Influence of different great trochanteric entry points on the outcome of intertrochanteric fractures: a retrospective cohort study.
The Proximal Femoral Nail Antirotation (PFNA) system for treatment of intertrochanteric fractures is currently widely applied worldwide. However, even though the PFNA has produced good clinical outcomes, a poor introduction technique with an inappropriate entry point can cause surgical complications. Some researchers suggest improving clinical outcomes by modifying the entry point, but no research has focused on this issue. The purpose of the present study is to compare the clinical and radiological outcomes of two different trochanteric entry points for the treatment of intertrochanteric fractures using the PFNA system. From May 2010 to October 2015, a total of 212 elderly patients with intertrochanteric fractures who were treated with the PFNA-II system were included into this retrospective cohort study. Group LA (98 patients) was treated using a lateral anterior trochanteric entry point, and group MP (114 patients) was treated using a medial posterior trochanteric entry point. All patients underwent follow-up assessments at 1, 3, 6, and 12 months after surgery. Radiographic evaluation was based on the impingement, tip-apex distance (TAD) and the position of the helical blade within the femoral head. Clinical evaluation was based on the surgical time, fluoroscopy time, blood loss, hospital stay, visual analogue scale (VAS), thigh pain, and Harris hip score. The impingement was significantly reduced (P = 0.011) in group MP. The helical blade positions were significantly lower (P = 0.001) in group MP. The TADs in group LA (22.40 ± 4.43) and group MP (23.39 ± 3.60) were not significantly different (P = 0.075). The fluoroscopy time of group LA (53.26 ± 14.44) was shorter than that of group MP (63.29 ± 11.12, P = 0.000). Five iatrogenic lateral proximal fractures and 3 helical blade cutouts occurred in group LA, but none occurred in group MP. At 1 and 3 months postoperation, the Harris hip scores were significantly higher in group MP (P = 0.001 and P = 0.000, respectively), and the VAS scores were lower (P < 0.05). The medial posterior trochanteric entry point achieved excellent nail and helical blade position, reduced surgical complications, and enabled early hip function recovery but required longer fluoroscopy time than the lateral anterior trochanteric entry point.


Rehabilitation of older patients: day hospital compared with rehabilitation at home. Clinical outcomes.
to test the hypothesis that older people and their informal carers are not disadvantaged by home-based rehabilitation (HBR) relative to day hospital rehabilitation (DHR). pragmatic randomised controlled trial. four geriatric day hospitals and four home rehabilitation teams in England. eighty-nine patients referred for multidisciplinary rehabilitation. The target sample size was 460. multidisciplinary rehabilitation either in the home or in the day hospital. the primary outcome measure was the Nottingham extended activities of daily living scale (NEADL). Secondary outcome measures included EQ-5D, hospital anxiety and depression scale, therapy outcome measures, hospital admissions and the General Health Questionnaire for carers. at the primary end point of 6 months NEADL scores were not significantly in favour of HBR cf. DHR; mean difference -2.139 (95% confidence interval -6.87 to 2.59, P = 0.37). A post hoc analysis suggested non-inferiority for HBR for NEADL but there was considerable statistical uncertainty. taken together the statistical analyses and lack of power of the trial outcomes do not provide sufficient evidence to conclude that patients in receipt of HBR are disadvantaged compared with those receiving DHR.


Distribution and correlation of the natural radionuclides in a coal mine of the West Macedonia Lignite Center (Greece).
The distribution and correlation of six natural nuclides in the West Macedonia Lignite Center, Northern Greece were studied. Fifty-five samples of lignite, aged from 1.8 to 5 million years, and corresponding steriles, beds of marls, clays and sands alternating with the lignite, were collected perpendicular to the mine benches and measured spectroscopically. The mean concentrations of (238)U and (226)Ra in lignites were found to be higher than that in steriles since these nuclides are associated with the organic material of lignite, whereas (238)U/(226)Ra equilibrium was not observed in either lignites or steriles. Finally, the ratio (226)Ra/(228)Ra in lignites was approximately double of that in steriles, confirming the affinity of the (238)U series with the coal matrix in contrast to the (232)Th series. No correlation was found between radionuclide concentrations and the depth of the sample, nor with the ash content of lignite.


Government environmental protection subsidies, environmental tax collection, and green innovation: evidence from listed enterprises in China.
The government has issued a series of environmental laws and regulations to solve ecological problems, regulate environmental pollution, and drive enterprises to carry out green innovations. This paper constructs a theoretical framework of environmental protection subsidies, environmental tax collection, and enterprise green innovation by taking the China A-share manufacturing listed enterprises as a research sample. Further, we explore the contingency impact of the market-expected performance gap and market competition on the enterprise green innovation. The empirical results show that there is a linear positive driving relationship between environmental protection subsidies and enterprise green innovation. The relationship between environmental tax collection and enterprise green innovation is a U-shaped relationship that first inhibits and then promotes. The market expectation performance gap moderates between environmental subsidy and enterprise green innovation. Market competition plays a reinforcing role in environmental subsidy, environmental tax collection, and enterprise green innovation. These research findings are conducive to providing theoretical support and reference for the government to encourage enterprises to actively carry out green innovation in practice, thereby helping to promote green development in the country.


GWAS-associated bacteria and their metabolites appear to be causally related to the development of inflammatory bowel disease.
Accumulating evidence has suggested that the imbalance of gut microbiota is commonly observed in patients with inflammatory bowel disease (IBD). However, it remains unclear whether dysbiosis is a cause or consequence of chronic intestinal inflammation. We aimed to investigate the causal relationships of gut microbiota and metabolites with IBD, including ulcerative colitis (UC) and Crohn's disease (CD). We applied two-sample Mendelian randomization using summary statistics from the gut microbiota genetic consortium (n = 1812), the Framingham Heart Study (n = 2076) and the International IBD Genetics Consortium (n = 86,640). Using the genetic approach, the increase in OTU10032 unclassified Enterobacteriaceae was associated with higher risks of IBD (OR, 1.03; 95% CI, 1.00-1.06; P = 0.033) and CD (1.04; 1.01-1.08; P = 0.015). Importantly, an Enterobacteriaceae-related metabolite taurine was positively associated with risks of IBD (1.04; 1.01-1.08; P = 0.016) and UC (1.05; 1.01-1.10; P = 0.024). Notably, we also found betaine, a downstream product of Enterobacteriaceae metabolism, was causally associated with a higher risk of CD (1.10; 1.02-1.18; P = 0.008). In addition, increased Erysipelotrichaceae family were causally related to lower risks of IBD (0.88; 0.78-0.98; P = 0.026) and UC (0.86; 0.75-0.99; P = 0.042), and Actinobacteria class (0.80; 0.65-0.98; P = 0.028) and Unclassified Erysipelotrichaceae (0.79; 0.64-0.98; P = 0.036) were associated with lower risks of UC and CD, respectively. Our finding provided new insights into the key role of gut metabolites such as taurine and betaine in host-microbiota interactions of IBD pathogenesis, indicating that host-microbe balance strongly influences inflammatory conditions.


The development and establishment of a heat inactivated preparation of Mycobacterium tuberculosis (H37Rv) as the first international standard for nucleic acid amplification techniques.
A need to develop an inactivated Mycobacterium tuberculosis (Mtb) preparation, to be used as a DNA standard, as an important and urgent requirement for Tuberculosis (TB) diagnostics standardization was identified in 2018. A candidate material was generated using a heat inactivated culture of Mtb strain H37Rv. A lyophilised preparation was evaluated for its suitability as an International Standard for molecular detection of Mtb DNA in an international collaborative study. Together with the use of quantitative PCR assays and rapid diagnostic tests, this candidate standard was demonstrated to be fit-for-purpose. Based on the results from this collaborative study, it is proposed this lyophilised heat inactivated Mtb preparation (NIBSC code: 20/152) to be established by the World Health Organization Expert Committee on Biological Standardization, as the First WHO International Standard for Mycobacterium tuberculosis (H37Rv) for nucleic acid amplification techniques with an assigned unitage of 6.3 log10 or 2 × 106 International Units per vial. The intended uses of this IS are for calibration of secondary or in-house reference preparations used in the assays for the molecular detection of Mtb DNA. It may also be used for assay validation and monitoring the performance in terms of limit of detection of rapid diagnostic tests.


Fully automated method for glaucoma screening using robust optic nerve head detection and unsupervised segmentation based cup-to-disc ratio computation in retinal fundus images.
Visual impairment affects a significant part of the population worldwide. Glaucoma is one of these main causes, a chronic eye disease leading to progressive vision loss. Early glaucoma screening is an important task, allowing a slowing down of the pathology spreading and avoidance of irreversible vision damages. When manual assessment by experts suffers from disadvantages, exploiting the relevant Cup-to-Disc Ratio (CDR) feature as a structural indicator to assess the damage to the optic nerve head (ONH) is an efficient way for early glaucoma screening and diagnosis. In this paper, we propose a new fully automated methodology for glaucoma screening and diagnosis from retinal fundus images. In order to allow eye examination in remote locations with limited access to clinical facilities, we focus in this work on the development of a computationally-efficient algorithm for further implementation on mobile devices. First, the method provides a robust optic disc (OD) detection method, combining a brightness criterion and a template matching technique, to effectively detect the optic disc (OD) even in the presence of bright lesions associated to pathological cases. Second, an efficient optic cup (OC) and optic disc (OD) segmentation is performed, using a texture-based and model-based approach. Finally, Cup-to-Disc Ratio (CDR) computation leads to glaucoma screening with a classification between healthy and glaucomatous patients. The proposed approach for glaucoma screening and diagnosis have been tested on the publicly available DRISHTI-GS1 dataset. Fifty retinal images are provided and labeled healthy or glaucomatous by trained specialists. The method achieves 98% of accuracy on final glaucoma screening and diagnosis, and excellent performance rates on evaluation metrics, outperforming the state-of-the-art CDR feature-based approaches. We proposed a fully automated method for glaucoma screening and diagnosis from retinal images. Excellent performance was obtained on final screening, classifying healthy and glaucomatous subjects. As it effectively detects the presence of glaucoma, in a low-computational manner, the approach can be part of a mobile help-diagnosis system, to improve the final diagnosis by the specialist and develop widespread visual health programs.


A fast-responsive fluorescent probe for detection of gold ions in water and synthetic products.
We have constructed a fast-responsive fluorescent gold ion probe based on the unexpected gold ion-mediated hydrolysis of acylsemicarbazides to carboxylic acids. The probe has been applied for sensing gold ions in the living cells and detecting residual gold content in gold-catalyzed synthetic samples for the first time.


