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It is well known that some life-style habits in pregnancy may influence fetal growth. Active maternal smoking is a well recognised risk of adverse pregnancy outcome, mainly low birth weight. Recent studies report that environmental tabacco smoke (ETS) exposure adversely affects fetal growth with an elevated risk of low birth weight. Also coffee or alcohol intake during pregnancy has been linked to adverse reproductive outcomes. The aim of this study was to investigate the effects of maternal smoking habits, ETS exposure and maternal coffee and alcohol intake throughout the last trimester of pregnancy on preterm delivery (PD) and on small for gestational age at term (term SGA).A case-control study was carried out between October 1999 and September 2000 in 9 italian cities (Genoa, Udine, Modena, Parma, Siena, Roma, L'Aquila, Naples and Catania). 525 preterm cases (children born between the 26th to the 38th week of pregnancy) and 317 term SGA (children born fron the 38th week and weighted under the 10th percentile of weight) were recruited. Controls (n. 871) were singleton birth matched to the cases by sex, center and calendar week of birth, whose gestational age was ≥38 weeks and weight ≥10th percentile. Data were collected by a validated, self-administered questionnaire; it referred the last trimester of pregnancy and included four parts. The first collected socio-demographic data, the second gathered information about nutritional habits and water consumption, the third assessed the woman's life stile during the last three months of pregnancy, the fourth gathered data on woman's health status. Univariate and multivariate logistic regression analyses were performed in order to estimate odds ratios.According to univariate analyses, risk of term SGA increased with increasing cigarette smoking during pregnancy (OR: 2.09, 95%CI: 1.45-3.00 for 1-9 cigarettes/day, and OR = 2.76, 95%CI: 1.67-4.45 for 10 cigarettes and more/day). Regarding to PD, it was observed a OR: 1.47, 95%CI: 1.05-2.04 for 1-9 cigarettes/day and a OR: 1,30 95%CI: 0.78-4.81 for 10 cigarettes/day. Exposure to ETS appeared to be mainly related to term SGA, when there were more than two smokers at home (OR: 3.05, 95%CI: 1.19-7.79). Alcohol and coffee intake were not associated with term SGA (OR: 1.31, 95%CI: 0.89-1.93 and OR: 0.90, 95%CI: 0.42-1.93, respectively). According to multivariate logistic analyses, adjusting for socio-demografic variables and life-stile habits, only the influence of active smoking on term SGA was confirmed (Adjusted OR = 2.49, 95%CI: 1.74-3.56).This study provides clear evidence that maternal smoke in pregnancy influence term SGA. No adverse effect on fetal growth was observed in ralation to coffee and alcohol intake, while maternal EST exposure didn't reach the statistical significance due to the small number of women heavily exposed. [ABSTRACT FROM AUTHOR]

Objectives: Among critically ill patients, the benefits of nutrition support may vary depending on severity of organ dysfunction. The objective of the current article was to explore the relationship between organ failure and calories exposure with hospital mortality during the first week of acute respiratory distress syndrome., Design: Retrospective observational study., Setting: Single-center ICU., Patients: Adults admitted to the ICU with a diagnosis of acute respiratory distress syndrome., Interventions: Calorie delivery from enteral nutrition, parenteral nutrition, propofol, and dextrose containing fluids were collected for 7 days following intubation. Sequential Organ Failure Assessment score was calculated at ICU admit and for the same 7 days to describe organ dysfunction; four different Sequential Organ Failure Assessment variables were created 1) Sequential Organ Failure Assessment at ICU admit, 2) average Sequential Organ Failure Assessment for the first 7 days following intubation, 3) the highest Sequential Organ Failure Assessment for the first 7 days following intubation, and 4) change in Sequential Organ Failure Assessment from intubation to 7 days later., Measurements and Main Results: A total of 298 patients were included. Sequential Organ Failure Assessment at ICU admit, average Sequential Organ Failure Assessment for the first 7 days following intubation, highest Sequential Organ Failure Assessment for the first 7 days following intubation, change in Sequential Organ Failure Assessment from intubation to 7 days later, and calorie delivery the first 7 days following intubation were all associated with increased likelihood of mortality. Compared with patients with low organ failure and low-calorie delivery, those with high-calorie delivery and low organ failure, low-calorie delivery and high organ failure, and the combination of both high organ failure with high-calorie delivery were associated with an incremental increase in the likelihood or mortality., Conclusions: Organ failure appears to modify the relationship between calorie exposure and ICU outcome. Additional research is needed to identify appropriate thresholds for safe calorie exposure with increased organ failure.

