Prevalence and correlates of lifetime deliberate self-harm and suicidal ideation in naturalistic outpatients: the Leiden Routine Outcome Monitoring study.
Deliberate self-harm and suicidal ideation (DSHI) are common phenomena in general and mental health populations. Identifying factors associated with DSHI may contribute to the early identification, prevention and treatment of DSHI. Aims of the study are to determine the prevalence and correlates of lifetime DSHI in a naturalistic sample of psychiatric outpatients with mood, anxiety or somatoform (MAS) disorders. Of 3798 consecutive patients from January 2004 to December 2006, 2844 (74.9%) patients were analyzed (mean age=37.5, SD=12.0; age range: 18-65; 62.7% women). Lifetime DSHI was assessed with routine outcome monitoring (ROM), including demographic parameters, DSM-IV diagnosis, depressive symptoms, symptoms of anxiety, general psychopathology and personality traits. Of the 2844 subjects, 55% reported lifetime DSHI. In multivariable logistic regression analysis, the most important factors associated with lifetime DSHI were being unmarried, low education, high number of psychiatric diagnoses, lower anxiety scores, higher depression scores and the personality trait of emotional dysregulation. Deliberate self-harm may have been under-reported in self-report questionnaires; The assessment of personality traits may have been influenced by state psychopathology; traumatic events were not assessed. The findings suggest that DSHI is common among psychiatric outpatients with MAS disorders and that current symptoms and underlying personality vulnerabilities were independently involved in DSHI. Whether symptoms of somatic anxiety are protective should be confirmed in subsequent studies. These findings may help clinicians in identifying patients at risk for deliberate self-harm and suicide.


The spirit of community psychology. 2001 Seymour B. Sarason Award Address.
Community psychology as a field may have lost some of its original spirit; a spirit dominant at the founding of the field. Spirit is a difficult concept to discuss since it is a concept beyond usual discourse in psychology as a denotative, measurable and verifiable concept. Taking the lead from William James, Spirit, however elusive, is most essential to a sense of self. I offer three suggestions to enhance and to make our individual and collective spirit more vital: (1) Continuing education in the history of community psychology; (2) Creating time to share stories about our work; (3) Creating safe settings to enlarge our spirit. These ideas are offered as pragmatic suggestions to enable us to create more coherence between our personal and professional selves.


Expression and regulation of RAB3 proteins in osteoclasts and their precursors.
The ruffled membrane, the resorptive organelle of the osteoclast, is generated by fusion of intracytoplasmic acidifying vesicles with the plasma membrane, an event analogous to regulated exocytosis. While the ruffled membrane is essential to the bone resorptive process, the mechanisms governing its generation are unknown. However, regulated exocytosis is mediated, in part, by isoforms of the Rab3 subset of Rab GTPases. Because of similarities between exocytosis and ruffled membrane formation, we asked if Rab3 proteins are expressed by osteoclasts or their precursors, and if so, are these molecules regulated by agents known to prompt the osteoclast phenotype? We find murine osteoclast precursors, in the form of bone marrow macrophages (BMMs), express at least two Rab3 isoforms, namely A and B/C, which are individually enhanced by a variety of hematopoietic cytokines. Consistent with the osteoclastogenic properties of a number of these cytokines, differentiation of BMMs into osteoclasts, in vitro, is associated with increased expression of both isoforms, particularly Rab3B/C. Finally, Rab3B/C localizes with the avian osteoclast H+ATPase (vacuolar proton pump) and pp60c-src, both intracellularly and within acidifying vesicles derived largely from the ruffled membrane. Thus, expression of specific rab3 proteins, an event which may control formation of the osteoclast ruffled membrane, is modulated by cytokines during osteoclastogenesis.


Multi-Criteria Decision Analysis in Food Safety Risk Management: The Case of Dioxins in Baltic Fish.
The Swedish risk management case of Baltic fatty fishes, in which dioxin levels may be too high, is a typical multidimensional food safety decision problem involving public health, economic, environmental and socio-cultural aspects. To effectively address the dioxin food safety problem, the multiple dimensions and conflicting interests of stakeholders have to be considered systematically when evaluating competing risk management options. The objectives of this study were to illustrate the applicability of the Multi-Criteria Decision Analysis (MCDA) method for multidimensional food safety risk management problems, and to evaluate the Swedish dioxin risk management using MCDA. The results show that the MCDA method is indeed a relevant tool for modelling the multifactorial Swedish dioxin problem and for initiating discussions amongst stakeholders to increase the acceptance of chosen strategies. Abolishing the derogation from the European Commission's maximum limits for the presence of dioxins in Swedish fish is the dominant strategy for risk assessors, whereas the preferences provided by the other stakeholders would suggest a continuation of the derogation without providing consumer information. However, the preferences of female consumers match with the 2011 decision of the Swedish government to ask for a derogation in combination with consumer information. The conclusion drawn from our MCDA analysis is comparable to the government's decision that-given the gradual reduction in dioxin concentrations in Baltic fish-the decision to continue providing consumer information or not mainly depends on how risk managers balance the preferences of the different stakeholders.


Tumor suppressor Lzap regulates cell cycle progression, doming, and zebrafish epiboly.
Initial stages of embryonic development rely on rapid, synchronized cell divisions of the fertilized egg followed by a set of morphogenetic movements collectively called epiboly and gastrulation. Lzap is a putative tumor suppressor whose expression is lost in 30% of head and neck squamous cell carcinomas. Lzap activities include regulation of cell cycle progression and response to therapeutic agents. Here, we explore developmental roles of the lzap gene during zebrafish morphogenesis. Lzap is highly conserved among vertebrates and is maternally deposited. Expression is initially ubiquitous during gastrulation, and later becomes more prominent in the pharyngeal arches, digestive tract, and brain. Antisense morpholino-mediated depletion of Lzap resulted in delayed cell divisions and apoptosis during blastomere formation, resulting in fewer, larger cells. Cell cycle analysis suggested that Lzap loss in early embryonic cells resulted in a G2/M arrest. Furthermore, the Lzap-deficient embryos failed to initiate epiboly--the earliest morphogenetic movement in animal development--which has been shown to be dependent on cell adhesion and migration of epithelial sheets. Our results strongly implicate Lzap in regulation of cell cycle progression, adhesion and migratory activity of epithelial cell sheets during early development. These functions provide further insight into Lzap activity that may contribute not only to development, but also to tumor formation.


Second Era of OMICS in Caries Research: Moving Past the Phase of Disillusionment.
Novel approaches using OMICS techniques enable a collective assessment of multiple related biological units, including genes, gene expression, proteins, and metabolites. In the past decade, next-generation sequencing ( NGS) technologies were improved by longer sequence reads and the development of genome databases and user-friendly pipelines for data analysis, all accessible at lower cost. This has generated an outburst of high-throughput data. The application of OMICS has provided more depth to existing hypotheses as well as new insights in the etiology of dental caries. For example, the determination of complete bacterial microbiomes of oral samples rather than selected species, together with oral metatranscriptome and metabolome analyses, supports the viewpoint of dysbiosis of the supragingival biofilms. In addition, metabolome studies have been instrumental in disclosing the contributions of major pathways for central carbon and amino acid metabolisms to biofilm pH homeostasis. New, often noncultured, oral streptococci have been identified, and their phenotypic characterization has revealed candidates for probiotic therapy. Although findings from OMICS research have been greatly informative, problems related to study design, data quality, integration, and reproducibility still need to be addressed. Also, the emergence and continuous updates of these computationally demanding technologies require expertise in advanced bioinformatics for reliable interpretation of data. Despite the obstacles cited above, OMICS research is expected to encourage the discovery of novel caries biomarkers and the development of next-generation diagnostics and therapies for caries control. These observations apply equally to the study of other oral diseases.


Improved Detection and Characterization of Copy Number Variations Among Diverse Pig Breeds by Array CGH.
As a major component of genomic variation, copy number variations (CNVs) are considered as promising markers for some phenotypic and economically important traits in domestic animals. Using a custom-designed 1M array CGH (aCGH), we performed CNV discovery in 12 pig samples from one Asian wild boar population, six Chinese indigenous breeds, and two European commercial breeds. In total, we identified 758 CNV regions (CNVRs), covering 47.43 Mb of the pig genome sequence. Of the total porcine genes, 1295 genes were completely or partially overlapped with the identified CNVRs, which enriched in the terms related to sensory perception of the environment, neurodevelopmental processes, response to external stimuli, and immunity. Further probing the potential functions of these genes, we also found a suite of genes related important traits, which make them a promising resource for exploring the genetic basis of phenotype differences among diverse pig breeds. Compared with previous relevant studies, the current study highlights that different platforms can complement each other, and the combined implementation of different platforms is beneficial to achieve the most comprehensive CNV calls. CNVs detected in diverse populations herein are essentially complementary to the CNV map in the pig genome, which would be helpful for understanding the pig genome variants and investigating the associations between various phenotypes and CNVs.


Omega-3 fatty acids influence mood in healthy and depressed individuals.
Depression is one of the most prevalent disorders in the United States, and rates of depression are higher for women than men. Despite their widespread use, drugs used in the treatment of depression are only moderately more effective than placebo in treating the disorder. Effective treatment of perinatal depression is of particular concern as treatment can influence both the mother and the developing child. Omega-3 polyunsaturated fatty acid (n-3 PUFA) supplementation may reduce symptoms of major depressive disorder and perinatal depression. The aim of the present review was to evaluate epidemiological studies examining PUFA intake and depressive symptoms in the general population, as well as double-blind, placebo-controlled trials assessing the influence of n-3 PUFA in healthy individuals and those with depression; specific consideration was given to perinatal depression and potential gender differences in the relationship. Although there is some evidence to suggest that n-3 PUFA intake is associated with reduced depressive symptoms, particularly in females, these results are generally limited to epidemiological studies, whereas results from randomized controlled trials are mixed.


