A liquid chromatography tandem mass spectrometry method for determining 18 per- and polyfluoroalkyl substances in source and treated drinking water.
Per- and polyfluoroalkyl substances (PFASs) have been determined in waters intended for human consumption, causing concern due to their potential toxic effects in humans and the environment. Drinking water is acknowledged to be one of the major routes of exposure to PFASs, which has led to the implementation of regulatory guidelines for PFASs in drinking water. In this study a fast, simple, sensitive and cost-effective method is developed for the determination of 18 PFASs in river and drinking water. The proposed method consists of directly injecting 900 µL of sample into a liquid chromatograph coupled to a triple quadrupole mass analyser, which involves minimal sample treatment as the sample only needs to be filtered. The method was validated in influent and effluent water from a drinking water treatment plant. Strong matrix effects were found for some of the target PFASs, and matrix-matched calibration curves were performed to enable accurate (87-114%) and precise (%RSD between 3 and 18%) quantification (n = 5, at 5 and 75 ng·L-1) with very good sensitivity (method quantitation limits between 0.1 and 2.0 ng·L-1). The method was applied to water samples from the influent and effluent of a drinking water treatment plant located in Catalonia (Spain), as well as in tap water and bottled water. The most abundant PFAS in all the types of water was PFBA, which represents 48%, 49%, 66% and 69% of total PFASs found in influent, effluent, tap and bottled water respectively. Relative mean abundances and the sum of mean concentrations in influent and effluent water suggests poor removal of PFASs during drinking water treatment. The concentrations of PFASs in bottled waters were generally lower than those in tap waters.


Endoscopic carbon dioxide laser diverticulostomy versus endoscopic staple-assisted diverticulostomy to treat Zenker's diverticulum.
The 2 most frequently used endoscopic methods to treat Zenker's diverticulum are staple-assisted and CO(2) laser esophagodiverticulostomy. The study centered around a retrospective evaluation of 107 patients with Zenker's diverticulum who were treated endoscopically by CO(2) laser (n = 72) or staple-assisted diverticulostomy (n = 35). Patients in the staple-assisted group had a shorter duration of postoperative hospitalization, attributed to earlier oral intake, than patients in the CO(2) laser group. There were no serious postoperative complications in either group. Postoperative fever and emphysema in the neck or mediastinum occurred more frequently in the CO(2) laser group, but this did not lead to any complications. Most patients reported partial or complete relief of their symptoms and there was no significant difference in the number of reoperations between the 2 treatment groups. Zenker's diverticulum was treated safely and effectively by the 2 endoscopic techniques, but the staple-assisted method seemed to be the most favorable.


Occurrence of 13 veterinary drugs in animal manure-amended soils in Eastern China.
The occurrence of 13 veterinary drugs were studied in soil fertilized with animal manures in Eastern China. The 69 soil samples were obtained from twenty-three vegetable fields in 2009 and analysed for selected veterinary drugs by HPLC-MS/MS at soil depths of 0-20, 20-40 and 40-60 cm, and two additional samples were re-analysed from an earlier study from November 2011. Results showed that animal wastes, especially those from poultry farms, were one of pollution sources of veterinary drugs in soil. The detection frequency of veterinary drugs in soil was 83%, 91% and 87% in the three soil depths, respectively. The detection rates for the five classes of drugs in soils followed the rank order cyromazine > tetracyclines > sulfonamides > fluoroquinolones > florfenicol. Veterinary drugs were detected in soil layers at 20-40 and 40-60 cm depth to a greater extent than at 0-20 cm depth. The results of the same point in years 2009 and 2011 indicated that veterinary drugs accumulate easily and persist in the deeper soil. In addition, residue levels of veterinary drugs in soil were related to the animal species the manure was derived from. Overall, the predominance of tetracyclines in sampled soils underscored the need to regulate their veterinary use in order to improve the management and treatment of associated releases.


Splicing in disease: disruption of the splicing code and the decoding machinery.
Human genes contain a dense array of diverse cis-acting elements that make up a code required for the expression of correctly spliced mRNAs. Alternative splicing generates a highly dynamic human proteome through networks of coordinated splicing events. Cis- and trans-acting mutations that disrupt the splicing code or the machinery required for splicing and its regulation have roles in various diseases, and recent studies have provided new insights into the mechanisms by which these effects occur. An unexpectedly large fraction of exonic mutations exhibit a primary pathogenic effect on splicing. Furthermore, normal genetic variation significantly contributes to disease severity and susceptibility by affecting splicing efficiency.


In-Hospital Fall Risk Prediction by Objective Measurement of Lower Extremity Function in a High-Risk Population.
Limited data exist regarding association between physical performance and in-hospital falls. This study was performed to investigate the association between physical performance and in-hospital falls in a high-risk population. Retrospective cohort study. The study population consisted of 1200 consecutive patients with a median age of 74 years (50.8% men) admitted to a ward with high incidence rates of falls, primarily in the departments of geriatrics and neurology, in a university hospital between January 2019 and December 2021. Short Physical Performance Battery (SPPB) was measured after treatment in the acute phase. As the primary end point of the study, the incidence of in-hospital falls was examined prospectively based on data from mandatory standardized incident report forms and electronic patient records. SPPB assessment was performed at a median of 3 days after admission, and the study population had a median SPPB score of 3 points. Falls occurred in 101 patients (8.4%) over a median hospital stay of 15 days. SPPB score showed a significant inverse association with the incidence of in-hospital falls after adjusting for possible confounders (adjusted odds ratio for each 1-point decrease in SPPB: 1.19, 95% CI 1.10-1.28; P < .001), and an SPPB score ≤6 was significantly associated with increased risk of in-hospital falls. Inclusion of SPPB with previously identified risk factors significantly increased the area under the curve for in-hospital falls (0.683 vs. 0.740, P = .003). This study demonstrated an inverse association of SPPB score with risk of in-hospital falls in a high-risk population and showed that SPPB assessment is useful for accurate risk stratification in a hospital setting.


Clinical application of high-risk scoring on an obstetric service.
Obstetric risk scoring is a formalized way of recognizing, documenting, and cumulating antepartum and intrapartum factors to predict later complications for mother, fetus, and infant. If simple, practical, and reliable, risk scoring can be clinically useful in determining appropriate levels of care. In this prospective study, antepartum and intrapartum risk scales were integrated into the clinical record, and the relationship of risk scores to outcome was evaluated for 1,275 consecutively delivered gravid women. The forms could be simply and quickly filled out by the staff. Increased risk on both scales was significantly related to lowered one- and five-minute Apgar scores. The perinatal mortality rate increased from 0 to 93.4 per thousand from the lowest to the highest risk group. More than 80% of all perinatal deaths occurred in the one quarter of patients in the highest risk group. These results suggest that this risk scoring system can be used effectively in a clinical setting to identify patients at increased risk for neonatal depression and perinatal death.


Structural characteristics, molecular properties and immunostimulatory effects of sulfated polysaccharide from freshwater Myriophyllum spicatum L.
Water-soluble polysaccharides were isolated from a freshwater plant, Myriophyllum spicatum L., at elevated temperature and purified using DEAE Sepharose FF column to elucidate their structural properties and immunopotentiating effects. Polysaccharides were composed of neutral sugars (73.9-78.2%), sulfate esters (12.8-16.8%) and uronic acids (3.1-4.9%). Weight average molecular weight (Mw) of polysaccharides varied between 217.4 and 529.0 × 103 g/mol. Polysaccharide structures were predominantly consisted of glucose (31.9-59.1%) and galactose (16.6-34.5%) with lower amounts of mannose, xylose, arabinose and rhamnose. As the most active fraction, MSF1 induced RAW264.7 murine macrophage cells to release nitric oxide and initiate the expression of TNF-α, IL-1β, IL-6 and IL-12 cytokines. Besides, MSF1 activated NK-92 cells to produce TNF-α and INF-γ cytokines and initiate cell-mediated cytotoxicity via perforin/granzyme B, NKG2D receptor and FasL pathways. Stimulation of RAW264.7 and NK-92 cells with MSF1 resulted in high expressions of phosphorylated NF-κB, ERK, JNK and p38 proteins revealing the involvement of NF-κB and MAPKs signaling pathways. MSF1 possessed a highly-branched structure consisting a combination of (1 → 4)-Glcp, (1 → 6)-Glcp, (1 → 4,6)-Glcp, (1 → 3,4)-Galp and (1 → 2,3)-Galp residues. Altogether, the present findings suggested the potential application of sulfated-polysaccharides from M. spicatum L. for immunostimulation and thus the necessity for further biomedical research.


Epigenetic ageing accelerates before antiretroviral therapy and decelerates after viral suppression in people with HIV in Switzerland: a longitudinal study over 17 years.
Accelerated epigenetic ageing can occur in untreated HIV infection and is partially reversible with effective antiretroviral therapy (ART). We aimed to make a long-term comparison of epigenetic ageing dynamics in people with HIV during untreated HIV infection and during suppressive ART. In this longitudinal study, conducted over 17 years in HIV outpatient clinics in Switzerland, we applied 5 established epigenetic age estimators (epigenetic clocks) in peripheral blood mononuclear cells (PBMCs) in Swiss HIV Cohort Study participants before or during suppressive ART. All participants had a longitudinal set of PBMC samples available at four timepoints (T1-T4). T1 and T2 had to be 3 years or longer apart, as did T3 and T4. We assessed epigenetic age acceleration (EAA) and a novel rate of epigenetic ageing. Between March 13, 1990, and Jan 18, 2018, we recruited 81 people with HIV from the Swiss HIV Cohort Study. We excluded one participant because a sample did not meet quality checks (transmission error). 52 (65%) of 80 patients were men, 76 (95%) were white, and the median patient age was 43 (IQR 37·5-47) years. Per year of untreated HIV infection (median observation 8·08 years, IQR 4·83-11·09), mean EAA was 0·47 years (95% CI 0·37 to 0·57) for Horvath's clock, 0·43 years (0·3 to 0·57) for Hannum's clock, 0·36 years (0·27 to 0·44) for SkinBlood clock, and 0·69 years (0·51 to 0·86) for PhenoAge. Per year of suppressive ART (median observation 9·8 years, IQR 7·2-11), mean EAA was -0·35 years (95% CI -0·44 to -0·27) for Horvath's clock, -0·39 years (-0·50 to -0·27) for Hannum's clock, -0·26 years (-0·33 to -0·18) for SkinBlood clock, and -0·49 years (-0·64 to -0·35) for PhenoAge. Our findings indicate that people with HIV epigenetically aged by a mean of 1·47 years for Horvath's clock, 1·43 years for Hannum's clock, 1·36 years for SkinBlood clock, and 1·69 years for PhenoAge per year of untreated HIV infection; and 0·65 years for Horvath's clock, 0·61 years for Hannum's clock, 0·74 years for SkinBlood clock, and 0·51 years for PhenoAge, per year of suppressive ART. GrimAge showed some change in the mean EAA during untreated HIV infection (0·10 years, 0·02 to 0·19) and suppressive ART (-0·05 years, -0·12 to 0·02). We obtained very similar results using the rate of epigenetic ageing. Contribution of multiple HIV-related, antiretroviral, and immunological variables, and of a DNA methylation-associated polygenic risk score to EAA was small. In a longitudinal study over more than 17 years, epigenetic ageing accelerated during untreated HIV infection and decelerated during suppressive ART, highlighting the importance of limiting the duration of untreated HIV infection. Swiss HIV Cohort Study, Swiss National Science Foundation, and Gilead Sciences.


