A new active vitamin D3 analog, eldecalcitol, prevents the risk of osteoporotic fractures--a randomized, active comparator, double-blind study.
Eldecalcitol is an analog of 1,25-dihydroxyvitamin D(3) that improves bone mineral density; however, the effect of eldecalcitol on the risk of fractures is unclear. The objective of this study is to examine whether eldecalcitol is superior to alfacalcidol in preventing osteoporotic fractures. This trial is registered with ClinicalTrials.gov, number NCT00144456. This 3 year randomized, double-blind, active comparator, superiority trial tested the efficacy of daily oral 0.75 μg eldecalcitol versus 1.0 μg alfacalcidol for prevention of osteoporotic fractures. 1054 osteoporotic patients 46 to 92 years old were randomly assigned 1:1 to receive eldecalcitol (n=528) or alfacalcidol (n=526). Patients were stratified by study site and serum 25-hydroxyvitamin D level. Patients with low serum 25-hydroxyvitamin D levels (<50 nmol/L) were supplemented with 400 IU/day vitamin D(3). Primary end point was incident vertebral fractures. Secondary end points included any non-vertebral fractures and change in bone mineral density and bone turnover markers. Compared with the alfacalcidol group, the incidence of vertebral fractures was lower in eldecalcitol group after 36 months of treatment (13.4 vs. 17.5%; hazard ratio, 0.74; predefined 90% confidence interval [CI], 0.56-0.97). Eldecalcitol reduced turnover markers and increased bone mineral density more strongly than alfacalcidol. Eldecalcitol reduced the incidence of three major non-vertebral fractures, which was due to a marked reduction in wrist fractures by a post-hoc analysis (1.1 vs. 3.6%; hazard ratio, 0.29; 95% CI, 0.11-0.77). Among the adverse events, the incidence of increase in serum and urinary calcium was higher in the eldecalcitol group, without any difference in glomerular filtration rate between the two groups. Eldecalcitol is more efficacious than alfacalcidol in preventing vertebral and wrist fractures in osteoporotic patients with vitamin D sufficiency, with a safety profile similar to alfacalcidol.


Thalidomide for refractory gastrointestinal bleeding from vascular malformations in patients with significant comorbidities.
Refractory gastrointestinal bleeding (GIB) secondary to gastrointestinal vascular malformations (GIVM) such as gastrointestinal angiodysplasia (GIAD) and gastric antral vascular ectasia (GAVE) remains challenging to treat when endoscopic therapy fails. Recently thalidomide has been suggested as a treatment option for refractory GIB. To determine the outcome of patients treated with thalidomide for refractory GIB due to GIVM. IRB approved, single center, retrospective review of electronic medical records from January 2012 to November 2018. Patients age > 18 years old, who had > 3 episodes of GIB refractory to medical or endoscopic therapy, and who had been treated with thalidomide for at least 3 mo were included. The primary endpoint was recurrence of GIB 6 mo after initiation of thalidomide. Fifteen patients were included in the study, all with significant cardiac, hepatic, or renal comorbidities. The cause of GIB was GIAD in 10 patients and GAVE in 5 patients. Two patients were lost to follow up. Of the 13 patients followed, 38.5% (n = 5) had no recurrent GIB or transfusion requirement after treatment with thalidomide. Furthermore, 84.6% (n = 11) of patients had a reduction in transfusion requirements and hospitalizations for GIB. Thalidomide was discontinued in 2 patients due to cost (n = 1) and medication interaction (n = 1). Reported adverse reactions included fatigue (n = 3), neuropathy (n = 2), dizziness (n = 1), and constipation (n = 1). Six patients died during follow up due to unknown cause (n = 4) and sepsis (n = 2). Thalidomide appears to be an effective treatment for refractory GIB due to GIAD or GAVE in a Western population with significant comorbidities.


Dislocation of the donor graft to the posterior segment in descemet stripping automated endothelial keratoplasty.
To report a series of dislocations of the donor graft into the posterior segment associated with Descemet stripping endothelial keratoplasty (DSAEK) and to identify possible risk factors for dislocation and clinical outcomes. Retrospective case series. Cases of donor graft dislocation into the posterior segment associated with endothelial keratoplasty were identified from the clinical experience of 7 surgeons. Observations included the preoperative surgical history of each eye, preoperative and postoperative visual acuity, management of the complication, and the postoperative clinical course. No identified cases were excluded from this series. Eight posterior graft dislocations were associated with DSAEK surgery. Each eye had a history of vitrectomy. Five eyes had sutured posterior chamber intraocular lenses, 1 eye had a sulcus intraocular lens, and 2 eyes were aphakic. Each eye required repeat grafting, and in 6 of 8 eyes, pars plana vitrectomy was used to remove the dislocated graft. Final visual acuities ranged from 20/30 to no light perception. Graft dislocation into the posterior segment is a rare complication of DSAEK surgery that can lead to permanent vision loss. It has occurred in eyes that have undergone previous vitrectomy and complicated intraocular lens placement or were aphakic. As is the case with a dropped lens nucleus during cataract extraction, visual acuities after a dropped DSAEK graft range from very good to no light perception. Better postoperative results seem to be associated with prompt removal of the posteriorly dislocated graft.


Error patterns of facial emotion recognition in patients with schizophrenia.
Error patterns of facial emotion recognition (FER) indicate how individuals misinterpret others' facial expressions, which helps clinicians to manage related deficits. However, previous investigations are limited and may have been biased due to methodological issues (e.g., no consideration of response bias). This study aimed to propose a detectability index (d') for adjusting response bias and examine the error patterns of FER in patients with schizophrenia. Responses to 168 photos showing seven basic emotions, obtained from 351 patients with schizophrenia and 101 healthy adults, were extracted from a previous study. The differences in the d's between the two groups (Δd') were calculated to examine the error patterns of FER among the seven emotions. The findings were generally overlapped with those identified by the traditional confusion matrix. Four error patterns were found. First, the patients were insensitive to some negative emotions (i.e., sadness [Δd' = 0.83] and fear [Δd' = 0.72]). Second, they misrecognized happy faces as showing negative emotions (e.g., disgust [Δd' = 0.43] and sadness [Δd' = 0.37]). Third, they misinterpreted surprised faces as all the other emotions (Δd' = 0.41-0.87), except neutral. Fourth, they confused some negative emotions (e.g., misrecognizing fear as anger [Δd' = 0.87]). Our findings suggest that patients with schizophrenia show four error patterns of FER compared to healthy adults. Accordingly, interventions could be selected to improve their sensitivity to faces with negative emotions, differentiation of faces among positive and negative emotions, understanding of surprised faces, and discrimination of faces with negative emotions.


Prevalence and correlates of violence among South African high school learners in uMgungundlovu District municipality, KwaZulu-Natal, South Africa.
Young people grow up in homes and communities where many are exposed daily to crime and antisocial behaviours. To investigate the prevalence of violence and the demographic factors associated with such violence among South African (SA)high school learners in the uMgungundlovu District, KwaZulu-Natal, SA. In a cross-sectional study, we used stratified random sampling to select 16 schools in uMgungundlovu District. All Grade 10 high school learners (N=1 741) completed a self-administered questionnaire (Centers for Disease Control Youth Risk Behavior Survey). Data analysis was carried out using STATA 13 statistical software (Statacorp, USA). Of the participants in this study, 420 (23.9%) had been bullied, 379 (21.7%) had missed school because of feeling unsafe, 468 (15.4%) had been involved in physical fights and 41 (2.4%) had carried weapons to school. There was a significant association between being in a physical fight and missing school (odds ratio (OR) 2.5, 95% confidence interval (CI) 1.9 - 3.3; p<0.001). There were higher odds of male learners carrying weapons than female learners (OR 5.9, 95% CI 2.0 - 15.0). Among learners living in rented rooms, the OR of feeling unsafe was 2.7 (95% CI 0.8 - 3.0), in an informal settlement the OR was 0.8 (95% CI 0.3 - 2.0) and in reconstruction and development programme houses it was 2.7 (95% CI 1.0 - 5.0), compared with learners residing in Zulu homesteads. Violence among learners attending high schools in uMgungundlovu District is a major problem and has consequences for both their academic and social lives. Urgent interventions are required to reduce the rates of violence among high school learners.


Dual educational rationality and acculturation in Mapuche people in Chile.
Even though Mapuche people represent the largest indigenous population in Chile, the "logic of double rationality" in their educational knowledge and its link with acculturation dynamics, has been scarcely studied. The aim of this study was to explore the relationships between the attitudes toward school education and the acculturation orientations of 468 Mapuche people, with ages from 17 to 53 years (M = 16.19; SD = 7.0). Participants were students of secondary schools and universities from urban and rural areas of different regions of Chile. Results showed that most of the participants presented a bicultural orientation (39.4%), followed by a group of segregated or ethnic identity profile (23.5%), while those who preferred assimilation (17.5%), and marginalization (20.7%) represented a minority. Results indicated that people identified as bicultural scored higher in the components of dual Mapuche/ Chilean Mestizo educational rationality than the other acculturation profiles. Also, the fluency in speaking Mapuche language was positively associated with the perception of cultural differences in knowledge and education between Mapuche and Chilean culture, the evaluation of the teaching of Mapuche culture, the perception of school as a factor of assimilation, the valuation of bicultural practices, and the justification of double rationality. Findings' contributions to the development of pertinent educational practices in contexts of social and cultural diversity are discussed.


Using immediate recall to assess language proficiency in deaf students.
We used an immediate recall paradigm to study the effects of list organization and semantic and grammatical features of printed stimuli on working memory capacity in deaf students with differing English language abilities. Thirty lists of five organizational types (random words, semantically related words, semantically paired words, scrambled sentences, and grammatical sentences) were presented to two groups of deaf students who differed in their proficiency in the English language. The students were required to recall the lists in writing. The results indicate that, overall, the students with higher levels of English language proficiency recalled significantly more than those with lower levels. Additionally, semantic and syntactic organization of the lists had different effects on the two groups of students. Semantic pairing aided the low-level group significantly more than the high-level group, whereas the syntactic organization of the grammatical sentences aided the high-level group significantly more. Implications for assessing language ability in deaf students are discussed.