Interactions Between Phosphorus, Zinc, and Iron Homeostasis in Nonmycorrhizal and Mycorrhizal Plants.
Phosphorus (P), zinc (Zn), and iron (Fe) are three essential elements for plant survival, and severe deficiencies in these nutrients lead to growth retardation and crop yield reduction. This review synthesizes recent progress on how plants coordinate the acquisition and signaling of Pi, Zn, and Fe from surrounding environments and which genes are involved in these Pi-Zn-Fe interactions with the aim of better understanding of the cross-talk between these macronutrient and micronutrient homeostasis in plants. In addition, identification of genes important for interactions between Pi, Zn, and/or Fe transport and signaling is a useful target for breeders for improvement in plant nutrient acquisition. Furthermore, to understand these processes in arbuscular mycorrhizal plants, the preliminary examination of interactions between Pi, Zn, and Fe homeostasis in some relevant crop species has been performed at the physiological level and is summarized in this article. In conclusion, the development of integrative study of cross-talks between Pi, Zn, and Fe signaling pathway in mycorrhizal plants will be essential for sustainable agriculture all around the world.


Human autologous rosette-forming cells. II. Specificity of the binding between lymphocytes and erythrocytes.
The relationship between autorosettes and allorosettes was investigated using a mixed rosette assay in which the origin of the erythrocytes was assessed by the fluorescein isothiocyanate (FITC) labeling of one type of erythrocyte. The data show that auto- and allorosettes belong to the same T-cell subset: in most of the subjects, the percentages of T cells binding autologous red blood cells (auto-RBC) are equivalent to those binding allogeneic RBC (allo-RBC); the percentage of rosettes formed after the simultaneous addition of auto- and allo-RBC is similar to that of autorosettes alone or allorosettes alone; and nearly 80% of the rosetting cells bind both types of RBC as directly visualized in the mixed rosette assay. The experiments in which the lymphocytes are rosetted first with one type of RBC, and then with the other type support the finding that auto- and allo-RBC may bind to the lymphocytes through a single receptor which exhibits a varying affinity for RBC according to their origin.


Coupling AFM and CLSM to investigate the effect of ageing on the bee structures of bitumen.
Bitumen's surface microstructure is in general well-documented and most recent theories postulate the effect of crystalline wax on the so-called bee structures. Although it is widely accepted that ageing has an effect on this unique microstructure yet conflicting literature exists on clear trends. This paper explores the effect of ageing on the bee structures of bitumen, employing two advanced microscopic techniques: an Atomic Force Microscopy (AFM) and a Confocal Laser Scanning Microscopy (CLSM). Four waxy and two wax-free bituminous binders are investigated before and after sequential laboratory short- and long-term ageing. The study demonstrates that the number of bees per μm2 and bee area percentage decrease with ageing, whereas their size is increasing. A systematic analysis of the waveform characteristics is also provided for the peaks and valleys as well as the shape probabilistic values of the bee structures. In conclusion, the results of the two techniques are in good agreement, reporting similar trends upon ageing for the relative bee density. Differences are mainly identified in the waveform calculations. It is believed that this systematic investigation may assist in enhancing the understanding of the effect of ageing on the surface microstructure, the wax distribution as well as on the wax crystallisation.


O-GlcNAcylation of Mef2c regulates myoblast differentiation.
Unlike other types of glycosylation, O-GlcNAcylation is a single glycosylation which occurs exclusively in the nucleus and cytosol. O-GlcNAcylation underlie metabolic diseases, including diabetes and obesity. Furthermore, O-GlcNAcylation affects different oncogenic processes such as osteoblast differentiation, adipogenesis and hematopoiesis. Emerging evidence suggests that skeletal muscle differentiation is also regulated by O-GlcNAcylation, but the detailed molecular mechanism has not been fully elucidated. In this study, we showed that hyper-O-GlcNAcylation reduced the expression of myogenin, a transcription factor critical for terminal muscle development, in C2C12 myoblasts differentiation by O-GlcNAcylation on Thr9 of myocyte-specific enhancer factor 2c. Furthermore, we showed that O-GlcNAcylation on Mef2c inhibited its DNA binding affinity to myogenin promoter. Taken together, we demonstrated that hyper-O-GlcNAcylation attenuates skeletal muscle differentiation by increased O-GlcNAcylation on Mef2c, which downregulates its DNA binding affinity.


A co-culture model system to quantify antibody-dependent cellular cytotoxicity in human breast cancer cells using an engineered natural killer cell line.
Current protocols measure antibody-dependent cellular cytotoxicity (ADCC) in vitro using peripheral blood mononuclear cells (PBMCs), but isolation and variability among donors limit the viability and reproducibility of this approach. Here, we present a standardized co-culture model system to quantify ADCC on human breast cancer cells. We describe steps to engineer a natural killer cell line that stably expresses FCγRIIIa (CD16), required to mediate ADCC. We then detail the steps for the cancer-immune co-culture setup, followed by cytotoxicity measurement and analysis.


Outcomes of Surgical Bioprosthetic Aortic Valve Replacement in Patients Aged ≤65 and >65 Years.
Implantation of a bioprosthetic valve is a reasonable choice for patients aged > 65 years. For middle-aged patients there is less certainty about whether a mechanical or bioprosthetic valve is best. The Pericardial Surgical Aortic Valve Replacement (PERIGON) Pivotal Trial is evaluating the safety and efficacy of the Avalus bioprosthesis (Medtronic). We evaluated clinical and echocardiographic outcomes through 5 years of follow-up, stratified by age ≤ 65 and >65 years. Two hundred seventy-one patients (24.2%) were ≤65 years old and 847 (75.8%) >65 years old. Most patients in both groups were men (217 [80.1%] vs 623 [73.6%], respectively; P = .031). Younger patients had a lower Society of Thoracic Surgeons risk of mortality (1.1% ± 0.9% vs 2.2% ± 1.4%, P < .001), better baseline New York Heart Association class (P = .004), and fewer comorbidities than older patients. At 5 years mortality was lower among younger than older patients (5.3% vs 14.0%, P < .001) and no cases of structural valve deterioration occurred in either group. Effective orifice area was similar between age groups (P = .11), and mean gradient was 13.9 ± 5.4 vs 12.0 ± 4.1 mm Hg (P < .001). Multivariable linear regression identified several parameters associated with mean aortic gradient at 5 years, including baseline age and mean aortic gradient, discharge stroke volume index and EOA, and implanted valve size. Ninety-five percent of patients were in New York Heart Association class I/II through 5 years in both age groups (P = .85). Findings from this analysis demonstrate satisfactory safety, hemodynamic performance, and durability of the Avalus bioprosthesis through a 5-year follow-up in patients aged ≤ 65 and >65 years.


Determining optimal needle size for decompression of tension pneumothorax in children - a CT-based study.
For neonates and children requiring decompression of tension pneumothorax, specific recommendations for the choice of needle type and size are missing. The aim of this retrospective study was to determine optimal length and diameter of needles for decompression of tension pneumothorax in paediatric patients. Utilizing computed tomography, we determined optimal length and diameter of needles to enable successful decompression and at the same time minimize risk of injury to intrathoracic structures and the intercostal vessels and nerve. Preexisting computed tomography scans of the chest were reviewed in children aged 0, 5 and 10 years. Chest wall thickness and width of the intercostal space were measured at the 4th intercostal space at the anterior axillary line (AAL) on both sides of the thorax. In each age group, three needles different in bore and length were evaluated regarding sufficient length for decompression and risk of injury to intrathoracic organs and the intercostal vessels and nerve. 197 CT-scans were reviewed, of which 58 were excluded, resulting in a study population of 139 children and 278 measurements. Width of the intercostal space was small at 4th ICS AAL (0 years: 0.44 ± 0.13 cm; 5 years: 0.78 ± 0.22 cm; 10 years: 1.12 ± 0.36 cm). The ratio of decompression failure to risk of injury at 4th ICS AAL was most favourable for a 22G/2.5 cm catheter in infants (Decompression failure: right: 2%, left: 4%, Risk of injury: right: 14%, left: 24%), a 22G/2.5 cm or a 20G/3.2 cm catheter in 5-year-old children (20G/3.2 cm: Decompression failure: right: 2.1%, left: 0%, Risk of injury: right: 2.1%, left: 17%) and a 18G/4.5 cm needle in 10-year-old children (Decompression failure: right: 9.5%, left: 9.5%, Risk of injury: right: 7.1%, left: 11.9%). In children aged 0, 5 and 10 years presenting with a tension pneumothorax, we recommend 22G/2.5 cm, 20G/3.2 cm and 18G/4.5 cm needles, respectively, for acute decompression.


QSAR, Molecular Docking, MD Simulation and MMGBSA Calculations Approaches to Recognize Concealed Pharmacophoric Features Requisite for the Optimization of ALK Tyrosine Kinase Inhibitors as Anticancer Leads.
ALK tyrosine kinase ALK TK is an important target in the development of anticancer drugs. In the present work, we have performed a QSAR analysis on a dataset of 224 molecules in order to quickly predict anticancer activity on query compounds. Double cross validation assigns an upward plunge to the genetic algorithm−multi linear regression (GA-MLR) based on robust univariate and multivariate QSAR models with high statistical performance reflected in various parameters like, fitting parameters; R2 = 0.69−0.87, F = 403.46−292.11, etc., internal validation parameters; Q2LOO = 0.69−0.86, Q2LMO = 0.69−0.86, CCCcv = 0.82−0.93, etc., or external validation parameters Q2F1 = 0.64−0.82, Q2F2 = 0.63−0.82, Q2F3 = 0.65−0.81, R2ext = 0.65−0.83 including RMSEtr < RMSEcv. The present QSAR evaluation successfully identified certain distinct structural features responsible for ALK TK inhibitory potency, such as planar Nitrogen within four bonds from the Nitrogen atom, Fluorine atom within five bonds beside the non-ring Oxygen atom, lipophilic atoms within two bonds from the ring Carbon atoms. Molecular docking, MD simulation, and MMGBSA computation results are in consensus with and complementary to the QSAR evaluations. As a result, the current study assists medicinal chemists in prioritizing compounds for experimental detection of anticancer activity, as well as their optimization towards more potent ALK tyrosine kinase inhibitor.


Biallelic mutations of CFAP251 cause sperm flagellar defects and human male infertility.
Multiple morphological abnormalities of flagella (MMAF) are human reproduction disorders due to the dysplastic development of sperm flagella. The spermatozoa of men with MMAF manifest absent, short, coiled, bent, and/or irregular-caliber flagella. Previous studies revealed genetic contributions to human MMAF, but known MMAF-associated genes only explained approximately 50% MMAF cases. In this study, we employed human whole-exome sequencing for genetic analysis and identified biallelic mutations of CFAP251 (cilia- and flagella-associated protein 251, also known as WDR66) in three (5%) of 65 Han Chinese men with MMAF. All these CFAP251 mutations are loss-of-function. The population genome data suggested that these CFAP251 mutations are extremely rare (only heterozygous) or absent from human populations. Our functional assays of gene expression and immunofluorescence staining in a CFAP251-deficient man, together with previous experimental evidence from model organisms, suggested that CFAP251 is involved in flagellar functions. Our observations suggested that CFAP251 is associated with sperm flagellar development and human male infertility.


