Dealing with workplace violence in emergency primary health care: a focus group study.
Prevention and management of workplace violence among health workers has been described in different health care settings. However, little is known about which phenomena the emergency primary health care (EPC) organization should attend to in their strategies for preventing and managing it. In the current study, we therefore explored how EPC personnel have dealt with threats and violence from visitors or patients, focusing on how organizational factors affected the incidents. A focus group study was performed with a sample of 37 nurses and physicians aged 25-69 years. Eight focus group interviews were conducted, and the participants were invited to talk about their experiences of violence in EPC. Analysis was conducted by systematic text condensation, searching for themes describing the participants' experiences. Four main themes emerged for anticipating or dealing with incidents of threats or violence within the system: (1) minimizing the risk of working alone, (2) being prepared, (3) resolving the mismatch between patient expectations and the service offered, and (4) supportive manager response. Our study shows a potential for development of better organizational strategies for protecting EPC personnel who are at risk from workplace violence.


Human Adipose Stem Cells Improve Mechanical Allodynia and Enhance Functional Recovery in a Rat Model of Neuropathic Pain.
Stem cells are a promising source of tissue engineering due to their differentiation potential. Today, direct transplantation of stem cells for cell therapy is commonly performed. However, in cases of nerve injury, direct transplantation of cells could lead to secondary nerve damage. Male Sprague-Dawley rats were randomized into four groups: the phosphate-buffered saline epineural transplantation (PBS-ENT) group, the PBS intraneural transplantation (PBS-INT) group, the human adipose-derived stem cells epineural transplantation (hASCs-ENT) group, and human adipose-derived stem cells intraneural transplantation (hASCs-INT) group. Transplantation was conducted 1 week later after inflicting a crush injury with subsequent observation for 5 weeks. To evaluate pain, each group was examined with regard to paw withdrawal latency and evoked potentials. The sciatic functional index (SFI) was calculated to estimate functional recovery. The sciatic nerve was also examined histologically. The hASCs-ENT group showed a more rapid paw withdrawal threshold and SFI recovery than the other groups (p<0.05). The hASCs-ENT group also showed shorter initial latencies in both somatosensory evoked potential (SSEP) and motor evoked potential (MEP) than the PBS-INT group (p<0.05). In addition, the N1 latency of the MEP and the N1 and P1 latencies of the SSEP were significantly shorter than those of the PBS-INT group (p<0.05). Histological examination revealed that the transplanted groups showed better neural recovery and remyelination than the groups injected with PBS. These results show that the transplantation of hASCs into the injured sciatic nerve improved mechanical allodynia and functional recovery as determined by the paw withdrawal test, SFI analysis, and electrophysiological studies. ENT is superior to INT in terms of invasiveness and better outcomes.


Silencing of c-Fos expression by microRNA-155 is critical for dendritic cell maturation and function.
MicroRNAs (miRNAs) are small, noncoding RNAs that regulate target mRNAs by binding to their 3' untranslated regions. There is growing evidence that microRNA-155 (miR155) modulates gene expression in various cell types of the immune system and is a prominent player in the regulation of innate and adaptive immune responses. To define the role of miR155 in dendritic cells (DCs) we performed a detailed analysis of its expression and function in human and mouse DCs. A strong increase in miR155 expression was found to be a general and evolutionarily conserved feature associated with the activation of DCs by diverse maturation stimuli in all DC subtypes tested. Analysis of miR155-deficient DCs demonstrated that miR155 induction is required for efficient DC maturation and is critical for the ability of DCs to promote antigen-specific T-cell activation. Expression-profiling studies performed with miR155(-/-) DCs and DCs overexpressing miR155, combined with functional assays, revealed that the mRNA encoding the transcription factor c-Fos is a direct target of miR155. Finally, all of the phenotypic and functional defects exhibited by miR155(-/-) DCs could be reproduced by deregulated c-Fos expression. These results indicate that silencing of c-Fos expression by miR155 is a conserved process that is required for DC maturation and function.


Prevention of human papillomavirus (HPV) infection and cervical cancer in China: how does HPV vaccination bring about benefits to Chinese women?
Cervical cancer is the second leading cause of cancer deaths among women in the world and more than 85% of cervical cancer cases occur in women living in developing countries. Human papillomavirus (HPV) infection is the major cause of cervical cancer. Since 2006, two prophylactic vaccines against the high-risk strains of HPV have been developed and approved in more than 100 countries around the world. However, in China, HPV vaccines are still under clinical trials for government approval. In this paper feasibility and justification of HPV vaccine introduction into China is examined by reviewing experiences in both developed and developing countries where the vaccination program has been implemented. The vaccination program has showed significant cost-effectiveness and great health and economic impacts on cervical cancer prevention and control in both high-income and middle- and low-income countries. On the other hand, based on the lessons from both developed and developing countries, secondary prevention alone cannot fully play a role to reduce the incidence and the disease burden, and neither does the vaccination program. The epidemiological characteristics in China suggest an urgent need to introduce the vaccines and the geographically diversified prevalence of oncogenic HPV types as well as socioeconomic status also highlight the importance of region-driven approaches for cervical cancer prevention and control by integration of a screening and vaccination program.


Femtosecond laser direct patterning of sensing materials toward flexible integration of micronanosensors.
Reported is femtosecond laser direct patterning of sensing materials toward flexible integration of micronanosensors (FIMS), meaning the capability to fabricate multiple functional sensors of smaller size on a nonflat surface of a substrate that is not limited to silicon. As a representative example, a photosensitive SnO(2) colloidal solution (sol) was developed, from which complex micronanostructures were written via a two-photon absorption process. After thermal decomposition of organic components, the patterned SnO(2) microsensors responded to relative humidity (RH) with a variation range of 5 orders of magnitude. FIMS would open a new door for miniaturization of micronanosensors expected in intelligent microsystems.


Transcranial magnetic stimulation for the treatment of epilepsy.
Epilepsy is a highly prevalent neurological condition characterised by repeated unprovoked seizures with various aetiologies. Although antiepileptic medications produce clinical improvement in many individuals, nearly a third of individuals have drug-resistant epilepsy that carries significant morbidity and mortality, and even individuals who have clinical improvement from antiepileptic medications often report iatrogenic symptoms. There remains a need for non-invasive and more effective therapies for this population. Transcranial magnetic stimulation (TMS) uses electromagnetic coils to excite or inhibit neurons, with repetitive pulses at low-frequency producing an inhibitory effect that could conceivably reduce cortical excitability associated with epilepsy. This is an updated version of the original Cochrane Review published in 2016. To assess the evidence for the use of TMS in individuals with drug-resistant epilepsy compared with other available treatments in reducing seizure frequency, improving quality of life, reducing epileptiform discharges, antiepileptic medication use, and side effects. For the latest update, we searched the Cochrane Register of Studies (CRS Web) and MEDLINE (Ovid 1946 to 2 June 2020). CRS Web includes randomised or quasi-randomised controlled trials from PubMed, Embase, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP), the Cochrane Central Register of Controlled Trials (CENTRAL), and the specialised registers of Cochrane Review Groups including Epilepsy. We included randomised controlled trials that were double-blinded, single-blinded, or unblinded, and placebo controlled, no treatment, or active controlled, which used repetitive transcranial magnetic stimulation (rTMS) without restriction of frequency, coil, duration or intensity on participants with drug-resistant epilepsy. We extracted information from each trial including methodological data; participant demographics including baseline seizure frequency, type of epileptic drugs taken; intervention details and intervention groups for comparison; potential biases; and outcomes and time points, primarily change in seizure frequency or responder rates, as well as quality of life and epileptiform discharges, adverse effects, and changes in medication use. The original search revealed 274 records from the databases that after selection provided seven full-text relevant studies for inclusion. The latest search identified 179 new records from the databases that after evaluation against the inclusion and exclusion criteria provided one additional full-text relevant study. The eight included studies (241 participants) were all randomised trials; seven of the studies were blinded. Methodological and design information in the included studies was unclear, particularly relating to randomisation and allocation concealment methods. We were not able to combine the results of the trials in analysis due to differences in the studies' designs. For the current update, two of the eight studies analysed showed a statistically significant reduction in seizure rate from baseline (72% and 78.9% reduction of seizures per week from the baseline rate, respectively), whilst the other six studies showed no statistically significant difference in seizure frequency following rTMS treatment compared with controls (low-certainty evidence). One study assessed quality of life and found that more participants showed improvement in quality of life scores with active treatments compared to the sham treatment, but this only involved seven participants (very low-certainty evidence). Four studies evaluated our secondary endpoint of mean number of epileptic discharges, three of which showed a statistically significant reduction in discharges after active rTMS treatment. Adverse effects were uncommon in the studies and typically involved headache, dizziness, and tinnitus; however increased seizure frequency did occur in a small number of individuals. The included trials reported no significant changes in medication use. Overall the risk of bias was either low or unclear, and the certainty of the evidence was low to very low. Overall, we judged the certainty of evidence for the primary outcomes of this review to be low to very low. We found some evidence to suggest that rTMS is safe but some adverse events were experienced. The variability in technique and outcome reporting prevented meta-analysis, and the evidence for efficacy of rTMS for seizure reduction is still lacking, despite reasonable evidence that it is effective at reducing epileptiform discharges.