Features of mildly dilated congestive cardiomyopathy compared with idiopathic restrictive cardiomyopathy and typical dilated cardiomyopathy.
Congestive cardiomyopathy was recognized in eight patients with only mildly dilated ventricles (an echocardiographic ventricular diastolic dimension index of less than 10% to 15% above the normal range) but with other features typical of end-stage congestive cardiomyopathy. Such patients with mildly dilated cardiomyopathy (MDCM) represented 5% of heart transplant recipients with cardiomyopathy, who were analyzed by us. The clinical, echocardiographic, and hemodynamic data, as well as the gross and microscopic pathologic findings of the hearts in this group were compared with similar data in five patients with idiopathic restrictive cardiomyopathy (IRCM) and 10 patients with typical dilated cardiomyopathy (DCM). Compared with IRCM and DCM, patients with MDCM had a higher incidence of familial cardiomyopathy (p less than 0.009). The echocardiographic features of patients with MDCM and DCM were virtually identical, showing globular hearts with predominant left ventricular dilation and diffuse poor left ventricular contraction. Patients with IRCM had marked atrial dilation but less abnormality of left ventricular size and contraction parameters. On the basis of echocardiographic data, patients with IRCM and MDCM could be well segregated. Cardiac index and light microscopic examinations were similar in the three groups. However, electron microscopy showed a lack of myofibrillar loss in patients with IRCM, little or no myofibrillar loss in those with MDCM, and almost total myofibrillar loss in those with DCM. Patients with MDCM have a high prevalence of familial cardiomyopathy. Absolute heart size and electron microscopic features of the MDCM group were intermediate between IRCM and DCM, but other clinical, echocardiographic and hemodynamic findings were similar to typical DCM.


Bariatric surgery reduces urinary albumin excretion in diabetic nephropathy: a systematic review and meta-analysis.
Bariatric surgery is found to prevent type 2 diabetes, improve glycemic control, and decrease long-term incidence of microvascular and macrovascular complications in obese persons. However, its effect on urinary albumin excretion (UAE) in patients with diabetic nephropathy (DN) is still unknown. This is a systematic review and meta-analysis of observational studies on bariatric surgery and change in UAE in patients with diabetes. To explore whether there is improvement in UAE after bariatric surgery. We comprehensively searched the databases of MEDLINE, Embase, and Cochrane. The inclusion criteria were published studies evaluating effects of bariatric surgery in patients with DN at baseline. The primary outcome was the pre- and postbariatric surgery UAE as characterized by urinary albumin-to-creatinine ratio and albuminuria. A meta-analysis comparing pre- and postsurgery UAE was performed. From 65 full-text articles, 15 observational studies met our inclusion criteria, and 11 studies were included in the meta-analysis based on the random effects model. There was a significant reduction in urinary albumin-to-creatinine ratio after bariatric surgery with a mean difference of -6.60 mg/g of creatinine (95% CI -9.19 to -4.02; P<.001). There was also a reduction in albuminuria with a mean difference of -55.76 mg/24 hours (95% CI -92.11 to -19.41; P<.001) after bariatric surgery. Bariatric surgery significantly decreases urinary albumin excretion in DN. However, studies comparing bariatric surgery and conventional or intensive care of diabetes on UAE outcome should be done.


Distribution and activity of anaerobic ammonium-oxidising bacteria in natural freshwater wetland soils.
Anaerobic ammonium oxidation (anammox) process plays a significant role in the marine nitrogen cycle. However, the quantitative importance of this process in nitrogen removal in wetland systems, particularly in natural freshwater wetlands, is still not determined. In the present study, we provided the evidence of the distribution and activity of anammox bacteria in a natural freshwater wetland, located in southeastern China, by using (15)N stable isotope measurements, quantitative PCR assays and 16S rRNA gene clone library analysis. The potential anammox rates measured in this wetland system ranged between 2.5 and 25.5 nmol N2 g(-1) soil day(-1), and up to 20% soil dinitrogen gas production could be attributed to the anammox process. Phylogenetic analysis of 16S rRNA genes showed that anammox bacteria related to Candidatus Brocadia, Candidatus Kuenenia, Candidatus Anammoxoglobus and two novel anammox clusters coexisted in the collected soil cores, with Candidatus Brocadia and Candidatus Kuenenia being the dominant anammox genera. Quantitative PCR of hydrazine synthase genes showed that the abundance of anammox bacteria varied from 2.3 × 10(5) to 2.2 × 10(6) copies g(-1) soil in the examined soil cores. Correlation analyses suggested that the soil ammonium concentration had significant influence on the activity of anammox bacteria. On the basis of (15)N tracing technology, it is estimated that a total loss of 31.1 g N m(-2) per year could be linked the anammox process in the examined wetland.


Activation of Toll-like receptors and dendritic cells by a broad range of bacterial molecules.
Activation of pattern recognition receptors such as Toll-like receptors (TLRs) by pathogens leads to activation and maturation of dendritic cells (DC), which orchestrate the development of the adaptive immune response. To create an overview of the effects of a broad range of pathogenic bacteria, their capacity to activate TLRs and to affect DC maturation, cytokine production and T cell polarizing capacity were determined. Different bacterial species differed in their potency to affect these parameters. In general, on the DC level differences were found in the maturation-inducing capacity of gram-negative and gram-positive bacteria. Remarkably, these differences did not result in differential polarization of the T cell response. With respect to TLRs, TLR4 activation by pathogens correlated with their ability to induce DC maturation, while for TLR2 and TLR5 such a correlation was absent. Taken together, this study provides insight into qualitative differences and general effects of pathogen-derived molecules on dendritic cells.


Hypoplastic left heart syndrome with anomalous origin of left coronary artery from the right pulmonary artery: successful surgical treatment in a neonate.
Anomalous origin of the left coronary artery from the right pulmonary artery in association with hypoplastic left heart syndrome is a rare congenital anomaly. We describe a successful simultaneous surgery for both anomalies during the first stage palliation in a neonate.


Structural differences between oxidized and reduced thioredoxin monitored by two-dimensional 1H NMR spectroscopy.
Two-dimensional high resolution NMR techniques have been applied to study the structural differences between the oxidized and reduced forms of Escherichia coli thioredoxin in solution. Sequential proton resonance assignments indicate only limited conformational changes; major chemical shift differences are found for a few residues in a beta-strand immediately preceding the active site S-S bridge and the active site itself. Additional resonance shifts are observed for several residues distant in the primary sequence. The X-ray structure of oxidized thioredoxin shows that these residues form a flat hydrophobic surface, close to the active site S-S bridge, which is probably involved in interactions with other protein molecules.


Influence of the organophosphorus compound DFP on inhibitory motor systems and esterase activity in the spinal cord of cats.
In high spinal cats, the acute time-dependent changes of both the activity of spinal reflex pathways and the activity of three different esterases (acetylcholinesterase, carboxylesterase and neurotoxicant target enzyme) in the spinal cord were investigated after intravenous application of the organophosphorus compound di-isopropyl phosphofluoridate (DFP). There is no general depression of spinal reflexes by DFP. While the recurrent inhibition is completely abolished for a long time and the reflexes to a flexor (PBSt) are depressed but with a shorter recovery time, the reflexes to an extensor (GS) are distinctly less depressed or even facilitated. Reflex pathways from skin afferents to motoneurones did not react in a uniform way to DFP, e.g. inhibitory nociceptive pathways were less affected than excitatory ones. Esterase activities were heavily depressed and recovered with different time courses. The acute DFP action cannot be explained by a uniform intoxication of all spinal functions but probably emerges from a differential action on different interneuronal systems.


MiRNA-1246 suppresses the proliferation and migration of renal cell carcinoma through targeting CXCR4.
To uncover the role of miRNA-1246 in influencing the proliferative and migratory capacities of RCC by binding CXCR4 and downregulating its level. Relative levels of miRNA-1246 and CXCR4 in 40 paired RCC tissues and adjacent normal tissues were determined. The binding relationship between miRNA-1246 and CXCR4 was confirmed by Dual-Luciferase reporter assay. Proliferative and migratory abilities of RCC regulated by miRNA-1246 and CXCR4 were assessed. MiRNA-1246 was downregulated in RCC tissues and cell lines. Overexpression of miRNA-1246 attenuated proliferative and migratory capacities of 786-O and 769-P cells. CXCR4 was the direct target of miRNA-1246 and its level was negatively regulated by miRNA-1246. Silence of CXCR4 inhibited RCC to proliferate and migrate. MiRNA-1246 attenuates proliferative and migratory abilities of RCC by downregulating CXCR4. MiRNA-1246/CXCR4 axis could be potential therapeutic target for RCC.


Advancing the development of tuberculosis therapy.
Although the development of novel drugs and combination regimens for tuberculosis has accelerated in recent years, the pipeline remains thin and major challenges remain to be addressed in efficiently evaluating newer drugs to improve treatment outcomes, shorten duration of therapy and tackle drug resistance.


Videodensitometric blood flow analysis of abdominal aortic aneurysm and intravascular coagulation.
We investigated the relation between flow pattern in abdominal aortic aneurysm (AAA) and intravascular coagulopathy characterized by increased fibrin degradation product d-dimer (FDP-DD) or thrombin-antithrombin complex (TAT). Materials and methods The ratio of AAA maximum endoluminal diameter (diameter of flow channel) (n = 23) to diameter of the aorta between the superior mesenteric and renal arteries (R ratio) was measured with three-dimensional computed tomography angiography. Digital subtraction angiography was performed with 20 mL (10 mL/s) of contrast agent injected from the suprarenal portion of the abdominal aorta. The duration between the time when average gray scale in the AAA reached maximum and average region of interest gray scale decreased to half-maximum (bolus transit time in AAA [BTT(AAA)]) was calculated. Single correlation coefficient with statistic significance was detected between R ratio and BTT(AAA) (BTT(AAA) = 2.54 x R ratio + 3.65; r(2) =.30; P =.042). Among the three-dimensional morphologic and videodensitometric variants, BTT(AAA) was the most determinant factor associated with FDP-DD (FDP-DD = - 8.647 + 2.029 x BTT(AAA); r(2) =.448; P =.005). The most efficient predictors for TAT were maximum AAA endoluminal diameter (R(endomax)) and BTT(AAA) (TAT = - 14.007 + 2.102 x BTT(AAA) + 0.296 x R(endomax), r(2) =.360; P =.0069). Our findings suggest a close link between abnormal flow pattern in AAA and activation of the coagulation-fibrinolysis system. Videodensitometric blood flow analysis can be useful in investigation of the pathophysiology of phenomena related to abnormal flow field in AAA.