Objectives: The aim of this study was to determine the effect of digested whole human milk (HM; first sample available after birth from mothers of premature infants) on inflammation, oxidative stress, and cytotoxicity in Caco-2 human intestinal epithelial cells stimulated with lipopolysaccharides or tumor necrosis factor (TNF) to mimic the potential in vivo insults facing the premature infant's gastrointestinal tract., Methods: Fully differentiated Caco-2 cells were exposed to digested HM (n = 10; samples from 10 different individuals) before stimulation with lipopolysaccharides, TNF, or no stimulation overnight. Inflammation was determined by production of interleukin-8, oxidative stress by levels of F2-isoprostane, and cytotoxicity by released lactate dehydrogenase., Results: HM significantly suppressed interleukin-8 production and cytotoxicity in TNF-stimulated cells, while also suppressing cell death under baseline conditions. Individual HM samples differed widely in their ability to modulate cellular responses., Conclusions: Results from this study provide evidence that digested HM can reduce both an exaggerated inflammatory response and intestinal damage that contribute to the pathogenesis of necrotizing enterocolitis.

Background: Fatigue is highly prevalent after hematopoietic stem cell transplantation (HCT). It has been described as intense and may last for years following treatment., Objective: The aim of this study is to compare fatigue, physical activity, sleep, emotional distress, cognitive function, and biological measures in HCT survivors with persistent fatigue (n = 25) with age- and gender-matched healthy controls with occasional tiredness (n = 25)., Methods: Data were collected using (a) objective, real-time assessments of physical activity and sleep over 7 days; (b) patient-reported fatigue assessments; (c) computerized objective testing of cognitive functioning; and (d) biological measures. Differences between groups were examined using multivariate analysis of variance., Results: Survivors of HCT reported increased physical (P < .001), mental (P < .001), and overall (P < .001) fatigue as well as increased anxiety (P < .05) and depression (P < .01) compared with healthy controls. Red blood cell (RBC) levels were significantly lower in HCT survivors (P < .001). Levels of RBC for both groups, however, were in the normal range. Tumor necrosis factor-α (P < .001) and interleukin-6 (P < .05) levels were significantly higher in HCT survivors., Conclusions: Persistent fatigue in HCT survivors compared with healthy controls with occasional tiredness is accompanied by increased anxiety and depression along with decreased RBC counts. Elevated tumor necrosis factor-α and interleukin-6 levels may be important biomarkers., Implications for Practice: This study provides preliminary support for the conceptualization of fatigue as existing on a continuum, with tiredness anchoring one end and exhaustion the other. Persistent fatigue experienced by HCT survivors is more severe than the occasional tiredness of everyday life.

Background: Reduced fat oxidation in hypertrophied hearts coincides with a shift of carnitine palmitoyl transferase I from muscle to increased liver isoforms. Acutely increased carnitine palmitoyl transferase I in normal rodent hearts has been shown to recapitulate the reduced fat oxidation and elevated atrial natriuretic peptide message of cardiac hypertrophy., Methods and Results: Because of the potential for reduced fat oxidation to affect cardiac atrial natriuretic peptide, and thus, induce adipose lipolysis, we studied peripheral and systemic metabolism in male C57BL/6 mice model of transverse aortic constriction in which left ventricular hypertrophy occurred by 2 weeks without functional decline until 16 weeks (ejection fraction, -45.6%; fractional shortening, -22.6%). We report the first evidence for initially improved glucose tolerance and insulin sensitivity in response to 2 weeks transverse aortic constriction versus sham, linked to enhanced insulin signaling in liver and visceral adipose tissue (epididymal white adipose tissue [WAT]), reduced WAT inflammation, elevated adiponectin, mulitilocular subcutaneous adipose tissue (inguinal WAT) with upregulated oxidative/thermogenic gene expression, and downregulated lipolysis and lipogenesis genes in epididymal WAT. By 6 weeks transverse aortic constriction, the metabolic profile reversed with impaired insulin sensitivity and glucose tolerance, reduced insulin signaling in liver, epididymal WAT and heart, and downregulation of oxidative enzymes in brown adipose tissue and oxidative and lipogenic genes in inguinal WAT., Conclusions: Changes in insulin signaling, circulating natriuretic peptides and adipokines, and varied expression of adipose genes associated with altered insulin response/glucose handling and thermogenesis occurred prior to any functional decline in transverse aortic constriction hearts. The findings demonstrate multiphasic responses in extracardiac metabolism to pathogenic cardiac stress, with early iWAT browning providing potential metabolic benefits., (© 2017 American Heart Association, Inc.)

