Season of birth and inflammatory response system in schizophrenia

Infective agents (e.g., viruses) together with functional alterations of the immune system have been hypothesized to be implicated in the multifactorial pathogenesis of schizophrenia. The viral hypothesis of schizophrenia has been supported by the observation of birth peaks in winter seasons, prenatal exposure to virus epidemics and specific geographic patterns. On the other hand, not all the data published have shown consistent results supporting the immune hypothesis. Thus, it is likely that immune response factors may play a role in the pathogenesis of the disease only in specific subgroups of patients. The aim of the study was to investigate for the presence of differences of IL-6, IL-6R, gp130 and CC16 among four groups of chronic schizophrenic patients categorized according to the season of birth. We hypothesized that patients born in winter and spring would have had increased values of these cytokines. No significant differences were found among the four groups in any of the measures considered. These preliminary results appear to exclude a major role of the season of birth in determining reported interleukins system alterations in chronic schizophrenia.     

Analysis of a complex health division at the Modena General Hospital by means of DRG indicators

The authors have assessed the activity of a complex division (three wards) at the Modena General Hospital. The parameters used were DRG indicators: Case-Mix Index; Performance Index and Resources Index. It is a in-house hospital analysis, since the benchmark is based on the three units average figures. The analysis covers 1479 patients hospitalized during the first 6 months of the year 2000. The authors have taken into account overall DGRs, surgical DGRs and recurrent DGRs. Making allowance for the limits of such comparison, the study shows some differences as regards efficiency and cost-curbing policies, with the surgical unit having the largest and most diversified number of cases.     

Characterization of wild-type (R100R) and mutated (Q100Q) GABAA alpha 6 subunit in Sardinian alcohol non-preferring rats (sNP)

Sardinian alcohol non-preferring (sNP) rats, selected for their low ethanol preference and consumption, carry a point mutation (R100Q) in the gene coding for GABA(A) receptor alpha(6) subunit, which becomes more sensitive to diazepam-evoked GABA currents. We performed binding studies in the cerebellum of normal (RR) and mutated (QQ) sNP rats using [3H]Ro 15-4513, an inverse agonist for the benzodiazepine site which binds both diazepam insensitive and diazepam sensitive sites. Saturation curves performed on cerebellar membrane from genotyped rats indicated an higher affinity of [3H]Ro 15-4513 for GABA(A) receptors in QQ with respect to RR rats (K(d) values 4.0+/-0.67 and 6.24+/-0.95 nM, respectively), with similar B(max) values (3.5+/-0.25 and 3.9+/-0.39 pmol/mg protein, respectively). Diazepam displacement curves showed a two component model for both genotypes, with similar K(i1) values for QQ and RR (3.6+/-0.62 and 4.9+/-0.33 nM, respectively). In QQ rats diazepam is able to completely displace [3H]Ro 15-4513 (K(i2)=1.48+/-0.27 microM), while in RR rats the diazepam sensitive sites are still present (K(i2)>10 microM). The basal mRNA and protein expression level of the alpha(6) subunit were similar in RR and QQ rats. The electrophysiological profile of oocytes of Xenopus laevis injected with cerebellar synaptosomes showed that ethanol positively modulated GABA-evoked currents significantly more in QQ than in RR rats. These data contribute to the characterization of the function of GABA(A) alpha(6) subunit and its involvement in determining alcohol related behavior.     

Therapeutic Biomarkers in Lung Neuroendocrine Neoplasia

The well-known classification of neuroendocrine neoplasms of the lung into four major subtypes (including typical and atypical carcinoids and small- and large-cell neuroendocrine carcinomas) has a proven prognostic validity but only partially helps to predict the response to specific therapies. Therapeutic biomarkers are incompletely known and include morphological, immunophenotypic, and molecular markers. Morphology alone has no specific predictive role, nor has any immunophenotypic marker been proven to bear predictive implications. Ki67 is a relevant prognostic marker and can indirectly predict response to chemotherapy, when levels are extremely high in high-grade neuroendocrine (NE) carcinomas. The expression of somatostatin receptors, especially of the type 2A, has been shown to predict response to somatostatin analog treatments, paralleling the information derived from octreotide scintigraphy. mTOR pathway is targeted by specific inhibitors, but the exact cellular molecules predicting response are still to be defined. It seems that high levels of phosphorylated forms of mTOR and of its downstream factor S6K are associated to a better response to rapalogs in experimental models. Data from gene expression profiling and mutational analyses are currently emerging, providing a more detailed map of different molecular activation pathways, potentially leading to a more accurate molecular classification of lung NE tumors as well as to the discovery of new therapeutic targets. The combination of mutational profiles with those of upregulated or downregulated genes also by gene gains or losses may ultimately provide a better characterization of NE tumor histological types in terms of response to specific chemotherapy or biotherapy.     

