18 kDa Translocator Protein TSPO Is a Mediator of Astrocyte Reactivity.
An increase in astrocyte reactivity has been described in Alzheimer's disease and seems to be related to the presence of a pro-inflammatory environment. Reactive astrocytes show an increase in the density of the 18 kDa translocator protein (TSPO), but TSPO involvement in astrocyte functions remains poorly understood. The goal of this study was to better characterize the mechanisms leading to the increase in TSPO under inflammatory conditions and the associated consequences. For this purpose, the C6 astrocytic cell line was used in the presence of lipopolysaccharide (LPS) or TSPO overexpression mediated by the transfection of a plasmid encoding TSPO. The results show that nonlethal doses of LPS induced TSPO expression at mRNA and protein levels through a STAT3-dependent mechanism and increased the number of mitochondria per cell. LPS stimulated reactive oxygen species (ROS) production and decreased glucose consumption (quantified by the [18F]FDG uptake), and these effects were diminished by FEPPA, a TSPO antagonist. The transfection-mediated overexpression of TSPO induced ROS production, and this effect was blocked by FEPPA. In addition, a synergistic effect of overexpression of TSPO and LPS on ROS production was observed. These data show that the increase of TSPO in astrocytic cells is involved in the regulation of glucose metabolism and in the pro-inflammatory response. These data suggest that the overexpression of TSPO by astrocytes in Alzheimer's disease would have rather deleterious effects by promoting the pro-inflammatory response.


Perceived vulnerability and HIV testing among youth in Cape Town, South Africa.
The importance of perceived vulnerability to risk-reducing behaviors, including HIV testing, is fairly established, especially among youth in sub-Saharan Africa. Yet, the majority of studies that examined this important relationship used cross-sectional data that inherently assume that perceived vulnerability does not change. While these studies have been useful, the assumption of perceived vulnerability as time invariant is a major flaw and has largely limited the practical usefulness of this variable in AIDS prevention and programing. Using longitudinal data and applying random-effects logit models, this study makes a major contribution to scholarship by examining if changes in perceived vulnerability associate with a change to test for HIV among 857 young people in Cape Town, South Africa. Results show that female youth who changed their risk perceptions were more likely to also change to test for HIV, but the effects were completely attenuated after controlling for theoretically relevant variables. No significant relationships were observed for males. Also, females who were virgins at wave 2 but had sex between waves were significantly more likely to have changed to test for HIV. Of most importance was that sexual behavior eliminated the effects of change in risk perceptions suggesting that a change in perception may have occurred as a result of changes in sexual behavior. AIDS prevention programs must pay particular attention to helping youth become aware of their vulnerability to HIV risks, especially as these have implications for risk-reducing behaviors, especially for females who are burdened.


B-BOX DOMAIN PROTEIN28 Negatively Regulates Photomorphogenesis by Repressing the Activity of Transcription Factor HY5 and Undergoes COP1-Mediated Degradation.
Plants have evolved a delicate molecular system to fine-tune their growth and development in response to dynamically changing light environments. In this study, we found that BBX28, a B-box domain protein, negatively regulates photomorphogenic development in a dose-dependent manner in Arabidopsis thaliana BBX28 interferes with the binding of transcription factor HY5 to the promoters of its target genes through physical interactions, thereby repressing its activity and negatively affecting HY5-regulated gene expression. In darkness, BBX28 associates with CONSTITUTIVELY PHOTOMORPHOGENIC1 (COP1) and undergoes COP1-mediated degradation via the 26S proteasome system. Collectively, these results demonstrate that BBX28 acts as a key factor in the COP1-HY5 regulatory hub by maintaining proper HY5 activity to ensure normal photomorphogenic development in plants.


[Oncogenic mechanism of Helicobacter pylori].
On a global scale, gastric carcinoma is the second leading course of the cancer-related deaths. Recent studies have provided evidence that cagA-positive Helicobacter pylori plays a causal role for the development of gastric carcinoma. The cagA-encoded CagA protein is delivered into H. pylori-attached gastric epithelial cells via the bacterial type IV secretion system (TFSS). Delivered CagA undergoes tyrosine phosphorylation by Src family kinases at the conserved EPIYA motifs and then specifically binds and deregulates SHP-2 tyrosine phosphatase, a bona fide oncoprotein involved in human malignancies. As a result, CagA causes aberrant mitogenic signal as well as elevated cell motility in gastric epithelial cells. Also, CagA specifically interacts with and inhibits PAR1b/MARK2 polarity-regulating kinase to disrupt tight junctions and cause loss of epithelial apical-basolateral cell polarity. These CagA activities have been suspected to play an important role in gastric carcinogenesis. Indeed, recently generated cagA-transgenic mice expressing CagA systemically developed gastrointestinal carcinomas as well hematopoietic malignancies such as myeloid leukemia and B-cell lymphoma. The observations collectively indicate that H. pylori CagA is the first identified bacterial oncoprotein involved in gastric carcinogenesis.


Role of Glucagon-Like Peptide-1 (GLP-1) Receptor Agonists in Cardiovascular Risk Management in Patients With Type 2 Diabetes Mellitus: A Systematic Review.
People with type 2 diabetes mellitus have a greater risk of developing cardiovascular problems. Since cardiovascular diseases are a major cause of mortality all over the world, we need to find more efficient measures to control this risk in the diabetes population in addition to conventional glycemic control. In this systematic review, we aim to explore the latest findings on the cardiovascular effects of glucagon-like peptide-1 (GLP-1) agonists and dual GLP-1/glucose-dependent insulinotropic peptide (GIP) agonists in patients with type 2 diabetes mellitus. We conducted a comprehensive literature search using PubMed and Google Scholar as the main sources for data collection. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 recommendations for conducting this review. The outcomes of interest included mortality due to cardiovascular causes, non-fatal myocardial infarction, stroke, effects on cardiovascular risk factors, heart failure, and development of arrhythmias. After thorough literature screening and quality analysis, 14 articles were finally included for qualitative synthesis. GLP-1 receptor agonists appeared to be effective in reducing the risk of cardiovascular mortality, myocardial infarction, and stroke. They were found to reduce the risk of composite major adverse cardiovascular event (MACE) outcomes by 12-14% when compared to placebo. Their role in preventing heart failure and arrhythmias is uncertain, and further trials are needed to confirm the same. The cardiovascular outcomes of GLP-1/GIP dual agonists are currently under investigation. Studies completed to date show that they do not increase the risk of cardiovascular disease when compared to placebo.


Acute ethanol exposure in pregnancy alters the insulin-like growth factor axis of fetal and maternal sheep.
Maternal ethanol intake during pregnancy impairs fetal growth, but mechanisms are not clearly defined. Reduced IGF abundance or bioavailability in the fetus and/or mother may contribute to this growth restriction. We hypothesized that an episode of acute ethanol exposure, mimicking binge drinking would restrict fetal growth and perturb the maternal and fetal IGF axes. Pregnant sheep were infused intravenously with saline or ethanol (1 g/kg maternal wt) over 1 h, on days 116, 117, and 118 of gestation (start of 1st infusion = time 0, term is 147 days). Maternal and fetal plasma IGF and IGF-binding protein (IGFBP) concentrations were measured before and after each infusion. Compared with controls, ethanol exposure reduced fetal weight at day 120 by 19%, transiently reduced maternal plasma IGF-I (-35%) at 30 h, and decreased fetal plasma IGF-II (-28%) from 24 to 54 h after the first infusion. Ethanol exposure did not alter maternal or fetal plasma concentrations of IGFBP-2 and IGFBP-3, measured by Western ligand blotting. We conclude that suppression of maternal and fetal IGF abundance may contribute to fetal growth restriction induced by acute or binge ethanol exposure.


Predicted vitamin D status during pregnancy in relation to offspring forearm fractures in childhood: a study from the Danish National Birth Cohort.
In a prospective cohort study, the association between maternal vitamin D status during pregnancy and offspring forearm fractures during childhood and adolescence was analysed in 30 132 mother and child pairs recruited to the Danish National Birth Cohort between 1996 and 2002. Data on characteristics, dietary factors and lifestyle factors were collected on several occasions during pregnancy. We analysed the association between predicted vitamin D status, based on a subsample with 25-hydroxyvitamin D (25(OH)D) biomarker measurements (n 1497) from gestation week 25, and first-time forearm fractures among offspring between birth and end of follow-up. Diagnoses were extracted from the Danish National Patient Register. Multivariable Cox regression models using age as the underlying time scale indicated no overall association between predicted vitamin D status (based on smoking, season, dietary and supplementary vitamin D intake, tanning bed use and outdoor physical activity) in pregnancy and offspring forearm fractures. Likewise, measured 25(OH)D, tanning bed use and dietary vitamin D intake were not associated with offspring forearm fractures. In mid-pregnancy, 91 % of the women reported intake of vitamin D from dietary supplements. Offspring of women who took >10 µg/d in mid-pregnancy had a significantly increased risk for fractures compared with the reference level of zero intake (hazard ratios (HR) 1·31; 95% CI 1·06, 1·62), but this was solely among girls (HR 1·48; 95% CI 1·10, 2·00). Supplement use in the peri-conceptional period exhibited similar pattern, although not statistically significant. In conclusion, our data indicated no protective effect of maternal vitamin D status with respect to offspring forearm fractures.


Diffuse Hypermetabolic Bone Marrow Infiltration in Severe Primary Hyperoxaluria on FDG PET.
A 24-year-old man, with type 1 primary hyperoxaluria (diagnosed at age 20 years after repeated renal lithiasis, due to a I244T mutation frequently encountered in Mediterranean countries) complicated by end-stage renal failure requiring dialysis, was admitted for pancytopenia, refractory to erythropoietin injections. On clinical examination, he presented a hepatosplenomegaly without palpable adenopathy. F-FDG PET/CT revealed intense and diffuse bone marrow uptake in the axial skeleton and preferential long bone metaphyseal uptake. Bone marrow aspiration showed Gaucher-like cells infiltration due to oxalate accumulation in macrophages, leading to the diagnosis of bone marrow involvement by primary hyperoxaluria.


