Naturally occurring anti-alpha-galactosyl antibodies: relationship to xenoreactive anti-alpha-galactosyl antibodies.
Antibodies produced by an individual without a known history of sensitization to the relevant antigen are called "natural" antibodies. Some natural antibodies, called xenoreactive antibodies, react with the cells of foreign species. Most xenoreactive antibodies in humans and higher primates bind to a nonreducing terminal galactose expressed by pigs and other lower mammals. Although human natural antibodies which bind to one or more of a variety of terminal alpha-galactosyl structures have been identified previously, the antigen recognized by anti-alpha-galactosyl antibodies on the cells of foreign species is thought to be exclusively Galalpha1-3Gal. Thus, anti-alpha-galactosyl antibodies which do not react with Galalpha1-3Gal are thought to be nonxenoreactive. Here, we identify natural antibodies in human serum which bind to Galalpha1-6Hexosepyrranosides but not Galalpha1-3Gal, indicating that these antibodies are not xenoreactive. Various lower mammals were found to have natural anti-Galalpha1-2Gal antibodies in their sera, suggesting that at least some anti-Galalpha1-2Gal antibodies might not be xenoreactive and indicating, surprisingly, that anti-alpha-galactosyl antibodies are much more phylogenetically disperse than previously known. Also surprising was the finding that some natural antibodies which bind to Galalpha1-3Gal in vitro do not bind to porcine xenografts. These studies show that naturally occurring anti-alpha-galactosyl antibodies in mammalian serum include antibodies with a greater variety of reactivities than previously thought, only some of which would bind to a porcine xenograft. Further, these studies show that the methods used to detect anti-alpha-galactosyl antibodies of relevance in xenotransplantation must be carefully evaluated to avoid detection of anti-alpha-galactosyl antibodies which would not bind to a porcine organ and which therefore are not involved in xenograft rejection.


FACTORS INFLUENCING ANTI-POLYRIBOSYLRIBITOL PHOSPHATE TITRES IN YOUNG NIGERIAN CHILDREN PRIMED WITH DTWP-HEPB-HIB VACCINE.
Recent research suggests that variation in vaccine-induced immune responses is influenced by genetic, nutritional, environmental, and vaccine-related factors, with significant vaccine design and programmatic policy implications. Haemophilus influenzae type b (Hib) Conjugate Vaccine (HCV) stimulates the production of antiPolyribosylribitol phosphate (anti-PRP) antibodies, which confer long-term protection against invasive Hib disease and nasopharyngeal colonization by Hib at titre levels ≥1μg/mL and ≥5μg/mL respectively. This study investigated the influence of these factors on the protective anti-PRP levels in children aged 6-23 months in Obi L.G.A. of Nasarawa State, Nigeria. The study was a cross-sectional, two-stage household-level cluster survey involving 267 children who had completed the E.P.I. schedule of HCV-containing DTwP-HepB-Hib. Validated questionnaires were used for enrolment and relevant clinical and laboratory evaluations including anti-PRP, ABO/Rhesus antigens, and Haemoglobin genotype assays were conducted. Regression analyses were performed using Stata to explore the correlation between sociodemographic/vaccine-related factors, nutritional status, genotype, ABO/Rhesus antigens, and protective anti-PRP titres. Bivariate analysis showed that age, breastfeeding practice, household size/under-five number, nutritional, socioeconomic, Measles/Yellow fever vaccination, and Rhesus statuses were significantly associated with anti-PRP titre. However, multivariate analysis revealed that age between 6-11 months (AOR=3.12,95%CI=1.15-8.50), households with less than three under-fives (AOR=2.33,95%CI=1.14-4.78), middle socioeconomic class (AOR=3.15,95%CI=1.42-6.98), wasting (AOR=2.27,95%CI=1.23-4.22) and Measles/Yellow fever vaccination (AOR=2.90,95%CI=1.38-6.07) were significantly correlated with protective anti-PRP titres. Results indicate that the family and socioeconomic milieu influence anti-PRP titre, and Measles/Yellow fever vaccines may have a beneficial non-specific effect on HCV-induced seroprotection in Nigerian children.


Clinical audit of adherence to hypertension treatment guideline and control rates in hospitals of different sizes in Thailand.
A clinical audit of hospitals in Thailand was conducted to assess compliance with the national hypertension treatment guidelines and determine hypertension control rates across facilities of different sizes. Stratified random sampling was used to select sixteen hospitals of different sizes from four provinces. These included community (<90 beds), large (90-120 beds), and provincial (>120 beds) hospitals. Among new cases, the audit determined whether (i) the recommended baseline laboratory assessment was completed, (ii) the initial choice of medication was appropriate based on the patient's cardiovascular risk, and (iii) patients received medication adjustments when indicated. The hypertension control rates at six months and at the last visit were recorded. Among the 1406 patients, about 75% had their baseline glucose and kidney function assessed. Nearly 30% (n = 425/1406) of patients were indicated for dual therapy but only 43% of them (n = 182/425) received this. During treatment, 28% (198/1406) required adjustments in medication but this was not done. The control of hypertension at six months after treatment initiation was 53% varying between 51% in community and 56% in large hospitals (p < .01). The hypertension control rate at last visit was 64% but varied between 59% in community hospitals and 71% in large hospitals (p < .01). Failure to adjust medication when required was associated with 30% decrease in the odds of hypertension control (OR 0.69, 95% CI 0. 50 to 0.90). Failure to comply with the treatment guidelines regarding adjustment of medication and lost to follow-up are possible target areas to improve hypertension control in Thailand.


Isolation and characterization of mevinolin resistant mutants of Saccharomyces cerevisiae.
Mutant of Saccharomyces cerevisiae resistant to mevinolin, a competitive inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme-A (HMGCoA) reductase (EC184.108.40.206) were isolated and one mutant (MV71) was extensively characterized. While growth of resistant strains in the presence of mevinolin was growth. Diploids produced by mutant/wild-type matings showed levels of mevinolin resistance which indicated incomplete dominance. Sterol synthesis in the presence of mevinolin was inhibited in strain MV71 but to a lesser degree than seen in the wild-type strain. All mevinolin resistant mutants also demonstrated a slight resistance to the antibiotic nystatin. The subcellular location of HMGCoA reductase activity in MV71 and the wild-type strain were determined and it was shown that yeast HMGCoA reductase is not regulated by a dephosphorylation mechanism as has been shown for mammalian reductases. In vivo and in vitro studies of strain MV71 and the wild-type indicated that mevinolin resistance did not result in changes in HNGCoA reductase activity as has been demonstrated in mammalian systems. Based on growth data, sterol analysis, and the lack of detection of HMGCoA reductase activity differences between strain MV71 and the wild-type, mevinolin resistance is concluded to result possibly from a mutation in HMG2, one of the two functional yeast HMGCoA reductase genes, which accounts for a minor (up to 17%) amount of total cellular reductase activity.


Patterns and predictors of health service utilization in adolescents with pain: comparison between a community and a clinical pain sample.
There is limited research describing the patterns of healthcare utilization in adolescents with chronic pain. This study describes healthcare utilization in a clinical chronic pain sample, and compares the patterns of service use of this group to a community sample with intermittent pain complaints. We also investigated demographic and clinical factors that predicted healthcare visits and medication use in the clinical sample. Data on 117 adolescents (aged 12-18; n = 59 clinical pain sample, n = 58 community) were collected. Caregivers and adolescents reported on sociodemographics, medical visits, current medications, pain, activity limitations, and depression. As hypothesized, the clinical pain sample had higher rates of healthcare consultation on all types of medical visits (general, specialty care, complementary medicine, mental health, OT/PT), and higher medication use compared to the community sample. Regression analyses revealed that higher annual income, greater pain frequency, and higher levels of caregiver-reported activity limitations were associated with a greater number of healthcare visits for the total sample. Within the clinical pain sample, higher pain frequency and greater activity limitations (caregiver report) predicted more specialty care visits. Additionally, higher income and greater levels of depressive symptoms predicted a higher number of prescribed medications. This study contributes to the limited available data on health service and medication use in a clinical chronic pain sample versus a community sample of adolescents. We also identify clinical factors (pain frequency, parent-reported activity limitations, depressive symptoms) and demographic factors (gender, income) associated with healthcare utilization.


Human IgE antibody-forming cells. Radio-resistant and radio-sensitive subpopulations.
In vitro IgE and antimite IgE antibody (IgE Ab) synthesis was investigated. Peripheral blood lymphocytes (PBL) from atopic patients depleted of E-rosetting T cells developed IgE and IgE Ab in the absence of pokeweed mitogen (PWM), and it was not significantly affected by addition of T cells of of PWM. 1,000 R irradiation decreased more than 50% of the IgE and IgE Ab-producing capacity in 2 of 8 cases, but the remainder were not significantly affected. Increase of the gamma-ray dose from 1,000 to 12,000 R did not result in more suppression. Radio-resistant as well as radio-sensitive subpopulations may exist in the PBL of atopic patients. The radio-sensitive component of IgE and IgE Ab formation was suppressed by PWM, while the radio-resistant component was not affected.


Complications and interventions associated with epidural analgesia for postoperative pain relief in a tertiary care hospital.
Epidural analgesia is one of the commonly used methods of postoperative pain control despite its associated complications. Early recognition and intervention is required to minimize the effect of these complications. Present audit was conducted to find out the incidence of complications and type of interventions required to change the outcome. The record of all the patients who had epidural catheter placed for postoperative pain management reviewed from the departmental acute pain management register. Parameters included level of insertion, drugs used, number of days infusion continued and complications like nausea, vomiting, motor block, sedation, dural tap, catheter pull out, hypotension and itching. In addition, the intervention done to manage these complications was also recorded. Total 1706 entries of epidurals were recorded in study period 2001 to 2007. The overall incidence of the complication was 26.6%. The common complications were motor block (13.4%), dural tap (1.2%), ineffective pain control (2.4%), accidental catheter pull outs (3.8%) and problems associated with the delivery system of drug (1.7%). The 12% of patients required intervention for the particular complications. The regime was discontinued in 28%, drug concentration changed in 21.5% while the other modes of pain management were used in 19% of patients. 0.9% of patients required epidural blood patch while 2% of patients required catheterization for urinary retention. This audit shows the importance of regular assessment and early intervention to manage epidural related complications in improving outcome.


