Management of acute distal humeral fractures in patients with rheumatoid arthritis. A case series.
The best surgical treatment for a patient with rheumatoid arthritis and an acute distal humeral fracture is not well established. Because of the distorted anatomy of the arthritic elbow joint and the adjacent osteoporotic bone, total elbow arthroplasty may be favored over open reduction and internal fixation in these patients. We retrospectively analyzed a series of patients with rheumatoid arthritis in whom an acute distal humeral fracture had been treated with either open reduction and internal fixation or total elbow arthroplasty; our purpose was to evaluate their outcomes and to identify any influence of age, fracture type, or the extent of the rheumatoid involvement of the elbow joint on the choice of procedure. Between 1982 and 2002, an acute distal humeral fracture was treated surgically in sixteen elbows in fourteen patients with rheumatoid arthritis, and the results were retrospectively reviewed at a minimum of twenty-four months postoperatively. Six elbows were treated with open reduction and internal fixation (Group 1) and ten elbows, with primary total elbow arthroplasty (Group 2). Postoperatively, the elbows were examined with standard radiographs, and the clinical outcome was assessed with the Mayo Elbow Performance Score (MEPS). Six patients (six elbows) died before the time of the study, but they had been followed for more than twenty-four months and therefore were included in the series. The eight patients (ten elbows) who were still alive were examined. The mean duration of follow-up was forty-nine months in Group 1 and sixty-six months in Group 2. The MEPS averaged 93 points in Group 1 and 96 points in Group 2. Radiographically, all fractures had healed uneventfully in Group 1 and no prosthesis was loose in Group 2. We could not identify any difference between Groups 1 and 2 with respect to patient age, fracture type, or extent of the rheumatoid arthritis. Distal humeral fractures in patients with rheumatoid arthritis can be treated successfully with immediate open reduction and internal fixation or with total elbow arthroplasty. Our data suggest that open reduction and internal fixation can be successful when there is mild arthritic involvement. We favor total elbow arthroplasty for patients with severe articular involvement. Therapeutic Level IV. See Instructions to Authors for a complete description of levels of evidence.


Eyes on Emotion: Dynamic Gaze Allocation During Emotion Perception From Speech-Like Stimuli.
The majority of emotional expressions used in daily communication are multimodal and dynamic in nature. Consequently, one would expect that human observers utilize specific perceptual strategies to process emotions and to handle the multimodal and dynamic nature of emotions. However, our present knowledge on these strategies is scarce, primarily because most studies on emotion perception have not fully covered this variation, and instead used static and/or unimodal stimuli with few emotion categories. To resolve this knowledge gap, the present study examined how dynamic emotional auditory and visual information is integrated into a unified percept. Since there is a broad spectrum of possible forms of integration, both eye movements and accuracy of emotion identification were evaluated while observers performed an emotion identification task in one of three conditions: audio-only, visual-only video, or audiovisual video. In terms of adaptations of perceptual strategies, eye movement results showed a shift in fixations toward the eyes and away from the nose and mouth when audio is added. Notably, in terms of task performance, audio-only performance was mostly significantly worse than video-only and audiovisual performances, but performance in the latter two conditions was often not different. These results suggest that individuals flexibly and momentarily adapt their perceptual strategies to changes in the available information for emotion recognition, and these changes can be comprehensively quantified with eye tracking.


Host cell entry of powdery mildew is correlated with endosomal transport of antagonistically acting VvPEN1 and VvMLO to the papilla.
Challenge by a nonadapted powdery mildew fungal pathogen leads to the formation of a local cell-wall apposition (papilla) beneath the point of attempted penetration. Several plasma membrane (PM) proteins with opposing roles in powdery mildew infection, including Arabidopsis thaliana PENETRATION1 (PEN1) and barley (Hordeum vulgare) MILDEW RESISTANCE LOCUS O (MLO), are localized to the site of powdery mildew attack. PEN1 contributes to penetration resistance to nonadapted powdery mildews, whereas MLO is a susceptibility factor required by adapted powdery mildew pathogens for host cell entry. Our previous studies have demonstrated that the vesicle and endosomal trafficking inhibitors, brefeldin A and wortmannin, have opposite effects on the penetration rates of adapted and nonadapted powdery mildews on grapevine. These findings prompted us to study the pathogen-induced intracellular trafficking of grapevine variants of MLO and PEN1. We first identified grapevine (Vitis vinifera) VvPEN1 and VvMLO orthologs that rescue Arabidopsis Atpen1 and Atmlo2 mlo6 mlo12 null mutants, respectively. By using endomembrane trafficking inhibitors in combination with fluorescence microscopy, we demonstrate that VvMLO3/VvMLO4 and VvPEN1 are co-trafficked together from the PM to the site of powdery mildew challenge. This focal accumulation of VvMLO3/VvMLO4 and VvPEN1 to the site of attack seems to be required for their opposing functions during powdery mildew attack, because their subcellular localization is correlated with the outcome of attempted powdery mildew penetration.


Glucagon-like peptide-1 as a treatment for chemotherapy-induced mucositis.
Glucagon-like peptide-2 (GLP-2) has been suggested for the treatment of mucositis, but the peptide has also been shown to accentuate colonic dysplasia in carcinogen-treated mice. Recently, an effect on intestinal growth was discovered for glucagon-like peptide-1 (GLP-1), OBJECTIVE: To determine whether endogenous GLP-1 contributes to the healing processes and if exogenous GLP-1 has a potential role in treating mucositis. Mice were injected with 5-fluorouracil (5-FU) or saline to induce mucositis and were then treated with GLP-1, GLP-2, GLP-2 (3-33), exendin (9-39) or vehicle. The mice were sacrificed 48 or 96 h after the 5-FU injections. The end points were intestinal weight, villus height, proliferation and histological scoring of mucositis severity. Rats were injected with 5-FU or saline, and after 48 h, blood was drawn and analysed for GLP-1 and GLP-2 concentration. GLP-1 and GLP-2 significantly prevented the loss of mucosal mass and villus height and significantly decreased the mucositis severity score in the duodenum and jejunum 48 h after chemotherapy. The effect was equivalent. Exendin (9-39) reduced the intestinal weight 96 h after chemotherapy. The GLP-1 levels in blood were increased more than 10-fold, and GLP-2 levels were increased sevenfold. GLP-1 and GLP-2 were secreted after intestinal injury, and recovery was delayed after treatment with exendin (9-39), indicating an important role for the peptides in the protection of the intestine from injury. GLP-1 treatment ameliorated mucositis, which suggests that mucositis and other acute intestinal disorders might benefit from treatment with GLP-1 analogues.


A Ca2+-ATPase Regulates E-cadherin Biogenesis and Epithelial-Mesenchymal Transition in Breast Cancer Cells.
Progression of benign tumors to invasive, metastatic cancer is accompanied by the epithelial-to-mesenchymal transition (EMT), characterized by loss of the cell-adhesion protein E-cadherin. Although silencing mutations and transcriptional repression of the E-cadherin gene have been widely studied, not much is known about posttranslational regulation of E-cadherin in tumors. We show that E-cadherin is tightly coexpressed with the secretory pathway Ca2+-ATPase isoform 2, SPCA2 (ATP2C2), in breast tumors. Loss of SPCA2 impairs surface expression of E-cadherin and elicits mesenchymal gene expression through disruption of cell adhesion in tumorspheres and downstream Hippo-YAP signaling. Conversely, ectopic expression of SPCA2 in triple-negative breast cancer elevates baseline Ca2+ and YAP phosphorylation, enhances posttranslational expression of E-cadherin, and suppresses mesenchymal gene expression. Thus, loss of SPCA2 phenocopies loss of E-cadherin in the Hippo signaling pathway and EMT-MET transitions, consistent with a functional role for SPCA2 in E-cadherin biogenesis. Furthermore, we show that SPCA2 suppresses invasive phenotypes, including cell migration in vitro and tumor metastasis in vivo. Based on these findings, we propose that SPCA2 functions as a key regulator of EMT and may be a potential therapeutic target for treatment of metastatic cancer. IMPLICATIONS: Posttranslational control of E-cadherin and the Hippo pathway by calcium signaling regulates EMT in breast cancer cells.


Attitudes towards bystander cardiopulmonary resuscitation: Results from a cross-sectional general population survey.
Survival from out-of-hospital cardiac arrest (OHCA) varies across the developed world. Although not all OHCA are recoverable, the survival rate in Scotland is lower than in comparable countries, with higher average survival rates of 7.9% in England and 9% across Europe. The purpose of this paper is to explore the barriers, facilitators and public attitudes to administering bystander cardiopulmonary resuscitation (CPR) which could inform future policy and initiatives to improve the rate of bystander CPR. Data was collected via a cross-sectional general population survey of 1027 adults in Scotland. 52% of respondents had been trained in CPR. Of those who were not trained, two fifths (42%) expressed a willingness to receive CPR training. Fewer than half (49%) felt confident administering CPR, rising to 82% if they were talked through it by a call handler. Multivariate analyses identified that people in social grade C2DE were less likely than those in social grade ABC1 to be CPR trained and less confident to administer CPR if talked through by a call handler. The older a person was, the less likely they were to be CPR trained, show willingness to be CPR trained or be confident to administer bystander CPR with or without instruction from an emergency call handler. These findings are particularly relevant considering that most OHCA happen in the homes of older people. In a developed country such as Scotland with widely available CPR training, only half of the adult population reported feeling confident about administering bystander CPR. Further efforts tailored specifically for people who are older, unemployed and have a lower social grade are required to increase knowledge, confidence and uptake of training in bystander CPR.


Argatroban use in heparin-induced thrombocytopenia.
Heparin-induced thrombocytopenia (HIT) is a serious, life-threatening complication which occurs in 1-3% of patients receiving heparin. Patients with untreated HIT have an up to 50% risk of developing life- and limb-threatening thromboembolic complications. Treatment is based upon clinical suspicion, stopping heparin therapy and initiation of anticoagulation with a rapidly acting alternative non-heparin anticoagulant, such as argatroban-a hepatically excreted direct thrombin inhibitor which is effective in the treatment of HIT. To summarize the pharmacological and clinical data, and discuss the impact of argatroban in the current treatment of HIT. A literature search was performed with the aid of Pubmed and Google. Search parameters of 'argatroban', 'heparin-induced thrombocytopenia' and 'treatment' were input into both search engines. Argatroban is a safe and effective treatment for HIT. In patients taking other hepatically cleared medications, lower initial doses may have to be used to avoid over-anticoagulation.