Effect of an ovulatory dose of luteinizing hormone on the concentration of oestrone, oestradiol and progesterone in the rabbit ovarian follicles.
This study was done to determine the effect of an ovulatory dose of LH on the concentration of oestrone, oestradiol and progesterone in the follicular tissue and in follicular fluid of ovaries of sexually mature female rabbits. Eight animals were sacrificed without treatment while others (4 to a group) were sacrificed at 1, 3, 4, 6, 8 and 10 h after administration of LH (50 mug). In each animal follicles from both ovaries were pooled and the follicular tissue was separated from the fluid. Determination of oestrone, oestradiol and progesterone was done by radioimmunoassay separately in the follicular tissue and in fluid. One hour after LH treatment oestrogen levels were found elevated, as compared to the control, in the fluid but not in the tissue. Thereafter oestrogen levels declined and reached levels much below control at times nearing ovulation. On the other hand, progesterone levels were elevated over the control in both the tissue and fluid at 1 and 3 h. The tissue progesterone levels were, however, below control at and after 6 h. The sustained high concentrations of tissue progesterone in the earlier period after LH stimulation could play a role in the chain of events leading to follicular rupture.


Microflora changes with the use of a vaginal microbicide.
The rate of HIV transmission is increasing more in women than in any other group. There is an urgent need for the development of microbicides with activity against this virus that women can use during intercourse. These products must be convenient, effective, and safe, and ideally they will cause minimal disruption in the normal vaginal ecosystem. The objective of this study was to evaluate changes in vaginal microflora, specifically Lactobacillus species, with the use of BufferGel. A prospective cohort study was performed to evaluate the change in vaginal flora before and after BufferGel use. BufferGel was applied vaginally once or twice daily for 14 days by low-risk abstinent and monogamous women. There was no change in frequency of Lactobacillus species after BufferGel use. However, there was a decrease in H2O2-producing lactobacilli (from 4.9 x 107 to 1.1 x 107 cfu; P = 0.001). The proportion of facultative gram-negative rods present increased from 27% to 65% after BufferGel use, whereas obligately anaerobic microbes decreased from 62% to 38%. Use of BufferGel once or twice daily for 14 days resulted in no clinically significant change in Lactobacillus colonization.


Wave communication across regular lattices.
We propose a novel way to communicate signals in the form of waves across a d-dimensional lattice. The mechanism is based on quantum search algorithms and makes it possible to both search for marked positions in a regular grid and to communicate between two (or more) points on the lattice. Remarkably, neither the sender nor the receiver needs to know the position of each other despite the fact that the signal is only exchanged between the contributing parties. This is an example of using wave interference as a resource by controlling localization phenomena effectively. Possible experimental realizations will be discussed.


An Unusual Case of Mucinous Adenocarcinoma of the Lung Presenting as Septic Emboli.
This is a case of a 92-year-old female with multiple hospitalizations for dyspnea on exertion and hypoxemia. Her symptoms were initially thought to be secondary to pneumonia, and on subsequent admission, culture-negative endocarditis. A computed tomography (CT) of the chest was remarkable for numerous bilateral lung nodules of varying size, some of which had a cavitary appearance raising concern for septic emboli. While a transthoracic echo was unremarkable, a transesophageal echo found a small 3 mm echodensity at the tip of the right coronary leaflet of the aortic valve and a possible mobile echodensity on the tricuspid valve leaflet. These findings further supported a clinical diagnosis of endocarditis with septic emboli in the lungs. Initial bronchoscopy yielded an unremarkable biopsy and a bronchial alveolar lavage with the growth of Actinomyces odontolyticus. During a subsequent hospitalization, a repeat bronchoscopy with transbronchial biopsy revealed a final diagnosis of invasive pulmonary mucinous adenocarcinoma. This case highlights a unique presentation of mucinous adenocarcinoma of the lung initially masquerading as septic emboli, resulting in a delay in the final diagnosis.


Prospective controlled randomized trial of prophylactic antiarrhythmic therapy in postmyocardial infarction patients with asymptomatic ventricular arrhythmias--study design and initial results.
In order to assess the effect of prophylactic antiarrhythmic therapy in asymptomatic patients with persistent complex ventricular ectopic activity after myocardial infarction, a prospective controlled trial was started in 1981 and is still ongoing. Until August 1986, 965 consecutive patients less than or equal to 70 hospitalized for acute myocardial infarction were screened without antiarrhythmic drugs by 24-h ECG before discharge from the hospital. In this group, 238 patients (28%) had ventricular arrhythmias Lown class III-IVb during at least 2 of 24 hours; they were randomly assigned to three treatment groups: (1) individualized antiarrhythmic therapy based on efficacy in multiple 24-h ECGs and drug level determinations (starting with mexiletine or quinidine; n = 79), (2) treatment with low-dose amiodarone (200-400 mg/day after a loading phase; n = 73), and (3) no antiarrhythmic therapy (n = 86). The three groups were comparable regarding age, gender, previous infarction, Q-wave infarction, ejection fraction, as well as incidence and severity of ventricular ectopic activity. Follow-up, including 24-h ECGs, was performed after 3, 6, and 12 months. Based on the results of this study which will be completed by the end of June 1988, it should be possible to estimate the benefit--or harm--of antiarrhythmic drug therapy as well as its cost in postmyocardial infarction patients with asymptomatic ventricular ectopic activity and to decide whether such treatment may improve survival.


Characteristics of the amino acid transport system in the mucosal border of rabbit ileum.
The specificity of the neutral amino acid transport system in the brush border was examined by studying the ability of amino acid analogues to inhibit the unidirectional influx of phenylalanine from mucosal solution into the cells. Effects were evaluated in terms of the affinity of various substrates for the amino acid site in the transport system. The affinity of amino acids for the site was proportional to the number of carbon atoms in the side chain. Electron-withdrawing substituents in the ring of phenylalanine increased affinity and electron-releasing groups decreased affinity. Removal of the alpha-amino group from phenylalanine decreased affinity by a factor of approximately 50 and removal of the carboxyl group decreased affinity 12-fold. Effects on affinity of variations in the side chain of the amino acid can be comparable in magnitude to that of the carboxyl group. The effect of sodium ion on the transport system appears to be similar for all compounds tested.


Head-to-head comparison of fundamental, tissue harmonic and contrast harmonic imaging with or without an air-filled contrast agent, levovist, for endocardial border delineation in patients with poor quality images.
Recent developments in tissue harmonic imaging and intravenous contrast agents have enhanced left ventricular endocardial border delineation (EBD). In a total of 48 patients with poor quality images, apical 4- and 2-chamber views were obtained with fundamental, tissue harmonic and contrast harmonic imaging with or without intravenous Levovist, an air-filled contrast agent. The left ventricle (LV) was divided into 12 segments, and the EBD of each segment was scored: (1) not visible, (2) barely visible, (3) well delineated. The EBD index (EBDI), defined as the sum of the endocardial scores divided by 12 was obtained for each patient. Of a total of 576 LV segments, 231 were scored as 1 by fundamental imaging and that number decreased to 125 segments by tissue harmonic imaging and 116 segments by fundamental imaging with Levovist. The number of segments scored as 1 decreased to 38 segments by tissue harmonic imaging with Levovist, and to 29 segments by contrast harmonic imaging with Levovist. The EBDI by fundamental imaging was 1.85+/-0.29, which improved significantly with the addition of Levovist (2.10+/-0.36, p<0.001) and was nearly identical to that by tissue harmonic imaging (2.15+/-0.32, p=NS). Tissue and contrast harmonic imaging with Levovist further enhanced the EBDI (2.43+/-0.26, 2.51+/-0.27, respectively). Levovist enhances EBD, even in the fundamental mode, to the level obtained with tissue harmonic imaging. Tissue harmonic and contrast harmonic imaging are the best modalities for enhancing EBD after Levovist injection.


Impact of parental anxiety on child emotional adjustment when a parent has cancer.
To describe the relationships among parent anxiety, child anxiety, and emotional adjustment in children who have a parent with cancer. Correlational. A large cancer center in the southeastern United States. Thirty-three child/parent with cancer dyads. Research packets were mailed to child/parent dyads who agreed to participate in the study. Parents completed a demographic questionnaire, a Spielberger State-Trait Anxiety Scale, and a Personality Inventory for Children (PIC). Children completed the child version of the Spielberger State-Trait Anxiety Scale. Parent anxiety, child anxiety, and child adjustment. Children who have a parent with cancer and parents who have experienced cancer report significantly higher state and trait anxiety compared to a normed population sample. Parental reports on the PIC indicated that latency-aged children (i.e., 6-12 years) showed significantly greater internalization and somatic symptoms compared to the sample norm. Parent state anxiety was negatively correlated with children's internalization and somatic symptoms. Parental anxiety accounted for the greatest variance in child adjustment. These study findings may provide nurses with a better understanding of the vulnerability of children who have a parent with cancer and can build a foundation for the development of supportive interventions for these children.


Novel anti-GARP antibody DS-1055a augments anti-tumor immunity by depleting highly suppressive GARP+ regulatory T cells.
Regulatory T (Treg) cells, which are essential for maintaining self-tolerance, inhibit anti-tumor immunity, consequently hindering protective cancer immunosurveillance, and hampering effective anti-tumor immune responses in tumor-bearing hosts. Here, we show that depletion of Treg cells via targeting glycoprotein A repetitions predominant (GARP) induces effective anti-tumor immune responses. GARP was specifically expressed by highly suppressive Treg cells in the tumor microenvironment (TME) of multiple cancer types in humans. In the periphery, GARP was selectively induced in Treg cells, but not in effector T cells, by polyclonal stimulation. DS-1055a, a novel afucosylated anti-human GARP monoclonal antibody, efficiently depleted GARP+ Treg cells, leading to the activation of effector T cells. Moreover, DS-1055a decreased FoxP3+CD4+ T cells in the TME and exhibited remarkable anti-tumor activity in humanized mice bearing HT-29 tumors. We propose that DS-1055a is a new Treg-cell-targeted cancer immunotherapy agent with augmentation of anti-tumor immunity.