Gastroprotective effect of Byrsonima sericea DC leaf extract against ethanol-induced gastric injury and its possible mechanisms of action.
Byrsonima sericea leaves are extensively used in folk medicine in Brazil against gastric disorders. This study investigated the chemical constituents of B. sericea leaf ethanolic extract (BSLE) and its potential gastroprotective activity, with its possible mechanism of the action using ethanol to induce gastric mucosal damage in mice. The phytochemical analysis was carried out to identify the active constituents present in the extract, and the HPLC analysis was performed for the identification of flavonoids. BSLE at oral doses of 125, 250 and 500 mg/kg markedly attenuated the ethanol-evoked gastric lesions by 53.2, 84.9 and 87.6 %, respectively. The BSLE (250 mg/kg) prevented the depletion of gastric mucus and gastric mucosal nonproteic-sulfhydryl groups, SOD and CAT, as well as the increase in the MDA content promoted by absolute ethanol. Moreover, the effect of BSLE against ethanol damage was found to be significantly reduced in mice pretreated with Capsazepine (i.p.), L-NAME (i.p.) or glibenclamide (i.p.), the respective blockers/inhibitors of TRPV1, NO synthase and K+ATP channel. The phytochemical investigation on BSLE revealed the presence of flavonoids rutin, isoquercitrin, kaempferol 3-O-rutinoside and quercetin, which are compounds well known for their antioxidant and gastroprotective properties. These results suggest that BSLE affords gastroprotection through multiple mechanisms, which may be helpful in the treatment of pathologies associated with gastric dysfunctions.


Multimodal Label-Free Imaging for Detecting Maturation of Engineered Osteogenic Grafts.
There is a critical need to develop noninvasive, nondestructive methods for assessing the quality of engineered constructs prior to implantation. Currently, the composition and maturity of engineered tissues are assessed using destructive, costly, and time-consuming biochemical and mechanical analyses. The goal of this study was to use noninvasive, multimodal imaging to monitor osteogenic differentiation and matrix deposition by human mesenchymal stem/stromal cells (MSCs) during in vitro culture. MSCs were encapsulated in alginate hydrogels and cultured in osteogenic conditions for 4 weeks. Samples were evaluated using fluorescence lifetime imaging (FLIm) and ultrasound backscatter microscopy (UBM) prior to traditional biochemical and mechanical testing. Using linear regression analysis, we identified strong correlations between imaging parameters (e.g., fluorescence lifetime and acoustic attenuation coefficient) and destructive mechanical and biochemical tests to assess the maturation of osteogenically induced constructs. These data demonstrate the promise of nondestructive label-free imaging techniques to noninvasively ascertain the progression and maturity of tissue engineered bone grafts.


Regioselective enzymatic diol esterification in batch and fixed-Bed adsorptive reactors: experiments and modeling.
The dynamic behavior of batch and fixed-bed adsorptive reactors is studied for the enzyme-catalyzed regioselective esterification of propionic acid and 2-ethyl-1,3-hexanediol in hexane. The reaction is equilibrium-limited with an apparent equilibrium constant of 0.6 +/- 0.1 at 22 degrees C. Moreover, accumulation of water produced in the reaction onto the biocatalyst causes a decrease in the catalytic activity. As a result, improvements in both reaction rate and final conversion can be achieved by operating in an adsorptive-reactor mode. Control of water in the reactor is achieved with a catalytically inert ion-exchange resin in Na-form. The resin prevents an excessive accumulation of water on the biocatalyst and reduces equilibrium limitations. The thermodynamic activity of water is identified as a key parameter for the design of such reactors. A mathematical model capable of predicting the water activity as a function of the varying concentrations of reactants and products is thus developed and found to successfully predict the experimental behavior observed in laboratory reactors. Substantial improvements in performance predicted by the model are seen experimentally in batch reactions and during the transient operation of continuous-flow fixed-bed reactors combining adsorptive and catalytic functions.


[Flow cytometric analysis of HLA-DR, IL-6 and IL-8 expression by conjunctival epithelial cells from patients with prolonged topical antiglaucoma treatments].
To investigate the expression of three inflammation markers, HLA-DR, IL-6, and IL-8, by conjunctival epithelial cells obtained using impression cytology (IC) samples from long-term treated glaucoma patients. IC samples were obtained from the 60 following individuals: 45 patients suffering from primary open-angle glaucoma and receiving topical treatments for at least 1 year and 15 subjects with no ophthalmological disease (controls). Membrane expression of HLA-DR and intracellular expression of IL-6 and IL-8 were quantified, respectively, by indirect and direct immunofluorescence techniques. Fluorescence levels were quantified using calibrated fluorescent beads. The percentage of HLA-DR-positive cells was significantly higher on IC samples from multitreated glaucoma patients and from patients treated by either preserved betablocker or preserved prostaglandin analogue than on IC samples from control individuals. Interestingly, the percentage of HLA-DR-positive cells was not significantly increased upon treatment with unpreserved betablocker. However, the percentage of IL-6- and IL-8-positive cells as well as IL-6 and IL-8 expression levels was significantly higher in patients than in controls, regardless of the treatment type and the presence of preservative. A significant positive correlation was found between HLA-DR and cytoplasmic IL-6 expression, between HLA-DR and cytoplasmic IL-8 as well as between IL-6 and IL-8 cytoplasmic expressions. The present study confirms that there is an increased expression of HLA-DR in treated glaucoma patients compared to controls and demonstrates that antiglaucoma treatments lead to increased IL-6 and IL-8 expressions. It also indicates that benzalkonium-preserved eyedrops and preserved multitherapy may induce stronger inflammatory responses than do unpreserved eyedrops, although further studies are needed to determine the respective inflammatory role of preservative and therapeutic molecules. In this study, flow cytometry was used to detect the intracellular pro-inflammatory cytokines in conjunctival cells obtained by impression cytology. This standardized and reliable technique was a useful tool to assess inflammatory and allergic ocular surface disorders.


A Smartphone App to Restore Optimal Weight (SPAROW) in Women With Recent Gestational Diabetes Mellitus: Randomized Controlled Trial.
Women with a history of gestational diabetes mellitus (GDM) are at an increased risk of developing type 2 diabetes mellitus (T2DM). Lifestyle interventions aimed at postpartum weight loss to reduce T2DM risk have been reported, but poor compliance remains a barrier. Smartphone-based interventions may improve compliance, but data on its use in women with recent GDM are limited. This trial aimed to investigate the efficacy of a smartphone app in restoring optimal weight following delivery in women with GDM, in the setting of a population with high rates of GDM and type 2 diabetes. In this unblinded randomized controlled trial, 200 women with GDM were randomized to receive the intervention or standard care following delivery. The intervention enabled logging of weight, meals, and activity, with web-based interaction with a team comprising dieticians, a physiotherapist, and an occupational therapist. The primary outcome was an achievement of optimal weight (defined as the restoration of first trimester weight if first trimester BMI≤23 kg/m2 or weight loss of at least 5% from first trimester weight if first trimester BMI>23 kg/m2) at 4 months post partum. Secondary outcome measures included absolute weight loss, serum metabolic markers, self-reported nutritional intake, health education, and quality of life via questionnaires and user engagement in the intervention group. In total, 40% (38/96) of women in the intervention group achieved optimal weight at 4 months post delivery compared with 32% (28/93) in the control group (P=.27). Compared with the control group, women in the intervention group reported significantly reduced caloric intake at 4 months after delivery (P<.001) and higher health-directed behavior scores (P=.045). The intervention group also reported increased emotional distress scores (P=.01). At 4 months, participant engagement with the intervention was maintained at 60.8% (SD 33.9%). Although a statistically significant increase in women achieving healthy weight was not observed, this app remains promising, as women in the intervention group reported improved health behaviors and lower caloric intake. Importantly, the high retention rates suggest that a larger study with a longer follow-up period might confirm the effectiveness of this app for weight management. ClinicalTrials.gov NCT03324737; https://clinicaltrials.gov/ct2/show/NCT03324737. RR2-10.1186/s12889-019-7691-3.


Neisseria gonorrhoeae elicits extracellular traps in primary neutrophil culture while suppressing the oxidative burst.
Neisseria gonorrhoeae (the gonococcus) causes gonorrhea and is uniquely adapted to survive within the human reproductive tract. Gonococci evade host immune surveillance in part by varying their pili and opacity-associated proteins. These variable surface antigens influence interactions with host epithelial and immune cells. A potent polymorphonuclear leukocyte (PMN) response is a hallmark of symptomatic gonococcal infection, with vast numbers of PMNs recruited to the site of infection. A large body of literature describes gonococcus-PMN interactions, but the factors driving the outcome of infection are not fully understood. Gonococci have been described to both induce and suppress the PMN oxidative burst, but we determined that gonococci differentially affect induction of the PMN oxidative burst depending on the multiplicity of infection (MOI). Infecting PMN at an MOI of <20 gonococci elicits an oxidative burst, while an MOI of >20 suppresses the burst. Oxidative burst in response to gonococci is enhanced by, but does not require, expression of pili or opacity proteins. Neutrophil extracellular traps (NETs) were observed in gonococcus-infected PMNs, a process which requires an oxidative burst, yet gonococci induced NETs under suppressing conditions. The NETs were unable to kill gonococci despite killing the common vaginal bacterium Lactobacillus crispatus. Thus, gonococci influence PMN biology to promote their own survival by suppressing the oxidative burst of PMNs and stimulating the formation of NETs, which do not effectively kill gonococci, illustrating how N. gonorrhoeae has evolved to modulate PMN responses to promote infection. Neisseria gonorrhoeae, the gonococcus, is the only causative agent of gonorrhea and is exclusively found within the human host. Gonococci stochastically vary the composition of antigens on their surface to evade immune surveillance. We used gonococcal mutants which stably express different surface antigens to dissect interactions between gonococci and primary human polymorphonuclear leukocytes (PMNs). We found that gonococci, depending on the number of bacteria present, either induce or suppress the oxidative burst of PMNs regardless of other stimuli. Gonococci also cause PMNs to release DNA, forming neutrophil extracellular traps (NETs) independently of the oxidative burst. The NETs were unable to kill gonococci but were able to kill commensal bacteria, suggesting that NET production can help gonococci outcompete other bacterial species. We propose that gonococci have evolved to manipulate PMN responses to promote their own survival during infection.


How big should the pilot study for my cluster randomised trial be?
There is currently a lot of interest in pilot studies conducted in preparation for randomised controlled trials. This paper focuses on sample size requirements for external pilot studies for cluster randomised trials. We consider how large an external pilot study needs to be to assess key parameters for input to the main trial sample size calculation when the primary outcome is continuous, and to estimate rates, for example recruitment rates, with reasonable precision. We used simulation to provide the distribution of the expected number of clusters for the main trial under different assumptions about the natural cluster size, intra-cluster correlation, eventual cluster size in the main trial, and various decisions made at the piloting stage. We chose intra-cluster correlation values and pilot study size to reflect those commonly reported in the literature. Our results show that estimates of sample size required for the main trial are likely to be biased downwards and very imprecise unless the pilot study includes large numbers of clusters and individual participants. We conclude that pilot studies will usually be too small to estimate parameters required for estimating a sample size for a main cluster randomised trial (e.g. the intra-cluster correlation coefficient) with sufficient precision and too small to provide reliable estimates of rates for process measures such as recruitment or follow-up rates.


