Effects of acute sleep loss on leptin, ghrelin, and adiponectin in adults with healthy weight and obesity: A laboratory study.
This study investigated whether blood concentrations of leptin, ghrelin, and adiponectin are affected by acute total sleep deprivation in a sex- and weight-specific manner. A total of 44 participants (mean age 24.9 years; 20 women; 19 with obesity) participated in a crossover design, including one night of sleep deprivation and one night of sleep in the laboratory. After each night, fasting blood was collected. After sleep deprivation, fasting levels of leptin were lower (mean [SE], vs. sleep: 17.3 [2.6] vs. 18.6 [2.8] ng/mL), whereas those of ghrelin and adiponectin were higher (839.4 [77.5] vs. 741.4 [63.2] pg/mL and 7.5 [0.6] vs. 6.8 [0.6] μg/mL, respectively; all p < 0.05). The changes in leptin and adiponectin following sleep loss were more pronounced among women. Furthermore, the ghrelin increase was stronger among those with obesity after sleep loss. Finally, the sleep loss-induced increase in adiponectin was more marked among normal-weight participants. Acute sleep deprivation reduces blood concentrations of the satiety hormone leptin. With increased blood concentrations of ghrelin and adiponectin, such endocrine changes may facilitate weight gain if persisting over extended periods of sleep loss. The observed sex- and weight-specific differences in leptin, ghrelin, and adiponectin call for further investigation.


DOAS measurements of tropospheric bromine oxide in mid-latitudes
Episodes of elevated bromine oxide (BrO) concentration are known to occur at high latitudes in the Arctic boundary layer and to lead to catalytic destruction of ozone at those latitudes; these events have not been observed at lower latitudes. With the use of differential optical absorption spectroscopy (DOAS), locally high BrO concentrations were observed at mid-latitudes at the Dead Sea, Israel, during spring 1997. Mixing ratios peaked daily at around 80 parts per trillion around noon and were correlated with low boundary-layer ozone mixing ratios.


Abnormalities of gastric emptying and pyloric reflux in uncomplicated hiatus hernia.
We have measured the rate of gastric emptying of solid and liquid meals by an external scanning technique and have studied pyloric reflux by a radiological technique. Investigations were performed in patients with uncomplicated hiatal hernia, patients with uncomplicated duodenal ulcer and normal controls. There was a significant delay in the emptying of both solid and liquid meals in the patients with hiatal hernia compared with both the duodenal ulcer patients (solid meals P less than 0.01, liquid meals P less than 0.025) and with normal controls (solid meals P less than 0.05, liquid meals P less than 0.001). Duodenogastric reflux was observed in 35% of hiatal hernia patients compared with 24% of duodenal ulcer patients and no incidence in the controls.


Insomnia symptoms during the early and late stages of the COVID-19 pandemic in China: a systematic review and meta-analysis.
Evidence suggests that the outbreak of the coronavirus disease 2019 (COVID-19) and the prevention/control measures for COVID-19 may cause insomnia during the acute phase of COVID-19 pandemic in China. However, it is unclear whether insomnia sustains during the later phases of the pandemic. We searched PubMed/Medline, EMBASE, PsycINFO and China National Knowledge Infrastructure from the 27th December 2019 to the 2nd February 2021. As early stage studies on COVID-19 pandemic in China were defined as those conducted prior to April 1st, 2020, while late stage studies were those conducted after April 1st, 2020. A total of 98 studies with 193,889 participants were included. The pooled prevalence of insomnia symptoms among all populations was 39.1% (95% CI 36.2-42.0%); the pooled prevalence of insomnia symptoms during the early and late stages of COVID-19 in China were 37.0% (95% CI 34.1-39.9%) and 41.8% (95% CI 33.6-50.0%), respectively. Importantly, there was no significant difference regarding the prevalence of insomnia symptoms between the early and late stages of COVID-19. Meta-regression showed that healthcare workers, COVID-19 patients, patients with chronic medical conditions and patients with mental disorders had a higher prevalence of insomnia symptoms compared to the general population. This association remained significant in healthcare workers and patients with chronic medical conditions after adjusting for age, gender, areas of high or low prevalence of COVID-19 cases, anxiety and depression. Over one third of our sample present insomnia symptoms during the early stage of COVID-19 pandemic in China. Interestingly, prevalence of insomnia symptoms sustains high during the late stage of the pandemic despite the control of the disease and the amelioration of its adverse effects. Our findings suggest that insomnia symptoms related to COVID-19 appear to persist of over time.


Acute and chronic changes in platelet volume and count after cardiopulmonary bypass induced thrombocytopenia in man.
Patients undergoing surgery for coronary artery bypass graft or heart valve replacement had their platelet count and mean volume measured pre-operatively, immediately post-operatively and serially for up to 48 days after the surgical procedure. The mean pre-operative platelet count of 1.95 +/- 0.11 X 10(11)/1 (n = 26) fell significantly to 1.35 +/- 0.09 X 10(11)/1 immediately post-operatively (p less than 0.001) (n = 22), without a significant alteration in the mean platelet volume. The average platelet count rose to a maximum of 5.07 +/- 0.66 X 10(11)/1 between days 14 and 17 after surgery while the average mean platelet volume fell from preparative and post-operative values of 7.25 +/- 0.14 and 7.20 +/- 0.14 fl respectively to a minimum of 6.16 +/- 0.16 fl by day 20. Seven patients were followed for 32 days or longer after the operation. By this time they had achieved steady state thrombopoiesis and their average platelet count was 2.44 +/- 0.33 X 10(11)/1, significantly higher than the pre-operative value (p less than 0.05), while their average mean platelet volume was 6.63 +/- 0.21 fl, significantly lower than before surgery (p less than 0.001). The pre-operative values for the platelet volume and counts of these patients were significantly different from a control group of 32 young males, while the chronic post-operative values were not. These long term changes in platelet volume and count may reflect changes in the thrombopoietic control system secondary to the corrective surgery.


Evidence of otitis media and mastoiditis in a Medieval Islamic skeleton from Spain and possible implications for ancient surgical treatment of the condition.
To evaluate lesions on a cranium from the Iberian Peninsula and assess its medico-historical and paleopathological significance. The skeletal remains of a juvenile individual found in a Medieval Islamic grave (10th -16th century) in Eastern Spain. Macroscopic examination of the left and right temporal bones, binocular microscopy, X-ray, and Scanning Electron Microscopy - Energy Dispersive X-ray Spectroscopy (SEM-EDS) were performed. A sub-oval perforation superior to the right mastoid process and pathological changes on the right temporal bone were identified. SEM-EDS confirmed the presence of copper in the surrounding area of the perforation. The observed pathological changes are most likely compatible with otitis media and subsequent mastoiditis. The sub-oval perforation could be interpreted either as an abscess or as evidence of a surgical procedure (mastoidectomy) or a combination of both; and the Cu traces may be the result of an associated object or, possibly, the application of a plaster with copper acetate used as medical treatment. This case contributes to the paleopathological record and the interpretation of similar cases, and also helps in the understanding of medical care and treatment in Medieval Islam. The lack of similar pre-modern cases of surgical intervention limits comparability to clinical cases. Suggestion for further research: Exploration into indicators of health care in past populations.


Norovirus Antigen Detection with a Combination of Monoclonal and Single-Chain Antibodies.
The performance of a norovirus antigen detection assay was assessed using monoclonal antibody NV23 and single-chain antibody HJT-R3-A9 to identify both virus-like particles and virus-containing fecal samples. The detection of 25 different norovirus genotypes as recombinant virus-like particles or in clinical samples was dependent on virus or antigen concentration.


The protein phosphatase calcineurin is essential for NaCl tolerance of Saccharomyces cerevisiae.
NaCl-sensitive yeast mutants were isolated to identify genes essential for NaCl tolerance. Complementation of a mutant highly sensitive to Na+ and Li+ led to the isolation of the CNB1 gene. This gene encodes the regulatory subunit (CNB) of the Ca2+/calmodulin-dependent protein phosphatase calcineurin. Cells deficient in CNB accumulated Li+ due to reduced expression of ENA1, a gene encoding a P-type ATPase involved in Na+ and Li+ efflux. In addition, the K+ transport system of cnb1 delta cells was not converted to the high affinity state that facilitates better discrimination of K+ over Na+. Thus the cnb1 delta strain resembled a trk1 mutant. These results indicate that adaptation to NaCl stress in Saccharomyces cerevisiae requires a signal transduction pathway involving Ca2+ and protein phosphorylation-dephosphorylation. In this pathway, calcineurin would coordinate gene expression and activity of ion transporters to facilitate ion homeostasis.


Enhanced DR5 binding capacity of nanovectorized TRAIL compared to its cytotoxic version by affinity chromatography and molecular docking studies.
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induces apoptosis of cancer cells when bound to its cognate receptors, TRAIL-R1 and TRAIL-R2 (DR4 and DR5), without being toxic to healthy cells. Nanovectorized TRAIL (abbreviated as NPT) is 10 to 20 times more efficient than one of the most potent soluble TRAIL used in preclinical studies (His-TRAIL). To determine whether differences in affinity may account for NPT superiority, a thermodynamic study was undertaken to evaluate NPT versus TRAIL binding affinity to DR5. Docking calculations showed that TRAIL in homotrimer configuration was more stable than in heterotrimer, because of the presence of one Zn ion in its structure. Indeed, TRAIL trimers can have head-to-tail orientations when Zn is missing. Altogether these data suggest that TRAIL homotrimer structures are predominant in solution and then are grafted on NPT. When docked to DR5, NPT carrying TRAIL homotrimer leads to a more stable complex than TRAIL monomer-based NPT. To comfort these observations, the extracellular domain of DR5 was immobilized on a chromatographic support using an "in situ" immobilization technique. The determination of the thermodynamic data (enthalpy ∆H° and entropy ∆S°*) of TRAIL and NPT binding to DR5 showed that the binding mechanism was pH dependent. The affinity of NPT to DR5 increased with pH, and the ionized energy was more important for NPT than for soluble TRAIL. Moreover, because of negative values of ∆H° and ∆S°* quantities, we demonstrated that van der Waals and hydrogen bonds governed the strong NPT-DR5 association for pH > 7.4 (as for TRAIL alone). Copyright © 2016 John Wiley & Sons, Ltd.


