Pili on meningococci from primary cultures of nasopharyngeal carriers and cerebrospinal fluid of patients with acute disease.
The nasopharynx of known meningococcal carriers without signs of acute meningococcal disease as well as cerebrospinal fluid from patients with acute meningococcal disease were cultured on Thayer-Martin agar. Pili were observed in negatively stained preparations of over 80% cells from all primary cultures of both nasopharnyx and cerebrospinal fluids. Although pili were abundant on cells from all primary cultures, all pili were lost on serial subculture in the laboratory. This loss of pili from the cell surface on laboratory subculture was not accompanied by a concomitant loss of cell wall blebs.


Sucrose as an analgesic for newborn infants.
The effectiveness of sucrose as an analgesic agent for newborn infants was assessed during two standard painful hospital procedures: blood collection via heel lance and circumcision. Infants who drank 2 mL of a 12% sucrose solution prior to blood collection cried 50% less during the blood collection procedure than did control infants who had received 2 mL of sterile water. Crying of infants who ingested sucrose returned to baseline levels within 30 to 60 seconds after blood collection whereas control infants required 2.5 to 3.0 minutes to return to baseline. Like findings were obtained for infants who received sucrose on a pacifier prior to and during circumcision. Specifically, control infants who underwent a standard circumcision procedure without intervention cried 67% of the time. A water-moistened pacifier reduced crying to 49% (P less than .01). Crying was reduced further to 31% (P less than .05) by providing infants with a sucrose-flavored pacifier to suck. These findings, which parallel results obtained in studies of pain in infant rats, provide a potent yet simple, benign intervention to help alleviate stress and pain routinely experienced by human infants.


Use of ultrasound by registered nurses-a systematic literature review.
In Western Australia (WA), most stable patients undergoing haemodialysis receive treatment in a satellite setting where no doctors are on-site during treatment hours, so nurses must make critical decisions about fluid removal. Some patients regularly experience adverse events during dialysis (intradialytic), often due to excessive ultrafiltration goals, with intradialytic hypotension being particularly challenging. Ultrasound of the inferior vena cava has been previously demonstrated being a rapid and non-invasive method for volume assessment on haemodialysis patients, thus could hold valuable information for the treating nurse. This paper examines the existing literature in regards to the use of ultrasound measurements of the inferior vena cava in patients on haemodialysis for objective assessment of their intravascular volume status by renal nurses. A systematic literature review was performed within medical and nursing databases including CINAHL Plus with Full Text, SCOPUS, Web of Science and MEDLINE. Renal nurses are conscious of the significance of intradialytic hypotension and have only limited options for its prevention. Ultrasound of the inferior vena cava could add another objective dimension for intravascular volume assessment and prevention of intradialytic hypotension, but to date renal nurses have not been using this technique. Ultrasound of the inferior vena cava has the potential to assist in defining the ultrafiltration goal for that particular dialysis session, thus reducing the risk of intradialytic hypotension. Additionally, it has potential to change current renal nursing practice when added to clinical nursing assessment methods. Further studies are required to validate this assessment tool carried out by a renal nurse compared with a skilled ultrasonographer.


A family of related ATP-binding subunits coupled to many distinct biological processes in bacteria.
Many biological processes are coupled to ATP hydrolysis. We describe here a class of closely related ATP-binding proteins, from several bacterial species, which are associated with a variety of cellular functions including membrane transport, cell division, nodulation in Rhizobium and haemolysin export. These proteins comprise a family of structurally and functionally related subunits which share a common evolutionary origin, bind ATP and probably serve to couple ATP hydrolysis to each of these biological processes. This finding suggests a specific role for ATP in cell division, nodulation during nitrogen fixation and protein export, and allows us to assign a probable function to one of the protein components from each of these systems.


A consideration for the utility of the post-operative Oswestry Disability Index for measuring outcomes after sacroiliac joint fusion.
Sacroiliac joint (SIJ) dysfunction and its surgical treatment remain a controversial topic in spine surgery. Determining success after SIJ fusion may be difficult due to preexisting back pain, lumbar fusion (LF), and functional disability. We examine the utility of Oswestry Disability Index (ODI) as a measure of clinical outcomes after minimally invasive SIJ fusion. A retrospective review of 24 patients with at least 12- months follow-up. Patients were divided into two groups based on presence of previous LF. Their post-operative ODI was compared with overall satisfaction, pain reduction, and return to work status. No difference in demographics was found in patients with and without prior LF with 92% of patients reporting lower post-operative pain and 96% being satisfied. Presence of LF did not show any statistically significant differences in pain or satisfaction. However, patient with prior LF reported lower ODI than those without LF at 1-year post-operatively (P=0.015). Postoperative ODI may give a falsely pessimistic impression of outcomes in SIJ fusion patients with prior LF, and its use and limitations should be carefully considered in future studies.


Management of Acute Gastroenteritis in Children: A Survey among Members of the Korean Society of Pediatric Gastroenterology, Hepatology, and Nutrition.
No national survey has yet described the guidelines followed by Korean pediatricians to treat acute gastroenteritis (AGE). An online survey was performed to investigate the management of AGE followed by members of The Korean Society of Pediatric Gastroenterology, Hepatology, and Nutrition, and the results were compared between pediatric gastroenterologists (PG) and general pediatricians (GP). Questionnaires were sent to pediatricians between June 2 and 4, 2018 regarding the type of hospital, indications for admission, antiemetic and antidiarrheal drugs and antibiotics prescribed, and dietary changes advised. Among the 400 pediatricians approached, 141 pediatricians (35.3%) responded to the survey. PG comprised 39% of the respondents and 72.7% worked at a tertiary hospital. Both PG and GP considered diarrhea or vomiting to be the primary symptom. The most common indication for hospitalization was severe dehydration (98.8%). Most pediatricians managed dehydration with intravenous fluid infusions (PG 98.2%, GP 92.9%). Antiemetics were prescribed by 87.3% of PG and 96.6% of GP. Probiotics to manage diarrhea were prescribed by 89.1% of PG and 100.0% of GP. Antibiotics were used in children with blood in diarrheal stool or high fever. Dietary changes were more commonly recommended by GP (59.3%) than by PG (27.3%) (p<0.05). Tests to identify etiological agents were performed primarily in hospitalized children. This survey assessing the management of pediatric AGE showed that the indications for admission and rehydration were similar between GP and PG. Drug prescriptions for diarrhea and dietary changes were slightly commonly recommended by GP than by PG.


Different familial association patterns of autoimmune diseases between juvenile-onset systemic lupus erythematosus and juvenile rheumatoid arthritis.
The aim of this study was to determine if the prevalence of autoimmune disorders in the relatives of patients with systemic lupus erythematosus (SLE) is greater than that of relatives of patients with juvenile rheumatoid arthritis (JRA). Interviews were used to obtain histories of the following autoimmune disorders among living or deceased first-, second-, and third-degree relatives of 91 SLE and 110 JRA families: ankylosing spondylitis, SLE, rheumatoid arthritis (RA), JRA, multiple sclerosis, juvenile dermatomyositis, Sjögren's syndrome, myasthenia gravis, psoriasis, and thyroid diseases. There were statistically significant differences between the SLE and JRA probands in mean age and gender ratio (19.1 +/- 4.8 vs 14.0 +/- 5.5 years; M (male)/F (female): 17/74 vs 62/48, p<0.005). The prevalence rate of autoimmune diseases in relatives of SLE families (20.9%) was greater than in JRA families (11.8%), but not statistically significantly so. The mean age (18.0 +/- 5.3 vs 14.0 +/- 4.3 years), mean age at diagnosis (13.4 +/- 4.3 vs 7.9 +/- 3.9 years) and gender ratio (F/M, 16/3 vs 5/8) of the patients with affected relatives between these 2 groups all had statistically significant differences. A higher prevalence of SLE in relatives was found in SLE families than in JRA cases. Furthermore, this study revealed a higher incidence of autoimmune disorders among second- and third-degree relatives of SLE or JRA probands versus first-degree ones, especially sisters (including 1 pair of twins) and the maternal aunt in SLE families. These data demonstrate that the prevalence of autoimmune disorders in the relatives of patients with SLE is greater than those of relatives of patients with JRA. This suggests that clinically different autoimmune phenotypes may share common susceptibility genes, which may act as risk factors for autoimmunity.


Isolation of distinct progenitor stem cell populations from dental pulp.
The present study compared the cellular characteristics of progenitor stem cell populations present in adult dental pulp, isolated by different methods utilizing 2 different features of stem cell biology. One population expressing high levels of beta1 integrin was isolated by preferential selection of adherent cells to fibronectin over 20 min. In an alternative approach, cells expressing the embryonic neural crest cell marker, low-affinity nerve growth factor receptor (LANGFR), were selected by magnetic-activated cell sorting. For each method, clonal cell lines were established and expanded in culture. One clone derived via the respective methods was examined for embryonic/progenitor cell markers by immunocytochemistry and RT-PCR. Both clonal populations demonstrated the expression of stro-1 and stained positive for vimentin, demonstrating mesenchymal lineage. Of note, cells selected for LANGFR cells demonstrated the additional expression of CD105 and Notch 2. For both clonal populations, expanded cultures demonstrated the ability to differentiate into osteoblasts, adipocytes and chondrocytes. These results would suggest the potential isolation of 2 progenitor cell populations exhibiting different cellular characteristics in terms of their embryonic nature. The potential for both cell populations to derive from a common origin is discussed.


Cellular mechanisms by which lipoic acid confers protection during the early stages of cerebral ischemia: a possible role for calcium.
Lipoic acid (LA) is a naturally occurring compound and dietary supplement with powerful antioxidant properties. Although LA is neuroprotective in models of stroke, little is known about the cellular mechanisms by which it confers protection during the early stages of ischemia. Here, using a rat model of permanent middle cerebral artery occlusion (MCAO), we demonstrated that administration of LA 30 min prior to stroke, reduces infarct volume in a dose dependent manner. Whole-cell patch clamp techniques in rat brain slices were used to determine if LA causes any electrophysiological alterations in either healthy neurons or neurons exposed to oxygen and glucose deprivation (OGD). In healthy neurons, LA (0.005 mg/ml and 0.05 mg/ml) did not significantly change resting membrane potential, threshold or frequency of action potentials or synaptic transmission, as determined by amplitude of excitatory post synaptic currents (EPSCs). Similarly, in neurons exposed to OGD, LA did not alter the time course to loss of EPSCs. However, there was a significant delay the onset of anoxic depolarization as well as in the time course of the depolarization. Next, intracellular calcium (Ca(2+)) levels were monitored in isolated neurons using fura-2. Pretreatment with 0.005 mg/ml and 0.05 mg/ml LA for 30 min and 6 h did not significantly alter resting Ca(2+) levels or Ca(2+) response to glutamate (250 μM). However, pretreatment with 0.5 mg/ml LA for 6 h significantly increased resting Ca(2+) levels and significantly decreased the Ca(2+) response to glutamate. In summary, these findings suggest that LA does not affect neuronal physiology under normal conditions, but can protect cells from an ischemic event.