Identification of microRNAs as a potential novel regulatory mechanism in HSD11B1 expression.
11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1, gene HSD11B1) converts glucocorticoid receptor-inert cortisone to receptor-active cortisol. Multiple evidence supports a causal role for 11β-HSD1 in the current obesity epidemic. In obese, HSD11B1 expression is increased in adipose tissue but typically decreased in liver, and the underlying tissue-specific mechanisms are largely unknown. In this context, we investigated a potential role of microRNAs (miRNAs). We used several miRNA target prediction tools to identify possible candidates and a publicly available miRNA expression atlas to further select candidates expressed in hepatocytes. Using a dual luciferase reporter assay, we identified three potential miRNAs, hsa-miR-340, -561 and -579, as potential negative regulators of HSD11B1 expression. Disruption of the corresponding microRNA response elements abolished repression of luciferase activity for hsa-miR-561 and -579, but not for hsa-miR-340. Furthermore, levels of firefly luciferase mRNA were not changed by miR-561 and -579, indicating a mechanism based on translational repression rather than mRNA degradation. Finally, we were able to detect both, miR-561 and -579, in human total liver RNA by reverse-transcription-polymerase chain reaction (RT-PCR). According to the presented results, miR-561 and -579 are likely to be involved in the tissue-specific regulation of HSD11B1 expression. Moreover, literature findings and a pathway enrichment analysis support a potential role of these two miRNAs in glucocorticoid metabolism and signalling and associated diseases.


The association of physiological cortisol and IVF treatment outcomes: a systematic review.
A systematic review was conducted to (1) collate and synthesise the available evidence for the role of cortisol in relation to IVF treatment outcomes; (2) to establish the strength of an association between cortisol and IVF; and (3) to assess the overall quality of the studies and guide future research in this area. Seven electronic databases, including the reference lists of published papers, were searched. Inclusion criteria qualified any prospective/observational cohort study that reported original data. Quality assessment of eligible studies was conducted using the STROBE statement, which was used to assess the risk of bias and the quality of observational studies included in this review. A total of eight studies reported a significant association between cortisol and IVF outcomes. Three studies found that higher cortisol may be associated with more favourable IVF outcomes, whereas five studies found that lower cortisol levels may be conducive to IVF success. Eleven of all studies included in this review were regarded as low quality publications. Study findings were that the evidence for the role of cortisol in relation to IVF outcomes is currently mixed. Future researchers are encouraged to consider the methodological limitations highlighted in this review and to utilise more robust assessment methods when examining the influence that chronic, rather than acute, stress may have on IVF outcomes.


Association of cytotoxic T lymphocyte-associated protein 4 gene -1772T/C polymorphism with gastric cancer risk: A prisma-compliant meta-analysis.
We performed a meta-analysis to more precisely evaluate the association between the cytotoxic T lymphocyte-associated protein 4 (CTLA-4) -1772T/C polymorphism and overall gastric cancer (GC) risk and the influence of ethnicity and the source of controls on that association. A systematic literature search was performed in PubMed, EMBASE, the Cochrane Library, Web of Science (WOS) Database, Chinese National Knowledge Infrastructure (CNKI), China biomedical literature database (CBM), Wanfang database, and VIP. Two investigators independently reviewed the articles, and disagreements were resolved by discussion and consensus. The odds ratio (OR) with 95% confidence intervals (CIs) was used to assess the strength of the association between the CTLA-4 -1722T/C polymorphism and GC risk, based on the genotype frequencies in cases and controls. The meta-analyses were performed with Stata 12.0, using two-sided P values. Trial sequential analysis (TSA) was calculated by TSA Software. Overall, we identified 5 studies including 1039 GC cases and 2136 controls that evaluated the association of the CTLA-4 -1722T/C polymorphism and GC risk. Overall, there was no significant association between the CTLA-4-1722T/C polymorphism and the risk of GC. In the subgroup analysis based on ethnicity, the results showed that the relationship between the CTLA-4 -1722T/C polymorphism and GC susceptibility was strongest in the Chinese population rather than in the Iranian population (TC vs CC: OR = 1.405, 95% CI: 1.100-1.796, P = .007; TC+TT vs CC: OR = 1.329, 95% CI: 1.052-1.680, P = .017). Then, there was a significant association between the CTLA-4 -1722T/C polymorphism and the risk of GC in studies with HB controls. However, the above correlation can only be reflected in specific populations and gene models. Therefore, we believe that the evidence of this correlation is insufficient. Our meta-analysis showed that the CTLA-4 -1722T/C polymorphism may be associated with the susceptibility to GC. However, the slight correlation can only be reflected in specific populations and gene models. Therefore, we believe that this association is negligible. The large and well-designed case-control studies are needed to validate our findings.


Relationship between adenosine A2a receptor polymorphism rs5751876 and fractional flow reserve during percutaneous coronary intervention.
Fractional flow reserve (FFR) assessed during adenosine-induced maximal hyperemia has emerged as a useful tool for the guidance of percutaneous coronary interventions (PCI). However, interindividual variability in the response to adenosine has been claimed as a major limitation to the use of adenosine for the measurement of FFR, carrying the risk of underestimating the severity of coronary stenoses, with potential negative prognostic consequences. Genetic variants of the adenosine receptor A2a (ADORA2A gene), located in the coronary circulation, have been involved in the modulation of the hyperemic response to adenosine. However, no study has so far evaluated the impact of the single nucleotide polymorphism rs5751876 of ADORA2A on the measurement of FFR in patients undergoing percutaneous coronary intervention that was, therefore, the aim of our study. We included patients undergoing coronary angiography and FFR assessment for intermediate (40-70%) coronary lesions. FFR measurement was performed by pressure-recording guidewire (Prime Wire, Volcano), after induction of hyperemia with intracoronary boli of adenosine (from 60 to 1440 μg, with dose doubling at each step). Restriction fragment length polymorphism (RFLP) analysis was performed to assess the presence of rs5751876 C>T polymorphism of ADORA2a receptor. We included 204 patients undergoing FFR measurement of 231 coronary lesions. A total of 134 patients carried the polymorphism (T allele), of whom 41 (30.6%) in homozygosis (T/T).Main clinical and angiographic features did not differ according to ADORA2A genotype. The rs5751876 C>T polymorphism did not affect mean FFR values (p = 0.91), the percentage of positive FFR (p = 0.54) and the duration of maximal hyperemia. However, the time to recovery to baseline FFR values was more prolonged among the T-allele carriers as compared to wild-type patients (p = 0.04). Based on these results, in patients with intermediate coronary stenoses undergoing FFR assessment with adenosine, the polymorphism rs5751876 of ADORA2A does not affect the peak hyperemic response to adenosine and the results of FFR. However, a more prolonged effect of adenosine was observed in T-carriers.


Comparison of the Orientation Angles of Volar Locking Plate Distal Ulnar Locking Screw for Distal Radius Fractures.
This study aimed to measure the angles between the screw and plate in 16 commercially available volar locking plates (VLPs) to determine the fixable intra-articular fragment size. Ulnar orientation angles (axial plane) and elevation angles (sagittal plane) between the distal ulnar screw and plate were measured for 14 fixed-angle VLPs and 2 variable-angle VLPs. Each VLP was simulated by 2 surgeons to sit distally and ulnarly in 10 normal distal radius models. The distance between the screw and distal/ulnar end of the distal radius on both the volar and dorsal sides, designated as the longitudinal/lateral distance, was measured to identify the fixable size of the 2 intra-articular fragments: volar lunate fragment and dorsoulnar fragment. Relationships between the ulnar orientation angle and dorsal-side lateral length as well as the elevation angle and dorsal-side longitudinal distance were analyzed. The ulnar orientation and elevation angles ranged from 6.5° to 16.9° and -5.8° to 34.3°, respectively, for fixed-angle VLPs and -12.5° to 32.2° and 3.1° to 42.1°, respectively, for variable-angle VLPs. The minimal longitudinal distances on the volar side with the fixed- and variable-angle VLPs were 4.3-10.9 mm and 5.8-5.9 mm, respectively. On the dorsal side, the lateral distance negatively correlated with the ulnar orientation angle (R = -0.74), and the longitudinal distance negatively correlated with the elevation angle (R = -0.89). The Depuy Synthes variable-angle VLP provides an advantage for fixating small intra-articular fragments. For fixed-angle VLPs, the Mizuho VLP provides an advantage for fixating small volar lunate fragments. A narrow dorsoulnar fragment can be fixated using a plate with a large ulnar orientation angle, such as the Zimmer Biomet or Mizuho VLP. The ability of each individual commercially available plate to capture specific intra-articular fragments should be known.


A vesicular glutamate transporter in lampreys: cDNA cloning and early expression in the nervous system.
Vesicular glutamate transporters (VGLUTs) accumulate glutamate into synaptic vesicles of glutamatergic neurons, and thus are considered to define the phenotype of these neurons. Glutamate also appears to play a role in the development of the nervous system of vertebrates. Here we report the characterization of a vesicular glutamate transporter of lamprey (lVGluT), a novel member of the VGluT gene family. Phylogenetic analysis indicates that lVGLUT cannot be assigned to any of the three VGLUT isoforms characterized in teleosts and mammals, suggesting that these classes may have been fixed after the splitting between cyclostomes and gnathostomes. Expression pattern analysis during lamprey embryogenesis and prolarval stages shows that lVGluT expression is restricted to the nervous system. The first structure to express lVGluT was the olfactory epithelium of late embryos. In the brain of early prolarvae, lVGluT was expressed in most of the neuronal populations that generate the early axonal scaffold. lVGluT expression was also observed in neuronal populations of the rhombencephalon and spinal cord and in ganglia of the branchiomeric, octaval and posterior lateral line nerves. In the rhombencephalon, lVGluT expression appears to be spatially restricted in dorsal and ventral longitudinal domains. Comparison of the early expression of VGluT genes between the lamprey and some anamniotan gnathostomes (frog, zebrafish) reveals a conserved expression pattern, likely to reflect ancestral vertebrate characteristics.


Do cilia put brakes on the cell cycle?
Two papers in this issue show that dynein-binding proteins may regulate the G1-S transition through an effect on cilia. Nde1, a known partner of dynein light chain LC8, controls ciliary length in vitro and in zebrafish, and influences the G1-S progression. The phosphorylation of Tctex1, a dynein light chain, modulates cilia length and accelerates G1-S, thereby regulating proliferation-differentiation decisions in the developing mouse neocortex.


Production of a spiked milk reference material.
A spiked milk reference material containing 134Cs and 137Cs has been successfully produced. The material has been characterised in a manner directly traceable to national standards of radioactivity. This work is part of a EUROMET project to produce spiked reference materials at a range of densities from 0.1 to 2.0 g/cm3.


