Estimating cancer incidence, prevalence, and the number of cancer patients treated with antitumor therapy in 2015 and 2020 - analysis of the Czech National Cancer Registry.
Cancer burden in the Czech population ranks among the highest worldwide, which introduces a strong need for a prospective modelling of cancer incidence and prevalence rates. Moreover, a prediction of number of cancer patients requiring active antitumor therapy is also an important issue. This paper presents the stage-specific predictions of cancer incidence and prevalence, and the stage- and region-specific patients requiring active antitumor therapy for the most common cancer diagnoses in the Czech Republic for years 2015 and 2020. The stage-specific estimates are also presented with regard to the treatment phase as newly diagnosed patients, patients treated for non-terminal recurrence, and patients treated for terminal recurrence. Data of the Czech National Cancer Registry from 1977 to 2011 has been used for the analysis, omitting the records of patients diagnosed as death certificate only or at autopsy. In total, 1,777,775 incidences have been considered for the estimation using a statistical model utilizing solely the population-based cancer registry data. All estimates have been calculated with respect to the changing demographic structure of the Czech population and the clinical stage at diagnosis. Considering year 2011 as the baseline, we predict 89%, 15%, 31% and 32% increase in prostate, colorectal, female breast and lung cancer incidence, respectively, in 2020 resulting in 13,153, 9,368, 8,695, and 8,604 newly dia-g--nosed cancer patients in that year, respectively. Regarding cancer prevalence in 2020, the estimated increase is 140%, 40%, 51%, and 17% for prostate, colorectal, female breast and lung cancer, respectively, meaning that more than 100,000 prevalent female breast cancer patients as well as more than 100,000 prevalent prostate cancer patients are expected in the Czech Republic. The estimated numbers of patients requiring active antitumor therapy for prostate, colorectal, female breast and lung cancer in the Czech Republic in 2020 are 23,652, 14,006, 14,759 and 8,272; respectively. The analysis documents a serious increase in cancer incidence and prevalence in the Czech Republic in years 2015 and 2020 when compared to the situation in 2011. Regarding the estimated numbers of patients requiring active antitumor therapy, the model confirms a continuous increase that must be accounted for in the future planning of health care in the Czech Republic.


The long-term outcome of retarded fetal growth.
Recent findings suggest that many human fetuses have to adapt to a limited supply of nutrients and in doing so they permanently change their physiology and metabolism. These "programmed" changes may be the origins of a number of diseases in later life, including coronary heart disease and the related disorders stroke, diabetes and hypertension.


Acute Kidney Injury Within 90Days of Radical Cystectomy for Bladder Cancer: Incidence and Risk Factors.
To report incidence of acute kidney injury (AKI) following radical cystectomy (RC) for bladder cancer and evaluate risk factors for AKI as well as the impact of AKI on development of long-term renal insufficiency. A retrospective analysis of patients undergoing RC between 2010 and 2020 at a high-volume tertiary referral center. AKI was graded according to the Kidney Disease Improving Global Outcome (KDIGO) criteria within 90days of surgery. Long-term renal insufficiency was defined as estimated glomerular function <45 mL/min. Cumulative incidence and Cox Proportional Hazards models were used to evaluate both short- and long-term loss of renal function and investigate their association with pre- and perioperative variables. AKI occurred in 332 out of 755 patients (44%) within 90days. Preoperative chronic hypertension and obesity were independent preoperative risk factors. Robot-assisted RC was associated with a higher risk of AKI compared to open RC in multivariable analyses. The absolute risk of developing long-term renal insufficiency was 8.7% (95%CI: 5.6-12) after 5years in patients without AKI and 26% (95%CI: 16-36) in patients with KDIGO-stage ≥2. In multivariable analysis, both KDIGO-stage 1 and ≥2 were independently associated with long-term estimated glomerular filtration rate <45 mL/min. A significant number of patients experienced AKI after RC, and even patients with KDIGO-stage 1 were at increased risk of long-term renal insufficiency. Recognizing pre- and perioperative risk factors can identify patients where close surveillance and early intervention may help minimize renal function decline following RC.


Desiccation as a long-term survival mechanism for the archaeon Methanosarcina barkeri.
Viable methanogens have been detected in dry, aerobic environments such as dry reservoir sediment, dry rice paddies and aerobic desert soils, which suggests that methanogens have mechanisms for long-term survival in a desiccated state. In this study, we quantified the survival rates of the methanogenic archaeon Methanosarcina barkeri after desiccation under conditions equivalent to the driest environments on Earth and subsequent exposure to different stress factors. There was no significant loss of viability after desiccation for 28 days for cells grown with either hydrogen or the methylotrophic substrates, but recovery was affected by growth phase, with cells desiccated during the stationary phase of growth having a higher rate of recovery after desiccation. Synthesis of methanosarcinal extracellular polysaccharide (EPS) significantly increased the viability of desiccated cells under both anaerobic and aerobic conditions compared with that of non-EPS-synthesizing cells. Desiccated M. barkeri exposed to air at room temperature did not lose significant viability after 28 days, and exposure of M. barkeri to air after desiccation appeared to improve the recovery of viable cells compared with that of desiccated cells that were never exposed to air. Desiccated M. barkeri was more resistant to higher temperatures, and although resistance to oxidative conditions such as ozone and ionizing radiation was not as robust as in other desiccation-resistant microorganisms, the protection mechanisms are likely adequate to maintain cell viability during periodic exposure events. The results of this study demonstrate that after desiccation M. barkeri has the innate capability to survive extended periods of exposure to air and lethal temperatures.


Characterization of a subline of P388 leukemia resistant to amsacrine: evidence of altered topoisomerase II function.
Sensitive (P388/S) and amsacrine-resistant (P388/amsacrine) sublines of P388 leukemia were cloned in vitro and tested for differential chemosensitivity against a panel of drugs. P388/amsacrine, resistant both in vivo and in vitro to amsacrine, was cross-resistant to other putative topoisomerase II inhibitors including teniposide, etoposide, bisantrene, and doxorubicin. P388/amsacrine, was however, as sensitive as cloned P388/S to camptothecin, an inhibitor of topoisomerase I. The pattern of cross-resistance suggested that an alteration in topoisomerase II may be involved in the resistance of P388/amsacrine to these drugs. No differences in the uptake of amsacrine were detected between the two sublines. Cross-resistance to vinblastine was evident in P388/amsacrine; however resistance to vinblastine was associated with alterations in uptake or efflux of the drug. The number of protein-concealed single-strand breaks induced in whole cells by amsacrine, teniposide, bisantrene, and camptothecin was measured. Diminished numbers of strand breaks in the resistant subline were consistent with decreases in DNA-protein crosslinks. In the absence of drug treatment, resistant cells sustained approximately one-half as many single-strand breaks and DNA-protein crosslinks as the sensitive cells during preparation of nuclei. As measured by the P4 phage DNA unknotting assay, 0.35 M NaCl nuclear extracts from P388/S contained approximately 2.3-fold more topoisomerase II catalytic activity than did extracts from P388/amsacrine. The amount of protein that immunoreacted with a specific antibody to calf thymus topoisomerase II was also decreased in the resistant cells. These data suggest that alterations in topoisomerase II which lead to differential drug sensitivities are partially responsible for the resistance of P388/amsacrine to a specific group of drugs.


Periodontitis severity plus risk as a tooth loss predictor.
Tooth loss can be a consequence of the natural history of periodontitis. Stratification of periodontitis severity, risk, and tooth loss exists within the United States adult population, and tooth loss correlates to severity and risk. We evaluated the loss of teeth for a periodontitis-affected population categorized by the combination of severity and risk in which the subjects predominantly did not receive periodontal treatment. The clinical records of 523 subjects enrolled in the Veterans Affairs Dental Longitudinal Study, covering a period of 15 years, were used. Disease severity, risk level, and the number of teeth lost for each subject were determined. A stepwise regression analysis showed that disease and risk scores predicted mean tooth loss rate. The P value for the disease score was <0.0005, and the P value for the risk score was 0.001. The ordinal logistic regression model showed that disease (P = 0.002) and risk scores (P = 0.000) were significantly associated with the probability of subjects losing a specific number of teeth. Tooth loss is more precisely and accurately predicted by the combination of risk score and periodontal disease score than by either score alone. The combined scores may be a surrogate variable for periodontal status. Because the scores are derived from routine clinical measurements, they may be useful for population surveillance and dynamics, practice management, patient care decisions, practice-based research, and the determination of treatment effectiveness and the factors required for successful treatment, resulting in improved oral health and higher clinician productivity and income.


Sterculia tragacantha Lindl Leaf Extract Ameliorates STZ-Induced Diabetes, Oxidative Stress, Inflammation and Neuronal Impairment.
Sterculia tragacantha is a medicinal plant commonly used in the western part of Nigeria, for managing diabetes mellitus. However, there is a dearth of scientific information on the antidiabetic and neuroprotective properties of the plant. The in silico, in vitro and in vivo models were used to evaluate the antioxidants, antidiabetic, anti-inflammatory and neuroprotective potential of aqueous extract of Sterculia tragacantha leaf (AESTL) in streptozotocin (STZ)-induced diabetic rats. Thirty (30) male albino rats (155.34±6.33 g) were intraperitoneal injected with 40 mg/kg of freshly prepared streptozotocin and were divided into 5 groups (A-E) of 6 animals each. Groups A-D were treated with 0, 150 and 300 mg/kg of AESTL, and 200 mg/kg body weight of metformin respectively, while group E serve as the normal control. The results of in vitro analysis revealed dose-dependent antioxidant activities; ABTS (IC50 = 63.03±2.57 μg/mL), DPPH (117.49±2.35 μg/mL), FRAP (15.19±0.98 mmol/100g), TAC (43.38±0.96 mg/100g), hypoglycaemic effect; α-amylase (IC50 = 77.21±4.35 μg/mL) and α-glucosidase (IC50 = 443.25±12.35), and anti-cholinesterase; AChE (IC50 = 113.07±3.42 μg/mL) and BChE (IC50 = 87.50±4.32 μg/mL) activities of AESTL. In vivo study revealed dose-dependent hypoglycemic effect and body weight improvement in rats treated with the AESTL. In addition, AESTL improved the antioxidant status and attenuated STZ-induced dysregulations of Na+-K+-ATPase, cholinesterases and neurotransmitters in the brain tissue of experimental rats. The results also demonstrated that AESTL could regulate anti-inflammatory response via inhibition of COX-2/NO signaling axis in the brain of diabetic rats. Molecular docking analysis revealed that epicatechin and procyanidin B2, the bioactive compounds from AESTL, docked well to the binding cavities of acetylcholinesterase, butyrylcholinesterase, α-amylase and α-glucosidase with binding affinities ranges between -8.0 and -11.4 kcal/mol, suggesting that these compounds are the bioactive component that could be responsible for the antidiabetic and neuroprotective activities of AESTL. The results of the present study strongly suggested that the AESTL extract could be very useful for halting diabetes progression and its associated neuroinflammation complications.