Indications for Use of Damage Control Surgery in Civilian Trauma Patients: A Content Analysis and Expert Appropriateness Rating Study.
To characterize and evaluate indications for use of damage control (DC) surgery in civilian trauma patients. Although DC surgery may improve survival in select, severely injured patients, the procedure is associated with significant morbidity, suggesting that it should be used only when appropriately indicated. Two investigators used an abbreviated grounded theory method to synthesize indications for DC surgery reported in peer-reviewed articles between 1983 and 2014 into a reduced number of named, content-characteristic codes representing unique indications. An international panel of trauma surgery experts (n = 9) then rated the appropriateness (expected benefit-to-harm ratio) of the coded indications for use in surgical practice. The 1107 indications identified in the literature were synthesized into 123 unique pre- (n = 36) and intraoperative (n = 87) indications. The panel assessed 101 (82.1%) of these indications to be appropriate. The indications most commonly reported and assessed to be appropriate included pre- and intraoperative hypothermia (median temperature <34°C), acidosis (median pH <7.2), and/or coagulopathy. Others included 5 different injury patterns, inability to control bleeding by conventional methods, administration of a large volume of packed red blood cells (median >10 units), inability to close the abdominal wall without tension, development of abdominal compartment syndrome during attempted abdominal wall closure, and need to reassess extent of bowel viability. This study identified a comprehensive list of candidate indications for use of DC surgery. These indications provide a practical foundation to guide surgical practice while studies are conducted to evaluate their impact on patient care and outcomes.


Maternal antibodies from mothers of children with autism alter brain growth and social behavior development in the rhesus monkey.
Antibodies directed against fetal brain proteins of 37 and 73 kDa molecular weight are found in approximately 12% of mothers who have children with autism spectrum disorder (ASD), but not in mothers of typically developing children. This finding has raised the possibility that these immunoglobulin G (IgG) class antibodies cross the placenta during pregnancy and impact brain development, leading to one form of ASD. We evaluated the pathogenic potential of these antibodies by using a nonhuman primate model. IgG was isolated from mothers of children with ASD (IgG-ASD) and of typically developing children (IgG-CON). The purified IgG was administered to two groups of female rhesus monkeys (IgG-ASD; n=8 and IgG-CON; n=8) during the first and second trimesters of pregnancy. Another control group of pregnant monkeys (n=8) was untreated. Brain and behavioral development of the offspring were assessed for 2 years. Behavioral differences were first detected when the macaque mothers responded to their IgG-ASD offspring with heightened protectiveness during early development. As they matured, IgG-ASD offspring consistently deviated from species-typical social norms by more frequently approaching familiar peers. The increased approach was not reciprocated and did not lead to sustained social interactions. Even more striking, IgG-ASD offspring displayed inappropriate approach behavior to unfamiliar peers, clearly deviating from normal macaque social behavior. Longitudinal magnetic resonance imaging analyses revealed that male IgG-ASD offspring had enlarged brain volume compared with controls. White matter volume increases appeared to be driving the brain differences in the IgG-ASD offspring and these differences were most pronounced in the frontal lobes.


Enhanced sensitivity to the HER1/epidermal growth factor receptor tyrosine kinase inhibitor erlotinib hydrochloride in chemotherapy-resistant tumor cell lines.
Erlotinib (Tarceva, OSI-774) is a potent and specific inhibitor of the HER1/epidermal growth factor receptor (EGFR) tyrosine kinase. In phase II clinical studies, oral erlotinib monotherapy has shown antitumor activity in patients with advanced non-small cell lung cancer, head and neck cancer, and ovarian cancer after the failure of standard chemotherapy. We hypothesized that some tumors treated with multiple cytotoxic therapies may become more dependent on the HER1/EGFR signaling pathways for survival. The growth-inhibitory effect of erlotinib was tested on 10 pairs of chemosensitive, parental, and chemoresistant tumor cell lines. Enhanced sensitivity to erlotinib was observed in the doxorubicin-resistant human breast cancer cell line MCF-7, paclitaxel-resistant human ovarian carcinoma cell line A2780, and cisplatin-resistant human cervical carcinoma cell line ME180. The IC(50) values of erlotinib in the resistant cell lines were 2- to 20-fold lower than those in the corresponding parental cell lines. This enhanced sensitivity to erlotinib correlated with higher HER1/EGFR and phospho-HER1/EGFR expression when compared with the corresponding parental cell lines. Acquired resistance to cytotoxic agents was not associated with cross-resistance to erlotinib. AE-ME180/CDDP-resistant xenografts showed greater sensitivity to erlotinib than parental ME180 xenografts did. Our findings suggest that acquired resistance to cytotoxic therapy in some tumors is associated with enhanced sensitivity to HER1/EGFR inhibitors, which correlates with increased HER1/EGFR expression. These data may explain some of the observed clinical activity of HER1/EGFR inhibitors in patients previously treated with multiple therapies. HER1/EGFR tyrosine kinase inhibitors may be more effective as second- or third-line treatment for certain patients with tumors that were previously treated with multiple chemotherapy regimens.


Generalised dissipative particle dynamics with energy conservation: density- and temperature-dependent potentials.
We present a generalised, energy-conserving dissipative particle dynamics (DPDE) method appropriate for the non-isothermal simulation of particle interaction force fields that are both density- and temperature-dependent. A detailed derivation is formulated in a bottom-up manner by considering the thermodynamics of small systems with the appropriate consideration of the fluctuations. Connected to the local volume is a local density and corresponding local pressure, which is determined from an equation-of-state based force field that depends also on a particle temperature. Compared to the original DPDE method, the formulation of the generalised DPDE method requires a change in the independent variable from the particle internal energy to the particle entropy. As part of the re-formulation, the terms dressed particle entropy and the corresponding dressed particle temperature are introduced, which depict the many-body contributions in the local volume. The generalised DPDE method has similarities to the energy form of the smoothed dissipative particle dynamics method, yet fundamental differences exist, which are described in the manuscript. The basic dynamic equations are presented along with practical considerations for implementing the generalised DPDE method, including a numerical integration scheme based on the Shardlow-like splitting algorithm. Demonstrations and validation tests are performed using analytical equation-of-states for the van der Waals and Lennard-Jones fluids. Particle probability distributions are analysed, where excellent agreement with theoretical estimates is demonstrated. As further validation of the generalised DPDE method, both equilibrium and non-equilibrium simulation scenarios are considered, including adiabatic flash heating response and vapour-liquid phase separation.


Native rat hippocampal 5-HT1A receptors show constitutive activity.
Previous studies have shown that human 5-hydroxytryptamine (5-HT)1A receptors stably expressed in transfected cell lines show constitutive G-protein activity, as revealed by the inhibitory effect of inverse agonists, such as spiperone, on basal guanosine-5'-O-(3-[35S]thio)-triphosphate ([35S]GTPgammaS) binding. In the present study, we evaluated the constitutive activity of native rat 5-HT1A receptors in hippocampal membranes. Using anti-Galphao-antibody capture coupled to scintillation proximity assay under low sodium (30 mM) conditions, we observed high basal [35S]GTPgammaS binding to Galphao subunits (defined as 100%). Under these conditions, 5-HT and the prototypic selective 5-HT1A agonist (+)8-hydroxy-2-(di-n-propylamino)tetralin [(+)-8-OH-DPAT] both stimulated [35S]GTPgammaS binding to Galphao to a similar extent, raising binding to approximately 130% of basal with pEC50 values of 7.91 and 7.87, respectively. The 5-HT1A-selective neutral antagonist [O-methyl-3H]-N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide trihydrochloride (WAY100,635) could block these effects in a competitive manner with pKb values (5-HT, 9.57; (+)-8-OH-DPAT, 9.52) that are consistent with its pKi value at r5-HT1A receptors (9.33). In this native receptor system, spiperone and methiothepin reduced basal [35S]GTPgammaS binding to Galphao in a concentration-dependent manner to 90% of basal with pIC50 values of 7.37 and 7.98, respectively. The inhibition of basal [35S]GTPgammaS binding induced by maximally effective concentrations of spiperone (10 microM) or methiothepin (1 microM) was antagonized by WAY100,635 in a concentration-dependent manner (pKb, 9.52 and 8.87, respectively), thus indicating that this inverse agonism was mediated by 5-HT1A receptors. These data provide the first demonstration that native rat serotonin 5-HT1A receptors can exhibit constitutive activity in vitro.


Characterization of rickettsial attachment to host cells by flow cytometry.
The mechanisms of rickettsial attachment have been studied by measuring quantitative changes in rickettsial binding to host cells by flow cytometry after different treatments of the rickettsiae and host cells. Time-dependent binding of Rickettsia conorii to host cells was demonstrated by the increasing intensity of host cell surface fluorescence of rickettsia-host cell combinations when examined with a rickettsia-specific monoclonal antibody. More than 70% of host cells had intensity of fluorescence above the threshold value after 10 min of incubation, owing to rickettsiae bound to the cell surface, and the greatest fluorescence intensity indicative of binding occurred at 20 min. The binding kinetics was rickettsial dose dependent. The binding of rickettsiae to host cells was greatly decreased when host cells or rickettsiae were treated with 1% paraformaldehyde for 30 min or 0.25% trypsin for 5 or 15 min, respectively. Rickettsiae that were heated at 56 degrees C for 15 min lost more than 80% of their ability to attach to host cells. R. rickettsii, an organism closely related to R. conorii, competitively inhibited the attachment of R. conorii (51% inhibition when mixed in equal numbers). These results indicate that the rickettsial binding structures are trypsin and heat sensitive and likely to be surface proteins.


Lgr5 homologues associate with Wnt receptors and mediate R-spondin signalling.
The adult stem cell marker Lgr5 and its relative Lgr4 are often co-expressed in Wnt-driven proliferative compartments. We find that conditional deletion of both genes in the mouse gut impairs Wnt target gene expression and results in the rapid demise of intestinal crypts, thus phenocopying Wnt pathway inhibition. Mass spectrometry demonstrates that Lgr4 and Lgr5 associate with the Frizzled/Lrp Wnt receptor complex. Each of the four R-spondins, secreted Wnt pathway agonists, can bind to Lgr4, -5 and -6. In HEK293 cells, RSPO1 enhances canonical WNT signals initiated by WNT3A. Removal of LGR4 does not affect WNT3A signalling, but abrogates the RSPO1-mediated signal enhancement, a phenomenon rescued by re-expression of LGR4, -5 or -6. Genetic deletion of Lgr4/5 in mouse intestinal crypt cultures phenocopies withdrawal of Rspo1 and can be rescued by Wnt pathway activation. Lgr5 homologues are facultative Wnt receptor components that mediate Wnt signal enhancement by soluble R-spondin proteins. These results will guide future studies towards the application of R-spondins for regenerative purposes of tissues expressing Lgr5 homologues.


