Adherence, safety, and choice of the monthly dapivirine vaginal ring or oral emtricitabine plus tenofovir disoproxil fumarate for HIV pre-exposure prophylaxis among African adolescent girls and young women: a randomised, open-label, crossover trial.
Half of new HIV acquisitions in Africa occur in adolescent girls and young women. Pre-exposure prophylaxis (PrEP) with oral tenofovir disoproxil fumarate plus emtricitabine or the monthly dapivirine vaginal ring is efficacious but has lower adherence and effectiveness among adolescent girls and young women. We aimed to assess product adherence, safety, and choice of oral PrEP compared with the dapivirine ring among African adolescent girls and young women. MTN-034/REACH was a randomised, open-label, phase 2a crossover trial among HIV-seronegative, non-pregnant adolescent girls and young women aged 16-21 years at four clinical research sites in South Africa, Uganda, and Zimbabwe. Participants were randomly assigned (1:1) to either the dapivirine ring or daily oral PrEP (200 mg of emtricitabine and 300 mg of tenofovir disoproxil fumarate) for 6 months, then switched to the other product option for 6 months, followed by a third 6-month period in which participants were given a choice of oral PrEP, the dapivirine ring, or neither. Fixed block randomisation was used, stratified by site. The primary adherence endpoint was use of each product during the randomised periods, with high use defined as tenofovir-diphosphate concentrations greater than or equal to 700 fmol/punch (associated with taking an average of four or more tablets per week in the previous month) and greater than or equal to 4 mg dapivirine released from the returned ring (continuous use for 28 days in the previous month) based on residual drug concentrations. The primary safety endpoint was grade 2 or higher adverse events during each randomised period of 24 weeks of ring and oral PrEP. This trial is registered at ClinicalTrials.gov, NCT03593655. From Feb 6, 2019 to Sept 9, 2021, 396 adolescent girls and young women were screened, 247 of whom were enrolled and randomly assigned (6 months of the ring followed by 6 months of oral PrEP n=124; 6 months of oral PrEP followed by 6 months of the ring n=123). Median age was 18 years (IQR 17-19). 54 grade 2 or higher product-related adverse events were reported during oral PrEP and five during dapivirine ring use, with no product-related serious adverse events. High adherence was observed in 753 (57%) of the 1316 oral PrEP visits and 806 (57%) of the 1407 dapivirine ring visits. Four women acquired HIV during follow-up. Adherence was moderately high and similar between oral PrEP and the dapivirine ring with favourable safety and tolerability. Oral PrEP and the dapivirine ring are effective, safe, and well tolerated HIV prevention options for adolescent girls and young women who would benefit from a choice of PrEP formulations to meet their needs and preferences. National Institutes of Health.


In vivo measurements of airway reactivity using high-resolution computed tomography.
Changes in airway resistance are reported to account for only a portion of changes in total lung resistance. The fraction of total lung resistance caused by airway resistance is difficult to quantify in vivo. High-resolution computed tomography (HRCT) has potential application for directly measuring changes in airway size in vivo. In the present investigation, we studied five anesthetized mongrel dogs using HRCT to locate and measure changes in airway area after aerosol histamine challenge in the absence and presence of deep inspiration. We also related changes in total lung resistance to changes in airway area. We found that in all dogs after histamine aerosol challenge, airway area decreased (range, 23 +/- 7 to 67 +/- 5%, mean +/- SEM), and total lung resistance increased (range, 191 to 378%). After deep inspiration (equal to three times tidal volume), four of the five dogs showed further significant decreases in airway area (range, 13 +/- 6 to 71 +/- 8%), whereas all five dogs showed decreases in RL (range, 3 to 35%). The fact that preconstricted airways constricted further after deep inspiration while the measured RL decreased suggests that RL may not always be a reliable indicator of changes in the size of conducting airways larger than 1 mm.


Reduction of inappropriate urinary catheter use at a Veterans Affairs hospital through a multifaceted quality improvement project.
Foley catheter (FC) use is a modifiable risk factor for hospital-acquired urinary tract infection, the most common type of nosocomial infection. It is unknown whether sustained, hospital-wide reductions in FC use are achievable by combining interventions with demonstrated short-term effectiveness in selected units. A multifaceted quality improvement project to decrease unnecessary FC use and increase order documentation was instituted throughout the Minneapolis Veterans Affairs Medical Center in March 2005, after a >2-year baseline period. Bundled interventions included multiple types of education, system redesign, rewards, and feedback (phases I and II), plus, in phase III, involvement of a dedicated FC nurse. The daily prevalence of FC use dropped steeply during intervention phase I (5.5 months), from a 15.2% baseline mean to a 9.3% nadir, but rebounded quickly during the subsequent hiatus phase (1.2 months). It dropped again (mean, 13.6%) during intervention phase II (27.3 months) and even further (mean, 12.0%) during intervention phase III (22.8 months) (P ≤ .001, phase II or III vs baseline). Compared with baseline, during phase III (with the dedicated FC nurse) the mean daily percentages of nonordered and nonindicated FCs dropped from 17% to 5.1% and from 15% to 1.2%, respectively. During phases II and III combined, an estimated total of 6691 FC days were avoided. Significant hospital-wide reductions in total and inappropriate FC use and improved FC order documentation were achieved through a multicomponent campaign. The greatest and most sustained improvements accompanied the involvement of a dedicated FC nurse.


Endosulfatases SULF1 and SULF2 limit Chlamydia muridarum infection.
The first step in attachment of Chlamydia to host cells is thought to involve reversible binding to host heparan sulfate proteoglycans (HSPGs), polymers of variably sulfated repeating disaccharide units coupled to diverse protein backbones. However, the key determinants of HSPG structure that are involved in Chlamydia binding are incompletely defined. A previous genome-wide Drosophila RNAi screen suggested that the level of HSPG 6-O sulfation rather than the identity of the proteoglycan backbone maybe a critical determinant for binding. Here, we tested in mammalian cells whether SULF1 or SULF2, human endosulfatases, which remove 6-O sulfates from HSPGs, modulate Chlamydia infection. Ectopic expression of SULF1 or SULF2 in HeLa cells, which decreases cell surface HSPG sulfation, diminished C. muridarum binding and decreased vacuole formation. ShRNA depletion of endogenous SULF2 in a cell line that primarily expresses SULF2 augmented binding and increased vacuole formation. C. muridarum infection of diverse cell lines resulted indownregulation of SULF2 mRNA. In a murine model of acute pneumonia, mice genetically deficient in both endosulfatases or in SULF2 alone demonstrated increased susceptibility to C. muridarum lung infection. Collectively, these studies demonstrate that the level of HSPG 6-O sulfation is a critical determinant of C. muridarum infection in vivo and that 6-O endosulfatases are previously unappreciated modulators of microbial pathogenesis.


Saccadic disinhibition in schizophrenia patients and their first-degree biological relatives. A parametric study of the effects of increasing inhibitory load.
Several studies have reported that patients with schizophrenia and their relatives perform poorly on antisaccade tasks and have suggested that this deficit represents saccadic disinhibition. If this proposition is correct, then varying task parameters that specifically increase the difficulty with which unwanted saccades can be inhibited should exacerbate deficits. Forty-two schizophrenia patients, 42 of their first-degree biological relatives, 21 psychotic affective disorder patients, and 38 nonpsychiatric comparison subjects were given fixation and antisaccade tasks. The introduction of distracters and the presence of visible fixation stimuli were parameters used to vary the difficulty in suppressing unwanted saccades (inhibitory load). It is known that the presence of a fixation stimulus at the time when a saccade must be inhibited results in fewer reflexive errors on antisaccade tasks. Performance on fixation tasks without (low load) vs with distracters (high load) and antisaccade tasks that had fixation stimuli still visible (low load) vs already extinguished (high load) at the time when the reflexive saccade must be inhibited was compared. The schizophrenia patients and their first-degree biological relatives showed evidence of increased saccadic disinhibition that was most pronounced during high inhibitory load conditions. These data indicate that dysfunctional inhibitory processes, at least in the oculomotor domain, are associated with the liability to schizophrenia. Results also suggest that this genetic liability may be related to dysfunctional prefrontal cortical areas that provide top-down inhibitory control over reflexive saccade generation.


Severe Sub-Acromial Bursitis with Rice Bodies in a Patient with Rheumatoid Arthritis: A Case Report and Review of Literature.
Multiple rice body formation is a rare presentation of chronic sub-acromial bursitis secondary to extensive underlying rheumatoid arthritis, sero-negative inflammatory arthritis or tuberculous joints. Although there is usually an accompanying inflammatory arthropathy, it can occur in the absence of any underlying systemic disorder. We report a case of five years old neglected rice body deposition in shoulder in a 54-years old lady diagnosed to be having rheumatoid arthritis. After initial investigations, arthroscopic removal of rice bodies with bursa excision relieved the symptoms. The underlying rheumatic condition continued its course, generally sparing the involved shoulder joint. We suggest thorough examination for systemic rheumatologic disease in patients diagnosed with such lesions.


Good clinical practice in developing countries: applying recommendations.
The recommendations for clinical research in developing countries were published in 2007 and the present article deals with issues which were not initially raised or discussed in depth. In particular, we discuss specific questions linked to trials conducted in developing countries with regard to informed consent, research project review by two ethics committees, standards of care, management of biological samples, study follow-up committees, notification of Serious Adverse Events, paediatric trials, and Contract Research Organizations.


[Changes of the brain stem neurocytes in newborn rats in the conditions of experimental model of hypoxia during neuroprotective correction].
The work includes a research of morphological and immune-histochemical specifics of baby rats' cerebral structures in the conditions of experimental hypoxia model and with the administration of Cerebrocurin. It was ascertained that the most pronounced changes in the form of pericellular and perivascular edema, spongiform loci and loci of necrosis, with the phenomena of apoptosis and aponeuroses, occurred during severe hypoxia. Administration of Cerebrocurin in baby rats, which experienced moderate hypoxia, causes a decrease in pathological changes in cerebral structures and the approximation of the level of CD95 APO-1/Fas and Bcl-21 gene expression to their level in intact animals.


