Efficient synthesis of organic thioacetates in water.

Thioacetates as precursors of thiols are interesting starting points for synthesizing other organosulfur compounds. Herein, we propose a simple, efficient and fast method to obtain organic thioacetates using water as a solvent. Taking into account the great attention that has been paid toward environmentally friendly synthetic procedures in the past decades, we prove the role and the strength of the thioacetate anion as a nucleophile for nucleophilic displacement reactions in an aqueous medium. The reactions were carried out under pH control, to prevent the decomposition of the mesylate starting materials, using potassium carbonate as a safe and mild base. A simple work up allows products to be obtained with excellent yield and acceptable purity.

Checking rounds for isolation precautions in the control of multidrug-resistant organisms: reduction achieved.

The objective of this investigation was to analyze the effectiveness of a quality improvement initiative in limiting the spread of multidrug-resistant organisms (MDROs) in the hospital setting. During the period 2011-2013, a multimodal intervention was activated at a tertiary care center in Italy. The intervention included: laboratory-based surveillance, interdisciplinary training sessions, monitoring the adoption of isolation precautions and daily supervision provided by infection control nurses, and a monthly feedback. Time series analysis was used to evaluate the trends and correlations between the MDROs rate, intensity of checking rounds, and hospital-wide data (i.e., transfer of patients, patients' days, site of isolation, etc.). A total of 149,251 patients were included in the study. The proportion of patients undergoing transmission-based isolation precautions within 24 h from a positive laboratory finding increased from 83% in 2011 to 99% in 2013 (p < 0.05). The wards appropriately adopting the correct isolation precaution increased from 83% in 2011 to 97.6% in 2013 (p < 0.05). The frequency of controls was significantly reduced after the observation of compliance in the appropriate wards (p < 0.05). After three years, the incidence rate changed from 5.8/1000 days of stay [95% confidence interval (CI) 5.6-6.1] in 2011 to 4.7 (95% CI 4.4-4.9) in 2013 (p < 0.0001). Moreover, microorganisms isolated from different types of specimens showed variable potential for transmission (i.e., skin as the most potential and urine the least). The results demonstrate the efficacy of the multimodal intervention, with sustained reduction of MDROs rate, besides check reduction, and highlight the long-term efficacy of checking rounds in changing professionals' behaviors.

Depression during the menopause transition: impact on quality of life, social adjustment, and disability.

The impact of depression on quality of life (QOL) and social support has neither been well characterized in clinical samples of women with perimenopausal depression (PMD) nor have the relative contributions of depression and other menopausal symptoms (e.g., hot flushes) to declining QOL been clarified. In this study, we compared QOL measures, social support, and functional disability in PMD and non-depressed perimenopausal women. We evaluated women aged 40-60 years who presented with menstrual cycle irregularity, elevated plasma FSH levels, and met criteria for perimenopause. A structured clinical interview was administered to determine the presence or absence of major and minor depression. Outcome measures included the Quality of Life Enjoyment Scale Questionnaire, the Sheehan Disability Scale, the Global Assessment of Functioning, the Social Adjustment Scale, and the Duke Social Support Index. Kruskal-Wallis tests and ANOVAs were used to compare outcome measures. Ninety women with PMD and 51 control women participated in this study. Women with PMD reported significantly decreased QOL, social support, and adjustment and increased disability compared with non-depressed perimenopausal women. Neither perimenopausal reproductive status alone nor the presence of hot flushes had a significant negative impact on QOL measures. PMD is accompanied by significant reductions in QOL, social support, and disability similar to depression in women at other stages of life. PMD may also contribute to decreased QOL in community- or clinic-based samples of perimenopausal women. It remains unclear whether the clinical characteristics we identified reflect pre-existing risk factors for depression during the perimenopause or the effects of a current depression. Future clinical and treatment studies in perimenopausal women should distinguish depressed women when outcome measures include QOL.

Impact of incident diabetes on atherosclerotic cardiovascular disease according to statin use history among postmenopausal women.

