Executive Function Moderates Functional Outcomes of Engagement Strategies During Rehabilitation in Older Adults.

OBJECTIVE: This study examined cognitive, affective, and medical impairments and their impact on rehabilitation approaches for improving functional outcome after hospitalization in older adults. DESIGN: A secondary analysis of a randomized clinical trial in 229 adults 65 yrs or older admitted to two skilled nursing facilities undergoing rehabilitation services was conducted. Patients were randomized to receive physical and occupational therapy by therapists trained in systematic approaches to engage patients, called Enhanced Medical Rehabilitation, or standard of care. The outcome of interest was functional improvement, defined as Barthel Index at discharge (controlling for Barthel Index upon admission). This study analyzed the relationship of measures of cognition, depression, and medical comorbidities as predictors of functional outcome and as moderators interacting with treatment group. RESULTS: Clock drawing score moderated treatment effect size; the functional improvement of Enhanced Medical Rehabilitation over standard of care therapy reduced with increasing executive impairment. In contrast, general cognitive abilities, depression, medical comorbidities, and readiness for rehabilitation were neither predictors nor moderators of functional improvement. CONCLUSIONS: For older adults undergoing rehabilitation, greater functional improvement with the motivational techniques of Enhanced Medical Rehabilitation was contingent on patients having intact executive function. Given that executive function impairments are common in rehabilitation populations, new strategies are needed to improve treatment outcomes in physical/occupational therapy. TO CLAIM CME CREDITS: Complete the self-assessment activity and evaluation online at http://www.physiatry.org/JournalCME. CME OBJECTIVES: Upon completion of this article, the reader should be able to (1) Discuss the role of baseline affective, cognitive, and medical impairments in impacting functional outcomes of older adults undergoing rehabilitation; (2) Describe the behavioral change and motivational approaches that are core features of the novel intervention known as Enhanced Medical Rehabilitation (E-MR); and (3) Determine the role of baseline executive function in moderating the effect of rehabilitation intervention on functional outcomes in older adults. LEVEL: Advanced. ACCREDITATION: The Association of Academic Physiatrists is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.The Association of Academic Physiatrists designates this Journal-based CME activity for a maximum of 1.0 AMA PRA Category 1 Credit(s)™. Physicians should only claim credit commensurate with the extent of their participation in the activity.

Density Based Characterization of Mechanical Cues on Cancer Cells Using Magnetic Levitation.

Extracellular matrix (ECM) stiffness is correlated to malignancy and invasiveness of cancer cells. Although the mechanism of change is unclear, mechanical signals from the ECM may affect physical properties of cells such as their density profile. The current methods, such as Percoll density-gradient centrifugation, are unable to detect minute density differences. A magnetic levitation device is developed (i.e., MagDense platform) where cells are levitated in a magnetic gradient allowing them to equilibrate to a levitation height that corresponds to their unique cellular density. In application of this system, MDA-MB-231 breast and A549 lung cancer cells are cultured and overall differences in cell density are observed in response to increasing collagen fiber density. Overall, density values are significantly more spread out for MDA-MB-231 cells extracted from the 1.44 mg mL-1 collagen gels compared to those from 0.72 mg mL-1 collagen, whereas no significant difference with A549 cell lines is observed. The MagDense platform can determine differences in cellular densities under various microenvironmental conditions. The imaging of cancer cells in a magnetic levitation device serves as a unique tool to observe changes in phenotypic properties of cancer cells as they relate to micromechanical cues encoded by the ECM.

Epithelial-to-Mesenchymal Transition (EMT) and Drug Response in Dynamic Bioengineered Lung Cancer Microenvironment.