Transfer of hyperpolarization from long T1 storage nuclei to short T1 neighbors using FLOPSY-8.
Nuclei with long T1s are optimal targets for dynamic nuclear polarization (DNP). Therefore, most of the agents used in metabolic imaging and spectroscopy studies are based on carboxylic acid moieties that lack protons, a strong source of dipolar relaxation. Metabolic flux information encoded into spectra of small molecule metabolites in the form of the 13C isotopomer data cannot be accessed using standard 13C hyperpolarization methods because protonated carbons relax too quickly through T1 dipolar relaxation. It is shown here that the longitudinal mixing sequence FLOPSY-8 can be used to transfer polarization from a long T1 storage nucleus to adjacent protonated carbons so that they may be detected with high sensitivity. We demonstrate that FLOPSY-8 allows a direct readout of isotopomer populations in butyrate and glutamate in vitro.


The role of endogenous opiates in the area postrema pressor pathway.
1. Intra-vertebral artery-administered angiotensin II acts at the area postrema to facilitate central sympathetic vasomotor activity. Recent evidence suggests a possible role of the opiate system in the mechanism of action of angiotensin II at the level of the brain stem. 2. In these experiments, we show that the morphine antagonist naloxone reduces significantly the magnitude of the pressor response to vertebral artery-infused angiotensin II. 3. Morphine, in contrast, doubled the peak of the vertebral response to identical doses of the peptide. Neither naloxone nor morphine affected the pressor responses to intravenously administered angiotensin II. 4. The data suggest that the endogenous opiate system in the medulla modulates the cardiovascular effects of angiotensin II at the level of the area postrema.


Pressure on the tracheal mucosa from cuffed tubes.
During cuffed intubation, damage to the trachea is least likely when the lateral wall pressure exerted by the cuff does not exceed the mean capillary perfusion pressure of the mucosa. A study was carried out of eight different types of endotracheal tubes. At the seal point the traditional red rubber tube and the armoured latex and Softway tubes exerted pressures above the mean systemic arterial pressure. Although the Portex and Mallinckrodt tubes exerted pressures close to the mean capillary perfusion pressure, much higher pressures resulted if they were overinflated. The Lanz tube, however, with its over-pressure safety balloon, maintained a lateral wall pressure below the mean capillary perfusion pressure even when inflated considerably beyond the seal point. Endotracheal cuffs are often overinflated in clinical practice. Since cuff-induced tracheal damage is most influenced by the lateral wall pressure, these results suggest that the use of Lanz-type tubes should be mandatory in intensive care units or when a cuffed tracheostomy tube is required and they should also be considered for use in more routine anaesthetic practice.


The let-60 locus controls the switch between vulval and nonvulval cell fates in Caenorhabditis elegans.
During induction of the Caenorhabditis elegans hermaphrodite vulva by the anchor cell of the gonad, six multipotent vulval precursor cells (VPCs) have two distinct fates: three VPCs generate the vulva and the other three VPCs generate nonspecialized hypodermis. Genes that control the fates of the VPCs in response to the anchor cell signal are defined by mutations that cause all six VPCs to generate vulval tissue (Multivulva or Muv) or that cause all six VPCs to generate hypodermis (Vulvaless or Vul). Seven dominant Vul mutations were isolated as dominant suppressors of a lin-15 Muv mutation. These mutations are dominant alleles of the gene let-60, previously identified only by recessive lethal mutations. Our genetic studies of these dominant Vul recessive lethal mutations, recessive lethal mutations, intragenic revertants of the dominant Vul mutations, and the closely mapping semi-dominant multivulva lin-34 mutations suggest that: (1) loss-of-function mutations of let-60 are recessive lethal at a larval stage, but they also cause a Vul phenotype if the lethality is rescued maternally by a lin-34 gain-of-function mutation. (2) The dominant Vul alleles of let-60 are dominant negative mutations whose gene products compete with wild-type activity. (3) lin-34 semidominant Muv alleles are either gain-of-function mutations of let-60 or gain-of-function mutations of an intimately related gene that elevates let-60 activity. We propose that let-60 activity controls VPC fates. In a wild-type animal, reception by a VPC of inductive signal activates let-60, and it generates into a vulval cell type; in absence of inductive signal, let-60 activity is low and the VPC generates hypodermal cells. Our genetic interaction studies suggest that let-60 acts downstream of let-23 and lin-15 and upstream of lin-1 and lin-12 in the genetic pathway specifying the switch between vulval and nonvulval cell types.


Cholangiocarcinoma: has there been any progress?
Cholangiocarcinoma is the second most common primary hepatic tumour after hepatocellular carcinoma. Primary sclerosing cholangitis is one of the most commonly recognized risk factors for cholangiocarcinoma; however, approximately 90% of patients have no identifiable risk factors. Extrahepatic type is its most common presentation. Cholangiocarcinoma is considered to be a devastating disease, with a poor survival rate and few therapeutic options. Although surgical resection has been considered the best treatment option for localized cholangiocarcinoma, local recurrences of this cancer are very common, and imply persistent micro-metastatic disease in lymph nodes or at surgical margins, even after extended surgical resection. Consequently, the five year survival rate after attempted curative resection is only 20% to 40%. Early studies of liver transplantation for cholangiocarcinoma did not show a survival benefit and, currently, this tumour is considered to be an absolute contraindication for liver transplantation in most transplant centres worldwide. Recently, neoadjuvant chemoradiation in combination with liver transplantation for highly selected patients with cholangiocarcinoma has shown impressive results, with five-year survival rates at approximately 76% to 82%--similar to other standard indications for liver transplantation, such as hepatocellular carcinoma or hepatitis C-induced cirrhosis. However, this success of liver transplantation applies to only a subset of patients and most of the data originated from a single centre. Wider application of this strategy, especially for patients with potentially resectable disease, will require validation by other centres.


Tertiary survey performance in a regional trauma hospital without a dedicated trauma service.
Initial management of trauma patients is focused on identifying life- and limb-threatening injuries and may lead to missed injuries. A tertiary survey can minimise the number and effect of missed injuries and involves a physical re-examination and review of all investigations within 24 h of admission. There is little information on current practice of tertiary survey performance in hospitals without a dedicated trauma service. We aimed to determine the rate of tertiary survey performance and the detail of documentation as well as the baseline rate of missed injuries. We performed a retrospective, descriptive study of all multitrauma patients who presented to an Australian level II regional trauma centre without a dedicated trauma service between May 2008 and February 2009. A medical records review was conducted to determine tertiary survey performance and missed injury rate. Of 252 included trauma patients, 20% (n = 51) had a tertiary survey performed. A total of nine missed injuries were detected in eight patients (3.2%). Of the multiple components of the tertiary survey, most were poorly documented. Documentation was more comprehensive in the subgroup of patients who did have a formal tertiary survey. Tertiary survey performance was poor, as indicated by low documentation rates. The baseline missed injury rate was comparable to previous that of retrospective studies, although in this study an underestimation of true missed injury rates is likely. Implementing a formal, institutional tertiary survey may lead to improved tertiary survey performance and documentation and therefore improved trauma care in hospitals without a dedicated trauma service.


Role of oxidative stress generated from the mitochondrial electron transport chain and mitochondrial glutathione status in loss of mitochondrial function and activation of transcription factor nuclear factor-kappa B: studies with isolated mitochondria and rat hepatocytes.
Mitochondria are an important source of reactive oxygen intermediates because they are the major consumers of molecular oxygen in cells. Respiration is associated with toxicity, which is related to the activation of oxygen to reactive intermediates. The purpose of the present study was to examine the role of reduced glutathione (GSH) in the maintenance of mitochondrial functions during oxidative stress induced through selective inhibition of the complex III segment of the electron transport chain. Hydrogen peroxide monitored by the fluorescence of dichlorofluorescein increased in a time- and dose-dependent manner on incubation of mitochondria with antimycin A (AA), an inhibitor of complex III. However, blockade of complex I or II with rotenone or thenoyltrifluoroacetone, respectively, did not result in accumulation of hydrogen peroxide. Depletion of mitochondrial GSH to 10-20% of control by preincubation with diethylmaleate (0.8 mM) or ethacrynic acid (250 microM) also increased dichlorofluorescein and malondialdehyde levels and resulted in an additional (2-3-fold) increase after AA. Similar results were obtained when mitochondrial GSH depletion was produced by treatment with buthionine L-sulfoximine before mirochondria isolation. The endogenous oxidative stress induced by AA was accompanied by a moderate loss of activity of ATPase complex (77% of control) and complex IV of respiration (75% of control), which was accentuated after depletion of mitochondrial GSH (51% and 45% of control, respectively). Similar results were observed in isolated hepatocytes in which depletion of mitochondrial GSH and AA led to peroxidation and mitochondrial dysfunction. In addition, with electrophoretic mobility shift assay of the transcription factor nuclear factor-kappa B (NF-kappa B), we detected its activation in response to AA (2-3-fold). Depletion of mitochondrial GSH in hepatocytes (20% of control) led to further enhancement of NF-kappa B activation (2-4-fold), which correlated with generation of hydrogen peroxide. Thus, our results suggest that GSH protects mitochondria against the endogenous oxidative stress produced at the ubiquinone site of the electron transport chain. Mitochondrial GSH depletion potentiates oxidant-induced loss of mitochondrial functions. Oxidant stress in mitochondria can promote extramitochondrial activation of NF-kappa B and therefore may affect nuclear gene expression.