Low yield of ED magnetic resonance imaging for suspected epidural abscess.
The aim of this study was to estimate the yield of emergency department (ED) magnetic resonance imaging (MRI) in detecting spinal epidural abscess (SEA) and to identify clinical factors predicting positive MRI results. We examined a cohort of patients who underwent MRI to rule out SEA, followed by a nested case-control comparison of those with positive results and a sample with negative results. A positive result was defined as osteomyelitis, discitis, or SEA. Predictor variables included temperature, presenting complaint, drug abuse status, history of SEA or back surgery, midline back tenderness, neurologic deficit, MRI level, mean white blood cell count, erythrocyte sedimentation rate, and C-reactive protein level. Fourteen of the 120 available MRIs were excluded; 7 (6.6%) of the remaining 106 were positive. Temperature was 1.1°C higher in cases than controls (95% CI, 0.6-1.7). Emergency department MRI for suspected SEA has a low yield. Clinical guidelines are needed to improve efficiency.


Two-Dimensional Spoiled Gradient-Recalled Echo Magnetic Resonance Imaging of the Liver Using Respiratory Navigator-Gating Techniques.
We assessed the feasibility of T1-weighted 2-dimensional spoiled gradient-recalled (2D SPGR) acquisition in steady-state imaging of the liver with various respiratory navigator gating techniques. A total of 12 healthy volunteers underwent in-phase and out-of-phase 2D SPGR imaging of the liver during breath-holding and free-breathing. Four techniques for respiratory navigation, 2 conventional navigator techniques and 2 self-navigator techniques, were used for free-breathing imaging. Good navigator waveforms were obtained in conventional navigation, whereas fluctuations were evident in self navigation. All of the 4 navigator-based methods provided better images in terms of background signals and visual image quality compared with images obtained with no respiratory control. However, differences remained in comparison with breath-holding. Superiority of self-navigation to conventional navigation was not shown. Navigator-gating techniques improved 2D SPGR images of the liver acquired during free-breathing, suggesting feasibility and beneficial effects, although navigator-based images were still inferior to breath-hold images.


Early Pulmonary Complications following Total Knee Arthroplasty under General Anesthesia: A Prospective Cohort Study Using CT Scan.
Postoperative pulmonary complications (PPCs) are common after major surgeries. However, the number of studies regarding PPCs following total knee arthroplasty (TKA) is limited. The aim of this study was to determine the incidence of early PPCs following TKA by computed tomography (CT) scan and to identify associated risk factors. Patients, who were diagnosed with osteoarthritis or rheumatoid arthritis and underwent primary TKA at our institution, were included in this prospective cohort study. Patients received a standard procedure of TKA under general anesthesia. Chest CT scan was performed during 5-7 days postoperatively. Univariate analysis and multivariate logistic regression analysis were employed to identify the risk factors. The total incidence of early PPCs following TKA was 45.9%. Rates of pneumonia, pleural effusion, and atelectasis were 14.4%, 38.7%, and 12.6%, respectively. Lower body mass index and perioperative blood transfusion were independent risk factors for PPCs as a whole and associated with atelectasis. Postoperative acute episode of hypoxemia increased the risk of pneumonia. Blood transfusion alone was related to pleural effusion. The incidence of early PPCs following TKA was high. For patients with relevant risk factors, positive measures should be adopted to prevent PPCs.


A Comparison of the Characteristics of Acupuncture- and Non-Acupuncture-Preferred Consumers: A Secondary Analysis of NHIS 2012 Data.
To determine whether acupuncture use, sociodemographic characteristics, and existing health conditions differ between acupuncture-preferred consumers (i.e., those who deem acupuncture to be one of the three most important complementary and alternative medicine [CAM] modalities used) and non-acupuncture-preferred consumers who used acupuncture in the past 12 months This is a secondary analysis of the National Health Interview Survey Sample Adult File and Adult Alternative Medicine datasets collected by the Centers for Disease Control and Prevention during 2012. The sample was drawn from the noninstitutionalized civilian population of the United States. The datasets yielded 34,525 respondents aged 18 years and older. Measures included in the analysis were acupuncture use in the past 12 months, sociodemographic characteristics, and existing health conditions. Analyses were performed by using Stata software, version 9.0 (Stata Corp., College Station, TX). Of the 10,158 adults who responded to the question regarding the "three most important" CAM modalities used, 572 (5.6%) had used acupuncture in the past 12 months. Of these, 456 (79.7%) chose acupuncture as one of the top three CAM modalities most important to their health. Acupuncture-preferred consumers reported significantly more visits to acupuncturists (7.46 versus 3.99 visits; p < 0.001), as well as higher out-of-pocket costs ($342.8 versus $246.4; p < 0.001), compared with non-acupuncture-preferred consumers. The logistic regression model revealed that with every additional CAM modality used, the likelihood of deeming acupuncture as one of the three CAM modalities most important to one's health decreased by 39% (odds ratio, 0.61; 95% confidence interval, 0.52-0.71; p < 0.001). Health conditions were not statistically significant predictors. A consumer's preference for acupuncture appeared not to be driven by health conditions but rather was related to sociodemographic factors. This suggests that health education regarding acupuncture may need to be tailored to certain consumer groups, such as those residing in the South, and could provide more information on the comparative effectiveness of acupuncture for various health conditions.


Smart Lacelock Sensor for the Balance Assessment of Community-Dwelling Older People.
This paper introduces a novel wearable shoe sensor named the Smart Lacelock Sensor. The sensor can be securely attached to the top of a shoe with laces and incorporates a loadcell to measure the force applied by the shoelace, providing valuable information related to ankle movement and foot loading. As the first step towards the automated balance assessment, this paper investigates the correlations between various levels of physical performance measured by the wearable Smart Lacelock Sensor and the SPPB clinical method in community-living older persons. 19 adults (age 76.84 ± 3.45 years), including those with and without recent fall history and SPPB score ranging from 4 to 12, participated in the study. The Smart Lacelock Sensor was attached to both shoes of each participant by skilled research staff, who then led them through the SPPB evaluation. The data obtained from the Smart Lacelock Sensors after the SPPB assessment were used to evaluate the deviation between the SPPB scores assigned by the research staff and the signals generated by the sensors for various participants. Results demonstrate that the standard deviation of the Smart Lacelock Sensor's loadcell response (both feet) for the side-by-side balance testing is significantly correlated (R2 = 0.68) with the SPPB score, demonstrating the capability of the Smart Lacelock Sensor in balance assessment.


Approach to the diagnosis of congenital myopathies.
Over the past decade there have been major advances in defining the genetic basis of the majority of congenital myopathy subtypes. However the relationship between each congenital myopathy, defined on histological grounds, and the genetic cause is complex. Many of the congenital myopathies are due to mutations in more than one gene, and mutations in the same gene can cause different muscle pathologies. The International Standard of Care Committee for Congenital Myopathies performed a literature review and consulted a group of experts in the field to develop a summary of (1) the key features common to all forms of congenital myopathy and (2) the specific features that help to discriminate between the different genetic subtypes. The consensus statement was refined by two rounds of on-line survey, and a three-day workshop. This consensus statement provides guidelines to the physician assessing the infant or child with hypotonia and weakness. We summarise the clinical features that are most suggestive of a congenital myopathy, the major differential diagnoses and the features on clinical examination, investigations, muscle pathology and muscle imaging that are suggestive of a specific genetic diagnosis to assist in prioritisation of genetic testing of known genes. As next generation sequencing becomes increasingly used as a diagnostic tool in clinical practise, these guidelines will assist in determining which sequence variations are likely to be pathogenic.


Microbial communities of aerobic granules: granulation mechanisms.
Aerobic granulation is an advanced biological wastewater treatment technology. This study for the first time identified the microbial communities of sliced samples of mature granules by polymerase chain reaction (PCR) amplification and denaturing gradient gel electrophoresis (DGGE) technique and those of whole growing granules by high-throughput sequencing technique. The sliced sample study revealed that mature granules have a spherical core with anaerobic Rhodocyclaceae covered by an outer spherical shell with both aerobic and anaerobic strains. The growing granule study showed that the flocculated flocs were first transited to young granules with increased abundances of Flavobacteriaceae, Xanthomonadaceae, Rhodobacteraceae and Microbacteriaceae, then the abundances of anaerobic strains were increased owing to the formation of anaerobic core. Since the present granules were cultivated from flocculated flocs, the microbial community data suggested that granules were formed via a deterministic rather than via a random aggregation-disintegration mechanism.


Utilization of a novel interactive mobile health platform to evaluate functional outcomes and pain following septoplasty and functional endoscopic sinus surgery.
Whether for research or quality improvement, assessment of postoperative quality of life outcomes faces a challenge in reliable data collection. Typical coordinator-led studies cite response rates from 35% to 70%. This study evaluates the utility of a digital patient engagement platform to track patient-reported outcome measures (PROMs) following septoplasty and functional endoscopic sinus surgery (FESS). A prospective cohort was recruited at a tertiary care center from January 2017 to March 2018. A mobile phone application relayed PROMs, including pain (assessed on a 0 to 10 visual analogue scale [VAS] every other day for 2 weeks, as well as the patient-reported outcome measure information system [PROMIS] pain interference short form 4a at baseline, 2 weeks, and 3 months) and timing of return to work. Of 288 patients enrolled, 249 (86.5%) provided clinical data, including 208 who underwent septoplasty or FESS. Granular VAS scores, submitted by 195 patients, demonstrated 80% of these patients achieved minimal pain by postoperative day 8. A nonsignificant trend of increased days to pain relief by procedure emerged: septoplasty (mean ± standard deviation [SD], 3.60 ± 2.44), FESS (3.96 ± 3.25), FESS with septoplasty (4.40 ± 3.04), and FESS with drilling (4.86 ± 3.68). Across procedures, PROMIS pain interference increased at 2 weeks (9.17 ± 4.15) and decreased at 3 months (5.32 ± 2.61) compared with baseline (7.09 ± 4.63), with greater improvement noted in the FESS subgroup at 3 months. Patients returned to work at mean 7.1 days regardless of procedure. With its high response rate, mobile digital patient engagement platforms may effectively track postoperative outcomes with the potential for reduced sample bias.