Tumor microenvironment and the interplay of physical and mechanical forces are key determinants of cancer initiation, progression, and response to drug treatment. However, the impact of tumor microenvironment on cancer progression is poorly understood, in large due to the lack of in vitro models that recapitulate the physical aspects of tumor microenvironment. Herein, a simple, dynamic 3D nonsmall cell lung carcinoma culture using a multichannel microfluidic model platform is developed for evaluating the contribution of flow-induced hydrodynamic shear stress on epithelial-to-mesenchymal transition (EMT). It is found that flow induces changes in cellular morphology and EMT in 2D and 3D when lung cancer A549 cells are cultured on a microfluidic chip under laminar flow for 4-5 days compared to traditional static cultures. The role of dynamic cell culture on chemotherapeutic effects is monitored. Drug response with an existing anti-cancer drug, e.g., erlotinib and an investigational drug (NSC-750212), shows distinct cytotoxic effects in flow compared to static cultures, suggesting a potential influence of flow on drug efficacy in 2D and 3D models. The platform demonstrates the ability to create a dynamic microscale tumor model, which could be explored as a tool for early drug screening and treatment monitoring in cancer and other diseases.

Hepatic ketogenic insufficiency reprograms hepatic glycogen metabolism and the lipidome.

While several molecular targets are under consideration, mechanistic underpinnings of the transition from uncomplicated nonalcoholic fatty liver disease (NAFLD) to nonalcoholic steatohepatitis (NASH) remain unresolved. Here we apply multiscale chemical profiling technologies to mouse models of deranged hepatic ketogenesis to uncover potential NAFLD driver signatures. Use of stable-isotope tracers, quantitatively tracked by nuclear magnetic resonance (NMR) spectroscopy, supported previous observations that livers of wild-type mice maintained long term on a high-fat diet (HFD) exhibit a marked increase in hepatic energy charge. Fed-state ketogenesis rates increased nearly 3-fold in livers of HFD-fed mice, a greater proportionate increase than that observed for tricarboxylic acid (TCA) cycle flux, but both of these contributors to overall hepatic energy homeostasis fueled markedly increased hepatic glucose production (HGP). Thus, to selectively determine the role of the ketogenic conduit on HGP and oxidative hepatic fluxes, we studied a ketogenesis-insufficient mouse model generated by knockdown of the mitochondrial isoform of 3-hydroxymethylglutaryl-CoA synthase (HMGCS2). In response to ketogenic insufficiency, TCA cycle flux in the fed state doubled and HGP increased more than 60%, sourced by a 3-fold increase in glycogenolysis. Finally, high-resolution untargeted metabolomics and shotgun lipidomics performed using ketogenesis-insufficient livers in the fed state revealed accumulation of bis(monoacylglycero)phosphates, which also accumulated in livers of other models commonly used to study NAFLD. In summary, natural and interventional variations in ketogenesis in the fed state strongly influence hepatic energy homeostasis, glucose metabolism, and the lipidome. Importantly, HGP remains tightly linked to overall hepatic energy charge, which includes both terminal fat oxidation through the TCA cycle and partial oxidation via ketogenesis.

New Biomarkers to Diagnose Ventilator Associated Pneumonia: Pentraxin 3 and Surfactant Protein D.

OBJECTIVE: To detect the most effective biomarker to confirm ventilator associated pneumonia (VAP). METHODS: Fifty patients with VAP suspicious diagnosis and 30 healthy patients were recruited. Suspicion of VAP was established if patients met the modified CPIS score ≥ 6 points. The confirmation of VAP was defined by the quantitative culture of nonbronchoscopic bronchoalveolar lavage (BAL) >105 CFU/ml of pathogenic microorganism. Serum samples for determination of C-reactive protein (CRP), procalcitonin (PCT), pentraxin 3 (PTX3), surfactant protein D (SPD) were collected on suspected VAP. RESULTS: Twenty seven of 50 patients were accepted as confirmed VAP group whose nonbronchoscopic BAL cultures were positive and rest of them were accepted as unconfirmed VAP group. PTX3, PCT and SPD levels were significantly higher in confirmed VAP group, (P = 0.021, P = 0.007, P < 0.001 respectively). There were no significant differences in CRP levels between the two groups (P = 0.062). The most sensitive marker for diagnosing VAP was SPD (P < 0.001). Receiver operating characteristic (ROC) curve for modified clinical pulmonary infection score (CPIS) to confirm VAP was evaluated (AUC 0.741 ± 0.07, P < 0.001) and the optimal cutoff value was >7 with a sensitivity of 51.85% and a specificity of 91.3%. SPD levels were significantly higher in Acinetobacter baumannii and Pseudomonas aeruginosa infected patients than culture negative patients (P < 0.001). CONCLUSIONS: The index findings suggest that serum SPD is the most sensitive biomarker in diagnosis of VAP and it can be used as an early and organism specific marker for Acinetobacter baumannii and Pseudomonas aeruginosa.

