Quality of family planning services in primary health centers of Jimma Zone, Southwest Ethiopia.
Good quality of care in family planning (FP) services help individuals and couples to meet their reproductive health needs safely and effectively. Therefore, assessment and improvement of the quality of family planning services could enhance family planning services utilization. This study was thus conducted to assess the quality of family planning services in primary health centers of Jimma Zone, Southwest Ethiopia. A cross-sectional facility based study was conducted from March 1(st)-25(th), 2011 among family planning clients of government primary health care centers in southwest Ethiopia. Exit interview of 301 family planning clients identified through systematic random sampling technique was carried out using a pre-tested structured questionnaire. Availability of resources was checked using provider interview and inventory checklist. Moreover, a total of 150 consultation sessions were observed using checklist. Descriptive statistics and linear regression coefficients were generated to meet the objective of the study. There was a shortage of some medical equipment, trained staffs, and information education and communication materials (IEC) in all of the family planning clinics. The mean waiting time at the service delivery points and consultation duration were 16.4 and 10.5 minutes, respectively. The providers used at least one information education and communication material in 33.3% of the consultation sessions. The overall satisfaction score was 8.64. Clients' perception on adequacy of information during consultation (β=0.24; ( 95%CI=0.02-0.16) ease of getting the clinic site, short waiting time (β=0.17; 95%CI=0.15-029) and educational level (β=0.09; 95%CI =0.09-0.29) were significantly associated with overall satisfaction. The findings of this study showed that there was lack of critical resources for the provision of quality family planning services in all of the primary health care centers included in the study. This has affected important aspects of service provision including the use of IEC materials during consultations. Hence, it is advisable that health managers of the health facilities and the district health office ensure improved availability of trained personnel, IEC materials and other supplies at the clinics.


Constitutive expression of the alpha4 integrin correlates with tumorigenicity and lymph node metastasis of the B16 murine melanoma.
The lymphatic system plays a critical role in melanoma metastasis, and yet, virtually no information exists regarding the cellular and molecular mechanisms that take place between melanoma cells and the lymphatic vasculature. Here, we generated B16-F1 melanoma cells that expressed high (B16alpha(4)+) and negligible (B16alpha(4)-) levels of alpha(4) integrin to determine how the expression of alpha(4) integrins affects tumor cell interactions with lymphatic endothelial cells in vitro and how it impacts lymphatic metastasis in vivo. We found a direct correlation between alpha(4) integrin expression on B16-F1 melanoma cells and their ability to form adhesive interactions with monolayers of lymphatic endothelial cells. Adhesion of B16-F1 melanoma cells to lymphatic endothelial cells was mediated by the melanoma cell alpha(4) integrin binding to its counterreceptor, vascular cell adhesion molecule 1 (VCAM-1), that was constitutively expressed on the lymphatic endothelial cells. VCAM-1 was also expressed on the tumor-associated lymphatic vessels of B16-F1 and B16alpha(4)+ tumors growing in the subcutaneous space of C57BL/6J mice. B16-F1 tumors metastasized to lymph nodes in 30% of mice, whereas B16alpha(4)+ tumors generated lymph node metastases in 80% of mice. B16-F1 melanoma cells that were deficient in alpha(4) integrins (B16alpha(4)-) were nontumorigenic. Collectively, these data show that the alpha(4) integrin expressed by melanoma cells contributes to tumorigenesis and may also facilitate metastasis to regional lymph nodes by promoting stable adhesion of melanoma cells to the lymphatic vasculature.


Social support for South Asian Muslim parents with life-limiting illness living in Scotland: a multiperspective qualitative study.
To explore experiences of social support needs among South Asian Muslim patients with life-limiting illness, living in Scotland, who are parents of young children. Secondary analysis of data from a multiperspective, longitudinal Scottish study involving in-depth semistructured interviews with patients, their nominated carers and healthcare professionals. Data were analysed using interpretive phenomenological analysis. Edinburgh, Scotland. South-Asian Muslim patients with life-limiting illness with children under the age of 18 (n=8), their carer (n=6) and their healthcare professional. Access and provision of social support in palliative care. Open-ended qualitative interviews identified four main themes: (1) parental sadness over being unable to provide tangible support; (2) parental desire to continue to provide emotional support; (3) limited availability of informal social support networks; and (4) differing perspectives between healthcare professionals and patients on patient access to social support sources, with a subtheme being the capacity of male carers to provide social support. South-Asian parents at the end of life had limited access to extended-network support. Gender roles appeared as challenging for healthcare providers who at times overestimated the amount of support a female carer could provide and underestimated the amount of support male carers provided. Implications for practice include the need for greater awareness by healthcare providers of the social support needs of ethnic minority and migrant parents with life-limiting illnesses and especially an awareness of the importance of the role of male and female carers. Further research is needed to explore how the timing of migration impacts the need for and availability of tangible and emotional informal social support among ethnic minority parents with life-limiting illness.


Visual Target Strategies in Infantile Nystagmus Patients With Horizontal Jerk Waveform.
The aim of this study was to propose a new pathophysiological hypothesis for involuntary eye oscillation in infantile nystagmus (IN): patients with IN exhibit impaired gaze fixation, horizontal smooth pursuit and optokinetic nystagmus (OKN) and use saccadic eye movements for these underlying impairments. In order to induce saccades, they make enough angle between gaze and target by precedent exponential slow eye movements. IN consists of the alternate appearance of the saccade and the slow eye movements. Unlike most previous theories, IN is therefore considered a necessary strategy allowing for better vision and not an obstacle to clear vision. In five patients with IN, eye movements were analyzed during the smooth pursuit test, saccadic eye movement test, OKN test and vestibulo-ocular reflex (VOR) test. Their gaze fixation, horizontal smooth pursuit, OKN and the last half of the slow phase of VOR were impaired. The lines obtained by connection of the end eye positions of fast phase of nystagmus coincided with the trajectories of targets. The findings indicate that patients followed the target by the fast but not the slow phase of nystagmus, which supports our hypothesis. By setting the direction of slow phase of nystagmus opposite to the direction of the OKN stimulation, enough angle can be effectively made between the gaze and target for the induction of saccade. This is the mechanism of reversed OKN response. In darkness and when eyes are closed, IN weakens because there is no visual target and neither the saccade for catching up the target or slow phase for induction of the saccade is needed.


Hydrogen-rich pure water prevents superoxide formation in brain slices of vitamin C-depleted SMP30/GNL knockout mice.
Hydrogen is an established anti-oxidant that prevents acute oxidative stress. To clarify the mechanism of hydrogen's effect in the brain, we administered hydrogen-rich pure water (H(2)) to senescence marker protein-30 (SMP30)/gluconolactonase (GNL) knockout (KO) mice, which cannot synthesize vitamin C (VC), also a well-known anti-oxidant. These KO mice were divided into three groups; recipients of H(2), VC, or pure water (H(2)O), administered for 33 days. VC levels in H(2) and H(2)O groups were <6% of those in the VC group. Subsequently, superoxide formation during hypoxia-reoxygenation treatment of brain slices from these groups was estimated by a real-time biography imaging system, which models living brain tissues, with Lucigenin used as chemiluminescence probe for superoxide. A significant 27.2% less superoxide formed in the H(2) group subjected to ischemia-reperfusion than in the H(2)O group. Thus hydrogen-rich pure water acts as an anti-oxidant in the brain slices and prevents superoxide formation.


Campylobacter jejuni induces transcytosis of commensal bacteria across the intestinal epithelium through M-like cells.
Recent epidemiological analyses have implicated acute Campylobacter enteritis as a factor that may incite or exacerbate inflammatory bowel disease (IBD) in susceptible individuals. We have demonstrated previously that C. jejuni disrupts the intestinal barrier function by rapidly inducing epithelial translocation of non-invasive commensal bacteria via a transcellular lipid raft-mediated mechanism ('transcytosis'). To further characterize this mechanism, the aim of this current study was to elucidate whether C. jejuni utilizes M cells to facilitate transcytosis of commensal intestinal bacteria. C. jejuni induced translocation of non-invasive E. coli across confluent Caco-2 epithelial monolayers in the absence of disrupted transepithelial electrical resistance or increased permeability to a 3 kDa dextran probe. C. jejuni-infected monolayers displayed increased numbers of cells expressing the M cell-specific marker, galectin-9, reduced numbers of enterocytes that stained with the absorptive enterocyte marker, Ulex europaeus agglutinin-1, and reduced activities of enzymes typically associated with absorptive enterocytes (namely alkaline phosphatase, lactase, and sucrase). Furthermore, in Campylobacter-infected monolayers, E. coli were observed to be internalized specifically within epithelial cells displaying M-like cell characteristics. These data indicate that C. jejuni may utilize M cells to promote transcytosis of non-invasive bacteria across the intact intestinal epithelial barrier. This mechanism may contribute to the inflammatory immune responses against commensal intestinal bacteria commonly observed in IBD patients.


Association between Brain and Kidney Near-Infrared Spectroscopy and Early Postresuscitation Mortality in Asphyxiated Newborn Piglets.
Early outcome predictors after delivery room cardiopulmonary resuscitation (CPR) of asphyxiated newborns are needed. To investigate if cerebral (rScO2) and renal (rSrO2) tissue oxygen saturation 30 min after return of spontaneous circulation (ROSC) are different between surviving versus nonsurviving piglets with asphyxia-induced cardiac arrest and CPR. Further, to investigate the relationship of rScO2 and rSrO2 to cardiac output (CO), blood pressure (BP), and biochemical variables 30 min and 4 h after ROSC. Anesthetized, mechanically ventilated piglets (1-3 days, 1.7-2.4 kg) were used. rScO2, rSrO2, SpO2, right common carotid artery flow, and arterial BP were measured continuously. CO was measured with echocardiography. The piglets were asphyxiated until cardiac arrest and resuscitated. Piglets that survived 4 h after ROSC (n = 12) were compared with piglets that died before planned euthanasia at 4 h (n = 13). Left ventricular, and kidney and brain tissue lactate were analyzed. Correlations between variables were assessed. Thirty minutes after ROSC, median rSrO2 (43% [n = 10] vs. 25% [n = 2], p = 0.003) but not rScO2 (46% [41-55] [n = 10] vs. 40% [22-45] [n = 5], p = 0.08) was higher in survivors than in nonsurvivors. Arterial lactate was negatively correlated and pH positively correlated with rScO2 and rSrO2. Left ventricular, but not kidney or brain lactate was negatively correlated with rScO2 and rSrO2. There was no correlation between CO or BP and rScO2 or rSrO2. Despite satisfactory CO and BP vital organ oxygenation can be poor. Tissue oxygen saturation, pH, and lactate, as measures of anaerobic metabolism, may reflect vital organ oxygenation and outcome.