Do motor vehicle airbags increase risk of ocular injuries in adults?
This study was undertaken to evaluate the risk of eye injury in motor vehicle accidents in which airbags deploy. An attempt was made to assess the possible associations between eye injuries and eyewear in these accidents. Retrospective observational case series and literature review with analysis. We conducted a literature review of 62 case reports and articles describing 110 adult cases of eye injury after deployment of an airbag and examined two Finnish accident cohorts. The fatal accident series (FAS; fatal injuries with one or more cars involved) included 121 individuals sitting behind an airbag that deployed (65 survivors), and the Airbag study (AB; nonfatal, relatively serious accidents) included 210 individuals (survivors). The type of eye injury, eyewear, and crash dynamics were studied in each of the reviewed case reports. The fatal accident series and AB studies were analyzed to disclose the eye injuries and use of eyewear and to estimate their possible relation to deployment of airbags. Analysis of the published reports revealed that airbag-induced eye injuries were not more frequently reported among wearers of eyeglasses than among nonwearers. However, open-eye injuries were reported three times more often among eyeglass wearers (P = 0.04), whereas all injuries from airbag chemicals occurred among nonwearers. With the exception of one orbital fracture with hyphema, all eye traumas (n = 7) in the FAS and AB cohorts were mild (eyebrow laceration, lid contusion, bruising). The risk of airbag-related eye injury was 2.5% for any eye injury and 0.4% for severe eye injury. In single accidents when seat belts were used, the risks were 2.0% and 0.5%, respectively. In the accidents from the FAS data no difference was observed in the risk for eye injury between survivors in incidents involving airbag deployment and incidents not involving airbags. This risk was not found to be greater among eyeglass wearers. Despite reported cases in the literature, we found that the risk of severe eye injury from airbags was very low (0.4%) in fatal or relatively serious accidents. Eyewear did not seem to increase this risk but might interfere with the injury pattern.


Surgery Versus Chemotherapy and Radiotherapy For Early and Locally Advanced Small Cell Lung Cancer: A Propensity-Matched Analysis of Survival.
The role of surgery in small cell lung cancer (SCLC) is controversial. Survival outcomes for resection of stage I-IIIA SCLC compared to chemotherapy-based non-surgical treatment (NST) were examined using propensity matching. 29,994 clinical stage I-IIIA SCLC patients, including 2,619 undergoing surgery, were identified in the National Cancer Database. Stage-specific propensity scores for receipt of surgery were created. Resected patients were matched 1:1 to those undergoing NST. Overall survival (OS) was assessed using Kaplan-Meier and multivariable Cox models. A separate match was performed comparing Stage I/II patients aged <85 with a Charlson score of 0 who underwent lobectomy with adjuvant chemotherapy (and radiotherapy if node positive) to those treated with multiagent chemotherapy and concurrent chest radiotherapy (CRT) of at least 40 gray. 2,089 patients were matched, and cohorts were well balanced. Surgery was associated with longer survival for Stage I (median OS 38.6 months vs. 22.9 months, HR 0.62 95%CI 0.57-0.69, p<0.0001), but survival differences were attenuated for Stage II (median OS 23.4 months vs. 20.7 months, HR 0.84 95%CI 0.70-1.01, p=0.06) and IIIA (median OS 21.7 vs. 16.0 months, HR 0.71 95%CI 0.60-0.83, p <0.0001). In analyses by T and N stage, longer OS was observed in resected patients with stage T3/T4 N0 (median OS 33.0 vs. 16.8 months, p=0.008) and node positivity(N1+ 24.4 vs. 18.3 months p=0.03; N2+ 20.1 vs. 14.6 months p=0.007). In the subgroup analysis, 507 stage I/II patients receiving lobectomy and adjuvant chemotherapy were matched to patients receiving concurrent CRT. In this cohort, lobectomy with adjuvant chemotherapy was associated with significantly longer survival (median OS 48.6 vs. 28.7 months, p<0.0001). Surgical resection is associated with significantly longer survival for early SCLC. New randomized trials should assess trimodality therapy in stages I/II, and in node negative disease.


MicroRNA-211-5p suppresses tumour cell proliferation, invasion, migration and metastasis in triple-negative breast cancer by directly targeting SETBP1.
Triple-negative breast cancer (TNBC) accounts for 15-20% of all breast cancer in women globally. This subtype often has early and high recurrence rates, resulting in poor survival, partially due to lack of targeted therapies. To date, the detailed molecular mechanisms underlying TNBC progression are unclear. Given the crucial role of microRNAs (miRNAs) in cancer metastasis, we aimed to analyse the expression and function of a metastasis-associated miRNA named miR-211-5p in TNBC. MiRNA array analysis was performed to search for metastasis-associated miRNAs in TNBC. The miR-211-5p expression in tumour tissues, adjacent non-tumourous breast tissues of TNBC patients and cell lines were evaluated by real-time PCR. The protein expression levels were analysed by western blot, immunohistochemistry and in situ hybridisation. Luciferase reporter assays were employed to validate the target of miR-211-5p. The effect of miR-211-5p on TNBC progression was investigated in vitro and in vivo. MiR-211-5p was significantly downregulated in TNBC, and its expression level was associated with overall survival in TNBC. The expression of miR-211-5p suppressed TNBC cell proliferation, invasion, migration and metastasis in vitro and in vivo. Furthermore, SETBP1 was identified as a target of miR-211-5p. Through gain-of-function and loss-of-function studies, SETBP1 was shown to significantly affect colony and cell number in vitro. Enforced expression of miR-211-5p inhibited the expression of SETBP1 significantly and the restoration of SETBP1 expression reversed the inhibitory effects of miR-211-5p on TNBC cell proliferation and metastasis. These findings collectively demonstrate a tumour suppressor role of miR-211-5p in TNBC progression by targeting SETBP1, suggesting that miR-211-5p could serve as a potential prognostic biomarker and therapeutic target for TNBC.


Cancer of the skin in blacks: a review of 128 patients with basal-cell carcinoma.
Basal cell carcinoma in black persons is generally believed to be rare, with cases only sporadically reported. Information about 148 basal cell carcinomas found in 128 black patients who were seen at Charity Hospital of Louisiana, New Orleans, between 1948 and 1979, was reviewed. As in whites, most of the tumors occurred on the sun-exposed areas of the head and neck.


Response to COVID-19 in Cyprus: Policy changes and epidemic trends.
In late July, Cyprus experienced the second epidemic wave of COVID-19. We present the steps taken by the government and evaluate their effect on epidemic trends. Cyprus Press and Information Office data were analysed. Using an R-based forecasting program, two models were created to predict cases up to 01/09/2020: Model 1, which utilised data up to 09/06/2020, when airports reopened to foreign travelers with COVID-19 screening; and Model 2, which utilised data until 24/06/2020, when screening for passengers from low-transmission countries was discontinued. PIO data revealed no significant policy changes between 24/06/2020 and 31/07/2020. Prediction models were robust and accurate (Model 1, R2 = 0.999, P < .001; Model 2, R2 = 0.998, P < .001). By August 30th, recorded cases exceeded those predicted by Model 1 by 24.47% and by Model 2 by 20.95%, with P values <.001 for both cases. The significant difference between recorded cases and those projected by Models 1 and 2 suggests that changes in epidemic trends may have been associated with policy changes after their respective dates. Discontinuation of major restrictions such as airport reopening, can destabilise the control of the epidemic, and may concomitantly necessitate a reevaluation of the current epidemic status. In the face of an evolving situation such as the COVID-19 pandemic, states are forced to balance the imposing of restrictions against their impact on the economy.


Where has all the chocolate gone? A national survey assesses the effects of recent legislation to improve the nutritional quality of English secondary-school vending.
Obesity levels are rising in almost all parts of the world, including the UK. School food offers children in Great Britain between 25 % and 33 % of their total daily energy, with vending typically offering products high in fat, salt or sugar. Government legislation of 2007 to improve the quality of school food now restricts what English schools can vend. In assessing the effect of this legislation on the quality of English secondary-school vending provision, the response of schools to these effects is explored through qualitative data. A longitudinal postal and visit-based inventory survey of schools collected vending data during the academic year 2006-2007 (pre-legislation), 2007-2008 and 2008-2009 (both post-legislation). Interviews with school staff explored issues of compliance. Product categorisation and analysis were carried out by product type, nutrient profiling and by categories of foods allowed or prohibited by the legislation. English secondary schools. A representative sample of 279 schools including sixty-two researcher-visited inventory schools participated in the research. School vending seems to have moved towards compliance with the new standards - now drinks vending predominates and is largely compliant, whereas food vending is significantly reduced and is mostly non-compliant. Sixth form vending takes a disproportionate share of non-compliance. Vending has declined overall, as some schools now perceive food vending as uneconomic. Schools adopting a 'whole-school' approach appeared the most successful in implementing the new standards. Government legislation has achieved significant change towards improving the quality of English school vending, with the unintended consequence of reducing provision.


Pathogenesis of macular edema with branch retinal vein occlusion and intraocular levels of vascular endothelial growth factor and interleukin-6.
To determine whether correlations between vascular endothelial growth factor (VEGF) or interleukin-6 (IL-6) contribute to the pathogenesis of macular edema in eyes of patients with branch retinal vein occlusion (BRVO). Retrospective case-control study. Nineteen patients with macular edema with BRVO and seven patients with non-ischemic ocular disease (control group) were studied. The degree of retinal ischemia was evaluated in terms of the area of capillary non-perfusion, and the severity of macular edema was examined by optical coherence tomography. Aqueous humor samples were obtained at the time of combined vitrectomy and cataract surgery, and VEGF and IL-6 levels in aqueous humor and plasma were determined by enzyme-linked immunosorbent assay. Aqueous levels of VEGF (351 +/- 273 pg/ml) and IL-6 (7.10 +/- 6.51 pg/ml) were significantly elevated in patients with BRVO compared with the control patients (119 +/- 38.7 pg/ml and 2.27 +/- 1.11 pg/ml, respectively) (P = .0017 and P = .0052, respectively). Aqueous level of VEGF was significantly correlated with that of IL-6 (P = .0396), and aqueous levels of VEGF and IL-6 were correlated with the size of the BRVO non-perfused area (P < .0001 and P = .0331, respectively). Aqueous level of VEGF was correlated with the severity of macular edema (P = .0306). VEGF and IL-6 may be involved in the pathogenesis of macular edema with BRVO. The increase in these cytokines might be used as a unique index of BRVO, through which we can determine the severity of the ischemic condition as being in a quiescent state or an exacerbation of macular edema.