Staphylococcus epidermidis Boosts Innate Immune Response by Activation of Gamma Delta T Cells and Induction of Perforin-2 in Human Skin.
Perforin-2 (P-2) is an antimicrobial protein with unique properties to kill intracellular bacteria. Gamma delta (GD) T cells, as the major T cell population in epithelial tissues, play a central role in protective and pathogenic immune responses in the skin. However, the tissue-specific mechanisms that control the innate immune response and the effector functions of GD T cells, especially the cross-talk with commensal organisms, are not very well understood. We hypothesized that the most prevalent skin commensal microorganism, Staphylococcus epidermidis, may play a role in regulating GD T cell-mediated cutaneous responses. We analyzed antimicrobial protein P-2 expression in human skin at a single cell resolution using an amplified fluorescence in situ hybridization approach to detect P-2 mRNA in combination with immunophenotyping. We show that S. epidermidis activates GD T cells and upregulates P-2 in human skin ex vivo in a cell-specific manner. Furthermore, P-2 upregulation following S. epidermidis stimulation correlates with increased ability of skin cells to kill intracellular Staphylococcus aureus. Our findings are the first to reveal that skin commensal bacteria induce P-2 expression, which may be utilized beneficially to modulate host innate immune responses and protect from skin infections.


Effects of permanent eradication or transient clearance of Helicobacter pylori on histology of gastric mucosa using omeprazole with or without antibiotics.
Changes in Helicobacter pylori-associated gastritis of the antrum and corpus were investigated in a large number of patients treated with omeprazole, with or without the addition of amoxycillin. To investigate the role of H. pylori-associated gastritis in ulcerogenesis and its interplay with omeprazole, biopsies were taken and evaluated according to the Sydney system. Successful eradication of H. pylori (assessed histologically 4 weeks after the end of therapy) led to prompt and persistent suppression of gastritis activity, slow, partial regression of mononuclear inflammation and an ulcer recurrence rate of only 14% during the 6 months' follow-up. In patients treated with omeprazole and placebo, or where eradication treatment with omeprazole and amoxycillin had failed, transient clearance of H. pylori from the antral (but not oxyntic) mucosa was seen. In both of these groups of patients transient regression in the antrum, and worsening in the corpus, of gastritis activity and mononuclear inflammation were evident, coupled with ulcer recurrence rates of 72 and 46%, respectively. It was concluded that H. pylori colonization and gastritis activity play a crucial role in ulcerogenesis, that acid inhibition treatment improves antral H. pylori gastritis and worsens the oxyntic mucosal gastritis, and that this can be prevented by eradication of the H. pylori infection.


IoT-Enabled Gait Assessment: The Next Step for Habitual Monitoring.
Walking/gait quality is a useful clinical tool to assess general health and is now broadly described as the sixth vital sign. This has been mediated by advances in sensing technology, including instrumented walkways and three-dimensional motion capture. However, it is wearable technology innovation that has spawned the highest growth in instrumented gait assessment due to the capabilities for monitoring within and beyond the laboratory. Specifically, instrumented gait assessment with wearable inertial measurement units (IMUs) has provided more readily deployable devices for use in any environment. Contemporary IMU-based gait assessment research has shown evidence of the robust quantifying of important clinical gait outcomes in, e.g., neurological disorders to gather more insightful habitual data in the home and community, given the relatively low cost and portability of IMUs. The aim of this narrative review is to describe the ongoing research regarding the need to move gait assessment out of bespoke settings into habitual environments and to consider the shortcomings and inefficiencies that are common within the field. Accordingly, we broadly explore how the Internet of Things (IoT) could better enable routine gait assessment beyond bespoke settings. As IMU-based wearables and algorithms mature in their corroboration with alternate technologies, such as computer vision, edge computing, and pose estimation, the role of IoT communication will enable new opportunities for remote gait assessment.


Improving medication reconciliation at hospital admission, discharge and ambulatory care through a transition of care team.
Medication reconciliation is an important component to the care of hospitalised patients and their safe transition to the ambulatory setting. In our Family Medicine Hospitalist Service, patient care is frequently transferred between the various physicians, residents, nurses and eventually to a separate group of providers who provide ambulatory management. Due to frequent transitions of care, there was no clear ownership of the medication reconciliation process. To improve the medication reconciliation process, a Transition of Care Team composed of registered nurses was created to oversee the entire reconciliation process. The team engaged the patient and their family, when needed, contacted patients' pharmacies and their providers, reconciled the patients' hospital medication list with the ambulatory list at hospital admission and within 24 hours of discharge, and attended the hospital follow-up visit to verify medications and provide continuity of care. Implementation of the team allowed for additional investigative resources, redundancy in preventing errors and early recovery should an error occur. The percent of medications with error after implementation of the Transition of Care Team was reduced from 131/386 (33.9%) to 147/787 (18.7%) at hospital admission, 81/354 (22.9%) to 42/834 (5.0%) at discharge and 43/337 (12.8%) to 6/809 (0.7%) at follow-up visit (two proportion tests, p<0.001). In addition, the percent of charts without any errors improved at hospital discharge from 8/31 (25.8%) to 46/70 (65.7%) and at hospital follow-up visit from 16/31 (51.6%) to 64/70 (91.4%) (two-proportion test, p<0.001). Previously viewed as three separate reconciliations occurring at admission, discharge and hospital follow-up, the approach to medication reconciliation was reframed as a continuous process occurring throughout the hospitalisation and hospital follow-up resulting in improved reconciliation accuracy and safer transitions to the ambulatory setting.


The incremental cost of traumatic brain injury during the first year after a road traffic accident.
This study aims to determine the incremental cost of TBI during the first year after a traffic accident, compared to other patients with similar non-TBI injuries. Secondly, identification of factors associated with medical costs of TBI is pursued. Analyses were performed on administrative data for traffic victims hospitalised in Belgium between 2009 and 2011. Medical costs attributable to the accident are estimated over one year post-injury. Cases with TBI were matched to controls with similar non-TBI injuries to determine the incremental cost of TBI. Both aims of this research were assessed using regression analysis. The incremental cost of TBI is estimated to range between € 10 042 (95%CI [€8198; €11 887]) and €21 715 (95%CI [€13 5889; €29 540]). Age, problems with self-reliance, survival status, the occurrence of acute events and severity of TBI are significant predictors of medical costs. As to healthcare utilisation, MRI usage, inpatient rehabilitation facilities, nursing homes and readmissions to acute hospital stand out as having most influence on costs. This study reveals a considerable incremental cost of TBI. Policy-making bodies should be made aware of this phenomenon and a diversified policy should be considered when financing programs are discussed.


Embedding and retrieving private metadata in electrocardiograms.
Due to the recent explosion of 'identity theft' cases, the safeguarding of private data has been the focus of many scientific efforts. Medical data contain a number of sensitive attributes, whose access the rightful owner would ideally like to disclose only to authorized personnel. One way of providing limited access to sensitive data is through means of encryption. In this work we follow a different path, by proposing the fusion of the sensitive metadata within the medical data. Our work is focused on medical time-series signals and in particular on Electrocardiograms (ECG). We present techniques that allow the embedding and retrieval of sensitive numerical data, such as the patient's social security number or birth date, within the medical signal. The proposed technique not only allows the effective hiding of the sensitive metadata within the signal itself, but it additionally provides a way of authenticating the data ownership or providing assurances about the origin of the data. Our methodology builds upon watermarking notions, and presents the following desirable characteristics: (a) it does not distort important ECG characteristics, which are essential for proper medical diagnosis, (b) it allows not only the embedding but also the efficient retrieval of the embedded data, (c) it provides resilience and fault tolerance by employing multistage watermarks (both robust and fragile). Our experiments on real ECG data indicate the viability of the proposed scheme.


Fetal Environment and Glycosylation Status in Neonatal Cord Blood: A Comprehensive Mass Spectrometry-based Glycosylation Analysis.
Fetal environment is known to be a major predictive factor of type 2 diabetes and cardiovascular disease. However, associations of fetal environment and cord blood glycoforms are uncertain. In this study, we aimed to determine whether glycosylation status in neonatal cord blood is associated with perinatal outcomes reflecting a poor fetal environment.Thirty-six low birth weight (LBW) infants and 120 normal birth weight infants were recruited from a longitudinal birth cohort. We conducted a comprehensive cord blood N-glycan analysis using matrix-assisted laser-desorption/ionization time-of-flight mass spectrometry. Associations of N-glycans with perinatal outcomes, including LBW, small for gestational age, and levels of cord blood leptin and adiponectin, were evaluated using logistic or multiple regression. We also prospectively explored correlations between N-glycans and 6 or 18-month rapid weight gain (>0.67 SD score).A total of 35 N-glycans were detected (m/z value 1362.481-3865.407). Of these, abundance levels of G3414 (m/z value 3414.238) were inversely correlated with LBW and small for gestational age. Abundance levels of G1915 (m/z value 1914.698), G2744 (m/z value 2743.994), G3049 (m/z value 3049.105), and G3719 (m/z value 3719.349) were inversely related to LBW. The total N-glycan abundance levels were strongly positively correlated with levels of leptin and adiponectin in cord blood. In a prospective exploratory analysis, the 5 LBW-related N-glycans (G1915, G2744, G3049, G3414, and G3719) were all inversely associated with 6 or 18-month rapid weight gain. These N-glycans are structurally categorized into 2 different categories: fucosylated bi or tri-antennary N-glycans; and tri or tetra-antennary N-glycans without fucosylation.In conclusion, mass spectrometry-based cord blood glycosylation analysis shows that 5 types of N-glycans are potential predictors of a poor fetal environment.


The inhibition of glycogen synthase kinase 3beta by a metabotropic glutamate receptor 5 mediated pathway confers neuroprotection to Abeta peptides.
Activation of glycogen synthase kinase 3beta (Gsk3beta) has been shown to be a key component in signaling pathways that underlie neurodegeneration and neurodegenerative disease. Conversely, inactivation of Gsk3beta by phosphoinositide 3-kinase (PI3K)/Akt is an important neuroprotective mechanism. Previous studies have shown that agonist activation of group I metabotropic glutamate receptors (mGluRs) can increase neuronal survival and prevent apoptosis. However, little is known about the signaling pathways that couple mGluR5 to neuroprotection. In this report, we investigated whether activation of the PI3K/Akt/Gsk3beta pathway, which has been shown to have an important neuroprotective mechanism, is required for mGluR5 activation mediated neuroprotection against beta-amyloid. We found that brief incubations of mouse hippocampal slices with (R,S)-3,5-dihydroxyphenylglycine (DHPG) resulted in increased phosphorylation of Akt and Gsk3beta. The PI3K inhibitors, LY294002 and wortmannin, blocked the DHPG-induced increased phosphorylation of Akt and Gsk3beta. Similar results were observed in rat primary hippocampal cultures. Finally, we found that the PI3K inhibitor LY294002 can block (R,S)-2-chloro-5-hydroxyphenylglycine (CHPG) mediated neuroprotection against beta-amyloid. Thus, these findings suggest that mGluR5 can modulate the PI3K/Akt/Gsk3beta pathway in the hippocampus, and that modulation of this signaling pathway can reverse beta-amyloid-induced neuronal toxicity.