Treatment of refractory Mycobacterium avium complex lung disease with a moxifloxacin-containing regimen.
Moxifloxacin (MXF) has in vitro and in vivo activity against Mycobacterium avium complex (MAC) in experimental models. However, no data are available concerning its treatment effect in patients with MAC lung disease. The aim of this study was to evaluate the clinical efficacy of an MXF-containing regimen for the treatment of refractory MAC lung disease. Patients with MAC lung disease who were diagnosed between January 2002 and December 2011 were identified from our hospital database. We identified 41 patients who received MXF for ≥ 4 weeks for the treatment of refractory MAC lung disease. A total of 41 patients were treated with an MXF-containing regimen because of a persistent positive culture after at least 6 months of clarithromycin-based standardized antibiotic therapy. The median duration of antibiotic therapy before MXF administration was 410 days (interquartile range [IQR], 324 to 683 days). All patients had culture-positive sputum when MXF treatment was initiated. The median duration of MXF administration was 332 days (IQR, 146 to 547 days). The overall treatment success rate was 29% (12/41), and the median time to sputum conversion was 91 days (IQR, 45 to 190 days). A positive sputum acid-fast-bacillus smear at the start of treatment with MXF-containing regimens was an independent predictor of an unfavorable microbiological response. Our results indicate that MXF may improve treatment outcomes in about one-third of patients with persistently culture-positive MAC lung disease who fail to respond to clarithromycin-based standardized antibiotic treatment. Prospective studies are required to assess the clinical efficacy of MXF treatment for refractory MAC lung disease.


Inconsistencies between actual and estimated blood alcohol concentrations in a field study of college students: do students really know how much they drink?
Alcohol use by college students is commonly measured through the use of surveys. The validity of such data hinge on the assumption that students are aware of how much alcohol they actually consume. Recent studies call this assumption into question. Students tend to overestimate the appropriate sizes of standard drinks, suggesting that they might underestimate how much alcohol they consume. If this is true, then students' actual blood alcohol concentrations (BACs) should be higher than BACs estimated based on self-report data. The present study examined this issue Breathalyzer readings and self-reported drinking data were collected from 152 college students during the fall of 2004. Estimated BACs were calculated by means of a standard formula, and the relation between actual and estimated BACs was examined. Factors contributing to discrepancies between the two values were identified Estimated BAC levels were significantly higher, not lower, than breath BAC measures. The accuracy of estimated BACs decreased as the number of drinks and amount of time spent drinking increased. Being male and drinking only beer predicted greater accuracy of estimated BACs Although laboratory data suggest that students underestimate how much they drink, the hypothesis was not supported by data collected in the field. It appears that students might actually overestimate rather than underestimate their levels of consumption when surveyed in the midst of a night of drinking. The findings corroborate observations made by other researchers and suggest that the findings of laboratory studies on college drinking do not necessarily extend to real-world settings.


Cancer trends and risk factors in Cyprus.
Cyprus, a European Union member state, is a small island in the Mediterranean with a population approaching 900,000 people. Cancer is the second leading cause of death; more therapeutic options for any patient with the disease are available in a central oncology centre in the capital of the island (Nicosia) and fewer therapeutic options (e.g. chemotherapy and hormone therapy only) in a few other public hospitals. Palliative care is offered in several hospices and hospitals, although the field needs improvement. With regards to screening, a national breast cancer screening programme has been in place countrywide since 2007 and is offered free of charge to women between the ages of 50 and 69 years, while colorectal and prostate cancer screening is performed on an individual basis (a pilot programme for colorectal cancer screening was recently initiated). Genetic testing is available for breast and colon cancer. To improve understanding of the causes of cancer in the country, a cancer research centre was established in 2010 (Mediterranean Centre for Cancer Research). Recent epidemiologic work has revealed increasing cancer trends in Cyprus; prostate cancer is the most common in men and breast cancer is the most common in women. Interestingly, thyroid cancer incidence in women has been rising from 1998 to 2008. Cancer of the colon and rectum is also on the rise affecting both sexes. Overall, cancer incidence in Cyprus is lower than other EuroMed countries with similar lifestyle and geography.


[Validity of the Nordic Musculoskeletal Questionnaire as morbidity measurement tool].
To validate the Portuguese version of the Nordic Musculoskeletal Questionnaire (NMQ), and to evaluate the relationship between musculoskeletal morbidity and demographic, occupational and behavior variables. Ninety government bank employees were interviewed using the Portuguese version of NMQ in Brasilia, Brazil, in 1999. The respondents' answers were compared to clinical data found in their medical records. Descriptive and associative variable analyses were carried out. Comparative statistical analysis was performed using Student t-test and Pearson's test was applied for correlational analysis. The results revealed an 86% agreement rate between symptoms reported in the NMQ and the respondent's clinical history. There were found differences in symptoms prevalence for the variables gender, occupation and physical activity. Women showed a higher severity average of symptoms for almost all body anatomical regions; managers reported greater severity of symptoms in the lumbar area than clerks; physical activity was associated to the lowest severity of symptoms in upper extremities. The results show that the Portuguese NMQ version includes a good validity indicator and is satisfactory as a musculoskeletal morbidity measurement tool. However, there is a need of (1) more items to measure the severity of symptoms; and (2) changes in scale layout in order to make it more easily understandable and less prone to avoidable missing data.


Improving early language and literacy skills: differential effects of an oral language versus a phonology with reading intervention.
This study compares the efficacy of two school-based intervention programmes (Phonology with Reading (P + R) and Oral Language (OL)) for children with poor oral language at school entry. Following screening of 960 children, 152 children (mean age 4;09) were selected from 19 schools on the basis of poor vocabulary and verbal reasoning skills and randomly allocated to either the P + R programme or the OL programme. Both groups of children received 20 weeks of daily intervention alternating between small group and individual sessions, delivered by trained teaching assistants. Children in the P + R group received training in letter-sound knowledge, phonological awareness and book level reading skills. Children in the OL group received instruction in vocabulary, comprehension, inference generation and narrative skills. The children's progress was monitored at four time points: pre-, mid- and post-intervention, and after a 5-month delay, using measures of literacy, language and phonological awareness. The data are clustered (children within schools) and robust confidence intervals are reported. At the end of the 20-week intervention programme, children in the P + R group showed an advantage over the OL group on literacy and phonological measures, while children in the OL group showed an advantage over the P + R group on measures of vocabulary and grammatical skills. These gains were maintained over a 5-month period. Intervention programmes designed to develop oral language skills can be delivered successfully by trained teaching assistants to children at school entry. Training using P + R fostered decoding ability whereas the OL programme improved vocabulary and grammatical skills that are foundations for reading comprehension. However, at the end of the intervention, more than 50% of at-risk children remain in need of literacy support.


Root caries in a sample of elderly persons.
With the anticipated increase in the aged adult population and the associated gingival recession, the prevalence of root caries is expected to increase. The purpose of this study was to determine the experience and distribution of root caries in a group of aged adults living in Kayelitsha. All non-institutionalized elderly black adults participating in a community geriatric programme were examined. Root caries was recorded using visual and tactile criteria and expressed as the root caries index (RCI) rate. The mean age of the subjects was 65.2 years, the mean number of teeth present was 17.3 and the mean RCI rate was 2.2 per cent. All subjects had gingival recession while only 23.8 per cent had root caries. No surfaces with restored root caries lesions were found. In the maxilla the highest RCI rate was observed on the interproximal surfaces of the posterior teeth (4.4 per cent) but in the mandible the buccal surfaces of the posterior teeth had the highest RCI rate (4.2 per cent). In both the maxilla and the mandible the lingual surfaces of the anterior teeth showed no root caries. Maxillary teeth did not have a significantly higher root caries attack rate than mandibular teeth. Root caries does not appear to be a public health problem in the sampled population.


Select nutrients, progesterone, and interferon tau affect conceptus metabolism and development.
Interferon tau (IFNT), a novel multifunctional type I interferon secreted by trophectoderm, is the pregnancy recognition signal in ruminants that also has antiviral, antiproliferative, and immunomodulatory bioactivities. IFNT, with progesterone, affects availability of the metabolic substrate in the uterine lumen by inducing expression of genes for transport of select nutrients into the uterine lumen that activate mammalian target of rapamycin (mTOR) cell signaling responsible for proliferation, migration, and protein synthesis by conceptus trophectoderm. As an immunomodulatory protein, IFNT induces an anti-inflammatory state affecting metabolic events that decrease adiposity and glutamine:fructose-6-phosphate amidotransferase 1 activity, while increasing insulin sensitivity, nitric oxide production by endothelial cells, and brown adipose tissue in rats. This short review focuses on effects of IFNT and progesterone affecting transport of select nutrients into the uterine lumen to stimulate mTOR cell signaling required for conceptus development, as well as effects of IFNT on the immune system and adiposity in rats with respect to its potential therapeutic value in reducing obesity.


A vaccine strategy with multiple prostatic acid phosphatase-fused cytokines for prostate cancer treatment.
Immunotherapy is one of the attractive treatment strategies for advanced prostate cancer. The US Food and Drug Administration (FDA) previously approved the therapeutic vaccine, sipuleucel-T, which is composed of autologous antigen-presenting cells cultured with a fusion protein [prostatic acid phosphatase (PAP) and granulocyte-macrophage colony-stimulating factor (GMCSF)]. Although sipuleucel-T has been shown to prolong the median survival of patients for 4.1 months, more robust therapeutic effects may be expected by modifying the vaccination protocol. In the present study, we aimed to develop and validate a novel vaccination strategy using multiple PAP-fused cytokines for prostate cancer treatment. Using a super gene expression (SGE) system that we previously established to amplify the production of a recombinant protein, significant amounts of PAP-fused cytokines [human GMCSF, interleukin-2 (IL2), IL4, IL7 and mouse GMCSF and IL4] were obtained. We examined the activity of the fusion proteins in vitro to validate their cytokine functions. A significant upregulation of dendritic cell differentiation from monocytes was achieved by PAP-GMCSF when used with the other PAP-fused cytokines. The PAP-fused human IL2 significantly increased the proliferation of lymphocytes, as determined by flow cytometry. We also investigated the in vivo therapeutic effects of multiple PAP-fused cytokines in a mouse prostate cancer model bearing prostate-specific antigen (PSA)- and PAP-expressing tumors. The simultaneous intraperitoneal administration of PAP-GMCSF, -IL2, -IL4 and -IL7 significantly prevented tumor induction and inhibited the tumor growth in the PAP-expressing tumors, yet not in the PSA-expressing tumors. The in vivo therapeutic effects with the multiple PAP-fused cytokines were superior to the effects of PAP-GMCSF alone. We thus demonstrated the advantages of the combined use of multiple PAP-fused cytokines including PAP-GMCSF, and propose a promising prostatic antigen-vaccination strategy to enhance the therapeutic effects.