Structural insights into complexes of glucose-regulated Protein94 (Grp94) with human immunoglobulin G. relevance for Grp94-IgG complexes that form in vivo in pathological conditions.
While the mechanism by which Grp94 displays its chaperone function with client peptides in the cell has been elucidated extensively, much less is known about the nature and properties of how Grp94 can engage binding to proteins once it is exposed on the cell surface or liberated in the extra-cellular milieu, as occurs in pathological conditions. In this work, we wanted to investigate the molecular aspects and structural characteristics of complexes that Grp94 forms with human IgG, posing the attention on the influence that glycosylation of Grp94 might have on the binding capacity to IgG, and on the identification of sites involved in the binding. To this aim, we employed both native, fully glycosylated and partially glycosylated Grp94, and recombinant, non-glycosylated Grp94, as well as IgG subunits, in different experimental conditions, including the physiological setting of human plasma. Regardless of the species and type, Grp94 engages a similar, highly specific and stable binding with IgG that involves sites located in the N-terminal domain of Grp94 and the hinge region of whole IgG. Grp94 does not form stable complex with Fab, F(ab)2 or Fc. Glycosylation turns out to be an obstacle to the Grp94 binding to IgG, although this negative effect can be counteracted by ATP and spontaneously also disappears in time in a physiological setting of incubation. ATP does not affect at all the binding capacity of non-glycosylated Grp94. However, complexes that native, partially glycosylated Grp94 forms with IgG in the presence of ATP show strikingly different characteristics with respect to those formed in absence of ATP. Results have relevance for the mechanism regulating the formation of stable Grp94-IgG complexes in vivo, in the pathological conditions associated with the extra-cellular location of Grp94.


Vocal copying of individually distinctive signature whistles in bottlenose dolphins.
Vocal learning is relatively common in birds but less so in mammals. Sexual selection and individual or group recognition have been identified as major forces in its evolution. While important in the development of vocal displays, vocal learning also allows signal copying in social interactions. Such copying can function in addressing or labelling selected conspecifics. Most examples of addressing in non-humans come from bird song, where matching occurs in an aggressive context. However, in other animals, addressing with learned signals is very much an affiliative signal. We studied the function of vocal copying in a mammal that shows vocal learning as well as complex cognitive and social behaviour, the bottlenose dolphin (Tursiops truncatus). Copying occurred almost exclusively between close associates such as mother-calf pairs and male alliances during separation and was not followed by aggression. All copies were clearly recognizable as such because copiers consistently modified some acoustic parameters of a signal when copying it. We found no evidence for the use of copying in aggression or deception. This use of vocal copying is similar to its use in human language, where the maintenance of social bonds appears to be more important than the immediate defence of resources.


The significance of Computed Tomography in invasive paranasal mucormycosis.
Early diagnosis of acute invasive fungal rhinosinusitis (AIFR) is crucial for patients prognosis and may reduce the extent of surgical debridement. Initial evaluation usually includes paranasal Computed Tomography (CT), with an emphasis on bony erosion which is considered a specific but insensitive radiologic sign. Most studies made no distinction between Aspergillus and Mucor species while addressing CT findings. In this study, we seek to evaluate whether bony erosion on paranasal CT is a significant and reliable finding in the initial evaluation of invasive paranasal mucormycosis. A retrospective review of pre-operative non-contrast craniofacial CT scans of patients diagnosed with acute invasive fungal rhinosinusitis (AIFR) caused by Mucor species for the presence of bony erosion. A total of 13 patients (9 males, 4 females) were included. Twelve patients were immunosuppressed due to various hematological malignancies. Six patients underwent debridement due to gross intraoperative findings of bony fungal invasion, but only one patient had evidence of bony erosion on the pre operative paranasal CT. Bony erosion on paranasal CT is an exceptionally insensitive radiologic sign for establishing or rejecting the diagnosis of Mucor induced AIFR. The mainstay of confirming or rejecting the diagnosis of AIFR is by physical examination, endoscopy and oriented biopsy of suspicious mucosal lesions.


Immediate changes in widespread pressure pain sensitivity, neck pain, and cervical range of motion after cervical or thoracic thrust manipulation in patients with bilateral chronic mechanical neck pain: a randomized clinical trial.
Randomized clinical trial. To compare the effects of cervical versus thoracic thrust manipulation in patients with bilateral chronic mechanical neck pain on pressure pain sensitivity, neck pain, and cervical range of motion (CROM). Evidence suggests that spinal interventions can stimulate descending inhibitory pain pathways. To our knowledge, no study has investigated the neurophysiological effects of thoracic thrust manipulation in individuals with bilateral chronic mechanical neck pain, including widespread changes on pressure sensitivity. Ninety patients (51% female) were randomly assigned to 1 of 3 groups: cervical thrust manipulation on the right, cervical thrust manipulation on the left, or thoracic thrust manipulation. Pressure pain thresholds (PPTs) over the C5-6 zygapophyseal joint, lateral epicondyle, and tibialis anterior muscle, neck pain (11-point numeric pain rating scale), and cervical spine range of motion (CROM) were collected at baseline and 10 minutes after the intervention by an assessor blinded to the treatment allocation of the patients. Mixed-model analyses of covariance were used to examine the effects of the treatment on each outcome variable, with group as the between-subjects variable, time and side as the within-subject variables, and gender as the covariate. The primary analysis was the group-by-time interaction. No significant interactions were found with the mixed-model analyses of covariance for PPT level (C5-6, P>.210; lateral epicondyle, P>.186; tibialis anterior muscle, P>.268), neck pain intensity (P = .923), or CROM (flexion, P = .700; extension, P = .387; lateral flexion, P>.672; rotation, P>.192) as dependent variables. All groups exhibited similar changes in PPT, neck pain, and CROM (all, P<.001). Gender did not influence the main effects or the interaction effects in the analyses of the outcomes (P>.10). The results of the current randomized clinical trial suggest that cervical and thoracic thrust manipulation induce similar changes in PPT, neck pain intensity, and CROM in individuals with bilateral chronic mechanical neck pain. However, changes in PPT and CROM were small and did not surpass their respective minimal detectable change values. Further, because we did not include a control group, we cannot rule out a placebo effect of the thrust interventions on the outcomes. Therapy, level 1b.J Orthop Sports Phys Ther 2012;42(9):806-814, Epub 18 June 2012. doi:10.2519/jospt.2012.4151.


Cardiac cath lab activation by the emergency physician without prior consultation decreases door-to-balloon time.
The purpose of this before-and-after study is to determine whether an ED strategy which calls for cardiac catheterization lab (cath lab) activation directly by the emergency physician (EP) is effective in decreasing door-to-balloon time (DTBT). In our active community teaching hospital ED, with an annual census of 55,000, the traditional practice for STEMI required cardiology consultation prior to cath lab notification. In November 2003 we instituted an ED protocol which mandated direct cath lab activation by the EP for eligible STEMI patients without prior notification of the cardiologist. We measured clinically relevant time intervals, including DTBT, prior to and after institution of the protocol. Twenty-four patients were enrolled after institution of the protocol; these were compared to twenty STEMI patients enrolled prior to the new protocol. DTBT decreased significantly, from 118 to 89 minutes, p=.039. Other ED parameters, including door to exam (17 vs. 15 minutes) and total ED time (80 vs. 56 minutes, p = .056) decreased post-protocol but were not significantly different for the two periods. Those arriving by ambulance continued to have a significantly lower DTBT than non-ambulance patients (pre: change of 47 minutes, p = .03, post: change of 33 minutes; p = .012). Both groups were affected similarly by the change in protocol, decreasing DTBT by approximately 25%. We conclude that a strategy which mandates cath lab activation by the emergency physician for STEMI without prior cardiology consultation, reduces door to balloon time.


Reducing errors and risk in a prenatal network with an electronic medical record.
In 2002 the Institute of Medicine called for implementation of information technologies in health care settings to improve quality of care and reduce the incidence of medical errors. Nowhere is this need more critical than in obstetrics. In recent years numerous electronic prenatal medical records have become available. To date there has been little literature to identify what constitutes the important features in these systems, nor research into whether these systems actually improve the quality of care or the outcome of pregnancies. In this article we will elucidate some of the features that we feel are critical if we are to achieve these goals. Some of these features are: (1) availability across a computer network so that providers can access the record in a variety of settings, (2) simplicity of the user interface to ensure provider compliance with the system, (3) an intelligent system to encourage completeness of documentation in the medical record, (4) a problem-oriented obstetric chart so that no issue is overlooked and each is adequately addressed, and (5) administrative features to allow evaluation to ensure improved quality of care. These features together, we believe, will help to minimize medical errors, improve patient outcomes and reduce liability exposure.


[The role of smoking as a risk factor in inflammatory bowel diseases: single center study in Korea].
Cigarette smoking is the most significant environmental factor identified in inflammatory bowel disease (IBD). Smoking has a beneficial effect on ulcerative colitis (UC) patients. In contrast, Crohn's disease (CD) is associated with smoking, and a detrimental effect of smoking on the course of CD has been demonstrated. The aim of this study was to explore the prevalence in smoking in CD and UC at the time of diagnosis compared with the general population in a single center study. Prevalence of smoking at the time of IBD diagnosis were compared between CD and UC patients in Kyung-Hee Medical Center with healthy general population at age-, gender-, and time period-adjusted rates. We investigated the smoking status of IBD patients at the time of diagnosis by telephone interview. There were 178 IBD patients (98 UC patients and 80 CD patients) between January 1995 and December 2004. The male to female ratio in CD and UC were 2:1 and 1:1.4, respectively. The onset of age was 28.2 years and 38.8 years, respectively. The prevalence of smoking was significantly lower in CD and UC patients than in the general population (CD; odds ratio 0.21, 95% confidence interval 0.12-0.41, p<0.001, UC; odds ratio 0.06, 95% confidence interval 0.03-0.14, p<0.001). After statistical adjustment for gender and age at the diagnosis of IBD, the odds ratio of a current smoker diagnosed as UC was 73% lower than that of CD (adjusted odds ratio 0.27, 95% confidence interval 0.12-0.59, p<0.001). In contrast, being a former smoker showed a risk of approximate 1.27-fold higher likelihood of having UC diagnosis (adjusted odds ratio 1.27, confidence interval 0.41-3.95, p=0.68). Cigarette smoking is protective against developing UC at any age, but is not associated with the development of CD in Korean population. Former smoking is not the high risk factor in developing UC.