To compare impact of incident diabetes on atherosclerotic cardiovascular disease (ASCVD) risk among postmenopausal women according to statin use. Prospective data from 120,499 postmenopausal women without prevalent diabetes or cardiovascular disease at baseline from the Women's Health Initiative were used. Incident diabetes was self-reported annually and defined as treatment with pills or injectable medication for diabetes. Current statin use was determined at enrollment and years 1, 3, 6, 9 and 13.5 in the three clinical trial arms, and at baseline, year 3, and 13.5 for the observational study. The primary outcome was incident ASCVD events, self-reported annually and adjudicated by blinded local and central physicians. Incident diabetes and statin use status were fitted as time-varying covariates in Cox regression models to assess ASCVD risk during an average follow-up of 13.6 years. For those not on statins at the time of diabetes diagnosis, there was a 42 % increased risk of ASCVD [hazard ratio (HR) 1.42, 95 % CI 1.28-1.58] among women with incident diabetes versus those without diabetes. Among women on statins, there was a 39 % increased risk of ASCVD (HR 1.39, 95 % CI 1.12-1.74) in women with incident diabetes versus those without diabetes. The increased ASCVD risk due to diabetes was similar between women before or after initiating statins (P = 0.89). Whether diabetes was diagnosed before or after statin use did not alter the increased risk of ASCVD associated with diabetes. Mitigating the increased incidence of diabetes in statin users could increase the ASCVD benefit-to-risk ratio of statins.

Single-component versus multicomponent dietary goals for the metabolic syndrome: a randomized trial.

BACKGROUND: Few studies have compared diets to determine whether a program focused on 1 dietary change results in collateral effects on other untargeted healthy diet components. OBJECTIVE: To evaluate a diet focused on increased fiber consumption versus the multicomponent American Heart Association (AHA) dietary guidelines. DESIGN: Randomized, controlled trial from June 2009 to January 2014. (ClinicalTrials.gov: NCT00911885). SETTING: Worcester, Massachusetts. PARTICIPANTS: 240 adults with the metabolic syndrome. INTERVENTION: Participants engaged in individual and group sessions. MEASUREMENTS: Primary outcome was weight change at 12 months. RESULTS: At 12 months, mean change in weight was -2.1 kg (95% CI, -2.9 to -1.3 kg) in the high-fiber diet group versus -2.7 kg (CI, -3.5 to -2.0 kg) in the AHA diet group. The mean between-group difference was 0.6 kg (CI, -0.5 to 1.7 kg). During the trial, 12 (9.9%) and 15 (12.6%) participants dropped out of the high-fiber and AHA diet groups, respectively (P = 0.55). Eight participants developed diabetes (hemoglobin A1c level ≥6.5%) during the trial: 7 in the high-fiber diet group and 1 in the AHA diet group (P = 0.066). LIMITATIONS: Generalizability is unknown. Maintenance of weight loss after cessation of group sessions at 12 months was not assessed. Definitive conclusions cannot be made about dietary equivalence because the study was powered for superiority. CONCLUSION: The more complex AHA diet may result in up to 1.7 kg more weight loss; however, a simplified approach to weight reduction emphasizing only increased fiber intake may be a reasonable alternative for persons with difficulty adhering to more complicated diet regimens. PRIMARY FUNDING SOURCE: National Heart, Lung, and Blood Institute.

An anti-inflammatory diet as treatment for inflammatory bowel disease: a case series report.

BACKGROUND: The Anti-Inflammatory Diet (IBD-AID) is a nutritional regimen for inflammatory bowel disease (IBD) that restricts the intake of certain carbohydrates, includes the ingestion of pre- and probiotic foods, and modifies dietary fatty acids to demonstrate the potential of an adjunct dietary therapy for the treatment of IBD. METHODS: Forty patients with IBD were consecutively offered the IBD-AID to help treat their disease, and were retrospectively reviewed. Medical records of 11 of those patients underwent further review to determine changes in the Harvey Bradshaw Index (HBI) or Modified Truelove and Witts Severity Index (MTLWSI), before and after the diet. RESULTS: Of the 40 patients with IBD, 13 patients chose not to attempt the diet (33%). Twenty-four patients had either a good or very good response after reaching compliance (60%), and 3 patients' results were mixed (7%). Of those 11 adult patients who underwent further medical record review, 8 with CD, and 3 with UC, the age range was 19-70 years, and they followed the diet for 4 or more weeks. After following the IBD-AID, all (100%) patients were able to discontinue at least one of their prior IBD medications, and all patients had symptom reduction including bowel frequency. The mean baseline HBI was 11 (range 1-20), and the mean follow-up score was 1.5 (range 0-3). The mean baseline MTLWSI was 7 (range 6-8), and the mean follow-up score was 0. The average decrease in the HBI was 9.5 and the average decrease in the MTLWSI was 7. CONCLUSION: This case series indicates potential for the IBD-AID as an adjunct dietary therapy for the treatment of IBD. A randomized clinical trial is warranted.