Alcohol: its health and social impact in India.
Alcoholic beverages have been used in human societies since the beginning of recorded history. The patterns of alcohol intake around the world are constantly evolving, and alcohol is ubiquitous today. Research has contributed substantially to our understanding of the relation of drinking to specific disorders, and has shown that the relation between alcohol consumption and health outcomes is complex and multidimensional. Increases in the average volume of drinking are predicted for the most populous regions of the world in Southeast Asia including India. Cultural differences apparently influence the pattern of alcohol consumption. In addition, alcohol is linked to categories of disease whose relative impact on the global burden is predicted to increase. Therefore, it is appropriate to implement policies with targeted harm reduction strategies. The crucial need, from a public health perspective, is for regular means of coordination whereby prevention of alcohol-related problems is taken fully into account in policy decisions about alcohol control and regulation in the market for alcoholic beverages.


Detailed Structural Analysis of a Self-Assembled Vesicular Amphiphilic NCN-Pincer Palladium Complex by Using Wide-Angle X-Ray Scattering and Molecular Dynamics Calculations.
Wide-angle X-ray scattering experiments and all-atomistic molecular dynamics calculations were performed to elucidate the detailed structure of bilayer vesicles constructed by self-assembly of an amphiphilic palladium NCN-pincer complex. We found an excellent agreement between the experimental and calculated X-ray spectra, and between the membrane thickness determined from a TEM image and that calculated from an electron-density profile, which indicated that the calculated structure was highly reliable. The analysis of the simulated bilayer structure showed that in general the membrane was softer than other phospholipid bilayer membranes. In this bilayer assemblage, the degree of alignment of complex molecules in the bilayer membrane was quite low. An analysis of the electron-density profile shows that the bilayer assemblage contains a space through which organic molecules can exit. Furthermore, the catalytically active center is near this space and is easily accessible by organic molecules, which permits the bilayer membrane to act as a nanoreactor. The free energy of permeation of water through the bilayer membrane of the amphiphilic complex was 12 kJ mol-1 , which is much lower than that for phospholipid bilayer membranes in general. Organic molecules are expected to pass though the bilayer membrane. The self-assembled vesicles were shown to be catalytically active in a Miyaura-Michael reaction in water.


The levels of IL-1beta, IL-4 and IL-6 in the serum and the liver tissue of chronic HCV-infected patients.
The pro-inflammatory interleukines play a major role in the progress of chronic hepatitis C. Among the patients with chronic hepatitis C virus (HCV) infection, the morphology of the liver was assessed and the levels of serum and liver-tissue IL-1beta, IL-4 and IL-6 were determined. The levels of the cytokines were related to the liver-tissue changes. RNA-HCV was measured by the RT-PCR method. Cytokine levels of the serum and liver tissue were measured by the Quantikine High Sensitivity test. The levels of serum IL-1beta, IL-4 and IL-6 (0.221, 0.104 and 1.393 pg/ml) in all HCV patients were higher in comparison with healthy adults (0.188, 0.025 and 0.600 pg/ml). The levels of liver tissue IL-1beta, IL-4 and IL-6 (4291.3, p<0.05; 1624.6, p<0.05; 1158.7 pg/g protein) in all HCV patients were higher compared with patients with liver cirrhosis without HBV or HCV infection (2319.9, 553.6 and 756.2 pg/g protein). Patients with HCV infection demonstrated a significant correlation between serum and liver-tissue levels of IL-1beta (Pearson: 0.61, p<0.05) and IL-4 (Pearson: 0.51). The level of serum IL-6 in patients with moderate chronic active hepatitis was higher when compared with patients with mild chronic persistent hepatitis. Among the patients with mild chronic persistent hepatitis, the levels of liver-tissue IL-6 were higher compared with those with moderate chronic active hepatitis. There was no correlation between histology changes and the levels of serum and liver-tissue IL-1beta and IL-4.


Antibiotic resistance among clinical isolates of Acinetobacter in the UK, and in vitro evaluation of tigecycline (GAR-936).
A survey was conducted of the antimicrobial susceptibilities of 595 Acinetobacter spp. isolated from routine clinical specimens in 54 sentinel laboratories throughout the UK during 2000. Isolates of the Acinetobacter baumannii complex (genomic groups 2, 3 and 13TU; n = 443) were distinguished from other genomic groups (n = 152) by PCR fingerprinting of tDNA spacer regions. MICs of amikacin, cefotaxime, ceftazidime, ciprofloxacin, colistin, gentamicin, imipenem, meropenem, minocycline, piperacillin, piperacillin/tazobactam, rifampicin, sulbactam and tetracycline were determined on IsoSensitest agar and interpreted, wherever possible, using BSAC breakpoints. Tigecycline (GAR-936), a new glycylcycline, was also tested. Resistance to cephalosporins, aminoglycosides and ciprofloxacin was widespread, but carbapenems, colistin, sulbactam, minocycline and tigecycline were each active against >80% of the isolates. Isolates of A. baumannii were more often resistant to cefotaxime, ceftazidime, piperacillin, piperacillin/tazobactam, ciprofloxacin, gentamicin and tetracyclines than those belonging to other genomic groups, but were less often resistant to colistin; no significant differences between genomic groups were noted in the susceptibilities to amikacin, carbapenems, rifampicin or sulbactam. The relative activities of the tetracyclines were minocycline > tigecycline > tetracycline. Thirteen carbapenem-resistant isolates (MICs > or =8 mg/L; 2.2%) were received from six centres; four centres sent single isolates; one sent three and one sent six. An allele of bla(IMP) was detected in one of these isolates, but the other 12 isolates either had carbapenemase-independent resistance, or undetectable carbapenemase activity combined with other resistance mechanisms. In conclusion, carbapenems, colistin and minocycline retained greatest activity against the Acinetobacter isolates collected. Tigecycline was less active than minocycline, but both agents overcame most tetracycline resistance.


Herpes zoster in eastern Saudi Arabia: clinical presentation and management.
Herpes zoster (HZ), caused by varicella zoster virus (VZV), initially produces chicken-pox, then the virus lies dormant in the dorsal root ganglia. The virus can reactivate after many years and results in HZ along ganglion's distribution. Old age, trauma, stress, diabetes mellitus, and immune suppression are important risk factors for the reactivation. Herpes zoster is characterized by unilateral radicular pain and vesicular eruption that is generally limited to the dermatome innervated by the affected ganglion. In immunocompromised individuals, disseminated zoster may develop. The aims of therapy in HZ are to control pain or reduce its severity by the use of analgesics, reduce the duration and eruption of new lesions, and prevent complications, particularly postherpetic neuralgia (PHN) by appropriate antiviral therapy. All cases of HZ seen in the dermatology clinic at King Fahd Hospital of the University (KFHU) from 1988 to 2006 were included in the study. Their diagnoses were based on the clinical presentation. The following parameters were collected and analyzed: age, sex, nationality, symptoms, dermatomal distribution, complications, coexisting diseases, and disease management. Of 22 749 new cases seen in the dermatology clinic over 18 years, 141 were HZ, with an occurrence of 0.62%. Male to female ratio was 2:1 and the age ranged from 14 months to 80 years. The thoracic dermatomes were the most commonly involved. The most frequent coexisting disease was diabetes mellitus, and the most common complication of HZ was PHN. Most patients with HZ ophthalmicus developed eye complications. The occurrence of HZ is 0.62% in patients reporting to the dermatology clinic of the hospital. Males are little more affected than females. The thoracic dermatomes are the most frequently involved. Diabetes mellitus is the most frequent coexisting disease. Postherpetic neuralgia is the most common complication of HZ.


Antiviral activity of an immunomodulatory lipophilic desmuramyl dipeptide analog.
BCH-527, the lipophilic hydrochloride salt of octadecyl D-alanyl L-glutamine, was evaluated for efficacy against experimentally induced murine cytomegalovirus (MCMV), influenza A (H1N1) (IV-A), and Punta Toro virus (PTV) infections in mice. The compound was administered i.p. every other day for a total of 4 injections commencing 24 h previrus exposure. Doses ranged from 12.5 to 200 mg/kg per injection in the various experiments. The MCMV infection was significantly inhibited in two experiments by doses of 25-200 mg/kg, as manifested by increased numbers of survivors and decreased titers of virus recoverable from tissues. The IV-A infection was weakly inhibited, with antiviral activity seen in lowered lung scores and lung weights and less decline in arterial oxygen saturation values. The PTV infection was not inhibited. BCH-527 was stimulatory to cytotoxic T-cells, natural killer (NK) cells, macrophages, and splenic B-cells. The highest dose tested, 200 mg/kg, was inhibitory to cytotoxic T-cell activity and to some extent to NK cell and macrophage activity. These data suggest BCH-527 functions as an immune modulator in exerting the observed antiviral activity.


Development of a Seniors' Mental Health Policy Lens: an analytical tool to assess policies and programs from a seniors' mental health perspective.
The Seniors Mental Health Policy Lens (SMHPL) is an analytical tool developed to identify unintended negative effects of current and planned policies, programs, and practices on seniors' mental health. It is designed (a) to promote social environments, including health services, supportive of older adults' mental health, and (b) to help ensure that the way mental health services are defined, delivered, and funded will result in increased emphasis on mental health promotion and on the prevention of mental health problems. The SMHPL incorporates Canadian seniors' perspectives on the factors influencing their mental health, and reflects the values of older adults.


Impaired tilt perception in Parkinson's disease: a central vestibular integration failure.
Impaired balance control is a hallmark symptom in Parkinson's disease (PD). Altered sensory-motor integration contributes to the deficiency. We aimed to determine whether impaired vestibular signal processing added to the disorder. We exposed patients (N = 11; 68±6y) and age-matched healthy subjects (hS: N = 19; 65±11y) on a motion platform in complete darkness to two consecutive forward tilt movements (12 series; N = 24; overall 288 trials) and asked them to indicate which tilt was perceived larger. By combing tilt movements with translations we manipulated vestibular sensory input in order to investigate whether putative impairment resulted from a deficiency of the sensory organs (semicircular canals in 'single-SCC-cue-condition', otoliths in 'single-OT-cue-condition') themselves or to a sensory integration failure ('multi-cue-condition'). Tilt discrimination in the multi-cue-condition was inferior in patients compared to hS (p = 0.02). No significant differences between the two groups were found for both single-cue-conditions. Comparison of multi-cue-condition with a prediction resulting from the combination of both single-cue-conditions by optimal observer theory revealed that patients (p = 0.04), in contrast to hS, failed to efficiently combine SCC and OT information to improve tilt perception. We found that PD patients distinguished forward tilts less precise than hS, suggesting impaired vestibular perception. Tilt discrimination in patients, moreover, did not improve as much as in hS in conditions where both SCC and OT information was available compared to conditions where only SCC or OT cues were activated. The latter provides evidence that tilt misperception in PD most likely results from an integration failure of vestibular signals.


