Protocol for a randomised controlled trial of a decision aid for the management of pain in labour and childbirth [ISRCTN52287533].
BACKGROUND: Women report fear of pain in childbirth and often lack complete information on analgesic options prior to labour. Preferences for pain relief should be discussed before labour begins. A woman's antepartum decision to use pain relief is likely influenced by her cultural background, friends, family, the media, literature and her antenatal caregivers. Pregnant women report that information about analgesia was most commonly derived from hearsay and least commonly from health professionals. Decision aids are emerging as a promising tool to assist practitioners and their patients in evidence-based decision making.Decision aids are designed to assist patients and their doctors in making informed decisions using information that is unbiased and based on high quality research evidence. Decision aids are non-directive in the sense that they do not aim to steer the user towards any one option, but rather to support decision making which is informed and consistent with personal values. METHODS/DESIGN: We aim to evaluate the effectiveness of a Pain Relief for Labour decision aid, with and without an audio-component, compared to a pamphlet in a three-arm randomised controlled trial. Approximately 600 women expecting their first baby and planning a vaginal birth will be recruited for the trial.The primary outcomes of the study are decisional conflict (uncertainty about a course of action), knowledge, anxiety and satisfaction with decision-making and will be assessed using self-administered questionnaires. The decision aid is not intended to influence the type of analgesia used during labour, however we will monitor health service utilisation rates and maternal and perinatal outcomes. This study is funded by a competitive peer-reviewed grant from the Australian National Health and Medical Research Council (No. 253635). DISCUSSION: The Pain Relief for Labour decision aid was developed using the Ottawa Decision Support Framework and systematic reviews of the evidence about the benefits and risks of the non-pharmacological and pharmacological methods of pain relief for labour. It comprises a workbook and worksheet and has been developed in two forms - with and without an audio-component (compact disc). The format allows women to take the decision aid home and discuss it with their partner.


In vivo label-free confocal imaging of the deep mouse brain with long-wavelength illumination.
Optical microscopy is a valuable tool for in vivo monitoring of biological structures and functions because of its non-invasiveness. However, imaging deep into biological tissues is challenging due to the scattering and absorption of light. Previous research has shown that 1300 nm and 1700 nm are the two best wavelength windows for deep brain imaging. Here, we combined long-wavelength illumination of ~1700 nm with reflectance confocal microscopy and achieved an imaging depth of ~1.3 mm with ~1-micrometer spatial resolution in adult mouse brains, which is 3-4 times deeper than that of conventional confocal microscopy using visible wavelength. We showed that the method can be added to any laser-scanning microscopy with simple and low-cost sources and detectors, such as continuous-wave diode lasers and InGaAs photodiodes. The long-wavelength, reflectance confocal imaging we demonstrated is label-free, and requires low illumination power. Furthermore, the imaging system is simple and low-cost, potentially creating new opportunities for biomedical research and clinical applications.


Variable, but not free-weight, resistance back squat exercise potentiates jump performance following a comprehensive task-specific warm-up.
Studies examining acute, high-speed movement performance enhancement following intense muscular contractions (frequently called "post-activation potentiation"; PAP) often impose a limited warm-up, compromizing external validity. In the present study, the effects on countermovement vertical jump (CMJ) performance of back squat exercises performed with or without elastic bands during warm-up were compared. After familiarization, fifteen active men visited the laboratory on two occasions under randomized, counterbalanced experimental squat warm-up conditions: (a) free-weight resistance (FWR) and (b) variable resistance (VR). After completing a comprehensive task-specific warm-up, three maximal CMJs were performed followed by three back squat repetitions completed at 85% of 1-RM using either FWR or VR Three CMJs were then performed 30 seconds, 4 minutes, 8 minutes, and 12 minutes later. During CMJ trials, hip, knee, and ankle joint kinematics, ground reaction force data and vastus medialis, vastus lateralis, and gluteus maximus electromyograms (EMG) were recorded simultaneously using 3D motion analysis, force platform, and EMG techniques, respectively. No change in any variable occurred after FWR (P > 0.05). Significant increases (P < 0.05) were detected at all time points following VR in CMJ height (5.3%-6.5%), peak power (4.4%-5.9%), rate of force development (12.9%-19.1%), peak concentric knee angular velocity (3.1%-4.1%), and mean concentric vastus lateralis EMG activity (27.5%-33.4%). The lack of effect of the free-weight conditioning contractions suggests that the comprehensive task-specific warm-up routine mitigated any further performance augmentation. However, the improved CMJ performance following the use of elastic bands is indicative that specific alterations in force-time properties of warm-up exercises may further improve performance.


Troponin T concentrations 72 hours after myocardial infarction as a serological estimate of infarct size.
After acute myocardial infarction, the structural protein T is released considerably longer than cytosolic creatine kinase (CK), CK MB isoenzyme (CK-MB), or lactate dehydrogenase (LDH) and late troponin T release (> 48 hours after onset of chest pain) appears to be less affected by early coronary reperfusion. To investigate the precision of a single measurement of circulating troponin T concentrations 72 hours after onset of chest pain compared with standard scintigraphic and enzymatic estimates of myocardial infarct size. Quantitative single photon emission computed tomography thallium-201 scintigraphy at rest was performed in 37 patients 2-3 weeks after myocardial infarction (group 1: 14 patients without early coronary reperfusion; group 2: 23 patients with early reperfusion achieved by thrombolytic therapy, by percutaneous transluminal coronary angioplasty, or by both). In both groups, the number of myocardial segments with abnormal thallium-201 uptake indicating the individual extent of irreversible myocardial damage correlated significantly with the troponin T concentrations 72 hours after infarction as well as with peak concentrations of CK, CK-MB, and LDH. The data show that a single measurement of circulating troponin T 72 hours after onset of chest pain--independent of reperfusion--is superior for the estimation of myocardial infarct size to measurement of peak CK, CK-MB, or LDH, which require serial determinations and depend on coronary reperfusion.


Incidence and risk factors for liver enzyme elevation among naive HIV-1-infected patients receiving ART in the ICONA cohort.
To evaluate the incidence and risk factors for liver enzyme elevations (LEE) in patients initiating first-line ART in the ICONA prospective observational cohort, between June 2009 and December 2017. In total, 6575 ART-naive patients were selected, initiating two NRTIs with the third drug being a boosted PI (n=2436; 37.0%), an NNRTI (n=2384; 36.3%) or an integrase strand transfer inhibitor (INSTI) (n=1755; 26.7%). HBV surface antigen and HCV RNA were detected in 3.9% and 5.8% of the study population. Inverse probability weighted Cox regression analysis was used to calculate the HRs, according to first-line regimen, for LEE, defined as ALT or AST increases of ≥2.5× upper limit of normal (ULN) for patients with normal baseline values or ≥2.5× baseline for patients with higher baseline values. One hundred and eighty-three LEE occurred over 20722 patient-years of follow-up. After adjusting for the main confounders, the risk of LEE halved with INSTIs compared with NNRTIs (HR 0.46, 95% CI 0.25-0.86), with a significant reduction in the raltegravir group (HR 0.11, 95% CI 0.02-0.84 using the NNRTI class as reference). HRs for LEE were significantly higher in subjects with HBV or HCV coinfection, in patients with poorly controlled HIV infection and in those who acquired HIV through homosexual transmission. In our study, INSTI use almost halved the risk of LEE compared with other regimens. This finding could be particularly important for choosing ART in patients with risk factors for liver toxicity such as HCV and HBV coinfections.


Determinants of Good Work Ability among Organic and Conventional Farmers in Finland.
Based on earlier studies, farmers have poorer work ability compared to workers in most other occupations. The aim of this study was to explore if organic production has a positive effect on producers' work ability while controlling for demographic and production characteristics. This study used telephone interview data collected by the Finnish Institute of Occupational Health in 2014-2015. The material consisted of 2,164 farmers: 231 in organic production and 1,933 in conventional production. Work ability was measured with a single question regarding the farmers' current work ability compared with their lifetime best on a scale of 0 to 10, with 0 meaning unable to work. The data were analyzed using multivariable logistic regression. Organic production had a negative effect on work ability, while larger farm size, experiencing economic uncertainty rarely/never/occasionally (vs. often), age under 55 years, having occupational health coverage, and experiencing low amounts of physical strain or mental strain had positive effects in a multivariable model. While this study could not consider potential biases from the farmers' existing health status at the time of switching to organic production and other sources, it is clear that greater attention needs to be paid to improving worker health, safety, and wellness in organic farming.


Lyapunov instability of rigid diatomic molecules in three dimensions: a simpler method.
We present a method to calculate Lyapunov exponents of rigid diatomic molecules in three dimensions ( 12N -dimensional phase space). The spectra of Lyapunov exponents are obtained for 32 rigid diatomic molecules interacting through the Weeks-Chandler-Anderson potential for various bond length and densities, and compared with those of Shin [Phys. Rev. E 64, 041106 (2001)]. Our algorithm is easy to implement and total CPU time is relatively inexpensive.


Flexible angioscopy seems faster and more specific than arteriography.
Fiberoptic angioscopy was performed with 2.5- and 3.3-mm angioscopes in 25 arteries and grafts in 19 patients. Radiologically normal and abnormal arteries and anastomotic sites were examined. All vessels and grafts were visualized and images of normal arterial wall, subclinical and obstructing atherosclerotic plaque, and suture lines were defined. Unexpected endovascular findings were noted in five patients (26%) and included large amounts of free-floating clot (one patient), atherosclerotic debris (two patients), and membranelike obstructions (two patients). Angioscopy required three to ten minutes and resulted in no complications. Experience with the flexible angioscope indicates that satisfactory visualization and specific recognition of angiographically unsuspected problems can be obtained. The flexible angioscope is faster and appears more etiologically specific than arteriography.


The new antibiotics, 1997.
Some of the antimicrobial agents released in the past few years possess characteristics suggesting real advantages over older agents (see Table I). These advantages include broader spectrum of activity, favorable pharmacokinetic profile allowing for infrequent dosing, low toxicity and lower pricing. Although older agents and agents with narrower spectra should be considered first-line in most circumstances, there may be some clinical scenarios in which these newer agents should be contemplated as reasonable alternatives.