Challenges in sodium intake reduction and meal consumption patterns among participants with metabolic syndrome in a dietary trial.

BACKGROUND: Dietary guidelines suggest limiting daily sodium intake to <2,300 mg for the general population, and <1,500 mg/d for those with certain cardiovascular risk factors. Despite these recommendations, few Americans are able to achieve this goal. Identifying challenges in meeting these guidelines is integral for successful compliance. This analysis examined patterns and amount of daily sodium intake among participants with metabolic syndrome enrolled in a one-year dietary intervention study. METHODS: Two hundred forty participants with metabolic syndrome enrolled in a dietary intervention trial to lose weight and improve dietary quality. Three 24-hour dietary recalls were collected at each visit which provided meal patterns and nutrient data, including sodium intake. A secondary data analysis was conducted to examine sodium consumption patterns at baseline and at one-year study visits. Sodium consumption patterns over time were examined using linear mixed models. RESULTS: The percentage of meals reported eaten in the home at both baseline and one-year follow-up was approximately 69%. Follow-up for the one-year dietary intervention revealed that the participants who consumed sodium greater than 2,300 mg/d declined from 75% (at baseline) to 59%, and those that consumed higher than 1,500 mg/d declined from 96% (at baseline) to 85%. Average sodium intake decreased from 2,994 mg at baseline to 2,558 mg at one-year (P < 0.001), and the sodium potassium ratio also decreased from 1.211 to 1.047 (P < 0.001). Sodium intake per meal varied significantly by meal type, location, and weekday, with higher intake at dinner, in restaurants, and on weekends. At-home lunch and dinner sodium intake decreased (P < 0.05), while dinner sodium intake at restaurant/fast food chains increased from baseline to one-year (P < 0.05). CONCLUSION: Sodium intake for the majority of participants exceeded the recommended dietary guidelines. Findings support actions that encourage low-sodium food preparation at home and encourage public health policies that decrease sodium in restaurants and prepared foods.

Point prevalence survey of antibiotic use and healthcare-associated infections in acute care hospitals: a comprehensive report from the Marche Region of Italy.

BACKGROUND: Healthcare-associated infections (HAIs) and antimicrobial resistance (AMR) are serious health challenges. Point prevalence surveys (PPSs) are valuable tools for monitoring HAIs and AMR. AIM: To describe results of the ECDC PPS 2022 dealing with the prevalence of HAIs, antimicrobial consumption, and associated factors, in acute care hospitals. METHODS: The survey was performed in November 2022 in 14 hospitals according to the protocol proposed by the European Centre for Disease Prevention and Control. Multilevel logistic regression was performed using geographical area/hospital type as cluster variable to evaluate the factors independently associated with HAIs and antibiotics. FINDINGS: The point prevalence of HAIs was 7.43%. Patients hospitalized for longer periods were more likely to have an HAI as well as those aged 15-44 years, with a rapidly fatal disease, intubated, and with one or two devices. Antibiotics prevalence was 47.30%. Males, unknown McCabe scores, minimally invasive/non-National Healthcare Safety Network (NHSN) surgery, patients with HAIs, hospitals with a higher alcohol hand-rub consumption, hospitals with a greater number of IPC personnel, geriatric wards, and hospitals with 300-600 beds were more likely to be under antimicrobial therapy. CONCLUSION: This PPS provided valuable information on the prevalence of HAIs and antimicrobial consumption and variables associated. The high prevalence of HAIs highlights the need for improved infection control measures.

Autologous haematopoietic stem cell transplantation with an intermediate intensity conditioning regimen in multiple sclerosis: the Italian multi-centre experience.