Detection of CN Emission from (2060) Chiron.
In the past decade there has been a gradual, but substantial change in our understanding of the physical nature of (2060) Chiron. Once thought to be the first known member of a population of asteroids orbiting between Saturn and Uranus, Chiron is now generally regarded as the largest known comet. The detection of CN emission in the spectrum of Chiron is reported. Not only do these observations underscore the cometary nature of Chiron, but, at a heliocentric distance exceeding 11 astronomical units, represent the most distant detection yet of a neutral gas species common in comets. These results are consistent with the outgassing from Chiron being primarily driven by isolated outbursts of CO(2) from a very small fraction of Chiron's surface. These may be indicative of primordial inhomogeneities.


The role of radiotherapy in the management of carcinoma in situ of the glottic larynx.
Carcinoma in situ of the glottic larynx is a rare malignancy, comprising only 1% to 2% of laryngeal biopsy. The management of these lesions remains controversial. In this article, the authors present results and analysis of the management of 20 patients having these lesions treated by radiotherapy. A total of 20 patients who had carcinoma in situ of the glottis were treated with curative intent with radiotherapy at the Veterans Administration Medical Center, Minneapolis, Minnesota, U.S.A. from November 1972 through March 1993. Before radiotherapy, eight patients had only biopsies of the glottic larynx, five had one stripping procedure, and seven patients had two or three stripping procedures. Of the 20 patients, 19 are available for retrospective analysis, with a minimum follow-up of 4 years and a median follow-up of 7.3 years. Treatment was given to all patients by megavoltage units (cobalt 60, 2; 4-mV linear accelerator, 18). Patients were treated using bilateral opposed wedged 6-cm x 6-cm fields, with a dose of 1.75 Gy per fraction to a total median dose of 68.4 Gy in 40 fractions over 56 elapsed treatment days. The Kaplan-Meier method was used for survival analysis. The 4-year disease-free survival was 95% after irradiation. The actuarial disease-free survival for 5 and 10 years was 95%. Surgical salvage failed in one patient who had a laryngectomy for recurrent invasive squamous cell carcinoma at 34 months after radiotherapy. Two patients developed severe shortness of breath because of laryngeal edema, which required tracheostomy. Sixteen patients reported subjective significant improvement of their voice quality, and four reported no change. Radiotherapy is an excellent choice for patients who have recurrent carcinoma in situ after undergoing stripping procedures or for those patients who live too far from a medical facility to allow close follow-up and repetitive surgical procedures. These results are comparable to those of other investigators who used radiotherapy with higher dose per fraction.


Increased resistin gene and protein expression in human abdominal adipose tissue.
Resistin, a novel signalling molecule isolated in mice has been suggested to be the putative hormone thought to link obesity with type 2 diabetes. The aim of this study was to examine resistin protein expression in human adipose tissue depots and resistin secretion in isolated adipose cells, to characterize resistin expression in human adipose tissue. Both resistin mRNA and protein expression were analysed from human adipose tissue (n = 5 adipose tissue samples: abdominal subcutaneous (Sc) n = 19, abdominal omental adipose tissue (Om) n = 10, thigh n = 9, breast n = 7). Resistin protein expression levels were similar in both the abdominal Sc and Om adipose tissue depots, and expression in abdominal fat depots were increased compared with thigh (p < 0.001) and breast tissue depots (p < 0.001). These findings were consistent with the mRNA expression studies. Resistin was secreted from both pre-adipocytes and adipocytes cells. Thus, resistin resides within isolated adipose cells and is expressed and secreted in human adipose tissue. In conclusion, this study confirms the expression of resistin in human adipose tissue and increased expression in abdominal fat, this suggests a potential role in linking central obesity to type 2 diabetes and/or cardiovascular disease.


An allergen-free antirabies vaccine.
Studies on the development of encephalitogenic activity in the cerebral tissue of various animals (rabbits, rats, mice and sheep) showed that the brains of albino rats did not become encephalitogenic until after the 18th day of life, which is later than in any of the other animals studied. On the basis of this finding, a method was developed for the preparation of an entirely allergen-free, non-encephalitogenic antirabies vaccine using the brains of suckling rats. The phenolized vaccine, both in liquid and in lyophilized form, consistently gave high antigenic titres when tested in animals and produced a good increase in virus-neutralizing antibodies in man. It also showed a low thromboplastic activity. More than 1500 litres of this vaccine have since been manufactured on an industrial scale and more than 9500 persons vaccinated. General reactions have been far less frequent than with the conventional Fermi vaccine and no neuroparalytic accidents or shock reactions have been reported. Vaccination with the allergen-free vaccine has proceeded smoothly even in persons considered to be especially at risk owing to previous vaccination with antirabies vaccine or a history of trauma or disease of the central nervous system.


A polymorphism in the histone deacetylase 1 gene is associated with the response to corticosteroids in asthmatics.
Recent investigations suggest that histone deacetylase 1 (HDAC1) and HDAC2 may be target molecules to predict therapeutic responses to corticosteroids. We evaluated the effects of variation in HDAC1 and HDAC2 on the response to corticosteroids in asthmatics. Two single nucleotide polymorphisms (SNPs) were selected after resequencing HDAC1 and HDAC2. For the first analysis, we evaluated the association between those SNPs and asthma severity in 477 asthmatics. For the second analysis, we evaluated the effects of these SNPs on lung function improvements in response to corticosteroid treatment in 35 independent adult asthmatics and 70 childhood asthmatics. We found that one SNP in HDAC1 (rs1741981) was significantly related to asthma severity in a recessive model (corrected p = 0.036). Adult asthmatics who were homozygous for the minor allele of rs1741981 showed significantly lower % forced expiratory volume in 1 second (%FEV1) increases in response to systemic corticosteroids treatment compared with the heterozygotes or those homozygous for the major allele (12.7% ± 7.2% vs. 37.4% ± 33.7%, p = 0.018). Similarly, childhood asthmatics who were homozygous for the minor allele of rs1741981 showed significantly lower %FEV1 increases in response to inhaled corticosteroid treatment compared with the heterozygotes or those homozygous for the major allele (14.1% ± 5.9% vs. 19.4% ± 8.9%, p = 0.035). The present study demonstrated that rs1741981 in HDAC1 was significantly associated with the response to corticosteroid treatment in asthmatics.


Thinking about a limited future enhances the positivity of younger and older adults' recall: Support for socioemotional selectivity theory.
Compared with younger adults, older adults have a relative preference to attend to and remember positive over negative information. This is known as the "positivity effect," and researchers have typically evoked socioemotional selectivity theory to explain it. According to socioemotional selectivity theory, as people get older they begin to perceive their time left in life as more limited. These reduced time horizons prompt older adults to prioritize achieving emotional gratification and thus exhibit increased positivity in attention and recall. Although this is the most commonly cited explanation of the positivity effect, there is currently a lack of clear experimental evidence demonstrating a link between time horizons and positivity. The goal of the current research was to address this issue. In two separate experiments, we asked participants to complete a writing activity, which directed them to think of time as being either limited or expansive (Experiments 1 and 2) or did not orient them to think about time in a particular manner (Experiment 2). Participants were then shown a series of emotional pictures, which they subsequently tried to recall. Results from both studies showed that regardless of chronological age, thinking about a limited future enhanced the relative positivity of participants' recall. Furthermore, the results of Experiment 2 showed that this effect was not driven by changes in mood. Thus, the fact that older adults' recall is typically more positive than younger adults' recall may index naturally shifting time horizons and goals with age.


Body composition of two human cadavers by neutron activation and chemical analysis.
In vivo neutron activation analysis (NAA) is currently used to measure body composition in metabolic and nutritional studies in many clinical situations, but has not previously been validated by comparison with chemical analysis of human cadavers. Total body nitrogen (TBN) and chlorine (TBCl) were measured in two human cadavers by NAA before homogenization and chemical analysis (CHEM) after (cadaver 1: TBN, 1.47 NAA, 1.51 CHEM; TBCl, 0.144 NAA, 0.147 CHEM; cadaver 2: TBN, 0.576 NAA, 0.572 CHEM; TBCl, 0.0227 NAA, 0.0250 CHEM). The homogenates were also analyzed by NAA, and no significant differences were found, indicating that the effects of elemental inhomogeneity on the measurement of TBN and TBCl are insignificant. Total body water, fat, protein, minerals, and carbohydrates were measured chemically for each cadaver and compared with estimates for these compartments obtained from a body composition model, which when used in vivo involves NAA and tritium dilution. The agreement found justifies the use of the model for the measurement of changes in total body protein, water, and fat in sequential studies in groups of patients.


Skeletal muscle-specific inducible AMPKα1/α2 knockout mice develop muscle weakness, glycogen depletion, and fibrosis that persists during disuse atrophy.
The 5' adenosine monophosphate-activated protein kinase (AMPK) is an important skeletal muscle regulator implicated as a possible therapeutic target to ameliorate the local undesired deconditioning of disuse atrophy. However, the muscle-specific role of AMPK in regulating muscle function, fibrosis, and transcriptional reprogramming during physical disuse are unknown. The purpose of this study was to determine how the absence of both catalytic subunits of AMPK in skeletal muscle influence muscle force production, collagen deposition, and the transcriptional landscape. We generated skeletal muscle-specific tamoxifen inducible AMPKα1/α2 knock out (AMPKα-/-) mice that underwent 14 days of hindlimb unloading (HU) or remained ambulatory for 14 days (AMB). We found that AMPKα-/- during ambulatory conditions altered body weight and myofiber size, decreased muscle function, depleted glycogen stores and TBC1 domain family member 1 (TBC1D1) phosphorylation, increased collagen deposition, and altered transcriptional pathways. Primarily pathways related to cellular senescence, and mitochondrial biogenesis and function were influenced by the absence of AMPKα. The effects of AMPKα-/- persisted, but were not worsened, following hindlimb unloading. Together, we report that AMPKα is necessary to maintain skeletal muscle quality.


[Systems of measurement of body temperature].
Measuring body temperature is a common practice in the area of care. There are various measuring instruments, ranging from simple glass thermometers to sophisticated electronics that allow measurement in different body sites. This article presents the advantages and disadvantages of different thermometers are currently on the market.