Managing postmastectomy lymphedema with low-level laser therapy.
We aimed to investigate the effects of low-level laser therapy (LLLT) in managing postmastectomy lymphedema. Postmastectomy lymphedema (PML) is a common complication of breast cancer treatment that causes various symptoms, functional impairment, or even psychosocial morbidity. A prospective, single-blinded, controlled clinical trial was conducted to examine the effectiveness of LLLT on managing PML. Twenty-one women suffering from unilateral PML were randomly allocated to receive either 12 sessions of LLLT in 4 wk (the laser group) or no laser irradiation (the control group). Volumetry and tonometry were used to monitor arm volume and tissue resistance; the Disabilities of Arm, Shoulder, and Hand (DASH) questionnaire was used for measuring subjective symptoms. Outcome measures were assessed before and after the treatment period and at the 4 wk follow-up. Reduction in arm volume and increase in tissue softening was found in the laser group only. At the follow-up session, significant between-group differences (all p < 0.05) were found in arm volume and tissue resistance at the anterior torso and forearm region. The laser group had a 16% reduction in the arm volume at the end of the treatment period, that dropped to 28% in the follow-up. Moreover, the laser group demonstrated a cumulative increase from 15% to 33% in the tonometry readings over the forearm and anterior torso. The DASH score of the laser group showed progressive improvement over time. LLLT was effective in the management of PML, and the effects were maintained to the 4 wk follow-up.


Dominant-negative Rac increases both inherent and ionizing radiation-induced cell migration in C6 rat glioma cells.
Rho-like GTPases, including Cdc42, Rac1 and RhoA, regulate distinct actin cytoskeleton changes required for cell adhesion, migration and invasion. In the present study, we examined the role of Rac signaling in inherent migration, as well as radiation-induced migration, of rat glioma cells. Stable overexpression of dominant-negative Rac1N17 in a C6 rat glioma cell line (C6-RacN17) promoted cell migration, and ionizing radiation further increased this migration. Migration was accompanied by decreased expression of the focal adhesion molecules FAK and paxillin. Focal contacts and actin stress fibers were also reduced in C6-RacN17 cells. Downstream effectors of Rac include JNK and p38 MAP kinases. Irradiation transiently activated p38, JNK and ERK1/2 MAP kinases in C6-RacN17 cells, while p38 and JNK were constitutively activated in C6 control cells. Blocking JNK activity with JNK inhibitor SP600125 inhibited migration, suggesting that the JNK pathway may regulate radiation-induced, as well as inherent, migration of C6-RacN17 cells. Additionally, the radiation-induced migration increase was also inhibited by SB203580, a specific inhibitor of p38 MAP kinase. However, PD98059, a MEK kinase 1 inhibitor, failed to influence migration. This is the first evidence that suppression of Rac signaling may be involved in invasion or metastasis of glioma cells before and/or after radiotherapy. These data further suggest that radiotherapy for malignant glioma needs to be used with caution because of the potential for therapy-induced cell migration or invasion and that pharmacological inhibition of cell migration and invasion through targeting the Rac signaling pathway may represent a new approach for improving the therapeutic efficacy of radiotherapy for malignant glioma.


The endothelial antigen ESAM marks primitive hematopoietic progenitors throughout life in mice.
Although recent advances have enabled hematopoietic stem cells (HSCs) to be enriched to near purity, more information about their characteristics will improve our understanding of their development and stage-related functions. Here, using microarray technology, we identified endothelial cell-selective adhesion molecule (ESAM) as a novel marker for murine HSCs in fetal liver. Esam was expressed at high levels within a Rag1(-) c-kit(Hi) Sca1(+) HSC-enriched fraction, but sharply down-regulated with activation of the Rag1 locus, a valid marker for the most primitive lymphoid progenitors in E14.5 liver. The HSC-enriched fraction could be subdivided into 2 on the basis of ESAM levels. Among endothelial antigens on hematopoietic progenitors, ESAM expression showed intimate correlation with HSC activity. The ESAM(Hi) population was highly enriched for multipotent myeloid-erythroid progenitors and primitive progenitors with lymphopoietic activity, and exclusively reconstituted long-term lymphohematopoiesis in lethally irradiated recipients. Tie2(+) c-kit(+) lymphohematopoietic cells in the E9.5-10.5 aorta-gonad-mesonephros region also expressed high levels of ESAM. Furthermore, ESAM was detected on primitive hematopoietic progenitors in adult bone marrow. Interestingly, ESAM expression in the HSC-enriched fraction was up-regulated in aged mice. We conclude that ESAM marks HSC in murine fetal liver and will facilitate studies of hematopoiesis throughout life.


Selective restoration of male fertility in mice lacking angiotensin-converting enzymes by sperm-specific expression of the testicular isozyme.
Although angiotensin-converting enzyme (ACE) has been studied primarily in the context of its role in blood pressure regulation, this widely distributed enzyme has many other physiological functions. The ACE gene encodes two isozymes. The somatic isozyme is expressed in many tissues, including vascular endothelial cells, renal epithelial cells, and testicular Leydig cells, whereas the testicular or germinal angiotensin-converting enzyme is expressed only in sperm. The ACE gene knockout mice lack both isozymes and they exhibit low blood pressure, kidney dysfunctions, and male infertility. Here, we report the use of a sperm-specific promoter and interbreeding of transgenic and gene knockout mice for generating a mouse strain that expressed ACE only in sperm. The experimental mice maintained the kidney defects of ACE-/- mice, but unlike the knockout strain, the males were fertile. Thus, we established that the role of ACE in male fertility is completely dependent on its exclusive expression in sperm. Our study clearly demonstrated how transgenic and knockout techniques can be combined for ascribing a specific physiological function to the expression of a multifunctional protein in a given tissue.


Meta-analysis of studies comparing adjuvant dexamethasone to glycerol to improve clinical outcome of bacterial meningitis.
Neurological complications are a problematic factor in acute bacterial meningitis; hence, its prevention is the key to ensure the success of meningitis treatment. Glycerol and dexamethasone are both applied in this regard. Oral glycerol is an appropriate alternative instead of intravenous dexamethasone because it does not have problems related to intravenous injection, the high cost, and drug complications. The main objective of this study was to compare the efficacy of adjuvant dexamethasone versus glycerol in order to improve the clinical outcome of bacterial meningitis. We conducted a search on the available resources including PubMed, Ovid, Elsevier, Cochrane, and another search engines such as Google till 2014. All clinical trials that were performed in the field of comparing the effectiveness of the two drugs and met the inclusion criteria were gathered and after extraction the relative risk (RR) values, the pooled RR was calculated. The main outcome was neurological complications. Meta-analysis of the data was performed in Stata version 11.2 using both fixed and random effect models, weighting each study by inverse of variance. In 5 comparative studies (1,340 patients), the rate of neurological complications of glycerol compared to that of dexamethasone was 1.02 [95% confidence interval (CI), 0.98 compared to 1.12]. The rate of neurological complications of dexamethasone compared to dexamethasone + glycerol was 1 (95% CI, 0.97 compared to 1.03), dexamethasone compared to placebo was 0.99 (95% CI, 0.97 compared to 1.03), glycerol compared to glycerol + dexamethasone was 0.98 (95% CI, 0.94 compared to 1.02), and glycerol compared to placebo was 0.97 (95% CI, 0.94 compared to 1.01). In these studies, no difference was reported between dexamethasone and glycerol in terms of reducing neurological complications. Although there were some weak evidences for the nonstatistical significant effect of glycerol in the prevention of neurologic complication after meningitis, there was no difference between glycerol and dexamethasone.


Monoclonal antibody reactive with the human epidermal-growth-factor receptor recognizes the blood-group-A antigen.
The hybridoma antibody TL5, which precipitates the EGF receptor from the human epidermoid carcinoma cell line A431, has been shown to recognize the blood-group-A carbohydrate structure. This conclusion has been reached from studies of (a) the binding of the antibody to glycoproteins and haemagglutination of erythrocytes with known blood-group-antigen activities and (b) the inhibition of binding of the antibody to a radiolabelled blood-group-A-active glycoprotein by structurally defined oligosaccharides.


Induction of human spermine oxidase SMO(PAOh1) is regulated at the levels of new mRNA synthesis, mRNA stabilization and newly synthesized protein.
The oxidation of polyamines induced by antitumour polyamine analogues has been associated with tumour response to specific agents. The human spermine oxidase, SMO(PAOh1), is one enzyme that may play a direct role in the cellular response to the antitumour polyamine analogues. In the present study, the induction of SMO(PAOh1) enzyme activity by CPENSpm [N1-ethyl-N11-(cyclopropyl)methyl-4,8,diazaundecane] is demonstrated to be a result of newly synthesized mRNA and protein. Inhibition of new RNA synthesis by actinomycin D inhibits both the appearance of SMO(PAOh1) mRNA and enzyme activity. Similarly, inhibition of newly synthesized protein with cycloheximide prevents analogue-induced enzyme activity. Half-life determinations indicate that stabilization of SMO(PAOh1) protein does not play a significant role in analogue-induced activity. However, half-life experiments using actinomycin D indicate that CPENSpm treatment not only increases mRNA expression, but also leads to a significant increase in mRNA half-life (17.1 and 8.8 h for CPENSpm-treated cells and control respectively). Using reporter constructs encompassing the SMO(PAOh1) promoter region, a 30-90% increase in transcription is observed after exposure to CPENSpm. The present results are consistent with the hypothesis that analogue-induced expression of SMO(PAOh1) is a result of increased transcription and stabilization of SMO(PAOh1) mRNA, leading to increased protein production and enzyme activity. These data indicate that the major level of control of SMO(PAOh1) expression in response to polyamine analogues exposure is at the level of mRNA.