BACKGROUND: Over recent years numerous patients with severe forms of multiple sclerosis (MS) refractory to conventional therapies have been treated with intense immunosuppression followed by autologous haematopoietic stem cell transplantation (AHSCT). The clinical outcome and the toxicity of AHSCT can be diverse, depending on the various types of conditioning protocols and on the disease phase. OBJECTIVES: To report the Italian experience on all the consecutive patients with MS treated with AHSCT with an intermediate intensity conditioning regimen, named BEAM/ATG, in the period from 1996 to 2008. METHODS: Clinical and magnetic resonance imaging outcomes of 74 patients were collected after a median follow-up period of 48.3 (range = 0.8-126) months. RESULTS: Two patients (2.7%) died from transplant-related causes. After 5 years, 66% of patients remained stable or improved. Among patients with a follow-up longer than 1 year, eight out of 25 subjects with a relapsing-remitting course (31%) had a 6-12 months confirmed Expanded Disability Status Scale improvement > 1 point after AHSCT as compared with one out of 36 (3%) patients with a secondary progressive disease course (p = 0.009). Among the 18 cases with a follow-up longer than 7 years, eight (44%) remained stable or had a sustained improvement while 10 (56%), after an initial period of stabilization or improvement with median duration of 3.5 years, showed a slow disability progression. CONCLUSIONS: This study shows that AHSCT with a BEAM/ATG conditioning regimen has a sustained effect in suppressing disease progression in aggressive MS cases unresponsive to conventional therapies. It can also cause a sustained clinical improvement, especially if treated subjects are still in the relapsing-remitting phase of the disease.

The short-term effects of estradiol, raloxifene, and a phytoestrogen in women with perimenopausal depression.

OBJECTIVE: We examined the short-term efficacies of three estrogen-like compounds under placebo-controlled conditions in women with perimenopause-related depression (PMD). METHODS: Women with PMD were randomized in a double-blind parallel design to one of four treatments: transdermal 17-beta estradiol (TE) (100 mcg/d); oral raloxifene (60 mg/d); a proprietary phytoestrogen compound, Rimostil (1,000 mg twice/d); or placebo for 8 weeks. The main outcome measures were the Center for Epidemiology Studies Depression Scale, 17-item Hamilton Rating Scale for Depression (HRSD), and the Beck Depression Inventory completed at each clinic visit. Secondary outcomes included a visual analogue self-rating completed at each clinic visit, and daily self-ratings of hot flush severity. Cognitive tests were performed at pretreatment baseline and at the end of the trial. In the primary analysis, we obtained four repeated measures in each woman in the four treatment arms. Analyses were done with SAS Version 9.4 software (SAS Institute, Inc, Cary, NC), using PROC MIXED (for mixed models). All models included the following four explanatory variables, regardless of whether they were statistically significant: 1) treatment group (TE, raloxifene, Rimostil, placebo); 2) week (W2, W4, W6, W8); 3) treatment group-by-week interaction; and 4) baseline value of the measure being analyzed. The inclusion of additional variables was evaluated individually for each outcome measure. RESULTS: Sixty-six women were randomized into the trial, four women dropped out of the trial, and 62 women were included in the final data analysis. No effect of treatment group was observed in either the Center for Epidemiology Studies Depression Scale (P = 0.34) or Beck Depression Inventory (P = 0.27) scores; however, there was a difference in HRSD scores between treatment groups (P = 0.0037) that pair-wise comparisons of the combined weekly scores in each treatment demonstrated TE's beneficial effects on HRSD scores compared with Rimostil (P = 0.0005), and less consistently with placebo (P = 0.099). The average (SD) of the baseline scores for each treatment group on the HRSD was as follows: TE-15.3 (4.5), raloxifene-16.0 (3.7), Rimostil-14.0 (2.7), and placebo-15.2 (3.0). Whereas the HRSD scores after 8 weeks of treatment (least-square means) were TE-5.2(1.1), raloxifene-5.8(1.2), Rimostil-11.2(1.4), and placebo-7.8(1.1). No differences were observed between raloxifene and either TE or placebo in any scale score. HRSD scores in women assigned to TE were improved compared with those on Rimostil during weeks 6 and 8 (P values = 0.0008, 0.0011, respectively). Cognitive testing at week 8 showed that none of the three active treatment groups performed better than placebo. CONCLUSIONS: This study did not identify significant therapeutic benefits of TE, Rimostil, or raloxifene compared with placebo in PMD. However, improvements in depression ratings were observed between TE compared with Rimostil. Thus, our findings do not support the role of ERbeta compounds in the treatment of PMD (and indeed could suggest a more important role of ERalpha).

The Cortisol and ACTH Response to Dex/CRH Testing in Women With and Without Perimenopausal Depression.