Family-to-Family Link Up Program: a community-based initiative supporting families caring for someone with an acquired brain injury.
The Family To Family Link Up Program (f2f Link Up) is a pilot program aimed to promote connections between families who have a family member with an Acquired Brain Injury. A total of 46 families participated in the program coordinated by The Bouverie Centre in Melbourne Victoria. Link-Ups, involving one or several sessions with members from two or more families. Link-Ups were conducted by Victorian metropolitan and regional ABI workers who were trained as Link-Up facilitators. A co-operative inquiry action research methodology was used to provide insights into the development and implementation of the program. Qualitative and quantitative data were collected from families and facilitators on the effectiveness of the program and their experience of each Link Up session. Evaluation of the program showed positive impacts for both families and facilitators and provided useful feedback on program implementation issues, benefits and constraints of the program. The opportunity to meet other families in brief, time-limited contacts with a trained facilitator is a useful and needed addition to a range of supports that might assist families caring for a member with an acquired brain injury.


Causes, consequences, and kin bias of human group fissions.
Fissions of human communities are monumental occasions with consequences for cultural and genetic variation and divergence through time by means of serial founder effects. An ethnographic review shows that most human group fissions are fueled primarily by internal political conflict and secondarily by resource scarcity. As found for other social animals, human fissions lead to subgroups that have higher levels of relatedness as compared with the original community because of kin-biased assortment known as the lineal effect. Fission processes that increase the average relatedness of subgroups are important because relatedness governs how strongly kin/group selection favors social behaviors such as warfare, peacekeeping, and other forms of collection action. However, random individual assortment is not an appropriate null model for evaluating lineage assortment because nuclear families and extended households are expected to remain together, which in and of itself forces higher relatedness in smaller subgroups. We develop a lineage assortment index where low values represent subgroups with coefficients of relatedness near those expected if nuclear and extended households had chosen to associate into random groupings. Two fissions of Ache villages (Paraguay) are examples of this type of fission with a low lineage assortment index not significantly different from zero as evaluated with controlled simulations. On the other extreme, a lineage assortment index near unity represents a lineal fission that maximizes the relatedness of subgroups such as the perfect split of a lineage into sublineages. A fission of Piaroa (Venezuela) fits this scenario. While previous discussions of fission have emphasized similarities among human studies and even other social mammals, we highlight the full range of potential kin bias in the formation of new communities.


Scalable growth of single-walled carbon nanotubes with a highly uniform structure.
Here, a scalable floating catalyst chemical vapor deposition (FCCVD) method is developed for the production of single-walled carbon nanotubes (SWCNTs) with a controlled structure. For the first time, water is used as the growth promoter in the FCCVD process to modulate the growth of SWCNTs. At an optimum water concentration of ca. 115 ppm, the water-assisted FCCVD process synthesizes SWCNTs with a significantly narrow chirality distribution. In particular, the proportion of (9,8) and (8,7) semiconducting tubes was dramatically enhanced to 45% with 27% of the (9,8) tube in the end product. This is attributed to the changes in both the SWCNT diameter and the chiral angle. The experiment results and accurate quantum chemical molecular dynamics simulations show that the addition of water affects the nucleation and the size distribution of nanoparticle catalysts, thus resulting in the growth of SWCNTs with a highly uniform structure. This direct and continuous water-assisted FCCVD provides the possibility for the mass production of high-quality SWCNTs with a controlled structure.


Impact of Improved Glycemic Control on Cardiac Function in Type 2 Diabetes Mellitus.
Patients with type 2 diabetes mellitus are at risk of heart failure. Specific therapeutic interventions for diabetic heart disease are still elusive. We aimed to examine the impact of improved glycemic control on left ventricular (LV) function in these patients. A total of 105 subjects with type 2 diabetes mellitus (aged 54±10 years) and poor glycemic control received optimization of treatment for blood glucose, blood pressure, and cholesterol to recommended targets for 12 months. LV systolic and diastolic function, measured by LV global longitudinal strain (GLS) and septal e' velocities, were compared before and after optimization. At baseline, patients had impaired LV systolic (GLS -14.9±3.2%) and diastolic function (e' 6.2±1.7 cm/s). After 12 months, glycated hemoglobin (HbA1c) decreased from 10.3±2.4% to 8.3±2.0%, which was associated with significant relative improvement in GLS of 21% and septal e' of 24%. There was a progressively greater improvement in GLS as patients achieved a lower final HbA1c. Patients achieving an HbA1c of <7.0% had the largest improvement. The 15 patients whose HbA1c worsened experienced a decline in GLS. Patients who improved their HbA1c by ≥1.0% had a significantly higher relative improvement in e' than those who did not (32% versus 8%; P=0.003). Baseline GLS, decrease in body mass index, and treatment with metformin were additional independent predictors of GLS improvement. Improvements in glycemic control over a 12-month period led to improvements in LV systolic and diastolic function. This may have long-term prognostic implications.


Gut microbiota profile of Indonesian stunted children and children with normal nutritional status.
The gut microbiota has been shown to play a role in energy metabolism of the host. Dysbiosis of the gut microbiota may predispose to obesity on the one hand, and stunting on the other. The aim of the study was to study the difference in gut microbiota composition of stunted Indonesian children and children of normal nutritional status between 3 and 5 years. Fecal samples and anthropometric measurements, in addition to economic and hygiene status were collected from 78 stunted children and 53 children with normal nutritional status in two regions in Banten and West Java provinces: Pandeglang and Sumedang, respectively. The gut microbiota composition was determined by sequencing amplicons of the V3-V4 region of the 16S rRNA gene. The composition was correlated to nutritional status and anthropometric parameters. Macronutrient intake was on average lower in stunted children, while energy-loss in the form of short-chain fatty acids (SCFA) and branched-chain fatty acids (BCFA) appeared to be higher in stunted children. In stunted children, at the phylum level the relative abundance of Bacteroidetes (44.4%) was significantly lower than in normal children (51.3%; p-value 2.55*10-4), while Firmicutes was significantly higher (45.7% vs. 39.8%; p-value 5.89*10-4). At the genus level, overall Prevotella 9 was the most abundant genus (average of 27%), and it was significantly lower in stunted children than in normal children (23.5% vs. 30.5%, respectively; q-value 0.059). Thirteen other genera were significantly different between stunted and normal children (q-value < 0.1), some of which were at low relative abundance and present in only a few children. Prevotella 9 positively correlated with height (in line with its higher relative abundance in normal children) and weight. In conclusion, Prevotella 9, which was the most abundant genus in the children, was significantly lower in stunted children. The abundance of Prevotella has been correlated with dietary fibre intake, which was lower in these stunted children. Since fibres are fermented by the gut microbiota into SCFA, and these SCFA are a source of energy for the host, increasing the proportion of Prevotella in stunted children may be of benefit. Whether this would prevent the occurrence of stunting or even has the potential to revert it, remains to be seen in follow up research.


COX6A2 deficiency leads to cardiac remodeling in human pluripotent stem cell-derived cardiomyocytes.
Cardiac remodeling is the initiating factor for the development of heart failure, which can result from various cardiomyopathies. Cytochrome c oxidase subunit 6A2 (COX6A2) is one of the components of cytochrome c oxidase that drives oxidative phosphorylation. The pathogenesis of myocardial remodeling caused by COX6A2 deficiency in humans remains unclear because there are no suitable research models. In this study, we established a COX6A2-deficient human cardiac myocyte (CM) model that mimics the human COX6A2 homozygous mutation and determined the effects of COX6A2 dysfunction and its underlying mechanism. A human COX6A2 homozygous knockout cardiomyocyte model was established by combining CRISPR/Cas9 gene editing technology and hiPSC-directed differentiation technology. Cell model phenotypic assays were done to characterize the pathological features of the resulting COX6A2-deficient cardiomyocytes. COX6A2 gene knockout did not affect the pluripotency and differentiation efficiency of hiPSCs. Myocardial cells with a COX6A2 gene knockout showed abnormal energy metabolism, increased oxidative stress levels, abnormal calcium transport activity, and decreased contractility. In addition, L-carnitine and trimetazidine significantly improved energy metabolism in the COX6A2-deficient human myocardial model. We have established a COX6A2-deficient human cardiomyocyte model that exhibits abnormal energy metabolism, elevated oxidative stress levels, abnormal calcium transport, and reduced contractility. This model represents an important tool to gain insight into the mechanism of action of energy metabolism disorders resulting in myocardial remodeling, elucidate the gene-phenotype relationship of COX6A2 deficiency, and facilitate drug screening.


Organization of delta-crystallin genes in the chicken.
Double-stranded DNA was synthesized from delta-crystallin mRNA prepared from lens fibers of 15-day-old chick embryos and cloned at the Pst I site of the plasmid pBR322. Using the cloned cDNA and single-stranded cDNA as hybridization probes, a number of genomic DNA fragments containing delta-crystallin gene sequences have been cloned from the partial and complete EcoRI digests of chick brain DNA. One of the clones from the partial digests contains a DNA fragment that consists of four EcoRI fragments of 7.6 kb, 4.0 kb, 2.6 kb, and 0.8 kb. The gene sequences reside in the (5')7.6 kb - 0.8 kb - 4.0 kb (3') fragments. Electron microscopy has provided evidence that the cloned DNA fragment includes the entire gene sequences complementary to delta-crystallin mRNA except for the 3' terminal poly(A) tail, and that the delta-crystallin gene is interrupted by at least 13 intervening sequences. Another clone contains a genomic fragment that consists of two EcoRI fragments of 3.0 kb and 11 kb. The DNA fragment in the latter clone represents a different delta-crystallin gene, as judged by restriction endonuclease mapping and by electron microscopy.


A new, higher yielding synthetic route towards dodecaphenyl cage silsesquioxanes: synthesis and mechanistic insights.
Cage dodecaphenylsilsesquioxane (T12-Phenyl) was synthesized in a one batch, mildly basic aqueous solution under room temperature conditions using a trialkoxysilane precursor. Significant improvements in synthetic yield (>95%) were observed compared with previous reports. Kinetic studies of the hydrolysis of phenyltrimethoxysilane were conducted and the condensation was monitored by (29)Si NMR which revealed the presence of a transient, intermediary T1 species as the pathway to dodecaphenylsilsesquioxane spherulites, and the tendency for T12 structures over T8, T10, and other substructures was explained through MM2 simulations.