The association between pain and prevalent and incident motoric cognitive risk syndrome in older adults.
The Motoric Cognitive Risk Syndrome (MCR) is a pre-dementia syndrome characterized by subjective cognitive complaints and slow gait in the absence of dementia and mobility disability. Worse cognitive and motoric function is associated with chronic pain in older adults. Our aim was to study the association between pain and prevalent and incident MCR in adults aged 65 years and older. We analyzed the cross-sectional association between severity of pain and prevalent MCR in 3244 older adults participating in the Health and Retirement Study (2008 wave) using logistic regression analysis adjusting for demographic, peripheral, central or biological risk factors. Additionally, we analyzed the longitudinal association between severity of pain and incident MCR in 362 participants in the Central Control of Mobility in Aging Study, using Cox regression analysis. The 155 Health and Retirement Study participants with severe pain had an increased risk of prevalent MCR (n = 249), compared to 2245 individuals without pain (adjusted for demographics OR: 2.78, 95 % CI:1.74-4.45). Over a mean follow-up of 3.01 years (SD 1.38), 29 individuals in the Central Control of Mobility in Aging Study developed incident MCR. Older adults with severe pain had over a five times increased risk of developing incident MCR, compared to those without pain even after adjusting for demographic variables (HR: 5.44, 95 % CI: 1.81-16.40). Older adults with severe pain have a higher prevalence and incidence of MCR. These findings should be further explored to establish if pain is a potentially modifiable risk factor to prevent cognitive decline.


The garlic-derived organosulfur component ajoene decreases basal cell carcinoma tumor size by inducing apoptosis.
Although the therapeutic role of ajoene, an organosulfur compound of garlic, in cardiovascular diseases and mycology has been established, its usefulness in cancer treatment has only recently been suggested. We applied ajoene topically to the tumors of 21 patients with either nodular or superficial basal cell carcinoma (BCC). A reduction in tumor size was seen in 17 patients. Immunohistochemical assays for Bcl-2 expression in a selection of these tumors before and after treatment showed a significant decrease in this apoptosis-suppressing protein. On average, the percentage of tumor cells expressing the proliferation marker Ki-67 was not decreased, which suggests that the action of ajoene is not explained by a cytostatic effect. To obtain further insight into the mode of action of ajoene, the BCC cell line TE354T and a short-term primary culture of BCC were analyzed for apoptosis induction after treatment with the drug. Apoptosis was detected by morphology of the cells and by flow cytometry. Ajoene induced apoptosis in a dose- and time-dependent manner in these cultures. Taking together the results of the in vivo and in vitro studies, we conclude that ajoene can reduce BCC tumor size, mainly by inducing the mitochondria-dependent route of apoptosis.


Label-free cytotoxicity screening assay by digital holographic microscopy.
We introduce a label-free technology based on digital holographic microscopy (DHM) with applicability for screening by imaging, and we demonstrate its capability for cytotoxicity assessment using mammalian living cells. For this first high content screening compatible application, we automatized a digital holographic microscope for image acquisition of cells using commercially available 96-well plates. Data generated through both label-free DHM imaging and fluorescence-based methods were in good agreement for cell viability identification and a Z'-factor close to 0.9 was determined, validating the robustness of DHM assay for phenotypic screening. Further, an excellent correlation was obtained between experimental cytotoxicity dose-response curves and known IC50 values for different toxic compounds. For comparable results, DHM has the major advantages of being label free and close to an order of magnitude faster than automated standard fluorescence microscopy.


Research priorities for public mental health in Europe: recommendations of the ROAMER project.
The ROAdmap for MEntal health Research in Europe project aimed to create an integrated European roadmap for mental health research. Leading mental health research experts across Europe have formulated consensus-based recommendations for future research within the public mental health field. Experts were invited to compile and discuss research priorities in a series of topic-based scientific workshops. In addition, a Delphi process was carried out to reach consensus on the list of research priorities and their rank order. Three web-based surveys were conducted. Nearly 60 experts were involved in the priority setting process. Twenty priorities for public mental health research were identified through the consensus process. The research priorities were divided into summary principles-encompassing overall recommendations for future public mental health research in Europe-and thematic research priorities, including area-specific top priorities on research topics and methods. The priorities represent three overarching goals mirroring societal challenges, that is, to identify causes, risk and protective factors for mental health across the lifespan; to advance the implementation of effective public mental health interventions and to reduce disparities in mental health. The importance of strengthening research on the implementation and dissemination of promotion, prevention and service delivery interventions in the mental health field needs to be emphasized. The complexity of mental health and its broader conceptualisation requires complementary research approaches and interdisciplinary collaboration to better serve the needs of the European population.


Optimal Perioperative Care in Major Head and Neck Cancer Surgery With Free Flap Reconstruction: A Consensus Review and Recommendations From the Enhanced Recovery After Surgery Society.
Head and neck cancers often require complex, labor-intensive surgeries, especially when free flap reconstruction is required. Enhanced recovery is important in this patient population but evidence-based protocols on perioperative care for this population are lacking. To provide a consensus-based protocol for optimal perioperative care of patients undergoing head and neck cancer surgery with free flap reconstruction. Following endorsement by the Enhanced Recovery After Surgery (ERAS) Society to develop this protocol, a systematic review was conducted for each topic. The PubMed and Cochrane databases were initially searched to identify relevant publications on head and neck cancer surgery from 1965 through April 2015. Consistent key words for each topic included "head and neck surgery," "pharyngectomy," "laryngectomy," "laryngopharyngectomy," "neck dissection," "parotid lymphadenectomy," "thyroidectomy," "oral cavity resection," "glossectomy," and "head and neck." The final selection of literature included meta-analyses and systematic reviews as well as randomized controlled trials where available. In the absence of high-level data, case series and nonrandomized studies in head and neck cancer surgery patients or randomized controlled trials and systematic reviews in non-head and neck cancer surgery patients, were considered. An international panel of experts in major head and neck cancer surgery and enhanced recovery after surgery reviewed and assessed the literature for quality and developed recommendations for each topic based on the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system. All recommendations were graded following a consensus discussion among the expert panel. The literature search, including a hand search of reference lists, identified 215 relevant publications that were considered to be the best evidence for the topic areas. A total of 17 topic areas were identified for inclusion in the protocol for the perioperative care of patients undergoing major head and neck cancer surgery with free flap reconstruction. Best practice includes several elements of perioperative care. Among these elements are the provision of preoperative carbohydrate treatment, pharmacologic thromboprophylaxis, perioperative antibiotics in clean-contaminated procedures, corticosteroid and antiemetic medications, short acting anxiolytics, goal-directed fluid management, opioid-sparing multimodal analgesia, frequent flap monitoring, early mobilization, and the avoidance of preoperative fasting. The evidence base for specific perioperative care elements in head and neck cancer surgery is variable and in many cases information from different surgerical procedures form the basis for these recommendations. Clinical evaluation of these recommendations is a logical next step and further research in this patient population is warranted.


Effects of breastfeeding on pain relief in full-term newborns.
Breastfeeding may be useful for relieving procedural pain experienced by neonates. Researchers have compared breastfeeding against other pain relieving approaches in several studies, presenting marked methodologic heterogeneity. To investigate the effectiveness of breastfeeding in reducing pain in newborns undergoing blood collection for newborn screening. The sample of this randomized clinical trial study consisted of 60 full-term newborns: 31 in the experimental group and 29 in the control group. The experimental group was breastfed 5 minutes before, during, and for 5 minutes after the blood collection procedure. Neonates in the control group were held in mothers' arms but not fed or given a soother. The duration of breastfeeding was prolonged in comparison to previous studies. The primary outcomes were Neonatal Facial Actions (Neonatal Facial Activity Coding System-upper face), sleep-wake state. Heart rate was considered as an index of arousal. Sucking frequency was only evaluated in the experimental group. Compared with the control group, the experimental group had significantly lower, Neonatal Facial Activity Coding System and sleep-wake state scores and heart rates changes. In the experimental group sucking frequency was highest during the first 5 minutes of breastfeeding before the procedure. This study innovates from earlier studies in 4 respects: the different phases of the procedure were evaluated separately; the breastfeeding intervention covered the period from 5 minutes before the blood collection until the end of recovery; sleep-wake state was fully assessed (not merely crying) and the sucking frequency in the experimental group was assessed during the procedure. The conclusion was that breastfeeding was effective in reducing pain caused by blood collection for newborn screening.


Alterations in excitatory and GABAergic inhibitory connections in hippocampal transplants.
Solid pieces of embryonic hippocampal tissue were implanted in a cavity formed by aspiration of the fimbria-fornix and the overlying cingulate cortex in adult rats. Six to 8 months after the transplantation, chronic recording electrodes were implanted into the graft and the host hippocampi for the recording of electroencephalogram and unit activity in the freely moving animal. Irregularly occurring sharp waves or electroencephalogram spikes and concurrent synchronous discharge of large groups of neurons dominated the electrical activity of the grafts, in contrast to the situation in normal animals. Light microscopy and GABA immunocytochemistry in the grafts revealed that the three major cell types of the hippocampal formation, i.e. pyramidal neurons, dentate granule cells and GABA-immunoreactive interneurons were present in the hippocampal grafts. At the ultrastructural level, however, significant alterations in connectivity were observed. The most striking finding was the absence or sparse occurrence of synapses on the axon initial segments of pyramidal neurons. The axon initial segments are normally densely covered by GABAergic synapses derived from a specialized type of interneuron, the chandelier or axo-axonic cell. On the other hand, numerous GABA-immunoreactive terminals were found in synaptic contact with somata of pyramidal neurons, suggesting that other types of GABAergic interneurons and their efferent connections may have developed in a normal manner. The cell bodies of pyramidal neurons received, in addition, several asymmetric synapses from GABA-negative terminals. These presumably excitatory synapses are not present on the somata of pyramidal cells in the normally developing hippocampus. We hypothesize that the somatic excitatory synapses originate, at least in part, from the axon collaterals of the neighbouring pyramidal cells in the graft. We suggest that the hyperexcitability of the neuronal circuitry within the graft is due to reduced inhibition (lack of axo-axonic synapses) coupled with increased collateral excitation of the pyramidal neurons.


