Sociodemographic, Psychosocial, and Health Behavior Risk Factors Associated with Sexual Risk Behaviors among Southeastern US College Students.
We examined correlates of 1) being a virgin; 2) drug or alcohol use prior to the last intercourse; and 3) condom use during the last intercourse in a sample of college students. We recruited 24,055 students at six colleges in the Southeast to complete an online survey, yielding 4840 responses (20.1% response rate), with complete data from 4514. Logistic regression indicated that correlates of virginity included being younger (p < 0.001), male (p = 0.01), being White or other ethnicity (p < 0.001), attending a four-vs. two-year school (p < 0.001), being single/never married (p < 0.001), lower sensation seeking (p < 0.001), more regular religious service attendance (p < 0.001), lower likelihood of smoking (p < 0.001) and marijuana use (p = 0.002), and less frequentdrinking (p < 0.001). Correlates of alcohol or drug use prior to most recent intercourse including being older (p = 0.03), being White (p < 0.01), attending a four-year college (p < 0.001), being homosexual (p = 0.041) or bisexual (p = 0.011), having more lifetime sexual partners (p = 0.005), lower satisfaction with life (p = 0.004), greater likelihood of smoking (p < 0.001) and marijuana use (p < 0.001), and more frequent drinking (p < 0.001). Correlates of condom use during the last sexual intercourse including being older (p = 0.003), being female (p < 0.001), being White (p < 0.001), attending a two-year school (p = 0.04), being single/never married (p = 0.005), being homosexual or bisexual (p = 0.04), and a more frequent drinking (p = 0.001). Four-year college attendees were more likely to be a virgin but, if sexually active, reported higher sexual risk behaviors. These nuances regarding sexual risk may provide targets for sexual health promotion programs and interventions.


[Innovations in pathogenetic therapy for peripheral affection of the cranial nerves in otorhinolaryngology].
A total of 150 patients with peripheral affection of the facialnerve, 100 patients with acute neurosensory hypoacusis, 50 patients with affection of the reciprocal nerve were treated by the method using reciprocal interaction between M- and H-cholinergic mechanisms. Treatment outcomes showed that anticholinesterase therapy raises the efficacy of rehabilitation in patients with peripheral affection of the cranial nerves.


The Toll-Like Receptor 2 Ligand Pam2CSK4 Activates Platelet Nuclear Factor-κB and Bruton's Tyrosine Kinase Signaling to Promote Platelet-Endothelial Cell Interactions.
Circulating platelets establish a variety of immunological programs and orchestrate inflammatory responses at the endothelium. Platelets express the innate immunity family of Toll-like receptors (TLRs). While TLR2/TLR1 ligands are known to activate platelets, the effects of TLR2/TLR6 ligands on platelet function remain unclear. Here, we aim to determine whether the TLR2/TLR6 agonists Pam2CSK4 and FSL-1 activate human platelets. In addition, human umbilical vein endothelial cells (HUVECs) and platelets were co-cultured to analyze the role of platelet TLR2/TLR6 on inflammation and adhesion to endothelial cells. Pam2CSK4, but not FSL-1, induced platelet granule secretion and integrin αIIbβ3 activation in a concentration-dependent manner. Moreover, Pam2CSK4 promoted platelet aggregation and increased platelet adhesion to collagen-coated surfaces. Mechanistic studies with blocking antibodies and pharmacologic inhibitors demonstrated that the TLR2/Nuclear factor-κB axis, Bruton's-tyrosine kinase, and a secondary ADP feedback loop are involved in Pam2CSK4-induced platelet functional responses. Interestingly, Pam2CSK4 showed cooperation with immunoreceptor tyrosine-based activation motif (ITAM)-mediated signaling to enhance platelet activation. Finally, the presence of platelets increased inflammatory responses in HUVECs treated with Pam2CSK4, and platelets challenged with Pam2CSK4 showed increased adhesion to HUVECs under static and physiologically relevant flow conditions. Herein, we define a functional role for platelet TLR2-mediated signaling, which may represent a druggable target to dampen excessive platelet activation in thrombo-inflammatory diseases.


Differential expression of ubiquitin within the rat brain: discretely localized increases following salt-loading.
Ubiquitin is thought to be a universal component of all eukaryotic cells. The recent finding of ubiquitin as a component of abnormal neuronal filaments in various neurodegenerative diseases has prompted the need for knowledge of its distribution within the normal nervous system. To determine this distribution, the rat brain was examined immunocytochemically. Ubiquitin immunoreactivity was found within many regions of the rat brain, although to strikingly different degrees. Staining was most intense in the hypothalamic suprachiasmatic and supraoptic nuclei, as well as the anterodorsal nucleus of the thalamus, medial and lateral habenular nuclei and associated fibre tracts. Following salt-loading, ubiquitin immunoreactivity increased dramatically in axons of the hypothalamo-neurohypophysial tract and its site of termination, the posterior pituitary. In colchicine-treated rats the ubiquitin staining became more prominent in many areas of the brain including the supraoptic nucleus, the habenular nuclei, anterodorsal thalamic nucleus, the hypothalamic arcuate nucleus and cells within the ventral pallidum/substantia innominata region showing a distribution similar to nucleus basalis of Meynert. Partial anterior hypothalamic deafferentation indicated ubiquitin to be axonally-transported at a considerably slower rate than neuropeptides. The differential distribution of ubiquitin within the brain suggests an involvement in processes not heretofore considered.


Formation of Matricaria chamomilla extract-incorporated Ag nanoparticles and size-dependent enhanced antimicrobial property.
Various concentrations of Matricaria chamomilla (M. chamomilla) flower extract was used for biosynthesis of Ag NPs with different sizes, 70±5 (Ag NP-1), 52±5 (Ag NP-1) and 37±4nm (Ag NP-3), and size-specific antimicrobial activity of them was evaluated towards Gram+ Staphylococcus aureus (S. aureus), Gram- Escherichia coli (E. coli) bacteria and Candida fungus albicans (C. albicans). We also examine the formation of Ag NPs as a function of the plant extract volume, Ag ion concentration (Ag+) and reaction time. M. chamomilla flower extract at 100ppm shows mild inhibitory effect by inhibiting growth of all target pathogens. The extract mediated Ag NPs even at low concentration (6.25ppm) caused reductions in cell densities of the pathogens. The potential reasons for the highly effective inhibitory activity of the extract mediated Ag NPs are: (1) synergistic effects due to combination of M. chamomile extract and Ag NP because Ag NP is an effective germicidal and M. chamomile plant itself shows mild inhibitory property, (2) high localized concentration of M. chamomile extract due to nano scale entrapment of it on surface of Ag NP and (3) size-specific antibacterial efficacy of Ag NP because small size increases the active surface area of Ag NP, which reacting bacterial cells and increases number of extract molecules anchored on the surface of Ag NP.


A murine Mll-AF4 knock-in model results in lymphoid and myeloid deregulation and hematologic malignancy.
The 2 most frequent human MLL hematopoietic malignancies involve either AF4 or AF9 as fusion partners; each has distinct biology but the role of the fusion partner is not clear. We produced Mll-AF4 knock-in (KI) mice by homologous recombination in embryonic stem cells and compared them with Mll-AF9 KI mice. Young Mll-AF4 mice had lymphoid and myeloid deregulation manifest by increased lymphoid and myeloid cells in hematopoietic organs. In vitro, bone marrow cells from young mice formed unique mixed pro-B lymphoid (B220(+)CD19(+)CD43(+)sIgM(-), PAX5(+), TdT(+), IgH rearranged)/myeloid (CD11b/Mac1(+), c-fms(+), lysozyme(+)) colonies when grown in IL-7- and Flt3 ligand-containing media. Mixed lymphoid/myeloid hyperplasia and hematologic malignancies (most frequently B-cell lymphomas) developed in Mll-AF4 mice after prolonged latency; long latency to malignancy indicates that Mll-AF4-induced lymphoid/myeloid deregulation alone is insufficient to produce malignancy. In contrast, young Mll-AF9 mice had predominately myeloid deregulation in vivo and in vitro and developed myeloid malignancies. The early onset of distinct mixed lymphoid/myeloid lineage deregulation in Mll-AF4 mice shows evidence for both "instructive" and "noninstructive" roles for AF4 and AF9 as partners in MLL fusion genes. The molecular basis for "instruction" and secondary cooperating mutations can now be studied in our Mll-AF4 model.


[Imaging fusion in the diagnosis of prostate cancer].
Ultrasonography (US) is extensively used in the diagnosis of prostate cancer; but with its disadvantages of poor sensitivity and specificity, frequently causes underdiagnosis, and over 50% of the results of transrectal ultrasound (TRUS)-guided biopsy fail to accord with those of surgical pathology. In addition to contrast-enhanced ultrasound and real-time elastography, various new ultrasonic techniques have been developed nowadays, such as prostate histoscanning, brachytherapy template-guided 3-dimensional mapping biopsy (3DMB), and MRI/US fusion. Prostate histoscanning is an ultrasound-based technology that uses computer-aided analysis to identify and characterize the foci of prostate cancer. 3DMB, involving the whole gland, has an even higher accuracy. MRI/US fusion integrates the advantages of pre-interventional MRI with those of peri-interventional ultrasonography, and offers high-resolution images and convenient puncturing. Constant development of ultrasonography will continue to add to its clinical application value.


Novel approach for pain control in patients undergoing prostate biopsy: iliohypogastric nerve block with or without topical application of prilocaine-lidocaine: a randomized controlled trial.
To investigate the efficacy of a novel anesthetic technique called iliohypogastric nerve block (INB) for pain control in patients undergoing prostate biopsy. A total of 59 consecutive patients who underwent transrectal ultrasound guided prostates biopsies were included in the study. Patients were randomized into four groups: (1) control, no method of anesthesia was administered, (2) intrarectal prilocaine-lidocaine cream application, (3) INB and (4) INB + intrarectal prilocaine-lidocaine cream application (combined group). Patients were asked to use a scale of 0-10 in a Visual Analogue Scale (VAS) questionnaire about pain during probe insertion (VAS 1) and prostate biopsy (VAS 2). The mean VAS 1 and VAS 2 scores were 0.7 and 4.9 for controls, 0.5 and 1.8 for INB, 0.5 and 2.6 for the intrarectal cream group, and 0.4 and 1.8 for the combined group. The mean VAS 1 scores were not different between groups. However, the mean VAS 2 scores were significantly lower in INB, prilocaine-lidocaine cream and combined groups compared to the control group (P < .001). In addition, the INB group had significantly lower VAS 2 scores compared to the cream application group (P = .03). On the other hand, there was no difference between the INB and combined groups (P = .8). Any form of anesthesia was superior to none. However, INB alone seemed to be superior to prilocaine-lidocaine cream application in patients undergoing prostate biopsy. Addition of prilocaine-lidocaine cream application to INB may not provide better analgesia.