Understanding the role of the gut ecosystem in diabetes mellitus.
Diabetes mellitus is a type of metabolic disorder whereby patients are unable to regulate glycemia. It is currently a worldwide public health issue, and is a burden to society because of its disabling and common complications. Diabetes is multifactorial, and also induces the onset of other diseases. In the present report, we review the labyrinth encompassing the gut microbiota and gut microbiota-derived metabolites in type 1 diabetes and type 2 diabetes pathogenesis. There have been exceptional improvements in deoxyribonucleic acid sequencing and mass spectrometry technologies throughout these past years, and these have allowed the comprehensive collection of information on our unique gut ecosystem. We would like to advocate incorporating metagenome and metabolome information for a comprehensive perspective of the complex interrelationships between the gut environment, host metabolism and diabetes pathogenesis. We hope that with this improved understanding we would be able to provide exciting novel therapeutic approaches to engineer an ideal gut ecosystem for optimal health.


Accelerated publication versus usual publication in 2 leading medical journals.
A number of medical journals have developed policies for accelerated publication of articles judged by the authors, the editors or the peer reviewers to be of special importance. However, the validity of these judgements is unknown. We therefore compared the importance of articles published on a "fast track" with those published in the usual way. We identified 12 "case" articles--6 articles from the New England Journal of Medicine that were prereleased on the journal's Web site before publication in print and 6 "fast-tracked" articles from The Lancet. We then identified 12 "control" articles matched to the case articles according to journal, disease or procedure of focus, theme area and year of publication. Forty-two general internists rated the articles, using 10-point scales, on dimensions addressing the articles' importance, ease of applicability and impact on health outcomes. For each dimension, the mean score for the case articles was significantly higher than the mean score for the control articles: importance to clinical practice 7.6 v. 7.1 respectively (p = 0.001), importance from a public health perspective 6.5 v. 6.0 (p < 0.001), contribution to advancement of medical knowledge 6.2 v. 5.8 (p < 0.001), ease of applicability in practice 7.0 v. 6.5 (p < 0.001), potential impact on health outcomes 6.5 v. 5.9 (p < 0.001). Despite these general findings, in 5 of the 12 matched pairs of articles the control article had a higher mean score than the case article across all the dimensions. The accelerated publication practices of 2 leading medical journals targeted articles that, on average, had slightly higher importance scores than similar articles published in the usual way. However, our finding of higher importance scores for control articles in 5 of the 12 matched pairs shows that current journal practices for selecting articles for expedited publication are inconsistent.


Valosin-containing protein (VCP) is a novel IQ motif-containing GTPase activating protein 1 (IQGAP1)-interacting protein.
Scaffold proteins play a pivotal role in making protein complexes, and organize binding partners into a functional unit to enhance specific signaling pathways. IQ motif-containing GTPase activating protein 1 (IQGAP1) is an essential protein for spine formation due to its role in scaffolding multiple signal complexes. However, it remains unclear how IQGAP1 interacts within the brain. In the present study, we screened novel IQGAP1-interacting proteins by a proteomic approach. As a novel IQGAP1-interacting protein, we identified valosin-containing protein (VCP) which is a causative gene in patients with inclusion body myopathy with Paget's disease of bone and frontotemporal dementia (IBMPFD). The physiological interaction of IQGAP1 with VCP was confirmed by an immunoprecipitation assay. Both the N-terminal (N-half) and C-terminal (C-half) fragments of IQGAP1 interacted with the N-terminal region of VCP. Co-localization of IQGAP1 and VCP was observed in the growth corn, axonal shaft, cell body, and dendrites in cultured hippocampal neurons at 4 days in vitro (DIV4). In cultured neurons at DIV14, IQGAP1 co-localized with VCP in dendrites. When HEK293T cells were co-transfected with IQGAP1 and VCP, an immunoprecipitation assay revealed that binding of IQGAP1 with disease-related mutant (R155H or A232E) VCP was markedly reduced compared to wild-type (WT) VCP. These results suggest that reduction of IQGAP1 and VCP interaction may be associated with the pathophysiology of IBMPFD.


Enhanced Performance of Ge Photodiodes via Monolithic Antireflection Texturing and α-Ge Self-Passivation by Inverse Metal-Assisted Chemical Etching.
Surface antireflection micro and nanostructures, normally formed by conventional reactive ion etching, offer advantages in photovoltaic and optoelectronic applications, including wider spectral wavelength ranges and acceptance angles. One challenge in incorporating these structures into devices is that optimal optical properties do not always translate into electrical performance due to surface damage, which significantly increases surface recombination. Here, we present a simple approach for fabricating antireflection structures, with self-passivated amorphous Ge (α-Ge) surfaces, on single crystalline Ge (c-Ge) surface using the inverse metal-assisted chemical etching technology (I-MacEtch). Vertical Schottky Ge photodiodes fabricated with surface structures involving arrays of pyramids or periodic nano-indentations show clear improvements not only in responsivity, due to enhanced optical absorption, but also in dark current. The dark current reduction is attributed to the Schottky barrier height increase and self-passivation effect of the i-MacEtch induced α-Ge layer formed on top of the c-Ge surface. The results demonstrated in this work show that MacEtch can be a viable technology for advanced light trapping and surface engineering in Ge and other semiconductor based optoelectronic devices.


[Therapeutic drug monitoring of 6-thioguanine nucleotides in inflammatory bowel disease: interest and limits].
Azathioprine, 6-mercaptopurine, and 6-thioguanine are immunosuppressive drugs indicated in the prevention of graft rejection, and treatment of auto-immune disease or inflammatory bowel disease. Their anti-nucleotidic properties are also used for the treatment of acute leukaemia. Their metabolism involves thiopurine methyl transferase, which activity varies according to genetic polymorphisms. In inflammatory bowel disease patients, there is no recommended therapeutic range of intra-erythrocyte 6-thioguanine nucleotide concentration, the active metabolite. Therapeutic drug monitoring of 6-thioguanine nucleotide concentrations is however proposed in the following clinical situations: to check the observance, to try to explain therapeutic failure, to manage patients with limited thiopurine methyl transferase activity or patients treated with associated drugs that can modify thiopurine methyl transferase activity. The literature review shows that high concentrations of 6-thioguanine nucleotides and methylated metabolites are associated with an increased risk of bone marrow toxicity. In addition, high concentrations of methylated metabolite might increase the risk of hepatic toxicity. These major side-effects can be prevented by the use of pre-treatment screening for thiopurine methyl transferase activity or genotype in inflammatory bowel disease patients in order to propose an adapted dosing.


Mesenchymal Cells Support the Oncogenicity and Therapeutic Response of the Hedgehog Pathway in Triple-Negative Breast Cancer.
The paracrine interaction between tumor cells and adjacent stroma has been associated with the oncogenic activity of the Hedgehog (Hh) pathway in triple-negative breast tumors. The present study developed a model of paracrine Hh signaling and examined the impact of mesenchymal cell sources and culture modalities in the oncogenicity of the Hh pathway in breast tumor cells. Studies consisted of tumor cell monocultures and co-cultures with cancer-associated and normal fibroblasts, tumor cells that undergo epithelial-mesenchymal transition (EMT), or adipose-derived mesenchymal stem cells (ADMSCs). Hh ligand and pathway inhibitors, GANT61 and NVP-LDE225 (NVP), were evaluated in both cell cultures and a mouse xenograft model. Results in monocultures show that tumor cell viability and Hh transcriptional activity were not affected by Hh inhibitors. In co-cultures, down-regulation of GLI1, SMO, and PTCH1 in the stroma correlated with reduced tumor growth rates in xenografted tumors and cell cultures, confirming a paracrine interaction. Fibroblasts and EMT cells supported Hh transcriptional activity and enhanced tumor cell growth. Mixed and adjacent culture modalities indicate that tumor growth is supported via fibroblast-secreted soluble factors, whereas enriched tumor stemness requires close proximity between tumor and fibroblasts. Overall this study provides a tumor-mesenchymal model of Hh signaling and highlights the therapeutic value of mesenchymal cells in the oncogenic activity of the Hh pathway.


Stress, nutrition and parental care in a teleost fish: exploring mechanisms with supplemental feeding and cortisol manipulation.
Parental care is an essential life-history component of reproduction for many animal species, and it entails a suite of behavioural and physiological investments to enhance offspring survival. These investments can incur costs to the parent, reducing their energetic and physiological condition, future reproductive capabilities and survival. In fishes, relatively few studies have focused on how these physiological costs are mediated. Male smallmouth bass provide parental care for developing offspring until the brood reaches independence. During this energetically demanding life stage, males cease active foraging as they vigorously defend their offspring. Experimental manipulation of cortisol levels (via implantation) and food (via supplemental feeding) in parental males was used to investigate the fitness consequences of parental care. Improving the nutritional condition of nest-guarding males increased their reproductive success by reducing premature nest abandonment. However, supplemental feeding and cortisol treatment had no effect on parental care behaviours. Cortisol treatment reduced plasma lymphocyte numbers, but increased neutrophil and monocyte concentrations, indicating a shift in immune function. Supplemental feeding improved the physiological condition of parental fish by reducing the accumulation of oxidative injury. Specifically, supplemental feeding reduced the formation of 8-hydroxy-2'-deoxyguanosine (8-OHdG) on DNA nucleotides. Increasing the nutritional condition of parental fish can reduce the physiological cost associated with intensive parental activity and improve overall reproductive success, illustrating the importance of nutritional condition as a key modulator of parental fitness.


Genetics in psychiatry: common variant association studies.
Many psychiatric conditions and traits are associated with significant heritability. Genetic risk for psychiatric conditions encompass rare variants, identified due to major effect, as well as common variants, the latter analyzed by association analyses. We review guidelines for common variant association analyses, undertaking after assessing evidence of heritability. We highlight the importance of: suitably large sample sizes; an experimental design that controls for ancestry; careful data cleaning; correction for multiple testing; small P values for positive findings; assessment of effect size for positive findings; and, inclusion of an independent replication sample. We also note the importance of a critical discussion of any prior findings, biological follow-up where possible, and a means of accessing the raw data.