Inhibition of casein kinase 2 sensitizes mantle cell lymphoma to venetoclax through MCL-1 downregulation.
BCL-2 family proteins are frequently aberrantly expressed in mantle cell lymphoma (MCL). Recently, the BCL-2-specific inhibitor venetoclax has been approved by the US Food and Drug Administration for chronic lymphocytic leukemia (CLL) and acute myeloid leukemia (AML). In MCL, venetoclax has shown promising efficacy in early clinical trials; however, a significant subset of patients is resistant. By conducting a kinome-centered CRISPR-Cas9 knockout sensitizer screen, we identified casein kinase 2 (CK2) as a major regulator of venetoclax resistance in MCL. Interestingly, CK2 is over-expressed in MCL and high CK2 expression is associated with poor patient survival. Targeting of CK2, either by inducible short hairpin RNA (shRNA)-mediated knockdown of CK2 or by the CK2-inhibitor silmitasertib, did not affect cell viability by itself, but strongly synergized with venetoclax in both MCL cell lines and primary samples, also if combined with ibrutinib. Furthermore, targeting of CK2 reduced MCL-1 levels, which involved impaired MCL-1 translation by inhibition of eIF4F complex assembly, without affecting BCL-2 and BCL-XL expression. Combined, this results in enhanced BCL-2 dependence and, consequently, venetoclax sensitization. In cocultures, targeting of CK2 overcame stroma-mediated venetoclax resistance of MCL cells. Taken together, our findings indicate that targeting of CK2 sensitizes MCL cells to venetoclax through downregulation of MCL-1. These novel insights provide a strong rationale for combining venetoclax with CK2 inhibition as therapeutic strategy for MCL patients.


Intraocular Pressure Measurement with Pneumatonometry and a Tonometer Tip Cover.
To investigate the precision and accuracy of IOP measurements using a pneumatonometer and a tonometer tip cover (Tono-Pen® tip cover) acting as a membrane between a cadaver eye model and pneumatonometer probe. A total of 480 paired IOP measurements, with and without a Tono-Pen cover, were collected across 4 pressure levels of 7, 10, 20 and 30 mmHg. IOP measurements were obtained by three different pneumatonometer units paired with three different masked operators (three configurations). Four eyes were sampled for each eye pressure level. The sequence of eye pressure, configuration, and measurements with vs. without the Tono-Pen cover was randomized. With the Tono-Pen cover in place, there was a negative bias with a mean IOP difference of - 1.18 mmHg for all 480 paired samples compared with the measurements absent the cover. Compared with the test pressure settings (i.e., 7, 10, 20, 30 mmHg), the overall mean bias was + 0.35 mmHg with the Tono-Pen cover present. With the Tono-Pen cover present, the overall repeatability %CV (percent coefficient of variation) was 3.4% and the reproducibility %CV was 3.8% compared with a repeatability %CV of 3.2% and reproducibility %CV of 5.7% without the Tono-Pen cover. Measurement of IOP via pneumatonometry with a Tono-Pen cover in place, also known as the excursion test method, yields precise, accurate and reproducible results. This developed method of pressure measurement is an acceptable and reliable form of IOP measurement.


Non-inferiority clinical trials: Practical issues and current regulatory perspective.
Non-inferiority clinical trials are being performed with an increasing frequency now-a-days, because it helps in finding a new treatment that have approximately the same efficacy, but may offer other benefits such as better safety profile. Non-inferiority clinical trials aim to demonstrate that the test product is no worse than the comparator by more than a pre-specified small amount. There are several fundamental differences between non-inferiority and superiority trials. Some practical issues concerning the non-inferiority trials are assay sensitivity, choice of the non-inferiority margin, sample size estimation, choice of active-control, and analysis of non-inferiority clinical trials. For serious infections such as hospital-acquired bacterial pneumonia/ventilator-associated bacterial pneumonia, community-acquired bacterial pneumonia, and acute bacterial skin and skin structure infections, the United States Food and Drug Administration (US FDA) has recently recommended that it is possible to define a reliable and consistent estimate of the efficacy of active treatment relative to placebo from available data, which can serve as the basis for defining a new inferiority margin for an active-controlled, non-inferiority trial. But for some indications with a high rate of resolution without antibacterial drug therapy such as acute bacterial sinusitis (ABS), acute bacterial exacerbation of chronic bronchitis (ABECB), and acute bacterial otitis media (ABOM), the US FDA has recommended that the available data will not support the use of a non-inferiority design and other trial designs (i.e., superiority designs) should be used to provide the evidence of effectiveness in these three indications.


Examination of a New Delivery Approach for Oral Cannabidiol in Healthy Subjects: A Randomized, Double-Blinded, Placebo-Controlled Pharmacokinetics Study.
Therapeutic effects of cannabidiol (CBD) in specialized populations continue to emerge. Despite supra-physiological dosing being shown to be tolerable in various pathologies, optimization of CBD absorption has obvious benefits for general health and recreational usage. Our objectives were to: (1) to investigate a joint pharmacokinetic-physiological time course of multiple recreational-equivalent (< 100 mg) dosages of oral CBD in young healthy adults and (2) evaluate a newly developed technology (TurboCBD™) for the enhanced delivery of CBD. In a double-blinded, placebo-controlled, cross-over design, 12 participants received placebo, generic 45 or 90 mg of CBD, or TurboCBD™ delivery technology capsules on five separate occasions. Although there were no differences in the 45 mg conditions, circulating CBD levels were higher with the TurboCBD™ 90 mg group at both 90 (+ 86%) and 120 (+ 65%) min compared with the 90 mg control (p < 0.05). Total area under the curve tended to be higher with TurboCBD™ 90 mg compared with 90 mg (10,865 ± 6322 ng ml-1 vs. 7114 ± 2978 ng ml-1; p = 0.088). Only the TurboCBD™ 90 mg dose was elevated greater than placebo at 30 min (p = 0.017) and remained elevated at 4 h (p = 0.002). Consistent with higher bioavailability, TurboCBD™ 90 mg at the peak CBD concentration was associated with an increase in cerebral perfusion and slight reduction in blood pressure compared with baseline and the 90 mg control. Further studies are needed to establish the mechanisms of action of this technology and to explore the therapeutic potential of acute and chronic dosing on more at-risk populations. Lexaria Bioscience Corp. ClinicalTrials.gov identifier, NCT03295903.


Isolation of secreted microRNAs (miRNAs) from cell-conditioned media.
MicroRNAs (miRNAs) have been found to be stable in the circulation of cancer patients raising their potential as circulating biomarkers of disease. The specific source and role, however, of miRNAs in the circulation is unknown and requires elucidation to determine their true potential. In this study, along with primary tissue explants and primary stromal cells, three breast cancer cell lines were employed, including T47D, MDA-MB-231 and SK-BR-3. Tissue explants were harvested in theatre, with informed patient consent, and included tumour, tumour associated normal, and diseased lymph node samples. Cell-conditioned media containing all factors secreted by the cells were harvested. MiRNAs were extracted from samples using 5 different extraction techniques including the blood protocol, RNeasy® (Qiagen), miRNeasy®mini kit (Qiagen), mirVana™ isolation kit (Ambion) and RNAqueous® kit (Ambion). MiRNAs were successfully isolated from all media samples collected from cell lines, primary cells and fresh tissue explants. However, there was remarkable variation in yield depending on the extraction method used. Aliquots of the same samples were extracted, revealing the two column extraction protocol of the mirVana® miRNA isolation kit to be the most suitable approach. A range of miRNAs, including miR-16, miR-195, miR-497 and miR-10b, were successfully amplified. While miR-16 and miR-195 were detected in media from both cell lines and tissue explants, miR-497 and miR-10b were only detected in secretions from whole tissue explants. The ability to achieve reliable and reproducible miRNA yields from cell-conditioned media is vital for the successful amplification of miRNAs by RQ-PCR.


Feasibility of totally extraperitoneal inguinal hernia repair in patients with previous prostatectomy.
Laparoscopic totally extraperitoneal inguinal hernia repair (TEP) surgery technique includes three key steps: reaching the preperitoneal space, reducing hernias, and placement of mesh. However, reaching the preperitoneal space can be complicated in patients with previous lower abdominal surgeries. This study aimed to assess the feasibility of laparoscopic inguinal TEP in patients with previous prostatectomies. Inguinal hernia patients who underwent laparoscopic TEP between January 2015 and February 2021 at Koç University Faculty of Medicine, Department of General Surgery, were included in this retrospective study. The operations were performed by five senior surgeons experienced in laparoscopy. Patients were divided into two study groups, as the radical prostatectomy (RP) group which included patients with previous prostatectomy non-RP which included patients without previous radical prostatectomy. Operative time (OT), length of hospital stay (LOS), and postoperative complications were compared within two groups. Three hundred and forty-nine patients underwent laparoscopic TEP, and 27 had previous prostatectomies. Among them, 190 patients had unilateral inguinal hernias, and 159 had bilateral inguinal hernias. Mean age of the patients in the non-RP and RP groups was 58.1 ± 14.7 and 73.9 ± 9.6 years, respectively. Only one (3.7%) case was complicated with urinary tract infection in the RP group, and 10 (3.1%) were complicated in the non-RP group. Complications for the non-RP group include hematomas in six cases, urinary tract infection in three cases, and urinary retention in one case. No significant difference in mean operative time was seen between non-RP and RP groups (p= 0.43). There was no significant difference in the means of the length of hospital stay between the two groups (p= 0.7). Laparoscopic TEP in patients with a previous prostatectomy can be performed safely without prolonging the operative time and increasing the length of hospital stay.