Seasonal variability of benthic indices: an approach to test the applicability of different indices for ecosystem quality assessment.
In recent studies, several benthic biological indices were developed or used to assess the ecological quality status of marine environments. In the present study the seasonal variability of several univariate and multimetric indices was studied on a monthly scale (September 2000 until May 2002) in different areas of the North Sea such as the German Bight, the Oyster Ground and the Dogger Bank. The stations were chosen to reflect a gradient in the hydrographic regime, temperature and organic matter supply. The seasonal variability was highest for the univariate indices such as the Shannon-Wiener Index and the Hurlbert Index. Thus, due to sensitivity to recruitment the corresponding ecological status ranged from 'good' to 'poor' depending on the season. For the multimetric indices such as the AMBI or the BQI the seasonal variability and the corresponding ecological status were low. The results are discussed concerning possible consequences for ecological quality assessment especially related to the Water Framework Directive (WFD).


Accurate and online quantification of viable Rhodobacter sphaeroides cells using a flow cytometry-dielectric spectroscopy (FCM-DS) method.
Accurate and online quantification of viable cells is one of the necessary requirements during the microbial fermentation process for high productivity. The flow cytometry (FCM)-based method accurately quantifies viable cells, but this offline method cannot reflect the counts constantly. The dielectric spectroscopy (DS) sensor is widely utilized to monitor viable cells online; however, accurately converting the capacitance value of the DS sensor to the viable bacterial cell counts has barely been tried. We have developed a method by coupling the principles and techniques of FCM and the DS sensor to quantify viable Rhodobacter sphaeroides cells. Using specific fluorescent antibodies and propidium iodide (PI), viable R. sphaeroides cells were accurately quantified within 30 min by FCM. The DS sensor was combined with the FCM to create a direct capacitance-viable cell count quantification system. The LOD (limit of detection) of the FCM-DS method was 8 × 108 CFU/mL, RSD (relative standard deviation) < 5%, along with good reproducibility of the results. Finally, the viable cell count, obtained from the FCM-DS method, was applied to regulate the specific oxygen uptake rate (QO2) that increased the production of coenzyme Q10 by 8.1%. Together, our results strongly suggest that viable cells can be accurately quantified online by the integrated FCM-DS method, which would help to devise precise fermentation control strategies.


Increasing β-carotene bioavailability and bioactivity in spinach demonstrated using excipient nanoemulsions-especially those of long-chain triglycerides.
This study sought to improve the biological fate of β-carotene obtained from spinach, using in vitro digestion, in situ single-pass intestinal perfusion, and in vivo approaches, to investigate the effects of excipient emulsions with medium- (MCT) and long-chain triglyceride (LCT) as a vehicle for improved health benefits of β-carotene. Results showed that the bioavailability and bioactivity of β-carotene were both significantly higher in the excipient emulsions relative to those without the emulsions. This was especially true when LCT was used as the vehicle. These results were confirmed by bioaccessibility, duodenal absorption, and in vivo absorption and metabolism. Furthermore, animal feeding studies revealed that LCT may have the potential to promote triglyceride and apo-B48 reconstitution and secretion. This suggested that LCT may facilitate the entry of carotenoids into circulation via the lymphatic pathway. These results highlight the importance of the optimization of excipient foods to improve the efficacy of lipophilic carotenoid.


The role of lysophosphatidylcholine and apolipoprotein A in the cholesterol-removing capacity of lipoprotein-deficient serum in tissue culture.
Lipoprotein-deficient serum (d greater than 1.21 or 1.25 g/ml fraction) is commonly used to deplete cellular cholesterol from cultured cells and presently we have studied some of the potential promoters of this process. Although serum albumin is the main protein component of the fraction, its cholesterol-removing capacity was quite limited, even in the presence of lysophosphatidylcholine, which is the major phospholipid of the d greater than 1.25 g/ml infranatant of serum. On the other hand, apolipoprotein A1 especially when complexed with lysophosphatidylcholine promoted considerable release of cellular cholesterol. The cholesterol-removing capacity of lysophosphatidylcholine alone was related to the fatty acid chain length and was low when the fatty acid chain length was below C-14. The release of cellular cholesterol is not related to shedding of surface glycoproteins and depends on the presence of suitable acceptors in the medium. Such acceptors were presently found in an ultrafiltrate of serum prepared by membrane filtration. It is proposed that in human serum there are low molecular weight protein-phospholipid complexes (less than 100,000), which can cross the capillary endothelial barrier, in preference to lipoproteins, and promote cholesterol removal from peripheral cells.


Alterations of dendritic branching and spine densities of hippocampal CA3 pyramidal neurons induced by operant conditioning in the phase of brain growth spurt.
An operant conditioning study was carried out on Wistar rat pups of brain-growth-spurt age to assess the plasticity of apical dendritic branching and the numerical spine densities of CA3 pyramidal neurons of the hippocampus. In rapid Golgi-stained material we studied the effects of operant conditioning commencing at 16 days of age and terminating on the 23rd day of age. The data of the learning group (L) were compared with those of the sham experimental control group (E) and of the control group reared under standard conditions (S). The results revealed a significant (ANOVA F test) increase in the number of branching points of the dendrites of the learning group compared with the other groups. The grand averages of spine densities also showed an overall increase in the learning group over the sham-experimental and standard groups. Segmental comparisons revealed a more interesting observation that significant changes in the spine densities of the learning and sham-experimental groups occurred in some segments of dendrites but not in all. A few segments showed moderate spine decreases also, compared with the control group. The spine differences of segments were mainly in the stalked types. Excrescences which are spines on which mossy fibers are known to synapse increased in both learning and sham-experimental groups, but not significantly (ANOVA). The dendritic branching and spines of nonmossy inputs of certain dendritic segments significantly increased after the learning experience in the hippocampus of the growing brain.


Bacterial and fungal infections after cardiac surgery in children.
Of 245 children operated on for congenital heart diseases in 1983-1984, bacterial and fungal infections occurred in 3.6% compared to 17.8% of 469 in 1968-1972. Staphylococcal infections decreased from 3.4%-0.8% and those by gram-negative bacteria from 6.9%-0%; Candida albicans infections increased from 0%-1.2%. Perioperative prophylaxis was performed with cefotaxime plus piperacillin in 1983-1984 versus oxacillin plus ampicillin in 1968-1972. It is argued that reduction of the infection rate is not only due to newer and more effective antibiotics but is mainly related to more advanced surgical techniques and improved hygiene in our intensive care units.


Diversity in protein domain superfamilies.
Whilst ∼93% of domain superfamilies appear to be relatively structurally and functionally conserved based on the available data from the CATH-Gene3D domain classification resource, the remainder are much more diverse. In this review, we consider how domains in some of the most ubiquitous and promiscuous superfamilies have evolved, in particular the plasticity in their functional sites and surfaces which expands the repertoire of molecules they interact with and actions performed on them. To what extent can we identify a core function for these superfamilies which would allow us to develop a 'domain grammar of function' whereby a protein's biological role can be proposed from its constituent domains? Clearly the first step is to understand the extent to which these components vary and how changes in their molecular make-up modifies function.


Reassessment of the relationship between M-protein decrement and survival in multiple myeloma.
The relationship between percentage M-protein decrement and survival is assessed in 134 multiple myeloma patients. The correlation did not achieve statistical significance (P = 0.069). Multivariate analysis using the Cox proportional hazards model, including a number of previously recognised prognostic factors, showed only percentage M-protein decrement, creatinine and haemoglobin to be significantly correlated with survival. However, the R'-statistic for each of these variables was low, indicating that their prognostic power is weak. We conclude that neither the percentage M-protein decrement nor the response derived from it can be used as an accurate means of assessing the efficacy of treatment in myeloma. Mature survival data alone should be used for this purpose.


Sequencing of K60, type strain of the major plant pathogen Ralstonia solanacearum.
Ralstonia solanacearum is a widespread and destructive plant pathogen. We present the genome of the type strain, K60 (phylotype IIA, sequevar 7). Sequevar 7 strains cause ongoing tomato bacterial wilt outbreaks in the southeastern United States. K60 generally resembles R. solanacearum CFBP2957, a Caribbean tomato isolate, but has almost 360 unique genes.


Intratumoral lipid metabolic reprogramming as a pro-tumoral regulator in the tumor milieu.
Reprogramming of the tumor microenvironment (TME) is a hallmark of cancer. Metabolic reprogramming is a vital approach to sustaining the energy supply in the TME. This alteration exists in both cancer cells and TME cells, collectively establishing an immunotolerant niche to facilitate tumor progression. Limited resources lead to metabolic competition and hinder the biological functions of anti-tumoral immunity. Reprogramming of lipid metabolism and tumor progression is closely related to each other. Due to the complexity of fatty acid (FA) types and the lack of an effective approach for detection, the mechanisms and effects of FA metabolic reprogramming have been unclear. Herein, we review FA metabolism in the tumor milieu, summarize how FA metabolic reprogramming influences antitumor immune response, suggest the mechanisms by which FAs affect immunotherapy against cancer, and discuss the potential of FA metabolism-based drugs in cancer treatment.


Aqueous adsorption of sulfamethoxazole on an N-doped zeolite beta-templated carbon.
A zeolite beta-templated carbon (BTC) and its N-doped form (nBTC) were prepared and used for the adsorptive removal of sulfamethoxazole (SMX) antibiotic from water. Both demonstrated excellent adsorption properties, and the maximum adsorption capacity of nBTC (1367 mg/g) was exceptionally high, and surpassed those of other adsorbents reported to date. Adsorption kinetic studies indicated that the adsorption was efficient, and adsorption equilibrium was reached within 10 min. The excellent adsorption performance of nBTC was attributed to the high-surface-area hydrophobic carbons with strong π-π interactions and H-bonding in the uniform microporous geometry of the material. The effect of the solution pH and thermodynamics of the adsorption process were subsequently investigated. nBTC was easily regenerated by washing with acetone, and a recyclability test confirmed that ~88% of the initial SMX adsorption capacity of nBTC was retained after the fifth adsorption-desorption cycle. Moreover, nBTC presented excellent capacity for the adsorptive removal of bisphenol A from water.