Ceftolozane/tazobactam for the treatment of serious Pseudomonas aeruginosa infections: a multicentre nationwide clinical experience

This study describes the largest clinical experience using ceftolozane/tazobactam (C/T) for different Pseudomonas aeruginosa infections. A retrospective study was performed at 22 hospitals in Italy (June 2016–March 2018). All adult patients treated with ≥4 days of C/T were enrolled. Successful clinical outcome was defined as complete resolution of clinical signs/symptoms related to P. aeruginosa infection and lack of microbiological evidence of infection. C/T treatment was documented in 101 patients with diverse infections, including nosocomial pneumonia (31.7%), acute bacterial skin and skin-structure infection (20.8%), complicated UTI (13.9%), complicated IAI (12.9%), bone infection (8.9%) and primary bacteraemia (5.9%). Over one-half of P. aeruginosa strains were XDR (50.5%), with 78.2% of isolates resistant to at least one carbapenem. C/T was used as first-line therapy in 39 patients (38.6%). When used as second-line or later, the most common reasons for discontinuation of previous antibiotics were in vitro resistance of P. aeruginosa and clinical failure of previous therapy. Concomitant antibiotics were reported in 35.6% of patients. C/T doses were 1.5 g q8h in 70 patients (69.3%) and 3 g q8h in 31 patients (30.7%); median duration of C/T therapy was 14 days. Overall clinical success was 83.2%. Significant lower success rates were observed in patients with sepsis or receiving continuous renal replacement therapy (CRRT). Mild adverse events were reported in only three patients. C/T demonstrated a favourable safety and tolerability profile regardless of the infection type. Clinicians should be aware of the risk of clinical failure with C/T therapy in septic patients receiving CRRT.     

A human and mouse pregnane X receptor reporter gene assay in combination with cytotoxicity measurements as a tool to evaluate species-specific CYP3A induction

Recent studies have demonstrated that a member of the nuclear receptor family, pregnane X receptor (PXR) is a key regulator of the expression of cytochrome P450 3A (CYP3A) in humans and rodents. It is also known that species specificity in the induction of CYP3A by xenobiotics is likely a consequence of differences at the level of PXR activation. Because of the importance of CYP3A4 in drug metabolism, the development of rapid and accurate in vitro assays for predicting the effects of compounds on CYP3A4 expression or activity in humans has been a long-standing goal within pharmaceutical industries. PXR activation measurements using an in vitro reporter gene approach appears to provide a rapid and relatively inexpensive means for predicting whether compounds will induce CYP3A levels in vivo. In this study, using an HepG2 cell based human and mouse PXR reporter gene assay, 23 compounds were tested for their potential to activate hPXR or mPXR. Data demonstrated that potent activators of hPXR had virtually no activity on mPXR and efficient activators of mPXR had weak activity on hPXR. In addition, a third category of moderate/weak activators of both hPXR and mPXR was identified. Exemestane was a strong activator of mPXR ( approximately 22-fold activation) with only minor effect on hPXR ( approximately 5-fold activation). The importance of cell viability measurements as part of the PXR reporter gene assay was demonstrated as significant cytotoxicity or inhibition of cell proliferation might underestimate the potential for PXR activation.     

Growing Strong and Healthy with Mister Bone: An Educational Program to Have Strong Bones Later in Life

Optimal peak bone mass and bone health later in life are favored by a sufficient calcium intake in infancy, childhood and adolescence. The purpose of this study was to test a new educational program created to monitor and to improve calcium and vitamin D intake in children. Nutritional habits in children were evaluated through a food frequency questionnaire (FFQ) to assess the intake of calcium, vitamin D, dairy products, and total caloric energy at baseline and after seven months of exposure to a unique educational program applied between November 2013 and May 2014 in 176 schoolchildren (48% male, 52% female) attending the fourth and fifth grades of two selected primary schools in Florence, Italy. A significant increase of calcium (from 870 ± 190 to 1100 ± 200 mg/day, p < 0.05), and vitamin D (from 3.6 ± 1.53 to 4.1 ± 2 µg/day) intake in children was documented after the educational program. The amount of specific foods important for bone health consumed, such as milk and vegetables, increased significantly, both in male and female children (p < 0.05). The proposed educational program appears to be effective in modifying calcium intake in children, with a significant increase in the consumption of dairy products and vegetables, but without a significant change in the total caloric intake.     

25(OH)D Levels in Relation to Gender,Overweight, Insulin Resistance,and Inflammation in a Cross-Sectional Cohort of Northern Italian Workers: Evidence in Support of Preventive Health Care Programs

Objective: In recent years, the welfare of workers and the prevention of chronic disabling diseases has become a topic of great interest. This study investigates serum levels of total 25-hydroxyvitamin D (25(OH)D) in a cohort of overweight–obese and insulin-resistant northern Italian indoor workers in apparent good health followed a nutritional education program.

Methods: An observational cross-sectional study on 385 patients (females = 291, males = 94), age range 18–69 years and body mass index (BMI) > 25 kg/m², was performed at the Department of Occupational Medicine Milan, Italy, latitude 45.465454 N. We evaluated nutritional intakes, occupational and leisure physical activity, anthropometric measurements, impedance evaluation, blood pressure, the presence of metabolic syndrome (MetS) and nonalcoholic fatty liver diseases (NAFLD) by fatty liver index (FLI). Hematologic and biochemical parameters and (25(OH)D) levels were evaluated from fasting blood samples.

Results: Only 10.91% of subjects had optimal values of 25(OH)D; 17.40% of the remaining 89.09% subjects were severely deficient, with no gender difference and insufficient intake of vitamin D. Only 28% declared leisure physical activity; 39.48% had metabolic syndrome and 62.60% had an FLI > 30. An inverse relationship between 25(OH)D levels and BMI was found, with a significant reduction of total 25(OH)D serum concentrations in winter. The homeostasis model assessment–insulin resistance (HOMA-IR) is positively related to BMI and inversely related to 25(OH)D concentrations. A positive correlation between vitamin D and leisure physical activity was found. At univariate analysis adjusted for age, gender and BMI, an inverse relationship between vitamin D and FLI was observed in both genders. The correlation between 25(OH)D levels, inflammation markers, BMI, and FLI showed an increased risk of cardiovascular disease in this cohort of workers.

Conclusion: Our results suggest the rationale for a large-scale screening program for vitamin D by means of easily implementable low-cost preventive supplementation.