Measuring Oral Mucositis of Pediatric Patients with Cancer: A Psychometric Evaluation of Chinese Version of the Oral Mucositis Daily Questionnaire.
Oral mucositis is a frequent clinical condition that has been shown to affect pediatric cancer patients. Oral Mucositis Daily Questionnaire (OMDQ) is one of the few available patient-reported outcome measures to assess the extent and impact of oral mucositis. The objectives of the study were to translate the Mouth and Throat Soreness-Related Questions of the OMDQ into Chinese (OMDQ MTS-Ch) for children and adolescents aged 6-18 years receiving chemotherapy and to evaluate its psychometric properties. This was part of a multicenter, prospective cohort study involving two phases. Phase I involved forward-backward translation to fit the cognitive and linguistic age level of the children and adolescents, followed by face and content validation, together with pretesting. In Phase II, which evaluated the internal consistency, test-retest reliability, and discriminant validity, a total of 140 patients completed the OMDQ MTS-Ch for 14 days. The OMDQ MTS-Ch had satisfactory face and content validities. The Cronbach's alpha coefficient of the OMDQ MTS-Ch was 0.984. All of the corrected item-total correlations were higher than 0.90. The test-retest intraclass correlation coefficient between consecutive days for the OMDQ MTS-Ch items ranged from 0.576 to 0.983; the only value that was not over 0.70 was that for the paired study days 7 and 8 for the item of talking. The mean area-under-the-curve OMDQ MTS-Ch item scores were significantly different among patients with different degrees of mucositis severity (P < 0.001), supporting the discriminant validity. It has been shown that the OMDQ MTS-Ch has a good level of reliability and discriminant validity and can be completed by children aged ≥6 years and adolescents on a daily basis to measure mucositis and its related functional limitations.


Comparison of a physical activity recall questionnaire with accelerometry in children and adolescents with obesity: a pilot study.
This study aimed to determine the validity of the Habitual Activity Estimation Scale (HAES) for assessing physical activity (PA) in children and adolescents with severe obesity. Data were obtained from participants (n = 17) in the High Impact Strategies Toward Overweight Reduction in Youth study at the Hospital for Sick Children in Toronto. Objective measurement of PA was recorded with accelerometers and interpreted using counts-per-minute (CPM) cut-points developed for children and adolescents. Self-report measurement of PA was collected using the HAES questionnaire. Pearson correlations revealed HAES significantly overestimated average daily duration of vigorous (+48 ± 64 min, p < 0.001) and moderate-light activity (+114 ± 129 min, p < 0.001) but not inactivity (+38 ± 158 min, p = 0.17). This disagreement may be explained by increased perceived exertion in obese participants when performing PA. Thus, the HAES should not be used to assess PA in obese youth. Further work to validate accelerometer CPM cut-points for obese children and adolescents calibrated to energy consumption and perceived exertion during PA in this group is warranted.


Imaging of Combat-Related Thoracic Trauma - Review of Penetrating Trauma.
Combat-related thoracic trauma is a significant contributor to morbidity and mortality of the casualties from Operation Enduring Freedom (OEF) and Operation Iraqi Freedom (OIF). Penetrating, blunt, and blast injuries were the most common mechanisms of trauma. Imaging plays a key role in the management of combat-related thoracic trauma casualties. This review discusses the imaging manifestations of thoracic injuries from penetrating trauma, emphasizing epidemiology and diagnostic clues seen during OEF and OIF. The assessment of radiologic findings in patients who suffer from combat-related thoracic trauma is the basis of this review article. The imaging modalities for this study include multi-detector computed tomography and chest radiography. High-velocity penetrating projectile injuries appear as hemorrhage and re-expansion pulmonary edema from the temporary cavity and a linear, blood-filled track from the permanent cavity. In cases where the projectile passes totally through the body, entrance wounds at the skin surface and tracks through the subcutaneous tissues may be the only indications of penetrating trauma. When assessing vascular injury, special attention should be paid to the right hilum in contrast-enhanced multi-detector computed tomography, as contrast is concentrated in the superior vena cava and superior cavoatrial junction may obscure small fragments. Additionally, CT angiography may show vessel disruption or extravasation of contrast distal to normal vessel location in addition to intraluminal filling defects and pseudo-aneurysms. Tension pneumopericardium may rarely complicate penetrating or blunt chest trauma. On imaging, distension of the pericardial sack by pneumopericardium and compression of the heart support the diagnosis of tension. On multi-detector computed tomography in the acute trauma setting, fluid in the pleural space should be considered hemothorax, particularly when Hounsfield units are above 35. Acutely, extravasated blood will have similar attenuation to the thoracic vasculature, whereas clotted blood will have higher values of 50-90 Hounsfield units. Combat-related thoracic trauma continues to be a significant contributor to the morbidity and mortality of those injured during OEF and OIF. This review of the imaging manifestations of penetrating thoracic injury during OEF and OIF focuses on key diagnostic findings for clinicians caring for combat casualties. The distinct injury pattern and atypical imaging manifestations of penetrating trauma are important to recognize early due to the acuity of this patient population and the influence of accurate diagnosis on clinical management.


Paranasal sinus radiography.
Infections of the paranasal sinuses are often seen in the Emergency Department. The use of plain film radiography is a safe and rapid way to confirm the diagnosis of such an infection. This article reviews the paranasal anatomy and appearance of non-neoplastic paranasal sinus diseases on plain films.


Literature searching for randomized controlled trials used in Cochrane reviews: rapid versus exhaustive searches.
To analyze sources searched in Cochrane reviews, to determine the proportion of trials included in reviews that are indexed in major databases, and to compare the quality of these trials with those from other sources. All new systematic reviews in the Cochrane Library, Issue1 2001, that were restricted to randomized controlled trials (RCTs) or quasi-RCTs were selected. The sources searched in the reviews were recorded, and the trials included were checked to see whether they were indexed in four major databases. Trials not indexed were checked to determine how they could be identified. The quality of trials found in major databases was compared with those found from other sources. The range in the number of databases searched per review ranged between one and twenty-seven. The proportion of the trials in the four databases were Cochrane Controlled Trials Register = 78.5%, MEDLINE = 68.8%, Embase = 65.0%, and Science/Social Sciences Citation Index = 60.7%. Searching another twenty-six databases after Cochrane Controlled Trials Register (CCTR), MEDLINE, and Embase only found 2.4% additional trials. There was no significant difference between trials found in the CCTR, MEDLINE, and Embase compared with other trials, with respect to adequate allocation concealment or sample size. There was a large variation between reviews in the exhaustiveness of the literature searches. CCTR was the single best source of RCTs. Additional database searching retrieved only a small percentage of extra trials. Contacting authors and manufacturers to find unpublished trials appeared to be a more effective method of obtaining the additional better quality trials.


Rate-determining process in MISIM photocells for optoelectronic conversion using photo-induced pure polarization current without carrier transfer across interfaces.
Recently, we proposed a [metal|insulator|semiconductor|insulator|metal] (MISIM) photocell, as a novel architecture for high-speed organic photodetectors. The electric polarization in the S layer, induced by modulated light illumination, propagates into the outside circuit as a polarization current through the I layers, without any carrier transfer across the interfaces. In the present work, we examined the MISIM photocells consisting of zinc-phthalocyanine(ZnPc)-C60 bilayers for the S layer and Parylene C for the two I layers, to understand the fundamental aspects of the MISIM photocells, such as current polarity and modulation-frequency dependence. It was found that, in such devices, the current polarity was primarily determined by the polarization in the S layer, which was induced by the donor-acceptor charge-transfer upon illumination. Furthermore, the ON and OFF current, which appeared in the periods of illumination-on and -off, respectively, exhibited significantly different dependence on the modulation frequency. This was well-explained by an imbalance between a quick polarization in the S layer during illumination and its slow relaxation in the dark.


Galectin-3's Complex Interactions in Pancreatic Ductal Adenocarcinoma: From Cellular Signaling to Therapeutic Potential.
Galectin-3 (Gal-3) plays a multifaceted role in the development, progression, and prognosis of pancreatic ductal adenocarcinoma (PDAC). This review offers a comprehensive examination of its expression in PDAC, its interaction with various immune cells, signaling pathways, effects on apoptosis, and therapeutic resistance. Additionally, the prognostic significance of serum levels of Gal-3 is discussed, providing insights into its potential utilization as a biomarker. Critical analysis is also extended to the inhibitors of Gal-3 and their potential therapeutic applications in PDAC, offering new avenues for targeted treatments. The intricate nature of Gal-3's role in PDAC reveals a complex landscape that demands a nuanced understanding for potential therapeutic interventions and monitoring.


The effect of a music programme during lunchtime on the problem behaviour of the older residents with dementia at an institution in Taiwan.
To study the effect of a music programme during lunchtime on problem behaviour among institutionalised older residents with dementia. Symptoms of dementia among older people include depression, problems with memory, insomnia and problem behaviours. Problem behaviour has been identified by families and nurses as the greatest challenge that needs to be addressed. Several studies have found that music therapy can reduce problem behaviours among dementia sufferers and, based on this finding, music has been recommended for incorporation as part of dementia management. This study used a quasi-experimental design with an eight-week time series follow-up. The intervention was background music when residents had their lunch meal. A purposive sampling technique was used. Forty-one participants were selected from an institution housing residents with dementia located in a city in Taiwan. The mean age of participants was 81.68 (SD 6.39) years old. The mean score for Mini-Mental State Examination (MMSE) was 10.66 (SD 6.85). The mean of Barthel Activity of Daily Living score was 56.83 (SD 38.12). The results showed that the music programme reduced, significantly, physical and verbal aggressive behaviour among the older residents with dementia. The study identified that there was a one-week time lag between the implementation of the music programme and a significant effect on the residents. The results from this study suggested that music is able to reduce the degree of problem behaviours among the older residents with dementia and this helps to ease work-load of nurse aides and nurses during meal times. The results may serve as a reference for the future treatment of problem behaviour among the older with dementia.