Dopamine modulation of Ih improves temporal fidelity of spike propagation in an unmyelinated axon.
We studied how conduction delays of action potentials in an unmyelinated axon depended on the history of activity and how this dependence was changed by the neuromodulator dopamine (DA). The pyloric dilator axons of the stomatogastric nervous system in the lobster, Homarus americanus, exhibited substantial activity-dependent hyperpolarization and changes in spike shape during repetitive activation. The conduction delays varied by several milliseconds per centimeter, and, during activation with realistic burst patterns or Poisson-like patterns, changes in delay occurred over multiple timescales. The mean delay increased, whereas the resting membrane potential hyperpolarized with a time constant of several minutes. Concomitantly with the mean delay, the variability of delay also increased. The variability of delay was not a linear or monotonic function of instantaneous spike frequency or spike shape parameters, and the relationship between these parameters changed with the increase in mean delay. Hyperpolarization was counteracted by a hyperpolarization-activated inward current (I(h)), and the magnitude of I(h) critically determined the temporal fidelity of spike propagation. Pharmacological block of I(h) increased the change in delay and the variability of delay, and increasing I(h) by application of DA diminished both. Consequently, the temporal fidelity of pattern propagation was substantially improved in DA. Standard measurements of changes in excitability or delay with paired stimuli or tonic stimulation failed to capture the dynamics of spike conduction. These results indicate that spike conduction can be extremely sensitive to the history of axonal activity and to the presence of neuromodulators, with potentially important consequences for temporal coding.


Psychological and social factors in undergoing reconstructive surgery among individuals with craniofacial conditions: an exploratory study.
Objective : Reconstructive surgery to improve psychological well-being is commonly offered to children with craniofacial conditions. Few studies have explored the challenges of reconstructive surgery beyond the physical risks: poor treatment outcomes, infection, brain damage, and death. This qualitative study aims to understand the psychological and social implications such interventions can have for individuals with craniofacial conditions. Design : A total of 38 individuals between the ages of 12 and 61 with such craniofacial conditions as Sturge-Weber syndrome, Treacher Collins syndrome, Möbius syndrome, cleft lip and palate, Noonan syndrome, Crouzon syndrome, and amniotic band syndrome participated in semistructured video-recorded interviews. Participants were recruited at conferences, through study flyers, and by word of mouth. Descriptive, thematic analysis was used to identify themes related to reconstructive surgery. Results : Dominant themes included undergoing surgery to reduce stigmatization, the psychological and social implications of the interventions, outcome satisfaction, parental involvement in decision making about surgery, and recommendations for parents considering surgery for their children with craniofacial conditions. Experiences with reconstructive surgery varied, with some participants expressing surgical benefits and others, disillusionment. Conclusions : The range of participant attitudes and experiences reflect the complexity of reconstructive surgery. Pediatric health care teams involved in the care of children with craniofacial conditions play an important role in advising patients (and their parents) about existing treatment options. The psychological and social implications of reconstructive surgery should be relayed to help families weigh the risks and benefits of surgery in an informed and meaningful way.


A standardized extract from Paeonia lactiflora and Astragalus membranaceus attenuates liver fibrosis induced by porcine serum in rats.
Paeonia lactiflora and Astragalus membranaceus are two popular traditional Chinese medicines, commonly used in Chinese herb prescription to treat liver disease. The extract prepared from the roots of Paeonia lactiflora and Astragalus membranaceus (PAE) demonstrated better hepatoprotective activity than the herbs used individually as shown in our previous studies. This study was carried out to investigate the effects of PAE on liver fibrosis induced by porcine serum (PS) in rats and to explore its possible mechanisms. Liver fibrosis was induced in male Wistar rats by injection with PS intraperitoneally. The rats were randomly divided into a normal control group, a liver fibrosis model group and a PAE (40, 80, 160 mg•kg-1) treated group. After a 16-week treatment, PAE-treated rats showed significantly reduced liver damage and symptoms of liver fibrosis upon pathological examination. Administration of PAE significantly decreased serum HA, PC III levels, and content of hydroxyproline in the liver tissue of fibrotic rats. It also restored the decrease in SOD and GSH-Px activities and inhibited the formation of lipid peroxidative products during PS treatment. In vitro, PAE also significantly decreased [3H]-thymidine incorporation in hepatic stellate cells (HSCs) stimulated with platelet-derived growth factor-B subunit homodimer (PDGF-BB). Moreover, PAE significantly decreased the expression of PDGF receptor beta (PDGFR-β) and p-ERK1/2, p-p38, p-JNK. The results showed that PAE displays antifibrotic effects in rats induced by PS, the mechanism by which might be associated with its ability to scavenge free radicals, decreasing the expression of PDGFR-β, inhibition of HSC proliferation and MAPK activation. These findings indicate that PAE is a potential agent for the prevention of liver fibrosis.


Interactions between actin filaments and between actin filaments and membranes in quick-frozen and deeply etched hair cells of the chick ear.
Replicas of the apical surface of hair cells of the inner ear (vestibular organ) were examined after quick freezing and rotary shadowing. With this technique we illustrate two previously undescribed ways in which the actin filaments in the stereocilia and in the cuticular plate are attached to the plasma membrane. First, in each stereocilium there are threadlike connectors running from the actin filament bundle to the limiting membrane. Second, many of the actin filaments in the cuticular plate are connected to the apical cell membrane by tiny branched connecting units like a "crow's foot." Where these "feet" contact the membrane there is a small swelling. These branched "feet" extend mainly from the ends of the actin filaments but some connect the lateral surfaces of the actin filaments as well. Actin filaments in the cuticular plate are also connected to each other by finer filaments, 3 nm in thickness and 74 +/- 14 nm in length. Interestingly, these 3-nm filaments (which measure 4 nm in replicas) connect actin filaments not only of the same polarity but of opposite polarities as documented by examining replicas of the cuticular plate which had been decorated with subfragment 1 (S1) of myosin. At the apicolateral margins of the cell we find two populations of actin filaments, one just beneath the tight junction as a network, the other at the level of the zonula adherens as a ring. The latter which is quite substantial is composed of actin filaments that run parallel to each other; adjacent filaments often show opposite polarities, as evidenced by S1 decoration. The filaments making up this ring are connected together by the 3-nm connectors. Because of the polarity of the filaments this ring may be a "contractile" ring; the implications of this is discussed.


Systematic implementation of clinical risk management in a large university hospital: the impact of risk managers.
For health care systems in recent years, patient safety has increasingly become a priority issue. National and international strategies have been considered to attempt to overcome the most prominent hazards while patients are receiving health care. Thereby, clinical risk management (CRM) plays a dominant role in enabling the identification, analysis, and management of potential risks. CRM implementation into routine procedures within complex hospital organizations is challenging, as in the past, organizational change strategies using a top-down approach have often failed. Therefore, one of our main objectives was to educate a certain number of risk managers in facilitating CRM using a bottom-up approach. To achieve our primary purpose, five project strands were developed, and consequently followed, introducing CRM: corporate governance, risk management (RM) training, CRM process, information, and involvement. The core part of the CRM process involved the education of risk managers within each organizational unit. To account for the size of the existing organization, we assumed that a minimum of 1 % of the workforce had to be trained in RM to disseminate the continuous improvement of quality and safety. Following a roll-out plan, CRM was introduced in each unit and potential risks were identified. Alongside the changes in the corporate governance, a hospital-wide CRM process was introduced resulting in 158 trained risk managers correlating to 2.0 % of the total workforce. Currently, risk managers are present in every unit and have identified 360 operational risks. Among those, 176 risks were scored as strategic and clustered together into top risks. Effective meeting structures and opportunities to share information and knowledge were introduced. Thus far, 31 units have been externally audited in CRM. The CRM approach is unique with respect to its dimension; members of all health care professions were trained to be able to identify potential risks. A network of risk managers supported the centrally coordinated CRM process. There is a strong commitment among management, academia, clinicians, and administration to foster cooperation. The introduction of CRM led to a visible shift with regard to patient safety culture throughout the entire organization. Still, there is a long way to go to keep people engaged in CRM and work on national and international patient safety initiatives to continuously decrease potential hazards.


Using cost-effective targeting to enhance the efficiency of conservation investments in payments for ecosystem services.
Ecosystem services are being protected and restored worldwide through payments for ecosystem services in which participants are paid to alter their land-management approaches to benefit the environment. The efficiency of such investments depends on the design of the payment scheme. Land features have been used to measure the environmental benefits of and amount of payment for land enrollment in payment for ecosystem services schemes. Household characteristics of program participants, however, may also be important in the targeting of land for enrollment. We used the characteristics of households participating in China's Grain-to-Green program, and features of enrolled land to examine the targeting of land enrollment in that program in Wolong Nature Reserve. We compared levels of environmental benefits that can be obtained through cost-effective targeting of land enrollment for different types of benefits under different payment schemes. The efficiency of investments in a discriminative payment scheme (payments differ according to opportunity costs, i.e., landholders' costs of forgoing alternative uses of land) was substantially higher than in a flat payment scheme (same price paid to all participants). Both optimal targeting and suboptimal targeting of land enrollment for environmental benefits achieved substantially more environmental benefits than random selection of land for enrollment. Our results suggest that cost-effective targeting of land through the use of discriminative conservation payments can substantially improve the efficiency of investments in the Grain-to-Green program and other payment for ecosystem services programs.