Highly visible street-based HIV rapid testing: is it an attractive option for a previously untested population? A cross-sectional study.
Given the shortage of community-based HIV testing initiatives in resource-rich countries not targeting most-at-risk populations, we aimed to evaluate whether a highly visible mobile programme promoting and offering rapid HIV testing in the street can attract persons at risk for infection who have never been tested. Between 2008 and 2011, the programme served 7552 persons in various Spanish cities who answered a brief questionnaire while awaiting their results. The factors associated with being tested for the first time were analysed using two logistic regression models, one for men who have sex with men (MSM) and the other for only heterosexual men (MSW) and women. 3517 participants (47%) were first-time testers (24% of MSM, 56% of MSW and 60% of women). Among them, 22 undiagnosed HIV infections were detected with a global prevalence of 0.6% and 3.1% in MSM. Undergoing a first HIV test was independently associated with age <30, being from Spain or another developed country, lack of university education, having fewer partners, having had unprotected sex with casual partners and not having been diagnosed with a sexually transmitted infection. In heterosexuals, also with never injected drugs, and in MSM, with not being involved in the gay community. Among those tested for the first time, 22% had never thought of being tested and 62% decided to be tested when they passed by and noticed the programme, regardless of their previous intentions. This community programme attracted a substantial number of persons previously untested and particularly hard to reach, such as those with low education and MSM who were least involved in the gay community. Programme visibility was a decisive factor for almost two of every three persons who had never been tested.


New scientific paradigms for probiotics and prebiotics.
The inaugural meeting of the International Scientific Association for Probiotics and Prebiotics (ISAPP) was held May 3 to May 5 2002 in London, Ontario, Canada. A group of 63 academic and industrial scientists from around the world convened to discuss current issues in the science of probiotics and prebiotics. ISAPP is a non-profit organization comprised of international scientists whose intent is to strongly support and improve the levels of scientific integrity and due diligence associated with the study, use, and application of probiotics and prebiotics. In addition, ISAPP values its role in facilitating communication with the public and healthcare providers and among scientists in related fields on all topics pertinent to probiotics and prebiotics. It is anticipated that such efforts will lead to development of approaches and products that are optimally designed for the improvement of human and animal health and well being. This article is a summary of the discussions, conclusions, and recommendations made by 8 working groups convened during the first ISAPP workshop focusing on the topics of: definitions, intestinal flora, extra-intestinal sites, immune function, intestinal disease, cancer, genetics and genomics, and second generation prebiotics.


Effect of Kinesio taping on clinical symptoms in people with fibromyalgia: A randomized clinical trial.
Fibromyalgia syndrome (FMS) is a disorder characterized by chronic widespread pain and muscle soreness. Because of its high prevalence, many therapeutic approaches have been proposed with the aim of improving overall physical function and reducing pain. Since low adherence is one of the major limitations among these patients, treatments that do not interfere with their daily routines, such as KT, would be a feasible option. The main goal of this study was to analyze the effect of Kinesio Tape (KT) on pain, posture, body comfort and quality of life (QoL) in people with FMS. Thirty-five women (between 17 and 70 years of age) with FMS were randomly allocated to two treatment groups, depending on the location of the KT: "Upper trunk group" (UTG) (n= 18) and "Global trunk group" (GTG) (n= 17). The intervention period lasted 3 weeks. Pain, comfort, trunk posture and QoL were assessed before and after the intervention. Both KT treatments were effective in reducing pain and improving neck and shoulder comfort (p< 0.05). The GTG achieved a significant improvement in thoracic comfort (p< 0.05), whereas the UTG experienced a significant improvement in non-dominant side trunk posture and showed a significant improvement in the QoL score (p< 0.05). GT and UT KT applications have positive effects on patients with FMS and may be considered as a suitable treatment option among this population.


Connectivity-based subdivisions of the human right "temporoparietal junction area": evidence for different areas participating in different cortical networks.
Controversy surrounds the role of the temporoparietal junction (TPJ) area of the human brain. Although TPJ has been implicated both in reorienting of attention and social cognition, it is still unclear whether these functions have the same neural basis. Indeed, whether TPJ is a precisely identifiable cortical region or a cluster of subregions with separate functions is still a matter of debate. Here, we examined the structural and functional connectivity of TPJ, testing whether TPJ is a unitary area with a heterogeneous functional connectivity profile or a conglomerate of regions with distinctive connectivity. Diffusion-weighted imaging tractrography-based parcellation identified 3 separate regions in TPJ. Resting-state functional connectivity was then used to establish which cortical networks each of these subregions participates in. A dorsal cluster in the middle part of the inferior parietal lobule showed resting-state functional connectivity with, among other areas, lateral anterior prefrontal cortex. Ventrally, an anterior TPJ cluster interacted with ventral prefrontal cortex and anterior insula, while a posterior TPJ cluster interacted with posterior cingulate, temporal pole, and anterior medial prefrontal cortex. These results indicate that TPJ can be subdivided into subregions on the basis of its structural and functional connectivity.


Extracellular vesicles for tissue repair and regeneration: Evidence, challenges and opportunities.
Extracellular vesicles (EVs) are biological nanoparticles naturally secreted by cells, acting as delivery vehicles for molecular messages. During the last decade, EVs have been assigned multiple functions that have established their potential as therapeutic mediators for a variety of diseases and conditions. In this review paper, we report on the potential of EVs in tissue repair and regeneration. The regenerative properties that have been associated with EVs are explored, detailing the molecular cargo they carry that is capable of mediating such effects, the signaling cascades triggered in target cells and the functional outcome achieved. EV interactions and biodistribution in vivo that influence their regenerative effects are also described, particularly upon administration in combination with biomaterials. Finally, we review the progress that has been made for the successful implementation of EV regenerative therapies in a clinical setting.


Endothelium-dependent vascular relaxation induced by Eucommia ulmoides Oliv. bark extract is mediated by NO and EDHF in small vessels.
The vasorelaxant effects of the aqueous extract prepared from the bark of the Chinese medicinal herb, Eucommia ulmoides Oliv. (also referred to as Tu-Chung or Du-Zhong), which is a common active ingredient in traditional antihypertensive herbal prescriptions in China, have recently been characterized in rat aorta and dog carotid artery. The vasorelaxant effect of eucommia bark extract on these large elastic arteries was found to be entirely endothelium-dependent and nitric oxide (NO)-mediated. Since smaller muscular arteries play a more dominant role in the change of peripheral resistance and thus the regulation of blood pressure, we have now compared the relaxant effects of eucommia bark extract using aorta and the proximal as well as the distal ends of the superior mesenteric arteries from the rat, with a specific objective to investigate whether smaller muscular arteries also elicit endothelium-dependent vascular relaxation (EDVR) in response to eucommia bark extract. We have also determined whether the EDVR, if indeed occurring in the mesenteric arteries, is mediated entirely by NO, or whether it also involves endothelium-derived hyperpolarizing factor (EDHF). We found that all three types of vessel preparations elicit EDVR in response to the eucommia bark extract concentration-dependently in a similar manner to the relaxant responses to carbachol (CCh). Although the NO synthase inhibitor L-NAME totally abolished the EDVR in aorta, it only partial abolished EDVR in mesenteric arteries isolated from each end, the distal end being more resistant to L-NAME. However, the residual L-NAME-resistant relaxation of the rat mesenteric arteries could be further inhibited by preincubation of the vessels with the combination of L-NAME and 15-20 mM KCl (KCl itself at this low concentration caused little or no contraction). Therefore, the EDVR induced by the eucommia extract and CCh in aorta is mediated entirely by NO, and that in mesenteric arteries by NO as well as EDHF, with the EDHF component (inhibited by KCl) larger in the smaller distal end of the rat mesenteric artery. Results of our study offer a plausible mechanistic basis for the vasorelaxing action of Eucommia ulmoides Oliv., which may account for its well-documented antihypertensive action.


CATCH: a clinical decision rule for the use of computed tomography in children with minor head injury.
There is controversy about which children with minor head injury need to undergo computed tomography (CT). We aimed to develop a highly sensitive clinical decision rule for the use of CT in children with minor head injury. For this multicentre cohort study, we enrolled consecutive children with blunt head trauma presenting with a score of 13-15 on the Glasgow Coma Scale and loss of consciousness, amnesia, disorientation, persistent vomiting or irritability. For each child, staff in the emergency department completed a standardized assessment form before any CT. The main outcomes were need for neurologic intervention and presence of brain injury as determined by CT. We developed a decision rule by using recursive partitioning to combine variables that were both reliable and strongly associated with the outcome measures and thus to find the best combinations of predictor variables that were highly sensitive for detecting the outcome measures with maximal specificity. Among the 3866 patients enrolled (mean age 9.2 years), 95 (2.5%) had a score of 13 on the Glasgow Coma Scale, 282 (7.3%) had a score of 14, and 3489 (90.2%) had a score of 15. CT revealed that 159 (4.1%) had a brain injury, and 24 (0.6%) underwent neurologic intervention. We derived a decision rule for CT of the head consisting of four high-risk factors (failure to reach score of 15 on the Glasgow coma scale within two hours, suspicion of open skull fracture, worsening headache and irritability) and three additional medium-risk factors (large, boggy hematoma of the scalp; signs of basal skull fracture; dangerous mechanism of injury). The high-risk factors were 100.0% sensitive (95% CI 86.2%-100.0%) for predicting the need for neurologic intervention and would require that 30.2% of patients undergo CT. The medium-risk factors resulted in 98.1% sensitivity (95% CI 94.6%-99.4%) for the prediction of brain injury by CT and would require that 52.0% of patients undergo CT. The decision rule developed in this study identifies children at two levels of risk. Once the decision rule has been prospectively validated, it has the potential to standardize and improve the use of CT for children with minor head injury.