Dexamethasone loaded Laponite®/porous calcium phosphate cement for treatment of bone defects.
In this research, nanocomposite porous calcium phosphate cements (CPCs) consisting of dexamethasone (DEX) loaded Laponite® nanoplates (LAP) (DEX-LAP) were fabricated and the effects of sodium bicarbonate (NaHCO3) as the foaming agent on the physical, mechanical, and biological characteristics of DEX-LAP loaded CPCs were investigated. Our findings showed that DEX-LAP encapsulation significantly reduced the final setting time (1.5 times) of CPCs and accelerated the total transformation of tricalcium phosphate to hydroxyapatite. Moreover, DEX-LAP nanoplates meaningfully enhanced the compressive strength (4 fold) and compressive modulus (4 fold) of cement. Additionally, incorporation of 6% foaming agent noticeably reduced setting time of cement to less than 10 min due to the enhanced surface area in contact with cement paste. Encapsulation of DEX within the LAP nanoplates and consequently loading of DEX-LAP nanoplates in the CPCs resulted in the significantly reduced burst release of DEX. Finally, the results also illustrated that the presence of interconnected micropores and DEX-LAP nanoplates in the CPC improved MG63 cell proliferation. These findings suggest that the porous DEX-LAP/CPC can potentially be developed as bone grafts for bone defects.


Xenobiotic stress induces hepatomegaly and liver tumors via the nuclear receptor constitutive androstane receptor.
The constitutive androstane receptor (CAR, NR1I3) is a central regulator of xenobiotic metabolism. CAR activation induces hepatic expression of detoxification enzymes and transporters and increases liver size. Here we show that CAR-mediated hepatomegaly is a transient, adaptive response to acute xenobiotic stress. In contrast, chronic CAR activation results in hepatocarcinogenesis. In both acute and chronic xenobiotic responses, hepatocyte DNA replication is increased and apoptosis is decreased. These effects are absent in CAR null mice, which are completely resistant to tumorigenic effects of chronic xenobiotic stress. In the acute response, direct up-regulation of Mdm2 expression by CAR contributes to both increased DNA replication and inhibition of p53-mediated apoptosis. These results demonstrate an essential role for CAR in regulating both liver homeostasis and tumorigenesis in response to xenobiotic stresses, and they also identify a specific molecular mechanism linking chronic environmental stress and tumor formation.


An exploratory study of long-term neurocognitive outcomes following recovery from opportunistic brain infections in HIV+ adults.
Central nervous system opportunistic infections (CNS-OI) are a significant cause of morbidity and mortality in AIDS. While current interventions are increasingly successful in treating CNS-OI, little information exists regarding long-term behavioral outcomes among survivors. In this exploratory study we examined neurocognitive data among three groups of adults with different AIDS-related CNS-OI: 15 with past cryptococcal meningitis (CM), 8 with toxoplasmosis encephalitis (TE), and 8 with progressive multifocal leukoencephalopathy (PML). A group of 61 individuals with AIDS, but without CNS-OI, was used as a comparison group. A battery of standardized neuropsychological tests assessing a variety of cognitive domains was administered upon entry. Results indicate that individuals with a history of CNS-OI were most impaired on measures of cognitive and psychomotor speed relative to the HIV+ comparison group. Among the CNS-OI groups, individuals with history of TE had the most severe and varied deficits. The results are discussed in relation to what is known about the neuropathological consequences of the various CNS-OIs. While this is the first systematic group study of residual CNS-OI effects on neurocognitive function, future studies employing more participants, perhaps focusing on specific CNS-OIs, will further characterize the long-term outcomes in AIDS-related CNS-OI.


Differences between gray matter and white matter water diffusion in stroke: diffusion-tensor MR imaging in 12 patients.
To investigate differences in water diffusion between white matter and gray matter in acute to early subacute stroke with diffusion-tensor magnetic resonance (MR) imaging. Twelve patients with unilateral middle cerebral arterial infarcts were examined with diffusion tensor-encoded echo-planar MR imaging 17 hours to 5 days after stroke onset. Isotropic diffusion coefficient (D) and diffusion anisotropy (A(sigma)) images were computed. (D) values were measured in ischemic and contralateral gray matter and white matter by using A(sigma) images to differentiate white matter from gray matter. (D) images were compared with unidirectional and directionally averaged diffusion-weighted images. In all patients, (D) images showed two distinct levels of diffusion reduction in the infarct; more severe reduction occurred exclusively in white matter. (D) values were significantly less in infarcted white matter than in infarcted gray matter, whereas (D) values in the contralateral white matter and gray matter were not significantly different. Relative to the contralateral side, (D) values in the infarct were reduced by 46% in white matter and by 31% in gray matter (P <.001). Diffusion-weighted imaging caused underestimation of the magnitude and, in some cases, the spatial extent of the white matter diffusion abnormality. Isotropic diffusion is more reduced in white matter than in gray matter in acute to early subacute middle cerebral arterial stroke. Diffusion-tensor imaging may be more sensitive than diffusion-weighted imaging to white matter ischemia.


Delayed activation of host innate immune pathways in streptozotocin-induced diabetic hosts leads to more severe disease during infection with Burkholderia pseudomallei.
Diabetes mellitus is a predisposing factor of melioidosis, contributing to higher mortality rates in diabetics infected with Burkholderia pseudomallei. To investigate how diabetes alters the inflammatory response, we established a streptozotocin (STZ) -induced diabetic murine acute-phase melioidosis model. Viable B. pseudomallei cells were consistently detected in the blood, liver and spleen during the 42-hr course of infection but the hyperglycaemic environment did not increase the bacterial burden. However, after 24 hr, granulocyte counts increased in response to infection, whereas blood glucose concentrations decreased over the course of infection. A genome-wide expression analysis of the STZ-diabetic murine acute melioidosis liver identified ~1000 genes whose expression was altered in the STZ-diabetic mice. The STZ-diabetic host transcriptional response was compared with the normoglycaemic host transcriptional response recently reported by our group. The microarray data suggest that the presence of elevated glucose levels impairs the host innate immune system by delaying the identification and recognition of B. pseudomallei surface structures. Consequently, the host is unable to activate the appropriate innate immune response over time, which may explain the increased susceptibility to melioidosis in the STZ-diabetic host. Nevertheless, a general 'alarm signal' of infection as well as defence programmes are still triggered by the STZ-diabetic host, although only 24 hr after infection. In summary, this study demonstrates that in the face of a B. pseudomallei acute infection, poor glycaemic control impaired innate responses during the early stages of B. pseudomallei infection, contributing to the increased susceptibility of STZ-induced diabetics to this fatal disease.


The C-fragment of beta-lipotropin: an endogenous neuroleptic or antipsychotogen?
Microinjection of the C-fragment (also called beta-endorphin), which is amino acid sequence 61-91 of the endogenous pituitary hormone, beta-lipotropin (beta-LPH), in the periaqueductal gray of the rat resulted in profound sedation and catalepsy, while microinjection of smaller fragments-that is, methionine-enkephalin [sequence beta-LPH-(61-65)] and its related pentapeptide, leucine enkephalin, and alpha-endorphin [sequence beta-LPH-(61-76)] resulted in attenuated forms of this behavior. This indicates that the C-fragment is an important neuromodulator of the central nervous system. The similarity of this behavior to that seen after systemic administration to experimental animals of exogenous neuroleptics suggests that a disturbance in the bioavailability of this neuropeptide to receptor sites in brain-perhaps due to lack of enzymatic cleavage from the circulating parent hormone, beta-lipotropin--may be an etiological factor in those psychopathological states for which the exogenous neuroleptics exert an ameliorative influence.


Integration of biomarkers including molecular targeted therapies in head and neck cancer.
Head and neck tumors comprise a wide spectrum of heterogeneous neoplasms for which biomarkers are needed to aid in earlier diagnosis, risk assessment and therapy response. The search for biomarkers includes evaluation of tumor tissues and surrogate materials by molecular, genomic and phenotypic means. Ideal biomarkers should be accurate and easy to perform, highly specific, objective, quantitative, and cost effective. Because of the heterogeneity of head and neck tumors, the integration of multiple selected markers in association with the histopathologic features is advocated for risk assessment. For targeted therapy, however, a single key molecule must be identified. Key molecules and pathways for targeted therapy include growth factor receptors, MAPk/ERk pathway, angiogenesis, and epithelial to mesenchymal transition. Over-expression and mutations of genes in these pathways including EGFR, VEGF, HER2, BRAF and RET, contribute to tumorigenesis in head and neck cancers from squamous carcinomas, to salivary adenocarcinomas and thyroid carcinomas, both follicular and c-cell derived. Monoclonal antibodies to the EGFR receptor and oral tyrosine kinase inhibitors are currently being studied in multiple phase II and III clinical trials to determine their efficacy in head and neck cancers and correlative studies for biomarkers are on-going.


The effect of back school integrated with core strengthening in patients with chronic low-back pain.
To assess the effect of back school integrated with core-strengthening exercises on back-specific disability and pain-coping strategies and to examine how reactions to pain affect the outcomes of back school in patients with chronic low back pain. A single-center prospective trial was conducted with 142 participants with chronic low-back pain (38 men and 104 women) who completed a back school program at the spine center of a university hospital. The subjects participated in a 4-wk program integrated with core-strengthening exercises. Back-specific disabilities were measured as a primary outcome before and after the program. Secondary outcomes were pain, Chronic Pain Coping Inventory, general health status assessed by the SF-36, and quantitative functional evaluations of factors, such as trunk muscle strength, endurance, and the back performance scale. A subgroup of 28 subjects (12 men and 16 women) of the total sample of 142 subjects was used to analyze the longitudinal association between coping strategies and the primary outcome in a long-term follow-up study. These participants were divided into three groups (much improved, slightly improved, and unimproved) based on changes in back-specific disability scores. Participants improved significantly in terms of back-specific disability, pain, general health, and quantitative functional tests according to the short-term evaluation. They used more relaxation and exercise/stretching techniques as coping strategies. Of the groups participating in the longer-term follow-up (T3), the much-improved group showed significant improvement between T1 (before back school) and T2 (after back school) in scores for relaxation (1.6 +/- 1.0 vs. 2.6 +/- 1.1), task persistence (2.9 +/- 1.2 vs. 3.7 +/- 1.2), and exercise (3.3 +/- 1.1 vs. 5.2 +/- 1.9), but the coping strategies of those in the slightly improved and unimproved groups did not change significantly at T2. Our back school program may help patients with chronic low back pain reduce back-specific disability and pain and develop wellness-focused coping strategies such as exercise and stretching.