The influence of population structure on gene expression and flowering time variation in the ubiquitous weed Capsella bursa-pastoris (Brassicaceae).
Population structure is a potential problem when testing for adaptive phenotypic differences among populations. The observed phenotypic differences among populations can simply be due to genetic drift, and if the genetic distance between them is not considered, the differentiation may be falsely interpreted as adaptive. Conversely, adaptive and demographic processes might have been tightly associated and correcting for the population structure may lead to false negatives. Here, we evaluated this problem in the cosmopolitan weed Capsella bursa-pastoris. We used RNA-Seq to analyse gene expression differences among 24 accessions, which belonged to a much larger group that had been previously characterized for flowering time and circadian rhythm and were genotyped using genotyping-by-sequencing (GBS) technique. We found that clustering of accessions for gene expression retrieved the same three clusters that were obtained with GBS data previously, namely Europe, the Middle East and Asia. Moreover, the three groups were also differentiated for both flowering time and circadian rhythm variation. Correction for population genetic structure when analysing differential gene expression analysis removed all differences among the three groups. This may suggest that most differences are neutral and simply reflect population history. However, geographical variation in flowering time and circadian rhythm indicated that the distribution of adaptive traits might be confounded by population structure. To bypass this confounding effect, we compared gene expression differentiation between flowering ecotypes within the genetic groups. Among the differentially expressed genes, FLOWERING LOCUS C was the strongest candidate for local adaptation in regulation of flowering time.


Fungal hydrophobins form a sheath preventing immune recognition of airborne conidia.
Aspergillus fumigatus is the most ubiquitous and the most threatful airborne fungal pathogen. In the atmosphere, there is thousands of conidia/m (3) originating from more than hundred fungal genera, which enter the host through the respiratory system and are eliminated by the innate immune defences. But how do A. fumigatus conidia survive long enough in the lung withstanding the host killing reactions? We demonstrated recently the role of the spore-surface rodlet layer made up of hydrophobic protein (hydrophobin) in preventing their recognition by the immune system. Upon removal of this rodlet layer by chemical, genetic or biological means, the resulting morphotypes were immunostimulatory in effect, confirming the essentiality of the role of the rodlet layer for the fungal survival in vivo.


Clinical evaluation of a hyaluronan-based gel following microsurgical reconstruction of peripheral nerves of the hand.
A controlled clinical trial was performed to investigate the safety and efficacy of the hyaluronate-based gel polymer Hyaloglide after microsurgical reconstruction of peripheral nerves of the hand. Thirty patients were randomized to receive either no postsurgical treatment (n = 16) or Hyaloglide (n = 14) and were clinically evaluated at various intervals for 1 year. The application of Hyaloglide posed no safety concerns. Efficacy was assessed by the recovery of sensitivity, measurement of pain, and progression of Tinel's sign. The Hyaloglide-treated group showed better improvement in recovery from pain, approaching statistical significance during the first 3 months postsurgery. Likewise, recovery of sensitivity was also higher in the Hyaloglide-treated group throughout the entire follow-up period, and the distance of Tinel's sign was longer in the Hyaloglide-treated group (P < 0.05 at day 30). The application of Hyaloglide may improve recovery of sensitivity and decrease pain following microsurgical repair of the peripheral nerves of the hand.


Coherence training in children with attention-deficit hyperactivity disorder: cognitive functions and behavioral changes.
Attention-deficit hyperactivity disorder (ADHD) is the most prevalent behavioral diagnosis in children, with an estimated 500 000 children affected in the United Kingdom alone. The need for an appropriate and effective intervention for children with ADHD is a growing concern for educators and childcare agencies. This randomized controlled clinical trial evaluated the impact of the HeartMath self-regulation skills and coherence training program (Institute of HeartMath, Boulder Creek, California) on a population of 38 children with ADHD in academic year groups 6, 7, and 8. Learning of the skills was supported with heart rhythm coherence monitoring and feedback technology designed to facilitate self-induced shifts in cardiac coherence. The cognitive drug research system was used to assess cognitive functioning as the primary outcome measure. Secondary outcome measures assessed teacher and student reposted changes in behavior. Participants demonstrated significant improvements in various aspects of cognitive functioning such as delayed word recall, immediate word recall, word recognition, and episodic secondary memory. Significant improvements in behavior were also found. The results suggest that the intervention offers a physiologically based program to improve cognitive functioning in children with ADHD and improve behaviors that is appropriate to implement in a school environment.


Ibuprofen enhances recovery from spinal cord injury by limiting tissue loss and stimulating axonal growth.
The GTP-binding protein RhoA regulates microfilament dynamics in many cell types and mediates the inhibition of axonal regeneration by myelin and chondroitin sulfate proteoglycans. Unlike most other nonsteroidal anti-inflammatory drugs, ibuprofen suppresses basal RhoA activity (Zhou et al., 2003). A recent report suggested that ibuprofen promotes corticospinal axon regeneration after spinal cord injury (Fu et al., 2007). Here, we confirm that ibuprofen reduces ligand-induced Rho signaling and myelin-induced inhibition of neurite outgrowth in vitro. Following 4 weeks of subcutaneous administration of ibuprofen, beginning 3 days after spinal cord contusion, animals recovered walking function to a greater degree, with twice as many rats achieving a hind limb weight-bearing status. We examined the relative role of tissue sparing, axonal sprouting, and axonal regeneration in the action of ibuprofen. Histologically, ibuprofen-treated animals display an increase in spared tissue without an alteration in astrocytic or microglial reaction. Ibuprofen increases axonal sprouting from serotonergic raphespinal axons, and from rostral corticospinal fibers in the injured spinal cord, but does not permit caudal corticospinal regeneration after spinal contusion. Treatment of mice with complete spinal cord transection demonstrates long-distance raphespinal axon regeneration in the presence of ibuprofen. Thus, administration of ibuprofen improves the recovery of rats from a clinically relevant spinal cord trauma by protecting tissue, stimulating axonal sprouting, and allowing a minor degree of raphespinal regeneration.


Generation and characterization of mice with a conditional null allele of the HtrA4 gene.
High temperature requirement factor A4 (HtrA4) is a member of the HtrA family of serine peptidases involved in regulating protein‑protein interactions. Little is known regarding the function of HtrA4 in humans and in mouse models. To gain insights into the role of HtrA4 in vivo, mice were generated with a conditional null allele of HtrA4 by flanking exons 4, 5 and 6 with loxP sites. Cre‑mediated recombination, using a ubiquitously active Rosa26‑Cre line, resulted in the deletion of the floxed region in the mouse genome. Mice homozygous for the recombinant allele (HtrA4‑/‑) were viable, fertile and appeared to be normal. The HtrA4 protein was detectable in coronary vessels and in the placenta. However, the loss of HtrA4 affected neither the basic heart nor placental functions. These mice, featuring a conditional null allele of HtrA4, may provide a valuable tool to investigate the role of HtrA4 in development and pathogenesis of coronary heart disease and preeclampsia.


Robot-assisted radical cystectomy with intracorporeal neobladder diversion: The Karolinska experience.
The aim of this report is to describe our surgical technique of totally intracorporeal robotic assisted radical cystectomy (RARC) with neobladder formation. Between December 2003 and March 2013, a total of 147 patients (118 male, 29 female) underwent totally intracorporeal RARC for urinary bladder cancer. We also performed a systematic search of Medline, Embase and PubMed databases using the terms RARC, robotic cystectomy, robot-assisted, totally intracorporeal RARC, intracorporeal neobladder, intracorporeal urinary diversion, oncological outcomes, functional outcomes, and complication rates. The mean age of our patients was 64 years (range 37-87). On surgical pathology 47% had pT1 or less disease, 27% had pT2, 16% had pT3 and 10% had pT4. The mean number of lymph nodes removed was 21 (range 0-60). 24% of patients had lymph node positive dAQ1isease. Positive surgical margins occurred in 6 cases (4%). Mean follow-up was 31 months (range 4-115 months). Two patients (1.4%) died within 90 days of their operation. Using Kaplan-Meier analysis, overall survival and cancer specific survival at 60 months was 68% and 69.6%, respectively. 80 patients (54%) received a continent diversion with totally intracorporeal neobladder formation. In the neobladder subgroup median total operating time was 420 minutes (range 265-760). Daytime continence and satisfactory sexual function or potency at 12 months ranged between 70-90% in both men and women. Our experience with totally intracorporeal RARC demonstrates acceptable oncological and functional outcomes that suggest this is a viable alternative to open radical cystectomy.


Development and numerical validation of a finite element model of the muscle standardized femur.
The human femur is one of the parts of the musculo-skeletal system most frequently analysed by means of the finite element (FE) method. Most FE studies of the human femur are based on computed tomography data sets of a particular femur. Since the geometry of the chosen sample anatomy influences the computed results, direct comparison across various models is often difficult or impossible. The aim of the present work was to develop and validate a novel three-dimensional FE model of the human femur based on the muscle standardized femur (MuscleSF) geometry. In the new MuscleSF FE model, the femoral attachment of each muscle was meshed separately on the external bone surface. The model was tested under simple load configurations and the results showed good agreement with the converged solution of a former study. In the future, using the validated MuscleSF FE model for numerical studies of the human femur will provide the following benefits: (a) the numerical accuracy of the model is known; (b) muscle attachment areas are incorporated in the model, therefore physiological loading conditions can be easily defined; (c) analyses of the femur under physiological load cases will be replicable; (d) results based on different load configurations could be compared across various studies.


Trends in E-Cigarette Awareness and Perceived Harmfulness in the U.S.
Electronic cigarettes (e-cigarettes) are gaining in popularity as an alternative to regular cigarettes, as they are viewed as potentially less harmful. However, it remains unclear how awareness about e-cigarettes is permeating through the general U.S. This study seeks to extend previous research and examine trends in e-cigarette awareness and perceived harmfulness, and their association with smoking-cessation efforts. Data from three cycles (2012, 2013, and 2014) of the Health Information National Trends Survey were combined into a single data set. Controlling for survey year, multivariate logit models were used to determine the association between demographic characteristics and e-cigarette awareness, perceived harmfulness, quit attempts, and quit intentions. Data were analyzed in 2015. Awareness of e-cigarettes increased from 77.1% in 2012 to 94.3% in 2014. Controlling for demographic characteristics, e-cigarette awareness significantly increased in both 2013 and 2014, relative to 2012. Perception that e-cigarettes were less harmful than regular cigarettes declined from 50.7% in 2012 to 43.1% in 2014. Among smokers, no relationship was observed between e-cigarette awareness and past-year quit attempts or quit intentions, but those that viewed e-cigarettes as less harmful were less likely to have a past-year quit attempt. These analyses reveal a continued increase in overall public awareness of e-cigarettes and shifting harm perceptions relative to regular cigarettes. New regulatory oversight by the U.S. Food and Drug Administration may have major effects on both dimensions, which are worth continued monitoring.