A comprehensive district-level laboratory intervention after the Ebola epidemic in Sierra Leone.
The 2014-2016 Ebola outbreak exposed the poor laboratory systems in Sierra Leone. Immense needs were recognised across all areas, from facilities, diagnostic capacity, supplies, trained personnel to quality assurance mechanisms. We aimed to describe the first year of a comprehensive intervention, which started in 2015, in a public hospital's general laboratory serving a population of over 500 000 in a rural district. The intervention focused on (1) supporting local authorities and healthcare workers in policy implementation and developing procedures to enhance access to services, (2) addressing gaps by investing in infrastructure, supplies, and equipment, (3) development of quality assurance mechanisms via mentorship, bench-side training, and the introduction of quality control and information systems. All work was performed alongside counterparts from the Ministry of Health and Sanitation. We observed a strong increase in patient visits and inpatient and outpatient testing volumes. Novel techniques and procedures were taken up well by staff, leading to improved and expanded service and safety, laying foundations for further improvements. This comprehensive approach was successful and the results suggest an increase in trust from patients and healthcare workers.


Prognostic analysis and treatment utilization of different treatment strategies in elderly esophageal cancer patients with distant metastases: a SEER database analysis.
The purpose of this study was to explore which therapeutic strategy is more beneficial for elderly esophageal cancer (EC) patients with distant metastasis, the treatment utilization status and the screening of factors related to prognosis, so as to better guide the treatment of these patients. Patients in the Surveillance Epidemiology and End Results (SEER) database were divided into chemoradiotherapy (Group A), chemotherapy (Group B), radiotherapy (Group C), and no treatment (Group D) according to different treatment methods. Propensity score matching (PSM) was performed to adjust for baseline differences between the two groups. Overall survival (OS) and esophageal cancer-specific survival (ECSS) was calculated using the Kaplan-Meier method and compared using the log-rank test. A total of 7027 patients were included in this study, 5739 males (81.7%) and 1288 females (18.3%) with the median age was 70 (60-98). In the original cohort, the number of patients in the four groups was 2260 (Group A), 2087 (Group B), 945 (Group C) and 1735 (Group D), respectively. After PSM, there was no significant difference in mean OS (A vs B, 13.5 months VS 13.4 months, P = 0.511) and mean ECSS (A vs B, 15.6 vs 15.5 months, P = 0.374), while both OS (B vs C, 7 vs 3 months, P < 0.001) and ECSS (B vs C, 8 vs 3 months, P < 0.001) of chemotherapy alone were significantly better than those of radiotherapy alone. Subgroup analysis of patients older than 80 years showed that the median OS (A vs B, 7 vs 6 months) and median ECSS (A vs B, 8 vs 7 months) of Group A were significantly better than those of Group B (P < 0.05). In addition, all patients were randomly divided into a training set and a validation set with a ratio of 7:3. Based on the independent risk factors for OS, a nomogram model was constructed and validated. For elderly EC patients with distant metastasis, aggressive treatment was still necessary after a comprehensive assessment of the patient's physical condition, especially for patients over 80 years old, and chemoradiotherapy maybe still the first choice. In addition, a nomogram model was constructed to intuitively and accurately evaluate the prognosis of this population.


[Business activity in medicine: economic analysis of medical support programs and characteristics of management in business risks in health care system (problems and perspectives)].
Current scientific data on the assessment of cost expenditure on the realization of programs to assist medically patients with cardiological, oncological, rheumatologic and other diseases were analyzed. Peculiarities of the management of business risks were considered in the article. It was concluded that the management of business risks in health care system should be improved.


The social neuroscience of biases in in-and-out-group face processing.
The validity and reliability of stereotypes in social perception confirms traditional early social psychological research. Already in 1954 Gordon Allport stated that stereotypes might have a "kernel of truth." Recent research in social neuroscience, however, contradicts Lee Jussims' (2012) claim that the application of stereotypes increases accuracy in person perception. Person perception is inaccurate as it is insufficient when it involves only one factor (even if that factor was a reliable predictor).


Anti-Gal antibody-mediated skin graft rejection requires a threshold level of Gal expression.
Despite overcoming xenograft hyperacute rejection (HAR), Gal (galactose-alpha1,3-galactose) expression may not be completely eliminated from the alpha1,3-galactosyltransferase gene knockout (Gal KO) pig because of alternative galactosyltransferases. Whether low levels of "residual" Gal are still susceptible to either complement fixing or non-complement fixing antibody beyond the HAR barrier remains unknown. Furthermore, it would be impossible to analyze the immune response specific to low-level Gal in a xenograft setting given the multitude of xenoantigens that could induce a recipient response. To investigate this question, we therefore used a skin graft model in BALB/c mice where the sole difference between donor and recipient was the expression of Gal, where rejection is caused by passively administered anti-Gal monoclonal antibody and where HAR does not occur. Gal expression over time was examined by immunohistochemistry in wildtype-to-Gal KO skin grafts. Graft rejection in response to passively administered anti-Gal monoclonal antibody at early and late time points was studied to determine changes in susceptibility to antibody. To independently test the effect of reduced Gal expression on antibody-mediated rejection, we used two separate lines of alpha1,2-fucosyltransferase transgenic mice as skin donors in the model. These mice have known reduced but different levels of Gal as determined by flow cytometry on peripheral blood leukocytes. Gal expression on skin grafts diminished with time with a corresponding reduction in susceptibility to antibody-mediated rejection. Skin grafts at day 30 (n = 7) and 150 (n = 11) had a rejection rate of 100% and 45% respectively in response to non-complement fixing anti-Gal antibody administered to the recipient. Similar results were demonstrated with a complement fixing anti-Gal antibody. When alpha1,2-fucosyltransferase transgenic mice skin was used in the model, the line with lowest level of Gal expression was resistant to antibody-induced rejection with a rate 0% (n = 9) vs. 60% (n = 5) in the alternative line with relatively more Gal expressed but still much less than normal mice. Resistance to anti-Gal antibody-mediated damage in the model was observed in skin grafts 100 to 150 days post-grafting but not earlier and was associated with a reduction in Gal expression. It is possible that below a threshold level of Gal expression, the grafts were not susceptible to anti-Gal antibody.


Trends in intussusception hospitalizations among US infants before and after implementation of the rotavirus vaccination program, 2000-2009.
Although US data have not documented an intussusception risk with current rotavirus vaccines, international data indicate a possible low risk, primarily after the first dose. Among infants in 26 US states comprising 75% of the birth cohort, we examined age-specific trends in population-level intussusception hospitalization rates before (2000-2005) and after (2007-2009) rotavirus vaccine introduction. Compared with 2000-2005 (35.3 per 100,000), the rate was greater in 2007 (39.0 per 100,000; rate ratio [RR], 1.10; 95% confidence interval [CI], 1.04-1.18), similar in 2008 (33.4 per 100,000; RR, 0.95; 95% CI, .89-1.01), and lower in 2009 (32.9 per 100,000; RR, 0.93; 95% CI, .87-.99). Among infants aged 8-11 weeks, compared with 2000-2005 (6.9 per 100,000), a small, significant increase was observed in each of 2007 (11.4 per 100,000; RR, 1.64; 95% CI, 1.08-2.50), 2008 (12.2 per 100,000; RR, 1.76; 95% CI, 1.17-2.65), and 2009 (11.0 per 100,000; RR, 1.59; 95% CI, 1.04-2.44). Following rotavirus vaccine introduction, a small increase in intussusception rates was seen among US infants aged 8-11 weeks, to whom most first doses of vaccine are given; no sustained population-level change in overall rates was observed.


Evaluation of a peer-led falls prevention program for older adults.
To evaluate measures of strength and balance and falls incidence in participants attending fall prevention exercise classes taught by volunteer peer leaders, paid professional (Age Concern Otago group), or a comparison class (comparison group). Quasi-experimental evaluation with 12-month follow-up. Community. Older adults with increased fall risk (N=118; mean age, 75.5 y; age range, 65-94 y), with 23% drop out at 12 months. Peer-led group (n=52) and Age Concern Otago (n=41) weekly 1-hour strength and balance classes adapted from a home-based nurse/physical therapist-administered program and comparison group (n=25) 1-hour weekly seated exercise classes. Timed Up and Go test, 30-second chair stand, functional reach, step touch, Single Leg Stand, and balance confidence at baseline, 10 weeks, and 6 and 12 months. Falls diaries collected monthly for 12 months. Continued exercise participation questionnaire at 6 and 12 months. At baseline, the peer-led group achieved normative standards on most tests and performed significantly better than the Age Concern Otago and comparison groups (overall P<.05). The Age Concern Otago group reached normative standards on most tests at 10 weeks. Functional improvements were similar in the peer-led group and Age Concern Otago groups from 10 weeks to 12 months, and all functional measures were significantly greater than in the comparison group (overall P<.02). Poisson regression showed a tendency for a 27% decrease in falls for the peer-led group compared with the comparison group (incidence rate ratio [IRR], .73; 95% confidence interval, .48-1.1; P=.07). Continued participation in strength and balance classes at 12 months was greater in the peer-led group and Age Concern Otago groups compared with the comparison group. This peer-led model maintained measures of strength and balance and was superior to seated exercise. People in the Age Concern Otago group chose to continue these classes over other activities, whereas the comparison group had discontinued exercise classes by 12 months. Peer-led classes may decrease the fall incidence, although larger studies are needed to confirm this finding.


Purification of exosome-like vesicles from urine.
Urinary exosome-like vesicles (ELVs), 20-200nm membrane-bound particles shed by renal epithelium, have been shown to interact with the primary cilia of distant epithelial cells of the nephron. These ELVs are emerging as an important source of protein, mRNA, and miRNA biomarkers to monitor renal disease. However, purification of ELVs is compromised by the presence of large amounts of the urinary protein Tamm-Horsfall Protein (THP). THP molecules oligomerize into long, double-helical strands several microns long. These linear assemblies form a three-dimensional gel which traps and sequesters ELVs in any centrifugation-based protocol. Here, we present a purification protocol that separates ELVs from THP and divides urinary ELVs into three distinct populations.