Discriminative and quantitative analysis of norepinephrine and epinephrine by surface-enhanced Raman spectroscopy with gold nanoparticle suspensions.
Surface-enhanced Raman spectroscopy (SERS) is a powerful analytical technique capable of increasing the Raman signal of an analyte using specific nanostructures. The close contact between those nanostructures, usually a suspension of nanoparticles, and the molecule of interest produces an important exaltation of the intensity of the Raman signal. Even if the exaltation leads to an improvement of Raman spectroscopy sensitivity, the complexity of the SERS signal and the numbers of parameters to be controlled allow the use of SERS for detection rather than quantification. The aim of this study was to develop a robust discriminative and quantitative analysis in accordance with pharmaceutical standards. In this present work, we develop a discriminative and quantitative analysis based on the previous optimized parameters obtained by the design of experiments fixed for norepinephrine (NOR) and extended to epinephrine (EPI) which are two neurotransmitters with very similar structures. Studying the short evolution of the Raman signal intensity over time coupled with chemometric tools allowed the identification of outliers and their removal from the data set. The discriminant analysis showed an excellent separation of EPI and NOR. The comparative analysis of the data showed the superiority of the multivariate analysis after logarithmic transformation. The quantitative analysis allowed the development of robust quantification models from several gold nanoparticle batches with limits of quantification of 32 µg/mL for NOR and below 20 µg/mL for EPI even though no Raman signal is observable for such concentrations. This study improves SERS analysis over ultrasensitive detection for discrimination and quantification using a handheld Raman spectrometer.


Non-Invasive Cardiac Output Monitoring in Cardiogenic Shock: The NICOM Study.
The bioreactance technique is a relatively new, totally noninvasive technique that is used to measure cardiac output (CO) and is easy to use. The Non-Invasive Cardiac Output Monitor (NICOM) is 1 such system. Although approved by the Food and Drug Administration for measurement of stroke volume, there is a paucity of literature validating this technology in decompensated heart failure and cardiogenic shock. Fifty patients admitted to our cardiac intensive care unit for cardiogenic shock and Swan-Ganz catheter-guided therapy were prospectively enrolled in the study after informed consent. Simultaneous measurements of CO were obtained using NICOM, indirect Fick and bolus thermodilution. The intraclass correlation coefficient (ICC) was used to assess the precision of NICOM for CO using the 3 repeated measurements of CO over the pooled data. The agreement of the NICOM device in the defined clinical population, compared to indirect Fick and thermodilution, was evaluated by comparing the Pearson correlation coefficient, the Bland-Altman plot and the Lin concordance correlation coefficient. The ICC for cardiac output measured by NICOM showed excellent repeatability (ICC = 0.93, 95% CI = 0.92-0.94, n = 262) in the pooled data. The Pearson correlation coefficient for cardiac output measured by NICOM was poor when compared to indirect Fick (n = 263, r = 0.132, P = 0.033) and TD (n = 258, r = 0.275, P < 0.001). NICOM technology is not a reliable method of measuring CO in patients with decompensated heart failure and cardiogenic shock.


Radially and azimuthally polarized laser induced shape transformation of embedded metallic nanoparticles in glass.
Radially and azimuthally polarized picosecond (~10 ps) pulsed laser irradiation at 532 nm wavelength led to the permanent reshaping of spherical silver nanoparticles (~30 - 40 nm in diameter) embedded in a thin layer of soda-lime glass. The observed peculiar shape modifications consist of a number of different orientations of nano-ellipsoids in the cross-section of each written line by laser. A Second Harmonic Generation cross-sectional scan method from silver nanoparticles in transmission geometry was adopted for characterization of the samples after laser modification. The presented approach may lead to sophisticated marking of information in metal-glass nanocomposites.


Visual determination of azodicarbonamide in flour by label-free silver nanoparticle colorimetry.
A very practical and competitive sensing strategy for the detection of azodicarbonamide in flour samples was developed by using label-free Ag NPs as a colorimetric probe. Well-dispersed Ag NPs in suspension can form aggregates upon reacting with glutathione (GSH) via Ag-SH covalent bonds and electrostatic attraction, with the color changing from bright yellow to red. However, azodicarbonamide can oxidize the -SH of GSH, preventing the aggregation of Ag NPs. Under the optimum conditions, the A550/A398 of Ag NPs is linearly related to the concentration of azodicarbonamide in the range of 0.33 μM to 1.7 μM. The proposed method can be used for the detection of azodicarbonamide in flour, with a detection limit of 0.09 μM and recovery between 95% and 97.4% (RSD < 6%). When the azodicarbonamide concentration reaches 0.33 μM, the color change can be detected by the naked eye.


Holter recordings with continuous marker annotation to evaluate pacemaker function.
Pacemaker marker annotations facilitate the interpretation of device behavior in addition to ECG recordings. However, they are only available in conjunction with a programmer. We studied the diagnostic value of a prototype Telemetry Holter Decoder (THD), providing continuous marker annotations on a conventional Holter. The study included 20 patients with VDD or DDDR pacemakers. A 24-hour Holter was performed using the THD. Marker annotations are transmitted from the pacemaker to the THD, which transforms them into analog signals, which are recorded on one of the Holter channels. During a total recording time of 458 hours, high quality marker annotations were retrieved for every patient. Artefacts disturbed the recordings during 184 min (0.67%). The THD provided information not discernible on the ECG: intermittent atrial undersensing during sinus rhythm (1096 times). Atrial tachycardias, not visible on the ECG, were detected in 2 patients. The activation of tachycardia response algorithms was clearly annotated in 11,516 events. A total of 8875 PVC's occurred, 57.8% of which were classified incorrectly in the event counters as conducted or fusion beats. Atrial far-field sensing or VA conduction was demonstrated 4294 times. Electromagnetic interferences, not visible on the ECG, could be seen three times. Recording of continuous high-quality marker annotation on a conventional Holter is feasible. The THD provides important information on device behavior, even in patients assumed to have regular device function, and shows to be clearly superior to ECG interpretation alone. Such data can be used for improved programming, troubleshooting and for the validation of new algorithms.


Deception and the ethics of placebo.
The placebo effect in many areas of neurological therapeutics is common and prominent. The importance of the response means that any new treatment must account for the placebo effect, but this in turn raises major challenges as to how to conduct scientifically meaningful research in an ethically acceptable fashion. Basic principles that may be in tension with one another are those of beneficence and respect for autonomy. It may be challenging to respect autonomy if the scientific design of a study depends upon the use of deception, but this is often mitigated by the information provided to trial participants as part of the informed consent process. Deception is a particular challenge if placebos are to be used in a clinical/therapeutic setting, outside the context of a clinical trial. While practice-based placebo use may on occasion be both beneficial and ethically acceptable, close attention must then be paid to ensuring that basic ethical principles are respected and that placebos are either prescribed in an open and honest fashion, or that any deception is authorized.


Intoxication strategy of Helicobacter pylori VacA toxin.
VacA toxin from the cancer-inducing bacterium Helicobacter pylori is currently classified as a pore-forming toxin but is also considered a multifunctional toxin, apparently causing many pleiotropic cell effects. However, an increasing body of evidence suggests that VacA could be the prototype of a new class of monofunctional A-B toxins in which the A subunit exhibits pore-forming instead of enzymatic activity. Thus, VacA may use a peculiar mechanism of action, allowing it to intoxicate the human stomach. By combining the action of a cell-binding domain, a specific intracellular trafficking pathway and a novel mitochondrion-targeting sequence, the VacA pore-forming domain is selectively delivered to the inner mitochondrial membrane to efficiently kill target epithelial cells by apoptosis.


Supernumerary tooth autotransplantation to replace missing maxillary central incisor using three-dimensional replica: A 6-year follow-up.
Tooth autotransplantation is a viable surgical treatment option for patients with missing permanent teeth. Premolars are generally used for autotransplantation but often require extensive modifications. This case report evaluates the use of supernumerary tooth as an alternative option for premolar autotransplantation. This report shows successful supernumerary tooth autotransplantation with 6-year follow-up. A 13-year-old male with non-contributory medical history was referred for a missing maxillary left central incisor (#9) and presence of a supernumerary tooth. The clinical and radiographic examination revealed presence of supernumerary tooth with similar dimensions to a central incisor. The treatment plan included autotransplantation of the supernumerary tooth to replace the missing central incisor (short-term) and future implant replacement of the autotransplanted tooth when jaw growth ceases (long-term). The patient and parents consented to treatment. A 3-D tooth replica was constructed based on CBCT analyses. Site #9 was prepared using split ridge technique to create a socket to house the 3-D replica. Upon achieving proper socket form, the supernumerary tooth was extracted and autotransplanted in the prepared socket. The supernumerary tooth was splinted, and the bite opened posteriorly using composite to eliminate any occlusal interferences. The patient was followed up clinically and radiographically. The autotransplanted supernumerary tooth integrated well within the newly created socket and remained functional at the 6-year follow-up. The current case presents successful management of supernumerary tooth autotransplantation with 6-year follow-up. The results show stable periodontium with satisfactory functional and aesthetic results.


Dysmorphology: an approach to a child with structural defects.
An approach to children with structural defects has been presented. The ultimate goal of this approach is a specific overall diagnosis. In such cases appropriate genetic counseling for the parents, accurate prognostication relative to the child's future development and an appropriate plan to help the child reach his potential usually are possible. When an overall diagnosis is lacking, the most that can be expected is a better understanding of the nature and onset of the problem. That in itself can often be helpful to patients and to all others dealing with children having structural defects.


Clinical and socioeconomic factors associated with negative pediatric appendicitis.
Misdiagnosing appendicitis may lead to unnecessary surgery. The study evaluates the risk factors for negative appendectomies, as well as the clinical and socioeconomic consequences of negative appendectomy across three states. Data were obtained from the California, New York, and Florida State Inpatient Databases 2005-2011. Patients (<18 years) who underwent nonincidental appendectomies (n = 156,660) were evaluated with hierarchical and multivariate negative binomial regression analyses on outcomes including hospital cost, length of stay (LOS), and associated morbidity. From 2005 to 2011, there was a decrease in the rate of negative appendicitis and perforated appendicitis, whereas the rate of true acute nonperforated appendicitis increased. Whites, females, and privately insured patients were associated with higher negative appendicitis rates, whereas those at an increased risk for perforated appendicitis were African-Americans, males, and those with public or no insurance. Compared to patients with acute nonperforated appendicitis, those with negative appendicitis have significantly higher morbidity (2.5% versus 1.3%), longer LOS (3.4 versus 1.8 d), and greater hospital costs averaged over time ($6926 versus $6492 per patient). Despite a low incidence, negative appendicitis is associated with greater morbidity, longer LOS, and higher cost than acute nonperforated appendicitis. Certain subpopulations are at higher risk for undergoing surgery for negative appendicitis, whereas others are at greater risk for presenting with perforated appendicitis. Further research is needed to understand what drives such disparities and to inform efforts to improve quality of hospital care across all groups of patients.