Carbon nanomaterials: multi-functional agents for biomedical fluorescence and Raman imaging.
Carbon based nanomaterials have emerged over the last few years as important agents for biomedical fluorescence and Raman imaging applications. These spectroscopic techniques utilize either fluorescently labelled carbon nanomaterials or the intrinsic photophysical properties of the carbon nanomaterial. In this review article we present the utilization and performance of several classes of carbon nanomaterials, namely carbon nanotubes, carbon nanohorns, carbon nanoonions, nanodiamonds and different graphene derivatives, which are currently employed for in vitro as well as in vivo imaging in biology and medicine. A variety of different approaches, imaging agents and techniques are examined and the specific properties of the various carbon based imaging agents are discussed. Some theranostic carbon nanomaterials, which combine diagnostic features (i.e. imaging) with cell specific targeting and therapeutic approaches (i.e. drug delivery or photothermal therapy), are also included in this overview.


The 2S albumin allergens of Arachis hypogaea, Ara h 2 and Ara h 6, are the major elicitors of anaphylaxis and can effectively desensitize peanut-allergic mice.
Ara h 2 and Ara h 6, co-purified together in a 13-25 kD fraction (Ara h 2/6; 20 kD fraction) on gel filtration chromatography, account for the majority of effector activity in a crude peanut extract (CPE) when assayed with RBL SX-38 cells sensitized with IgE from human peanut allergic sera. To determine if Ara h 2/6 are the primary peanut allergens responsible for allergic reactions in vivo and to determine if Ara h 2/6 would be sufficient to prevent allergic reactions to a complete CPE. An oral sensitization mouse model of peanut allergy was used to assess the activity of Ara h 2/6 (20 kD) and CPE without the 20 kD fraction (CPE w/o 20 kD) for allergic provocation challenge and immunotherapy. The activity of these preparations was also tested in an assay of histamine release from human basophils in whole blood. Compared with mice challenged with control CPE, mice challenged with CPE w/o 20 kD experienced reduced symptoms (P < 0.05) and a smaller decrease in body temperature (P < 0.01). Results with the basophil histamine release assay corroborated these findings (P < 0.01). The mouse model was also used to administer Ara h 2/6 (20 kD) in an immunotherapy protocol, in which peanut-allergic mice treated with the 20 kD fraction experienced significantly reduced symptoms, changes in body temperature, and mast cell protease (MMCP-1) release compared with placebo (P < 0.01 for all parameters). Importantly, immunotherapy with the 20 kD fraction was just as effective as treatment with CPE, whereas CPE w/o 20 kD was significantly less effective for higher dose peanut challenges. Ara h 2/6 are the most potent peanut allergens in vivo and can be used to desensitize peanut-allergic mice. These results have potential implications for clinical research in the areas of diagnosis and immunotherapy for peanut allergy.


Annual ambient black carbon associated with shorter telomeres in elderly men: Veterans Affairs Normative Aging Study.
Telomere length reflects biological age and is inversely associated with risk of cardiovascular disease (CVD). Ambient air pollution is associated with CVD, but its effect on telomere length is unknown. We investigated whether ambient black carbon (BC), a marker for traffic-related particles, is associated with telomere length in the Normative Aging Study (NAS). Among 165 never-smoking men from the NAS, leukocyte telomere length (LTL) was measured repeatedly approximately every 3 years from 1999 through 2006 using quantitative real-time polymerase chain reaction (qRT-PCR). BC concentration at their residences during the year before each LTL measurement was estimated based on a spatiotemporal model calibrated with BC measurements from 82 locations within the study area. The median [interquartile range (IQR)] annual moving-average BC concentration was 0.32 (0.20-0.45) microg/m3. LTL, expressed as population-standardized ratio of telomere repeat to single-copy gene copy numbers, had a geometric mean (geometric SD) of 1.25 (1.42). We used linear mixed-effects models including random subject intercepts and adjusted for several potential confounders. We used inverse probability of response weighting to adjust for potential selection bias due to loss to follow-up. An IQR increase in annual BC (0.25 microg/m3) was associated with a 7.6% decrease (95% confidence interval, -12.8 to -2.1) in LTL. We found evidence of effect modification, with a stronger association among subjects > or = 75 years of age compared with younger participants (p = 0.050) and statin medications appearing protective of the effects of BC on LTL (p = 0.050). Telomere attrition, linked to biological aging, may be associated with long-term exposures to airborne particles, particularly those rich in BC, which are primarily related to automobile traffic.


Bone infection.
Osteomyelitis, or bone infection, affects all age groups and develops from various sources including haematogenously from distant infection foci, from external sources such as post-operative or post-traumatic wound infections and from adjoining soft tissue infections. Staphylococcus aureus, Streptococcus pyogenes and Haemophilus influenzae are the most common pathogens of haematogenous osteomyelitis. Aerobic and facultative gram-negative bacteria have emerged as significant pathogens in some types of osteomyelitis while anaerobic bacteria are increasingly recognized as potential pathogens in non-haematogenous osteomyelitis. The emergence of antibiotic resistance is of increasing concern, although improvements in radiologic imaging, antibiotic treatment and heightened awareness have led to earlier detection such that long-term sequelae and morbidity are now primarily due to delays in diagnosis and inadequate treatment.


South-east Asian ovalocytosis and the cryohydrocytosis form of hereditary stomatocytosis show virtually indistinguishable cation permeability defects.
The hereditary stomatocytoses are a group of dominantly inherited conditions in which the osmotic stability of the red cell is compromised by abnormally high cation permeability. This report demonstrates the very marked similarities between the cryohydrocytosis form of hereditary stomatocytosis and the common tropical condition south-east Asian ovalocytosis (SAO). We report two patients, one showing a novel cryohydrocytosis variant (Ser762Arg in SLC4A1) and a case of SAO. Both cases showed a mild haemolytic state with some stomatocytes on the blood film, abnormal intracellular sodium and potassium levels which were made markedly abnormal by storage of blood at 0°C, increased cation 'leak' fluxes at 37°C and increased Na(+) K(+) pump activity. In both cases, the anion exchange function of the mutant band 3 was destroyed. Extensive electrophysiological studies comparing the cation leak and conductance in Xenopus laevis oocytes expressing the two mutant genes showed identical patterns of abnormality. These data are consistent with the cryohydrocytosis form of hereditary stomatocytosis and we conclude that the cation leak in SAO is indistinguishable from that in cryohydrocytosis, and that SAO should be considered to be an example of hereditary stomatocytosis.


Mutations that permit residual CFTR function delay acquisition of multiple respiratory pathogens in CF patients.
Lung infection by various organisms is a characteristic feature of cystic fibrosis (CF). CFTR genotype effects acquisition of Pseudomonas aeruginosa (Pa), however the effect on acquisition of other infectious organisms that frequently precede Pa is relatively unknown. Understanding the role of CFTR in the acquisition of organisms first detected in patients may help guide symptomatic and molecular-based treatment for CF. Lung infection, defined as a single positive respiratory tract culture, was assessed for 13 organisms in 1,381 individuals with CF. Subjects were divided by predicted CFTR function: 'Residual': carrying at least one partial function CFTR mutation (class IV or V) and 'Minimal' those who do not carry a partial function mutation. Kaplan-Meier estimates were created to assess CFTR effect on age of acquisition for each organism. Cox proportional hazard models were performed to control for possible cofactors. A separate Cox regression was used to determine whether defining infection with Pa, mucoid Pa or Aspergillus (Asp) using alternative criteria affected the results. The influence of severity of lung disease at the time of acquisition was evaluated using stratified Cox regression methods by lung disease categories. Subjects with 'Minimal' CFTR function had a higher hazard than patients with 'Residual' function for acquisition of 9 of 13 organisms studied (HR ranging from 1.7 to 3.78 based on the organism studied). Subjects with minimal CFTR function acquired infection at a younger age than those with residual function for 12 of 13 organisms (p-values ranging: < 0.001 to 0.017). Minimal CFTR function also associated with younger age of infection when 3 alternative definitions of infection with Pa, mucoid Pa or Asp were employed. Risk of infection is correlated with CFTR function for 8 of 9 organisms in patients with good lung function (>90%ile) but only 1 of 9 organisms in those with poorer lung function (<50%ile). Residual CFTR function correlates with later onset of respiratory tract infection by a wide spectrum of organisms frequently cultured from CF patients. The protective effect conferred by residual CFTR function is diminished in CF patients with more advanced lung disease.


Evaluation of molecules or extracts modulating seborrhea and its consequences, using normal human culture of sebocytes and keratinocytes, skin explants models and in vivo methods: a case study.
Skin produces sebum through sebocytes. Hyper-seborrhea creates conditions for the development of inflamed cutaneous alterations through bacteria colonization triggering dead cell accumulation and pro-inflammatory mediator release. Study of sebum production, its modulation, and its consequences requires complementary in vitro models in order to evaluate the effect of molecules on cell metabolisms. Clinical studies need to be performed to confirm in vitro results. Effects of phenylpropanoids, obtained by elicitation and purification from plant cell culture of Syringa vulgaris (CCSV), were studied on sebocytes, keratinocytes, and explants, all derived from normal human skins. Normal human sebocytes (NHSs) expressed markers such as cytokeratin-7, cytokeratin-4, and perilipin-2 (PLIN-2) (1); the latter being colocalized with lipid droplets. Lipid droplets clearly appeared and their size increased rapidly when lipogenic agents were used. NHS, normal human keratinocytes (NHK), and explants reacted to presence of bacterial fragments which trigger pre-inflammatory mediator release. CCSV reduced lipid storage and release of pre-inflammatory mediators in NHS, NHK and explants. CCSV also reduced P. acnes growth and triggered beta-defensin-2 and cathelicidin synthesis by NHS, two natural antimicrobial peptides. On volunteers, sebum production, inflamed blemishes, and retentional lesions were significantly reduced after 1 month treatment with CCSV.