Surgical Strategies for Spondylodiscitis due to Lumbar Disc Surgery.

AIM: Despite different surgical treatment protocols at different centers for spondylodiscitis due to lumbar surgery, there is no consensus on its surgical indications. In this study, we aimed to clarify the steps to be followed in the management and treatment of postoperative spondylodiscitis. MATERIAL AND METHODS: The data of 20 cases with postoperative spondylodiscitis were evaluated. C-reactive protein (CRP) was used for diagnosis and follow-up. According to culture results of the infected material obtained from the operated cases, appropriate antibiotic treatment was initiated. In non-operated cases, parenteral empirical antibiotic treatment was implemented. Surgical treatment was planned for cases with clinical and radiological instability, abscess on imaging and those who were nonrespondent to empirical antibiotic treatment. For the cases that clinically recovered and had normal CRP levels, oral antibiotic treatment was continued after parenteral antibiotic treatment. RESULTS: Of the cases; 13 were male (65%) and 7 were femals (35%). The mean age was 56.3 years (32-74). The most prevalent complaints in referral were waist and leg pain. Except one, all cases had increased CRP levels. All patients had spondylodiscitis on magnetic resonance imaging. Seven had radiological and clinical instability and 3 had epidural abscess. The most commonly growing microorganism in culture was Staphylococcus aureus. Surgical treatment was applied to seven cases and medical treatment to 13 cases. CONCLUSION: In cases with waist pain in the postoperative period, the first potential diagnosis to be considered is spondylodiscitis. Surgical treatment should be implemented for cases resistant to empirical antibiotic treatment, with abscess on imaging, or with lumbar instability.

Does antimicrobial usage before meningitis lead to a higher risk of adult postsurgical Acinetobacter baumannii meningitis than that of Enterobacteriaceae meningitis?

Acinetobacter baumannii and Enterobacteriaceae are two pathogens responsible for postneurosurgical meningitis. The aim of this retrospective study was to evaluate the factors that influenced the outcomes in patients with postneurosurgical meningitis caused by A. baumannii and Enterobacteriaceae. Patients with post-surgical meningitis were identified from infection control committee charts between 2007 and 2015. Subjects over 16 years old who had positive cerebral spinal fluid cultures for A. baumannii or Enterobacteriaceae were enrolled in the study. Clinical and laboratory data for 30 patients with A. baumannii meningitis were compared with those of 12 patients with Enterobacteriaceae meningitis. The mean age of patients was 51.9 years and 57.1% were male. Eleven patients had comorbidities, the most common being diabetes mellitus. Most patients were due to intracranial haemorrhage (78.6%). The rate of the patients who received an appropriate antimicrobial therapy was 35.7%, and the crude mortality rate was 64.3%. In univariate analysis, previous antibiotic use, an infection before meningitis and mechanical ventilation had an increased risk of A. baumannii meningitis. Moreover, intrathecal antimicrobial use, inappropriate empirical antimicrobial use, antimicrobial resistance and alanine aminotransferase elevation were significantly higher in patients with A. baumannii meningitis than in those with Enterobacteriaceae meningitis. Antimicrobial use before meningitis (8.84 times) and mechanical ventilation (7.28 times) resulted in an increased risk of A. baumannii meningitis. None of the results affected 30-day mortality. Avoidance of unnecessarily prolonged antimicrobial usage may help to prevent a selection of A. baumannii.

[Investigation of carbapenemases in carbapenem-resistant Escherichia coli and Klebsiella pneumoniae strains isolated in 2014 in Turkey]. / Türkiye'de 2014 yili içinde izole edilen karbapeneme dirençli Escherichia coli ve Klebsiella pneumoniae izolatlarinda karbapenemaz varliginin arastirilmasi.