The influence of passengers on the risk of the driver causing a car collision in Spain. Analysis of collisions from 1990 to 1999.
To determine how the number of passengers, their age and their sex influence the risk of different types of Spanish drivers causing a collision between two or more cars. We selected, from the Spanish database of traffic crashes resulting in personal injuries or death, those collisions between two or more cars that occurred between 1990 and 1999 in which only one of the involved drivers committed a driving infraction. These drivers were considered the cases; non-infractor drivers were considered their matched controls. We collected information on the number, age and sex of the passengers in each vehicle, along with some potential confounding variables of the drivers and the vehicles involved. Crude and adjusted odds ratios were calculated for the main categories of driver and passenger. A protective effect for the presence of passengers was detected (adjusted odds ratio: 0.69; 95% CI: 0.67-0.70). The protective effect was higher for drivers aged more than 45 years and lower for the youngest drivers (<24 years old). The strongest association was observed for female passengers who accompanied male drivers. The protective effect was lower for passengers older than 64 years. Our results suggest that drivers are less likely to cause a car collision between two or more cars that results in personal injuries or death when they are accompanied by passengers, regardless of driver or passenger characteristics.


Human germline editing in the era of CRISPR-Cas: risk and uncertainty, inter-generational responsibility, therapeutic legitimacy.
Clustered Regularly Interspaced Short Palindromic Repeats-associated (CRISPR-Cas) technology may allow for efficient and highly targeted gene editing in single-cell embryos. This possibility brings human germline editing into the focus of ethical and legal debates again. Against this background, we explore essential ethical and legal questions of interventions into the human germline by means of CRISPR-Cas: How should issues of risk and uncertainty be handled? What responsibilities arise regarding future generations? Under which conditions can germline editing measures be therapeutically legitimized? For this purpose, we refer to a scenario anticipating potential further development in CRISPR-Cas technology implying improved accuracy and exclusion of germline transmission to future generations. We show that, if certain concepts regarding germline editing are clarified, under such conditions a categorical prohibition of one-generation germline editing of single-cell embryos appears not to be ethically or legally justifiable. These findings are important prerequisites for the international debate on the ethical and legal justification of germline interventions in the human embryo as well as for the harmonization of international legal standards.


Chemically engineered unzipped multiwalled carbon nanotube and rGO nanohybrid for ultrasensitive picloram detection in rice water and soil samples.
Picloram (4-Amino-3,5,6-trichloro pyridine-2-carboxylic acid) is a chlorinated herbicide that has been discovered to be tenacious and relatively durable in both soil and water. It is known to have adverse and unpleasant effects on humans causing several health complications. Therefore, the determination of picloram is profoundly effective because of its bio-accumulative and persistent nature. Because of this, a sensitive, rapid, and robust detection system is essential to detect traces of this molecule. In this study, we have constructed a novel nanohybrid system comprising of an UZMWCNT and rGO decorated on AuNPs modified glassy carbon electrode (UZMWCNT + rGO/AuNPs/GCE). The synthesized nanomaterials and the developed system were characterized using techniques such as SEM, XRD, SWV, LSV, EIS, and chronoamperometry. The engineered sensor surface showed a broad linear range of 5 × 10-2 nM to 6 × 105 nM , a low limit of detection (LOD) of 2.31 ± 0.02 (RSD < 4.1%) pM and a limit of quantification (LOQ) of 7.63 ± 0.03 pM. The response time was recorded to be 0.2 s, and the efficacy of the proposed sensor system was studied using rice water and soil samples collected from the agricultural field post filtration. The calculated recovery % for picloram in rice water was found to be 88.58%-96.70% (RSD < 3.5%, n = 3) and for soil it was found to be 89.57%-93.24% (RSD < 3.5%, n = 3). In addition, the SWV responses of both the real samples have been performed and a linear plot have been obtained with a correlation coefficient of 0.97 and 0.96 for rice and soil samples, respectively. The interference studies due to the coexisting molecules that may be present in the samples have been found to be negligible. Also, the designed sensor has been evaluated for stability and found to be highly reproducible and stable towards picloram detection.


Using intermittent self-catheters: experiences of people with neurological damage to their spinal cord.
The aim of this study was to investigate the experiences of using intermittent self-catheters (ISCs) among people with neurological damage to their spinal cord. This study sought to highlight the impact of using specific ISCs on users' daily lives and to identify key features of product design which affected ease of use. In-depth interviews were conducted with 16 ISC users to elicit their views and experiences of ISC use. Interviewees were purposively sampled, primarily from the spinal cord injury population, via a variety of sources. Transcripts were analysed using the Framework method. Key product characteristics which influenced ease of use both inside and outside the home were identified (e.g. gauge, rigidity and packaging); preferences were highly personal. ISC users were conscious of health consumer issues such as the financial costs, the environmental costs and the trustworthiness of the manufacturer. Wider self-catheterisation issues such as anxiety, self-image and control over bladder management were also important to interviewees. This study provides new information on key issues associated with experiences of ISC use by people living in a community setting who have neurological damage to their spinal cord.


Impact of Using a Novel Gastric Feeding Tube Adaptor on Patient's Comfort and Air Leaks During Non-invasive Mechanical Ventilation.
The presence of oral or naso-enteral probes during non-invasive mechanical ventilation (NIMV) increases the risk of leakage and patient discomfort. The objective of this study was to evaluate the effectiveness of a novel tube adapter for NIMV (TA-NIMV) in relation to leakage and comfort level. A non-randomized quasi-experimental design was performed in an adult intensive care unit of a highly complex hospital, in which patients were their own controls. We included adult patients who required NIV with oronasal mask and who simultaneously had oral or naso-enteric tubes. The interventions were as follows: every participant received two therapies, one with the TA-NIMV and one conventional therapy of NIMV (CT-NIMV). Comfort could be evaluated in 99 patients with a Glasgow Coma Scale of 15. The outcomes of interest was the average percentage of air leak and patient comfort during each intervention. 196 patients were included in the study during a 16-month period. The mean air leak percentage was 9.2% [standard deviation (SD), 7.7] during TA-NIMV and 32.5% (SD, 12.5) during CT-NIMV (p<0.001). 84.9% reported being comfortable or very comfortable during TA-VMNI. 66.7% Uncomfortable or Very uncomfortable during CT-NIMV (p<0.001). Higher comfort levels and lower air leakage volume percentages were achieved using the TA-NIMV than those achieved by CT-NIMV.


Screening for Axis II personality disorders in women with bulimic eating disorders.
The Personality Diagnostic Questionnaire (PDQ) was completed by 628 eating-disordered women: 300 with normal-weight bulimia, 15 with anorexia nervosa with bulimic features, and 313 with subdiagnostic eating disorders. Three-quarters (75%) of subjects with normal-weight bulimia had personality disorder diagnoses, compared with 50% of those with subdiagnostic eating disorders. The average number of separate PDQ diagnoses was 2.7 for the normal-weight bulimia group, 2.5 for the group with anorexia nervosa with bulimic traits, and 1.5 for the subdiagnostic group. The most common PDQ diagnoses were schizotypal, histrionic, and borderline disorders, but avoidant and dependent personality features also occurred. Personality disturbances may be common in patients with eating disorders.


Relationship between volume and in-hospital mortality in digestive oncological surgery.
The results previously obtained in Spain in the study of the relationship between surgical caseload and in-hospital mortality are inconclusive. The aim of this study is to evaluate the volume-outcome association in Spain in the setting of digestive oncological surgery. An analytical, cross-sectional study was conducted with data from patients who underwent surgical procedures with curative intent of esophageal, gastric, colorectal and pancreatic neoplasms between 2006-2009 with data from the Spanish MBDS. In-hospital mortality was used as outcome variable. Control variables were patient, health care and hospital characteristics. Exposure variable was the number of interventions for each disease, dividing the hospitals in 3 categories: high volume (HV), mid volume (MV) and low volume (LV) according to the number of procedures. An inverse, statistically significant relationship between procedure volume and in-hospital mortality was observed for both volume categories in both gastric (LV: OR=1,50 [IC 95%: 1,28-1,76]; MV: OR=1,49 (IC 95%: 1,28-1,74)) and colorectal (LV: OR=1,44 [IC 95%: 1,33-1,55]; MV: OR=1,24 [IC 95%: 1,15-1,33]) cancer surgery. In pancreatic procedures, this difference was only statistically significant between LV and HV categories (LV: OR=1,89 [IC 95%: 1,29-2,75]; MV: OR=1,21 [IC 95%: 0,82-1,79]). Esophageal surgery also showed an inverse relationship, which was not statistically significant (LV: OR=1,89 [IC 95%: 0,98-3,64]; MV: OR=1,05 [IC 95%: 0,50-2,21]). The results of this study suggest the existence in Spain of an inverse relationship between caseload and in-hospital mortality in digestive oncological surgery for the procedures analyzed.


Performances of biological aerated filter employing hollow fiber membrane segments of surface-improved poly (sulfone) as biofilm carriers.
Using the surface of poly (sulfone) hollow fiber membrane segments as grafted layer, the hydrophilic acrylamide chain was grafted on by UV-photoinduced grafting polymerization. The gained improvement of surface wettability for the modified membrane was tested by measuring the contact-angle as well as FTIR spectra. Then correlation between the hydrophilic ability of support material and the biofilm adherence ability was demonstrated by comparing the pollutant removal rates from urban wastewater via two identical lab-scale up-flow biological aerated filters, one employed the surface wettability modified poly (sulfone) hollow fiber membrane segment as biofilm carrier and the other employed unmodified membrane segment as biofilm carrier. The experimental results showed that under the conditions of influent flux 5 L/h, hydraulic retention time 9 h and gas to liquid ratio (G/L) 10:1, the removal rates of chemical oxygen demand (COD) and ammonium nitrogen (NH4(+)-N) for the modified packing filter and the unmodified packing filter was averaged at 83.64% and 96.25%, respectively, with the former filter being 5%-20% more than the latter. The effluent concentration of COD, NH4(+)-N and turbidity for the modified packing filter was 25.25 mg/L, 2 mg/L and 8 NTU, respectively. Moreover, the ammonium nitrogen removal performance of the filter packing the modified PSF was compared with the other bioreactor packing of an efficient floating medium. The biomass test indicated that the modified membrane matrixes provided better specific adhesion (3310-5653 mg TSS/L support), which gave a mean of 1000 mg TSS/L more than the unmodified membrane did. In addition, the phenomenon of simultaneous denitrification on the inner surface of the support and nitrification on the outer surface was found in this work.