Long-term follow-up of a randomized trial of family foundations: effects on children's emotional, behavioral, and school adjustment.
This study examines long-term effects of a transition to parenthood program, Family Foundations, designed to enhance child outcomes through a strategic focus on supporting the coparenting relationship. Roughly 5 to 7 years after baseline (pregnancy), parent and teacher reports of internalizing and externalizing problems and school adjustment were collected by mail for 98 children born to couples enrolled in the randomized trial. Teachers reported significantly lower levels of internalizing problems among children in the intervention group compared with children in the control group and, consistent with prior findings at age 3, lower levels of externalizing problems for boys in the intervention group. Baseline level of observed couple negative communication moderated intervention effects for parent and teacher report of child adjustment and teacher report of school adjustment and adaptation. Effect sizes ranged from 0.40 to 0.98. Results indicate that relatively brief preventive programs for couples at the transition to parenthood have the capacity to promote long-term positive benefits for children's adjustment. Although we attended to missing data issues in several ways, high levels of attrition in this long-term follow-up study is a cause for caution.


The effect of gravity on coral morphology.
Coral morphological variability reflects either genetic differences or environmentally induced phenotypic plasticity. We present two coral species that sense gravity and accordingly alter their morphology, as characterized by their slenderness (height to diameter) ratio (SR). We experimentally altered the direction (and intensity) of the gravitational resultant force acting along or perpendicular to the main body axis of coral polyps. We also manipulated light direction, in order to uncouple gravity and light effects on coral development. In the experiments, vertically growing polyps had significantly higher SR than their horizontal siblings even when grown in a centrifuge (experiencing different resultant gravitational forces in proximal and distal positions). Lowest SR was in horizontal side-illuminated polyps, and highest in vertical top-illuminated polyps. Adult colonies in situ showed the same pattern. Gravitational intensity also affected polyp growth form. However, polyp volume, dry skeleton weight and density in the various centrifuge positions, and in aquaria experiments, did not differ significantly. This reflects the coral's ability to sense altered gravity direction and intensity, and to react by changing the development pattern of their body morphology, but not the amount of skeleton deposited.


Volunteer Service and Service Learning: Opportunities, Partnerships, and United Nations Millennium Development Goals.
This article explores approaches to service involvement and provides direction to nurse leaders and others who wish to begin or further develop global (local and international) service or service learning projects. We review types of service involvement, analyze service-related data from a recent survey of nearly 500 chapters of the Honor Society of Nursing, Sigma Theta Tau International (STTI), make recommendations to guide collaborative partnerships and to model engagement in global and local service and service learning. This article offers a literature review and describes results of a survey conducted by the STTI International Service Learning Task Force. Results describe the types of service currently conducted by STTI nursing members and chapters, including disaster response, service learning, and service-related responses relative to the Millennium Development Goals (MDGs). The needs of chapter members for information about international service are explored and recommendations for promoting global service and sustainability goals for STTI chapters are examined. Before engaging in service, volunteers should consider the types of service engagement, as well as the design of projects to include collaboration, bidirectionality, sustainability, equitable partnerships, and inclusion of the United Nations Sustainable Development Goals. STTI supports the learning, knowledge, and professional development of nurses worldwide. International service and collaboration are key to the advancement of the nursing profession. Culturally relevant approaches to international service and service learning are essential to our global organization, as it aims to impact the health status of people globally.


Socio-cultural determinants of health-seeking behaviour on the Kenyan coast: a qualitative study.
Severe childhood illnesses present a major public health challenge for Africa, which is aggravated by a suboptimal response to the child's health problems with reference to the health-seeking behaviour of the parents or guardians. We examined the health-seeking behaviour of parents at the Kenyan coast because understanding impediments to optimal health-seeking behaviour could greatly contribute to reducing the impact of severe illness on children's growth and development. Health-seeking behaviour, and the factors influencing this behaviour, were examined in two traditional communities. We held in-depth interviews with 53 mothers, fathers and caregivers from two rural clinics at the Kenyan Coast. Biomedical medicine (from health facilities and purchased over the counter) was found to be the most popular first point of treatment. However, traditional healing still plays a salient role in the health care within these two communities. Traditional healers were consulted for various reasons: a) attribution of causation of ill-health to supernatural sources, b) chronic illness (inability of modern medicine to cure the problem) and c) as prevention against possible ill-health. In developing an explanatory model of decision-making, we observed that this was a complex process involving consultation at various levels, with elders, but also between both parents, depending on the perceived nature and chronicity of the illness. However, it was reported that fathers were the ultimate decision makers in relation to decisions concerning where the child would be taken for treatment. Health systems need to see traditional healing as a complementary system in order to ensure adequate access to health care. Importantly, fathers also need to be addressed in intervention and education programs.


MERVL/Zscan4 Network Activation Results in Transient Genome-wide DNA Demethylation of mESCs.
Mouse embryonic stem cells are dynamic and heterogeneous. For example, rare cells cycle through a state characterized by decondensed chromatin and expression of transcripts, including the Zscan4 cluster and MERVL endogenous retrovirus, which are usually restricted to preimplantation embryos. Here, we further characterize the dynamics and consequences of this transient cell state. Single-cell transcriptomics identified the earliest upregulated transcripts as cells enter the MERVL/Zscan4 state. The MERVL/Zscan4 transcriptional network was also upregulated during induced pluripotent stem cell reprogramming. Genome-wide DNA methylation and chromatin analyses revealed global DNA hypomethylation accompanying increased chromatin accessibility. This transient DNA demethylation was driven by a loss of DNA methyltransferase proteins in the cells and occurred genome-wide. While methylation levels were restored once cells exit this state, genomic imprints remained hypomethylated, demonstrating a potential global and enduring influence of endogenous retroviral activation on the epigenome.


Vagus Nerve as Modulator of the Brain-Gut Axis in Psychiatric and Inflammatory Disorders.
The vagus nerve represents the main component of the parasympathetic nervous system, which oversees a vast array of crucial bodily functions, including control of mood, immune response, digestion, and heart rate. It establishes one of the connections between the brain and the gastrointestinal tract and sends information about the state of the inner organs to the brain via afferent fibers. In this review article, we discuss various functions of the vagus nerve which make it an attractive target in treating psychiatric and gastrointestinal disorders. There is preliminary evidence that vagus nerve stimulation is a promising add-on treatment for treatment-refractory depression, posttraumatic stress disorder, and inflammatory bowel disease. Treatments that target the vagus nerve increase the vagal tone and inhibit cytokine production. Both are important mechanism of resiliency. The stimulation of vagal afferent fibers in the gut influences monoaminergic brain systems in the brain stem that play crucial roles in major psychiatric conditions, such as mood and anxiety disorders. In line, there is preliminary evidence for gut bacteria to have beneficial effect on mood and anxiety, partly by affecting the activity of the vagus nerve. Since, the vagal tone is correlated with capacity to regulate stress responses and can be influenced by breathing, its increase through meditation and yoga likely contribute to resilience and the mitigation of mood and anxiety symptoms.


Identification of Users for a Smoking Cessation Mobile App: Quantitative Study.
The number of mobile apps that support smoking cessation is growing, indicating the potential of the mobile phone as a means to support cessation. Knowledge about the potential end users for cessation apps results in suggestions to target potential user groups in a dissemination strategy, leading to a possible increase in the satisfaction and adherence of cessation apps. This study aimed to characterize potential end users for a specific mobile health (mHealth) smoking cessation app. A quantitative study was conducted among 955 Dutch smokers and ex-smokers. The respondents were primarily recruited from addiction care facilities and hospitals through Web-based media via websites and forums. The respondents were surveyed on their demographics, smoking behavior, and personal innovativeness. The intention to use and the attitude toward a cessation app were determined on a 5-point Likert scale. To study the association between the characteristics and intention to use and attitude, univariate and multivariate ordinal logistic regression analyses were performed. The multivariate ordinal logistic regression showed that the number of previous quit attempts (odds ratio [OR] 4.1, 95% CI 2.4-7.0, and OR 3.5, 95% CI 2.0-5.9) and the score on the Fagerstrom Test of Nicotine Dependence (OR 0.8, 95% CI 0.8-0.9, and OR 0.8, 95% CI 0.8-0.9) positively correlates with the intention to use a cessation app and the attitude toward cessation apps, respectively. Personal innovativeness also positively correlates with the intention to use (OR 0.3, 95% CI 0.2-0.4) and the attitude towards (OR 0.2, 95% CI 0.1-0.4) a cessation app. No associations between demographics and the intention to use or the attitude toward using a cessation app were observed. This study is among the first to show that demographic characteristics such as age and level of education are not associated with the intention to use and the attitude toward using a cessation app when characteristics related specifically to the app, such as nicotine dependency and the number of quit attempts, are present in a multivariate regression model. This study shows that the use of mHealth apps depends on characteristics related to the content of the app rather than general user characteristics.