From intra- to inter-molecular hydrogen bonds with the surroundings: steady-state and time-resolved behaviours.
We report on the photodynamics of 2-(2'-hydroxyphenyl)benzoxazole (HBO), compared to its amino derivatives, 6-amino-2-(2'-hydroxypheny)benzoxazole (6A-HBO) and 5-amino-2-(2'-hydroxypheny)benzoxazole (5A-HBO) in N,N-dimethylformamide (DMF) solutions. HBO at S0 shows a reversible deprotonation reaction leading to the production of anionic forms. However, for 6A-HBO and 5A-HBO, DMF containing KOH is necessary to produce the anions. Excited HBO in DMF exhibits intra- as well as inter-molecular proton transfer (ESIPT and ESPT) reactions. With excitation at 330 nm, we observed the open-enol, anti-enol and keto forms with different emission and lifetimes (620 ps, 1.5 ns, and 74 ps, respectively), while with the excitation at 433 nm, only the anionic species emission was detected (3.7 ns). Contrary to HBO, 6A-HBO and 5A-HBO do not exhibit any proton transfer process, and only the emissions of the open-enol charge-transferred forms (open-ECT) were observed, which are comparable to those of their methylated derivatives (6A-MBO and 5A-MBO). Femtosecond studies of 6A-MBO and 6A-HBO in DMF indicate that an intramolecular charge-transfer (ICT) reaction (∼80 fs) and solvent relaxation process (2 ps) take place at S1. Remarkably, the photoinduced breaking of the intramolecular hydrogen bond of 6A-HBO and the formation of an intermolecular hydrogen bond with DMF molecules occurs in 80 ps, while for 5A-HBO, this process occurs in less than 10 ps. In this study, we have demonstrated that the presence and position of the amino group in the HBO framework change both the S0 and S1 behaviours of the intramolecular H-bonds; a result which might be useful for the design and better understanding of supramolecular systems based on intra- and intermolecular H-bonds.


Using core public health functions to promote BRCA best practices among health plans.
The Michigan Department of Community Health (MDCH) Cancer Genomics Program sought to increase the number of health plans with a written policy aligned with the United States Preventive Services Task Force (USPSTF) Grade B Recommendation stating that women whose family history is associated with an increased risk for deleterious mutations in BRCA1 or BRCA2 be referred for genetic counseling and evaluation for BRCA testing. Through a cooperative agreement with the Centers for Disease Control and Prevention, MDCH with health plan partners utilized multiple methods (i.e. surveillance, education, federal and state policies, partnerships, and dissemination) to increase the number of health plans with a written policy aligned with the USPSTF Grade B BRCA Recommendation between 2008 and 2011. Since 2008, the number of health plans that have policies consistent with USPSTF Grade B BRCA Recommendation in Michigan increased from 4 to 11. These 11 health plans provide coverage to over 7 million Michigan residents. Honors were bestowed by MDCH to these 11 health plans for their exemplary written policies. MDCH has implemented a novel and effective approach to promote cancer genomics best practices through health plan policies that serves as a model for federal and state agencies.


Online resources for persons recently diagnosed with HIV/AIDS: an analysis of HIV-related webpages.
The Internet is a major source of HIV-related information and resources for persons recently diagnosed with HIV/AIDS (PRDHA). This study examined the types of HIV-related websites that appear as a result of HIV-related keyword searches and the extent to which website information targets PRDHA. The first page of HIV-related webpages from 18 keyword searches was coded. Among 137 webpages meeting inclusion criteria, 63% represented HIV-informational websites, 31% targeted HIV-positive individuals, and over half contained or provided access to HIV prevention, treatment, and transmission information. Thirty-three percent of webpages contained or provided access to PRDHA-targeted information, with a greater percentage of those webpages having mobile, non-English, and "Ask the Expert" features compared with non-PRDHA targeted webpages. Implications for PRDHA include the following: (1) they should explore HIV-related websites to gain insight into the credibility of the information contained on those sites; (2) PRDHA must be aware that HIV-related websites have the potential to elicit dated, emotionally distressing, or irrelevant information; and (3) to obtain information that relates to their demographic and situational profile, they may wish to use specific key terms (e.g., "HIV women") rather than attempting to navigate webpages that arise from general search terms (e.g., "HIV"). Recommendations for future development of online resources for PRDHA include providing HIV-relevant information in a stepwise fashion, providing demographically targeted HIV information, and greater utilization of mobile technology.


Hydrological properties predict the composition of microbial communities cycling methane and nitrogen in rivers.
Sediment microbial communities drive the biogeochemical cycles that make rivers globally important sources and sinks of carbon (C) and nitrogen (N). The structure of these communities is strongly determined by the local physico-chemical environment. However, we currently lack an understanding of the factors that determine microbial community structures at the catchment scale. Here, we show that the contribution of groundwater to total river flow (quantified as base flow index; BFI) predicts the structure and diversity of the different microbial functional groups that cycle N and C across nine UK rivers, spanning a geological BFI gradient from 0.23 (clay sediment) to 0.95 (chalk gravel sediment). Furthermore, the GC-content (percentage of guanine-cytosine bases in a DNA sequence) and codon-usage bias of ammonia monooxygenase DNA sequences, and the hydrophobicity and net-charge of the corresponding amino acid sequences, were all strongly correlated with BFI, likely reflecting physiological adaptations to different riverbed sediment structure along the BFI gradient. Our results offer an opportunity to overcome the "paradox of scales" that has seen microbial ecologists focus on small- rather than large-scale environmental variables, enabling us to scale-up our understanding of microbial biogeochemistry to the catchment and beyond.


[Surgical treatment for pseudoaneurysm of the sinus of valsalva ruptured into the right atrium after mycotic right coronary artery aneurysm repair;report of a case].
A 67-year-old man was admitted to our hospital by ambulance after syncope due to complete A-V block. He had received surgical treatment for mycotic aneurysm of the right coronary artery 3 months before, with patch plasty of the right sinus of Valsalva and bypass grafting to the right coronary artery (RCA) as well as the left anterior descending branch. Computed tomography revealed pseudoaneurysm of the right Valsalva sinus of about 8 cm in diameter and a shunt flow to the right atrium. The previous bypass graft to RCA had been occluded due to compression by the aneurysm. As he was in a shock state, emergency operation was performed. Cardiopulmonary bypass was first established, and after the rectal temperature reached to 26 degrees centigrade, the chest was opened. The pseudoaneurysm burst out when the sternum was re-opened. Under circulatory arrest, the ascending aorta was clamped, and then the circulation was resumed. The previous bovine pericardium patch repairing the Valsalva sinus was detached due to infection, and mural thrombus and pus were observed in the aneurysm. At the bottom of the aneurysm, a fistula connected to the right atrium was found. Debridement around the aneurysm was performed as much as possible. The defect of the Valsalva sinus was repaired with a Dacron patch immersed in gentian violet. The postoperative course was uneventful without any recurrence of infection.


High Rates of Indeterminate TB Tests Among Hospitalized Patients: Can We Optimize Use of Gamma Interferon Release Assays in Tuberculosis?
In the United States, high concern for iatrogenic reactivation to tuberculosis (TB) disease secondary to prescribed immunosuppression has resulted in increased use of the QuantiFERON-TB Gold In-Tube test (QFT-GIT) to screen for Mycobacterium tuberculosis (Mtb) infection. The aim of our study was to determine indications for QFT-GIT testing and risk factors for indeterminate QFT-GIT results. We retrospectively identified patients with QFT-GIT testing over a six-month period in a tertiary care academic health care system and performed a record review. Inpatients were 11 times more likely to have an indeterminate QFT-GIT result than outpatients (95% CI 7.6-16.2). 61.5% inpatient QFT-GITs were ordered during workup of active TB. Providers treating exogenously or endogenously immunosuppressed patients ordered the most QFT-GITs. We highlight the significant limitations of TB screening tests in the inpatient setting and the need to test earlier in those requiring immunosuppressive therapy to avoid indeterminate results.


Distinct Localization of SNAP47 Protein in GABAergic and Glutamatergic Neurons in the Mouse and the Rat Hippocampus.
Synaptosomal-associated protein of 47 kDa (SNAP47) isoform is an atypical member of the SNAP family, which does not contribute directly to exocytosis and synaptic vesicle (SV) recycling. Initial characterization of SNAP47 revealed a widespread expression in nervous tissue, but little is known about its cellular and subcellular localization in hippocampal neurons. Therefore, in the present study we applied multiple-immunofluorescence labeling, immuno-electron microscopy and in situ hybridization (ISH) and analyzed the localization of SNAP47 in pre- and postsynaptic compartments of glutamatergic and GABAergic neurons in the mouse and rat hippocampus. While the immunofluorescence signal for SNAP47 showed a widespread distribution in both mouse and rat, the labeling pattern was complementary in the two species: in the mouse the immunolabeling was higher over the CA3 stratum radiatum, oriens and cell body layer. In contrast, in the rat the labeling was stronger over the CA1 neuropil and in the CA3 stratum lucidum. Furthermore, in the mouse high somatic labeling for SNAP47 was observed in GABAergic interneurons (INs). On the contrary, in the rat, while most INs were positive, they blended in with the high neuropil labeling. ISH confirmed the high expression of SNAP47 RNA in INs in the mouse. Co-staining for SNAP47 and pre- and postsynaptic markers in the rat revealed a strong co-localization postsynaptically with PSD95 in dendritic spines of pyramidal cells and, to a lesser extent, presynaptically, with ZnT3 and vesicular glutamate transporter 1 (VGLUT1) in glutamatergic terminals such as mossy fiber (MF) boutons. Ultrastructural analysis confirmed the pre- and postsynaptic localization at glutamatergic synapses. Furthermore, in the mouse hippocampus SNAP47 was found to be localized at low levels to dendritic shafts and axon terminals of putative INs forming symmetric synapses, indicating that this protein could be trafficked to both post- and presynaptic sites in both major cell types. These results reveal divergent localization of SNAP47 protein in mouse and rat hippocampus indicating species- and cell type-specific differences. SNAP47 is likely to be involved in unique fusion machinery which is distinct from the one involved in presynaptic neurotransmitter release. Nonetheless, our data suggest that SNAP47 may be involved not only postsynaptic, but also in presynaptic function.


Dispersal syndromes and the use of life-histories to predict dispersal.
Due to its impact on local adaptation, population functioning or range shifts, dispersal is considered a central process for population persistence and species evolution. However, measuring dispersal is complicated, which justifies the use of dispersal proxies. Although appealing, and despite its general relationship with dispersal, body size has however proven unsatisfactory as a dispersal proxy. Our hypothesis here is that, given the existence of dispersal syndromes, suites of life-history traits may be alternative, more appropriate proxies for dispersal. We tested this idea by using butterflies as a model system. We demonstrate that different elements of the dispersal process (i.e., individual movement rates, distances, and gene flow) are correlated with different suites of life-history traits: these various elements of dispersal form separate syndromes and must be considered real axes of a species' niche. We then showed that these syndromes allowed accurate predictions of dispersal. The use of life-history traits improved the precision of the inferences made from wing size alone by up to five times. Such trait-based predictions thus provided reliable dispersal inferences that can feed simulation models aiming at investigating the dynamics and evolution of butterfly populations, and possibly of other organisms, under environmental changes, to help their conservation.


