Predictors and health-related outcomes of positive body image in adolescent girls: A prospective study.
This study aimed to investigate prospective predictors and health-related outcomes of positive body image in adolescent girls. In so doing, the modified acceptance model of intuitive eating was also examined longitudinally. A sample of 298 girls aged 12 to 16 years completed a questionnaire containing measures of body appreciation, potential predictors, and a range of health outcomes, at 2 time points separated by 1 year. Longitudinal change regression models showed that perceived body acceptance by others (positively), self-objectification and social comparison (negatively), and body appreciation (positively) prospectively predicted intuitive eating 1 year later, consistent with the acceptance model of intuitive eating. Perceived body acceptance by others was the only proposed predictor to prospectively predict an increase in body appreciation over time. Time 1 body appreciation prospectively predicted a decrease in dieting, alcohol, and cigarette use, and an increase in physical activity 1 year later. In particular, girls with low body appreciation were more likely than girls with high body appreciation to take up alcohol and cigarette use between time points. The results highlight body appreciation as an important target for interventions designed to prevent or delay the uptake of alcohol and cigarette consumption among girls. More broadly, they suggest that a positive body image can confer considerable benefit for adolescent girls.


Treatment of delayed union and nonunion with an implanted direct current stimulator.
A multicentered research program on direct electrical current for stimulation of bone healing was performed by 30 Australian orthopedic surgeons. The program was designed to test an implanted device named direct current bone growth stimulation (DCBGS). The DCBGS achieved union in 72 of 84 (86%) cases of ununited fractures of long bones. These results are comparable to those obtained with other devices. The time to achieve sound union however, appears to be significantly less than by conventional bone grafting techniques. The procedure is safe and simple, with a short hospital stay and low rate of complications. Certain technical details have been stressed. The presence of previous infection is not a contraindication to this procedure. The procedure has advantages over Phemister or Charnley bone graft operations in that it produces less pain, generally avoids the need for a cancellous bone graft and allows an anterior approach to the shaft of the tibia when this might otherwise not be possible. The results for the various techniques of applying electric stimulation to bone are generally comparable although the clinical indications favoring one technique over another have yet to be determined. Electric stimulation used as described is an effective method of treatment for ununited fractures of long bones.


Alveolar bone loss in T helper 1/T helper 2 cytokine-deficient mice.
The role of cytokines in bone loss is important in the context of periodontitis, where inflammation-induced bone destruction is a major manifestation. Numerous cytokines have been implicated as mediators of bone resorption. The purpose of this study was to observe the impact of targeted gene deletion of T helper 1 (Th1) and T helper 2 (Th2) cytokines on naturally occurring alveolar bone loss in genetically modified mice. Alveolar bone loss was measured histomorphometrically in interleukin-4, interleukin-10, interleukin-12p40, interferon-gamma (IFN-gamma) and tumor necrosis factor (TNF) knockout mice at 6, 16 and 30 wk of age. Both Th1 (interleukin-12p40, IFN-gamma, TNF) and Th2 (interleukin-10, interleukin-4) knockout mice exhibited significantly more alveolar bone loss than their respective wild-type control mice (p<0.001). Interleukin-10-/- and interleukin-12p40-/- mice exhibited a three-fold increase in alveolar bone loss at 30 wk of age, whereas bone loss in IFN-gamma-/-, TNF-/- and interleukin-4-/- mice was 1.5- to two-fold higher compared with wild-type control mice. The results of the present study indicate that both Th1 and Th2 cytokines play an important role in maintaining alveolar bone homeostasis. The kinetics of alveolar bone loss seen in cytokine gene knockout mice indicates that bone loss is age dependent and late in onset.


Predictors of mortality in cancer patients who need intensive care unit support: a two center cohort study
Cancer patients frequently need intensive care support due to respiratory failure. We aimed to evaluate the predictors of mortality in cancer patients who were admitted to the intensive care unit (ICU). This study was performed in the ICUs of two centers between 1 January 2008 and 31 December 2015. Demographic data, cancer type, causes of respiratory failure, comorbidities, APACHE II scores, treatments, and mortality rates were recorded. A total number of 583 cancer patients (477 males) were enrolled from the two centers. Of those, 472 patients had lung cancer (81%), while 111 had extrapulmonary malignancies (19%), having similar mortality rates. Causes of respiratory failure were mostly invasion of the cancer itself in 84% of cases and due to infection in 12%. ICU mortality rate was 53% and the 1-year mortality rate was 80%. APACHE II scores were significantly higher in nonsurvivors (P < 0.001). One-year survival was found to be significantly shorter in females than males (9 days vs. 12 days) in patients with lung cancer. Mortality rates of cancer patients who need ICU support are higher than overall ICU mortality. High APACHE II scores and female sex seem to be related to mortality in these patients.


Care After Presenting with Seizures (CAPS): An analysis of the impact of a seizure referral pathway and nurse support on neurology referral rates for patients admitted with a seizure.
The National Audit of Seizure Management in Hospitals (NASH) identified low referral rates to neurology and epilepsy services after an emergency department attendance or admission with a seizure. National Health Service Secondary Users Service (SUS) data were used to assess the impact of a seizure pathway at seven hospitals in Cheshire & Merseyside, which was implemented in 2014. Three of these hospitals also had a nurse employed part-time to support the pathway. Patients admitted with a seizure between 2011 and 2018 inclusive were identified using an algorithm based on ICD-10 codes, and the primary outcome was a neurology referral within 3 months of admission. Regression models were used to assess the impact of age, deprivation and comorbidity on post admission clinic referral rates. 13,285 admissions with seizure were included in the analysis. 5,677 had not attended a neurology clinic appointment in the 12 months before the admission. The percentage of whom that were offered an appointment following the admission was: 16.0% before the pathway and 35.9% with the nurse-supported pathway, which was significant in the regression model. 4,700 admissions had attended a neurology clinic appointment in the 12 months before the admission. Of this group, the percentage of whom that were offered an appointment following the admission was: 55.2% before the pathway and 62.4% with the nurse-supported pathway, an increase that was not significant in the regression model. The regression models identified significant health inequalities whereby older patients, those with comorbidities and those living in deprived areas were significantly less likely to be referred. Neurology out-patient appointment rates following an admission with seizures are low, worryingly so for those with no neurology appointment in the previous 12 months. A nurse-supported pathway can improve appointment rates, but the effect is modest. Further service redesign is required; the impact of which should be rigorously evaluated.


Removal of fluoride by thermally activated carbon prepared from neem (Azadirachta indica) and kikar (Acacia arabica) leaves.
The present investigation deals with fluoride removal from aqueous solution by thermally activated neem (Azadirachta indica) leaves carbon (ANC) and thermally activated kikar (Acacia arabica) leaves carbon (AKC) adsorbents. In this study neem leaves carbon and kikar leaves carbon prepared by heating the leaves at 400 degrees C in electric furnace was found to be useful for the removal of fluoride. The adsorbents of 0.3 mm and 1.0 mm sizes of neem and kikar leaves carbon was prepared by standard sieve. Batch experiments done to see the fluoride removal properties from synthetic solution of 5 ppm to study the influence of pH, adsorbent dose and contact time on adsorption efficiency The optimum pH was found to be 6 for both adsorbents. The optimum dose was found to be 0.5g/100 ml forANC (activated neem leaves carbon) and 0.7g/100 ml forAKC (activated kikar leaves carbon). The optimum time was found to be one hour for both the adsorbent. It was also found that adsorbent size of 0.3 mm was more efficient than the 1.0 mm size. The adsorption process obeyed Freundlich adsorption isotherm. The straight line of log (qe-q) vs time at ambient temperature indicated the validity of langergren equation consequently first order nature of the process involved in the present study. Results indicate that besides intraparticle diffusion there maybe other processes controlling the rate which may be operating simultaneously. All optimized conditions were applied for removal of fluoride from four natural water samples.


Intracranial dural arteriovenous fistula successfully treated by combined open-endovascular procedure.
Intracranial dural arteriovenous fistulas constitute a rare though potentially devastating disease. Because the arterial (high-pressure) blood flow drains directly into the low-pressure venous system, there is a high risk of bleeding and associated neurological deficit. The classifications by Borden and Cognard underline the correlation between bleeding risk and venous drainage pattern of the fistula. There are different treatment options for this vascular pathology, which always poses a challenge for the physicians involved to offer the optimal treatment for an individual patient. This case report illustrates how combining forces between the neurosurgical and endovascular team benefits outcome. Simultaneously, this contributes to the growing amount of evidence that a new endovascular technique with transarterial ONYX embolisation enables complete obliteration of the vascular malformation.


MLLT11 siRNA Inhibits the Migration and Promotes the Apoptosis of MDA-MB-231 Breast Cancer Cells.
Breast cancer is considered the most prevalent malignancy due to its high incidence rate, recurrence, and metastasis in women that makes it one of the deadliest cancers. The current study aimed to predict the genes associated with the recurrence and metastasis of breast cancer and to validate their effect on MDA-MB-231 cells. Through the bioinformatics analysis, the transcription factor 7 cofactor (MLLT11) as the target gene was obtained. MLLT11-specific siRNA was synthesized and transfected into MDA-MB-231 cells. The results demonstrated that the siRNA significantly reduced the MLLT11 mRNA levels. Moreover, cell migration and invasion, as well as the protein levels of phosphatidylinositol 3-kinase (PI3K), AKT, matrix metalloproteinase (MMP) 2, and MMP9, were significantly lower in the groups treated with siRNA while the apoptosis was augmented. Collectively, MLLT11 siRNA elicited ameliorative properties on breast cancer cells, possibly via the inhibition of the PI3K/AKT signaling pathway.


TnTIN and TnTAP: mini-transposons for site-specific proteolysis in vivo.
Tobacco etch virus (TEV) protease recognizes a 7-aa consensus sequence, Glu-Xaa-Xaa-Tyr-Xaa-Gln-Ser, where Xaa can be almost any amino acyl residue. Cleavage occurs between the conserved Gln and Ser residues. Because of its distinct specificity, TEV protease can be expressed in the cytoplasm without interfering with viability. Polypeptides that are not natural substrates of TEV protease are proteolyzed if they carry the appropriate cleavage site. Thus, this protease can be used to study target proteins in their natural environment in vivo, as well as in vitro. We describe two TnS-based mini-transposons that insert TEV protease cleavage sites at random into target proteins. TnTIN introduces TEV cleavage sites into cytoplasmic proteins. TnTAP facilitates the same operation for proteins localized to the bacterial cell envelope. By using two different target proteins, SecA and TolC, we show that such modified proteins can be cleaved in vivo and in vitro by TEV protease. Possible applications of the site-specific proteolysis approach are topological studies of soluble as well as of inner and outer membrane proteins, protein inactivation, insertion mutagenesis experiments, and protein tagging.