Human platelet antigen antibody induction in uncomplicated pregnancy is associated with HLA sensitization.
Alloimmunization against human platelet antigens (HPAs) during pregnancy is rare but can lead to severe bleeding disorders, such as fetal and neonatal alloimmune thrombocytopenia. In a cohort of 241 uncomplicated pregnancies, we investigated the immunogenicity of HPA mismatches and correlated HLA sensitization with HPA antibody formation. HPA antibodies were measured with a Luminex-based multiplex assay. HPA mismatches were observed in 109 of 241 pregnancies (45%), but child-specific HPA antibodies were only found in two of 109 cases (2%), indicating a low immunogenicity. Only nine of 241 women (4%) had detectable HPA antibodies. HLA sensitization was identified as a strong and independent predictor for HPA antibody formation (hazard ratio, 10.2; 95% confidence interval, 1.8-193; p = 0.006), whereas the number of pregnancies was not. Our observational data indicated a low immunogenicity of HPA and suggest that a broader immune response-inferred by HLA sensitization-is probably associated with HPA antibody induction.


Case report: severe heat stroke with multiple organ dysfunction - a novel intravascular treatment approach.
We report the case of a patient who developed a severe post-exertional heat stroke with consecutive multiple organ dysfunction resistant to conventional antipyretic treatment, necessitating the use of a novel endovascular device to combat hyperthermia and maintain normothermia. A 38-year-old male suffering from severe heat stroke with predominant signs and symptoms of encephalopathy requiring acute admission to an intensive care unit, was admitted to a ten-bed neurological intensive care unit of a tertiary care hospital. The patient developed consecutive multiple organ dysfunction with rhabdomyolysis, and hepatic and respiratory failure. Temperature elevation was resistant to conventional treatment measures. Aggressive intensive care treatment included forced diuresis and endovascular cooling to combat hyperthermia and maintain normothermia. Analyses of serum revealed elevation of proinflammatory cytokines (TNF alpha, IL-6), cytokines (IL-2R), anti-inflammatory cytokines (IL-4) and chemokines (IL-8) as well as signs of rhabdomyolysis and hepatic failure. Aggressive intensive care treatment as forced diuresis and endovascular cooling (CoolGard and CoolLine) to combat hyperthermia and maintain normothermia were used successfully to treat this severe heat stroke. In this case of severe heat stroke, presenting with multiple organ dysfunction and elevation of cytokines and chemokines, which was resistant to conventional cooling therapies, endovascular cooling may have contributed significantly to the reduction of body temperature and, possibly, avoided a fatal result.


Postmenopausal Osteoporosis: Latest Guidelines.
Significant development has occurred in the treatment of postmenopausal osteoporosis. We review the most recent guidelines from the American Association of Clinical Endocrinologists/American College of Endocrinology, Endocrine Society, and the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis/International Osteoporosis Foundation Guidelines.


Copper(i)/Ganphos catalysis: enantioselective synthesis of diverse spirooxindoles using iminoesters and alkyl substituted methyleneindolinones.
A copper-catalyzed asymmetric 1,3-dipolar cycloaddition of glycine iminoesters with alkyl substituted 3-methylene-2-oxindoles is described. By using de novo design of P-stereogenic phosphines as ligands, spiro[pyrrolidin-3,3'-oxindole]s are generated in good to excellent yields with high asymmetric induction. A further reduced catalyst loading of 0.1 mol% is sufficient to achieve a satisfactory enantioselectivity of 90% ee. The DFT calculations suggest the second Michael addition of the 1,3-dipole to be the rate- and enantio-determining step. A key feature of this 1,3-dipolar cycloaddition is the wide substrate applicability, even with alkyl aldehyde-derived azomethine ylide; thus it has streamlined a highly enantioselective access to a new class of antiproliferative agents, MDM2-p53.


Changes in adsorption mechanisms of radioactive barium, cobalt, and strontium ions using spent coffee waste biochars via alkaline chemical activation: Enrichment effects of O-containing functional groups.
The single adsorption of radioactive barium (Ba(II)), cobalt (Co(II)), and strontium (Sr(II)) ions using pristine (SCWB-P) and chemically activated spent coffee waste biochars with NaOH (SCWB-A) were thoroughly explored in order to provide deeper insights into the changes in their adsorption mechanisms through alkaline chemical activation. The greater removal efficiencies of SCWB-A (76.6-97.3%) than SCWB-P (45.6-75.2%) and the consistency between the adsorptive removal patterns (Ba(II) > Sr(II) > Co(II)) and oxygen bond dissociation enthalpies (BaO (562 kJ/mol) > SrO (426 kJ/mol) > CoO (397 kJ/mol)) of radioactive species supported the assumption that the adsorption removal of radioactive species with spent coffee waste biochars highly depended on the abundances of O-containing functional groups. The calculated R2 values of the pseudo-first-order (SCWB-P = 0.998-0.999; SCWB-A = 0.850-0.921) and pseudo-second-order kinetic models (SCWB-P = 0.988-0.998; SCWB-A = 0.935-0.966) are evident that the physisorption mainly controlled the adsorption of radioactive species toward SCWB-P and the chemisorption played a crucial role in their adsorptive removal with SCWB-A. From the calculated intra-particle diffusion, isotherm, thermodynamic parameters, it can be concluded that the intra-particle diffusion and monolayer adsorption primarily governed the adsorption of radioactive species using SCWB-P and SCWB-A, and their adsorption processes occurred spontaneously and endothermically. The dominant adsorption mechanism of spent coffee waste biochars was changed from physisorption (ΔH° of SCWB-P = 21.6-29.8 kJ/mol) to chemisorption (ΔH° of SCWB-A = 42.4-81.3 kJ/mol) through alkaline chemical activation. The distinctive M-OH peak in the O1s XPS spectra of SCWB-A directly corresponding to the decrease in the abundances of O-containing functional groups confirms again that the enrichment of O-containing functional groups markedly facilitated the adsorption removal of radioactive species by chemisorption occurred at the inner and outer surfaces of spent coffee waste biochars.


Electron paramagnetic resonance studies of cytochrome P-450 and adrenal ferredoxin in single whole rat adrenal glands. Effect of corticotropin.
Low and high spin ferric cytochrome P-450 and reduced adrenal ferredoxin (adrenodoxin) have been directly studied by EPR techniques in whole rat adrenal glands. The spectra obtained correspond closely to those obtained from sub-cellular fractions except in the case of low spin ferric cytochrome P-450, where there are differences in the shape of the g = 2.41 line. The relative magnitudes of these peaks in anaerobic and aerobic rapidly frozen adrenals from control and corticotropin stimulated hypophysectomised rats were used to investigate the control and rate limiting steps in adrenal steroid biosynthesis via cytochrome P-450. All adrenals showed a close to maximal level of reduced adrenodoxin and aerobic and anaerobic glands from control rats and aerobic glands from corticotropin stimulated rats showed similar quantities of low spin ferric cytochrome P-450. On anaerobiosis the quantity of low spin ferric cytochrome in adrenals from corticotropin stimulated rats dropped to 30--40% of the aerobic level. Treatment of the rats with cycloheximide prior to administration of corticotropin prevented these changes. Approximately 0.4% of the total cytochrome P-450 was high spin ferric in control adrenals and in aerobic stimulated adrenals this rose to approximately to 0.6%. These results demonstrate that association of substrate with cytochrome P-450 is the rate limiting step in adrenal steroidogenesis via cytochrome P-450. It is suggested on the basis of these and mitochondrial optical and EPR experiments that the limiting step being observed is cholesterol binding to cholesterol side chain cleavage cytochrome P-450, and that the rate of this association is stimulated by corticotropin.


Levels of PCDDs, PCDFs and dl-PCBs in the blood of childbearing-aged women living in the vicinity of a chemical plant in Tianjin: a primary study.
Several studies have suggested that maternal exposure to Polychlorinated dibenzo-p-dioxins (PCDDs), poly-chlorinated dibenzofurans (PCDFs) and dioxin-like polychlorinated biphenyls (PCBs) may affect foetal growth and infant development. The aim of our study was to determine whether the childbearing-aged residents living near a chemical plant have a greater exposure risk. Concentrations of 17 PCDD/Fs congeners and 12 non-ortho and mono-ortho dioxin-like PCBs were measured using HRGC-HRMS in the blood of 30 non-occupational childbearing-aged women living near a chemical plant (Dagu) that had been producing chlorinated pesticides from 1958 to 2004. The factors that influenced the body burden were investigated based on responses to a questionnaire. Levels of PCDD/Fs+PCBs were in the range of 16.43-155.29pg WHO 2005-TEQg(-1) lipid. PCDDs and PCDFs contributed 56.72% and 34.44%, respectively, to the total TEQ value. Total WHO-TEQ was approximately tenfold higher in the participants living in the vicinity of the plant (distance: 1.52±0.148km) than in the groups living farther away (distance: 4.93±1.124km). A negative correlation between total WHO-TEQ and distance to Dagu was observed by multiple linear regression models. The data provide basic information for monitoring dioxin-like chemicals in the district and for the future study of the relationship between POPs and pregnancy outcomes.


Development of a human scFv antibody targeting the lethal Iranian cobra (Naja oxiana) snake venom.
Snakebite is one of the health concerns worldwide. Naja oxiana is one of the venomous snakes with a high mortality rate. Anti-serum therapy is the only treatment of the victims. However, in some cases, antiserum injection leads to some side effects in host like serum sickness and anaphylactic shock. It is crucial to develop a neutralizing agent with low side effects. The human antibody library (non-immunized library) was used to isolate specific antibodies against N.oxiana venom components. Four rounds of biopanning were performed to enrich scFv-displaying phages against the venom of N. oxiana. Enrichment of scFv-displaying phages against N. oxiana venom was analyzed by polyclonal Enzyme-Linked Immunosorbent Assay (ELISA). Specific antibody fragments against N. oxiana venom were selected through monoclonal ELISA, and were expressed in E. coli bacterial cells. Purification of the selected clones was performed by using nickel affinity chromatography. Neutralization and protective capacity of specific antibody fragments were analyzed in C57BL/6 mice (i.v. injection). Results of biopanning and polyclonal ELISA demonstrate a successful enrichment process. Five specific antibody fragments with the highest signal in monoclonal ELISA were selected, expressed, and purified. The purity of expressed antibody fragments was monitored by SDS-PAGE and Western blot. The selected antibody fragments were able to neutralize two LD50 of N. oxiana venom and protected all mice when injected 15 min post-envenomation. The data indicate that such selected antibodies are promising tools for further studies and in the development of novel protective agents against N. oxiana venom.