Surfactant suppresses NF-kappa B activation in human monocytic cells.
In addition to biophysical properties, pulmonary surfactant has immunomodulatory activity. We previously demonstrated that both synthetic (Exosurf) and modified natural surfactant (Survanta) downregulated endotoxin-stimulated inflammatory c ytokine mRNA levels and protein products (tumor necrosis factor-alpha [TNF], interleukin-1-beta [IL-1], interleukin-6 [IL-6]) in human alveolar macrophages. In this study, we report that both Exosurf and Survanta suppress TNF mRNA and secretion (85 +/- 4% mean percent inhibition +/- SEM by Exosurf; 71 +/- 6% by Survanta) by endotoxin-stimulated THP-1, a human monocytic cell line. Because surfactant downregulated inflammatory cytokine production similarly in both normal human alveolar macrophages and the THP-1 cell line, we used this cell line to investigate whether surfactant affected transcriptional mechanisms. Specifically, we examined nuclear factor-kappa B (NF-kappa B) activation because it is crucial in transcriptional regulation of many inflammatory cytokine genes including TNF, IL-1, and IL-6. Electrophoretic mobility shift assays showed that both surfactants decreased activation of NF-kappa B. The presence of both p65 and p50 NF-kappa B components in LPS-activated THP-1 cells was confirmed by specific antibody induction of supershifts in mobility assays. These results are the first to suggest that surfactant's suppressive effects on inflammatory cytokine production may involve transcriptional regulation through inhibition of NF-kappa B activation.


Changes in Long-Term Functional Independence in Patients with Moderate and Severe Ischemic Stroke: Comparison of the Responsiveness of the Modified Barthel Index and the Functional Independence Measure.
This study investigated the long-term functional changes in patients with moderate-to-severe ischemic stroke. In addition, we investigated whether there was a difference between the modified Barthel Index (MBI) and Functional Independence Measure (FIM) according to severity. To evaluate the changes in the long-term functional independence of the subjects, six evaluations were conducted over 2 years, and the evaluation was performed using MBI and FIM. A total of 798 participants participated in this study, of which 673 were classified as moderate and 125 as severe. During the first 3 months, the moderate group showed greater recovery than the severe group. The period of significant change in the National Institutes of Health Stroke Scale (NIHSS) score was up to 6 months after onset in the moderate group, and up to 3 months after onset in the severe group. In the severe group, MBI evaluation showed significant changes up to 6 months after onset, whereas FIM showed significant changes up to 18-24 months. Our results showed that functional recovery of patients with ischemic stroke in the 3 months after onset was greater in the moderate group than in the severe group. FIM is more appropriate than MBI for evaluating the functional status of patients with severe stroke.


Extreme Y chromosome polymorphism corresponds to five male reproductive morphs of a freshwater fish.
Loss of recombination between sex chromosomes often depletes Y chromosomes of functional content and genetic variation, which might limit their potential to generate adaptive diversity. Males of the freshwater fish Poecilia parae occur as one of five discrete morphs, all of which shoal together in natural populations where morph frequency has been stable for over 50 years. Each morph uses a different complex reproductive strategy and morphs differ dramatically in colour, body size and mating behaviour. Morph phenotype is passed perfectly from father to son, indicating there are five Y haplotypes segregating in the species, which encode the complex male morph characteristics. Here, we examine Y diversity in natural populations of P. parae. Using linked-read sequencing on multiple P. parae females and males of all five morphs, we find that the genetic architecture of the male morphs evolved on the Y chromosome after recombination suppression had occurred with the X. Comparing Y chromosomes between each of the morphs, we show that, although the Ys of the three minor morphs that differ in colour are highly similar, there are substantial amounts of unique genetic material and divergence between the Ys of the three major morphs that differ in reproductive strategy, body size and mating behaviour. Altogether, our results suggest that the Y chromosome is able to overcome the constraints of recombination loss to generate extreme diversity, resulting in five discrete Y chromosomes that control complex reproductive strategies.


Efavirenz promotes β-secretase expression and increased Aβ1-40,42 via oxidative stress and reduced microglial phagocytosis: implications for HIV associated neurocognitive disorders (HAND).
Efavirenz (EFV) is among the most commonly used antiretroviral drugs globally, causes neurological symptoms that interfere with adherence and reduce tolerability, and may have central nervous system (CNS) effects that contribute in part to HIV associated neurocognitive disorders (HAND) in patients on combination antiretroviral therapy (cART). Thus we evaluated a commonly used EFV containing regimen: EFV/zidovudine (AZT)/lamivudine (3TC) in murine N2a cells transfected with the human "Swedish" mutant form of amyloid precursor protein (SweAPP N2a cells) to assess for promotion of amyloid-beta (Aβ) production. Treatment with EFV or the EFV containing regimen generated significantly increased soluble amyloid beta (Aβ), and promoted increased β-secretase-1 (BACE-1) expression while 3TC, AZT, or, vehicle control did not significantly alter these endpoints. Further, EFV or the EFV containing regimen promoted significantly more mitochondrial stress in SweAPP N2a cells as compared to 3TC, AZT, or vehicle control. We next tested the EFV containing regimen in Aβ - producing Tg2576 mice combined or singly using clinically relevant doses. EFV or the EFV containing regimen promoted significantly more BACE-1 expression and soluble Aβ generation while 3TC, AZT, or vehicle control did not. Finally, microglial Aβ phagocytosis was significantly reduced by EFV or the EFV containing regimen but not by AZT, 3TC, or vehicle control alone. These data suggest the majority of Aβ promoting effects of this cART regimen are dependent upon EFV as it promotes both increased production, and decreased clearance of Aβ peptide.


Sulforaphane Rescues Ethanol-Suppressed Angiogenesis through Oxidative and Endoplasmic Reticulum Stress in Chick Embryos.
Our previous study showed that ethanol exposure inhibited embryonic angiogenesis mainly due to the excessive stimulation of reactive oxygen species (ROS) production. In this study, we investigated whether sulforaphane (SFN), a known dietary bioactive compound, could ameliorate ethanol-suppressed angiogenesis using chick embryo angiogenesis models. Using chick yolk sac membrane (YSM) and chorioallantoic membrane (CAM) models, we demonstrated that administration of low concentrations of SFN (2.5-10 μM) alone increased angiogenesis, but high concentrations of SFN (20-40 μM) inhibited angiogenesis. SFN administration alleviated ethanol-suppressed angiogenesis and angiogenesis-related gene expression in both angiogenesis models. Ethanol exposure caused cell apoptosis in chick CAM, and the cell apoptosis could be remitted by administration of SFN. Subsequently, we demonstrated that the ethanol-induced increase in production of ROS and reduction of antioxidant enzymes' activity were partially rescued by SFN. Similar results were obtained in endoplasmic reticulum (ER) stress determination, indicated by ATF6 and GRP78 expression or thapsigargin-induced ER stress in the presence or absence of SFN. Taken together, our experiments show that SFN administration can ameliorate ethanol-suppressed embryonic angiogenesis, and this is mainly achieved by alleviating excessive ROS production and ER stress. This study suggests that SFN, in appropriate concentrations, could be a potential candidate compound for preventing the negative impact of alcohol on angiogenesis.


Comparison of methods for extraction of bacterial adenine nucleotides determined by firefly assay.
Adenine nucleotides in Escherichia coli, Bacillus cereus, Klebsiella pneumoniae, Staphylococcus aureus, and Pseudomonas aeruginosa were extracted using 10 different methods. Extracts were assayed for adenosine 5'-triphosphate (ATP), adenosine 5'-diphosphate (ADP), and adenosine 5'-monophosphate (AMP) by the firefly method using an improved procedure. Analytical interference by bacterial enzymes not inactivated during the extraction was found to be a major problem. However, these enzymes were inactivated to a considerable extent by the inclusion of ethylenediaminetetraacetate in the extraction reagent. The 10 extraction methods were compared with respect to yield of adenine nucleotides, interference with the enzymic assay, reproducibility of the method, and stability of the extracts. Results indicated that extraction with trichloroacetic acid was the method most closely reflecting actual levels of ATP, ADP and AMP in intact bacterial cells. However, for the extraction of ATP in some bacterial strains several other methods may be used and may be advantageous from a practical point of view.


Assessment of laboratory logistics management information system practice for HIV/AIDS and tuberculosis laboratory commodities in selected public health facilities in Addis Ababa, Ethiopia.
Logistics management information system for health commodities remained poorly implemented in most of developing countries. To assess the status of laboratory logistics management information system for HIV/AIDS and tuberculosis laboratory commodities in public health facilities in Addis Ababa. A cross-sectional descriptive study was conducted from September 2010-January 2011 at selected public health facilities. A stratified random sampling method was used to include a total of 43 facilities which, were investigated through quantitative methods using structured questionnaires interviews. Focus group discussion with the designated supply chain managers and key informant interviews were conducted for the qualitative method. There exists a well-designed logistics system for laboratory commodities with trained pharmacy personnel, distributed standard LMIS formats and established inventory control procedures. However, majority of laboratory professionals were not trained in LMIS. Majority of the facilities (60.5%) were stocked out for at least one ART monitoring and TB laboratory reagents and the highest stock out rate was for chemistry reagents. Expired ART monitoring laboratory commodities were found in 25 (73.5%) of facilities. Fifty percent (50%) of the assessed hospitals and 54% of health centers were currently using stock/bin cards for all HIV/AIDS and TB laboratory commodities in main pharmacy store, among these only 25% and 20.8% of them were updated with accurate information matching with the physical count done at the time of visit for hospitals and health centers respectively. Even though there exists a well designed laboratory LMIS, keeping quality stock/bin cards and LMIS reports were very low. Key ART monitoring laboratory commodities were stock out at many facilities at the day of visit and during the past six months. Based on findings, training of laboratory personnel's managing laboratory commodities and keeping accurate inventory control procedures were recommended.


Subwavelength waveguide grating for mode conversion and light coupling in integrated optics.
We propose a new method for mode conversion and coupling between an optical fiber and a sub-micrometer waveguide using a subwavelength grating (SWG) with a period less than the 1st order Bragg period. The coupler principle is based on gradual modification of the waveguide mode effective index by the SWG effect that at the same time frustrates diffraction and minimizes reflection loss. We demonstrate the proposed principle by two-dimensional Finite Difference Time Domain (FDTD) calculations of various SWG structures designed for the silicon-on-insulator (SOI) platform with a Si core thickness of 0.3 microm. We found a coupling loss as small as 0.9 dB for a 50 microm-long SWG device and low excess loss due to fiber misalignment, namely 0.07 dB for a transverse misalignment of +/-1 microm, and 0.24 dB for an angular misalignment of +/-2 degrees. Scaling of the SWG coupler length down to 10 microm is also reported on an example of a 2D slab waveguide coupling structure including aspect ratio dependent etching and micro-loading effects. Finally, advantages of the proposed coupling principle for fabricating 3D coupling structures are discussed.