Carbapenems are the choice of treatment in infections caused by multidrug resistant Enterobacteriaceae. In recent years carbapenem-resistant Enterobacteriaceae isolates due to carbapenemases have been increasingly reported worldwide. Multicenter studies on carbapenemases are scarce in Turkey. The aim of this study was to determine the distribution of carbapenemases from different parts of Turkey as a part of the European Survey of Carbapenemase Producing Enterobacteriaceae (EuSCAPE) project. Beginning in November 2013, carbapenem-resistant isolates resistant to at least one of the agents, namely imipenem, meropenem, and ertapenem were sent to the coordinating center. Minimum inhibitory concentrations for these carbapenems were determined by microdilution tests following EUCAST guidelines. Production of carbapenemase was confirmed by combination disk synergy tests. Types of carbapenemases were investigated using specific primers for VIM, IMP; NDM, KPC and OXA-48 genes by multiplex polymerase chain reaction. In a six month period, 155 suspected carbapenemase-positive isolates were sent to the coordinating center of which 21 (13.5%) were E.coli and 134 (86.5%) were K.pneumoniae. Nineteen (90.5%) strains among E.coli and 124 (92.5%) strains among K.pneumoniae were shown to harbour at least one carbapenemase gene by molecular tests, with a total of 92.3% (143/155). Carbapenemases were determined as a single enzyme in 136 strains (OXA-48: 84.6%; NDM: 6.3%; VIM: 2.8%; IMP: 1.4%) and as a combination in seven isolates (OXA-48 + NDM: 2.1%; OXA-48 + VIM: 2.1%; VIM + NDM: 0.7%). KPC was not detected in any of the isolates. According to the microdilution test results, resistance to imipenem, meropenem and ertapenem in OXA-48 isolates were 59.5%, 52.9% and 100%, respectively. The combination disk synergy test was 100% compatible with the molecular test results. As most of the OXA-48 producing isolates were susceptible to meropenem but all were resistant to ertapenem, ertapenem seems to be the most sensitive agent in screening carbapenemases in areas where OXA-48 is prevalent and phenotypic combination tests can be useful in centers where molecular tests are not available.

Evaluation of the effect of intranasal infiltrated botulinum toxin-A on a model of allergic rhinitis in rabbits: An Experimental Study.

INTRODUCTION: Allergic Rhinitis (AR) effects 20-40% of the global population and its prevalance increases. Medical treatment and immunotherapy could be used in AR management. But they are not definitive solution. Medical treatment must be used a long time and has side effects. Immunotherapy cannot be applied to every patient and it also takes a long time. The aim of this study is to evaluate symptomatic and histopathological effects of intranasal infiltrated Botulinum Toxin-A (Btx-A) on an animal model of AR. MATERIAL-METHOD: 15 rabbits were divided into 3 groups as control, disease and treatment. AR was formed in disease and treatment groups by intraperitoneal and intranasal ovalbumine. Allergic symptoms were observed and serum IgE levels were estimated to prove forming of AR. Btx-A was infiltrated in inferior turbinates of rabbits in treatment group. Rabbits were sacrified on 32nd day. Paranasal structures were disected and investigated histopathologically. RESULTS: Serous nasal discharge and sneezing were observed after ovalbumine applying in disease and treatment groups. Serum IgE levels on 21st day were higher than 1st day and this difference was significant statistically in disease and treatment groups. Serous discharge and sneezing decreased after Btx-A infiltration in treatment group. In histopathological examination, there were significant difference between disease and treatment group in terms of some histopathological findings. CONCLUSION: Considering the effect of Btx-A on AR in animal, it can be said that Btx-A can decrease symptoms and reorganize histopathological findings of AR.

Molecular epidemiology of quinolon resistant strains of extended spectrum beta-lactamase producing Escherichia coli.