Using Opioids With Surgical Patients: Nurses' Attitudes and Experiences.
Opioids such as morphine are effective analgesics and have been recognized worldwide for many years; yet, they are underutilized. The study explores the attitudes and experiences relating to opioids, in general, and morphine, in particular, among Jordanian surgical nurses. The Opioids Attitudes Scale was used. A total of 123 questionnaires were distributed, and 120 were returned, achieving a response rate of 96%. Focus group discussions (n = 4) were conducted with surgical nurses (n = 34). The majority of nurses believe that the addiction is the most serious side effects of opioids. Qualitative analysis revealed 2 major themes. The first theme was referred to as "not being in the same boat," highlighting a lack of teamwork, and comprised 2 subthemes: blame culture and physicians versus nurses. The second "morphine as the last on the list" was also made up of 2 subthemes: the lack of confidence and the fear of legal persecution. Nurses showed negative attitudes and misconceptions about opioids and morphine use within a fragmented surgical unit culture. Therefore, serious efforts must be made to create and sustain an effective unit culture reform and communications path from patient to nurse and doctor.


Effect of community-based group exercises combined with action observation on physical and cognitive performance in older adults during the Covid-19 pandemic: A randomized controlled trial.
This study investigates the impact of community-based exercises with action observation therapy (AOT) on the physical and cognitive performance of older adults experiencing social isolation during the COVID-19 pandemic. One hundred participants aged 65-80 years were randomly divided into two groups: the AOT group, which engaged in balance, strengthening, and mobility exercises guided by 15-minute action observation videos before a 45-minute exercise session, and the control group, which performed the same exercises without action observation. Both groups underwent three sessions per week for eight weeks (24 sessions in total). The assessment tools used in this study included the following: For evaluating mobility and fall risk in older adults, the Timed Up-and-Go (TUG) Test was employed. To assess functional strength of lower extremities, balance, and fall risk, the Five Times Sit-to-Stand (5XSST) Test was administered. Balance and gait were measured using the Tinetti Balance and Gait Assessment (TBGA), utilizing the Tinetti Scale. Individuals' confidence in performing daily activities without falling or losing balance was assessed using the Activities-Specific Balance Confidence Scale (ABC). Furthermore, cognitive functions across multiple domains, including attention-concentration, executive function, memory, language, visual construction skills, abstract thinking, calculation, and orientation, were evaluated using the Montreal Cognitive Assessment (MoCA) Tests. Results revealed significant improvements in both groups. Group I, which received Action Observation Therapy (AOT) in addition to exercise, demonstrated superior outcomes in the 5XSit-to-Stand test (Δ = -1.92, p < 0.0001, Cohen's d = 0.77), Tinetti Balance and Gait Scale (Balance: Δ = 2.77, p < 0.0001, Cohen's d = 0.91), and Timed Up and Go test (Δ = -1.98, p < 0.0005, Cohen's d = 0.83). On the other hand, Group II, which received exercise only, exhibited substantial gains in the Tinetti Balance and Gait Scale (Walking: Δ = 0.52, p < 0.01, Cohen's d = 0.27) and Activity-Specific Balance Confidence Scale (Δ = 5.77, p < 0.0001, Cohen's d = 0.26). These findings underscore the effectiveness of AOT-enhanced community-based exercises in enhancing both physical and cognitive performance among older adults facing social isolation during the pandemic, with Group I (AOT + exercise) showing particularly promising results. This study was registered with ClinicalTrials.gov Identifier: NCT04759690, ClinicalTrials Protocol ID: p3957ghb.


Chloroplast ribonuclease P does not utilize the ribozyme-type pre-tRNA cleavage mechanism.
The transfer RNA 5' maturation enzyme RNase P has been characterized in Bacteria, Archaea, and Eukarya. The purified enzyme from all three kingdoms is a ribonucleoprotein containing an essential RNA subunit; indeed, the RNA subunit of bacterial RNase P RNA is the sole catalytic component. In contrast, the RNase P activity isolated from spinach chloroplasts lacks an RNA component and appears to function as a catalytic protein. Nonetheless, the chloroplast enzyme recognizes a pre-tRNA substrate for E. coli RNase P and cleaves it as efficiently and precisely as does the bacterial enzyme. To ascertain whether there are differences in catalytic mechanism between an all-RNA and an all-protein RNase P, we took advantage of the fact that phosphodiester bond selection and hydrolysis by the E. coli RNase P ribozyme is directed by a Mg2+ ion coordinated to the nonbridging pro-Rp oxygen of the scissile bond, and is blocked by sulfur replacement of this oxygen. We therefore tested the ability of the chloroplast enzyme to process a precursor tRNA containing this sulfur substitution. Partially purified RNase P from spinach chloroplasts can accurately and efficiently process phosphorothioate-substituted pre-tRNAs; cleavage occurs exclusively at the thio-containing scissile bond. The enzymatic throughput is fivefold slower, consistent with a general chemical effect of the phosphorothioate substitution rather than with a metal coordination deficiency. The chloroplast RNase P reaction mechanism therefore does not involve a catalytic Mg2+ bonded to the pro-Rp phosphate oxygen, and hence is distinct from the mechanism of the bacterial ribozyme RNase P.


Genomic characterization of the first insectivoran papillomavirus reveals an unusually long, second non-coding region and indicates a close relationship to Betapapillomavirus.
Knowledge about biological diversity is the prerequisite to reliably reconstruct the evolution of pathogens such as papillomaviruses (PV). However, complete genomes of non-human PV have only been cloned and sequenced from 8 out of 18 orders within the Placentalia, although the host-specific variety of PV is considered much larger. We isolated and sequenced the complete genome of the first insectivoran PV type from hair follicle cells of the European hedgehog (Erinaceus europaeus), designated EHPV. We conducted phylogenetic analyses (maximum-likelihood criterion and Bayesian inference) with the genomic information of a systematically representative set of 67 PV types including EHPV. As inferred from amino acid sequence data of the separate genes E1, E2 and L1 as well as of the gene combination E6-E7-E1-E2-L1, EHPV clustered within the beta-gamma-pi-Xi-PV supertaxon and constituted the closest relative of genus Betapapillomavirus infecting primates. Beside the typical organization of the PV genome, EHPV exhibited a 1172 bp, non-coding region between the E2 and the L2 open reading frames. This trait has been previously described for the only distantly related Lambdapapillomavirus, but a common evolutionary origin of both non-coding regions is unlikely. Our results underscore the modular organization of the PV genome and the complex natural history of PV.


Expression of osteopontin correlates with portal biliary proliferation and fibrosis in biliary atresia.
The acquired or perinatal form of biliary atresia is a Th1 fibro-inflammatory disease affecting both the extrahepatic and intrahepatic bile ducts. Osteopontin (OPN) is a Th1 cytokine implicated in several fibro-inflammatory and autoimmune diseases. We examined the expression of OPN in acquired biliary atresia in comparison to normal liver and several pediatric cholestatic liver diseases. We also assessed OPN expression by cultured human bile duct epithelial cells. We found that liver OPN mRNA and protein expression were significantly increased in biliary atresia versus normal and other cholestatic diseases. OPN expression in biliary atresia was localized to epithelium of proliferating biliary structures (ductules and/or ducts) and bile plugs contained therein. No portal biliary OPN expression could be demonstrated in normal liver, syndromic biliary atresia, biliary obstruction not due to biliary atresia, and idiopathic neonatal hepatitis. OPN expression by human bile duct epithelial cells in culture was responsive to IL-2 and TNF-alpha. Our results demonstrate an up-regulation of OPN expression by interlobular biliary epithelium in biliary atresia, which correlates with biliary proliferation and portal fibrosis. These findings suggest a role for OPN in the pathogenesis of biliary atresia.


Predictors of Emerging Suicide Death Among Military Personnel on Social Media Networks.
Suicide is a leading cause of death in the United States and is the second leading cause of death in the U.S. military. Previous research suggests that data obtained from social media networks may provide important clues for identifying at-risk individuals. To test this possibility, the social media profiles from 315 military personnel who died by suicide (n = 157) or other causes (n = 158) were coded for the presence of stressful life situations (i.e., triggers), somatic complaints or health issues (i.e., physical), maladaptive or avoidant coping strategies (i.e., behaviors), negative mood states (i.e., emotion), and/or negative cognitive appraisals (cognition). Content codes were subsequently analyzed using multilevel models from a dynamical systems perspective to identify temporal change processes characteristic of suicide death. Results identified temporal sequences unique to suicide, notably social media posts about triggers followed by more posts about cognitions, posts about cognitions followed by more posts about triggers, and posts about behaviors followed by fewer posts about cognitions. Results suggest that certain sequences in social media content may predict cause of death and provide an estimate of when a social media user is likely to die by suicide.


Prophylactic feeding tubes for patients with locally advanced head-and-neck cancer undergoing combined chemotherapy and radiotherapy-systematic review and recommendations for clinical practice.
This work aimed to determine the benefits and risks of prophylactic feeding tubes for adult patients with squamous cell carcinoma of the head and neck who receive combined chemotherapy and radiotherapy with curative intent and to make recommendations on the use of prophylactic feeding tubes and the provision of adequate nutrition to this patient population. A national multidisciplinary panel conducted a systematic review of the evidence and formulated recommendations to guide clinical decision-making. The draft evidence summary and recommendations were distributed to clinicians across Canada for their input. No randomized controlled trials have directly addressed this question. Evidence from studies in the target population was limited to seven descriptive studies: two with control groups (one prospective, one retrospective) and five without control groups. Results from ten controlled studies in patients treated with radiotherapy alone were also reviewed. The available evidence was insufficient to draw definitive conclusions about the effectiveness of prophylactic feeding tubes in the target patient population or to support an evidence-based practice guideline. After review of the evidence, of guidelines from other groups, and of current clinical practice in Canada, the multidisciplinary panel made consensus-based recommendations regarding comprehensive interdisciplinary clinical care before, during, and after cancer treatment. The recommendations are based on the expert opinion of the panel members and on their understanding of best clinical practice.


Laparoscopic Harvest of the Rectus Abdominis for Perineal Reconstruction.
The rectus abdominis is a workhorse flap for perineal reconstruction, in particular after abdominoperineal resection (APR). Laparoscopic and robotic techniques for abdominoperineal surgery are becoming more common. The open harvest of the rectus abdominis negates the advantages of these minimally invasive approaches. (Sentence relating to advantages of laparoscopic rectus deleted here.) We present our early experience with laparoscopic harvest of the rectus muscle for perineal reconstruction. Three laparoscopic unilateral rectus abdominis muscle harvests were performed for perineal reconstruction following minimally invasive colorectal and urological procedures. The 2 patients who underwent APR also had planned external perineal skin reconstruction with local flaps. (Sentence deleted here to shorten abstract.) All rectus muscle harvests were performed laparoscopically. Two were for perineal reconstruction following laparoscopic APR, and 1 was for anterior vaginal wall reconstruction. This was done with 4 ports positioned on the contralateral abdomen. The average laparoscopic harvest time was 60-90 minutes. The rectus muscle remained viable in all cases. One patient developed partial necrosis of a posterior thigh fasciocutaneous flap after cancer recurrence. There were no pelvic abscesses, or abdominal wall hernias. Laparoscopic harvest of the rectus appears to be a cost-effective, reliable, and reproducible procedure for perineal with minimal donor-site morbidity. Larger clinical studies are needed to further establish the efficacy and advantages of the laparoscopic rectus for perineal reconstruction.