CONTEXT: Abnormalities in the hypothalamic-pituitary-adrenal (HPA) axis are frequent accompaniments of depression, and studies have documented the role of stress and stressful life events in the ontogeny of perimenopausal depressions (PMD). Because HPA axis function in women is further modulated both by aging and ovarian steroids, it is possible that a dysregulated HPA axis contributes to the increased risk of PMD. OBJECTIVE: We examined HPA axis function in perimenopausal women with and without depression using the combined dexamethasone-corticotropin-releasing hormone (Dex/CRH) test. METHODS: Dex/CRH tests were performed on 20 women with PMD and 20 women who were also perimenopausal but without current or past depression (control women). Main outcome measures were plasma levels of cortisol and adrenocorticotropin (ACTH) and 24-hour urinary free cortisol (UFC). Five women took chronic stable medications, otherwise all women were medically healthy, and both groups were comparable with respect to reproductive stage and age. Standardized symptom rating scales were administered to each woman prior to Dex/CRH testing. RESULTS: No group differences were present in either baseline or stimulated ACTH and cortisol secretion. Baseline plasma measures of estradiol, progesterone, and 24-hour UFC levels similarly did not differ in PMD and control women. CONCLUSION: Despite reports of increased stress responsiveness in PMD, we observed no abnormalities of HPA axis activity associated with PMD compared with women without depression. These findings suggest that PMD is not uniformly associated with HPA dysregulation and could reflect underlying pathophysiologic processes that are distinct from women with nonreproductive-related depressions.

Early effects of roflumilast on insulin sensitivity in adults with prediabetes and overweight/obesity involve age-associated fat mass loss - results of an exploratory study.

PURPOSE: Roflumilast (Daliresp, Daxas) is a FDA-approved phosphodiesterase 4 (PDE4) inhibitor for the treatment of moderate-to-severe chronic obstructive pulmonary disease. In mice and in limited human studies, this oral medication can cause weight loss and improve insulin sensitivity. We set out to determine the mechanism of its effect on insulin sensitivity. PATIENTS AND METHODS: Eight adults with overweight/obesity and prediabetes received roflumilast for 6 weeks. Before and after roflumilast, subjects underwent tests of insulin sensitivity, mixed meal test, body composition, markers of inflammation, and mitochondria function. Dietary intake and physical activity were also assessed. Our primary outcome was the change in peripheral insulin sensitivity, as assessed by the hyper-insulinemic euglycemic clamp. RESULTS: This study was underpowered for the primary outcome. Pre- and post-roflumilast mean peripheral insulin sensitivity were 48.7 and 70.0 mg/g fat free mass/minute, respectively, (P-value=0.18), respectively. Among the mixed meal variables, roflumilast altered glucagon-like peptide 1 (GLP-1) hormone the most, although the average effect was not statistically significant (P=0.18). Roflumilast induced a trend toward significance in 1) decreased energy intake (from 11,095 KJ to 8,4555 KJ, P=0.07), 2) decreased fat mass (from 34.53 to 32.97 kg, P=0.06), 3) decreased total and LDL cholesterol (P=0.06 for both variables), and 4) increased plasma free fatty acids (from 0.40 to 0.50 mEq/L, P=0.09) The interval changes in adiposity and free fatty acid were significantly associated with the subject's age (P-value range= <0.001 to 0.02 for the correlations). Inflammatory and adhesion markers, though unchanged, significantly correlated with one another and with incretin hormones only after roflumilast. CONCLUSION: We demonstrate, for the first time in humans, increasing percentage of fat mass loss from roflumilast with increasing age in adults with prediabetes and overweight/obesity. We also demonstrate novel associations among roflumilast-induced changes in incretin hormones, inflammatory markers, peripheral insulin sensitivity, and adiposity. We conclude that roflumilast's early effects on insulin sensitivity is indirect and likely mediated through roflumilast's prioritization of lipid over glucose handling. CLINICAL TRIALS REGISTRATION: NCT01862029.

Liquid chromatographic analysis of guanidino compounds using furoin as a new fluorogenic reagent.

Furoin, a benzoin analogue, was examined as novel fluorogenic reagent for the selective and sensitive LC determination of various guanidines after pre-column derivatization. The derivatization reaction was carried out at 100 degrees C for 5 min to give adducts that were separated on a Phenomenex Synergi MAX-RP column and detected at lambda(em)=410 nm with lambda(ex)=325 nm. The reagent showed to be useful both for determining together arginine (Arg) and creatine (CT) in dietary supplements under elution isocratic conditions and for the simultaneous analysis of a variety of guanidines in biological samples (human plasma and urine) under elution gradient conditions. The detection limits ranged from 7 to 25 fmol. Recovery studies showed good results for all determined guanidino compounds (85.6-106.2%; R.S.D.=1.1-6.2%).