A randomized clinical trial of CPI-1189 for HIV-associated cognitive-motor impairment.
CPI-1189 is a compound with antioxidant properties that blocks tumor necrosis factor-alpha (TNFalpha) effects in animal models. It has neuroprotective properties in model systems for HIV-associated neurotoxicity and thus is a candidate for neuroprotective therapy in humans with HIV-associated CNS disease. To assess the tolerability and safety of CPI-1189 in treating HIV-associated cognitive-motor impairment. Sixty-four subjects with mild to moderate HIV-associated cognitive-motor impairment were randomized to receive either placebo or 50 or 100 mg daily of CPI-1189 in addition to optimal HIV therapy. Subjects were followed prospectively in a double-masked study for 10 weeks. The primary assessment was tolerability and safety of the compound. Secondary objectives examined neuropsychological and functional change associated with this treatment. The study compound was well tolerated, with 91% of CPI-1189-treated subjects and 76% of placebo-treated subjects completing the trial. Skin rash was seen equally in placebo and active arms, but the only study withdrawals due to skin rash occurred in CPI-1189-treated subjects (n = 2). One subject developed a cataract on drug (100 mg/day). CD4 lymphocyte counts and plasma HIV viral load remained stable in all groups throughout the trial. No significant treatment effects were observed on the change in composite Z-scores for eight neuropsychologic measures (NPZ-8). The Grooved Pegboard Test (nondominant) showed improved performance with CPI-1189 at 100 mg/day (p = 0.01), but no other neuropsychometric or functional measures demonstrated significant improvement. CPI-1189 was well tolerated in HIV subjects with cognitive-motor disorder. This study was not powered to conclusively determine efficacy and showed no consistent treatment-associated improvement in cognitive or functional measures.


Stochastic simulations of normal aging and Werner's syndrome.
Human cells typically consist of 23 pairs of chromosomes. Telomeres are repetitive sequences of DNA located at the ends of chromosomes. During cell replication, a number of basepairs are lost from the end of the chromosome and this shortening restricts the number of divisions that a cell can complete before it becomes senescent, or non-replicative. In this paper, we use Monte Carlo simulations to form a stochastic model of telomere shortening to investigate how telomere shortening affects normal aging. Using this model, we study various hypotheses for the way in which shortening occurs by comparing their impact on aging at the chromosome and cell levels. We consider different types of length-dependent loss and replication probabilities to describe these processes. After analyzing a simple model for a population of independent chromosomes, we simulate a population of cells in which each cell has 46 chromosomes and the shortest telomere governs the replicative potential of the cell. We generalize these simulations to Werner's syndrome, a condition in which large sections of DNA are removed during cell division and, amongst other conditions, results in rapid aging. Since the mechanisms governing the loss of additional basepairs are not known, we use our model to simulate a variety of possible forms for the rate at which additional telomeres are lost per replication and several expressions for how the probability of cell division depends on telomere length. As well as the evolution of the mean telomere length, we consider the standard deviation and the shape of the distribution. We compare our results with a variety of data from the literature, covering both experimental data and previous models. We find good agreement for the evolution of telomere length when plotted against population doubling.


Computer numerically controlled plasma chemical vaporization machining with a pipe electrode for optical fabrication.
We have developed a chemical vaporization machining device that has computer numerically controlled plasma, by using a pipe electrode for optical fabrications. In this device, less than approximately 1 atm of pressure, plasma is generated around the tip of a pipe electrode. During the process, a workpiece is scanned against the electrode under computer control to achieve the desired shape to be removed. A workpiece of silica glass plate is shaped by use of this device, and the removal characteristics of the device are examined. The equations to characterize numerically the shape resulting from scanning of a workpiece have been derived. The new device allows the high precision of optics from the micrometer to the nanometer level with high-speed removal. The shaped surface is sufficiently smooth to be suitable for optical use.


Impact of obesity and binge eating disorder on patients with idiopathic intracranial hypertension.
Background Idiopathic intracranial hypertension (IIH) is associated with obesity, and obesity is associated with binge eating disorder (BED). The aim of this paper is to address the presence and impact of BED in patients undergoing an IIH diagnostic protocol. Methods This was a cross-sectional study. Consecutive patients suspected of IIH underwent neurological, neuro-ophthalmologic and psychological examinations, neuroimaging studies and intracranial pressure (ICP) measurements through lumbar puncture in the recumbent position. IIH diagnosis was based on International Classification of Headache Disorders, 2nd Edition criteria; BED diagnosis was based on Diagnostic and Statistical Manual of Mental Disorders, 5th Edition criteria. The presence of oligoclonal bands (OCBs) in the cerebrospinal fluid was also assessed. Results Forty-five patients were enrolled: 33 were diagnosed with IIH and five of them (15%) were obese with BED. Compared to non-obese patients, those who were obese, and particularly those who were obese with BED, were more likely to have an IIH diagnosis (χ2 = 14.3; p = 0.001), ICP > 200 mmH2O (χ2 = 12.7; p = 0.002) and history of abuse or neglect (χ2 = 11.2; p = 0.004). No association with OCBs was found. Conclusions We reported for the first time the presence of BED among patients with IIH and showed that BED is associated to IIH, ICP and history of abuse or neglect.


Lettuce for human consumption collected in Costa Rica contains complex communities of culturable oxytetracycline- and gentamicin-resistant bacteria.
The present widespread use of antimicrobials in crop farming is based upon their successful application in human medicine. However, recent evidence suggests that the massive anthropogenic release of antimicrobials into the biosphere has selected for resistant bacteria and facilitated the transfer of resistance genes among them. This work deals with the examination of iceberg lettuce collected at 10 farms from two regions in Costa Rica. Farmers from nine sampling sites regularly apply commercial formulations containing gentamicin, oxytetracycline, streptomycin, or a combination of them without being able to indicate how often and how much of these products have been sprayed onto the crops. One organic farm was also investigated for comparative purposes. Oxytetracycline- and gentamicin-resistant bacteria were abundantly detected using selective enrichment cultures. Furthermore, colony mixtures from selective plates were characterized by chemotaxonomical and molecular fingerprinting methods. Both types of resistant communities accounted for a significant fraction of all culturable bacteria and included several resistance genes as well as factors for their potential horizontal transfer. Given the fact that lettuce is eaten raw, it may contribute to the dissemination of antimicrobial-resistant bacteria and/or their resistance genes from the environment to the microbial biota of the human intestine.


The Emerging Role of Gβ Subunits in Human Genetic Diseases.
Environmental stimuli are perceived and transduced inside the cell through the activation of signaling pathways. One common type of cell signaling transduction network is initiated by G-proteins. G-proteins are activated by G-protein-coupled receptors (GPCRs) and transmit signals from hormones, neurotransmitters, and other signaling factors, thus controlling a number of biological processes that include synaptic transmission, visual photoreception, hormone and growth factors release, regulation of cell contraction and migration, as well as cell growth and differentiation. G-proteins mainly act as heterotrimeric complexes, composed of alpha, beta, and gamma subunits. In the last few years, whole exome sequencing and biochemical studies have shown causality of disease-causing variants in genes encoding G-proteins and human genetic diseases. This review focuses on the G-protein β subunits and their emerging role in the etiology of genetically inherited rare diseases in humans.


Acute-phase protein response is impaired in severely malnourished children.
1. The responses of plasma levels of C-reactive protein and serum amyloid A were assessed in two groups of malnourished children. 2. Sixty-six severely malnourished children were studied at admission. Fifty of these had clinical and/or laboratory evidence of infection. C-reactive protein was not elevated in 23 (46%) and serum amyloid A was not raised in 29 (58%) of these 50 children. 3. Surviving children (n = 62) received two doses of diphtheria-pertussis-tetanus vaccine, to which the C-reactive protein and serum amyloid A responses were measured. The first was given early in recovery, the second after nutritional rehabilitation. Ten mildly malnourished children acted as controls, receiving a single dose of diphtheria-pertussis-tetanus vaccine. 4. The responses of both C-reactive protein and serum amyloid A to diphtheria-pertussis-tetanus vaccine were significantly less in early recovery than after nutritional recovery. The response of the mildly malnourished group was no different from that of the severely malnourished group in early recovery, but was less than their response on discharge. 5. The acute-phase protein response of malnourished children is impaired. This may have prognostic implications as the response plays a central role in promoting healing.


Pathogenesis of acute ulceration response (AUR) in hybrid striped bass.
In a previous study, we discovered that acute confinement stress causes rapid ulceration of the fins of hybrid striped bass Morone saxatilis female x M. chrysops male (Noga et al. 1998. Vet Pathol 35:102-107). In this paper, we report the development of a reproducible model for studying this phenomenon in juvenile hybrid striped bass. We also determined how quickly ulceration could develop in acutely stressed fish and documented the sequential light microscopic and ultrastructural changes associated with this response. When hybrid striped bass were subjected to a standardized confinement protocol, the pathological response was extremely rapid (fin ulceration began to develop within 15 min of confinement). Grossly, the distal edges of the fins became blanched, and melanophores aggregated near the basement membrane and dermis after 15 min of confinement. Microscopically, the earliest detectable change in the fins, which occurred within 15 min of confinement, was swelling and loss of microridges of the outermost epidermal cells; this was followed by epidermal erosion. After 30 min of stress, epidermal ulceration developed at the distal edges of the fins. At this time, both necrotic and apoptotic epidermal cells were present. The middle and basal epidermal layers were severely spongiotic and the dermis and hypodermis were edematous. Over longer periods (up to 2 h), lesions were similar but increasingly more severe, progressing from the distal edge of the fin towards the base. The response to acute stress showed a significant correlation between confinement period and severity of the pathological changes (epidermal degeneration, epidermal ulceration and leukocyte infiltration). Also, we demonstrated that epidermal damage was not restricted to the fins but also affected the body skin and eyes. The ventral area of the body and the corneal epithelium of stressed fish were ulcerated; however, skin on the head and operculum was not affected, suggesting a site-specific mode of damage. In stressed fish, epidermal ulceration was found in 67 to 97% of all fins, 88% of skin on the ventrum, and 67% of corneas, while control fish had only very mild epidermal ulceration in the few fish in which it was present (on 5 to 10% of the fins, but not on the ventral skin or corneas). Due to the widespread damage to epidermal tissues of the body surface, we have named this the acute ulceration response (AUR). Our study indicates that acute confinement can rapidly cause significant damage to epidermal and ocular epithelium. AUR might be a primary cause of morbidity in acutely stressed fish.