Vitamin B status in patients with type 2 diabetes mellitus with and without incipient nephropathy.
To investigate the vitamin B status, with particular focus on vitamin B6, in adults with and without incipient nephropathy secondary to type 2 diabetes mellitus. Plasma and/or urine concentrations of vitamins B₆, B₁, B₁₂, related vitamers and biomarkers (including total homocysteine, methylmalonic acid) were measured in 120 adults with type 2 diabetes (including 46 patients with microalbuminuria) and 52 non-diabetic control subjects. Plasma concentrations of pyridoxal 5'-phosphate (PLP) were significantly lower in patients with type 2 diabetes than in control subjects (median: 22.7 nmol/L, diabetes with microalbuminuria; 26.8 nmol/L, diabetes without microalbuminuria; 39.5 nmol/L, non-diabetic control; p<0.0001). The prevalence of low PLP (<30 nmol/L) was 63%, 58%, and 25% in the diabetes groups with and without microalbuminuria and the control group, respectively. Plasma levels of pyridoxine and pyridoxal were also lower (p<0.0001), but levels of pyridoxamine, pyridoxamine 5'-phosphate, and pyridoxic acid were higher in both groups with diabetes compared to the control group (p<0.001). Thiamine deficiency was highly prevalent in all groups, whereas low vitamin B₁₂ and elevated methylmalonic acid were rare. Increased levels of C-reactive protein and soluble vascular cell adhesion molecule-1 were observed in the groups with diabetes (p<0.05, versus healthy control). Deficiency of vitamin B₆ (PLP, pyridoxine, pyridoxal) and vitamin B₁ (thiamine) was prevalent in type 2 diabetes. Incipient nephropathy was associated with more pronounced alterations in vitamin B₆ metabolism and stronger indications of endothelial dysfunction and inflammation.


Management of heart failure in Canadian long-term care facilities.
In long-term care (LTC) facilities, heart failure is common but undertreated. No Canadian studies of heart failure in LTC facilities have been reported. To estimate the prevalence of heart failure in Canadian LTC facilities; to document the management of heart failure in LTC; and to describe characteristics of LTC residents with heart failure and predictors of adherence to treatment guidelines. Cross-sectional survey in eight LTC facilities lodging 1223 residents. The prevalence of heart failure was 20%. LTC residents with heart failure were older, more often women, and more functionally impaired and burdened by comorbidity than were participants in heart failure trials. Documentation supporting the heart failure diagnosis was inadequate, with some symptoms possibly misattributed to chronic obstructive pulmonary disease. Angiotensin-converting enzyme (ACE) inhibitors were prescribed to 55% of residents, although only 45% received appropriate doses. Residents with hypertension or diabetes mellitus, using nitrates or who were male were more likely to receive ACE inhibitors. Appropriate ACE inhibitor doses were associated with functional impairment, nitrate use and recent hospitalization. Documentation of systolic dysfunction was associated with a greater likelihood of ACE inhibitor use. Beta-blockers were prescribed to 25% of residents, who were more likely to be using nitrates, have ischemic heart disease or had been recently hospitalized, and less likely to have chronic obstructive pulmonary disease. Residents with atrial fibrillation were more likely to be prescribed digoxin. Potentially hazardous regimens were prescribed to 43% of residents. Heart failure is common in Canadian LTC facilities. Management of heart failure in LTC does not conform to guidelines. Improved diagnostic methods tailored for frail elderly patients must be developed. Studies are needed to understand and identify factors influencing prescribing for heart failure medication in LTC.


Risk factors associated with hospital mortality in mitral valve reoperation.
to identify the factors associated with mortality in mitral valve reoperation, to create a predictive model of mortality and to evaluate the EuroSCORE. a total of 65 patients were evaluated from January 2008 to December 2017. It was verified the association of variables with death and a multiple logistic regression model was used to stratify patients. hospital mortality was 13.8% and in the Death Group: EuroSCORE was 12.33±8.87 (p=0.017), the left ventricular ejection fraction (LVEF) was 45.33±5.10 (p=0.000), the creatinine was 1.56±0.29 (p=0.002), the prothrombin time (TAP) was 1.64 (p=0.001), pulmonary artery systolic pressure (PSAP): 66.1±13.6 (p=0.002), female: 88% (p=0.000), malnutrition: 77.7% (p=0.007), associated tricuspid disease: 44,4% (p=0.048), presence of ventricular arrhythmia: 77.7% (p=0.005), implantation of a biological prosthesis: 55.5% (p=0.034), bronchopneumonia and sepsis: 33,3% (p=0.048), systemic inflammatory response syndrome (SIRS): 55.5% (p=0.001), low cardiac output syndrome (LCOS): 88.8% (p=0.000). the factors associated with mortality were: EuroSCORE, LVEF, creatinine, TAP, PSAP, female, malnutrition, tricuspid disease, ventricular arrhythmia, implantation of biological prosthesis, SIRS, SBDC, bronchopneumonia and sepsis. The explanatory variables of death of the model were: EuroSCORE, creatinine, TAP, LVEF, length of stay in the intensive care unit (ICU), interval between surgeries and presence of ventricular arrhythmia. The high EuroSCORE is related to higher mortality.


Dietary total fat intake and ischemic stroke risk: the Northern Manhattan Study.
Dietary fat intake is associated with coronary heart disease risk, but the relationship between fat intake and ischemic stroke risk remains unclear. We hypothesized that total dietary fat as part of a Western diet is associated with increased risk of ischemic stroke. As part of the prospective Northern Manhattan Study, 3,183 stroke-free community residents over 40 years of age underwent evaluation of their medical history and had their diet assessed by a food-frequency survey. Cox proportional hazard models calculated risk of incident ischemic stroke. The mean age of participants was 69 years, 63% were women, 21% were white, 24% black and 52% Hispanic. During a mean of 5.5 years of follow-up, 142 ischemic strokes occurred. After adjusting for potential confounders, risk of ischemic stroke was higher in the upper quintile of total fat intake compared to the lowest quintile (HR 1.6, 95% CI 1.0-2.7). Total fat intake >65 g was associated with increased risk of ischemic stroke (HR 1.6, 95% CI 1.2-2.3). Risk was attenuated after controlling for caloric intake. The results suggest that increased daily total fat intake, especially above 65 g, significantly increases risk of ischemic stroke.


Reconstitution of human hematopoietic function with autologous cryopreserved circulating stem cells.
Complete hematopoietic reconstitution using nonleukemic peripheral blood mononuclear cells has been achieved in animal models but not in humans. We treated two patients who had metastatic breast carcinoma involving the bone marrow and who had failed conventional therapy with high-dose chemotherapy and total body radiation. Cryopreserved autologous peripheral blood mononuclear cells (6.3-8.4 X 10(8)/kg patient weight) obtained by leukapheresis before high-dose therapy were returned to the patients intravenously. In one patient, evidence of bone marrow engraftment was present, but the patient died before full reconstitution of the peripheral blood cells occurred. Bone marrow engraftment and return of all cell lines to the peripheral blood occurred in the second patient. These findings demonstrate that human hematopoietic reconstitution can be achieved with autologous, peripheral blood, mononuclear cell transfusions following high-dose therapy. This approach may be useful to patients who have contraindications for a bone marrow harvest but who are otherwise candidates for autologous bone marrow transplantation.


Efficacy and safety of direct oral factor Xa inhibitors compared with warfarin in patients with morbid obesity: a single-centre, retrospective analysis of chart data.
Because studies of direct oral anticoagulants in patients with venous thromboembolism and non-valvular atrial fibrillation have had minimal representation of morbidly obese patients (ie, body-mass index [BMI] ≥40 kg/m2), their efficacy and safety in this population are unclear. We investigated whether apixaban and rivaroxaban are as effective and safe as warfarin in morbidly obese patients. We did a single-centre, retrospective analysis of chart data for all adult patients aged at least 18 years at Montefiore Medical Center (Bronx, NY, USA) with a BMI of at least 40 kg/m2 who were prescribed apixaban, rivaroxaban, or warfarin for either venous thromboembolism or atrial fibrillation between March 1, 2013, and March 1, 2017. Patients who had both venous thromboembolism and atrial fibrillation were excluded, as were patients with indications other than atrial fibrillation and venous thromboembolism. Outcomes of recurrent venous thromboembolism, stroke, and bleeding were measured from the first prescription date to the earliest of a thrombotic event, medication discontinuation, death, or end of study on June 30, 2017. Analyses were stratified by anticoagulation indication and adjusted for comorbidities, CHA2DS2-VASc score, and age where appropriate. Outcome rates were compared using Pearson's χ2 or Fisher's exact test. Time-to-event analyses accounting for length of follow-up were used to compare risks of outcomes. We obtained data for 795 patients: 150 prescribed apixaban, 326 rivaroxaban, and 319 warfarin. In 366 patients prescribed an anticoagulant for venous thromboembolism, the incidence of recurrent venous thromboembolism was similar between the apixaban, rivaroxaban, and warfarin cohorts (1/47 [2·1%, 95% CI 0·0-6·3], 3/152 [2·0%, 0·0-4·2], and 2/167 [1·2%, 0·0-2·9], respectively; p=0·74). Incidence of major bleeding in this patient group was also similar between the treatment cohorts (1/47 patients on apixaban [2·1%, 95% CI 0·0-6·3], 2/152 on rivaroxaban [1·3%, 0·0-3·1], and 4/167 on warfarin [2·4%, 0·1-4·7]; p=0·77). In 429 patients prescribed an anticoagulant for atrial fibrillation, incidence of stroke was similar between the treatment cohorts (1/103 patients on apixaban [1·0%, 95% CI 0·0-2·9], 4/174 on rivaroxaban [2·3%, 0·1-4·5], and 2/152 on warfarin [1·3%, 0·0-3·1], p=0·71). In this patient group, major bleeding occurred in 3/103 patients on apixaban (2·9%, 95% CI 0·0-6·2), 5/174 on rivaroxaban (2·9%, 0·4-5·4), and 12/152 on warfarin (7·9%, 3·6-12·2); p=0·063. Time-to-event analyses showed that risk of all outcomes in patients with venous thromboembolism, and stroke and composite bleeding in patients with atrial fibrillation, were similar between the anticoagulant cohorts. Our retrospective study provides further evidence of similar efficacy and safety between the direct oral anticoagulants apixaban and rivaroxaban, and warfarin in morbidly obese patients with atrial fibrillation and venous thromboembolism. These data, if confirmed in prospective studies, might enable patients with a BMI of at least 40 kg/m2 to benefit from more convenient, and possibly safer, anticoagulants. None.


