Variability in clinical assessment of clade IIb mpox lesions.
The ongoing global outbreak of mpox, caused by clade IIb mpox virus, poses significant challenges in accurately categorizing and assessing the diversity of lesions. With lesion resolution being a key endpoint in clinical trials and observational studies, it is essential to evaluate the inter-rater reliability and agreement of clade IIb mpox lesion assessment among clinicians. Clinicians experienced in clade IIb mpox disease were surveyed online with 20 lesion images. They categorized lesions into active, crusted, resolved, or unclassifiable groups. Reliability was assessed with Fleiss' kappa and agreement with proportion of exact agreement. Fifty-three clinicians completed the survey, with a median self-reported confidence rating of 7 (on a scale of 1 to 10) in assessing mpox lesions. The inter-rater reliability was found to be moderate, with a Fleiss' kappa coefficient of 0.417 (P <0.05, 95% confidence interval: 0.409-0.425). The inter-rater agreement was 61%. This study demonstrates moderate inter-rater reliability and agreement in clade IIb mpox lesion assessment among clinicians. The findings emphasize the importance of standardizing lesion classification systems to facilitate clinical care (e.g., decision to start treatment) and public health (e.g. isolation) decisions and a need to explore alternative endpoints for clinical trials.


Antiviral Efficacy and Host Innate Immunity Associated with SB 9200 Treatment in the Woodchuck Model of Chronic Hepatitis B.
SB 9200, an oral prodrug of the dinucleotide SB 9000, is being developed for the treatment of chronic hepatitis B virus (HBV) infection and represents a novel class of antivirals. SB 9200 is thought to activate the viral sensor proteins, retinoic acid-inducible gene 1 (RIG-I) and nucleotide-binding oligomerization domain-containing protein 2 (NOD2) resulting in interferon (IFN) mediated antiviral immune responses in virus-infected cells. Additionally, the binding of SB 9200 to these sensor proteins could also sterically block the ability of the viral polymerase to access pre-genomic RNA for nucleic acid synthesis. The immune stimulating and direct antiviral properties of SB 9200 were evaluated in woodchucks chronically infected with woodchuck hepatitis virus (WHV) by daily, oral dosing at 15 and 30 mg/kg for 12 weeks. Prolonged treatment resulted in 2.2 and 3.7 log10 reductions in serum WHV DNA and in 0.5 and 1.6 log10 declines in serum WHV surface antigen from pretreatment level with the lower or higher dose of SB 9200, respectively. SB 9200 treatment also resulted in lower hepatic levels of WHV nucleic acids and antigen and reduced liver inflammation. Following treatment cessation, recrudescence of viral replication was observed but with dose-dependent delays in viral relapse. The antiviral effects were associated with dose-dependent and long-lasting induction of IFN-α, IFN-β and IFN-stimulated genes in blood and liver, which correlated with the prolonged activation of the RIG-I/NOD2 pathway and hepatic presence of elevated RIG-I protein levels. These results suggest that in addition to a direct antiviral activity, SB 9200 induces antiviral immunity during chronic hepadnaviral infection via activation of the viral sensor pathway.


The Effectiveness of Trunk and Balance Warm-up Exercises in Prevention, Severity, and Length of Limitation From Overuse and Acute Lower Limb Injuries in Male Volleyball Players.
Injuries in volleyball players are most common in the ankles and knees. Many volleyball players suffer from overuse injuries because of the strain placed on the lower extremities from repeated jumping. A characteristic of players who are most at risk for lower extremity injuries is the tendency to display trunk instability during landing, such as lateral flexion and rotation. Research has shown the effectiveness of exercise-based warm-up interventions for acute volleyball injuries. However, comprehensive analyses on the use of lower extremity, trunk, and balance programs to prevent overuse injuries are lacking. To examine the effects of trunk and balance warm-up exercises on the prevention, severity, and length of limitation of overuse and acute lower limb injuries in male volleyball players. Prospective, single-cohort study. This study involved the 2019 (control group) and 2021 (intervention group) male volleyball teams. The control and intervention groups were on the same team; however, seven players joined in 2021 through a sports referral program through which different players are recruited. Measurements included injury incidence rate, injury severity, and injury burden. The intervention involved the addition of trunk and balance exercises during the 2021 season. There was no significant difference in injury incidence rates between groups. Injury severity decreased by 3.7 days for overuse injuries (p=0.04). Injury burden decreased by 11.8 (days/1000 player hours) overall and by 7.1 (days/1000 player hours) for overuse injuries. The results show that an exercise-based warm-up aimed at improving trunk posture during landing did not reduce the incidence rate of injury in men's volleyball. However, the addition of this warm-up did significantly reduce the severity of overuse injury. Level 3B.


Cognitive change in patients undergoing hypnotherapy for irritable bowel syndrome.
Impaired quality of life and psychological distress are common in irritable bowel syndrome (IBS) and may be associated with unhelpful cognitions. Hypnotherapy (HT) is effective in improving both symptoms and quality of life in patients with IBS, and this study was designed to determine whether this improvement is reflected in cognitive change using a validated scale recently developed for use in such patients. A total of 78 IBS patients completed a validated symptom-scoring questionnaire, the Hospital Anxiety and Depression (HAD) Scale and the Cognitive Scale for Functional Bowel Disorders (FBDs), before and after 12 sessions of gut-focused HT. HT resulted in improvement of symptoms, quality of life and scores for anxiety and depression (all P's<.001). IBS-related cognitions also improved, with reduction in the total cognitive score (TCS; P<.001) and all component themes related to bowel function (all P<.001). Cognitions were related to symptom severity because the most abnormal cognitive scores were observed in patients with the highest symptom scores (P<.001). Furthermore, a reduction in symptom score following treatment correlated with an improvement in the cognitive score (P<.001). Regression analysis confirmed that the cognitive score had independence from the other scores and did not serve solely as a proxy for symptom improvement. This study shows that symptom improvement in IBS with HT is associated with cognitive change. It also represents an initial step in unravelling the many possible mechanisms by which treatments such as HT might bring about improvement.


Induced production of brominated aromatic compounds in the alga Ceramium tenuicorne.
In the Baltic Sea, high concentrations of toxic brominated aromatic compounds have been detected in all compartments of the marine food web. A growing body of evidence points towards filamentous algae as a natural producer of these chemicals. However, little is known about the effects of environmental factors and life history on algal production of brominated compounds. In this study, several congeners of methoxylated polybrominated diphenyl ethers (MeO-PBDEs), hydroxylated polybrominated diphenyl ethers (OH-PBDEs) and brominated phenols (BPs) were identified in a naturally growing filamentous red algal species (Ceramium tenuicorne) in the Baltic Sea. The identified substances displayed large seasonal variations in the alga with a concentration peak in July. Production of MeO-/OH-PBDEs and BPs by C. tenuicorne was also established in isolated clonal material grown in a controlled laboratory setting. Based on three replicates, herbivory, as well as elevated levels of light and salinity in the culture medium, significantly increased the production of 2,4,6-tribromophenol (2,4,6-TBP). Investigation of differences in production between the isomorphic female, male and diploid clonal life stages of the alga grown in the laboratory revealed a significantly higher production of 2,4,6-TBP in the brackish water female gametophytes, compared to the corresponding marine gametophytes. Even higher concentrations of 2,4,6-TBP were produced by marine male gametophytes and sporophytes.


Schoolchildren cooperate more successfully with non-kin than with siblings.
Cooperation plays a key role in the development of advanced societies and can be stabilized through shared genes (kinship) or reciprocation. In humans, cooperation among kin occurs more readily than cooperation among non-kin. In many organisms, cooperation can shift with age (e.g. helpers at the nest); however, little is known about developmental shifts between kin and non-kin cooperation in humans. Using a cooperative game, we show that 3- to 10-year-old French schoolchildren cooperated less successfully with siblings than with non-kin children, whether or not non-kin partners were friends. Furthermore, children with larger social networks cooperated better and the perception of friendship among non-friends improved after cooperating. These results contrast with the well-established preference for kin cooperation among adults and indicate that non-kin cooperation in humans might serve to forge and extend non-kin social relationships during middle childhood and create opportunities for future collaboration beyond kin. Our results suggest that the current view of cooperation in humans may only apply to adults and that future studies should focus on how and why cooperation with different classes of partners might change during development in humans across cultures as well as other long-lived organisms.


Systematic prevention of overweight and obesity in adults: a qualitative and quantitative literature analysis.
To date, most interventions aimed at preventing obesity have underemphasized the application of systematic intervention development, implementation and evaluation. The present review provides a thorough insight in factors promoting implementation and/or effectiveness in interventions aimed at preventing overweight/obesity among adults. A total of 46 studies evaluating interventions aimed at preventing obesity were reviewed, followed by both qualitative and quantitative analyses. The Intervention Mapping protocol and the Environmental Research framework for weight Gain prevention (EnRG) were applied to analyse and classify the included studies. The interventions were categorized by setting (workplace, community, health care) and target group (ethnic minorities, pregnant women, [pre]menopausal women, smokers, people with intellectual disabilities). Generally, interventions were found to have potential in changing energy balance-related behaviours and anthropometric outcomes. Effect sizes for changes in body mass index ranged between -0.09 and 0.45. When the programme goal specifically aimed at weight management, the intervention was found to be more successful than interventions with programme goals that were aimed at preventing cardiovascular disease or improving general health status. Although a considerable part of studies included motivational interventions, only some actually assessed the effects on potential cognitive mediators. A general lack of reporting underlying theoretical models for behaviour change was observed as well as the inclusion of linkage groups and strategies to promote empowerment.


Effects of hardness and dimension of pinna and auricular hematoma on detection threshold of cartilage conduction.
In cartilage conduction (CC), a vibrator is presented onto the cartilage of the ear instead of the bony parts of the head used in ordinary bone conduction (BC). Because the auricle cartilage is softer and lighter than the bone, it doesn't require as much pressure as BC, which may cause discomfort (or pain) in the area where a BC transducer is being pressed. However, CC is a relatively new technology, and whether the less dense characteristics of cartilage, which varies from person to person, result in a better sound perception is still being studied. In this paper, we focused on investigating how the hardness and size of the auricle or pinna affect the effectiveness of CC. We used pure-tone hearing thresholds to evaluate this objectively. We also measured the thresholds of CC in subjects with auricular hematoma or "cauliflower ear" (misshapen ears commonly caused by close contact sports) to see if it affected CC differently. Our results indicate that the hardness and size of the auricle affect CC thresholds and that subjects with auricular hematoma have different perceptual characteristics compared to the normal ear group. These differences are believed to be caused by changes in hardness and mass.