Clinical implication of tumor-associated and immunological parameters in melanoma patients treated with ipilimumab.
Ipilimumab, the first immune-checkpoint inhibitor extending overall survival (OS) in metastatic melanoma patients, has a survival benefit only in a proportion of patients and the development of reliable predictive biomarkers is still an unmet need. To meet this request, we used a multivariate statistical approach to test whether myeloid-derived suppressor cells (MDSC) or other tumor-associated and immunological parameters may serve as predictive or prognostic biomarkers in melanoma patients receiving ipilimumab. By using a standardized approach to determine the circulating levels of four MDSC subsets, we observed a significant expansion of three MDSC subsets at baseline, as compared to controls and, upon treatment, that high levels of CD14+/IL4Rα+ MDSCs were an independent prognostic factor of reduced OS. On the contrary, longer OS was associated to low levels of the proinflammatory proteins IL-6 and CRP and tumor-associated factors S100B and LDH both at baseline and after treatment. Increasing number of total T cells and especially of PD-1+/CD4+ T cells were associated with better prognosis, and upregulation of PD-1+ expression on CD4+ T cells upon treatment was associated with lower toxicity. As several parameters were associated to OS, we included these factors in a multivariate survival model, and we identified IL-6 and ECOG PS as independent biomarkers associated with improved OS, whereas high levels of LDH and CD14+/IL4Rα+ MDSCs were negative independent markers of reduced OS.


Translational coupling of nasST expression in Azotobacter vinelandii prevents overexpression of the nasT gene.
The nasST operon encodes the transcriptional regulators of assimilatory nitrate reductase operons in phylogenetically diverse bacteria. NasT is a RNA-binding antiterminator and helps RNA polymerase read through the regulatory terminator sequences upstream of the structural genes. NasS senses nitrate and nitrite and regulates the activity of NasT through stoichiometric interaction. In this study, we analyzed the nasST sequence in Azotobacter vinelandii and revealed that the nasS and nasT genes overlap by 19 nucleotides. Our genetic analyses suggested that translational initiation of NasT was coupled with NasS translation, a regulatory mechanism that prevents overproduction of NasT. The significance of tight control of nasT expression was demonstrated in a nasT-overexpression strain, where expression of the assimilatory nitrate reductase operon was deregulated.


Distinguishing the direct and indirect products of a gas-surface reaction.
It has long been postulated that gas-surface chemical reactions can occur by means of two distinct mechanisms: direct reaction on a single gas-surface encounter or reaction between two adsorbed species. It is shown here that these mechanisms have distinct dynamical signatures, as illustrated by the reaction of hydrogen with chlorine on gold(111). The direct reaction product leaves the surface with a high kinetic energy in a narrow angular distribution that displays a "memory" of the direction and energy of the incident hydrogen atom. The indirect reaction product has a near-thermal energy distribution and an angular distribution that is close to that of a cosine function.


Plasmid profile and pulsed-field gel electrophoresis analysis of Salmonella enterica isolates from humans in Turkey.
This study was conducted for typing Salmonella enterica subspecies enterica strains in Turkey using pulsed-field gel electrophoresis (PFGE) and plasmid DNA profile analysis. Fourty-two strains were isolated from clinical samples obtained from unrelated patients with acute diarrhea. The samples were collected from state hospitals and public health laboratories located at seven provinces in different regions of Turkey at different times between 2004 and 2010. The strains were determined to belong to 4 different serovars. The Salmonella enterica strains belonged to the serovars Salmonella Enteritidis (n = 23), Salmonella Infantis (n = 14), Salmonella Munchen (n = 2), and Salmonella Typhi (n = 3). Forty-two Salmonella enterica strains were typed with PFGE methods using XbaI restriction enzyme and plasmid analysis. At the end of typing, 11 different PFGE band profiles were obtained. Four different PFGE profiles (type 1, 4, 9, and 10) were found among serotype S. Enteritidis species, 3 different PFGE profiles (type 3, 5, 6) were found among S. Infantis species, 2 different PFGE profiles were found among S. Typhi species (type 2 and 11), and 2 different PFGE profiles were found among S. Munchen species (type 7, 8). The UPGMA dendrogram was built on the PFGE profiles. In this study, it was determined that 4 strains of 42 Salmonella enterica strains possess no plasmid, while the isolates have 1-3 plasmids ranging from 5.0 to 150 kb and making 12 different plasmid profiles (P1-P12). In this study, we have applied the analysis of the PFGE patterns and used bioinformatics methods to identify both inter and intra serotype relationships of 4 frequently encountered serotypes for the first time in Turkey.


Integrated photoacoustic ophthalmoscopy and spectral-domain optical coherence tomography.
Both the clinical diagnosis and fundamental investigation of major ocular diseases greatly benefit from various non-invasive ophthalmic imaging technologies. Existing retinal imaging modalities, such as fundus photography, confocal scanning laser ophthalmoscopy (cSLO), and optical coherence tomography (OCT), have significant contributions in monitoring disease onsets and progressions, and developing new therapeutic strategies. However, they predominantly rely on the back-reflected photons from the retina. As a consequence, the optical absorption properties of the retina, which are usually strongly associated with retinal pathophysiology status, are inaccessible by the traditional imaging technologies. Photoacoustic ophthalmoscopy (PAOM) is an emerging retinal imaging modality that permits the detection of the optical absorption contrasts in the eye with a high sensitivity. In PAOM nanosecond laser pulses are delivered through the pupil and scanned across the posterior eye to induce photoacoustic (PA) signals, which are detected by an unfocused ultrasonic transducer attached to the eyelid. Because of the strong optical absorption of hemoglobin and melanin, PAOM is capable of non-invasively imaging the retinal and choroidal vasculatures, and the retinal pigment epithelium (RPE) melanin at high contrasts. More importantly, based on the well-developed spectroscopic photoacoustic imaging, PAOM has the potential to map the hemoglobin oxygen saturation in retinal vessels, which can be critical in studying the physiology and pathology of several blinding diseases such as diabetic retinopathy and neovascular age-related macular degeneration. Moreover, being the only existing optical-absorption-based ophthalmic imaging modality, PAOM can be integrated with well-established clinical ophthalmic imaging techniques to achieve more comprehensive anatomic and functional evaluations of the eye based on multiple optical contrasts. In this work, we integrate PAOM and spectral-domain OCT (SD-OCT) for simultaneously in vivo retinal imaging of rat, where both optical absorption and scattering properties of the retina are revealed. The system configuration, system alignment and imaging acquisition are presented.


Two-dimensional gel analysis of complex DNA families: methodology and apparatus.
We describe a reproducible protocol for the analysis of individual members of complex mammalian gene families by gel fractionation in two dimensions within a specially designed, easily built electrophoretic apparatus. We have used this protocol to resolve the family of mouse H-2 class I genes, with approximately 30 members, as well as two different families of endogenous retroviral-like sequences, each of which has approximately 180 members dispersed throughout the genome. The results demonstrate the feasibility of using this protocol for rapid, whole genome analysis of individual animals and cell lines. Two-dimensional DNA analysis of highly repeated retroviral-like DNA families could be applied to genetic mapping and cloning experiments as well as to obtaining whole genome fingerprints in the analysis of somatic cell hybrid lines that contain a subset of chromosomes from the genome of interest.


[Lipid peroxidation and cytochrome P-450-dependent metabolism of xenobiotics in patients with coronary heart disease and multiple organ failure].
The aim of the investigation was to study oxidative stress and hepatic monooxygenase function (HMF) in coronary heart disease (CHD) patients with multiple organ dysfunction (MOD) after myocardial revascularization. Twenty-seven CHD patients with signs of MOD and 38 patients with an uncomplicated postoperative period were examined. The intensity of MOD was rated by the SOFA scale; oxidative stress was estimated from the values of malondialdehyde, conjugate trienes, ceruplasmin, and catalase, and HMF was evaluated from antipyrine pharmacokinetic data. On postoperative day 1, the study group showed significant signs of MOD, as well as activated lipid peroxidation (LPO) and a 1.5-fold reduction in HMF. The control group displayed an insignificant HMF suppression under less marked oxidative stress. On days 3-4 after surgery, the total MOD index was noticeably lowered. Both groups exhibited a high LPO rate and enhanced HMF. On days 10-12 postoperatively, the severity of MOD corresponded to the previous period. There was a decrease in LPO activity in both groups. HMF was found to substantially reduce in the study group and to be in line with the baseline values in the control one. Correlation analysis revealed direct and inverse relationships of the indices of MOD with LPO rates and HMF. Therefore, MOD in patients with CHD is attended by increased oxidative stress and leads to a more significant HMF reduction as compared with those with an uncomplicated postoperative period. At the same time, LPO activation is one of the cardinal causes of HMF suppression. Reduced HMF may enhance the sensitivity of CHD patients to drug therapy.


Comparative analysis of structural properties of the C-type-lectin-like domain (CTLD).
The superfamily of proteins containing the C-type-lectin-like domain (CTLD) is a group of abundant extracellular metazoan proteins characterized by evolutionary flexibility and functional versatility. Several CTLDs are also found in parasitic prokaryotes and viruses. The 37 distinct currently available CTLD structures demonstrate significant structural conservation despite low or undetectable sequence similarity. Our aim in this study was to perform an extensive comparative analysis of all available CTLD structures to establish the most conserved structural features of the fold, and to test and extend the early analysis of Drickamer. By implication, these features should be those critical for maintenance of integrity of the fold. By analyzing CTLD structures superimposed by several methods, we have established groups of conserved structural positions involved in fold maintenance but not in ligand binding; these are consistent with the fold's known functional flexibility. In addition to the well-recognized disulfide bridges, groups of conserved residues are involved in hydrophobic interactions stabilizing the core of the fold and the long loop region, and in an alpha2-beta1-beta5 polar interaction. Evaluation of the conclusions of the structure comparison study compared with alignments of all available human, mouse and Caenorhabditis elegans CTLD sequences showed that conservation patterns are preserved throughout the whole CTLD sequence space. Our observations provide an improved understanding of CTLD structure, and will help in identification of new CTLDs and the mechanisms that drive and constrain the coevolution of the structure and function of the fold.