Post-Translational Modification and Subcellular Compartmentalization: Emerging Concepts on the Regulation and Physiopathological Relevance of RhoGTPases.
Cells and tissues are continuously exposed to both chemical and physical stimuli and dynamically adapt and respond to this variety of external cues to ensure cellular homeostasis, regulated development and tissue-specific differentiation. Alterations of these pathways promote disease progression-a prominent example being cancer. Rho GTPases are key regulators of the remodeling of cytoskeleton and cell membranes and their coordination and integration with different biological processes, including cell polarization and motility, as well as other signaling networks such as growth signaling and proliferation. Apart from the control of GTP-GDP cycling, Rho GTPase activity is spatially and temporally regulated by post-translation modifications (PTMs) and their assembly onto specific protein complexes, which determine their controlled activity at distinct cellular compartments. Although Rho GTPases were traditionally conceived as targeted from the cytosol to the plasma membrane to exert their activity, recent research demonstrates that active pools of different Rho GTPases also localize to endomembranes and the nucleus. In this review, we discuss how PTM-driven modulation of Rho GTPases provides a versatile mechanism for their compartmentalization and functional regulation. Understanding how the subcellular sorting of active small GTPase pools occurs and what its functional significance is could reveal novel therapeutic opportunities.


Dietary Patterns and Clinical Outcomes in Chronic Kidney Disease: The CKD.QLD Nutrition Study.
Emerging evidence suggests that dietary patterns are associated with survival in people with chronic kidney disease (CKD). This study evaluated the relationship between dietary habits and renal-related clinical outcomes in an established CKD cohort. Prospective cohort study. Three outpatient nephrology clinics in Queensland, Australia. A total of 145 adult patients with Stage 3 or 4 CKD (estimated glomerular filtration rate 15-59 mL/minute/1.73 m2). Dietary intake was measured using 24-hour recall and the HeartWise Dietary Habits Questionnaire (DHQ), which evaluates 10 components of dietary patterns in relation to cooking habits and intake of food groups. The primary outcome was a composite end point of all-cause mortality, commencement of dialysis, and doubling of serum creatinine. Secondary outcome was all-cause mortality alone. Multivariate cox regression analyses calculated hazard ratios (HRs) for associations between DHQ domains and occurrence of composite outcome and adjusted for confounders, including comorbidities and renal function. Over a median follow-up of 36 months, 32% (n = 47) reached the composite end point, of which 21% died (n = 30). Increasing DHQ score was associated with a lower risk of the composite end point with increasing intake of fruits and vegetables (HR: 0.61; 95% CI, 0.39-0.94) and limiting alcohol consumption (HR, 0.79; 95% CI: 0.65-0.96). For the secondary outcome of all-cause mortality, there was a significant association with adequate intake of fruits and vegetables (HR: 0.35; 95% CI, 0.15-0.83). Healthy dietary patterns consisting of adequate fruits and vegetables and limited alcohol consumption are associated with a delay in CKD progression and improved survival in patients with Stage 3 or 4 CKD.


Reexamination of the Doppler effect through Maxwell's equations.
In this work, the electric field emitted from a moving source, an electric point dipole, is analyzed for the purpose of illustrating the physics behind the Doppler effect. It is found that if the (translational) motion of the source is nonrelativistic, the Doppler effect is realized in two steps: the motion of the source first causes the dyadic Green function associated with the electric field to acquire an oscillation frequency in the far-field region of the source, and then the frequency leads to the Doppler effect. It is also demonstrated that the Doppler effect is observable only in the far-field region of the source.


Effects of music listening on stress, anxiety, and sleep quality for sleep-disturbed pregnant women.
Prenatal sleep disturbance has been associated with undesirable birthing outcomes. To determine the effectiveness of listening to music at home in improving sleep quality, 121 Taiwanese pregnant women with poor sleep quality (Pittsburgh Sleep Quality Index [PSQI] score > 5) were systematically assigned, with a random start to music listening (n = 61) or control (n = 60) group. Participants in the music listening group self-regulated listening to music in addition to receiving general prenatal care similar to that in the control group for 2 weeks. The PSQI and State-Anxiety Inventory were used to assess outcomes. ANCOVA analyses were used with the pretest scores as covariates and showed significant improvement in sleep quality, stress, and anxiety in the music listening group compared with the control group. The most frequently used music genre by participants in the experimental group was lullabies, followed by classical music and crystal baby music. This study supported the theory that 2-week music listening interventions may reduce stress, anxiety, and yield better sleep quality for sleep-disturbed pregnant women. The analysis of participants' journals also implied that the expectant mothers' choices of musical genres may correlate more with perceived prenatal benefits or the desire to interact with their unborn child.


Prolonged catatonic stupor successfully treated with aripiprazole in an adolescent male with schizophrenia: a case report.
We present the case of a fifteen-year-old adolescent male with schizophrenia who had long-term catatonic stupor and was successfully treated with aripiprazole. The onset of his stupor manifested rapidly after experiencing prodromal symptoms for two months. He was left untreated without adequate food ingestion for three weeks because of his parents' religious faith, and was severely dehydrated and malnourished upon admission to our hospital. After his physical recovery, treatment with risperidone (0.5-2.0 mg, 5 weeks) was started. However, hypersedation occurred, and the risperidone was switched to aripiprazole, with dose increases up to 18 mg/day (5 months). As a result, he recovered from his totally noncommunicative state. Aripiprazole, which has a unique pharmacological mechanism of action distinct from other atypical antipsychotics and an excellent safety profile, may be effective in the treatment of some schizophrenic patients with stupor, which sometimes carries a risk of physical debilitation and requires special attention due to the risk of adverse drug reactions.


Comparison of outcomes of HCT in blast phase of BCR-ABL1- MPN with de novo AML and with AML following MDS.
Comparative outcomes of allogeneic hematopoietic cell transplantation (HCT) for BCR-ABL1- myeloproliferative neoplasms (MPNs) in blast phase (MPN-BP) vs de novo acute myeloid leukemia (AML), and AML with prior myelodysplastic syndromes (MDSs; post-MDS AML), are unknown. Using the Center for International Blood and Marrow Transplant Research (CIBMTR) database, we compared HCT outcomes in 177 MPN-BP patients with 4749 patients with de novo AML, and 1104 patients with post-MDS AML, using multivariate regression analysis in 2 separate comparisons. In a multivariate Cox model, no difference in overall survival (OS) or relapse was observed in patients with MPN-BP vs de novo AML with active leukemia at HCT. Patients with MPN-BP in remission had inferior OS in comparison with de novo AML in remission (hazard ratio [HR], 1.40 [95% confidence interval [CI], 1.12-1.76]) due to higher relapse rate (HR, 2.18 [95% CI, 1.69-2.80]). MPN-BP patients had inferior OS (HR, 1.19 [95% CI, 1.00-1.43]) and increased relapse (HR, 1.60 [95% CI, 1.31-1.96]) compared with post-MDS AML. Poor-risk cytogenetics were associated with increased relapse in both comparisons. Peripheral blood grafts were associated with decreased relapse in MPN-BP and post-MDS AML (HR, 0.70 [95% CI, 0.57-0.86]). Nonrelapse mortality (NRM) was similar between MPN-BP vs de novo AML, and MPN-BP vs post-MDS AML. Total-body irradiation-based myeloablative conditioning was associated with higher NRM in both comparisons. Survival of MPN-BP after HCT is inferior to de novo AML in remission and post-MDS AML due to increased relapse. Relapse-prevention strategies are required to optimize HCT outcomes in MPN-BP.


Concentrate minimization and water recovery enhancement using pellet precipitator in a reverse osmosis process treating textile wastewater.
Industrial wastewater reuse together with zero or near zero liquid discharges have been a growing trend due to the requirement of sustainable water management mandated by water scarcity and tightening discharge regulations. Studies have been conducted on the reclamation of textile industry wastewater using RO processes. However a lot of scientific attention has been drawn upon limiting the amount of concentrate generated from RO processes, which depends on the concentrations of scale forming ions in the concentrate stream. Hence, this study aims at investigating the applicability of an ultra-filtration (UF) membrane integrated pellet reactor to remove scale forming ions, i.e. Ca2+, Mg2+ and Si from the concentrate of a pilot-scale textile industry RO process, for the first time in the literature. The resulting effluent was further tested in a secondary RO process to decrease concentrate volume and increase total water recovery. The pellet reactor operated at an extremely low hydraulic retention time of 0.1 h removed scale forming ions, i.e. Ca2+, Mg2+, with 90-95% efficiency, which improved the secondary RO process performance up to 92-94% overall water recovery, i.e. near zero liquid discharge was reached. Ozonation of the concentrate partially removed COD and color, which further improved the secondary RO filtration performance.


Spin effects as a tool to study photoinduced processes in (S/R)-ketoprofen-(S)-N-methylpyrrolidine dyads.
(S/R)-Ketoprofen (KP) is considered to be the strongest photosensitizer among nonsteroidal anti-inflammatory drugs. The photosensitizing reactions are caused by a substituted benzophenone chromophore. It produces various toxic effects through the formation of active paramagnetic intermediates and photoproducts able to attack biological substrates. Photoinduced transformations of KP have been extensively studied in order to identify paramagnetic intermediates. Considerable attention is also paid to photoinduced processes in dyads, where KP is linked with chiral partners, since such processes believed to model the binding of chiral drugs with enzymes and receptors. In the present study, the dyads containing (S)/(R)-KP covalently linked with (S)-N-methylpyrrolidine have been synthesized to examine the peculiarities of photoinduced electron transfer (ET) and hydrogen transfer (HT) in chiral systems. To detect short-lived paramagnetic intermediates, in dyad's excited triplet state, such as biradical zwitter ion (BZI) and neutral biradical (BR), spin chemistry methods [chemically induced dynamic nuclear polarization (CIDNP) and chemically induced dynamic electron polarization (CIDEP) in arbitrary magnetic fields], allowing indirect detection of transient paramagnetic particles by NMR, have been utilized. Both mentioned processes have been found to begin with the excitation of KP into the triplet state followed by the formation of BZI for ET and BR for HT, respectively. Products of stereoselective attachment of the N-methylpyrrolidine residue to the carbonyl carbon atom of KP occurring in both BZI and BR have been detected by NMR spectral analysis. The value of electronic exchange interaction in biradicals has been determined from the position of the characteristic maximum of hyperpolarization in the CIDNP magnetic field dependences.