Imaging in the diagnosis and prognosis of traumatic brain injury.
Traumatic brain injury (TBI) is a major cause of death and disability worldwide. Improved understanding of the impact of head injury and the extent and development of neuronal loss and cognitive dysfunction could lead to improved therapy and outcome for patients. This paper reviews the currently available imaging techniques and defines their role in the diagnosis, management and prediction of outcome following traumatic brain injury. These imaging techniques provide delineation of the structural, physiological and functional derangements that result following acute injury, and map their development and association with late functional deficits. Imaging tools also have a role in defining the pathophysiological mechanisms responsible for further neuronal loss following the primary injury. Finally, this paper provides an overview of the role of functional imaging in classifying unresponsive coma and defining functional reorganisation of the brain following injury. Brain imaging is of key importance in TBI management, enabling efficient and accurate diagnoses to be made, informing management decisions and contributing to prognostication. Developments in imaging techniques promise to improve understanding of the structural and functional derangements, improve management and guide the development and implementation of novel neuroprotective strategies following head injury.


Evolution-based hierarchical feature fusion for ultrasonic liver tissue characterization.
This paper presents an evolution-based hierarchical feature fusion system that selects the dominant features among multiple feature vectors for ultrasonic liver tissue characterization. After extracting the spatial gray-level dependence matrices, multiresolution fractal feature vectors and multiresolution energy feature vectors, the system utilizes evolution-based algorithms to select features. In each feature space, features are selected independently to compile a feature subset. As the features of different feature vectors contain complementary information, a feature fusion process is used to combine the subsets generated from different vectors. Features are then selected from the fused feature vector to form a fused feature subset. The selected features are used to classify ultrasonic images of liver tissue into three classes: hepatoma, cirrhosis, and normal liver. Experiment results show that the classification accuracy of the fused feature subset is superior to that derived by using individual feature subsets. Moreover, the findings demonstrate that the proposed algorithm is capable of selecting discriminative features among multiple feature vectors to facilitate the early detection of hepatoma and cirrhosis via ultrasonic liver imaging.


[Population biology of parasites: current status and prospects].
The present state of parasite population biology is reviewed with special reference to parasites of fish. Mathematical models have provided a coherent body of theory which is supported by many laboratory investigations. There is nevertheless some disagreement between predictions based on this theory and data obtained from investigations of natural parasite populations. It is suggested that this is partly due to the oversimplifications and limitations of the models, and partly to the unsystematic approach of many field investigations and the resulting shortage of data of the right sort. In freshwater habitats disagreement may also be due to the rapid and extensive changes that are taking place in the habitats themselves as a direct consequence of human activities. Future developments should involve models becoming more realistic, and field investigations being conducted in a more systematic and analytical manner in order to obtain quantitative measurements of the essential population parameters.


Selection-marker-free modification of the murine beta-casein gene using a lox2272 [correction of lox2722] site.
Gene targeting and site-specific recombination strategies allow the precise modification of the eukaryotic genome. Many of the recombination strategies currently used, however, will introduce a selection marker gene at the modified site. DNA sequences of prokaryotic origin like vector sequences, selection marker, and reporter genes have been shown to markedly influence the regulation of the modified genomic loci. In order to avoid the insertion of excess sequences, a biphasic recombination strategy involving homologous recombination and Cre-recombinase-mediated cassette exchange (RMCE) was devised and used to insert a foreign gene into the beta-casein gene in murine embryonic stem cells. The incompatibility of the heterospecific lox sites used for the recombinase-mediated cassette exchange was found to be critical for the success of the strategy. The frequently used mutant site lox511, which differs from the natural loxP site by a single point mutation, proved unsuitable for this approach. A mutant lox site carrying two point mutations, however, was highly effective and 90% of the selected cell clones carried the desired modification. This biphasic recombination strategy allows for the efficient and precise modification of gene loci without the concomitant introduction of a selectable marker gene.


[Psychotropic effect of phenibut salts and their compositions with organic acids].
The spectra of psychotropic action of some phenibut salts (succunate, maleate, nicotinate) and a composition of phenibut with glutamic acid were studied. It is established, that the substances studied show psychotropic activity spectrum generally similar to that of phenibut, but different in expressiveness of some particular effects. Compound RSPU-149 exhibited the most pronounced psychotropic action: its anxiolytic effect was below, the antidepressant effect was comparable with, and the nootrope action exceeded that of phenibut.


Comparison of In-Hospital Outcomes in Patients Having Limb-Revascularization With Versus Without Atrial Fibrillation.
The impact of atrial fibrillation (AF) on clinical outcomes among patients with peripheral artery disease (PAD) who undergo limb revascularization procedures is not well understood. We aim to compare in-hospital outcomes for patients with and without AF who underwent limb revascularization. We identified patients with PAD aged ≥18 years that underwent limb revascularization using endovascular or surgical approaches in the National Inpatient Sample between 2002 and 2014. Multivariate logistic regression analysis was performed to examine in-hospital outcomes. A total of 2,283,568 patients underwent limb revascularization during the study duration and 294,469 (12.9%) had AF. Patients with AF were older (mean age 76.1 ± 10.0 years), more likely to be women and white, compared with non-AF group. Among patients who had surgical revascularization, AF was associated with a higher rates of in-hospital mortality (6.4% vs 2.5%, adjusted odds ratio [aOR]: 1.09 [95% confidence interval {CI}: 1.05 to 1.12]) and major amputation (5.2% vs 3.8%, aOR: 1.05 [95% CI: 1.02 to 1.08]), compared with non-AF group. Among patients who had endovascular intervention (EVI), AF was associated with a higher rates of in-hospital mortality (3.8% vs 1.6%, aOR: 1.29 [95% CI: 1.24 to 1.33]) and major amputation (5.2% vs 3.9%, aOR: 1.07 [95% CI: 1.04 to 1.10]), compared with non-AF group. Within study period, EVI utilization increased in patients with and without AF (Ptrend <0.001); whereas, surgical revascularization utilization decreased in patients with and without AF (Ptrend <0.001). In conclusion, among patients with PAD who undergo limb revascularization, AF appears to be associated with poor in-hospital outcomes.


Gender, underutilization of cardiac resynchronization therapy, and prognostic impact of QRS prolongation and left bundle branch block in heart failure.
It has been suggested that cardiac resynchronization therapy (CRT) is less utilized, dyssynchrony occurs at narrower QRS, and CRT is more beneficial in women compared with men. We tested the hypotheses that (i) CRT is more underutilized and (ii) QRS prolongation and left bundle branch block (LBBB) are more harmful in women. We studied 14 713 patients (28% women) with left ventricular ejection fraction (LVEF) <40% in the Swedish Heart Failure Registry. In women vs. men, CRT was present in 4 vs. 7% (P < 0.001) and was absent but with indication in 30 vs. 31% (P = 0.826). Next, among 13 782 patients (28% women) without CRT, 9% of women and 17% of men had non-specific intraventricular conduction delay (IVCD) and 27% of women and 24% of men had LBBB. One-year survival with narrow QRS was 85% in women and 88% in men, with IVCD 74 and 78%, and with LBBB 84 and 82%, respectively. Compared with narrow QRS, IVCD had a multivariable hazard ratio of 1.24 (95% CI 1.05-1.46, P = 0.011) in women and 1.30 (95% CI 1.19-1.42, P < 0.001) in men, and LBBB 1.03 (95% CI 0.91-1.16, P = 0.651) in women and 1.16 (95% CI 1.07-1.26, P < 0.001) in men, P for interaction between gender and QRS morphology, 0.241. While the proportion with CRT was lower in women, CRT was equally underutilized in both genders. QRS prolongation with or without LBBB was not more harmful in women than in men. Efforts to improve CRT implementation should be directed equally towards women and men.


Transhepatic Insertion of Percutaneous Endoscopic Gastrostomy Tube.
Inadvertent injury to interposing organs during percutaneous endoscopic gastrostomy (PEG) tube placement is a feared complication of this common and generally safe procedure. Transhepatic PEG insertion is likely an underrepresented complication which may be identified incidentally on imaging or present with life-threatening conditions such as sepsis or massive bleeding. Use of ultrasound in patients with known hepatomegaly may possibly help avoid this complication. We hereby report a case of transhepatic PEG insertion, one of 16 only other cases published in the literature, and review the characteristics of the previous reported cases.


Association between benign prostatic hyperplasia, body mass index, and metabolic syndrome in Chinese men.
Previous studies have showed that men suffering from diabetes mellitus, metabolic syndrome (MetS) and obesity have a higher risk of benign prostatic hyperplasia (BPH). The present study aimed to examine the association between BPH, obesity, and features of MetS among men of the Hunan area of China. For this cross-sectional study, 904 males (aged 50-59 years) were included. MetS parameters, International Prostate Symptom Score (IPSS), prostate-specific antigen (PSA) levels, total prostate volume (TPV), postvoid residual volume (PVR) and maximum urine flow rate (Qmax) were measured. Results showed that MetS was associated with TPV (P = 0.048), PVR (P = 0.004) and IPSS (P = 0.011), but not with other indicators of BPH progression such as PSA levels or Qmax. MetS was associated with the voiding symptoms score (P < 0.05), but not with the storage symptom score. In addition, body mass index and fasting blood glucose positively correlated with TPV (r = 0.416, P< 0.001; and r = 0.310, P= 0.011, respectively). In conclusion, results suggest that MetS is associated with higher prostatic volume, prostate symptom score and voiding symptoms, but not with other features of prostatic hyperplasia such as PSA levels or Qmax. Changes in lifestyle factors, including physical activity and prevention of MetS, might be useful to prevent BPH and its progression, but further studies are needed.


[Correlation between the count of the various intraepithelial mononuclear leukocytes and tumor progression in the stomach].
A study of 35 gastrobioptates sampled from benign epithelial proliferates, adenomas with advanced epithelial dysplasia and adenocarcinomas was conducted using standard original procedures of staining and DNA identification. Also, the method of direct immunoluminescence using fluoroesceinisothiocymate-labeled monoclonal antibodies against human antigens CD4, CD8, CD25 and CD45 was employed. It was found that, among microscopic intraepithelial mononuclear leukocytes, only few bear the immunohistochemical markers of activity. The distribution of intraepithelial mononuclear leukocytes in the stomach of a cancer patient is changed.