Rabies epidemiology and control in India: a review.
Rabies, though a disease of low public health priority, still continues to be a major public health problem in India. In humans, rabies is almost invariably fatal once clinical symptoms have developed. WHO reports around 50 000 rabies deaths every year, out of which 20 000 are estimated to occur in India alone. There is often gross under-reporting of human rabies deaths in India. Despite potent anti-rabies vaccines and immunoglobulins available, rabies is far from control and elimination. An effective strategy for control of rabies takes into account the epidemiology of animal bites, rabies and factors influencing post exposure treatment. Hence it becomes pertinent to review the current status of rabies and strategies for its control in the country. In this article, an attempt has been made to discuss the epidemiology of Rabies, pathogenesis, diagnosis and its prevention and control including the various regimens of anti-rabies vaccines and immunoglobulins available for post-exposure prophylaxis. The importance of primary preventive measures like Animal Birth Control (ABC) and vaccination of dogs has also been highlighted. It is emphasized that rabies should be recognized as priority public health problem and cell culture vaccines should be made available free of cost at all government health facilities. Other important measures include generation of awareness about rabies and first aid of animal bites.


Self-injury and harm minimisation on acute wards.
Practitioners' attitudes to self-injury vary widely. While some healthcare professionals are comfortable providing advice about safe self-injury in the inpatient setting, others believe they have a duty of care to protect patients from harming themselves, including removing all potentially sharp implements and increasing observation levels. This article describes work undertaken at South Staffordshire and Shropshire Healthcare NHS Foundation Trust to explore self-injurious behaviour in inpatient settings, including staff knowledge and perceptions and service users' experiences. Development of clinical guidelines for safe self-injury is also discussed.


The human brain distinguishes between single odorants and binary mixtures.
Single odors are processed differently from odor mixtures in the cortex of rodents. We investigated whether single and binary odor mixtures activate different regions also in the human brain. We analyzed data from positron emission tomography scans using pyridine, citral, and 5 mixtures of pyridine and citral in proportions varying from 10/90 to 90/10, with 50/50 being the most impure. Comparing mixtures with single odorants gave activation in the left cingulate and right parietal and superior frontal cortices and bilateral activation in the anterior and lateral orbitofrontal cortices. We also found that brain activity in the lateral orbitofrontal cortex (OFC) increased with odorant impurity, whereas the anterior OFC was activated for binary odor mixtures and deactivated for single components. We conclude that binary odor mixtures and their individual components are processed differently by the human brain. The lateral portion of the OFC responds to mixture impurity in a graded fashion, whereas the anterior portion acts like an on-off detector of odor mixtures.


Prognostic significance of platelet function in the early phase of ST-elevation myocardial infarction treated with primary angioplasty.
There are limited data concerning global platelet function response to antiplatelet therapy in ST-segment elevation myocardial infarction (STEMI). The aim was to determine the frequency and clinical significance of inadequate inhibition of two major platelet activation pathways: the thromboxane A2 (TXA2)- and ADP-dependent, in the early phase of STEMI. Platelet function was measured with a Platelet Function Analyzer-100 in 125 consecutive survivors of STEMI on days 3 (48+/-2 h) and 30 after stenting. Inadequate inhibition of the TXA2-dependent activation pathway was defined as a collagen-epinephrine closure time <193 and of the ADP-dependent as a collagen-adenosine closure time <130 seconds. The study population was divided into groups I (n=67/53%; both pathways inhibited, complete inhibition), II (n=21/17%; one pathway inhibited, partial inhibition), and III (n=37/30%; neither pathway inhibited, no inhibition). LV remodeling occurred more frequently in groups II and III than in group I (40% and 62% vs. 14%, P=0.038 and <0.0001, respectively). At six months the combined rate of death, nonfatal reinfarction, stroke, and rehospitalization for heart failure was 3% in group I, 23.8% in II, and 54.1% in III (log rank=39.2, P for trend <0.0001). By multivariate regression analysis, no or partial inhibition were independent predictors of LV remodeling and combined clinical outcome. Inadequate platelet function inhibition in acute phase STEMI despite standard antiplatelet therapy is associated with increased risk of poor LV performance and combined clinical events. This may suggest the need for intensified antiplatelet therapy in the early phase of STEMI.


Microbial Metabolism Modulates Antibiotic Susceptibility within the Murine Gut Microbiome.
Although antibiotics disturb the structure of the gut microbiota, factors that modulate these perturbations are poorly understood. Bacterial metabolism is an important regulator of susceptibility in vitro and likely plays a large role within the host. We applied a metagenomic and metatranscriptomic approach to link antibiotic-induced taxonomic and transcriptional responses within the murine microbiome. We found that antibiotics significantly alter the expression of key metabolic pathways at the whole-community and single-species levels. Notably, Bacteroides thetaiotaomicron, which blooms in response to amoxicillin, upregulated polysaccharide utilization. In vitro, we found that the sensitivity of this bacterium to amoxicillin was elevated by glucose and reduced by polysaccharides. Accordingly, we observed that dietary composition affected the abundance and expansion of B. thetaiotaomicron, as well as the extent of microbiome disruption with amoxicillin. Our work indicates that the metabolic environment of the microbiome plays a role in the response of this community to antibiotics.


Mesh fixation with a barbed anchor suture results in significantly less strangulation of the abdominal wall.
Laparoscopic ventral hernia repair using an underlay mesh frequently requires suture fixation across the abdominal wall, which results in significant postoperative pain. This study investigates the utility of a novel mesh fixation technique to reduce the strangulation force on the abdominal wall. Multiple 2-cm(2) pieces of polyester mesh (Parietex Composite, Covidien) were placed as an underlay against a porcine abdominal wall. Fixation was accomplished using either the standard 0-polyglyconate or the 0-polyglyconate barbed anchor suture designed to hold in tissue without the need to tie a knot (V-Loc 180; Covidien). Suture fixation began with a stab wound incision in the skin. A suture-passing device then was used to pass the suture across the abdominal wall and through the mesh. The suture passer was removed and reintroduced through the same stab wound incision but at a different fascial entry point 1.5 cm away. The tail of the suture was grasped and pulled up through both the mesh and the abdominal wall, creating a full-thickness U-stitch. One tail of the suture was attached to a tensiometer, and the strangulation force on the abdominal wall was measured while the suture was tied (standard) or looped (barbed). To compare pullout force, the tensiometer was attached to either the mesh or the suture, and traction was applied until material failure or suture pull through. Results are expressed as mean ± standard deviation. Comparisons were performed using Student's t-test. Eight pieces of mesh were placed for each suture. The average force required to secure the barbed suture (0.59 ± 0.08 kg) was significantly less than the force needed to secure the standard suture (2.17 ± 0.58 kg) (P < 0.0001). Table 1 compares the suture pullout forces with the mesh failure forces. Although the pullout force for the standard suture is significantly greater than for the barbed suture, both sutures have a pullout strength significantly greater than the mesh failure force. Table 1 Suture fixation forces for standard and barbed sutures Suture fixation force (kg) Standard suture 2.17 ± 0.58 Barbed suture 0.59 ± 0.08 P < 0.0001 A barbed anchor suture used to secure mesh to the abdominal wall requires nearly 75% less strangulation force than a standard monofilament suture while still providing significantly greater pullout force than that required for the mesh to tear and fail. This method of mesh fixation should result in less postoperative pain and warrants a clinical trial.


The BREV neuropsychological test: Part I. Results from 500 normally developing children.
The Battery for Rapid Evaluation of Cognitive Functions (Batterie Rapide d'Evaluation des Fonctions Cognitives: BREV) was designed to provide health professionals with a quick clinical tool for screening acquired and developmental cognitive deficits in children aged 4 to 8 years. The BREV explores oral language in both its expressive and receptive forms, non-verbal functions, attention, verbal and visuo-spatial memory, and main learning acquisition. Results of the first phase of validation are presented in this report consisting of internal validity measurements gained by testing 500 normally developing school children (257 females, 243 males; mean age 6 years 7 months, SD 1 year 6 months. The validation provides appropriate values for each of the 17 subtests assessing cognitive functions (oral language, non-verbal abilities, attention and memory, educational achievement) in 10 age groups, from 4 to 8 years of age. All subtests with the same content for any age revealed values which increased significantly with age. Interreliability was tested in a retest for 70 children and scores obtained on retesting correlated significantly with initial values. The BREV is a reliable test with carefully established normative values, appropriate for preschool and school-age children.


Accelerating spiral deblurring with square kernels and low-pass preconditioning.
Robust implementation of spiral imaging requires efficient deblurring. A deblurring method was previously proposed to separate and deblur water and fat simultaneously, based on image-space kernel operations. The goal of this work is to improve the performance of the previous deblurring method using kernels with better properties. Four types of kernels were formed using different models for the region outside the collected k-space as well as low-pass preconditioning (LP). The performances of the kernels were tested and compared with both phantom and volunteer data. Data were also synthesized to evaluate the SNR. The proposed "square" kernels are much more compact than the previously used circular kernels. Square kernels have better properties in terms of normalized RMS error, structural similarity index measure, and SNR. The square kernels created by LP demonstrated the best performance of artifact mitigation on phantom data. The sizes of the blurring kernels and thus the computational cost can be reduced by the proposed square kernels instead of the previous circular ones. Using LP may further enhance the performance.


GnRH II as a possible cytostatic regulator in the development of endometriosis.
GnRH II is the second form of GnRH and is widely distributed in peripheral tissues of the female reproductive tract as well as in the central nervous system. In the present study, we studied the possible implication of GnRH II in endometriosis. Effects of GnRH II on 5-bromo-2'-deoxyuridine (BrdU) uptake by cultured endometriotic stromal cells were examined. Effects of GnRH II on interleukin (IL)-1beta-induced expression of cyclooxygenase (COX)-2 and IL-8 were also studied. mRNA levels of GnRH I, GnRH II, type I GnRH receptor and type II GnRH receptor were determined by real-time quantitative RT-PCR in endometrial tissues of women with or without endometriosis and in endometriotic tissues. GnRH II dose-dependently suppressed BrdU uptake by endometrial stromal cells. Treatment with IL-1beta markedly increased mRNA levels of COX-2 and IL-8 in endometrial stromal cells and IL-8 protein secretion by these cells, while these increments were significantly suppressed by supplementation with GnRH II. The mRNA levels of GnRH II were lower in endometrial and endometriotic tissues of women with endometriosis than in endometrial tissues of women without endometriosis, both in the proliferative phase and the secretory phase. In addition, as for GnRH I, type I GnRH receptor and type II GnRH receptor, the mRNA levels were lower in endometrial tissues of women with endometriosis than in those without endometriosis in the secretory phase. In the light of the demonstrated antiproliferative and anti-inflammatory effects of GnRH II on endometrial stromal cells, the lower expression of GnRH II in eutopic and ectopic endometrium of women with endometriosis suggests that endogenous GnRH II-mediated cytostatic regulation may be impaired in the development of endometriosis.