The effects of mitral regurgitation alone are sufficient for leaflet remodeling.
Although chronic mitral regurgitation results in adverse left ventricular remodeling, its effect on the mitral valve leaflets per se is unknown. In a chronic ovine model, we tested whether isolated mitral regurgitation alone was sufficient to remodel the anterior mitral leaflet. Twenty-nine sheep were randomized to either control (CTRL, n=11) or experimental (HOLE, n=18) groups. In HOLE, a 2.8- to 4.8-mm diameter hole was punched in the middle scallop of the posterior mitral leaflet to create "pure" mitral regurgitation. At 12 weeks, the anterior mitral leaflet was analyzed immunohistochemically to assess markers of collagen and elastin synthesis as well as matrix metalloproteinases and proteoglycans. A semiquantitative grading scale for characteristics such as intensity and delineation of stain between layers was used to quantify differences between HOLE and CTRL specimens across the heterogeneous leaflet structure. At 12 weeks, mitral regurgitation grade was greater in HOLE versus CTRL (3.0+/-0.8 versus 0.4+/-0.4, P<0.001). In HOLE anterior mitral leaflet, saffron-staining collagen (Movat) decreased, consistent with an increase in matrix metalloproteases throughout the leaflet. Type III collagen expression was increased in the midleaflet and free edge and expression of prolyl-4-hydroxylase (indicating collagen synthesis) was increased in the spongiosa layer. The proteoglycan decorin, also involved in collagen fibrillogenesis, was increased compared with CTRL (all P</=0.05). In HOLE anterior mitral leaflet, the increased expression of proteins related to collagen synthesis and matrix degradation suggests active matrix turnover. These are the first observations showing that regurgitation alone can stimulate mitral leaflet remodeling. Such leaflet remodeling needs to be considered in reparative surgical techniques.


[Gastrointestinal stroma tumor].
Gastrointestinal stromal tumor (GIST) represents less than 3% of gastrointestinal malignancies. However, it is the most common mesenchymal tumor of the digestive tract. GIST is characterized by the expression tyrosine kinase CD117, which differentiates it from other mesenchymal tumors such as leiomyomas, leio-miosarcomas, leiomyoblastoma and neurogenic tumors that do not express this protein. 70-80% of the GIST are benign and located mostly in the stomach and small intestine (> 90%).They can also arise from any portion of the digestive tract, mesentery, omentum and retroperitoneum. Malignant GISTs are usually large (> 5 cm), with a high mitotic index, and it can metastasize to the liver and peritoneum. The treatment is surgical resection.Good results have been reported with tyrosine kinase inhibitor STI571. The treatment is the surgical resection; in cases of surgical resection tumors cannot do it, radiotherapy and chemotherapy is carried out. A 43 year-old patient is presented, admitted to present pain in the epigastrium, melena in an occasion. The ecography, CT scan, and laparoscopic view, showed a tumor in the second portion of the duodenum, approximately 10 cm size. Whipple's operation was carried out (cephalic pancreatoduodenectomy) with conservation of the pylorus (Traverso-Longmire), resecting the entirely tumor. Final results of pathological anatomy informed: fusocelular tumor of the gastrointestinal estroma (GIST of duodenal wall), with high potential of malignancy. Size of the tumor 9,5 cm, mitotic index of 9 for 50 HPF with high positive for CD117, CD34. Two years later of the intervention he presents a good evolution.


Esophageal manometry in systemic sclerosis: findings and association with clinical manifestations.
Systemic sclerosis (SSC) is an autoimmune disorder that affects several organs of unknown etiology, characterized by vascular damage and fibrosis of the skin and organs. Among the organs involved are the esophagus and the lung. To relate the profile of changes in esophageal electromanometry (EM), the profile of skin involvement, interstitial pneumopathy (ILD), and esophageal symptoms in SSC patients. This is an observational, cross-sectional study carried out at the SSC outpatient clinic of the Hospital de Clínicas of the Federal University of Uberlândia. After approval by the Ethics Committee and signed the terms of consent, 50 patients were initially enrolled, from 04/12/2014 to 06/25/2015. They were submitted to the usual investigations according to the clinical picture. The statistical analysis was descriptive in percentage, means, and standard deviation. The Chi-square test was used to evaluate the relationship between EM, high-resolution tomography, and esophageal symptoms. 91.9% of the patients had some manometric alterations. 37.8% had involvement of the esophageal body and lower esophageal sphincter. 37.8% had ILD. 24.3% presented the diffuse form of SSC. No association was found between manometric changes and clinical manifestations (cutaneous, pulmonary, and gastrointestinal symptoms). The present study confirms that esophageal motility alterations detected by EM are frequent in SSC patients, but may not be related to cutaneous extension involvement, the presence of ILD, or the gastrointestinal complaints of patients.


Synthesis and photophysical properties of stilbeneoctasilsesquioxanes. Emission behavior coupled with theoretical modeling studies suggest a 3-D excited state involving the silica core.
A set of stilbene-substituted octasilicates [p-RStil(x)Ph(8-x)SiO(1.5)](8) (R = H, Me, MeO, Cl, NMe(2) and x = 5.3-8) and [o-MeStilSiO(1.5)](8) were prepared. Model compounds were also prepared including the corner and half cages: [p-MeStilSi(OEt)(3)], [p-Me(2)NStilSi(OSiMe(3))(3)], and [p-Me(2)NStilSi(O)(OSiMe)](4). These compounds were characterized by MALDI-TOF, TGA, FTIR, and (1)H NMR techniques. Their photophysical properties were characterized by UV-vis, two-photon absorption, and cathodoluminescence spectroscopy (on solid powders), including studies on the effects of solvent polarity and changes in concentration. These molecules are typically soluble, easily purified, and robust, showing T(d(5%)) > 400 degrees C in air. The full and partial cages all show UV-vis absorption spectra (in THF) identical to the spectrum of trans-stilbene, except for [o-MeStilSiO(1.5)](8), which exhibits an absorption spectrum blue-shifted from trans-stilbene. However, the partial cages show emissions that are red-shifted by approximately 20 nm, as found for stilbene-siloxane macrocycles, suggesting some interaction of the silicon center(s) with the stilbene pi* orbital in both the corner and half cages. In contrast, the emission spectra of the full cages show red-shifts of 60-100 nm. These large red-shifts are supported by density functional theoretical calculations and proposed to result from interactions of the stilbene pi* orbitals with a LUMO centered within the cage that has 4A(1) symmetry and involves contributions from all Si and oxygen atoms and the organic substituents. Given that this LUMO has 3-D symmetry, it appears that all of the stilbene units interact in the excited state, consistent with theoretical results, which show an increased red-shift with an increase in the functionalization of a single corner to functionalization of all eight corners with stilbene. In the case of the Me(2)N- derivatives, this interaction is primarily a charge-transfer interaction, as witnessed by the influence of solvent polarity on the emission behavior. More importantly, the two-photon absorption behavior is 2-3 times greater on a per p-Me(2)Nstilbene basis for the full cage than for the corner or half cages. Similar observations were made for p-NH(2)stilbenevinyl(8)OS cages, where the greater conjugation lengths led to even greater red-shifts (120 nm) and two-photon absorption cross sections. Cathodoluminescence studies done on [p-MeStilSiO(1.5)](8) or [p-MeStilOS](8) powders exhibit essentially the same emissions as seen in solution at high dilution. Given that only the emissions are greatly red-shifted in these molecules, whereas the ground-state UV-vis absorptions are not changed from trans-stilbene, except for the ortho derivative, which is blue-shifted 10 nm. It appears that the interactions are only in the excited state. Theoretical results show that the HOMO and LUMO states are always the pi and pi* states on the stilbene, which show very weak shifts with increasing degrees of functionalization, consistent with the small changes in the UV-vis spectra. The band gap between the lowest unoccupied 4a1 symmetry core state localized inside the silsesquioxane cage and the highest occupied state (pi state on stilbene), however, is markedly decreased as the number of stilbene functional groups is increased. This is consistent with the significant red-shifts in the emission spectra. The results suggest that the emission occurs from the 4a1 state localized on the cage. Moreover, for the compounds [p-RStil(6-7)Ph(2-1)OS](8), the emissions are blue-shifted compared to those of the fully substituted compounds, suggesting the molecular symmetry is reduced (from cubic), thereby reducing the potential for 3-D delocalization and raising the energy of the LUMO. The implications are that these octafunctional molecules exhibit some form of 3-D interaction in the excited state that might permit their use as molecular transistors as well as for energy collection and dispersion as molecular antennas, for example, and for nonlinear optical applications.


RBR3, a member of the retinoblastoma-related family from maize, is regulated by the RBR1/E2F pathway.
Retinoblastoma-related (RBR) proteins regulate cell division in higher eukaryotes by controlling the adenovirus E2 promoter binding factor (E2F)/dimerization partner (DP) family of transcription factors that regulate expression of many genes involved in cell-cycle progression. We identified a previously undescribed member of the maize RBR family, RBR3, which has the characteristic structure and binding activities of pocket proteins, where interaction depends on a LxCxE motif in the partner proteins and a critical cysteine within the B pocket domain. Like other RBR proteins, RBR3 appears to be regulated by phosphorylation mediated by cyclin-dependent kinases. During endosperm development, RBR3 expression is restricted to the mitotic stage preceding the onset of endoreduplication. This finding suggests a role distinct from RBR1, which is constitutively expressed. Two sites in the RBR3 promoter bind to complexes containing maize E2F1 and DP proteins. Expression of wheat dwarf virus RepA protein, which blocks RBR1 activity and stimulates cell proliferation, dramatically up-regulates RBR3, but not RBR1, RNA in embryogenic maize calli. The results indicate that RBR3 expression is controlled by RBR1 through the activity of E2F/DP and that RBR3 is the maize equivalent of mammalian p107. Furthermore, maize and related grasses might have evolved a compensatory mechanism among distinct types of RBR proteins to ensure robust control of pocket protein activity.