The Natural History and Transmission Potential of Asymptomatic Severe Acute Respiratory Syndrome Coronavirus 2 Infection.
Little is known about the natural history of asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We conducted a prospective study at a quarantine center for coronavirus disease 2019 in Ho Chi Minh City, Vietnam. We enrolled quarantined people with reverse-transcription polymerase chain reaction (RT-PCR)-confirmed SARS-CoV-2 infection, collecting clinical data, travel and contact history, and saliva at enrollment and daily nasopharyngeal/throat swabs (NTSs) for RT-PCR testing. We compared the natural history and transmission potential of asymptomatic and symptomatic individuals. Between 10 March and 4 April 2020, 14 000 quarantined people were tested for SARS-CoV-2; 49 were positive. Of these, 30 participated in the study: 13 (43%) never had symptoms and 17 (57%) were symptomatic. Seventeen (57%) participants imported cases. Compared with symptomatic individuals, asymptomatic people were less likely to have detectable SARS-CoV-2 in NTS collected at enrollment (8/13 [62%] vs 17/17 [100%]; P = .02). SARS-CoV-2 RNA was detected in 20 of 27 (74%) available saliva samples (7 of 11 [64%] in the asymptomatic group and 13 of 16 [81%] in the symptomatic group; P = .56). Analysis of RT-PCR positivity probability showed that asymptomatic participants had faster viral clearance than symptomatic participants (P < .001 for difference over the first 19 days). This difference was most pronounced during the first week of follow-up. Two of the asymptomatic individuals appeared to transmit SARS-CoV-2 to 4 contacts. Asymptomatic SARS-CoV-2 infection is common and can be detected by analysis of saliva or NTSs. The NTS viral loads fall faster in asymptomatic individuals, but these individuals appear able to transmit the virus to others.


Effects of oral or parenteral iron supplementation on haematological parameters, blood iron status and growth in newborn calves fed milk replacer.
This study aimed to assess the influence of early life iron supplementation on the haematological parameters of calves fed milk replacer on a high plane of nutrition. Thirty calves were allocated to receive either a sham treatment (CON), injection of 1000 mg Fe3+ (INJ) or oral administration of 1050 mg Fe3+ (ORAL), all administered less than 1 hour after birth. Blood was obtained before treatment, on days 1, 3, 5 and 7 of life and once weekly until week 9. Samples were analysed for haemoglobin (Hb), packed cell volume (PCV) and estimated transferrin saturation (%TSAT). The Hb and PCV of calves in the INJ and ORAL groups were above the values of those in the CON group throughout the study. Hb and PCV of the CON group remained within the reference range for calves. The %TSAT exceeded reported ranges in the ORAL group in the first week. Values for the CON group were below the INJ and ORAL groups throughout the entire study. Average daily gain did not differ between treatments. The sample size was insufficient to assess the influence of iron supplementation on disease development. Furthermore, the study was set in a controlled environment and not performed under field conditions. Oral and subcutaneous iron administration had similar effects on haematological development but resulted in numerically different transferrin saturation. Control animals showed lower Hb and PCV but did not develop overt anaemia.


Revascularization surgery: impact on lower extremity amputations.
The effect of revascularization surgery on the amputee population of 2 hospitals (VA and private) was studied in 2 time periods a decade apart--1969-70 and 1979-80. In the VA hospital there was a trend toward below-knee surgery over time; however, for patients who had prior vascular reconstruction and who ultimately came to amputation there was no change in the proportion of below-knee to above-knee surgery at either hospital. At the private hospital the average age of patients who underwent amputation increased significantly and the proportion of patients requiring amputation to the total number of patients undergoing vascular reconstruction significantly decreased in the later time period.


Pyogenic streptococci--danger of re-emerging pathogens.
Beta-hemolytic, pyogenic streptococci are classified according to type of major surface antigen into A (Streptococcus pyogenes), B (Streptococcus agalactiae), C (multiple species including Streptococcus dysagalactiae) and G (multiple species including Streptococcus canis) Lancefield groups. Group A Streptococcus causes each year hundreds of thousands deaths globally as a result of infections and post-infectional sequelae. An increasing number of severe, invasive infections is caused by selected, specialized pathogenic clones. Within the last 50 years, an increasing number of human infections caused by groups B, C and G Streptococcus (GBS, GCS, GGS) has been observed worldwide. GBS was first identified as animal pathogen but the spectrum of diseases caused by GBS quickly shifted to human infections. Groups C and G Streptococcus are still regarded mostly as animal pathogens, however, an increased number of severe infections caused by these groups is observed. The increasing number of human infections caused worldwide by GCS/GGS can be a sign of similar development from animal to human pathogen as observed in case of GBS and this group will gain much more clinical interest in the future.The situation in Poland regarding invasive infections caused by pyogenic streptococci is underestimated.


Laguna Negra Virus Infection Causes Hantavirus Pulmonary Syndrome in Turkish Hamsters (Mesocricetus brandti).
Laguna Negra virus (LNV) is a New World hantavirus associated with severe and often fatal cardiopulmonary disease in humans, known as hantavirus pulmonary syndrome (HPS). Five hamster species were evaluated for clinical and serologic responses following inoculation with 4 hantaviruses. Of the 5 hamster species, only Turkish hamsters infected with LNV demonstrated signs consistent with HPS and a fatality rate of 43%. Clinical manifestations in infected animals that succumbed to disease included severe and rapid onset of dyspnea, weight loss, leukopenia, and reduced thrombocyte numbers as compared to uninfected controls. Histopathologic examination revealed lung lesions that resemble the hallmarks of HPS in humans, including interstitial pneumonia and pulmonary edema, as well as generalized infection of endothelial cells and macrophages in major organ tissues. Histologic lesions corresponded to the presence of viral antigen in affected tissues. To date, there have been no small animal models available to study LNV infection and pathogenesis. The Turkish hamster model of LNV infection may be important in the study of LNV-induced HPS pathogenesis and development of disease treatment and prevention strategies.


Potential of urinary metabolites for diagnosing multiple sclerosis.
A definitive diagnostic test for multiple sclerosis (MS) does not exist; instead physicians use a combination of medical history, magnetic resonance imaging, and cerebrospinal fluid analysis (CSF). Significant effort has been employed to identify biomarkers from CSF to facilitate MS diagnosis; however, none of the proposed biomarkers have been successful to date. Urine is a proven source of metabolite biomarkers and has the potential to be a rapid, noninvasive, inexpensive, and efficient diagnostic tool for various human diseases. Nevertheless, urinary metabolites have not been extensively explored as a source of biomarkers for MS. We demonstrate that urinary metabolites have significant promise for monitoring disease-progression, and response to treatment in MS patients. NMR analysis of urine permitted the identification of metabolites that differentiate experimental autoimmune encephalomyelitis (EAE)-mice (prototypic disease model for MS) from healthy and MS drug-treated EAE mice.


Neutrophil-to-lymphocyte ratio predicts survival in European patients with hepatocellular carcinoma administered sorafenib.
Neutrophil-to-lymphocyte ratio (NLR) is considered a prognostic factor in patients with hepatocellular carcinoma (HCC). Our aim is to investigate the prognostic significance of NLR in patients with HCC treated with sorafenib. Median follow-up time was 7 months. Patients were mostly in the intermediate (27.3%) or advanced (72.7%) BCLC stages, 38.6% had vascular invasion and 27.5% extrahepatic disease. A large proportion (38.9%) had been previously treated with TACE. Liver function was preserved: 65.8% were classed as Child A. Median overall survival was 7.7 months (95% CI: 5.8-9.6). In univariate analysis, vascular invasion (P = 0.004), ECOG-PS ≥ 1 (P < 0.001), high bilirubin (P < 0.001), clinical ascites (P = 0.036), BCLC stage (P = 0.004), no previous TACE (P = 0.041) and NRL ≥ 2.3 (P = 0.005) were predictors of poor survival. Skin toxicity (P = 0.039) or hypertension (P = 0.033) during treatment were related to better survival. In multivariate analysis NLR ≥ 2.3 [HR 1.72 (95% CI: 1.03-2.71)], hyperbilirubinemia [HR 3.42 (95% CI: 1.87-6.25)] and ECOG-PS ≥ 1 [HR 1.97 (95% CI: 1.19-3.26)] were found as independent indicators of poor overall survival. Dermatologic adverse effects were an indicator of good overall survival [HR 0.59 (95% CI: 0.38-0.92)]. One hundred and fifty-four consecutive HCC patients treated with sorafenib in four different Spanish hospitals between August 2005 and October 2013 were analysed. Clinical, laboratory, and tumour features were obtained. Survival was calculated from the moment sorafenib treatment was initiated. Log-rank and Cox regression were used to analyse the ability of NLR to predict survival. NLR is an independent prognostic indicator for overall survival in HCC patients treated with sorafenib.


Effect of donor and culture age on the function of neutrophils harvested from long-term bone marrow culture.
Neutrophils harvested from the supernatants of long-term bone marrow cultures that were initiated from young and old mice were tested for their functional activity. Superoxide generation was measured, as was the secretion of the enzymes lysozyme, myeloperoxidase, and glucuronidase, both basally and following stimulation by phorbol myristate acetate. The function of the neutrophils harvested from cultures that were initiated from young mice was identical to that of cells derived from young mouse peritoneal cavities at the time of death. A minimal decline in function in culture-derived cells was seen over the 15-18 weeks of study. For each of the above measurements examined, neutrophils obtained from cultures initiated from old mice gave values significantly lower than those in neutrophils recovered from cultures initiated from young mice. For some parameters (superoxide generation, myeloperoxidase), the rate of decline in function was more rapid for neutrophils from old rather than young mouse cultures. For other measurements the rates of decline were equal. The results indicated adequate neutrophil function in long-term bone marrow culture for extended periods of time. They also demonstrated that the age-related diminution in neutrophil function observed in vivo persisted in in vitro culture.