Objective: Currently, there is no therapy for severe acute pancreatitis (AP) except for supportive care. The lipase inhibitor orlistat, the peroxisome proliferator-activated receptor γ agonist rosiglitazone, and the chemokine receptor 2 antagonists attenuate the severity of AP in rodents if administered before or at the time of induction of pancreatitis. However, it is unknown whether these treatments are effective if administered therapeutically after induction of pancreatitis., Methods: Male C57BL6 mice with diet-induced obesity received 2 injections of mrIL-12 (150 ng per mouse) and mrIL-18 (750 ng per mouse) intraperitoneally at 24-hour intervals. The mice were injected 2, 24, and 48 hours after the second injection of IL-12 + IL-18 with orlistat (2 mg per mouse), rosiglitazone (0.4 mg per mouse), RS102895 (0.3 mg per mouse), or vehicle (20 μL of DMSO and 80 μL of canola oil) and euthanized after 72 hours., Results: Orlistat decreased intra-abdominal fat necrosis compared with vehicle (P < 0.05). However, none of the drug treatments produced significant decreases in pancreatic edema, acinar necrosis, or intrapancreatic fat necrosis., Conclusions: Drugs previously shown to improve the severity of AP when given before or at the time of induction of pancreatitis failed to do so when administered therapeutically in the IL-12 + IL-18 model.

The prevalence of obesity, especially among the young, is dramatically increasing in the United States. Obesity is associated with accelerated atherosclerosis and increased rates of cardiovascular death. There are many plausible mechanisms by which an increase in adipose tissue could adversely affect the vessel wall. These include the changes in blood pressure, glucose level, lipid/lipoprotein metabolism, and systemic inflammation. In addition, factors secreted by adipose tissue may directly influence vessel wall homeostasis by influencing the function of endothelial cells, arterial smooth muscle cells, and macrophages in the vessel wall. There is general agreement that central, as opposed to peripheral, adipose tissue confers the most cardio-metabolic risk. Although the basis of this differential risk has not been not established, the pattern of gene expression and secretory products in visceral fat would be predicted to be more atherogenic compared with that in subcutaneous peripheral fat. Numerous studies have shown the beneficial effects of weight loss on markers of cardiovascular risk but fewer have demonstrated improvement in direct measures of large vessel disease. The unfolding role of adipose tissue as an important metabolic and secretory organ provides new opportunities for developing more effective approaches for preventing obesity and its atherosclerotic complications.

Leptin is a pleiotrophic protein mainly produced by adipocytes that has been implicated as a link between nutritional status and immune function. Severe bacterial infection is associated with elevated plasma levels of leptin. To determine the role of leptin in the host response to bacterial pneumonia leptin deficient ob/ob mice and normal wild-type (WT) mice were intranasally infected with different doses of the Gram-positive pathogen Streptococcus (S.) pneumoniae or the Gram-negative bacterium Klebsiella (K.) pneumoniae. After infection with lower doses of either pathogen ob/ob mice displayed lower pulmonary levels of proinflammatory cytokines, in particular tumor necrosis factor-alpha and chemokines. However, after infection with a higher dose of S. pneumoniae or K. pneumoniae the lung concentrations of these inflammatory mediators did not differ between ob/ob and WT mice. In addition, the extent and severity of lung inflammation, as assessed by semi-quantitative histopathology scores, were similar in both mouse strains. Finally, leptin deficiency did not impact on the bacterial outgrowth in the lungs during either Gram-positive or Gram-negative pneumonia irrespective of the infective dose. These data suggest that although leptin may play a modest role in the regulation of inflammation during bacterial pneumonia, it does not contribute to host defense mechanisms that act to limit the outgrowth of S. pneumoniae or K. pneumoniae in the lower airways.