Lymphangioleiomyomatosis (LAM): a review of clinical and morphological features.
A review is presented of the clinical and morphological manifestations of lymphangioleiomyomatosis (LAM), a systemic disorder of unknown etiology that affects women. The clinical features include dyspnea, hemoptysis, recurrent pneumothorax, chylothorax, and chylous ascites. It is characterized by: 1) proliferation of abnormal smooth muscle cells (LAM cells) in pulmonary interstitium and along the axial lymphatics of the thorax and abdomen; 2) thin-walled pulmonary cysts, and 3) a high incidence of angiomyolipomas. The pulmonary cystic lesions have a characteristic appearance on high resolution computed tomography. The most specific method for diagnosing LAM is lung biopsy to demonstrate the presence of LAM cells, either by their characteristic histological appearance or by specific immunostaining with HMB-45 antibody. LAM cells differ in several important respects from the types of smooth muscle cells normally present in lung. Their reactivity with HMB-45 antibody is localized in stage I and stage II melanosomes. LAM cells show additional evidence of incomplete melanogenesis, and the significance of these observations remains to be determined. Two types of LAM cells are recognized: 1) small, spindle-shaped cells that are centrally located in the LAM nodules and are highly immunoreactive for matrix metalloproteinase-2 (MMP-2), its activating enzyme (MT-1-MMP), and proliferating cell nuclear antigen (PCNA), and 2) large, epithelioid cells that are distributed along the periphery of the nodules and show a high degree of immunoreactivity with HMB-45 antibody and with antibodies against estrogen and progesterone receptors. Types of treatment used for LAM include oophorectomy, administration of Lupron or progesterone and in very severe cases, pulmonary transplantation (following the onset of respiratory insufficiency, not relieved by O(2)).


Reliability and Clinical Usefulness of Current Classifications in Traumatic Thoracolumbar Fractures: A Systematic Review of the Literature.
A validated classification remains the key to an appropriate treatment algorithm of traumatic thoracolumbar fractures. Considering the development of many classifications, it is remarkable that consensus about treatment is still lacking. We conducted a systematic review to investigate which classification can be used best for treatment decision making in thoracolumbar fractures. A comprehensive search was conducted using PubMed, Embase, CINAHL, and Cochrane using the following search terms: classification (mesh), spinal fractures (mesh), and corresponding synonyms. All hits were viewed by 2 independent researchers. Papers were included if analyzing the reliability (kappa values) and clinical usefulness (specificity or sensitivity of an algorithm) of currently most used classifications (Magerl/AO, thoracolumbar injury classification and severity score [TLICS] or thoracolumbar injury severity score, and the new AO spine). Twenty articles are included. The presented kappa values indicate moderate to substantial agreement for all 3 classifications. Regarding the clinical usefulness, > 90% agreement between actual treatment and classification recommendation is reported for most fractures. However, it appears that over 50% of the patients with a stable burst fracture (TLICS 2, AO-A3/A4) in daily practice are operated, so in these cases treatment decision is not primarily based on classification. AO, TLICS, and new AO spine classifications have acceptable accuracy (kappa > 0.4), but are limited in clinical usefulness since the treatment recommendation is not always implemented in clinical practice. Differences in treatment decision making arise from several causes, such as surgeon and patient preferences and prognostic factors that are not included in classifications yet. The recently validated thoracolumbar AO spine injury score seems promising for use in clinical practice, because of inclusion of patient-specific modifiers. Future research should prove its definite value in treatment decision making. 2. Without the appropriate treatment, the impact of traumatic thoracolumbar fractures can be devastating. Therefore it is important to achieve consensus in the treatment of thoracolumbar fractures.


The role of automobiles for the future of aluminum recycling.
To reach required product qualities with lowest costs, aluminum postconsumer scrap is currently recycled using strategies of downgrading and dilution, due to difficulties in refining. These strategies depend on a continuous and fast growth of the bottom reservoir of the aluminum downgrading cascade, which is formed by secondary castings, mainly used in automotive applications. A dynamic material flow model for the global vehicle system was developed to assess the likelihood, timing, and extent of a potential scrap surplus. The results demonstrate that a continuation of the above-mentioned strategies will lead to a nonrecyclable scrap surplus by around 2018 ± 5 if no additional measures are taken. The surplus could grow to reach a level of 0.4-2 kg/cap/yr in 2050, corresponding to a loss of energy saving potential of 43-240 TWh/yr electricity. Various intervention options for avoiding scrap surplus are discussed. Effective strategies need to include an immediate and rapid penetration of dramatically improved scrap sorting technologies for end-of-life vehicles and other aluminum applications.


Clicked tacrine conjugates as acetylcholinesterase and β-amyloid directed compounds.
The multifaceted nature of Alzheimer's disease (AD) has led to the development of multi-targeted compounds based on the classical AD drug, tacrine, first known to inhibit the acetylcholine-degrading enzyme acetylcholinesterase (AChE). In the present work, we explore the potentiality of multimers of tacrine in this field. The synthesis using the so-called "click chemistry" and the in vitro study of the conjugates are described. Two or four copies of the tacrine molecule are "clicked" on a constrained cyclopeptide template proven to be a convenient tool for multimeric presentation. The multimers significantly inhibit self-induced amyloid fibril formation from Aβ(40) at low inhibitor to Aβ molar ratios at which the tacrine monomer is fully inactive (Thioflavin T assays and AFM observation). Moreover, they have the capacity to bind to Aβ(40) fibrils (SPR assays) while retaining the AChE inhibitory activity of the parent tacrine.


Lateral flow device for water fecal pollution assessment: from troubleshooting of its microfluidics using bioluminescence to colorimetric monitoring of generic Escherichia coli.
Water is the most important ingredient of life. Water fecal pollution threatens water quality worldwide and has direct detrimental effects on human health and the global economy. Nowadays, assessment of water fecal pollution relies on time-consuming techniques that often require well-trained personnel and highly-equipped laboratories. Therefore, faster, cheaper, and easily-used systems are needed to in situ monitor water fecal pollution. Herein, we have developed colorimetric lateral flow strips (LFS) able to detect and quantify Escherichia coli species in tap, river, and sewage water samples as an indicator of fecal pollution. The combination of LFS with a simple water filtration unit and a commercially available colorimetric reader enhanced the assay sensitivity and enabled more accurate quantification of bacteria concentration down to 104 CFU mL-1 in 10 minutes, yielding recovery percentages between 80% and 90% for all water samples analyzed. Overall, this system allows for monitoring and assessing water quality based on E. coli species as a standard microbiological indicator of fecal pollution. Furthermore, we have developed a novel bioluminescent, bacteria-based method to quickly characterize the performance of a great variety of LFS materials. This new method allows evaluating the flow rate of big analytes such as bacteria through the LFS materials, as a suggestive means for selecting the appropriate materials for fabricating LFS targeting big analytes (≈2 μm). As a whole, the proposed approach can accelerate and reduce the costs of water quality monitoring and pave the way for further improvement of fecal pollution detection systems.


Preferential coupling of an incident wave to reflection eigenchannels of disordered media.
Light waves incident to a highly scattering medium are incapable of penetrating deep into the medium due to the multiple scattering process. This poses a fundamental limitation to optically imaging, sensing, and manipulating targets embedded in opaque scattering layers such as biological tissues. One strategy for mitigating the shallow wave penetration is to exploit eigenchannels with anomalously high transmittance existing in any scattering medium. However, finding such eigenchannels has been a challenging task due to the complexity of disordered media. Moreover, it is even more difficult to identify those eigenchannels from the practically relevant reflection geometry of measurements. In this Letter, we present an iterative wavefront control method that either minimizes or maximizes the total intensity of the reflected waves. We proved that this process led to the preferential coupling of incident wave to either low or high-reflection eigenchannels, and observed either enhanced or reduced wave transmission as a consequence. Since our approach is free from prior characterization measurements such as the recording of transmission matrix, and also able to keep up with sample perturbation, it is readily applicable to in vivo applications. Enhancing light penetration will help improving the working depth of optical sensing and treatment techniques.


Comparison of costs of home and facility-based basic obstetric care in rural Bangladesh.
This study compared the costs of providing antenatal, delivery and postnatal care in the home and in a basic obstetric facility in rural Bangladesh. The average costs were estimated by interviewing midwives and from institutional records. The main determinants of cost in each setting were also assessed. The cost of basic obstetric care in the home and in a facility was very similar, although care in the home was cheaper. Deliveries in the home took more time but this was offset by the capital costs associated with facility-based care. As use-rates increase, deliveries in a facility will become cheaper. Antenatal and postnatal care was much cheaper to provide in the facility than in the home. Facility-based delivery care is likely to be a cheaper and more feasible method for the care provider as demand rises. In settings where skilled attendance rates are very low, home-based care will be cheaper.


Genetic inactivation of the vesicular glutamate transporter 2 (VGLUT2) in the mouse: what have we learnt about functional glutamatergic neurotransmission?
During the past decade, three proteins that possess the capability of packaging glutamate into presynaptic vesicles have been identified and characterized. These three vesicular glutamate transporters, VGLUT1-3, are encoded by solute carrier genes Slc17a6-8. VGLUT1 (Slc17a7) and VGLUT2 (Slc17a6) are expressed in glutamatergic neurons, while VGLUT3 (Slc17a8) is expressed in neurons classically defined by their use of another transmitter, such as acetylcholine and serotonin. As glutamate is both a ubiquitous amino acid and the most abundant neurotransmitter in the adult central nervous system, the discovery of the VGLUTs made it possible for the first time to identify and specifically target glutamatergic neurons. By molecular cloning techniques, different VGLUT isoforms have been genetically targeted in mice, creating models with alterations in their glutamatergic signalling. Glutamate signalling is essential for life, and its excitatory function is involved in almost every neuronal circuit. The importance of glutamatergic signalling was very obvious when studying full knockout models of both VGLUT1 and VGLUT2, none of which were compatible with normal life. While VGLUT1 full knockout mice die after weaning, VGLUT2 full knockout mice die immediately after birth. Many neurological diseases have been associated with altered glutamatergic signalling in different brain regions, which is why conditional knockout mice with abolished VGLUT-mediated signalling only in specific circuits may prove helpful in understanding molecular mechanisms behind such pathologies. We review the recent studies in which mouse genetics have been used to characterize the functional role of VGLUT2 in the central nervous system.