Characteristics and Predictors of Educational and Occupational Disengagement Among Outpatient Youth With Borderline Personality Disorder.
This study aimed to investigate predictors of vocational disengagement (referred to as Not in Employment, Education, or Training [NEET]) in young people with borderline personality disorder (BPD). The sample comprised 112 outpatients with a BPD diagnosis, aged 15-25 years, who participated in a randomized controlled trial (ANZCTR12610000100099). The proportion of participants who were NEET (39.3%) at study entry did not improve after 18 months and NEET status frequently changed. Therefore, multinomial regression analyses were used to study three groups: Non-NEET, NEET, and Unstable NEET status. NEET status was predicted by not achieving expected age-appropriate educational milestones, greater instability in identity, and emptiness. Greater instability in interpersonal relationships and identity predicted Unstable NEET status. The findings suggest that specific vocational interventions, that also incorporate a focus on interpersonal functioning, emptiness, and identity disturbance, are needed to improve functioning in youth with BPD, especially when educational milestones are not achieved.


Loss of αβ but not γδ T cells in chickens causes a severe phenotype.
The availability of genetically modified mice has facilitated the study of mammalian T cells. No model has yet been developed to study these cells in chickens, an important livestock species with a high availability of γδ T cells. To investigate the role of γδ and αβ T cell populations in birds, we generated chickens lacking these T cell populations. This was achieved by genomic deletion of the constant region of the T cell receptor γ or β chain, leading to a complete loss of either γδ or αβ T cells. Our results show that a deletion of αβ T cells but not γδ T cells resulted in a severe phenotype in KO chickens. The αβ T cell KO chickens exhibited granulomas associated with inflammation of the spleen and the proventriculus. Immunophenotyping of αβ T cell KO chickens revealed a significant increase in monocytes and expectedly the absence of CD4+ T cells including FoxP3+ regulatory T cells. Surprisingly there was no increase of γδ T cells. In addition, we observed a significant decrease in immunoglobulins, B lymphocytes, and changes in the bursa morphology. Our data reveal the consequences of T cell knockouts in chickens and provide new insights into their function in vertebrates.


[Effect of phosphocreatine and phosphocreatinine on membrane phospholipid metabolism in acute myocardial ischemia].
The effect of phosphocreatine and phosphocreatinine on changes in crude lysophosphoglycerides (LPG) in the plasmatic membranes of canine heart, induced by short-term ischemia (an 8-minute-long occlusion of the left descending coronary artery), was examined. Ischemia caused a considerable rise in LPG level, with a mean 83% rise in lysophosphatidyl choline and a 168% rise in lysophosphatidyl ethanolamine. Intravenous administration of 300 mg/kg phosphocreatine or phosphocreatinine completely prevented the accumulation of LPG in the ischemic area. Since LPG have pronounced arrhythmogenic properties, the data obtained suggest that anti-arrhythmic activity of phosphocreatine and phosphocreatinine in acute myocardial ischemia results from the effect these substances have on membrane phospholipid metabolism in the ischemized area.


Effects of Exogenous Androgens on Platelet Activity and Their Thrombogenic Potential in Supraphysiological Administration: A Literature Review.
Anabolic androgenic steroids (AAS), simply called "androgens", represent the most widespread drugs used to enhance performance and appearance in a sporting environment. High-dosage and/or long-term AAS administration has been associated frequently with significant alterations in the cardiovascular system, some of these with severe endpoints. The induction of a prothrombotic state is probably the most life-threatening consequence, suggested by numerous case reports in AAS-abusing athletes, and by a considerable number of human and animal studies assessing the influence of exogenous androgens on hemostasis. Despite over fifty years of research, data regarding the thrombogenic potential of exogenous androgens are still scarce. The main reason is the limited possibility of conducting human prospective studies. However, human observational studies conducted in athletes or patients, in vitro human studies, and animal experiments have pointed out that androgens in supraphysiological doses induce enhanced platelet activity and thrombopoiesis, leading to increased platelet aggregation. If this tendency overlaps previously existing coagulation and/or fibrinolysis dysfunctions, it may lead to a thrombotic diathesis, which could explain the multitude of thromboembolic events reported in the AAS-abusing population. The influence of androgen excess on the platelet activity and fluid-coagulant balance remains a subject of debate, urging for supplementary studies in order to clarify the effects on hemostasis, and to provide new compelling evidence for their claimed thrombogenic potential.


Depression and prescription opioid misuse among chronic opioid therapy recipients with no history of substance abuse.
Opioid misuse in the context of chronic opioid therapy (COT) is a growing concern. Depression may be a risk factor for opioid misuse, but it has been difficult to tease out the contribution of co-occurring substance abuse. This study aims to examine whether there is an association between depression and opioid misuse in patients receiving COT who have no history of substance abuse. A telephone survey was conducted at Group Health Cooperative and Kaiser Permanente of Northern California. We interviewed 1,334 patients on COT for noncancer pain who had no history of substance abuse. Patients were asked about 3 forms of opioid misuse: (1) self-medicating for symptoms other than pain, (2) self-increasing doses, and (3) giving to or getting opioids from others. Depression was evaluated by the 8-item Patient Health Questionnaire (PHQ-8). Compared with patients who were not depressed (PHQ-8 score 0 to 4), patients with moderate depression (PHQ-8 score 10 to 14) and severe depression (PHQ-8 score 15 or higher) were 1.8 and 2.4 times more likely, respectively, to misuse their opioid medications for non-pain symptoms. Patients with mild (PHQ-8 score 5 to 9), moderate, and severe depression were 1.9, 2.9, and 3.1 times more likely, respectively, to misuse their opioid medications by self-increasing their dose. There was no statistically significant association between depression and giving opioids to or getting them from others. In patients with no substance abuse history, depressive symptoms are associated with increased rates of some forms of self-reported opioid misuse. Clinicians should be alert to the risk of patients with depressive symptoms using opioids to relieve these symptoms and thereby using more opioids than prescribed.


Serine palmitoyltransferase assembles at ER-mitochondria contact sites.
The accumulation of sphingolipid species in the cell contributes to the development of obesity and neurological disease. However, the subcellular localization of sphingolipid-synthesizing enzymes is unclear, limiting the understanding of where and how these lipids accumulate inside the cell and why they are toxic. Here, we show that SPTLC2, a subunit of the serine palmitoyltransferase (SPT) complex, catalyzing the first step in de novo sphingolipid synthesis, localizes dually to the ER and the outer mitochondrial membrane. We demonstrate that mitochondrial SPTLC2 interacts and forms a complex in trans with the ER-localized SPT subunit SPTLC1. Loss of SPTLC2 prevents the synthesis of mitochondrial sphingolipids and protects from palmitate-induced mitochondrial toxicity, a process dependent on mitochondrial ceramides. Our results reveal the in trans assembly of an enzymatic complex at an organellar membrane contact site, providing novel insight into the localization of sphingolipid synthesis and the composition and function of ER-mitochondria contact sites.


Patient acceptability of 3D printed medicines.
Patient-centric medicine is a derivative term for personalised medicine, whereby the pharmaceutical product provides the best overall benefit by meeting the comprehensive needs of the individual; considering the end-user from the beginning of the formulation design process right through development to an end product is a must. One way in which to obtain personalised medicines, on-site and on-demand is by three-dimensional printing (3DP). The aim of this study was to investigate the influence of the shape, size and colour of different placebo 3D printed tablets (Printlets™) manufactured by fused deposition modelling (FDM) 3DP on end-user acceptability regarding picking and swallowing. Ten different printlet shapes were prepared by 3DP for an open-label, randomised, exploratory pilot study with 50 participants. Participant-reported outcome (PRO) and researcher reported outcome (RRO) were collected after picking and swallowing of selected printlet geometries including sphere, torus, disc, capsule and tilted diamond shapes. The torus printlet received the highest PRO cores for ease of swallowing and ease of picking. Printlets with a similar appearance to conventional formulations (capsule and disc shape) were also found to be easy to swallow and pick which demonstrates that familiarity is a critical acceptability attribute for end-users. RRO scores were in agreement with the PRO scores. The sphere was not perceived to be an appropriate way of administering an oral solid medicine. Smaller printlet sizes were found to be preferable; however it was found that the perception of size was driven by the type of shape. Printlet colour was also found to affect the perception of the end-user. Our study is the first to guide the pharmaceutical industry towards developing patient-centric medicine in different geometries via 3DP. Overall, the highest acceptability scores for torus printlets indicates that FDM 3DP is a promising fabrication technology towards increasing patient acceptability of solid oral medicines.


Mechanistic interplay between ceramide and insulin resistance.
Recent research adds to a growing body of literature on the essential role of ceramides in glucose homeostasis and insulin signaling, while the mechanistic interplay between various components of ceramide metabolism remains to be quantified. We present an extended model of C16:0 ceramide production through both the de novo synthesis and the salvage pathways. We verify our model with a combination of published models and independent experimental data. In silico experiments of the behavior of ceramide and related bioactive lipids in accordance with the observed transcriptomic changes in obese/diabetic murine macrophages at 5 and 16 weeks support the observation of insulin resistance only at the later phase. Our analysis suggests the pivotal role of ceramide synthase, serine palmitoyltransferase and dihydroceramide desaturase involved in the de novo synthesis and the salvage pathways in influencing insulin resistance versus its regulation.