Leisure-time physical activity patterns and relationship to generalized distress among Canadians with arthritis or rheumatism.
Little is known about the epidemiology and possible mental health benefits of leisure-time physical activity (LTPA) for persons with arthritis and other rheumatic conditions. We examined the prevalence of LTPA and its association to generalized distress among Canadians with rheumatic conditions. The 1996-97 National Population Health Survey interview data from respondents with rheumatic conditions (n = 10,700) and persons with no chronic conditions (n = 19791) in the same age range (20-79 yrs) were selected for analyses. Self-reported data on forms and frequency of LTPA engaged in over the past 3 months were collected. Intensity of LTPA was expressed as total energy expenditure, with respondents classified as Active (> or = 3.0 kcal/kg/day), Moderate (1.5-2.9 kcal/kg/day), and Inactive (< 1.5 kcal/kg/day). Generalized distress was assessed using a subset of items from the Composite International Diagnostic Interview. Similar to persons with no chronic conditions, roughly 56% of persons with rheumatic conditions engaged in regular LTPA (12 or more 15-minute sessions per month). Only 13.2% of women and 18.9% of men with rheumatic conditions were sufficiently active at the level recommended to yield optimal health benefits. Both moderate and higher intensity LTPA was associated with less generalized distress. This relationship was more pronounced for women and for middle-aged and older patients with rheumatic conditions. A significant proportion of Canadians with rheumatic conditions are physically inactive. Even moderate intensity LTPA is associated with decreased generalized distress. Better efforts must be directed at promoting LTPA as part of the multidisciplinary management of this condition.


Early Endoscopic Ventricular Irrigation for the Treatment of Neonatal Posthemorrhagic Hydrocephalus: A Feasible Treatment Option or Not? A Multicenter Study.
Neonatal intraventricular hemorrhage (IVH) usually results in posthemorrhagic hydrocephalus (PHH). This multicenter study describes the approach of early neuroendoscopic ventricular irrigation for the treatment of IVH/PHH and compares the results with the cases that have been initially treated only with conventional temporary cerebrospinal fluid (CSF) diversion techniques. The data of 74 neonatal PHH cases, that have been treated at three pediatric neurosurgery centers, were retrospectively analyzed. 23 neonates with PHH underwent early endoscopic ventricular irrigation (Group-A). 29 neonates were initially treated with conventional methods (Group-B). 22 neonates underwent ventriculosubgaleal shunt placement (Group-C). Complications, shunt dependency rates, incidence of multiloculated hydrocephalus and incidence of CSF infection were evaluated and compared retrospectively. Group-A, Group-B and Group-C cases did not differ significantly regarding gestational age and birth weight. In Group-A, 60.8% of the patients required a later shunt insertion, as compared with 93.1% of the cases in Group-B and 77.2% of the cases in Group-C. Group-A patients were also associated with significantly fewer CSF infections as well as significantly lower incidence for multiloculated hydrocephalus development as compared with Group-B and Group-C. Early removal of intraventricular blood degradation products and residual hematoma via neuroendoscopic ventricular irrigation is feasible and safe for the treatment of PHH in neonates with IVH. Neuroendoscopic technique seems to offer significantly lower shunt rates and fewer complications such as infection and development of multiloculated hydrocephalus in those cases.


Main and moderated effects of moral cognition and status on bullying and defending.
This study analyzed the relations of two dimensions of moral cognition (i.e., acceptance of moral transgression and moral disengagement) and two forms of status in the peer group (i.e., social preference and perceived popularity) with bullying and defending among 235 primary-school children and 305 middle-school early adolescents. Social status was tested as a moderator of the associations between moral cognition and bullying and defending. Participants completed self-reports assessing the two dimensions of moral cognition and peer nominations for status, bullying, and defending. Both acceptance of moral transgression and moral disengagement were associated to bullying among early adolescents only, whereas in childhood moral disengagement was linked to defending among girls. Social status moderated the associations between morality dimensions and bullying and defending. The moderating effects of status were discussed considering status as a magnifying lens for the relations between individual characteristics and social behavior. The results were also discussed with reference to age and gender differences in the associations.


A Preliminary Study of a Novel Reference Plane of the Head: Comparing With the True Horizontal Plane.
A new reference plane of the head, based on soft tissue landmarks and suitable for clinical analysis and soft tissue measurements, is needed. We recently discovered a novel reference plane, that is, the COs plane, which was formed by bilateral Lateral Canthus and bilateral Otobasion Superius and might be horizontal at the natural head position (NHP). In this study, we investigated the angles between the COs plane and the true horizontal (TrH) plane while sitting and standing, aiming to explore whether the new plane could be used as a substitution for the reference plane in clinical practice. Briefly, 26 volunteers were enrolled. Their sitting and standing NHP were recorded using the 3dMDface system. In the pitch axis, the mean angle of COs/TrH was 0.29 degrees and 0.41 degrees for sitting and standing positions, respectively, showing no statistical difference ( P >0.05). However, in the roll axis, the mean angle of COs/TrH for sitting position and standing positions was 1.08 and 1.33 degrees ( P <0.05), which was considered to be the result of habitual canting of the head. Moreover, there were no significant differences between the sitting and standing NHP, considering the COs/TrH angles ( P >0.05). To sum up, we concluded that the COs plane could be used as a reliable reference plane in certain soft tissue analysis and clinical applications.


Histopathological correlates of magnetic resonance imaging-defined chronic perinatal white matter injury.
Although magnetic resonance imaging (MRI) is the optimal imaging modality to define cerebral white-matter injury (WMI) in preterm survivors, the histopathological features of MRI-defined chronic lesions are poorly defined. We hypothesized that chronic WMI is related to a combination of delayed oligodendrocyte (OL) lineage cell death and arrested maturation of preoligodendrocytes (preOLs). We determined whether ex vivo MRI can distinguish distinct microglial and astroglial responses related to WMI progression and arrested preOL differentiation. We employed a preterm fetal sheep model of global cerebral ischemia in which acute WMI results in selective preOL degeneration. We developed novel algorithms to register histopathologically-defined lesions with contrast-weighted and diffusion-weighted high-field ex vivo MRI data. Despite mild delayed preOL degeneration, preOL density recovered to control levels by 7 days after ischemia and was ~2 fold greater at 14 days. However, premyelinating OLs were significantly diminished at 7 and 14 days. WMI evolved to mostly gliotic lesions where arrested preOL differentiation was directly proportional to the magnitude of astrogliosis. A reduction in cerebral WM volume was accompanied by four classes of MRI-defined lesions. Each lesion type displayed unique astroglial and microglial responses that corresponded to distinct forms of necrotic or non-necrotic injury. High-field MRI defined 2 novel hypointense signal abnormalities on T(2) -weighted images that coincided with microscopic necrosis or identified astrogliosis with high sensitivity and specificity. These studies support the potential of high-field MRI for early identification of microscopic necrosis and gliosis with preOL maturation arrest, a common form of WMI in preterm survivors.


Significance of cervicovaginal cytology after radiation therapy for cervical carcinoma.
During follow-up examinations; 1,338 cervicovaginal cytologic smears were obtained from 254 women who had irradiation therapy for cervical cancer. These specimens were meticulously searched for the various cellular phenomena that may characterize such preparations, and some of the findings were subjectively quantitated. Correlations were made with histopathologic diagnoses, clinical findings, and results of treatment. Patients with malignant postradiation cells who were promptly treated for latent new or recurrent tumors generally responded well to treatment of the secondary tumor. The presence of malignant cells at any time after completion of therapy is an ominous sign, irrespective of the clinical status, and should lead to intensive effort to identify the site of a new or persisting lesion. The significance of dysplasia in postradiation smears is not entirely clear, and in certain instances it is difficult to distinguish severely dysplastic cells from either repair cells or malignant cells.


The Toxicology Investigators Consortium Case Registry--the 2012 experience.
In 2010, the American College of Medical Toxicology (ACMT) established its Case Registry, the Toxicology Investigators Consortium (ToxIC). All cases are entered prospectively and include only suspected and confirmed toxic exposures cared for at the bedside by board-certified or board-eligible medical toxicologists at its participating sites. The primary aims of establishing this Registry include the development of a realtime toxico-surveillance system in order to identify and describe current or evolving trends in poisoning and to develop a research tool in toxicology. ToxIC allows for extraction of data from medical records from multiple sites across a national and international network. All cases seen by medical toxicologists at participating institutions were entered into the database. Information characterizing patients entered in 2012 was tabulated and data from the previous years including 2010 and 2011 were included so that cumulative numbers and trends could be described as well. The current report includes data through December 31st, 2012. During 2012, 38 sites with 68 specific institutions contributed a total of 7,269 cases to the Registry. The total number of cases entered into the Registry at the end of 2012 was 17,681. Emergency departments remained the most common source of consultation in 2012, accounting for 61 % of cases. The most common reason for consultation was for pharmaceutical overdose, which occurred in 52 % of patients including intentional (41 %) and unintentional (11 %) exposures. The most common classes of agents were sedative-hypnotics (1,422 entries in 13 % of cases) non-opioid analgesics (1,295 entries in 12 % of cases), opioids (1,086 entries in 10 % of cases) and antidepressants (1,039 entries in 10 % of cases). N-acetylcysteine (NAC) was the most common antidote administered in 2012, as it was in previous years, followed by the opioid antagonist naloxone, sodium bicarbonate, physostigmine and flumazenil. Anti-crotalid Fab fragments were administered in 109 cases or 82 % of cases in which a snake envenomation occurred. There were 57 deaths reported in the Registry in 2012. The most common associated agent alone or in combination was the non-opioid analgesic acetaminophen, being reported in 10 different cases. Other common agents and agent classes involved in death cases included ethanol, opioids, the anti-diabetic agent metformin, sedatives-hypnotics and cardiovascular agents, in particular amlodipine. There were significant trends identified during 2012. Abuse of over-the-counter medications such as dextromethorphan remains prevalent. Cases involving dextromethorphan continued to be reported at frequencies higher than other commonly abused drugs including many stimulants, phencyclidine, synthetic cannabinoids and designer amphetamines such as bath salts. And, while cases involving synthetic cannabinoids and psychoactive bath salts remained relatively constant from 2011 to 2012 several designer amphetamines and novel psychoactive substances were first reported in the Registry in 2012 including the NBOME compounds or "N-bomb" agents. LSD cases also spiked dramatically in 2012 with an 18-fold increase from 2011 although many of these cases are thought to be ultra-potent designer amphetamines misrepresented as "synthetic" LSD. The 2012 Registry included over 400 Adverse Drug Reactions (ADRs) involving 4 % of all Registry cases with 106 agents causing at least 2 ADRs. Additional data including supportive cares, decontamination, and chelating agent use are also included in the 2012 annual report. The Registry remains a valuable toxico-surveillance and research tool. The ToxIC Registry is a unique tool for identifying and characterizing confirmed cases of significant or potential toxicity or complexity to require bedside care by a medical toxicologist.