We studied the reliability of biologic indices for monitoring perchlorethylene (PCE) exposure at low environmental solvent concentrations. Environmental monitoring was performed by personal sampling, biologic monitoring by measuring PCE in alveolar air (PCE-Alv), blood (PCE-B), and urine (PCE-U) in 26 low-exposed dry-cleaners. Correlation coefficients (r) between environmental PCE and PCE-B, PCE-Alv, and PCE-U were 0.94, 0.81, and 0.67 respectively. A high correlation was also found among biologic indices: r value was 0.96 between PCE-B and PCE-Alv, 0.95 between PCE-B and PCE-U, and 0.87 between alveolar PCE-Alv and PCE-U. The examined biologic indices proved sensitive enough for biologic monitoring of low exposure to PCE and can give substantially similar information in terms of exposure evaluation. PCE-Alv offers some advantages because it correlated better with exposure and is analytically simpler.

Background: To evaluate associations between exposure to disinfection byproducts in drinking water and adverse birth outcomes, personal exposure to disinfection byproducts must take into consideration multiple routes of exposure., Methods: We assessed the reproducibility and validity of a questionnaire measuring water consumption, showering and bathing habits, use of chlorine-based products, and swimming pool attendance in 237 pregnant Italian women enrolled between June and December 1999. The questionnaire was completed during the last trimester of pregnancy (preQ) and again a few days after delivery (postQ). Data from postQ were compared with a 7-day diary completed during the last trimester., Results: According to postQ, total water intake was 2.6 liters per day, whereas tap water intake was 0.6 liters per day. Intraclass correlation coefficients of postQ compared with preQ were 0.85 for tap water daily intake and 0.77 for duration of showering and bathing. Pearson's correlation coefficients were 0.84 for tap water daily intake, 0.81 for frequency of showering, and 0.94 for bathing. The kappa statistics were 0.76 (95% confidence limits = 0.68, 0.85) for use of domestic chlorine-based products and 0.82 (0.70, 0.94) for indoor swimming. Pearson's coefficients for postQ compared with the diary were 0.78 for tap water daily intake, 0.62 for frequency of showering, and 0.64 for bathing. Compared with the diary, the sensitivity and specificity of postQ in assessing indoor swimming were 75% and 90%, respectively., Conclusions: The questionnaire appears to be a valid and reliable method for assessing exposure to disinfection byproducts in the last trimester of pregnancy.

Background: A growing body of evidence suggests a role for inflammation in acute coronary syndromes. The aim of this study was to assess the role of proinflammatory cytokines, their time course, and their association with prognosis in unstable angina., Methods and Results: We studied 43 patients aged 62+/-8 years admitted to our coronary care unit for Braunwald class IIIB unstable angina. In each patient, serum levels of interleukin-1 receptor antagonist (IL-1Ra), interleukin-6 (IL-6) (which represent sensitive markers of biologically active IL-1beta and tumor necrosis factor-alpha levels, respectively), and troponin T were measured at entry and 48 hours after admission. Troponin T-positive patients were excluded. Patients were divided a posteriori into 2 groups according to their in-hospital outcome: group 1 comprised 17 patients with an uneventful course, and group 2 comprised 26 patients with a complicated in-hospital course. In group 1, mean IL-1Ra decreased at 48 hours by 12%, and IL-6 diminished at 48 hours by 13%. In group 2, IL-1Ra and IL-6 entry levels were higher than in group 1 and increased respectively by 37% and 57% at 48 hours (P<0.01)., Conclusions: These findings indicate that although they receive the same medical therapy as patients who do not experience an in-hospital event, patients with unstable angina and with complicated in-hospital courses have higher cytokine levels on admission. A fall in IL-1Ra and IL-6 48 hours after admission was associated with an uneventful course and their increase with a complicated hospital course. These findings may suggest novel therapeutic approaches to patients with unstable angina.

Cytokines play a pathogenetic role in a variety of infective and inflammatory diseases. In the present study, we had two objectives: (a) to define the kinetics of tumor necrosis factor (TNF) in plasma after acute myocardial infarction (AMI) in patients treated with early thrombolysis, and (b) to measure other cytokines, interleukin-1 (IL-1) and TNF receptor antagonists, in plasma. TNF-alpha, but not IL-1 beta or IL-8, was present in plasma of 6 of 7 patients with severe AMI (Killip class 3 or 4). No TNF (< 50 pg/ml) was detected in a group of 11 patients with uncomplicated myocardial infarction (Killip class 1) or in control patients without AMI. Soluble TNF receptor type I and IL-1 receptor antagonist (IL-1Ra) were also significantly increased in the group with severe AMI compared with those with uncomplicated AMI. Circulating TNF is increased only in AMI complicated by heart failure at hospital admission. This finding may have diagnostic and therapeutic relevance.