Increased expression of fatty acid synthase (OA-519) in ovarian neoplasms predicts shorter survival.
Certain cancers exhibit derangement of de novo fatty acid biosynthesis, manifested as overexpression and hyperactivity of the lipogenic enzyme fatty acid synthase (FAS). Correlation of elevated FAS with high tumor grade and advanced stage in primary breast, prostate, and colorectal cancers has drawn attention to the enzyme as a possible marker of poor prognosis. To find a similar utility of FAS in ovarian neoplasms, we compared FAS expression in 68 ovarian tumors with their histological features and clinical outcome. Immunohistochemical localization of FAS was observed in 48 (71%) cases in which staining was either focal (defined as positive staining in 1% to 20% of cells) or multifocal/diffuse (positive staining in >20% of cells). Most (83%) of the 48 cases were represented by endometrioid, serous, or mucinous carcinomas and malignant mixed mullerian tumors (MMMTs). In contrast, ovarian adenomas and tumors of low malignant potential (LMPs) contained little or no FAS. Association between FAS expression and histological diagnosis was statistically significant. The extent of FAS immunostaining was also predictive of prognosis. Among all patients with ovarian malignancies (including LMPs), median survival was 64.8 months, when their tumors exhibited no or focal immunostaining for FAS, as opposed to 31.2 months, when staining was multifocal/diffuse (P = .005). Similar median survival values were obtained when cases were limited to endometrioid, serous, and mucinous carcinomas. Short-term survival at 1 and 2 years was significantly higher in patients whose tumors showed no or focal expression of FAS compared with multifocal/diffuse expression. Thus, elevated FAS may serve as an independent marker for predicting poor clinical outcome in patients with ovarian cancer.


Comparative Regimens of Lipid Rescue From Bupivacaine-Induced Asystole in a Rat Model.
It is currently unknown whether bupivacaine-induced asystole is better resuscitated with lipid emulsion (LE) administered peripherally or centrally, and whether different LE regimens administered peripherally demonstrated similar effects. In this study, we compared the effects of various regimens of lipid administration in a rat model of bupivacaine-induced asystole. Forty-five adult male Sprague-Dawley rats were subjected to bupivacaine-induced asystole and randomly divided into 3 lipid regimens groups: (1) 20% LE was administered continuously via the internal jugular vein (CV-infusion group); (2) 20% LE was administered continuously via the tail vein (PV-infusion group); and (3) 20% LE was administered as divided boluses via the tail vein (PV-bolus group). The maximum dose of LE did not exceed 10 mL·kg(-1). External chest compressions were administered until the return of spontaneous circulation (ROSC) or the end of a 40-minute resuscitation period. The survival rate, rate of ROSC, systolic blood pressure, heart rate, heart rate-blood pressure product, and coronary perfusion pressure during 2-40 minutes in the CV-infusion and PV-bolus groups were significantly higher than those in the PV-infusion group (P < .01), and the plasma total bupivacaine concentration and myocardial bupivacaine content were significantly lower (P < .05). Time to heartbeat return and time to ROSC in the CV-infusion and PV-bolus groups were significantly shorter than those in the PV-infusion group (P < .05). In the rat model of bupivacaine-induced asystole, a divided LE bolus regimen administered peripherally provided a better resuscitation outcome than that of a continuous LE infusion regimen peripherally, and performed in a similar fashion as the continuous LE infusion regimen administered centrally.


Initial reactions to tobacco and cannabis smoking: a twin study.
Initial subjective reactions to cannabis and tobacco, broadly classified as positive or negative, have previously been explored for their associations with onset and maintenance of subsequent abuse/dependence. We examine (i) the factorial architecture of self-reported initial reactions to cannabis and tobacco; (ii) whether these factors associate with concurrently reported age at onset of DSM-IV diagnosis of nicotine dependence and cannabis abuse/dependence; and (iii) estimate heritable variation in and covariation between the factors. Factorial and exploratory structural equation modeling was conducted to examine the factor structure of initial reactions. Cox proportional hazards modeling was employed to examine their association with time to onset of diagnosis of DSM-IV nicotine dependence and cannabis abuse/dependence. Classical twin modeling, using univariate and multivariate models, was used to parse variance in each factor (and the covariance between factors) to their additive genetic, shared environmental and non-shared environmental sources. General population sample of Caucasian female twins aged 18-32 years, with a life-time history of tobacco [n = 2393] and cannabis [n = 1445] use. Self-report of initial subjective reactions to tobacco (cigarettes) and cannabis the first time they were used and time to onset of life-time history of DSM-IV diagnosis of abuse (cannabis) and dependence (cannabis or nicotine). Factors representing putatively positive and negative reactions to cannabis and tobacco emerged. Initial reactions to tobacco were associated with onset of DSM-IV diagnosis of nicotine dependence and cannabis abuse/dependence while initial reactions to cannabis were associated with onset of DSM-IV diagnosis of cannabis abuse/dependence alone. Genetic factors played a moderate role in each factor (heritability of 27-35%, P < 0.05), with the remaining variance attributed to individual-specific environment. Covariation across the factors indexing positive and negative initial reactions was attributable to genetic sources (0.18-0.58, P < 0.05) and to overlapping individual-specific environmental factors (-0.16 to 0.36, P < 0.05). Initial subjective reactions to tobacco are associated with onset of DSM-IV diagnosis of nicotine dependence and cannabis abuse/dependence while initial subjective reactions to cannabis are only associated with onset of diagnosis of DSM-IV cannabis abuse/dependence. Genetic and environmental factors underpin the overlap across the factors representing initial reactions, both positive and negative.


The Anti-Inflammatory Effect of Hydrogen Gas Inhalation and Its Influence on Laser-Induced Choroidal Neovascularization in a Mouse Model of Neovascular Age-Related Macular Degeneration.
Age-related macular degeneration (AMD) is a leading cause of blindness in the elderly. Choroidal neovascularization (CNV) is the major pathologic feature of neovascular AMD. Oxidative damages and the ensuing chronic inflammation are representative of trigger events. Hydrogen gas (H2) has been demonstrated as an antioxidant and plays a role in the regulation of oxidative stress and inflammation. This experiment aimed to investigate the influence of H2 inhalation on a mouse model of CNV. Laser was used to induce CNV formation. C57BL/6J mice were divided into five groups: the control group; the laser-only group; and the 2 h, 5 h, and 2.5 h/2.5 h groups that received laser and H2 inhalation (21% oxygen, 42% hydrogen, and 37% nitrogen mixture) for 2 h, 5 h, and 2.5 h twice every day, respectively. The severity of CNV leakage on fluorescence angiography showed a significant decrease in the H2 inhalation groups. The mRNA expression of hypoxia-inducible factor 1 alpha and its immediate downstream target vascular endothelial growth factor (VEGF) showed significant elevation after laser, and this elevation was suppressed in the H2 inhalation groups in an inhalation period length-related manner. The mRNA expression of cytokines, including tumor necrosis factor alpha and interlukin-6, also represented similar results. H2 inhalation could alleviate CNV leakage in a laser-induced mouse CNV model, and the potential mechanism might be related to the suppression of the inflammatory process and VEGF-driven CNV formation.


EDUCOM: Interuniversity Communications Council.
The Interuniversity Communications Council has been formed to provide collaboration among institutions of higher learning in their efforts to utilize the emerging communication sciences. Given a W. K. Kellogg Foundation grant for administration, eight charter members announced the nonprofit organization in June 1965. There now are 50 institutional members, representing 167 separate campuses. Interuniversity task forces have been assigned to the study of computerized regional and national educational information processing networks, educational systems and technology, computer-based systems for clinical activities, the copyright problems inherent in the new media, the use of the new information technologies in continuing education, and the use of computers in academic management. Other task forces will also be established. All information-processing activities in higher education are of concern to EDUCOM, including computational use of computers, computerized programmed instruction, library automation, educational radio and television, computerized cognitive aids, and the use of computers in clinical operations and university administration. Its primary purposes are to organize interuniversity cooperation in these fields, to disseminate reports on the state of educational information technologies, to investigate areas of critical development, and to facilitate useful applications.


Genetic transfer of amylovoran and stewartan synthesis between Erwinia amylovora and Erwinia stewartii.
DNA fragments with ams genes of Erwinia amylovora and cps genes of Erwinia stewartii were transferred to exopolysaccharide (EPS)-deficient mutants of the other species. The resulting EPSs were characterized by sensitivity to EPS-dependent bacteriophages, staining with amylovoran-specific fluorescein-isothiocyanate-labelled lectin and chemical techniques, such as determination of the sugar composition and methylation analysis in order to distinguish between amylovoran and stewartan. Degradation by the stewartan-dependent phage phi-K9 was used to detect stewartan production, and staining with a lectin from Abrus precatorius detected amylovoran capsules. The patterns of sugar linkages were determined by methylation analysis. Stewartan contained a significantly higher glucose to galactose ratio than amylovoran and produced a characteristic signal from 6-linked glucose residues. By these criteria, most E. stewartii cps mutants displayed exclusively amylovoran synthesis when complemented with the E. stewartii cps genes produced stewartan. The complementation to an EPS-positive phenotype may require most genes of the ams or the cps operon. An exception was an E. stewartii cpsK mutant that made predominantly stewartan when complemented with the ams cosmid. IR spectra showed that both amylovoran and stewartan were acylated when synthetized in E. amylovora, but not in E. stewartii. The amylovoran-producing E. stewartii merodiploids regained virulence to corn seedlings when mucoidy was restored by the ams cluster, but the stewartan-producing E. amylovora ams-/cps+ strains were weakly virulent on pear slices and avirulent on apple seedlings.