Partitioning of rearranged Ig genes by mutation analysis demonstrates D-D fusion and V gene replacement in the expressed human repertoire.
The accurate partitioning of Ig H chain V(H)DJ(H) junctions and L chain V(L)J(L) junctions is problematic. We have developed a statistical approach for the partitioning of such sequences, by analyzing the distribution of point mutations between a determined V gene segment and putative Ig regions. The establishment of objective criteria for the partitioning of sequences between V(H), D, and J(H) gene segments has allowed us to more carefully analyze intervening putative nontemplated (N) nucleotides. An analysis of 225 IgM H chain sequences, with five or fewer V mutations, led to the alignment of 199 sequences. Only 5.0% of sequences lacked N nucleotides at the V(H)D junction (N1), and 10.6% at the DJ(H) junction (N2). Long N regions (>9 nt) were seen in 20.6% of N1 regions and 17.1% of N2 regions. Using a statistical analysis based upon known features of N addition, and mutation analysis, two of these N regions aligned with D gene segments, and a third aligned with an inverted D gene segment. Nine additional sequences included possible alignments with a second D segment. Four of the remaining 40 long N1 regions included 5' sequences having six or more matches to V gene end motifs, which may be the result of V gene replacement. Such sequences were not seen in long N2 regions. The long N regions frequently seen in the expressed repertoire of human Ig gene rearrangements can therefore only partly be explained by V gene replacement and D-D fusion.


Positron emission tomography for preoperative staging in patients with locally advanced or metastatic colorectal adenocarcinoma in lymph node metastasis.
The impact of positron emission tomography was prospectively evaluated using 18 (F)-fluoro-deoxyglucose (FDG-PET) for the detection of lymph node (LN) metastasis in preoperative locally advanced colorectal adenocarcinoma, compared with computed tomography (CT) and pathologic findings. Fifty-three patients who were suspected of LN involvement by CT were staged preoperatively for LN metastasis using FDG-PET and CT. Regional LNs were classified into 3 groups, N1, N2-3, and N4, according to the Japanese General Rules for Clinical and Pathological Studies on Cancer of the Colon, Rectum and Anus (6th Edition). A comparison of pathologic findings with CT and FDG-PET findings was used to calculate sensitivity, specificity, and accuracy. The sensitivity, specificity and accuracy of CT/FDG-PET were 91.3%/52.2%, 91.7%/75.0% and 65.9%/72.3%, respectively, for N1, 91.7%/75.0%, 72.2%/94.4% and 77.1%/89.6%, respectively, for N2-3, and 100%/100%, 17.6%/100% and 41.7%/100%, respectively, for N4. The detection rate of the num ber of metastatic N1 LNs by CT was significantly higher than by FDG-PET, and not significantly in the N2-4 area. LNs hidden by strong halation of the primary tumor were not detected by FDG-PET. While FDG-PET is markedly more sensitive than CT for detection of N4 LN involve. ment, the number of metastatic LNs is difficult to determine.


Acute effects of leg heat therapy on walking performance and cardiovascular and inflammatory responses to exercise in patients with peripheral artery disease.
Lower-extremity peripheral artery disease (PAD) is associated with increased risk of cardiovascular events and impaired exercise tolerance. We have previously reported that leg heat therapy (HT) applied using liquid-circulating trousers perfused with warm water increases leg blood flow and reduces blood pressure (BP) and the circulating levels of endothelin-1 (ET-1) in patients with symptomatic PAD. In this sham-controlled, randomized, crossover study, sixteen patients with symptomatic PAD (age 65 ± 5.7 years and ankle-brachial index: 0.69 ± 0.1) underwent a single 90-min session of HT or a sham treatment prior to a symptom-limited, graded cardiopulmonary exercise test on the treadmill. The primary outcome was the peak walking time (PWT) during the exercise test. Secondary outcomes included the claudication onset time (COT), resting and exercise BP, calf muscle oxygenation, pulmonary oxygen uptake (V̇O2 ), and plasma levels of ET-1, interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α). Systolic, but not diastolic BP, was significantly lower (~7 mmHg, p < .05) during HT when compared to the sham treatment. There was also a trend for lower SBP throughout the exercise and the recovery period following HT (p = .057). While COT did not differ between treatments (p = .77), PWT tended to increase following HT (CON: 911 ± 69 s, HT: 954 ± 77 s, p = .059). Post-exercise plasma levels of ET-1 were also lower in the HT session (CON: 2.0 ± 0.1, HT: 1.7 ± 0.1, p = .02). Calf muscle oxygenation, V̇O2 , COT, IL-6, and TNF-α did not differ between treatments. A single session of leg HT lowers BP and post-exercise circulating levels of ET-1 and may enhance treadmill walking performance in symptomatic PAD patients.


Occurrence of the CTX-M, SHV and the TEM Genes Among the Extended Spectrum β-Lactamase Producing Isolates of Enterobacteriaceae in a Tertiary Care Hospital of North India.
The present study was carried out to assess the prevalence of the Extended Spectrum Beta Lactamases (ESBLs) and to characterize the ESBL types which were prevalent in our hospital. Five hundred gram negative isolates which belonged to the family, Enterobacteriaceae, which were isolated during the study period of 2009 to 2011, were investigated for ESBL production. Clinical isolates from urine (344), pus (109), blood (15), IV/ central line tip (10), sputum (12) and body fluid (10) specimens were processed. The organisms which were identified, included E.coli (351), Klebsiella pneumoniae (74), Klebsiella oxytoca (21), Proteus mirabilis (15), Proteus vulgaris (9), Enterobacter spp (15) and Citrobacterspp (15). Antimicrobial susceptibility testing was done. The ESBL detection was carried out for all the isolates by the CLSI confirmatory method. The MIC of ceftazidime and ceftazidime plus clavulanic acid was determined by the E-test. Molecular typing of the ESBLs was performed by multiplex PCR among 93 ESBL isolates. 45.8% isolates were found to be ESBL producers by the CLSI confirmatory method and they were confirmed by the E-test ESBL strips. A majority of E.coli in the study possessed the CTX-M genes (59.32%). Among the Klebsiella isolates, a majority were co producers of the ESBL genes; either 2 or all the 3 genes co-existed together. An indiscriminate use of the higher antibiotics should be restricted as far as possible. The infection control programmes should be monitored continuously in hospitals, to contain these ESBL producers. We are reporting the presence of all types of ESBL genes among the Enterobacteriaceae isolates from our hospital setting.


A comprehensive evaluation of the toxicology of different cut widths of tobacco in experimental cigarettes.
Literature suggests that the width of tobacco strips in cigarettes may affect the smoke chemistry and toxicology of such products. A comprehensive analysis of smoke from experimental cigarettes can be used to determine whether different cut widths of tobacco result in different toxicological activity. A battery of tests was used to compare the chemistry and in vitro and in vivo toxicology of smoke from experimental cigarettes made with tobacco cut to different widths. Different cut widths of tobacco did not elicit consistent and significant differences in cigarette smoke chemistry, responses in in vitro mutagenicity or cytotoxicity assays or most endpoints in 90-d rat inhalation studies. Of note, however, were atypical in-life observations and slightly depressed body weights observed in two rat inhalation studies. Most of our data indicate that different cut widths of tobacco used in cigarettes are unlikely to change the toxicity of mainstream cigarette smoke; however, without additional investigation, the atypical in-life observations and depression in body weights cast doubt on the toxicological acceptability of cutting the tobacco into wider shreds.


Using Re-scaled Resilience Screening Index Results and Location Quotients for Socio-Ecological Characterizations in U.S. Coastal Regions.
In terms of natural hazard events, resilience characterizations provide a means of identifying risk profiles, degrees of preparedness, and the ability of communities to respond and recover. While nationally consistent measures of community resilience to natural hazards are needed to address widespread socio-ecological impacts from a broad policy perspective, geographically specific resilience characterizations are needed to target local resources to increase community resilience. The Climate Resilience index (CRSI) was developed to characterize the resilience of socio-ecological systems in the context of governance and risk to natural hazard events for all U.S. counties for the years 2000-2015. Those resilience characterizations were based on the full range of nationwide county domain scores. This paper presents a re-scaled application of CRSI, where county domain scores are limited to the range of scores within a specific set of U.S. coastal and shoreline counties within each of eight coastal regions. The re-scaled CRSI values for selected counties/parishes in the Gulf of Mexico (GOM) region are also presented in conjunction with calculated Location Quotients (LQ) values >1.0, which represent a high employment dependence on ocean economy sectors. Using a combination of re-scaled CRSI and LQ values provides a more holistic picture of vulnerability and resilience in these U.S. coastal shoreline counties. The relative resilience assessments presented for coastal regions are useful in identifying potential strengths and weaknesses in resilience aspects given similar hazard profiles, a signature otherwise diluted in nation-wide county-level assessments. The unique approach of combining CRSI and LQ for characterizing natural hazard resilience described could be transferred to other specific geographies as defined by population groups, hazard profiles and economic dependence.


The juvenile court: a view from the bench.
This article describes the changing role of the juvenile court from the perspective of an urban juvenile court judge. The author's experiences as the administrative judge for Baltimore City's juvenile court address typical current juvenile court dilemmas such as lack of funding, physical space that is inadequate for the needs of the court and those it serves, and limited dispositional options for juvenile offenders. Examples of effective judicial advocacy are presented, as are suggestions for positive court reform.


Dorsomedial Striatal Activity Tracks Completion of Behavioral Sequences in Rats.
For proper execution of goal-directed behaviors, individuals require both a general representation of the goal and an ability to monitor their own progress toward that goal. Here, we examine how dorsomedial striatum (DMS), a region pivotal for forming associations among stimuli, actions, and outcomes, encodes the execution of goal-directed action sequences that require self-monitoring of behavior. We trained rats to complete a sequence of at least five consecutive lever presses (without visiting the reward port) to obtain a reward and recorded the activity of individual cells in DMS while rats performed the task. We found that the pattern of DMS activity gradually changed during the execution of the sequence, permitting accurate decoding of sequence progress from neural activity at a population level. Moreover, this sequence-related activity was blunted on trials where rats did not complete a sufficient number of presses. Overall, these data suggest a link between DMS activity and the execution of behavioral sequences that require monitoring of ongoing behavior.