Hsa_circ_0006948 enhances cancer progression and epithelial-mesenchymal transition through the miR-490-3p/HMGA2 axis in esophageal squamous cell carcinoma.
Increasing studies have indicated that circular RNAs (circRNAs) are important in cancer progression. However, few circRNAs associated with epithelial-mesenchymal transition (EMT) have been elucidated in esophageal squamous cell carcinoma (ESCC). In this study, we aimed to identify whether hsa_circ_0006948 promotes ESCC cell EMT and explore its biological mechanisms. We first screened circRNA expression profiles using a circRNA microarray, and found that the expression of a novel circRNA, hsa_circ_0006948, is increased in 153 ESCC tissues and cell lines compared with noncancerous tissues and cell lines. Additionally, high hsa_circ_0006948 levels were positively associated with lymphatic metastasis and poor prognosis. Functionally, the assays indicated that cell proliferation, migration and invasion were promoted by hsa_circ_0006948 both in vitro and in vivo. Furthermore, we analyzed the relationship between hsa_circ_0006948 and miR-490-3p through bioinformatics, luciferase reporter assays, RNA immunoprecipitation and qRT-PCR. We found that hsa_circ_0006948 could bind directly to miR-490-3p which targets the 3'UTR of the oncogene HMGA2 to induce EMT. In conclusion, hsa_circ_0006948 was overexpressed in ESCC tissues and promoted cancer progression, and it could induce EMT by enhancing HMGA2 by sponging miR-490-3p, suggesting that hsa_circ_0006948 could be a biomarker for ESCC.


Animal models of osteoarthritis in an era of molecular biology.
Animal models of osteoarthritis (OA) are used to study the pathogenesis of cartilage degeneration and to evaluate potential anti-arthritic drugs for clinical use. In general, these models fall into 2 categories, spontaneous and induced (surgical instability or genetic manipulation). Animal models of naturally occurring OA occur in knee joints of guinea pigs, mice and Syrian hamsters. Commonly utilized surgical instability models include medial meniscal tear in guinea pigs and rats, medial or lateral partial meniscectomy in rabbits, medial partial or total meniscectomy or anterior cruciate transection in dogs. Transgenic models have been developed in mice. These models all have potential use in the study of molecular mechanisms associated with OA development via use of immunohistochemistry, biochemistry and molecular probes to identify altered matrix molecules at different stages in disease progression. Testing of specific types of inhibitors developed through evaluation of matrix changes in the disease process will ultimately help identify key processes which initiate and perpetuate the disease and will lead to discovery of new disease modifying pharmaceutical agents for OA patients. This paper will focus on the discussion of several models which are likely to be useful in the molecular dissection of processes involved in cartilage degeneration.


Blood glucose concentrations and progression of diabetic retinopathy: the seven year results of the Oslo study.
To study insulin dependent diabetic patients for change in non-proliferative retinopathy and its relation to glycaemic control and to various clinical background data. Prospective study with follow up for seven years. Outpatient departments of university hospitals. Glycated haemoglobin concentration; degree of retinopathy. Retinopathy worsened by an overall increase in counts of microaneurysms and haemorrhages from 17 (SD 25) to 45 (58) (p = 0.005). Intensified insulin treatment and home blood glucose monitoring improved concentrations of glycated haemoglobin (HbA1) from 11.2% (2.2%) at the start of the study to a mean of 9.5% (1.5%) over the seven years of the study (p less than 0.0001). A mean value for HbA1 greater than 10% was associated with an increased risk of progression of retinopathy and a mean value less than 8.7% was associated with a diminished risk. Multiple regression analysis identified four independent variables as indicative of outcome of retinopathy after seven years: HbA1 value at baseline; the change in HbA1 from start to the mean level through the seven years; duration of diabetes; and retinopathy at start. Age, blood pressure, and urinary albumin excretion were not related to the presence or progression of retinopathy. Secondary intervention by long term lowering of glycated haemoglobin has a beneficial impact on non-proliferative retinopathy. A four factor regression model can determine patients at high risk of severe retinopathy.


Chest-wall invasion by carcinoma of the lung: detection by MR imaging.
Nineteen patients with bronchogenic carcinoma were studied by MR imaging to determine the presence of chest-wall invasion. All studies were carried out at 1.5 T, and the results were correlated with chest radiographs or CT scans. All MR studies were interpreted before surgery (13 cases) and without knowledge of the results of other radiologic studies. MR findings indicative of chest-wall invasion included a high-signal focus within the chest wall and/or chest-wall thickening with increased signal on spin-echo (SE) images having a repetition time of 2500 msec and an echo time of 50-100 msec (SE 2500/50-100). In one case, noncontour-deforming high-signal intensity within chest-wall musculature (but no other abnormality) was demonstrated on SE 2500/50-100 images. Coronal or sagittal imaging facilitated identification of tumor contiguity with extrathoracic structures in apical lesions. Contrast differences between normal and invaded chest wall on T2-weighted images were the most helpful in assessing chest-wall involvement. These preliminary observations indicate that MR imaging is useful in the evaluation of chest-wall invasion by carcinoma of the lung.


Aspirin-Induced Ordering and Faster Dynamics of a Cationic Bilayer for Drug Encapsulation.
The lipid dynamics and phase play decisive roles in drug encapsulation and delivery to the intracellular target. Thus, understanding the dynamic and structural alterations of membranes induced by drugs is essential for targeted delivery. To this end, united-atom molecular dynamics simulations of a model bilayer, dioctadecyldimethylammonium bromide (DODAB), are performed in the absence and presence of the usual nonsteroidal anti-inflammatory drug (NSAID), aspirin, at 298, 310, and 345 K. At 298 and 310 K, the bilayers are in the interdigitated two-dimensional square phases, which become rugged in the presence of aspirin, as evident from height fluctuations. At 345 K, the bilayer is in the fluid phase in both the absence and presence of aspirin. Aspirin is preferentially located near the oppositely charged headgroup and creates void space, which leads to an increase in the interdigitation and order parameters. Although the center of mass of lipids experiences structural arrest, they reach the diffusive regime faster and have higher lateral diffusion constants in the presence of aspirin. Results are found to be consistent with recent quasi-elastic neutron scattering studies that reveal that aspirin acts as a plasticizer and enhances lateral diffusion of lipids in both ordered and fluid phases. Different relaxation time scales of the bonds along the alkyl tails of DODAB due to the multitude of lipid motions become faster upon the addition of aspirin. Our results show that aspirin insertion is most favorable at physiological temperature. Thus, the ordered, more stable, and faster DODAB bilayer can be a potential drug carrier for the protected encapsulation of aspirin, followed by targeted and controlled drug release with antibacterial activity in the future.


Use of polyelectrolyte complex-stabilized calcium alginate gel for entrapment of beta-amylase.
Calcium alginate gel stabilized with a polyelectrolyte complex (PEC) consisting of potassium poly(vinyl alcohol) sulfate (KPVS) and trimethylammonium glycol chitosan iodide (TGCI) was used for the immobilization of beta-amylase. The immobilization was made by gelling aqueous droplets of enzyme solution including both sodium alginate and KPVS in a CaCl(2) solution containing TGCI. The activity of the enzyme entrapped into the stabilized gel beads was evaluated by studying the batch reaction kinetics of enzyme-catalyzed hydrolysis of maltotetraose. Repeated kinetic measurements, totaling 18, were carried out at fixed time intervals. After each measurement the beads were stirred for 1 day in a freshly prepared 10 mM NaCl solution at 3 degrees C. It was found that the immobilized system remained stable without leading to a serious loss of the activity or to a large leakage of the enzyme from the support. This was explained as being due to a PEC-crosslinked contracted network structure of the stabilized gel matrix.


Incorporating Advances in Molecular Pathology Into Brain Tumor Diagnostics.
Recent advances in molecular pathology have reshaped the practice of brain tumor diagnostics. The classification of gliomas has been restructured with the discovery of isocitrate dehydrogenase (IDH) 1/2 mutations in the vast majority of lower grade infiltrating gliomas and secondary glioblastomas (GBM), with IDH-mutant astrocytomas further characterized by TP53 and ATRX mutations. Whole-arm 1p/19q codeletion in conjunction with IDH mutations now define oligodendrogliomas, which are also enriched for CIC, FUBP1, PI3K, NOTCH1, and TERT-p mutations. IDH-wild-type (wt) infiltrating astrocytomas are mostly primary GBMs and are characterized by EGFR, PTEN, TP53, NF1, RB1, PDGFRA, and CDKN2A/B alterations, TERT-p mutations, and characteristic copy number alterations including gains of chromosome 7 and losses of 10. Other clinically and genetically distinct infiltrating astrocytomas include the aggressive H3K27M-mutant midline gliomas, and smaller subsets that occur in the setting of NF1 or have BRAF V600E mutations. Low-grade pediatric gliomas are both genetically and biologically distinct from their adult counterparts and often harbor a single driver event often involving BRAF, FGFR1, or MYB/MYBL1 genes. Large scale genomic and epigenomic analyses have identified distinct subgroups of ependymomas tightly linked to tumor location and clinical behavior. The diagnosis of embryonal neoplasms also integrates molecular testing: (I) 4 molecularly defined, biologically distinct subtypes of medulloblastomas are now recognized; (II) 3 histologic entities have now been reclassified under a diagnosis of "embryonal tumor with multilayered rosettes (ETMR), C19MC-altered"; and (III) atypical teratoid/rhabdoid tumors (AT/RT) now require SMARCB1 (INI1) or SMARCA4 (BRG1) alterations for their diagnosis. We discuss the practical use of contemporary biomarkers for an integrative diagnosis of central nervous system neoplasia.