Analysis of porcine adipose tissue transcriptome reveals differences in de novo fatty acid synthesis in pigs with divergent muscle fatty acid composition.
In pigs, adipose tissue is one of the principal organs involved in the regulation of lipid metabolism. It is particularly involved in the overall fatty acid synthesis with consequences in other lipid-target organs such as muscles and the liver. With this in mind, we have used massive, parallel high-throughput sequencing technologies to characterize the porcine adipose tissue transcriptome architecture in six Iberian x Landrace crossbred pigs showing extreme phenotypes for intramuscular fatty acid composition (three per group). High-throughput RNA sequencing was used to generate a whole characterization of adipose tissue (backfat) transcriptome. A total of 4,130 putative unannotated protein-coding sequences were identified in the 20% of reads which mapped in intergenic regions. Furthermore, 36% of the unmapped reads were represented by interspersed repeats, SINEs being the most abundant elements. Differential expression analyses identified 396 candidate genes among divergent animals for intramuscular fatty acid composition. Sixty-two percent of these genes (247/396) presented higher expression in the group of pigs with higher content of intramuscular SFA and MUFA, while the remaining 149 showed higher expression in the group with higher content of PUFA. Pathway analysis related these genes to biological functions and canonical pathways controlling lipid and fatty acid metabolisms. In concordance with the phenotypic classification of animals, the major metabolic pathway differentially modulated between groups was de novo lipogenesis, the group with more PUFA being the one that showed lower expression of lipogenic genes. These results will help in the identification of genetic variants at loci that affect fatty acid composition traits. The implications of these results range from the improvement of porcine meat quality traits to the application of the pig as an animal model of human metabolic diseases.


HPC-CLUST: distributed hierarchical clustering for large sets of nucleotide sequences.
Nucleotide sequence data are being produced at an ever increasing rate. Clustering such sequences by similarity is often an essential first step in their analysis-intended to reduce redundancy, define gene families or suggest taxonomic units. Exact clustering algorithms, such as hierarchical clustering, scale relatively poorly in terms of run time and memory usage, yet they are desirable because heuristic shortcuts taken during clustering might have unintended consequences in later analysis steps. Here we present HPC-CLUST, a highly optimized software pipeline that can cluster large numbers of pre-aligned DNA sequences by running on distributed computing hardware. It allocates both memory and computing resources efficiently, and can process more than a million sequences in a few hours on a small cluster. Source code and binaries are freely available at http://meringlab.org/software/hpc-clust/; the pipeline is implemented in Cþþ and uses the Message Passing Interface (MPI) standard for distributed computing.


Biphasic modulation of potassium release in rat parotid gland by carbachol and phenylephrine.
Both 86Rb and 42K appeared to serve as useful markers for potassium movements in rat parotid gland slices. Carbachol and phenylephrine elicited a biphasic increase in potassium release (86Rb release) that was dose related and could be blocked by atropin and phentolamine, respectively. The early transient phase of 86Rb release lasted from 3 to 6 minutes and was not blocked by removal of external Ca. These observations suggested that the transient phase corresponded to the transient hyperpolarization seen by others in response to alpha adrenergic or cholinergic agents. The latter sustained phase of 86Rb release was qualitatively blocked by chelation of external Ca ions or by 1 mM LaCl3. Thus, the sustained phase of release appeared to relate to the loss of total potassium seen by others with this tissue and to the mechanisms responsible for transporting water from blood to saliva.


Activity of resveratrol on the influence of aflatoxin B1 on the testes of Sprague dawley rats.
Twenty eight male Sprague Dawley rats (aged 3 months) were used in the study. The animals were given feed and water as ad libitum. Sprague dawley rats were randomly divided into 4 groups as 7 rats in each group. Except for the control one, aflatoxin B1 (7.5 μg / 200 g), resveratrol (60 mg / kg) was administered to rats of 3 other groups. At the end of the 16th day, blood, semen and tissue specimens were taken by decapitation under ether anesthesia. When we evaluate the spermatological parameters, it is understood that resveratrol has a statistically significant difference in terms of sperm motility and viability (membrane integrity) compared to the control group and aflatoxin B1 administration groups, indicating a protective effect on spermatological parameters. In terms of pathological parameters - histopathological examination - in the control and resveratrol groups, seminiferous tubules were observed to be in normal structure. In the group treated with aflatoxin, the regular structure of the spermatogenic cells deteriorated and the seminiferous tubules became necrotic and degenerative. In the group treated with Afb1 + res, the decreasing of necrotic and degenerative changes were determined compared with in the group treated with aflatoxin. As immunohistochemical examination, cleaved caspase 3 expression was found to be very low in the control and resveratrol groups. Cleaved caspase 3 expression was severely exacerbated in seminiferous tubules in aflatoxin group but cleaved caspase 3 expression level decreased in Afb1 + res. In the biochemical direction, resveratrol has been shown to inhibit the adverse effects of aflatoxin on antioxidant levels and to show a protective effect. For this purpose, the use of resveratrol with antioxidant activity was investigated in preventing or ameliorating damage to aflatoxin B1. It has been concluded that resveratrol effectively prevent the aflatoxin-induced testicular damage and lipid peroxidation. It has also been shown that resveratrol has protective effects on sperm motility and viability.


Burden and typing of rotavirus group A in Latin America and the Caribbean: systematic review and meta-analysis.
The efficacy of licensed rotavirus vaccines has only been shown against certain rotavirus group A (RV-A) types. It is critical to understand the burden of rotavirus gastroenteritis (RVGE) and its prevalent types to assess the potential impact of these vaccines in Latin America and the Caribbean (LA&C). We performed a systematic review and meta-analyses of all the available evidence reported from 1990 to 2009 on the burden of rotavirus disease and strains circulating in LA&C. Eligible studies--185 country-level reports, 174 951 faecal samples--were selected from MEDLINE, Cochrane Library, EMBASE, LILACS, regional Ministries of Health, PAHO, regional proceedings, doctoral theses, reference lists of included studies and consulting experts. Arc-sine transformations and DerSimonian-Laird random-effects model were used for meta-analyses. The proportion of gastroenteritis cases due to rotavirus was 24.3% (95%CI 22.3-26.4) and the incidence of RVGE was 170 per 1000 children-years (95%CI 130-210). We estimated a global annual mortality for 22 countries of 88.2 (95%CI 79.3-97.1) deaths per 100 000 under 5 years (47 000 deaths).The most common G type detected was G1 (34.2%), followed by G9 (14.6%), and G2 (14.4%). The most common P types detected were P[8] (56.2%), P[4] (22.1%) and P[1] 5.4%, and the most prevalent P-G type associations were P[8]G1 17.9%, P[4]G2 9.1% and P[8]G9 8.8%. In the last 10 years, G9 circulation increased remarkably and G5 almost disappeared. More recently, G12 appeared and P[4]G2 re-emerged. To our knowledge, this is the first meta-analysis of rotavirus infection and burden of disease in LA&C.


Organic Solvent Effects in Biomass Conversion Reactions.
Transforming lignocellulosic biomass into fuels and chemicals has been intensely studied in recent years. A large amount of work has been dedicated to finding suitable solvent systems, which can improve the transformation of biomass into value-added chemicals. These efforts have been undertaken based on numerous research results that have shown that organic solvents can improve both conversion and selectivity of biomass to platform molecules. We present an overview of these organic solvent effects, which are harnessed in biomass conversion processes, including conversion of biomass to sugars, conversion of sugars to furanic compounds, and production of lignin monomers. A special emphasis is placed on comparing the solvent effects on conversion and product selectivity in water with those in organic solvents while discussing the origins of the differences that arise. We have categorized results as benefiting from two major types of effects: solvent effects on solubility of biomass components including cellulose and lignin and solvent effects on chemical thermodynamics including those affecting reactants, intermediates, products, and/or catalysts. Finally, the challenges of using organic solvents in industrial processes are discussed from the perspective of solvent cost, solvent stability, and solvent safety. We suggest that a holistic view of solvent effects, the mechanistic elucidation of these effects, and the careful consideration of the challenges associated with solvent use could assist researchers in choosing and designing improved solvent systems for targeted biomass conversion processes.


Selective cerebral revascularization as an adjunct in the treatment of giant anterior circulation aneurysms.
Cerebral revascularization, an indispensable component of neurovascular surgery, has been performed in the treatment of cranial base tumors, complex cerebral aneurysms, and occlusive cerebrovascular disease. The goal of a revascularization procedure is to augment blood flow distally. It can therefore be used as an adjunctive measure in the treatment of complex neurosurgical disease processes that require parent artery sacrifice for definitive treatment. In the treatment of giant anterior circulation aneurysms, for instance, a cerebral revascularization procedure may be considered in patients in whom the collateral circulation is marginal and in whom lesions may be treated either using a Hunterian-based strategy or clip-assisted reconstruction requiring a prolonged period of temporary occlusion. To date, there is no entirely effective method known to produce long-term tolerance to carotid artery (CA) sacrifice and, largely for that reason, some neurovascular surgeons advocate universal revascularization. The authors of this report, however, prefer to perform revascularization only in the limited subset of patients in whom preoperative assessment has revealed risk factors for cerebral ischemia due to hypoperfusion. In this paper, the authors introduce their protocol for assessing cerebrovascular reserve capacity, indications for cerebral revascularization in the treatment of complex anterior circulation aneurysms, and discuss their rationale for choosing to practice selective, rather than universal, revascularization.


Estrogen signaling prevents diet-induced hepatic insulin resistance in male mice with obesity.
The development of insulin resistance in the liver is a key event that drives dyslipidemia and predicts diabetes and cardiovascular risk with obesity. Clinical data show that estrogen signaling in males helps prevent adiposity and insulin resistance, which may be mediated through estrogen receptor-α (ERα). The tissues and pathways that mediate the benefits of estrogen signaling in males with obesity are not well defined. In female mice, ERα signaling in the liver helps to correct pathway-selective insulin resistance with estrogen treatment after ovariectomy. We assessed the importance of liver estrogen signaling in males using liver ERα-knockout (LKO) mice fed a high-fat diet (HFD). We found that the LKO male mice had decreased insulin sensitivity compared with their wild-type floxed (fl/fl) littermates during hyperinsulinemic euglycemic clamps. Insulin failed to suppress endogenous glucose production in LKO mice, indicating liver insulin resistance. Insulin promoted glucose disappearance in LKO and fl/fl mice similarly. In the liver, insulin failed to induce phosphorylation of Akt-Ser(473) and exclude FOXO1 from the nucleus in LKO mice, a pathway important for liver glucose and lipid metabolism. Liver triglycerides and diacylglycerides were also increased in LKO mice, which corresponded with dysregulation of insulin-stimulated ACC phosphorylation and DGAT1/2 protein levels. Our studies demonstrate that estrogen signaling through ERα in the liver helps prevent whole body and hepatic insulin resistance associated with HFD feeding in males. Augmenting hepatic estrogen signaling through ERα may lessen the impact of obesity on diabetes and cardiovascular risk in males.