Effects of Noise Damage on the Purinergic Signal of Cochlear Spiral Ganglion Cells in Guinea Pigs.
To observe the expression changes of P2 protein in cochlear spiral ganglion cells before and after noise injury, and to explore the relationship between the changes of purinergic receptors in spiral ganglion cells and noise-induced hearing loss, so that the signal transduction of purinergic receptors can be used to treat SNHL The target point provides a theoretical basis. The experimental animals were randomly divided into normal and experimental groups. The experimental group was given 120 dB white noise continuous exposure for 10 days and 3 h a day. The auditory brainstem response was measured before and after the noise exposure. After the noise exposure, the two groups of animals were collected. Do immunofluorescence staining, western blot, fluorescence real-time quantitative PCR to observe the expression of P2 protein. The average hearing threshold of the animals in the experimental group increased to 38.75 ± 6.44 dB SPL after 7 days of noise exposure, and the high-frequency hearing loss was lower and severe; the average hearing threshold increased to 54.38 ± 6.80 dB SPL after 10 days of noise exposure, and the hearing loss at 4 k Hz was relatively high. Light; Frozen sections of cochlear spiral ganglion cells and staining of isolated spiral ganglion cells found that P2X2, P2X3, P2X4, P2X7, P2Y2, and P2Y4 proteins were all expressed in cochlear spiral ganglion cells before noise exposure. Among them, P2X3 expression increased and P2X4, the down-regulation of P2Y2 expression was statistically significant (P < 0.05); Western blot and real-time quantitative PCR detection results showed that the expression of P2X3 was significantly increased after noise exposure than before noise exposure (P < 0.05), and P2X4 and P2Y2 were expressed after noise exposure The amount was significantly lower than before noise exposure (P < 0.05). (Figure. 4). After noise exposure, the expression of P2 protein is upregulated or downregulated. By affecting the Ca2+ cycle, the transmission of sound signals to the auditory center is blocked, which provides a theoretical basis for the signal transduction of purinergic receptors to become a target for the treatment of SNHL.


Correction to: Transcriptomics of manually isolated Amborella trichopoda egg apparatus cells.
The article Transcriptomics of manually isolated Amborella trichopoda egg apparatus cells, written by María Flores-Tornero, Sebastian Proost, Marek Mutwil, Charles P. Scutt, Thomas Dresselhaus, Stefanie Sprunck, was originally published electronically on the publisher's internet portal (currently SpringerLink) on 1 February 2019 without open access.


Eyelid pilomatrixoma: a description of 16 cases and a review of the literature.
Pilomatrixoma is an uncommon benign neoplasm that originates from the matrix of the hair root. It occurs more frequently in the head and neck region of children and adolescents, often involving the eyelid or eyebrow. Pilomatrixoma is often misdiagnosed clinically and the correct diagnosis can be established only after excision and histological examination. Pathologic diagnosis of pilomatrixoma is based on the finding of large masses of shadow cells, combined with basophilic cells, inflammation, foreign body giant cells, calcification, and ossification. We report 16 cases of eyelid pilomatrixoma that were treated in our department, and review the relevant literature.


Congenital Mesoblastic Nephroma Presenting With Hematuria in a Neonate: A Case Report.
Congenital mesoblastic nephroma (CMN) is the most frequent renal neoplasm of newborns and young infants. Four cases presenting with hemorrhagic manifestations have been reported in the English literature (Hu et al, 2006; Bolande et al, 1967). We report the unusual clinical and radiographic findings of a 2-day-old neonate with hematuria secondary to a CMN. The first ultrasound was equivocal. Repeat ultrasound followed by magnetic resonance imaging confirmed the diagnosis. He underwent a right nephroureterectomy with histopathology revealing a cellular variant of CMN without classical translocation (t12:15). Neonates presenting with hematuria require close follow-up and serial imaging to rule out occult renal tumors. Classical translocation may not be demonstrable in all the cases.


Population pharmacokinetic modelling and estimation of dosing strategy for NXY-059, a nitrone being developed for stroke.
NXY-059 (disufenton sodium, Cerovive, a nitrone with neuroprotective and free radical trapping properties (in experimental stroke) is under development for the treatment of acute stroke. The objectives of this study were to develop a population pharmacokinetic model for NXY-059 in acute stroke patients and to estimate individualised dosing strategies for NXY-059 using preclinical pharmacological and clinical pharmacokinetic information and knowledge of characteristics of the patient population. NXY-059 was given as a continuous intravenous infusion for 72 hours, including a 1-hour loading infusion. Maintenance infusion rates were individualised based on creatinine clearance (CL(CR)). Population pharmacokinetic models were derived using NONMEM software. Optimal dosing strategies, individualised based on CL(CR) or bodyweight, were estimated using the population pharmacokinetic models, empirical covariate distributions relevant for the target population, and a target definition. Dosing strategies were selected based on target fulfillment criteria and parsimony. Pharmacokinetic data from 179 patients with acute ischaemic or haemorrhagic stroke, included in two clinical studies, were used for the analyses. Patients were aged 34-92 years with varying degrees of renal impairment (estimated CL(CR) 20-143 mL/min). The final population model based on data from both studies comprised a two-compartment model with unexplained interpatient variability for clearance (23% coefficient of variation [CV]) and central volume of distribution (40% CV). Part of the variability in clearance and volume of distribution was explained by CL(CR) and bodyweight, respectively. Typical clearance was estimated to 4.54 L/h in a patient with CL(CR) of 70 mL/min. The preferred dosing strategy for NXY-059 comprised an initial loading infusion (the same for all patients) followed by an individualised maintenance infusion on the basis of CL(CR) (three dosing categories) with cut-off values (at which infusion rates are incremented or decremented) of 50 and 80 mL/min. The results illustrate how an individualised dosing strategy, given a pharmacokinetic target, for NXY-059 was successfully optimised through estimation using the increasing pharmacokinetic and pharmacodynamic knowledge during a clinical drug development programme. The chosen dosing strategy of NXY-059 provides an easily adapted treatment regimen for acute stroke, resulting in early achievement of target plasma concentrations.


Differential fluorescence labelling with 5-dimethyl-aminonaphthalene-1-sulfonyl chloride of intact cells and isolated membranes in Salmonella typhimurium and Acholeplasma laidlawii.
For fluorescence labelling intact cells and isolated cell envelopes (membranes) from Salmonella typhimurium and Acholeplasma laidlawii were treated with mixed dansylchloride-lecithin-cholesterol vesicles. This kind of dansylation, which has been supposed to be specific for cell surface proteins, produced fluorescent protein pattern after SDS-polyacrylamide gel electrophoresis only when isolated envelopes were dansylated. Acid hydrolysis of fluorescent cell envelopes of Salmonella typhimurium yielded O-dansyltryosine and epsilon-N-dansyl-lysine besides the free sulfonic acid and unidentified compounds. However, no fluorescent proteins were detectable in cell envelopes isolated from dansylated intact bacteria from Salmonella typhimurium. In accord Acholeplasma laidlawii showed only fluorescence from proteins with a molecular weight higher than 100000.


What's in a name? Address practices in Swedish residential care facilities.
Encountering residents living with dementia who come from diverse linguistic and cultural backgrounds is a common aspect of everyday life in residential care homes. These facilities may have systems of address that differ from those used in residents' respective cultures of origin. Residents' forms of address are elements of identity established in accordance with their life histories. The aim of this article is to investigate empirically the role of address forms for residents and care-providing staff in multilingual residential settings. The findings rely on observational and interactional data as well as interviews. The observational and interactional data includes 23 participants, consisting of five residents and 18 members of care-providing staff. The interviews consist of informal conversations and a corpus based on open-ended interviews with 21 staff members and five residents in two residential homes in Sweden. On the one hand, the findings indicate that addressing the residents with their first name is a prevalent address practice by the staff. They also displayed 20 additional types of address practices. On the other hand, these practices, which are chosen with the best of intentions, often seem to be inconsistent with the residents' preferred address forms. These data lend support to the large body of gerontological literature arguing that sensitivity to the life histories of residents, here the established forms of address, is vital to sustaining their identity.


Effects of embryonic exposure to chromium (VI) on blood parameters and liver microstructure of 1-day-old chickens.
Hexavalent chromium (Cr(VI)) has carcinogenic, nephrotoxic, hepatotoxic, and neurotoxic effects. Exposure to Cr(VI) can also lead to hematological alterations and blood biochemical changes. The literature on Cr(VI) toxicity concerns mostly adult forms of vertebrates. In this study, an attempt was made to determine the effect on the developing chicken embryo of Cr(VI) in ovo administration. It was observed that chromium affected the hatchability of chicks in a dose-dependent manner. At a dose from 25 to 250 μg per egg, Cr(VI) resulted in a statistically significant reduction of hatchability. Chromium administrated at lower doses (1.56 and 2.5 μg per egg) caused a statistically insignificant increase of hatchability. However, chromium at a level of LD50 (15.6 μg per egg) or 1/10 LD50 (1.56 per egg) did not cause major changes in hematological parameters or plasma biochemical indices in newly hatched chicks. The same doses did not lead to any histopathological changes in the liver.


Evaluation of fan-beam kilovoltage computed tomography image quality on a novel biological-guided radiotherapy platform.
A recently developed biology-guided radiotherapy platform, equipped with positron emission tomography (PET) and computed tomography (CT), provides both anatomical and functional image guidance for radiotherapy. This study aimed to characterize performance of the kilovoltage CT (kVCT) system on this platform using standard quality metrics measured on phantom and patient images, using CT simulator images as reference. Image quality metrics, including spatial resolution/modular transfer function (MTF), slice sensitivity profile (SSP), noise performance and image uniformity, contrast-noise ratio (CNR) and low-contrast resolution, geometric accuracy, and CT number (HU) accuracy, were evaluated on phantom images. Patient images were evaluated mainly qualitatively. On phantom images the MTF10% is about 0.68 lp/mm for kVCT in PET/CT Linac. The SSP agreed with nominal slice thickness within 0.7 mm. The diameter of the smallest visible target (1% contrast) is about 5 mm using medium dose mode. The image uniformity is within 2.0 HU. The geometric accuracy tests passed within 0.5 mm. Relative to CT simulator images, the noise is generally higher and the CNR is lower in PET/CT Linac kVCT images. The CT number accuracy is comparable between the two systems with maximum deviation from the phantom manufacturer range within 25 HU. On patient images, higher spatial resolution and image noise are observed on PET/CT Linac kVCT images. Major image quality metrics of the PET/CT Linac kVCT were within vendor-recommended tolerances. Better spatial resolution but higher noise and better/comparable low contrast visibility were observed as compared to a CT simulator when images were acquired with clinical protocols.