Development and validation of a liquid chromatographic method for the determination of ascorbic acid, dehydroascorbic acid and acetaminophen in pharmaceuticals.

A reversed-phase ion pair liquid chromatographic method (RP-LC) for the determination of dehydroascorbic acid (DHA) and ascorbic acid (AA) and also acetaminophen, which is combined in pharmaceuticals, is proposed and validated. AA and acetaminophen were analyzed directly, while DHA was determined after pre-column derivatization with 4,5-dimethyl-1,2-phenylenediamine (DMPD). The derivatization reaction was carried out under mild conditions (10min at ambient temperature) in the dark in sodium acetate buffer (80mM; pH 3.7) solution containing EDTA as metal scavenger. The chromatographic separations were performed on a Phenomenex Synergi 4u hydro-RP (150mmx4.6mm) under isocratic elution conditions, using cetyltrimethylammonium bromide (CTAB) as ion-pairing reagent in the mobile phase. Linear responses were observed for each compound. The intra-day precision (R.S.D.) was < or =1.40% and there was no significant difference between intra- and inter-day data. Recovery studies showed good results for all compounds (99.7-101.8%) with R.S.D. ranging from 0.56 to 1.82%. The limits of quantitation were about 40, 50 and 140pmol for acetaminophen, AA and DHA, respectively. The DHA impurity values found in dosage forms were < or =0.2% of AA.

A therapeutic dose of FK506 does not affect collagen turnover pathways in healthy human gingival fibroblasts.

We previously demonstrated that a high dose of tacrolimus (1 mumol/L) induced expression of matrix metalloproteinase (MMP) proteins in human cultured gingival fibroblasts, suggesting a molecular mechanism maintaining gingival collagen homeostasis in tacrolimus-treated patients. Herein we have analyzed whether the effect on collagen turnover might be influenced by a therapeutic tacrolimus dose. Human gingival fibroblasts were incubated for 72 hours with 10 nmol/L, 100 nmol/L, and 1 mumol/L tacrolimus, or left untreated (CT). Collagen type I and III (COL-I, COL-III), lysyl hydroxylase 2b (LH2b), MMP-1 and -2, tissue inhibitor of MMP-1 and transforming growth factor-beta1 (TGF-beta1) mRNA levels were assayed by reverse-transcriptase polymerase chain reaction, collagen protein levels by dot blot, and MMP activity by sodium dodecyl sulfate zymography. Tacrolimus did not affect COL-I, COL-III, or MMP gene expression, while LH2b and TGF-beta1 tended to be down-regulated after 1 mumol/L FK506. Conversely, protein levels of MMP-1 (P = NS) and MMP-2 (P < .05 vs CT, 10 nmol/L, 100 nmol/L) were up-regulated after 1 mumol/L tacrolimus. Our findings confirmed that a high dose of tacrolimus does not induce interstitial collagen overexpression by gingival fibroblasts and induces up-regulation of MMPs protein levels. Interestingly, at doses corresponding to whole blood trough levels, tacrolimus did not exert any evident effect on collagen turnover pathways, suggesting that tacrolimus is likely to not affect collagen homeostasis in the gingival connective tissue compartment of FK506-immunosuppressed subjects. This effect did not seem to be dose-dependent.

Reticulocytes in untreated obstructive sleep apnoea.

BACKGROUND AND AIM: The short, repetitive hypoxaemic episodes observed in obstructive sleep apnoea (OSA) may determine small augmentations in mature red blood cells. It is unknown whether they affect reticulocyte release. This study explored whether the number and degree of maturation of circulating reticulocytes may be altered in OSA, possibly through the effect of erythropoietin. METHODS: Fifty male adult patients with suspected OSA, normoxic during wakefulness, were studied. After nocturnal polysomnography, a blood sample was withdrawn for blood cells count, erythropoietin, iron and transferrin determination. Reticulocyte concentration and degree of immaturity [high (H), medium (M), or low (L)] were also determined. Immature reticulocyte fraction (IRF) was calculated as (M+H) percentage of reticulocytes. RESULTS: A wide range of OSA severity was found [apnoea/hypopnoea index (AHI): 44.3 +/- 30.4, range 0.3-105; sleep time spent at oxyhaemoglobin saturation <90%: 18.1 +/- 22.2%, range 0-81%]. Both reticulocyte count and IRF slightly exceeded the normal range. Patients with a reticulocyte concentration > 2% had higher EPO levels (p < 0.05), but not worse nocturnal desaturations, than those with values < 2%. By contrast, subjects with IRF < 15% showed worse desaturations (p < 0.05), but similar EPO concentrations, when compared to subjects whose IRF was < 10%. At univariate analysis, reticulocyte count correlated to erythropoietin, while IRF to transferrin saturation, BMI and OSA severity. At multiple regression, only lowest nocturnal oxygen saturation remained a significant contributor to IRF (r2 0.223, p < 0.05). CONCLUSIONS: This data suggests that hypoxaemia due to OSA could influence the release of immature reticulocytes, but this effect is not mediated by erythropoietin.

