes/imunologia , Criança , Competência Clínica/normas , Competência Clínica/estatística & dados numéricos , Dessensibilização Imunológica/métodos , Dessensibilização Imunológica/normas , Necessidades e Demandas de Serviços de Saúde/estatística & dados numéricos , Humanos , Himenópteros/imunologia , Mordeduras e Picadas de Insetos/imunologia , Mordeduras e Picadas de Insetos/terapia , Itália , Pediatras/normas , Pediatras/estatística & dados numéricos , Guias de Prática Clínica como Assunto , Padrões de Prática Médica/normas , Padrões de Prática Médica/estatística & dados numéricos , Inquéritos e Questionários/estatística & dados numéricosRESUMO
BACKGROUND: Dysregulation of receptor tyrosine kinase MET by various mechanisms occurs in 3%-4% of non-small-cell lung cancer (NSCLC) and is associated with unfavorable prognosis. While MET is a validated drug target in lung cancer, the best biomarker strategy for the enrichment of a susceptible patient population still remains to be defined. Towards this end we analyze here primary data from a phase I dose expansion study of the MET inhibitor capmatinib in patients with advanced MET-dysregulated NSCLC. PATIENTS AND METHODS: Eligible patients [≥18 years; Eastern Cooperative Oncology Group (ECOG) performance status ≤2] with MET-dysregulated advanced NSCLC, defined as either (i) MET status by immunohistochemistry (MET IHC) 2+ or 3+ or H-score ≥150, or MET/centromere ratio ≥2.0 or gene copy number (GCN) ≥5, or (ii) epidermal growth factor receptor wild-type (EGFRwt) and centrally assessed MET IHC 3+, received capmatinib at the recommended dose of 400 mg (tablets) or 600 mg (capsules) b.i.d. The primary objective was to determine safety and tolerability; the key secondary objective was to explore antitumor activity. The exploratory end point was the correlation of clinical activity with different biomarker formats. RESULTS: Of 55 patients with advanced MET-dysregulated NSCLC, 40/55 (73%) had received two or more prior systemic therapies. All patients discontinued treatment, primarily due to disease progression (69.1%). The median treatment duration was 10.4 weeks. The overall response rate per RECIST was 20% (95% confidence interval, 10.4-33.0). In patients with MET GCN ≥6 (n = 15), the overall response rate by both the investigator and central assessments was 47%. The median progression-free survival per investigator for patients with MET GCN ≥6 was 9.3 months (95% confidence interval, 3.8-11.9). Tumor responses were observed in all four patients with METex14. The most common toxicities were nausea (42%), peripheral edema (33%), and vomiting (31%). CONCLUSIONS: MET GCN ≥6 and/or METex14 are suited to predict clinical activity of capmatinib in patients with NSCLC (NCT01324479).
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Benzamidas , Biomarcadores , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Humanos , Imidazóis , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Mutação , Proteínas Proto-Oncogênicas c-met/genética , TriazinasRESUMO
BACKGROUND AND OBJECTIVE: Drug Hypersensitivity Reactions (DHRs) are considered adverse effects of medications that resemble allergy symptoms. The reported positive clinical history of pediatric drug reactions is about 10%, however, after allergy investigations, only a small percent is confirmed as hypersensitivity. The aim of this study was to analyze the clinical history, allergy work-up results and sensitization profile of children and adolescents referred to our Allergy Unit for suspected DHRs. METHODS: The study evaluated data related to a group of children with a positive history of drug reactions during a two-year period. The allergy work-up consisted of in vivo and in vitro tests, in accordance with the recommendations of the ENDA/EAACI guidelines. RESULTS: Data from a group of 637 patients [348 M (54.6%); 289 F (45.4%)] were retrospectively analyzed. Beta lactams (BLs) were the most common drugs involved in the reported clinical history, followed by non-steroidal anti-inflammatory drugs (NSAIDs). Severe cutaneous adverse reactions (SCARs) were most frequently observed during BL treatment. The confirmation of BL hypersensitivity was higher for immediate reactions (IRs) [9.4%; 5.1% through positive skin tests (STs) and 5.5% through drug provocation test (DPT)] compared to non-immediate reactions (non-IRs) (8.1%; 2.2% through STs and 6.2% through DPT). A higher number of positive results was obtained for BLs and macrolides when the tests were performed within 12 months after the index reaction (p < 0.05). During DPTs with amoxicillin-clavulanic acid, four hypersensitivity reactions (including one anaphylaxis) occurred despite negative STs. CONCLUSION: Our data demonstrated that only 9.1% of patients resulted in being positive to allergy tests which is in line with the data in literature. An allergy work-up is mandatory for excluding suspected hypersensitivity.