No association between polymorphisms of neuronal oxide synthase 1 gene (NOS1) and schizophrenia in a Japanese population.
The neuronal nitric oxide synthase gene (NOS1) is located on 12q24, in a susceptibility region for schizophrenia, and produces nitric oxide (NO) in the brain. NO plays a role in neurotransmitter release and is the second messenger of the N-methyl-D-aspartate (NMDA) receptor. Furthermore, it is connected to the dopaminergic and serotonergic neural transmission systems. Therefore, abnormalities in the NO pathway are thought to be involved in the pathophysiology of schizophrenia. Several genetic studies showed an association of NOS1 with schizophrenia. However, results of replication studies have been inconsistent. Therefore, we conducted a replication study of NOS1 with schizophrenia in a Japanese sample. We selected seven SNPs (rs41279104, rs3782221, rs3782219, rs561712, rs3782206, rs2682826, and rs6490121) in NOS1 that were positively associated with schizophrenia in previous studies. Two SNPs showed an association with Japanese schizophrenic patients (542 cases and 519 controls, rs3782219: P allele = 0.0291 and rs3782206: P allele = 0.0124, P genotype = 0.0490), and almost these significances remained with an increased sample size (1154 cases and 1260 controls, rs3782219: P allele = 0.0197 and rs3782206: P allele = 0.0480). However, these associations also might have resulted from type I error on account of multiple testing (rs3782219: P allele = 0.133 and rs3782206: P allele = 0.168). In conclusion, we could not replicate the association between seven SNPs in NOS1 and schizophrenia found in several earlier studies, using larger Japanese schizophrenia and control samples.


Effects of testosterone treatment on body composition in males with testosterone deficiency syndrome.
We evaluated the safety of testosterone treatment and its efficacy on body composition in males with testosterone deficiency syndrome (TDS) over 24 months. 50 males aged 50-65 years with TDS (Aging Males Symptoms Scale [AMS] > 26 and calculated free testosterone [cFT] 250 pmol/l) were administered 50 mg testosterone gel daily for one year. During the second year, patients received 1000 mg of testosterone undecanoate every 2-3 months. Outcome measures were clinical chemistry values and total testosterone; sex hormone-binding globulin and cFT, changes in AMS and International Prostate Symptom Score; and changes in body composition measured by dual-energy-x-ray absorptiometry. There were no clinically significant changes in clinical chemistry safety parameters. There were significant improvements in both total and cFT and in AMS scores after three months (p < 0.001). Lean mass increased 2.35% at 12 months and 4.5% at 24 months, but proportionally more muscle mass was gained in arms and legs than in the trunk. Fat mass decreased 4.2% at 12 months and 9.1% at 24 months. Testosterone treatment in males with TDS leads to body changes affecting lean and fat mass with significant improvement in AMS scores, and has an excellent safety profile.


Spine kinematics exhibited during the stop-jump by physically active individuals with adolescent idiopathic scoliosis and spinal fusion.
Individuals with adolescent idiopathic scoliosis post spinal fusion often return to exercise and sport. However, the movements that individuals with spinal fusion for adolescent idiopathic scoliosis (SF-AIS) use to compensate for the loss of spinal flexibility during high-effort tasks are not known. The objective of this study was to compare the spinal kinematics of the trunk segments displayed during the stop-jump, a maximal effort task, between SF-AIS and healthy control groups. The study used a case-controlled design. Ten SF-AIS (physically active, posterior-approach spinal fusion: 11.2±1.9 fused segments, postop time: 2±.6 years) and nine control individuals, pair matched for gender, age (17.4±1.3 years and 20.6±1.5 years, respectively), mass (63.50±12.2 kg and 66. 40±10.9 kg), height (1.69±.09 m and 1.72±.08 m), and level of physical activity, participated in the study. Individuals with spinal fusion for adolescent idiopathic scoliosis and controls (CON) performed five acceptable trials of the stop-jump task. Spatial locations of 21 retroreflective trunk and pelvis markers were recorded via high-speed motion capture methodology. Mean differences and analysis of covariance (jump height=covariate, p<.05) were used to compare the groups' relative angle (RelAng) and segmental angle (SegAng) of the three trunk segments (trunk segments=upper trunk [C7-T8], middle trunk [MT: T9-T12], lower trunk [LT: L1-L5]) for each rotation plane in the three phases of interest (flight, stance, and the vertical flight phases). No significant group differences for jump height and RelAng were detected in the three phases of stop-jump. Individuals with spinal fusion for adolescent idiopathic scoliosis displayed 3.2° greater transverse plane RelAng of LT compared with CON (p=.059) in the stance phase. Group differences for RelAng ranged from 0° to 15.3°. For SegAng in the stance phase, LT demonstrated greater SegAng in the sagittal and frontal planes (mean difference: 3.2°-6.2°), whereas SegAng for MT was 5.1° greater in the sagittal plane and had a tendency of 2° greater displacement in the frontal plane (p=.070). In the vertical flight phase, greater LT displacement in the frontal plane was observed for SF-AIS than CON. In the flight phase, LT had a tendency for greater SegAng for SF-AIS than for CON in the transverse plane (p=.089). Overall, SF-AIS who participate in physical activity on a regular basis are able to demonstrate similar trunk kinematics during a high-intensity stop-jump task as their matched healthy peers. Fewer group differences for relative angular displacements of the spine were observed than anticipated. This finding suggests that the fused MT appeared to be moving synchronously with the LT, thereby suggesting a compensatory adaptation of SF-AIS to achieve sufficient trunk movements during this high-effort movement.


A Clinicopathological Study of Benign Phyllodes Tumour of Breast with Emphasis on Unusual Features.
Benign Phyllodes Tumours (PTs) are rare fibroepithelial neoplasms that resemble fibroadenoma. But unlike fibroadenoma, benign PT can recur and both stromal & epithelial components can progress to malignancy. Contrary to earlier belief that benign PT is a stromal neoplasm and possibly arises from fibroadenoma, more recent molecular studies have suggested that both stroma and epithelium can become neoplastic. Sometimes, benign PT can occur synchronously with fibroadenoma. Here histomorphologic analysis of eleven cases of benign PT are presented including some unusual features. Eleven cases of benign PT diagnosed between Dec 2014 and Jan 2016 in the Department of Pathology were studied. The demographic and clinicopathological features were analysed. The most common age group affected was 20-30 years (range: 13-45). Clinical features included pain, lump and bleeding from nipple. The tumour size varied from 2.5-18 cm in diameter. H&E stained sections showed secondary changes (haemorrhage, myxoid, change, cystic degeneration), epithelial hyperplasia (8), squamous & columnar metaplasia (1), benign tubular adenoma like areas (1), Ductal Carcinoma In Situ (DCIS) (1), Invasive Ductal Carcinoma (IDC) (1), Pseudoangiomatous Stromal Hyperplasia (PASH) (1), histologic infarction (2), tumour necrosis (1) and synchronous fibroadenoma (1). Unusual histologic features included atypical ductal hyperplasia, DCIS, IDC, synchronous fibroadenoma and tubular adenoma like areas arising within benign PT. This study shows a spectrum of hyperplastic, metaplastic, dysplastic, benign, in-situ-malignancy and even invasive ductal malignancy occurring in benign PT. Therefore adequate and extensive sampling is recommended for accurate diagnosis.


Parent reported home smoking bans and toddler (18-30 month) smoke exposure: a cross-sectional survey.
To study the relation between the use of parent reported home smoking bans and smoke exposure among children aged 18-30 months. A total of 309 smoking households with children aged 18-30 months, who were part of the Coventry Cohort study, consented to participate in this cross-sectional survey. Although parents in almost 88% of smoking households reported using harm reduction strategies to protect their toddlers from smoke exposure, only 13.9% reported smoking bans in the house. Mean log urinary cotinine:creatinine ratio was significantly lower for those children whose parents reported no smoking in the house (1.11, 95% CI 0.64 to 1.49) compared with none/less strict strategies (1.87, 95% CI 1.64 to 2.10). In linear regression models fitted on log cotinine:creatinine ratio, no smoking in the house was independently associated with a significant reduction in cotinine:creatinine ratio (B = -0.55, 95% CI -0.89 to -0.20) after adjusting for mother's and partner's average daily cigarette consumption, housing tenure, and overcrowding. The final model accounted for 44.3% of the variance. Not smoking in the house was associated with a reduction in mean urinary cotinine:creatinine ratio in children aged 18-30 months; the relation persisted after adjustment for levels of mother's and partner's daily cigarette consumption and sociodemographic factors. Results suggest that home smoking bans in this age group have a small but significant effect on smoke exposure independent of levels of parental tobacco consumption.


Antiestrogen-induced remissions in stage IV breast cancer.
Tamoxifen (NSC-180973, ICI-46474), an antiestrogen, was administered to 39 women with stage IV breast cancer at a dose of 20 mg orally every 12 hours. Patients were selected as eligible for endocrine ablative treatment and with disease not so aggressive as to jeopardize further treatment in case the experimental drug failed. Objective remission was obtained in 19 patients (49%) with a mean duration of 11+ months and ten patients are still in remission. No progression was seen in seven patients (18%) lasting 13+ months with only one patient in relapse. Thirteen patients (33%) have failed. Objective remission was obtained in two premenopausal women even though menstrual cycles were not suppressed; bilateral oophorectomy in one of these patients induced a second remission after relapse from tamoxifen. Objective remissions were obtained in two women with proven complete hypophysectomy a direct action of antiestrogens at the tumor level. Positive estrogen receptors were suggestive of being a good predictor of response. Menopausal status and dominant site of metastasis did not affect the response to tamoxifen in this small series. Tamoxifen did not alter prolactin secretion, and side effects from the drug were usually mild and transient in nature. We conclude that tamoxifen is an effective antitumor agent in patients with stage IV breast cancer; further studies are necessary to determine whether it will equal the therapeutic effect of oophorectomy, adrenalectomy, and hypophysectomy.


Liquid membrane electrodes for the selective determination of nicotine in cigarette smoke.
Five liquid membrane electrode systems responsive to the nicotinium cation are described. These electrodes are based on the use of the ion-association complexes of the nicotinium cation with tetraphenylborate, 5-nitrobarbiturate, flavianate, reineckate and picrolonate counter anions in nitrobenzene solvent as ion-exchange sites. The performance characteristics of these electrodes, evaluated according to IUPAC recommendations, reveal fast, stable and near-Nernstian responses for 10(-2)-10(-5) M nicotine over the pH range 3.5-7. Many inorganic and organic cations do not interfere. The direct potentiometric determination of 3 micrograms ml-1-1.6 mg ml-1 of nicotine in aqueous solutions showed an an average recovery of 99.5% and a mean standard deviation of 1.2%. The electrodes were also used for monitoring the titration of nicotine with sodium tetraphenylborate, measuring the pK of nicotine and determining nicotine in the smoke from different cigarettes. The results compare favourably with those obtained by the standard gas chromatographic method.