Effect of Circadian Clock and Light-Dark Cycles in Onchidium reevesii: Possible Implications for Long-Term Memory.
The sea slug Onchidium reevesii inhabits the intertidal zone, which is characterized by a changeable environment. Although the circadian modulation of long-term memory (LTM) is well documented, the interaction of the circadian clock with light-dark masking in LTM of intertidal animals is not well understood. We characterized the LTM of Onchidium and tested the expression levels of related genes under a light-dark (LD) cycle and constant darkness (i.e., dark-dark, or DD) cycle. Results indicated that both learning behavior and LTM show differences between circadian time (CT) 10 and zeitgeber time (ZT) 10. In LD, the cry1 gene expressed irregularly, and per2 expression displayed a daily pattern and a peak expression level at ZT 18. OnCREB1 (only in LD conditions) and per2 transcripts cycled in phase with each other. In DD, the cry1 gene had its peak expression at CT 10, and per2 expressed its peak level at CT 18. OnCREB1 had two peak expression levels at ZT 10 or ZT 18 which correspond to the time node of peaks in cry1 and per2, respectively. The obtained results provide an LTM pattern that is different from other model species of the intertidal zone. We conclude that the daily transcriptional oscillations of Onchidium for LTM were affected by circadian rhythms and LD cycle masking.


The premenstrual syndrome: a review of the present status of therapy.
Treatment of the premenstrual syndrome is complicated by many factors, but principally by its unknown aetiology. In addition, diagnosis, definition and symptom evaluation methods are unclear. The multitudinous studies of treatment regimens have been largely inconclusive; this is partly due to difficulties in numerically evaluating the symptoms, but more to the lack of appreciation of the marked placebo effect which has been estimated as being up to 50%. The majority of studies have been open studies, and therefore interpretation of the results have been almost impossible. The end result is that great claims have been made for a large number of therapeutic agents on ill-founded evidence. Some of the drugs used in the treatment of the premenstrual syndrome, however, have been better evaluated than others, although even with those studied more extensively results have often been variable. Thus, hormonal agents such as progestagens and oral contraceptives, diuretics, pyridoxine, bromocriptine and danazol have been effective in some studies but not universally so. The latter 2 agents seem to be effective in relieving breast symptoms, but have only a limited effect on other symptoms. It is therefore important to realise that one drug does not cure all patients or all symptoms, although it is often claimed that this is the case. It has been suggested that more than 40% of women suffer from premenstrual syndrome. Greater awareness of the problem, both by patients and doctors, necessitates a more rational approach to therapy.


[Diagnosis and surgical treatment of solid-pseudopapillary tumor of the pancreas].
To study the diagnosis and treatment of solid-pseudopapillary tumor of the pancreas (SPTP). The clinical course, surgical treatment, and pathological findings of 13 patients with SPTP were analyzed. SPTP has no specific clinical symptoms. The patients mostly have abdominal pain and space occupying symptoms. Laboratory investigations of some patients showed decreased pancreatic exocrine function and elevated CA242 of tumor markers. Ultrasonography and CT revealed large solid cystic tumor of pancreas. Digital subtraction angiography (DSA) showed lacked-blood-supply space occupying lesion. All tumors were resected successfully. The histological findings showed a large encapsulated tumor and the section of tumor surrounded by hemorrhagic and necrotic areas. The solid areas are composed of small and medium size tumor cells, which had no obvious atypia. Psudopapillary structures were found in the cystic degeneration areas. Immunohistochemically, most of the tumors were positive for alpha-antitrypsin (alpha-AT) and vimentin and negative for chromogrannin. No patients recurrence during the follow-up. Most of SPTP can be removed successfully after diagnosis. The tumor and local infiltration tissue should be removed completely, and the long-term prognosis of SPTP is good.


Effective equilibrium picture in the xy model with exponentially correlated noise.
We study the effect of exponentially correlated noise on the xy model in the limit of small correlation time, discussing the order-disorder transition in the mean field and the topological transition in two dimensions. We map the steady states of the nonequilibrium dynamics into an effective equilibrium theory. In the mean field, the critical temperature increases with the noise correlation time τ, indicating that memory effects promote ordering. This finding is confirmed by numerical simulations. The topological transition temperature in two dimensions remains untouched. However, finite-size effects induce a crossover in the vortices proliferation that is confirmed by numerical simulations.


Trust, but verify. The errors and misinterpretations in the Cochrane analysis by O. J. Storebo and colleagues on the efficacy and safety of methylphenidate for the treatment of children and adolescents with ADHD.
A recent Cochrane review published by O. J. Storebo and colleagues (2015) raised substantial doubts about the benefit from stimulant medication with methylphenidate in the treatment of childhood ADHD due to the overall poor quality of studies. The systematic review thus contradicts all previous reviews and meta-analyses. We here detail various examples of errors, inconsistencies, and misinterpretations in the review which led to false results and inadequate conclusions. We demonstrate that the study selection is flawed and undertaken without sufficient scientific justification resulting in an underestimation of effect sizes, which, furthermore, are inadmissibly clinically interpreted. The methodology of the assessment of bias and quality is not objective and cannot be substantiated by the data. Cochrane reviews lay claim to a high scientific quality and substantial relevance for evidence-based clinical decisions. The systematic review by Storebo and colleagues (2015) illustrates that, despite adhering to strict standards and high-quality protocols, even Cochrane works should be critically read and verified, sometimes with surprising results.


Facilitating Weight Shifting During Treadmill Training Improves Walking Function in Humans With Spinal Cord Injury: A Randomized Controlled Pilot Study.
The aim of the study was to determine whether the integration of dynamic weight shifting into treadmill training would improve the efficacy of treadmill training in humans with spinal cord injury. Sixteen humans with spinal cord injury were randomly assigned to receive robotic or treadmill-only training and underwent 6 wks of training. A force was applied to the pelvis for facilitating weight shifting and to the legs for assisting with leg swing for participants in the robotic group. No assistance force was applied for participants in the treadmill-only group. Outcome measures consisted of overground walking speed, 6-min walking distance, and other clinical measures and were assessed before, after 6 wks of training, and 8 wks after the end of training. A greater improvement in 6-min walking distance was observed after robotic training than that after treadmill-only training (P = 0.03), but there was not a significant difference between the two groups in improvements in walking speed. However, a greater improvement was observed for the participants who underwent robotic training than those who underwent treadmill-only training (i.e., 15% vs. 2%). Applying a pelvis assistance force for facilitating weight shifting during treadmill training may improve locomotor function in humans with spinal cord injury.


Potential Expanded Indications for Neprilysin Inhibitors.
The goal of this article is to review potential expanded indications for neprilysin inhibitors. This article reviews the rationale and design for ongoing and future trials of sacubitril/valsartan in cardiovascular and non-cardiovascular disease. Randomized trial data are lacking for use of sacubitril/valsartan in acute heart failure and advanced heart failure. Mechanistic data from animal studies suggest a role for neprilysin inhibition in the treatment of post-myocardial infarction systolic dysfunction and heart failure with preserved ejection fraction. Beyond the cardiovascular system, renal and neurological function may be impacted by neprilysin inhibition. Forthcoming randomized trials will address the clinical impact of sacubitril/valsartan on these conditions. Neprilysin inhibition with sacubitril/valsartan offers a new therapeutic strategy with a broad range of potential therapeutic actions. In PARADIGM-HF, the combination of neprilysin and RAAS inhibition was proven to be superior to enalapril for patients with stable NYHA class II-III heart failure and reduced left ventricular ejection fraction. Preliminary data suggests it may also have a role in other cardiovascular and non-cardiovascular disease. Several ongoing and planned studies will determine the extent of its benefit for these other indications.


Bending 30-gauge needles using a needle guide: fatigue life evaluation.
Dentists bend needles prior to certain injections; however, there are concerns regarding needle fracture, lumen occlusion, and sharps handling. A previous study found that a 30-gauge needle fractures after four to nine 90° bends. This fatigue life study evaluated how many 90° bends a 30-gauge dental needle will sustain before fracture when bent using a needle guide. Two operators at Element Materials Technology, an independent testing, inspection, and certification company tested 48 30-gauge needles. After applying the needle guide, the operators bent the needle to a 90° angle and expressed the anesthetic from the tip. The needle was then bent back to a 0° angle, and the functionality was tested again. This process was repeated until the anesthetic failed to pass through the end of the needle due to fracture or obstruction. Each operator tested 24 needles (12 needles from each lot), and the number of sustained bends before the needle fracture was recorded. The average number of sustained bends before needle failure was 40.33 (95% confidence interval = 37.41-43.26), with a minimum of 20, median of 40, and a maximum of 54. In each trial, the lumen remained patent until the needle fractured. The difference between the operators was statistically significant (P < 0.001). No significant differences in performance between needle lots were observed (P = 0.504). Our results suggest that using a needle guide increases the number of sustained bends before needle fracture (P < 0.000001) than those reported in previous studies. Future studies should further evaluate the use of needle guides with other needle types across a variety of operators. Furthermore, additional opportunities lie in exploring workplace safety considerations and clinical applications of anesthetic delivery using a bent needle.


Copper(II) hypophosphite: the alpha- and beta-forms at 270 and 100 K, and the gamma-form at 270 K.
Copper(II) hypophosphite has been shown to exist as several polymorphs. The crystal structures of monoclinic alpha-, orthorhombic beta- and orthorhombic gamma-Cu(H(2)PO(2))(2) have been determined at different temperatures. The geometry of the hypophosphite anion in all three polymorphs is very close to the idealized one, with point symmetry mm2. Despite having different space groups, the structures of the alpha- and beta-polymorphs are very similar. The polymeric layers formed by the Cu atoms and the hypophosphite ions, which are identical in the alpha- and beta-polymorphs, stack in the third dimension in different ways. Each hypophosphite anion is coordinated to three Cu atoms. On cooling, a minimum amount of contraction was observed in the direction normal to the layers. The structure of the polymeric layers in the gamma-polymorph is quite different. There are two symmetry-independent hypophosphite anions; the first is coordinated to two Cu atoms, while the second is coordinated to four Cu atoms. In all three polymorphs, the Cu atoms are coordinated by six O atoms of six hypophosphite anions, forming tetragonal bipyramids; in the alpha- and beta-polymorphs, there are four short and two long Cu-O distances, while in the gamma-polymorph, there are four long and two short Cu-O distances.