Nasal bridles for securing nasoenteric tubes: a meta-analysis.
Nasoenteric feeding tubes may easily become dislodged due to patient mental status, transfers, or positional changes. Nasal bridles were introduced to provide a better, more reliable system to secure these tubes. This meta-analysis was performed to evaluate the effectiveness of nasal bridles compared with the traditional method of adhesive tape alone in securing enteral feeding tubes. Multiple databases were searched (October 2013). All studies that evaluated the use of nasal bridles in adult patients were included in the analysis. Meta-analysis for the outcomes from use of a nasal bridle vs the more traditional method of adhesive tape alone for securing nasoenteric tubes was analyzed by calculating pooled estimates of dislodgement, skin complications, and sinusitis. Statistical analysis was performed using RevMan 5.1. Six studies (n = 594) met the inclusion criteria. Use of a nasal bridle for securing enteral tubes resulted in a statistically significant reduction in tube dislodgement compared with traditional adhesive tape alone (odds ratio [OR], 0.16; 95% confidence interval [CI], 0.10–0.27; P < .01). The use of nasal bridles was associated with a higher rate of skin complications compared with traditional adhesive tape (OR, 4.27; 95% CI, 1.79–10.23; P < .01). Incidence of sinusitis was no different between the 2 groups (OR, 0.26; 95% CI, 0.03–2.28; P = .22). Nasal bridles appear to be more effective at securing nasoenteric tubes and preventing dislodgement than traditional use of tape alone.


Over-expression of Activated Signal Transducer and Activator of Transcription 3 Predicts Poor Prognosis in Upper Tract Urothelial Carcinoma.
Background: Signal transducer and activator of transcription proteins (STATs) play important roles in gene regulation, cell proliferation, and cell differentiation. We aimed to establish the relationship between phosphorylated STAT3 (p-Ser-STAT3) expression and the prognosis of upper tract urothelial carcinoma (UTUC). Methods: This study retrospectively reviewed 100 patients with pathologically confirmed UTUC at Kaohsiung Medical University Hospital. We quantified the expression of p-Ser-STAT3 in cancer cells by immunohistochemistry, and determined the clinicopathological significance of p-Ser-STAT3 expression and prognostic outcomes in patients with UTUC. Results: High p-Ser-STAT3 expression was detected in 52% of UTUC patients. High p-Ser-STAT3 expression was associated with poor recurrence-free survival (p = 0.018) and overall survival (p = 0.026). In advanced cancer samples (stage T3/T4), p-Ser-STAT3 expression is the only independent prognostic factor for recurrence-free survival (hazard ratio = 5.91, p = 0.01) and cancer-specific survival (hazard ratio = 8.83, p = 0.039). Conclusions: The expression of p-Ser-STAT3 can be a potential prognostic marker for cancer recurrence and survival in UTUC, especially in advanced stage cases.


USP44+ Cancer Stem Cell Subclones Contribute to Breast Cancer Aggressiveness by Promoting Vasculogenic Mimicry.
Vasculogenic mimicry (VM), a newly defined pattern of tumor blood supply, describes the functional plasticity of aggressive cancer cells that form vascular networks. In our previous study, breast cancer stem cells (CSC) were shown to potentially participate in VM formation. In this study, breast CSCs presented centrosome amplification (CA) phenotype and ubiquitin-specific protease 44 (USP44) upregulation. USP44 expression contributed to the establishment of bipolar spindles in breast CSCs with supernumerary centrosomes by localizing at pole-associated centrosomes. The bipolar spindle patterns of breast CSCs with CA, including planar-like and apico-basal-like, functioned differently during the VM process of CSCs. Moreover, the ability of transendothelial migration in VM-forming cells was increased. In vivo experiment results showed that CSC xenografts presented linearly patterned programmed cell necrosis, which provided a spatial foundation for VM formation as well as angiogenesis. Breast CSCs further showed increased levels of IL6 and IL8. However, USP44 silencing induced spindle multipolarity, abated VM, reduced transendothelial migration, and consequently decreased IL6 and IL8 levels in breast CSCs. Finally, USP44(+) CSC subclones (ALDH1(+)/USP44(+)/IL6(+)/IL8(+)) were identified in breast cancer specimens through consecutive sections scanning. The subclones were related not only to CA, but also to VM. Statistical analysis suggested that USP44(+) CSC subclones could be used as an independent prognostic biomarker of poor clinical outcomes in patients with breast cancer. Collectively, the identification of USP44(+) CSC subclones may contribute to the prediction of VM formation and aggressive behavior. This study provides novel insights into the therapy for advanced breast cancer.


A combination of galantamine and memantine modifies cognitive function in subjects with amnestic MCI.
Mild cognitive impairment (MCI) is etiologically heterogeneous, and a substantial proportion of MCI subjects will develop different dementia disorders. One subtype of this syndrome, amnestic MCI, occurs preferentially but not exclusively in prodromal AD and is characterized by defined deficits of episodic memory. For a 2-year, double-blinded, placebo-controlled study MCI patients, presenting with an amnestic syndrome but not necessarily based on presumed prodromal AD were randomized. Patients received (a) a combination of 16 mg galantamine plus 20 mg memantine, or (b) 16 mg galantamine alone or (c) placebo. The primary objective was to explore the differential impact of these interventions on the progression to dementia and on cognitive changes as measured by the ADAScog. After recruitment of 232 subjects, the trial was halted before reaching the planned sample size, because safety concerns arose in other studies with galantamine in MCI. This resulted in a variable treatment duration of 2-52 weeks. The statistical analysis plan was amended for studying cognitive effects of discontinuing the study medication, which was done separately for galantamine and memantine, and under double-blind conditions. There was one death, no unexpected severe adverse events, and no differences of severe adverse events between the treatment arms. The cognitive changes on the ADAScog were not different among the groups. Only for the subgroup of amnestic MCI with presumed AD etiology, a significant improvement of ADAScog score over placebo before the discontinuation of medication was observed, while amnestic MCI presumably due to other etiologies showed no cognitive changes with broad variation. Cognitive improvement was numerically larger in the combination treatment group than under galantamine alone. Patients who received placebo declined as expected. Discontinuation of galantamine, either as part of the combination regimen or as mono treatment, resulted in a transient decline of the ADAScog score in amnestic MCI of presumed AD etiology, while discontinuation of Memantine did not change the cognitive status. In an interrupted trial with amnestic MCI subjects the combination of galantamine plus memantine were generally well tolerated. In the subgroup of MCI subjects with presumed AD etiology, a cognitive benefit of a short-term combination treatment of galantamine plus memantine was observed, and cognitive decline occurred after discontinuation of galantamine.


Airway responsiveness to methacholine and incidence of COPD: an international prospective cohort study.
It has been debated, but not yet established, whether increased airway responsiveness can predict COPD. Recognising this link may help in identifying subjects at risk. We studied prospectively whether airway responsiveness is associated with the risk of developing COPD. We pooled data from two multicentre cohort studies that collected data from three time points using similar methods (European Community Respiratory Health Survey and Swiss Cohort Study on Air Pollution and Lung and Heart Diseases in Adults). We classified subjects (median age 37 years, 1st-3rd quartiles: 29-44) by their level of airway responsiveness using quintiles of methacholine dose-response slope at the first examination (1991-1994). Then, we excluded subjects with airflow obstruction at the second examination (1999-2003) and analysed incidence of COPD (postbronchodilator FEV1/FVC below the lower limit of normal) at the third examination (2010-2014) as a function of responsiveness, adjusting for sex, age, education, body mass index, history of asthma, smoking, occupational exposures and indicators of airway calibre. We observed 108 new cases of COPD among 4205 subjects during a median time of 9 years. Compared with the least responsive group (incidence rate 0.6 per 1000/year), adjusted incidence rate ratios for COPD ranged from 1.79 (95% CI 0.52 to 6.13) to 8.91 (95% CI 3.67 to 21.66) for increasing airway responsiveness. Similar dose-response associations were observed between smokers and non-smokers, and stronger associations were found among subjects without a history of asthma or asthma-like symptoms. Our study suggests that increased airway responsiveness is an independent risk factor for COPD. Further research should clarify whether early treatment in patients with high responsiveness can slow down disease progression.


Osteogenic relationship between the lateral plantar process and the peroneal tubercle in the human calcaneus.
The osteogenic relationship between the lateral plantar process and the peroneal tubercle has been an uncertainty for researchers over several decades. While some argue there to be no developmental relationship between these two calcaneal structures, others have suggested that there is an inverse relationship, the lateral plantar process forming from a part of the peroneal tubercle. However, no previous studies have offered quantitative measurements to test these hypotheses. In this study, we measured the size of the peroneal tubercle, retrotrochlear eminence, and the size and area of the lateral plantar process in 73 subjects using magnetic resonance imaging (MRI). Navicular height was measured using weight-bearing radiographs as a measurement of longitudinal arch in 35 of these subjects. Age, body mass, and body mass index (BMI) were also recorded for all subjects. We determined that there was a significant positive correlation between the lateral plantar process and size of the peroneal tubercle, body mass, and BMI. Thus, assertions that there is an inverse relationship between the size of the lateral plantar process and the peroneal tubercle are here unfounded. We also determined there to be a positive correlation between the peroneal tubercle and both the size of the retrotrochlear eminence and the height of the navicular. In conclusion, we relate these novel findings to hominin fossil calcanei and discuss the evolutionary and biomechanical implications.