Immune cell profiles associated with measured exposure to phthalates in the Norwegian EuroMix biomonitoring study - A mass cytometry approach in toxicology.
Phthalate exposure has been associated with immune-related diseases such as asthma and allergies, but there is limited knowledge on mechanisms, effect biomarkers and thus biological support of causality. To investigate associations between exposure to the phthalates DEHP (di(2-ethylhexyl) phthalate) and DiNP (diisononyl phthalate) and functional immune cell profiles. Peripheral blood mononuclear cells (PBMCs) from 32 healthy adult Norwegian participants in the EuroMix biomonitoring study were selected based on high or low (n = 16) levels of urine metabolites of DEHP and DiNP. High-dimensional immune cell profiling including phenotyping and functional markers was performed by mass cytometry (CyTOF) using two broad antibody panels after PMA/ionomycin-stimulation. The CITRUS algorithm with unsupervised clustering was used to identify group differences in cell subsets and expression of functional markers, verified by manual gating. The group of participants with high phthalate exposure had a higher proportion of some particular innate immune cells, including CD11c positive NK-cell and intermediate monocyte subpopulations. The percentage of IFNγ TNFα double positive NK cells and CD11b expression in other NK cell subsets were higher in the high exposure group. Among adaptive immune cells, however, the percentage of IL-6 and TNFα expressing naïve B cell subpopulations and the percentage of particular naïve cytotoxic T cell populations were lower in the high exposure group. Cell subset percentages and expression of functional markers suggest that DEHP and DiNP phthalate exposure may stimulate subsets of innate immune cells and suppress adaptive immune cell subsets. By revealing significant immunological differences even in small groups, this study illustrates the promise of the broad and deep information obtained by high-dimensional single cell analyses of human samples to answer toxicological questions regarding health effects of environmental exposures.


Metformin accelerates wound healing in type 2 diabetic db/db mice.
Wound healing impairment is increasingly recognized to be a consequence of hyperglycemia‑induced dysfunction of endothelial precursor cells (EPCs) in type 2 diabetes mellitus (T2DM). Metformin exhibits potential for the improvement of endothelial function and the wound healing process. However, the underlying mechanisms for the observed beneficial effects of metformin application remain to be completely understood. The present study assessed whether metformin, a widely used therapeutic drug for T2DM, may accelerate wound closure in T2DM db/db mice. Genetically hyperglycemic db/db mice were used as the T2DM model. Metformin (250 mg/kg/day; intragastric) was administered for two weeks prior to EPC collection and wound model creation in db/db mice. Wound healing was evaluated by alterations in the wound area and the number of platelet endothelial cell adhesion molecule‑positive cells. The function of the isolated bone marrow‑derived EPCs (BM‑EPCs) was assessed by a tube formation assay. The number of circulating EPCs, and the levels of intracellular nitric oxide (NO) and superoxide (O2‑) were detected by flow cytometry. Thrombospondin‑1 (TSP‑1) expression was determined by western blot analysis. It was observed that treatment with metformin accelerated wound healing, improved angiogenesis and increased the circulating EPC number in db/db mice. In vitro, treatment with metformin reversed the impaired BM‑EPC function reflected by tube formation, and significantly increased NO production while decreasing O2‑ levels in BM‑EPCs from db/db mice. In addition, TSP‑1 expression was markedly attenuated by treatment with metformin in cultured BM‑EPCs. Metformin contributed to wound healing and improved angiogenesis in T2DM mice, which was, in part, associated with stimulation of NO, and inhibition of O2‑ and TSP‑1 in EPCs from db/db mice.


Coverage and quality of DNA barcode references for Central and Northern European Odonata.
Dragonflies and damselflies (Odonata) are important components in biomonitoring due to their amphibiotic lifecycle and specific habitat requirements. They are charismatic and popular insects, but can be challenging to identify despite large size and often distinct coloration, especially the immature stages. DNA-based assessment tools rely on validated DNA barcode reference libraries evaluated in a supraregional context to minimize taxonomic incongruence and identification mismatches. This study reports on findings from the analysis of the most comprehensive DNA barcode dataset for Central European Odonata to date, with 103 out of 145 recorded European species included and publicly deposited in the Barcode of Life Data System (BOLD). The complete dataset includes 697 specimens (548 adults, 108 larvae) from 274 localities in 16 countries with a geographic emphasis on Central Europe. We used BOLD to generate sequence divergence metrics and to examine the taxonomic composition of the DNA barcode clusters within the dataset and in comparison with all data on BOLD. Over 88% of the species included can be readily identified using their DNA barcodes and the reference dataset provided. Considering the complete European dataset, unambiguous identification is hampered in 12 species due to weak mitochondrial differentiation and partial haplotype sharing. However, considering the known species distributions only two groups of five species possibly co-occur, leading to an unambiguous identification of more than 95% of the analysed Odonata via DNA barcoding in real applications. The cases of small interspecific genetic distances and the observed deep intraspecific variation in Cordulia aenea (Linnaeus, 1758) are discussed in detail and the corresponding taxa in the public reference database are highlighted. They should be considered in future applications of DNA barcoding and metabarcoding and represent interesting evolutionary biological questions, which call for in depth analyses of the involved taxa throughout their distribution ranges.


[Effect of antipsychotic amisulpride on immune reactivity].
The effect of atypical antipsychotic solian (amisulpride), binding predominantly to dopamine D2/D3-receptors, on the immune reactivity has been studied in mice of the CBA strain with different psychoemotional states (aggressive and submissive behavior). In addition, the effect of solian on the expression of various CD-markers of lymphocytes in has been analyzed in vitro for patients with schizophrenia diagnosis. Chronic (10 days) administration of solian in mice at a dose of 5.0 mg/kg resulted in a significant suppression of the immune response to T-dependent antigen (sheep red blood cells). This effect was manifested in animals with both psychoemotional states, but was more expressed in aggressive animals. In the in vitro system, solian produced opposite effects on the expression of surface CD receptors in lymphocytes of patients with schizophrenia. It is suggested that solian does not only affects immune function through D2 receptors of the brain, but also directly influences immunocompetent cells.


Reflections on Ethics and Humanity in Pediatric Neurology: the Value of Recognizing Ethical Issues in Common Clinical Practice.
Our goals in this reflection are to (i) identify the ethical dimensions inherent in any clinical encounter and (ii) bring to the forefront of our pediatric neurology practice the myriad of opportunities to explore and learn from these ethical questions. We highlight specifically Beauchamp and Childress's principles of biomedical ethics. We use the terms ethics in common clinical practice and an ethical lens to remind people of the ubiquity of ethical situations and the usefulness of using existing ethical principles to analyze and resolve difficult situations in clinical practice. We start with a few common situations with which many of us tend to struggle. We describe what we understand as ethics and how and why developments in technology, novel potential interventions, policies, and societal perspectives challenge us to think about and debate ethical issues. Individual patients are not a singular population; each patient has their own unique life situations, culture, goals, and expectations that need to be considered with a good dose of humanity and humility. We believe that using an ethical lens-by which we mean making an explicit effort to identify and consider these issues openly-will help us to achieve this goal in practice, education, and research.


Long non‑coding RNA NEAT1 regulates glioma cell proliferation and apoptosis by competitively binding to microRNA‑324‑5p and upregulating KCTD20 expression.
Previous studies have demonstrated that long non‑coding RNAs (lncRNAs) serve a key role in the development and progression of several types of cancer, including glioma. The lncRNA nuclear paraspeckle assembly transcript 1 (NEAT1) contributes to cancer growth through its effects on cell proliferation, migration, invasion and drug resistance. However, the exact regulatory mechanisms via which NEAT1 acts in glioma are unclear. In the present study, the expression levels and function of NEAT1 in glioma tissues and cell lines were examined in vitro and in vivo. By reverse transcription‑quantitative PCR and fluorescence in situ hybridization analysis, NEAT1 expression was upregulated in glioma tissues compared with in adjacent normal brain tissues, and elevated NEAT1 levels were associated with poor prognosis. Cell Counting Kit‑8, colony formation, ethynyldeoxyuridine, flow cytometry and western blotting assays were performed to detect the effects of NEAT1 on cell biological behavior. Knockdown of NEAT1 in glioma cell lines was associated with cell cycle arrest at the G0/G1 phase, decreased proliferation and elevated apoptosis in vitro, and resulted in reduced tumor growth and increased survival in a mouse xenograft model of glioma. Using bioinformatics analysis, RNA immunoprecipitation experiments and luciferase reporter assays, it was demonstrated that NEAT1 may competitively bind to microRNA (miR)‑324‑5p, thus blocking its interaction with target mRNAs. Potassium channel tetramerization protein domain containing 20 (KCTD20) was identified as a specific miR‑324‑5p target. Accordingly, the inhibition of NEAT1 resulted in the downregulation of KCTD20 through competitive binding with miR‑324‑5p, decreased cell proliferation and increased apoptosis. Concomitant NEAT1 knockdown and inhibition of miR‑324‑5p partially reversed the effects of NEAT1 knockdown on cell proliferation and apoptosis, and further regulated KCTD20 expression. Collectively, the present findings demonstrated that NEAT1 acted as a competing endogenous RNA for miR‑324‑5p, and identified the NEAT1/miR‑324‑5p/KCTD20 axis as a novel regulatory axis and a potential therapeutic target for human glioma.