Neuro- and hepato-toxicity of polystyrene nanoplastics and polybrominated diphenyl ethers on early life stages of zebrafish.
Nanoplastics (NPs) are good carriers of persistent organic pollutants (POPs) such as polybrominated diphenyl ethers (PBDEs) and can modify their bioavailability and toxicity to aquatic organisms. This study highlights the single and combined toxic effects of polystyrene nanoplastics (PS-NPs) and 2,2 ',4,4 '-tetrabromodiphenyl ether (BDE-47, one of the major PBDE congeners) on zebrafish embryos after an exposure of up to 120 hpf. Our results showed that PS-NPs and BDE-47 formed larger particle aggregates during co-exposure, which attached to the surface of the yolk membrane and even changed its structure, and these particles also bioaccumulated in the intestine of zebrafish larvae, compared with the PS-NPs single exposure. Further, the co-exposure significantly increased mortality, accelerated voluntary movements, enhanced hatching rate, and decreased heart rate. Hepatoxicity analyses revealed that the mixture exposure induced a darker/browner liver colour, atrophied liver and greater hepatotoxicity in zebrafish larvae. In addition to increased ROS accumulation, the reduced expression of the antioxidant gpx1a gene and increased expression of cyp1a1 were found after co-treatment. Moreover, ache and chrn7α genes associated with neurocentral development, were significantly downregulated, mainly in the co-exposure group. In conclusion, simultaneous exposure to PS-NPs and BDE-47 exacerbated oxidative stress, developmental impacts, hepatotoxicity, and neurodevelopmental toxicity in zebrafish larvae. Therefore, neurotoxic effects of complex chemical interactions between PS-NPs and persistent organic pollutants in freshwater environments should be paid more attention.


Pediatric solid organ transplant recipients: transition to home and chronic illness care.
Pediatric SOT recipients are medically fragile and present with complex care issues requiring high-level management at home. Parents of hospitalized children have reported inadequate preparation for discharge, resulting in problems transitioning from hospital to home and independently self-managing their child's complex care needs. The aim of this study was to investigate factors associated with the transition from hospital to home and chronic illness care for parents of heart, kidney, liver, lung, or multivisceral recipients. Fifty-one parents from five pediatric transplant centers completed questionnaires on the day of hospital discharge and telephone interviews at three wk, three months, and six months following discharge from the hospital. Care coordination (p = 0.02) and quality of discharge teaching (p < 0.01) was significantly associated with parent readiness for discharge. Readiness for hospital discharge was subsequently significantly associated with post-discharge coping difficulty (p = 0.02) at three wk, adherence with medication administration (p = 0.03) at three months, and post-discharge coping difficulty (p = 0.04) and family management (p = 0.02) at six months post-discharge. The results underscore the important aspect of education and care coordination in preparing patients and families to successfully self-manage after hospital discharge. Assessing parental readiness for hospital discharge is another critical component for identifying risk of difficulties in managing post-discharge care.


Molecular cloning and functional expression of a cDNA encoding the human V1b vasopressin receptor.
Arginine vasopressin modulates the release of adrenocorticotropic hormone, beta-endorphin, and prolactin from the anterior pituitary. Release is mediated by the V1b receptor through the mobilization of intracellular Ca2+ by phosphatidylinositol hydrolysis. In contrast to its well characterized peripheral actions, such as antidiuresis, contraction of vascular smooth muscle, and stimulation of hepatic glycogenolysis, the exact site and mechanism of vasopressin action in the pituitary remain unclear. This is largely due to a lack of information on the molecular identity and exact localization of the V1b receptor. This lack prompted us to try to isolate this receptor subtype. Here we report the molecular cloning and functional expression of a complementary DNA encoding the human V1b receptor. The deduced 424-amino acid sequence of the receptor has highest overall homology with the V1a, V2, and oxytocin receptors, with homologies of 45, 39, and 45%, respectively. The receptor expressed in COS-1 cells has a single binding site for arginine vasopressin with a Kd of 0.17 +/- 0.04 nM. It binds various agonists and antagonists of vasopressin with affinities distinct from those of V1a and V2 receptors but consistent with those anticipated for the V1b receptor on the basis of the pharmacological studies. Furthermore, arginine vasopressin evoked calcium-dependent chloride current in Xenopus oocytes transfected with the receptor, which was not affected by a V1a/V2 antagonist. In contrast, the current evoked in oocytes transfected with V1a receptor was abolished by the antagonist. Northern blot analysis revealed that the receptor expression is restricted to the pituitary. These data clearly indicate that the cloned cDNA encodes the V1b receptor.


Skeletonized versus pedicled internal thoracic artery and risk of sternal wound infection after coronary bypass surgery: meta-analysis and meta-regression of 4817 patients.
It is suggested that the internal thoracic artery (ITA) harvesting technique influences the incidence of sternal wound infection (SWI) after coronary artery bypass graft (CABG). To determine if there is any real difference between skeletonized vs pedicled ITA, we performed a meta-analysis to determine if there is any real difference between these two established techniques in terms of SWI. We performed a systematic review using MEDLINE, EMBASE, CENTRAL/CCTR, SciELO, LILACS, Google Scholar and reference lists of relevant articles to search for studies that compared the incidence of SWI after CABG between skeletonized vs pedicled ITA until June 2012. The principal summary measures were odds ratio (OR) with 95% confidence interval (CI) and P values (statistically significant when <0.05). The ORs were combined across studies using the weighted DerSimonian-Laird random effects model and weighted Mantel-Haenszel fixed effects. Meta-analysis, sensitivity analysis and meta-regression were completed using the software Comprehensive Meta-Analysis version 2 (Biostat, Inc., Englewood, NJ, USA). Twenty-two studies involving 4817 patients (2424 skeletonized; 2393 pedicled) met the eligibility criteria. There was no evidence for important heterogeneity of effects among the studies. The overall OR (95% CI) of SWI showed a statistically significant difference in favour of skeletonized ITA (fixed effect model: OR 0.443, 95% CI 0.323-0.608, P < 0.001; random effect model: OR 0.443, 95% CI 0.323-0.608, P < 0.001). In the sensitivity analysis, the difference in favour of skeletonized ITA was also observed in subgroups such as diabetic, bilateral ITA and diabetic with bilateral ITA; we also observed that there was a difference in the type of study, since non-randomized studies together demonstrated the benefit of skeletonized ITA in comparison with pedicled ITA, but the randomized studies together did not show this difference (although close to statistical significance and with the tendency to favour the skeletonized group). In meta-regression, we observed a statistically significant coefficient for SWI and proportion of diabetic patients (coefficient -0.02, 95% CI -0.03 to -0.01, P = 0.016). In conclusion, skeletonized ITA appears to reduce the incidence of postoperative SWI in comparison with pedicled ITA after CABG, with this effect being modulated by the presence of diabetes.


Smaller inner ear sensory epithelia in Neurog 1 null mice are related to earlier hair cell cycle exit.
We investigated whether co-expression of Neurog 1 and Atoh 1 in common neurosensory precursors could explain the loss of hair cells in Neurog 1 null mice. Analysis of terminal mitosis, using BrdU, supports previous findings regarding timing of exit from cell cycle. Specifically, we show that cell cycle exit occurs in spiral sensory neurons in a base-to-apex progression followed by cell cycle exit of hair cells in the organ of Corti in an apex-to-base progression, with some overlap of cell cycle exit in the apex for both hair cells and spiral sensory neurons. Hair cells in Neurog 1 null mice show cell cycle exit in an apex-to-base progression about 1-2 days earlier. Atoh 1 is expressed in an apex-to-base progression rather then a base-to-apex progression as in wildtype littermates. We tested the possible expression of Atoh1 in neurosensory precursors using two Atoh 1-Cre lines. We show Atoh 1-Cre mediated beta-galactosidase expression in delaminating sensory neuron precursors as well as undifferentiated epithelial cells at E11 and E12.5. PCR analysis shows expression of Atoh 1 in the otocyst as early as E10.5, prior to any histology-based detection techniques. Combined, these data suggest that low levels of Atoh 1 exist much earlier in precursors of hair cells and sensory neurons, possibly including neurosensory precursors. Analysis of Atoh 1-Cre expression in E18.5 embryos and P31 mice reveal beta-galactosidase stain in all hair cells but also in vestibular and cochlear sensory neurons and some supporting cells. A similar expression of Atoh 1-LacZ exists in postnatal and adult vestibular and cochlear sensory neurons, and Atoh 1 expression in vestibular sensory neurons is confirmed with RT-PCR. We propose that the absence of NEUROG 1 protein leads to loss of sensory neuron formation through a phenotypic switch of cycling neurosensory precursors from sensory neuron to hair cell fate. Neurog 1 null mice show a truncation of clonal expansion of hair cell precursors through temporally altered terminal mitosis, thereby resulting in smaller sensory epithelia.


Rebutting Existing Misconceptions About Multiple Imputation as a Method for Handling Missing Data.
Missing data is a problem that occurs frequently in many scientific areas. The most sophisticated method for dealing with this problem is multiple imputation. Contrary to other methods, like listwise deletion, this method does not throw away information, and partly repairs the problem of systematic dropout. Although from a theoretical point of view multiple imputation is considered to be the optimal method, many applied researchers are reluctant to use it because of persistent misconceptions about this method. Instead of providing an(other) overview of missing data methods, or extensively explaining how multiple imputation works, this article aims specifically at rebutting these misconceptions, and provides applied researchers with practical arguments supporting them in the use of multiple imputation.