The cloning of FRAXF: trinucleotide repeat expansion and methylation at a third fragile site in distal Xqter.
Three fragile sites, FRAXA, FRAXE and FRAXF lie in the Xq27-28 region of the human X chromosome. The expression of FRAXA is associated with the fragile X syndrome, the most prevalent form of inherited mental retardation whilst the expression of FRAXE is associated with a rarer and comparatively milder form of mental handicap. Both the FRAXA and FRAXE sites have been cloned and the fragile site expression found to be due to the expansion of analogous CGG/GCC trinucleotide repeat arrays. We describe here the cloning of the third fragile site, FRAXF, and demonstrate that it involves the expansion of a (GCCGTC)n(GCC)n compound array. PCR analyses across the repeat of normal individuals show that the number of triplets in the array ranges from 12-26 and the most common allele consists of 14 triplet units. Sequencing analyses show that 95% of normal individuals have three copies of the GCCGTC motif and in these individuals, the size variation observed by PCR is due to copy number alterations in the GCC array. In a cytogenetically positive male with developmental delay, the array is expanded by > 900 triplets and the adjacent CpG-rich region is methylated. The array is also expanded in cytogenetically positive carrier females from the family originally used to define the FRAXF site. We conclude that the expanded array corresponds to the FRAXF fragile site.


Methodology for the Canadian Activase for Stroke Effectiveness Study (CASES). CASES Investigators.
Intravenous recombinant tissue plasminogen activator (tPA, alteplase) was conditionally licensed for the treatment of acute ischemic stroke (AIS) in Canada on February 17, 1999. As a condition of licensure, the Canadian Activase for Stroke Effectiveness Study (CASES) was established to monitor the use of alteplase for AIS in Canada. The study involves multiple stakeholders. CASES is a prospective registry of patients treated with alteplase for AIS. The purposes of this registry are to ensure the safety of the drug in the Canadian context, to assess effectiveness of alteplase for AIS and to gather further information to try to establish which patients are most likely to benefit from treatment. Both community (n=25) and tertiary centres (n=35) have enrolled a total of 944 patients to date. Early results suggest that thrombolytic stroke treatment is both safe and effective among these centres. This paper outlines the development of and methods for the CASES study. The study is an example of a multi-stakeholder collaboration to advance the care of patients with acute stroke.


A Latent Class IRT Approach to Defining and Measuring Language Proficiency.
English language learner (EL) status has high stakes implications for determining when and how ELs should be evaluated for academic achievement. In the US, students designated as English learners are assessed annually for English language proficiency (ELP), a complex construct whose conceptualization has evolved in recent years to reflect more precisely the language demands of content area achievement as reflected in the standards of individual states and state language assessment consortia, such as WIDA and ELPA21. The goal of this paper was to examine the possible role for and utility of using content area assessments to validate language proficiency mastery criteria. Specifically, we applied mixture item response models to identify two classes of EL students: (1) ELs for whom English language arts and math achievement test items have similar difficulty and discrimination parameters as they do for non-ELs and (2) ELs for whom the test items function differently. We used latent class IRT methods to identify the two groups of ELs and to evaluate the effects of different subscales of ELP (reading, writing, listening, and speaking) on group membership. Only reading and writing were significant predictors of class membership. Cut-scores based on summary scores of ELP were imperfect predictors of class membership and indicated the need for finer differentiation within the top proficiency category. This study demonstrates the importance of linking definitions of ELP to the context for which ELP is used and suggests the possible value of psychometric analyses when language proficiency standards are linked to the language requirements for content area achievement.


Individual and family characteristics associated with BRCA1/2 genetic testing in high-risk families.
Little is known about family members' interrelated decisions to seek genetic testing for breast cancer susceptibility. The specific aims of this cross-sectional, descriptive, cohort study were (i) to examine whether individual and family characteristics have a direct effect on women's decisions to use genetic testing for hereditary susceptibility to breast cancer and (ii) to explore whether family characteristics moderate the relationships between individual characteristics and the decision to use genetic testing. Participants were women (>18 years old) who (i) received genetic testing for hereditary breast cancer and who agreed to invite one of their female relatives into the study and (ii) female relatives who had NOT obtained genetic testing and were identified by pedigree analysis as having >10% chances of hereditary susceptibility to breast cancer. The final sample consisted of 168 English-speaking, family dyads who completed self-administered, mailed surveys with validated instruments. Multivariate conditional logistic regression analyses showed that the proposed model explained 62% of the variance in genetic testing. The factors most significantly associated with genetic testing were having a personal history of cancer; perceiving genetic testing to have more benefits than barriers; having greater family hardiness; and perceiving fewer negative consequences associated with a breast cancer diagnosis. No significant interaction effects were observed. Findings suggest that both individual and family characteristics are associated with the decision to obtain genetic testing for hereditary breast cancer; hence, there is a need for interventions that foster a supportive family environment for patients and their high-risk relatives.


Interactive CO-learning for Research Engagement and Education (I-COREE) Curriculum to Build Capacity Between Community Partners and Academic Researchers.
The voice of diverse communities continues to be minimal in academic research. Few models exist for education and training of new research topics and terminology and building partnership capacity in community-engaged research. Little is known about integrative education and training when building participatory research partnerships for sustainability and developing trust and rapport. Community partners at an Asian community-based health and social services center in a large metropolitan area wanted to explore the cultural context of a health-assistive smart home that monitors and auto-alerts with changes in health. With historical and recent rising trends in culturally insensitive research in several diverse communities, the concept of technology-enabled monitoring in the privacy of one's home brings uncertainty. Academic nurse researchers and community partners co-created a culturally safe integrative education and training curriculum, the Interactive CO-learning for Research Engagement and Education (I-COREE). The purpose was to design, implement, and evaluate the curriculum to respond to the community partners' needs to create a culturally safe space through an integrative education and training to facilitate building partnership capacity for research engagement including developing trust and rapport and addressing uncertainties in health-assistive technologies. Popular education tenets informed the curriculum. Twelve academic and community partners participated, four were team teachers who co-led the session. Implementation of the experiential, multimodal co-learning activities were conducted within ahalf-day. The curriculum evaluation indicated that it helped bridge critical conversations about partners' fears of the unknown, approach culturally sensitive topics safely, and trust and rapport. Key elements may be translatable to other partnerships.


MEGGASENSE - The Metagenome/Genome Annotated Sequence Natural Language Search Engine: A Platform for the Construction of Sequence Data Warehouses.
The MEGGASENSE platform constructs relational databases of DNA or protein sequences. The default functional analysis uses 14 106 hidden Markov model (HMM) profiles based on sequences in the KEGG database. The Solr search engine allows sophisticated queries and a BLAST search function is also incorporated. These standard capabilities were used to generate the SCATT database from the predicted proteome of Streptomyces cattleya. The implementation of a specialised metagenome database (AMYLOMICS) for bioprospecting of carbohydrate-modifying enzymes is described. In addition to standard assembly of reads, a novel 'functional' assembly was developed, in which screening of reads with the HMM profiles occurs before the assembly. The AMYLOMICS database incorporates additional HMM profiles for carbohydrate-modifying enzymes and it is illustrated how the combination of HMM and BLAST analyses helps identify interesting genes. A variety of different proteome and metagenome databases have been generated by MEGGASENSE.


[Propolis. The bee glue as presented by the Graeco-Roman literature].
The bee glue, commonly known as propolis, has been employed for medical purposes already in teh ancient world. More than 15 Greek and Roman authors report on the preparation and application of the so-called third natural product of the bees (besides honey and wax). Aristoteles described the fundamental issues of its biology in his 'Historia Animalium' correctly. The bulk of propolis is obtained from the barks of poplars. Once carried in the hives, the glue is used to stabilize the cells and honeycombs and to protect the bees against invaders and cold weather. Propolis has been chiefly employed for the preparation of ointment and plasters. For this purpose, the viscous raw material was purified, moulded and boiled. In most preparations, the bee glue was only one of many (up to 20) pharmacologically active constituents and came to five to 20% of the mixture. Only rarely, a single drug therapy was using propolis was carried out. The application of the glue was most successful in general surgery and casualties. In that respect, the ancient physicians took advantage of the anti-edematous and anti-infectious properties of the substance. Thus, it was used to treat bumps, indurations, and slow-healing wounds. Moreover, cataplasms against swollen cervical nodes and indurations of the female breast often contained propolis. Finally, bee glue proved successful for the treatment of chronic backache and pain in the hip as well as fresh injuries of muscles and tendons. In the sector of skin diseases, lichens and condylomata were found to respond well to propolis. ALl this indications have been a matter of several records. However, the successful use of propolis in diseases of the stomach and liver has ben reported solely by Alexander of Tralles (6th century AD). Not counting the internal diseases, the spectrum of indications for propolis has not substantially changed as compared to the classical antiquity. Interestingly, radiation therapists have adopted the ancient remedy and use propolis successfully for the treatment of actinic stomatitis and mucositis.


ESCRT-III is required for scissioning new peroxisomes from the endoplasmic reticulum.
Dynamic control of peroxisome proliferation is integral to the peroxisome's many functions. The endoplasmic reticulum (ER) serves as a source of preperoxisomal vesicles (PPVs) that mature into peroxisomes during de novo peroxisome biogenesis and support growth and division of existing peroxisomes. However, the mechanism of PPV formation and release from the ER remains poorly understood. In this study, we show that endosomal sorting complexes required for transport (ESCRT)-III are required to release PPVs budding from the ER into the cytosol. Absence of ESCRT-III proteins impedes de novo peroxisome formation and results in an aberrant peroxisome population in vivo. Using a cell-free PPV budding assay, we show that ESCRT-III proteins Vps20 and Snf7 are necessary to release PPVs from the ER. ESCRT-III is therefore a positive effector of membrane scission for vesicles budding both away from and toward the cytosol. These findings have important implications for the evolutionary timing of emergence of peroxisomes and the rest of the internal membrane architecture of the eukaryotic cell.