In-vivo sagittal plane knee kinematics: ACL intact, deficient and reconstructed knees.
Sagittal plane video fluoroscopy was used to analyse the bilateral knee kinematics of patients with unilateral ACL deficiency (ACLD) before, and 4 months after, hamstrings graft ACL reconstruction. Kinematics were studied during weight resisted knee extension, passive knee extension, and a step up. Thigh EMG records were also obtained from five subjects. In addition, six uninjured control subjects were analysed to establish normal kinematics. Kinematics were analysed by calculating the angle between the long axis of the tibia and the patella tendon through the range of knee flexion. Shear forces were calculated using a model of knee extension and force plate data. A maximum anterior TT of 7.3 (S.D. 2.1) mm was recorded in ACL intact (ACLI) knees during the weightbearing activity. Hamstrings activity was able to control ATT in the ACLD tibia to within the normal range of translation of the ACLI knee. Despite clinical improvements, ATT increased postoperatively in the reconstructed knees to 11.6 (S.D. 3.8) mm (P<0.048). The findings suggest that the ACL has only a minor role in the control of ATT during activity, and that the extent of ATT is more closely related to the level of quadriceps-generated shear force. A reduction in hamstrings force is proposed as the most likely cause for increased ATT post reconstruction. These findings have implications for the development of ACL rehabilitation regimes, and also may modify graft choice and the surgical aims of the procedure.


Embryonic and neonatal phenotyping of genetically engineered mice.
Considerable progress has been made in adapting existing and developing new technologies to enable increasingly detailed phenotypic information to be obtained in embryonic and newborn mice. Sophisticated methods for imaging mouse embryos and newborns are available and include ultrasound and magnetic resonance imaging (MRI) for in vivo imaging, and MRI, vascular corrosion casts, micro-computed tomography, and optical projection tomography (OPT) for postmortem imaging. In addition, Doppler and M-mode ultrasound are useful noninvasive tools to monitor cardiac and vascular hemodynamics in vivo in embryos and newborns. The developmental stage of the animals being phenotyped is an important consideration when selecting the appropriate technique for anesthesia or euthanasia and for labeling animals in longitudinal studies. Study design also needs to control for possible differences between inter- and intralitter variability, and for possible long-term developmental effects caused by anesthesia and/or procedures. Noninvasive or minimally invasive intravenous or intracardiac injections or blood sampling, and arterial pressure and electrocardiography (ECG) measurements are feasible in newborns. Whereas microinjection techniques are available for embryos as young as 6.5 days of gestation, further advances are required to enable minimally invasive fluid or tissue samples, or blood pressure or ECG measurements, to be obtained from mouse embryos in utero. The growing repertoire of techniques available for phenotyping mouse embryos and newborns promises to accelerate knowledge gained from studies using genetically engineered mice to understand molecular regulation of morphogenesis and the etiology of congenital diseases.


Emergency neurological life support: airway, ventilation, and sedation.
Airway management is central to the resuscitation of the neurologically ill. These patients often have evolving processes that threaten the airway and adequate ventilation. Therefore, airway, ventilation, and sedation were chosen as an Emergency Neurological Life Support (ENLS) protocol. Reviewed topics include airway management; the decision to intubate; when and how to intubate with attention to cardiovascular status; mechanical ventilation settings; and the use of sedation, including how to select sedative agents based on the patient's neurological status.


[Influence of lipril on the myocardial ultrastructure in rats with spontaneous hypertension].
In the spontaneous hypertensive rats (SHR)--line NISAG--most cardiac hystiocytes of the left ventriculum have signs of ultrastructure damage to a variable extent. First of all the contractile and energetic function of cardiac hystiocytes has different abnormalities. Administration of Lipril (20 mg/kg daily, during three months) showed the normalization of the ultrastructure of myocardium of SHR. This was evident through decreased in overcontractility of muscular fibrils till complete or partial disappearance of structuring sarcomers. Most mitochondria preserve ultrastructural organization. There are practically no damages in the endothelium, except non-significant vasoconstriction. The comparative analysis of the ultrastructural changes of cardiac hystiocyte of SHR after 3 months of treatment of Lipril showed that current medication has the recoverable effect on the structural organization of cardiac hystiocytes, mitochondrion and blood vessels.


External carotid artery in internal carotid artery occlusion. Angiographic, therapeutic, and prognostic considerations.
Twenty-three instances of internal carotid artery occlusion occurring with minimal neurological deficit in 22 patients are described. Although each of these patients was referred to the neurosurgical service for evaluation for an extracranial-intracranial microvascular bypass procedure, complete arteriographic evaluations of their cerebrovasculature suggested that alternative methods should be the treatment of choice. For each patient reported the ipsilateral external carotid artery was demonstrated by angiography to be an important source of collateral blood supply to the cerebral hemispheres or retinae distal to the occluded internal carotid arteries. Ten patients with no significant atherosclerotic narrowing or ulceration of the external carotid artery have remained free of symptoms of cerebral ischemia for 6 to 40 months. In twelve patients who developed delayed recurrent cerebral or retinal ischemia ipsilateral to their internal carotid artery occlusion, there were found obstructive and/or ulcerative plaques involving the common and/or external carotid arteries. Thromboendarterectomy in 11 of these patients gave complete relief of ischemic symptoms during the 4 to 36 months of postoperative follow up. One of these 12 patients refused operation and went on to develop a major cerebral infarction. Angiographic identification of a functionally important external carotid artery ipsilateral to an internal carotid artery occlusion carries considerable prognostic and therapeutic significance.


Ewe fertility in the STAR accelerated lambing system.
Effects of environmental factors such as ewe age, season of exposure, and time from lambing to exposure on fertility were evaluated using records on 1,084 Dorset ewes in the STAR accelerated lambing system. The STAR program consisted of five 30-d concurrent breeding and lambing periods per year beginning on January 1, March 15, May 27, August 8, and October 20. Fertility in the flock changed in a cyclic and predictable fashion during the year. Changes in prolificacy were less consistent but also tended to show cyclic variation. Matings that occurred within the typical breeding season (August, October, and January) were more fertile than those occurring in March and June. However, fertility also varied with the age of the ewe and the time since the ewe's last lambing. Except in June, fertility at the first postpartum mating increased as ewes aged. In March and June matings, adult ewes that had just weaned lambs were less fertile than ewes that had failed to conceive in the previous season and therefore had longer postpartum intervals. However, in October and January, ewes that had just weaned lambs were more fertile. A matrix of expected pregnancy rates, or probabilities of fertility, was constructed using a mixed GLM to describe the combined effect of season, ewe age, and time since lambing on ewe fertility in accelerated lambing.


Nuclear pore localization and nucleocytoplasmic transport of eIF-5A: evidence for direct interaction with the export receptor CRM1.
Eukaryotic initiation factor 5A (eIF-5A) is the only cellular protein known to contain the unusual amino acid hypusine. The exact in vivo function of eIF-5A, however, is to date unknown. The finding that eIF-5A is an essential cofactor of the human immunodeficiency virus type 1 (HIV-1) Rev RNA transport factor suggested that eIF-5A is part of a specific nuclear export pathway. In this study we used indirect immunofluorescence and immunogold electron microscopy to demonstrate that eIF-5A accumulates at nuclear pore-associated intranuclear filaments in mammalian cells and Xenopus oocytes. We are able to show that eIF-5A interacts with the general nuclear export receptor, CRM1. Furthermore, microinjection studies in somatic cells revealed that eIF-5A is transported from the nucleus to the cytoplasm, and that this nuclear export is blocked by leptomycin B. Our data demonstrate that eIF-5A is a nucleocytoplasmic shuttle protein.


Augmented locomotor recovery after spinal cord injury in the athymic nude rat.
The immune response contributes to ongoing secondary tissue destruction following spinal cord injury (SCI). Although infiltrating neutrophils and monocytes have been well studied in this process, T-cells have received less attention. The objective of this study was to assess locomotor recovery and tissue morphology after SCI in athymic (nude) rats, in which T-cell numbers are reduced. Results in athymic rats were compared with heterozygote littermates with normal T-cell profiles and with Sprague-Dawley rats from previous studies in our lab. Following transection of rat spinal cords at T10, we assessed the animals' locomotor recovery on a weekly basis for up to 11 weeks, using the Basso-Beattie-Bresnahan locomotor rating scale. Nude rats showed better locomotor recovery than did heterozygote or Sprague-Dawley rats, achieving scores of 5.6 +/- 0.8 versus 1.0 +/- 0.0, respectively (p = 0.002), at 4 weeks postinjury. The improved recovery of nude rats persisted for the 11-week postinjury assessment period, and was consistent with improved spinal reflexes rather than with recovery of descending motor pathways. Anatomical evaluation at 11 weeks indicated no difference in nude versus heterozygote rats in the size or distribution of cavities caudal to the transection site, but secondary damage was more severe rostral to the transection site in heterozygote rats. In neither group did cavities extend beyond 4 mm caudal to the transection site, and were therefore not directly responsible for the functional differences between the two groups. Cellular expression of the microglia/macrophage antigen ectodysplasin A (ED1) was reduced in nude rats as compared to heterozygotes, but no difference was observed in expression levels of 5-hydroxytryptamine, the 200-kDa neurofilament, or glial fibrillary acidic protein. The findings of the study show that a reduction in T-cell numbers significantly improves locomotor recovery after spinal cord transection, indicating a deleterious role for these immune cells in neural repair after trauma.