Separate domains of the insulin receptor contain sites of autophosphorylation and tyrosine kinase activity.
We have studied the structure and function of the solubilized insulin receptor before and after partial proteolytic digestion to define domains in the beta-subunit that undergo autophosphorylation and contain the tyrosine kinase activity. Wheat germ agglutinin purified insulin receptor from Fao cells was digested briefly at 22 degrees C with low concentrations (5-10 micrograms/mL, pH 7.4) of trypsin, staphylococcal V8 protease, or elastase. Autophosphorylation of the beta-subunit was carried out before and after digestion, and the [32P]phosphoproteins were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, detected by autoradiography, and analyzed by tryptic peptide mapping by use of reverse-phase high-performance liquid chromatography. Mild trypsin digestion reduced the apparent molecular mass of the beta-subunit from 95 to 85 kDa, and then to 70 kDa. The 85-kDa fragment was not immunoprecipitated by an antibody directed against the C-terminal domain of the beta-subunit (alpha Pep-1), indicating that this region of the receptor was lost. The 85-kDa fragment contained about half of the [32P]phosphate originally found in the beta-subunit, and tryptic peptide mapping showed that two major tryptic phosphopeptides (previously called pY2 and pY3) were removed. Three other tryptic phosphopeptides (pY1, pY1a, and pY4) were found in the 85- and 70-kDa fragments. Treatment of the intact receptor with staphylococcal V8 protease also converted the beta-subunit to an 85-kDa fragment that did not bind to alpha Pep-1, contained about 50% of the initial radioactivity, and lacked pY2 and pY3. Elastase rapidly degraded the receptor to inactive fragments between 37 and 50 kDa.(ABSTRACT TRUNCATED AT 250 WORDS)


Cruciferous indole-3-carbinol inhibits apolipoprotein B secretion in HepG2 cells.
The cardioprotective effect of consuming cruciferous vegetables may be attributed to a number of unique indole-based compounds. We investigated the potential role and mechanism of action of an indole-based compound, indole-3-carbinol (I-3-C), on apolipoprotein B-100 (apoB) production using HepG2 cells. I-3-C reduced apoB secretion into the media dose dependently by 56% at 100 micromol/L. Relative to the untreated control cells, no change in the density of the secreted lipoproteins was noted. Significant decreases in cellular lipid synthesis, including triglycerides (TG) and cholesterol esters (CE), were observed in cells treated with I-3-C, indicating that limited lipid availability is a major factor in the regulation of apoB secretion. The decrease in TG synthesis was associated with significantly decreased diacylglycerol acyltransferase-1 and -2 activity and reduced fatty acid synthase (FASN) gene expression. The decreased CE synthesis was associated with significantly decreased acyl CoA:cholesterol acyltransferase gene expression and activity. The effect on FASN was shown to be mediated by sterol regulatory element binding protein-1, an important transcription factor involved in fatty acid synthesis. Further investigative work revealed that LDL uptake and fatty acid oxidation were not involved in the I-3-C-mediated reduction of apoB secretion. The results indicate that plant indoles have beneficial effects on lipid synthesis that could contribute to their potential cardioprotective effect.


How I treat hematologic emergencies in adults with acute leukemia.
Acute myeloid leukemia and acute lymphoblastic leukemia remain devastating diseases. Only approximately 40% of younger and 10% of older adults are long-term survivors. Although curing the leukemia is always the most formidable challenge, complications from the disease itself and its treatment are associated with significant morbidity and mortality. Such complications, discussed herein, include tumor lysis, hyperleukocytosis, cytarabine-induced cellebellar toxicity, acute promyelocytic leukemia differentiation syndrome, thrombohemorrhagic syndrome in acute promyelocytic leukemia, L-asparaginase-associated thrombosis, leukemic meningitis, neutropenic fever, neutropenic enterocolitis, and transfussion-associated GVHD. Whereas clinical trials form the backbone for the management of acute leukemia, emergent clinical situations, predictable or not, are common and do not readily lend themselves to clinical trial evaluation. Furthermore, practice guidelines are often lacking. Not only are prospective trials impractical because of the emergent nature of the issue at hand, but clinicians are often reluctant to randomize such patients. Extensive practical experience is crucial and, even if there is no consensus, management of such emergencies should be guided by an understanding of the underlying pathophysiologic mechanisms.


Unusual technical procedures in reconstructive urological surgery.
Three successful technical procedures for the correction of complex defects of the urinary excretory pathway and the renal vessels are described. The authors emphasize their original technique which allowed kidney preservation and yielded good long-term results. They suggest that this conservative approach be used in more patients to avoid unnecessary nephrectomies.


Constrictive epicarditis: turtle cage or waffle operation?
A 72-year-old man, presenting with signs of pericarditis, was found at operation to have constrictive epicarditis. Operation consisted of pericardiectomy and creation of multiple longitudinal and transverse incisions of the epicardium.


Differences in hydration coupled to specific and nonspecific competitive binding and to specific DNA Binding of the restriction endonuclease BamHI.
Using the osmotic stress technique together with a self-cleavage assay we measure directly differences in sequestered water between specific and nonspecific DNA-BamHI complexes as well as the numbers of water molecules released coupled to specific complex formation. The difference between specific and nonspecific binding free energy of the BamHI scales linearly with solute osmolal concentration for seven neutral solutes used to set water activity. The observed osmotic dependence indicates that the nonspecific DNA-BamHI complex sequesters some 120-150 more water molecules than the specific complex. The weak sensitivity of the difference in number of waters to the solute identity suggests that these waters are sterically inaccessible to solutes. This result is in close agreement with differences in the structures determined by x-ray crystallography. We demonstrate additionally that when the same solutes that were used in competition experiments are used to probe changes accompanying the binding of free BamHI to its specific DNA sequence, the measured number of water molecules released in the binding process is strikingly solute-dependent (with up to 10-fold difference between solutes). This result is expected for reactions resulting in a large change in a surface exposed area.


Comparison of Engineered Liver 3D Models and the Role of Oxygenation for Patient-Derived Tumor Cells and Immortalized Cell Lines Cocultured with Tumor Stroma in the Detection of Hepatotoxins.
In metabolically active tumors, responses of cells to drugs are heavily influenced by oxygen availability via the surrounding vasculature alongside the extracellular matrix signaling. The objective of this study is to investigate hepatotoxicity by replicating critical features of hepatocellular carcinoma (HCC). This includes replicating 3D structures, metabolic activities, and tumor-specific markers. The internal environment of spheroids comprised of cancerous human patient-derived hepatocytes using microparticles is modulated to enhance the oxygenation state and recreate cell-extracellular matrix interactions. Furthermore, the role of hepatic stellate cells in maintaining hepatocyte survival and function is explored and hepatocytes from two cellular sources (immortalized and patient-derived) to create four formulations with and without microparticles are utilized. To investigate drug-induced changes in metabolism and apoptosis in liver cells, coculture spheroids with and without microparticles are exposed to three hepatotoxic drugs. The use of microparticles increases levels of apoptotic markers in both liver models under drug treatments. This coincides with reduced levels of anti-apoptotic proteins and increased levels of pro-apoptotic proteins. Moreover, cells from different origins undergo apoptosis through distinct apoptotic pathways in response to identical drugs. This 3D microphysiological system offers a viable tool for liver cancer research to investigate mechanisms of apoptosis under different microenvironmental conditions.


Understanding anesthesia: making genetic sense of the absence of senses.
The discovery of the phenomenon of anesthesia over 150 years ago was a watershed event that revolutionized the practice of medicine. Despite their annual use in millions of patients, the mechanism by which volatile anesthetics produce reversible loss of consciousness remains a mystery. The inherent problems in studying loss of consciousness in humans are legion. However, multiple model organisms are currently being exploited to apply the powerful tools of modern molecular genetics to this question. Mutants in yeast, nematodes, fruit flies and mice have been produced that display abnormalities in their response to volatile anesthetics. Each organism possesses unique advantages and difficulties as a model system, and each reveals different molecules that control its response to anesthetics. Nonetheless, the accumulating body of genetic evidence points to multiple targets for volatile anesthetics. Not only will understanding how volatile anesthetics work yield better and safer anesthetics, but, in addition, these remarkable compounds may ultimately serve as probes to understand the nature of consciousness itself.


A Study on Sexual Dimorphism of Adult Wet Scaphoid Specimens.
Background Sexual dimorphism in human bones has mostly been confined to the study of the bony pelvis. However, considerable changes also exist in the other parts of the skeletal system. This study focuses on the differences in the morphometry of male and female adult scaphoids. Aims and objectives We aim to study the morphometry of male and female adult human scaphoids and determine the differences between the same. Materials and methods A total of 100 scaphoids were freshly dissected from both hands of 25 male and 25 female cadavers in Saveetha Medical College, Chennai, India. The soft tissues were loosened using 5% potassium hydroxide (KOH) solution. Further, the soft tissues were removed by meticulous dissection. For the measurements, vernier calipers and threads for circumference measurement were used. Results The morphometric parameters included length, proximal width, width of the middle part (waist), distal width and circumference of the waist, and circumference of the tubercle in scaphoids. Statistical differences were found in most of the parameters. Conclusion A statistically significant difference exists between the morphometric measurements of male and female adult scaphoids, which may prove helpful in the fracture fixation of the scaphoid, as scaphoid fracture has a risk of avascular necrosis.


Determination of meropenem by capillary electrophoresis using direct injection of serum.
Concentration determination of meropenem, a carbapenem antibiotic, using a capillary electrophoresis method by direct injection of serum samples without any pretreatment is described herein. Sodium tetraborate (25 mM)-sodium hydroxide (0.1 M) containing sodium dodecyl sulfate (90 mM) is used as a run buffer (pH 10.0). Meropenem is detected at its absorption maximum at 297 nm. Migration time of meropenem is approximately 7.2 min, and the detection limit of the assay is 2.0 mg/L at a signal-to-noise ratio of 3.0. The relative standard deviations of intra- and interassay accuracies are 3.43-8.87% and 4.28-8.54%, respectively, at a nominal concentration of 6.3-100.0 mg/L, and their recovery rates are 94-111% and 92-105%, respectively.


Emetine and/or its metabolites are genotoxic in somatic cells of Drosophila melanogaster.
Emetine is one of the two active ingredients of syrup of ipecac which is used medicinally as antiparasitic and emetic, however little is known about its genotoxic activity. The goal of this study was to determine whether and how emetine and/or its metabolites might produce mitotic recombination using the in vivo Drosophila w/w+ eye somatic assay. A standard strain (which expresses basal levels of cytochrome P450 enzymes) and an insecticide-resistant strain (which constitutively over-expresses P450 genes) were employed. The results showed that emetine and/or its metabolites are active in the assay and that the genotoxic potential is significantly influenced in the presence of higher than normal concentrations of P450.


Preparation of F-18 labeled annexin V: a potential PET radiopharmaceutical for imaging cell death.
The clinical response to antitumor therapy is measured using imaging, such as CT or MRI, 6-12 weeks following chemotherapy treatment. The images at that time reflect both tumor cell death and new growth. Therefore, the amount of tumor cell death caused by chemotherapy cannot be efficiently quantified with current imaging modalities. A quantitative measurement of tumor cell death immediately following chemotherapy is needed to help validate both new agents and to optimize administration of existing therapies. Annexin V is a 36kD protein that binds to exposed phosphatidylserine (PS) on dying cells. In order to synthesize a probe that can detect cell death in vivo, the positron emitter F-18 was conjugated to annexin V via the compound N- succinimidyl-4-[18F]fluorobenzoate, [18F]SFB. The decay corrected radiochemical yield of F-18 labeled annexin V from 18F fluoride was 17.6 +/- 5.6% (n = 4) in three hours. The stepwise radiochemical yield of the conjugation step with annexin V was as high as 70% when a protein concentration of 5 mg/ml was used. Cancer cells treated with the chemotherapeutic agent, etoposide, showed an 88% increase in the binding of F-18 labeled annexin V compared to untreated cells. We conclude that [18F] labeled annexin V can be readily prepared by the conjugation of annexin V with [18F]SFB and that the positron-emitting compound is biologically active in detecting apoptosis.