Regulation of SREBP processing and membrane lipid production by phospholipids in Drosophila.
Animal cells exert exquisite control over the physical and chemical properties of their membranes, but the mechanisms are obscure. We show that phosphatidylethanolamine, the major phospholipid in Drosophila, controls the release of sterol regulatory element-binding protein (SREBP) from Drosophila cell membranes, exerting feedback control on the synthesis of fatty acids and phospholipids. The finding that SREBP processing is controlled by different lipids in mammals and flies (sterols and phosphatidylethanolamine, respectively) suggests that an essential function of SREBP is to monitor cell membrane composition and to adjust lipid synthesis accordingly.


Functional Maps at the Onset of Auditory Inputs in Very Early Preterm Human Neonates.
During the last trimester of human gestation, neurons reach their final destination and establish long- and short-distance connections. Due to the difficulties obtaining functional data at this age, the characteristics of the functional architecture at the onset of sensory thalamocortical connectivity in humans remain largely unknown. In particular, it is unknown to what extent responses evoked by an external stimulus are general or already sensitive to certain stimuli. In the present study, we recorded high-density event-related potentials (ERPs) in 19 neonates, tested ten weeks before term (28-32 weeks gestational age (wGA), that is, at an average age of 30 wGA) by means of a syllable discrimination task (i.e., a phonetic change: ba vs. ga; and a voice change: male vs. female voice). We first observed that the syllables elicited 4 peaks with distinct topographies implying a progression of the sensory input along a processing hierarchy; second, repetition induced a decrease in the amplitude (repetition suppression) of these peaks, but their latencies and topographies remained stable; and third, a change of stimulus generated mismatch responses, which were more precisely time-locked to event onset in the case of a phonetic change than in the case of a voice change. A hierarchical and parallel functional architecture is therefore able to process environmental sounds in a timely precise fashion, well before term birth. This elaborate functional architecture at the onset of extrinsic neural activity suggests that specialized areas weakly dependent on the environment are present in the perisylvian region as part of the genetic endowment of the human species.


Blood pressure regulation during cardiac autonomic blockade: effect of fitness.
The purpose of this study was to determine the role of the autonomic nervous system's control of the heart in fitness-related differences in blood pressure regulation. The cardiovascular responses to progressive lower-body negative pressure (LBNP) were studied during unblocked (control) and full blockade (experimental) conditions in 10 endurance-trained (T) and 10 untrained (UT) men, aged 20-31 yr. The experimental conditions included beta 1-adrenergic blockade (metoprolol tartrate), parasympathetic blockade (atropine sulfate), or complete blockade (metoprolol and atropine). Heart rate, blood pressure, forearm blood flow, and cardiac output were measured at rest and -16 and -40 Torr LBNP. Forearm vascular resistance, peripheral vascular resistance, and stroke volume were calculated from these measurements at each stage of LBNP. Blood pressure was maintained, primarily by augmented vasoconstriction, equally in T and UT subjects during complete and atropine blockade. The fall in systolic and mean pressure from 0 to -40 Torr was greater (P less than 0.05) in the T subjects during the unblocked and metoprolol blockade conditions. This reduced blood pressure control during unblocked condition was attributable to attenuated vaso-constrictor and chronotropic responses in the T subjects. We hypothesize that an autonomic imbalance (elevated base-line parasympathetic activity) in highly trained subjects restricts reflex cardiac responses, which accompanied by an attenuated vasoconstrictor response, results in attenuated blood pressure control during a steady-state hypotensive stress.


[Neurobiology of substance-related addiction: findings of neuroimaging].
Neuroimaging provides insight into the main biological mechanisms underlying drug and alcohol dependence. Cardinal symptoms of drug dependence are the development of tolerance against drug effects, withdrawal symptoms, drug craving, reduced control over drug intake and harmful consequences of drug consumption. Brain imaging studies support the hypothesis that tolerance development can be understood as a neuroadaptive mechanism to ensure homeostasis during chronic drug intake. When drug consumption is suddenly interrupted during detoxification, the loss of homeostasis can manifest as a withdrawal syndrome. While tolerance development reduces the effects of chronic drug intake, sensitization is a neuroadaptive process that increases the effects of a drug dose. Brain imaging studies indicate that sensitisation and drug craving are associated with neuroadaptive processes in the brain reward system. Harmful consequences of drug intake include neurotoxic effects on the central nervous system. Besides discussing brain imaging studies on the neurobiological correlates of drug dependence, this review also presents studies on vulnerability factors that predispose individuals to excessive drug intake.


The Warburg Effect in Yeast: Repression of Mitochondrial Metabolism Is Not a Prerequisite to Promote Cell Proliferation.
O. Warburg conducted one of the first studies on tumor energy metabolism. His early discoveries pointed out that cancer cells display a decreased respiration and an increased glycolysis proportional to the increase in their growth rate, suggesting that they mainly depend on fermentative metabolism for ATP generation. Warburg's results and hypothesis generated controversies that are persistent to this day. It is thus of great importance to understand the mechanisms by which cancer cells can reversibly regulate the two pathways of their energy metabolism as well as the functioning of this metabolism in cell proliferation. Here, we made use of yeast as a model to study the Warburg effect and its eventual function in allowing an increased ATP synthesis to support cell proliferation. The role of oxidative phosphorylation repression in this effect was investigated. We show that yeast is a good model to study the Warburg effect, where all parameters and their modulation in the presence of glucose can be reconstituted. Moreover, we show that in this model, mitochondria are not dysfunctional, but that there are fewer mitochondria respiratory chain units per cell. Identification of the molecular mechanisms involved in this process allowed us to dissociate the parameters involved in the Warburg effect and show that oxidative phosphorylation repression is not mandatory to promote cell growth. Last but not least, we were able to show that neither cellular ATP synthesis flux nor glucose consumption flux controls cellular growth rate.


Diversity of structure and function at mammalian central synapses.
Our appreciation of the relationship between synaptic structure and function, and in particular our understanding of quantal synaptic transmission, is derived from classical studies on the neuromuscular junction. However, physiological studies of quantal transmission at mammalian CNS synapses have produced a variety of results, and thus no consensus of opinion has emerged. This variability could be due, in part, to experimental and analytical limitations or to differences in the structural and functional features of central synapses, or both. Some of the experimental limitations have recently been overcome by the use of novel preparations that permit direct measurement of quantal synaptic events in the CNS. Although these studies reveal similarities between the synaptic mechanisms of the neuromuscular junction and CNS synapses, important differences and specializations are also evident. The purpose of this review is to highlight the structural and functional diversity of synapses in the mammalian CNS, and to discuss the potential relevance of structural features to synaptic function.


Probing for membrane domains in the endoplasmic reticulum: retention and degradation of unassembled MHC class I molecules.
Quality control of protein biosynthesis requires ER-retention and ER-associated degradation (ERAD) of unassembled/misfolded molecules. Although some evidence exists for the organization of the ER into functionally distinct membrane domains, it is unknown if such domains are involved in the retention and ERAD of unassembled proteins. Here, it is shown that unassembled MHC class I molecules are retained in the ER without accumulating at ER-exit sites or in the ERGIC of beta2m-/- cells. Furthermore, these molecules did not cluster in the ER membrane and appeared to be highly mobile even when ERAD or their association with calnexin were inhibited. However, upon ATP depletion, they were reversibly segregated into an ER membrane domain, distinct from ER exit sites, which included calnexin and COPII, but not the ERGIC marker protein p58. This quality control domain was also observed upon prolonged inhibition of proteasomes. Microtubules were required for its appearance. Segregation of unfolded proteins, ER-resident chaperones, and COPII may be a temporal adaptation to cell stress.


Circulating endothelial cells as predictor of long-term mortality and adverse cardiovascular outcomes in hemodialysis patients.
Circulating endothelial cells (CEC) are thought to be markers of endothelial injury. We hypothesized that the numbers of CEC may provide a novel means for predicting long-term survival and cardiovascular events in hemodialysis patients. 54 hemodialysis patients underwent enumeration of their CEC number. We retrospectively analyzed their survival and incidence of adverse cardiovascular events. 22 deaths (41%) were noted over the median follow up period of 3.56 years (IQR 1.43-12) and 6 were attributed to cardiovascular deaths (11%) of which 1 (4%) was in the low CEC (CEC<20 cells/ml) and 5 (19%) in the high CEC (CEC≥20 cells/ml) group. High CEC was associated with worse cardiovascular survival (p = 0.05) and adverse cardiac events (p = 0.01). In multivariate analysis, CEC >20 cells/ml was associated with a 4-fold increased risk of adverse cardiac events (OR, 4.16 [95% CI,1.38-12.54],p = 0.01) while all-cause mortality and cardiovascular mortality were not statistically different. In this hemodialysis population, a single measurement of CEC was a strong predictor of long term future adverse cardiovascular events. We propose that CEC may be a novel biomarker for assessing cardiovascular risk in dialysis patients.


Empathy or objectivity: The forensic examiner's dilemma?
Examiners are ethically bound to manage personal biases that may infect their expert opinions. Empathy-related issues that lead to bias in forensic assessment of adjudicative competence arise in evaluation interactions with defendants (therapeutic empathy) and from examiners' personal views of issues that these assessments address (empathy-bias). This article first summarizes flexible adjudicative competence legal standards that invite bias by forensic experts. Then, after reviewing the therapeutic empathy issue, the article examines empathy-bias and its effects on the development of expert opinions. The authors assert that, properly managed, the often assumed dilemma between empathy and objectivity is a false one. Using case law, research psychology, and professional guidelines, the authors first emphasize that examiners must actively generate plausible alternative explanations of evaluation data as they form their opinions, not afterwards. Then the authors present a practical model to help experts develop opinions that best explain the data while minimizing empathy-bias.