Visual assessment in Down Syndrome: The relevance of early visual functions.
Children with Down Syndrome (DS) have a high prevalence of ocular disorders, and even when ophthalmological deficits (i.e. refractive errors or strabismus) are corrected, visual acuity seems to have a different developmental trend compared to typical children. Unfortunately, there is no consensus about the age at which it is fundamental to perform a first comprehensive visual assessment in this population. We analyzed early visual functions in a sample of 42 Italian children with DS, in order to achieve new insights for early surveillance and intervention. DS children were evaluated with the Early Neurovisual Assessment, including Teller Acuity Cards (at 6, 12 and 18 months of age) and the Pediatric Ophthalmological Examination (within the 36th months of age). Visual acuity in our sample was lower than findings reported in the literature on healthy Italian children, but the values were within the confidence interval reported in previous studies on DS children. Moderate or severe refractive errors (> 3diopters) were present in five children (four had hyperopia and one myopia). Abnormalities in ocular motility were observed in 15 children and pathological findings for fundus oculi or lens were found in another eight. Furthermore, ophthalmological findings correlated with visual acuity at 18 months of age. According to our results, the Early Neurovisual Assessment at 18 months of life is a reliable tool for early detection of visual disorders in children with DS and it is useful for programming early intervention to promote their neurodevelopment.


[Results of self-centering patellofemoral prosthesis: a retrospective study of 57 implants].
The aim of this retrospective analysis was to report results obtained with a self-centering patellofemoral prosthesis. We wanted to determine whether self-centering still has indications for the treatment of patellofemoral osteoarthritis. This was a continuous series of 57 knees operated on since 1986 in the same center for implantation of a self-centering patellofemoral prosthesis (Medinov then Depuy). Eight patients died and four were lost to follow-up. Two knees were excluded from the analysis after revision with a PFP. We report here the outcome of 43 prostheses at mean follow-up of six years two months (range 78 months to 15 years). The IKS score (200 points) and the ADL scale (in %) were recorded. The position of the prosthesis was assessed on plain X-rays. Mean age at implantation was 67.2 years. The main reasons for surgery were osteoarthritis secondary to dysplasia (60%) and primary disease (31.1%). At last follow-up, the IKS score was 157.2 points (range 76-195). The mean ADL score was 74.1/100 (48.8-96.3). The IKS evaluation showed good outcome in 66.7% of knees. The ADL scale gave a less satisfactory outcome: 57.7% good outcome for this scale which takes into account all knee functions for activities of daily life. Outcome was better among patients with trochlear dysplasia. Eleven patients (24.4%) had had revision surgery for total knee arthroplasty. Preoperatively, the trochlear angle was smaller in revision cases (p=0.023). In these patients, the first prosthesis was more anterior (p=0.004) with a greater horizontal axis (p=0.015). Our outcomes were less satisfactory than the average results in the literature. It must be noted however, that the concept of a good outcome depends on the scale used for assessment. We found in our series a 10% difference between the ADL scale and the IKS score. Independently of the assessment scale used, outcome was better in knees with osteoarthritis secondary to dysplasia. An analysis of the X-ray findings disclosed technical errors leading to failure. The outcome of patellofemoral prosthesis depends essentially on two factors: technical precision and patient selection. In light of these findings, we have come to limit still further the rare indications for patellofemoral prostheses. The typical indication is isolated advanced patellofemoral osteoarthritis secondary to patellofemoral dysplasia unresponsive to medical treatment in patients aged 50-70 years. Revision with a total knee arthroplasty required changing the patellar insert if worn. We have not had any particular problem with revision total knee arthroplasty after patellofemoral prosthesis.


Predictors of outcome in a cohort of women with chronic pelvic pain - a follow-up study.
Chronic pelvic pain (CPP) in women is a long-lasting condition. To explore changes in pain intensity, adjustment to pain, pain appraisal and coping strategies as well as to evaluate whether baseline pain appraisals and coping strategies and their changes were associated with outcome in the long term. A follow-up study was conducted on all consecutive women who had visited a CPP-team of a university hospital. After an average period of 3.2 years 64% of them (N=84) completed questionnaires at baseline and follow-up. A reduction in pain intensity (p<.001, d=.6), improvement in adjustment to pain (SF-36 Physical Component Summary (p<.001, d=.4) and depressive symptoms (p<.01, d=.2)), as well as a reduction in catastrophizing pain (p<.01, d=.4) and an increase in perceived pain control (p<.01, d=.3) were observed. Neither biographic nor clinical variables were related with these changes. Pain appraisal and coping strategies at baseline did not predict changes from baseline in pain intensity. However, baseline levels of perceived pain control correlated with a change in depressive symptoms (r=-.27, p<.05), also after adjustment for pain intensity at baseline (r=-.28, p<.05). Changes from baseline in levels of catastrophizing pain were associated with changes in pain intensity (r=.44, p<.01), SF-36 Physical Component Summary (r=-.34, p<.01) and depressive symptoms (r=.71, p<.01). At a 3 year follow-up, improvement in pain intensity in women with CPP was not associated with baseline pain appraisals and coping strategies. A reduction in catastrophizing was related to better outcome in the long term.


Induce defense response of DADS in eggplants during the biotrophic phase of Verticillium dahliae.
Verticillium wilt is a destructive vascular disease in eggplants. The complex defensive mechanisms of eggplant against this disease are very limited. Our work examined the bioactive properties of garlic allelochemical diallyl disulfide (DADS) as potential biostimulants for defense against V. dahliae in eggplant seedlings. We, therefore, foliar sprayed DADS on eggplants to study the defense response during the early biotrophic phase of V. dahliae (a hemibiotroph). DADS application significantly increased root peroxidase (POD), phenylalanine-ammonia lyase (PAL) enzyme activity, and reduced H2O2 levels after 24 h of fungal inoculation. Salicylic acid (SA) in leaves and roots was significantly increased while, the jasmonic acid (JA), indole acetic acid (IAA), and abscisic acid (ABA) levels were decreased. The microscopic examinations of V. dahliae infection in roots displayed that the progression of infection was restricted in DADS-treated plants. Depositions of lignin and phenolic compounds such as ferulic acid, p-coumaric acid, and caffeic acid content were significantly higher in DADS-treated plants at 48 h post-inoculation. Similarly, the DADS application up-regulated pathogenesis-related (PR1, PR2, and PR5), mitogen-activated protein kinase (MPK1), and lipoxygenase (LOX) genes. Furthermore, DADS-treated plants exhibited a lower disease severity index (23.3% vs. 57.0% in controls), indicating successful defense against V. dahliae. Our findings concluded that the biological function of garlic allelochemical DADS has a prominent role in the higher defense resistance of eggplants during the early infection of V. dahliae.


Early "step-down" transfer of low-risk patients with chest pain. A controlled interventional trial.
To determine whether providing private practitioners with triage criteria for their low-risk chest pain patients would safely enhance bed utilization efficiency in coronary and intermediate care units. Prospective, controlled, interventional trial using an alternate month study design. A large teaching community hospital. Cohort of 404 low-risk patients with chest pain for whom a diagnosis of myocardial infarction has been excluded and who have not sustained complications, required interventions, or developed unstable comorbidity. During intervention months, private practitioners caring for low-risk patients in the coronary and intermediate care units were contacted 24 hours after admission. Physicians were informed that the transfer of low-risk patients to nonmonitored beds could probably be done safely, based on the results of a pilot study. The practitioner had the option of agreeing to or deferring patient transfer. During control months, physicians were not contacted in this way. Use of the triage criteria by private practitioners reduced lengths of stay in the intermediate and coronary care units by 36% and 53%, respectively. Bed availability increased by 744 intermediate and 372 coronary care unit bed-days per year. Charges decreased by $2.6 million per year and profits improved by $390,000 per year. There were not significant differences in complications between control and intervention patients and in no case (95% CI, 0% to 1.6%) did the triage criteria adversely affect quality of care. The early transfer triage criteria may be a safe and efficacious decision aid for improving bed utilization in intermediate and coronary care units. In addition, this study shows the feasibility of and potential benefits from applying practice guidelines at a community hospital.


Head scanning during admission through the Accident and Emergency Department.
In order to illustrate our current pattern of use, 50 patients were reviewed who were examined by computerized tomography (CT) of the head during admission through the Accident and Emergency (A & E) Department. Fourteen (28 per cent) had no history of head injury but exhibited diminished conscious level, epilepsy, headache, or hemiplegia. The 36 cases of head injury were analysed in order to see whether they met certain criteria proposed by other authors, and to suggest the advantage to be gained when CT was available in a district general hospital (with teaching status).


Management and outcome of low anorectal malformations.
Low anorectal malformation comprises about half of all anorectal anomalies. Most of the literature concerning management of anorectal anomalies is centred around the treatment and outcome of high anomalies. The management of low anomalies has been considered significantly less challenging than high anomalies. Also, the outcome of low anomalies has traditionally been considered good. However, recent more critical long-term follow-up reports show a different picture. Many patients with low anomalies suffer from long-term anorectal functional problems, especially constipation but also soiling that occurs in a significant percentage of patients. In this review, we compile the recent views on the diagnosis, surgical treatment and outcome of low anorectal anomalies. We also present an algorithm for the management of these anomalies. The emphasis on the surgical management of low anorectal anomalies is to use as minimally invasive operative methods as possible and preserve the native mechanisms of continence that usually are much better preserved than in more severe high anomalies.


Quantitative structure-activity relationships. VI. Non-linear dependence of biological activity on hydrophobic character: calculation procedures for bilinear model.
The bilinear model, log 1/C = a log P--b log (betaP + 1) + c, is a new model for the qunatitative description of non-linear relationships between hydrophobic character and biological activity. In contrast to the parabolic Hansch model the bilinear model considers the particular effect that a linear relationship exists between lipophilicity and biological activity up to a point where this linear relationship breaks down to a non-linear relationship. Two different calculation procedures for the bilinear mode, a stepwise iteration method and the Taylor series iteration method, are explained and demonstrated with examples. The bilinear model and the parabolic Hansch model are compared by means of the statistical parameters r, s and F, by a partial F test and by an analysis of the residuals obtained with both models.


A permanently implanted endocardial electrode complicating ventricular tachycardia with a second VT.
A VVI pacemaker was permanently implanted for the purpose of suppressing recurrent ventricular tachycardia (VT). Not only did the device fail to suppress the VT, but also the permanent endocardial electrode caused a second VT which was more rapid and clinically more severe. When a new VT occurs in the presence of a permanently implanted ventricular pacing system, the implanted electrode should be considered as one of the possible etiologic causes for the VT.