Production of collagen synthesis inhibitory lymphokine by human leukemic T-lymphocyte cell lines.
It has been previously shown that normal human peripheral blood mononuclear cells produce a soluble factor(s) that causes selective inhibition of collagen production by cultured human diploid fibroblasts, and that stimulation of the mononuclear cells by appropriate mitogens greatly enhances its production. Because of the difficulties inherent in obtaining sufficient peripheral blood lymphocytes to purify the collagen synthesis inhibitory factor (CSIF) further and to study in detail its mechanisms of action, we have examined CSIF production by several leukemic human T- and B-lymphocyte cell lines. From the 10 lines tested (4 T- and 6 B-lymphocyte cell lines), we found 2 T-lymphocyte cell lines which produced CSIF constitutively. When the effects of various lymphocyte mitogens on CSIF production by these cell lines were examined, it was found that only phorbol myristic acid was stimulatory. Further studies demonstrated that optimal CSIF production by the phorbol myristic acid-stimulated leukemic T-lymphocytes could be achieved in a chemically defined, serum-free medium. The CSIF in the supernatants from such cultures was further purified by ammonium sulfate precipitation and gel filtration chromatography and it was shown that it had similar properties to those of CSIF produced by normal human peripheral blood lymphocytes. These findings indicate that certain leukemic T-lymphocyte cell lines are capable of CSIF production in continuous cultures. These results will permit the large scale production of CSIF and a better understanding of its mechanisms of action.


Mouse forward genetics in the study of the peripheral nervous system and human peripheral neuropathy.
Forward genetics, the phenotype-driven approach to investigating gene identity and function, has a long history in mouse genetics. Random mutations in the mouse transcend bias about gene function and provide avenues towards unique discoveries. The study of the peripheral nervous system is no exception; from historical strains such as the trembler mouse, which led to the identification of PMP22 as a human disease gene causing multiple forms of peripheral neuropathy, to the more recent identification of the claw paw and sprawling mutations, forward genetics has long been a tool for probing the physiology, pathogenesis, and genetics of the PNS. Even as spontaneous and mutagenized mice continue to enable the identification of novel genes, provide allelic series for detailed functional studies, and generate models useful for clinical research, new methods, such as the piggyBac transposon, are being developed to further harness the power of forward genetics.


Akreos Adapt AO Intraocular lens opacification after vitrectomy in a diabetic patient: a case report and review of the literature.
Postoperative optic opacification of hydrophilic acrylic intraocular lenses (IOLs) is an uncommon complication leading to IOL explantation. In the past decade, several studies reported that the granular deposits responsible for the opacification were probably calcium and phosphate salts; however, the exact mechanism causing calcification of IOLs is unknown. The aim of this study is to describe clinical and laboratory findings of a case of late postoperative opacification of an aspheric hydrophilic acrylic IOL (Akreos Adapt AO) after vitrectomy. A 60-year-old woman diagnosed with cataract and severe nonproliferative diabetic retinopathy (NPDR) underwent uneventful phacoemulsification and hydrophilic acrylic IOL (Akreos Adapt AO, Bausch & Lomb) implantation in both eyes. Seven months later, the woman came back with a complaint of blurry vision in the left eye. Fundus examination revealed vitreous hemorrhage in the left eye veiling the retinal detail. A 23-gauge vitrectomy with endolaser treatment was performed in the left eye. Ten months after the vitrectomy, the patient complained of decreased visual acuity in the left eye again. On slit-lamp examination, we observed a well circumscribed centrally and paracentrally located opacification within the pupillary area localized to the anterior surface of the IOL. The IOL was explanted from the left eye together with the capsular bag, and an iris-claw lens (Artisan Aphakia OPHTEC) was implanted. The explanted IOL was examined under pathological evaluation (alizarin red method). IOL opacification is a rare event. We described a case of postoperative opacification of the Akreos Adapt AO IOL after vitrectomy in a patient with proliferative diabetic retinopathy and found the deposits on the anterior surface of the IOL consisted of calcium aggregates. Given the higher frequency of postoperative opacification observed in diabetic patients, hydrophilic acrylic IOLs should be used with caution in patients with diabetes.


Remarkable enhancement in the N2 selectivity of NH3-SCR over the CeNb3Fe0.3/TiO2 catalyst in the presence of chlorobenzene.
The simultaneous removal of NOx and dioxins is the frontier of environmental catalysis, which is still in the initial stage and poses several challenges. In this study, a series of CeNb3Fex/TiO2 (x = 0, 0.3, 0.6, and 1.0) catalysts were prepared by the sol-gel method and examined for the synergistic removal of NOx and CB. The CeNb3Fe0.3/TiO2 catalyst exhibits an optimum catalytic performance, with an NOx conversion greater than 95% at 260-380 °C. It also exhibits an optimal CB oxidation activity, in which CB promoted both the NOx conversion and N2 selectivity below 250 °C. Moreover, the more favorable ratios of Ce4+ to Ce3+ and plentiful surface-adsorbed oxygen species are the reasons why CeNb3Fe0.3/TiO2 catalyst has better catalytic activity than other catalysts at the lower temperature. Simultaneously, owing to the modulation of Fe to the redox properties of Ce and Nb, the large number of oxygen vacancies and acid sites was generated, and the CeNb3Fe0.3/TiO2 catalyst is beneficial to NOx reduction and CB oxidation. Furthermore, the results of in situ DRIFTS study reveal the NH3-SCR reactions over CeNb3Fe0.3/TiO2 catalysts are mainly conformed to by the L-H mechanism (< 350 °C) and E-R mechanism (> 350 °C), respectively, and the multi-pollutant conversion mechanism in the synergistic reaction was systematically studied.


Interaction of Berberine derivative with protein POT1 affect telomere function in cancer cells.
The protein POT1 plays an important role in telomere protection, which is related with telomere elongation and cell immortality. The protein has been recognized as a promising drug target for cancer treatment. In the present study, we cloned, overexpressed in Escherichia coli for the first time, and purified recombinant human POT1. The protein was proved to be active through filter binding assay, FRET and CD experiments. In the initial screening for protein binding ligands using SPR, compound Sysu-00692 was found to bind well with the POT1, which was confirmed with EMSA. Its in vivo activity study showed that compound Sysu-00692 could interfere with the binding between human POT1 and the telomeric DNA through chromatin immunoprecipitation. Besides, the compound showed mild inhibition on telomerase and cell proliferation. As we know, compound Sysu-00692 is the first reported POT1-binding ligand, which could serve as a lead compound for further improvement. This work offered a potentially new approach for drug design for the treatment of cancers.


Sacrospinous ligament fixation for hysteropexy: does concomitant anterior and posterior fixation improve surgical outcome?
Uterine preservation in uterine prolapse is an option for young patients. We hypothesized that sacrospinous hysteropexy (SSH) with anchorage to both the anterior and posterior cervix (SSH-ap) would have a better outcome than SSH with anchorage to the posterior cervix only (SSH-p). This was a retrospective study including 75 patients who underwent SSH at Chang Gung Memorial Hospital between March 2008 and August 2013. Five were excluded due to incomplete data. Of the remaining 70 patients, 35 underwent SSH-p between March 2008 and June 2011, and 35 underwent SSH-ap between June 2010 and August 2013. The primary outcome was the objective anatomical result, and a successful outcome was considered anatomical correction (POP-Q stage 1 or less) of anterior and apical prolapse. Subjective outcome was evaluated using the POPDI-6 questionnaire, and a patient response of "No or mild abdominal organ falling out sensation" together with "No or mild heaviness" was considered to indicate a successful outcome. Anterior fornix and cervical diameter measurements were included. The secondary outcome was quality of life according to the UDI-6, IIQ-7, POPDI-6, and PISQ-12 questionnaires. The 3-year outcome was used for comparison. The subjective overall cure rates were significantly different between the SSH-p and SSH-ap groups (74.3% and 94.3%, respectively; p = 0.023). However, the objective overall cure rates were not significantly different (74.3% and 82.9%, respectively). Anchorage of the anterior cervix and vaginal wall together with the usual posterior anchorage yield better subjective outcomes and apical suspension at 3 years after surgery than anchorage of the posterior cervix and vaginal wall only. The cervix position affected the subjective outcome. Concurrent trachelectomy did not affect the outcome.


Fatigue fracture of the distal femur arising in the elderly.
Fatigue fractures most frequently involve the tibia and metatarsal bones in the young. We report a very unusual case of fatigue fracture in the distal femur of a 62-year-old man. The differential diagnosis was a pathological fracture due to a metastatic bone tumor. The diagnosis of fatigue fracture was based on the fact that the patient walked every day for a long time, together with the following radiological features: no definite cortical destruction, a radiolucent area surrounded by sclerosis on CT, no extraskeletal mass, and sharp linear low signal intensities in the center of the lesion on MR images. Rest and restricted walking improved his symptoms and fracture healing. Fatigue fracture should be ruled out even in the elderly, especially those who engage in sports activities for long periods.


Efficacy of inhaled N-acetylcysteine monotherapy in patients with early stage idiopathic pulmonary fibrosis.
Idiopathic pulmonary fibrosis (IPF) is a fatal disorder for which there are currently no specific or effective medical treatments. A multicentre, prospective, randomized, controlled clinical trial was conducted to assess the efficacy of inhaled N-acetylcysteine (NAC) monotherapy in Japanese patients with early stage IPF. Eligible patients had well-defined IPF of mild-to-moderate severity, with no desaturation on exercise. Of 100 patients screened, 76 were randomly assigned to an NAC treatment group (group A; n = 38) that received 352.4 mg of NAC by inhalation twice daily or to a control group (group B; n = 38) that received no therapy. The primary endpoint was the change from baseline in forced vital capacity (FVC) at 48 weeks. There were no significant overall differences in the change in FVC between groups A and B. Post hoc exploratory analyses showed that NAC therapy was associated with stability of FVC in (i) a subset of patients with initial FVC <95% of predicted (n = 49; difference in FVC decline 0.12 L; P = 0.02) and (ii) in patients with initial diffusing capacity of carbon monoxide <55% of predicted (n = 21; difference in FVC decline 0.17 L; P = 0.009). These findings indicate that NAC monotherapy may have some beneficial effect in patients with early stage IPF. Further trials in more select IPF populations with progressive disease are required to prove the efficacy of inhaled NAC.


Diode laser transscleral cyclophotocoagulation in the treatment of refractory glaucoma with iris melanocytoma.
Iris melanocytoma is a rare melanocytic nevus with distinctive clinical and pathologic features. Secondary glaucoma may develop rapidly and respond poorly to glaucoma medication in some cases. However, few data are available in the literature with respect to the appropriate treatment for refractory glaucoma associated with iris melanocytoma. Herein, we present a 28-year-old man with blurred vision and an elevated intraocular pressure (IOP) of 40 mmHg in his right eye while on multiple glaucoma medications. A dark brown lobulated iris mass with surrounding small pigmented lesions was noted between the 4 and 5:30 o'clock positions. Sector iridectomy was performed and pathologic examination revealed an iris melanocytoma. After surgery, antiglaucomatous medications still failed to control IOP. The patient then underwent diode laser transscleral cyclophotocoagulation (TSCP). At the last follow-up of 15 months, IOP had returned to normal without the need for medication.