Ethanol administration produces divergent changes in GABAergic neuroactive steroid immunohistochemistry in the rat brain.
The 5α-reduced pregnane neuroactive steroid (3α,5α)-3-hydroxypregnan-20-one (3α,5α-THP or allopregnanolone) is a potent positive modulator of GABAA receptors capable of modulating neuronal activity. In rats, systemic ethanol (EtOH) administration increases cerebral cortical and hippocampal levels of 3α,5α-THP, but the effects of EtOH on 3α,5α-THP levels in other brain regions are unknown. There is a large body of evidence suggesting that 3α,5α-THP enhances EtOH sensitivity, contributes to some behavioral effects of EtOH, and modulates EtOH reinforcement and motivation to drink. In this study, we used immunohistochemistry (IHC) to determine EtOH-induced changes in cellular 3α,5α-THP expression in brain regions associated with EtOH actions and responses. Male Wistar rats were administered EtOH (2 g/kg) or saline intraperitoneally and after 60 minutes transcardially perfused. IHC was performed on free-floating sections (3 to 4 sections/animal/brain region) using an affinity purified anti-3α,5α-THP primary antibody, and immunoreactivity was visualized with 3,3'-diaminobenzidine. EtOH significantly increased 3α,5α-THP immunoreactivity by 24 ± 6% in the medial prefrontal cortex, 32 ± 12% in the hippocampal Cornu Ammonis area 1 (CA1) pyramidal cell layer, 52 ± 5% in the polymorph cell layer of the dentate gyrus (DG), 44 ± 15% in the bed nucleus of the stria terminalis, and 36 ± 6% in the paraventricular nucleus of the hypothalamus. In contrast, EtOH administration significantly reduced 3α,5α-THP immunoreactivity by 25 ± 5% in the nucleus accumbens "shore" and 21 ± 3% in the central nucleus of the amygdala. No changes were observed in the ventral tegmental area, dorsomedial striatum, granule cell layer of the DG, or the lateral and basolateral amygdala. The results suggest acute EtOH (2 g/kg) produces divergent, brain region specific, effects on cellular 3α,5α-THP levels. Regional differences in the effects of EtOH suggest there may be regional brain synthesis of 3α,5α-THP independent of the adrenal glands and novel mechanisms that reduce cellular 3α,5α-THP. Regional differences in EtOH-induced changes in 3α,5α-THP levels likely contribute to EtOH effects on neuronal function in brain.


'Stand still …, and move on' , an early neurologically-focused follow-up for cardiac arrest survivors and their caregivers: a process evaluation.
A cardiac arrest can lead to hypoxic-ischaemic brain injury which can result in cognitive and emotional impairments and may negatively affect daily functioning, participation in society and quality of life. Furthermore, the impact on the family of the patient can be high. We designed an intervention called 'Stand still …, and move on', which is a concise, individualised, semi-structured intervention for survivors of cardiac arrest and their caregivers, consisting of between one and six face-to-face consultations provided by a trained nurse. The intervention is directed at early detection of cognitive and emotional problems, provision of information, promotion of self-management and referral to specialised care if necessary. The effectiveness of the intervention is being examined in a randomised controlled trial [ISRCTN74835019]. Alongside this trial we performed a process evaluation which aims to investigate the feasibility of the intervention by assessing: 1) the attendance and dose delivered; 2) performance according to protocol; and 3) the opinion of patients, caregivers and nurses on the intervention. Participants of this process evaluation were 97 patients allocated to the intervention group of the RCT, their 91 caregivers, and six nurses who conducted the intervention. Measurement instruments used were evaluation forms for patients and caregivers, registration and evaluation forms for nurses, and semi-structured interviews with nurses. Seventy-nine of the patients (81%) allocated to the intervention group and 65 caregivers (71%) participated in the intervention. The mean (SD) number of consultations per patient was 1.8 (1.0), and most consultations were conducted at the patients' home. The intervention was performed largely according to protocol, except that the intervention usually started later than intended, consultations were longer than expected, and the topic of self-management was not regularly addressed. Patients marked the quality of the intervention with a mean score of 7.5 and the performance of the nurse with an 8.0 out of ten. Overall, the intervention was positively evaluated by patients, caregivers and nurses. The intervention 'Stand still …, and move on' is a promising intervention which was performed largely according to protocol and seems feasible for implementation after some adaptations, if it is found to be effective.


Neurite outgrowth of neuroblastoma cells: dependence on adhesion surface--cell surface interactions.
Neurite outgrowth of C 1300 neuroblastoma cells, which were dispersed from adherent cultures or grown in suspension, was studied on different protein-coated surfaces. Of 29 different surface structures studied, including surfaces treated with various fibronectins, lectins, glycosidases, or glycosyltransferases capable of stimulating fibroblast spreading, only the surfaces coated with plasma fibronectin or with a protein mixture secreted by C6 glioma cells displayed an extensive activity in the sprouting assay. Neurite outgrowth was inhibited by brain gangliosides and by colominic acid (a sialic acid polymer). A 50% inhibition of neurite outgrowth of N18 neuroblasts induced by the glioma cell proteins was observed at the following approximate concentration: 100 microM (0.2 mg/ml) GD1A ganglioside, 20 microM (0.04 mg/ml) GT1B ganglioside, and 5 mg/ml colominic acid. Specificity of inhibition was suggested by the finding that a few polyanionic substances tested were not inhibitory in the sprouting assay, and that the type of gangliosides inhibiting sprouting were found to be major sialoglycolipids of the neuroblasts. A hypothesis is discussed, according to which neurite outgrowth of neuroblasts is stimulated by adhesion involving interactions of the adhesion-mediating protein with cell surface carbohydrates characteristic of brain gangliosides.


Cholesterol binding, efflux, and a PDZ-interacting domain of scavenger receptor-BI mediate HDL-initiated signaling.
The binding of HDL to scavenger receptor-BI (SR-BI) mediates cholesterol movement. HDL also induces multiple cellular signals, which in endothelium occur through SR-BI and converge to activate eNOS. To determine the molecular basis of a signaling event induced by HDL, we examined the proximal mechanisms in HDL activation of eNOS. In endothelial cells, HDL and methyl-beta-cyclodextrin caused comparable eNOS activation, whereas cholesterol-loaded methyl-beta-cyclodextrin had no effect. Phosphatidylcholine-loaded HDL caused greater stimulation than native HDL, and blocking antibody against SR-BI, which prevents cholesterol efflux, prevented eNOS activation. In a reconstitution model in COS-M6 cells, wild-type SR-BI mediated eNOS activation by both HDL and small unilamellar vesicles (SUVs), whereas the SR-BI mutant AVI, which is incapable of efflux to SUV, transmitted signal by only HDL. In addition, eNOS activation by methyl-beta-cyclodextrin was SR-BI dependent. Studies of mutant and chimeric class B scavenger receptors revealed that the C-terminal cytoplasmic PDZ-interacting domain and the C-terminal transmembrane domains of SR-BI are both necessary for HDL signaling. Furthermore, we demonstrated direct binding of cholesterol to the C-terminal transmembrane domain using a photoactivated derivative of cholesterol. Thus, HDL signaling requires cholesterol binding and efflux and C-terminal domains of SR-BI, and SR-BI serves as a cholesterol sensor on the plasma membrane.


Ghrelin receptor antagonism decreases alcohol consumption and activation of perioculomotor urocortin-containing neurons.
The current therapies for alcohol abuse disorders are not effective in all patients, and continued development of pharmacotherapies is needed. One approach that has generated recent interest is the antagonism of ghrelin receptors. Ghrelin is a gut-derived peptide important in energy homeostasis and regulation of hunger. Recent studies have implicated ghrelin in alcoholism, showing altered plasma ghrelin levels in alcoholic patients as well as reduced intakes of alcohol in ghrelin receptor knockout mice and in mice treated with ghrelin receptor antagonists. The aim of this study was to determine the neuroanatomical locus/loci of the effect of ghrelin receptor antagonism on alcohol consumption using the ghrelin receptor antagonist, D-Lys3-GHRP-6. In Experiment 1, male C57BL/6J mice were injected with saline 3 hours into the dark cycle and allowed access to 15% (v/v) ethanol or water for 2 hours in a 2-bottle choice experiment. On test day, the mice were injected with either saline or 400 nmol of the ghrelin receptor antagonist, D-Lys3-GHRP-6, and allowed to drink 15% ethanol or water for 4 hours. The preference for alcohol and alcohol intake were determined. In Experiment 2, the same procedure was followed as in Experiment 1 but mice were only allowed access to a single bottle of 20% ethanol (v/v), and alcohol intake was determined. Blood ethanol levels were analyzed, and immunohistochemistry for c-Fos was carried out to investigate changes in neural activity. To further elucidate the mechanism by which D-Lys3-GHRP-6 affects alcohol intake, in Experiment 3, the effect of D-Lys3-GHRP-6 on the neural activation induced by intraperitoneal ethanol was investigated. For the c-Fos studies, brain regions containing ghrelin receptors were analyzed, i.e. the perioculomotor urocortin population of neurons (pIIIu), the ventral tegmental area (VTA), and the arcuate nucleus (Arc). In Experiment 4, to test if blood ethanol concentrations were affected by D-Lys3-GHRP-6, blood samples were taken at 2 time-points after D-Lys3-GHRP-6 pretreatment and systemic ethanol administration. In Experiment 1, D-Lys3-GHRP-6 reduced preference to alcohol and in a follow-up experiment (Experiment 2) also dramatically reduced alcohol intake when compared to saline-treated mice. The resulting blood ethanol concentrations were lower in mice treated with the ghrelin receptor antagonist. Immunohistochemistry for c-Fos showed fewer immunopositive cells in the pIIIu of the antagonist-treated mice but no difference was seen in the VTA or Arc. In Experiment 3, D-Lys3-GHRP-6 reduced the induction of c-Fos by intraperitoneal ethanol in the pIIIu but had no effect in the VTA. In the Arc, there was a significant increase in the number of c-Fos immunopositive cells after D-Lys3-GHRP-6 administration, but the antagonist had no effect on ethanol-induced expression of c-Fos. D-Lys3-GHRP-6-pretreatment also did not affect the blood ethanol concentrations observed after a systemic injection of ethanol when compared to saline-pretreated mice (Experiment 4). These findings indicate that the action of ghrelin on the regulation of alcohol consumption may occur via the pIIIu.


Screening of circulating microRNA biomarkers for prevalence of abdominal aortic aneurysm and aneurysm growth.
MicroRNA (miR) are important regulators of gene expression and biological processes and have recently been suggested as possible biomarkers for abdominal aortic aneurysm (AAA) disease. The aim of the present study was to assess the role of miR as biomarkers for initiation and progression of AAA disease, through evaluation of a wide range of miRs in a large population-based cohort, with AAA patients with linked clinical data regarding risk factors, AAA size and growth, as well as controls. The expression of the 172 most commonly expressed miRs in plasma was analyzed by real-time PCR in samples from 169 screening-detected AAA patients and 48 age-matched controls. For 103 miRs, there was a significant difference in expression between AAA and controls. Of these, 20 miRs were differently expressed between fast and slow growing aneurysms. These miRs target genes known to be involved in AAA disease as well as novel genes and pathways. By combining the top altered miRs together with clinical variables, strong predictive values, determining growth of AAA, were obtained (area under curve = 0.86, p < 0.001). This large cohort study identified several novel miRs with altered expression in AAA patients when compared to controls. Assessment of miR expression may offer an opportunity to predict disease progression and aneurysm growth.