Shear moduli in bcc-fcc structure transition of colloidal crystals.
Shear moduli variation in the metastable-stable structure transition of charged colloidal crystals was investigated by the combination techniques of torsional resonance spectroscopy and reflection spectrometer. Modulus of the system increases with the proceeding of the transition process and it finally reaches the maximum value at the end of the transition. For colloidal crystals in stable state, the experimental moduli show good consistence with theoretical expectations. However, in the transition process, the moduli are much smaller than theoretical ones and this can be chalked up to crystalline imperfection in the transition state.


Binding of non-substrate nucleotides to a restriction endonuclease: a model for the interaction of bam HI with its recognition sequence.
The kinetic constants of the site-specific endonuclease Bam HI for various substrates were determined and binding of non-substrate nucleotides to the enzyme was studied. Agarose gel assays in combination with an integrated Michaelis-Menten equation were used for the evaluation of data. The turnover number was 2.2 min-1 at 37 degrees C with pJC80 DNA as the substrate. It depends on the conformation and base composition of the substrate. Michaelis constants also depend on substrate conformation. Non-substrate polynucleotides were found to inhibit Bam competitively with KI ranging from 10(-6) to > 10(-3) M depending on base composition, base pairing, and helix conformation. Dinucleotides showed sequence-specific, competitive inhibition with KIs ranging from 10(-5) to > 10(-3) M. Mononucleotides and -nucleosides acted noncompetitively. Binding was influenced by the extent of phosphorylation, but not by the nature of the base. KIs varied between 10(-3) and 10(-2) M. The results are discussed with respect to the recognition requirements of Bam HI.


[Acute cholangiocholecystitis].
In analysis of a group of 48 patients, the authors describe an entity they call acute cholangio-cholecystitis (or acute cholecystitis of choledochal origin) and define it by 4 obligatory criteria: 1. vesicular lesion of acute cholecystitis type; 2. the obstruction of the main bile duct in the direction of its junction with the cystic duct; 3. free duct communication between the gallbladder and the main bile ducts; 4. fluid content (purulent gallbladder) found identical over the whole biliary territory (the gallbladder the main bile ducts the intrahepatic bile ducts). This entity represents 7.6% of the total of acute cholecystitis and was met in 2.8% of the total of the interventions for the main bile ducts obstruction. The deficient biological background of the patients (60% over 60 years old), and other seriousness factors--vesicular destructive lesions associated with biliary peritonitis (7/48), the existence of the duct obstruction, usually calculous (42/48), but also hydatic (3/48) or tumoural (3/48), the multitude and seriousness of the associated lesions are emphasized. The surgery, performed in over 80% emergent cases, was directed to the decomprimation of the main biliary axis to which the increase of the gangrenous cholecyst, treatment of the duct obstructive factor, repair of the internal biliary fistulas, treatment of the consequent peritonitis were added. The results, very often good (71%), were shadowed by a series of complications (29%) which ended in deaths (14.5%). The paper pleads for the early surgery of the lithiasic biliary disease, before the appearance of the inevitable complications.


Characterization of intravitreally delivered capsid mutant AAV2-Cre vector to induce tissue-specific mutations in murine retinal ganglion cells.
Targeted expression of Cre recombinase in murine retinal ganglion cells (RGCs) by viral vector is an effective strategy for creating tissue-specific gene knockouts for investigation of genetic contribution to RGC degeneration associated with optic neuropathies. Here we characterize dosage, efficacy and toxicity for sufficient intravitreal delivery of a capsid mutant Adeno-associated virus 2 (AAV2) vector encoding Cre recombinase. Wild type and Rosa26 (R26) LacZ mice were intravitreally injected with capsid mutant AAV2 viral vectors. Murine eyes were harvested at intervals ranging from 2 weeks to 15 weeks post-injection and were assayed for viral transduction, transgene expression and RGC survival. 10(9) vector genomes (vg) were sufficient for effective in vivo targeting of murine ganglion cell layer (GCL) retinal neurons. Transgene expression was observed as early as 2 weeks post-injection of viral vectors and persisted to 11 weeks. Early expression of Cre had no significant effect on RGC survival, while significant RGC loss was detected beginning 5 weeks post-injection. Early expression of viral Cre recombinase was robust, well-tolerated and predominantly found in GCL neurons suggesting this strategy can be effective in short-term RGC-specific mutation studies in experimental glaucoma models such as optic nerve crush and transection experiments. RGC degeneration with Cre expression for more than 4 weeks suggests that Cre toxicity is a limiting factor for targeted mutation strategies in RGCs.


Impacts of inter- and intra- ethnic partnerships/relationships on traditional gift giving in a cohort of Pacific mothers.
Traditional gift-giving (TGG) is an important element of familial obligations among Pacific families. Migration from Pacific homelands to New Zealand and other countries has had an impact on participation in TGG., Many anecdotal accounts have suggested that TGG diminishes when Pacific persons marry outside their ethnic groups. While TGG is an indicator of social cohesion TGG can have direct influence on disposable income. The practice of TGG impacts on health as Income and social cohesion are key determinants of health. Thus TGG Health and social cohesion are closely interrelated and interdependent. The data for this paper is taken from a longitudinal cohort study of 1,398 Pacific children and their families in South Auckland, New Zealand. The study sought participants' responses to questions pertaining to the amounts gifted, the frequency of giving, recipients of the gifting and their reasons for participating and not participating in TGG. The assumption explored in this paper is that as Pacific peoples move outside their social sphere and become more acculturated with other ethnic groups, TGG was more likely to diminish rather than increase. This paper addresses the TGG participation rates among Pacific peoples in inter-ethnic relationships and intra-ethnic relationships. It argues that couples in an intra-ethnic intimate relationship are more likely to participate in traditional gift-giving than those who are in inter-ethnic intimate relationships. While this is true for most PI inter ethnic relationships the level of participation increases further with inter-ethnic intimate relationships among Tongans and Samoans who are also the largest participators of all ethnic groups in traditional gift-giving.


The effect of different recovery methods on blood lactate removal in wrestlers.
The first aim of this study was to compare the VO₂at lactate threshold (LT) and maximum rate of fat oxidation (Fat(max)) intensity in wrestlers. A secondary aim was to compare the different recovery trials in wrestlers for finding effective methods of lactate removal post-match. Eight wrestlers (mean ± SD; age, 23.2 ± 1 year; VO(2max), 55.2 ± 3.4 mL.min⁻¹.kg⁻¹) completed four recovery trials in a counter-balanced order. Maximal oxygen uptake (VO(2max)), Fat(max), individual anaerobic threshold (IAT), individual ventilatory threshold (IVT), and LT were determined during a graded exercise test. Different recovery methods were performed at a similar time of the day after three 2 min wrestling match. Lactate concentration was obtained at rest, and at 0, 5, 10, 15 and 20 min of post-match. In wrestler, Fat(max) was significantly correlated with LT (r=0.47, P<0.05) and lactate concentration (mean ± SD) significantly increased during the match from (1.7 ± 0.2 mmol.L⁻¹) to (15.1 ± 1.3 mmol.L⁻¹). At 5 minute, IVT method provides greater reduce in blood lactate (79% ∆La) and in other time point (10, 15 and 20 min) Fat(max) intensity provides more reduce. Fat(max) intensity is the most effective method for removal lactate concentration in wrestlers. There may be a relationship between improve in endurance capacity and training at the Fat(max) intensity.


Mortality and morbidity associated with legal abortions in Hungary, 1960-1973.
In Hungary, with 10 million inhabitants, the number of induced abortions in the 1960's first approached and then reached 200,000 cases annually. These data mean that the number of induced abortions has increased substantially compared with earlier decades. A qualitative change has also occurred, from criminal abortions to, in most cases, legally induced abortions performed in hospitals. On the basis of 32 deaths directly resulting from legal induced abortion in the first trimester during 1960-1972, maternal mortality is about 1.5 per 100,000 abortions in Hungary, the lowest rat observed until the present anywhere in the world. According to a special survey conducted in Budapest in 1966, the overall morbidity rate was 41.6 per 1,000 abortions of which 0.9 was due to perforations, 22.7 to post-abortal hemorrhages, and 18.0 to inflammatory complications, i.e., early post-abortal complications had to be reckoned with in every 25th case. Data in the present study suggest a correlation between induced abortions and the incidence of placenta previa, premature separation of the placenta, and premature births.


Trichinella detection: identification and statistical evaluation of sources of error in the magnetic stirrer method for pooled sample digestion.
Proficiency testing (PT) is the use of inter-laboratory comparisons to determine the performance of individual laboratories for specific tests or measurements, and to monitor a laboratory's performance. Participation in proficiency testing provides laboratories with an objective means of assessing and demonstrating the reliability of the data they are producing. To ensure the reliability of Trichinella detection and meat hygiene within the European Union and afford optimal protection to the consumer, PT is conducted under the direction of the European National Reference Laboratories for Trichinella. Evaluation of data from the national PT showed that lab-internal shortcomings are frequent. These shortcomings are specifically related to: (1) improper sample collection and preparation; (2) incorrect transposition and application of the protocol as laid down in Annex I, Chapter I, Nr. 3 (a-g) of the Commission Regulation (EC) No. 2075/2005; (3) insufficient sedimentation times; and (4) improper equipment.(e.g. Prost and Nowakowski, 1990; Rossi and Pozio, 2008; Forbes and Gajadhar, 1999; Rossi and Pozio, 2008). To test the hypothesis that both method based errors as well as internal lab errors can influence the accuracy and precision of the magnetic stirrer method for pooled sample digestion (MSM), we initiated a study to evaluate the analytical uncertainty of the MSM. Results presented here are based on: (i) data from PT in Germany (2008, 2009, and 2010); (ii) within-lab performance conducting high volumes of MSM; (iii) larval recovery experiments; and (iv) statistical evaluation of data resulting from these procedures. Quantitative data from the PT show that on average only 60% of Trichinella larvae were detected. Even laboratories that showed relatively good performance (>80% larva recovery, no false negative or false positive results), frequently reported samples with an unexpectedly low larval count (loss of >2 larvae). In our own laboratory, high numbers of repeated analyses of standards and re-analyses of residual fluids indicated that these outliers could be described by a binomial distribution based on a laboratory-specific Trichinella-detection probability. Results of recovery experiments indicate that only a part of the total larval losses can be attributed to lab-internal shortcomings inasmuch as a significant number of L1 could be isolated from the residual and washing fluids.