Social competence, sense of loneliness, and speech intelligibility of young children with hearing loss in individual inclusion and group inclusion.
The study focused on social competence (SC) and perceived sense of loneliness of preschool children with hearing loss (HL) in group inclusion (GI, a small group of children with HL is integrated in a standard classroom) and individual inclusion (II, each child with HL is individually integrated into a standard classroom). The relations between these factors and the child's speech intelligibility were performed. Sixty-four children aged 4-7 years participated: 22 from an II and 42 from a GI. SC, perceived sense of loneliness, and speech intelligibility were evaluated through the use of questionnaires completed by the preschool teachers. The results showed that the SC of children in II was higher than the SC of the children in GI, while interacting with normal hearing (NH) children. In GI, the children's SC with other children with HL was higher compared with their SC with NH children. In both groups, there were relationships between speech intelligibility and SC with NH children. In addition, in the II setting, there were relationships between the speech intelligibility and the perceived sense of loneliness. These relationships were not found in the GI setting. The findings support the need for coenrollment of preschool children with HL and emphasize the crucial impact of speech intelligibility of children with HL on the success of their social enrollment with NH children, already at a young age.


Kinematic performance of medial pivot total knee arthroplasty.
Total knee arthroplasty (TKA) implants have continued to evolve to accommodate new understandings of knee mechanics. The medial-pivot implant is a newer design, which is intended to limit anterior-posterior translation in the medial compartment while allowing lateral compartment translation. However, evidence for a generalized medial-pivot characteristic across all activities is limited. The purpose of the study was to quantify and compare in vivo knee joint kinematics using high-speed stereo radiography during activities of daily living in patients who have undergone a TKA with a cruciate sacrificing medial-pivot implant to age- and sex-matched native controls. There were fifteen participants (7 patients, 4 women, mean age 70 years [range, 61 to 76] and 8 non-symptomatic controls, 4 women, mean age 64 years, [range, 56 to 81]) who performed 6 functional tasks in high-speed stereo radiography: deep-knee lunge; chair rise; step down; gait, gait with 90° turn; and seated knee extension. Translational differences between groups (surgical vs. control) were assessed for the medial and lateral condyle, while pivot location was normalized to subject-specific tibial plateau geometry. The emerging kinematic trend among the surgical cohort was a more constrained medial condyle that provided greater stability of the medial compartment and did not result in the paradoxical anterior translation at mid-flexion angles during weightbearing activities, but was associated with less condylar translation than native knees. Additionally, the transverse tibial pivot location occurs most commonly in the middle third of the tibial plateau and secondarily on the medial third. Some variability in pivot location occurs between activities and is greater in non-symptomatic, native knee controls.


Adolescent chronic fatigue syndrome; a follow-up study displays concurrent improvement of circulatory abnormalities and clinical symptoms.
The pathophysiology of chronic fatigue syndrome (CFS) in adolescents is unknown, and the clinical course and prognosis is still questioned. Recent research indicates that abnormalities of autonomic cardiovascular control may play an important role. The aim of this research project was to perform a follow-up study of adolescents with chronic fatigue syndrome, focusing on clinical symptoms and autonomic cardiovascular control. 47 adolescents (12-18 years old) with CFS were recruited from the outpatient clinic at the Department of Pediatrics, Oslo University Hospital. In a primary visit and a follow-up visit (3-17 months later), we evaluated: a) a wide range of complaints and symptoms and b) cardiovascular variables at baseline and during a 20° head-up tilt-test (HUT). At the second visit, patients reported significant improvement regarding functional impairments, fatigue severity, muscular pain, concentration problems, post-exertional malaise and the problem of non-relieving rest. Also, at the second visit, baseline heart rate (HR), blood pressure, total peripheral resistance index (TPRI) and LF/HF (low-frequency:high-frequency heart rate variability ratio, an index of sinus node sympathovagal balance derived from spectral analyses of heart rate) were significant lower, and the increases in HR, mean blood pressure (MBP), diastolic blood pressure (DBP) and TPRI during tilt were significantly less pronounced as compared to the first visit. There was a significant correlation between changes in autonomic symptom score, fatigue severity score and functional impairment score from the first to the second visit. The majority of adolescents with CFS experienced an improvement over time in functional impairment, self-reported fatigue and additional symptoms, and a concurrent improvement of autonomic cardiovascular control. A possible connection between clinical symptoms and abnormal autonomic control in CFS might represent a focus for further research.


Mapping of the GEVA Items to the ICF: Preliminary Results Based on the Content of a Tool Guide Used to Assess the Needs of Persons With Disabilities in France.
The aim of this research is two-fold. Firstly, mapping the GEVA items on to the ICF will allow identifying those items that are covered by the ICF and assist in improving the data collection process. Secondly this work will provide a first exploration of the items that are not covered by the ICF and that could lead to potential proposals for updating the ICF. The preliminary results show that the items of the GEVA 2008 general version are partly covered by the ICF 2017 Browser version categories. In every section of the GEVA, some of the items might be coded with ICF codes coming from the following ICF components: Body functions, Activities and Participation, Environmental factors, Personal factors. The items of the section 6 remains those mostly covered by the ICF. Throughout the GEVA, many environmental factors are documented. Although further analysis is needed to better inform the use of qualifiers (performance, capacity, satisfaction) together with the activities and the environmental factors, the identified ICF codes could assist in improving the data collection process. Finally, some items might be discussed to become potential ICF updates proposals.


Green tea polyphenol (-)-epigallocatechin gallate reduces matrix metalloproteinase-9 activity following transient focal cerebral ischemia.
Green tea polyphenol (-)-epigallocatechin gallate (EGCG) has been reported to reduce neuronal damage after cerebral ischemic insult. EGCG is known to reduce matrix metalloproteinase (MMP) activity. MMP can play an important role in the pathophysiology of neurological disorders including cerebral ischemia. The purpose of the current study was to investigate whether EGCG shows an inhibitory effect on MMP activity and neural tissue damage following transient focal cerebral ischemia. In the present study, C57BL/6 mice were subjected to 80 min of focal ischemia induced by middle cerebral artery occlusion (MCAO). Animals were killed 24 h after ischemia. EGCG (50 mg/kg) was administered intraperitoneally immediately after ischemia. Gelatin gel zymography showed an increase in the active form of MMP-9 after ischemia. EGCG reduced ischemia-induced up-regulation of the active form of MMP-9. In in situ zymography, EGCG reduced up-regulation of gelatinase activity induced by cerebral ischemia. Co-incubation with EGCG reduced gelatinase activity directly in postischemic brain section. In 2,3,5-triphenyltetrazolium chloride (TTC) assay, brain infarction was remarkable in the middle cerebral artery territory after focal cerebral ischemia. In EGCG-treated mice, infarct volume was significantly reduced compared with vehicle-treated mice. These results demonstrate that EGCG, a green tea polyphenol, may reduce up-regulation of MMP-9 activity and neuronal damage following transient focal cerebral ischemia. In addition to its antioxidant effect, MMP-9 inhibition might be a possible mechanism potentially involved in the neuroprotective effect of a green tea polyphenol, EGCG.


Visceral leishmaniasis in eastern Africa--current status.
Visceral leishmaniasis (VL) is among the most neglected of the tropical diseases, afflicting the poorest of the poor. In eastern Africa, VL causes at least 4000 deaths annually, a loss of approximately 385,000 disability-adjusted life years. Due to the chronicity of underlying causes, it is likely that the caseload will increase in the foreseeable future. While efforts should be pursued to develop novel case management and prevention tools, several effective interventions already exist but are rarely deployed. Funds are needed now to procure commodities and strengthen health systems, so that effective VL control can be delivered to populations at risk.


Wikis and collaborative writing applications in health care: a scoping review.
Collaborative writing applications (eg, wikis and Google Documents) hold the potential to improve the use of evidence in both public health and health care. The rapid rise in their use has created the need for a systematic synthesis of the evidence of their impact as knowledge translation (KT) tools in the health care sector and for an inventory of the factors that affect their use. Through the Levac six-stage methodology, a scoping review was undertaken to explore the depth and breadth of evidence about the effective, safe, and ethical use of wikis and collaborative writing applications (CWAs) in health care. Multiple strategies were used to locate studies. Seven scientific databases and 6 grey literature sources were queried for articles on wikis and CWAs published between 2001 and September 16, 2011. In total, 4436 citations and 1921 grey literature items were screened. Two reviewers independently reviewed citations, selected eligible studies, and extracted data using a standardized form. We included any paper presenting qualitative or quantitative empirical evidence concerning health care and CWAs. We defined a CWA as any technology that enables the joint and simultaneous editing of a webpage or an online document by many end users. We performed qualitative content analysis to identify the factors that affect the use of CWAs using the Gagnon framework and their effects on health care using the Donabedian framework. Of the 111 studies included, 4 were experimental, 5 quasi-experimental, 5 observational, 52 case studies, 23 surveys about wiki use, and 22 descriptive studies about the quality of information in wikis. We classified them by theme: patterns of use of CWAs (n=26), quality of information in existing CWAs (n=25), and CWAs as KT tools (n=73). A high prevalence of CWA use (ie, more than 50%) is reported in 58% (7/12) of surveys conducted with health care professionals and students. However, we found only one longitudinal study showing that CWA use is increasing in health care. Moreover, contribution rates remain low and the quality of information contained in different CWAs needs improvement. We identified 48 barriers and 91 facilitators in 4 major themes (factors related to the CWA, users' knowledge and attitude towards CWAs, human environment, and organizational environment). We also found 57 positive and 23 negative effects that we classified into processes and outcomes. Although we found some experimental and quasi-experimental studies of the effectiveness and safety of CWAs as educational and KT interventions, the vast majority of included studies were observational case studies about CWAs being used by health professionals and patients. More primary research is needed to find ways to address the different barriers to their use and to make these applications more useful for different stakeholders.


Force sensing and generation in cell phases: analyses of complex functions.
Cellular morphology is determined by motility, force sensing, and force generation that must be finely controlled in a dynamic fashion. Contractile and extensile functions are integrated with the overall cytoskeleton, including linkages from the cytoplasmic cytoskeleton to the extracellular matrix and other cells by force sensing. During development, as cells differentiate, variations in protein expression levels result in morphological changes. There are two major explanations for motile behavior: either cellular motility depends in a continuous fashion on cell composition or it exhibits phases wherein only a few protein modules are activated locally for a given time. Indeed, in support of the latter model, the quantification of cell spreading and other motile activities shows multiple distinct modes of behavior, which we term "phases" because there exist abrupt transitions between them. Cells in suspension have a basal level of motility that enables them to probe their immediate environment. After contacting a matrix-coated surface, they rapidly transition to an activated spreading phase. After the development of a significant contact area, the cells contract repeatedly to determine the rigidity of the substrate and then develop force on matrix contacts. When cells are fully spread, extension activity is significantly decreased and focal complexes start to assemble near the cell periphery. For each of these phases, there are significant differences in protein activities, which correspond to differences in function. Thus overall morphological change of a tissue is driven by chemical signals and force-dependent activation of one or more motile phases in limited cell regions for defined periods.