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Hipersensibilidade a Drogas/epidemiologia , Adolescente , Criança , Pré-Escolar , Feminino , Hospitais Pediátricos , Humanos , Imunoglobulina E/sangue , Lactente , Itália/epidemiologia , Masculino , Estudos Retrospectivos , Testes Cutâneos , Atenção Terciária à SaúdeRESUMO
BACKGROUND/OBJECTIVE: We evaluated the usefulness of the 2017 definition of borderline pancreatic ductal adenocarcinoma (BR-PDAC) in fit patients (performance status 0-1) based on anatomical (A) and biological dimensions (B). METHODS: From 2011 to 2018, 139 resected patients with BR-PDAC according to the 2017 definition were included: 18 patients underwent upfront pancreatectomy (CA 19-9 > 500 U/mL and/or regional lymph node metastasis; BR-B group), and 121 received FOLFIRINOX (FX) induction chemotherapy and were divided into BR-A (CA 19-9 < 500 U/mL, no regional lymph node metastasis; n = 68) and BR-AB (CA 19-9 > 500 U/mL and/or regional lymph node metastasis; n = 53) groups. RESULTS: The 3 groups were comparable according to patient characteristics (except for back pain (P < .01) and CA 19-9 (P < .01)), intraoperative data, and postoperative courses. BR-AB patients required more venous resections (P < .01). The 3 groups were comparable on pathologic findings, except that BR-B patients had more lymph node invasions (P = .02). Median overall survival (OS) of the 121 patients was 45 months. In multivariate analysis, venous resection (P = .039) and R1 resection (P = .012) were poorly linked with OS, whereas BR-A classification (P < .01) independently favored OS. Median survival times of BR-A, BR-AB, and BR-B groups were undetermined, 27 months, and 20 months (P < .001), respectively. CONCLUSIONS: The 2017 definition was relevant for sub-classifying patients with BR-PDAC. The anatomical dimension (BR-A) was a favorable prognostic factor, whereas the biological dimension (BR-AB and BR-B) poorly impacted survival.
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Carcinoma Ductal Pancreático/cirurgia , Neoplasias Pancreáticas/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Ductal Pancreático/tratamento farmacológico , Consenso , Feminino , Fluoruracila/uso terapêutico , Humanos , Irinotecano/uso terapêutico , Leucovorina/uso terapêutico , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Oxaliplatina/uso terapêutico , Pancreatectomia , Neoplasias Pancreáticas/tratamento farmacológico , Padrões de Referência , Análise de Sobrevida , Resultado do TratamentoRESUMO
The structural properties of the Yb2Pd2(In1-x Sn x ) system were investigated at room temperature by synchrotron x-ray powder diffraction. All the inspected compositions (x = 0.0, 0.3, 0.4, 0.5, 0.6, 0.8, 0.9) crystallize in the tetragonal space group P4/mbm; the cell parameters exhibit a non-linear dependence on composition, whereas cell volume changes more regularly, with a minimum at x = 0.8. Samples with Sn content x = 0.5, 0.6, 0.9 were also analysed by neutron diffraction down to 0.5 K. No evidence for a structural transition can be detected at low temperature, whereas an antiferromagnetic ordering is observed, characterized by a propagation vectors k = (0,0,½). Magnetic moments order in the tetragonal ab-plane and the magnetic structure belongs to the Shubnikov magnetic space group P4/mbm.
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BACKGROUND: Serum IgE evaluation of peanut, hazelnut and walnut allergens through the use of component-resolved diagnosis (CRD) can be more accurate than IgE against whole food to associate with severe or mild reactions. OBJECTIVES: The aim of the study was to retrospectively define the level of reaction risk in children with peanut, hazelnut and walnut sensitization through the use of CRD. METHODS: 34 patients [n=22 males, 65%; median age eight years, interquartile range (IQR) 5.0-11.0 years] with a reported history of reactions to peanut and/or hazelnut and/or walnut had their serum analyzed for specific IgE (s-IgE) by ImmunoCAP® and ISAC® microarray technique. RESULTS: In children with previous reactions to peanut, the positivity of Arah1 and Arah2 s-IgE was associated with a history of anaphylaxis to such food, while the positivity of Arah8 s-IgE were associated with mild reactions. Regarding hazelnut, the presence of positive Cora9 and, particularly, Cora14 s-IgE was associated with a history of anaphylaxis, while positive Cora1.0401 s-IgE were associated with mild reactions. Concerning walnut, the presence of positive Jug r 1, Jug r 2, Jug r 3 s-IgE was associated with a history of anaphylaxis to such food. ImmmunoCAP® proved to be more useful in retrospectively defining the risk of hazelnut anaphylaxis, because of the possibility of measuring Cor a14 s-IgE. CONCLUSIONS: Our data show that the use of CRD in patients with allergy to peanut, hazelnut and walnut could allow for greater accuracy in retrospectively defining the risk of anaphylactic reaction to such foods.