Relationship between a network's indicators and basic factors with high-risk behavior of injection among injecting drug users (IDU) via the multiple membership multilevel model.
Among various methods and types of drug abuse, injection receives a great deal of importance because of its related dangerous behavior and health consequences. It seemed that some of the network's indicators affect dangerous behavior of injection. To determine the relationship between a network's indicators and basic factors with high-risk behavior of injection among injecting drug users (IDU) via the multiple memberships multilevel model. In this cross-sectional study, the data related to 147 IDUs in Kerman province, who were interviewed from October 2013 through March 2014, were used, and these addicts were chosen for interview from specific resorts used for common injection. In this study, for analyzing data, multiple membership multilevel model and MLwiN 2.02 software were used. In this study, the mean age of people, who were mostly men, was 37.2±9.02. Based on the result, it becomes obvious that variables of in-degree with OR=1.49 (p=0.006) and the whole number of people related to the person with OR=1.18 (p=0.003) influences the high-risk behavior of injection. Also, none of the demographic variables influenced the high-risk behavior of injection. Totally based on the results of this study, one can find a suitable method in the social network of IDUs in order to create essential strategies, reducing the risk throughout the country. In addition, in minimum time with fewer expenses, aggravation of dangerous behavior especially high-risk behavior of injection can be prevented.


Comparative effectiveness of membrane technologies and disinfection methods for virus elimination in water: A review.
The pandemic of the 2019 novel coronavirus disease (COVID-19) has brought viruses into the public horizon. Since viruses can pose a threat to human health in a low concentration range, seeking efficient virus removal methods has been the research hotspots in the past few years. Herein, a total of 1060 research papers were collected from the Web of Science database to identify technological trends as well as the research status. Based on the analysis results, this review elaborates on the state-of-the-art of membrane filtration and disinfection technologies for the treatment of virus-containing wastewater and drinking water. The results evince that membrane and disinfection methods achieve a broad range of virus removal efficiency (0.5-7 log reduction values (LRVs) and 0.09-8 LRVs, respectively) that is attributable to the various interactions between membranes or disinfectants and viruses having different susceptibility in viral capsid protein and nucleic acid. Moreover, this review discusses the related challenges and potential of membrane and disinfection technologies for customized virus removal in order to prevent the dissemination of the waterborne diseases.


Evidence Map: Reporting of Results by Sex or Gender in Randomized, Controlled Trials with Women Veteran Participants (2008 to 2018).
Higher participation of women in randomized, controlled trials (RCTs) has not led to significantly improved reporting of sex-stratified results. A recent evidence map of research on women veterans revealed that many studies did not report results by sex or gender. This study's objectives were to compare characteristics of RCTs with women veteran participants that did or did not report results by sex or gender and to assess how sex and gender are addressed in research with women veterans. We extended the prior evidence map with a systematic search for RCTs with women veterans, published between 2008 and 2018. We compared the characteristics of RCTs that reported results by sex or gender with those of RCTs that did not, and reviewed methodology and reporting of sex/gender analyses. In addition to 11 studies from the prior evidence map, we assessed 1,820 abstracts for relevance and ultimately included 45 unique RCTs. Five trials included only women and 40 included both men and women (median, 14.3% women). Ten studies reported results by sex or gender. These trials were larger (median study size of n = 343.5 vs. n = 125.5) and included a higher median proportion of women participants (16.8% vs. 11.2%) than studies without sex/gender results. Ten of 11 trials that tested pharmacologic or device interventions did not report results by sex or gender. Reporting of results by sex or gender remains low in veteran research, but may improve with larger studies and increased recruitment of women veterans into trials. Trials of pharmacologic or device interventions may be targets for future reporting requirements. Standardization could improve attention to sex and gender in methodology and reporting.


Challenges and opportunities associated with neglected tropical disease and water, sanitation and hygiene intersectoral integration programs.
Recent research has suggested that water, sanitation, and hygiene (WASH) interventions, in addition to mass drug administration (MDA), are necessary for controlling and eliminating many neglected tropical diseases (NTDs). This study investigated the integration of NTD and WASH programming in order to identify barriers to widespread integration and make recommendations about ideal conditions and best practices critical to future integrated programs. Twenty-four in-depth, semi-structured interviews were conducted with key stakeholders in the global NTD and WASH sectors to identify barriers and ideal conditions in programmatic integration. The most frequently mentioned barriers to WASH and NTD integration included: 1) differing programmatic objectives in the two sectors, including different indicators and metrics; 2) a disproportionate focus on mass drug administration; 3) differences in the scale of funding; 4) siloed funding; and 5) a lack of coordination and information sharing between the two sectors. Participants also conveyed that a more holistic approach was needed if future integration efforts are to be scaled-up. The most commonly mentioned requisite conditions included: 1) education and advocacy; 2) development of joint indicators; 3) increased involvement at the ministerial level; 4) integrated strategy development; 5) creating task forces or committed partnerships; and 6) improved donor support. Public health practitioners planning to integrate NTD and WASH programs can apply these results to create conditions for more effective programs and mitigate barriers to success. Donor agencies should consider funding more integration efforts to further test the proof of principle, and additional support from national and local governments is recommended if integration efforts are to succeed. Intersectoral efforts that include the development of shared indicators and objectives are needed to foster conditions conducive to expanding effective integration programs.


Mortality in a neonate with molybdenum cofactor deficiency illustrates the need for a comprehensive rapid precision medicine system.
Neonatal encephalopathy with seizures is a presentation in which rapid whole-genome sequencing (rWGS) has shown clinical utility and improved outcomes. We report a neonate who presented on the third day of life with seizures refractory to antiepileptic medications and neurologic and computerized tomographic findings consistent with severe generalized brain swelling. rWGS revealed compound heterozygous variants in the molybdenum cofactor synthesis gene, type 1A (MOCS1 c.*7 + 5G > A and c.377G > A); a provisional diagnosis of molybdenum cofactor deficiency on day of life 4. An emergency investigational new drug application for intravenous replacement of the MOCS1 product, cyclic pyranopterin monophosphate, was considered, but felt unsuitable in light of the severity of disease and delay in the start of treatment. The patient died on day of life 9 despite having a precise molecular diagnosis within the first week of life. This case illustrates that an rWGS-based molecular diagnosis within the first week of life may be insufficient to improve outcomes. However, it did inform clinical decision-making with regard to resuscitation and predicted long-term outcome. We suggest that to achieve optimal reductions in morbidity and mortality, rWGS must be implemented within a comprehensive rapid precision medicine system (CRPM). Akin to newborn screening (NBS), CRPM will have onboarding, diagnosis, and precision medicine implementation components developed in response to patient and parental needs. Education of health-care providers in a learning model in which ongoing data analyses informs system improvement will be essential for optimal effectiveness of CRPM.


Monte Carlo Planning Method Estimates Planning Horizons during Interactive Social Exchange.
Reciprocating interactions represent a central feature of all human exchanges. They have been the target of various recent experiments, with healthy participants and psychiatric populations engaging as dyads in multi-round exchanges such as a repeated trust task. Behaviour in such exchanges involves complexities related to each agent's preference for equity with their partner, beliefs about the partner's appetite for equity, beliefs about the partner's model of their partner, and so on. Agents may also plan different numbers of steps into the future. Providing a computationally precise account of the behaviour is an essential step towards understanding what underlies choices. A natural framework for this is that of an interactive partially observable Markov decision process (IPOMDP). However, the various complexities make IPOMDPs inordinately computationally challenging. Here, we show how to approximate the solution for the multi-round trust task using a variant of the Monte-Carlo tree search algorithm. We demonstrate that the algorithm is efficient and effective, and therefore can be used to invert observations of behavioural choices. We use generated behaviour to elucidate the richness and sophistication of interactive inference.


A non-invasive assessment of intracranial volume reserve by measuring cerebrospinal fluid volume with the aid of CT imaging.
Monitoring changes in the intracranial volume (ICV) reserve and intracranial pressure (ICP) is one of the key issues in the treatment of intracranial pathologies. The aim of this study is to develop a method of monitoring the ICV reserve by analyzing CSF volume measured using CT in specific regions. A total of 20 patients with cerebral injury were evaluated. Analysis was performed using imaging software. On selected scans (three at the basal cistern level and three at the pineal level), the following regions were analyzed: total cerebral surface (TC1, TC2) and bilateral ambient cistern (AC) only at the basal cistern level for cerebrospinal fluid (CSF) volume. Results were correlated with patients' Glasgow Coma Scale (GCS) scores. An increase of CSF volume was observed with an improvement in the GCS. From the examined regions, only AC volume showed a statistically significant linear correlation (p < 0.0005) with GCS. Mean AC: 0.021, 0.454, and 0.678 mL CSF/scan in severe (3-8 pts GCS), moderate (9-12 pts GCS), and mild (13-15 pts GCS) TBI groups, respectively. Assessment of CSF volume changes in mL CSF/scan can be conducted using CT. Counting voxels corresponding to the CSF eliminates mistakes due to inaccurate region demarcation. The obtained results (AC volume) show a high correlation with patient state.