Impact of the Medicare Chronic Disease Management program on the conduct of Australian dietitians' private practices.
This study explored private practice dietitians' perceptions of the impact of the Australian Chronic Disease Management (CDM) program on the conduct of their private practice, and the care provided to patients. Twenty-five accredited practising dietitians working in primary care participated in an individual semistructured telephone interview. Interview questions focussed on dietitians' perceptions of the proportion of patients receiving care through the CDM program, fee structures, adhering to reporting requirements and auditing. Transcript data were thematically analysed using a process of open coding. Half of the dietitians (12/25) reported that most of their patients (>75%) received care through the CDM program. Many dietitians (19/25) reported providing identical care to patients using the CDM program and private patients, but most (17/25) described spending substantially longer on administrative tasks for CDM patients. Dietitians experienced pressure from doctors and patients to keep their fees low or to bulk-bill patients using the CDM program. One-third of interviewed dietitians (8/25) expressed concern about the potential to be audited by Medicare. Recommendations to improve the CDM program included increasing the consultation length and subsequent rebate available for dietetic consultations, and increasing the number of consultations to align with dietetic best-practice guidelines. The CDM program creates challenges for dietitians working in primary care, including how to sustain the quality of patient-centred care and yet maintain equitable business practices. To ensure the CDM program appropriately assists patients to receive optimal care, further review of the CDM program within the scope of dietetics is required.


[Cardiovascular behavior after local anesthesia in the jaw region with added vasoconstrictor agents].
The authors studied the cardiovascular behaviour after injection of different amounts of xylocitin added with adrenalin (1:80 000) and noradrenalin (1:20 000), respectively. The evaluation of the blood-pressure values, pulse rates and electrocardiograms leads to the conclusion that noradrenalin produces considerable side effects at the above-mentioned concentration. The well-known headache phenomena caused by the addition of noradrenalin are analysed.


Successful treatment with intravenous high-dose immunoglobulin for cardiomyopathy in dermatomyositis complicated with rapid progressive interstitial pneumonia.
Cardiomyopathy and rapid progressive interstitial pneumonia (IP) are potentially fatal complications in polymyositis/dermatomyositis. We experienced a dermatomyositis patient with multiple adverse prognostic factors, complicating rapid progressive IP, macrophage activation syndrome (MAS), and cardiomyopathy. IP and MAS improved with strong immunosuppressive therapy, despite which cardiomyopathy developed. Therefore, we applied intravenous high-dose immunoglobulin therapy (IVIg), and cardiac function improved dramatically. This is the first report to present the effectiveness of IVIg for cardiomyopathy in dermatomyositis.


[Biopsychosocial predictors of preterm labor and preterm delivery? Results of a prospective study].
In addition to medical, job related, sociodemographic risk factors, and health related behavior, topics that traditionally have been less in the focus of attention in this context, such as biographic data, coping with stress, personality variables, pregnancy related attitudes, fears, and the social network were examined. 589 women between 16(th) and 22(nd) week of pregnancy were examined using a questionnaire that was designed for the study. This resulted in 508 women pregnant with a single child, whose pregnancy and delivery were examined based on their medical records. Factor analysis and main component analysis with subsequent varimax rotation resulted in factors that were subject to a proof of reliability. Statistical analysis was based on logistic regression. 129 (27.7%) of women displayed signs/indices of an imminent preterm delivery, 29% (5.8%) of whom later actually had a preterm delivery before the end of the 37(th) week of pregnancy. Pregnant women who were in treatment for an imminent preterm delivery appear to have been subject to higher social stress as compared to those, who later later actually gave birth before completing the 37(th) week of pregnancy. Lack of a female network and lack of emotional understanding from the partner are correlated to both of these complications. Specifically, actual preterm delivery appears to be significantly influenced by partner relationship. Another significant predicting variable for imminent and actual preterm delivery appears to be a history of gynecological problems. A distinct risk factor for delivery before completion of the 37(th) week of pregnancy was a history of colpitis. In addition, pronounced anxieties in respect to the pregnancy, and low general anxiety were significant predicting variables for delivery before completion of the 37(th) week of pregnancy. Partner relationship, female networks, psychosomatic reactivity in terms of diseases/disorders of the reproductive organs, and anxieties appear to be worthwhile targets in the prevention of preterm delivery.


Psychosexual health in gynecologic cancer.
More people are living with the long-term effects of cancer owing to improvements in cancer treatments and an aging population. Many people diagnosed with cancer report a negative impact on sexual identity, sexual functioning, and their sexual relationship. Gynecologic cancer survivors are often the most severely affected. These cancers involve cancers of the ovaries, uterus, cervix, vagina, and vulva. The impact of these cancers on sexual health results not only from the disease process itself, but may also be due to the necessary treatments required. These can have a profound impact on psychological, physiological, and social well-being both in the short and long term, which may result in negative impact on the quality of life of the patient as well as her partner. Although most patients express that they would like to be more informed about sexual health and would like to have the opportunity to discuss these issues with their therapeutic team, sexual health is often not discussed with the patient.


Detection of anomalous origin of the left coronary artery by transesophageal echocardiography and magnetic resonance imaging.
Anomalous origin of the left coronary artery can lead to angina pectoris, acute myocardial infarction or even sudden death, especially during exercise. We present a patient in whom the anomalous origin of the left coronary artery from the posterior aortic (non-coronary) sinus produced ischemic chest pain. The anomaly was identified by transesophageal echocardiography (TEE) and magnetic resonance imaging (MRI) as well as by coronary angiography. TEE and MRI are useful for detecting anomalies of the coronary artery both clearly and noninvasively and for evaluating the mechanism of ischemia.


Analysis of the aetiology of diarrhoea in outpatients in 2007, Henan province, China.
The purpose of this study was to determine the aetiology of acute diarrhoea and improve knowledge of gastrointestinal pathogens in China. Faecal specimens from 1526 outpatients with diarrhoea were collected from 20 hospitals in Henan province and the prevalence of seven bacterial and five viral diarrhoeagenic pathogens were determined. Bacterial pathogens were recovered from 279/1526 (18·3%) stool specimens and viral pathogens were detected in 178/1526 (11·7%) stool specimens. The top five pathogenic species were diarrhoeagenic E. coli (n = 140, 9·2%), rotavirus (n = 79, 5·2%), Shigella spp. (n = 69, 4·5%), Salmonella spp. (n = 66, 4·3%) and norovirus (n = 56, 3·7%). The prevalence of pathogens showed correlation with age, season and clinical symptoms. Several dominant serotypes were identified in Shigella and Salmonella isolates, and high prevalence of multiple drug-resistant isolates was observed in both species. This important information will have a significant effect on public health policy development and resource prioritization practices.


Toxocara canis infection in dogs in Beersheba, Israel.
In the desert city of Beersheba, Israel, a survey was made of the infection rate of Toxocara canis in dogs. 3.0% of dogs destroyed at the municipal dog pound had intestinal T. canis. 7% of faecal samples gathered from day care centres throughout the city were shown to contain T. canis eggs. This low rate of infection could possibly be explained by the hot, arid climatic conditions which may render eggs non-infective or by the sandy soil in the area that may cover faeces containing T. canis ova and make the eggs unavailable to other dogs.


Current concepts: the stabilizing structures of the glenohumeral joint.
Significant contemporary advances have permitted a more comprehensive understanding and development of some interesting concepts about the glenohumeral joint. The purpose of this review paper was to discuss current concepts related to the anatomic stabilizing structures of the shoulder joint complex and their clinical relevance to shoulder instability. The clinical syndrome of shoulder instability represents a wide spectrum of symptoms and signs which may produce various levels of dysfunction, from subtle subluxations to gross joint instability. The glenohumeral joint attains functional stability through a delicate and intricate interaction between the passive and active stabilizing structures. The passive constraints include the bony geometry, glenoid labrum, and the glenohumeral joint capsuloligamentous structures. Conversely, the active constraints, also referred to as the active mechanisms, include the shoulder complex musculature, the proprioceptive system, and the musculoligamentous relationship. The interaction of the active and passive mechanisms which provide passive and active glenohumeral joint stability will be thoroughly discussed in this paper.


Perceptual characteristics of nutritional supplements determine the expected effectiveness in boosting strength, endurance, and concentration performances.
The aim of this work was to examine the link between the physical-perceptual characteristics of nutritional supplements and their expected effectiveness in enhancing sport performance. Participants (n = 267) ranked nine images of fictive nutritional supplements, varying in shape, color, and route of administration (e.g., pill, powder, lotion, etc.), in ranked- order of expected effectiveness. They performed the task three times, (1) for strength, (2) endurance, and (3) for concentration. Results have revealed that the perceived effectiveness of the supplements was statistically significantly different for the three types of performances (p < .001). A significant interpersonal variability was observed in the ranking-order of the supplements. The findings reveal that perceptual characteristics of 'believed to be nutritional supplements', aimed at sport performance enhancement, influence their perceived effectiveness. Future inquiries in sport nutrition should examine the relationship between expected and experienced effectiveness of various nutritional supplements in enhancing sport performance.