Translational approaches to obsessive-compulsive disorder: from animal models to clinical treatment.
Obsessive-compulsive disorder (OCD) is characterized by obsessions (intrusive thoughts) and compulsions (repetitive ritualistic behaviours) leading to functional impairment. Accumulating evidence links these conditions with underlying dysregulation of fronto-striatal circuitry and monoamine systems. These abnormalities represent key targets for existing and novel treatment interventions. However, the brain bases of these conditions and treatment mechanisms are still not fully elucidated. Animal models simulating the behavioural and clinical manifestations of the disorder show great potential for augmenting our understanding of the pathophysiology and treatment of OCD. This paper provides an overview of what is known about OCD from several perspectives. We begin by describing the clinical features of OCD and the criteria used to assess the validity of animal models of symptomatology; namely, face validity (phenomenological similarity between inducing conditions and specific symptoms of the human phenomenon), predictive validity (similarity in response to treatment) and construct validity (similarity in underlying physiological or psychological mechanisms). We then survey animal models of OC spectrum conditions within this framework, focusing on (i) ethological models; (ii) genetic and pharmacological models; and (iii) neurobehavioural models. We also discuss their advantages and shortcomings in relation to their capacity to identify potentially efficacious new compounds. It is of interest that there has been rather little evidence of 'false alarms' for therapeutic drug effects in OCD models which actually fail in the clinic. While it is more difficult to model obsessive cognition than compulsive behaviour in experimental animals, it is feasible to infer cognitive inflexibility in certain animal paradigms. Finally, key future neurobiological and treatment research areas are highlighted.


Trends in racial/ethnic disparities in medical and oral health, access to care, and use of services in US children: has anything changed over the years?
The 2010 Census revealed the population of Latino and Asian children grew by 5.5 million, while the population of white children declined by 4.3 million from 2000-2010, and minority children will outnumber white children by 2020. No prior analyses, however, have examined time trends in racial/ethnic disparities in children's health and healthcare. The study objectives were to identify racial/ethnic disparities in medical and oral health, access to care, and use of services in US children, and determine whether these disparities have changed over time. The 2003 and 2007 National Surveys of Children's Health were nationally representative telephone surveys of parents of 193,995 children 0-17 years old (N = 102,353 in 2003 and N = 91,642 in 2007). Thirty-four disparities indicators were examined for white, African-American, Latino, Asian/Pacific-Islander, American Indian/Alaskan Native, and multiracial children. Multivariable analyses were performed to adjust for nine relevant covariates, and Z-scores to examine time trends. Eighteen disparities occurred in 2007 for ≥1 minority group. The number of indicators for which at least one racial/ethnic group experienced disparities did not significantly change between 2003-2007, nor did the total number of specific disparities (46 in 2007). The disparities for one subcategory (use of services), however, did decrease (by 82%). Although 15 disparities decreased over time, two worsened, and 10 new disparities arose. Minority children continue to experience multiple disparities in medical and oral health and healthcare. Most disparities persisted over time. Although disparities in use of services decreased, 10 new disparities arose in 2007. Study findings suggest that urgent policy solutions are needed to eliminate these disparities, including collecting racial/ethnic and language data on all patients, monitoring and publicly disclosing disparities data annually, providing health-insurance coverage and medical and dental homes for all children, making disparities part of the national healthcare quality discussion, ensuring all children receive needed pediatric specialty care, and more research and innovative solutions.


[Inflammatory reaction in the intestinal wall of rats: can intraperitonial urine cause damage?].
To observe the intensity of the inflammatory reaction caused by urine on the intestinal wall of rats. Experimental model, using 20 Wistar rats divided into two groups. All the animals were submitted to abdominal puncture at the right inferior quadrant, twice daily for five days. In Group I (control group) no substance was inoculated during the procedure, while in Group II (urine group), 3 ml of neonatal urine were inoculated. The animals were killed on the sixth day. A small-bowel specimen was fixed in paraffin and stained with hematoxylin-eosin. Microscopic analysis was performed by the same pathologist in all cases for determination of the degree of inflammatory reaction in the intestinal wall. All animals completed the experiment. In group I (control group) serositis was observed in six animals and enteritis in one. In group II (urine group) serositis was observed in nine animals and enteritis in four. The groups were similar in terms of the intensity of the inflammatory reaction observed (p = 0.1). The intra-abdominal inoculation of neonatal urine did not produce significant inflammatory reactions in the intestinal wall of rats.


Presence and secretion of atrial natriuretic peptide from cultured human aortic endothelial cells.
The endothelium is the production site of several potent vasoactive substances that modulate vascular tone and growth. The present study was undertaken to investigate the presence and secretion of atrial natriuretic peptide (ANP) immunoreactivity from vascular endothelial cells. ANP immunoreactivity was present in cultured human aortic endothelial cells by both immunohistochemical staining and radioimmunoassay. ANP immunoreactivity was also detectable in culture medium from human aortic endothelial cells in low picogram concentrations. These findings suggest that vascular endothelium is a site of ANP production and secretion of ANP. There was a differential distribution of ANP and endothelin-1 (ET-1), with a higher ANP concentration in cell extracts and a higher ET-1 concentration in cell culture media. Although ANP has been conceived as a circulating endocrine hormone, these findings are consistent with ANP functioning also as an autocrine and paracrine modulator in the regulation of vascular tone and growth.


Origin, imports and exports of HIV-1 subtype C in South Africa: A historical perspective.
While the HIV epidemic in South Africa had a later onset than epidemics in other southern African countries, prevalence grew rapidly during the 1990's when the country was going through socio-political changes with the end of Apartheid. South Africa currently has the largest number of people living with HIV in the world and the epidemic is dominated by a unique subtype, HIV-1 subtype C. This large epidemic is also characterized by high level of genetic diversity. We hypothesize that this diversity is due to multiple introductions of the virus during the period of change. In this paper, we apply novel phylogeographic methods to estimate the number of viral imports and exports from the start of the epidemic to the present. We assembled 11,289 unique subtype C pol sequences from southern Africa. These represent one of the largest sequence datasets ever analyzed in the region. Sequences were stratified based on country of sampling and levels of genetic diversity were estimated for each country. Sequences were aligned and a maximum-likelihood evolutionary tree was inferred. Least-Squares Dating was then used to obtain a dated phylogeny from which we estimated the number of introductions into and exports out of South Africa using parsimony-based ancestral location reconstructions. Our results identified 189 viral introductions into South Africa with the largest number of introductions attributed to Zambia (n=109), Botswana (n=32), Malawi (n=26) and Zimbabwe (n=13). South Africa also exported many viral lineages to its neighbours. The bulk viral imports and exports appear to have occurred between 1985 and 2000, coincident with the period of socio-political transition. The high level of subtype C genetic diversity in South Africa is related to multiple introductions of the virus to the country. While the number of viral imports and exports we identified was highly sensitive to the number of samples included from each country, they mostly clustered around the period of rapid political and socio-economic change in South Africa.


Spectral tuning in sensory rhodopsin I from Salinibacter ruber.
Organisms utilize light as energy sources and as signals. Rhodopsins, which have seven transmembrane α-helices with retinal covalently linked to a conserved Lys residue, are found in various organisms as distant in evolution as bacteria, archaea, and eukarya. One of the most notable properties of rhodopsin molecules is the large variation in their absorption spectrum. Sensory rhodopsin I (SRI) and sensory rhodopsin II (SRII) function as photosensors and have similar properties (retinal composition, photocycle, structure, and function) except for their λ(max) (SRI, ∼560 nm; SRII, ∼500 nm). An expression system utilizing Escherichia coli and the high protein stability of a newly found SRI-like protein, SrSRI, enables studies of mutant proteins. To determine the residue contributing to the spectral shift from SRI to SRII, we constructed various SRI mutants, in which individual residues were substituted with the corresponding residues of SRII. Three such mutants of SrSRI showed a large spectral blue-shift (>14 nm) without a large alteration of their retinal composition. Two of them, A136Y and A200T, are newly discovered color tuning residues. In the triple mutant, the λ(max) was 525 nm. The inverse mutation of SRII (F134H/Y139A/T204A) generated a spectral-shifted SRII toward longer wavelengths, although the effect is smaller than in the case of SRI, which is probably due to the lack of anion binding in the SRII mutant. Thus, half of the spectral shift from SRI to SRII could be explained by only those three residues taking into account the effect of Cl(-) binding.


Contribution of postoperative vertebral remodeling to reversal of vertebral wedging and prevention of correction loss in patients with adolescent Scheuermann's kyphosis.
This study aimed to investigate reversal of vertebral wedging and to evaluate the contribution of vertebral remodeling to correction maintenance in patients with adolescent Scheuermann's kyphosis (SK) after posterior-only instrumented correction. A retrospective cohort study of patients with SK was performed. In total, 45 SK patients aged 10-20 years at surgery were included. All patients received at least 24 months of follow-up and had Risser sign greater than grade 4 at latest follow-up. Patients with Risser grade 3 or less at surgery were assigned to the low-Risser group, whereas those with Risser grade 4 or 5 were assigned to the high-Risser group. Radiographic data and patient-reported outcomes were collected preoperatively, immediately postoperatively, and at latest follow-up and compared between the two groups. Remarkable postoperative correction of global kyphosis was observed, with similar correction rates between the two groups (p = 0.380). However, correction loss was slightly but significantly less in the low-Risser group during follow-up (p < 0.001). The ratio between anterior vertebral body height (AVBH) and posterior vertebral body height (PVBH) of deformed vertebrae notably increased in SK patients from postoperation to latest follow-up (p < 0.05). Loss of correction of global kyphosis was significantly and negatively correlated with increased AVBH/PVBH ratio. Compared with the high-Risser group, the low-Risser group had significantly greater increase in AVBH/PVBH ratio during follow-up (p < 0.05). The two groups had similar preoperative and postoperative Scoliosis Research Society-22 questionnaire scores for all domains. Obvious reversal in wedge deformation of vertebrae was observed in adolescent SK patients. Patients with substantial growth potential had greater vertebral remodeling and less correction loss. Structural remodeling of vertebral bodies has a positive effect and protects against correction loss. These results could be help guide treatment decision-making.