[Organization of the treatment of children with cranio-cerebral injuries].
The character of craniocerebral injuries in 2743 children admitted to a children's traumatological division within 1976 to 1979 is analyzed. Clinical data characterizing craniocerebral injuries of various gravity are presented, and principles of individualized treatment of the patients are described. A great diagnostic value of special examination methods, such as cerebrospinal fluid examination, electroencephalography, rheoencephalography, and electromyography is demonstrated. The multiform neuropsychic changes revealed in most of 192 children on subsequent clinico-psychological examinations stress the urgent necessity of purposeful rehabilitation measures.


Characterization of detergent-insoluble proteins in ALS indicates a causal link between nitrative stress and aggregation in pathogenesis.
Amyotrophic lateral sclerosis (ALS) is a progressive and fatal motor neuron disease, and protein aggregation has been proposed as a possible pathogenetic mechanism. However, the aggregate protein constituents are poorly characterized so knowledge on the role of aggregation in pathogenesis is limited. We carried out a proteomic analysis of the protein composition of the insoluble fraction, as a model of protein aggregates, from familial ALS (fALS) mouse model at different disease stages. We identified several proteins enriched in the detergent-insoluble fraction already at a preclinical stage, including intermediate filaments, chaperones and mitochondrial proteins. Aconitase, HSC70 and cyclophilin A were also significantly enriched in the insoluble fraction of spinal cords of ALS patients. Moreover, we found that the majority of proteins in mice and HSP90 in patients were tyrosine-nitrated. We therefore investigated the role of nitrative stress in aggregate formation in fALS-like murine motor neuron-neuroblastoma (NSC-34) cell lines. By inhibiting nitric oxide synthesis the amount of insoluble proteins, particularly aconitase, HSC70, cyclophilin A and SOD1 can be substantially reduced. Analysis of the insoluble fractions from cellular/mouse models and human tissues revealed novel aggregation-prone proteins and suggests that nitrative stress contribute to protein aggregate formation in ALS.


#CRCFREE: Using Social Media to Reduce Colorectal Cancer Risk in Rural Adults.
Objectives: In this study, we pilot-tested #CRCFree, a Facebook-based intervention aimed at reducing colorectal cancer (CRC) risk in rural Appalachian adults at risk for CRC. Methods: Participants were 56 rural Appalachian adults aged > 50 years. Daily #CRCFree Facebook posts addressed diet, physical activity, and CRC screening. Participants' sociodemographics, diet, body mass index, physical activity, and CRC screening status were measured pre- and post-intervention. The Healthy Eating Index (HEI) and the Dietary Inflammatory Index (DII) assessed dietary patterns. Facebook engagement was measured throughout the intervention. A post-intervention focus group evaluated intervention acceptability. Results: Participants were Caucasian, aged 58 ± 6 years, and predominantly female (66%). Post-intervention, HEI scores increased (49.9 ± 9.9 vs 58.6 ± 12.1, p = <.001), and DII scores decreased from baseline (2.8 ± 1.1 vs 1.6 ± 1.7, p = .002). There was no change in physical activity, BMI, or CRC screening status. Focus group participants found the intervention to be educational and motivating. Conclusions: These results provide preliminary evidence to support using Facebook to address CRC risk in this population. Participants were responsive to this intervention, and Facebook is a novel and accessible modality for health promotion.


Evolution of Cellular Immunity Effector Cells; Perspective on Cytotoxic and Phagocytic Cellular Lineages.
The immune system has evolved to protect organisms from infections caused by bacteria, viruses, and parasitic pathogens. In addition, it provides regenerative capacities, tissue maintenance, and self/non-self recognition of foreign tissues. Phagocytosis and cytotoxicity are two prominent cellular immune activities positioned at the base of immune effector function in mammals. Although these immune mechanisms have diversified into a wide heterogeneous repertoire of effector cells, it appears that they share some common cellular and molecular features in all animals, but also some interesting convergent mechanisms. In this review, we will explore the current knowledge about the evolution of phagocytic and cytotoxic immune lineages against pathogens, in the clearance of damaged cells, for regeneration, for histocompatibility recognition, and in killing virally infected cells. To this end, we give different immune examples of multicellular organism models, ranging from the roots of bilateral organisms to chordate invertebrates, comparing to vertebrates' lineages. In this review, we compare cellular lineage homologies at the cellular and molecular levels. We aim to highlight and discuss the diverse function plasticity within the evolved immune effector cells, and even suggest the costs and benefits that it may imply for organisms with the meaning of greater defense against pathogens but less ability to regenerate damaged tissues and organs.


Vena cava filter use in cancer patients with acute venous thromboembolism in California.
Few studies have evaluated the use of vena cava filters (VCF) in cancer patients with acute venous thromboembolism (VTE). Hospital discharge records of patients who were admitted with a principal diagnosis of lower extremity deep-vein thrombosis or pulmonary embolism and cancer in California between January 1, 2005 and December 31, 2009 were analyzed. Multivariable logistic regression analysis was used to identify variables associated with VCF use. A VCF was placed in 2747 (19.6%) of 14,000 cancer patients. The percentage of patients treated with a VCF varied widely across hospitals, from 0% to 52% (mean=19.2%, median=17.2%), and by cancer type, ranging from 8% for lip/oral to 43% for brain. Using multivariable analysis, the strongest predictors of VCF use were a diagnosis of brain cancer (OR=4.6, CI: 3.7 -5.6), undergoing major surgery (OR=4.9, CI: 3.9 -6.1), and bleeding (OR=2.7, CI: 2.0-3.5). Other factors significantly associated with VCF insertion included hospital characteristics (larger, urban and private), and greater severity-of-illness at the time of admission. Only 1083 (7.7%) of patients had an absolute contraindication to anticoagulation (bleeding or surgery). A VCF was deployed in approximately 20% of acute VTE patients with cancer, but use varied widely between hospitals and cancer types. The strongest risk factors were undergoing surgery, active bleeding, and having brain cancer. Only 21% of VCF treated cancer patients had a strict contraindication to anticoagulation therapy. Further research is needed to determine if VCF use is of any benefit in cancer patients with acute VTE.


Evolved Aztreonam Resistance Is Multifactorial and Can Produce Hypervirulence in Pseudomonas aeruginosa.
While much attention has been focused on acquired antibiotic resistance genes, chromosomal mutations may be most important in chronic infections where isolated, persistently infecting lineages experience repeated antibiotic exposure. Here, we used experimental evolution and whole-genome sequencing to investigate chromosomally encoded mutations causing aztreonam resistance in Pseudomonas aeruginosa and characterized the secondary consequences of resistance development. We identified 19 recurrently mutated genes associated with aztreonam resistance. The most frequently observed mutations affected negative transcriptional regulators of the mexAB-oprM efflux system and the target of aztreonam, ftsI While individual mutations conferred modest resistance gains, high-level resistance (1,024 µg/ml) was achieved through the accumulation of multiple variants. Despite being largely stable when strains were passaged in the absence of antibiotics, aztreonam resistance was associated with decreased in vitro growth rates, indicating an associated fitness cost. In some instances, evolved aztreonam-resistant strains exhibited increased resistance to structurally unrelated antipseudomonal antibiotics. Surprisingly, strains carrying evolved mutations which affected negative regulators of mexAB-oprM (mexR and nalD) demonstrated enhanced virulence in a murine pneumonia infection model. Mutations in these genes, and other genes that we associated with aztreonam resistance, were common in P. aeruginosa isolates from chronically infected patients with cystic fibrosis. These findings illuminate mechanisms of P. aeruginosa aztreonam resistance and raise the possibility that antibiotic treatment could inadvertently select for hypervirulence phenotypes.IMPORTANCE Inhaled aztreonam is a relatively new antibiotic which is being increasingly used to treat cystic fibrosis patients with Pseudomonas aeruginosa airway infections. As for all antimicrobial agents, bacteria can evolve resistance that decreases the effectiveness of the drug; however, the mechanisms and consequences of aztreonam resistance are incompletely understood. Here, using experimental evolution, we have cataloged spontaneous mutations conferring aztreonam resistance and have explored their effects. We found that a diverse collection of genes contributes to aztreonam resistance, each with a small but cumulative effect. Surprisingly, we found that selection for aztreonam resistance mutations could confer increased resistance to other antibiotics and promote hypervirulence in a mouse infection model. Our study reveals inherent mechanisms of aztreonam resistance and indicates that aztreonam exposure can have unintended secondary effects.


Determining the gaps between Cochrane reviews and trials of effectiveness of interventions for acute respiratory infections: an audit.
Cochrane primarily aims to systematically review trials of effectiveness that are important to inform clinical decisions. Editorial groups support authors to achieve high-quality reviews and prioritise review proposals in their clinical domain that are submitted or elicited. Prioritising proposals requires two approaches, identifying (1) clinical practises for which the evidence of effectiveness is uncertain and (2) interventions in which there are trials of effectiveness (especially randomised controlled trials (RCTs)) not systematically reviewed. This study addresses this second approach for the Cochrane Acute Respiratory Infections Group (CARIG) in order to identify RCTs of acute respiratory infections that have not been systematically reviewed. We exported, on the 9th of September 2014, and then compared the group's trials register of RCTs against a list of current Cochrane ARI (systematic) Reviews to identify gaps in topics (the same intervention and health condition) where completed trials have not been systematically reviewed. We assigned a principle intervention and health condition to each of 157 Cochrane reviews (CRs) and 5393 RCTs. A majority of topics had been systematically reviewed; however, a substantial number (2174 or 41%) of RCTs were not included in any review. The topic that had been systematically reviewed the most was antibiotic vs placebo for pneumonia with 11 CRs and 205 RCTs. The topic that was the subject of most RCTs was vaccination for influenza with 525 RCTs and 6 CRs. Also, 6 CRs had no RCTs ('empty reviews'). We identified many RCT topics that have not been systematically reviewed. They need to be addressed in a separate process to establish their priority to clinicians.