Integrating Animal-Assisted Therapy Into TF-CBT for Abused Youth With PTSD: A Randomized Controlled Feasibility Trial.
This clinical trial examined animal-assisted therapy (AAT) as an adjunct to Trauma-Focused Cognitive-Behavioral Therapy (TF-CBT) for abused youth with posttraumatic stress disorder (PTSD). Youth between the ages of 6 and 17 (M = 11.79, SD = 3.08) were randomized to receive standard TF-CBT or TF-CBT with adjunctive AAT (TF-CBT+AAT) employing retired service dogs. Feasibility metrics evaluating the addition of AAT were collected in addition to common clinical outcomes evaluated in TF-CBT trials. The inclusion of AAT increased the number of potential participants who declined participation and there were no noted benefits for treatment retention or satisfaction with services. Analyses showed that the inclusion of AAT did not enhance improvement of PTSD symptom severity (β = .90, t = .94, p = .351) or a number of other outcomes. On the contrary, there were indications from analyses and clinician feedback that AAT may have attenuated improvement in many cases. This study identified a number of important feasibility considerations in the design of studies testing AAT. However, the results examining clinical outcomes suggest that the inclusion of AAT with TF-CBT in the treatment of maltreated youth with PTSD is not warranted at this time.


Hepatitis C Virus Cure in Human Immunodeficiency Virus Coinfection Dampens Inflammation and Improves Cognition Through Multiple Mechanisms.
Chronic inflammation in human immunodeficiency virus (HIV)/hepatitis C virus (HCV) coinfection increases cognitive impairment. With newer, direct-acting antiviral therapies for HCV, our objective was to determine whether chronic inflammation would be decreased and cognition improved with HCV sustained viral response (SVR) in coinfection. We studied 4 groups longitudinally: 7 HCV-monoinfected and 12 HIV/HCV-coinfected persons before and after treatment for HCV, 12 HIV-monoinfected persons, and 9 healthy controls. We measured monocyte activation and gene expression, monocyte-derived exosome micro-ribonucleic acid (miRNA) expression, plasma inflammation, and cognitive impairment before and after therapy. Plasma soluble CD163 and neopterin were decreased in HCV mono- and coinfected persons. Blood CD16+ monocytes were decreased in coinfection after HCV treatment. Global deficit score improved 25% in coinfection with the visual learning/memory domain the most improved. Hepatitis C virus SVR decreased monocyte interferon genes MX1, IFI27, and CD169 in coinfection and MX1, LGALS3BP, and TNFAIP6 in HCV monoinfection. Monocyte exosomes from coinfected persons increased in microRNA (miR)-19a, miR-221, and miR-223, all of which were associated with decreasing inflammation and nuclear factor-κB activation. Hepatitis C virus cure in coinfection brings monocyte activation to levels of HIV alone. Cognitive impairment is significantly improved with cure but not better than HIV infection alone, which strong suggests that cognitive impairment was driven by both HIV and HCV.SummaryHCV cure in HIV coinfection improves monocyte and plasma activation markers and increases cognitive function in the visual learning/memory domain.


Transitions in the flow patterns and aerodynamic characteristics of the flow around staggered rows of cylinders.
A two-dimensional numerical study of flow across rows of identical square cylinders arranged in staggered fashion is carried out. This study will unreveal complex flow physics depending upon the Reynolds number (Re) and gap spacing (g) between the cylinders. The combined effect of Reynolds number and gap spacing on the flow physics around staggered rows of cylinders are numerically studied for 20 ≤ Re ≤ 140 and 1 ≤ g ≤ 6. We use the lattice Boltzmann method for numerical computations. It is found that with increase in gap spacing between the cylinders the critical Reynolds number for the onset of vortex shedding also increases. We observed a strong effect of Reynolds number at g = 2 and 4. Secondary cylinder interaction frequency disappears for large Reynolds number at g = 6 and 5 and the flow around cylinders are fully dominated by the primary vortex shedding frequency. This ensures that at large gap spacing with an increase in the Reynolds number the wakes interaction between and behind the cylinders is weaken. Furthermore, it also ensures that the wake interaction behind the cylinders is strongly influenced by the jets in the gap spacing between the cylinders. We also found that g = 2 is the critical gap spacing for flow across rows of staggered square cylinders for the considered range of Reynolds number. Depending on the Reynolds number we observed; synchronous, quasi-periodic-I, quasi-periodic-II, and chaotic flow patterns. In synchronous flow pattern, an in-phase and anti-phase characteristics of consecutive cylinders has been observed. The important physical parameters are also analyzed and discussed in detail.


Genetic Color Polymorphism of the Whitelined Sphinx Moth larva (Lepidoptera: Sphingidae).
For a trait to be considered polymorphic, it must fulfill both genetic and ecological criteria. Genetically, a polymorphic trait must have multiple heritable variants, potentially from the same female, in high-enough frequency as to not be due to mutation. Ecologically, in a single wild population, these variants must co-occur, and be capable of interbreeding. Polymorphism is frequently considered in the context of either geographical cause or genetic consequence. However, the incorporation of both in a single study can facilitate our understanding of the role that polymorphism may play in speciation. Here, we ask if the two color morphs (green and yellow) exhibited by larvae of the whitelined sphinx moth, Hyles lineata (Fabricius), co-occur in wild populations, in what frequencies, and whether they are genetically determined. Upon confirmation from field surveys that the two color morphs do co-occur in wild populations, we determined heritability. We conducted a series of outcrosses, intercrosses and backcrosses using individuals that had exhibited yellow or green as laboratory-reared larvae. Ratios of yellow:green color distribution from each familial cross were then compared with ratios one would expect from a single gene, yellow-recessive model using a two-sided binomial exact test. The offspring from several crosses indicate that the yellow and green coloration is a genetic polymorphism, primarily controlled by one gene in a single-locus, two-allele Mendelian-inheritance pattern. Results further suggest that while one gene primarily controls color, there may be several modifier genes interacting with it.


Novel Ionic Conducting Composite Membrane Based on Polymerizable Ionic Liquids.
In this work, the design and characterization of new supported ionic liquid membranes, as medium-temperature polymer electrolyte membranes for fuel-cell application, are described. These membranes were elaborated by the impregnation of porous polyimide Matrimid® with different synthesized protic ionic liquids containing polymerizable vinyl, allyl, or methacrylate groups. The ionic liquid polymerization was optimized in terms of the nature of the used (photo)initiator, its quantity, and reaction duration. The mechanical and thermal properties, as well as the proton conductivities of the supported ionic liquid membranes were analyzed in dynamic and static modes, as a function of the chemical structure of the protic ionic liquid. The obtained membranes were found to be flexible with Young's modulus and elongation at break values were equal to 1371 MPa and 271%, respectively. Besides, these membranes exhibited high thermal stability with initial decomposition temperatures > 300 °C. In addition, the resulting supported membranes possessed good proton conductivity over a wide temperature range (from 30 to 150 °C). For example, the three-component Matrimid®/vinylimidazolium/polyvinylimidazolium trifluoromethane sulfonate membrane showed the highest proton conductivity-~5 × 10-2 mS/cm and ~0.1 mS/cm at 100 °C and 150 °C, respectively. This result makes the obtained membranes attractive for medium-temperature fuel-cell application.


Hypoxia Tolerance of 10 Euphausiid Species in Relation to Vertical Temperature and Oxygen Gradients.
Oxygen Minimum Zones prevail in most of the world's oceans and are particularly extensive in Eastern Boundary Upwelling Ecosystems such as the Humboldt and the Benguela upwelling systems. In these regions, euphausiids are an important trophic link between primary producers and higher trophic levels. The species are known as pronounced diel vertical migrators, thus facing different levels of oxygen and temperature within a 24 h cycle. Declining oxygen levels may lead to vertically constrained habitats in euphausiids, which consequently will affect several trophic levels in the food web of the respective ecosystem. By using the regulation index (RI), the present study aimed at investigating the hypoxia tolerances of different euphausiid species from Atlantic, Pacific as well as from Polar regions. RI was calculated from 141 data sets and used to differentiate between respiration strategies using median and quartile (Q) values: low degree of oxyregulation (0.25 < RI median < 0.5); high degree of oxyregulation (0.5 < RI median < 1; Q1 > 0.25 or Q3 > 0.75); and metabolic suppression (RI median, Q1 and Q3 < 0). RI values of the polar (Euphausia superba, Thysanoessa inermis) and sub-tropical (Euphausia hanseni, Nyctiphanes capensis, and Nematoscelis megalops) species indicate a high degree of oxyregulation, whereas almost perfect oxyconformity (RI median ≈ 0; Q1 < 0 and Q3 > 0) was identified for the neritic temperate species Thysanoessa spinifera and the tropical species Euphausia lamelligera. RI values of Euphausia distinguenda and the Humboldt species Euphausia mucronata qualified these as metabolic suppressors. RI showed a significant impact of temperature on the respiration strategy of E. hanseni from oxyregulation to metabolic suppression. The species' estimated hypoxia tolerances and the degree of oxyconformity vs. oxyregulation were linked to diel vertical migration behavior and the temperature experienced during migration. The results highlight that the euphausiid species investigated have evolved various strategies to deal with different levels of oxygen, ranging from species showing a high degree of oxyconformity to strong oxyregulation. Neritic species may be more affected by hypoxia, as these are often short-distance-migrators and only adapted to a narrow range of environmental conditions.


Pneumoperitoneum secondary to pneumocolon examination.
A patient had pneumoperitoneum after an air contrast barium examination. We therefore reviewed perforations secondary to barium enema examinations and concluded that conservative management of this most unusual complication may be considered if there is no evidence of barium extravasation and if the clinical course is benign.