A controlled study of 2 doses of idebenone in the treatment of Alzheimer's disease.
Two doses of idebenone were studied in a prospective, randomized, double-blind, placebo-controlled multicentre study in patients suffering from dementia of the Alzheimer type (DAT) of mild to moderate degree. Diagnosis was based on DSM-III-R (primary degenerative dementia) and NINCDS-ADRDA criteria (probable Alzheimer's disease). A total of 300 patients were randomized to either placebo, idebenone 30 mg t.i.d. or 90 mg t.i.d. (n = 100, each) and treated for 6 months. The primary outcome measure was the total score of the Alzheimer's Disease Assessment Scale (ADAS-Total) at month 6. Secondary outcome measures were the ADAS cognitive (ADAS-Cog) and noncognitive scores (ADAS-Noncog), the clinical global response (CGI-Improvement), the MMSE, the Digit Symbol Substitution test (DSS) and several scales for the assessment of daily activities (the self- and observer-rating scales NAA and NAB of the Nuremberg Age Inventory NAI and Greene's Assessment). Safety parameters were adverse events, vital signs, ECG and clinical laboratory parameters. Clinical and psychometric evaluations were performed at baseline, and after 1, 3 and 6 months of treatment. After month 6 idebenone 90 mg t.i.d. showed statistically significant improvement in the primary efficacy variable ADAS-Total and in ADAS-Cog. An analysis of therapy responders performed for 3 outcome measures (CGI-global improvement, ADAS-Cog, ADAS-Noncog), selected to represent different domains of assessment, revealed significant superiority of idebenone 90 mg t.i.d. with respect to placebo in each of the 3 variables and in the concordance of responses across the 3 measures. Exploratory results for a subgroup of patients (ADAS-Total > or = 20) showed dose-related superiority of idebenone additionally on ADAS-Noncog and the CGI-Improvement scale. Safety results were inconspicuous for all assessments. The study results demonstrate the efficacy and safety of idebenone in the treatment of DAT patients.


Human gamma-melanotropin precursor potentiates corticotropin-induced adrenal steroidogenesis by stimulating mRNA synthesis.
Circulating human gamma-melanotropin precursor (76 amino acids) [N-POC(1-76) enhances the corticosterone and aldosterone response to corticotropin by isolated perfused rat adrenal cells [Al-Dujaili, Hope, Estivariz, Lowry & Edwards (1981) Nature (London) 291, 156-159]. Actinomycin D (4 x 10(-6) mol/litre) did not significantly affect corticotropin-induced corticosterone or aldosterone outputs, but completely inhibited the potentiating action of gamma-melanotropin precursor on rat adrenal cells. This suggests that the precursor enhances corticotropin-induced steroidogenesis via an increase in available mRNA produced from DNA transcription.


Neuroprotective effects of genistein on SH-SY5Y cells overexpressing A53T mutant α-synuclein.
Genistein, a potent antioxidant compound, protects dopaminergic neurons in a mouse model of Parkinson's disease. However, the mechanism underlying this action remains unknown. This study investigated human SH-SY5Y cells overexpressing the A53T mutant of α-synuclein. Four groups of cells were assayed: a control group (without any treatment), a genistein group (incubated with 20 μM genistein), a rotenone group (treated with 50 μM rotenone), and a rotenone + genistein group (incubated with 20 μM genistein and then treated with 50 μM rotenone). A lactate dehydrogenase release test confirmed the protective effect of genistein, and genistein remarkably reversed mitochondrial oxidative injury caused by rotenone. Western blot assays showed that BCL-2 and Beclin 1 levels were markedly higher in the genistein group than in the rotenone group. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling revealed that genistein inhibited rotenone-induced apoptosis in SH-SY5Y cells. Compared with the control group, the expression of NFE2L2 and HMOX1 was significantly increased in the genistein + rotenone group. However, after treatment with estrogen receptor and NFE2L2 channel blockers (ICI-182780 and ML385, respectively), genistein could not elevate NFE2L2 and HMOX1 expression. ICI-182780 effectively prevented genistein-mediated phosphorylation of NFE2L2 and remarkably suppressed phosphorylation of AKT, a protein downstream of the estrogen receptor. These findings confirm that genistein has neuroprotective effects in a cell model of Parkinson's disease. Genistein can reduce oxidative stress damage and cell apoptosis by activating estrogen receptors and NFE2L2 channels.


Effect of TGF-beta 1, TGF-alpha, and EGF on cell proliferation and cell death in rat ventral prostatic epithelial cells in culture.
A tissue culture system for rat prostatic epithelial cells was developed, and the effect of epidermal growth factor (EGF), transforming growth factor alpha (TGF-alpha), and transforming growth factor beta 1 (TGF-beta 1) on these cells was evaluated. The primary culture was prepared by DNAse/collagenase dissociation of minced ventral prostates. Cells were initially plated in RPMI-1640 medium containing 10% fetal bovine serum to allow the preferential attachment of stromal cells. Twenty-four hours later, the unattached epithelial cells were replated in WAJC-404 medium supplemented with insulin (5 micrograms/ml), transferrin (5 micrograms/ml), and selenious acid (5 ng/ml). Bovine pituitary extract (BPE) (30 micrograms/ml), EGF (10 ng/ml), and TGF-beta 1 (0, 0.1, and 1.0 ng/ml) were added either alone or in combination according to experimental requirements. The rate of cell proliferation was assessed by counting the total cell number and by [3H]thymidine incorporation. Prostatic epithelial cells exhibited a bell-shaped growth curve in a span of 7-8 days, with a growth peak at day 3 or 4 of culture. Treatment of cells with EGF or TGF-alpha resulted in a concentration-dependent increase in cell growth, whereas addition of TGF-beta 1 into the culture resulted in an inhibition of cell proliferation that could be reversed with increasing concentrations of EGF. Cell death was assessed using the terminal deoxynucleotidyl transferase (TdT)-mediated immunoperoxidase-digoxigenin nick end labeling technique and the trypan blue exclusion test. Epithelial cells cultured in media containing EGF had the lowest incidence of cell death. Cells cultured in the absence of EGF demonstrated a marked increase in cells undergoing cell death. The addition of TGF-beta 1 into the EGF-depleted medium caused a further increase of cell death. These results indicated that cell proliferation and cell death in rat prostatic epithelial cells in culture could be modulated by EGF and TGF-beta 1. The former stimulated cell proliferation and prevented cell death, whereas the latter inhibited proliferation in the presence or absence of EGF and induced cell death.


Mechanistic inhibition of Monkeypox and Marburg virus infection by O-rhamnosides and Kaempferol-o-rhamnosides derivatives: a new-fangled computational approach.
The increasing incidence of Monkeypox virus (Mpox) and Marburg virus (MARV) infections worldwide presents a significant challenge to global health, as limited treatment options are currently available. This study investigates the potential of several O-rhamnosides and Kaempferol-O-rhamnosides as Mpox and MARV inhibitors using molecular modeling methods, including ADMET, molecular docking, and molecular dynamics/MD simulation. The effectiveness of these compounds against the viruses was assessed using the Prediction of Activity Spectra for Substances (PASS) prediction. The study's primary focus is molecular docking prediction, which demonstrated that ligands (L07, L08, and L09) bind to Mpox (PDB ID: 4QWO) and MARV (PDB ID: 4OR8) with binding affinities ranging from -8.00 kcal/mol to -9.5 kcal/mol. HOMO-LUMO based quantum calculations were employed to determine the HOMO-LUMO gap of frontier molecular orbitals (FMOs) and to estimate chemical potential, electronegativity, hardness, and softness. Drug similarity and ADMET prediction assessments of pharmacokinetic properties revealed that the compounds were likely non-carcinogenic, non-hepatotoxic, and rapidly soluble. Molecular dynamic (MD) modeling was used to identify the most favorable docked complexes involving bioactive chemicals. MD simulations indicate that varying types of kaempferol-O-rhamnoside are necessary for successful docking validation and maintaining the stability of the docked complex. These findings could facilitate the discovery of novel therapeutic agents for treating illnesses caused by the Mpox and MARV viruses.


Predicting postoperative pain by preoperative pressure pain assessment.
The goal of this study was to evaluate whether preoperative pressure pain sensitivity testing is predictive of postoperative surgical pain. Female subjects undergoing lower abdominal gynecologic surgery were studied. A pressure algometer was used preoperatively to determine the pressure pain threshold and tolerance. A visual analog scale (VAS) was used to assess postoperative pain. A State-Trait Anxiety Inventory was used to assess patients' anxiety. Subjects received intravenous patient-controlled analgesia for postoperative pain control. The preoperative pain threshold and tolerance were compared with the postoperative VAS pain score and morphine consumption. Forty women were enrolled. Their preoperative pressure pain threshold and tolerance were 141 +/- 65 kPa and 223 +/- 62 kPa, respectively. The VAS pain score in the postanesthesia care unit and at 24 h postoperatively were 81 +/- 24 and 31 +/- 10, respectively. Highly anxious patients had higher VAS pain scores in the postanesthesia care unit (P < 0.05). Pressure pain tolerance was significantly correlated with the VAS at 24 h postoperatively (P < 0.001, r = -0.52). Pressure pain tolerance after fentanyl administration (mean, 272 +/- 68 kPa) correlated significantly with morphine consumption in the first 24 h postoperatively (P < 0.002, r = -0.48). Assessment of preoperative pressure pain tolerance is significantly correlated with the level of postoperative pain. Pain tolerance assessment after fentanyl was administered and fentanyl sensitivity predicted the dose of analgesics used in the first 24 h after surgery. The algometer is thus a simple, useful tool for predicting postoperative pain and analgesic consumption.


Anisotropic surface strain in single crystalline cobalt nanowires and its impact on the diameter-dependent Young's modulus.
Understanding and measuring the size-dependent surface strain of nanowires are essential to their applications in various emerging devices. Here, we report on the diameter-dependent surface strain and Young's modulus of single-crystalline Co nanowires investigated by in situ X-ray diffraction measurements. Diameter-dependent initial longitudinal elongation of the nanowires is observed and ascribed to the anisotropic surface stress due to the Poisson effect, which serves as the basis for mechanical measurements. As the nanowire diameter decreases, a transition from the "smaller is softer" regime to the "smaller is tougher" regime is observed in the Young's modulus of the nanowires, which is attributed to the competition between the elongation softening and the surface stiffening effects. Our work demonstrates a new nondestructive method capable of measuring the initial surface strain and estimating the Young's modulus of single crystalline nanowires, and provides new insights on the size effect.