Monocytic Cell Adhesion to Oxidised Ligands: Relevance to Cardiovascular Disease.
Atherosclerosis, the major cause of vascular disease, is an inflammatory process driven by entry of blood monocytes into the arterial wall. LDL normally enters the wall, and stimulates monocyte adhesion by forming oxidation products such as oxidised phospholipids (oxPLs) and malondialdehyde. Adhesion molecules that bind monocytes to the wall permit traffic of these cells. CD14 is a monocyte surface receptor, a cofactor with TLR4 forming a complex that binds oxidised phospholipids and induces inflammatory changes in the cells, but data have been limited for monocyte adhesion. Here, we show that under static conditions, CD14 and TLR4 are implicated in adhesion of monocytes to solid phase oxidised LDL (oxLDL), and also that oxPL and malondialdehyde (MDA) adducts are involved in adhesion to oxLDL. Similarly, monocytes bound to heat shock protein 60 (HSP60), but this could be through contaminating lipopolysaccharide. Immunohistochemistry on atherosclerotic human arteries demonstrated increased endothelial MDA adducts and HSP60, but endothelial oxPL was not detected. We propose that monocytes could bind to MDA in endothelial cells, inducing atherosclerosis. Monocytes and platelets synergized in binding to oxLDL, forming aggregates; if this occurs at the arterial surface, they could precipitate thrombosis. These interactions could be targeted by cyclodextrins and oxidised phospholipid analogues for therapy.


Characterization of prostate microstructure using water diffusion and NMR relaxation.
For many pathologies, early structural tissue changes occur at the cellular level, on the scale of micrometers or tens of micrometers. Magnetic resonance imaging (MRI) is a powerful non-invasive imaging tool used for medical diagnosis, but its clinical hardware is incapable of reaching the cellular length scale directly. In spite of this limitation, microscopic tissue changes in pathology can potentially be captured indirectly, from macroscopic imaging characteristics, by studying water diffusion. Here we focus on water diffusion and NMR relaxation in the human prostate, a highly heterogeneous organ at the cellular level. We present a physical picture of water diffusion and NMR relaxation in the prostate tissue, that is comprised of a densely-packed cellular compartment (composed of stroma and epithelium), and a luminal compartment with almost unrestricted water diffusion. Transverse NMR relaxation is used to identify fast and slow T 2 components, corresponding to these tissue compartments, and to disentangle the luminal and cellular compartment contributions to the temporal evolution of the overall water diffusion coefficient. Diffusion in the luminal compartment falls into the short-time surface-to-volume (S/V) limit, indicating that only a small fraction of water molecules has time to encounter the luminal walls of healthy tissue; from the S/V ratio, the average lumen diameter averaged over three young healthy subjects is measured to be 217.7±188.7 μm. Conversely, the diffusion in the cellular compartment is highly restricted and anisotropic, consistent with the fibrous character of the stromal tissue. Diffusion transverse to these fibers is well described by the random permeable barrier model (RPBM), as confirmed by the dynamical exponent ϑ = 1/2 for approaching the long-time limit of diffusion, and the corresponding structural exponent p = -1 in histology. The RPBM-derived fiber diameter and membrane permeability were 19.8±8.1 μm and 0.044±0.045 μm/ms, respectively, in agreement with known values from tissue histology and membrane biophysics. Lastly, we revisited 38 prostate cancer cases from a recently published study, and found the same dynamical exponent ϑ = 1/2 of diffusion in tumors and benign regions. Our results suggest that a multi-parametric MRI acquisition combined with biophysical modeling may be a powerful non-invasive complement to prostate cancer grading, potentially foregoing biopsies.


Evaluation of medication adherence and its relevant factors among hypertensive patients: A cross-sectional study in Shahrekord health-care system.
Medication adherence means compliance with patient adherence to medication orders, including timely and correct consumption of medication prescribed by a physician. The present study aimed to determine the extent of adherence to hypertension drug medication in patients covered by comprehensive health service centers of Shahrekord, Iran. A cross-sectional study examined 401 hypertensive patients registered in the Integrated Health Record System (SIB). SIB is a Persian term related to Health Record System. To collect data, Morisky Medication Adherence Scale was used. The questionnaire was completed by the patients and analyzed using SPSS (SPSS Inc., Chicago, Illinois, USA, version 26), Chi-square test, independent t-test, and analysis of variance. The results indicated that adherence to antihypertensive medication was low in 5.7% of patients, while 63.3% of patients had sufficient compliance. Forgetting to take medications (52.9%) was the most common reason for nonadherence to medication in hypertensive patients. Given that forgetting to take medications was the main reason for nonadherence to medication in hypertensive patients, designing and implementing necessary trainings by comprehensive health centers to realize the importance of daily use of medication by hypertensive patients and their families are recommended.


Genetic and morphological differentiation in Populus nigra L.: isolation by colonization or isolation by adaptation?
Identifying processes underlying the genetic and morphological differences among populations is a central question of evolutionary biology. Forest trees typically contain high levels of neutral genetic variation, and genetic differences are often correlated with geographic distance between populations [isolation by distance (IBD)] or are due to historic vicariance events [isolation by colonization (IBC)]. In contrast, morphological differences are largely due to local adaptation. Here, we examined genetic (microsatellite) and morphological (from a common garden experiment) variation in Populus nigra L., European black poplar, collected from 13 sites across western Europe and grown in a common garden in Belgium. Significant genetic differentiation was observed, with populations from France displaying greater admixture than the distinct Spanish and central European gene pools, consistent with previously described glacial refugia (IBC). Many quantitative traits displayed a bimodal distribution, approximately corresponding to small-leaf and large-leaf ecotypes. Examination of nine climatic variables revealed the sampling locations to have diverse climates, and although the correlation between morphological and climatic differences was significant, the pattern was not consistent with strict local adaptation. Partial Mantel tests based on multivariate summary statistics identified significant residual correlation in comparisons of small-leaf to large-leaf ecotypes, and within the small-leaf samples, but not within large-leaf ecotypes, indicating that variation within the small-leaf morphotype in particular may be adaptive. Some small-leaf populations experience climates very similar to those in large-leaf sites. We conclude that adaptive differentiation and persistent IBC acted in combination to produce the genetic and morphological patterns observed in P. nigra.


Getting evidence-based pressure ulcer prevention into practice: a multi-faceted unit-tailored intervention in a hospital setting.
The aim of the study was to evaluate whether a multi-faceted, unit-tailored intervention using evidenced-based pressure ulcer prevention affects (i) the performance of pressure ulcer prevention, (ii) the prevalence of pressure ulcers and (iii) knowledge and attitudes concerning pressure ulcer prevention among registered and assistant nurses. A quasi-experimental, clustered pre- and post-test design was used. Five units at a hospital setting were included. The intervention was based on the PARIHS framework and included a multi-professional team, training and repeated quality measurements. An established methodology was used to evaluate the prevalence and prevention of pressure ulcers. Nurses' knowledge and attitudes were evaluated using a validated questionnaire. A total of 506 patients were included, of whom 105 patients had a risk to develop pressure ulcer. More patients were provided pressure ulcer prevention care (P = 0·001) and more prevention care was given to each patient (P = 0·021) after the intervention. Corresponding results were shown in the group of patients assessed as being at risk for developing pressure ulcers. Nurses' knowledge about pressure ulcer prevention increased (P < 0·001). Positive attitudes towards pressure ulcer prevention remained high between pre- and post-test surveys. This multi-faceted unit-tailored intervention affected pressure ulcer prevention. Facilitation and repeated quality measurement together with constructed feedback of results seemed to be the most important factor for pressure ulcer prevention.


Age-related changes in red blood cell complement regulatory proteins and susceptibility to severe malaria.
Severe malaria-associated anemia and cerebral malaria are life-threatening complications of Plasmodium falciparum infection. Red blood cell (RBC) complement regulatory proteins (CRPs) have been implicated in the pathogenesis of both. We sought to determine whether there are age-related changes in the expression of CRPs that could explain the susceptibility to severe malaria-associated anemia in young children and the susceptibility to cerebral malaria in older children and adults. In cross-sectional surveys in malaria-endemic and -nonendemic areas of Kenya and in Reims, France, the level of RBC CRPs was lowest in young children and increased into adulthood. In case-control studies, patients with cerebral malaria and matched control subjects had higher levels of RBC CRPs than did patients with severe anemia and matched control subjects, especially during convalescence. We conclude that RBC CRP levels vary with age and that the lower levels of these proteins in young children in areas of high transmission, such as western Kenya, may place these children at greater risk of severe malaria-associated anemia than cerebral malaria.


Correlating the effect of pretreatment on the enzymatic hydrolysis of straw.
Avicell, Alkali-treated straw cellulose (ATSC), and wheat straw were ball-milled to reduce crystallinity; wheat straw was delignified by hot (120 degrees C) sodium hydroxide solutions of various concentrations. The physically and chemically pretreated cellulosic materials were hydrolyzed by the cellulases of Fusarium oxysporum strain F3. Enzymic hydrolysis data were fitted by the hyperbolic correlation of Holtzapple, which involves two kinetic parameters, the maximum conversion (X(max)), and the enzymic hydrolysis time corresponding to 50% of X(max) (t(1/2)). An empirical correlation between X(max) and cellulose crystallinity, lignin content, and degree of delignification has been found under our experimental conditions. Complete cellulose hydrolysis is shown to be possible at less than 60% crystallinity indices or less than 10% lignin content.


Magnetic resonance arthrography of labral disorders in hips with dysplasia and impingement.
Despite the fact that classic studies on osteoarthritis of the hip have shown the periphery of the hip to be prone to degeneration, it was not until recently that an abnormal acetabular labrum has been associated with osteoarthritis. This study was designed to determine whether magnetic resonance arthrography can show differences in disorders of the labrum (tears, size, ganglion formation) expected in symptomatic patients with developmental dysplasia of the hip and anterior femoroacetabular impingement. Fourteen patients in each group were evaluated preoperatively not only clinically but also with conventional radiographs and magnetic resonance arthrographs. In both conditions, disorders of the labrum localized identically with a predilection to the anterosuperior quadrant of the acetabulum. Labral tears were observed in nine hips of each group. The labrum was enlarged in 12 hips with dysplasia but in none of the hips with impingement. Ganglion formation in the periacetabular area was seen in 10 hips with dysplasia and three hips with impingement. These findings provide evidence that the anterosuperior acetabulum represents the initial fatiguing site of the hip under both conditions. Based on these data, the size of the labrum and the presence of soft tissue ganglia seem to be good predictors for the presence of developmental dysplasia, whereas the presence of tears did not differentiate between conditions. The capability of magnetic resonance arthrography to show these differences in labral disorders suggests this method is a helpful diagnostic tool that can aid in defining the most appropriate treatment strategy.