The effects of acute BPA exposure on skeletal muscle mitochondrial function and glucose metabolism.
Bisphenol A (BPA) is an environmental pollutant that has been associated with adverse health effects including skeletal muscle insulin resistance, a major contributor to the pathogenesis of type 2 diabetes (T2D). Early mitochondrial dysfunction and oxidative stress are linked to impaired glucose metabolism in skeletal muscle. In this study, we investigated the effects of BPA on skeletal muscle mitochondrial function and insulin sensitivity. L6 myotubes were treated with BPA (1 nM-105 nM) during the last 24 h of differentiation. Following exposure to 105 nM of BPA, resting and maximal oxygen consumption rates were decreased, whereas mitochondrial proton leak was increased. Overall metabolic activity, measured by redox ability, was decreased in L6 myotubes exposed to 105 nM of BPA. At this concentration, insulin-stimulated glucose uptake was increased, which corresponded to an increased phosphorylation of the insulin signaling protein Akt, and increased glycolysis measured by extracellular acidification rate (ECAR). Acute BPA exposure did not alter levels of oxidative stress markers in muscle cells, but significantly increased mitochondrial proton leak, which is known to be involved in decreased ROS production. The effects of BPA on glucose uptake, but not mitochondrial function, were reversed by the use of an estrogen receptor antagonist. These results suggest that acute exposure of L6 myotubes at only high concentrations of BPA alters glucose metabolism, which is likely a compensatory response to reduced mitochondrial energy production capacity.


A nomogram based on tumor response to induction chemotherapy may predict survival in locoregionally advanced nasopharyngeal carcinoma.
To evaluate the clinical significance of tumor response to induction chemotherapy (IC) in locoregionally advanced nasopharyngeal carcinoma (LANPC) patients and further to develop a nomogram for predicting survival prognosis. A total of 498 patients with stage III-IVA NPC applying IC and concurrent chemotherapy were reviewed (training cohort, n = 376; validation cohort, n = 122). Tumor response was an independent predictor for clinical outcomes. The nomogram included age, N stage, pretreatment Epstein-Barr virus DNA, lymphocyte-to-monocyte ratio, and tumor response achieved an ideal C-index of 0.703 (95% CI 0.655-0.751) in the validation cohort for predicting overall survival (OS), which outperformed than that of the TNM system alone (C-index, 0.670, 95% CI: 0.622-0.718). In addition, the nomogram could successfully classified patients into different risk groups. We established and validated a precise and convenient nomogram based on tumor response for predicting the OS of LANPC patients.


SIGS vs HIGS: a study on the efficacy of two dsRNA delivery strategies to silence Fusarium FgCYP51 genes in infected host and non-host plants.
CYP3RNA, a double-stranded (ds)RNA designed to concomitantly target the two sterol 14α-demethylase genes FgCYP51A and FgCYP51B and the fungal virulence factor FgCYP51C, inhibits the growth of the ascomycete fungus Fusarium graminearum (Fg) in vitro and in planta. Here we compare two different methods (setups) of dsRNA delivery, viz. transgene expression (host-induced gene silencing, HIGS) and spray application (spray-induced gene silencing, SIGS), to assess the activity of CYP3RNA and novel dsRNA species designed to target one or two FgCYP51 genes. Using Arabidopsis and barley, we found that dsRNA designed to target two FgCYP51 genes inhibited fungal growth more efficiently than dsRNA targeting a single gene, although both dsRNA species reduced fungal infection. Either dsRNA delivery method reduced fungal growth stronger than anticipated from previous mutational knock-out (KO) strategies, where single gene KO had no significant effect on fungal viability. Consistent with the strong inhibitory effects of the dsRNAs on fungal development in both setups, we detected to a large extent dsRNA-mediated co-silencing of respective non-target FgCYP51 genes. Together, our data further support the valuation that dsRNA applications have an interesting potential for pesticide target validation and gene function studies, apart from their potential for crop protection.


Association of platelet and leukocyte counts with delayed cerebral ischemia in aneurysmal subarachnoid hemorrhage.
A proinflammatory prothrombotic state may increase the risk of delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (SAH). We studied the relationship of levels of leukocytes, platelets, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) with the development of DCI and with clinical outcome in patients with aneurysmal SAH. In 125 patients admitted within 72 h after aneurysmal SAH, we dichotomized initial blood levels at their median values and investigated the prediction of DCI with Cox proportional hazard analysis and of poor clinical outcome with logistic regression analysis. We also analyzed concentrations before and after onset of DCI with the paired-samples t test and compared changes with those in patients without DCI. During the development of DCI (unrelated to treatment), patients had a larger increase in counts of platelets (difference 49 x 10(9)/l; 95% CI: 2-98) and leukocytes (difference 2.6 x 10(9)/l; 95% CI: 0.4-5.0) than patients without DCI during the same period. CRP increased during DCI and decreased in patients without DCI (difference 14 mg/l; 95% CI: -29 to 58). ESR increased slightly in both groups (difference 3 mm/h; 95% CI: -15 to 20). None of the determinants at baseline predicted the development of DCI. An increased risk of poor outcome predicted by a high initial leukocyte count (OR 2.5; 95% CI: 1.1-5.7) decreased after adjustment for clinical variables (OR 2.1; 95% CI: 0.8-5.5). Counts of platelets and leukocytes disproportionally increase during the occurrence of DCI after aneurysmal SAH. Drugs with anti-thrombotic or anti-inflammatory properties should be studied for prevention and treatment of DCI.


Effects of San-Huang-Xie-Xin-tang, a traditional Chinese prescription for clearing away heat and toxin, on the pacemaker activities of interstitial cells of Cajal from the murine small intestine.
San-Huang-Xie-Xin-Tang (SHXXT) is a traditional Chinese medicinal formula composed of Coptidis rhizoma (Coptis chinesis Franch), Scutellariae radix (Scutellaria baicalensis Georgi), and Rhei rhizoma (Rheum officinale Baill) and is widely used in Eastern Asia, especially to ameliorate the symptoms of gastrointestinal (GI) disorders related to gastritis, gastric bleeding, peptic ulcers, and abnormal GI motility Interstitial cells of Cajal (ICCs) are pacemaker cells in the GI tract that generate rhythmic oscillations in membrane potentials known as slow waves. Because GI disorders, especially abnormal GI motility, are major lifelong problems, the authors investigated the effects of SHXXT on mouse small intestine ICCs, and sought to identify the receptors and the action mechanisms involved. Enzymatic digestions were used to dissociate ICCs from small intestines, and the whole-cell patch-clamp configuration was used to record potentials generated by cultured ICCs. SHXXT produced membrane depolarization in current-clamp mode, and Y25130 (a 5-HT3 receptor antagonist) and RS39604 (a 5-HT4 receptor antagonist) blocked SHXXT-induced membrane depolarizations, whereas SB269970 (a 5-HT7 receptor antagonist) did not. However, during external Ca2+ free conditions or in the presence of thapsigargin, SHXXT did not exhibit membrane depolarization. Furthermore, the application of flufenamic acid (a nonselective cation channel (NSCC) blocker) or DIDS (a chloride channel blocker) abolished pacemaker potential generation and blocked SHXXT-induced membrane depolarizations. In addition, SHXXT-induced membrane depolarizations, which are dependent on G-protein, in ICCs were blocked by PD 98059 (a p42/44 mitogen-activated protein kinase (MAPK) inhibitor), SB203580 (a p38 MAPK inhibitor), and by a c-jun NH2-terminal kinase (JNK) II inhibitor. Regarding the components of SHXXT, Coptidis rhizome and Rhei rhizoma modulated ICC pacemaking activity, whereas Scutellariae radix did not. SHXXT modulates pacemaker potentials via 5-HT3 and 5-HT4 receptor-mediated pathways, external Ca2+ influx, and Ca2+ release from internal stores. Furthermore, NSCCs and Cl- channels play important roles in the regulation of pacemaking activity in a MAPK dependent manner in ICCs. The regulation of pacemaking activity by SHXXT may be due to the activity of Coptidis rhizome and Rhei rhizome. The study shows SHXXT can modulate the pacemaking activity of ICCs in the GI tract, and thus, suggests SHXXT has potential pharmacological relevance for the treatment of GI motility disorders.


Establishment of prenatal diagnosis for beta-thalassaemia: a step towards its control in a developing country.
Beta-thalassaemia constitutes a major health burden on the limited health resources of India and prenatal diagnosis is seen as an important preventive measure to reduce the burden of the disease. Prenatal diagnosis has been offered to 99 women in 112 pregnancies by fetal DNA analysis, using a PCR-based Amplification Refractory Mutation System (ARMS) for the common and uncommon Indian mutations. Restriction fragment length polymorphism (RFLP) for the beta-globin gene was used when the mutation remained unidentified in one of the parents or to complement the ARMS result. In 53 cases the fetus tested had beta-thalassaemia trait (betaTT) (47.3%), 22 were normal (19.6%) and 31 had thalassaemia major (27.6%). In five cases (4.5%), a definitive report could not be given due to maternal contamination. In one case (0.9%), there was a misdiagnosis. Pitfalls encountered in the diagnosis were maternal contamination and occasional non-amplification of the primers. Having established a regional centre for the prenatal diagnosis for thalassaemia, the screening programmes will be enlarged both to identify carriers and prevent the birth of further homozygous children, even during the first pregnancy.


Controlling nuclear JAKs and STATs for specific gene activation by IFNγ.
We previously showed that gamma interferon (IFNγ) and its receptor subunit, IFNGR1, interacted with the promoter region of IFNγ-activated genes along with transcription factor STAT1α. Recent studies have suggested that activated Janus kinases pJAK2 and pJAK1 also played a role in gene activation by phosphorylation of histone H3 on tyrosine 41. This study addresses the question of the role of activated JAKs in specific gene activation by IFNγ. We carried out chromatin immunoprecipitation (ChIP) followed by PCR in IFNγ treated WISH cells and showed association of pJAK1, pJAK2, IFNGR1, and STAT1 on the same DNA sequence of the IRF-1 gene promoter. The β-actin gene, which is not activated by IFNγ, did not show this association. The movement of activated JAK to the nucleus and the IRF-1 promoter was confirmed by the combination of nuclear fractionation, confocal microscopy and DNA precipitation analysis using the biotinylated GAS promoter. Activated JAKs in the nucleus was associated with phosphorylated tyrosine 41 on histone H3 in the region of the GAS promoter. Unphosphorylated JAK2 was found to be constitutively present in the nucleus and was capable of undergoing activation in IFNγ treated cells, most likely via nuclear IFNGR1. Association of pJAK2 and IFNGR1 with histone H3 in IFNγ treated cells was demonstrated by histone H3 immunoprecipitation. Unphosphorylated STAT1 protein was associated with histone H3 of untreated cells. IFNγ treatment resulted in its disassociation and then re-association as pSTAT1. The results suggest a novel role for activated JAKs in epigenetic events for specific gene activation.