Bedside estimation of the inspiratory work of breathing during mechanical ventilation.
The work of chest inflation, WI, is a primary determinant of the need for ventilatory support and an integrative index of elastic and resistive impedance. Although the mechanical work performed by a ventilator in moving gas into the passive chest (WI = integral of PV dt) can be determined by measuring the area enclosed by a display of airway pressure (P) against delivered volume (V), the instrumentation required is not routinely available at the bedside. Under conditions of constant flow, however, inspiratory time represents an analog of delivered volume, and airway pressure can be recorded easily by equipment normally employed to monitor pulmonary vascular pressures. We reasoned that the area beneath the airway pressure vs time tracing should accurately reflect WI for unassisted breaths delivered by the ventilator at constant flow. We computed estimates of WI from simultaneous pressure-volume (PV) and pressure-time (PT) plots during square-wave inflation in 20 acutely ill patients. Ventilator settings were varied over the usual clinical range for tidal volume (10 to 15 ml/kg) and inspiratory flow (40 to 80 L/min). PV and PT estimates agreed closely; across the four setting combinations tested, the difference between PV and PT estimates averaged 2.4 +/- 5.6 percent (means +/- SD, r = 0.99). Furthermore, the reproducible geometric configuration of the curves generated allowed accurate estimation of WI from routine beside observations of tidal volume and peak dynamic and static inflation pressures, without the need for specialized equipment or area measurement. Such simplified estimates could serve in clinical practice to gauge the ventilatory workload and to monitor changes in respiratory impedance.


[Resistance to chemotherapeutic agents in the treatment of cancer. Emphasizing the multiresistant phenotype].
Despite considerable efforts, rather limited progress has been achieved in the treatment of disseminated cancer with chemotherapeutic agents during the last decade. Most tumours, especially those of epithelial origin, are more or less resistant to cytostatics right from initiation of therapy. Other tumours, on the other hand, like leukemias and lymphomas, are highly responsive initially but may become resistant during the course of therapy (secondary resistance). This type of resistance is due to random mutations in the malignant cells. Several mechanisms of cellular resistance have been described, the most important being characterized by simultaneous resistance to several unrelated chemotherapeutic agents (pleiotropic drug resistance or multidrug resistance). This mechanism is due to a membrane-associated efflux pump which transports the cytostatic agents out of the cells. The clinical importance of multidrug resistance and the possibility of inhibiting the function of the pump by pharmacological agents are currently being examined.


Bleeding profile associated with 1-year use of the segesterone acetate/ethinyl estradiol contraceptive vaginal system: pooled analysis from Phase 3 trials.
To describe bleeding patterns among users of the segesterone acetate (SA) and ethinyl estradiol (EE) contraceptive vaginal system (CVS), and identify factors associated with unscheduled bleeding/spotting (B/S). We pooled results from two multicenter, single-arm, open-label, pivotal, phase 3 studies of the SA/EE CVS conducted in 17 US and 7 international sites. Participants (age 18-40 years; BMI ≤29 kg/m2) followed a 21/7-day in/out schedule of CVS use for up to 13 cycles and recorded vaginal bleeding daily in paper diaries. Scheduled and unscheduled B/S were summarized by cycle. We used multiple logistic regression to identify factors associated with unscheduled bleeding/spotting, based on the first 4 cycles only. Analysis included data from 2070 participants (16,408 cycles). Ninety-eight percent documented scheduled B/S [mean (SD): 4.9 (1.1) days/cycle)]. Absence of scheduled B/S was 5-8% of women/cycle. Unscheduled B/S ranged from 13.2% to 21.7% of women per cycle. Few women (1.8%) discontinued prematurely due to unacceptable bleeding. Black women were more likely to report unscheduled B/S than White women [Adjusted odds ratio (AOR) = 1.49, 95% confidence interval (CI) = 1.14-1.94]. Women with fewer years of schooling [<high school (AOR=0.62, 95% CI=0.43-0.90); high school graduate (AOR: 0.76, 95% CI=0.60-0.97)] were less likely to report any episode of unscheduled B/S compared to college graduates. Participants using the SA/EE CVS up to 13 cycles reported good cycle control. Discontinuation due to unacceptable bleeding was very low. Further research into demographic/other differences with reported unscheduled bleeding is warranted. Since good cycle control is a key factor influencing contraceptive selection, adherence and continuation of combined hormonal contraceptives, the favorable bleeding profiles experienced by women during the SA/EE CVS clinical trials provide reassuring information for prospective users.


Continuous arteriovenous and intermittent hemofiltration in renal failure.
The clinical applications of continuous arteriovenous and intermittent hemofiltration (CAVH and IHF) have changed the concept of renal failure treatment which was previously understood to be hemodialysis (HD). To perform such treatments a reliable vascular access is a vital priority. Unfortunately, multiple vascular access problems are frequently seen among chronic HD or HF patients despite the reliability of the conventional arteriovenous fistula. In this study a needleless prosthetic vascular access device (Hemasite) has been tried (32 devices in 28 HD/HF patients) as an alternative solution. The five-year follow-up showed that the Hemasite device offered an immediate and reliable vascular access with adequate blood flow. The one-year cumulative survival rate was 55%. Thrombosis and infection were the two main causes for the implant loss. On the other hand, evaluation of our experience with acute vascular access in acute renal failure (ARF) in 76 patients showed that the most commonly used one was the Buselmeier shunt (75%), followed by the femoral catheters (23%) for femoral vessels catheterization, and the Scribner shunt (2%). The Buselmeier shunt gave adequate blood flow. It was safe and easy to manipulate in case of trouble during treatment (e.g. clotting). The outcome of CAVH as a first choice treatment modality for ARF in our centre, since 1982, was evaluated in 40 critically ill intensive care patients during the period July 1987-December 1988. The total survival improved from 45% (in a previous and similar study) to 55%. However, CAVH was found of limited role in uremic control in severe hypercatabolic states. In order to find an alternative solution, CAVH and continuous hemodialysis (CAVHD) were compared in 13 ARF patients. Better results in uremic control were achieved with CAVHD. The net ultrafiltration (UF) volume was lower in CAVHD. Furthermore both UF and diffusion could be combined during CAVHD treatment to give freedom for nutritional support as well as fluid removal. Renal failure patients are prone to infections because they are often critically ill, in case of ARF, or because of their disturbed immune system in case of chronic renal failure. Such patients are in need of urgent and adequate antibiotic treatment. Both renal failure and IHF create difficulties in antibiotics dosing. The pharmacokinetics of a potent broad spectrum antibiotic (imipenem/cilastatin) was studied during IHF for the purpose of dose adjustment. 75% of the given dose was eliminated by HF. Dosage recommendations were given. Fluid overload is a common finding in renal failure.(ABSTRACT TRUNCATED AT 400 WORDS)


Cardiorenal Outcomes in the CANVAS, DECLARE-TIMI 58, and EMPA-REG OUTCOME Trials: A Systematic Review.
In this systematic review, we sought to summarize the 3 recent sodium-glucose cotransporter 2 inhibitor (SGLT2i) trials (Dapagliflozin Effect on CardiovasculAR Events (DECLARE-TIMI 58), Canagliflozin Cardiovascular Assessment Study (CANVAS) Program, and Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes (EMPA-REG OUTCOME)) and to explore the potential causes for their different results. We found that the major adverse cardiovascular event rates per 1000 patient-years for drug and placebo, as well as the corresponding relative risk reductions, were 22.6, 24.2, 7%; 26.9, 31.5, 14%; 37.4, 43.9, 14% for DECLARE-TIMI 58, CANVAS, and EMPA-REG OUTCOME, respectively. DECLARETIMI 58 had the fewest cardiorenal events (across treatment and control arms) and EMPA-REG OUTCOME the most. DECLARE-TIMI 58 used alternative inclusion criterion for baseline renal function (creatinine clearance ≧ 60 mL/min) compared to the other trials (estimated glomerular filtration rate (eGFR) > 30 mL/min/1.73 m2 bodysurface area). Therefore, the DECLARE-TIMI 58 study cohort had higher eGFR (mean eGFR 85.2 mL/min/1.73 m2 compared to 76.5 and 74 in CANVAS and EMPAREG OUTCOME, respectively); this may have caused the difference in results. Additionally contributing to the high event rate in EMPA-REG OUTCOME was the requirement of prior confirmed cardiovascular disease (CVD), resulting in 99.2% of patients with CVD compared to only 65.6% and 40.6% in CANVAS and DECLARE-TIMI 58, respectively (which did not require CVD). In conclusion, there is a need for large-scale studies of SGLT2i with matching inclusion/exclusion criteria and appropriate endpoints to ensure a truly direct comparison of the drugs.


[Physiological mechanisms of hypothalamic influence on the erychron].
Stimulation of the rabbit anterior hypothalamus reduced the amount of reticulocytes in the blood, decreased the hematocrit, redistributed the intrarenal blood flow reducing the blood supply of the renal cortex. Stimulation of the posterior hypothalamus led to an increase in the reticulocytes amount and an isolated increase in the blood supply of the cortical nephrones' glomeruli. No changes of the plasma erythropoietic activity occurred. The data obtained suggest the hypothalamus-induced changes of the hemodynamics (in bone marrow and kidneys particularly) as one of the possible hypothalamic influences upon the erythrone.


Mechanisms of early and late hypermetabolism and fever after localized tissue injury in rats.
Inflammation and localized tissue injury were induced in rats by intramuscular injection of turpentine. This caused rapid and sustained (2-24 h) increases in colonic temperature (Tc; up by 2.5 degrees C) and oxygen consumption (VO2; up by 30%) as well as hypophagia (57%). The early responses (0-2 h) were attenuated by anesthesia, C-fiber deafferentation, peripheral but not central injection of a cyclooxygenase inhibitor, or central injection of a neutralizing antibody to corticotropin-releasing factor (CRF). In contrast, the later (18-20 h) changes in Tc and VO2 were unaffected by anesthesia, C-fiber deafferentation, or central injection of a CRF antibody but were inhibited by either peripheral or central administration of a cyclooxygenase inhibitor. beta-Adrenoceptor blockade reduced both phases of the response, and brown adipose tissue activity was significantly elevated from 4 to 24 h after turpentine injection. These data suggest that different mechanisms mediate the metabolic response to localized tissue injury, the early phase involving neural mechanisms characteristic of stress and inflammation, whereas the later phase appears to depend on humoral factors that are commonly associated with infection.