Subchondral trabecular structural changes in the proximal tibia in an ovine model of increased bone turnover.
Ovariectomized (OVX) sheep are now considered to be useful models for a variety of metabolic bone disorders. The specific aim of this study was to determine the effects of ovariectomy on the structural parameters and material density of the subchondral bone of the ovine tibial plateau as measured by microcomputed tomography (MicroCT). Twenty-three sheep were examined in this study; 10 of the sheep underwent ovariectomy (OVX), and the remainder (n=13) were kept as controls (CON). These animals were then sacrificed at 12 months post-operatively. Three-dimensional analyses were performed of osteochondral samples (15 mm deep) which were obtained from the medial tibial plateau using MicroCT. Bone volume fraction of the subchondral trabecular bone was reduced in the ovariectomized sheep as compared to control animals (0.439 vs. 0.483, P=0.038). Trabeculae were also significantly thinner in the OVX group (0.220 vs. 0.252 mm, P=0.010), with reduced connectivity density (7.947 vs. 11.524 mm(-3) , P=0.014). There was a trend towards lower numbers of individual trabeculae present in the OVX group as compared to controls, but this did not reach significance (2.817 vs. 3.288 mm(-1) , P=0.1). There was also increased trabecular separation in the OVX group, which again fell short of significance (0.426 vs. 0.387 mm, P=0.251). There was no difference in hydroxyapatite concentration (HA) between the two groups (929 vs. 932 mgHA cm(-3) , P=0.687). In conclusion, significant alterations of the trabecular architecture under the tibial plateau were observed following 12 months of oestrogen-deficiency in this ovine model. Despite these marked morphological and structural density differences, the material densities were equal in the two groups.


Hologram copying by Gabor holography of transparencies.
The copying of holograms by constructing Gabor type holograms from the originals is discussed mathematically. The analysis is based on plane wave expansions, and the paraxial approximation is not used. Two sets of double images of the original scene appear in the reconstruction process with the copy hologram when emulsion thickness is not important. The separation of the double images is equal to twice the separation of the two photographic emulsions during the copying process. The importance of the extra images is discussed and ways to eliminate them are described. Double images are not produced by copies of wide angle holograms with interference fringe spacing that is small compared to the emulsion thickness.


Cooperative interaction of Hsp40 and TPR1 with Hsp70 reverses Hsp70-HspBp1 complex formation.
Hsp40 and TPR1 are chaperone adaptors that regulate Hsp70-dependent folding processes by interacting with the amino terminal and carboxy terminal domains of Hsp70, respectively. In this study, we report cooperative interactions involving Hsp70, Hsp40, and TPR1 that enhance Hsp70-dependent folding of chemically denatured substrates. Hsp40 and Hsp70 dependent folding of chemically denatured luciferase was enhanced by up to 80% when TPR1 was also present. HspBp1, a negative modulator of Hsp70, completely inhibited Hsp70-dependent folding in the presence of Hsp40. However, when TPR1 was included in the reaction, the inhibitory effect of HspBp1 was reversed. To analyze the interactions, Kd analysis and competition assays were carried out. The Kds of the interactions of Hsp40, TRP1, and HspBp1 with Hsp70 were 0.5, 0.6, and 0.04 mM, respectively. Interestingly, the Hsp70/HspBp1 complex could only be dissociated in the presence of both Hsp40 and TPR1, suggesting cooperative interaction between Hsp70, Hsp40 and TPR1. To examine these interactions in vivo, we established a tetracycline-regulatable Hela cell line that expresses Hsp70 in the absence of doxycycline. Expression of HspBp1 inhibited Hsp70-dependent folding of heat-denatured luciferase, and this effect was only reversed in the presence of Hsp40 and TPR1. Our findings reveal a novel mechanism of positive regulation of Hsp70-dependent folding.


Phenotypic characterization of xpr, a global regulator of extracellular virulence factors in Staphylococcus aureus.
We recently described a Tn551 insertion in the chromosome of Staphylococcus aureus S6C that resulted in drastically reduced expression of extracellular lipase (M. S. Smeltzer, S. R. Gill, and J. J. Iandolo, J. Bacteriol. 174:4000-4006, 1992). The insertion was localized to a chromosomal site (designated omega 1058) distinct from the lipase structural gene (geh) and the accessory gene regulator (agr), both of which were structurally intact in the lipase-negative (Lip-) mutants. In this report, we describe a phenotypic comparison between strains S6C, a hyperproducer of enterotoxin B; KSI9051, a derivative of S6C carrying the Tn551 insertion at omega 1058; ISP546, an 8325-4 strain that carries a Tn551 insertion in the agr locus; and ISP479C, the parent strain of ISP546 cured of the Tn551 delivery plasmid pI258repA36. Compared with their respective parent strains, ISP546 and KSI9051 produced greatly reduced amounts of lipase, alpha-toxin, delta-toxin, protease, and nuclease. KSI9051 also produced reduced amounts of staphylococcal enterotoxin B. Coagulase production was increased in ISP546 but not in KSI9051. Using a mouse model, we also demonstrated that ISP546 and KSI9051 were far less virulent than ISP479C and S6C. We have designated the genetic element defined by the Tn551 insertion at omega 1058 xpr to denote its role as a regulator of extracellular protein synthesis. We conclude that xpr and agr are similar and possibly interactive regulatory genes that play an important role in pathogenesis of staphylococcal disease.


Choosing organic pesticides over synthetic pesticides may not effectively mitigate environmental risk in soybeans.
Selection of pesticides with small ecological footprints is a key factor in developing sustainable agricultural systems. Policy guiding the selection of pesticides often emphasizes natural products and organic-certified pesticides to increase sustainability, because of the prevailing public opinion that natural products are uniformly safer, and thus more environmentally friendly, than synthetic chemicals. We report the results of a study examining the environmental impact of several new synthetic and certified organic insecticides under consideration as reduced-risk insecticides for soybean aphid (Aphis glycines) control, using established and novel methodologies to directly quantify pesticide impact in terms of biocontrol services. We found that in addition to reduced efficacy against aphids compared to novel synthetic insecticides, organic approved insecticides had a similar or even greater negative impact on several natural enemy species in lab studies, were more detrimental to biological control organisms in field experiments, and had higher Environmental Impact Quotients at field use rates. These data bring into caution the widely held assumption that organic pesticides are more environmentally benign than synthetic ones. All pesticides must be evaluated using an empirically-based risk assessment, because generalizations based on chemical origin do not hold true in all cases.


The fine anatomy of the optic nerve of anurans--an electron microscope study.
In the optic nerve of Anurans numerous myelinated and unmyelinated axons appear under the electron microscope as compact bundles that are closely bounded by one or several glial cells. In these bundles the unmyelinated fibers (0.15 to 0.6 micro in diameter) are many times more numerous than the myelinated fibers, and are separated from each other, from the bounding glial cells, or from adjacent myelin sheaths, by an extracellular gap that is 90 to 250 A wide. This intercellular space is continuous with the extracellular space in the periphery of the nerve through the numerous mesaxons and cell boundaries which reach the surface. Numerous desmosomes reinforce the attachments of adjacent glial membranes. The myelinated axons do not follow any preferential course and, like the unmyelinated ones, have a sinuous path, continuously shifting their relative position and passing from one bundle to another. At the nodes of Ranvier they behave entirely like unmyelinated axons in their relations to the surrounding cells. At the internodes they lie between the unmyelinated axons without showing an obvious myelogenic connection with the surrounding glial cells. In the absence of connective tissue separating individual myelinated fibers and with each glial cell simultaneously related to many axons, this myelogenic connection is highly distorted by other passing fibers and is very difficult to demonstrate. However, the mode of ending of the myelin layers at the nodes of Ranvier and the spiral disposition of the myelin layers indicate that myelination of these fibers occurs by a process similar to that of peripheral nerves. There are no incisures of Schmidt-Lantermann in the optic myelinated fibers.


Post-transplant malignancies in pediatric liver transplant recipients: Experience of two centers in Turkey.
A liver transplant is the preferred treatment for patients with end-stage liver disease, as it usually results in longterm survival. However, due to the use of chronic immunosuppressive therapy, which is necessary to prevent rejection, de novo cancer is a major risk after transplantation. The aim of this study was to assess the incidence of post-transplant malignancies in children after liver transplantations. The study group consisted of 206 liver transplant recipients, with no history of cancer, including hepatocellular carcinoma, in two liver transplantation centers in Turkey between 1997 and 2015. Data were obtained from patient's data chart. In the study group, de novo cancer was diagnosed in 13 of the 206 patients. Post-transplant lymphoproliferative disease (PTLD) occurred in seven (53.8%) patients and other malignancies in six of the 13 patients. The types of PTLD were as follows: B-cell origin (n=2), Epstein-Barr virus (EBV)-related (n=2), T-cell origin (n=1), and Hodgkin's lymphoma (n=2). EBV DNA was isolated from seven patients, three of whom developed PTLD. The others developed Kaposi's sarcomas, Burkitt's lymphomas, cutaneous large-cell lymphomas, Hodgkin's lymphomas, and liver sarcomas. After transplantation, immunosuppressive treatment is unavoidable, increasing the risk of malignancies. However, a close follow-up and periodic screening can reduce cancer-related mortality and morbidity.


Mycoplasma pneumoniae endophthalmitis in a Cuban pediatric patient.
Bacterial endophthalmitis is the most severe form of vision-threatening ocular infection. Mycoplasma pneumoniae is a primary respiratory pathogen that has been associated with several extrapulmonary manifestation, including ocular infection. In this work, we presented the microbiology diagnosis of an endophalmitis by M. pneumoniae using a novel A.R.I. WELL D-ONE® (CPM Scientifica, Italy) commercial micromethod in a Cuban pediatric patient. After positive M. pneumoniae confirmation, treatment with levofloxacin was initiated and successfully eliminated the ocular infection.


Inviting parents to take part in paediatric palliative care research: a mixed-methods examination of selection bias.
Recruitment to paediatric palliative care research is challenging, with high rates of non-invitation of eligible families by clinicians. The impact on sample characteristics is unknown. To investigate, using mixed methods, non-invitation of eligible families and ensuing selection bias in an interview study about parents' experiences of advance care planning (ACP). We examined differences between eligible families invited and not invited to participate by clinicians using (1) field notes of discussions with clinicians during the invitation phase and (2) anonymised information from the service's clinical database. Families were eligible for the ACP study if their child was receiving care from a UK-based tertiary palliative care service (Group A; N = 519) or had died 6-10 months previously having received care from the service (Group B; N = 73). Rates of non-invitation to the ACP study were high. A total of 28 (5.4%) Group A families and 21 (28.8%) Group B families (p < 0.0005) were invited. Family-clinician relationship appeared to be a key factor associated qualitatively with invitation in both groups. In Group A, out-of-hours contact with family was statistically associated with invitation (adjusted odds ratio 5.46 (95% confidence interval 2.13-14.00); p < 0.0005). Qualitative findings also indicated that clinicians' perceptions of families' wellbeing, circumstances, characteristics, engagement with clinicians and anticipated reaction to invitation influenced invitation. We found evidence of selective invitation practices that could bias research findings. Non-invitation and selection bias should be considered, assessed and reported in palliative care studies.