Complex regional pain syndrome type I as a consequence of trauma or surgery to upper extremity: management with intravenous regional anaesthesia, using lidocaine and methyloprednisolone.
Complex regional pain syndrome type I (CRPS-I) is a known complication after surgery or trauma to the upper extremity and is difficult to treat. A simple and easily tolerated method of treatment that includes intravenous regional anaesthetic block with lidocaine and methyloprednisolone is presented. One hundred and sixty-eight patients with CRPS-I of the upper extremity were treated in a 5-year period. At the end of treatment 88% of the patients reported minimal or no pain. After a mean follow-up of 5 years (range 28 months to 7 years) complete absence of pain was reported by 92% of patients. The symptoms of the acute phase of the syndrome were reversed. Early recognition and prompt initiation of treatment is very important for the course of the disease as symptoms can be reversible when treatment starts early. Permanent results with a functional upper extremity and very satisfactory pain relief can be anticipated.


Assay of excised oxidative DNA lesions: isolation of 8-oxoguanine and its nucleoside derivatives from biological fluids with a monoclonal antibody column.
An immunoaffinity column is described that facilitates the analysis of oxidative damage products of DNA and RNA in urine, blood plasma, and medium isolated from cultures of Escherichia coli. In intact animals, lesions (adducts) excised from DNA are transported from the cell through the circulation and excreted in urine. In bacteria, DNA adducts are excreted directly into the medium. In either case, the adducts can be assayed as a measure of oxidative damage to DNA. A monoclonal antibody that recognizes 8-oxo-7,8-dihydro-2'-deoxyguanosine (oxo8dG;8-hydroxy-2'-deoxyguanosine), a bio-marker of oxidative damage to DNA, has been isolated, and its substrate binding properties have been characterized. The relative binding affinities of this monoclonal antibody for oxo8dG, unmodified nucleosides, or derivatives of Gua made it suitable for the preparation of immunoaffinity columns that greatly facilitate the isolation of oxo8dG, 8-oxo-7,8-dihydroguanine, and 8-oxo-7,8-dihydroguanosine from various biological fluids. Quantitative analysis of these adducts in urine of rats fed a nucleic acid-free diet and in the medium from cultures of E. coli suggests that oxo8-7,8-dihydroguanine is the principal repair product from oxo8-dG in DNA of both eukaryotes and prokaryotes. The results support our previous estimate of about 10(5) oxidative lesions to DNA being formed and excised in an average rat cell per day.


Genome-wide SNP and population divergence of finless porpoises.
Single nucleotide polymorphisms (SNPs) are rapidly becoming the population genomic markers in addressing ecology, evolution, and conservation issues for their high capacity to access variability across the genome. We isolated a total of 140 ideal SNPs from the finless porpoise and used 78 (under Hardy-Weinberg equilibrium) of them to conduct those issues especially for addressing population genetic differentiation. Bayesian clustering and principal component analyses all suggested that finless porpoises in Chinese waters could be divided into three distinct genetic groupings. Low levels of within-population genetic variation (mean HE = 0.3405, standard deviation = 0.1188) and significant differentiation among populations (FST = 0.1050-0.1628, P < 0.01) were confirmed. Limited gene flow was found especially between the freshwater Yangtze River porpoise and the oceanic Yellow Sea and South China Sea populations, which strongly suggested that some barriers might have restricted their genetic exchange. These evidences not only support a recent subdivision of the finless porpoise into two species but also suggest a full species status for the Yangtze finless porpoise, especially considering the significant genetic divergence between freshwater and marine porpoises, in combination with the unique distribution of Yangtze finless porpoises in freshwater and their distinctness in physiological and morphological features.


Impact of dietary chitosan oligosaccharide and its effects on coccidia challenge in broiler chickens.
1. Two experiments were conducted, the first to determine the optimum inclusion of chitosan oligosaccharide (COS) in broiler diets to support growth performance, digestive functions, intestinal morphology, and immune organs. The second experiment evaluated the immune-protective properties of COS on broiler chickens during coccidia challenge (CC).2. Experiment 1 investigated the effect of graded dietary concentration of COS in the diets of broiler chickens using eight cage replicates for each of the six diets. A corn-soybean meal-based diet was used as the basal diet and supplemented with 0.0, 0.5, 1.0, 1.5, 2.0, or 2.5 g of COS/kg feed to form the six treatments.3. The diet supplemented with 1.0 g COS/kg of feed provided the optimal inclusion level for broiler chickens regarding body weight (BW) gain, jejunal villus height, villus height to crypt depth ratio, and ileal energy digestibility at d 22 of age.4. Experiment 2 investigated the immune-protective properties of COS in broiler chickens during CC. A total of 224 male broiler chicks were randomly assigned to eight replicate cages in a 2 × 2 factorial arrangement of treatments with two COS concentrations (0 or 1 g of COS/kg of diet), with or without CC.5. On d 18 of age, birds in the CC group received twice the recommended coccidia vaccine dose of 30 doses/kg BW.6. Coccidia challenge reduced (P < 0.05) and dietary COS increased (P < 0.05) BW gain, and feed intake. Dietary COS mitigated (P < 0.05) the CC-induced effects on gain:feed. Dietary COS supplementation attenuated the CC-induced effects (P < 0.05) on the expression of occludin genes.7. In conclusion, dietary COS improved performance, and the immune-related beneficial impact of COS supplementation was associated with reduced expression of pro-inflammatory cytokine genes.


Quality of life after coronary artery bypass graft & percutaneous transluminal coronary angioplasty: A follow up study from India.
Coronary artery bypass graft (CABG) and percutaneous transluminal coronary angioplasty (PTCA) are treatments of choice for coronary artery disease. Quality of life (QoL) is an important factor in determining optimum treatment. This study was aimed to compare changes in QoL, six months post procedure, between CABG and PTCA, and to understand the confounding effect of various contributing factors. Thirty stable angina patients each in CABG and PTCA groups, were followed up for six months. QoL was assessed with WHO-QoL-BREF. Depression was rated on the Hamilton Depression Rating Scale. Changes in QoL and depression within and between CABG and PTCA groups were compared. Multinomial logistic regression was used to measure the predictive strength of treatment type (CABG and PTCA) on QoL, controlling for significant confounders. Although scores of QoL and depression significantly changed over time in both the groups, time×group interaction did not reach to a significance. Significant confounding effects of diabetes (P<0.01), hypertension (P<0.05) and diet restriction (P<0.05) were found. Controlling for confounding effects of these factors, group distribution to PTCA, compared to CABG, significantly predicted greater improvements in QoL (P<0.01).


Evaluation of the effectiveness and compliance of intermittent preventive treatment (IPT) in the control of malaria in pregnant women in south eastern Nigeria.
Controlling malaria in pregnancy has been an important component of the millennium development goal and intermittent preventive treatment (IPT) is considered an important tool in controlling malaria among pregnant women. In this study, we evaluated the level of compliance to IPT use as well as its effect on malaria infection among pregnant women attending antenatal clinic in south eastern Nigeria. Peripheral blood smears and placental histology were used as diagnostic tools to determine infection rate. Our data show that compliance to IPT use was poor (33%) when compared with non-compliance (67%). Infection rate was significantly lower among IPT users (39%) than in non-users (71%) (X(2) = 39·95; P<0·05). Maternal anaemia was also lower in IPT users (4%) than in non-users (18%). Taken together, IPT use appears to be important in reducing infection rate and maternal anaemia. Therefore, its adoption is highly recommended and this could be improved through public enlightenment campaign and adequate funding.


Reducing inappropriate, anticholinergic and psychotropic drugs among older residents in assisted living facilities: study protocol for a randomized controlled trial.
Use of inappropriate drugs is common among institutionalized older people. Rigorous trials investigating the effect of the education of staff in institutionalized settings on the harm related to older people's drug treatment are still scarce. The aim of this trial is to investigate whether training professionals in assisted living facilities reduces the use of inappropriate drugs among residents and has an effect on residents' quality of life and use of health services. During years 2011 and 2012, a sample of residents in assisted living facilities in Helsinki (approximately 212) will be recruited, having offered to participate in a trial aiming to reduce their harmful drugs. Their wards will be randomized into two arms: one, those in which staff will be trained in two half-day sessions, including case studies to identify inappropriate, anticholinergic and psychotropic drugs among their residents, and two, a control group with usual care procedures and delayed training. The intervention wards will have an appointed nurse who will be responsible for taking care of the medication of the residents on her ward, and taking any problems to the consulting doctor, who will be responsible for the overall care of the patient. The trial will last for twelve months, the assessment time points will be zero, six and twelve months. The primary outcomes will be the proportion of persons using inappropriate, anticholinergic, or more than two psychotropic drugs, and the change in the mean number of inappropriate, anticholinergic and psychotropic drugs among residents. Secondary endpoints will be, for example, the change in the mean number of drugs, the proportion of residents having significant drug-drug interactions, residents' health-related quality of life (HRQOL) according to the 15D instrument, cognition according to verbal fluency and clock-drawing tests and the use and cost of health services, especially hospitalizations. To our knowledge, this is the first large-scale randomized trial exploring whether relatively light intervention, that is, staff training, will have an effect on reducing harmful drugs and improving QOL among institutionalized older people. ACTRN12611001078943.


Different Aspects of Head and Neck Squamous Cell Carcinoma: Cancer Stem Cells, their Niche and Targeted Therapy.
Head and Neck Squamous Cell Carcinoma (HNSCC) is categorized as the sixth most common cancer worldwide, with an incidence of more than 830,000 cases per year and a mortality rate of 50%. Tobacco use, alcohol consumption, and Human Papillomavirus infection are the prominent risks for HNSCC. Despite significant developments in the treatment of HNSCC, a high rate of recurrences makes the clinical situation worse and results in poor survival rates. Recent perspectives demonstrate that although epithelial transformation plays a crucial role in cancer development, tumor surrounding microenvironment takes part in the progression of cancer as well. Cancer Stem Cells (CSCs), which harbor unlimited self-renewal capacity, have a crucial role in the growth of HNSCC and this cell population is responsible for tumor recurrence unless eliminated by targeted therapy. CSCs are not only a promising target for tumor therapy but also a crucial biomarker to determine the patients at high risk for undetermined results and disease development, just as the bone marrow, which is the niche of hematopoietic and mesenchymal stem cells, is important for stem cell maintenance. Similarly, the concept of microenvironment is also important for the maintenance of CSCs. Apart from the cell-cell interactions, there are many parameters in the cancer microenvironment that affect the development of cancer, such as extracellular regulation, vascularization, microbial flora, pH, and oxygenation. The purpose of this review is to introduce HNSCC, explain the role of CSCs and their microenvironment, and refer to the conventional and novel targeted therapy for HNSCC and CSCs.