Extracellular vesicles as an emerging tool for the early detection of Alzheimer's disease.
Alzheimer's disease (AD) is characterized by a series of interacting pathophysiological cascades, including the aggregation of β-amyloid plaques and the formation of neurofibrillary tangles derived from hyperphosphorylated tau proteins. AD is the cause of approximately 70 % of dementia, an irreversible and untreatable syndrome at its late stage. Hence, more efforts should be devoted to identifying at-risk or preclinical AD populations for early intervention and the improved design of drug trials. The exosome, a nanoscale subtype of extracellular vesicle that serves as a cell-to-cell communication messenger, is an emerging liquid biopsy tool for various diseases including AD. Recently, it has been discovered that brain-derived exosomes can flow through the blood-brain barrier to the peripheral blood, containing important protein and nucleic acid biomarkers that are associated with the pathogenesis and progression of AD. Other reports showed a strong involvement of exosomes in synaptic function, insulin resistance, and neuroinflammation, among others. Here, we summarize those studies and assess the value of exosomes as an emerging tool for the early detection of AD in conjunction with the current clinical diagnosis paradigm.


The effects of nitrogen fixation, soil nitrate, and defoliation on the growth, alkaloids, and nitrogen levels of Lupinus succulentus (Fabaceae).
We examined the effects of nitrogen nutrition and defoliation on the alkaloids, nitrogen levels, and growth of Lupinus succulentus by growing plants under five nitrogen/defoliation treatments: 1) fertilization with a high-nitrate nutrient solution, 2) fertilization with a low-nitrate solution, 3) inoculation with N-fixing bacteria but without available soil nitrogen, 4) high-nitrate solution plus periodic partial defoliation, and 5) low-nitrate plus defoliation. In the absence of defoliation, plants from both the N-fixing and high-N treatments had higher concentrations of alkaloids and nitrogen, and higher growth rates than the low-N plants. Periodic defoliation had little effect on the high-N plants, but defoliated N-fixing plants were severely stunted and had lower alkaloid and nitrogen levels. The experimental treatments also affected the relative concentrations of the alkaloids. Our results indicate that 1) alkaloid composition and concentration in L. succulentus are determined by both nitrogen availability and developmental state, 2) plants relying solely on N-fixation respond quite differently to defoliation than those with adequate soil nitrogen, and 3) the food value of the plant tissue can be affected by an interaction between the effects of defoliation and nitrogen status.


Analysis of CCN2 promoter activity in PANC-1 cells: regulation by ras/MEK/ERK.
Connective tissue growth factor (CTGF, CCN2) is overexpressed in pancreatic cancer. We mapped the minimal CCN2 promoter active in PANC-1 cells, a human pancreatic cancer cell line. Within this region, Sp1, BCE-1 and Ets elements were important for the activity of the CCN2 promoter. Constitutive hyperactivated ras is a hallmark of cancers, including that of the pancreas. Treatment of PANC-1 cells with the MEK inhibitor U0126 or the Sp1 inhibitor mithramycin reduced CCN2 mRNA and promoter activity. Mutation of the BCE-1, but not Sp1 or Ets, site abolished the responsiveness of the CCN2 promoter to U0126. Overexpressing constitutively active MEK1 or ras activated CCN2 promoter activity. Thus CCN2 is likely to act downstream of ras in PANC-1 cells. CCN2 is overexpressed in cancer cells. Activated ras/MEK/ERK is a hallmark of cancer, and we have shown that the elevated CCN2 expression in pancreatic cancer cells is dependent on this pathway.


Lentivirus transduced interleukin-1 receptor antagonist gene expression in murine bone marrow-derived mesenchymal stem cells in vitro.
Genetically modified mesenchymal stem cells have been used in attempts to increase the expression of interleukin‑1 receptor antagonist (IL‑1Ra); however, the attempts thus far have been unsuccessful. The aim of the present study was to investigate whether the lentivirus transduced IL‑1Ra gene was able to be stably expressed in murine bone marrow‑derived mesenchymal stem cells (mBMSCs) in vitro. In the present study, third generation lentiviral (Lv) vectors transducing the IL‑1Ra/green fluorescent protein (copGFP) gene were constructed and transfected into mBMSCs to establish the Lv.IL‑1Ra.copGFP/mBMSCs, which were evaluated using fluorescence microscopy, flow cytometry, cell viability analysis using a cell counting kit‑8 kit, Trypan blue staining and an MTT growth kinetics assay. The expression of IL‑1Ra was analyzed using reverse transcription-quantitative polymerase chain reaction and western blotting. The results demonstrated that the Lv.IL‑1Ra/copGFP vector was successfully constructed. The mBMSCs exhibited a short proliferation life, however they had good growth kinetics at an early stage and improved viability following efficient transduction of the IL‑1Ra gene. IL‑1Ra was overexpressed following transfection of mBMSCs. In conclusion, lentiviral vector transduced mBMSCs were able to efficiently express exogenous Il‑1Ra under certain conditions and had a marked capacity for proliferation.


Ethnobotanical survey of Zagori (Epirus, Greece), a renowned centre of folk medicine in the past.
Zagori is a group of villages in and around the National Park of Vikos-Aoos, in Epirus, north-west Greece. It was renowned in previous centuries as a major centre of folk medicine, and its practitioners, called 'vikoyiatri' or 'komboyiannites', were famous beyond the borders of Greece. Given the rich biological and cultural heritage of Zagori, we have tried to evaluate the present status concerning the medicinal flora of the area and its uses in the everyday life of the Zagori inhabitants. About 100 plants and their uses for therapeutic and other purposes are reported. Information included comes from both literature sources and interviewed informants. Traditional healing has not been altogether wiped out of Zagori. However, it no longer reflects the famous past and rich medicinal flora of the area.


Structural analysis reveals the formation and role of RNA G-quadruplex structures in human mature microRNAs.
Here we identify hundreds of RNA G-quadruplex (rG4) candidates in microRNAs (miRNAs), characterize the miRNA structure and miRNA-mRNA interactions on several mammalian-conserved miRNAs, and reveal the formation of rG4s in miRNAs. Notably, we study the effect of these rG4s in cells and uncover the role of rG4s in miRNA-mediated post-transcriptional regulation.


A surviving intact branch stabilizes remaining axon architecture after injury as revealed by in vivo imaging in the mouse spinal cord.
The complex morphology of axons presents a challenge in understanding axonal responses to injury and disease. By in vivo two-photon imaging of spinal dorsal column sensory axons, we systematically examined the effect of injury location relative to the main bifurcation point on axon degeneration and regeneration following highly localized laser injuries. Retrograde but not anterograde degeneration was strongly blocked at the bifurcation point at both the acute and subacute phases. Eliminating either the ascending or descending branch led to a poor regenerative response, while eliminating both led to a strong regenerative response. Thus, a surviving intact branch suppresses both retrograde degeneration and regeneration of the injured branch, thereby preserving the remaining axon architecture. Regenerating axons exhibited a dynamic pattern with alternating phases of regeneration and pruning over a chronic period. In vivo imaging continues to reveal new insights on axonal responses to injury in the mammalian spinal cord.


Cyclophosphamide-resistant Yoshida ascites tumor cells and their cross resistance to some alkylating agents.
A cyclophosphamide-resistant subline of a Yoshida ascites tumor was developed by giving increasing doses of the drug after transplantation. The effect of several alkylating agents on the cell proliferation of both the sensitive and resistance cell line was compared establishind dose response curves and D50 values. The developed subline revealed a 260 fold resistance to cyclophosphamide. It was completely cross-resistant to hydroperoxycyclophosphamide, whereas for triaziquone, N-oxide-mustard, and N-methyl-mustard only a partial cross resistance existed. These results give further evidence that cyclophosphamide and hydropeoxycyclophosphamide have the same mechanism of action. Regarding the other alkylating agents the results demonstrate differences concerning either the molecular mode of action or protecting effects. A decreased activation or uptake of substance is probably not the base for resistance.


Sodium currents in mammalian muscle.
1. A method is described which allows the approximate computation of membrane current from measurements with three electrodes in the mid-region of a muscle fibre.2. Measurements of inward sodium current in frog muscle are compared with the results of previous clamping studies to test the validity of the new method.3. Sodium current in rat muscle (extensor digitorum longus) is in general similar to sodium current in frog muscle. Two differences in detail have been found between sodium current in rat and frog muscle: (a) at the same temperature (in the range 0-20 degrees C) inactivation is slower in the rat than in the frog; (b) in rat the steady-state activation is shifted negatively on the voltage axis by some 10-15 mV.4. Delayed outward current and charge movement (Schneider & Chandler, 1973) are present in rat muscle.5. Rat muscle fibres are more resistant than frog muscle fibres to the action of tetrodotoxin. Inward current is still detectable in rat muscle at 100 nM tetrodotoxin. We found no evidence to suggest the existence in rat muscle of two kinds of sodium channel, one sensitive and one less sensitive to tetrodotoxin.


Effects of watershed char and climate variables on annual runoff in different climatic zones in China.
The complex interactions between climate and watershed characteristics lead to diverse annual runoff responses. Understanding the mechanism by which different climatic and watershed factors affect annual runoff is helpful in understanding the resulting changes in the hydrological process. In this study, the characteristics of 73 watersheds were analyzed. The basins were divided into three categories according to their climatic regions: temperate continental climate (n = 7); temperate monsoon climate(n = 36); and subtropical monsoon climate(n = 30). Correlation analysis, linear regression, and path analysis were used to quantify the effects of selected watershed characteristics and meteorological conditions on long-term runoff. Results showed that the average annual runoff coefficient was strongly correlated with basin area, showing a scale effect. The average annual runoff depth was strongly positively correlated with precipitation for the all watersheds. As the drought index (DI, the ratio of annual evaporation capacity to annual precipitation) increased, the annual runoff depth decreased logarithmically. The average annual rainfall and runoff depth of watersheds in the subtropical monsoon climate zone were significantly higher than those in other climatic zones, and there was no significant difference in potential evaporation between the temperate monsoon climate and subtropical monsoon climate zones. With increases in both the drought index (Ep/P) and moisture index (E/P), the vegetation distribution in the basin showed an increasing trend in farmland area and decreasing trend in forest area. Path analysis showed that rainfall had a positive effect on annual average runoff depth (ranging from 31 to 62%) while actual evapotranspiration had a negative impact (ranging from 17 to 47%). For all basins, a negative effect (13-25%) of basin area on runoff depth was observed, while forestland area had a positive effect (7-39%) on runoff depth. This study further quantified the effects of climatic and geographical factors on the long-term water balance in different climatic regions.