Mid-term Incidence of Tarsometatarsal Joint Arthrodesis Following Open Reduction With Internal Fixation (ORIF) of Lisfranc Injuries.
Open reduction with internal fixation (ORIF) of Lisfranc injuries are associated with an increased risk for secondary surgery including hardware removal and salvage arthrodesis. In the current literature, rates of salvage arthrodesis vary due to small sample sizes and a low incidence of Lisfranc injuries. There is little evidence to identify specific surgical and patient-related variables that may result in later arthrodesis. The purpose of this study is to determine the rate of tarsometatarsal joint arthrodesis following Lisfranc ORIF in a relatively large sample size. This retrospective review included patients who underwent ORIF for a Lisfranc injury between January 2007 and December 2012. A total of 146 patients met our criteria. Trans-articular fixation was used in 109 (74.6%) patients, 33 (22.6%) received percutaneous fixation and 4 (2.7%) extraarticular fixation. Five out of 120 (4.2%) patients required a salvage arthrodesis for post-traumatic arthritis that had a follow-up greater than 5 y but up to 10 y. The mean age of patients who underwent arthrodesis after ORIF was 24.5 ± 11.95 (16-48) y compared to 40.9 ± 15.8 (16-85) y. Patients who required an arthrodesis also had earlier hardware removal than patients who did not have an arthrodesis, 71.2 ± 28.3 (38-100) days and 131.4 ±101.2 (37-606) days, respectively. Patients who required salvage arthrodesis tended to be younger and hardware was removed earlier compared to those patients who did not require an arthrodesis. Four of the 5 patients who underwent a secondary arthrodesis had a loss of correction after hardware removal.


Nosocomial acute-onset postoperative endophthalmitis survey. A 10-year review of incidence and outcomes.
The purpose of the study was to evaluate the incidence of acute-onset (within 6 weeks after surgery) postoperative endophthalmitis and to assess the visual acuity outcomes after treatment over a 10-year period at one institution. This retrospective study reviews all surgical cases performed between January 1, 1984 and December 30, 1994 at the Anne Bates Leach Eye Hospital, Bascom Palmer Eye Institute, University of Miami Medical Center, for the occurrence of nosocomial acute-onset postoperative endophthalmitis. The overall 10-year incidence of acute-onset postoperative endophthalmitis after intraocular surgery was 0.093% (54/58, 123). The incidences of culture-proven acute-onset postoperative endophthalmitis by surgical category were as follows: cataract surgery with or without intraocular lens (IOL) (0.082%, 34/41, 654), pars plana vitrectomy (PPV) (0.046%, 3/6557), penetrating keratoplasty (0.178%, 5/2805), secondary IOL placement (0.366%, 5/1367), glaucoma surgeries (0.124%, 4/3233), combined trabeculectomy and cataract surgery (0.114%, 2/1743), and combined penetrating keratoplasty and cataract surgery (0.194%, 1/515). The median visual acuity after endophthalmitis treatment was 20/200. The median visual acuities after endophthalmitis treatment by procedure were as follows: cataract surgery with or without IOL (20/133), PPV (no light perception), penetrating keratoplasty (2/200), secondary IOL implantation (20/40), glaucoma surgery (20/80), and combined trabeculectomy and cataract surgery with or without IOL (20/150). The overall incidence of endophthalmitis after intraocular surgery was 0.093%. The incidence of endophthalmitis was higher after secondary IOL implantation than after cataract extraction (P = 0.008, Fisher's exact test). After treatment, the visual acuity outcomes were worse in the patients who developed endophthalmitis after PPV than after cataract extraction, glaucoma procedures, or secondary IOL implantation (P < 0.05, analysis of variance, Duncan's multiple range test). Acuity outcomes after treatment of endophthalmitis were better among the patients with secondary IOL implantation than after penetrating keratoplasty or PPV (P < 0.05, analysis of variance, Duncan's multiple range test). The results of this 10-year review from a large teaching center may serve as a source of comparison for other centers and future studies.


Perceptual learning and adult cortical plasticity.
The visual cortex retains the capacity for experience-dependent changes, or plasticity, of cortical function and cortical circuitry, throughout life. These changes constitute the mechanism of perceptual learning in normal visual experience and in recovery of function after CNS damage. Such plasticity can be seen at multiple stages in the visual pathway, including primary visual cortex. The manifestation of the functional changes associated with perceptual learning involve both long term modification of cortical circuits during the course of learning, and short term dynamics in the functional properties of cortical neurons. These dynamics are subject to top-down influences of attention, expectation and perceptual task. As a consequence, each cortical area is an adaptive processor, altering its function in accordance to immediate perceptual demands.


Microstimulation in the region of the human thalamic principal somatic sensory nucleus evokes sensations like those of mechanical stimulation and movement.
We explored the region of human thalamic somatic sensory nucleus (ventral caudal, Vc), corresponding to monkey ventral posterior (VP), with threshold microstimulation (TMIS) during stereotactic procedures for the treatment of tremor. Of 122 sites in 116 patients (124 thalami) where mechanical (touch, pressure, and sharp) or movement [movement through the body (movement) and vibration] sensations were evoked, 72 sites were found in the core or in adjacent regions, posterior-inferior (33), inferior (4), and posterior to the core (13). Sites where TMIS evoked touch were less frequently found in the core than those where movement or pressure sensations were evoked. Pressure was more commonly (P < 0.05) evoked than vibration at sites where cells had intraoral receptive fields (RFs). Touch and vibration were more commonly (P < 0.05) evoked than pressure at sites where cells had facial RFs, consistent with the relative density of rapidly adapting (RA) receptors in the mouth and face. Sites described as deep and movement were found superior and anterior in the core, consistent with the location of cells responding to stimulation of muscle afferents. At 72 of 122 sites, TMIS evoked the same sensation at two or more sites in the same plane. Of these sites, 58 are adjacent to each other, in a cluster, consistent with studies of the localization of cells responding to different modalities. These results demonstrate that mechanical and movement sensations can be evoked by stimulation in the region of Vc. The characteristics of these sites suggest that the sensations are evoked by stimulation of pathways specific to cutaneous and deep mechanoreceptors.


Effective treatment of H838 human non-small cell lung carcinoma with a targeted cytotoxic somatostatin analog, AN-238.
The accumulation of radioactive somatostatin analog [111In]pentetreotide in non-small cell lung cancer (non-SCLC) during scintigraphy of patients provides a rationale for investigating the efficacy of somatostatin receptor-based chemotherapy in non-SCLC. Consequently, in this study, we evaluated the antitumor effects of cytotoxic somatostatin analog AN-238 on H838 human non-SCLC xenografted into nude mice in comparison with its cytotoxic radical, 2-pyrrolinodoxorubicin (AN-201). The expression of messenger RNA (mRNA) for human somatostatin receptor subtypes 2 (hsst2) and 5 (hsst5) in H838 cells, and tumors was also investigated using reverse-transcription polymerase chain reaction (RT-PCR). Somatostatin receptors on H838 tumors were characterized by ligand competition assay using radiolabeled somatostatin analog, RC-160. Three i.v. injections of AN-238 at 150 nmol/kg, given on days 1, 7 and 21, resulted in a significant (p<0.05) tumor growth inhibition, the final tumor volume being 60% smaller than in the controls. The tumor doubling time was also extended significantly (p<0.05) from 9.65+/-0.56 days in the controls to 17.52+/-3.3 days. Only one of 8 mice died due to toxicity. In contrast, cytotoxic radical AN-201 was ineffective and more toxic, killing 2 of 7 animals. mRNA for hsst2 was found in H838 xenografts, but not in H838 cells from which the xenografts originated. Interestingly, H838 cells grown in a special, serum-free medium did express mRNA for hsst2. mRNA for hsst5 was not found in any samples tested. Binding studies demonstrated the presence of high affinity (K(d) = 7.3+/-1.2 nM) binding sites for RC-160 with a mean maximal binding capacity (B(max)) of 953.3+/-45.3 fmol/mg protein. AN-238 at 3.14+/-0.93 nM concentration displaced 50% of radiolabeled RC-160 binding to somatostatin receptors in H838 tumors. Our results indicate that patients with inoperable non-SCLC may benefit from chemotherapy targeted to somatostatin receptors based on AN-238.


Not Frozen in the Ice: Large and Dynamic Rearrangements in the Mitochondrial Genomes of the Antarctic Fish.
The vertebrate mitochondrial genomes generally present a typical gene order. Exceptions are uncommon and important to study the genetic mechanisms of gene order rearrangements and their consequences on phylogenetic output and mitochondrial function. Antarctic notothenioid fish carry some peculiar rearrangements of the mitochondrial gene order. In this first systematic study of 28 species, we analyzed known and undescribed mitochondrial genome rearrangements for a total of eight different gene orders within the notothenioid fish. Our reconstructions suggest that transpositions, duplications, and inversion of multiple genes are the most likely mechanisms of rearrangement in notothenioid mitochondrial genomes. In Trematominae, we documented an extremely rare inversion of a large genomic segment of 5,300 bp that partially affected the gene compositional bias but not the phylogenetic output. The genomic region delimited by nad5 and trnF, close to the area of the Control Region, was identified as the hot spot of variation in Antarctic fish mitochondrial genomes. Analyzing the sequence of several intergenic spacers and mapping the arrangements on a newly generated phylogeny showed that the entire history of the Antarctic notothenioids is characterized by multiple, relatively rapid, events of disruption of the gene order. We hypothesized that a pre-existing genomic flexibility of the ancestor of the Antarctic notothenioids may have generated a precondition for gene order rearrangement, and the pressure of purifying selection could have worked for a rapid restoration of the mitochondrial functionality and compactness after each event of rearrangement.


Concise review: maturation phases of human pluripotent stem cell-derived cardiomyocytes.
Human pluripotent stem cell-derived cardiomyocytes (hPS-CM) may offer a number of advantages over previous cardiac models, however, questions of their immaturity complicate their adoption as a new in vitro model. hPS-CM differ from adult cardiomyocytes with respect to structure, proliferation, metabolism and electrophysiology, better approximating fetal cardiomyocytes. Time in culture appears to significantly impact phenotype, leading to what can be referred to as early and late hPS-CM. This work surveys the phenotype of hPS-CM, including structure, bioenergetics, sensitivity to damage, gene expression, and electrophysiology, including action potential, ion channels, and intracellular calcium stores, while contrasting fetal and adult CM with hPS-CM at early and late time points after onset of differentiation.


Neurologic complications in adult living donor liver transplant recipients.
Neurologic complications (NC) after liver transplantation are not uncommon, with serious complications such as central pontine myelinolysis (CPM), often causing disability. We investigated the incidence and features of NC following liver transplantation in adult recipients. We retrospectively reviewed the medical records of 319 adult patients who underwent liver transplantation between January 2004 and May 2005 at the Asan Medical Center. Neurologic complications developed in 49 of 319 patients (15.4%). Although most of these complications were minor, including tremor and foot drop, three patients developed CPM, and one each developed posterior leukoencephalopathy, cerebral hemorrhage, and cerebral infarction. One-yr survival rates were 95.9% in patients without NC and 83.7% in patients with NC (p = 0.004). Hospital stay was prolonged in patients with NC. Graft-to-recipient body weight ratio (GRWR) did not affect occurrence of NC. Neurologic complications were not uncommon in liver transplant recipients. These complications contributed to prolongation of hospital stay, increased in-hospital mortality, and decreased graft and patient survival. Every effort should be made to prevent NC, as well as to detect and treat them as soon as possible.