Clinical benefit of ixazomib plus lenalidomide-dexamethasone in myeloma patients with non-canonical NF-κB pathway activation.
Evaluating potential relationships between progression-free survival (PFS) and tumor gene expression patterns and mutational status was an exploratory objective of the phase 3 TOURMALINE-MM1 study (NCT01564537) of ixazomib-lenalidomide-dexamethasone (IRd) vs placebo-Rd in 722 patients with relapsed/refractory multiple myeloma (MM). We utilized gene expression and mutation data from screening bone marrow aspirates to identify tumors with non-canonical nuclear factor-κB (NF-κB) signaling pathway activation. DNA/RNA sequencing data were available for 339 (47.0%)/399 (55.2%) patients; 49/339 (14.5%) patients had non-canonical NF-κB pathway gene mutations (tumor-necrosis-factor receptor-associated factor 2, 3 [TRAF2, TRAF3], baculoviral-inhibitor-of-apoptosis repeat-containing 2/3 [BIRC2/3]), and PFS was significantly longer with IRd vs placebo-Rd in these patients (hazard ratio [HR] 0.23). In patients with lower TRAF3 expression (median not reached vs 11 months, HR 0.47) and higher NF-κB-inducing kinase (NIK) expression (median not reached vs 14 months, HR 0.45), both associated with non-canonical NF-κB pathway activation, PFS was significantly longer with IRd vs placebo-Rd. TRAF3 expression was decreased in patients harboring t(4;14) and 1q21 amplification, suggesting increased non-canonical NF-κB pathway activation. Adding ixazomib to Rd provides clinical benefit in MM tumors with increased non-canonical NF-κB pathway activity. This is a potential mechanism for activity in 1q21 amplified high-risk tumors.


Polymorphisms in genes involved in sex hormone metabolism may increase risk of benign prostatic hyperplasia.
This study investigates associations between polymorphisms in genes involved in sex hormone metabolism and measures of benign prostatic hyperplasia (BPH). Community-dwelling Caucasian men (n=510, median age 60 years in 2000) from the Olmsted County, MN, participated in a longitudinal study of BPH. From 1990 through 2000, urologic measures of BPH were assessed biennially from lower urinary tract symptom severity, peak flow rates, prostate volume, serum prostate specific antigen (PSA) level, acute urinary retention, and treatment for BPH. Men were genotyped for polymorphisms in genes involved in sex hormone metabolism. With the wildtype genotype as reference, men with HSD3B1 (c.1100 A/C) heterozygous genotype (hazard ratio (HR)=0.7, 95% confidence intervals (CI)=0.6, 0.9) were at decreased risk of an enlarged prostate and men with CYP19 (TTTA)(n) genotype homozygous for >or=175 TTTA repeats (HR=1.5, 95% CI=1.1, 2.1), and CYP19 (c.1531 C/T) homozygous T variant (HR=1.6, 95% CI=1.1, 2.2) were at increased risk of an enlarged prostate. The homozygous A variant of the PSA gene (g.-252 G/A), was associated with treatment for BPH (HR=2.3, 95% CI=1.2, 4.4). In multivariate analyses, the homozygous variant genotypes of AKR1C3 (c.15 G/A and c.90 G/A) were associated with a decreased risk of an enlarged prostate (HR=0.56, 95% CI=0.35, 0.90 and HR=0.57, 95% CI=0.33, 0.98). Polymorphisms in HSD3B1, CYP19, AKR1C3 genes may be associated with an enlarged prostate in older men. These data provide insights into genes that should be examined further for their potential role in the pathogenesis of BPH.


A photoelastic study of stress concentrations produced by retention pins in amalgam restorations.
Photoelastic models of pin-amalgam restorations were constructed to simulate different pin-dentin-amalgam relationships. The stress-raising effect of a pin is influenced by the axial stiffness of the pin and its capability of bonding with the amalgam. The stress produced by a very stiff non-bonded pin could cause failure of the restoration.


Development of highly polymorphic microsatellite markers for Campanula glomerata L. (Campanulaceae).
Campanula glomerata L. (Campanulaceae) is a self-incompatible, insect-pollinated herb occurring in calcareous grasslands, and is declining and (critically) endangered in many parts of its European distribution range. It often exists as small and isolated populations. A recovery plan of C. glomerata has been implemented in southern Belgium, involving plant translocations. We developed microsatellite markers using an enriched genomic library and characterized 16 loci in 111 individuals from eight populations. These 16 loci were highly polymorphic, with 11 to 31 alleles per locus for a total of 329 alleles, and expected heterozygosity (He) ranging from 0.470 to 0.938. These highly polymorphic loci constitute a promising tool for detailed genetic analyses: assigning individuals to distinct multilocus genotypes will allow quantifying pollen dispersal, clonal propagation and sexual recruitment and identifying admixed seed progeny and their pollen donors. Evaluating the genetic status of existing populations and a genetic monitoring of the translocated populations will contribute to optimize success in restoring viable and evolutionary resilient populations.


Integrating transcriptional controls for plant cell expansion.
The plant hormones auxin and brassinosteroid promote cell expansion by regulating gene expression. In addition to independent transcriptional responses generated by the two signals, recent microarray analyses indicate that auxin and brassinosteroid also coordinate the expression of a set of shared target genes.


Solitary 18F-fluorodeoxyglucose avid spinous process cholangiocarcinoma metastasis proven on CT guided percutaneous needle bone biopsy.
A 65-year-old female with newly diagnosed cholangiocarcinoma was referred for a FDG PET/CT for initial staging. There was a region of moderate FDG avidity localizing to the hepatic hilum representing the primary site of malignancy. An unexpected moderately FDG avid focus was demonstrated in the spinous process of the T11 vertebra with no corresponding mass lesion seen on low dose CT and no evidence of distant metastatic disease elsewhere. A percutaneous CT guided needle bone biopsy was performed which confirmed a solitary T11 spinous process metastasis on histopathology.


The comparative effects of periodized lower body strength training versus high intensity circuit programming in experienced runners.
The purpose of this study was to compare the effects of supplementing habitual run training with periodized lower body strength training versus high intensity circuit strength training on running performance and related variables in experienced runners. Nineteen (N.=19) participants performed 8 weeks of 2 d·wk-1 periodized lower body strength training (PLB), N.=9, or high intensity circuit training (CT), N.=10. PLB sessions included 2 sets of the back squat, standing calf raise, leg press, and dumbbell lunge, with intensity linearly periodized. CT sessions simulated CrossFit-style programming and included 2-4 heavy (>10-RM) sets of a compound lift, followed by a high intensity, whole body resistance circuit. Three-km time trial (TT), V̇O<inf>2</inf>max, relative leg press 1-RM, running economy (RE) at 2 standard submaximal velocities (SV1, SV2) between 11 and 14 km∙hr-1, RPE at SV1/SV2, and peak/mean power were assessed pre and postintervention. Similar (P≤0.02) increases occurred in RE at 11 km∙hr-1 (36.4±3.1 to 35.4±2.4 mL·kg-1·min-1) and RPE at SV1 (12.5±1.3 to 11.4±1.6). Relative 1-RM (2.54±0.41 to 3.40±0.72) and RPE at SV2 (14.1±1.3 to 12.9±1.8) improved in both groups (P≤0.03). However, PLB showed larger improvements in 1-RM (0.43±0.18 vs. 0.2±1.9, t=2.75, P=0.015) and RPE at SV2 (-1.75±0.9 vs. -0.63±1.1, t=2.30, P=0.037). TT, V̇O<inf>2</inf>max, RE at 12-14 km∙hr-1, and power were unchanged (P≥0.27). PLB and CT enhanced 1-RM, RE at 11 km∙hr-1 and RPE at SV1/SV2, but neither modality improved TT performance, V̇O<inf>2</inf>max, anaerobic power, or RE at faster velocities. PLB resulted in greater improvements in 1-RM and RPE at SV2.


Neurologic consultations in a general hospital. Spectrum of latrogenic disease.
In a prospective study of 1,500 neurologic consultations during 1978 and 1984 within the Johns Hopkins Hospital, iatrogenic neurologic conditions were found in 14 percent of patients. The most common antecedents were angiography, cardiac surgery, and immunosuppression. Neurologists found previously unsuspected significant neurologic conditions in 27 percent of patients. Determining the underlying causes of delirium posed a special diagnostic problem. The accuracy of general physicians and surgeons in the application of criteria for brain death was low. Consultations for solely medical-legal reasons are increasing. These findings indicate the need for improved surveillance of neurological injury in hospitals, earlier recognition of delirium and research into its mechanisms, and additional education about criteria for brain death.


Use of Phenols as Nucleophiles in the Zbiral Oxidative Deamination of N-Acetyl Neuraminic Acid: Isolation and Characterization of Tricyclic 3-Keto-2-deoxy-nonulosonic Acid (KDN) Derivatives via an Intermediate Vinyl Diazonium Ion.
It is well established that the N-nitrosoamide derived from peracetylated derivatives of N-acetyl neuraminic acid on treatment with a mixture of sodium isopropoxide and trifluoroethanol, followed by the addition of acetic acid, gives an oxidative deamination product, in which the AcN(NO)-C5 bond is replaced with a AcO-C5 bond with the retention of configuration, affording a practical synthesis of 2-keto-3-deoxy-d-glycero-d-galactononulosonic acid (KDN) derivatives. Application of other strong acids, including hydrogen fluoride, thioacetic acid, trifluoromethanesulfonic acid, and hydrogen azide, functions similarly to afford KDN derivatives functionalized at the 5-position. We describe our attempts to extend the range of useful nucleophiles employed in this oxidative deamination process to include phenols and thiophenols, resulting in the discovery of a new branch of the general reaction and the formation of a series of products resulting from substitution of the 5-acetamido group and of the 4-acetoxy group from neuraminic acid. A mechanistic rationale for the formation of these products is advanced according to which, in the absence of acids of pKa ≤ 8, the intermediate diazonium ion resulting from the elimination of acetic acid and nitrogen from the nitrosoacetamide undergoes elimination of acetic acid from the 4-position to afford a highly electrophilic alkenediazonium ion. Reversible conjugate addition of the nucleophile to the 4-position then initiates the reaction cascade leading to the ultimate products.


Submental island flap.
The submental island flap is a local flap that is simple to raise and is useful for oral and lower face reconstruction of soft tissue defects. It is based on the submental artery and the facial vein. Using a retrograde flow design allows for reconstruction of forehead, temporal, and periorbital defects. Raising the flap with the ipsilateral digastric and a portion of the mylohyoid muscle is helpful in protecting the vascular pedicle. Extra care is required when raising the flap when performing an elective or therapeutic neck dissection, because Level I lymph-node-bearing tissue may be harvested with the flap.


Physical examination of the knee.
Regardless of whether knee pain is acute or chronic in presentation, the primary care physician must be confident and practiced in his or her musculoskeletal examination skills to perform a thorough assessment. Keeping in mind the types of problems that tend to occur in different age groups and in certain patient populations with particular risk factors, a preconceived differential diagnosis list should be present in the physician's mind. In most cases, the history and physical examination findings are sufficient to formulate a definitive diagnosis. Plain radiography (multiple views) and laboratory studies if indicated may narrow the differential. Advanced imaging studies will affirm the clinical findings. Referral may be necessary for surgical management, particularly in pediatric and unstable orthopedic cases (eg, suspected growth plate injury, compartment syndromes, displaced or intra-articular fractures). Consultation should always be readily available if questions arise on preliminary clinical work-up and management.