Antimicrobial agent resistance in bacterial isolates from patients with diarrhea and urinary tract infection in the Sudan.
Antimicrobial sensitivity tests were performed on four-hundred and ninety-seven bacterial isolates from Sudanese patients with diarrhea or urinary tract infections. Shigella dysenteriae type I and enteropathogenic Escherichia coli showed high resistance rates (percentage of isolates showing antibiotic resistance) against the commonly-used antimicrobial agents: ampicillin, amoxicillin, chloramphenicol, tetracycline, cotrimoxazole, nalidixic acid, sulfonamide, and neomycin, and were completely sensitive to ciprofloxacin. Eighteen resistance patterns against nine antimicrobial agents tested were observed in enteric pathogens. Resistance to ampicillin, amoxicillin, tetracycline, cotrimoxazole, and sulfonamide was the most frequent pattern. The common urinary pathogens, E. coli, Klebsiella pneumoniae, and Proteus mirabilis showed high rates of resistance to ampicillin, amoxicillin, cotrimoxazole, tetracycline, sulfonamide, trimethoprim, streptomycin, and carbenicillin. We recommend that physicians seek updated knowledge of the common antibiotic-sensitivity patterns when starting empirical antibiotic therapy in Sudanese patients with diarrhea or urinary tract infection.


Assembly of whole-chromosome pseudomolecules for polyploid plant genomes using outbred mapping populations.
Despite advances in sequencing technologies, assembly of complex plant genomes remains elusive due to polyploidy and high repeat content. Here we report PolyGembler for grouping and ordering contigs into pseudomolecules by genetic linkage analysis. Our approach also provides an accurate method with which to detect and fix assembly errors. Using simulated data, we demonstrate that our approach is of high accuracy and outperforms three existing state-of-the-art genetic mapping tools. Particularly, our approach is more robust to the presence of missing genotype data and genotyping errors. We used our method to construct pseudomolecules for allotetraploid lawn grass utilizing PacBio long reads in combination with restriction site-associated DNA sequencing, and for diploid Ipomoea trifida and autotetraploid potato utilizing contigs assembled from Illumina reads in combination with genotype data generated by single-nucleotide polymorphism arrays and genotyping by sequencing, respectively. We resolved 13 assembly errors for a published I. trifida genome assembly and anchored eight unplaced scaffolds in the published potato genome.


The impact of timely cancer diagnosis on age disparities in colon cancer survival.
We described the role of patient-related and clinical factors on age disparities in colon cancer survival among patients aged 50-99 using New Zealand population-based cancer registry data linked to hospitalisation data. We included 21,270 new colon cancer cases diagnosed between 1 January 2006 and 31 July 2017, followed up to end 2019. We modelled the effect of age at diagnosis, sex, ethnicity, deprivation, comorbidity, and emergency presentation on colon cancer survival by stage at diagnosis using flexible excess hazard regression models. The excess mortality in older patients was minimal for localised cancers, maximal during the first six months for regional cancers, the first eighteen months for distant cancers, and over the three years for missing stages. The age pattern of the excess mortality hazard varied according to sex for distant cancers, emergency presentation for regional and distant cancers, and comorbidity for cancer with missing stages. Ethnicity and deprivation did not influence age disparities in colon cancer survival. Factors reflecting timeliness of cancer diagnosis most affected age-related disparities in colon cancer survival, probably by impacting treatment strategy. Because of the high risk of poor outcomes related to treatment in older patients, efforts made to improve earlier diagnosis in older patients are likely to help reduce age disparities in colon cancer survival in New Zealand.


Sulforaphane Alleviates Lipopolysaccharide-induced Spatial Learning and Memory Dysfunction in Mice: The Role of BDNF-mTOR Signaling Pathway.
Peripheral immune activation could cause neuroinflammation, leading to a series of central nervous system (CNS) disorders, such as spatial learning and memory dysfunction. However, its pathogenic mechanism and therapeutic strategies are not yet determined. The present study aimed to investigate the therapeutic effects of sulforaphane (SFN) on lipopolysaccharide (LPS)-induced spatial learning and memory dysfunction, and tried to elucidate its relationship with the role of hippocampal brain-derived neurotrophic factor (BDNF)-mammalian target of rapamycin (mTOR) signaling pathway. Intraperitoneal injection of LPS for consecutive 7 days to mice caused abnormal behaviors in Morris water maze test (MWMT), while systemic administration of SFN notably reversed the abnormal behaviors. In addition, hippocampal levels of inflammatory cytokines, synaptic proteins, BDNF-tropomyosin receptor kinase B (TrkB) and mTOR signaling pathways were altered in the processes of LPS-induced cognitive dysfunction and SFN's therapeutic effects. Furthermore, we found that ANA-12 (a TrkB inhibitor) or rapamycin (a mTOR inhibitor) could block the beneficial effects of SFN on LPS-induced cognitive dysfunction, and that hippocampal levels of synaptic proteins, BDNF-TrkB and mTOR signaling pathways were also notably changed. In conclusion, the results of the present study suggest that SFN could elicit improving effects on LPS-induced spatial learning and memory dysfunction, which is likely related to the regulation of hippocampal BDNF-mTOR signaling pathway.


Enhancement of the lithium ion conductivity of Ta-doped Li7La3Zr2O12 by incorporation of calcium.
Fast ion conducting garnet materials have been identified as promising electrolytes for all solid-state batteries. However, reliable synthetic routes to materials with fully elucidated cation site occupancies where an enhancement in lithium conductivity is observed remains a challenge. Ca-Incorporation is developed here as a promising approach to enhance the ionic conductivity of garnet-type Li7-xLa3Zr2-xTaxO12 phases. Here we present a new sol-gel synthetic strategy as a facile route to the preparation of materials of a desired stoichiometry optimized for Li+ conductivity. We have found that the ionic conductivity of Li6.4La3Zr1.4Ta0.6O12 is increased by a factor of four by the addition of 0.2 mol of Ca per formula unit. Ca is incorporated in the garnet lattice where it has no effect on the sinterability of the material and is predominately located at the La sites. We anticipate that the ease of our synthetic route and the phases presented here represents a starting point for the further realization of solid state electrolyte compositions with similarly high Li+ conductivities using this methodology.


Direct and indirect responses of a freshwater food web to a potent synthetic oestrogen.
Endocrine-disrupting chemicals (EDCs) in municipal effluents directly affect the sexual development and reproductive success of fishes, but indirect effects on invertebrate prey or fish predators through reduced predation or prey availability, respectively, are unknown. At the Experimental Lakes Area in northwestern Ontario, Canada, a long-term, whole-lake experiment was conducted using a before-after-control-impact design to determine both direct and indirect effects of the synthetic oestrogen used in the birth control pill, 17α-ethynyloestradiol (EE2). Algal, microbial, zooplankton and benthic invertebrate communities showed no declines in abundance during three summers of EE2 additions (5-6 ng l(-1)), indicating no direct toxic effects. Recruitment of fathead minnow (Pimephales promelas) failed, leading to a near-extirpation of this species both 2 years during (young-of-year, YOY) and 2 years following (adults and YOY) EE2 additions. Body condition of male lake trout (Salvelinus namaycush) and male and female white sucker (Catostomus commersonii) declined before changes in prey abundance, suggesting direct effects of EE2 on this endpoint. Evidence of indirect effects of EE2 was also observed. Increases in zooplankton, Chaoborus, and emerging insects were observed after 2 or 3 years of EE2 additions, strongly suggesting indirect effects mediated through the reduced abundance of several small-bodied fishes. Biomass of top predator lake trout declined by 23-42% during and after EE2 additions, most probably an indirect effect from the loss of its prey species, the fathead minnow and slimy sculpin (Cottus cognatus). Our results demonstrate that small-scale studies focusing solely on direct effects are likely to underestimate the true environmental impacts of oestrogens in municipal wastewaters and provide further evidence of the value of whole-ecosystem experiments for understanding indirect effects of EDCs and other aquatic stressors.


CORTICO-SUBCORTICAL HOMEOSTASIS IN THE CAT'S BRAIN.
Transcortical polarization of one cerebral hemisphere, while producing the well-known changes in the amplitude of the evoked potentials in the ipsilateral cortex, induced opposite behavior of these indicators in the contralateral cortex. With the corpus callosum sectioned, the reciprocal relationship was enhanced. Anesthetic doses of barbiturates not only eliminated reciprocity but made the potentials on both sides react in unison to unilateral polarization. These findings suggest the existence of a negative feedback system between the cerebral cortex and the subcortex and the existence of a "left-right equalizing" mechanism carried by pathways in the corpus callosum.


How patients choose acupuncturists: a mixed-methods project.
Patients can have difficulties choosing acupuncturists in the United Kingdom because acupuncturists are not all subject to statutory regulation. Research has identified factors that influence patients' choice of general practitioner. However, how patients choose acupuncturists has not been studied. The aim was to investigate how patients choose acupuncturists and to identify which factors might influence this choice. A mixed-methods design used an exploratory qualitative study followed by a quantitative study. The qualitative study explored patients' experiences of acupuncture. The quantitative vignette study investigated the impact of patient gender and practitioner factors (gender, training location, and qualifications) on choice of acupuncturist. In the qualitative study, 35 acupuncture patients (recruited through maximum variation sampling from seven clinics and the community) participated in semistructured interviews about their acupuncture experiences. In the quantitative study, 73 participants imagined wanting to consult an acupuncturist for back pain. They rated 8 fictional acupuncturists; ratings were analyzed using analysis of covariance. Patients wanted qualified, personable acupuncturists and valued recommendations from trusted others. Without such recommendations, potential patients preferred female acupuncturists (F(1,69)=4.504, p<0.05) and those with medical qualifications (F(1,69)=44.832, p<0.01). The decision to consult a particular acupuncturist is not straightforward. Acupuncturists' trustworthiness and technical competence are important to (potential) patients; practitioner gender also influenced preferences. Patients need to be informed about proposals concerning statutory regulation in CAM and its implications; conventional practitioners might be able to better support their patients wanting to consult acupuncturists.