Analyzing effects of pesticides on invertebrate communities in streams.
The aim of this investigation was to find patterns in aquatic invertebrate community composition that are related to the effects of pesticides. Investigations were carried out in 20 central European streams. To reduce the site-specific variation of community descriptors due to environmental factors other than pesticides, species were classified and grouped according to their vulnerability to pesticides. They were classified as species at risk (SPEAR) and species not at risk (SPEnotAR). Ecological traits used to define these groups were sensitivity to toxicants, generation time, migration ability, and presence of aquatic stages during time of maximum pesticide application. Results showed that measured pesticide concentrations of 1:10 of the acute 48-h median lethal concentration (LC50) of Daphnia magna led to a short- and long-term reduction of abundance and number of SPEAR and a corresponding increase in SPEnotAR. Concentrations of 1:100 of the acute 48-h LC50 of D. magna correlated with a long-term change of community composition. However, number and abundance of SPEAR in disturbed stream sections are increased greatly when undisturbed stream sections are present in upstream reaches. This positive influence compensated for the negative effect of high concentrations of pesticides through recolonization. The results emphasize the importance of considering ecological traits and recolonization processes on the landscape level for ecotoxicological risk assessment.


Trace gas detection with short-external-cavity InGaAsP diode laser transmitter modules operating at 1.58 microm.
Detection of CO(2) and CO at 1.58 microm (6322 cm(-1)) using an InGaAsP diode laser and mode control is described.Mode control is a technique whereby a short cavity, external to the laser, is used to force the laser to operate in a single mode. By monitoring the voltage across the terminals of the laser and using electronic feedback it is possible to optimize continually the external cavity so that the laser operates reliably in the mode of choice for scans >3.5 cm(-1). This technique offers the possibility of high-sensitivity detection over a region of ~30 cm(-1) with continuous coverage in overlapping sections of ~3 cm(-1) with conventional (and hence inexpensive) multimode diode lasers.


[Hoarding as the core symptom of the Diogenes Syndrome. A case study].
The subject of this case study is a 69-year-old woman with the Diogenes syndrome. Hoarding, the major symptom of this syndrome, has been investigated more thoroughly in the literature than the syndrome itself. However, so far no consensus has been reached about the pathogenesis. Selective serotonin reuptake inhibitors or antipsychotics can be useful as treatment, depending on the underlying aetiology. Non-pharmacological forms of treatment such as behavioural and environmental interventions may also be required. The limited information about the prognosis is not encouraging.


A Molecular Perspective on Procedures and Outcomes with Assisted Reproductive Technologies.
The emerging association of assisted reproductive technologies with adverse perinatal outcomes has prompted the in-depth examination of clinical and laboratory protocols and procedures and their possible effects on epigenetic regulatory mechanism(s). The application of various approaches to study epigenetic regulation to problems in reproductive medicine has the potential to identify relative risk indicators for particular conditions, diagnostic biomarkers of disease state, and prognostic indicators of outcome. Moreover, when applied genome-wide, these techniques are likely to find novel pathways of disease pathogenesis and identify new targets for intervention. The analysis of DNA methylation, histone modifications, transcription factors, enhancer binding and other chromatin proteins, DNase-hypersensitivity and, micro- and other noncoding RNAs all provide overlapping and often complementary snapshots of chromatin structure and resultant "gene activity." In terms of clinical application, the predictive power and utility of epigenetic information will depend on the power of individual techniques to discriminate normal levels of interindividual variation from variation linked to a disease state. At present, quantitative analysis of DNA methylation at multiple loci seems likely to hold the greatest promise for achieving the level of precision, reproducibility, and throughput demanded in a clinical setting.


Believing doesn't make it so: forensic education and the search for truth.
The American Academy of Psychiatry and the Law (AAPL) was organized in 1969, in large part through the efforts of Dr. Jonas Rappeport. The founders of AAPL emphasized that an important purpose of the organization was to advance knowledge in the area of psychiatry and the law. The science of forensic psychiatry has since been vigorously debated. In 2005, Congress enacted a statute authorizing the National Academy of Sciences (NAS) to conduct a study on the state of the forensic sciences in the United States. As a result of this legislation, a forensic science committee was formed, and the report, "Strengthening Forensic Science in the United States: A Path Forward," was produced, emphasizing the need for research in the forensic disciplines, particularly those that rely on more subjective assessments. The committee also identified two important factors relevant to standards of evidence admissibility: the scientific methodology used and the impact of bias on the interpretation of data. In this article, I apply the NAS committee's findings to the field of forensic psychiatry, with specific recommendations to assist educators in achieving more objective assessment methodologies, critical in forensic education and the search for truth.


[Cyclic GMP mimicks potentiation effect of the nootropic agent vinpocetine on the high threshold A-current in the mollusk neurons].
High-threshold transient K+ current (IAht) was recorded using a two-microelectrode voltage clamp technique in isolated neurons of the land snail. Effect of the nootropic drug vinpocetine on this current was studied and compared with cyclic nucleotides. The drug either enhanced or left unaltered the IAht, and dibutyryl cyclic GMP (dcGMP) imitated the effect. These two effects were not additive. Dibutyryl cyclic AMP did not imitate, the vinpocetine effect and decreased the amplitude of the IAht. The findings suggest that the cGMP mediated the vinpocetine effect on the Iaht.


Lumbar spine bone mineral density in US adults: demographic patterns and relationship with femur neck skeletal status.
This analysis examines lumbar spine bone mineral density (BMD) of US adults from NHANES 2005-2008 by age, sex, and race/ethnicity. Prevalence of low spine BMD and agreement between the prevalence of low BMD at the spine and femur neck in older adults are also assessed. Lumbar spine BMD data from a representative sample of the US population have not been previously available. We used data from the National Health and Nutrition Examination Survey 2005-2008 to examine demographic patterns in lumbar spine BMD among US adults age ≥20 years and the prevalence of low lumbar spine BMD in adults age ≥50 years. Agreement between the prevalence of low BMD at the femur neck and spine in older adults was also assessed. Dual-energy X-ray absorptiometry was used to measure lumbar spine and femur neck BMD. World Health Organization definitions were used to categorize skeletal status as normal, osteopenia, or osteoporosis. Compared to non-Hispanic whites, non-Hispanic blacks had higher and Mexican Americans had lower lumbar spine BMD. Lumbar spine BMD declined with age in women, but not in men. Approximately 4.7 million (10%) older US women and 1 million (3%) older men had lumbar spine osteoporosis in 2005-2008. Roughly one third of them differed in skeletal status at the spine and hip but most were normal at one site and osteopenic at the other. Only 3-10%, depending on sex, had osteoporosis at one skeletal site but not at the other skeletal site. Between 76% and 87% with discordant skeletal status had lumbar spine T-scores within 1 unit of the category threshold. These findings suggest that measuring either the femur neck or the lumbar spine will correctly classify the majority of individuals who present for care as osteoporotic or not.


Gated photochromism and acidity photomodulation of a diacid dithienylethene dye.
The present study quantitatively analyses the gated photochromism and the acidity photomodulation properties of a diacid dithienylethene compound. Photoisomerisation between the open and closed isomers was investigated by UV/visible and (1)H NMR spectroscopy. It was found that the photocyclisation quantum yield of the diacid form was remarkably high (around 90%). Partial neutralisation of the open isomer revealed a gated photochromism as the photocyclisation quantum yield of the mono- and dianion were 50 and 67%, respectively. A considerable photomodulation of the acidity was observed: the closed isomer is more acid than the open one by more than one pK(a) unit. This effect has been shown to be exploitable for a reversible photo-acid generation. This is the first time that a complete quantitative investigation that allows for the determination of the main photochromic, spectral and thermodynamic parameters of a base-sensitive photochromic diarylethene has been carried out.


Workers' compensation program experience, 1981.
Although the workers' compensation program covered more workers and paid more in benefits in 1981 than it did a year earlier, the rise in both of these indicators was slightly smaller than those in 1980 and considerably smaller than the increases that took place in the 1970's. Employers paid $22.9 billion in premiums in 1981, less than 3 percent more than the previous year and the smallest annual increase since 1958. The cost-payroll ratio also showed a 12-point drop in 1981, the first such decline since 1959 and a sharp contrast to the almost 9 percentage point average annual rise in the 1970's. The Black Lung program, which made up more than a fifth of the benefit payments under workers' compensation in 1973, accounted for only about an eighth by 1981.


Pharmacokinetics and effects of recombinant human erythropoietin after intravenous and subcutaneous injections in healthy volunteers.
A double-blind, placebo-controlled study of the pharmacokinetics and safety of multiple doses of recombinant human erythropoietin [rHuEPO 150 or 300 U/kg either by intravenous (IV) bolus or subcutaneously (SC)] in normal male subjects demonstrated that rHuEPO had a dose-related effect on the hematocrit independent of the route of administration and that multiple doses of rHuEPO had no direct pressor effects. When rHuEPO was injected IV, a monoexponential decrease in serum EPO level was evident for 18 to 24 hours postdose. Absorption of SC injected rHuEPO occurred more slowly, with relatively low serum EPO levels being maintained for 48 hours. All rHuEPO antibody titer determinations were negative. With the exception of significant increases in hemoglobin and hematocrit, no clinically significant changes occurred. No hypertensive, convulsive, or thrombotic events were observed. Of the adverse experiences observed in 10 subjects, none was considered clinically significant, and none of the subjects dropped out because of adverse experiences.


The two essential elements for planning tip surgery in primary and secondary rhinoplasty: observations based on review of 100 consecutive patients.
Nasal tip surgery has become significantly more complex since the introduction of tip grafting and the many suture designs that followed the resurgence of open rhinoplasty. Independent of the surgeon's technical approach, however, is the need to identify the critical anatomical characteristics that will make nasal tip surgery successful. It is the author's contention that only two such features require mandatory preoperative identification: (1) whether the tip is adequately projecting and (2) whether the alar cartilage lateral crura are orthotopic or cephalically rotated ("malpositioned"). Data were generated from a review of 100 consecutive primary rhinoplasty patients on whom the author had operated. The results indicate that only 33 percent of the entire group had adequate preoperative tip projection and only 54 percent had orthotopic lateral crura (axes toward the lateral canthi). Forty-six percent of the patients had lateral crura that were cephalically rotated (axes toward the medial canthi). Both inadequate tip projection and convex lateral crura were more common among patients with malpositioned lateral crura (78 percent and 61 percent) than in patients with orthotopic lateral crura (57 percent and 20 percent, respectively). Tip projection can be reliably assessed by the relationship of the tip lobule to the septal angle. Malposition is characterized by abnormal lateral crural axes, long alar creases that extend to the nostril rims, alar wall hollows, frequent nostril deformities, and associated external valvular incompetence. The data suggest that the surgeon treating the average spectrum of primary rhinoplasty patients will see a majority (61 percent) who need increased tip support and a significant number (46 percent) with an anatomical variant (alar cartilage malposition) that places these patients at special risk for postoperative functional impairment. Correction of external valvular incompetence doubles nasal airflow in most patients. As few as 23 percent of primary rhinoplasty patients (the number with orthotopic, projecting alar cartilages in this series) may be proper candidates for reduction-only tip procedures. When tip projection and lateral crural orientation are accurately determined before surgery, nasal tip surgery can proceed successfully and secondary deformities can be avoided.