EURRECA/WHO workshop report: 'Deriving Micronutrient Recommendations: Updating Best Practices'.
This paper describes the outcome of the workshop 'Deriving Micronutrient Recommendations: Updating Best Practices' which took place in Brussels in April 2012. The workshop was organised jointly by the European Micronutrient Recommendations Aligned (EURRECA) Network of Excellence and the World Health Organization (WHO) Regional Office for Europe. The delegates included, among others, representatives from nutrient recommendation setting bodies (NRSBs) across Europe. The current paper focuses on the gaps and needs of NRSBs as identified by the workshop participants: (i) practical tools and best practices to adapt dietary reference values, (ii) comparable nationally representative food consumption data (including updated and complete food composition databases), (iii) adequate financial resources and technical capacity, (iv) independence and transparency in expert selection, research conduct and communication of research results and (v) clear correspondence of terminology used at national levels.


Comparative proteomic analysis provides insight into the key proteins as potential targets underlying the effect of malachite green against Ichthyophthirius multifiliis.
Target identification is important for drug discovery. Unfortunately, no drug targets have been found in Ichthyophthirius multifiliis until now and further limited development of the novel drug for Ichthyophthiriasis. In this study, an iTRAQ-based quantitative proteomic analysis was used to find the target of malachite green (MG), exhibiting greater efficacy than the existing drugs, against I. multifiliis trophonts in situ. We also verified the proteomic results by RT-qPCR, TEM and cell apoptosis assay. Our results showed that major variations in protein abundance were found among many of the ribosome proteins, indicating ribosome might be a candidate target. Furthermore, GO and KEGG pathway analyses of differentially expressed proteins (DEPs) revealed that ribosome and PI3K-Akt signalling pathway were remarkably enriched. Taken together, the above DEPs were also verified by RT-qPCR and morphological observations. This study provides insights into the key proteins enriched in PI3K-Akt signal pathway and ribosome pathway as potential targets of MG killing I. multifiliis, which could be served as targets for other less toxic drugs and be tested as potential treatments for I. multifiliis.


Treatment of Bifurcation Lesions by Bail-Out TAP or Culotte: Lost in Translation?
Coronary bifurcated lesions (CBL) represent a hot topic of interventional cardiology. Provisional stenting, i.e. implantation of a drug-eluting (DES) in the main branch followed by side-branch (SB) intervention in case of suboptimal SB result, represents the gold standard to treat the vast majority of CBL undergoing percutaneous coronary interventions (PCI). The best technique for bail-out SB stenting has not been established. Prospective randomized trials comparing different stenting techniques may help provide important insights regarding the best way to conduct PCI in patients with CBL. The recently published Bifurcations Bad Krozingen (BBK) II trial is the last important randomized study in the field of bifurcation PCI and is focused on the search for the best management of those patients with suboptimal SB result during provisional stenting. Two different SB implantation strategies after provisional stenting have been compared. In the present manuscript, we employed BBK II results in the context of available literature highlighting important specific features of the study with main emphasis on patient selection process and techniques applied.


Oxidative damage and mutagenesis in Saccharomyces cerevisiae: genetic studies of pathways affecting replication fidelity of 8-oxoguanine.
Oxidative damage to DNA constitutes a major threat to the faithful replication of DNA in all organisms and it is therefore important to understand the various mechanisms that are responsible for repair of such damage and the consequences of unrepaired damage. In these experiments, we make use of a reporter system in Saccharomyces cerevisiae that can measure the specific increase of each type of base pair mutation by measuring reversion to a Trp+ phenotype. We demonstrate that increased oxidative damage due to the absence of the superoxide dismutase gene, SOD1, increases all types of base pair mutations and that mismatch repair (MMR) reduces some, but not all, types of mutations. By analyzing various strains that can revert only via a specific CG→AT transversion in backgrounds deficient in Ogg1 (encoding an 8-oxoG glycosylase), we can study mutagenesis due to a known 8-oxoG base. We show as expected that MMR helps prevent mutagenesis due to this damaged base and that Pol η is important for its accurate replication. In addition we find that its accurate replication is facilitated by template switching, as loss of either RAD5 or MMS2 leads to a significant decrease in accurate replication. We observe that these ogg1 strains accumulate revertants during prolonged incubation on plates, in a process most likely due to retromutagenesis.


Neural network recognition and classification of aerosol particle distributions measured with a two-spot laser velocimeter.
This paper describes the use of a neural computational network model for pattern recognition and classification of aerodynamic particle size distributions associated with a number of environmental, bacterial, and artificial aerosols. The aerodynamic particle size distributions are measured in real time with high resolution using a two-spot He-Ne laser velocimeter. The technique employed here for the recognition and classification of aerosols of unknown origin is based on a three-layered neural network that has been trained on a training set consisting of 75 particle size distributions obtained from three distinct types of aerosols. The training of the neural network was accomplished with the back-propagation learning algorithm. The effects of the number of processing units in the hidden layer and the level of noise corrupting the training set, the test set, and the connection weights on the learning rate and classification efficiency of the neural network are studied. The ability of the trained network to generalize from the finite number of size distributions in the training set to unknown size distributions obtained from uncertain and unfamiliar environments is investigated. The approach offers the opportunity of recognizing, classifying, and characterizing aerosol particles in real time according to their aerodynamic particle size spectrum and its high recognition accuracy shows considerable promise for applications to rapid real-time air monitoring in the areas of occupational health and air pollution standards.


Clinico-epidemiological study of tinea incognito with microbiological correlation.
Tinea incognito is a dermatophytic infection with a clinical presentation that is modified due to previous treatment with topical or systemic steroids, as well as topical immunomodulators. It tends to mimic other dermatological conditions. To evaluate the various clinical manifestations, sites, predisposing factors and causative agents of tinea incognito. A prospective observational study was done on one hundred clinically suspected cases of tinea incognito, with a history of topical or systemic steroid use for a period of at least six weeks. They were subject to direct microscopy and fungal culture, and re-evaluated at the end of the third and sixth week. Eczema-like conditions were the most common clinical manifestation, followed by inflammatory, autoimmune and infective conditions. The face was the most commonly affected site. Direct microscopy was positive in 85% of cases, and fungal culture was positive in 63% of cases. Trichophyton rubrum was the most common species isolated. Pharmacists were responsible for 78% of tinea incognito cases, and betamethasone dipropionate was the most common drug used. As this was a hospital outpatient-based study, cases with severe systemic problems could have attended other departments. Cases involving the hair and nails were negligible. Tinea incognito is a commonly encountered, yet poorly reported entity in the study population. An increased level of awareness and vigilance on the sale of steroid containing compounds will help control this dermatological condition.


Inhibitory effect of commercial green tea and rosemary leaf powders on the growth of foodborne pathogens in laboratory media and oriental-style rice cakes.
The antimicrobial effects of green tea and rosemary added to foods as antagonists to foodborne pathogens were determined in laboratory media and oriental-style rice cakes. The growth of each pathogen (Bacillus cereus, Salmonella Typhimurium, Enterobacter sakazakii, Escherichia coli O157:H7, Staphylococcus aureus, and Listeria monocytogenes) in tryptic soy broth or rice cake with or without addition of green tea or rosemary leaf powders before autoclaving or cooking, respectively, was investigated after inoculation. The addition of 1% green tea or rosemary produced similar results for inhibiting the growth of pathogens in tryptic soy broth. However, green tea was more effective than rosemary for inhibiting the growth of L. monocytogenes. Both botanicals had inhibitory effects against all pathogens tested in this study. Green tea was particularly effective against B. cereus, S. aureus, and L. monocytogenes, and rosemary was strongly inhibitory against B. cereus and S. aureus. The addition of 1 or 3% green tea or rosemary to rice cakes did not significantly reduce total aerobic counts; however, levels of B. cereus and S. aureus were significantly reduced in rice cakes stored for 3 days at room temperature (22 degrees C). The order of antimicrobial activities against B. cereus in rice cake was 1% rosemary < 1% green tea < 3% rosemary = 3% green tea. These results indicate that the use of natural plant materials such as green tea and rosemary could improve the microbial quality of foods in addition to their functional properties.


Plasma catecholamines and glucose during moderate exercise in the trout: comparison with bursts of violent activity.
A sensitive radioenzymatic method was used to measure the plasma adrenaline and noradrenaline levels in Salmo gairdneri during and after long but moderate exercise (30 min, 2.2 body length s-1), and after brief but violent exercise (3 min chasing). No significant change occurred under the former experimental conditions whereas adrenaline increased significantly under the second. Plasma glucose increased only after violent exercise. These results suggest that plasma catecholamines do not participate in physiological regulations related to exercise when trout is swimming at velocities up to 2.2 body length s-1.


Metagenomic characterization of 'Candidatus Defluviicoccus tetraformis strain TFO71', a tetrad-forming organism, predominant in an anaerobic-aerobic membrane bioreactor with deteriorated biological phosphorus removal.
In an acetate-fed anaerobic-aerobic membrane bioreactor with deteriorated enhanced biological phosphorus removal (EBPR), Defluviicoccus-related tetrad-forming organisms (DTFO) were observed to predominate in the microbial community. Using metagenomics, a partial genome of the predominant DTFO, 'Candidatus Defluviicoccus tetraformis strain TFO71', was successfully constructed and characterized. Examining the genome confirmed the presence of genes related to the synthesis and degradation of glycogen and polyhydroxyalkanoate (PHA), which function as energy and carbon storage compounds. TFO71 and 'Candidatus Accumulibacter phosphatis' (CAP) UW-1 and CAP UW-2, representative polyphosphate-accumulating organisms (PAO), have PHA metabolism-related genes with high homology, but TFO71 has unique genes for PHA synthesis, gene regulation and granule management. We further discovered genes encoding DTFO polyphosphate (polyP) synthesis, suggesting that TFO71 may synthesize polyP under untested conditions. However, TFO71 may not activate these genes under EBPR conditions because the retrieved genome does not contain all inorganic phosphate transporters that are characteristic of PAOs (CAP UW-1, CAP UW-2, Microlunatus phosphovorus NM-1 and Tetrasphaera species). As a first step in characterizing EBPR-associated DTFO metabolism, this study identifies important differences between DTFO and PAO that may contribute to EBPR community competition and deterioration.


Clinical information in psychiatric practice: what do doctors know, what do they think is known and what do they record?
Deficiencies in recording clinical information are a widespread problem in both psychiatry and medicine. Previous studies have not established whether information not recorded in the notes is nonetheless known to clinicians. This study compared both the information known to individual clinicians and that recorded in the notes with previously established criteria. Overall, individual clinicians recalled more information than was recorded in the notes (median values: clinicians 47-63% of criteria; notes 42%) and when all this individual knowledge was pooled, 88% of the preset criteria were satisfied. Consultants, but not more junior staff, recalled significantly more about subsections of the history which they considered to be especially relevant to the management plan for a given patient. Only a third of data not known to clinicians, but thought by them to be recorded in the notes, was actually present. The implications of these findings for clinical audit and medical education are discussed.