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Anafilaxia/epidemiologia , Hipersensibilidade Alimentar/diagnóstico , Imunoglobulina E/sangue , Adolescente , Alérgenos/imunologia , Anafilaxia/etiologia , Arachis/imunologia , Criança , Pré-Escolar , Corylus/imunologia , Feminino , Hipersensibilidade Alimentar/complicações , Humanos , Imunização , Itália/epidemiologia , Juglans/imunologia , Masculino , Estudos Retrospectivos , RiscoRESUMO
We report on synthesis, crystal structure and physical properties of the isotypic compounds YbPdSn2 and EuPdSn2 crystallizing in the MgCuAl2-type structure. In both stannides a divalent state of respective rare earth element was found from analysis of the magnetic susceptibilities. Whereas in YbPdSn2 only weak paramagnetic behaviour is observed, in EuPdSn2 a long-range magnetic phase transition occurs at 12.5 K with complex magnetic behaviour evidenced by magnetic susceptibity and specific heat measurements. Under the influence of magnetic field, the magnetic behaviour was found to evolve from an antiferromagnetic to a ferromagnetic state as a consequence of a re-arrangement of magnetic moments.
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Summary: The number of patients with uncontrolled asthma is growing especially in young people. Although current therapies improve the disease management, the heterogeneity of clinical outcomes results in patients whose asthma is refractory to standard therapies. To understand not responsive phenotypes, we instituted a web-registry aimed to collect real life data of adolescent and adult patients. One-hundred and five Italian medical Centers are part of the network. Participants above 14 years and affected by severe asthma will be included in the study. Demographic and clinical data will be collected for 5 years on a dedicated electronic database. For the first time in Italy, our study will provide information on epidemiological, clinical and therapeutic aspects related to the natural course of the disease, filling the gap between adolescents and adults.
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Asma/epidemiologia , Sistema de Registros , Adolescente , Adulto , Progressão da Doença , Feminino , Seguimentos , Humanos , Itália/epidemiologia , Masculino , Qualidade de Vida , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de DoençaRESUMO
The ground state magnetic behaviour of Ce2(Pd0.8Ag0.2)2In and Ce2(Pd0.5Ag0.5)2In, found in the ferromagnetic branch of Ce2Pd2In, has been investigated by neutron powder diffraction at low temperature. Ce2(Pd0.8Ag0.2)2In is characterized by a ferromagnetic structure with the Ce moments aligned along the c-axis and values of 0.96(2) µ B. The compound retains the P4/mbm throughout the magnetic transition, although the magnetic ordering is accompanied by a significant decrease of the lattice strain along [0 0 l], suggesting a magnetostructural contribution. The magnetic behaviour of Ce2(Pd0.5Ag0.5)2In is very different; this compound exhibits an extremely reduced magnetic scattering contribution in the diffraction pattern, that can be ascribed to a different kind of ferromagnetic ordering, with extremely reduced magnetic moments (~0.1 µ B) aligned along [0 l 0]. These results point to a competition between different types of magnetic correlations induced by Ag-substitution, giving rise to a magnetically frustrated scenario in Ce2(Pd0.5Ag0.5)2In.
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BACKGROUND: The query "are there animals at home?" is usually administered for collecting information on anamnesis. This modality to consider exposure to pet allergens constitutes a potential bias in epidemiological studies and in clinical practice. The aim of our study was to evaluate/quantify different modalities of exposure to cat/dog in inducing allergic sensitization. METHODS: Thirty Italian Allergy units participated in this study. Each centre was required to collect the data of at least 20 consecutive outpatients sensitized to cat/dog allergens. A standardized form reported all demographic data and a particular attention was paid in relieving possible modalities of exposure to cat/dog. RESULTS: A total 723 patients sensitized to cat/dog were recorded, 359 (49.65%) reported direct pet contact, 213 patients (29.46%) were pet owners, and 146 subjects (20.19%) were exposed to pets in other settings. Other patients were sensitized by previous pet ownership (150-20.75%) or indirect contact (103-14.25%), in 111 subjects (15.35%) any contact was reported. CONCLUSIONS: Only 213 patients (29.46%) would be classified as "exposed to animals" and 510 (70.54%) as "not exposed" according to usual query. Our classification has shown that many "not-exposed" subjects (399-55.19%) were "really exposed". The magnitude of exposure to pet allergens at home is not related exclusively to pet ownership. These considerations should be taken into account during the planning of epidemiological studies and in clinical practice for the management of pet allergic individuals.