Rubella immune status among immigrant and nonimmigrant women in Spain.
A cross-sectional study of seroprevalence of rubella antibodies was carried out in all immigrant pregnant women (1,627) from February 2006 to June 2010. For each immigrant woman one Spanish pregnant woman was recruited. The seroprevalence of IgG antibodies against rubella in immigrant women was 92% (95% confidence interval [CI]: 90.4-93.3), and in native women was 97.7% (95%CI: 96.7-98.4) (P < 0.001). Immunity against was lowest among women from Latin America (odds ratio [OR]: 0.17), followed by women from Asia (OR: 0.20), Sub-Saharan Africa (OR: 0.27) and Northern Africa (OR: 0.37). Female immigrants from developing countries should be targeted for immunization to reduce the risk of congenital rubella.


Novel screening strategy reveals a potent Bacillus antagonist capable of mitigating wheat take-all disease caused by Gaeumannomyces graminis var. tritici.
Take-all is a severe root disease of wheat worldwide that is caused by the soilborne fungal pathogen Gaeumannomyces graminis var. tritici (Ggt). In this study, 272 Bacillus isolates were screened for their antifungal activity in vitro to Ggt. Of the 128 strains that demonstrated an antagonistic action, 24 of these exhibited at least three of the four plant growth promotion parameters (i.e. indole acetic acid and siderophore production, inorganic phosphorus solubilization and organic phosphorus solubilization) that were tested in wheat plants. The most effective strain found was Bacillus subtilis Pnf-12; its disease reduction effect reached 69%. Pnf-12 also caused a significant improvement (P < 0·05) in the root and shoot weights of wheat plants, though their root length and shoot height were similar to the noninoculated treatment (P > 0·05). The mechanism for this disease control may be linked to the production of the antifungal lipopeptides surfactin, iturin and fengycin production, all of which were detected in the cell-free supernatant of Pnf-12. Take-all, which is caused by the soilborne fungal pathogen Gaeumannomyces graminis var. tritici (Ggt), is one of the most widespread and devastating root diseases of wheat plants. This study focuses on a novel screening strategy of Bacillus isolates to evaluate their potential biological control capacity for suppressing wheat take-all. The joint assessment of antifungal activities, growth promotion factors and variety of antibiotic synthesis genes, in addition to greenhouse experiments, allowed for the identification and demonstration of the Bacillus isolate Pnf-12 as an effective disease control agent.


Piroplasmal sporozoites in the Argasid Ornithodoros erraticus (Lucas).
The infective forms of Nuttallia meri, a small-mammal piroplasm, first appear as spindle-shaped sporozoites in and around the salivary glands of Ornithodoros erraticus (small race) 30 days after the ticks had fed on infected blood. O. erraticus is the only soft tick so far proved to transmit a piroplasm.


Risk factors and management approach for deep sternal wound infection after cardiac surgery at a tertiary medical centre.
Deep sternal wound infection (DSWI) is a rare but severe complication following cardiac surgery. Our study investigated the risk factors and treatment options for patients who developed DSWI at our institution between May 1988 and April 2008. Data was collected prospectively in a database and information on demographics reviewed retrospectively on 5649 patients who underwent cardiac surgery during this period. The incidence of DSWI was 34/5649 (0.6%). These patients were older (mean age 66.1 vs. 64.5), more likely to die (in hospital mortality 11.8% vs. non DSWI group 1.8%) and had longer hospital stays (DSWI group mean stay 25 days vs. non DSWI group 9 days). Using Fisher's exact test the risk predictors for DSWI determined at our institution included diabetes managed with oral medications (p=0.021), previous cardiac surgery (p=0.038), BMI≥30 (p=0.041), LVEF≤30 (p=0.010), IABP usage (p=0.028) and homologous blood usage (p<0.001). Most commonly bilateral pectoralis major muscle flap (BPMMF) was used for treatment of DSWI (11/30, 36.7%). Ultimately our data was comparable to published data in the literature on known risk predictors.


Feasibility of a hospital-based, family-centered intervention to reduce weight gain in overweight children and adolescents.
To evaluate the effects of a hospital-based, family-centered lifestyle program (Kids N Fitness) on weight and health in overweight 7-17-year-old children. The Kids N Fitness program consisting of up to twelve 90-min sessions was conducted in an outpatient setting. The program comprised interactive nutrition and exercise sessions with behavior modification. Subjects completed a logbook and child's health questionnaire. Measures and surveys were taken before, during, and after the program. Two hundred and sixty-four overweight children (137 female, 73% Hispanic), mean age 11.5+/-2.1 years, with body mass index (BMI)=85th percentile, no physical limitations, and attendance of >or=50% of sessions. A subgroup of 115 children was observed for up to 6 months prior to program. INTERVENTION RESULTS: Weight and BMI velocity, and BMI, and BMI z-score were lower during the program than during the pre-program observation period. Compared, subjects in the 12-week program had significantly reduced gains in weight and greater losses in body mass index, than in 8 weeks. Improvements in emotional well-being and behavior correlated positively with weight loss (p=0.005). Positive health outcomes suggest that family-centered programs, stressing healthy eating strategies, participation in team-oriented physical activities, and behavior modification, are effective in improving weight dynamics and psychological functioning.


Association Between Shared Decision-Making During Family Meetings and Surrogates' Trust in Their ICU Physician.
Although trust is central to successful physician-family relationships in ICUs, little is known about how to promote surrogates' trust of ICU physicians in this setting. Does the conduct of family conferences and physicians' use of shared decision-making (SDM) within family conferences impact surrogates' trust in the physician? A mixed-methods secondary analysis was done of a multicenter prospective cohort study of 369 surrogate decision-makers of 204 decisionally incapacitated patients at high risk of death or severe functional impairment within 13 ICUs at six US medical centers between 2008 and 2012. Surrogates completed the Abbreviated Wake Forest Physician Trust Scale (range, 5-25) before and after an audio-recorded family conference conducted within 5 days of ICU admission. We qualitatively coded transcribed conferences to determine physicians' use of five SDM behaviors: discussing surrogate's role, explaining medical condition and prognosis, providing emotional support, assessing understanding, and eliciting patient's values and preferences. Using multivariable linear regression with adjustment for clustering, we assessed whether surrogates' trust in the physician increased after the family meeting; we also examined whether the number of SDM behaviors used by physicians during the family meeting impacted trust scores. In adjusted models, conduct of a family meeting was associated with increased trust (average change, pre- to post family meeting: 0.91 point [95% CI, 0.4-1.4; P < .01]). Every additional element of SDM used during the family meeting, including discussing surrogate's role, providing emotional support, assessing understanding, and eliciting patient's values and preferences, was associated with a 0.37-point increase in trust (95% CI, 0.08-0.67; P = .01). If all four elements were used, trust increased by 1.48 points. Explaining medical condition or prognosis was observed in nearly every conference (98.5%) and was excluded from the final model. The conduct of family meetings and physicians' use of SDM behaviors during meetings were both associated with increases in surrogates' trust in the treating physician.


Machine learning enables new insights into genetic contributions to liver fat accumulation.
Excess liver fat, called hepatic steatosis, is a leading risk factor for end-stage liver disease and cardiometabolic diseases but often remains undiagnosed in clinical practice because of the need for direct imaging assessments. We developed an abdominal MRI-based machine-learning algorithm to accurately estimate liver fat (correlation coefficients, 0.97-0.99) from a truth dataset of 4,511 middle-aged UK Biobank participants, enabling quantification in 32,192 additional individuals. 17% of participants had predicted liver fat levels indicative of steatosis, and liver fat could not have been reliably estimated based on clinical factors such as BMI. A genome-wide association study of common genetic variants and liver fat replicated three known associations and identified five newly associated variants in or near the MTARC1, ADH1B, TRIB1, GPAM, and MAST3 genes (p < 3 × 10-8). A polygenic score integrating these eight genetic variants was strongly associated with future risk of chronic liver disease (hazard ratio > 1.32 per SD score, p < 9 × 10-17). Rare inactivating variants in the APOB or MTTP genes were identified in 0.8% of individuals with steatosis and conferred more than 6-fold risk (p < 2 × 10-5), highlighting a molecular subtype of hepatic steatosis characterized by defective secretion of apolipoprotein B-containing lipoproteins. We demonstrate that our imaging-based machine-learning model accurately estimates liver fat and may be useful in epidemiological and genetic studies of hepatic steatosis.


Construction of Porous Mo3 P/Mo Nanobelts as Catalysts for Efficient Water Splitting.
A novel synthesis strategy is demonstrated to prepare Mo3 P/Mo nanobelts with porous structure for the first time. The growth and formation mechanism of the porous Mo3 P/Mo nanobelt structure was disclosed by varying the contents of H2 /PH3 and the reaction temperature. During the hydrogen evolution reaction (HER) catalysis, the optimized porous Mo3 P/Mo nanobelts exhibited a small overpotential of 78 mV at a current density of 10 mA cm-2 and a low Tafel slope of 43 mV dec-1 , as well as long-term stability in alkaline media, surpassing Pt wire. Density functional theory (DFT) calculations reveal that the H2 O dissociation on the surface of Mo3 P is favorable during the HER.


Population differentiation of migratory directions in birds: comparison between ringing results and orientation behaviour of hand-raised migrants.
Blackcaps (Sylvia atricapilla) from five areas in Central Europe were hand-raised. Their autumn migratory orientation was tested in funnel-shaped cages. Their directional choices were compared to recoveries of conspecifics ringed during the breeding season in the same areas, which are situated on a transect across a migratory divide between southeastward and southwestward migrating populations. Results from ringing and orientation tests were in good agreement with respect to mean direction and dispersion of flight directions. An exception is the area around Linz (NW Austria), right on the migratory divide, where ringing yielded a strong scatter, but hand-raised birds chose westerly directions. The recent establishment of a novel migration route toward the British Isles was reflected in both data sets: in southern Germany the percentage of northwestward migrants is 6.8% according to orientation tests and 11.8% according to ringing recoveries. Testing the orientation of young passerines in captivity can yield valuable information about population differentiation of migratory behaviour. It is more efficient than ringing in this respect, because it circumvents the low recovery rates and is free of biases affecting ringing data. In the blackcap, geographic differentiation of migratory directions occurs on a finer scale than previously recognized and can change significantly within 2-3 decades.