OBJECTIVE: To determine the clonal relationship of ESBL-producing and quinolone resistant E.coli strains and to investigate the risk factors for infections with these microorganisms. METHODS: A total of 95 ESBL-producing and quinolone resistant E.coli strains isolated from various clinical specimens of inpatients and outpatients in our hospital were included in the study. Risk factors for infections with ESBL-producing E.coli and demographic data of the patients were obtained from hospital records. The rep-PCR method was used for the determination of the genetic relationship of the strains. RESULTS: Of the strains included in the study, 33(34.7%) were isolated from inpatients and 62(65.3%) from outpatients. At least one risk factor has been identified in all patients for infection with ESBL producing E.coli and the mean of the risk factors of patients was 4.2. The most common risk factor was urinary catheter insertion (57.9%). The distribution of the strains in each clone was as fallows: clone A: 9(9.5%), clone B: 10(10.5%), clone C: 38(40%), clone D: 12(12.5%), clone E: 6(6.3%), clone F: 7(7.3%) and clone G 5(5.3%). The clones A, D and C (dominant clone) were isolated from hospital and community acquired infections. Clones E, F and G were identified as nosocomial clones. CONCLUSION: Infections with multidrug resistant bacteria may be related to the hospital although they were isolated from outpatients. Developing a medical record system is vitally important to prevent the occurence and spread of resistant bacterial infections in the community.

Evaluation of the Abbott Real Time HCV genotype II assay for Hepatitis C virus genotyping.

OBJECTIVE: The determination of HCV genotypes and subtypes is very important for the selection of antiviral therapy and epidemiological studies. The aim of this study was to evaluate the performance of Abbott Real Time HCV Genotype II assay in HCV genotyping of HCV infected patients in Kayseri, Turkey. METHODS: One hundred patients with chronic hepatitis C admitted to our hospital were evaluated between June 2012 and December 2012, HCV RNA levels were determined by the COBAS® AmpliPrep/COBAS® TaqMan® 48 HCV test. HCV genotyping was investigated by the Abbott Real Time HCV Genotype II assay. With the exception of genotype 1, subtypes of HCV genotypes could not be determined by Abbott assay. Sequencing analysis was used as the reference method. RESULTS: Genotypes 1, 2, 3 and 4 were observed in 70, 4, 2 and 24 of the 100 patients, respectively, by two methods. The concordance between the two systems to determine HCV major genotypes was 100%. Of 70 patients with genotype 1, 66 showed infection with subtype 1b and 4 with subtype 1a by Abbott Real Time HCV Genotype II assay. Using sequence analysis, 61 showed infection with subtype 1b and 9 with subtype 1a. In determining of HCV genotype 1 subtypes, the difference between the two methods was not statistically significant (P>0.05). HCV genotype 4 and 3 samples were found to be subtype 4d and 3a, respectively, by sequence analysis. There were four patients with genotype 2. Sequence analysis revealed that two of these patients had type 2a and the other two had type 2b. CONCLUSION: The Abbott Real Time HCV Genotype II assay yielded results consistent with sequence analysis. However, further optimization of the Abbott Real Time HCV Genotype II assay for subtype identification of HCV is required.

Is rapid antibacterial susceptibility testing medium reliable for routine laboratory practices?

OBJECTIVE: Early detection of antibiotic susceptibility profile of the isolates has critical importance in terms of immediate beginning of the appropriate treatment and increasing of treatment success, such as meningitis, bacteriemia and sepsis. In the present study, it was aimed to compare the antibiotic susceptibility results of Quicolor (Salubris Inc., Massachusetts, USA) and standard disk diffusion method. METHODS: One hundred twenty three isolates were included in this study (80 Enterobacteriaceae, 15 Staphylococci and 28 nonfermentative Gram-negative bacteria). Antibiotic susceptibility in clinical isolates was evaluated using Mueller-Hinton (MH) agar and Quicolor (ES and NF) agar plates. RESULTS: For Enterobacteriaceae, frequency of total concordance, major error, and minor error between the tests were found as 96.8%, 0.8%, and 2.4%, respectively. For Staphylococci, frequency of total concordance, major error, and minor error among the tests were found as 95.7%, 3.5%, and 0.8%, respectively. For non fermentative bacteria, frequency of total concordance, major error, and minor error among the tests were found as 83.9%, 9.6%, and 6.4%, respectively. CONCLUSIONS: Quicolor media provided reliable susceptibility results in enteric bacteria and Staphylococci. However, further studies including higher number of nonfermentative bacteria are required to determine whether the chromogenic media are appropriate for this group of bacteria.

Ketogenesis prevents diet-induced fatty liver injury and hyperglycemia.