Connexin47, connexin29 and connexin32 co-expression in oligodendrocytes and Cx47 association with zonula occludens-1 (ZO-1) in mouse brain.
Gap junctions between glial cells in mammalian CNS are known to contain several connexins (Cx), including Cx26, Cx30 and Cx43 at astrocyte-to-astrocyte junctions, and Cx29 and Cx32 on the oligodendrocyte side of astrocyte-to-oligodendrocyte junctions. Recent reports indicating that oligodendrocytes also express Cx47 prompted the present studies of Cx47 localization and relationships to other glial connexins in mouse CNS. In view of the increasing number of connexins reported to interact directly with the scaffolding protein zonula occludens-1 (ZO-1), we investigated ZO-1 expression and Cx47/ZO-1 interaction capabilities in brain, spinal cord and Cx47-transfected HeLa cells. From counts of over 9000 oligodendrocytes labeled by immunofluorescence in various brain regions, virtually all of these cells were found to express Cx29, Cx32 and Cx47. Oligodendrocyte somata displayed robust Cx47-immunopositive puncta that were co-localized with punctate labeling for Cx32 and Cx43. By freeze-fracture replica immunogold labeling, Cx47 was abundant on the oligodendrocyte-side of oligodendrocyte/astrocyte gap junctions. By immunofluorescence, labeling for Cx47 along myelinated fibers was sparse in most brain regions, whereas Cx29 and Cx32 were previously found to be concentrated along these fibers. By immunogold labeling, Cx47 was found in numerous small gap junctions linking myelin to astrocytes, but not within deeper layers of myelin. Brain subcellular fractionation revealed a lack of Cx47 enrichment in myelin fractions, which nevertheless contained an enrichment of Cx32 and Cx29. Oligodendrocytes were immunopositive for ZO-1, and displayed almost total Cx47/ZO-1 co-localization. ZO-1 was found to co-immunoprecipitate with Cx47, and pull-down assays indicated binding of Cx47 to the second PDZ domain of ZO-1. Our results indicate widespread expression of Cx47 by oligodendrocytes, but with a distribution pattern in relative levels inverse to the abundance of Cx29 in myelin and paucity of Cx29 in oligodendrocyte somata. Further, our findings suggest a scaffolding and/or regulatory role of ZO-1 at the oligodendrocyte side of astrocyte-to-oligodendrocyte gap junctions.


Dynamic cerebral autoregulation in stroke patients with a central sympathetic deficit.
To investigate the functional role of the sympathetic innervation on cerebral autoregulation. Seventeen patients with infarction of the dorsolateral medulla oblongata affecting central sympathetic pathways (Wallenberg's syndrome) and 21 healthy controls were included in the study. Cerebral blood flow velocity (CBFV) in the medial cerebral artery was investigated using transcranial Doppler ultrasound during decrease in cerebral perfusion pressure induced by leg-cuff test and tilt table. Upon leg-cuff test, changes of cerebral blood flow and mean arterial blood pressure as well as autoregulatory index did not differ between patients or controls. No differences were found in changes of CBFV, mean arterial blood pressure and heart rate between patients or controls during the tilt table test. We suggest that the sympathetic nervous system does not have an influence on cerebral autoregulation after decrease in perfusion pressure under normotonous conditions.


A Long-Term Follow-Up of the Efficacy of Nature-Based Therapy for Adults Suffering from Stress-Related Illnesses on Levels of Healthcare Consumption and Sick-Leave Absence: A Randomized Controlled Trial.
Stress-related illnesses are a growing health problem in the Western world; which also has economic significance for society. As a consequence; there is a growing demand for effective treatments. The study investigates the long-term efficacy of the Nacadia® nature-based therapy (NNBT) by comparing it to the efficacy of a validated cognitive behavioral therapy, called STreSS. The study is designed as a randomized controlled trial in which 84 participants are randomly allocated between the treatments. Long-term efficacy is investigated through data extracts from the national database of Statistics Denmark on the sick leave and the health-care consumption. The results show that both the NNBT and the STreSS lead to a significant decrease in number of contacts with a general practitioner in the period from twelve months prior to treatment to twelve months after treatment; and, a significant decrease in long-term sick leave from the month prior to treatment to twelve months after treatment. The positive long-term effects provide validation for the NNBT as an efficient treatment of stress-related illnesses.


Delayed repair of distal biceps tendon ruptures is successful: a case-control study.
The literature has shown an increased complication rate with a delay to surgical repair of acute distal biceps tendon ruptures; however, little has been documented regarding the outcome of delayed repairs. This case-control study compared a study cohort of delayed (>21 days) distal biceps tendon repairs with a control cohort repaired acutely (<21 days). Sixteen delayed repair cases were reviewed and matched with acute controls (1:3) based on repair technique, age, and workers' compensation status. The delayed cohort was reviewed and completed isometric strength testing and the Disabilities of the Arm, Shoulder and Hand questionnaire; Patient-Rated Elbow Evaluation; and American Shoulder and Elbow Surgeons elbow questionnaire. The time to surgery averaged 37 ± 12 days in the delayed cohort versus 10 ± 6 days in the acute cohort. Complications occurred in 63% of patients in the delayed cohort versus 29% in the acute cohort (P = .04); however, 90% of the delayed cohort's complications consisted of transient paresthesias. Follow-up scores on the Patient-Rated Elbow Evaluation, Disabilities of the Arm, Shoulder and Hand questionnaire, and American Shoulder and Elbow Surgeons elbow questionnaire were not statistically different between cohorts (P > .37, P > .22, and P > .46, respectively). Despite a high rate of initial complications, patients treated with distal biceps tendon repair after a delay (>21 days) can expect similar functional outcomes to those treated acutely.


Low levels of relatedness on black grouse leks despite male philopatry.
In lekking species, males cluster on specific areas for display (the leks) and females generally prefer to copulate with males on large aggregations. The maintenance of leks in which only a few males reproduce might be explained if subordinate males gain indirect fitness benefits. By joining a lek on which relatives are displaying, subordinates might attract more females to the lek thereby increasing the mating opportunities of their kin. In black grouse, a genetic structure among leks has previously been found suggesting that relatives could display together. Using 11 microsatellite loci, we extended this result by testing for the presence of kin structures in nine black grouse leks (101 males). The genetic differentiation among flocks was higher in males than in females, suggesting female-biased dispersal and male philopatry. Because of this genetic structure, males were more related within than among leks. However, the mean relatedness within each lek hardly differed from zero. The lekking males were not more related than random assortments of males from the winter flocks and there were no kin clusters within leks. Thus, black grouse males do not choose to display with and close to relatives. Male philopatry alone was not sufficient to induce elevated levels of relatedness on the leks either because of male partial dispersal or a rapid turnover of the successful males. The indirect fitness benefits associated with males' settlement decision are probably limited compared to the direct benefits of joining large aggregations such as increased current and future mating opportunities.


Presence of simian virus 40 DNA sequences in human lymphoid and hematopoietic malignancies and their relationship to aberrant promoter methylation of multiple genes.
The simian polyoma virus SV40 has been detected in specific human tumors including non-Hodgkin's lymphomas, although a causative role for the virus has not been convincingly demonstrated. Aberrant methylation of CpG islands in promoter regions is a frequent method of silencing tumor suppressor genes (TSGs) in cancers and may be induced by oncogenic viruses. We investigated the relationship between the presence of SV40 or EBV DNA sequences and the methylation profiles for 10 TSGs in 90 cases of non-Hodgkin's lymphomas/leukemias and 56 control tissues. SV40 sequences were present in 33/90 (37%) non-Hodgkin's lymphomas/leukemias, and EBV was present in 11/42 (26%) of non-Hodgkin's lymphomas. We found a highly significant correlation between the presence of SV40 and methylation of seven genes (P values, 0.006 to <0.0001). In lymphomas, there was no relationship between EBV and methylation. Oncogenic viruses and methylation were rarely present in control tissues. We investigated methylation of the same 10 TSGs in peripheral blood mononuclear cells (PBMC) from a healthy volunteer infected with EBV or EBV and SV40. Promoter methylation of CDH1 and CDH13 were noted in dual SV40- and EBV-infected PBMC, and these two genes were also highly significantly correlated to the presence of SV40 sequences in tumors. SV40 infection also resulted in appearance of the lymphoma/leukemia-specific marker, methylated SHP1. Methylation was completely absent in uninfected and EBV-infected PBMC. Our results demonstrate that the presence of SV40 in hematological malignancies is associated with promoter methylation of TSGs and that in all probability, the virus plays a role in tumor pathogenesis.


Sex modifies exercise and cardiac adaptation in mice.
How an individual's sex and genetic background modify cardiac adaptation to increased workload is a topic of great interest. We systematically evaluated morphological and physiological cardiac adaptation in response to voluntary and forced exercise. We found that sex/gender is a dominant factor in exercise performance (in two exercise paradigms and two mouse strains) and that females of one of these strains have greater capacity to increase their cardiac mass in response to similar amounts of exercise. To explore the biochemical mechanisms for these differences, we examined signaling pathways previously implicated in cardiac hypertrophy. Ca2+/calmodulin-dependent protein kinase (CaMK) activity was significantly greater in males compared with females and increased after voluntary cage-wheel exposure in both sexes, but the proportional increase in CaMK activity was twofold higher in females compared with males. Phosphorylation of glycogen synthase kinase-3beta (GSK-3beta) was evident after 7 days of cage-wheel exposure in both sexes and remained elevated in females only by 21 days of exercise. Despite moderate increases in myocyte enhancer factor-2 (a downstream effector of CaMK) transcriptional activity and phosphorylation of Akt with exercise, there were no sex differences. Mitogen-activated protein kinase signaling components (p38 mitogen-activated protein kinase and extracellular regulated kinase 1/2) were not different between male and female mice and were not affected by exercise. We conclude that females have increased exercise capacity and increased hypertrophic response to exercise. We have also identified sex-specific differences in hypertrophic signaling within the cardiac myocyte that may contribute to sexual dimorphism in exercise and cardiac adaptation to exercise.