Fully automated fluorescence assay for determining total homocysteine in plasma.
Homocysteine exists in human plasma as various (mixed) disulfides. Most plasma homocysteine (about 70%) is protein bound, probably via a disulfide bond to albumin, whereas homocysteine-cysteine mixed disulfide is the predominating form in the free fraction. We here present a method for the determination of total homocysteine, which includes both fractions. Plasma was initially treated with sodium borohydride to reduce the disulfide bonds, and the liberated thiols were derivatized with monobromobimane. The derivatized sample, still containing the plasma proteins, was injected onto a strong cation-exchange column, from which the homocysteine derivative was directed by column switching into a cyclohexyl silica (CH) column. The homocysteine derivative was top-concentrated on the CH column, then rapidly eluted with a steep gradient of methanol. Both the derivatization procedure and chromatography were performed with a combined sample processor and sample injector from Gilson (Model 232-401). Within-run and between-run precision (CV) was less than 4%, and the detection limit of 0.2 pmol was sufficiently low for monitoring homocysteine in plasma. We verified the assay against two established manual methods for the determination of total homocysteine in plasma. This, the first fully automated assay for total plasma homocysteine, allows the unattended analysis of 70 samples per 24 h.


UBE2S activates NF-κB signaling by binding with IκBα and promotes metastasis of lung adenocarcinoma cells.
Nuclear factor (NF)-κB signaling in cancer cells has been reported to be involved in tumorigenesis. Phosphorylation and degradation of inhibitor of NF-κBα (IκBα) is a canonical pathway of NF-κB signaling. Here, we aimed to identify and characterize noncanonical activation of NF-κB signaling by ubiquitin-conjugating enzyme E2S (UBE2S) in lung adenocarcinoma cells. TCGA and the Human Atlas Protein Database were used to analyze the survival rate of lung adenocarcinoma patients in conjunction with UBE2S expression. In addition, PC9, H460, H441 and A549 lung adenocarcinoma cells were used in this study. PC9 and H460 cells were selected for further analysis because they expressed different UBE2S protein levels. Specific IKK inhibitors, PS1145 and SC514, were used to assess IκBα phosphorylation. Western blot analysis was used to assess protein levels in PC9 and H460 cells. A scratch wound-healing assay was used to analyze the migrative abilities of PC9 and H460 cells. Overexpression and knockdown of UBE2S in H460 and PC9 cells were used to analyze their effects on downstream protein levels. Immunoprecipitation, immunofluorescent staining, glutathione S transferase (GST) pull-down and in vitro binding assays were used to analyze the interaction between UBE2S and IκBα. A luciferase assay was used to analyze activation of NF-κB signaling regulated by UBE2S. An in vivo zebrafish xenograft model was used to assess metastasis of PC9 cells regulated by UBE2S. We found that UBE2S expression in lung adenocarcinoma patients was negatively related to survival rate. The protein level of UBE2S was higher in PC9 cells than in H460 cells, which was opposite to that observed for IκBα. PC9 cells showed a higher UBE2S expression and migrative ability than H460 cells. Phosphorylation of IκBα was not changed by treatment with the IKK-specific inhibitors PS1145 and SC514 in PC9 and H460 cells. Overexpression and knockdown of UBE2S in H460 and PC9 cells revealed that the protein levels of IκBα were inversely regulated. Immunoprecipitation, immunofluorescent staining, GST pull-down and in vitro binding assays revealed direct binding of UBE2S with IκBα. Nuclear P65 protein levels and luciferase assays showed that NF-κB signaling was regulated by UBE2S. The expression of epithelial-to-mesenchymal (EMT) markers and the migrative ability of lung adenocarcinoma cells were also regulated by UBE2S. A zebrafish xenograft tumor model showed a reduction in the metastasis of PC9 cells that was induced by UBE2S knockdown. Higher UBE2S expression in lung adenocarcinomas may lead to increased binding with IκBα to activate NF-κB signaling and promote adenocarcinoma cell metastasis. UBE2S may serve as a potential therapeutic target for lung adenocarcinomas.


Influence of genetic background on host resistance to experimental murine tularemia.
The host response to experimental murine tularemia was examined in different inbred mouse strains. The kinetics of growth of Francisella tularensis live vaccine strain (LVS) in the livers and spleens of A and C57BL/6 mice were monitored, and it was observed that mice of the A strain were more susceptible to the proliferation of LVS than were C57BL/6 mice. The difference was most marked 5 days following infection, when the number of bacteria isolated from the spleens of A mice was found to exceed that of C57BL/6 mice by 100-fold. In addition, the C57BL/6 strain exhibited a more pronounced splenomegaly 8 days after infection than did the A strain. When the response of other inbred strains was evaluated by determining the splenic count of LVS on day 5 postinfection, several levels of antiularemic resistance were observed. Mice of the AKR, BALB/cBy, C57BL/10, and SJL strains were found to be most resistant, while SM mice were most susceptible to the proliferation of LVS. The DBA/2, CBA, 129, C3H/HeJ, and A strains expressed a resistance phenotype which was intermediate between the two extremes, with A and C3H/HeJ mice being somewhat more susceptible than DBA/2, CBA, or 129 mice. The trait of resistance or susceptibility was analyzed genetically in (C57BL/6 x A)F1 hybrid mice and in F2 generation and recombinant inbred (RI) mouse strains derived from C57BL/6 (resistant) and A (susceptible) strain progenitors. The F1 progeny exhibited a level of resistance to infection which was similar to that of the resistant parent. In both the F2 generation mice and the RI strains, a continuous spectrum of resistance levels was observed. The results of these experiments indicate that the genetic background of the host influences host resistance to experimental murine tularemia and that multiple genetic loci are involved in this response.


Autoimmunity and B-cell dysfunction in chronic proliferative disorders of large granular lymphocytes/natural killer cells.
Clinical and laboratory findings of B-cell immune dysfunction were evaluated in ten patients with a large granular lymphocyte/natural killer cell proliferative disease (LGL/NK-PD). Increased immunoglobulin synthesis with autoantibody formation was documented: polyclonal hypergammaglobulinaemia (six patients), neutrophil autoantibody (one patient), antinuclear antibody (one patient), and rheumatoid factor (five patients). In addition, serum beta 2-microglobulin level was raised in seven patients, a benign monoclonal gammopathy was detected in one, and concurrent B-type hairy cell leukemia in another. Most patients experienced the complications of hemocytopenia, polyarthritis or rheumatoid arthritis, and immediate allergic reactions to drugs or environmental substances, rather than from symptoms of progressive LGL/NK-PD. A review of the literature confirms that an increased immunoglobulin production is common in LGL/NK-PD, and that patients are likely to develop multiple autoantibodies. The incapacity of proliferating, abnormal LGL/NK cells to suppress B-cell activation and immunoglobulin synthesis, documented by several in vitro studies, offers a pathogenetic explanation for these phenomena. This study shows that an anomalous B-cell function contributes greatly to the morbidity of disease in LGL/NK-PD, and points out the utility of investigating the LGL/NK cell system in patients with autoimmune pathologic characteristics of unclear origin.


Predicting non-organ-confined prostate cancer in men diagnosed after 2000.
The objective of this study was to preoperatively predict non-organ-confined disease in patients considering radical prostatectomy. To account for the stage migration seen in prostate cancer, we included only those patients who underwent prostatectomy after the year 2000. Information on a cohort of 1895 patients who underwent radical prostatectomy from 2000 to 2008 was retrieved from the Duke Prostate Center database. Race (African American, non-African American), body mass index, age at surgery, PSA, biopsy Gleason sum (<7, 7 and >7) and clinical tumor stage (cT1, cT2/3) were analyzed by univariate analysis followed by logistic regression analysis. The Duke Interactive Clinical Equation for staging (DICE-S score) was calculated from the logistic regression model. The model was then internally validated using a bootstrapping technique. Biopsy Gleason sums 7 and >7 were more likely to have non-organ-confined disease compared with <7 (OR=2.97, Gleason sum=7; OR=3.25, Gleason sum>7). Clinical tumor stage, cT2/3, predicted non-organ-confined disease (OR=1.58). Older age was associated with non-organ-confined disease (OR=1.02), as was greater PSA (OR=1.12). DICE-S equation x=ln (p/1-p)=-3.627+0.019 (age)+0.109 (PSA)+1.087 (bGleason=7)+1.180 (bGleason >7)+0.459 (clinical T stage >T1), where p=(e(x))/(1+e(x)). A concordance index (prediction accuracy) of 0.73 was reached on internal validation. Using the DICE-S score, age, PSA, biopsy Gleason sum and clinical tumor stage, we can predict non-organ-confined disease in radical prostatectomy at an acceptable accuracy. Preoperative information on disease stage may aid in treatment decisions and surgical approach.


Efficient expansion of mesenchymal stromal cells from umbilical cord under low serum conditions.
Mesenchymal stromal cells (MSC) are of clinical interest for their potential use in regenerative medicine and immunotherapy. Originally derived from bone marrow (BM), MSC have now been isolated from most tissues, including umbilical cord (UC) and UC blood (UCB). If MSC from UC are biologically equivalent to those from BM, they would be attractive as a readily available and non-invasive source for cellular therapies. Sections of UC were separated into vascular and Wharton's jelly (WJ) fractions, which were then digested individually to release MSC that were isolated by plastic adherence in a 10% fetal calf serum (FCS) medium, or a low serum medium designed for multipotent adult progenitor cells (MAPC). The resulting perivascular (PV) and WJ MSC lines were assayed for expression of characteristic markers and differentiation and immunosuppressive properties. MSC lines were readily derived from most UC tested. Cells grown in MAPC medium (MM) tended to be smaller and more elongated and expressed more nestin, but did not differ substantially in their growth rate, expression of other markers and differentiation capacity. All UC lines tested were adipogenic but poorly osteogenic, and were equivalent in their ability to suppress T-cell proliferation induced by phytohemagglutinin (PHA), activation beads and allostimulation. UC is a convenient, efficient source of MSC that can be expanded under low serum conditions for application on future studies of tissue regeneration and immunosuppression.