Precise measurement of functional leg length inequality and changes due to cervical spine rotation in pain-free students.
A series of blinded studies to determine the feasibility of documenting functional leg length inequalities and changes in functional leg length in normal and non-normal patients were performed. A new apparatus designed to minimize or eliminate subjective components of inequality assessment, while attaining high levels of precision, was developed. Subjects were evaluated for presence of cervical spine lesion by five independent examiners and grouped into "lesioned" and "nonlesioned" categories. Subjects' leg length inequalities were measured by different evaluators as well as multiple measurements by a single evaluator to determine interrater and intrarater reliability coefficients. Measurements were taken on both flat and hi-low tables for changes during active cervical spine rotation. In addition, leg length measurements were taken during induced tetanic contraction by ipsilateral galvanic paravertebral muscle stimulation. Results indicated an absence of any significant effect of head rotation, type of table, galvanic stimulation, or any difference between persons classified as cervically lesioned or not cervically lesioned. Interrater and intrarater reliability coefficients for the measuring apparatus were statistically significant with small error variances. Failure to obtain subjects with frank pain as well as absence of an applied cephalad pressure (as is performed clinically) during leg length evaluation were considered as possible explanations for the failure to detect an effect of head rotation in the leg lengths. Discussion addresses the need for sensitive leg length inequality assessment techniques which eliminate subjectivity and contribute to decreased error variances.


Multimorbidity in randomized controlled trials of behavioral interventions: A systematic review.
As the population with multiple chronic conditions (MCC) increases, it is essential that randomized controlled trials (RCTs) consider MCC. Behavioral interventions have the potential to positively impact MCC patient outcomes; however, a comprehensive review of consideration of MCC in these trials has not been conducted. The purpose of this systematic review is to determine the frequency with which participants with MCC are represented in behavioral intervention RCTs targeting chronic illness published 2000-2014. MEDLINE and EMBASE were searched from 2000 to 2014 to identify RCTs testing behavioral interventions among adults with chronic illness. A random sampling selection process was performed to identify 600 eligible studies representative of the literature. Two reviewers independently extracted information on consideration of MCC in eligibility criteria and evaluated the reporting and consideration of MCC in trial analyses. Risk of bias was assessed using the Cochrane Collaboration Risk of Bias Tool. In 600 behavioral intervention RCTs, targeting MCC was rare (4.3%). Exclusion of MCC was common (68.3%) and was done through general, specific, or vague exclusion criteria. 218 (36.3%) trials reported presence of MCCs through general or condition-specific measures. Comorbidities were only considered in 4.8% of all trial analyses. In this comprehensive systematic review of 600 studies published from 2000-2014, RCTs testing behavioral interventions rarely consider individuals with MCC, limiting generalizability. Given the public health relevance and limited evidence base, this work highlights the urgent need to improve the consideration of MCC in clinical trial research. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


[Atypical cytologic findings in pregnancy].
The clinical significance of dysplasia and precancerous lesions of the cervix in pregnancy, frequency, age distribution and etiological factors is demonstrated based upon the clinical material of the Department of Obstetrics and Gynaecology of the University of Tübingen from 1970 to 1984. The diagnostic and therapeutic guidelines (cytology, colposcopy, histology by biopsy, conisation or hysterectomy) during pregnancy and associated problems are presented in detail. From a total of 168 patients included in the study, 128 revealed the histological classification Pap III/IIID, 38 Pap IVa/b and 2 cases Pap V. Histological carcinoma in situ was verified in 16 cases, microinvasive carcinoma in 6 cases and in 4 cases invasive cancer. From the data obtained, the following conclusions can be drawn: 1. Many of the dysplastic lesions of the cervix in pregnancy are found accidentally because of the limited participation of the patients in the routine cancer screening programme. 2. The precancerous lesions, even unfavourable stages, increase markedly in pregnancy. There is a shift towards younger women. 3. The known risk factors for cervical pre-invasive and invasive cervical abnormalities are confirmed. 4. For the management of cervical dysplasia in pregnancy it could be concluded, that observation by cytology and colposcopy should be done in cases with Pap III/IIID. In cases with Pap IVa/b, careful observation is mandatory, also by biopsy. Doubtful findings require conisation. Generally, this is also possible in pregnancy without complications. If invasion is excluded, an observant attitude may be adopted until delivery.(ABSTRACT TRUNCATED AT 250 WORDS)


Clinical Comparison of Dexketoprofen Trometamol and Dipyrone in Postoperative Dental Pain.
A total of 125 outpatients with moderate to severe pain after surgical removal of one impacted third molar were randomly assigned to receive dexketoprofen trometamol 12.5 or 25 mg or dipyrone 575 mg. For first-dose assessments, patients rated their pain intensity and its relief at regular intervals. From 60 min post dose to the end of the 6-h observation period, both doses of dexketoprofen trometamol had higher pain relief scores than dipyrone: Between 3 and 6 h the differences were statistically significant. In addition, peak measures (PIDmax and PARmax ) were statistically superior after both doses of dexketoprofen trometamol compared to dipyrone. The overall efficacy assessed at the end of the first-dose phase was rated as good or excellent by 90%, 83.3%, and 70% of patients receiving dexketoprofen trometamol 25 mg, dexketoprofen trometamol 12.5 mg, and dipyrone, respectively. The number of patients who required remedication during the 6-h period was significantly lower in both dexketoprofen groups. Repeated-dose data were also obtained. No significant differences were found in the efficacy after repeated doses, the number of doses taken, or the mean time elapsed between doses. The overall efficacy at the end of the repeated-dose phase was rated as good or excellent by 84.2%, 66.7%, and 70% of patients receiving dexketoprofen trometamol 25 mg, dexketoprofen trometamol 12.5 mg, and dipyrone, respectively. The frequency of adverse events was similar for all treatments and no serious adverse events were reported during the study.


US outbreak of human Salmonella infections associated with aquatic frogs, 2008-2011.
Although amphibians are known Salmonella carriers, no such outbreaks have been reported. We investigated a nationwide outbreak of human Salmonella Typhimurium infections occurring predominantly among children from 2008 to 2011. We conducted a matched case-control study. Cases were defined as persons with Salmonella Typhimurium infection yielding an isolate indistinguishable from the outbreak strain. Controls were persons with recent infection with Salmonella strains other than the outbreak strain and matched to cases by age and geography. Environmental samples were obtained from patients' homes; traceback investigations were conducted. We identified 376 cases from 44 states from January 1, 2008, to December 31, 2011; 29% (56/193) of patients were hospitalized and none died. Median patient age was 5 years (range <1-86 years); 69% were children <10 years old (253/367). Among 114 patients interviewed, 69 (61%) reported frog exposure. Of patients who knew frog type, 79% (44/56) reported African dwarf frogs (ADF), a type of aquatic frog. Among 18 cases and 29 controls, illness was significantly associated with frog exposure (67% cases versus 3% controls, matched odds ratio 12.4, 95% confidence interval 1.9-infinity). Environmental samples from aquariums containing ADFs in 8 patients' homes, 2 ADF distributors, and a day care center yielded isolates indistinguishable from the outbreak strain. Traceback investigations of ADFs from patient purchases converged to a common ADF breeding facility. Environmental samples from the breeding facility yielded the outbreak strain. ADFs were the source of this nationwide pediatric predominant outbreak. Pediatricians should routinely inquire about pet ownership and advise families about illness risks associated with animals.


In pain thou shalt bring forth children: the peak-and-end rule in recall of labor pain.
Childbirth is usually the most painful event of a mother's life, and resonates in individual and collective memory for years. The current study examined the relationship between the experience of labor pain and its recollection 2 days and 2 months after delivery. We found that despite the exceptional physical and emotional experiences of childbirth, the memory of the pain involved in labor was biased toward the average of the peak pain and the end pain, whereas the duration of the delivery had a relatively negligible effect on the recollected intensity of pain. A comparison of mothers whose labor ended with or without epidural analgesia corroborated previous findings that the level of pain toward the end of an experience greatly influences the way the overall experience is remembered. Although both short- and long-term retention of memories of labor exhibited the peak-and-end effect, having given birth before weakened the effect 2 months after delivery.


Interaction of melittin with a human lymphoblastoid cell line, HMy2.
We have examined the cytolytic effects of the membrane-active peptide, melittin, on a human lymphoblastoid cell line (HMy2) in the context of the use of melittin as the toxic component of an immunotoxin. The toxicity of melittin for HMy2 cells was linear over the concentration range 0.875-3.5 microM. Increased incubation times failed to result in significant cell death at concentrations of melittin below 0.875 microM. Kinetic analysis revealed that the cytolytic activity of melittin was independent of time of exposure beyond 90 min. Flow cytometric analysis of HMy2 cells incubated with FITC-labeled melittin demonstrated that the cells could incorporate up to 2.5 x 10(5) FITC-melittin molecules per cell with no reduction in viability. Extrapolation of this data indicates that 10(6) melittin molecules per cell are required for maximum cytotoxicity to HMy2 cells. Further analysis of HMy2 cells that incorporated melittin, but that remained viable, revealed that these cells were able to reduce the number of melittin molecules per cell over time. The data indicate a potential threshold value for the number of melittin molecules that may be required to be delivered to the cell surface in the form of an immunotoxin if effective selective cell death is to be achieved.


Development of leydig cells in the insulin-like growth factor-I (igf-I) knockout mouse: effects of igf-I replacement and gonadotropic stimulation.
Targeted gene deletion of insulin-like growth factor-I (IGF-I) results in diminished numbers of Leydig cells (LCs) and lower circulating testosterone (T) levels in adult males. The impact of endogenous IGF-I withdrawal on proliferation (labeling index, LI) and differentiation of LCs was investigated, testing for restorative effects of IGF-I replacement and/or LH stimulation. With IGF-I replacement in mutant mice, LIs increased more than 200% (P < 0.05). LC numbers were also increased by 200%, whereas the numbers of intermediate cell progenitors (PLCs) were unchanged compared to mutant vehicle controls. LIs of PLCs in wild-type males increased by 200% after LH stimulation, and LC numbers increased by 50% compared to vehicle-treated controls (P < 0.05). In contrast, there was no effect of LH on LI in mutant mice, but LC numbers still increased by 30% (P < 0.05). Additive effects on LI and cell numbers were observed in response to IGF-I plus LH in mutants, implying that the two hormones use separate signaling pathways. Serum T and LH levels in wild-type and mutant males were equivalent. Exogenous LH increased T production 8-fold in wild-type males (P < 0.01). In mutant mice, neither LH stimulation nor IGF-I alone affected serum T levels, but IGF-I plus LH stimulation increased serum T 2-fold (P < 0.05). These data support the conclusions that 1) IGF-I is a critical autocrine and/or paracrine factor in the control of adult LC numbers and function; and 2) LH is not a direct mitogenic factor for LCs, and acts in part through IGF-I to stimulate proliferative activity.