Hypnosis in the treatment of anxiety.
Hypnotherapy and training in self-hypnosis can help persons achieve remarkable success in alleviating anxiety, not only in anxiety disorders, but also in any problem involving anxiety. The author describes the role of hypnosis in the treatment of several disorders and provides clinical examples illustrating treatment of generalized anxiety, phobias, and posttraumatic stress disorders. He concludes that because hypnosis exploits the intimate connection between mind and body, it provides relief through improved self-regulation and also beneficially affects cognition and the experience of self-mastery.


The promise and perils of microarray analysis.
Microarray analysis has provided a novel means of identifying clues into the mechanisms of disease development. As a methodology, microarray analysis holds the promise for genome-wide screening in which 2 tissues (diseased and normal) are compared, and molecular pathways that defined the phenotype of the disease could be precisely defined. Alternatively, microarray experiments can be used to differentially compare pathologically similar diseased tissues to predict response to chemotherapy and risk of recurrence. However, the clinician should be aware that various sources of error can influence microarray analysis results. Sources of error can be minimized but not eliminated, explaining why meticulously conducted experiments in different laboratories or using different platforms result in different lists of genes. Confirmation and validation of genome-wide microarray results using ancillary methods remains a critical step. With proper confirmatory studies and cautious interpretation, microarray analysis represents a powerful tool for molecular discovery.


Changes in causes of acute gastroenteritis in the United Kingdom over 15 years: microbiologic findings from 2 prospective, population-based studies of infectious intestinal disease.
Large-scale, prospective studies of infectious intestinal disease (IID) in developed countries are uncommon. Two studies of IID incidence and etiology have been conducted in the United Kingdom: the Infectious Intestinal Disease Study in England (IID1) in 1993-1996 and the Second Study of Infectious Intestinal Disease in the Community (IID2) in 2008-2009. We examined changes in etiology and diagnostic yield of IID cases over 15 years. Fecal samples submitted by IID cases were examined for a range of bacterial, viral, and protozoal pathogens using traditional and molecular microbiological methods. We calculated the percentage of specimens positive for each organism based on traditional methods and on traditional and molecular methods combined. We compared the distributions of organisms in the 2 studies. For pathogens investigated in both studies, 40% of fecal samples submitted by cases in IID2 were positive compared with 28% in IID1. Viruses were most frequent among community cases in IID2. Campylobacter was the most common bacterial pathogen among cases presenting to healthcare. Major differences between the 2 studies were increases in the detection of norovirus and sapovirus and a decline Salmonella. Most fecal specimens were negative for the pathogens tested in both studies, so new strategies are needed to close the diagnostic gap. Among known pathogens, effective control of norovirus, rotavirus, and Campylobacter remain high priorities. The reduction in nontyphoidal salmonellosis demonstrates the success of Europe-wide control strategies, notably an industry-led Salmonella control program in poultry in the United Kingdom.


Occupational risk factors in inflammatory bowel disease.
Crohn's disease and ulcerative colitis are the two main forms of inflammatory bowel disease (IBD). Although the aetiology of IBD is not completely understood, an interaction between genetic and environmental factors has been proposed. In this context, however, environmental epidemiology lacks a comprehensive evaluation of the possible role of occupational exposures in IBD development and progression. Therefore, aim of our review was to evaluate how certain occupational risk factors may affect IBD pathogenesis, clinical history and severity of disease manifestations. A critical revision of available literature concerning exposure to groups of potential workplace hazardous agents and IBD, as it appears in Medline and Web of knowledge, was performed. The role of workplace exposures to chemical and biological agents, ionizing or non-ionizing radiations, shift-works, indoor, and sedentary works as well as job strain on IBD has been critically revised. However, the limited number of studies addressing these issues prevented us from extrapolating definite conclusions. Our review pointed out some critical aspects concerning the relationship between occupational factors and IBD, in terms of causative pathways, hazardous exposure, susceptibility and consequences of IBD functional limitations on career choice and fitness for work that need future investigations. Overall, this seems a challenging public health issue, considering the strong IBD impact on patients' quality of life, work productivity and costs to society. Moreover, this review may encourage concerted actions of health care specialists, occupational physicians, employers and IBD workers to plan preventive and protective measures for "healthier patterns of work" for IBD and to develop innovative perspectives for an integrated management of "IBD at work".


Gender Similarities and Differences in Casual Sex Acceptance Among Lesbian Women and Gay Men.
Popular wisdom and scientific evidence suggest women desire and engage in casual sex less frequently than men; however, theories of gender differences in sexuality are often formulated in light of heterosexual relations. Less is understood about sexual behavior among lesbian and gay people, or individuals in which there is arguably less motivation to pursue sex for reproductive purposes and fewer expectations for people to behave in gender-typical ways. Drawing from scripts theory and pleasure theory, in two studies (N1 = 465; N2 = 487) we examined lesbian and gay people's acceptance of casual sex. We asked participants who had been propositioned for casual sex whether they accepted the offer and to rate their perceptions of the proposer's sexual capabilities and sexual orientation. They also reported on their awareness of stigma surrounding casual sex. We found a gender difference in acceptance: Gay men were more likely than lesbian women to have accepted a casual sex offer from other gay/lesbian people, and this difference was mediated by participants' stigma awareness. We also found the proposer's sexual orientation played a role in people's acceptance. Lesbian women and gay men were equally likely to accept offers from bisexual proposers but expressed different acceptance rates with "straight-but-curious" proposers, which was mediated by expected pleasure. We discuss dynamics within lesbian and gay communities and implications for studying theories of sexual behavior and gender differences beyond heterosexual contexts.


Glucosa-Insulin-Potassium (GIK) solution used with diabetic patients provides better recovery after coronary bypass operations.
Tight blood glucose control has become a therapeutical goal for anesthetic management for patients scheduled for cardiac surgery, especially if they are diabetic patients. This study was created to confirm the benefits of intraoperative GIK solution usage during coronary bypass operation of diabetic patients. Patients with type 1 and 2 diabetes mellitus (DM) referred for coronary artery bypass grafting (CABG) were randomized to receive GIK solution (GIK--study group) in the first 24 hours intraoperatively or to receive official Clinical protocol without GIK solution (non GIK - control group). The primary clinical outcome was the cardiac index (CI) since it represents the most sensitive measure of cardiac work in the immediate postoperative period, and the secondary clinical outcomes were the glycemic control, insulin consumption, duration of mechanical ventilation (MV), potassium level and atrial fibrillation (AF) appearance. One hundred diabetic patients, divided into two groups, were included in the study. The cardiac index did not show a significant difference, although the study group had CI with only minor variations than those of the controlled group, hence the reason we considered the study group as the more stable. The atrial fibrillation showed a difference between two groups, with 14 (28%) patients with postoperative AF in the control group compared with 3 (6%) patients with postoperative AF in the study group. As potassium values were stable in study group, we concluded that it can be one of the reasons for less postoperative AF in this group. The duration of MV showed a significant difference (0,003) between the two groups as well. In the study group the average MV time was 534,38 minutes, compared with the control group with 749,20 minutes. The average value of glucose was 11.1 mmol/l in the control group vs. 9.8 mmol/l in the study group. The study group had less insulin consumption in order to maintain target glycemia (p = 0.001). In the non GIK group average insulin consumption was 44 IJ per patient vs. 28.5 IJ in the GIK group. Intraoperative GIK solution given to diabetic patients with CABG operation provides more stable CI, shorter time of MV, more stable values of potassium which provides normal rhythm and less AF onset, less insulin to maintain target glycemia. All the above mentioned provides more stable intraoperative hemodynamic and better recovery of diabetic


[Sphinctocystis phyllodoces gen. n., sp. n. (Eugregarinida: Lecudinidae)--a new gregarine from Phyllodoce citrina (Polychaeta: Phyllodocidae)].
A new species of aseptate gregarine, Sphinctocystis phyllodoces gen. n., sp. n., from the gut of a polychaete Phyllodoce citrina Malmgren, 1865 from White Sea is described. The electron and light microscopic data on trophozoits are presented. Taxonomy of the described species is discussed. Certain ultrastructural characters are included in generic and specific diagnoses. Order Eugregarinida Leger, 1900; suborder Aseptata Chakravarty, 1960; family Lecudinidae Kamm, 1922. Characters of the family. Free trophozoits elongated, often with several annular constrictions. Anterior end asymmetric, without hooks, not separated from the body, with small apical papilla encircled by smooth area. Epicyte "classical", without additional axial formations at the tops of folds; epicytic folds high, monomorphic in cross sections, finger-shaped, with parallel sidewalls. In the gut of polychaetes. The new genus differs from Lecudina by having asymmetric anterior end, developed smooth area around the apical papilla, and monomorphic epicytic folds looking finger-shaped in cross sections. It also differs from Lankesteria by the absence of additional axial formations at the tops of the epicytic folds. It differs from both named genera by presence of annular constrictions on the trophozoit body. Sphinctocystis phyllodoces sp. n. Characters of the genus. Free trophozoits elongated, large, up to 617 x x 77 um. The average height of epicytic folds 976 nm, thickness 194 nm; there are 6-8 apical filaments and rippled dense structures per fold. Nucleus spherical (ellipsoid after fixation), 24-52 microm along longest axis, localised in anterior third of the body, carries several karyosomes of various size; 25-30 nm thick fibrils (possible fragments of nucleolonema) may be present in karyolymph. Other stages unknown. TYPE SERIES: Microscope preparation with 7 trophozoits, Karacci's haematoxylin stained, is kept in the Zoological museum of the Moscow State University (collection number: Z-1). TYPE HOST: Phyllodoce citrina Malmgren, 1865 (Polychaeta: Phyllodocidae). LOCALISATION: Mid-gut. TYPE LOCALITY: White Sea Biological Station of the Moscow State University, Yeremeyevsky Rapid, Velikaya Salma Strait, Kandalaksha Bay, White Sea.