Dietary and Microbial Determinants in Food Allergy.
The steep rise in food allergy (FA) has evoked environmental factors involved in disease pathogenesis, including the gut microbiota, diet, and their metabolites. Early introduction of solid foods synchronizes with the "weaning reaction," a time during which the microbiota imprints durable oral tolerance. Recent work has shown that children with FA manifest an early onset dysbiosis with the loss of Clostridiales species, which promotes the differentiation of ROR-γt+ regulatory T cells to suppress FA. This process can be reversed in pre-clinical mouse models by targeted bacteriotherapy. Here, we review the dominant tolerance mechanisms enforced by the microbiota to suppress FA and discuss therapeutic intervention strategies that act to recapitulate the early life window of opportunity in stemming the FA epidemic.


Evolution of coronavirus frameshifting elements: Competing stem networks explain conservation and variability.
The frameshifting RNA element (FSE) in coronaviruses (CoVs) regulates the programmed -1 ribosomal frameshift (-1 PRF) mechanism common to many viruses. The FSE is of particular interest as a promising drug candidate. Its associated pseudoknot or stem loop structure is thought to play a large role in frameshifting and thus viral protein production. To investigate the FSE structural evolution, we use our graph theory-based methods for representing RNA secondary structures in the RNA-As-Graphs (RAG) framework to calculate conformational landscapes of viral FSEs with increasing sequence lengths for representative 10 Alpha and 13 Beta-CoVs. By following length-dependent conformational changes, we show that FSE sequences encode many possible competing stems which in turn favor certain FSE topologies, including a variety of pseudoknots, stem loops, and junctions. We explain alternative competing stems and topological FSE changes by recurring patterns of mutations. At the same time, FSE topology robustness can be understood by shifted stems within different sequence contexts and base pair coevolution. We further propose that the topology changes reflected by length-dependent conformations contribute to tuning the frameshifting efficiency. Our work provides tools to analyze virus sequence/structure correlations, explains how sequence and FSE structure have evolved for CoVs, and provides insights into potential mutations for therapeutic applications against a broad spectrum of CoV FSEs by targeting key sequence/structural transitions.


System-Level Patient Safety Practices That Aim to Reduce Medication Errors Associated With Infusion Pumps: An Evidence Review.
In this literature review, we discuss 2 system-level, nurse-targeted patient safety practices (PSPs) that aim to reduce medication errors associated with infusion pumps, including smart pumps. One practice focuses on implementing structured process changes and redesigning workflows to improve efficiencies with pump use. The other focuses on investing in initial and ongoing staff training on the correct use, maintenance, and monitoring of infusion pumps. Two databases were searched for "infusion pumps" and related synonyms, along with relevant terms for each PSP. Articles were excluded if outcomes were not directly relevant to the PSP addressed in this review, the article was out of scope, or study design was insufficiently described. Limited research was found on best practices for reducing errors and improving infusion pump use through workflow and process changes, as well as education and training. Four studies reported medication administration errors, procedural errors, or deviations from hospital policy as clinical outcomes of workflow or process changes. Mixed results were found examining process outcomes related to pump handling. Education on the correct use of smart pumps was found to decrease medication errors and adverse drug events, and 2 studies found an increase in nurses' adherence to using the medication safety software library as a result of education. Standardization of process and integration of technology and workflows were found as facilitators. Type and content of education provided were identified as facilitators, whereas time and energy constraints on nurse educators can be barriers to implementing large hospital-wide education programs.


A putative NEM1 homologue regulates lipid droplet biogenesis via PAH1 in Tetrahymena thermophila.
Nuclear envelope morphology protein 1 (NEM1) along with a phosphatidate phosphatase (PAH1) regulates lipid homeostasis and membrane biogenesis in yeast and mammals. We investigated four putative NEM1 homologues (TtNEM1A, TtNEM1B, TtNEM1C and TtNEM1D) in the Tetrahymena thermophila genome. Disruption of TtNEM1B, TtNEM1C or TtNEM1D did not compromise normal cell growth. In contrast, we were unable to generate knockout strain of TtNEM1A under the same conditions, indicating that TtNEM1A is essential for Tetrahymena growth. Interestingly, loss of TtNEM1B but not TtNEM1C or TtNEM1D caused a reduction in lipid droplet number. Similar to yeast and mammals, TtNem1B of Tetrahymena exerts its function via Pah1, since we found that PAH1 overexpression rescued loss of Nem1 function. However, unlike NEM1 in other organisms, TtNEM1B does not regulate ER/nuclear morphology. Similarly, neither TtNEM1C nor TtNEM1D is required to maintain normal ER morphology. While Tetrahymena PAH1 was shown to functionally replace yeast PAH1 earlier, we observed that Tetrahymena NEM1 homologues did not functionally replace yeast NEM1. Overall, our results suggest the presence of a conserved cascade for regulation of lipid homeostasis and membrane biogenesis in Tetrahymena. Our results also suggest a Nem1-independent function of Pah1 in the regulation of ER morphology in Tetrahymena.


Patient Expectations of Adult Spinal Deformity Correction Surgery.
There is a growing interest in examining preoperative expectations as a potential predictor of postoperative outcome. However, it has never been studied in the setting of adult spinal deformity (ASD). This study aims to characterize patient expectations before ASD surgery and examine the relationship between preoperative expectation and postoperative patient-reported outcomes (PROs). Analysis of prospectively collected clinical and PRO data was performed on patients who underwent ASD surgery. Inclusion criteria were age >18 years, a diagnosis of ASD, >3 vertebral level instrumentation, and completed pre- and postoperative surveys. The preoperative expectation survey included expectations of surgical outcome, pain reduction, complications, and the duration of postoperative recovery. Relationships between patient expectations and PROs were assessed. Twenty-seven patients who underwent operative management of ASD met the inclusion criteria. In their preoperative survey, 66% of patients expected highly successful surgery, whereas 22% had a moderate expectation of complications. Patients anticipated an average 71% reduction in back pain (range 42%-100%) and 68% reduction in leg pain (range 0%-100%). Patients who met their expectations of leg pain reduction had significantly greater satisfaction scores than those who did not. There were moderate-to-strong positive correlations between preoperative expectation and observed improvement in back pain, leg pain, and mental health. While substantial variability in patient expectation exists for the surgical management of ASD, patients anticipated a positive outcome with a significant reduction in pain. Greater postoperative satisfaction was associated with patients who met the expected improvement in leg pain. Preoperative expectation was positively correlated with change in pain and mental health scores.


Externalities of energy sources: The operation of a municipal solid waste-to-energy incineration facility in the greater Thessaloniki area, Greece.
There is much debate around promoting waste to energy incineration facilities in many communities globally, mainly because of social opposition against potential negative health effects of the operation of these installations close to urban areas. In this paper, a novel decision support approach is developed and its applicability is demonstrated for the greater Thessaloniki area, Greece. In this area, the incineration facilities are hotly debated, mainly due to the "Not In My Back Yard" syndrome related with health considerations. The exclusive method of treatment is landfilling. Health impacts and corresponding externalities attributed to the operation of an incineration facility are reliably estimated. Three potential alternative sites and three scenarios of emission rates are considered, depending on the abatement technology used. The estimated externalities are compared to the corresponding ones attributed to other pressures in the area. The "Years of Life Lost (YOLL)" indicator attributed to the operation of the facility is 2.8 YOLL in the worst-case scenario. This corresponds to a minimal added implication in comparison with the 11,044 YOLL estimated for the area due to the other environmental pressures (road traffic, space heating, industrial activity). The externalities ratio (externalities due to incineration facility/total externalities) for the region is approximately 0.03%. Thus, the impact of this operation on human health is negligible -and preferable to landfilling- even in the case that maximum emission rates are considered. Efforts should be targeted towards enhancing public awareness and militating the widely acknowledged "Not In My Back Yard" syndrome by local communities.


Does a predialysis education program increase the number of pre-emptive renal transplantations?
Renal transplantation (RT) is the most appropriate form of treatment for end-stage renal disease (ESRD). Pre-emptive RT decreases the rates of delayed graft function and acute rejection episodes, increasing patient and graft survival, while reducing costs and complications associated with dialysis. In this study, we investigated the relationship between a predialysis education program (PDEP) for patients and their relatives and pre-emptive RT. We divided 88 live donor kidney transplant recipients into 2 groups: transplantation without education (non-PDEP group; n = 27), and enrollment in an education program before RT (PDEP group n = 61). Five patients in the non-PDEP group underwent pre-emptive transplantation, versus 26 of the PDEP group. The rate of pre-emptive transplantations was significantly higher among the educated (42.62%) versus the noneducated group (18.51%; P < .001). PDEP increased the number of pre-emptive kidney transplantations among ESRD patients.


The effect of the irrigant QMix on removal of canal wall smear layer: an ex vivo study.
The aim of this study is to evaluate the effectiveness over application time of different formulations of a novel endodontic irrigant (QMix™ 2in1) composed of a polyaminocarboxylic acid chelating agent, a bisbiguanide antimicrobial agent, a surfactant and deionized water to remove the root canal smear layer and expose patent dentinal tubules compared to a standard solution of 17% EDTA. Eighty human tooth roots from extracted, single-rooted teeth were instrumented (size 40.06) using 0.2 mL of sodium hypochlorite (6.15%) between each file size with a 3 mL water rinse after final instrumentation. Eight groups of 10 roots were irrigated with 3 mL of different formulations of QMix: QMix A, QMix B, and QMix C, or 17% EDTA for 60 and 90 s, respectively, then rinsed with 5 mL of sterile water. The roots were irrigated using a standard irrigation syringe and a 30 ga side-vent needle with an apical-coronal motion to within 1 mm of the working length. The coronal, middle and apical thirds of one canal surface of each root was evaluated at 1000× using scanning electron microscopy. The presence of smear layer was scored using a 5-point scale. Data were analyzed with the Kruskal-Wallis rank sums test, the Steel-Dwass, all-pairs comparison test, and the Steel method (with control) test. Irrigant type was highly significant (p < 0.007). Combined 60 and 90 s exposure data indicated QMix A (p = 0.014) and QMix C (p = 0.028) were superior to EDTA. While at the 90 s exposure time, smear layer removal by solutions QMix A (p = 0.043), QMix B (p = 0.018), and QMix C (p = 0.011) was superior to EDTA. All irrigants removed smear layer more effectively at the coronal and middle levels compared to the apical level (p < 0.001). Analysis showed all three QMix formulations were superior to EDTA in smear layer removal and exposure of dentinal tubules in the root canal system in single-rooted teeth.