Umbilical cord antiseptics for preventing sepsis and death among newborns.
The umbilical cord is a structure made of blood vessels and connective tissue that connects the baby and placenta in utero. The umbilical cord is cut after birth, which separates the mother and her baby both physically and symbolically. Omphalitis is defined as infection of the umbilical cord stump. Tracking of bacteria along the umbilical vessels may lead to septicaemia that can result in neonatal morbidity and mortality, especially in developing countries. To determine the effect of application of antimicrobials on newborn's umbilical cord versus routine care for prevention of morbidity and mortality in hospital and community settings. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (1 October 2012). In addition, we also searched LILACS (1982 to 11 October 2012) and HERDIN NeON (October 2012) We included randomized, cluster-randomized and quasi-randomized controlled trials of topical cord care compared with no topical care, and comparisons between different forms of care. Two review authors independently assessed trials for inclusion, trial quality and subsequently extracted data. Data were checked for accuracy. The search identified 77 trials. We included 34 trials in the review involving 69,338 babies, five studies are awaiting classification and there are two ongoing community trials. Included studies were conducted in both developed and developing countries. Among the 34 included trials, three were large, cluster-randomized trials conducted in community settings in developing countries and 31 studies were conducted in hospital settings mostly in developed countries. Data for community and hospital studies were analyzed separately. The three trials conducted in community settings contributed 78% of the total number of children included in this review. Of the trials conducted in hospital settings, the majority had small sample sizes. There were 22 different interventions studied across the included trials and the most commonly studied antiseptics were 70% alcohol, triple dye and chlorhexidine.Only one antiseptic, chlorhexidine was studied in community settings for umbilical cord care. Three community trials reported data on all-cause mortality that comprised 1325 deaths in 54,624 participants and combined results showed a reduction of 23% (average risk ratio (RR) 0.77, 95% confidence interval (CI) 0.63 to 0.94, random-effects, T² = 0.02, I² = 50%) in the chlorhexidine group compared with control. The reduction in omphalitis ranged from 27% to 56% depending on the severity of infection. Cord separation time was increased by 1.7 days in the chlorhexidine group compared with dry cord care (mean difference (MD) 1.75 days, 95% CI 0.44 to 3.05, random-effects, T² = 0.88, I² = 100%). Washing of umbilical cord with soap and water was not advantageous compared with dry cord care in community settings.Among studies conducted in hospital settings, no study reported data for mortality or tetanus. No antiseptic was advantageous to reduce the incidence of omphalitis compared with dry cord care in hospital settings. Topical triple dye application reduced bacterial colonization with Staphylococcus aureus compared with dry cord care (average RR 0.15, 95% CI 0.10 to 0.22, four studies, n = 1319, random-effects, T² = 0.04, I² = 24%) or alcohol application (average RR 0.45, 95% CI 0.25 to 0.80, two studies, n = 487, random-effects, T² = 0.00, I² = 0%). There was no advantage of application of alcohol and triple dye for reduction of colonization with streptococcus. Topical alcohol application was advantageous in reduction of colonization with Enterococcus coli compared with dry cord care (average RR 0.73, 95% CI 0.58 to 0.92, two studies, n = 432, random-effects, T² = 0.00, I² = 0%) and in a separate analysis, triple dye increased the risk of colonization compared with alcohol (RR 3.44, 95% CI 2.10 to 5.64, one study, n = 373). Cord separation time was significantly increased with topical application of alcohol (MD 1.76 days, 95% CI 0.03 to 3.48, nine studies, n = 2921, random-effects, T² = 6.54, I² = 97%) and triple dye (MD 4.10 days, 95% CI 3.07 to 5.13, one study, n = 372) compared with dry cord care in hospital settings. The number of studies was insufficient to make any inference about the efficacy of other antiseptics. There is significant evidence to suggest that topical application of chlorhexidine to umbilical cord reduces neonatal mortality and omphalitis in community and primary care settings in developing countries. It may increase cord separation time however, there is no evidence that it increases risk of subsequent morbidity or infection.There is insufficient evidence to support the application of an antiseptic to umbilical cord in hospital settings compared with dry cord care in developed countries.


[Ultrasound tomography of the liver and its diseases].
The systematical ultrasound investigation of the liver includes parallel sections series as well as vessel oriented sonography. The border between the right and left liver lobe runs through the middle liver vein, through portal and bile duct branchings respectively, and through the gallbladder in a sagittal direction. Liver ultrasound tomography allows differentiation of diseased liver from normal findings as well as subcategorizing into diffuse, focal, vascular, and biliary diseases. The sensitivity for fatty liver and cirrhosis ranges about 80%. The differential diagnosis of different liver diseases by ultrasound tomography will only allow suspected diagnosis. A certain differentiation between benign and malign alteration is only achieved by histological or cytological methods alone. In comparison to other indirect non invasive diagnostical procedures like computerized tomography, scintigraphy and nuclear spin tomography ultrasound tomography appears to be of primary importance.


Measurement of masseter and temporalis muscle thickness using ultrasonographic technique.
Ultrasonography was found to be a highly reliable and accurate method for imaging and measuring masticatory muscle thickness. No age and sex related variations were observed in this study on comparisons between the two groups. Similarly no changes were seen in the muscle thickness and different facial morphologies. Since no earlier studies on this type of investigation was done, it will be too premature to give a final verdict on the correlation between the masticatory muscle thickness and facial morphology for all the recorded cases. A long term follow up will provide a wealth of information for future clinical purposes. No age and sex related variations were observed in this study on comparisons between the two groups. Similarly no changes were seen in the muscle thickness and different facial morphologies.


Structural and biochemical analysis of a unique phosphatase from Bdellovibrio bacteriovorus reveals its structural and functional relationship with the protein tyrosine phosphatase class of phytase.
Bdellovibrio bacteriovorus is an unusual δ-proteobacterium that invades and preys on other Gram-negative bacteria and is of potential interest as a whole cell therapeutic against pathogens of man, animals and crops. PTPs (protein tyrosine phosphatases) are an important class of enzyme involved in desphosphorylating a variety of substrates, often with implications in cell signaling. The B. bacteriovorus open reading frame Bd1204 is predicted to encode a PTP of unknown function. Bd1204 is both structurally and mechanistically related to the PTP-like phytase (PTPLP) class of enzymes and possesses a number of unique properties not observed in any other PTPLPs characterized to date. Bd1204 does not display catalytic activity against some common protein tyrosine phosphatase substrates but is highly specific for hydrolysis of phosphomonoester bonds of inositol hexakisphosphate. The structure reveals that Bd1204 has the smallest and least electropositive active site of all characterized PTPLPs to date yet possesses a unique substrate specificity characterized by a strict preference for inositol hexakisphosphate. These two active site features are believed to be the most significant contributors to the specificity of phytate degrading enzymes. We speculate that Bd1204 may be involved in phosphate acquisition outside of prey.


Protein folding assisted by the GroEL/GroES chaperonin system.
The chaperonin system GroEL/GroES assists in the folding of proteins in the bacterial cytosol. Recent applications of biophysical techniques for the structural analysis of GroEL, GroES, and chaperonin-bound protein folding intermediates have provided the basis for understanding the molecular mechanism of GroEL/GroES action. GroEL, a double-ring complex, binds unfolded proteins at its inner ring surface. Protein folding proceeds in the central cavity of GroEL, after dissociation of the polypeptide has been triggered by ATP hydrolysis in GroEL. Premature release of unfolded protein into external solution is prevented by binding of the cofactor GroES on top of the GroEL cylinder, resulting in an enclosed cage. Upon ATP-dependent dissociation of GroES, substrate protein is eventually released from GroEL in a native or native-like conformation. While current in vitro results about the structure, function, and molecular mechanism of GroEL/GroES-assisted protein folding have led to a quite detailed picture of this complex process, the extent to which the GroEL/GroES system actually participates in the folding of newly-synthesized proteins in the cell is less defined and remains a subject for further studies. Ingenious biochemical and genetic approaches will be necessary to show whether our current view of chaperonin action indeed accurately reflects its modus operandi inside a living cell.


The electronic structure of CdSe/CdS core/shell seeded nanorods: type-I or quasi-type-II?
The electronic structure of CdSe/CdS core/shell seeded nanorods of experimentally relevant size is studied using a combination of molecular dynamics and semiempirical pseudopotential techniques with the aim to address the transition from type-I to a quasi-type-II band alignment. The hole is found to be localized in the core region regardless of its size. The overlap of the electron density with the core region depends markedly on the size of the CdSe core. For small cores, we observe little overlap, consistent with type-II behavior. For large cores, significant core-overlap of a number of excitonic states can lead to type-I behavior. When electron-hole interactions are taken into account, the core-overlap is further increased. Our calculations indicate that the observed transition from type-II to type-I is largely due to simple volume effects and not to band alignment.


Choosing continence aids.
Caring for people with continence problems is challenging, rewarding and every nurse's concern. This article will discuss the choice and use of continence-related aids. Future articles will examine aids for containing incontinence, their place in high quality continence care, and the importance of value for money.


ABCB1 genetic variation influences the toxicity and clinical outcome of patients with androgen-independent prostate cancer treated with docetaxel.
Polymorphisms that are associated with ABCB1 expression and function may be linked to treatment efficacy and the development of neutropenia and neurotoxicity in patients with androgen-independent prostate cancer receiving docetaxel. Patients with androgen-independent prostate cancer treated with docetaxel alone (n = 23) or docetaxel and thalidomide (n = 50) were genotyped for the ABCB1 1236C>T, 2677 G>T/A, and 3435 C>T alleles by direct sequencing, and diplotypes were constructed using an EM algorithm. The data were then compared with duration to onset of peripheral neuropathy, neutropenia grade, and survival after docetaxel. For patients receiving docetaxel alone, individuals carrying a diplotype consisting of the 1236C-2677G-3435C linked alleles had improved overall survival after treatment (P = 0.0017). Additionally, patients treated with docetaxel and thalidomide carrying a diplotype consisting of the 2677T-3435T haplotype had a shorter median survival (P = 0.045). After adjusting for a particular set of polymorphisms and diplotype groupings, a hazard ratio of 10.87 was found for patients carrying the 2677GG genotype versus patients carrying other genotypes (P = 0.0048) in the docetaxel and thalidomide cohort. Among both treatment arms together, individuals carrying the 2677GG genotype also had a significantly longer time to neuropathy (P = 0.035). Finally, there was a strong trend toward patients carrying the 2677TT-3435TT diplotype having higher grades of neutropenia (P = 0.053). The data suggest that docetaxel-induced neuropathy, neutropenia grade, and overall survival could be linked to ABCB1 allelic variants with ensuing negative implications for docetaxel treatment in patients carrying ABCB1 variant genotypes.