[Why psychotic patients are not drug compliant?].
Improving patient's compliance with antipsychotics is a major issue in psychosis management. As the point is to convince patients to take their drugs, we have to better understand why they should want or not want to do that. Compliance is actually a complex behavior, involving many psychosocial factors. Thus, we conducted a survey to assess compliance rate and to investigate determinant compliance factors of psychotic outpatients (according to CIM-10 diagnosis). Method - Investigated factors were selected according both to biomedical researches and to psychosocial theories (Health Belief Model). Around 20 influential factors, described in publication, were investigated. The questionnaire design conformed to sociological survey's rules. More, in order to promote patients frankness, the investigator was independent of the medical team. We processed the answers of 63 patients (61% men, average age 40 years), having presented with psychotic disorders for an average of 10 years, without addictive comorbidity (CIM-10). Results - The compliance rate was only 47%. Biomedical factors related to patients (sex, age, social way of life, professional state, and study level), as well as those related to treatment (complexity, duration, side effects occurring), don't affect compliance behavior. The psychosocial factors investigation reveals more interesting results. If the patient trusts his medicines, and do not subscribe to drug's negative beliefs , compliance rate is significantly improved (p=0,0062). It appears to be the survey's best factor for a good compliance, but it concerns only 29% of the investigated patients. When patients aknowledge the whole positive effects of their medicines, compliance is also inclined to improved (p=0,075). But compliance significantly decreases when patients felt that adverse effects are difficult to undergo or unbearable (p=0,04). It also inclined to decrease when family or friends have a negative opinion or are hostile to the pharmacological treatment. None of the other factors influence patient's compliance. Conclusion - These results demonstrate that convincing psychotic patients to be compliant is mandatory. As determinant compliance factors appear to be complex psychosocial ones, it also demonstrates that information procedure needs to be extensively structured.


Association Between Onset Age of Coronary Heart Disease and Incident Dementia: A Prospective Cohort Study.
The association of age at coronary heart disease (CHD) onset with incident dementia remains unexplored. This study aimed to examine whether younger onset age of CHD is associated with a higher risk of incident dementia. Data were obtained from the UK Biobank. Information on the diagnosis of CHD and dementia was collected at baseline and follow-ups. Propensity score matching method and Cox proportional hazards models were used to evaluate the association between different ages at CHD onset and incident dementia. A total of 432 667 adults (mean±SD age, 56.9±8.1 years) were included, of whom 11.7% had CHD. Compared with participants without CHD, participants with CHD exhibited higher risks of developing all-cause dementia, Alzheimer's disease, and vascular dementia. More importantly, younger age at CHD onset (per 10-year decrease) was significantly associated with elevated risks of all-cause dementia (hazard ratio [HR], 1.25 [95% CI, 1.20-1.30]; P<0.001), Alzheimer's disease (HR, 1.29 [95% CI, 1.20-1.38]; P<0.001), and vascular dementia (HR, 1.22 [95% CI, 1.13-1.31]; P<0.001). After propensity score matching, patients with CHD had significantly higher risks of all-cause dementia, Alzheimer's disease, and vascular dementia than matched controls among all onset age groups, and the HRs gradually elevated with decreasing age at CHD onset. Younger onset age of CHD is associated with higher risks of incident all-cause dementia, Alzheimer's disease, and vascular dementia, underscoring the necessity to pay attention to the neurocognitive status of individuals diagnosed with CHD at younger age to conduct timely interventions to attenuate subsequent risk of incident dementia.


A Somatic Movement Approach to Fostering Emotional Resiliency through Laban Movement Analysis.
Although movement has long been recognized as expressing emotion and as an agent of change for emotional state, there was a dearth of scientific evidence specifying which aspects of movement influence specific emotions. The recent identification of clusters of Laban movement components which elicit and enhance the basic emotions of anger, fear, sadness and happiness indicates which types of movements can affect these emotions (Shafir et al., 2016), but not how best to apply this knowledge. This perspective paper lays out a conceptual groundwork for how to effectively use these new findings to support emotional resiliency through voluntary choice of one's posture and movements. We suggest that three theoretical principles from Laban Movement Analysis (LMA) can guide the gradual change in movement components in one's daily movements to somatically support shift in affective state: (A) Introduce new movement components in developmental order; (B) Use LMA affinities-among-components to guide the expansion of expressive movement range and (C) Sequence change among components based on Laban's Space Harmony theory to support the gradual integration of that new range. The methods postulated in this article have potential to foster resiliency and provide resources for self-efficacy by expanding our capacity to adapt emotionally to challenges through modulating our movement responses.


A rapid tissue extraction method for determining liver copper content by atomic absorption spectroscopy.
A simple method using tissue extraction of Copper (Cu) in 8M nitric acid for 45 minutes at 100 degrees C, followed by sample dilution and Cu quantitation by flame atomic absorption spectroscopy is described. The detection limit of the method is 16 micromol Cu/kg liver. The mean recovery of added Cu was 100.4%. This method for liver copper analysis correlated well with a method using nitric/perchloric acid digestion and atomic absorption spectroscopy (r2 = .986) and is faster, less expensive and less hazardous.


Live lecture versus video-recorded lecture: are students voting with their feet?
In light of educators' concerns that lecture attendance in medical school has declined, the authors sought to assess students' perceptions, evaluations, and motivations concerning live lectures compared with accelerated, video-recorded lectures viewed online. The authors performed a cross-sectional survey study of all first- and second-year students at Harvard Medical School. Respondents answered questions regarding their lecture attendance; use of class and personal time; use of accelerated, video-recorded lectures; and reasons for viewing video-recorded and live lectures. Other questions asked students to compare how well live and video-recorded lectures satisfied learning goals. Of the 353 students who received questionnaires, 204 (58%) returned responses. Collectively, students indicated watching 57.2% of lectures live, 29.4% recorded, and 3.8% using both methods. All students have watched recorded lectures, and most (88.5%) have used video-accelerating technologies. When using accelerated, video-recorded lecture as opposed to attending lecture, students felt they were more likely to increase their speed of knowledge acquisition (79.3% of students), look up additional information (67.7%), stay focused (64.8%), and learn more (63.7%). Live attendance remains the predominant method for viewing lectures. However, students find accelerated, video-recorded lectures equally or more valuable. Although educators may be uncomfortable with the fundamental change in the learning process represented by video-recorded lecture use, students' responses indicate that their decisions to attend lectures or view recorded lectures are motivated primarily by a desire to satisfy their professional goals. A challenge remains for educators to incorporate technologies students find useful while creating an interactive learning culture.


MRP8 and MRP14 control microtubule reorganization during transendothelial migration of phagocytes.
MRP14 (S100A9) is the major calcium-binding protein of neutrophils and monocytes. Targeted gene disruption reveals an essential role of this S100 protein for transendothelial migration of phagocytes. The underlying molecular mechanism comprises major alterations of cytoskeletal metabolism. MRP14, in complex with its binding partner MRP8 (S100A8), promotes polymerization of microtubules. MRP14 is specifically phosphorylated by p38 mitogen-activated protein kinase (MAPK). This phosphorylation inhibits MRP8/MRP14-induced tubulin polymerization. Phosphorylation of MRP14 is antagonistically regulated by binding of MRP8 and calcium. The biologic relevance of these findings is confirmed by the fact that MAPK p38 fails to stimulate migration of MRP14(-/-) granulocytes in vitro and MRP14(-/-) mice show a diminished recruitment of granulocytes into the granulation tissue during wound healing in vivo. MRP14(-/-) granulocytes contain significantly less polymerized tubulin, which subsequently results in minor activation of Rac1 and Cdc42 after stimulation of p38 MAPK. Thus, the complex of MRP8/MRP14 is the first characterized molecular target integrating MAPK- and calcium-dependent signals during migration of phagocytes.


Combined Tumor Environment Triggered Self-Assembling Peptide Nanofibers and Inducible Multivalent Ligand Display for Cancer Cell Targeting with Enhanced Sensitivity and Specificity.
Many new technologies, such as cancer microenvironment-induced nanoparticle targeting and multivalent ligand approach for cell surface receptors, are developed for active targeting in cancer therapy. While the principle of each technology is well illustrated, most systems suffer from low targeting specificity and sensitivity. To fill the gap, this work demonstrates a successful attempt to combine both technologies to simultaneously improve cancer cell targeting sensitivity and specificity. Specifically, the main component is a targeting ligand conjugated self-assembling monomer precursor (SAM-P), which, at the tumor site, undergoes tumor-triggered cleavage to release the active form of self-assembling monomer capable of forming supramolecular nanostructures. Biophysical characterization confirms the chemical and physical transformation of SAM-P from unimers or oligomers with low ligand valency to supramolecular assemblies with high ligand valency under a tumor-mimicking reductive microenvironment. The in vitro fluorescence assay shows the importance of supramolecular morphology in mediating ligand-receptor interactions and targeting sensitivity. Enhanced targeting specificity and sensitivity can be achieved via tumor-triggered supramolecular assembly and induces multivalent ligand presentation toward cell surface receptors, respectively. The results support this combined tumor microenvironment-induced cell targeting and multivalent ligand display approach, and have great potential for use as cell-specific molecular imaging and therapeutic agents with high sensitivity and specificity.


Survival of Enterohemorrhagic Escherichia coli O157:H7 During the Manufacture and Curing of Cheddar Cheese †.
The ability of enterohemorrhagic Escherichia coli O157:H7 to survive a standard Cheddar cheese manufacturing process and subsequent curing was determined. Two treatments with added E. coli O157:H7 were designed with target levels 1 × 103 CFU/ml and 1 CFU/ml of cheese milk. Cheese samples were analyzed for E. coli O157:H7 during manufacture at 14, 28, 42, 60, and 74 days, and at 28-day intervals thereafter until the organism could no longer be detected using direct plating or enrichment in two successive samples. Typical colonies on 3M Petrifilm® E. coli Count Plates were counted as presumptive E. coli O157:H7 and were confirmed with the 3M Petrifilm® Test Kit-HEC for hemorrhagic E. coli O157:H7. When no E. coli O157:H7 were detected in the cheese with the Petrifilm®plates, a 25-g sample of cheese was enriched in modified EC broth with novobiocin to detect viable E. coli O157:H7. Cheese made with 103 CFU/ml of milk showed a 2-log-unit reduction after 60 days of ripening, with viable E. coli O157:H7 still being detected in 25 g of cheese after 158 days. Cheese made with 1 CFU/ml of milk showed a reduction in E. coli Ol57:H7 to 1 or <1 CFU/g in 60 days, with no E. coli being detected in 25 g of cheese at 158 days. However, both treatments resulted in the survival of E. coli O157:H7 during manufacture and for more than 60 days of curing at 2.75 to 3.76% salt in the moisture phase.