Continuous flow 2H/1H and 18O/16O analysis of water samples with dual inlet precision.
A method for isotope ratio analysis of water samples is described comprising an on-line high-temperature reduction technique in a helium carrier gas. Using a gas-tight syringe, injection of 0.5 to 1 microL sample is made through a heated septum into a glassy carbon reactor at temperatures in excess of 1300 degrees C. More than 150 injections can be made per day and both isotope ratios of interest, delta2H and delta18O, can be measured with the same setup. The technique has the capability to transfer high-precision stable isotope ratio analysis of water samples from a specialized to a routine laboratory task compatible with other common techniques (automated injection for GC, LC, etc.). Experiments with an emphasis on the reactor design were made in two different laboratories using two different commercially available high-temperature elemental analyser (EA) systems. In the Jena TC/EA unit, sample-to-sample memory (single injection) has been reduced to approximately 1% and high precision of about 0.1 per thousand for delta18O and < 1 per thousand for delta2H has been achieved by a redesign of the glassy carbon reactor and by redirecting the gas flow of the commercial TC/EA unit. With the modified reactor, the contact of water vapour with surfaces other than glassy carbon is avoided completely. The carrier gas is introduced at the bottom of the reactor thereby flushing the outer tube compartment of the tube-in-tube assembly before entering the active heart of the reactor.With the Leipzig high-temperature reactor (HTP) similar precision was obtained with a minor modification (electropolishing) of the injector metal sleeve. With this system, the temperature dependence of the reaction has been studied between 1100 and 1450 degrees C. Complete yield and constant isotope ratio information has been observed only for temperatures above 1325 degrees C. For temperatures above 1300 degrees C the reactor produces an increasing amount of CO background from reaction of glass carbon with the ceramic tube. This limits the usable temperature to a maximum of 1450 degrees C. Relevant gas permeation through the Al2O3 walls has not been detected up to 1600 degrees C.


Associations of developmental imbalance between sensation seeking and premeditation in adolescence and heavy episodic drinking in emerging adulthood.
Dual systems theories suggest that greater imbalance between higher reward sensitivity and lower cognitive control across adolescence conveys risk for behaviors such as heavy episodic drinking (HED). Prior research demonstrated that psychological analogues of these systems, sensation seeking and premeditation, change from childhood through emerging adulthood, and each has been independently linked with HED. However, few studies have assessed whether change over time in these developing analogues is prospectively associated with HED. Moreover, we know of no research that has shown whether within-person differences between higher sensation seeking and relatively lower premeditation across the adolescent period predict HED in emerging adulthood. Prospective data from the National Consortium on Alcohol and NeuroDevelopment in Adolescence study (n = 715) were used to examine the association of sensation seeking and premeditation with HED among adolescents ages 16 to 20 years. We used novel applications of latent difference score modeling and growth curve analysis to test whether increasing sensation seeking, premeditation, and their imbalance over time are associated with HED across the study period, and whether these associations differed by sex. Whereas premeditation increased linearly from adolescence through emerging adulthood across sexes, males reported growth and females reported decline in sensation seeking. Sensation seeking in adolescence (and not premeditation) was associated with higher levels of HED by emerging adulthood. Importantly, greater imbalance between sensation seeking and premeditation was associated with higher levels of HED by emerging adulthood though we note that variability capturing this imbalance correlated highly (r = 0.86) with baseline levels of sensation seeking. Developmental imbalance between higher sensation seeking and lower premeditation in late adolescence may be a risk factor for greater HED in emerging adulthood.


Pharmacokinetics of Transfer of Azithromycin into the Breast Milk of African Mothers.
Azithromycin (AZI) is used for its antibiotic and antimalarial properties in pregnancy. Reported estimates of AZI breast milk transfer, based on concentrations in mostly single samples from small numbers of women, have suggested that infant intake is safe. To better characterize infant intake and the associated potential benefits and risks, AZI was measured by liquid chromatography-mass spectrometry in four breast milk samples taken over 28 days postpartum from each of 20 Gambian women given 2 g AZI during labor. A population pharmacokinetic model utilizing published parameters for AZI disposition in pregnancy, the present breast milk concentrations, and increasing/decreasing sigmoid maximum-effect (Emax) functions adequately described temporal changes in the milk/plasma ratio. The median estimated absolute and relative cumulative infant doses were 4.5 mg/kg of body weight (95% prediction interval, 0.6 to 7.0 mg/kg) and 15.7% (95% prediction interval, 2.0 to 27.8%) of the maternal dose, respectively; the latter exceeded the recommended 10% safety limit. Although some infants with bacterial infections may benefit from AZI in breast milk, there is a risk of hypertrophic pyloric stenosis with a worst-case number needed to harm of 60 based on the present and available epidemiologic data. (This study has been registered at ClinicalTrials.gov under registration no. NCT01800942.).


Speedy revelations: how alarm calls can convey rapid, reliable information about urgent danger.
In the perpetual struggle between high-speed predators and their prey, individuals need to react in the blink of an eye to avoid capture. Alarm calls that warn of danger therefore need to do so sufficiently rapidly that listeners can escape in time. Paradoxically, many species produce more elements in their alarm calls when signalling about more immediate danger, thereby increasing the reliability of transmission of critical information but taking longer to convey the urgent message. We found that New Holland honeyeaters, Phylidonyris novaehollandiae, incorporated more elements in alarm calls given to more dangerous predators, but video analysis revealed that listeners responded in 100 ms, after only the first element. Consistent with this rapid response, the acoustic structure of the first element varied according to the danger, and playbacks confirmed that birds need hear only the first element to assess risk. However, birds hid for longer and were more likely to flee, after calls with more elements. The dual mechanisms of varying both element structure and number may provide a widespread solution to signalling rapidly and reliably about immediate danger.


Do professional communities enhance the personal and professional well-being of minority women? The case of Ultra-Orthodox women in Israel.
The labour market in industrialised countries around the world today faces various challenges associated with the 4th Industrial Revolution, specifically three major developments: innovations in technology and science, demographic changes, and social change. Policymakers and employers are required to examine the economy in light of these changes, which are expected to affect the labour market and the level of employment. In this study, we chose to focus on one of the most prominent areas leading to change in the employment market: the social changes and the adoption of new social platform in the employment market. Israeli society is undergoing a significant change with the increasing entrance of members of Ultra-Orthodox society, specifically Ultra-Orthodox women, into the advanced employment market. The purpose of this qualitative study is to examine whether and how state-funded professional communities help Ultra-Orthodox women to progress at work and enhance their personal and social well-being. The main themes are based on content analysis of two focus groups that included members of a variety of professional communities, content analysis of correspondence on social networks, and five in-depth interviews with the managers of these groups. The findings are analysed through the lens of positive psychology theory and show that professional communities contribute significantly to five personality strengths of the employed women: positivity, engagement and connectedness, positive relationships, meaning, and success. Additionally, these communities help to cultivate the women's professional talents, contribute to strengthening the relationship between general Israeli society and the Ultra-Orthodox community, and, ultimately, all of these help produce satisfaction at work.


Haloanaerobium fermentans sp. nov., a strictly anaerobic, fermentative halophile isolated from fermented puffer fish ovaries.
A strain of strictly anaerobic and moderately halophilic bacteria isolated from salted puffer fish ovaries was studied phenotypically, genotypically and phylogenetically. On the basis of its physiological and morphological characteristics, the new isolate is considered to be a member of the genus Haloanaerobium. It is a motile, rod-shaped, non-spore-forming, gram-negative, obligate anaerobe that grows in the presence of 25% (w/v) NaCl. The optimum salt concentration for growth is 10% (w/v). It grows well at 15 and 45 degrees C, but not at 10 or 50 degrees C. The optimum temperature for growth is 35 degrees C. It grows at pH 6.0-9.0 and the optimum pH for growth is 7.5. It ferments N-acetylglucosamine, cellobiose, fructose, galactose, D-glucose, lactose, maltose, D-mannose, raffinose, D-ribose, sucrose and D-xylose. It ferments D-glucose with the production of hydrogen, carbon dioxide, ethanol and organic acids such as acetate, formate and lactate. 16S rRNA gene sequence information confirmed the phylogenetic position of the new isolate, strain R-9T, as a member of the genus Haloanaerobium. DNA-DNA hybridization data revealed that isolate R-9T exhibited low levels of reassociation (less than 30%) with previously described Haloanaerobium species. Based on these results, the new isolate appears to represent a new Haloanaerobium species, for which the name Haloanaerobium fermentans sp. nov. is proposed. The type strain is R-9T (= JCM 10494T).


A brief temporal gradient of retrograde amnesia independent of situational change.
Rats were given a single electroconvulsive shock at varying intervals after receiving a punishing shock to the feet immediately after stepping into a compartment. Significant amounts of retrograde amnesia for the memory of the punishment was shown when electroconvulsive shock was administered up to and including 30 seconds after the punishment but not at 60 seconds. This brief temporal gradient cannot be explained in ternis of changed stimulus cues or learned interference analogouS to retroactive inhibition.


Verification and evaluation of monochloropropanediol (MCPD) esters and glycidyl esters in palm oil products of different regions in Malaysia.
This study was conducted to investigate on the effect of different sampling regions of palm-refined oils and fats on the 2- and 3-monochloropropanediol fatty acid esters (MCPDE) and glycidol fatty acid esters (GE) levels. The American Oil Chemists' Society (AOCS) Official Method Cd 29a-13 on the determination of MCPDE and GE in edible oils and fats by acid transesterification was successfully verified and optimised, with slight modification using 7890A Agilent GC system equipped with 5975C quadrupole detector. The determined limits of detection (LOD) for MCPDE were 0.02 mg kg-1 and 0.05 mg kg-1 for GE. The method performance has showed good recovery between 80% and 120% for all pertinent compounds with seven replicates assayed in three separate days. Round robin test with two European laboratories, i.e. Eurofins and SGS, has shown compliance results with those of the present study. Among the sampling regions, only one refinery located in the central region of Malaysia showed a significant increment of the MCPDE and GE levels after refining process. The GE level averaging at 2.5 mg kg-1 was slightly higher than that of 3-MCPDE averaging at 1.3 mg kg-1. Both esters were preferentially partitioned into the liquid phase rather than the solid phase after fractionation. However, the overall results exhibited no direct correlation between the esters content and the different sampling locations of the palm oil products in Malaysia. Analysis of total chlorine content also displayed significant variations between sampling locations which clearly show its effect on the chlorine content in the CPO samples.