Nonalcoholic fatty liver disease (NAFLD) spectrum disorders affect approximately 1 billion individuals worldwide. However, the drivers of progressive steatohepatitis remain incompletely defined. Ketogenesis can dispose of much of the fat that enters the liver, and dysfunction in this pathway could promote the development of NAFLD. Here, we evaluated mice lacking mitochondrial 3-hydroxymethylglutaryl CoA synthase (HMGCS2) to determine the role of ketogenesis in preventing diet-induced steatohepatitis. Antisense oligonucleotide-induced loss of HMGCS2 in chow-fed adult mice caused mild hyperglycemia, increased hepatic gluconeogenesis from pyruvate, and augmented production of hundreds of hepatic metabolites, a suite of which indicated activation of the de novo lipogenesis pathway. High-fat diet feeding of mice with insufficient ketogenesis resulted in extensive hepatocyte injury and inflammation, decreased glycemia, deranged hepatic TCA cycle intermediate concentrations, and impaired hepatic gluconeogenesis due to sequestration of free coenzyme A (CoASH). Supplementation of the CoASH precursors pantothenic acid and cysteine normalized TCA intermediates and gluconeogenesis in the livers of ketogenesis-insufficient animals. Together, these findings indicate that ketogenesis is a critical regulator of hepatic acyl-CoA metabolism, glucose metabolism, and TCA cycle function in the absorptive state and suggest that ketogenesis may modulate fatty liver disease.

Impairments of hepatic gluconeogenesis and ketogenesis in PPARα-deficient neonatal mice.

Peroxisome proliferator activated receptor-α (PPARα) is a master transcriptional regulator of hepatic metabolism and mediates the adaptive response to fasting. Here, we demonstrate the roles for PPARα in hepatic metabolic adaptations to birth. Like fasting, nutrient supply is abruptly altered at birth when a transplacental source of carbohydrates is replaced by a high-fat, low-carbohydrate milk diet. PPARα-knockout (KO) neonatal mice exhibit relative hypoglycemia due to impaired conversion of glycerol to glucose. Although hepatic expression of fatty acyl-CoA dehydrogenases is imparied in PPARα neonates, these animals exhibit normal blood acylcarnitine profiles. Furthermore, quantitative metabolic fate mapping of the medium-chain fatty acid [(13)C]octanoate in neonatal mouse livers revealed normal contribution of this fatty acid to the hepatic TCA cycle. Interestingly, octanoate-derived carbon labeled glucose uniquely in livers of PPARα-KO neonates. Relative hypoketonemia in newborn PPARα-KO animals could be mechanistically linked to a 50% decrease in de novo hepatic ketogenesis from labeled octanoate. Decreased ketogenesis was associated with diminished mRNA and protein abundance of the fate-committing ketogenic enzyme mitochondrial 3-hydroxymethylglutaryl-CoA synthase (HMGCS2) and decreased protein abundance of the ketogenic enzyme ß-hydroxybutyrate dehydrogenase 1 (BDH1). Finally, hepatic triglyceride and free fatty acid concentrations were increased 6.9- and 2.7-fold, respectively, in suckling PPARα-KO neonates. Together, these findings indicate a primary defect of gluconeogenesis from glycerol and an important role for PPARα-dependent ketogenesis in the disposal of hepatic fatty acids during the neonatal period.

Impact of peripheral ketolytic deficiency on hepatic ketogenesis and gluconeogenesis during the transition to birth.