Meningioma resection and venous thromboembolism incidence, management, and outcomes.
Meningioma resection is associated with the risk of venous thromboembolism (VTE). To determine the incidence and risk factors for VTE following meningioma resection and VTE outcomes based on the type and timing of anticoagulation. From 2011 to 2019, 901 consecutive patients underwent meningioma resection. We retrospectively evaluated the postoperative incidence of VTE and bleeding. For VTE, we determined the treatment strategy and rate of VTE complications and bleeding. Pharmacologic prophylaxis was administered to 665 (73.8%) patients. The cumulative incidence for total postoperative VTE was 8.7% (95% CI: 6.9%-10.6%), and for symptomatic VTE was 6.0% (95% CI: 4.6%-7.7%). A multivariable model identified the following independent predictors of symptomatic VTE: history of VTE, obesity, and lack of pharmacologic prophylaxis. Following postoperative VTE, 58 (74.3%) patients received therapeutic anticoagulation either initially (33.3%) or after a median delay of 23.5 days (41.0%). Symptomatic recurrent VTE occurred in 13 (16.6%) patients. Following VTE, the use of subtherapeutic anticoagulation was associated with a lower rate of total VTE extension than no anticoagulation (17.5% vs 42.9%, OR 0.28, 95% CI: 0.09-0.93). In total, 14 patients (1.6%) experienced clinically relevant bleeding: 4 received therapeutic anticoagulants, 8 received prophylactic anticoagulation, and 2 received no anticoagulation. Among patients with VTE, 4 (5.1%) experienced bleeding. Recognition of risk factors for VTE following meningioma resection may help improve approaches to thromboprophylaxis. The management of postoperative VTE is highly variable, but most VTE patients are ultimately treated with therapeutic anticoagulants.


Natural compounds as anti-atherogenic agents: Clinical evidence for improved cardiovascular outcomes.
Atherosclerosis, a chronic progressive inflammatory condition characterized by the formation of lipid-laden lesions in arterial walls, is associated with substantial morbidity (including ischaemic stroke and myocardial infarction) and mortality. Risk factors for atherosclerosis are well understood and can be ameliorated by evidence-based and guideline-directed pharmaceutical agents (e.g. the reduction of circulating concentrations of low-density lipoprotein cholesterol by statins). Additionally, many natural products (usually food derivatives) and 'nutraceuticals' (pharmaceutical formulations prepared from components of foods) have been shown to have favourable effects on risk factors for atherosclerotic cardiovascular disease. This literature review summarises the evidence for anti-atherogenic natural compounds. The article focuses on agents which are discussed in international guidelines and are supported by extensive high-quality randomized-controlled trial (RCT) data. We focus on micronutrients (compounds present in food in small quantities) and nutraceuticals, in particular, phytosterols, polyunsaturated ω-3 fatty acids and red-yeast rice. We conclude that the 'nutraceutical approach' (identify the active ingredients in natural products; produce high-quality products according to Good Manufacturing Practice guidelines; evaluate them in long-term outcomes trials) is the mechanism by which the domains of natural product research and evidence-based medicine can move closer together.


[Use of CO2 laser in the treatment of condylomata acuminata of the anogenital region in pregnant women].
The first results of treatment of condylomata acuminata of anogenital region in 11 pregnant women were presented. The analysis were made in Department of Reproduction, Institute of Gynecology and Obstetrics, Academy of Medicine, Poznań. All patients were treated between 28 and 35 week of pregnancy. After first laser-therapy the healing achieved in 9 women. The second lasertherapy was required in 2 patients. It was done after 3 weeks. Complete destruction of pathological changes was obtained. All women had vaginal delivery and no complications (connected with HPV infection) in their newborns were found. The authors said that CO2-lasertherapy under colposcopic control is a reliable method for treatment of condylomata acuminata in pregnant women.


Novel 29 kDa heparin-binding lectin from human foetal brain.
Heparin inhibitable lectins are physiologically important because of their interactions with extracellular matrix and with other cell surface glycoconjugates. However, due to the unstable nature of these animal lectins, it becomes necessary to purify them in the shortest possible time. In the present study, a chromatographic procedure was developed to separate heparin inhibitable lectin activity. Lectin activities from human foetal brain were separated on a Q-Sepharose column employing different equilibration conditions. When proteins were loaded on to a phosphate-buffered saline (PBS) equilibrated column and eluted with salt gradient, only one lectin peak was obtained. However, when proteins were loaded on to a hypotonic equilibrated column and eluted with a salt gradient, four lectin peaks were obtained. The lectin peak obtained from the PBS equilibrated column was characterized as heparin inhibitable lectin. On SDS-PAGE analysis, it gave a single band of 29 kDa. For optimum lectin activity, a pH of around 7.0 was required. Lectin activity was stimulated by Mn++; amino acid composition was different from other known lectins. The lectin was particularly rich in acidic amino acids. Regional distribution of 29 kDa lectin in different foetal brain regions gave the highest content in the cerebral cortex, showing a caudoroastral distribution. Determination of the subcellular distribution of the lectin in the foetal cerebral cortex gave the highest value with a mitochondrial fraction.


Taxonogenomics description of Parabacteroides timonensis sp. nov. isolated from a human stool sample.
Intensive efforts have been made to describe the human microbiome and its involvement in health and disease. Culturomics has been recently adapted to target formerly uncultured bacteria and other unclassified bacterial species. This approach enabled us to isolate in the current study a new bacterial species, Parabacteroides timonensis strain Marseille-P3236T , from a stool sample of a healthy 39-year-old pygmy male. This strain, is an anaerobic, gram-negative, nonspore-forming motile rod. Its genome is made up of 6,483,434 bp with 43.41% G+C content, 5046 protein-encoding genes, and 84 RNA genes. We herein provide the full description of Parabacteroides timonensis strain Marseille-P3236T through the taxonogenomic approach.


Bacterial DNA content in the intestinal wall from infants with necrotizing enterocolitis.
The objective of our study was to quantify mucosal bacterial DNA within specimens from neonates undergoing small bowel resection for necrotizing enterocolitis (NEC). We obtained clinical information and pathologic specimens from all infants diagnosed with NEC who underwent surgical treatment at our institution from 1999 to 2008. Bacterial and human DNA were isolated from paraffin-embedded surgical specimens, and real time polymerase chain reaction was used to amplify bacterial and human genes. Linear regression was used to quantify the amount of human and bacterial DNA in our specimens. From a cohort of 50 infants, we identified 23 infants who underwent both surgical resection and subsequent intestinal reanastomosis. Thirteen (59%) of the neonates had Bell stage III NEC, and 9 (41%) had stage II. There was significantly more bacterial DNA in the resection specimens than in the reanastomosis specimens. This corresponds to a median (interquartile range) increase of 1.81 (1.11-4.69)-fold bacterial DNA in the resection specimen compared with the reanastomosis specimen (P < .05). There is more bacterial DNA in infants with acute NEC compared with the same infants after the NEC had clinically resolved. These findings underscore the potential relevance of adherent or invasive bacteria across the bowel wall in the pathogenesis of NEC.


Immunoelectron microscopic localization of penicillinase in Bacillus licheniformis.
Penicillinase was localized in log-phase cells of Bacillus licheniformis 749/C by labeling with ferritin-anti-penicillinase immunoglobulin G conjugate. Mildly fixed homogenized cells, isolated subcellular fractions, and frozen thin sections were labeled. The label was distributed in discrete patches in the cell envelope. The patches extended from the inside part of the membrane to the outside part of the wall. The inside part of the membrane was labeled more extensively than the outside part. The cytoplasm also bound some ferritin-immunoglobulin G conjugate. Immunoelectrophoresis and biochemical assay of cytosol material suggest that the cytoplasmic antigenic sites are a protease-sensitive form of penicillinase.


Molecular analysis of Y chromosome microdeletions in idiopathic cases of male infertility in Serbia.
The aim of this study was to detect frequency of microdeletions of Y chromosome in idiopathic cases of male infertility in Serbian population. Patients were subjected to detailed clinical, endocrinological and cytogenetic examinations. Ninety patients with normal cytogenetic findings with azoospermia and severe oligozoospermia were included in the study. In these patients microdeletion analysis was performed by multiplex polymerase chain reaction (PCR) method on DNA extracted from peripheral blood. In each case 6 markers in azoospermia factor (AZF) regions were tested: sY84, sY86 (AZFa); sY127, sY134 (AZFb); sY254, sY255 (AZFc). Deletions on Y chromosome were detected in 14 of 90 cases (15.6%), 9 with azoospermia and 5 with severe oligozoospermia. Of total number of 17 deletions, 11 (64.7%) were detected in AZFc region, 3 (17.6%) in AZFa region and 3 (17.6%) in AZFb region. Microdeletions in AZF region of Y chromosome, especially AZFc microdeletions, represent common genetic cause of idiopathic azoospermia and severe oligozoospremia in Serbian infertile men. Therefore, testing for Y chromosome microdeletions should be considered as an important element in diagnosis and genetic counseling of infertile men in Serbia and decisions regarding the assisted reproduction should be made based on the presence and type of AZF microdeletions.


Analysis of sub-bandage pressure of compression bandages during exercise.
The sub-bandage pressure produced by any compression bandaging system is likely to vary during the physical activities taken by the patient. It is of significant importance to understand the variation of sub-bandage pressure during the exercise of calf muscle pump. The present paper aims to analyse the dominating factors and their interactions on the sub-bandage pressure during exercise. In this work the circumferential change of the leg because of the exercise of the calf muscle pump (expansion or contraction) is simulated using expansion or contraction actions of an air bladder placed on a mannequin. The study has been carried out using an indigenously developed prototype by pumping or squeezing of air in air bladder using cylinder-piston arrangement. A series of commercially available bandages were studied and the impact of the major factors, namely bandage extensibility (E), bandage tension (T) and the amount of bladder expansion or contraction (A) on the sub-bandage pressure during one cycle of expansion or contraction of air bladder have been analysed. Different levels of the factors have been chosen and a complete factorial design was prepared to obtain the sub-bandage pressure at all combination of the levels of the factors. The results showed that the sub-bandage pressure variations were higher for short-stretch bandage under dynamic mode (p value < 0.05). The variation in sub-bandage pressure were increased by increasing the amount of expansion or contraction of the air bladder and also increased when the bandage was wrapped at higher tension level (p-value < 0.05). N-way ANOVA results showed that some of the interactions effects of these above factors (EA and AT) also significantly affecting the sub-bandage pressure variations (p-value < 0.05). The prototype provides a simpler method to assess the bandage behaviour under different conditions without doing in vivo sub-bandage pressure measurement, and hence could be used to evaluate and compare the effectiveness of different compression bandage under different conditions, prior to their application on the wounded leg.