Myocardial uptake kinetics and pharmacodynamics of propafenone in the isolated perfused rabbit heart.
The myocardial disposition of propafenone was studied in an isolated perfused rabbit heart. Six hearts were perfused with a modified Krebs-Henseleit buffer containing propafenone 110 +/- 5 ng/ml. Pharmacokinetic parameters were determined by fitting the coronary sinus effluent propafenone concentration-time data to a one-compartment pharmacokinetic model. The mean half-life of myocardial uptake (T1/2d) was 22.3 +/- 5.9 min and the average time to approach steady-state tissue levels was 112 +/- 29 min. Propafenone accumulated extensively in myocardium and at equilibrium the average (+/- S.D.) myocardial concentration was 114 +/- 21 times that of the perfusate. The electrophysiological effect was measured as percentage of change of the baseline QRS duration. The half-life of onset of effect (T1/2e) and the effect at steady state were determined by fitting the effect-time data to a monoexponential function. The T 1/2e averaged 26.0 +/- 9.4 min and did not differ significantly from T 1/2d. The relationship between myocardial propafenone concentration and effect was linear but there was interexperimental variability in the slopes of the lines of this concentration-effect relationship. The interexperimental differences in steady-state effect could not be accounted for by differences in myocardial concentration.


Sex and Race Differences in N-Terminal Pro-B-type Natriuretic Peptide Concentration and Absolute Risk of Heart Failure in the Community.
Sex- and race-based differences in N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentrations are poorly understood. Clinical decisions are often informed by absolute-as opposed to relative-risk, but absolute risk of incident heart failure (HF) associated with NT-proBNP concentration across these important demographic categories is unclear. To determine whether physiologic determinants of NT-proBNP concentrations account for sex and race differences, and to more uniformly predict HF risk using NT-proBNP in these demographic subgroups. In the longitudinal Atherosclerosis Risk in Communities epidemiologic prospective community-based cohort study, the association of NT-proBNP concentration with relative and absolute risk of HF by sex- and race-based categories was assessed at study visit 2 (1990-1992) and study visit 5 (2011-2013) using Cox and Poisson regression. These data were analyzed from June 2018 to October 2021. The contribution of clinical, anthropometric, echocardiographic, and laboratory parameters to sex- and race-based differences in NT-proBNP concentration was assessed at visit 5 using linear regression. Participants included were free of HF in midlife (visit 2; a total of 12 750 participants) and late life (visit 5; a total of 5191 participants). NT-proBNP concentration. Incident HF or death. Among the 5191 HF-free participants at visit 5, the mean (SD) age was 76.0 (5.2) years, 2104 (41%) were male, 1043 (20%) were Black, and the median (IQR) NT-proBNP concentration was 124 (64-239) pg/. In both midlife and late life, NT-proBNP concentration was lowest in Black men (median [IQR] concentration: visit 2, 30 [14-67] pg/mL; visit 5, 74 [34-153] pg/mL) and highest in White women (median [IQR] concentration: visit 2, 70 [42-111] pg/mL; visit, 5, 154 [82-268] pg/mL). Sex and race differences in NT-proBNP concentration persisted after accounting for age, income, education, area deprivation index, cardiovascular diseases, left ventricular structure (LV), LV function, LV wall stress, weight and fat mass, and estimated glomerular filtration rate. Substantial differences in the absolute risk of incident HF or death existed across the sex- and race-based categories at any NT-proBNP concentration (eg, 7-fold [rate ratio, 6.7; 95% CI, 4.6-9.9] and 3-fold [rate ratio, 2.7; 95% CI, 1.7-4.1] difference at visit 2 and visit 5, respectively, at guideline-recommended thresholds) with higher risk consistently observed among Black men and lower risk in White women. Results were replicated in a cohort of participants from the Cardiovascular Health Study. In this study, sex- and race-based differences in NT-proBNP persisted after accounting for known physiologic determinants. Absolute risk associated with a given value of NT-proBNP varied substantially by sex and race. Consideration of NT-proBNP values in the context of sex and race allows for more uniform prediction of absolute risk across important demographic subgroups.


[Ambulatory surgical treatment of uncomplicated inguinal hernia with minimal local anesthesia].
At a time when scientific progress is to the forefront in the field of anesthesia, by the increased knowledge and use of anesthetic drugs and their antidotes, and by the increasing sophistication of anesthetic and intensive care apparatuses, it could appear absurd to wish to make local anesthesia in treatment of uncomplicated inguinal hernia a commonplace procedure. However, confronted with the usual risks of general anesthesia and the minimal incidence of accidents after local injection of 2% xylocaine, the authors have developed a technique of infiltration of certain key-zones to ensure maximum effectiveness of 4 to 6 cc of the compound. Results are reported of the use of the method in 100 ambulatory patients, age range 15 to 70 years, of both sexes. A full discussion on the procedure adopted follows a brief summary of the anatomy and nerve supply of the inguinal region.


Parasite-specified phagocytosis of Chlamydia psittaci and Chlamydia trachomatis by L and HeLa cells.
Phagocytosis of the 6BC strain of Chlamydia psittaci and the lymphogranuloma venereum 440L strain of Chlamydia trachomatis by L cells and HeLa 229 cells occurred at rates and to extents that were 10 to 100 times greater than those observed for the phagocytosis of Escherichia coli and polystyrene latex spheres. Both species of Chlamydia were efficiently taken up by host cells of a type they had not previously encountered. Phagocytosis of chlamydiae was brought about by the interaction of parasite surface ligands with elements of the host cell surface. The chlamydial ligands were readily denatured by heat, were masked by antibody, and were resistant to proteases and detergents. The host cell components were reversibly removed by proteases. Chlamydial phagocytosis was inhibited when host cells were incubated for many hours with cycloheximide. It was suggested that the presence on the chlamydial cell surface of ligands with high affinity for normal, ubiquitously occurring structures on the surface of host cells is an evolutionary adaptation to intracellular existence. The term parasite-specified phagocytosis was used to describe the efficient phagocytosis of chlamydiae by nonprofessional phagocytes and to distinguish it from the host-specified immunological and non-immunological phagocytosis carried out by professional phagocytes.


What triggers healthcare-seeking behaviour when experiencing a symptom? Results from a population-based survey.
The decision process of whether or not to contact the GP is influenced by different factors which have not all been well examined. The aim of this study was to analyse whether contact to the GP is associated with concern about the symptom, influence on daily activities and symptom burden, such as the total number of symptoms experienced by each person in a general population. This Danish nationwide cross-sectional study comprises a random sample of 100 000 people, representative of the adult Danish population ≥20 years. Baseline data were collected in a web-based survey conducted from June to December 2012. In total 49 706 (52.5%) individuals answered the questionnaire; 45 483 (91.5%) individuals experienced at least one of 44 predefined symptoms during the 4 weeks preceding the completion of the questionnaire. They reported 268 772 symptom experiences of which 58 370 symptoms (21.7%) resulted in contact with a GP. A high level of concern and influence on daily activities was associated with significantly higher odds for GP contact. A high burden of symptoms was associated with lower odds of contact with the GP. Approximately every fifth symptom reported by individuals from the general population leads to GP contact. Influence on daily activities, burden of symptoms, and concern about the symptom were significant factors associated with the decision of whether to contact the GP. No overall association between sex and GP contact was observed.


Retrospective reports of parental physical affection and parenting style: a study of Finnish twins.
Individual differences in parenting behaviors are due, in part, to genetic factors. In the present study, the authors sought to determine whether the degree of genetic influence varied according to the type of parental behavior under consideration. A population-based sample of 2,334 pairs of Finnish twins provided ratings on the physical affection, control, abusiveness, and indifference shown by their father and mother during childhood. Genetic influences, shared environmental influences, and nonshared environmental influences accounted for a small-to-medium proportion (17%-30%), a small-to-large proportion (22%-44%), and a medium-to-large proportion (37%-55%) of the variance in each parenting measure, respectively. There were no significant differences in effect sizes for mothers and fathers or across the 4 types of parental behavior. The genetic results may reflect characteristic styles with which parents respond to genetically influenced behaviors of individuals (gene-environment correlations) or individual perceptions of this relationship (gene-person correlation processes). The findings have implications for intervention and prevention work with families and for interpretation of evidence for interactions between genes and parenting behaviors.


Ontogenetic changes in visual sensitivity of the parasitic salmon louse Lepeophtheirus salmonis.
The salmon louse, Lepeophtheirus salmonis, is an ectoparasitic copepod of salmonid fishes whose life cycle involves two broadly defined, free-living larval stages, the nauplius and the copepodid. After settling on a host, the copepodid goes through various transformations to become a mobile adult. We recorded swimming responses of free-swimming salmon lice at the naupliar, copepodid and adult stages to the onset (ON) and offset (OFF) of lights of varying spectral irradiance and polarization. Nauplii showed a prominent swim-up OFF response across the spectrum 352-652 nm, but no ON response. Copepodids exhibited a swim-up ON response and a passive (sinking) OFF response across the same spectral range. Adults showed active swim-up responses to both ON and OFF stimuli, although the OFF response was proportionately stronger. The spectral range of the adult ON and OFF responses was the same as that of the copepodids and slightly greater than that of the nauplii, which did not exhibit responses at 652 nm. The absolute sensitivity of copepodids under white light (approx. 10(-13) photons m(2) s(1)) was higher than that of nauplii (approx. 10(-17) photons(-1) m(2 )s, OFF response) and that of adult female lice (approx. 10(-14) photons(-1)m(2)s). This suggests that the naupliar visual system is best suited for detection of shadows (e.g. the host) under a bright light field (daylight hours), while copepodids and adults may be more specialized for host detection at crepuscular periods and during the night, when light levels are low. None of the developmental stages responded to the rotation of the plane of polarized light or exhibited any difference in directed response when polarized light was used in place of diffuse light.