Preservation of bioenergetic homeostasis during the transition from the carbohydrate-laden fetal diet to the high fat, low carbohydrate neonatal diet requires inductions of hepatic fatty acid oxidation, gluconeogenesis, and ketogenesis. Mice with loss-of-function mutation in the extrahepatic mitochondrial enzyme CoA transferase (succinyl-CoA:3-oxoacid CoA transferase, SCOT, encoded by nuclear Oxct1) cannot terminally oxidize ketone bodies and develop lethal hyperketonemic hypoglycemia within 48 h of birth. Here we use this model to demonstrate that loss of ketone body oxidation, an exclusively extrahepatic process, disrupts hepatic intermediary metabolic homeostasis after high fat mother's milk is ingested. Livers of SCOT-knock-out (SCOT-KO) neonates induce the expression of the genes encoding peroxisome proliferator-activated receptor γ co-activator-1a (PGC-1α), phosphoenolpyruvate carboxykinase (PEPCK), pyruvate carboxylase, and glucose-6-phosphatase, and the neonate's pools of gluconeogenic alanine and lactate are each diminished by 50%. NMR-based quantitative fate mapping of (13)C-labeled substrates revealed that livers of SCOT-KO newborn mice synthesize glucose from exogenously administered pyruvate. However, the contribution of exogenous pyruvate to the tricarboxylic acid cycle as acetyl-CoA is increased in SCOT-KO livers and is associated with diminished terminal oxidation of fatty acids. After mother's milk provokes hyperketonemia, livers of SCOT-KO mice diminish de novo hepatic ß-hydroxybutyrate synthesis by 90%. Disruption of ß-hydroxybutyrate production increases hepatic NAD(+)/NADH ratios 3-fold, oxidizing redox potential in liver but not skeletal muscle. Together, these results indicate that peripheral ketone body oxidation prevents hypoglycemia and supports hepatic metabolic homeostasis, which is critical for the maintenance of glycemia during the adaptation to birth.

Adipocyte lipid chaperone AP2 is a secreted adipokine regulating hepatic glucose production.

Proper control of hepatic glucose production is central to whole-body glucose homeostasis, and its disruption plays a major role in diabetes. Here, we demonstrate that although established as an intracellular lipid chaperone, aP2 is in fact actively secreted from adipocytes to control liver glucose metabolism. Secretion of aP2 from adipocytes is regulated by fasting- and lipolysis-related signals, and circulating aP2 levels are markedly elevated in mouse and human obesity. Recombinant aP2 stimulates glucose production and gluconeogenic activity in primary hepatocytes in vitro and in lean mice in vivo. In contrast, neutralization of secreted aP2 reduces glucose production and corrects the diabetic phenotype of obese mice. Hyperinsulinemic-euglycemic and pancreatic clamp studies upon aP2 administration or neutralization demonstrated actions of aP2 in liver. We conclude that aP2 is an adipokine linking adipocytes to hepatic glucose production and that neutralizing secreted aP2 may represent an effective therapeutic strategy against diabetes.

The prevalence of Pediculus humanus capitis in two primary schools of Hacilar, Kayseri.

OBJECTIVE: Pediculosis capitis is a worldwide public health concern, and today, head lice are seen in all socio-economic levels. The infestation usually occurs by head-to-head contact and children, primarily girls, aged 3-12 years are mostly affected. In the present study a total of 405 pupils (214 boys and 191 girls) from two pre- and primary schools in the Kayseri-Hacilar region were examined for pediculosis capitis during March 2010. METHODS: Lice and/or eggs were detected by visual examination of the children's hair. RESULTS: Out of 405 children, 44 (10.9%) were infested with head lice. There were significant differences between the schools and the gender while no significant differences could be found between infestation and child's age, education of the parents, income of the family, housing type, source of water, and the presence or absence of a bathroom. CONCLUSION: Head lice remain a public health problem and more emphasis should be given to the education of parents regarding their biology and control.

[Genotyping of nosocomial methicillin-resistant Staphylococcus aureus strains isolated from clinical specimens by rep-PCR]. / Klinik Örneklerden Izole Edilen Hastane Kaynakli Metisiline Dirençli Staphylococcus aureus Suslarinin rep-PCR ile Genotiplendirilmesi.