Glucose-dependent insulinotropic peptide-overexpressing transgenic mice have increased bone mass.
Glucose-dependent insulinotropic peptide (GIP) is an intestinally secreted hormone the release of which is stimulated by nutrient ingestion. We previously reported that GIP receptors are present in osteoblastic cells and that GIP increases collagen type I synthesis and alkaline phosphatase activity in isolated osteoblasts. We have also shown that osteoclasts express GIP receptors and that GIP inhibits osteoclastic activity and differentiation. In addition, using GIP receptor knockout mice we demonstrated that absence of GIP receptor signaling resulted in a low bone mass phenotype. To further define GIP's role as an anabolic hormone in vivo, we utilized a genetically altered mouse model, a transgenic mouse overexpressing GIP under the control of the metallothionein promoter (Tg+). Tg+ mice had significantly higher mean GIP levels even in the absence of added dietary zinc. Tg+ animals also had a significant increase in markers of bone formation and a decrease in markers of bone resorption. Consistent with these biochemical data, GIP transgenic mice had a significant increase in bone mass as measured by densitometry and histomorphometry. These data support the conclusion that GIP inhibits bone resorption and stimulates bone formation and that excess signaling through the GIP receptor results in gain of bone mass. In view of GIP's role in nutrient absorption, our data suggest that this hormone may serve an important role in linking nutrient ingestion to bone formation.


Global health economics: The Equitable Impact Sensitive Tool (EQUIST) - development, validation, implementation and evaluation of impact (2011 to 2022).
The Equitable Impact Sensitive Tool (EQUIST) was developed to address the limitations of the traditional cost-effectiveness analysis (CEA) in global health, which often overlooked equity considerations. Its primary aim was to create more effective and efficient health systems by explicitly incorporating equity as a key driver in health policy decisions. This was done in response to the recognition that, while CEA helped reduce mortality rates through interventions like childhood vaccinations, it was insufficient in addressing growing inequalities in health, especially in low-and-middle-income countries (LMICs). The development of EQUIST involved a multi-stage process which began in 2011 with the recognition of the need for a more nuanced approach than CEA alone. This led to a proposal for creating a tool that balanced cost-effectiveness with equity. The conceptual framework, developed between March and May 2012, included assessments of intervention efficiency by equity strata, effectiveness, impact, and cost-effectiveness. Key to EQUIST's development was its integration with other data science platforms, notably the Lives Saved Tool and the Marginal Budgeting for Bottlenecks tool, allowing EQUIST to draw on comprehensive data sets and thus enabling a more detailed analysis of health interventions' impacts across different socio-economic strata. EQUIST was validated in 2012 through applications in five representative countries, demonstrating its ability to identify more equitable and cost-effective health interventions which targeted vulnerable populations, leading to more lives saved compared to traditional methods. It was then used to develop investment cases for the Global Financing Facility, resulting in significant funding being made available for maternal and child health programmes. Consequently, EQUIST directly influenced the development of national health policies and resource allocations in over 26 African countries. EQUIST has proven to be a valuable tool in developing health policies that are both cost-effective and equitable. In the future, it will be further integrated with other tools and expanded in scope to address broader health issues, including adolescent health and human immunodeficiency virus/acquired immunodeficiency syndrome programme planning. Overall, EQUIST represents a paradigm shift in global health economics, emphasising the importance of equity alongside cost-effectiveness in health policy decisions. Its development and implementation have had a tangible impact on health outcomes, particularly in LMICs, where it has been instrumental in reducing maternal and child mortality while addressing health inequities.


Immunoreactivity and biologic activity of semisynthetic [LeuB-30]-insulin: potential value in the treatment of insulin antibody-mediated insulin resistance.
Insulin analogues with different amino acids, including threonine, alanine, L-leucine, D-leucine, L-leucine amide, phenylalanine, tri-alanine, or desalanine, at the B-30 position were semisynthesized from pork insulin by the new enzymatic method. The order of ability of the insulin analogues to bind to anti-insulin sera was [AlaB-30] greater than desalanine greater than [ThrB-30] greater than [Ala-Ala-AlaB-30] greater than [D-LeuB-30], [Leu-NH2B-30],[PheB-30] greater than desoctapeptide greater than or equal to [LeuB-30]. The ability of insulin analogues with different amino acids at B-30 to bind to receptors, as well as their biologic potency tested with glucose uptake in isolated rat adipocytes, was comparable among the analogues. These results suggest that [LeuB-30]-insulin demonstrated the least immunoreactivity and has full activity in receptor binding and biologic effect, and that it may be useful for treatment of anti-insulin antibody-mediated insulin resistance.


Role of migratory birds in spreading Crimean-Congo hemorrhagic fever, Turkey.
We investigated migratory birds' role in spreading Crimean-Congo hemorrhagic fever virus (CCHFV) through attached ticks. We detected CCHFV RNA in ticks on migratory birds in Turkey. Two isolates showed similarity with CCHFV genotype 4, suggesting a role for ticks in CCHFV epidemics in Turkey and spread of CCHFV by birds.


Impact of closed loop stimulation on prognostic cardiopulmonary variables in patients with chronic heart failure and severe chronotropic incompetence: a pilot, randomized, crossover study.
Clinical effects of rate-adaptive pacing in heart failure patients with chronotropic incompetence (CI) undergoing cardiac resynchronization therapy (CRT) remain unclear. Closed loop stimulation (CLS) is a new rate-adaptive sensor in CRT devices. We evaluated the effectiveness of CLS in CRT patients with severe CI, focusing primarily on key prognostic variables assessed by cardiopulmonary exercise (CPX) testing. In the randomized, crossover, multicentre BIO|CREATE study, 20 CRT patients with severe CI and NYHA Class II/III (60%/40%) were randomized 1:1 to the sequence DDD-40 mode to DDD-CLS mode, or the sequence DDD-CLS mode to DDD-40 mode (1 month in each mode). Patients underwent symptom-limited treadmill-based CPX test in each mode. An improvement (decrease) of the ventilatory efficiency (VE) slope of ≥5% during CLS was regarded as positive response to CLS. Seventeen patients with full data sets had a mean intra-individual VE slope change of -1.8 ± 3.0 (-4.1%) with CLS (P = 0.23). Eight patients (47%) were CLS responders, with a -6.1 ± 2.7 (-16.4%) slope change (P = 0.029). Compared to non-responders, CLS responders had a higher left ventricular (LV) ejection fraction (46 ± 3 vs. 36 ± 9%; P = 0.0070), smaller end-diastolic LV volume (121 ± 34 vs. 181 ± 41 mL; P = 0.0085), smaller end-systolic LV volume (65 ± 23 vs. 114 ± 39 mL; P = 0.0076), and were predominantly in NYHA Class II (P = 0.0498). The data of the present pilot study are compatible with the notion that CLS activation may improve VE slope in CRT patients with severe CI and less advanced heart failure. Further research is needed to determine the long-term clinical outcomes of CLS.


Drivers of cousin marriage among British Pakistanis.
Why has the apparently high rate of cousin marriage among Bradford Pakistanis been sustained, 50 years since Pakistani migration to Britain began? A review of the anthropological literature on Pakistani migration and settlement, British Pakistani marriage patterns and the phenomenon of transnational marriage. British Pakistanis are diverse in regional origins and social class characteristics, with many Bradford Pakistanis originating from the Mirpur district and northern Punjab. British Pakistani marriages often involve a partner from Pakistan who joins a spouse in the UK. Transnational marriage of first cousins offers relatives in Pakistan opportunities for a 'better' life in the West and are important for British Pakistanis for economic, social, cultural and emotional reasons. These processes are also differentially influenced by region of origin and class characteristics in Pakistan as well as by education, employment and locality in Britain. The pattern observed in Bradford may not be applicable nationally. Further research examining marital decisions over several generations in families differing by social class, region of origin in Pakistan and locality in Britain is necessary to contextualise the findings from Bradford.


Abdominal ultrasound examination in pregnant blunt trauma patients.
The ability of abdominal ultrasound to detect intraperitoneal fluid in the pregnant trauma patient has been questioned. Pregnant blunt trauma patients admitted to a Level I trauma center during an 8-year period were reviewed. Ultrasound examinations were used to detect intraperitoneal fluid and considered positive if such fluid was identified. One hundred twenty-seven (61%) of 208 pregnant patients had abdominal ultrasound during initial evaluation in the emergency department. Seven patients had intra-abdominal injuries, and six had documented hemoperitoneum. Ultrasound identified intraperitoneal fluid in five of these six patients (sensitivity, 83%; 95% confidence interval, 36-100%). In the 120 patients without intra-abdominal injury, ultrasound was negative in 117 (specificity, 98%; 95% confidence interval, 93-100%). The three patients without intra-abdominal injury but with a positive ultrasound had the following: serous intraperitoneal fluid and no injuries at laparotomy (one) and uneventful clinical courses of observation (two). The sensitivity and specificity of abdominal ultrasonography in pregnant trauma patients is similar to that seen in nonpregnant patients. Occasional false negatives occur and a negative initial examination should not be used as conclusive evidence that intra-abdominal injury is not present. Ultrasound has the advantages of no radiation exposure.


Contrasting the social cognition of humans and nonhuman apes: the shared intentionality hypothesis.
Joint activities are ubiquitous in the animal kingdom, but they differ substantially in their underlying psychological states. Humans attribute and share mental states with others in the so-called shared intentionality. Our hypothesis is that our closest nonhuman living relatives also attribute some psychological mechanisms such as perceptions and goals to others, but, unlike humans, they are not necessarily intrinsically motivated to share those psychological states. Furthermore, it is postulated that shared intentionality is responsible for the appearance of a suite of behaviors, including joint attention, declarative communication, imitative learning, and teaching, that are the basis of cultural learning and the social norms and traditions present in every human culture.


Thixotropic silk nanofibril-based hydrogel with extracellular matrix-like structure.
Silk fibroin (SF) based materials have been widely studied and applied in bio-related areas due to their excellent structural and biological properties. Here, we present an injectable hydrogel formed by SF nanofibrils via simple fibrillation and centrifugation approach. The hydrogels with extracellular matrix-like structure not only perform the sufficient mechanical properties, but also show outstanding thixotropic character, whose storage modulus (G') can recover to 93% within 40 seconds after a large shearing strain (5000 %). More importantly, the injectable hydrogel exhibits significant biocompatibility for L929 cells cultured in hydrogel after injection, illustrated by cell viability and cytotoxicity assays. All of these results indicate that such SF nanofibril-based hydrogel has promise in application such as a cell therapy carrier.


Amplification of chromosome 8 genes in lung cancer.
Chromosomal alterations are frequent events in lung carcinogenesis and usually display regions of focal amplification containing several overexpressed oncogenes. Although gains and losses of chromosomal loci have been reported copy number changes of the individual genes have not been analyzed in lung cancer. In this study 22 genes were analyzed by MLPA in tumors and matched normal tissue samples from 82 patients with non-small cell lung cancer. Gene amplifications were observed in 84% of the samples. Chromosome 8 was found to harbor the most frequent copy number alterations. The most frequently amplified genes were ZNF703, PRDM14 and MYC on chromosome 8 and the BIRC5 gene on chromosome 17. The frequency of deletions were much lower and the most frequently deleted gene was ADAM9. Amplification of the ZNF703, PRDM14 and MYC genes were highly correlated suggesting that the genes displaying high copy number changes on chromosome 8 collaborate during lung carcinogenesis.