A Brief Prenatal Intervention of Behavioral Change to Reduce the Risk of Maternal Cytomegalovirus: A Randomized Controlled Trial.
To estimate the effects of a brief prenatal behavioral intervention on risk behaviors for maternal cytomegalovirus (CMV) infection. Women were screened with CMV serology during prenatal care before 20 weeks of gestation and followed for at least 10 weeks. Women without serologic evidence of primary CMV infection were approached. Participants were apprised of serostatus and then randomized 2:1 to either a brief behavioral intervention during their prenatal care visit or to standard care (a brochure). The 7- to 10-minute in-office intervention included a video and hygiene education using motivational interviewing. Participants were then given a reminder calendar to take home and weekly text message reminders. The primary outcome was change in behavioral compliance score on a scale of 0-100. Secondary outcomes included process evaluation and domains of behavior change. A sample size of 180 participants was planned to compare the behavioral compliance score change of at least 15% between intervention and control groups with 80% power and 2.5% two-sided α. From April 2013 to October 2014, 197 women were randomized. One hundred eighty-seven (96%) had outcome data available. Mean gestational age at screening and randomization was 9 4/7 and 13 6/7 weeks of gestation, respectively. Primary outcome assessment occurred at a mean of 28 4/7 weeks of gestation. Baseline behavioral compliance scores increased modestly in the intervention group (mean: 7-point increase from 80.7 to 87.7, 95% CI 2.4-5.9) compared with the comparison group (mean: 4-point increase from 79.7 to 84.1, 95% CI 5.9-8.4; mean difference in change score: 3.0, 95% CI, 0.8-5.2; P=.007). Those in the intervention group reported change in risk perception related to perceived severity and susceptibility, self-efficacy, and perceived norms (P<.05 for all). A brief behavioral intervention delivered in the prenatal care setting was modestly effective at changing behaviors related to CMV infection risk. ClinicalTrials.gov, NCT01819519.


Subclinical psychosis and suicidal behavior in England: Findings from the 2007 Adult Psychiatric Morbidity Survey.
Psychotic disorders have been associated with suicidality but information on the association between subclinical psychosis and suicidality in the general adult population is scarce. Data from the 2007 Adult Psychiatric Morbidity Survey (n=7403) were analyzed. This was a nationally representative survey of the English adult household population (aged ≥16years). Five types of psychotic symptoms (hypomania, thought control, paranoia, strange experience, auditory hallucination) occurring in the past 12months were assessed with the Psychosis Screening Questionnaire. Participants with probable or definite psychosis were excluded. Logistic regression analysis was used to assess the association between psychotic symptoms and suicidal ideation and suicide attempt in the past 12months. The prevalence of at least one psychotic symptom was 5.4%. After adjusting for potential confounders including mental disorders, each individual psychotic symptom was significantly associated with suicidal ideation with odds ratios (ORs) ranging from 3.22 to 4.20. With the exception of thought control, all symptoms were also associated with significantly higher odds for suicide attempt (ORs 3.95 to 10.23). Having at least one psychotic symptom was associated with ORs of 3.13 (95%CI 2.09-4.68) and 3.84 (95%CI 1.67-8.83) for suicidal ideation and suicide attempt respectively. In addition, a greater number of psychotic symptoms was associated with higher odds for suicidal ideation and suicide attempt. Psychotic symptoms, regardless of the type, were independently associated with higher odds for suicidal ideation and suicide attempt. Assessment and management of suicide risk in individuals with psychotic symptoms may be important for suicide prevention.


Family nurture intervention (FNI): methods and treatment protocol of a randomized controlled trial in the NICU.
The stress that results from preterm birth, requisite acute care and prolonged physical separation in the Neonatal Intensive Care Unit (NICU) can have adverse physiological/psychological effects on both the infant and the mother. In particular, the experience compromises the establishment and maintenance of optimal mother-infant relationship, the subsequent development of the infant, and the mother's emotional well-being. These findings highlight the importance of investigating early interventions that are designed to overcome or reduce the effects of these environmental insults and challenges. This study is a randomized controlled trial (RCT) with blinded assessment comparing Standard Care (SC) with a novel Family Nurture Intervention (FNI). FNI targets preterm infants born 26-34 weeks postmenstrual age (PMA) and their mothers in the NICU. The intervention incorporates elements of mother-infant interventions with known efficacy and organizes them under a new theoretical context referred to collectively as calming activities. This intervention is facilitated by specially trained Nurture Specialists in three ways: 1) In the isolette through calming interactions between mother and infant via odor exchange, firm sustained touch and vocal soothing, and eye contact; 2) Outside the isolette during holding and feeding via the Calming Cycle; and 3) through family sessions designed to engage help and support the mother. In concert with infant neurobehavioral and physiological assessments from birth through 24 months corrected age (CA), maternal assessments are made using standard tools including anxiety, depression, attachment, support systems, temperament as well as physiological stress parameters. Quality of mother-infant interaction is also assessed. Our projected enrolment is 260 families (130 per group). The FNI is designed to increase biologically important activities and behaviors that enhance maternally-mediated sensory experiences of preterm infants, as well as infant-mediated sensory experiences of the mother. Consequently, we are enlarging the testing of preterm infant neurodevelopment beyond that of previous research to include outcomes related to mother-infant interactions and mother-infant co-regulation. Our primary objective is to determine whether repeated engagement of the mother and her infant in the intervention's calming activities will improve the infant's developmental trajectory with respect to multiple outcomes. Our secondary objective is to assess the effectiveness of FNI in the physiological and psychological co-regulation of the mother and infant. We include aspects of neurodevelopment that have not been comprehensively measured in previous NICU interventions. ClinicalTrials.gov: NCT01439269.


Prototypic and arkypallidal neurons in the dopamine-intact external globus pallidus.
Studies in dopamine-depleted rats indicate that the external globus pallidus (GPe) contains two main types of GABAergic projection cell; so-called "prototypic" and "arkypallidal" neurons. Here, we used correlative anatomical and electrophysiological approaches in rats to determine whether and how this dichotomous organization applies to the dopamine-intact GPe. Prototypic neurons coexpressed the transcription factors Nkx2-1 and Lhx6, comprised approximately two-thirds of all GPe neurons, and were the major GPe cell type innervating the subthalamic nucleus (STN). In contrast, arkypallidal neurons expressed the transcription factor FoxP2, constituted just over one-fourth of GPe neurons, and innervated the striatum but not STN. In anesthetized dopamine-intact rats, molecularly identified prototypic neurons fired at relatively high rates and with high regularity, regardless of brain state (slow-wave activity or spontaneous activation). On average, arkypallidal neurons fired at lower rates and regularities than prototypic neurons, and the two cell types could be further distinguished by the temporal coupling of their firing to ongoing cortical oscillations. Complementing the activity differences observed in vivo, the autonomous firing of identified arkypallidal neurons in vitro was slower and more variable than that of prototypic neurons, which tallied with arkypallidal neurons displaying lower amplitudes of a "persistent" sodium current important for such pacemaking. Arkypallidal neurons also exhibited weaker driven and rebound firing compared with prototypic neurons. In conclusion, our data support the concept that a dichotomous functional organization, as actioned by arkypallidal and prototypic neurons with specialized molecular, structural, and physiological properties, is fundamental to the operations of the dopamine-intact GPe.


Identification and quantification of soundscape components in the Marginal Ice Zone.
Acoustic experiments using an integrated ice station were carried out during August 2012 and September 2013 in the Marginal Ice Zone (MIZ) of Fram Strait. The two experiments lasted four days each and collected under-ice acoustic recordings together with wave-in-ice and meteorological data. Synthetic aperture radar satellite data provided information on regional ice conditions. Four major components of the under-ice soundscape were identified: ship cavitation noise, seismic airgun noise, marine mammal vocalizations, and natural background noise. Ship cavitation noise was connected to heavy icebreaking. It dominated the soundscape at times, with noise levels (NLs) 100 km from the icebreaker increased by 10-28 dB. Seismic airgun noise that originated from seismic surveys more than 800 km away was present during 117 out of 188 observation hours. It increased NLs at 20-120 Hz by 2-6 dB. Marine mammal vocalizations were a minor influence on measured NLs, but their prevalence shows the biological importance of the MIZ. The 10th percentile of the noise distributions was used to identify the ambient background noise. Background NLs above 100 Hz differed by 12 dB between the two experiments, presumably due to variations in natural noise sources.


Autoradiographic characterization of (+-)-1-(2,5-dimethoxy-4-[125I] iodophenyl)-2-aminopropane ([125I]DOI) binding to 5-HT2 and 5-HT1c receptors in rat brain.
The 5-HT2 (serotonin) receptor has traditionally been labeled with antagonist radioligands such as [3H]ketanserin and [3H]spiperone, which label both agonist high-affinity (guanyl nucleotide-sensitive) and agonist low-affinity (guanyl nucleotide-insensitive) states of this receptor. The hallucinogen 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) is an agonist which labels the high-affinity guanyl nucleotide-sensitive state of brain 5-HT2 receptors selectively. In the present study, conditions for autoradiographic visualization of (+/-)-[125I]DOI-labeled 5-HT2 receptors were optimized and binding to slide-mounted sections was characterized with respect to pharmacology, guanyl nucleotide sensitivity and anatomical distribution. In slide-mounted rat brain sections (+/-)-[125I]DOI binding was saturable, of high affinity (KD approximately 4 nM) and displayed a pharmacologic profile typical of 5-HT2 receptors. Consistent with coupling of 5-HT2 receptors in the high-affinity state to a guanyl nucleotide regulatory protein, [125I]DOI binding was inhibited by guanyl nucleotides but not by adenosine triphosphate. Patterns of autoradiographic distribution of [125I]DOI binding to 5-HT2 receptors were similar to those seen with [3H]ketanserin- and [125I]-lysergic acid diethylamide-labeled 5-HT2 receptors. However, the density of 5-HT2 receptors labeled by the agonist [125I]DOI was markedly lower (30-50%) than that labeled by the antagonist [3H]ketanserin. High densities of [125I]DOI labeling were present in olfactory bulb, anterior regions of cerebral cortex (layer IV), claustrum, caudate putamen, globus pallidus, ventral pallidum, islands of Calleja, mammillary nuclei and inferior olive. Binding in hippocampus, thalamus and hypothalamus was generally sparse. Of note, choroid plexus, a site rich in 5-HT1c receptors had a high density of [125I]DOI binding sites but [3H]ketanserin binding in this region was low. Studies in which [125I]DOI binding to 5-HT2 receptors was blocked with spiperone revealed persisting robust [125I]DOI binding in choroid plexus, which was guanyl nucleotide-sensitive and displayed a pharmacologic profile consistent with its binding to 5-HT1c receptors. These studies suggest that [125I]DOI may be useful as a radiolabel for visualizing the agonist high-affinity state of 5-HT2 receptors and for visualizing 5-HT1c receptors.