Inversion-recovery echo-planar MR in adult brain neoplasia.
A T1-weighted multishot inversion-recovery (IR) echo-planar MR imaging (EPI) sequence was developed to improve intracranial tissue differentiation; its diagnostic utility was compared with that of conventional axial T1-weighted spin-echo and axial T2-weighted turbo spin-echo sequences. Eighteen patients with known or suspected primary or metastatic brain neoplasia were imaged in a 1.5-T unit with IR-EPI sequences. Three observers measured gray/white matter contrast-to-noise ratios and subjectively compared IR-EPI sequences with T1-weighted spin-echo and T2-weighted turbo spin-echo sequences for gray/white matter discrimination, visibility of intracranial and vascular structures, overall lesion conspicuity, size of lesion(s), and presence and severity of artifacts. Twenty-four lesions (including neoplasia, infarction, treatment-associated encephalomalacia, nonneoplastic white matter signal abnormalities, and basilar artery dolichoectasia) were detected in 12 patients. Basilar artery dolichoectasia was not included in subsequent statistical analysis. Pulsatile flow artifacts were markedly reduced on IR-EPI sequences relative to those on T1-weighted spin-echo sequences. Gray/white matter contrast was greater on IR-EPI images than on T1-weighted spin-echo images. Periaqueductal gray matter, basal ganglia, optic tracts, cranial nerve V, and claustrum were seen better or as well on IR-EPI images as compared with T1-weighted spin-echo images. IR-EPI was more sensitive to magnetic sensitivity effects, with resultant decreased visibility of cranial nerves VII and VIII and the orbital portion of the optic nerves. For noncontrast sequences, lesion conspicuity was better on IR-EPI images than on T1-weighted spin-echo images in 16 (70%) of 23 lesions and was equal on the two sequences in seven (30%) of 23 lesions. Lesion size, including surrounding edema, was greater on IR-EPI images than on T2-weighted turbo spin-echo images in two (9%) of 23 cases and equal in 21 (91%) of 23 cases. Hyperintense foci of methemoglobin were more conspicuous on T1-weighted spin-echo images. Multishot IR-EPI is superior to conventional T1-weighted spin-echo imaging for parenchymal tissue contrast and lesion conspicuity, and is equal to T2-weighted turbo spin-echo imaging in sensitivity to pathologic entities.


Jarisch-Herxheimer reaction among HIV-positive patients with early syphilis: azithromycin versus benzathine penicillin G therapy.
The Jarisch-Herxheimer reaction, a febrile inflammatory reaction that often occurs after the first dose of chemotherapy in spirochetal diseases, may result in deleterious effects to patients with neurosyphilis and to pregnant women. A single 2-g oral dose of azithromycin is an alternative treatment to benzathine penicillin G for early syphilis in areas with low macrolide resistance. With its potential anti-inflammatory activity, the impact of azithromycin on the incidence of the Jarisch-Herxheimer reaction in HIV-positive patients with early syphilis has rarely been investigated. In HIV-positive patients with early syphilis, the Jarisch-Herxheimer reaction was prospectively investigated using the same data collection form in 119 patients who received benzathine penicillin G between 2007 and 2009 and 198 who received azithromycin between 2012 and 2013, when shortage of benzathine penicillin G occurred in Taiwan. Between 2012 and 2013, polymerase chain reaction (PCR) assay was performed to detect Treponema pallidum DNA in clinical specimens, and PCR restriction fragment length polymorphism of the 23S ribosomal RNA was performed to detect point mutations (2058G or A2059G) that are associated with macrolide resistance. The overall incidence of the Jarisch-Herxheimer reaction was significantly lower in patients receiving azithromycin than those receiving benzathine penicillin G (14.1% vs. 56.3%, p<0.001). The risk increased with higher rapid plasma reagin (RPR) titres (adjusted odds ratio [AOR] per 1-log2 increase, 1.21; confidence interval [CI], 1.04-1.41), but decreased with prior penicillin therapy for syphilis (AOR, 0.37; 95% CI, 0.19-0.71) and azithromycin treatment (AOR, 0.15; 95% CI, 0.08-0.29). During the study period, 310 specimens were obtained from 198 patients with syphilis for PCR assays, from whom T. pallidum was identified in 76 patients, one of whom (1.3%) was found to be infected with T. pallidum harbouring the macrolide resistance mutation (A2058G). In subgroup analyses confined to the 75 patients infected with T. pallidum lacking resistance mutation, a statistically significantly lower risk for the Jarisch-Herxheimer reaction following azithromycin treatment was noted. Treatment with azithromycin was associated with a lower risk for the Jarisch-Herxheimer reaction than that with benzathine penicillin G in HIV-positive patients with early syphilis. Previous benzathine penicillin G therapy for syphilis decreased the risk, whereas higher RPR titres increased the risk, for the reaction.


Relatedness and the evolution of mechanisms to divide labor in microorganisms.
Division of labor occurs when cooperating individuals specialize to perform different tasks. In bacteria and other microorganisms, some species divide labor by random specialization, where an individual's role is determined by random fluctuations in biochemical reactions within the cell. Other species divide labor by coordinating across individuals to determine which cells will perform which task, using mechanisms such as between-cell signaling. However, previous theory, examining the evolution of mechanisms to divide labor between reproductives and sterile helpers, has only considered clonal populations, where there is no potential for conflict between individuals. We used a mixture of analytical and simulation models to examine nonclonal populations and found that: (a) intermediate levels of coordination can be favored, between the extreme of no coordination (random) and full coordination; (b) as relatedness decreases, coordinated division of labor is less likely to be favored. Our results can help explain why coordinated division of labor is relatively rare in bacteria, where groups may frequently be nonclonal.


National Study of Childhood Traumatic Events and Adolescent and Adult Criminal Justice Involvement Risk: Evaluating the Protective Role of Social Support From Mentors During Adolescence.
With nearly 11 million people in the United States arrested in 2015, the need to identify antecedent risk factors driving criminal justice involvement (CJI) and possible mitigating factors is crucial. This study examines the relation between childhood trauma and CJI in adolescence and adulthood and assesses how this relation is moderated by mentoring during young adulthood. The analysis included 3 waves of data-adolescents, young adults, and adults-collected from 1995 to 2008 from 12,288 adolescents who participated in the National Longitudinal Study of Adolescent to Adult Health, a nationally representative study of adolescents in grades 7 to 12. Logistic regression was used to examine how having a close mentor in adolescence moderated the relation between criminal justice involvement and 9 childhood traumatic events: (1) neglect, (2) emotional abuse, (3) physical abuse, (4) sexual abuse, (5) parental incarceration, (6) parental binge drinking, (7) witnessed violence, (8) threatened with violence, and (9) experienced violence. Cumulative exposure to childhood trauma was associated with CJI in adolescence (adjusted odds ratios [AORs] ranging from 2.24 to 25.98) and adulthood (AOR range, 1.82-6.69), and parental incarceration was consistently one of the, if not the, most strongly associated with each form of CJI; the strength of these associations was weakened for those who reported a close mentor compared to those who did not. This study advances the literature regarding trauma and CJI, highlighting the role of social support and mentorship as protective factors for youth who experience childhood trauma. Interventions aimed at protecting vulnerable children from the harms of trauma should be the next priority.


Sympathetic overactivity in the development of eyelid retraction in a patient with euthyroid Graves' disease evaluated by accommodation.
It is known that measurement of accommodation is useful to evaluate the sympathetic activity of intraocular muscles. To find if sympathetic overactivity is involved in eyelid retraction in euthyroid Graves' disease, we measured accommodation in two patients with this disease, whose serum concentrations of free T3, free T4 and TSH were within reference ranges. Accommodation was measured with a computer-assisted infrared optometer with an iriscoder, and the results were expressed as the change in the eye's refractive power (in diopters) in response to the movement of a target beam. In patient 1, the accommodation amplitude was low, indicating sympathetic overactivity. This amplitude rose to near the reference range when timolol maleate drops were used, and the eyelid retraction disappeared when guanethidine drops were given. During the use of guanethidine drops, accommodation remained normal. In patient 2, who had normal accommodation, eyelid retraction did not change with guanethidine administration, but improved with intravenous methylprednisolone pulse therapy. These two cases suggested that even in euthyroid Graves' disease, eyelid retraction is caused by sympathetic overactivity, and pulse therapy with methylprednisolone may be effective for eyelid retraction when guanethidine drops are not effective.


Treatment of rheumatoid arthritis patients with abatacept and methotrexate significantly improved health-related quality of life.
This study examined the effect of abatacept, a costimulation modulator, on the health-related quality of life (HRQOL) of patients with rheumatoid arthritis (RA). Three hundred thirty-nine patients with RA on a background of methotrexate (MTX), who participated in a multicenter, double-blind, placebo-controlled trial, were randomized to abatacept 2 mg/kg, abatacept 10 mg/kg, or placebo. HRQOL was assessed at pretreatment, and at 3, 6, and 12 months posttreatment using the SF-36 Health Survey (SF-36). Changes in SF-36 scores from baseline to 12 months were compared across treatment and placebo groups to examine HRQOL benefits of abatacept. A link between American College of Rheumatology improvement and changes in SF-36 scores was established to demonstrate the association between HRQOL outcomes and clinical response. After 12 months of treatment, patients randomized to abatacept 10 mg/kg showed significantly better HRQOL outcomes overall versus patients randomized to placebo (MANOVA F = 4.71, p < 0.001) or to abatacept 2 mg/kg (MANOVA F = 1.97, p = 0.05). Differences in SF-36 change scores between abatacept 10 mg/kg and placebo groups reached statistical significance on all 8 domain scales, the 2 summary measures, and the SF-36 utility index (SF-6D). Differences in SF-36 change scores between abatacept 10 mg/kg and abatacept 2 mg/kg reached statistical significance on 5 of the 8 domain scales, the physical summary measure, and the SF-6D. Improvement in HRQOL was highly related to clinical response. CONCLUSION Abatacept 10 mg/kg plus MTX demonstrated a stronger HRQOL response than placebo plus MTX. The abatacept 2 mg/kg arm showed a very weak and transient response.