Effect of photobiomodulation on the efficacy of anesthesia in maxillary permanent molar teeth with molar incisor hypomineralization: A randomized clinical trial.
Difficulty in anesthetizing teeth that have been diagnosed with molar incisor hypomineralization (MIH) is a frequently reported clinical problem. The effects of low-level laser application (photobiomodulation) on the efficacy of anesthesia during the dental treatment of patients with MIH have not yet been studied. To assess the effects of photobiomodulation therapy (PBMT) on the efficacy of anesthesia in maxillary permanent molar teeth with MIH. This prospective, parallel-arm control, randomized, triple-blind clinical trial included children aged 7-12 years. Maxillary permanent first molar teeth with MIH that required pulpotomy treatment were included. Seventy participants were randomly divided into two groups: experimental (with PBMT) and control (placebo). In the experimental group, before the administration of local infiltration anesthesia, PBMT (diode laser: 940 nm; continuous mode; 0.5 W; 78 J/cm2 ) was applied to the oral mucosa for 60 s each. In the control group, the laser probe was channeled toward the mucosa but was not activated. Pain scores were evaluated during the access cavity preparation of the pulpotomy treatment (when using the dentin cutting handpiece and while entering into the pulp) using the Face, Legs, Activity, Cry, Consolability (FLACC) scale. Additional anesthesia requirements were assessed in both groups. The data obtained were analyzed for statistical significance (p < .05). The chi-squared test was used to determine the effect of PBMT on categorical outcomes. The no-pain scores of the experimental group were higher than those of the control group (29% vs. 20%). Moderate-to-high pain was more frequent in the control group than in the experimental group (43% vs. 20%). While 31% of the experimental group required supplemental anesthesia, 49% of the control group required supplemental anesthesia during pulpotomy of the tooth with MIH. No statistical difference, however, was found between the two groups in terms of pain scores and the need for supplemental anesthesia (p = .235, p = .143). Anesthesia with and without PBMT caused no difference in pain during the treatment of maxillary molar teeth with MIH.


Antibacterial effect of mango (Mangifera indica Linn.) leaf extract against antibiotic sensitive and multi-drug resistant Salmonella typhi.
Alternative herbal medicine has been used to treat various infections from centuries. Natural plants contain phytoconstituents having similar chemical properties as of synthetic antibiotics. Typhoid fever is a serious infection and failure of its treatment emerged multi-drug resistant (MDR) bugs of Salmonella typhi. Due to multiple and repeated issues with antibiotics efficacy, it became essential to evaluate biological properties of plants from different geographical origins. Mango leaves have been Reported for various medicinal effects like antioxidant, antimicrobial, antihelminthic, antidiabetic and antiallergic etc. Objective of present study was to investigate anti-typhoid properties of acetone mango leaf extract (AMLE) against antibiotic sensitive and MDR S. typhi isolates. A total of 50 isolates of S. typhi including MDR (n=30) and antibiotic sensitive (n=20) were investigated. Staphylococcus aureus (ATCC 25923) and Salmonella typhimurium (ATCC14028) were used as quality control strains. AMLE was prepared and its antibacterial activity was evaluated by agar well diffusion screening method and minimum inhibitory concentration (MIC), by agar dilution technique. Zone of inhibition (mm) of AMLE against MDR and antibiotic sensitive isolates was 18±1.5mm (Mean±S.D). Zone of S. aureus (ATCC 25923) and S. typhimurium (ATCC14028) was 20±1.5mm (Mean±S.D). MIC of AMLE was Reported in range from 10-50 mg/ml. The present study described the inhibitory effects of mango leaves against S. typhi.


Results on Search for the Broad Fish Tapeworm Dibothriocephalus Latus (Linnaeus, 1758), (syn. Diphyllobothrium Latum) (Cestoda: Diphyllobothriidea), in the Danube River.
Diphyllobothriosis is a fish-borne parasitic zoonosis caused by so-called "broad tapeworms" or "fish tapeworms" of different genera of the order Diphyllobothriidea. Dibothriocephalus latus (Linnaeus 1758), (syn. Diphyllobothrium latum), is a medically important type species of the genus, whose occurrence in various European regions is either regular, e.g. in the Alpine lakes region, or occasional and sporadic, e. g. in the Danube River region. For the latter, data on the detection of D. latus plerocercoids in the second intermediate fish host (European perch Perca fluviatilis), as well as in definitive hosts (human and dog), in which infection was directly linked to the consumption of infected fish from the Danube, were published more than 50 years ago. In order to assess the current situation, we aimed to find out whether D. latus is present in the natural environment of the Danube River. In total, 700 perch from five sampling sites in the Slovak part of the Danube River were examined. Plerocercoids were not detected in any fish examined, which leads to the conclusion that D. latus is currently not present in the studied aquatic environment.


One-Year Clinical Outcomes of a Corneal Inlay for Presbyopia.
To report the results of a 1-year follow-up analysis of the safety and efficacy of the Flexivue Microlens corneal inlay. The Flexivue Microlens corneal inlay was implanted in the nondominant eye of patients with emmetropic presbyopia (a spherical equivalent of -0.5 to 1.00 diopter) after the creation of a 300-μm deep stromal pocket, using a femtosecond laser. The patients were followed up according to a clinical protocol involving refraction, anterior segment imaging analysis (Oculyzer), and optical quality analysis (OPD-Scan). Thirty-one patients were enrolled in this ongoing study. The mean age was 50.7 years (range 45-60 yrs), and 70% of the patients were female. The mean uncorrected near visual acuity improved to Jaeger 1 in 87.1% of the eyes treated with the inlays. All eyes improved 4 lines at all visits. The binocular uncorrected distance visual acuity was 20/20 in all patients. Ninety percent of the patients reported that their near vision was good or excellent. Some of the patients (16.1%) lost more than 3 lines of corrected distance visual acuity. At the latest follow-up, induction of a corneal spherical aberration to improve near visual acuity was statistically significant. No other intraoperative or postoperative complication was noted. The Flexivue Microlens provided patients with improved near vision, as a result of a negative spherical aberration. A significant loss of corrected distance visual acuity in the operated eyes was observed. Overall, this intracorneal inlay was an effective alternative to other procedures for the correction of presbyopia.


Potential anti-cancer activity of N-hydroxy-7-(2-naphthylthio) heptanomide (HNHA), a histone deacetylase inhibitor, against breast cancer both in vitro and in vivo.
Histone deacetylase (HDAC) is an attractive target for cancer therapy because it plays a key role in gene expression and carcinogenesis. N-hydroxy-7-(2-naphthylthio) heptanomide (HNHA) is a novel synthetic HDAC inhibitor (HDACI) that shows better pharmacological properties than a known HDACI present in the human fibrosarcoma cell: suberoylanilide hydroxamic acid (SAHA). Here, we investigate the anti-cancer activity of HNHA against breast cancer both in vitro and in vivo. HNHA arrested the cell cycle at the G(1) /S phase via p21 induction, which led to profound inhibition of cancer cell growth in vitro. In addition, HNHA-treated cells showed markedly decreased levels of VEGF and HIF-1α than SAHA and fumagillin (FUMA) when accompanied by increased histone acetylation. HNHA significantly inhibited tumor growth in an in vivo mouse xenograft model. HNHA-treated mice survived significantly longer than SAHA- and FUMA-treated mice. Dynamic MRI showed significantly decreased blood flow in the HNHA-treated mice, implying that HNHA inhibits tumor neovascularization. This finding was accompanied by marked reductions of proangiogenic factors and significant induction of angiogenesis inhibitors in tumor tissues. We have shown that HNHA is an effective anti-tumor agent in breast cancer cells in vitro and in breast cancer xenografts in vivo. Collectively, these findings indicate that HNHA may be a potent anti-cancer agent against breast cancer due to its multi-faceted inhibition of HDAC activity, as well as anti-angiogenesis activity.


Glycoprotein labeling using engineered variants of galactose oxidase obtained by directed evolution.
A directed evolution approach has been used for the generation of variants of galactose oxidase (GOase) that can selectively oxidize glycans on glycoproteins. The aldehyde function introduced on the glycans D-mannose (Man) and D-N-acetyl glucosamine (GlcNAc) by the enzyme variants could then be used to label the glycoproteins and also whole cells that display mannosides on their surface.


[Initial clinical experience with the use of 31P MR spectroscopy in the examination of children with neuromuscular diseases].
31P MR spectroscopy (MRS) was used to investigate neuromuscular diseases of different origin in 35 patients, mostly children. After elaboration of the procedure of MR examination and evaluation of results the method of pattern recognition analysis was used. According to the results of 31P MR spectroscopy patients can be divided into three groups. Group A comprises patients with severe muscular lesions such as Duchenne dystrophy. The second group B is characterized by milder atrophic changes of muscle fibres. The third group comprises obscure cases. The 31P MRS method was also used for investigating the development of the disease in time--a drop of parameter PCR/Pi corresponds to a deterioration of the clinical condition of patients from group one. Maintenance of approximately the same values was observed in group B. An increase of PCR/Pi was also observed during administration of Prednisone in patients with child polymyositis.


[Chorioretinitis caused by toxoplasma in children].
In a period of 5 years, 21 children with ocular lesions caused by toxoplasma (chorioretinitis due to toxoplasma) were seen at "Pedro Kourí" Tropical Medicine Institute. Of the 21 children, 5 (23.8%) had lesions in both eyes and 16 (76.1%) in one eye (9 in the left eye and 7 in the right one). 9 children (42.8%) initially had active lesions that responded satisfactorily to medical treatment whereas 12 (57.1%) came to the hospital with healed lesions that did not require any treatment. They were all followed up as outpatients with favorable evolution in all cases.


Homocysteine and cognitive function in elderly people.
Dementia is highly prevalent among elderly people, and projections show that the number of people affected might triple over the next 50 years, mainly because of a large increase in the oldest-old segment of the population. Because of this and the disease's devastating effects, measures for the prevention and early detection of dementia are crucial. Age and years of education are among the most relevant risk factors for dementia, but in recent years the role of homocysteine has also been investigated. Homocysteine is an amino acid produced in the metabolism of methionine, a process dependent on the B vitamins cobalamin, vitamin B6 and folic acid. There is evidence that increased serum homocysteine levels are associated with declining cognitive function and dementia. We review this evidence in addition to the potential mechanisms through which homocysteine acts on the brain to cause cognitive dysfunction, the metabolism of homocysteine and factors associated with alteration of the normal metabolism.