Methicillin-resistant Staphylococcus aureus (MRSA) infections are associated with increased cost, mortality and length of hospital stay compared with the other infections. Therefore, controlling the spread of this pathogen by screening patients, personnel and the environment remains as a high priority in infection control programs. The aim of this study was to detect the clonal relationship between nosocomial MRSA strains by using repetitive-sequence-based polymerase chain reaction (rep-PCR) method which has several advantages owing to its speed and ease of use. A total of 100 MRSA stock strains that had been isolated from various clinical samples of hospitalized patients in Erciyes University Medical Faculty Hospitals between September 2008-October 2009, were included in the study. Methicillin resistance of the strains were determined by cefoxitin disc diffusion test according to CLSI guidelines. Rep-PCR (Diversilab, bioMerieux, France) method was performed in the following four steps in order to determine genetic proximity of MRSA strains: (1) Manual DNA extraction (UltraClean Microbial DNA Isolation Kit; MoBio Laboratories, USA), (2) Rep-PCR by using fingerprinting kits in the thermocycler (Diversilab DNA Fingerprinting Kit), (3) Automated microfluidic electrophoresis by bioanalyzer (Diversilab DNA LabChip kit), (4) Analysis and rapid evaluation with the use of web-based DiversiLab software (version 2.1.66). Rep-PCR analysis have shown the presence of a total 11 clones, including 3 major clones [A (4 subtypes), B (2 subtypes) and C (2 subtypes)] and 8 unique clones (DK). Clone A was found to be the dominant type. Seventy-eight percent of the 100 MRSA isolates belonged to clone A (63 were A1; 9 were A2; 4 were A3, 2 were A4), 11% belonged to clone B (10 were B1, 1 was B2), 3% belonged to clone C (2 were C1, 1 was C2), and one of each belonged to the other clones (D, E, F, G, H, I, J, K). Clone A was isolated from 93.3% (14/15) of the samples sent from internal diseases intensive care unit (ICU), from 66.6% (10/15) of the samples sent from infectious diseases ward and 91% (10/11) of hematology-oncology ward samples. All MRSA strains isolated from anesthesiology and newborn ICU were of clone A. The isolation dates of these strains were in proximity. In conclusion, MRSA strains showed clonal dissemination in our hospital, clone A being the predominant one during the study period. Rep-PCR which is a rapid and reliable method, can easily be applied for molecular epidemiological purposes and aid to infection control measures.

[Investigation of intestinal parasites among primary school students in Kayseri-Hacilar]. / Kayseri-Hacilar'da Ilkögretim Okulu Ögrencilerinde Bagirsak Parazitlerinin Arastirilmasi

OBJECTIVE: Parasitic infections are an important health problem which affect children more than adults. Especially in growth-age children, this leads to problems such as malnutrition, malabsorption, growth retardation and learning disabilities. In this study, 328 students who were investigated in two primary schools between the ages of 6 and 14 in Kayseri-Hacilar region were analyzed for intestinal parasites. METHODS: Stool samples were analyzed by light microscopy for the detection of helminths and protozoon using the native-lugol method. Cellophane tape samples were also analyzed by light microscopy for the detection of Enterobius vermicularis and Taenia spp. RESULTS: At least one or more intestinal parasite species were found in 116 (35.4 %) children. The distribution of parasites which were detected in stool samples was as follows; Blastocystis hominis, 77 (23.5%); Enterobius vermicularis, 35 (10.7%); Giardia intestinalis, 14 (4.3%); Entamoeba coli, 15 (4.6%); Endolimax nana, 6 (1.8%); Hymenolepis nana, 1 (0.3%); Iodamoeba butschlii, 1 (0.3%). CONCLUSION: Parasitic diseases are a major public health problem and we believe that education about personal hygiene, sanitation rules and parasitic diseases is important to overcome this problem.

Antifungal activity of the honeybee products against Candida spp. and Trichosporon spp.

Honeybee products (honey, royal jelly, pollen, and propolis) were evaluated for their ability to inhibit the growth of 40 yeast strains of Candida albicans, Candida glabrata, Candida krusei, and Trichosporon spp. The broth microdilution method was used to assess the antifungal activity of honeybee products against yeasts. Fluconazole was selected as the antifungal control agent. Using the broth microdilution method, minimal inhibitory concentration ranges with regard to all isolates were 5-80% (vol/vol), 0.06-1 µg/mL, 0.002-0.25 µg/mL, 0.006-0.1 µg/mL, and 0.02-96 µg/mL for honey, royal jelly, pollen, propolis, and fluconazole, respectively. The antifungal activities of each product decreased in the following order: propolis >pollen > royal jelly > > honey. This study demonstrated that honeybee products, particularly propolis and pollen, can help to control some fluconazole-resistant fungal strains.