Toxicity of electronic waste leachates to Daphnia magna: screening and toxicity identification evaluation of different products, components, and materials.
Electronic waste has become one of the fastest growing waste problems in the world. It contains both toxic metals and toxic organics. The aim of this study was to (1) investigate to what extent toxicants can leach from different electronic products, components, and materials into water and (2) identify which group of toxicants (metals or hydrophobic organics) that is causing toxicity. Components from five discarded electronic products (cell phone, computer, phone modem, keyboard, and computer mouse) were leached in deionised water for 3 days at 23°C in concentrations of 25 g/l for metal components, 50 g/l for mixed-material components, and 100 g/l for plastic components. The water phase was tested for acute toxicity to Daphnia magna. Eighteen of 68 leachates showed toxicity (with immobility of D. magna ≥ 50% after 48 h) and came from metal or mixed-material components. The 8 most toxic leachates, with 48 h EC(50)s ranging from 0.4 to 20 g/l, came from 2 circuit sheets (key board), integrated drive electronics (IDE) cable clips (computer), metal studs (computer), a circuit board (computer mouse), a cord (phone modem), mixed parts (cell phone), and a circuit board (key board). All 5 electronic products were represented among them. Toxicity identification evaluations (with C18 and CM resins filtrations and ethylenediaminetetraacetic acid addition) indicated that metals caused the toxicity in the majority of the most toxic leachates. Overall, this study has shown that electronic waste can leach toxic compounds also during short-term leaching with pure water.


Cardiac arrest and resuscitation epidemiology in Singapore (CARE I study).
To describe the epidemiology of out-of-hospital cardiac arrest (OHCA) in Singapore, the emergency medical services (EMS) response, and to identify possible areas for improvement. This prospective observational study constitutes phase I of the Cardiac Arrest and Resuscitation Epidemiology (CARE) project. Included were all patients with nontraumatic OHCA conveyed by the national emergency ambulance service. Patient characteristics, cardiac arrest circumstances, EMS response, and outcomes were recorded according to the Utstein style. From October 1, 2001, to April 30, 2002, 548 patients were enrolled into the study. Mean (standard deviation [SD]) age was 62.2 (17.9) years, with a male predominance (65.6%). A total of 59.8% of collapses occurred at home, 35.3% of arrests were not witnessed, and bystander cardiopulmonary resuscitation was present for 20.6%. Mean (SD) time from collapse to call received by EMS was 10.6 (13.1) minutes. Mean (SD) EMS response time was 10.2 (4.3) minutes. Mean (SD) time from call to defibrillation was 16.7 (7.2) minutes. Mean (SD) on-scene time was 9.9 (4.5) minutes. First presenting rhythm at the scene was asystole in 54.5%, pulseless electrical activity 22.9%, ventricular fibrillation 19.6%, and ventricular tachycardia 0.4%. Of all cardiac arrests, 351 had resuscitation attempted and were of cardiac origin. Among these patients, 17.9% had return of spontaneous circulation, 8.5% survived to hospital admission, and 2.0% survived to discharge. CARE I establishes the baseline for the evaluation of incremental introduction of prehospital Advanced Cardiac Life Support interventions planned for future phases. Continuing efforts should be made to strengthen all chains of survival. This represents the most comprehensive OHCA study yet conducted in Singapore.


Drops That Change Their Mind: Spontaneous Reversal from Spreading to Retraction.
A liquid drop may spread faster on surfaces when surfactants are added. Here we show that after some time the spreading in such systems can, under certain conditions, spontaneously reverse to retraction and the droplet pulls itself back, receding from areas it has just recently wetted, elevating its center of mass in a jerklike motion. The duration from drop placement to the onset of retraction ranges from hours to less than a second primarily as a function of surfactant concentration. When the retraction is asymmetric, it results in drop motion, and when it is symmetric, the mass of the drop collects itself on its spot. This phenomenon, which was predicted theoretically in 2014, is apparently a general one for drops with surfactants; however, other factors, such as evaporation and contamination, prevented its observance so far.


Determinants of the adoption of injury risk reduction programmes in athletics (track and field): an online survey of 7715 French athletes.
To identify individual characteristics associated with the adoption of injury risk reduction programmes (IRRP) and to investigate the variations in sociocognitive determinants (ie, attitudes, subjective norms, perceived behavioural control and intentions) of IRRP adoption in athletics (track and field) athletes. We conducted a cross-sectional study using an online survey sent to athletes licensed with the French Federation of Athletics to investigate their habits and sociocognitive determinants of IRRP adoption. Sociodemographic characteristics, sports practice and history of previous injuries were also recorded. Logistic regression analyses and group comparisons were performed. The final sample was composed of 7715 athletes. From the multivariable analysis, competing at the highest level was positively associated with IRRP adoption (adjusted OR (AOR)=1.66; 99.9% CI 1.39 to 1.99 and AOR=1.48; 99.9% CI 1.22 to 1.80) and presenting a low number of past injuries was negatively associated with IRRP adoption (AOR=0.48; 99.9% CI 0.35 to 0.65 and AOR=0.61; 99.9% CI 0.44 to 0.84), both during their lifetime and the current season, respectively. These results were supported by higher scores of sociocognitive determinants among athletes who reported IRRP adoption compared with other athletes. Some characteristics of athletes seem to be associated with IRRP adoption either positively (competing at the highest level) or negatively (presenting a lower number of past injuries), whereas all the sociocognitive determinants tested appear to be linked to IRRP adoption. Since many athlete characteristics are difficult or impossible to change, IRRP promotion may be enhanced by targeting athletes' beliefs and intentions to adopt an IRRP.


Sep(t)arate or not – how some cells take septin-independent routes through cytokinesis.
Cytokinesis is the final step of cell division, and is a process that requires a precisely coordinated molecular machinery to fully separate the cytoplasm of the parent cell and to establish the intact outer cell barrier of the daughter cells. Among various cytoskeletal proteins involved, septins are known to be essential mediators of cytokinesis. In this Commentary, we present recent observations that specific cell divisions can proceed in the absence of the core mammalian septin SEPT7 and its Drosophila homolog Peanut (Pnut) and that thus challenge the view that septins have an essential role in cytokinesis. In the pnut mutant neuroepithelium, orthogonal cell divisions are successfully completed. Similarly, in the mouse, Sept7-null mutant early embryonic cells and, more importantly, planktonically growing adult hematopoietic cells undergo productive proliferation. Hence, as discussed here, mechanisms must exist that compensate for the lack of SEPT7 and the other core septins in a cell-type-specific manner. Despite there being crucial non-canonical immune-relevant functions of septins, septin depletion is well tolerated by the hematopoietic system. Thus differential targeting of cytokinesis could form the basis for more specific anti-proliferative therapies to combat malignancies arising from cell types that require septins for cytokinesis, such as carcinomas and sarcomas, without impairing hematopoiesis that is less dependent on septin.


Automated splicing mutation analysis by information theory.
Information theory-based software tools have been useful in interpreting noncoding sequence variation within functional sequence elements such as splice sites. Individual information analysis detects activated cryptic splice sites and associated splicing regulatory sites and is capable of distinguishing null from partially functional alleles. We present a server (https://splice.cmh.edu) designed to analyze splicing mutations in binding sites in either human genes, genome-mapped mRNAs, user-defined sequences, or dbSNP entries. Standard HUGO-approved gene symbols and HGVS-approved systematic mutation nomenclature (or dbSNP format) are entered via a web portal. After verifying the accuracy of input variant(s), the surrounding interval is retrieved from the human genome or user-supplied reference sequence. The server then computes the information contents (Ri) of all potential constitutive and/or regulatory splice sites in both the reference and variant sequences. Changes in information content are color-coded, tabulated, and visualized as sequence walkers, which display the binding sites with the reference sequence. The software was validated by analyzing approximately 1,300 mutations from Human Mutation as well as eight mapped SNPs from dbSNP designated as splice site variants. All of the splicing mutations and variants affected splice site strength or activated cryptic splice sites. The server also detected several missense mutations that were unexpectedly predicted to have concomitant effects on splicing or appeared to activate cryptic splicing.


Phonotactic probability of brand names: I'd buy that!
Psycholinguistic research shows that word-characteristics influence the speed and accuracy of various language-related processes. Analogous characteristics of brand names influence the retrieval of product information and the perception of risks associated with that product. In the present experiment we examined how phonotactic probability-the frequency with which phonological segments and sequences of segments appear in a word-might influence consumer behavior. Participants rated brand names that varied in phonotactic probability on the likelihood that they would buy the product. Participants indicated that they were more likely to purchase a product if the brand name was comprised of common segments and sequences of segments rather than less common segments and sequences of segments. This result suggests that word-characteristics may influence higher-level cognitive processes, in addition to language-related processes. Furthermore, the benefits of using objective measures of word characteristics in the design of brand names are discussed.


[Topical treatment with eberconazole of the experimental guinea pig cutaneous candidosis.].
Eberconazole is a new azole antifungal drug for topical treatment of superficial mycoses. The usefulness of this drug was evaluated in an experimental model of cutaneous candidosis in guinea pigs comparing with the classical clotrimazole in a single blind trial. Twenty-five animals were inoculated in two symmetrical areas of the back with Candida albicans developing skin infection. One group of 10 animals were treated once per day with clotrimazole 1% cream in one side and with excipient in the other. Other group of 10 guinea pigs received eberconazole 1% cream and excipient. Five animals did not receive any treatment and were used as controls. After five days of treatment most lesions cured or improved and cultures were negative when clotrimazole or eberconazole were applied. Seventy per cent of lesions treated with excipient were clinically improved and 10% cured, but 85% of cultures remained positive for C. albicans. The therapeutic efficacy of eberconazole 1% cream was similar to clotrimazole 1% cream in the guinea ping model of cutaneous candidosis. Tolerance of both drugs was excellent. These results suggest the usefulness of eberconazole in human cutaneous infections due to C. albicans.