Hypnotic susceptibility in patients with conversion disorder.
Conversion disorder has been associated with hypnotic susceptibility for over a century and is currently still believed to be a form of autohypnosis. There is, however, little empirical evidence for the relation between hypnotic susceptibility and conversion symptoms. The authors compared 50 patients with conversion disorder with 50 matched control patients with an affective disorder on measures of hypnotic susceptibility, cognitive dissociation, and somatoform dissociation. Conversion patients were significantly more responsive to hypnotic suggestions than control patients. In addition, conversion patients showed a significant correlation between hypnotic susceptibility and the number of conversion complaints. These results provide the first evidence of a relationship between hypnotic susceptibility and the presence and number of conversion symptoms.


Clinical efficacy, safety, and tolerability of fingolimod for the treatment of relapsing-remitting multiple sclerosis.
Fingolimod is a selective immunosuppressive agent approved worldwide for the treatment of relapsing-remitting multiple sclerosis (MS), a chronic and potentially disabling neurological condition. Randomized double-blind clinical trials have shown that fingolimod significantly reduces relapse rate and ameliorates a number of brain MRI measures, including cerebral atrophy, compared to both placebo and intramuscular interferon-β1a. The effect on disability progression remains controversial, since one Phase III trial showed a significant benefit of treatment while two others did not. Although fingolimod has a very convenient daily oral dosing, the possibility of serious cardiac, ocular, infectious, and other rare adverse events justified the decision of the European Medicines Agency to approve the drug as a second-line treatment for MS patients not responsive to first-line therapy, or those with rapidly evolving course. In the United States, fingolimod is instead authorized as a first-line treatment. The aim of this review is to describe and discuss the characteristics of fingolimod concerning its efficacy, safety, and tolerability in the clinical context of multiple sclerosis management.


EEG electrode localization with 3D iPhone scanning using point-cloud electrode selection (PC-ES).

EEG source imaging (ESI) is a valuable tool in clinical evaluation for epilepsy patients but is underutilized in part due to sensitivity to anatomical modeling errors. Accurate localization of scalp electrodes is instrumental to ESI, but existing localization devices are expensive and not portable. As a result, electrode localization challenges further impede access to ESI, particularly in inpatient and intensive care settings.

Approach:
To address this challenge, we present a portable and affordable electrode digitization method using the 3D scanning feature in modern iPhone models. This technique combines iPhone scanning with semi-automated image processing using PC-ES (Point-Cloud Electrode Selection), a custom MATLAB desktop application. We compare iPhone electrode localization to state-of-the-art photogrammetry technology in a human study with over 6,000 electrodes labeled using each method. We also characterize the performance of PC-ES with respect to head location and examine the relative impact of different algorithm parameters.

Main Results:
The median electrode position variation across reviewers was 1.50 mm for PC-ES scanning and 0.53 mm for photogrammetry, and the average median distance between PC-ES and photogrammetry electrodes was 3.4 mm. These metrics demonstrate comparable performance of iPhone/PC-ES scanning to currently available technology and sufficient accuracy for EEG source imaging.

Significance:
Low cost, portable electrode localization using iPhone scanning removes barriers to ESI in inpatient, outpatient, and remote care settings. While PC-ES has current limitations in user bias and processing time, we anticipate these will improve with software automation techniques as well as future developments in iPhone 3D scanning technology.&#xD.


Burden of osteoporosis and fractures in developing countries.
The burden of osteoporosis in developing countries is increasing dramatically with the aging of the population and demographic trends; however, there is a lack of direct epidemiologic data. There are clear differences at present between and within populations that limits the validity of many estimates and more data is needed. Existing data and estimates are considered in terms of bone mass, bone structure, 10-year and lifetime probability of fracture, numbers sustaining fractures, the outcome of fracture, importance of differences in fracture management, and risk factors for their occurrence and outcome. Future trends are also considered.


Comparison of Home Advantage in College and Professional Team Sports in the United States.
Home advantage in seven American college team sports (baseball, basketball, football, hockey, lacrosse, soccer and women's basketball) was compared with professional leagues in the United States for the same sports and for the same time period. A total of 81,063 college games and 22,477 professional games were analyzed for the four seasons 2006-07 to 2009-10. There was a significant home advantage, as measured by home winning percentage, in all sports, both college and professional. The overall home advantage in college sports was significantly greater than in professional sports (p<0.015). The mean difference was 3.73 home winning percentage points, being greatest for baseball, basketball, and hockey (all p<0.001). Plausible explanations for these results include differences in college and professional competition in terms of familiarity with local conditions, referee bias, territoriality and psychological factors. However, the influence of travel fatigue was inconclusive. Only for soccer was the home advantage greater for professionals. This was the only sport where crowd size appeared to be having an effect. In addition the rules of college soccer allow more substitution and hence greater coach intervention than in professional soccer, a factor that could also be reducing home advantage.


Temporal and spatial expression patterns of canonical clock genes and clock-controlled genes in the suprachiasmatic nucleus.
In mammals, the suprachiasmatic nuclei (SCN) of the hypothalamus control endogenous circadian rhythms and entrainment to the environment. A core SCN region of calbindin (CalB)-containing cells is retinorecipient and the cells therein lack rhythmic expression of clock genes and electrical activity. The core is surrounded by a 'shell' of rhythmic oscillator cells. In the present experiments, we studied the spatial arrangement of oscillator cells by examining the spatial and temporal patterns of expression of the canonical clock genes Per1, Per2 and vasopressin mRNA, a clock-controlled gene. Surprisingly, in the SCN shell, the dorsomedial cells were the first to rhythmically express both Per1 and VP mRNA, with gene expression then spreading very slowly through much of the nucleus for the next 12 h then receding to baseline levels. Following a light pulse, Per expression increased after 1 h in the core SCN and after 1.5 h in the shell. Although expression in the shell occurred earlier in light-pulsed animals than in those housed in constant darkness, it still followed the same spatial and temporal expression pattern as was observed in constant darkness. The results suggest that not only is the SCN organized into light-responsive and rhythmic regions but also that the rhythmic region of the SCN itself has an ordered arrangement of SCN oscillator cells.


Nephrotoxicity and genotoxicity of silver nanoparticles in juvenile rats and possible mechanisms of action.
Because of their widespread use and potential adverse effects in young developing organism, this study focused on the nephrotoxicity and genotoxicity of chronic low-dose exposure to silver nanoparticles (AgNPs) in 32 14-day-old male Wistar rats, randomly divided into three groups receiving AgNP solution (3 mg/kg body weight) intraperitoneally for one, two, or three weeks and the untreated control group (eight animals per group). When the rats were eight weeks old, blood creatinine and urine microalbumin were tested, followed by haematoxylin and eosin (H&E) staining. Proteinuria was found in the animals treated with AgNP for three weeks, and H&E staining revealed pathological changes in the kidney sections of this group. DNA damage was detected with the alkaline comet assay in the groups treated for two and three weeks. All results indicate that chronic exposure, even at a low dose, may affect animal health. The main culprit might be increased and time-dependent reactive oxygen species (ROS) production. Highly reactive ROS could cause a major structural damage to proteins and DNA, change the expression of ion channel proteins, and trigger inflammation. The findings of our in vivo experiment raise concern about nephrotoxic and genotoxic effects of silver nanoparticles in young organisms and call for further investigation of nanoparticle properties that can be modified to minimise the risks.


Deletion of σ(54) (rpoN) alters the rate of autolysis and biofilm formation in Enterococcus faecalis.
Transcription initiation is a critical step in bacterial gene regulation and is often controlled by transcription regulators. The alternate sigma factor (σ(54)) is one such regulator that facilitates activator-dependent transcription initiation and thus modulates the expression of a variety of genes involved in metabolism and pathogenesis in bacteria. This study describes the role of σ(54) in the nosocomial pathogen Enterococcus faecalis. Biofilm formation is one of the important pathogenic mechanisms of E. faecalis, as it elevates the organism's potential to cause surgical site and urinary tract infections. Lysis of bacterial cells within the population contributes to biofilm formation by providing extracellular DNA (eDNA) as a key component of the biofilm matrix. Deletion of rpoN rendered E. faecalis resistant to autolysis, which in turn impaired eDNA release. Despite the significant reduction in eDNA levels compared to the parental strain, the rpoN mutant formed more robust biofilms as observed using laser scanning confocal microscopy and Comstat analysis, indicating and emphasizing the presence of other matrix components. Initial adherence to a polystyrene surface was also enhanced in the mutant. Proteinase K treatment at early stages of biofilm development significantly reduced the accumulation of biofilm by the rpoN mutant. In conclusion, our data indicate that other factors in addition to eDNA might contribute to the overall composition of the enterococcal biofilm and that the regulatory role of σ(54) governs the nature and composition of the biofilm matrix.


Psychiatric medication and abnormal behavior as predictors of progression in probable Alzheimer disease.
To examine whether the use of psychiatric medication and the presence of abnormal behaviors affects the progression of Alzheimer disease. Cross-sectional with longitudinal follow-up and the likelihood of arriving at 4 end points: (1) Mini-Mental State Examination score of 9 or lower; (2) Blessed Dementia Rating Scale score of 15 or higher for activities of daily living; (3) nursing home admission; and (4) death, evaluated using a proportional hazard model with 9 variables: psychosis, insomnia, wandering, aggression, psychomotor agitation, depression, and use of antidepressants, antipsychotic agents, or sedatives/hypnotics. Multidisciplinary dementia research clinic. We examined baseline and follow-up behavioral symptoms and the use of psychiatric medication in 179 mildly to moderately impaired patients with probable Alzheimer disease participating in a longitudinal study of dementia. Patients were observed from 2.4 to 172 months (mean duration +/- SD, 49.5+/-27.4 months). Nine patients (5%) were taking sedatives/ hypnotics; 16 (9%), antipsychotic agents; and 22 (12%), antidepressants at study entry. Patients taking antipsychotic agents had lower Mini-Mental State Examination scores and higher Blessed Dementia Rating Scale scores for activities of daily living than patients not taking any medication. Using proportional hazard analysis with time-dependent covariates for individual psychiatric symptoms and medications, we found that the development of psychosis was associated with functional decline (time to Blessed Dementia Rating Scale score of > or =15), institutionalization, aggression, and agitation with functional decline after adjusting for age at study entry, education, Mini-Mental State Examination scores, and Blessed Dementia Rating Scale scores. Use of antipsychotic medication was associated with functional decline, and sedatives/hypnotics with death. Neither the presence of psychiatric symptoms nor use of medication was associated with rate of cognitive decline (time to Mini-Mental State Examination score of < or =9). These findings indicate that the use of antipsychotic agents and sedatives can affect the natural course of Alzheimer disease. Psychosis, agitation, and aggression are important predictors of outcome, even when the effects of medication to treat them is taken into account.