Developmental exposure of zebrafish to neonicotinoid pesticides: Long-term effects on neurobehavioral function.
Neonicotinoid compounds are commonly used insecticides which have become increasingly used as replacements of older generations of insecticides, such as organophosphates. Given the established neurotoxicity of cholinergic toxicants, developmental neurotoxicity studies are needed to identify in vertebrate species the potential toxicity of these insecticides which act on nicotinic cholinergic receptors. Previously, developmental exposure to a neonicotinoid insecticide imidacloprid was shown to cause persisting neurobehavioral toxicity in zebrafish. The current study evaluated neurobehavioral effects of embryonic exposure to two other neonicotinoid insecticides, clothianidin (1-100 µM) and dinotefuran (1-100 µM) in zebrafish (5-120 h post-fertilization), concentrations below the threshold for increased lethality and overt dysmorphogenesis. Neurobehavioral tests were conducted at larval (6 days), adolescent (10 weeks) and adult (8 months) ages. Both compounds caused short-term behavioral effects on larval motility, although these effects were distinct from one another. At a lower concentration (1 µM) clothianidin increased dark-induced locomotor stimulation the second time the lights turned off, while a higher concentration (100 µM) reduced activity in the dark at its second presentation. By contrast, dinotefuran (10-100 µM) caused a general decrease in locomotion. Specific longer-term neurobehavioral toxicity after early developmental exposure was also seen. clothianidin (100 µM) reduced locomotor activity in the novel tank in adolescence and adulthood, as well as reduced baseline activity in the tap startle test (1-100 µM) and reduced activity early (1-10 µM) or throughout the predator avoidance test session (100 µM). In addition to locomotor effects, clothianidin altered the diving response in a dose-, age- and time-block-dependent manner (1 µM, 100 µM), causing fish to remain further away from a fast predator cue (100 µM) relative to controls. Dinotefuran produced comparatively fewer effects, increasing the diving response in adulthood (10 µM), but not adolescence, and suppressing initial locomotor activity in the predator avoidance test (1-10 µM). These data indicate that neonicotinoid insecticides may carry some of the same risks for vertebrates posed by other classes of insecticides, and that these adverse behavioral consequences of early developmental exposure are evident well into adulthood.


The maize leaf lipidome shows multilevel genetic control and high predictive value for agronomic traits.
Although the plant lipidome show an enormous level of structural and functional diversity, our knowledge about its genetic control and its connection to whole-plant phenotypes is very limited. Here, we profiled 563 lipid species with UPLC-FT-MS in 289 field-grown inbred lines genotyped with 56,110 SNPs. Genome-wide association study identified 174 associations for 76 lipids explaining up to 31.4% of the genetic variance (P-value 8.4 × 10(-18)). Candidate genes were found for lipid synthesis, breakdown, transfer, and protection against peroxidation. The detected SNP-lipid associations could be grouped into associations with 1) individual lipids, 2) lipids from one biochemical class, and 3) lipids from several classes, suggesting a multilevel genetic control architecture. We further found a strong connection between the lipidome and agronomic traits in field-evaluated hybrid progeny. A cross-validated prediction model yielded correlations of up to 0.78 suggesting that the lipidome accurately predicts agronomic traits relevant in hybrid maize breeding.


Efficacy and limitations of cyclophosphamide-induced tolerance against alphaGal antigen.
In the present study, we have elucidated the efficacy of two cyclophosphamide (CP)-induced tolerance protocols for the induction of B-cell tolerance against Galalpha1-3Galbeta1-4GlcNAc (alphaGal) antigens. alpha1,3-galactosyltransferase-deficient (GalT-/-; H-2(b/d)) mice received with 1 x 10(8) AKR (alphaGal+/+ H-2k) spleen cells (SC) followed by 200 mg/kg CP, or alternatively followed by 200 mg/kg CP, 30 mg/kg Busulfan (BU) and 1 x 10(8) T-cell-depleted AKR bone marrow cells (BMC). The generation of both anti-alphaGal and anti-donor antibodies were completely suppressed, but normal antibody production against third party antigens was observed after BALB/c skin grafting in both groups of GalT-/- mice. In GalT-/- mice, treated with SC and CP, mixed chimerism was not observed. Cellular rejection was observed in grafted donor AKR hearts with an absence of humoral rejection, whereas humoral rejection was observed in untreated GalT-/- mice. On the other hand, long-term mixed chimerism and permanent acceptance of donor AKR skin graft and heart graft were achieved in GalT-/- mice treated with SC, CP, BU and BMC. These results demonstrate the efficacy of classical drug-induced tolerance in the induction of B-cell tolerance against alphaGal antigens. However, induction of stable mixed chimerism was required for the suppression of cellular rejection.


[Microbial settlement of paint- and building-materials in the sphere of drinking-water. 2. Information: experimental examination of bitumen paint under working conditions (author's transl)].
A bituminous coating material for drinking water reservoirs was applied on testing plates for a microbial examination. In function of the chlorine content of the water a microbial slime layer could be found on the testing plates. The amount of slime became less in course of the time or was not produced at all, when the plates were desiccated before the experiment for some months. A slime layer could never be observed on plates of asbestos cement and polyacryl as inert materials for comparison. Different microbial populations were observed.


A new procedure for the isolation of the brain myelin basic protein in a lipid-bound form.
Myelin basic protein has been isolated from bovine brain using the nonionic detergent n-octyl-polydisperse oligooxyethylene. The purified basic protein contains large amounts of heterogeneous lipids.


Increasing coverage of insecticide-treated nets in rural Nigeria: implications of consumer knowledge, preferences and expenditures for malaria prevention.
The coverage of insecticide-treated nets (ITNs) remains low despite existing distribution strategies, hence, it was important to assess consumers' preferences for distribution of ITNs, as well as their perceptions and expenditures for malaria prevention and to examine the implications for scaling-up ITNs in rural Nigeria. Nine focus group discussions (FGDs) and questionnaires to 798 respondents from three malaria hyper-endemic villages from Enugu state, south-east Nigeria were the study tools. There was a broad spectrum of malaria preventive tools being used by people. The average monthly expenditure on malaria prevention per household was 55.55 Naira ($0.4). More than 80% of the respondent had never purchased any form of untreated mosquito net. People mostly preferred centralized community-based sales of the ITNS, with installment payments. People were knowledgeable about malaria and the beneficial effects of using nets to protect themselves from the disease. The mostly preferred community-based distribution of ITNs implies that the strategy is a potential untapped additional channel for scaling-up ITNs in Nigeria and possibly other parts of sub-Saharan Africa.


Medicolegal consequences of thoracic gossypiboma: A case report.
The term gossypiboma is used to describe a retained surgical sponge after operation. It is a rare but it is associated with severe medical and legal consequences. The diagnosis can be missed despite radiological investigations. We report a case of a 15-year-old female who presented with fever, cough, dyspnea and hemoptysis. She had a history of hydatid cyst operation 2 years ago. Post-discharge follow up occurred for two years on hospital where hydatid cyst surgery had been done. Radiological investigations were inconclusive in detecting the retained sponge despite radiopaque marker. So gossypiboma should be kept in mind as a differential diagnosis in postoperative cases presenting as persistent respiratory symptoms after the operation.


Glucocorticoids and the osteoclast.
Glucocorticoid-induced osteoporosis uniformly represents suppression of bone formation. The steroid's effects on osteoclasts are, however, controversial. While glucocorticoid administration to patients with inflammatory diseases accelerates bone resorption, osteoclast function falls below normal with prolonged treatment. Thus, administration of anti-resorptive agents, such as bisphosphonates, is justified during early glucocorticoid therapy, but further suppression of osteoclasts, by these drugs, in chronically treated patients will dampen bone remodelling and may compromise skeletal quality, predisposing to fracture.


Phase partitioning detects differences between phospholipase-released forms of alkaline phosphatase--a GPI-linked protein.
A number of enzymes are known to release alkaline phosphatase and other glycan phosphatidylinositol-anchored proteins from membrane surfaces. We describe a novel approach to detect and measure these activities by partitioning in aqueous phase systems. The procedures avoid the complications of micelle-formation involving hydrophobic molecules that may arise with detergent-based partition systems and can clearly distinguish between inositol-specific phospholipase C and D activities.


Mortality in a cohort of long-term users of community psychiatric services.
A cohort of 181 users of community psychiatric services in Camberwell with at least one year's history of contact was traced for two years following a census day. Four of the eight patients who had been given a primary diagnosis of an organic condition died during this period. For the others the population-standardized mortality risk was 2.4, similar to rates previously found for in-patients with acute disorders. The causes of death were those that are common in the population. Only one suicide was recorded.


Range and Frequency of Congenital Malformations Among Children With Cleft Lip and/or Palate.
To assess the range and frequency of additional congenital malformations identified among children born alive with CL/P. Analysis of patient-level data from a national registry of cleft births linked to national administrative data of hospital admissions. National Health Service, England. Children born between 2000 and 2012 receiving cleft care in English NHS hospitals. The proportion of children with ICD-10 codes for additional congenital malformations, according to cleft type. The study included 9403 children. Of these 2114 (22.5%) had CL±A, 4509 (48.0%) had CP, 1896 (20.2%) had UCLP, and 884 (9.4%) had BCLP. A total of 3653 (38.8%) children had additional congenital malformations documented in their hospital admission records. The prevalence of additional congenital malformations was greatest among children with CP (53.0%), followed by those with BCLP (33.5%), UCLP (26.3%), and then CL±A (22.2%) (P < .001). Among those with UCLP, children with right-sided clefts were more likely to have additional malformations than those with left-sided clefts (31.6% vs 23.0%, P < .001). Malformations of the skeletal system and circulatory system were most common, affecting 10.5% and 10.2% of the included children, respectively. A total of 16.8% of children had additional congenital malformations affecting 2 or more structural systems. Congenital malformations are common among children born alive with a cleft, affecting over half of some cleft subgroups. Given the frequency of certain structural malformations, clinicians should consider standardized screening for these children. Establishing good links with pediatric and genetic services is recommended.