Identification of type A and type C virus particles in BF murine osteosarcoma.
Two types of virus particles, intracisternal type A and extracellular type C with budding, were detected in the same cells of BF osteosarcoma, its cultured cell lines, and their BFO tumors in CBA mice. The type C particles were approximately 100 microns in diameter. The buoyant density of the virions was 1.16g/ml in sucrose and 1.07 g/ml in Ficoll. A 72S RNA was demonstrated by gel electrophoresis, but no DNA was detected. Reverse transcriptase activity was also demonstrated in detergent-treated virions. Thus, the particles seem to be RNA virus. Cellular transformation and focus formation were observed after rat and mouse embryo cell monolayers were infected with the virus. The same kind of osteosarcoma was produced by inoculation of cloned transformed cells (BFOSV) of CBA embryo cells into CBA mice. Thus, the virus seems to be an oncornavirus.


The value of noncognitive factors in predicting students' first-year academic probation.
To test the value of Sedlacek's Noncognitive Questionnaire (NQ) in predicting the risk of academic probation for first-year students at the College of Human Medicine at Michigan State University. Ninety-six of 106 students completed the NQ during their first week of medical school. The NQ assesses the students in eight noncognitive domains such as academic positive self-concept and realistic self-appraisal. Using a previously derived grade-point average (GPA) and Medical College Admission Test (MCAT)-based risk-prediction equation, students were classified as high- or low-risk for first-year academic probation. At the end of their first year, students actually on probation were identified. High-risk students scored significantly higher than did low-risk students in both academic positive self-concept and realistic self-appraisal. The NQ factors alone predicted risk at a 70% accuracy rate, slightly lower than when the previously derived risk equation was used (74%). Sedlacek's noncognitive factors did not improve upon a prediction of academic probation based on GPA and MCAT scores. Sedlacek's NQ may lack the sensitivity required for use with medical students. Further research may identify more appropriate noncognitive factors.


Thyroid cancers in France and the Chernobyl accident: risk assessment and recommendations for improving epidemiological knowledge.
From 1975 to 1995, the incidence of thyroid cancer in the French population increased by a factor of 5.2 in men and 2.7 in women, thereby raising public concerns about its association with the nuclear accident at Chernobyl. A study performed at the request of French health authorities sought to quantify the potential risk of thyroid cancer associated with the Chernobyl fallout in France in order to determine if this risk could be observed through an epidemiological approach. The study focused on the most exposed population: those living in eastern France and younger than 15 y at the time of the Chernobyl nuclear power plant accident (26 April 1986). The number of spontaneous thyroid cancers in this population was predicted from French cancer registry data, and the thyroid doses were estimated from all available data about contamination in France. Associated risks were calculated with different risk models, all based on a linear no-threshold dose-effect relationship. Under this hypothesis, from 1.3 to 22 excess thyroid cancer cases were predicted for the 1991-2000 period, compared with the 212 spontaneous cases (0.5 to 10.5%) predicted, and from 11.2 to 55.2 excess cases were predicted for 1991-2015, compared with the 1,342 spontaneous cases (0.8 to 4.1%) predicted. These risk calculations indicate that the Chernobyl fallout cannot explain the entire increase in thyroid cancers in France, and that it is improbable that an epidemiological study could demonstrate such an excess. The surveillance of thyroid cancers in France should be enhanced.


Standardization of stinging insect extracts.
The measurement of IgE Ab to insects (bee etc.) can be accomplished using RAST-discs. This prevents the non-specific wheal and flare produced when skin tests in higher concentrations of either whole body or venom are used. It will also eliminate the possibility of a serious systemic reaction by direct skin testing. The in vitro neutralization of IgE antibody by pure fractions and or components employing the RAST disc method may well be a useful tool for standardization of allergens.


Photorefractive effects in tantalum-doped potassium niobate.
Photorefractive gain is measured in poled 1% tantalum-doped potassium niobate (KNbO(3)). Two-wave mixing experiments are presented which exploit the r(42) coefficient of KNbO(3) by employing nonsymmetric geometries which rotate the grating vector away from the optic axis. The effect of this rotation on the exponential gain coefficient is shown. Experimental results are compared to an analytic expression derived for this parameter. The experiments were performed using an argon laser stabilized at lambda = 514.5 nm. The light was extraordinarily polarized, and the beams were incident on the b-face of the crystal. The absorption and the response time of the crystal were measured. Losses due to scattering and phase conjugation were also investigated.


GW150914: First results from the search for binary black hole coalescence with Advanced LIGO.
On September 14, 2015 at 09:50:45 UTC the two detectors of the Laser Interferometer Gravitational-wave Observatory (LIGO) simultaneously observed the binary black hole merger GW150914. We report the results of a matched-filter search using relativistic models of compact-object binaries that recovered GW150914 as the most significant event during the coincident observations between the two LIGO detectors from September 12 to October 20, 2015. GW150914 was observed with a matched filter signal-to-noise ratio of 24 and a false alarm rate estimated to be less than 1 event per 203000 years, equivalent to a significance greater than 5.1 σ.


Prospective, randomized, double-blind study of the efficacy and tolerability of the extended-release formulations of oxybutynin and tolterodine for overactive bladder: results of the OPERA trial.
To compare the efficacy and tolerability of extended-release formulations of oxybutynin chloride and tolterodine tartrate in women with overactive bladder. The OPERA (Overactive bladder: Performance of Extended Release Agents) trial was a randomized, double-blind, active-control study performed at 71 US study centers from November 21, 2000, to October 18,2001. Extended-release formulations of oxybutynin at 10 mg/d or tolterodine at 4 mg/d were given for 12 weeks to women with 21 to 60 urge urinary incontinence (UUI) episodes per week and an average of 10 or more voids per 24 hours. Episodes of UUI (primary end point), total (urge and nonurge) incontinence, and micturition were recorded in 24-hour urinary diaries at baseline and at weeks 2, 4, 8, and 12 and compared. Adverse events were also evaluated. Improvements in weekly UUI episodes were similar for the 790 women who received extended-release formulations of oxybutynin (n = 391) or tolterodine (n = 399). Oxybutynin was significantly more effective than tolterodine in reducing micturition frequency (P = .003), and 23.0% of women taking oxybutynin reported no episodes of urinary incontinence compared with 16.8% of women taking tolterodine (P = .03). Dry mouth, usually mild, was more common with oxybutynin (P = .02). Adverse events were generally mild and occurred at low rates, with both groups having similar discontinuation of treatment due to adverse events. Reductions in weekly UUI and total incontinence episodes were similar with extended-release formulations of oxybutynin and tolterodine. In the oxybutynin group, micturition frequency was significantly lower, and the percentage of women reporting no urinary incontinence episodes was significantly higher compared with the tolterodine group. Dry mouth was more common with oxybutynin, but tolerability was otherwise comparable, including adverse events involving the central nervous system.


Cardiovascular magnetic resonance in an adult human population: serial observations from the multi-ethnic study of atherosclerosis.
The Multi-Ethnic Study of Atherosclerosis (MESA) is the first large-scale multi-ethnic population study in the U.S. to use advanced cardiovascular magnetic resonance (CMR) imaging. MESA participants were free of cardiovascular disease at baseline between 2000 and 2002, and were followed up between 2009 and 2011 with repeated CMR examinations as part of MESA. CMR allows the clinician to visualize and accurately quantify volume and dimensions of all four cardiac chambers; measure systolic and diastolic ventricular function; assess myocardial fibrosis; assess vessel lumen size, vessel wall morphology, and vessel stiffness. CMR has a number of advantages over other imaging modalities such as echocardiography, computed tomography, and invasive angiography, and has been proposed as a diagnostic strategy for high-risk populations. MESA has been extensively evaluating CMR imaging biomarkers, as markers of subclinical disease, in the last 15 years for low-risk populations. On a more practical level, some of the imaging biomarkers developed and studied are translatable to at-risk populations. In this review, we discuss the progression of subclinical cardiovascular disease and the mechanisms responsible for the transition to symptomatic clinical outcomes based on our findings from MESA.


The advantage of temporarily maintained posterior paraneurium and external epineurium for indirect nerve repair.
In this report, the advantages of temporarily maintained posterior paraneurium and external epineurium are presented during indirect nerve repair with a nerve graft. By using this technique, it is possible to overcome the retraction of the proximal and distal nerve stumps. In addition, an accurate prediction for the required length of nerve graft can be made and an optimal coaptation can be performed easily since the alignment of the fascicles is maintained.


Genetic Consequences of Biologically Altered Environments.
Evolvable traits of organisms can alter the environment those organisms experience. While it is well appreciated that those modified environments can influence natural selection to which organisms are exposed, they can also influence the expression of genetic variances and covariances of traits under selection. When genetic variance and covariance change in response to changes in the evolving, modified environment, rates and outcomes of evolution also change. Here we discuss the basic mechanisms whereby organisms modify their environments, review how those modified environments have been shown to alter genetic variance and covariance, and discuss potential evolutionary consequences of such dynamics. With these dynamics, responses to selection can be more rapid and sustained, leading to more extreme phenotypes, or they can be slower and truncated, leading to more conserved phenotypes. Patterns of correlated selection can also change, leading to greater or less evolutionary independence of traits, or even causing convergence or divergence of traits, even when selection on them is consistent across environments. Developing evolutionary models that incorporate changes in genetic variances and covariances when environments themselves evolve requires developing methods to predict how genetic parameters respond to environments-frequently multifactorial environments. It also requires a population-level analysis of how traits of collections of individuals modify environments for themselves and/or others in a population, possibly in spatially explicit ways. Despite the challenges of elucidating the mechanisms and nuances of these processes, even qualitative predictions of how environment-modifying traits alter evolutionary potential are likely to improve projections of evolutionary outcomes.


Interleukin 17 and senescent cells regulate the foreign body response to synthetic material implants in mice and humans.
Medical devices and implants made of synthetic materials can induce an immune-mediated process when implanted in the body called the foreign body response, which results in formation of a fibrous capsule around the implant. To explore the immune and stromal connections underpinning the foreign body response, we analyzed fibrotic capsules surrounding surgically excised human breast implants from 12 individuals. We found increased numbers of interleukin 17 (IL17)-producing γδ+ T cells and CD4+ T helper 17 (TH17) cells as well as senescent stromal cells in the fibrotic capsules. Further analysis in a murine model demonstrated an early innate IL17 response to implanted synthetic material (polycaprolactone) particles that was mediated by innate lymphoid cells and γδ+ T cells. This was followed by a chronic adaptive CD4+ TH17 cell response that was antigen dependent. Synthetic materials with varying chemical and physical properties implanted either in injured muscle or subcutaneously induced similar IL17 responses in mice. Mice deficient in IL17 signaling established that IL17 was required for the fibrotic response to implanted synthetic materials and the development of p16INK4a senescent cells. IL6 produced by senescent cells was sufficient for the induction of IL17 expression in T cells. Treatment with a senolytic agent (navitoclax) that killed senescent cells reduced IL17 expression and fibrosis in the mouse implant model. Discovery of a feed-forward loop between the TH17 immune response and the senescence response to implanted synthetic materials introduces new targets for therapeutic intervention in the foreign body response.