Regeneration of the periodontium for preservation of the damaged tooth.
The population of the world grows every year, and life expectancy tends to increase. Thus, long-term preservation of teeth in aged individuals is an urgent issue. The main causes of tooth loss are well known to be periodontitis, caries, fractures, and orthodontic conditions. Although implant placement is a widely accepted treatment for tooth loss, most patients desire to preserve their own teeth. Many clinicians and researchers are therefore challenged to treat and preserve teeth that are irreversibly affected by deep caries, periodontitis, fractures, and trauma. Tissue engineering techniques are beneficial in addressing this issue; stem cells, signal molecules, and scaffolds are the main elements of such techniques. In this review, we describe these three elements with respect to their validation for regeneration of the periodontium and focus particularly on the potency of diverse scaffolds. In addition, we provide a short overview of the ongoing studies of 4-methacryloxyethyl trimellitate anhydride/methyl methacrylate-tri-n-butyl-borane resin including calcium chloride or hydroxyapatite for periodontium regeneration.


Local DNA sequence control of deletion formation in Escherichia coli plasmid pBR322.
The specificity of deletion formation was studied using tests involving reversion of palindromic insertion mutations. Insertions of a Tn5-related transposon at 13 sites in the ampicillin-resistance (amp) gene of plasmid pBR322 were shortened to a nested set of perfect palindromes, 22, 32 and 90 bp long. We monitored frequencies of reversion to Ampr, which is the result of deletion of the palindrome plus one copy of the flanking 9 bp direct repeats (which had been formed by transposition). Revertant frequencies were found to depend on the location and the sequence of the palindromic insert. Changing a 45-kb interrupted palindrome to a 22-bp perfect palindrome stimulated deletion formation by factors of from fourfold to 545-fold among the 13 sites, while elongation of the perfect palindrome from 22 to 90 bp stimulated deletion formation by factors of from eight- to 18,000-fold. We conclude that deletion formation is strongly affected by subtle features of DNA sequence or conformation, both inside and outside the deleted segment, and that these effects may reflect specific interactions of DNA processing proteins with template DNAs.


Invisible walls within multidisciplinary teams: Disciplinary boundaries and their effects on integrated care.
Delivery of interdisciplinary integrated care is central to contemporary health policy. Hospitals worldwide are therefore attempting to move away from a functional organisation of care, built around discipline-based specialisation, towards an approach of delivering care through multidisciplinary teams. However, the mere existence of such teams may not guarantee integrated and collaborative work across medical disciplines, which can be hindered by boundaries between and within professions. This paper analyses the boundaries that affect collaboration and care integration in newly created multidisciplinary teams. Empirical data are drawn from an ethnographic research conducted in the sub-intensive stroke unit of an Italian public hospital. Data collection involved 180 h of observations and conversations with 42 healthcare providers. Findings show that disciplinary boundaries hinder both intra-professional and inter-professional collaboration. Doctors from different disciplines adopt different, and sometimes conflicting, clinical approaches, doctors and nurses construct discipline-specific professional identities, and conflicts emerge between doctors and nurses from different disciplines over the regulation of the medical-nursing boundary. Achieving collaboration and integration between professionals from different disciplines may be particularly challenging when the group with less institutional power (nurses, in this case) has developed a high level of expertise on the needs of the patients targeted by the team. Effective interdisciplinary work thus requires not only bridging boundaries within the medical professional group, but also addressing the dynamics of resistance in merging doctors and nurses with different disciplinary backgrounds. In the paper, we summarise these results in a framework that contributes knowledge to the field of professional boundaries in healthcare while offering practical insights to forge new interdisciplinary relationships, which are more embedded in the daily experience of care providers.


Pesticide exposures and respiratory health in general populations.
Human exposures to pesticides can occur in the workplace, in the household and through the ambient environment. While several articles have reviewed the impact of pesticide exposures on human respiratory health in occupational settings, to the best of our knowledge, this article is the first one to review published studies on the association between pesticide exposures and human respiratory health in the general populations. In this article, we critically reviewed evidences up to date studying the associations between non-occupational pesticide exposures and respiratory health in general populations. This article also highlighted questions arising from these studies, including our recent analyses using the data from the Canadian Health Measures Survey (CHMS), for future research. We found few studies have addressed the impact of environmental pesticide exposures on respiratory health, especially on lung function, in general populations. In the studies using the data from CHMS Cycle 1, exposures to OP insecticides, pyrethroid insecticides, and the organochlorine pesticide DDT were associated with impaired lung function in the Canadian general population, but no significant associations were observed for the herbicide 2,4-D. Future research should focus on the potential age-specific and pesticide-specific effect on respiratory health in the general population, and repeated longitudinal study design is critical for assessing the temporal variations in pesticide exposures. Research findings from current studies of non-occupational pesticide exposures and their health impact in general population will help to improve the role of regulatory policies in mitigating pesticide-related public health problems, and thereafter providing greater benefit to the general population.


The Impact of Hospital Acquisition of Physician Practices on Referral Patterns.
Multiple parties influence the choice of facility for hospital-based inpatient and outpatient services. The patient is the central figure, but their choice of facility is guided by their physician and influenced by hospital characteristics. This study estimated changes in referral patterns for inpatient admissions and outpatient diagnostic imaging associated with changes in ownership of three multispecialty clinic systems headquartered in Minneapolis-St. Paul, MN. These clinic systems were acquired by two hospital-owned integrated delivery systems (IDSs) in 2007, increasing the probability that hospital preferences influenced physician guidance on facility choice. We used a longitudinal dataset that allowed us to predict changes in referral patterns, controlling for health plan enrollee, coverage, and clinic system characteristics. The results are an important empirical contribution to the literature examining the impact of hospital ownership on location of service. When this change in ownership forged new relationships, there was a significant reduction in the use of facilities historically selected for inpatient admissions and outpatient imaging and an increase in the use of the acquiring IDS's facilities. These changes were weaker in the IDS acquiring two clinic systems, suggesting that management of multiple acquisitions simultaneously may impact the ability of the IDS to build strong referral relationships.


Disposition of ipriflavone (TC-80) in rats and dogs.
Oral 14C-ipriflavone was absorbed by rats to give a maximum plasma 14C level at 1.5 h and a half-life of 5.8 h. In dogs, after po dosing, the plasma 14C peaked at 0.5 h, followed by gradual decline. The plasma of both animals contained mostly metabolites, with small amounts of unchanged ipriflavone. In rats, 14C was distributed widely in tissues, with relatively high concns. in the liver, kidney and gut. Distribution in rat thigh bone of unmetabolized ipriflavone was also demonstrated. 14C-Ipriflavone was eliminated mostly as metabolites within 48 and 72 h, respectively, in rats and dogs. Rats excreted more 14C in urine than in feces, whereas the reverse was noted in dogs. Biliary excretion and reabsorption of 14C were also obvious in both animals.


Physiological Correlates of Moral Decision-Making in the Professional Domain.
Moral decision-making is central to guide our social behavior, and it is based on emotional and cognitive reasoning processes. In the present research, we investigated the moral decision-making in a company context by the recording of autonomic responses (skin conductance response, heart rate frequency, and variability), in three different moral conditions (professional fit, company fit, social fit) and three different offers (fair, unfair, neutral). In particular, the first professional fit condition required participants to accept or reject some offers proposing the money subdivision for a work done together with a colleague. The second company fit condition required participants to evaluate offers regarding the investment of a part of the money in the introduction of some company's benefits. Finally, the third social fit condition required participants to accept or refuse a money subdivision to support a colleague's relative with health problems financially. Results underlined the significant effect of both the condition, with increased autonomic effects more for personal and social than company fit, and the offer type, with differences for fair and neutral offers compared to unfair ones. This research shows how individual, situational, and contextual factors influence moral decision-making in a company context.


Holding Firm: Power, Push-Back, and Opportunities in Navigating the Liminal Space of Critical Qualitative Health Research.
Critical qualitative health researchers typically occupy and navigate liminal academic spaces and statuses, with one foot planted in the arts and social sciences and the other in biomedical science. We are at once marginalized and empowered, and this liminality presents both challenges and opportunities. In this article, we draw on our experiences of being (often the lone) critical qualitative health scholars on thesis advisory committees and dissertation examinations, as well as our experiences of publishing and securing funding, to illuminate how power and knowledge relations create conditions that shape the nature of our roles. We share strategies we have developed for standing our theoretical and methodological ground. We discuss how we use the power of our liminality to hold firm, push back, and push forward, to ensure that critical qualitative research is not further relegated to the margins and its quality and integrity sustained.


[Retracted] KIF4A promotes the development of bladder cancer by transcriptionally activating the expression of CDCA3.
Following the publication of the above paper, it was drawn to the Editor's attention by a concerned reader that certain of the tumour images in Fig. 3A and the immunohistochemistry data in Fig. 3C on p. 7, and colony formation assay data shown in Fig. 4F on p. 8 were strikingly similar to data that had already appeared in previous publications. Owing to the fact that the contentious data in the above article had already been published elsewhere, or were under consideration for publication, prior to its submission to International Journal of Molecular Medicine, the Editor has decided that this paper should be retracted from the Journal. After having been in contact with the authors, they accepted the decision to retract this paper. The Editor apologizes to the readership for any inconvenience caused. [International Journal of Molecular Medicine 47: 99, 2021; DOI: 10.3892/ijmm.2021.4932].


Dendrimersomes: Biomedical applications.
In recent years, dendrimer-based vesicles, known as dendrimersomes, have garnered significant attention as highly promising alternatives to lipid vesicles in a variety of biomedical applications. Dendrimersomes offer several advantages, including relatively straightforward synthesis, non-immunogenic properties, stability in circulation, and minimal size variability. These vesicles are composed of Janus dendrimers, which are polymers characterized by two dendritic wedges with different terminal groups - hydrophilic and hydrophobic. This dendrimer structure enables the self-assembly of dendrimersomes. The purpose of this highlight is to provide an overview of recent advancements achieved through the utilization of biomimetic dendrimersomes in various biomedical applications such as drug and nucleic acid delivery.