Non-steroidal anti-inflammatory drugs for low back pain.
Non-steroidal anti-inflammatory drugs (NSAIDs) are the most frequently prescribed medications worldwide and are widely used for patients with low back pain. The objective of this systematic review was to assess the effects of NSAIDs in the treatment of non-specific low back pain and to assess which type of NSAID is most effective. We searched the Medline and Embase databases and the Cochrane Controlled Trials Register (CCTR) up to and including September 1998 if reported in English, Dutch or German. We also screened references given in relevant reviews and identified trials. Randomised trials and double-blind controlled trials of NSAIDs in non-specific low back pain with or without radiation were included. Two reviewers blinded with respect to authors, institution and journal independently extracted data and assessed methodological quality. A methodological quality score was applied, and studies meeting at least six of 11 specified criteria were considered high quality studies. If data were considered clinically homogeneous, a meta-analysis was performed using a fixed effects model for statistically homogeneous subgroups and a random effects model for statistically heterogeneous subgroups. If data were considered clinically heterogeneous, a qualitative analysis was performed using a rating system with four levels of evidence (strong, moderate, limited, no). A total of 51 trials (total number of patients = 6057) were included in this review, of which 46 were published in English and five in German. Sixteen trials (31%) were of high quality. The pooled Relative Risk for global improvement after one week was 1.24 (95% CI 1.10, 1.41) and for additional analgesic use 1.29 (95% CI 1.05, 1.57), indicating a statistically significant effect in favour of NSAIDs compared to placebo. The results of the qualitative analysis showed that there is conflicting evidence (level 3) that NSAIDs are more effective than paracetamol for acute low back pain, and that there is moderate evidence (level 2) that NSAIDs are not more effective than other drugs for acute low back pain. There is strong evidence (level 1) that various types of NSAIDs are equally effective for acute low back pain. In conclusion, the evidence from the 51 trials included in this review suggests that NSAIDs are effective for short-term symptomatic relief in patients with acute low back pain. Furthermore, there does not seem to be a specific type of NSAID which is clearly more effective than others. Sufficient evidence on chronic low back pain is still lacking.


Using transcriptome profiling to characterize QTL regions on chicken chromosome 5.
Although many QTL for various traits have been mapped in livestock, location confidence intervals remain wide that makes difficult the identification of causative mutations. The aim of this study was to test the contribution of microarray data to QTL detection in livestock species. Three different but complementary approaches are proposed to improve characterization of a chicken QTL region for abdominal fatness (AF) previously detected on chromosome 5 (GGA5). Hepatic transcriptome profiles for 45 offspring of a sire known to be heterozygous for the distal GGA5 AF QTL were obtained using a 20 K chicken oligochip. mRNA levels of 660 genes were correlated with the AF trait. The first approach was to dissect the AF phenotype by identifying animal subgroups according to their 660 transcript profiles. Linkage analysis using some of these subgroups revealed another QTL in the middle of GGA5 and increased the significance of the distal GGA5 AF QTL, thereby refining its localization. The second approach targeted the genes correlated with the AF trait and regulated by the GGA5 AF QTL region. Five of the 660 genes were considered as being controlled either by the AF QTL mutation itself or by a mutation close to it; one having a function related to lipid metabolism (HMGCS1). In addition, a QTL analysis with a multiple trait model combining this 5 gene-set and AF allowed us to refine the QTL region. The third approach was to use these 5 transcriptome profiles to predict the paternal Q versus q AF QTL mutation for each recombinant offspring and then refine the localization of the QTL from 31 cM (100 genes) at a most probable location confidence interval of 7 cM (12 genes) after determining the recombination breakpoints, an interval consistent with the reductions obtained by the two other approaches. The results showed the feasibility and efficacy of the three strategies used, the first revealing a QTL undetected using the whole population, the second providing functional information about a QTL region through genes related to the trait and controlled by this region (HMGCS1), the third could drastically refine a QTL region.


Periosteal augmentation of allograft bone and its effect on implant fixation - an experimental study on 12 dogs().
Periosteum provides essential cellular and biological components necessary for fracture healing and bone repair. We hypothesized that augmenting allograft bone by adding fragmented autologous periosteum would improve fixation of grafted implants. In each of twelve dogs, we implanted two unloaded cylindrical (10 mm x 6 mm) titanium implants into the distal femur. The implants were surrounded by a 2.5-mm gap into which morselized allograft bone with or without addition of fragmented autologous periosteum was impacted. After four weeks, the animals were euthanized and the implants were evaluated by histomorphometric analysis and mechanical push-out test. Although less new bone was found on the implant surface and increased volume of fibrous tissue was present in the gap around the implant, no difference was found between treatment groups regarding the mechanical parameters. Increased new bone formation was observed in the immediate vicinity of the periosteum fragments within the bone graft. The method for periosteal augmentation used in this study did not alter the mechanical fixation although osseointegration was impaired. The observed activity of new bone formation at the boundary of the periosteum fragments may indicate maintained bone stimulating properties of the transplanted cambium layer. Augmenting the bone graft by smaller fragments of periosteum, isolated cambium layer tissue or cultured periosteal cells could be studied in the future.


[Prevalence study of biotinidase deficiency in newborns].
Biotinidase deficiency is an inheritable disorder of biotin metabolism. This disorder fulfills major criteria for consideration for newborn screening: the affected children do no show clinical signs in the newborn period; the disease is highly disabling; treatment is effective in preventing neurological sequelae if undertaken promptly. Screening of 125,000 infants born in Paraná State was carried out to establish the prevalence of biotinidase deficiency. A simple colorimetric procedure was used to detect two infants with biotinidase deficiency (1:62,500), one of them with profound deficiency (1:125,000) and the other with partial deficiency (1:125,000) of the enzyme. There were no known false-negative test results and 0.12% were false-positive, defined by further blood samples which were negative upon repeated testing. Sensitivity was 100% and specificity was 99.88%. Repeat blood samples could not be obtained in 63 (30%) suspected cases. Newborn screening for biotinidase is useful in identifying affected children, is inexpensive and allows early intervention, which may prevent irreversible neurological damage.


Anti-Aging Effect of Nigella Sativa Fixed Oil on D-Galactose-Induced Aging in Mice.
Aging is an unconscious and gradual process that can lead to changes in biological systems. Induction of oxidative stress and apoptosis, hepatotoxicity and neurotoxicity are involved in the aging process. Regarding the antioxidant property of black seed oil, the aim of this study was to evaluate the anti-aging effect of Nigella sativa (N. sativa) oil on d-galactose-induced aging in mice. For induction of aging, D-galactose (500 mg/kg, subcoutaneously SC) was administrated to male mice for 42 days. Animals were treated with D-galactose alone or with b lack seed oil (0.1, 0.2, 0.5 mL/kg, intraperitoneally (ip)). Additionally, vitamin E (200 mg/kg) was used as a positive control. At the end of treatment, the malondialdehyde (MDA) and the glutathione (GSH) contents in brain and liver tissues were measured. Also, enzymes in serum, including aspartate aminotransferase (AST) and alanine amino transferase (ALT), were determined. The levels of the proteins Bax, Bcl2, caspase-3 (pro and cleaved) in brain and liver tissues were evaluated. Administration of D-galactose (500 mg/kg, SC) for 42 days increased serum levels of ALT and AST, as well as the MDA content, in brain and liver tissues, but decreased the GSH content. Additionally, the levels of apoptotic proteins, including Bax, procaspase-3 and caspase-3 cleaved, were markedly increased. N. sativa oil (0.1 and 0.2 mL/kg) diminished the levels of the biochemical markers ALT and AST. Administration of black seed oil (0.1, 0.2 and 0.5 mL/kg) reduced lipid peroxidation and at doses 0.1 and 0.2 mL/kg significantly recovered the GSH content. The oil decreased Bax/Bcl2 levels and at 0.1 mL/kg down-regulated the expressions of caspase-3 (pro and cleaved) proteins in brain and liver tissues. Through its antioxidant and anti-apoptosis properties, black seed oil exhibited an anti-aging effect in a model of aging induced with D-galactose.


Influence of offspring on quality of life among cancer patients and survivors: results from the Korean longitudinal study of aging (KLoSA), 2008-2011.
To examine whether offspring improve or reduce quality of life (QOL) among cancer patients and survivors. We used data from the Korean Longitudinal Study of Aging (KLoSA) from 2008 to 2011. There were 490 research subjects in our study: 245 cancer patients and survivors and 245 controls matched using propensity scores. For cancer patients and survivors with no offspring, the QOL estimate was -2.831 lower (SE: 5.508, p-value: 0.623) than that of those with two offspring, while for those with five or more offspring, the QOL estimate was 7.336 higher (SE: 2.840, p-value: 0.036). For non-cancer patients and survivors with one child, the QOL estimate was -11.258 lower (SE: 2.430, p-value: 0.002) than that of those with two offspring, while for those with five or more offspring, the QOL estimate was -4.881 lower (SE: 2.484, p-value: 0.090). This article provides evidence for a beneficial effect of offspring upon QOL in cancer patients and survivors, indicating that offspring are important for them.


Creation and imitation of a milk flavour.
Flavour plays a crucial role in food and is the most important aspect of milk. Milk has a pleasant smell and milk flavour can be used in several products. However, how to recreate milk flavour has rarely been reported. Therefore, the creation of milk flavour is of great interest. This study focused on the creation and imitation of milk flavour. The approach to flavour creation involves identifying the attributes of the flavour and developing an impactful, authentic flavour. Accordingly, to create a milk flavour, the notes of milk flavour were identified by smelling and tasting milk. Based on the identified notes, aroma ingredients were selected to blend into a milk-flavour. After olfactory discrimination, several modifications and adjustments were made and a typical milk flavour formula was obtained. The results showed that the milk flavour has the following notes: milky, acidic, vanilla-like, caramel-like, aldehydic, fruity, beany, buttery, meaty, and vegetative. Lactones, acids, aldehydes, alcohols, ketones, esters, sulphur compounds, furans, and nitrogen compounds can provide these notes. Based on the developed formula, a harmonious flavour with typical characteristics of milk was obtained by blending the selected aroma ingredients.