TGF-β signaling regulates SPOP expression and promotes prostate cancer cell stemness.
SPOP, a substrate binding adaptor of E3 ubiquitin ligase Cullin3, is frequently mutated in human prostate cancer (PCa). However, whether and how SPOP is regulated at transcriptional level in PCa remain unclear. Here, we report that SPOP is down-regulated in PCa stem-like cells (CSCs) and tissues. Our study reveals that SPOP expression is repressed by TGF-β / SMAD signaling axis in PCa CSCs. SPOP promoter contains SMAD-binding elements (SBEs), which can interact with SMAD3. Moreover, TGF-β signaling inhibitor SB431542 promotes the SPOP expression and abrogates PCa stemness. Clinically, SPOP expression is downregulated in PCa patients, which is significantly related to a poor prognosis and lower survival rate. Thus, our findings uncover a mechanism of how SPOP expression is mediated in PCa CSCs via TGF-β/ SMAD3 signaling.


The effect of a patient portal with electronic messaging on patient activation among chronically ill patients: controlled before-and-after study.
It has been suggested that providing patients with access to their medical records and secure messaging with health care professionals improves health outcomes in chronic care by encouraging and activating patients to manage their own condition. The aim was to evaluate the effect of access to a patient portal on patient activation among chronically ill patients. Further, the relationship between temporal proximity of a severe diagnosis and patient activation were assessed. A total of 876 chronically ill patients from public primary care were allocated to either an intervention group receiving immediate access to a patient portal that included their medical records, care plan, and secure messaging with a care team, or to a control group receiving usual care. Patient Activation Measure (PAM) at baseline and at 6-month follow-up was obtained from 80 patients in the intervention group and 57 patients in the control group; thus, a total of 137 patients were included in the final analysis. No significant effect of access to patient portal on patient activation was detected in this study (F1,133=1.87, P=.17, η(2)=0.01). Patients starting at a lower level of activation demonstrated greater positive change in activation compared to patients starting at higher levels of activation in both the intervention and control groups. Further, patients diagnosed with a severe diagnosis during the intervention showed greater positive change in patient activation compared to patients whose last severe diagnosis was made more than 2 years ago. The results also suggest that the intervention had greatest effect on patients starting at the highest level of patient activation (difference in change of patient activation=4.82, P=.13), and among patients diagnosed within a year of the intervention (difference in change of patient activation=7.65, P=.12). Time since last severe diagnosis and patient activation at baseline may affect changes in patient activation, suggesting that these should be considered in evaluation of activating chronic care interventions and in the specification of possible target groups for these interventions. This may be relevant in designing services for a heterogeneous group of patients with a distinct medical history and level of activation.


Computerized Cognitive Behavioral Therapy for Substance Use Disorders in a Specialized Primary Care Practice: A Randomized Feasibility Trial to Address the RT Component of SBIRT.
Screening, Brief Intervention, and Referral to Treatment (SBIRT) has demonstrated efficacy for addressing unhealthy alcohol use in primary care, yet recent research indicates weaker efficacy for drug use as well as very limited success in referral to specialty care for patients with substance use disorder (SUD). Technology-based interventions for SUD delivered in primary care settings are a potential strategy of efficiently delivering treatment to those who need it. We conducted a randomized clinical trial evaluating feasibility, satisfaction, and substance use outcomes for 58 individuals with SUD. Participants being treated in a primary care practice which provides integrated addiction treatment were randomized to standard care or standard care plus access to a web-based SUD intervention (computer-based training in cognitive behavioral therapy, or CBT4CBT). Self-reported substance use and urine toxicology screens were assessed at 8 weeks after randomization. Uptake of CBT4CBT in this setting was high; 77% of those assigned to this condition accessed the program at least once; of those, 77% completed all 7 modules. Satisfaction with the program was very high. Participants reported >90% days abstinent for all classes of drugs; with no significant differences between conditions. This study demonstrates feasibility of implementing technology-based treatments in primary care settings to address weak follow-through with the referral component of SBIRT. The overall positive outcomes in this specialized, integrated treatment setting may have undercut the ability to demonstrate differential effects on substance use; results suggest evaluation in less specialized primary care settings is warranted. clinicaltrials.gov NCT03013478.


Growth Disturbances Following Paediatric Anterior Cruciate Ligament Reconstruction: A Systematic Review.
Growth disturbances after transphyseal paediatric anterior cruciate ligament (ACL) reconstruction have led to the development of physeal-sparing techniques. The aim of this study is to investigate growth disturbances following paediatric ACL reconstruction and identify associated risk factors. A systematic search on PubMed, Scopus and Web of Science databases was conducted using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to identify case series reporting paediatric ACL reconstructions. Of 518 articles, 78 met the inclusion criteria, and data related to growth disturbances and graft failures were extracted. A total of 2,693 paediatric ACL reconstructions resulted in 70 growth disturbances (2.6%): 17 were varus, 26 were valgus, 13 were shortening, 14 were lengthening and five patients had reduced tibial slope. Some patients showed deformities in more than one plane. Coronal plane deformities were seen more frequently with eccentric physeal arrest and lengthening with intraepiphyseal tunnelling. Shortening and reduced tibial slope were related to large central physeal arrest and anterior tibial physeal arrest, respectively. Sixty-two studies documented 166 graft failures in 2,120 reconstructions (7.8%). The extraphyseal technique was least likely to result in growth disturbances and graft failure. Paediatric ACL reconstruction is a safe and effective treatment of rupture. Growth disturbances are least likely following extraphyseal tunnelling, and those resulting from transphyseal techniques can be minimised by reducing drill size, drilling steep and avoiding the physeal periphery. The insertion of hardware, synthetic material, or a bone plug through the drilled physis should be avoided. There is a greater need for robust long-term data collection, such as national ligament registries, to standardise practice and evaluate the risk of growth disturbance and re-ruptures in this treatment.


Are self-enhancing cognitions associated with healthy or unhealthy biological profiles?
Self-enhancement is variously portrayed as a positive illusion that can foster health and longevity or as defensive neuroticism that can have physiological-neuroendocrine costs. In a laboratory stress-challenge paradigm, the authors found that high self-enhancers had lower cardiovascular responses to stress, more rapid cardiovascular recovery, and lower baseline cortisol levels, consistent with the positive illusions predictions and counter to the predictions of the defensive neuroticism position. A second set of analyses, replicating the "illusory mental health paradigm" (J. Shedler, M. Mayman, & M. Manis, 1993), also did not support the defensive neuroticism hypothesis. The association between self-enhancement and cortisol was mediated by psychological resources; analyses of the cardiovascular results provided no definitive mediational pathway. Discussion centers on the potential stress-buffering effects of self-enhancing beliefs.


Prey growth and size-dependent predation in juvenile estuarine fishes: experimental and model analyses.
The outcome of predation interactions between growing, size-structured predator and prey cohorts is difficult to predict. We manipulated the food resources available to juvenile spot subject to predation from southern flounder in a 60-day replicated pond experiment to test the hypothesis that spot growing slowly would experience higher predation mortality and stronger selection against small individuals than those growing rapidly. A nearly threefold difference in average growth rate between fast- and slow-growth treatments led to twofold higher predation mortality of slow-growing spot. Relative to no-flounder controls, larger spot were overrepresented at the end of the experiment in both treatments, but the magnitude of flounder size selection was much greater in the slow-growth treatment. The experimental results agreed qualitatively, but not quantitatively, with predictions from a prior size-dependent foraging model. In particular, the model significantly underestimated observed shifts in spot size structure to larger sizes. We hypothesized that competitive release and associated increases in spot growth due to thinning by flounder might reconcile this difference, and extended the model to incorporate this process. We then used the model to estimate the relative contribution of these two confounded predator effects (size-selective predation and thinning) to observed shifts in spot size structure. Model simulations indicated that the combined effects of size-selective predation and thinning could account for nearly all of the observed shift in spot size structure, but that thinning was the more important process. Our results highlight the utility of combining experimental and modeling approaches to unravel the complexities underlying interactions between growing, size-structured predator and prey cohorts.


Neurosteroids for a successful pregnancy.
Steroid hormones play a critical role in the initiation and maintenance of pregnancy. In particular, the important role that the progesterone metabolite, and neurosteroid, allopregnanolone, may play in fetal and adolescent development is becoming increasingly evident. Unlike steroid hormones, neurosteroids act at nontraditional targets in the central and peripheral nervous systems, including GABA(A) receptor complexes. This commentary discusses the three works in this issue that elucidate the important role of allopregnanolone in the mechanisms that regulate stress hypo-sensitivity of rodents in late pregnancy, neuroprotective effects in fetal sheep exposed to a hypoxic insult, and the continuing role that prefrontal cortex formation of allopregnanolone may play on the cognitive development of gestationally stressed rat offspring, grown to adolescence. The narrative that these works comprise was facilitated by the 5(th) International Meeting on Steroids and the Nervous System (Torino, Italy), which is organized to update our knowledge on the relationships between steroid hormones synthesized in different organs and the nervous system. Topics covered in this most recent meeting included sex differences in, and hormonal influences on, cannabinoid-regulated biology; steroids and pain; the importance of co-regulatory factors for steroid receptor action in the brain; mechanism and role of estrogen-induced nonclassical signaling in the brain; vitamin D as the forgotten neurosteroid; neurosteroids and GABA(A) receptors; and pathogenic mechanisms mediated by glucocorticoid receptors in psychiatric disorders. The 6(th) International Meeting on Steroids and the Nervous System will be held in Torino, Italy in February 2011.


High sulfur loading cathodes fabricated using peapodlike, large pore volume mesoporous carbon for lithium-sulfur battery.
Porous carbon materials with large pore volume are crucial in loading insulated sulfur with the purpose of achieving high performance for lithium-sulfur batteries. In our study, peapodlike mesoporous carbon with interconnected pore channels and large pore volume (4.69 cm(3) g(-1)) was synthesized and used as the matrix to fabricate carbon/sulfur (C/S) composite which served as attractive cathodes for lithium-sulfur batteries. Systematic investigation of the C/S composite reveals that the carbon matrix can hold a high but suitable sulfur loading of 84 wt %, which is beneficial for improving the bulk density in practical application. Such controllable sulfur-filling also effectively allows the volume expansion of active sulfur during Li(+) insertion. Moreover, the thin carbon walls (3-4 nm) of carbon matrix not only are able to shorten the pathway of Li(+) transfer and conduct electron to overcome the poor kinetics of sulfur cathode, but also are flexible to warrant structure stability. Importantly, the peapodlike carbon shell is beneficial to increase the electrical contact for improving electronic conductivity of active sulfur. Meanwhile, polymer modification with polypyrrole coating layer further restrains polysulfides dissolution and improves the cycle stability of carbon/sulfur composites.