Prevalence of prediabetes in Mexico: a retrospective analysis of nationally representative surveys spanning 2016-2022.
Characterizing prediabetes phenotypes may be useful in guiding diabetes prevention efforts; however, heterogeneous criteria to define prediabetes have led to inconsistent prevalence estimates, particularly in low- and middle-income countries. Here, we estimated trends in prediabetes prevalence in Mexico across different prediabetes definitions and their association with prevalent cardiometabolic conditions. We conducted a serial cross-sectional analysis of National Health and Nutrition Surveys in Mexico (2016-2022), totalling 22 081 Mexican adults. After excluding individuals with diagnosed or undiagnosed diabetes, we defined prediabetes using ADA (impaired fasting glucose [IFG] 100-125 mg/dL and/or HbA1c 5.7-6.4%), WHO (IFG 110-125 mg/dL), and IEC criteria (HbA1c 6.0-6.4%). Prevalence trends of prediabetes over time were evaluated using weighted Poisson regression and its association with prevalent cardiometabolic conditions with weighted logistic regression. The prevalence of prediabetes (either IFG or high HbA1c [ADA]) in Mexico was 20.9% in 2022. Despite an overall downward trend in prediabetes (RR 0.973, 95% CI 0.957-0.988), this was primarily driven by decreases in prediabetes by ADA-IFG (RR 0.898, 95% CI 0.880-0.917) and WHO-IFG criteria (RR 0.919, 95% CI 0.886-0.953), while prediabetes by ADA-HbA1c (RR 1.055, 95% CI 1.033-1.077) and IEC-HbA1C criteria (RR 1.085, 95% CI 1.045-1.126) increased over time. Prediabetes prevalence increased over time in adults >40 years, with central obesity, self-identified as indigenous or living in urban areas. For all definitions, prediabetes was associated with an increased risk of cardiometabolic conditions. Prediabetes rates in Mexico from 2016 to 2022 varied based on defining criteria but consistently increased for HbA1c-based definitions and high-risk subgroups. This research was supported by Instituto Nacional de Geriatría in Mexico. JAS was supported by NIH/NIDDK Grant# K23DK135798.


Validation of the Telephone Interview of Cognitive Status and Telephone Montreal Cognitive Assessment Against Detailed Cognitive Testing and Clinical Diagnosis of Mild Cognitive Impairment After Stroke.
Assessment of cognitive status poststroke is recommended by guidelines but follow-up can often not be done in person. The Telephone Interview of Cognitive Status (TICS) and the Telephone Montreal Cognitive Assessment (T-MoCA) are considered useful screening instruments. Yet, evidence to define optimal cut-offs for mild cognitive impairment (MCI) after stroke is limited. We studied 105 patients enrolled in the prospective DEDEMAS study (Determinants of Dementia After Stroke; NCT01334749). Follow-up visits at 6, 12, 36, and 60 months included comprehensive neuropsychological testing and the Clinical Dementia Rating scale, both of which served as reference standards. The original TICS and T-MoCA were obtained in 2 separate telephone interviews each separated from the personal visits by 1 week (1 before and 1 after the visit) with the order of interviews (TICS versus T-MoCA) alternating between subjects. Area under the receiver-operating characteristic curves was determined. Ninety-six patients completed both the face-to-face visits and the 2 interviews. Area under the receiver-operating characteristic curves ranged between 0.76 and 0.83 for TICS and between 0.73 and 0.94 for T-MoCA depending on MCI definition. For multidomain MCI defined by multiple-tests definition derived from comprehensive neuropsychological testing optimal sensitivities and specificities were achieved at cut-offs <36 (TICS) and <18 (T-MoCA). Validity was lower using single-test definition, and cut-offs were higher compared with multiple-test definitions. Using Clinical Dementia Rating as the reference, optimal cut-offs for MCI were <36 (TICS) and approximately 19 (T-MoCA). Both the TICS and T-MoCA are valid screening tools poststroke, particularly for multidomain MCI using multiple-test definition.


Implant-related fractures of the femur following hip fracture surgery.
Most hip fractures are treated surgically, with use of either internal fixation or prosthetic replacement of the femoral head. The presence of these implants increases the risk of a later femoral fracture in susceptible osteoporotic patients. The purpose of this study was to analyze the incidence of and risk factors for implant-related fractures of the femur after previous hip fracture surgery. Over a ten-year period from January 1988 to December 1997, 6230 patients (median age, eighty-two years; male:female ratio, 1247:4983) who sustained a total of 6696 hip fractures were admitted to the Edinburgh Orthopaedic Trauma Unit. Demographic information on the patients and details of the original treatment of the hip fracture were prospectively coded and entered into a trauma database. All subsequent readmissions due to a femoral fracture related to the implant were prospectively audited and extracted for the purposes of this study. One hundred and forty-one patients sustained an ipsilateral fracture of the femur at a median of twenty-four weeks following the original hip fracture surgery. Survivorship analysis of the hip fracture population revealed an overall rate of subsequent femoral fracture of 2.9% at five years, which increased to 5.1% at ten years. The median age and gender distribution of the patients who sustained a subsequent femoral fracture were similar to those of the hip fracture population as a whole. Two-thirds of the fractures propagated from the tip of the implant. Analysis of the subsequent fractures according to the type of implant used to treat the original fracture revealed considerable differences in incidence. The incidence was relatively high in the patients initially treated with a Gamma nail (18.74 fractures per 1000 person-years) or a cementless hemiarthroplasty (11.72 per 1000 person-years) and was relatively low in those treated with a compression hip screw (4.46 per 1000 person-years), cannulated screws (4.50 per 1000 person-years), or a primary arthroplasty with cement (6.2 per 1000 person-years). The highest incidence of fracture was seen in the patients who had required an arthroplasty with cement as a revision procedure following failure of a primary implant (22.39 per 1000 person-years). Implant-related fractures following hip fracture surgery are more common than has previously been appreciated. The risk of later ipsilateral femoral fracture is increased by the use of a Gamma nail or a cementless hemiarthroplasty to treat the original hip fracture.


Dynamic relations between mentalization techniques and therapeutic alliance in psychodynamic child therapy: An evidence-based case study.
Therapeutic alliance and mentalization are common factors inherent to all effective treatments. Mentalization-based interventions have the potential to create a safe relationship, which makes further mentalizing interventions possible. However, to date, no study has examined the bidirectional relationship between these variables in child psychotherapy. In an evidence-based case study design, psychodynamic therapy processes of two Turkish children (age: 9 and 10 years) who presented with social withdrawal problems were compared. All their sessions (34 sessions from Case No. 1 and 31 from Case No. 2) were coded using the Therapy Process Observational Coding System-Alliance Scale and Mentalization-Based Treatment for Children Adherence Scale. Outcome scales pertaining to symptoms, attachment, and mentalization were administered at baseline and at termination. Time-series Granger Causality tests revealed that in the case with clinically significant outcome, mentalization techniques predicted therapeutic alliance in the subsequent sessions, which predicted the use of further mentalization interventions. However, this relationship was not supported in the case with no significant improvement. Selected sessions were clinically analyzed with verbatim session vignettes. Our findings indicate that mentalization techniques in child therapy are closely related to the therapeutic relationship. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


Association of p53 polymorphisms with breast cancer: a case-control study in Slovak population.
Protein p53 is the tumor suppressor involved in cell cycle control and apoptosis. As a transcription factor p53 controls many cell processes and helps in prevention of cancer development. The p53 gene is polymorphic. Polymorphisms can affect the important regions involved in protein tumor suppressor activity. The well-known polymorphisms are the polymorphisms BstUI in exon 4 and MspI in intron 6. Both are supposed to be associated with cancer development. The purpose of this study was to investigate the genotype frequencies and associations of these polymorphisms with breast cancer in Slovak population. We observed the prevalence of BstUIPro (27.47%) and MspIA1 (17.58%) alleles and BstUIPro/Pro (8.79%) and MspIA1/A1 (5.49%) genotypes in breast cancer patients in comparison with controls 23.40%, 14.10%, 5.77%, 1.92% respectively. However the differences were not significant. After division of the cases and controls according to the age the prevalence of the risk alleles and genotypes in women at the age 50 years or less was higher as compared to women older than 50 years. In the younger women group, the p53 BstUI polymorphism genotype frequencies were 6.2% for BstUIPro/Pro, 31.0% for BstUIArg/Pro and 62.8% for BstUIArg/Arg in controls and 11.11 %, 40.74% and 48.15% in cases respectively. The risk of disease for BstUIPro/Pro genotype was more than two-fold higher in comparison with the BstUIArg/Arg (OR=2.34, 95% CI=0.53-10.24). In p53 MspI the genotype frequencies were 1.77% for MspIA1/A1, 24.78% for MspIA1/A2 and 73.45% for MspIA2/A2 in controls and 11.11%, 18.52% and 70.37% in cases respectively. The risk of disease for MspIA1/A1 genotype was more than six-fold higher in comparison with the MspIA2/A2 (OR=6.55, 95% CI=1.02-41.98). When we evaluated the association of both polymorphisms together with the breast cancer risk we observed that the highest risk was connected with the genotype BstUIPro/Pro / MspIA1/A1 (OR=2.99, 95% CI=0.69-13.06). Our results indicate that both BstUI and MspI p53 polymormphisms might play the role in the breast cancer development especially in women younger than 50 years.


Prediction of neuropeptide cleavage sites in insects.
The production of neuropeptides from their precursor proteins is the result of a complex series of enzymatic processing steps. Often, the annotation of new neuropeptide genes from sequence information outstrips biochemical assays and so bioinformatics tools can provide rapid information on the most likely peptides produced by a gene. Predicting the final bioactive neuropeptides from precursor proteins requires accurate algorithms to determine which locations in the protein are cleaved. Predictive models were trained on Apis mellifera and Drosophila melanogaster precursors using binary logistic regression, multi-layer perceptron and k-nearest neighbor models. The final predictive models included specific amino acids at locations relative to the cleavage sites. Correct classification rates ranged from 78 to 100% indicating that the models adequately predicted cleaved and non-cleaved positions across a wide range of neuropeptide families and insect species. The model trained on D.melanogaster data had better generalization properties than the model trained on A. mellifera for the data sets considered. The reliable and consistent performance of the models in the test data sets suggests that the bioinformatics strategies proposed here can accurately predict neuropeptides in insects with sequence information based on neuropeptides with biochemical and sequence information in well-studied species.