Clinical spectrum of diffuse crescentic glomerulonephritis in Chinese patients.
To investigate retrospectively the incidence, distribution of primary disease and clinicopathologic characteristics of diffuse crescentic glomerulonephritis (DCGN) in Chinese patients. One hundred and seventy-two consecutive patients diagnosed as having DCGN out of 9828 cases of non-transplanting renal biopsies over sixteen years, were studied. DCGN is categorized into three types according to immunopathologic characteristics. The incidence of this disease, its primary diseases, clinical characteristics and serum antineutrophil cytoplasmic antibodies (ANCAs) were analyzed. The distribution of patients among the three classifications was 8.7% type I, 68.6% type II and 22.7% type III. Clinically, the majority of patients (69.8%) presented rapidly progressive glomerulonephritis (RPGN), but 30.2% manifested a chronic nephritic syndrome or chronic renal failure. In terms of related conditions, 93% were anemic, 61.6% had hypertension, 50.6% oliguria, 45.3% nephrotic syndrome, 43% uremic syndrome and 39.5% displayed gross hematuria. Those patients who were positive in serum for ANCAs had predominantly type III DCGN. Two cases with anti-GBM-antibody crescentic glomerulonephritis and three with lupus nephritis were also positive for ANCAs in serum. DCGN is not rare in Chinese patients. A majority of patients in our study presented with RPGN, but 30.2% manifested a chronic renal failure. Lupus patients with DCGN that were positive for ANCAs had more severe vasculitic lesions.


Evaluating pharmacological models of high and low anxiety in sheep.
New tests of animal affect and welfare require validation in subjects experiencing putatively different states. Pharmacological manipulations of affective state are advantageous because they can be administered in a standardised fashion, and the duration of their action can be established and tailored to suit the length of a particular test. To this end, the current study aimed to evaluate a pharmacological model of high and low anxiety in an important agricultural and laboratory species, the sheep. Thirty-five 8-month-old female sheep received either an intramuscular injection of the putatively anxiogenic drug 1-(m-chlorophenyl)piperazine (mCPP; 1 mg/kg; n = 12), an intravenous injection of the putatively anxiolytic drug diazepam (0.1 mg/kg; n = 12), or acted as a control (saline intramuscular injection n = 11). Thirty minutes after the treatments, sheep were individually exposed to a variety of tests assessing their general movement, performance in a 'runway task' (moving down a raceway for a food reward), response to startle, and behaviour in isolation. A test to assess feeding motivation was performed 2 days later following administration of the drugs to the same animals in the same manner. The mCPP sheep had poorer performance in the two runway tasks (6.8 and 7.7 × slower respectively than control group; p < 0.001), a greater startle response (1.4 vs. 0.6; p = 0.02), a higher level of movement during isolation (9.1 steps vs. 5.4; p < 0.001), and a lower feeding motivation (1.8 × slower; p < 0.001) than the control group, all of which act as indicators of anxiety. These results show that mCPP is an effective pharmacological model of high anxiety in sheep. Comparatively, the sheep treated with diazepam did not display any differences compared to the control sheep. Thus we suggest that mCPP is an effective treatment to validate future tests aimed at assessing anxiety in sheep, and that future studies should include other subtle indicators of positive affective states, as well as dosage studies, so conclusions on the efficacy of diazepam as a model of low anxiety can be drawn.


Inhibiting Protein Aggregation Using Cellulose Nanocrystal in MALDI-TOF MS Analysis: Improving the Sensitivity and Repeatability of Intact Protein in Pueraria.
Protein aggregation can induce low sensitivity and poor repeatability of matrix-assisted laser desorption/ionization time-of-fight mass spectrometry (MALDI-TOF MS) analysis for intact protein. Herein, we introduced a strategy to decrease protein aggregation in the sample solution by using cellulose nanocrystal (CNC). The results indicated that protein granule size was effectively reduced by adding CNC to the sample solution. Through MALDI-TOF MS analysis, the signal-to-noise ratio of [M + H]+ peak increased 2-fold, and the detection of limit was <10 μg/mL for intact protein. The CNC also contributed to excellent point-to-point repeatability for MALDI-TOF MS analysis with the coefficient of variation (CV) of 10.0% with CNC vs 48.9% without CNC in Hb solution. Also, the repeatability of Pueraria protein ion signals was improved by using CNC, and the CV with and without CNC was 16.1% and 39.6%, respectively. Moreover, protein ion intensity exhibited great linear relationship (y = 53.04x - 3.474, R2 = 0.9936) with the concentrations (ranging from 0.1 to 10 mg/mL) when using CNC. Further investigation revealed that m/z 19,000 and m/z 21,000 peaks of Pueraria could be used for the adulteration analysis and post-translational modification research, demonstrating our method has the potential for broad applications.


Factors associated with demoralisation syndrome in patients before and after cardiac surgery.
To investigate the incidence of and contributors to demoralisation syndrome among patients before and after cardiac surgery. Demoralisation syndrome is a common but neglected phenomenon in nursing practice. Patients who require cardiac surgery experience demoralisation syndrome more often than they experience depression. A prospective correlational design was applied. A convenience sample of 76 participants undergoing cardiac surgery was recruited from the cardiovascular wards of two medical centres in Taiwan. The instruments applied included the Demoralization Scale (DS), the Patient Outcome Questionnaire-9 (PHQ-9) and the Perception of Intensive Care Unit (ICU) Stay Questionnaire. High demoralisation was present in 44.7% of the participants before surgery but significantly decreased to 36.8% after surgery (p < .05); conversely, depression was present in 15.8% of participants before surgery and did not significantly decrease after surgery (rate after surgery, 9.2%; p > .05). A multiple regression analysis using the backward-selection method showed that depression (p < .001) and retirement (p < .05) were important predictors of pre-operative demoralisation syndrome (R2 = 0.250), whereas depression (p < .001) and perceptions of ICU stay (p > .05) remained in the regression model after surgery (R2 = 0.291). The study findings suggest that demoralisation syndrome is highly prevalent in patients undergoing cardiac surgery but is significantly reduced after cardiac surgery. Before surgery, depression and retirement were significant predictors of demoralisation. After surgery, depression was the only predictor. Although the perception of ICU stay was not an important predictor, it was significantly correlated with demoralisation. Before cardiac surgery, nurses should emphasise the importance of demoralisation development among patients who suffer from depressive symptoms and are retired. After cardiac surgery, continued follow-up is needed for the early detection and minimisation of the effect of depression and the development of demoralisation.


Endoscopic Sleeve Gastroplasty (ESG) Is a Reproducible and Effective Endoscopic Bariatric Therapy Suitable for Widespread Clinical Adoption: a Large, International Multicenter Study.
Endoscopic sleeve gastroplasty (ESG), an incisionless endoscopic bariatric procedure, has shown impressive results in case series. This study examines the reproducibility, efficacy, and safety in three centers across two countries, and identifies key determinants for procedural success. Patients who underwent ESG between February 2016 and May 2017 at one of three centers (Australia and USA) were retrospectively analyzed. All procedures were performed on an outpatient basis using the Apollo OverStitch device (Apollo Endosurgery, Austin, TX). Primary outcomes included absolute weight loss (ΔWeight, kg), change in body mass index (∆BMI, in kg/m2), total body weight loss (TBWL, %), excess weight loss (EWL, in %), and immediate and delayed adverse events. In total, 112 consecutive patients (male 31%, age 45.1 ± 11.7 years, baseline BMI 37.9 ± 6.7 kg/m2) underwent ESG. At 1, 3, and 6 months, Δweight was 9.0 ± 4.6 kg (TBWL 8.4 ± 4.1%), 12.9 ± 6.4 kg (TBWL 11.9 ± 4.5%), and 16.4 ± 10.7 kg (TBWL 14.9 ± 6.1%), respectively. The proportion of patients who attained greater than 10% TBWL and 25% EWL was 62.2 and 78.0% at 3 months post-ESG and 81.0 and 86.5% at 6 months post-ESG. Weight loss was similar between the three centers. Multivariable analysis showed that male sex, greater baseline body weight, and lack of prior endoscopic bariatric therapy were predictors of greater Δweight at 6 months. Three (2.7%) severe adverse events were observed. ESG is an effective, reproducible, and safe weight loss therapy that is suitable for widespread clinical adoption.


[Prevalence and risk factor structure of cerebral stroke in people of the Khanty-Mansi autonomous okrug].
Based on the data of cerebral stroke register carried out in the Khanty-Mansi autonomous okrug in 2004-2007, the information on the prevalence of main risk factors has been obtained. Arterial hypertension is the most significant risk factor for all forms of acute cerebral blood flow disturbance. Comparison of prevalence of main risk factors of stroke in residents of this region and people of other regions of the Russian Federation has revealed significant differences for all factors, with the exception of alcohol abuse. The structure of risk factor prevalence in the autonomous okrug differs from that in Russia. The statistically significant differences in the prevalence of all factors for ischemic stroke and non-traumatic intracranial hemorrhages studied were found in men and women living in the okrug as well as in the settled population and in watchmen. Highly significant direct correlations (p<0.0005) between the number of risk factors and the level of early 28 day mortality were revealed.


Understanding of emotions based on counterfactual reasoning in children with autism spectrum disorders.
The understanding of emotions based on counterfactual reasoning was studied in children with high-functioning autism spectrum disorders (n = 71) and in typically developing children (n = 71), aged 6-12 years. Children were presented with eight stories about two protagonists who experienced the same positive or negative outcome, either due to their own action or by default. Relative to the comparison group, children with high-functioning autism spectrum disorder were poor at explaining emotions based on downward counterfactual reasoning (i.e. contentment and relief). There were no group differences in upward counterfactual reasoning (i.e. disappointment and regret). In the comparison group, second-order false-belief reasoning was related to children's understanding of second-order counterfactual emotions (i.e. regret and relief), while children in the high-functioning autism spectrum disorder group relied more on their general intellectual skills. Results are discussed in terms of the different functions of counterfactual reasoning about emotion and the cognitive style of children with high-functioning autism spectrum disorder.