Inhibition of cholesterol biosynthesis through RNF145-dependent ubiquitination of SCAP.
Cholesterol homeostasis is maintained through concerted action of the SREBPs and LXRs. Here, we report that RNF145, a previously uncharacterized ER membrane ubiquitin ligase, participates in crosstalk between these critical signaling pathways. RNF145 expression is induced in response to LXR activation and high-cholesterol diet feeding. Transduction of RNF145 into mouse liver inhibits the expression of genes involved in cholesterol biosynthesis and reduces plasma cholesterol levels. Conversely, acute suppression of RNF145 via shRNA-mediated knockdown, or chronic inactivation of RNF145 by genetic deletion, potentiates the expression of cholesterol biosynthetic genes and increases cholesterol levels both in liver and plasma. Mechanistic studies show that RNF145 triggers ubiquitination of SCAP on lysine residues within a cytoplasmic loop essential for COPII binding, potentially inhibiting its transport to Golgi and subsequent processing of SREBP-2. These findings define an additional mechanism linking hepatic sterol levels to the reciprocal actions of the SREBP-2 and LXR pathways.


Prostate Cancer in Pilots.
Aviation exposes pilots to various occupationally related hazards, including ionizing radiation and chemical combustion. The possibility of increased prostate cancer incidence and mortality among pilots is a subject of debate. This systematic review and meta-analysis aims to summarize the supporting evidence and determine the magnitude of association. All studies reporting prostate cancer incidence and mortality in pilots compared to the general population were included regardless of language or size. The comprehensive search included multiple databases and manual search. A random effect model was used to pool relative risks (RR) across studies. The final search yielded nine studies with good methodological quality. Four studies reported the incidence of prostate cancer while six reported on mortality. Pilots had a small but statistically significant increase in the risk of developing prostate cancer [RR 1.20; 95% confidence interval (CI), 1.08-1.33], but not in prostate cancer mortality (RR 1.20; 95% CI, 0.91-1.60). Pilots appear to have a very small increase in prostate cancer incidence, but not in mortality. The clinical significance of this finding is uncertain.


Tenascins in stem cell niches.
Tenascins are extracellular matrix proteins with distinct spatial and temporal expression during development, tissue homeostasis and disease. Based on their expression patterns and knockout phenotypes an important role of tenascins in tissue formation, cell adhesion modulation, regulation of proliferation and differentiation has been demonstrated. All of these features are of importance in stem cell niches where a precise regulation of growth versus differentiation has to be guaranteed. In this review we summarize the expression and possible functions of tenascins in neural, epithelial and osteogenic stem cell niches during normal development and organ turnover, in the hematopoietic and pro-inflammatory niche as well as in the metastatic niche during cancer progression.


A double-blind comparison of lithium carbonate and maprotiline in the prophylaxis of the affective disorders.
A double-blind prospective study was carried out comparing the prophylactic effect of maprotiline and lithium carbonate over a period of one year in patients suffering from recurrent affective disorders. The average Affective Morbidity Index was lower, but not significantly so, in patients treated with lithium. A further analysis, based on dividing patients into those with no affective morbidity and those who showed some affective morbidity during the study, demonstrated lithium carbonate to be significantly superior to maprotiline both in the group as a whole and in unipolar depressives. A correlation between high plasma maprotiline concentration and low morbidity was observed and was in line with an earlier report. A highly significant negative correlation (r=-0-97; p less than 0-001) was found between plasma maprotiline concentration and body weight. Although the results showed lithium carbonate to be superior to maprotiline in the study, it should be emphasized that the plasma levels of lithium were constantly monitored and maintained at what is considered to be its optimum concentration, whereas the maprotiline treated patients were kept on a fixed dosage regime irrespective of plasma levels.


New Insights into Phasmatodea Chromosomes.
Currently, approximately 3000 species of stick insects are known; however, chromosome numbers, which range between 21 and 88, are known for only a few of these insects. Also, centromere banding staining (C-banding) patterns were described for fewer than 10 species, and fluorescence in situ hybridization (FISH) was applied exclusively in two Leptynia species. Interestingly, 10-25% of stick insects (Phasmatodea) are obligatory or facultative parthenogenetic. As clonal and/or bisexual reproduction can affect chromosomal evolution, stick insect karyotypes need to be studied more intensely. Chromosome preparation from embryos of five Phasmatodea species (Medauroidea extradentata, Sungaya inexpectata, Sipyloidea sipylus, Phaenopharos khaoyaiensis, and Peruphasma schultei) from four families were studied here by C-banding and FISH applying ribosomal deoxyribonucleic acid (rDNA) and telomeric repeat probes. For three species, data on chromosome numbers and structure were obtained here for the first time, i.e., S. inexpectata, P. khaoyaiensis, and P. schultei. Large C-positive regions enriched with rDNA were identified in all five studied, distantly related species. Some of these C-positive blocks were enriched for telomeric repeats, as well. Chromosomal evolution of stick insects is characterized by variations in chromosome numbers as well as transposition and amplification of repetitive DNA sequences. Here, the first steps were made towards identification of individual chromosomes in Phasmatodea.


Incident Diabetes Risk Is Not Increased in Transgender Individuals Using Hormone Therapy.
In trans women receiving hormone therapy, body fat and insulin resistance increases, with opposite effects in trans men. These metabolic alterations may affect the risk of developing type 2 diabetes in trans women and trans men. We aimed to compare the incidence of type 2 diabetes of adult trans women and trans men during hormone therapy with rates from their birth-assigned sex in the general population. Retrospective data from the Amsterdam Cohort of Gender Dysphoria with transgender individuals on hormone therapy between 1972 and 2018 were linked to a nationwide health data registry. Because no central registry of diabetes is available, the occurrence of diabetes was inferred from the first dispense of a glucose-lowering agent. Standardized incidence ratios (SIR) were computed for trans women and trans men in comparison with the same birth sex from the general population. Compared with their birth-assigned sex in the general population, no difference in the incidence of type 2 diabetes mellitus was observed in trans women (N = 2585, 90 cases; SIR 0.94; 95% CI, 0.76-1.14) or trans men (N = 1514, 32 cases; SIR 1.40; 95% CI, 0.96-1.92). Despite studies reporting an increase in insulin resistance in feminizing hormone therapy and a decrease in insulin resistance in masculinizing hormone therapy, the incidence of diabetes in transgender individuals after initiation of hormone therapy was not different compared with the general population.


'Cup cell disease' in the colonial tunicate Botryllus schlosseri.
A new progressive, fatal disease called 'cup cell disease' was characterized in ex situ cultures of Botryllus schlosseri, a colonial tunicate. The disease originated as a few dark spots growing within zooids. The infected colonies then started to deteriorate, morphologically diagnosed by ampullar retraction, lethargic blood circulation and by a swollen and soft tunic matrix. In later stages of the disease, developed buds were also affected. Many large black dots were scattered within the tunic matrix, and zooids were transformed to opaque, dilated, sac-like structures, signaling impending death. Colonies were infected periodically, even without direct tissue contact. The time course from first appearance to colony death ranged between 30 and 45 d. Histological studies, in vitro culturing of blood cells and blood smears revealed the existence of numerous cup-like cells (up to 4.8 microm diameter on average) with a yellowish cell wall and transparent cytoplasm that was not stained by various dyes (except azocarmine-G). Cells were refractive under bright-field illumination and revealed a flattened wall with flanges, characteristic of species of the phylum Haplosporidia. Cup cells aggregated in blood vessels and in internal parts of zooids and buds and were phagocytosed by blood cells. In a single case, plasmodia-like structures were found only in the tunic matrix of an infected colony. This is the first record in botryllid ascidians of an infectious lethal disease associated with haplosporidian protists.


B-mode ultrasound scanning in the detection of proximal venous thrombosis after total hip replacement.
A prospective study of the accuracy of real-time B-mode ultrasonography in detecting deep venous thrombosis in the femoral and popliteal veins of the lower extremity was conducted on a consecutive series of patients who had had a total hip replacement. Ascending venography was used as a diagnostic standard. One hundred and forty-three patients had ultrasound studies of both lower extremities and a venographic study of the operatively treated lower extremity at an average of 7.6 days postoperatively. The two tests were done within twenty-four hours of each other. Both ultrasonography and venography were done on 152 extremities. Two paired studies were excluded from the analysis of results because the ultrasound scans could not be interpreted. In 131 extremities, both diagnostic tests were negative for proximal thrombosis. Eight extremities had isolated thrombosis of a vein in the calf that was detected only by venography. In nineteen extremities, old or fresh thrombosis was diagnosed by venography. In four extremities, an old thrombosis of the superficial femoral vein was detected by both studies. In four of the extremities that had a new thrombus in the common femoral vein and in nine that had a new thrombus in the superficial femoral vein, abnormal findings on ultrasound scans correlated with those on venograms. There were two false-negative ultrasound scans and one false-negative venogram. The sensitivity, specificity, and accuracy of ultrasonography were 89, 100, and 99 per cent for the diagnosis of thrombosis of the proximal veins of the lower limb and 63, 100, and 93 per cent for the diagnosis of thrombosis when the entire venous system of the limb was included.(ABSTRACT TRUNCATED AT 250 WORDS)


Extending the LOINC conceptual schema to support standardized assessment instruments.
To extend the Clinical LOINC (Logical Observation Identifiers, Names, and Codes) semantic schema to support (1) the representation of common types of assessment instruments and (2) the disambiguation of versions and variants that may have differing reliability and validity. Psychometric theory and survey research framework, plus an existing tool for implementing many types of assessment instruments (Dialogix), were used to identify and model the attributes of instruments that affect reliability and validity. Four modifications to the LOINC semantic schema were proposed as a means for completely identifying, disambiguating, and operationalizing a broad range of assessment instruments. Assess the feasibility of modeling these attributes within LOINC, with and without the proposed extensions. The existing LOINC schema for supporting assessment instruments was unable to consistently meet either objective. In contrast, the proposed extensions were able to meet both objectives, because they are derived from the Dialogix schema, which already performs those tasks. These extensions to LOINC can facilitate the use, analysis, and improvement of assessment instruments and thereby may improve the detection and management of errors.


Mediation of diurnal fluctuations in pain sensitivity in the rat by food intake patterns: reversal by naloxone.
Rats maintained on a 12-hour light-dark cycle were tested for pain sensitivity after being deprived of food during either the dark or the light phase of the cycle. Diurnal fluctuations in pain sensitivity were observed. The fluctuations followed food intake patterns rather than a natural circadian rhythm, with food deprivation producing a decrease in pain sensitivity. The analgesic response produced by this mild food deprivation was strongly attenuated by naloxone or feeding, suggesting that endogenous opioid systems may be related to patterns of food intake.