Arousal and activation effects on physiological and behavioral responding during a continuous performance task.
Based on previous work indicating different neural substrates, two aspects of energetic state, "arousal" and "activation", have been conceptualized separately in our laboratory. "Arousal" has been defined as the energetic state at any particular time, and task-related "activation" as the task-related change in state from resting baseline to the task situation. Both are reflected in electrodermal activity and measured by skin conductance level. Our previous studies in this area have indicated that physiological responses to stimuli in a task are dependent on the arousal level at the time of stimulus presentation, rather than the task-related activation. In contrast, performance on the task is dependent on the task-related activation, rather than the current arousal level. That is, different aspects of the individual's state determine physiological and behavioral responses. Those studies had examined between-subjects differences in arousal and activation. The present study investigated the relevance of this separation in an across-subjects examination of fluctuations in arousal and activation, and their effects on physiological and behavioral responses, during a continuous performance task. It was found that the magnitude of the phasic orienting reflex to the targets during the task was dependent mainly on arousal, rather than task-related relative activation. Reaction time improved with increasing relative activation, but not with arousal. These findings support our earlier conclusions relating to the usefulness of arousal and activation as distinguishable features of the energetics of physiological and behavioral functions.


Adaptation and validation of the Charlson Index for Read/OXMIS coded databases.
The Charlson comorbidity index is widely used in ICD-9 administrative data, however, there is no translation for Read/OXMIS coded data despite increasing use of the General Practice Research Database (GPRD). Our main objective was to translate the Charlson index for use with Read/OXMIS coded data such as the GPRD and test its association with mortality. We also aimed to provide a version of the comorbidity index for other researchers using similar datasets. Two clinicians translated the Charlson index into Read/OXMIS codes. We tested the association between comorbidity score and increased mortality in 146 441 patients from the GPRD using proportional hazards models. This Read/OXMIS translation of the Charlson index contains 3156 codes. Our validation showed a strong positive association between Charlson score and age. Cox proportional models show a positive increasing association with mortality and Charlson score. The discrimination of the logistic regression model for mortality was good (AUC = 0.853). We have translated a commonly used comorbidity index into Read/OXMIS for use in UK primary care databases. The translated index showed a good discrimination in our study population. This is the first study to develop a co-morbidity index for use with the Read/OXMIS coding system and the GPRD. A copy of the co-morbidity index is provided for other researchers using similar databases.


Quantification of the effect of 4-tert-butylpyridine addition to I-/I3- redox electrolytes in dye-sensitized nanostructured TiO2 solar cells.
Addition of 4-tert-butylpyridine (4TBP) to redox electrolytes used in dye-sensitized TiO2 solar cells has a large effect on their performance. In an electrolyte containing 0.7 M LiI and 0.05 M I2 in 3-methoxypropionitrile, addition of 0.5 M 4TBP gave an increase of the open-circuit potential of 260 mV. Using charge extraction and electron lifetime measurements, this increases could be attributed to a shift of the TiO2 band edge toward negative potentials (responsible for 60% of the voltage increase) and to an increase of the electron lifetime (40%). At a lower 4TBP concentration the shift of the band edge was similar, but the effect on the electron lifetime was less pronounced. The working mechanism of 4TBP can be summarized as follows: (1) 4TBP affects the surface charge of TiO2 by decreasing the amount of adsorbed protons and/or Li+ ions. (2) It decreases the recombination of electrons in TiO2 with triiodide in the electrolyte by preventing triiodide access to the TiO2 surface and/or by complexation with iodine in the electrolyte.


Controlling the conformation and interplay of p-sulfonatocalix[6]arene as lanthanide crown ether complexes.
Control over the conformational flexibility of p-sulfonatocalix[6]arene in the solid state is possible in the presence of varied stoichiometric amounts of [18]crown-6 and selected lanthanide(III) chlorides. Complexes 1 and 2 have the calixarene in the elusive up-up double cone conformation, whilst complex 3 has the calixarene in the centrosymmetric up-down double partial cone conformation, whereby it acts as a divergent receptor. Complex 1 has a double molecular capsule arrangement which is composed of two p-sulfonatocalix[6]arenes shrouding two [18]crown-6 molecules, also with both coordinated and homoleptic aquated lanthanide ions around the hydrophilic sulfonate rims of the calixarenes. Complex 2 has a ferris wheel arrangement with one lanthanide metal centre coordinated to a sulfonate group and another coordinated to the crown ether whilst tethered to a sulfonate group of the calixarene. Complex 3 forms from a solution with large excess of [18]crown-6, and possesses a crown ether molecule in each of the partial cones and has homoleptic aquated lanthanide ions involved in a complicated hydrogen-bonding regime within the extended structure.


Plasma immunoreactive endothelin-1 in experimental malignant hypertension.
We measured plasma concentrations of immunoreactive endothelin-1 (irET-1) in the prehypertensive and hypertensive phases in spontaneously hypertensive rats (SHR) and in malignant hypertension caused by deoxycorticosterone acetate (DOCA)-salt administration in SHR. We also measured concentrations of this peptide in another model of malignant hypertension, the two-kidney, one clip (2K1C) renovascular hypertensive rats chronically given caffeine. Plasma irET-1 concentrations in young (6-week-old) and mature (18-week-old) SHR did not differ from those of age-matched Wistar-Kyoto (WKY) rats. Four weeks of treatment with DOCA-salt increased blood pressure, blood urea nitrogen, serum creatinine, and plasma irET-1 in SHR but not in WKY rats. Eight weeks of DOCA-salt treatment further increased these values in SHR. Plasma irET-1 concentrations were not increased in the 2K1C rats. Six weeks of caffeine administration increased blood pressure, blood urea nitrogen, serum creatinine, plasma renin activity, and plasma irET-1 in the 2K1C rats but not in the sham-operated rats. High-performance liquid chromatographic profiles of plasma extracts pooled from these rats with malignant hypertension showed that a major component of irET-1 eluted in the position of synthetic ET-1 (1-21). Furthermore, acute hypertension induced by angiotensin II or phenylephrine did not affect the plasma irET-1 concentration in rats. The results suggested that the plasma ET-1 concentration is increased in rat models of malignant hypertension and that the high blood pressure itself is not the main factor involved in the increase of plasma ET-1.


Preventing respiratory complications of tube feedings: evidence-based practice.
The most dreaded complication of tube feedings is tracheobronchial aspiration of gastric contents. Strong evidence indicates that most critically ill tube-fed patients receiving mechanical ventilation aspirate gastric contents at least once during their early days of tube feeding. Those who aspirate frequently are about 4 times more likely to have pneumonia develop than are those who aspirate infrequently. Although a patient's illness might not be modifiable, some risk factors for aspiration can be controlled; among these are malpositioned feeding tubes, improper feeding site, large gastric volume, and supine position. A review of current research-based information to support modification of these risk factors is provided.


Menatetrenone versus alfacalcidol in the treatment of Chinese postmenopausal women with osteoporosis: a multicenter, randomized, double-blinded, double-dummy, positive drug-controlled clinical trial.
To evaluate whether the efficacy and safety of menatetrenone for the treatment of osteoporosis is noninferior to alfacalcidol in Chinese postmenopausal women. This multicenter, randomized, double-blinded, double-dummy, noninferiority, positive drug-controlled clinical trial was conducted in five Chinese sites. Eligible Chinese women with postmenopausal osteoporosis (N=236) were randomized to Group M or Group A and received menatetrenone 45 mg/day or alfacalcidol 0.5 μg/day, respectively, for 1 year. Additionally, all patients received calcium 500 mg/day. Posttreatment bone mineral density (BMD), new fracture onsets, and serum osteocalcin (OC) and undercarboxylated OC (ucOC) levels were compared with the baseline value in patients of both groups. A total of 213 patients (90.3%) completed the study. After 1 year of treatment, BMD among patients in Group M significantly increased from baseline by 1.2% and 2.7% at the lumbar spine and trochanter, respectively (P<0.001); and the percentage increase of BMD in Group A was 2.2% and 1.8%, respectively (P<0.001). No difference was observed between groups. There were no changes in femoral neck BMD in both groups. Two patients (1.9%, 2/108) in Group M and four patients (3.8%, 4/105) in Group A had new fracture onsets (P>0.05). In Group M, OC and ucOC decreased from baseline by 38.7% and 82.3%, respectively (P<0.001). In Group A, OC and ucOC decreased by 25.8% and 34.8%, respectively (P<0.001). Decreases in serum OC and ucOC were more obvious in Group M than in Group A (P<0.001). The safety profile of menatetrenone was similar to alfacalcidol. Menatetrenone is an effective and safe choice in the treatment of postmenopausal osteoporosis in Chinese women.


Multiple mating but not recombination causes quantitative increase in offspring genetic diversity for varying genetic architectures.
Explaining the evolution of sex and recombination is particularly intriguing for some species of eusocial insects because they display exceptionally high mating frequencies and genomic recombination rates. Explanations for both phenomena are based on the notion that both increase colony genetic diversity, with demonstrated benefits for colony disease resistance and division of labor. However, the relative contributions of mating number and recombination rate to colony genetic diversity have never been simultaneously assessed. Our study simulates colonies, assuming different mating numbers, recombination rates, and genetic architectures, to assess their worker genotypic diversity. The number of loci has a strong negative effect on genotypic diversity when the allelic effects are inversely scaled to locus number. In contrast, dominance, epistasis, lethal effects, or limiting the allelic diversity at each locus does not significantly affect the model outcomes. Mating number increases colony genotypic variance and lowers variation among colonies with quickly diminishing returns. Genomic recombination rate does not affect intra- and inter-colonial genotypic variance, regardless of mating frequency and genetic architecture. Recombination slightly increases the genotypic range of colonies and more strongly the number of workers with unique allele combinations across all loci. Overall, our study contradicts the argument that the exceptionally high recombination rates cause a quantitative increase in offspring genotypic diversity across one generation. Alternative explanations for the evolution of high recombination rates in social insects are therefore needed. Short-term benefits are central to most explanations of the evolution of multiple mating and high recombination rates in social insects but our results also apply to other species.