A novel intraoral diabetes screening approach in periodontal patients: results of a pilot study.
This pilot study examines whether a novel diabetes screening approach using gingival crevicular blood (GCB) could be used to test for hemoglobin A1c (HbA1c) during periodontal visits. Finger-stick blood (FSB) samples from 120 patients and GCB samples from those patients with adequate bleeding on probing (BOP) were collected on special blood collection cards and analyzed for HbA1c levels in a laboratory. The Pearson correlation coefficient was used to measure correlation between FSB and GCB HbA1c values for 75 paired FSB and GCB samples. A receiver-operator characteristic curve (ROC) analysis was performed to determine an optimal GCB HbA1c criterion value for a positive diabetes screen. For the 75 paired samples, the Pearson correlation coefficient was 0.842. The ROC analysis identified a criterion value of 6.3% for the GCB HbA1c test with high sensitivity (0.933) and high specificity (0.900), corresponding to FSB HbA1c values ≥6.5% (in the diabetes range). Using this GCB HbA1c criterion value for 27 additional paired samples, in which there was an unidentified component observed to coelute within the elution window of GCB HbA1c in the laboratory, there was agreement between FSB and GCB values for 24 of the pairs according to whether both were within or outside of the diabetes range. Using a criterion value of 6.3%, GCB samples are acceptable for HbA1c testing to screen for diabetes in most persons with BOP at the GCB collection site.


Surgical treatment of traumatic lesions of the axillary nerve. A retrospective study of 33 cases.
The purpose of this study was to evaluate the recovery of muscular strength after surgical intervention in axillary nerve injuries. Surgery was elected when no signs of recovery were noted after three months of conservative treatment. Between 1980 and 1996, 46 traumatic lesions of the axillary nerve were surgically treated. Thirteen patients were excluded from the study for various reasons. Among the remaining 33, 20 with interruption of the nerve trunk were treated with nerve grafts and 13 lesions with the nerve in continuity underwent neurolysis. After a mean follow-up of more than two years, deltoid muscle strength was good or fair in 18 patients and poor in 15 cases. The outcome seemed to be better in isolated lesions than in complex nerve lesions with a favourable outcome in 6/10 patients vs 8/14, in patients younger than 25 years compared to older patients (8/14 vs 8/19), in patients treated with neurolysis (9/13) compared to grafting (9/20), and when graft length was limited (4/4 patients with a graft 6cm or less, 5/8 with a graft over 6cm in length). The outcome was less favourable when associated osteoarticular lesions were present (8/23 versus 8/10) and most convincingly, when surgery was delayed beyond six months (10/22 versus 8/11).


Evidence-based protocol-led management of renal angiomyolipoma: A review of literature.
Renal angiomyolipomas (R-AMLs) are rare benign tumors, which occur sporadically and in association with genetic conditions such as tuberous sclerosis complex (TSC) and lymphangioleiomyomatosis (LAM). The key clinical concern is life-threatening hemorrhage. There is uncertainty about the optimal management strategy for patients with R-AMLs. We aim to review the evidence and provide a protocolled approach for the management of R-AMLs. A literature search of R-AML was conducted using MEDLINE and EMBASE for articles published between January 1990 and March 2020. Patient with TSC and sporadic cases were included. Treatment strategies, including active surveillance, surgery, selective arterial embolization (SAE), ablation, and systemic therapies, were reviewed. Outcomes from contemporary case series of active surveillance, surgery, and SAE were collated. There were no randomized controlled trials on this topic. The retrospective case series reviewed showed that many R-AMLs can be managed safely with active surveillance. Tumor size is the most important predictor of bleeding, and other factors such as rate of growth, women of child-bearing age, aneurysm size, and symptoms should be considered when deciding on prophylactic treatment. There is limited evidence for the traditional 4-cm cutoff for treatment, which may lead to overtreatment. The primary intervention options are SAE and surgery; whereas SAE is a less invasive option, nephron sparing surgery offers a lower risk of recurrence. Both appear to have similar morbidity, and the current evidence does not recommend one over the other in most cases. Thermal ablation has promising results but has only been trialed in small case series. Patients with TSC can be offered mammalian target of rapamycin inhibitors of which everolimus appears to cause the greatest shrinkage of tumors with an acceptable side-effect profile. R-AMLs should be assessed for their risk of bleeding. Low-risk tumors should be treated with active surveillance. High-risk tumors should be treated with SAE or surgery. Systemic treatments are the first-line of treatment for patients with TSC to preserve renal parenchyma.


Driving on ice: impaired driving skills in current methamphetamine users.
Previous research indicates a complex link between methamphetamine (METH) and driving performance. Acute dosing with amphetamines has improved driving-related performance in some laboratory studies, while epidemiological studies suggest an association between METH use, impaired driving, and accident culpability. Current METH users were compared to a control group of nonusers on driving simulator performance. Groups were matched for age, gender, and driving experience. Subjects were assessed for current drug use, drug dependence, and drug levels in saliva/blood as well as personality variables, sleepiness, and driving performance. METH users, most of whom met the criteria for METH dependence, were significantly more likely to speed and to weave from side to side when driving. They also left less distance between their vehicle and oncoming vehicles when making a right-hand turn. This risky driving was not associated with current blood levels of METH or its principal metabolite, amphetamine, which varied widely within the METH group. Other drugs were detected (principally low levels of THC or MDMA) in some METH users, but at levels that were unlikely to impair driving performance. There were higher levels of impulsivity and antisocial personality disorder in the METH-using cohort. These findings confirm indications from epidemiological studies of an association between METH use and impaired driving ability and provide a platform for future research to further explore the factors contributing to increased accident risk in this population.


[Health, healthy family and healthy child: views and relationships of community agents].
This article reports the experience lived by the authors during their training time in one of the practical activities of the Nursing Teaching Course. In the context of a Continued Education Project developed with community agents of the Family Health Program, the research approaches a discussion that was triggered off on a meeting about the subject: "Health, Healthy Family and Healthy Child", when some manifestations of persons involved in the project were argued. The authors concluded that, as a pedogogic strategy, the use of group dynamics enlarges the possibilities of using the experience and knowledge that determines the person's action, as a teaching-learning process base.


Rational design of the microtubule-targeting anti-breast cancer drug EM015.
We studied in silico docking of noscapine onto tubulin, combined with calculations of surface charge, pi-pi, van der Waals, and hydrogen bonding interactions, to rationally design a new compound, EM015. This tubulin-binding semisynthetic compound is a selective and potent anti-breast cancer agent and displays a 20-fold lower IC(50) against many tumor cells compared with our founding compound, (S)-6,7-dimethoxy-3-((R)-4-methoxy-6-methyl-5,6,7,8-tetrahydro[1,3]-dioxolo-[4,5-g]isoquinolin-5-yl)isobenzo-furan-1(3H)-one (noscapine). Furthermore, EM015 is also effective against a variety of drug-resistant cells. Surprisingly, the cell cycle profile of nontumorigenic normal cells is not affected. Many antimicrotubule cancer drugs in clinic today, particularly taxanes and Vincas, face challenges including frequent visits to the hospital for prolonged i.v. infusions, toxicities, and tumor recurrences due to drug resistance. EM015, on the other hand, is orally available, regresses breast tumor xenografts in nude mice models, and increases longevity. Furthermore, we have failed to observe any detectable toxicity in tissues, such as liver, kidney, spleen, lung, heart, and brain, as well as neurons, which are common targets of antimicrotubule drug therapy. Thus, EM015 has a great promise in the clinic.


Predictors of Inpatient Psychiatric Hospitalization for Children and Adolescents with Autism Spectrum Disorder.
Autism Spectrum Disorder (ASD) is associated with significant healthcare expenditures and a greater utilization of psychiatric health services. High utilization may not be evenly distributed across individuals with ASD. The objective of this study was to identify individual and family characteristics that increase the risk of psychiatric hospitalization. Naturalistic study of two age- and gender-matched ASD cohorts, inpatients enrolled in the Autism Inpatient Collection (AIC) and outpatients enrolled in the Rhode Island Consortium of Autism Research and Treatment (RI-CART), revealed a number of factors associated with hospitalization. Multiple logistic regression analyses revealed that adaptive functioning, ASD symptom severity, primary caregiver's marital status, the presence of mood disorders, and the presence of sleep problems independently increased the risk of psychiatric hospitalization.


Metabolic flux pattern of glucose utilization by Xanthomonas campestris pv. campestris: prevalent role of the Entner-Doudoroff pathway and minor fluxes through the pentose phosphate pathway and glycolysis.
The well-studied plant pathogenic bacterium Xanthomonas campestris pv. campestris (Xcc) synthesizes the biotechnologically important polysaccharide xanthan gum, which is also regarded as a virulence factor in plant interactions. In Xcc, sugars like glucose are utilized as a source to generate energy and biomass for growth and pathogenicity. In this study, we used [1-(13)C]glucose as a tracer to analyze the fluxes in the central metabolism of the bacterium growing in a minimal medium. (13)C-Metabolic flux analysis based on gas chromatography-mass spectrometry (GC-MS) confirmed the prevalent catabolic role of the Entner-Doudoroff pathway. Comparative nuclear magnetic resonance (NMR)-based isotopologue profiling of a mutant deficient in glycolysis gave evidence for a moderate flux via glycolysis in the wild-type. In addition to reconfirming the Entner-Doudoroff pathway as a catabolic main route, this approach affirmed a numerically minor but important flux via the pentose phosphate pathway.