A Multi-Sectoral Approach Improves Early Child Development in a Disadvantaged Community in Peru: Role of Community Gardens, Nutrition Workshops and Enhanced Caregiver-Child Interaction: Project "Wawa Illari".
Background: Multi-dimensional monitoring evaluation and learning strategies are needed to address the complex set of factors that affect early child development in marginalized populations, but few studies have explored their effectiveness. Objective: To compare improvement of health and development of children 0-3 years between intervention communities (IC) and control communities (CC) from peripheral settlements of Lima. Sequential interventions included: (1) home and community gardens, (2) conscious nutrition, and (3) parenting workshops following the International Child Development Program (ICDP). Methods: Interventions were delivered by community health promoters (CHPs) using a "step-by-step" learning system. Both IC and CC were monitored before the interventions began, at 8 and 12 months (n = 113 IC and 127 CC children). Data were collected on household characteristics, diet, food security, health indicators (history of diarrhea and respiratory infections, hemoglobin, intestinal parasites, anthropometry), caregiver-child interactions and stress, and achievement of Pan-American Health Organization age-specific developmental milestones. Stepwise multiple logistic regressions were used to determine if the interventions affected food insecurity, as well as motor, social/cognitive and language delays. Results: At baseline, 2.6% were categorized as "suspected developmental delay" and 14.2% were on "alert for development delay." Food insecurity, diarrhea and respiratory infections were lowered following the interventions. Through the "step-by-step" approach, caregivers in IC gained skills in gardening, conscious nutrition and parenting that reduced the risk of food insecurity [Adjusted Risk Ratio = 0.20 (95% CI: 0.08-0.51)] and language delay [0.39 (0.19-0.82)] but not motor or social/cognitive delay. Use of a multiple micronutrient supplement decreased the risk of motor delay [0.12 (0.03-0.56)], but more pets were associated with higher risk of motor [3.24 (1.47-7.14)] and social/cognitive delay [2.72 (1.33-5.55)], and of food insecurity [1.73 (1.13-2.66)]. Conclusion: The combined interventions delivered by CHPs helped to mitigate the impact of adversity on food insecurity and language delay. Additional improvements may have been detected if the interventions had continued for a longer time. Our results indicate that control of infections and pets may be needed to achieve measurable results for motor and social/cognitive development. Continuous monitoring facilitated adjusting implementation strategies and achieving positive developmental outcomes.


Plant Phenylalanine/Tyrosine Ammonia-lyases.
Aromatic amino acid deaminases are key enzymes mediating carbon flux from primary to secondary metabolism in plants. Recent studies have uncovered a tyrosine ammonia-lyase that contributes to the typical characteristics of grass cell walls and contributes to about 50% of the total lignin synthesized by the plant. Grasses are currently preferred bioenergy feedstocks and lignin is the most important limiting factor in the conversion of plant biomass to liquid biofuels, as well as being an abundant renewable carbon source that can be industrially exploited. Further research on the structure, evolution, regulation, and biological function of functionally distinct ammonia-lyases has multiple implications for improving the economics of the agri-food and biofuel industries.


The role of uric acid in chronic kidney disease patients.
Chronic kidney disease (CKD) is always associated with hyperuricaemia. However, the studies evaluating the clinical implications of hyperuricaemia have shown conflicting results in these patients. A retrospective observational study was conducted in 2408 stage 3-5 CKD patients. Instead of one baseline uric acid (UA) level, the averaged level of the two consecutive measurements for each participant was used as the predictor for the outcomes of the study, which included mortality, renal outcomes, and hospitalization risk. A multivariate Cox proportional hazards model and logistic regression model were performed to determine the independent risk factor. The mean UA level was 0.46 ± 0.106 mmol/L. Of the 2408 patients, there were 563 (23.3%) deaths, 143 (5.9%) cardiovascular deaths, 652 (27%) subjects commencing renal replacement therapy (RRT), 664 (27.5%) subjects with rapid renal progression, 1937 (58%) patients requiring hospitalization and 404 (16.7%) patients with CVD hospitalization during a mean follow-up of approximately 3.03 years. After multivariate adjustments, a 1-mg/dL increase in uric acid level was associated with a hazard ratio (HR) of 1.26 for RRT (P = 0.002), an odds ratio (OR) of 1.27 for rapid renal progression (P = 0.001), an HR of 1.19 for all-cause hospitalization (P < 0.001), and an HR of 1.12 for cardiovascular disease (CVD) hospitalization (P = 0.02), but not significantly with all-cause mortality and cardiovascular death at the end of follow-up. In stage 3-5 CKD patients, hyperuricaemia was associated with a higher risk of renal replacement therapy, rapid renal progression and hospitalization for all causes or CVD, but not with all-cause mortality or cardiovascular mortality.


Detection and assessment of the phytotoxicity of residual organic pollutants in sediment contaminated with pulp and paper mill effluent.
The safe disposal of pulp and paper mill effluent is still a threat to the environment due to the presence of several unknown organic pollutants. The comparative physico-chemical analysis of pulp and paper mill effluent-contaminated sediment (PPECS) of site 1 and site 2 showed that the sediment had an alkaline nature and was loaded with several organic pollutants and heavy metals. SEM-EDX examination showed a porous structure with a heterogeneous distribution of particles, allowing the adsorption of metal and other complex organic ions. FTIR analysis depicted the presence of a variety of functional groups, i.e., alkyl halides, phenolics, and lignin, in the contaminated sediment. GC-MS analysis showed the major presence of organic pollutants, i.e., 2-methyl-4-keto-2-pentan-2-ol and 3,7-dioxa-2,8-disilanonane,2,2,8,8-tetramethyl-5-[(trimethylsilyl)oxy], in the site 1 sediment contaminated with pulp and paper mill waste, while 2-methyl-4-keto-2-trimethylsiloxypentane, 4-ethyl-2-methoxyphenol, ethyl-2-octynoate, cis-9-hexadecenoic acid, and octadecenoic acid were detected in the site 2 sediment contaminated with pulp and paper mill waste. The genotoxicity of PPECS determined by examining Allium cepa root cell division showed chromosomal aberration. In this study, several compounds that have not been reported before were identified.


The role of decompressive craniectomy in the management of traumatic brain injury: a critical review.
Brain swelling and intracranial hypertension following severe head injury are known to contribute to secondary brain damage, and have been shown to adversely affect patient outcome. The use of unilateral craniectomy following the evacuation of a mass lesion, such as acute subdural haematoma or traumatic intracerebral haematoma, is accepted practice. The following review focuses on a bi-fronto-temporal decompressive craniectomy, used as an isolated operation for the control of intracranial hypertension, secondary to diffuse brain swelling refractory to medical management. Though the operation is being increasingly used, current opinion is still divided regarding its overall effects on outcome. This review examines the experimental and clinical evidence for and against the use of decompressive craniectomy, highlights the lack of class I evidence relevant to this topic and emphasises the necessity for well-designed prospective randomised controlled trials.


Endometrioid carcinoma of the ovary presenting as primary carcinoma of the breast. A case report and review of the literature.
A case is presented of endometrioid carcinoma of the ovary, metastasizing to the breast in a 63-year old woman. Differentiation of metastatic cancer to the breast for primary breast carcinoma and discovering the primary tumor site are rather important for treatment and prognosis. Lumpectomy, followed by panhysterectomy, was performed and six courses of cisplatinum and cyclophosphamide were given. No signs of recurrence or metastasis are apparent 16 months after the discovery of the breast lesion.


Structural modifications in contraceptive steroids altering their metabolism and toxicity.
Norethisterone and, to a lesser extent, d-norgestrel are metabolically activated by rat liver microsomal enzymes to intermediates which are capable of irreversibly binding to proteins. This microsomal activation in vitro depends on presence of NADPH and is inhibited by glutathione. Irreversible binding of metabolites of progesterone, nortestosterone acetate and cyproterone acetate is very low, compared to that of norethisterone metabolites. Phenol as a reference compound shows quantitatively a similar binding behaviour as norethisterone. Norethisterone-4beta,5beta-epoxide, a microsomal metabolite of norethisterone, binds non-enzymatically to albumin, at a rate of 380 pmol/mg albumin per hour (at 37 degrees). The corresponding rate for norgestrel-4beta,5beta-epoxide, 42 pmol/mg albumin per hour, indicates a considerably lower reactivity of norgestrel-epoxide. The non-SH-proteins concanavalin A and bovine gamma-globulin do not react with either norethisterone-epoxide or norgestrel-epoxide. Also, DNA and RNA show no binding reaction. Thus, the requirements for irreversible protein binding of the 19-nortestosterone progestagens norethisterone and norgestrel are similar to those found for oestrogens which, when activated by rat liver microsomes, only bind to proteins with SH-groups, not to DNA or RNA.


Adenoviral-mediated gene transfer of insulin-like growth factor 1 enhances wound healing and induces angiogenesis.
Chronic wounds are characterized by a wound healing and neovascularization deficit. Strategies to increase neovascularization can significantly improve chronic wound healing. Insulin-like growth factor (IGF)-1 is reported to be a keratinocyte mitogen and is believed to induce angiogenesis via a vascular endothelial growth factor (VEGF)-dependent pathway. Using a novel ex vivo human dermal wound model and a diabetic-impaired wound healing murine model, we hypothesized that adenoviral overexpression of IGF-1 (Ad-IGF-1) will enhance wound healing and induce angiogenesis through a VEGF-dependent pathway. Ex vivo: 6-mm full-thickness punch biopsies were obtained from normal human skin, and 3-mm full-thickness wounds were created at the center. Skin explants were maintained at air liquid interface. Db/db murine model: 8-mm full-thickness dorsal wounds in diabetic (db/db) mice were created. Treatment groups in both human ex vivo and in vivo db/db wound models include 1×10(8) particle forming units of Ad-IGF-1 or Ad-LacZ, and phosphate buffered saline (n=4-5/group). Cytotoxicity (lactate dehydrogenase) was quantified at days 3, 5, and 7 for the human ex vivo wound model. Epithelial gap closure (hematoxylin and eosin; Trichrome), VEGF expression (enzyme-linked immunosorbent assay), and capillary density (CD 31+CAPS/HPF) were analyzed at day 7. In the human ex vivo organ culture, the adenoviral vectors did not demonstrate any significant difference in cytotoxicity compared with phosphate buffered saline. Ad-IGF-1 overexpression significantly increases basal keratinocyte migration, with no significant effect on epithelial gap closure. There was a significant increase in capillary density in the Ad-IGF-1 wounds. However, there was no effect on VEGF levels in Ad-IGF-1 samples compared with controls. In db/db wounds, Ad-IGF-1 overexpression significantly improves epithelial gap closure and granulation tissue with a dense cellular infiltrate compared with controls. Ad-IGF-1 also increases capillary density, again with no significant difference in VEGF levels in the wounds compared with control treatments. In two different models, our data demonstrate that adenoviral-mediated gene transfer of IGF-1 results in enhanced wound healing and induces angiogenesis via a VEGF-independent pathway. Understanding the underlying mechanisms of IGF-1 effects on angiogenesis may help produce novel therapeutics for chronic wounds or diseases characterized by a deficit in neovascularization.