Maternal history of Oceania from complete mtDNA genomes: contrasting ancient diversity with recent homogenization due to the Austronesian expansion.
Archaeology, linguistics, and existing genetic studies indicate that Oceania was settled by two major waves of migration. The first migration took place approximately 40 thousand years ago and these migrants, Papuans, colonized much of Near Oceania. Approximately 3.5 thousand years ago, a second expansion of Austronesian-speakers arrived in Near Oceania and the descendants of these people spread to the far corners of the Pacific, colonizing Remote Oceania. To assess the female contribution of these two human expansions to modern populations and to investigate the potential impact of other migrations, we obtained 1,331 whole mitochondrial genome sequences from 34 populations spanning both Near and Remote Oceania. Our results quantify the magnitude of the Austronesian expansion and demonstrate the homogenizing effect of this expansion on almost all studied populations. With regards to Papuan influence, autochthonous haplogroups support the hypothesis of a long history in Near Oceania, with some lineages suggesting a time depth of 60 thousand years, and offer insight into historical interpopulation dynamics. Santa Cruz, a population located in Remote Oceania, is an anomaly with extreme frequencies of autochthonous haplogroups of Near Oceanian origin; simulations to investigate whether this might reflect a pre-Austronesian versus Austronesian settlement of the island failed to provide unequivocal support for either scenario.


The effect of transcranial direct current stimulation on motor sequence learning and upper limb function after stroke.
To assess the impact of electrode arrangement on the efficacy of tDCS in stroke survivors and determine whether changes in transcallosal inhibition (TCI) underlie improvements. 24 stroke survivors (3-124months post-stroke) with upper limb impairment participated. They received blinded tDCS during a motor sequence learning task, requiring the paretic arm to direct a cursor to illuminating targets on a monitor. Four tDCS conditions were studied (crossover); anodal to ipsilesional M1, cathodal to contralesional M1, bihemispheric, sham. The Jebsen Taylor hand function test (JTT) was assessed pre- and post-stimulation and TCI assessed as the ipsilateral silent period (iSP) duration using transcranial magnetic stimulation. The time to react to target illumination reduced with learning of the movement sequence, irrespective of tDCS condition (p>0.1). JTT performance improved after unilateral tDCS (anodal or cathodal) compared with sham (p<0.05), but not after bihemispheric (p>0.1). There was no effect of tDCS on change in iSP duration (p>0.1). Unilateral tDCS is effective for improving JTT performance, but not motor sequence learning. This has implications for the design of future clinical trials.


Association of a Targeted Population Health Management Intervention with Hospital Admissions and Bed-Days for Medicaid-Enrolled Children.
As the proportion of children with Medicaid coverage increases, many pediatric health systems are searching for effective strategies to improve management of this high-risk population and reduce the need for inpatient resources. To estimate the association of a targeted population health management intervention for children eligible for Medicaid with changes in monthly hospital admissions and bed-days. This quality improvement study, using difference-in-differences analysis, deployed integrated team interventions in an academic pediatric health system with 31 in-network primary care practices among children enrolled in Medicaid who received care at the health system's hospital and primary care practices. Data were collected from January 2014 to June 2017. Data analysis took place from January 2018 to June 2019. Targeted deployment of integrated team interventions, each including electronic medical record registry development and reporting alongside a common longitudinal quality improvement framework to distribute workflow among interdisciplinary clinicians and community health workers. Trends in monthly inpatient admissions and bed-days (per 1000 beneficiaries) during the preimplementation period (ie, January 1, 2014, to June 30, 2015) compared with the postimplementation period (ie, July 1, 2015, to June 30, 2017). Of 25 460 children admitted to the hospital's health system during the study period, 8418 (33.1%) (3869 [46.0%] girls; 3308 [39.3%] aged ≤1 year; 5694 [67.6%] black) were from in-network practices, and 17 042 (67.9%) (7779 [45.7%] girls; 6031 [35.4%] aged ≤1 year; 7167 [41.2%] black) were from out-of-network practices. Compared with out-of-network patients, in-network patients experienced a decrease of 0.39 (95% CI, 0.10-0.68) monthly admissions per 1000 beneficiaries (P = .009) and 2.20 (95% CI, 0.90-3.49) monthly bed-days per 1000 beneficiaries (P = .001). Accounting for disproportionate growth in the number of children with medical complexity who were in-network to the health system, this group experienced a monthly decrease in admissions of 0.54 (95% CI, 0.13-0.95) per 1000 beneficiaries (P = .01) and in bed-days of 3.25 (95% CI, 1.46-5.04) per 1000 beneficiaries (P = .001) compared with out-of-network patients. Annualized, these differences could translate to a reduction of 3600 bed-days for a population of 93 000 children eligible for Medicaid. In this quality improvement study, a population health management approach providing targeted integrated care team interventions for children with medical and social complexity being cared for in a primary care network was associated with a reduction in service utilization compared with an out-of-network comparison group. Standardizing the work of care teams with quality improvement methods and integrated information technology tools may provide a scalable strategy for health systems to mitigate risk from a growing population of children who are eligible for Medicaid.


Use of personal electronic devices by psychiatric inpatients: benefits, risks and attitudes of patients and staff.
The study aimed to evaluate the attitudes of patients and staff in relation to the potential benefits and risks of allowing psychiatric inpatients controlled access to personal electronic devices (PEDs), and to document a snapshot audit of practice within the mental health inpatient units of New South Wales, Australia. Psychiatric inpatients and staff at Royal North Shore Hospital's Mental Health inpatient units were surveyed, and an audit of the policies of the psychiatric inpatients of New South Wales was undertaken. Access to PEDs is denied in 85% of New South Wales psychiatric inpatient units. While patients and staff appear to concur on the risks of access to PEDs and the need for risk assessment and rules, compared to patients, staff appear to underestimate the importance of PEDs to maintaining social connection and recovery. This study may assist in the formulation of local policy and procedure to allow a more recovery-oriented approach to the question of whether patients should have access to their PEDs while in hospital.


Supplemention with tetrahydrobiopterin suppresses the development of hypertension in spontaneously hypertensive rats.
It has been suggested that tetrahydrobiopterin (H(4)B), a cofactor of NO synthase, can reverse endothelial dysfunction caused by cardiovascular diseases, including atherosclerosis, coronary artery disease, and hypertension. Moreover, an impairment of H(4)B biosynthesis in spontaneously hypertensive rats (SHR) was observed. Thus, we hypothesized that the defect of the H(4)B synthesis system may play an important role in the development of hypertension in SHR. In the present study H(4)B (10 mg/kg per day IP) was used to treat SHR and Wistar-Kyoto rats (WKY) from the age of 5 through 16 weeks. Results demonstrated that chronic treatment with H(4)B significantly improved the impaired vascular responses to acetylcholine and suppressed the development of hypertension in SHR but did not affect WKY. The increase of inducible NO synthase expression, nitrotyrosine immunostaining, NO production, and superoxide anion formation in adult SHR were also significantly suppressed by chronic treatment with H(4)B. In contrast, H(4)B had no effect on WKY. In conclusion, this study demonstrated that H(4)B significantly attenuated the development of hypertension in SHR. The antihypertensive effect of H(4)B might be mediated through its direct antioxidant activity and/or decreasing oxygen free radical production from NO synthase, thereby reducing inducible NO synthase expression and peroxynitrite formation. Thus, the present study proposed that supplementation with H(4)B might be beneficial in preventing pathological conditions such as essential hypertension.


"I smile, but Without Showing My Teeth": The Lived Experience of Cleft, Lip, and Palate in Adults.
To explore and describe the experience of growing up with unilateral cleft lip and palate (CLP) in adults. Face-to-face interviews. Giorgi's phenomenological method was used for analysis. Twenty-one (mean age: 40.8 years) adults treated for unilateral CLP during childhood and adolescence participated in the study. Growing up with CLP meant to become aware of bodily otherness. The possible reactions from peers early in life complicated the striving for inclusion outside the close family. Being self-confident, clever in school, physically fit, and having trusted friends represented barriers against teasing and bullying. Nevertheless, the reflected image, in mirrors, windows, and photos, reminded the participants of the objectifying looks from others and often led to bodily adjustments that persisted into adulthood. The trajectory of treatment was not questioned during childhood, and the participants accepted the decisions on care made by experts and parents. Although problems related to the cleft could persist or return after the termination of ordinary treatment, a more hesitant view on the possible benefits of additional surgery was typical in adulthood. In retrospect, growing up with a unilateral CLP was found to have been an unquestioned part of the adult participants' childhood, a burden that they feared would, to some extent, also be passed to their own children. However, the CLP had not prevented them from achieving goals and satisfaction in life. The occurrence of persisting psychological, functional, and esthetic challenges in adults suggests the need for an individualized, lifelong, and multidisciplinary perspective on CLP follow-up.


"I Felt Like a Hero:" Adolescents' Understanding of Resolution-Promoting and Vengeful Actions on Behalf of Their Peers.
Bystander intervention on behalf of victims of peer aggression is credited with reducing victimization, yet little is known about how bystanders evaluate their intervention efforts. African-, European-, Mexican-, and Native-American adolescents (N = 266) between 13 and 18 years (Mage = 15.0, 54% female) recounted vengeful and peaceful responses to a peer's victimization. For comparison, they also described acts of personal revenge. Youth's explanations of how they evaluated each action were coded for goals and outcomes. Befitting its moral complexity, self-evaluative rationales for third-party revenge cited more goals than the other two conditions. References to benevolence and lack thereof were more frequent after third-party revenge compared to personal revenge. Concerns that security was compromised and that actions contradicted self-direction were high after both types of revenge. Third-party resolution promoted benevolence, competence, self-direction, and security more than third-party revenge. Epistemic network analyses and thematic excerpts revealed the centrality of benevolence goals in adolescents' self-evaluative thinking. Self-focused and identity-relevant goals were cited in concert with benevolence after third-party intervention.