Risk Factors for Abdominal Aortic Aneurysm in Population-Based Studies: A Systematic Review and Meta-Analysis.
Abdominal aortic aneurysm (AAA) represents an important public health problem with a prevalence between 1.3% and 12.5%. Several population-based randomized trials have evaluated ultrasound screening for AAA providing evidence of a reduction in aneurysm-related mortality in the screened population. The aim of our study was to perform a systematic review and meta-analysis of the risk factors for AAA. We conducted a systematic review of observational studies and we performed a meta-analysis that evaluated the following risk factors: gender, smoking habits, hypertension, coronary artery disease and family history of AAA. Respect to a previous a meta-analysis we added the funnel plot to examine the effect sizes estimated from individual studies as measure of their precision; sensitivity analysis to check the stability of study findings and estimate how the overall effect size would be modified by removal of one study; cumulative analysis to evaluate the trend between studies in relation to publication year. Abdominal aortic aneurysm prevalence is higher in smokers and in males. On the other hand, while diabetes is a risk factor for many cardiovascular diseases, it is not a risk factor for AAA. In addition, it is important to underline that all countries, where AAA screening was set up, had high income level and the majority belong to Western Europe (United Kingdom, Sweden, Italy, Poland, Spain and Belgium). Abdominal aortic aneurysm screening is fundamental for public health. It could avoid deaths, ruptures, and emergency surgical interventions if abdominal aortic aneurysm was diagnosed early in the population target for screening.


Differential divalent cation requirements uncouple the assembly and catalytic reactions of human immunodeficiency virus type 1 integrase.
Previous in vitro analyses have shown that the human immunodeficiency virus type 1 (HIV-1) integrase uses either manganese or magnesium to assemble as a stable complex on the donor substrate and to catalyze strand transfer. We now demonstrate that subsequent to assembly, catalysis of both 3' end processing and strand transfer requires a divalent cation cofactor and that the divalent cation requirements for assembly and catalysis can be functionally distinguished based on the ability to utilize calcium and cobalt, respectively. The different divalent cation requirements manifest by these processes are exploited to uncouple assembly and catalysis, thus staging the reaction. Staged 3' end processing and strand transfer assays are then used in conjunction with exonuclease III protection analysis to investigate the effects of integrase inhibitors on each step in the reaction. Analysis of a series of related inhibitors demonstrates that these types of compounds affect assembly and not either catalytic process, therefore reconciling the apparent disparate results obtained for such inhibitors in assays using isolated preintegration complexes. These studies provide evidence for a distinct role of the divalent cation cofactor in assembly and catalysis and have implications for both the identification and characterization of integrase inhibitors.


Flowering genes in Metrosideros fit a broad herbaceous model encompassing Arabidopsis and Antirrhinum.
Molecular studies were conducted on Metrosideros excelsa to determine if the current genetic models for flowering with regard to inflorescence and floral meristem identity genes in annual plants were applicable to a woody perennial. MEL, MESAP1 and METFL1, the fragments of LEAFY (LFY), APETALA1 (AP1) and TERMINAL FLOWER1 (TFL1) equivalents, respectively, were isolated from M. excelsa. Temporal expression patterns showed that MEL and MESAP1 exhibited a bimodal pattern of expression. Expression exhibited during early floral initiation in autumn was followed by down-regulation during winter, and up-regulation in spring as floral organogenesis occurred. Spatial expression patterns of MEL showed that it had greater similarity to FLORICAULA (FLO) than to LFY, whereas MESAP1 was more similar to AP1 than SQUAMOSA. The interaction between MEL and METFL1 was more similar to the interaction between FLO and CENTRORADIALIS than that between LFY and TFL1. Consequently, the three genes from M. excelsa fit a broader herbaceous model encompassing Antirrhinum as well as Arabidopsis, but with differences, such as the bimodal pattern of expression seen with MEL and MESAP1. In mid-winter, at the time when both MEL and MESAP1 were down-regulated, GA(1) was below the level of detection in M. excelsa buds. Even though application of gibberellin inhibits flowering in members of the Myrtaceae, MEL was responsive to gibberellin with expression in juvenile plants up-regulated by GA(3). However, MESAP1 was not up-regulated indicating that meristem competence was also probably required to promote flowering in M. excelsa.


Performance of a pilot-scale, three-stage constructed wetland system for domestic wastewater treatment.
This study investigates the effects of season, organic matter loadings, hydraulic conditions, recycling, and rapid drainage on water quality in a pilot-scale, three-stage subsurface flow constructed wetland (SSF CW) system. The pilot CW system consisted of a vertical flow-gravel filtration (v-GF) wetland in the first stage, a horizontal-subsurface flow (h-SSF) bed planted with Iris in the second stage, and a vertical-subsurface flow (v-SSF) bed vegetated with Phragmites in the third stage. The objective of this study was to evaluate the potential of these CW systems to remove organic matter from domestic wastewater on a pilot-scale three-stage SSF CW system. Comparisons of average influent and effluent concentrations showed that the multistage system could effectively reduce total suspended solids (TSS), biological oxygen demand (BOD) and chemical oxygen demand (COD) levels in effluent by as much as 98% and total organic carbon (TOC) by as much as 79%. Contributions of the first, second and third stages to the overall treatment were approximately 10%, 45% and 45%, respectively. The average TSS, COD, and TOC concentrations were reduced in the entire CW system by 70%, 80% and 90%, respectively. The BOD and TOC removal efficiencies displayed seasonal variations with average removals generally increasing in warmer seasons. Our results also demonstrate that there were strong correlations between removal efficiencies and loading rates. Average removals decreased with an increase in the hydraulic retention time (HRT). The rapid drainage and recycling operation increased the efficiency of BOD removal only.


Al2 O3 -coated BiVO4 Photoanodes for Photoelectrocatalytic Regioselective C-H Activation of Aromatic Amines.
Photoelectrochemistry is becoming an innovative approach to organic synthesis. Generally, the current photoelectrocatalytic organic transformations suffer from limited reaction type, low conversion efficiency and poor stability. Herein, we develop efficient and stable photoelectrode materials using metal oxide protective layer, with a focus on achieving regioselective activation of amine compounds. Notably, our photoelectrochemistry process is implemented under mild reaction conditions and does not involve any directing groups, transition metals or oxidants. The results demonstrate that beyond photocatalysis and electrocatalysis, photoelectrocatalysis exhibits high efficiency, remarkable repeatability and good functional group tolerance, highlighting its great potential for applications.


Identification of circulating nonclassic human leukocyte antigen G (HLA-G)-like molecules in exudates.
HLA-G in biological fluids has been proposed to be useful as a tumor marker as both a diagnostic and prognostic factor. Most HLA-G measurement procedures are based on ELISA methods using highly specific antibodies. However, results of published studies are in conflict regarding the clinical utility and even the nature of HLA-G present in circulation. We collected 118 exudates, 94 from cancer patients and 24 from patients without tumors. We measured HLA-G concentrations by ELISA using MEM-G/9 or G233 as capture antibody. Samples were immunoprecipitated with an anti-HLA-G antibody and analyzed by Western blot using a different anti-HLA-G antibody. Discrepancies in HLA-G concentrations in exudates were observed depending on what capture anti-HLA-G antibody was used for ELISA (r = 0.376). These discrepancies were not observed when the ELISAs were performed using culture supernatants from HLA-G1-transfected cells (r = 0.983). Immunoprecipitation and Western blot of cell culture supernatants with 2 different anti-HLA-G antibodies produced the typical band at 39 kDa assigned to HLA-G. When the immunoprecipitation and western blot were performed with exudates, however, there were bands at 53 kDa and 70-76 kDa, higher molecular weights than those usually assigned to HLA-G. These HLA-G-like molecules were associated with β(2)-microglobulin and could also form disulfide bridges with other HLA-G-like molecules. The main HLA-G antigenic molecules in exudates are HLA-G-like complexes, a factor that should be considered when analyzing HLA-G in biological fluids.


Exploring the Proteomic Profile of Soybean Bran: Unlocking the Potential for Improving Protein Quality and Quantity.
Soybean is a rich source of vegetal protein for both animal and human consumption. Despite the high levels of protein in soybean seeds, industrial processing to obtain soybean bran significantly decreases the final protein content of the byproducts. To overcome this problem, cultivars with higher protein contents must be developed. However, selecting the target proteins is difficult because of the lack of information on the proteome profile of soybean bran. Therefore, this study obtained the comparative proteomic profiles of both natural coatless seeds and defatted bran from an elite tropical-soybean cultivar. Thus, their extracts were characterized using LC-MS/MS and a total of 550 proteins were identified. Among these, 526 proteins were detected in coatless seeds and 319 proteins in defatted bran. Moreover, a total of 139 proteins were identified as presenting different levels of content in coatless seeds and defatted bran. Among them, only 46 were retained after the seed processing. These proteins were clustered in several important metabolic pathways, such as amino-acid biosynthesis, sugar biosynthesis, and antioxidant activity, meaning that they could act as targets for bioactive products or genome editing to improve protein quality and quantity in soybean grains. These findings can enhance our understanding regarding protein robustness for both soybean crops and the commercial bran improvement because target proteins must remain intact after processing and must be bioactive when overexpressed. Overall, the soybean bran proteomic profile was explored for the first time, providing a valuable catalogue of target proteins that can tolerate the industrial process.


Systemic antioxidant properties of L-carnitine in two different models of arterial hypertension.
In spite of a wide range of drugs being available in the market, treatment of arterial hypertension still remains a challenge, and new therapeutic strategies could be developed in order to improve the rate of success in controlling this disease. Since oxidative stress has gained importance in the last few years as one of the mechanisms involved in the origin and development of hypertension, and considering that L-carnitine (LC) is a useful compound in different pathologies characterized by increased oxidative status, the aim of the present study was to investigate the systemic antioxidant effect of LC and its correlation to blood pressure in two experimental models of hypertension: (1) spontaneously hypertensive rats (SHR) and (2) rats with hypertension induced by N(omega)-nitro-L-arginine methyl ester (L-NAME). Treatment with captopril was also performed in SHR in order to compare the antioxidant and antihypertensive effects of LC and captopril. The antioxidant defense capacity, in terms of antioxidant enzyme activity, glutathione system availability and plasma total antioxidant capacity, was measured in both animal models with or without an oral, chronic treatment with LC. All the antioxidant parameters studied were diminished in SHR and in L-NAME-treated animals, an alteration that was in general reversed after treatments with LC and captopril. In addition, LC produced a significant but not complete reduction of systolic and diastolic blood pressure levels in these two models of hypertension, whereas captopril was able to normalize blood pressure. Both LC and captopril prevented the reduction in nitric oxide (NO) levels observed in hypertensive animals. This suggests a decrease in the systemic oxidative stress and a higher availability of NO induced by LC in a similar way to captopril's effects, which could be relevant in the management of arterial hypertension eventually.