Does MDMA have treatment potential in sexual dysfunction? A systematic review of outcomes across the female and male sexual response cycles.
Sexual health, an integral component of overall well-being, is frequently compromised by common yet underdiagnosed sexual dysfunctions. Traditional interventions encompass pharmaceutical and psychological treatments. Unconventional therapies, like MDMA, offer hope for sexual dysfunction. This review delves into MDMA's effects on sexual responsiveness and its potential role in treating sexual dysfunction. The purpose of this review is to elucidate effects of MDMA on different domains of the female and male sexual response cycles. We conducted a systematic review on the effects of MDMA on each domain of the female and male sexual response cycles. PubMed, MEDLINE, and EMBASE were queried, and results were screened using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Search terms utilized were "MDMA" or "ecstasy" in combination with "desire," "arousal," "lubrication," "orgasm," "pleasure," "libido," "erection," and "ejaculation." Inclusion criteria for this review were MDMA use by study subjects and sexual outcomes in at least 1 domain of the female and/or male sexual response cycles were described and measured. Randomized controlled trials, cohort studies (both prospective and retrospective), surveys, and literature reviews published between January 2000 and June 2022 were included. Case reports and studies that did not address conditions of interest were excluded from analysis. Duplicated search results were screened out. The remaining studies were then read in full text to ensure they met inclusion and exclusion criteria for analysis. We identified 181 studies, of which 6 met criteria for assessment of the female sexual response cycle and 8 met criteria for assessment of the male sexual response cycle. Four of 6 studies reported increased sexual desire with MDMA use among women. Arousal and lubrication were improved with MDMA use in 3 of 4 studies, but they were not affected in 1 randomized control study. In men, 7 studies evaluated the effects of MDMA on desire and/or arousal, 5 studies measured impact on erection, 3 on orgasm, and 2 on ejaculation. Sixty percent of interview-based studies reported increased sexual desire in men, while 40% reported mixed or no effect. Two studies reported impairment of erection, 2 reported mixed effects, and 1 reported fear of erection impairment. In both men and women, all studies evaluating orgasm reported delay in achieving orgasm but increased intensity and pleasure if achieved. Primary outcome measures were variable and largely qualitative. Our findings suggest that MDMA generally increases sexual desire and intensifies orgasm when achieved. While producing conflicting evidence on sexual arousal in both sexes, MDMA may impair erectile and ejaculatory function in men.


Accuracy and Usefulness of Select Methods for Assessing Complete Collection of 24-Hour Urine: A Systematic Review.
Twenty-four-hour urine collection is the recommended method for estimating sodium intake. To investigate the strengths and limitations of methods used to assess completion of 24-hour urine collection, the authors systematically reviewed the literature on the accuracy and usefulness of methods vs para-aminobenzoic acid (PABA) recovery (referent). The percentage of incomplete collections, based on PABA, was 6% to 47% (n=8 studies). The sensitivity and specificity for identifying incomplete collection using creatinine criteria (n=4 studies) was 6% to 63% and 57% to 99.7%, respectively. The most sensitive method for removing incomplete collections was a creatinine index <0.7. In pooled analysis (≥2 studies), mean urine creatinine excretion and volume were higher among participants with complete collection (P<.05); whereas, self-reported collection time did not differ by completion status. Compared with participants with incomplete collection, mean 24-hour sodium excretion was 19.6 mmol higher (n=1781 specimens, 5 studies) in patients with complete collection. Sodium excretion may be underestimated by inclusion of incomplete 24-hour urine collections. None of the current approaches reliably assess completion of 24-hour urine collection.


Mode of replication of plasmid lambda-dv-1.
About 20 copies of plasmid lambda-dv are perpetuated per host chromosome in Escherichia coli K12 cells. The mode of DNA replication of this plasmid lambda-dv was studied, using the density-labelling technique followed by banding in DsCl. It was shown that all the copies of plasmid lambda-dv are potentially capable of replicating roughly once a cell generation. Their replication occurs by random, that is a copy of the plasmid is taken out at random for replication from a pool, to which the two replicas resulting from replication are returned. Chloramphenicol did not inhibit the initiation of a new round of replication of the plasmid molecules, indicating that selection from the replication pool does not require concomitant protein synthesis.


What do midwives think about interprofessional working and learning?
This study describes the views of midwives and educators regarding interprofessional working and learning within midwifery care. Qualitative methods using semi-structured interviews and focus groups. 39 participants, drawn from three participant groups--midwifery educators, newly qualified midwives and Heads of Midwifery--from four university sites throughout the U.K. took part in the research. Midwives are called upon to work collaboratively with other professionals during the daily provision of maternity care. Midwives are aware of the competencies required for effective collaboration and are supportive of the inclusion of interprofessional education in the training of student midwives. However, the relevance of this education was questioned by some participants because it is not apparent whether its inclusion will result in midwives who are better able to collaborate. Midwives are supportive of interprofessional learning for students but are uncertain whether it will result in changes in practice. Interprofessional education may support collaboration in practice, but future educational research aimed at understanding how learning is applied to practice is needed.


Interacting effects of L-carnitine and malonyl-CoA on rat liver carnitine palmitoyltransferase.
Malonyl-CoA significantly increased the Km for L-carnitine of overt carnitine palmitoyltransferase in liver mitochondria from fed rats. This effect was observed when the molar palmitoyl-CoA/albumin concentration ratio was low (0.125-1.0), but not when it was higher (2.0). In the absence of malonyl-CoA, the Km for L-carnitine increased with increasing palmitoyl-CoA/albumin ratios. Malonyl-CoA did not increase the Km for L-carnitine in liver mitochondria from 24h-starved rats or in heart mitochondria from fed animals. The Km for L-carnitine of the latent form of carnitine palmitoyltransferase was 3-4 times that for the overt form of the enzyme. At low ratios of palmitoyl-CoA/albumin (0.5), the concentration of malonyl-CoA causing a 50% inhibition of overt carnitine palmitoyltransferase activity was decreased by 30% when assays with liver mitochondria from fed rats were performed at 100 microM-instead of 400 microM-carnitine. Such a decrease was not observed with liver mitochondria from starved animals. L-Carnitine displaced [14C]malonyl-CoA from liver mitochondrial binding sites. D-Carnitine was without effect. L-Carnitine did not displace [14C]malonyl-CoA from heart mitochondria. It is concluded that, under appropriate conditions, malonyl-CoA may decrease the effectiveness of L-carnitine as a substrate for the enzyme and that L-carnitine may decrease the effectiveness of malonyl-CoA to regulate the enzyme.


New insights, recent advances, and current challenges in the biological treatment of multiple myeloma.
The availability of thalidomide, lenalidomide, and bortezomib has radically changed multiple myeloma (MM) treatment and significantly improved patients' outcome. Nevertheless, MM is still an incurable disease due to the development of resistance and relapse practically in all patients. Unraveling MM pathogenesis, identifying prognostically high-risk patient populations, and optimizing current treatment strategies are among the challenges we are facing to reach a cure for this disease. This article reviews recent advances of the genomic analysis of malignant plasma cells and summarizes new insights into the pathophysiologic role of the MM microenvironment and the clinical assessment of derived novel therapeutic strategies. Moreover, current efforts to improve risk stratification and drug development are discussed, and most recent results of Phase II and III clinical trials that aim to optimize existing treatment regimens and to assess the next-generation anti-MM strategies are discussed. A systematic search was conducted of the Pubmed Medline, Embase, and Cochrane Library databases for primary articles, as well as of conference abstracts (e.g., of the American Society of Hematology, the American Society of Clinical Oncology, the American Association of Cancer Research, the European Hematology Association, and the Multiple Myeloma Workshop 2013), practice guidelines, and registries of clinical trials. Given continuing advances to overcome current treatment challenges in MM, we are confident that long-lasting responses can be expected in many of our patients within the next decade.


[Association between central body anthropometric measures and metabolic syndrome components in a probabilistic sample of adolescents from public schools].
It was investigated the association of waist circumference (WC), abdominal circumference (AC), Waist-to-Hip ratio(WHR) and Waist-Height ratio (WHtR) adjusted by body mass index (BMI) and % body fat (BF) with metabolic syndrome components in a probabilistic sample of 610 adolescents aged 12-19 years (222 boys and 388 girls) from public schools of Niterói, Rio de Janeiro. Fasting glucose and lipids were assayed using automated enzymatic method and insulin was determined by radioimmuno assay. Systolic (SBP) and diastolic (DBP) blood pressure were measured using an automated recorder and % BF by electric bioimpedance. The association of the anthropometric measures with metabolic syndrome components was evaluated by multivariate linear regression adjusted according to the age, BMI or %BF. In boys, a positive association between WC (beta=1.03 p<0.01) and WHtR (beta= 2.33, p< 0.05; beta=2.12 and p< 0.01) with triglycerides was maintained after BMI and % BF adjusting, respectively. WC was associated with SBP after % BF adjusting both for boys (beta= 0.70 p<0.01) and girls (beta=0.68 p<0.01). In conclusion, WC was the measure of central body fat that presented the best association with components of metabolic syndrome in adolescents.


Fabrication and characterization of spongy denuded amniotic membrane based scaffold for tissue engineering.
As a biological tissue material, amniotic membrane (AM) has low immunogenicity and to date has been widely adopted in clinical practice. However, some features such as low biomechanical consistency and rapid biodegradation is limited the application of AM. Therefore, in this study, we fabricated a novel three-dimensional (3D) spongy scaffold made of the extracellular matrix (ECM) of denuded AM. Due to their unique characteristics which are similar to the skin, these scaffolds can be considered as an alternative option in skin tissue engineering. In this experimental study, cellular components of human amniotic membrane (HAM) were removed with 0.03% (w/v) sodium dodecyl sulphate (SDS). Quantitative analysis was performed to determine levels of Glycosaminoglycans (GAGs), collagen, and deoxyribonucleic acid (DNA). To increase the low efficiency and purity of the ECM component, especially collagen and GAG, we applied an acid solubilization procedure hydrochloridric acid (HCl 0.1 M) with pepsin (1 mg/ml). In the present experiment 1-ethyl-3-(3-dimethyl aminopropyl) carbodiimide hydrochloride (EDC)/N-hydroxysuccinimide (NHS) cross linker agent was used to improve the mechanical properties of 3D lyophilized AM scaffold. The spongy 3D AM scaffolds were specified, by scanning electron microscopy, hematoxylin and eosin (H&E) staining, a swelling test, and mechanical strength and in vitro biodegradation tests. Human fetal fibroblast culture systems were used to establish that the scaffolds were cytocompatible. Histological analysis of treated human AM showed impressive removal of cellular components. DNA content was diminished after treatment (39 ± 4.06 μg/ml vs. 341 ± 29.60 μg/ml). Differences were observed between cellular and denude AM in matrix collagen (478 ± 18.06 μg/mg vs. 361 ± 27.47 μg/mg).With the optimum concentration of 1 mM NHS/EDC ratio1:4, chemical cross-linker agent could significantly increase the mechanical property, and resistance to collagenase digestion. The results of 2, 4, 6-Trinitrobenzenesulfonic acid (TNBS) test showed that cross-linking efficiency of AM derived ECM scaffolds was about 65% ± 10.53. Scaffolds treated with NHS/EDC cross-linker agent by 100 μg/ml collagenase, lost 75% of their dry weight after 14 days. The average pore size of 3D spongy scaffold was 160 µm measured from scanning electron microscope (SEM) images that it is suitable for cell penetration, nutrients and gas change. In addition, the NHS/ EDC cross-linked AM scaffolds were able to support human fetal fibroblast cell proliferation in vitro. Extracts and contact prepared from the 3D spongy scaffold of AM showed a significant increase in the attachment and proliferation of the human fetal fibroblasts cells. The extra-cellular matrix of denuded AM-based scaffold displays the main properties required for substitute skin including natural in vitro biodegradation, similar physical and mechanical characterization, nontoxic biomaterial and no toxic effect on cell attachment and cell proliferation.