Differential global and extra-cellular matrix focused gene expression patterns between normal and glaucomatous human lamina cribrosa cells.
Marked extracellular matrix (ECM) remodeling occurs in the human optic nerve head in primary open angle glaucoma (POAG). The glial fibrillary acid protein (GFAP) negative lamina cribrosa cell may play an important role in this remodeling process. We report the first study of global and ECM-focused gene transcription differentials between GFAP-negative lamina cribrosa (LC) cells from normal and POAG human donors. GFAP-negative LC cell lines were generated from the optic nerve tissue of four normal (n=4) and four POAG (n=4) human donors. Using Affymetrix U133A arrays the transcriptional profile between the normal and diseased groups were compared. Bioinformatic analysis was performed using robust multichip average (RMA Express) and EASE/David. Real time TaqMan PCR and immunohistochemistry analyses were performed to validate the microarray data. 183 genes were upregulated by greater than 1.5 fold and 220 were down regulated by greater than 1.5 fold in the POAG LC cells versus normal controls. Upregulated genes in POAG LC cells included, transforming growth factor beta 1 (TGFbeta1), secreted acid protein cysteine rich (SPARC), periostin (POSTN), thrombospondin-1 (THBS1), cartilage linking protein-1 (CRTL-1), and collagen type I (COL1A1), collagen type V (COL5A1), and collagen type XI (COL11A1). Downregulated ECM genes in POAG included fibulin 1 (FBLN1), decorin (DCN), and collagen type XVIII (COL18A1). All TaqMan PCR validation assays were significant (*p<0.05) and consistent with the array data. Immunohistochemistry of one target (periostin) confirmed its differential expression at the protein level in POAG optic nerve head tissue compared with non-glaucomatous controls. Functional annotation and over-representation analysis identified ECM genes as a statistically over-represented class of genes in POAG LC cells compared with normal LC cells. This study reports for the first time that POAG LC cells in-vitro demonstrate upregulated ECM and pro-fibrotic gene expression compared with normal LC cells. This may be a pathological characteristic of this cell type in POAG in-vivo. We believe that the LC cell may be a pivotal regulator of optic nerve head ECM remodeling in POAG and an attractive target for molecular therapeutic strategies in the future.


Opportunities to encourage mail order pharmacy delivery service use for diabetes prescriptions: a qualitative study.
Medication non-adherence is a major contributor to poor outcomes in diabetes. Previous research has shown an association between use of mail order pharmacy delivery and better medication adherence, but little is known about the barriers and facilitators to mail order pharmacy use in diabetes patients. This qualitative study examined factors related to mail order pharmacy use versus traditional "brick and mortar" pharmacies to refill prescriptions. We conducted four 90-min focus groups in 2016 among 28 diabetes patients in the Hawaii and Northern California regions of Kaiser Permanente, a large integrated health care delivery system. We queried participants on their preferred mode for refilling prescriptions and perceived barriers and facilitators of mail order pharmacy use. One researcher independently coded each focus group transcript, with two of these transcripts double-coded by a second researcher to promote reliability. We employed thematic analysis guided by the Capability, Opportunity, Motivation, and Behavior (COM-B) framework using NVivo 11 software. A total of 28 diabetes patients participated. Participants' average age was 64.1 years; 57% were female; and racial/ethnic backgrounds included Asian/Native Hawaiian/Pacific Islander (36%), Black/African-American (21%) Hispanic/Latino (7%), and non-Hispanic White (36%). Analysis uncovered 26 themes related to the decision to use mail order pharmacy, with each theme representing a barrier or facilitator mapped to the COM-B framework. Most themes (20/26) fell into the COM-B category of 'Opportunity.' Opportunity barriers to mail order pharmacy use included unpredictability of medication delivery date, concerns about mail security, and difficulty coordinating refill orders for multiple prescriptions. In contrast, facilitators included greater access and convenience (e.g., no need to wait in line or arrange transportation) compared to traditional pharmacies. Motivational facilitators to mail order pharmacy use included receiving a pharmacy benefit plan incentive of a free one-month supply of prescriptions. This study found that while patients with diabetes may benefit from mail order pharmacy use, they perceive numerous barriers to using the service. These findings will inform the design of interventions and quality improvement initiatives to increase mail order pharmacy use, which in turn may improve medication adherence and outcomes in diabetes patients, across health care systems.


Web-Based and mHealth Interventions for Intimate Partner Violence Victimization Prevention: A Systematic Review.
Mobile health (mHealth) technologies are increasingly used across health programming including intimate partner violence (IPV) prevention to optimize screening, educational outreach, and linkages to care via telehealth. We systematically evaluated current web-based and mHealth interventions, which include web- or mobile-based delivery methods for primary, secondary, and tertiary IPV victimization prevention. We searched MEDLINE/PubMed, Embase, CINAHL, PsycINFO, Open Grey, and Google Scholar for empirical studies published 1998-2019. Studies were included if they considered empirical data, participants in adult romantic relationships, IPV as a primary or secondary outcome, and an mHealth component. The Mixed Methods Appraisal Tool was used to record critical ratings of quality among studies selected for inclusion. We assessed variation in targeted populations, types of IPV addressed, and mHealth approaches used. Of 133 studies identified for full-text review, 31 were included. Computer-based screening with or without integrated education was the most common mHealth approach (n = 8, 26%), followed by safety decision aids (n = 7, 23%). Feasibility and acceptability were found to be generally high where assessed (23% of studies, n = 7). There was limited evidence around whether mHealth interventions better addressed population needs compared to conventional interventions. mHealth tools for IPV prevention are especially acceptable in health-care settings, on mobile phone platforms, or when connecting victims to health care. Despite enthusiasm in pilot projects, evidence for efficacy compared to conventional IPV prevention approaches is limited. A major strength of mHealth IPV prevention programming is the ability to tailor interventions to individual victim needs without extensive human resource expenditure by providers.


Learning while doing: program evaluation of the Medical Library Association Systematic Review Project.
The Medical Library Association (MLA) Systematic Review Project aims to conduct systematic reviews to identify the state of knowledge and research gaps for fifteen top-ranked questions in the profession. In 2013, fifteen volunteer-driven teams were recruited to conduct the systematic reviews. The authors investigated the experiences of participants in this large-scale, volunteer-driven approach to answering priority research questions and fostering professional growth among health sciences librarians. A program evaluation was conducted by inviting MLA Systematic Review Project team members to complete an eleven-item online survey. Multiple-choice and short-answer questions elicited experiences about outputs, successes and challenges, lessons learned, and future directions. Participants were recruited by email, and responses were collected over a two-week period beginning at the end of January 2016. Eighty (8 team leaders, 72 team members) of 198 potential respondents completed the survey. Eighty-four percent of respondents indicated that the MLA Systematic Review Project should be repeated in the future and were interested in participating in another systematic review. Team outputs included journal articles, conference presentations or posters, and sharing via social media. Thematic analysis of the short-answer questions yielded five broad themes: learning and experience, interpersonal (networking), teamwork, outcomes, and barriers. A large-scale, volunteer-driven approach to performing systematic reviews shows promise as a model for answering key questions in the profession and demonstrates the value of experiential learning for acquiring synthesis review skills and knowledge. Our project evaluation provides recommendations to optimize this approach.


Cannabidiol as a Therapeutic Alternative for Post-traumatic Stress Disorder: From Bench Research to Confirmation in Human Trials.
Post-traumatic stress disorder (PTSD) is characterized by poor adaptation to a traumatic experience. This disorder affects approximately 10% of people at some point in life. Current pharmacological therapies for PTSD have been shown to be inefficient and produce considerable side effects. Since the discovery of the involvement of the endocannabinoid (eCB) system in emotional memory processing, pharmacological manipulation of eCB signaling has become a therapeutic possibility for the treatment of PTSD. Cannabidiol (CBD), a phytocannabinoid constituent of Cannabis sativa without the psychoactive effects of Δ9-tetrahydrocannabinol, has gained particular attention. Preclinical studies in different rodent behavioral models have shown that CBD can both facilitate the extinction of aversive memories and block their reconsolidation, possibly through potentialization of the eCB system. These results, combined with the currently available pharmacological treatments for PTSD being limited, necessitated testing CBD use with the same therapeutic purpose in humans as well. Indeed, as observed in rodents, recent studies have confirmed the ability of CBD to alter important aspects of aversive memories in humans and promote significant improvements in the symptomatology of PTSD. The goal of this review was to highlight the potential of CBD as a treatment for disorders related to inappropriate retention of aversive memories, by assessing evidence from preclinical to human experimental studies.


FZD4 as a mediator of ERG oncogene-induced WNT signaling and epithelial-to-mesenchymal transition in human prostate cancer cells.
TMPRSS2-ERG and other gene fusions involving ETS factors and genes with strong promoter elements are common in prostate cancer. Although ERG activation has been linked to invasive properties of prostate cancers, the precise mechanisms and pathways of ERG-mediated oncogenesis remain poorly understood. Here, we show that ERG knockdown in VCaP prostate cancer cells causes an activation of cell adhesion, resulting in strongly induced active beta(1)-integrin and E-cadherin expression as well as changes in WNT signaling. These observations were corroborated by data from ERG-overexpressing nontransformed prostate epithelial cells as well as gene expression data from clinical prostate cancer samples, which both indicated a link between ERG and epithelial-to-mesenchymal transition (EMT). Upregulation of several WNT pathway members was seen in ERG-positive prostate cancers, with frizzled-4 (FZD4) showing the strongest overexpression as verified by both reverse transcription-PCR and immunostaining. Both ERG knockin and knockdown modulated the levels of FZD4 expression. FZD4 silencing could mimic the ERG knockdown phenotype by inducing active beta(1)-integrin and E-cadherin expression, whereas FZD4 overexpression reversed the phenotypic effects seen with ERG knockdown. Taken together, our results provide mechanistic insights to ERG oncogenesis in prostate cancer, involving activation of WNT signaling through FZD4, leading to cancer-promoting phenotypic effects, including EMT and loss of cell adhesion.