Successful medical treatment of pyogenic liver abscess.
Between 1976 and 1978, 6 patients with proven or probable pyogenic liver abscess were successfully treated at Los Angeles County-University of Southern California Medical Center without surgical drainage. Although surgical therapy is necessary in patients with coexisting intraabdominal pathology, antibiotic therapy without surgical intervention is an option to be considered in patients with pyogenic liver abscess and no evidence of other intraabdominal disease.


Isoenzymes of carbohydrate metabolism in primary cultures of hepatocytes from thioacetamide-induced rat liver necrosis: responses to growth factors.
Hepatocytes isolated from the liver of rats after a necrotizing dose of thioacetamide (6.6 mmol/kg) were used to study the postnecrotic process of liver regeneration. Flow cytometry analysis revealed populations of dedifferentiated hepatocytes exhibiting physical properties (size and fluorescence emission at 530 nm) similar to those found in fetal (22 days old) liver cells. The percentage of these cells increased progressively from 24 to 48 and 72 hr after thioacetamide administration. In primary cultures of hepatocytes the effects of phorbol 12-myristate 13-acetate, bombesin and insulin were investigated on the 6-phosphofructo 2-kinase/fructose 2,6 bisphosphate system. Bombesin and insulin stimulated 6-phosphofructo 2-kinase activity and fructose 2,6-bisphosphate content both in control and in thioacetamide-treated hepatocytes. However, phorbol 12-myristate 13-acetate stimulated 6-phosphofructo 2-kinase activity and increased fructose 2,6-bisphosphate concentration in thioacetamide-treated liver cells, whereas no similar response was found in hepatocytes from control rats. The response of postnecrotic thioacetamide-treated hepatocytes to phorbol 12-myristate 13-acetate was similar to that obtained from 22-day-old fetal liver cells, which reveals that different methods might control fructose 2,6-bisphosphate content and therefore the mechanisms of glycolysis and gluconeogenesis at this regulatory step. The lack of response to glucagon of glycogen phosphorylase a and 6-phosphofructo 2-kinase from thioacetamide-treated hepatocytes may indicate that the expression of specific enzymes of carbohydrate metabolism undergoes transitions to less-differentiated isoenzymatic forms. Moreover, the isoenzyme pattern of hexokinases elicits a complete disturbance in glucokinase and hexokinases activities.(ABSTRACT TRUNCATED AT 250 WORDS)


Caffeine to optimize cognitive function for military mission-readiness: a systematic review and recommendations for the field.
In 2001 the Institute of Medicine (IOM) released a report on the use of caffeine during sustained military operations in which recommendations for research and practice were made. This systematic review serves as an update on the current quality of the evidence and addresses gaps in the current literature surrounding the effects of caffeinated foods and beverages on cognitive functioning in healthy adult populations exposed to military-like moderators. PubMed, CINAHL, Embase, PsycInfo, and the Cochrane Library were searched. Peer-reviewed randomized controlled trials published in the English language since 1998 were eligible. Twenty-five trials were included and assessed for methodological quality, and descriptive data were extracted according to each military-like moderator identified. Moderators included sleep deprivation (n = 17), physical or mental exertion (n = 4), sleep deprivation combined with a sustained military operation (n = 3), and physical exertion combined with low ambient temperature (n = 1). The effects of caffeine supplementation on cognitive functioning in sleep-deprived subjects included improvements in attention and vigilance, complex reaction time, and problem solving and reasoning in the trials reviewed. These findings are consistent with the conclusions reached in the 2001 IOM report. This review contributes to the field by addressing gaps outlined in the IOM report.


Preparation and characterization of polyaniline-containing Na-AlMCM-41 as composite material with semiconductor behavior.
Composite material formed from a mesoporous aluminosilicate, Na-AlMCM-41, with conducting polyaniline (PANI) has been synthesized by an in situ polymerization technique. Studies of aniline adsorption over mesoporous Na-AlMCM-41 synthesized in our laboratory allowed us to find the modes in which aniline interacts with the active sites of Na-AlMCM-41. In order to obtain the best reaction conditions to polymerize aniline onto Na-AlMCM-41, aniline was first polymerized to produce pure PANI. Hence, the oxidative in situ polymerization was carried out by two procedures, differing in the polymerization time and in static or stirring conditions. Studies of infrared spectroscopy and UV-vis spectroscopy indicated that higher polymerization time and static conditions allowed us to obtain mainly polyaniline in emeraldine form on the host. The N(2) isotherm of the polyaniline/Na-AlMCM-41 composite (PANI/MCM) indicated that the shape was similar to that of MCM, but the shift to saturation transition to lower partial pressure shows that the channels are occupied by PANI and they are now narrowed. The thermal properties of PANI, Na-AlMCM-41, and composite were investigated by TGA analyses and we found that the polymer shows higher thermal stability when it is forming the composite. Scanning electron microscopy indicated that PANI is not on the outer surface of the host. Conductivity studies show that PANI/Na-AlMCM-41 exhibits semiconductor behavior at room temperature and its conductivity was 7.0 x 10(-5) S/cm, smaller than that of pure polyaniline. PANI/Na-AlMCM-41 conductivity shows an increase as temperature increases. Magnetic measurements at room temperature confirmed that the composite has paramagnetic behavior; at lower temperatures the composite became diamagnetic.


Salivary antibody responses to ten-valent pneumococcal conjugate vaccination following two different immunization schedules in a healthy birth cohort.
Pneumococcal conjugate vaccines reduce pneumococcal colonization via serotype-specific immunoglobulin G (IgG) at mucosal surfaces. The infant immunization schedule with the ten-valent pneumococcal conjugate vaccine (PCV10) changed from a 3 + 1 schedule (2-3-4-11 months) to a 2 + 1 schedule (2-4-11 months) in The Netherlands in 2013. We compared anti-pneumococcal IgG concentrations in saliva between the schedules. IgG was measured using a fluorescent bead-based multiplex immunoassay at the ages of 6 (post-primary) and 12 (post-booster) months in 51 infants receiving the 3 + 1 schedule and 68 infants receiving the 2 + 1 schedule. Post-primary IgG geometric mean concentrations (GMCs) were comparable between schedules for all vaccine serotypes. Post-booster IgG GMCs were significantly lower after the 2 + 1 schedule for serotypes 4 (p = 0.035), 7F (p = 0.048) and 23F (p = 0.0056). This study shows small differences in mucosal IgG responses between a 3 + 1 and a 2 + 1 PCV10 schedule. Future studies should establish correlates of protection against pneumococcal colonization for mucosal antibodies.


Increasing Access to WIC through Discount Variety Stores: Findings from Qualitative Research.
Many low-income neighborhoods do not include a full-service grocery store. In these communities, discount variety stores (DVS) can be convenient points of food access. However, no identified DVS are authorized to accept Special Supplemental Nutrition Program for Women, Infants, and Children Program (WIC) benefits. One national DVS retailer implemented WIC in 10 stores located in low-income communities in North Carolina over a 10-month pilot period to assess WIC feasibility. To better understand the facilitators and barriers to WIC implementation from the perspective of DVS staff, we analyzed 36 in-depth interviews with employees of this DVS chain at corporate, manager, and store clerk levels. Most participants provided positive feedback about implementing and offering WIC. Many store employees had personal experience participating in WIC, which increased their understanding of the WIC shopping experience. Store staff's prior WIC participation and customers' proximity to DVS locations were facilitators to implementation. Primary barriers included limited choice of store products for customers, complicated or unclear labeling of WIC products, and difficulty training employees to process WIC vouchers. These findings suggest that whereas most employees viewed WIC positively, barriers related to product selection and training must be addressed. Notably, North Carolina's recent change to an electronic system to process WIC transactions requires minimal manual employee training and should address several barriers to implementation. However, the computer system upgrades necessary to accept electronic WIC transactions may be a barrier for DVS to continued WIC acceptance. Future research is needed to evaluate implementation of electronic WIC transactions in DVS.


Exophthalmus--prenatal ultrasonic features for diagnosis of Crouzon syndrome.
Prenatal real-time ultrasonographic diagnosis of exophthalmus is presented. Diagnosis was made at the 35th week of gestation in a fetus of a patient affected with Crouzon syndrome (craniofacial dysotosis). Recognition of exophthalmus as a part of Crouzon syndrome and the easy visualization of the eye balls and palpebrae in the third trimester made the diagnosis possible.


Cardiac stem cell niche, MMP9, and culture and differentiation of embryonic stem cells.
Embryonic stem cells (ESC) are totipotent, self-renewing, and clonogenic, having potential to differentiate into a wide variety of cell types. Due to regenerative capability, it has tremendous potential for treating myocardial infarction (death of myocardial tissue) and type 1 diabetes (death of pancreatic beta cells). Understanding the components regulating ESC differentiation is the key to unlock the regenerative potential of ESC-based therapies. Both the stiffness of extracellular matrix (ECM) and surrounding niche/microenvironment play pivotal roles in ESC differentiation. Matrix metalloproteinase-9 (MMP9) induces fibrosis that causes stiffness of the ECM and impairs differentiation of cardiac stem cells into cardiomyocytes. Here, we describe the method of ESC culture and differentiation, and the expression of MMP9 and its inhibitor, tissue inhibitor of metalloproteinase-4 (TIMP4) in differentiating ESC.


Rapid changes in profiles from stored materials used in scent training of explosive detection dogs.
Canines trained on scents from materials emitting vapours of explosives and related compounds are widely used to detect explosives in civilian, military and forensic applications. Despite the importance of these training materials, there is limited knowledge on how long these subsamples can be stored and whether vapour profiles change over time. We developed a sampling methodology that makes use of a secondary chamber for stabilisation of headspace concentration to allow reliable and reproducible determination of scent profiles. The effect of aging was investigated by following the response of volatile markers emitted from eight common explosives in open and closed containers over two months or two years. The initial headspace air volume consisted of a wide variety of chemical substances related to explosives, with levels varying in magnitude from low ppb to ppm. All included subsamples were affected by aging by demonstrating exponentially lower levels, and five subsamples showed a significant change in their scent profile. The dominant components decreased on a short time scale for plastic explosives based on RDX, PETN and dynamite as well as for granules of octol and ammonium nitrate mixed with fuel. For flakes of TNT, granules of Comp B and nitrocellulose powder, headspace air concentrations declined, but the overall character of their profiles were in general more stable. The overall changes, i.e., lower levels and/or changed profiles, justifies regular checks of the scent status of training materials. Considering these results together with data displaying marginal changes in energetic performance, it is advisable to complement scent training with training materials subjected to different durations of aging.