Quantitative Point-of-Care Colorimetric Assay Modeling Using a Handheld Colorimeter.
Colorimetric assays typically offer a rapid and convenient method to assess analytes that span healthcare monitoring to water quality testing. However, such tests can only provide qualitative results when employed in resource-limited settings or require bulky and expensive equipment such as lab spectrophotometers to allow quantitative measurements. In this paper, we report on the use of a handheld colorimeter to quantitatively determine the concentration of analytes in a manner that is independent of ambient lighting or initial sample color. The method combines the response of the sensor with first-principles modeling that better describes the nature of the assay compared to linear-in-parameters regression modeling that is typically performed in other studies. This method was successfully demonstrated using a number of colorimetric assays: (1) determination of solution pH using a universal indicator, (2) quantification of the DNase presence using a DNA-gold nanoparticle assay, and (3) quantification of the concentration of the antibiotic tetracycline using a cell-based assay.


[Effect of selenium on the bile-forming function of the liver].
The paper deals with efficiency of sodium selenite in case of acute damage of the liver in rats as well as with its effect on main functions of the liver in norm and pathology, especially on biligenesis, synthesis and secretion of bile acids, bilirubin and cholesterol. The preparation in doses of 1 and 10 Mg per 100 g of weight is established to produce a normalizing effect of intensity of biliation synthesis and secretion of bile acids, secretion of bilirubin and excretion of cholesterol in the animals with the affected liver. The preparation has a cholagogic effect as well. In the healthy rats sodium selenite increases the intensity of bile secretion, intensifies synthesis and secretion of bile acids and bilirubin. A stimulating effect of the preparation on biligenesis is maintained with the liver dystrophy induced by carbon tetrachloride and polychlorines as well. Under these conditions it is manifested to a greater extent than in the healthy animals.


Differential effects of trisomy on brain shape and volume in related aneuploid mouse models.
Down syndrome (DS) results from inheritance of three copies of human chromosome 21 (Hsa21). Individuals with DS have a significantly smaller brain size overall and a disproportionately small cerebellum. The small cerebellum is seen in Ts65Dn mice, which have segmental trisomy for orthologs of about half the genes on Hsa21 and provide a genetic model for DS. While small cerebellar size is well-established in mouse and humans, much less is known about the shape of the brain in trisomy. Here we conduct a morphometric analysis of the whole brain and cerebellum in Ts65Dn mice and show that the differences with euploid littermates are largely a function of volume and not of shape. This is not the case in two aneuploid mouse models that have fewer genes orthologous to Hsa21 than Ts65Dn. Ts1Rhr is trisomic for genes corresponding to the so-called Down syndrome critical region (DSCR), which was purported to contain a dosage sensitive gene or genes responsible for many phenotypes of DS. Ms1Rhr is monosomic for the same segment. These models show effects on cerebellum and overall brain that are different from each other and from Ts65Dn. These models can help to identify the contributions of genes from different regions of the chromosome on this and other aspects of brain development in trisomy.


Two-color emissive probes for click reactions.
Cu(I)-catalyzed azide-alkyne cyclization (CuAAC) is the paradigmatic click reaction of continuous interest. Especially fluorogenic and FRET probes have become indispensable tools for life sciences. Here, we present a fluorescent alkyne for monitoring CuAAC, which undergoes a bathochromic shift upon reaction. Application in single-molecule and catalysis research is foreseen.


A goat's head on a sheep's body? Manufacturing good practices for Tibetan medicine.
The production of Tibetan pharmaceuticals underwent a far-reaching transformation over the past decade. The introduction of good manufacturing practices (GMP) marked the beginning of rapid industrialization: new factories were built, and the companies re-oriented themselves to the requirements of the market. While officially regarded a great success, many doctors and pharmacists see GMP as fundamentally incompatible with traditional production methods and notions of quality. In this article, I address this incompatibility and examine where and how it affects the actual practice of producing medicines. While the problem exists, I argue that it does not stem from conflicting epistemologies but rather from the side effects of a quick and forced implementation, which often contradicts the spirit and letter of the regulations themselves. The case sheds new light on the way in which ideas about quality and safety, forged in the global arena, are locally recontextualized.


Hypoxia, bradykinin, and prostaglandins stimulate ischemically sensitive visceral afferents.
Ischemia of abdominal visceral organs is known to reflexly stimulate the cardiovascular system. The purpose of this study was to determine which of several potential chemical stimuli present during ischemia either directly stimulate or sensitize these afferents to respond to ischemia. Impulse activity was recorded in the right splanchnic nerve of anesthetized cats. First, we determined whether the afferents were ischemically sensitive by subjecting them to 2-6 min of regional ischemia through occlusion of the descending thoracic aorta. We then examined the afferents' response to systemic hypoxia by decreasing the inspired O2 and arterial injection of bradykinin or the prostaglandins (PG) E2, PGF2 alpha, or prostacyclin (PGI2). Sixty-one percent of the rapidly adapting A fibers and 47% of the C fibers were stimulated by ischemia, and of these, 78% of the A fibers and 44% of the C fibers tested were stimulated by hypoxia. The latency of response to hypoxia (60 +/- 12 s) was significantly longer than the chemoreceptor-induced pressor response (45 +/- 11 s). Each afferent stimulated by ischemia and/or hypoxia innervated a receptive field in the pylorus, intestine, porta hepatis, gallbladder or biliary tract, pancreas, or mesentery. Ninety percent of the ischemically sensitive A fibers and 80% of the ischemically sensitive C fibers responded to bradykinin, whereas 40% of the A fibers and 62% of the C fibers responded to PGE2, PGF2 alpha, or PGI2. Several endings responded to ischemia or hypoxia only after bradykinin or PGI2 had been injected. Thus approximately 50% of slowly adapting A and C fiber endings in abdominal visceral organs respond, or can be sensitized by bradykinin or PGI2 to respond, to ischemia and/or hypoxia. However, they are not as sensitive to hypoxia as carotid and aortic body chemoreceptors, since they respond well after the chemoreceptor-induced pressor response.


Monocyte/macrophage dysfunctions do not impair the promotion of myelofibrosis by high levels of thrombopoietin.
Several lines of evidence indicate that the megakaryocyte/platelet lineage is crucial in myelofibrosis induction. The demonstration that NOD/SCID mice with functionally deficient monocytes do not develop fibrotic changes when exposed to thrombopoietin (TPO) also suggests an important role for monocyte/macrophages. However, in this animal model, the development of myelofibrosis is dependent on the level of TPO. This study was conducted to investigate whether NOD/SCID mice exposed to high TPO levels mediated by a retroviral vector would be refractory to the development of bone marrow fibrosis. We show that TPO and TGF-beta1 in plasma from NOD/SCID and SCID mice engrafted with TPO-overexpressing hemopoietic cells reach levels similar to the ones reached in immunocompetent mice, and all animals develop a myeloproliferative disease associated with a dense myelofibrosis at 8 wk posttransplantation. Monocytes in NOD/SCID mice are functionally deficient to secrete cytokines such as IL-1alpha in response to stimuli, even under TPO expression. Surprisingly, the plasma of these mice displays high levels of IL-alpha, which was demonstrated to originate from platelets. Together, these data suggest that completely functional monocytes are not required to develop myelofibrosis and that platelets are able, under TPO stimulation, to synthesize inflammatory cytokines, which may be involved in the pathogenesis of myelofibrosis and osteosclerosis.


The role of thoracoscopy in the management of retained thoracic collections after trauma.
Retained hemothorax and infected thoracic collections after trauma can be seen in up to 20% of patients initially treated with tube thoracostomy and have traditionally been treated nonoperatively, often with prolonged hospital stays. Twenty-five patients with retained thoracic collections were reviewed. They underwent 26 thoracoscopies to evacuate undrained blood with or without infection. In 19 patients (76%), the collections were evacuated thoracoscopically. In 4 patients the procedure was converted to an open thoracotomy, and 2 patients required additional procedures to drain these collections. Failure of thoracoscopy correlated with the time between injury and operation and the type of collection, but not with the mechanism of injury. When thoracoscopy was performed in less than 7 days after admission, no cases of empyema were noted at operation. Videothoracoscopy is an accurate, safe, and reliable operative therapy to evacuate retained thoracic collections. In 90% of the patients in whom the procedure was completed, good results were obtained, reducing hospital stay and possible complications. Videothoracoscopy should be the initial treatment in trauma patients with retained thoracic collections and should be used earlier and more frequently in these patients.


Antibody to chlamydial hsp60 predicts an increased risk for chlamydial pelvic inflammatory disease.
To determine whether serum antibody to Chlamydia trachomatis antigens alters the risk of C. trachomatis pelvic inflammatory disease (PID), 280 female sex workers were prospectively evaluated over a 33-month period for incident C. trachomatis and Neisseria gonorrhoeae cervical infection and for clinical PID. At enrollment, women were tested for antibody to C. trachomatis elementary bodies by an indirect microimmunofluorescence assay and to recombinant chlamydial hsp60 (Chsp60) by an ELISA format. At each follow-up visit, women were tested for cervical chlamydial and gonococcal infection and were identified as having clinical PID if they complained of lower abdominal pain and were found to have uterine and adnexal tenderness on pelvic examination. The data demonstrate that antibody to Chsp60 predicts a 2- to 3-fold increased risk for C. trachomatis PID.


Neuronal systems underlying behaviors related to nicotine addiction: neural circuits and molecular genetics.
Nicotine addiction is a complex behavioral phenomenon comprising effects on several neural systems. Recent studies have expanded initial observations that the actions of nicotine on dopaminergic systems increase dopaminergic activity and release, leading to nicotine-induced reinforcement. Indeed, the actions of nicotine on many systems, including brainstem cholinergic, GABAergic, noradrenergic, and serotonergic nuclei, may help to mediate nicotine effects related to addiction. Furthermore, studies of mice lacking nicotinic acetylcholine receptor subunits or expressing supersensitive forms of these subunits have begun to tie together the molecular, neurochemical, and behavioral effects of nicotine. The use of multiple techniques by many laboratories provides optimism that the field is advancing toward elucidating the basic mechanisms of nicotine dependence.