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BACKGROUND: The prevalence of senile dementia is increasing worldwide, especially in the developed countries. Nevertheless, drug therapy isn't often enough to treat this condition. Researchers are evaluating the possible impact of a preventive approach, based on an improvement of lifestyle and the intake of micronutrients. Moreover, there is an increasing interest for combined nutraceuticals that can act as memory and learning enhancers, with a significant and beneficial potential on the cognitive disorders. OBJECTIVE: To evaluate the effects of a rational assemblage of nutraceuticals on cognitive functions in a sample of 30 elderly subjects. DESIGN: Double bind, cross-over designed trial versus placebo Setting: outpatient clinical practice. PARTICIPANTS: 30 elderly subjects with basal Mini-Mental State Examination score between 20 and 27 and self-perceived cognitive decline. INTERVENTION: Treatment with a combination of nutraceuticals based on Bacopa monnieri, L-theanine, Crocus sativus, copper, folate and vitamins of B and D group. After2 months of treatment or placebo. MEASUREMENTS: Patients were evaluated with Mini-Mental State Examination (MMSE), Perceived Stress Questionnaire (PSQ) and Index and Self-Rating Depression Scale (SRDS). RESULTS: MMSE and PSQ Index significantly improved in the active treatment arm, both versus baseline and versus the parallel arm. Both groups experienced a significant improving in the SRDS scores. CONCLUSIONS: We obtained a good and significant improvement of the cognitive functions tested with the MMSE, PSQ-Index and SRDS score, after 2 months of combined therapy of nutraceuticals. Further confirmation will be needed to verify these observations on the middle and long term in a larger number of subjects.
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Cognição , Disfunção Cognitiva/dietoterapia , Depressão/dietoterapia , Suplementos Nutricionais , Estresse Psicológico/dietoterapia , Disfunção Cognitiva/complicações , Disfunção Cognitiva/psicologia , Estudos Cross-Over , Depressão/complicações , Autoavaliação Diagnóstica , Método Duplo-Cego , Humanos , Testes Neuropsicológicos , Percepção , Projetos Piloto , Estresse Psicológico/complicações , Resultado do TratamentoRESUMO
BACKGROUND AND AIMS: No data exist in the current literature on the glycemic index (GI) and glycemic load (GL) of the diet of phenylketonuric (PKU) children. The aims of this study were to examine the dietary GI and GL in PKU children on a low-phenylalanine (Phe)-diet and to evaluate whether an association may exist between the carbohydrate quality and the metabolic profile. METHODS: Twenty-one PKU children (age 5-11 years) and 21 healthy children, gender and age matched, were enrolled. Dietary (including GI and GL) and blood biochemical assessments were performed. RESULTS: No difference was observed for daily energy intake between PKU and healthy children. Compared to healthy controls, PKU children consumed less protein (p = 0.001) and fat (p = 0.028), and more carbohydrate (% of total energy, p = 0.004) and fiber (p = 0.009). PKU children had higher daily GI than healthy children (mean difference (95% confidence interval), 13.7 (9.3-18.3)) and higher GL (31.7 (10.1-53.2)). PKU children exhibited lower blood total and low density lipoprotein cholesterol (LDL) levels (p < 0.01) and higher triglyceride level (p = 0.014) than healthy children, while glucose and insulin concentrations did not differ. In PKU children the dietary GL was associated with triglyceride glucose index (Spearman's correlation coefficient = 0.515, p = 0.034). CONCLUSION: In PKU children a relationship of the dietary treatment with GI and GL, blood triglycerides and triglyceride glucose index may exist. Improvement towards an optimal diet for PKU children could include additional attention to the management of dietary carbohydrate quality.