Chromatin Dynamics in Lineage Commitment and Cellular Reprogramming.
Dynamic structural properties of chromatin play an essential role in defining cell identity and function. Transcription factors and chromatin modifiers establish and maintain cell states through alteration of DNA accessibility and histone modifications. This activity is focused at both gene-proximal promoter regions and distally located regulatory elements. In the three-dimensional space of the nucleus, distal elements are localized in close physical proximity to the gene-proximal regulatory sequences through the formation of chromatin loops. These looping features in the genome are highly dynamic as embryonic stem cells differentiate and commit to specific lineages, and throughout reprogramming as differentiated cells reacquire pluripotency. Identifying these functional distal regulatory regions in the genome provides insight into the regulatory processes governing early mammalian development and guidance for improving the protocols that generate induced pluripotent cells.


Symptomatology, quality of life and economic features of irritable bowel syndrome--the effect of hypnotherapy.
The purposes of this study were to quantify the effects of severe irritable bowel syndrome on quality of life and economic functioning, and to assess the impact of hypnotherapy on these features. A validated quality of life questionnaire including questions on symptoms, employment and health seeking behaviour was administered to 25 patients treated with hypnotherapy (aged 25-55 years; four male) and to 25 control irritable bowel syndrome patients of comparable severity (aged 21-58 years; two male). Visual analogue scales were used and scores derived to assess the patients' symptoms and satisfaction with each aspect of life. Patients treated with hypnotherapy reported less severe abdominal pain (P < 0.0001), bloating (P < 0.02), bowel habit (P < 0.0001), nausea (P < 0.05), flatulence (P < 0.05), urinary symptoms (P < 0.01), lethargy (P < 0.01), backache (P = 0.05) and dyspareunia (P = 0.05) compared with control patients. Quality of life, such as psychic well being (P < 0.0001), mood (P < 0.001), locus of control (P < 0.05), physical well being (P < 0.001) and work attitude (P < 0.001) were also favourably influenced by hypnotherapy. For those patients in employment, more of the controls were likely to take time off work (79% vs. 32%; p = 0.02) and visit their general practitioner ( 58% vs. 21%; P = 0.056) than those treated with hypnotherapy. Three of four hypnotherapy patients out of work prior to treatment resumed employment compared with none of the six in the control group. This study has shown that in addition to relieving the symptoms of irritable bowel syndrome, hypnotherapy profoundly improves the patients' quality of life and reduces absenteeism from work. It therefore appears that, despite being relatively expensive to provide, it could well be a good long-term investment.


[Studies on the antipregnancy effect of LHRH-A in mid gestational rats].
In the present study, the antipregnancy effect of (D-Ala6, Pro9-Ethylamide10) LHRH (LHRH-A) on midgestation rats was observed. The results indicate that LHRH-A could terminate pregnancy of all experimented rats by abortion after subcutaneous administration of 200 micrograms LHRH-A (dissolved in vegetable oil) once a day at days 9 to 11 of their pregnancy. It was also found that the serum progesterone level was significantly lowered after the administration of LHRH-A (P less than 0.05); the concomitant administration of megestrol acetate with LHRH-A could almost completely block the antipregnancy effect of LHRH-A on the midgestation rats; LHRH-A showed a strong direct inhibitory effect on luteal cell progesterone secretion in pseudopregnant and midgestation rats. Hence, it is considered that the probable mechanisms for the antipregnancy effect of LHRH-A may be mainly due to the decrease of serum progesterone level caused by the direct inhibitory effect of LHRH-A on midgestation corpus luteum progesterone production.


A Bayesian approach to analyzing ecotoxicological data.
Standardized chronic toxicity tests are usually analyzed using a NOEC (no observed effect concentration) or ECx (x% effect concentration) calculation. However,these methods provide very little information for the material cost they entail. It has been proposed that biology-based methods, such as the DEBtox approach, would make better use of the data available. DEBtox deals with the energy balance between physiological processes, and gives insight on how a compound disturbs it. We propose that data analysis can be further improved by estimating the DEBtox parameters using the considerable expertise available in laboratories and/or the literature. The Bayesian inference appears to be an appropriate estimation method for this purpose, as this technique takes expertise into account as prior probability distribution for each parameter, and provides the corresponding posterior distributions given the data. From these posterior distributions, point estimates can easily be deduced, but also credible intervals which are ideal for use in risk assessment. In this paper, we demonstrate this approach through the analysis of two 21-day Daphnia reproduction tests.


Can the generic antiretroviral industry support access to a universal antiretroviral regimen?
The generic antiretroviral (ARV) industry played a critical role in the massive scale-up of HIV treatment in low-income and middle-income countries since 2000. As the global community looks ahead to a universal antiretroviral regimen, this article considers the industry's role in supporting universal access to affordable, simpler, more durable, and tolerable HIV treatment regimens. Generic manufacturers made treatment scale-up in low-income and middle-income countries possible through reducing prices, combining molecules from different originator companies to develop optimal fixed-dose combinations, and investing in production capacity to meet escalating demand. Achieving scale-up of a universal regimen will require continued partnership in these areas. Collaboration on the demand and supply sides of the ARV marketplace will be required to foster a healthy and sustainable marketplace for new regimens. This includes clear priority setting from the global treatment community on priority products; predictable demand; regulatory prioritization of optimal products; effective tendering and procurement practices that enable multiple suppliers to participate in the market; coordinated product introduction efforts between Ministries of Health, partners, and civil society; and transparency from both buyers and suppliers to promote and monitor supply security. New regimens will benefit people living with HIV, as well as buyers and generic suppliers, by maximizing existing production capacity and treatment budgets to reach the 90-90-90 goals.


An Asymmetry in the Automatic Detection of the Presence or Absence of a Frequency Modulation within a Tone: A Mismatch Negativity Study.
The infrequent occurrence of a transient feature (deviance; e.g., frequency modulation, FM) in one of the regular occurring sinusoidal tones (standards) elicits the deviance related mismatch negativity (MMN) component of the event-related brain potential. Based on a memory-based comparison, MMN reflects the mismatch between the representations of incoming and standard sounds. The present study investigated to what extent the infrequent exclusion of an FM is detected by the MMN system. For that purpose we measured MMN to deviances that either consisted of the exclusion or inclusion of an FM at an early or late position within the sound that was present or absent, respectively, in the standard. According to the information-content hypothesis, deviance detection relies on the difference in informational content of the deviant relative to that of the standard. As this difference between deviants with FM and standards without FM is the same as in the reversed case, comparable MMNs should be elicited to FM inclusions and exclusions. According to the feature-detector hypothesis, however, the deviance detection depends on the increased activation of feature detectors to additional sound features. Thus, rare exclusions of the FM should elicit no or smaller MMN than FM inclusions. In passive listening condition, MMN was obtained only for the early inclusion, but not for the exclusions nor for the late inclusion of an FM. This asymmetry in automatic deviance detection seems to partly reflect the contribution of feature detectors even though it cannot fully account for the missing MMN to late FM inclusions. Importantly, the behavioral deviance detection performance in the active listening condition did not reveal such an asymmetry, suggesting that the intentional detection of the deviants is based on the difference in informational content. On a more general level, the results partly support the "fresh-afferent" account or an extended memory-comparison based account of MMN.


Establishing a Regional Monitoring Strategy: The Pacific Northwest Forest Plan.
/ This paper identifies lessons learned and issues raised during the development of an ecosystem monitoring strategy intended to support the Northwest Forest Plan. Adaptive ecosystem management, which requires monitoring as essential feedback to management, recognizes that action is necessary or appropriate, although knowledge may be imperfect. We suggest that this principle be explicitly acknowledged in the design of monitoring programs, and we coin the term adaptive monitoring design. Adaptive monitoring design is an iterative process that refines the specifications for monitoring over time as a result of experience in implementing a monitoring program, assessing results, and interacting with users. An adaptive design therefore facilitates ecosystem management. We also discuss lessons of temporal and spatial scales raised by the consideration of a design for ecosystem management. Three additional issues-integration of information from different sources, institutional infrastructure, and the roles of individuals working in an interagency setting-are also identified, but not developed in detail. KEY WORDS: Northwest Forest Plan; Monitoring; Ecosystem management; Adaptive management; Adaptive monitoring


A loss of short-latency excitatory caudate unitary responses to motor cortex but not to motor thalamic nuclei stimulation in MPTP-treated cats.
The effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP, 5 mg/kg i.m. for 5 days) on the evoked activity of caudate neurones were studied extracellularly in ketamine-anaesthetized and myorelaxant-immobilized cats. Two days after the last MPTP injection the latency of caudate neurone responses to the motor cortex stimulation increased as compared to intact animals, due to a 10-fold decrease in the number of neurones with short-latency responses (from 1.8 up to 8.0 ms). At the same time, no essential changes were observed under the influence of MPTP in the distribution pattern of the latency of caudate neurone responses to the stimulation of the ventral anterior and ventral lateral nuclei of the thalamus. The suggestion that dopamine protects monosynaptic transmission of impulses from the cerebral cortex to neostriatum neurones is discussed.


Plasticity of TRPM1 expression and localization in the wild type and degenerating mouse retina.
The light response in retinal ON bipolar cells is associated with disinhibition of current flow through cation channels recently identified as type 1 members of the melastatin transient receptor potential (TRPM) family. We determined the developmental expression of Trpm1 in the wild type C57BL/6, DBA/2J, DBA2J-Gpnmb mouse retinas and in Pde6brd1 retinas characterized by degeneration of rod photoreceptors. Trpm1 mRNA in wild type retinas was low at birth but exhibited progressive increases in abundance up to early adulthood at postnatal day 21 (P21). Retinal Trpm1 mRNA content did not decrease following loss of photoreceptors. At P21, TRPM1-immunopositive perikarya migrated into the outer nuclear layer. The TRPM1 protein was trafficked to discrete postsynaptic puncta in wild type retinas whereas in adult Pde6brd1 mouse retinas, TRPM1 translocated to bipolar perikarya and bar-like structures in the distal inner nuclear layer. These findings show that expression and localization of the TRPM1 in the mouse retina is plastic, modulated by use-dependence and availability of sustained excitatory input.