Renal inflammatory pseudotumor.
A previously healthy 37-year-old man had evaluation of abdominal pain, which had persisted after abrupt onset with fever and hematuria. Although the fever and hematuria had spontaneously resolved after 1 week, the abdominal pain had worsened over a 4-month period. Predicated upon computed tomography and with a presumed diagnosis of renal cell adenocarcinoma, left radical nephrectomy was done. Histopathologic analysis was negative for malignancy but compatible with inflammatory pseudotumor of the urogenital tract--a pathologic entity that is common in the urinary bladder and prostate gland but is rarely diagnosed in the kidney.


Innovation in Breast Surgery: Practical and Ethical Considerations.
The adoption of innovation is essential to the evolution of patient care. Breast surgical oncology advances through incorporating new techniques, devices, and procedures. Historical changes in practice standards from radical to modified radical mastectomy or axillary node dissection to sentinel node biopsy reduced morbidity without sacrifice in oncologic outcome. Contemporary oncoplastic techniques afford broader consideration for breast conservation and the potential for improved cosmetic outcomes. At present, many breast surgeons face the decision of which wireless device to use for localization of nonpalpable lesions. Consideration for future changes, such as robotic mastectomy, are on the horizon. No guideline exists to assist breast surgeons in the adoption of innovation into practice. The Ethics Committee of the American Society of Breast Surgeons acknowledges that breast surgeons confront many questions associated with onboarding innovation. This paper aims to provide a framework for asking relevant questions along with the ethical principles to consider when integrating an innovation into practice.


Snapshot of medication abortion provision in the primary health care setting of regional and rural Victoria.
This study aimed to identify enablers and barriers to the provision of medication abortion in the primary health care setting of regional and rural areas of Victoria, Australia. An online cross-sectional questionnaire was used. Regional and rural areas of Victoria, Australia. Thirty-nine GPs and 30 primary health care nurses. Abortion views, medication abortion knowledge and practice, interest in medication abortion training and provision, and perceived uptake barriers. Most participants reported being consulted by women with unintended pregnancies and most of them included abortion counselling in their consultation. However, familiarity with provision of medication abortion was limited, and only five GPs and two primary health care nurses were currently medication abortion providers. The majority of participants expressed a high level of interest in receiving medication abortion training, but indicated a wide range of barriers to service provision, such as a lack of training opportunities, legal uncertainties or surgical access concerns in case of complications. Findings demonstrate the need for education on medication abortion and training opportunities. Most identified barriers to service uptake are addressable and relate to a lack of local support services, including the absence of a 24-hour contact advice service, insufficient follow-up access and a lack of local ultrasound facilities. These barriers require educational programs at professional, organisational and community level to ensure that interested rural and regional primary health care providers can start offering medication abortion for their patients.


Nucleotide sequence of the polyhedrin gene region of Helicoverpa zea single nucleocapsid nuclear polyhedrosis virus: placement of the virus in lepidopteran nuclear polyhedrosis virus group II.
The polyhedrin gene (polh) of Helicoverpa zea single nucleocapsid nuclear polyhedrosis virus (HzSNPV) was identified and shown by sequence analysis of the EcoRI I genomic fragment to encode a 246 amino acid polypeptide that has greater than 80% sequence identity to known polyhedrins. It is preceded by an AT-rich region containing the conserved late promoter motif TAAG, which was identified as a transcription start point. Downstream of polh there were several similarities in genome arrangement to other nuclear polyhedrosis viruses (NPVs). These include open reading frame (ORF) 8, immediately downstream of polh, encoding a 412 amino acid protein with multiple tandem proline residues, which is homologous to ORF8 (ORF1629) of Autographa californica multiple nucleocapsid NPV. Phylogenetic analysis of the polh gene region shows that HzSNPV is a member of the previously described lepidopteran NPV group II and that it is most closely related to polh of the NPVs of Malacosoma nuestria, Spodoptera littoralis, Orgyia pseudotsugata (single nucleocapsid-type virus) and Buzura supressaria.


Linkage analysis of idiopathic generalised epilepsy in families of probands with Juvenile Myoclonic Epilepsy and marker loci in the region of EPM 1 on chromosome 21 q: Unverricht-Lundborg disease and JME are not allelic variants.
The locus for Unverricht-Lundborg disease, EPM 1, has recently been mapped to chromosome 21q22.3. A locus, EJM 1, predisposing to idiopathic generalised epilepsy in families of probands with juvenile myoclonic epilepsy has been localised to chromosome 6p by evidence of linkage to the HLA region. However, segregation analysis suggests a two-locus model for JME and evidence has been obtained for genetic heterogeneity within the JME/IGE phenotype. EPM 1 was therefore investigated as a candidate locus in the set of families segregating for IGE and JME which do not show linkage to markers on chromosome 6p. Linkage analysis was carried out in 25 families using three microsatellite DNA markers around the EPM 1 gene region using different models of inheritance. Multipoint linkage analysis provided definite exclusion for 20cM around PFKL, the closet linked marker to EPM 1, under three out of four models tested. These results strongly suggest that the EPM 1 gene is not linked to the phenotype expressed in these families, and therefore that Unverricht-Lundborg disease and juvenile myoclonic epilepsy are not allelic variants.


A peripheral protein associated with the cis-Golgi network redistributes in the intermediate compartment upon brefeldin A treatment.
Human autoantibodies offer unique tools for the study of cellular constituents since they usually recognize highly conserved components, the most difficult to detect due to their low immunogenicity. The serum from a patient with Sjögren's syndrome (RM serum) showing a very high reactivity to the Golgi complex has been shown to immunoprecipitate and to immunodetect by Western blotting experiments a protein mol wt 210,000 (p210) that was shown to be peripheral and cytoplasmically disposed. A close examination of the p210 labeling revealed some differences with Golgi markers: RM serum staining was slightly more extensive than several Golgi markers and showed a discontinuous or granular appearance. Nocodazole induced a specific and early segregation of many p210-associated vesicles or tubules from Golgi apparatus. Upon brefeldin A treatment, p210 did not redistribute in the ER as did other Golgi proteins. In contrast, it exhibited a vesicular pattern reminiscent to that displayed by proteins residing in the intermediate compartment. Double staining immunofluorescence using the RM serum and the marker of the intermediate compartment, p58, revealed segregation of both proteins in control conditions but colocalization in BFA-treated cells. We have further demonstrated by combining different drug treatments that p210-containing elements in brefeldin A-treated cells belong indeed to the intermediate compartment. Experiments on brefeldin A recovery suggested that these p210 elements might play a role in reformation and repositioning of the Golgi apparatus. Ultrastructural localization performed by immunoperoxidase staining allowed us to establish that p210 interacted with the external side of an abundant tubulo-vesicular system on the cis side of the Golgi complex which extended to connecting structures and vesicles between saccules or stacks of cisternae, p210 appears to be a novel protein residing in the cis-Golgi network that may cycle between the Golgi apparatus and the intermediate compartment.


RNA Virus-Based Episomal Vector with a Fail-Safe Switch Facilitating Efficient Genetic Modification and Differentiation of iPSCs.
A gene delivery system that allows efficient and safe stem cell modification is critical for next-generation stem cell therapies. An RNA virus-based episomal vector (REVec) is a gene transfer system developed based on Borna disease virus (BoDV), which facilitates persistent intranuclear RNA transgene delivery without integrating into the host genome. In this study, we analyzed susceptibility of human induced pluripotent stem cell (iPSC) lines from different somatic cell sources to REVec, along with commonly used viral vectors, and demonstrated highly efficient REVec transduction of iPSCs. Using REVec encoding myogenic transcription factor MyoD1, we further demonstrated potential application of the REVec system for inducing differentiation of iPSCs into skeletal muscle cells. Of note, treatment with a small molecule, T-705, completely eliminated REVec in persistently transduced cells. Thus, the REVec system offers a versatile toolbox for stable, integration-free iPSC modification and trans-differentiation, with a unique switch-off mechanism.


The limits of the decentred state: the case of policing insurance claims fraud.
Existing research clearly shows that the public-private divide is continuously being challenged, recast and transformed. However, this article argues that a sharp distinction between public and private continues to operate as an important norm for professionals involved in the investigation of insurance claims fraud in Sweden. It shows how power within private insurance companies and the police authority is organized around the public-private divide, which is in turn mobilized to justify repression and to give investigations legitimacy. The article indicates that the formal public-private distinction is far more thoroughly maintained than is suggested by the existing literature. Rather than challenging the centrality of state power, private insurers and the police construct, maintain and have a stake in the reproduction of a state-centric monopoly of crime control.


Virtual reality-based 3-dimensional localization of stereotactic EEG (SEEG) depth electrodes and related brain anatomy in pediatric epilepsy surgery.
The increasing use of stereoelectroencephalography (SEEG) in the USA and the need for three-dimensional (3D) appreciation of complex spatial relationships between implanted stereotactic EEG depth electrodes and surrounding brain and cerebral vasculature are a challenge to clinicians who are used to two-dimensional (2D) appreciation of cortical anatomy having been traditionally trained on 2D radiologic imaging. Virtual reality and its 3D renderings have grown increasingly common in the multifaceted practice of neurosurgery. However, there exists a paucity in the literature regarding this emerging technology in its utilization of epilepsy surgery. An IRB-approved, single-center retrospective study identifying all SEEG pediatric patients in which virtual reality was applied was observed. Of the 46 patients identified who underwent an SEEG procedure, 43.5% (20/46) had a 3D rendering (3DR) of their SEEG depth electrodes. All 3DRs were used during patient-family education and discussion among the Epilepsy multidisciplinary team meetings, while 35% (7/20) were used during neuronavigation in surgery. Three successful representative cases of its application were presented. Our institution's experience regarding virtual reality in the 3D representation of SEEG depth electrodes and the application to pre-surgical planning, patient-family education, multidisciplinary communication, and intraoperative neuronavigation demonstrate its applicability in comprehensive epilepsy patient care.