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Glicemia/metabolismo , LDL-Colesterol/sangue , Dieta com Restrição de Proteínas , Carboidratos da Dieta/sangue , Índice Glicêmico , Carga Glicêmica , Fenilalanina , Fenilcetonúrias/dietoterapia , Triglicerídeos/sangue , Fatores Etários , Biomarcadores/sangue , Estudos de Casos e Controles , Criança , Pré-Escolar , Carboidratos da Dieta/administração & dosagem , Comportamento Alimentar , Feminino , Humanos , Masculino , Fenilcetonúrias/sangue , Fenilcetonúrias/diagnósticoRESUMO
The present study was aimed at establishing whether the mTOR pathway and its downstream effector p70S6K in CA3 pyramidal neurons are under the modulation of the cholinergic input to trigger the formation of long term memories, similar to what we demonstrated in CA1 hippocampus. We performed in vivo behavioral experiments using the step down inhibitory avoidance test in adult Wistar rats to evaluate memory formation under different conditions. We examined the effects of rapamycin, an inhibitor of mTORC1 formation, scopolamine, a muscarinic receptor antagonist or mecamylamine, a nicotinic receptor antagonist, on short and long term memory formation and on the functionality of the mTOR pathway. Acquisition was conducted 30min after i.c.v. injection of rapamycin. Recall testing was performed 1h, 4h or 24h after acquisition. We found that (1) mTOR and p70S6K activation in CA3 pyramidal neurons were involved in long term memory formation; (2) rapamycin significantly inhibited mTOR and of p70S6K activation at 4h, and long term memory impairment 24h after acquisition; (3) scopolamine impaired short but not long term memory, with an early increase of mTOR/p70S6K activation at 1h followed by stabilization at longer times; (4) mecamylamine and scopolamine co-administration impaired short term memory at 1h and 4h and reduced the scopolamine-induced increase of mTOR/p70S6K activation at 1h and 4h; (5) mecamylamine and scopolamine treatment did not impair long term memory formation; (6) unexpectedly, rapamycin increased mTORC2 activation in microglial cells. Our results demonstrate that in CA3 pyramidal neurons the mTOR/p70S6K pathway is under the modulation of the cholinergic system and is involved in long-term memory encoding, and are consistent with the hypothesis that the CA3 region of the hippocampus is involved in memory mechanisms based on rapid, one-trial object-place learning and recall. Furthermore, our results are in accordance with previous reports that selective molecular mechanisms underlie either short term memory, long term memory, or both. Furthermore, our discovery that administration of rapamycin increased the activation of mTORC2 in microglial cells supports a reappraisal of the beneficial/adverse effects of rapamycin administration.
Assuntos
Aprendizagem da Esquiva/efeitos dos fármacos , Região CA3 Hipocampal/efeitos dos fármacos , Memória de Longo Prazo/efeitos dos fármacos , Proteínas Quinases S6 Ribossômicas 70-kDa/metabolismo , Sirolimo/farmacologia , Serina-Treonina Quinases TOR/metabolismo , Animais , Região CA3 Hipocampal/metabolismo , Masculino , Mecamilamina/farmacologia , Memória de Curto Prazo/efeitos dos fármacos , Antagonistas Muscarínicos/farmacologia , Antagonistas Nicotínicos/farmacologia , Fosforilação/efeitos dos fármacos , Ratos , Ratos Wistar , Escopolamina/farmacologiaRESUMO
Low temperature thermal and magnetic measurements performed on ferro-magneticl (FM) alloys of composition Ce2.15(Pd1-x Ag x )1.95In0.9 are presented. Pd substitution by Ag depresses [Formula: see text] from 4.1 K down to 1.1 K for x = 0.5, which is related to the increase of band electrons, with a critical concentration extrapolated to [Formula: see text]. The [Formula: see text] decrease is accompanied by a weakening of the magnetization of the FM phase. At high temperature (T > 30 K) the inverse magnetic susceptibility reveals the presence of robust magnetic moments ([Formula: see text] [Formula: see text]), whereas the low value of the Curie-Weiss temperature [Formula: see text] K excludes any relevant effect from Kondo screening. The specific heat jump at [Formula: see text] decreases accordingly, while an anomaly emerges at a fixed temperature [Formula: see text] K. This unexpected anomaly does not show any associated sign of magnetism checked by AC-susceptibility measurements. Since the total magnetic entropy (evaluated around [Formula: see text]) practically does not change with Ag concentration, the transference of degrees of freedom from the FM component to the non-magnetic T (*) anomaly is deduced. The origin of this anomaly is attributed to an arising magnetic frustration of the ground state and the consequent entropy bottleneck produced by the divergent increasing of density of excitations at low temperature.