Characterizing the secondary structure and identifying functionally essential nucleotides of pH6DZ1, a fluorescence-signaling and RNA-cleaving deoxyribozyme.
pH6DZ1 is a synthetic deoxyribozyme that is able to couple catalysis with fluorescence signal generation. This deoxyribozyme has the ability to cleave itself at a lone ribonucleotide that is present between a pair of deoxyribothymidines, one modified with a fluorophore (fluorescein) and the other with a quencher (DABCYL). Herein, we report on the sequence truncation and secondary structure characterization of pH6DZ1 as well as the identification of functionally important nucleotides within this deoxyribozyme. Our data indicate that pH6DZ1 has a four-way, junction-like secondary structure comprised of four short duplexes, three hairpin loops, and three interhelical unpaired elements. Ten nucleotides, all located in two separate single-stranded regions, were identified as functionally indispensable nucleotides (complete loss of the catalytic function was obtained upon mutation). Nine nucleotides, most of which are also distributed in three single-stranded DNA elements, were identified as functionally vital nucleotides (at least a 1000-fold activity reduction was obtained upon mutation). Our study has shown that pH6DZ1 has a secondary structure that is more complex than those reported for other RNA-cleaving deoxyribozymes. The identification of functionally important nucleotides lays the foundation for future mechanistic studies on this DNAzyme. The elucidation of the secondary structure of pH6DZ1 should facilitate the future exploration of this unique DNAzyme for the development of DNAzyme-based biosensors.


Modulating the dose-rate differently affects the responsiveness of human epithelial prostate- and mesenchymal rhabdomyosarcoma-cancer cell line to radiation.
Purpose: Radiation therapy (RT), by using ionizing radiation (IR), destroys cancer cells inducing DNA damage. Despite several studies are continuously performed to identify the best curative dose of IR, the role of dose-rate, IR delivered per unit of time, on tumor control is still largely unknown.Materials and methods: Rhabdomyosarcoma (RMS) and prostate cancer (PCa) cell lines were irradiated with 2 or 10 Gy delivered at dose-rates of 1.5, 2.5, 5.5 and 10.1 Gy/min. Cell-survival rate and cell cycle distribution were evaluated by clonogenic assays and flow cytometry, respectively. The production of reactive oxygen species (ROS) was detected by cytometry. Quantitative polymerase chain reaction assessed the expression of anti-oxidant-related factors including NRF2, SODs, CAT and GPx4 and miRNAs (miR-22, -126, -210, -375, -146a, -34a). Annexin V and caspase-8, -9 and -3 activity were assessed to characterize cell death. Senescence was determined by assessing β-galactosidase (SA-β-gal) activity. Immunoblotting was performed to assess the expression/activation of: i) phosphorylated H2AX (γ-H2AX), markers of DNA double strand breaks (DSBs); ii) p19Kip1/Cip1, p21Waf1/Cip1 and p27Kip1/Cip1, senescence-related-markers; iii) p62, LC3-I and LC3-II, regulators of autophagy; iv) ATM, RAD51, DNA-PKcs, Ku70 and Ku80, mediators of DSBs repair.Results: Low dose-rate (LDR) more efficiently induced apoptosis and senescence in RMS while high dose-rate (HDR) necrosis in PCa. This paralleled with a lower ability of LDR-RMS and HDR-PCa irradiated cells to activate DSBs repair. Modulating the dose rate did not differently affect the anti-oxidant ability of cancer cells.Conclusion: The present results indicate that a stronger cytotoxic effect was induced by modulating the dose-rate in a cancer cell-dependent manner, this suggesting that choose the dose-rate based on the individual patient's tumor characteristics could be strategic for effective RT exposures.


Measurements of tumor tissue oxygen tension using a time-resolved luminescence-based optical oxylite probe: comparison with a paired survival assay.
Recently, a system that measures tissue oxygen tension using time-resolved luminescence-based optical sensors has become available commercially (Oxford Optronix, Oxford, England). Two experiments were conducted using this system. First, the oxygen tension distribution was measured in two tumor lines: a spontaneous mouse fibrosarcoma, FSa-II, and a human squamous cell carcinoma xenograft, FaDu. The area in which the pO(2) was equal to or lower than 2.5 mmHg was defined as the hypoxic lesion, and the hypoxic cell fraction was taken as the fraction of these measurements in a tumor. The measured hypoxic cell fractions were compared with those determined by the paired cell survival assay for tumors of various sizes. Second, the tumor tissue pO(2) was measured continuously after administration of two different anesthetics to evaluate the effect of these drugs on tissue pO(2). Results indicated a good agreement between the hypoxic cell fractions measured by this system and those determined by the paired cell survival curve assay for tumors smaller than approximately 500 mm(3). For tumors larger than approximately 500 mm(3), the hypoxic cell fractions measured by the oxygen probe system were higher than those measured by the paired cell survival assay. This may suggest that the hypoxic cell fraction measured by the oxygen probes included both hypoxic and necrotic areas in large tumors where necrotic lesions occupied a significant portion of the tumor. Continuous measurements of pO(2) after anesthesia (Nembutal, or ketamine plus xylazine) showed a consistent rise in the pO(2) during the first 20-30 min of measurement. Subsequently, the pO(2) values became constant or continued to rise slowly. For comparison, the tumor cell survivals were assayed after a dose of 20 Gy given in air at 5, 20 and 60 min after anesthesia. The result showed a decrease in cell survival only in tumors irradiated 20 min after an injection of Nembutal.


Activity-crowding coupling effect on the diffusion dynamics of a self-propelled particle in polymer solutions.
The anomalous diffusion dynamics of an active particle in polymer solutions is studied based on a Langevin Brownian dynamics simulation. Firstly, the mean-square displacement (MSD) is investigated under various system parameters of active force Fa, probe size σa, polymer volume fraction φ and polymer chain length N. A very novel transition between superdiffusion and subdiffusion is observed with varying Fa and φ, owing to the activity and crowding competition effect. The two anomalous diffusion regimes are identified in the parameter space diagram. The increment of the MSD under activity is examined on intermediate time scales, which manifests a power law relation with the particle's dynamical persistence length L, i.e., ΔMSD = 2Lm, where the exponent m decreases with φ. Secondly, we explicitly evaluate the long-time diffusion coefficients D in a pure solvent and Da in polymer solutions. The dependence of relative diffusivity Da/D on volume fraction φ reproduces the well-known Phillies' equation exp(-κφμ). The fitting parameters show μ≃ 1, but κ apparently increases with activity. More importantly, our simulation justifies a multi-length scaling relation in a very similar form to that for passive probes, depending on simple structural parameters of the probe-polymer system. With the aid of an activation energy model, we find a counterintuitive activity-crowding coupling effect: activity enhances the effective viscosity experienced by the probe and thus strengthens the crowding-induced slowing of diffusion.


Retinopathy of prematurity: a global perspective of the epidemics, population of babies at risk and implications for control.
Globally at least 50,000 children are blind from retinopathy of prematurity (ROP) which is now a significant cause of blindness in many middle income countries in Latin American and Eastern Europe. Retinopathy of prematurity is also being reported from the emerging economies of India and China. The characteristics of babies developing severe disease varies, with babies in middle and low income countries having a much wider range of birth weights and gestational ages than is currently the case in industrialized countries. Rates of disease requiring treatment also tend to be higher in middle and low income countries suggesting that babies are being exposed to risk factors which are, to a large extent, being controlled in industrialised countries. The reasons for this "third epidemic" of ROP are discussed as well as strategies for control, including the need for locally relevant, evidence based criteria which ensure that all babies at risk are examined.


Health research capacity building in Georgia: a case-based needs assessment.
Research capacity building in the health sciences in low- and middle-income countries (LMICs) has typically focused on bench-science capacity, but research examining health service delivery and health workforce is equally necessary to determine the best ways to deliver care. The Republic of Georgia, formerly a part of the Soviet Union, has multiple issues within its healthcare system that would benefit from expended research capacity, but the current research environment needs to be explored prior to examining research-focused activities. The purpose of this project was to conduct a needs assessment focused on developing research capacity in the Republic of Georgia with an emphasis on workforce and network development. A case study approach guided by a needs assessment format. We conducted in-country, informal, semi-structured interviews in English with key informants and focus groups with faculty, students, and representatives of local non-governmental organizations. Purposive and snowball sampling approaches were used to recruit participants, with key informant interviews scheduled prior to arrival in country. Documents relevant to research capacity building were also included. Interview results were coded via content analysis. Final results were organized into a SWOT (strengths, weaknesses, opportunities, threat) analysis format, with the report shared with participants. There is widespread interest among students and faculty in Georgia around building research capacity. Lack of funding was identified by many informants as a barrier to research. Many critical research skills, such as proposal development, qualitative research skills, and statistical analysis, were reported as very limited. Participants expressed concerns about the ethics of research, with some suggesting that research is undertaken to punish or 'expose' subjects. However, students and faculty are highly motivated to improve their skills, are open to a variety of learning modalities, and have research priorities aligned with Georgian health needs. This study's findings indicate that while the Georgian research infrastructure needs further development, Georgian students and faculty are eager to supplement its gaps by improving their own skills. These findings are consistent with those seen in other developing country contexts.


Anti-GM1 IgG antibodies in Guillain-Barré syndrome: fine specificity is associated with disease severity.
Clinical severity of Guillain-Barré syndrome (GBS) is highly variable, but the immunopathological reason is unknown. The study was designed to show which antibody parameters are associated with disease severity in GBS patients with serum anti-GM1 IgG antibodies. Thirty-four GBS patients with anti-GM(1) IgG antibodies were grouped into two categories according to disease severity at nadir: mild (grades 1-3 by Hughes functional scale, n=13) and severe (grades 4 and 5, n=21). Titre, affinity, fine specificity and cell binding of anti-GM(1) antibodies were obtained and compared between the two groups. No differences in antibody titre (GM(1)-ELISA) or affinity were found between the two patient groups. In contrast, the severe group showed a significantly higher frequency (95%, vs 46% in the mild group, p=0.002) of specific (not cross-reacting with GD(1b)) anti-GM(1) antibodies. In addition, the severe group also exhibited a higher antibody binding titre to cellular GM(1). Differences in fine specificity of antibodies are strong indications that different regions of the GM(1)-oligosaccharide are involved in antibody binding. High titres of specific anti-GM(1) antibody binding to cellular GM(1) can be explained by antigen exposure, that is, GM(1) exposes or forms mainly epitopes recognised by specific antibodies, and 'hides' those involved in binding of cross-reacting antibodies. Thus, the fine specificity of anti-GM(1) antibodies may influence disease severity by affecting antibody binding to cellular targets. Additionally, since antibody specificity studies are relatively easy to implement, fine specificity could be considered a useful predictor of disease severity.