Moxifloxacin (Avelox): a novel fluoroquinolone with a broad spectrum of activity.
Moxifloxacin (Avelox) is a recently-developed fluoroquinolone that has a broad spectrum of antimicrobial activity, including typical respiratory pathogens, atypical and intracellular respiratory pathogens, Gram-negative pathogens and many anaerobes. This spectrum of activity makes moxifloxacin particularly suitable for the therapy of community-acquired respiratory tract infections. It also has enhanced activity against specific bacteria, such as Mycobacteria spp. and Legionella. Moxifloxacin has pharmacologic characteristics that support once-daily dosing regimens and dual routes of excretion that require little or no adjustment for renal or hepatic insufficiency. The drug has maintained an excellent safety profile based upon broad global usage, and no adverse events have occurred that were unanticipated. Streptococcus pneumoniae, which are resistant to earlier fluoroquinolones, are less likely to be resistant to moxifloxacin.


Supplemental ERAS application for radiology residency match: A primer.
The supplemental ERAS application that includes three components: past experiences, geographic preferences, and program signals was introduced in 2022 to complement the standard ERAS CV material. The goal was to help programs identify optimal candidates to interview and to improve the chances of applicants being invited for interviews at programs that align with their goals and interests. Based on limited data, Program signal is the most emphasized component by the programs. Applicants should realize that programs have used signals to determine who to interview (aligned with AAMC guidance), and to determine the program's candidate rank list (contrary to AAMC guidance). We have herein suggested options for leveraging benefits from the ERAS supplemental application which has now been incorporated into the full ERAS application.


[A case of hypopharyngeal ulceration due to cytomegarovirus infection].
Cytomegalovirus (CMV) is a common opportunistic infection in immunosuppressive patients. One of the organs often involved is the gastrointestinal tract, but the pharynx, especially hypopharyngeal involvement, is rare. In this report, we present a case of a 61-year-old male compromised host, admitted to the hospital for the treatment of dermatomyositis, who presented with hypopharyngeal ulceration due to cytomegalovirus infection. Multiple deep ulcerative lesions with thick belaque, or with a protruding bony edge were observed in the adjacent areas in/around the hypopharynx, which repeatedly demonstrated exacerbation and remission in a relatively short period. The lesions developed acute bleeding and required emergency operative hemostasis. The ulcerations completely disappeared after the treatment with gancyclovir. We reviewed our case as well as other cases reported so far, and extracted the points we should be aware of when we encounter a case of hypopharyngeal ulceration based on cytomegalovirus infection; 1. acute bleeding, 2. paralysis of the vocal cords and subsequent breathing difficulty, 3. pharyngeal perforation.


Interplay between microdynamics and macrorheology in vesicle suspensions.
The microscopic dynamics of objects suspended in a fluid determines the macroscopic rheology of a suspension. For example, as shown by Danker and Misbah [Phys. Rev. Lett., 2007, 98, 088104], the viscosity of a dilute suspension of fluid-filled vesicles is a non-monotonic function of the viscosity contrast (the ratio between the viscosities of the internal encapsulated and the external suspending fluids) and exhibits a minimum at the critical point of the tank-treading-to-tumbling transition. By performing numerical simulations, we recover this effect and demonstrate that it persists for a wide range of vesicle parameters such as the concentration, membrane deformability, or swelling degree. We also explain why other numerical and experimental studies lead to contradicting results. Furthermore, our simulations show that this effect even persists in non-dilute and confined suspensions, but that it becomes less pronounced at higher concentrations and for more swollen vesicles. For dense suspensions and for spherical (circular in 2D) vesicles, the intrinsic viscosity tends to depend weakly on the viscosity contrast.


Perceptions of psychosocial disability amongst psychiatric service users and caregivers in South Africa.
In many parts of South Africa there is little support for people with psychosocial disability caused by schizophrenia, beyond provision of psychotropic medications. Appropriate community-based psychosocial rehabilitation interventions are a crucial element of mental health service development. This study aimed to use an explanatory model of illness framework to document experiences of illness, disability and recovery amongst service users with schizophrenia and their caregivers in a poorly resourced area in the North West Province. Data were used to provide recommendations for a contextually appropriate non-specialist facilitated group psychosocial rehabilitation intervention. Eighteen in-depth individual interviews were conducted: nine with schizophrenia service users and nine with caregivers. Interviews were conducted by two trained field researchers; both clinical psychologists fluent in the first language of participants. All interviews were recorded, translated and transcribed. Data were thematically analysed using NVivo 9. Participants linked the illness to witchcraft, poverty and stress. Family conflict was recognised in the course of the illness, causing stress and challenges for emotional well-being. Knowledge of diagnosis and biomedical treatment was minimal. Key factors recognised by service users as promoting recovery were the ability to work, and the support of traditional healers and religious structures. Based on the findings of this study, a group psychosocial rehabilitation intervention emerged as a recommendation, with the incorporation of psycho-education, adherence support, coping skills, and opportunities for income generation and productive activity. The importance of also enlisting the support of religious leaders and traditional healers in supporting recovery is emphasised.


The benzodiazepine receptor. An update.
A short update about the data accumulated so far on the brain-specific binding sites of the benzodiazepines is the subject of this paper. Today, a large variety of biochemical and pharmacological data clearly indicates that these benzodiazepine receptors are the endogenous targets which mediate the pharmacological effects of the benzodiazepines. Furthermore, considerable evidence suggests that the benzodiazepine receptor serves as an amplifying system for GABAergic transmission by increasing the affinity of the GABA receptor. Since the physiological function of this receptor and its endogenous ligand are not yet known, one of the major topics of future research will be to finally identify the endogenous ligand(s) of the benzodiazepine receptor.


Endoscopic follow-up of Barrett's esophagus: protocol and implications.
The purpose of endoscopic surveillance in Barrett's esophagus is to detect dysplasia and to diagnose carcinoma in an early, treatable stage. Prospective trials that study the efficacy of a surveillance program in reducing mortality from esophageal adenocarcinoma are lacking. Retrospective studies have shown a significantly better outcome in patients with esophageal cancer that is detected during a surveillance program. Obviously, surveillance is only indicated for those patients fit enough to undergo esophagectomy if high-grade dysplasia (HGD) or malignancy is detected. There is no consensus upon what to do with HGD: some recommend esophagectomy when HGD is diagnosed, because an important proportion of these patients host an adenocarcinoma; others feel that histological proof of malignancy should be established before esophagectomy is proposed. Dysplasia is not a uniform process, causing sampling problems. Using a strict biopsy protocol is helpful to differentiate HGD from carcinoma, but contradictory results about this type of rigorous biopsy protocol have been published. Most groups propose four biopsy specimens, in a circular fashion, from every 2 cm of the Barrett-epithelium, with additional biopsies from any mucosal abnormality. Patients with long-segment Barrett's esophagus need endoscopic surveillance, even if they underwent antireflux surgery. At this moment there are not enough data to support a systematic surveillance of patients with short-segment's Barrett's esophagus. The following endoscopic strategy can be proposed. No dysplasia: surveillance every 2 years. Low-grade dysplasia: surveillance every year; in these cases it is recommended to repeat four-quadrant biopsies at 1 cm interval if numerous biopsies reveal dysplasia to detect foci of HGD/cancer. High-grade dysplasia: repeat immediately four-quadrant biopsies at 1 cm interval; if HGD is confirmed esophagectomy is advised to a patient with acceptable operative risk. Ablation therapy remains experimental.


Role of TGF-β Signaling in Remodeling of Noncoronary Artery Aneurysms in Kawasaki Disease.
Coronary artery aneurysms (CAA) remain an important complication of Kawasaki disease (KD), the most common form of pediatric acquired heart disease in developed countries. Potentially life-threatening CAA develop in 25% of untreated children and 5% of children treated with high-dose intravenous immunoglobulin during the acute phase of the self-limited vasculitis. Noncoronary artery aneurysms (NCAA) in extraparenchymal, muscular arteries occur in a minority of patients with KD who also have CAA, yet little is understood about their formation and remodeling. We postulated that activation of the transforming growth factor-β (TGF-β) pathway in KD may influence formation and remodeling of aneurysms in iliac, femoral, and axillary arteries, the most common sites for NCAA. We studied a resected axillary artery from one adult and endarterectomy tissue from the femoral artery from a second adult, both with a history of CAA and NCAA following KD in infancy. Histology of the axillary artery aneurysm revealed destruction of the internal elastic lamina and recanalization of organized thrombus, while the endarterectomy specimen showed dense calcification and luminal myofibroblastic proliferation. Immunohistochemistry for molecules in the TGF-β signaling pathway revealed increased expression of TGF-β2, TGF-β receptor 2, and phosphorylated SMAD3. These findings suggest ongoing tissue remodeling of the aneurysms decades after the acute injury and demonstrate the importance of the TGF-β signaling pathway in this process.


The impact of piezoelectric PVDF on medical ultrasound exposure measurements, standards, and regulations.
This paper describes the development of PVDF hydrophones for characterizing medical ultrasound fields. The polymer hydrophone approaches that have resulted from this work are discussed, with emphasis given to the spot-poled membrane design that has become the de facto reference device for these measurements. The various national and international standards and regulations that have followed from the successful use of PVDF hydrophones also are summarized. The works discussed encompass polymer-based hydrophones designed primarily for diagnostic and lithotripsy exposure measurements, both in water and in vivo. The advent of these hydrophones has made possible accurate and reliable measurements of exposure levels encountered in medical ultrasound and, thus, has allowed questions of ultrasound bioeffects and device safety to be addressed in a consistent and scientifically sound manner.