Investigating the role of brain-derived neurotrophic factor in relapsing-remitting multiple sclerosis.

Multiple sclerosis (MS) is a common, heterogeneous disorder of the central nervous system with a complex trait composed of both genetic and environmental factors. Recently, scientific interest has increased in defining factors that possibly contribute to brain functional plasticity; the results might be useful to assess the relationship between MS lesion burden and clinical events, as well as explaining the well-known phenotypic heterogeneity of the disease. In this study, we explored the effect of the Val66Met brain-derived neurotrophic factor (BDNF) functional polymorphism on cognitive performances and volumetric measurements obtained by magnetic resonance imaging of the brain in a selected population of relapsing-remitting MS (RRMS) patients, with relatively short disease duration and minimal clinical disability, compared to gender, age and educational-level matched healthy subjects. We found that in the RRMS group, the BDNF Met-allele was significantly associated with the lower volume of cerebral grey matter (GM) (P = 0.005). Furthermore, a significant (P = 0.013) interaction effect between 'MS-status' and the BDNF genotype was found for GM volumes, with the result that patients carrying the BDNF Met-allele showed a higher risk of developing global GM atrophy than the homozygous Val/Val. No BDNF-related impact on global neuropsychological functions resulted in either RRMS patients or controls. Our data seem to be consistent with the reported influence of BDNF in neuronal plasticity, thus suggesting that the Met-allele might have a negative prognostic effect on cortical morphometry in RRMS patients.

Development and validation of a liquid chromatographic method for the determination of branched-chain amino acids in new dosage forms.

A reversed-phase liquid chromatographic method (RP-LC) is proposed and validated for the analysis of branched-chain amino acids (l-leucine, l-isoleucine and l-valine) in new pharmaceutical formulations. The pre-column derivatization reaction of these amino acids with 2,4-dinitrofluorobenzene (DNFB) has been investigated considering the matrix effect. The compound reacts at 60 degrees C for 10 min at pH 9 with the amino function, in presence of cetyltrimethylammonium bromide (CTAB), to give adducts that have been separated on a RP amide C16 column and detected at lambda=360 nm. Linear responses were observed for each derivative. The intra-day precision (R.S.D.) was

Comparing the performance of three panels rules of blood smear review criteria on an Italian multicenter evaluation.

BACKGROUND: The aims of this study were to compare the diagnostic accuracy of blood smear review criteria, by means of three different panel rules, those proposed by: the International Consensus Group for Hematology [41-ICGH rules], the Italian Survey [IS rules] and the Working Group on Hematology-SIBioC (WGH) consensus rules (WGH rules). METHODS: This study is based on 2707 peripheral blood (PB) samples referred for routine hematological testing to the WGH-associated laboratories displaced all over the Italian territory. The PB samples were processed on seven different hematology analyzers (HAs): Advia 2120i, XE-2100, BC-6800, ABX Pentra, XN-1000, Cell-DYN Sapphire, and DxH800, respectively. All the results provided by the HAs were analyzed through the application of three different blood smear review criteria: that is, the 41-ICGH, IS, and WGH rules. Finally, data were compared with those obtained by optical microscopy (OM), as the current gold standard. RESULTS: The overall the agreement OM classification with ICGH, IS, and WGH panel rules is 0.83, 0.83, and 0.85, respectively. The false negatives are 2.1%, 3.0%, and 2.9%, while false positives are 15.1%, 13.7%, and 11.7%, respectively. All the seven HAs showed variable interinstrument performance, as three different criteria for OM review were adopted on each of them from time to time. CONCLUSION: These results presented show that the customization of validation rules is necessary for enhancing the quality of hematological testing and optimizing workflow.