Amyloid Precursor-like Protein 2 and Sortilin Do Not Regulate the PCSK9 Convertase-mediated Low Density Lipoprotein Receptor Degradation but Interact with Each Other.
Amyloid precursor-like protein 2 (APLP2) and sortilin were reported to individually bind the proprotein convertase subtilisin/kexin type 9 (PCSK9) and regulate its activity on the low-density lipoprotein receptor (LDLR). The data presented herein demonstrate that mRNA knockdowns of APLP2, sortilin, or both in the human hepatocyte cell lines HepG2 and Huh7 do not affect the ability of extracellular PCSK9 to enhance the degradation of the LDLR. Furthermore, mice deficient in APLP2 or sortilin do not exhibit significant changes in liver LDLR or plasma total cholesterol levels. Moreover, cellular overexpression of one or both proteins does not alter PCSK9 secretion, or its activity on the LDLR. We conclude that PCSK9 enhances the degradation of the LDLR independently of either APLP2 or sortilin both ex vivo and in mice. Interestingly, when co-expressed with PCSK9, both APLP2 and sortilin were targeted for lysosomal degradation. Using chemiluminescence proximity and co-immunoprecipitation assays, as well as biosynthetic analysis, we discovered that sortilin binds and stabilizes APLP2, and hence could regulate its intracellular functions on other targets.


Recognition of human histocompatibility leukocyte antigen (HLA)-E complexed with HLA class I signal sequence-derived peptides by CD94/NKG2 confers protection from natural killer cell-mediated lysis.
Human histocompatibility leukocyte antigen (HLA)-E is a nonclassical HLA class I molecule, the gene for which is transcribed in most tissues. It has recently been reported that this molecule binds peptides derived from the signal sequence of HLA class I proteins; however, no function for HLA-E has yet been described. We show that natural killer (NK) cells can recognize target cells expressing HLA-E molecules on the cell surface and this interaction results in inhibition of the lytic process. Furthermore, HLA-E recognition is mediated primarily through the CD94/NKG2-A heterodimer, as CD94-specific, but not killer cell inhibitory receptor (KIR)-specific mAbs block HLA-E-mediated protection of target cells. Cell surface HLA-E could be increased by incubation with synthetic peptides corresponding to residues 3-11 from the signal sequences of a number of HLA class I molecules; however, only peptides which contained a Met at position 2 were capable of conferring resistance to NK-mediated lysis, whereas those having Thr at position 2 had no effect. Interestingly, HLA class I molecules previously correlated with CD94/NKG2 recognition all have Met at residue 4 of the signal sequence (position 2 of the HLA-E binding peptide), whereas those which have been reported not to interact with CD94/NKG2 have Thr at this position. Thus, these data show a function for HLA-E and suggest an alternative explanation for the apparent broad reactivity of CD94/NKG2 with HLA class I molecules; that CD94/NKG2 interacts with HLA-E complexed with signal sequence peptides derived from "protective" HLA class I alleles rather than directly interacting with classical HLA class I proteins.


A belief-based model for characterizing the spread of awareness and its impacts on individuals' vaccination decisions.
During an epidemic, individuals' decisions on whether or not to take vaccine may affect the dynamics of disease spread and, therefore, the effectiveness of disease control. Empirical studies have shown that such decisions can be subjected to individuals' awareness about disease and vaccine, such as their perceived disease severity and vaccine safety. The aim of this paper is to gain a better understanding of individuals' vaccination behaviour by modelling the spread of awareness in a group of socially connected individuals and examining the associated impacts on their vaccination decision-making. In our model, we examine whether or not individuals will get vaccinated as well as when they would. In doing so, we consider three possible decisions from an individual, i.e., to accept, to reject, and yet to decide, and further associate them with a set of belief values. Next, we extend the Dempster-Shafer theory to characterize individuals' belief value updates and their decision-making, having incorporated the awareness obtained from their connected neighbours. Furthermore, we examine two factors that will affect individuals' vaccination decisions: (i) reporting rates of disease- and vaccine-related events, and (ii) fading coefficient of awareness spread. By doing so, we can assess the impacts of awareness spread by evaluating the vaccination dynamics in terms of the number of vaccinated individuals. The results have demonstrated that the former influences the ratio of vaccinated individuals, whereas the latter affects the time when individuals decide to take vaccine.


Outbreak of E. coli O157:H7 associated with lettuce served at fast food chains in the Maritimes and Ontario, Canada, Dec 2012.
Identification and control of multi-jurisdictional foodborne illness outbreaks can be complex because of their multidisciplinary nature and the number of investigative partners involved. To describe the multi-jurisdictional outbreak response to an E. coli O157:H7 outbreak in Canada that highlights the importance of early notification and collaboration and the value of centralized interviewing. Investigators from local, provincial and federal jurisdictions, using a national outbreak response protocol to clarify roles and responsibilities and facilitate collaboration, conducted a rapid investigation that included centralized re-interview of cases, descriptive methods, binomial probability, and traceback findings to identify the source of the outbreak. There were 31 laboratory confirmed cases identified in New Brunswick, Nova Scotia, and Ontario. Thirteen cases (42%) were hospitalized and one case (3%) developed hemolytic uremic syndrome; there were no deaths. Due to early notification a coordinated investigation was initiated before laboratory subtyping was available. Re-interview of cases identified 10 cases who had not initially reported exposure to the source of the outbreak. Less than one week after the Outbreak Investigation Coordinating Committee was formed, consumption of shredded lettuce from a fast food chain was identified as the likely source of the illnesses and the implicated importer/processor initiated a precautionary recall the same day. This outbreak investigation highlights the importance of early notification, prompt re-interviewing and collaboration to rapidly identify the source of an outbreak.


Nanoparticle-Enabled Selective Destruction of Prostate Tumor Using MRI-Guided Focal Photothermal Therapy.
The Magnetic Resonance Imaging (MRI)-guided focal laser therapy has shown early promise in Phase 1 trial treating low/intermediate-risk localized prostate cancer (PCa), but the lack of tumor selectivity and low efficiency of heat generation remain as drawbacks of agent-free laser therapy. Intrinsic multifunctional porphyrin-nanoparticles (porphysomes) have been exploited to treat localized PCa by MRI-guided focal photothermal therapy (PTT) with significantly improved efficiency and tumor selectivity over prior methods of PTT, providing an effective and safe alternative to active surveillance or radical therapy. The tumor accumulation of porphysomes chelated with copper-64 was determined and compared with the clinic standard (18) F-FDG in an orthotropic PCa mouse model by positron emission tomography (PET) imaging, providing quantitative assessment for PTT dosimetry. The PTT was conducted with MRI-guided light delivery and monitored by MR thermometry, mimicking the clinical protocol. The efficacy of treatment and adverse effects to surround tissues were evaluated by histology analysis and tumor growth in survival study via MRI. Porphysomes showed superior tumor-to-prostate selectivity over (18) F-FDG (6:1 vs. 0.36:1). MR thermometry detected tumor temperature increased to ≥55°C within 2 min (671 nm at 500 mW), but minimal increase in surrounding tissues. Porphysome enabled effective PTT eradication of tumor without damaging adjacent organs in orthotropic PCa mouse model. Porphysome-enabled MRI-guided focal PTT could be an effective and safe approach to treat PCa at low risk of progression, thus addressing the significant unmet clinical needs and benefiting an ever-growing number of patients who may be over-treated and risk unnecessary side effects from radical therapies. Prostate 76:1169-1181, 2016. © 2016 Wiley Periodicals, Inc.


Body size, medullary thickness, and urine concentrating ability in mammals.
B. H. Blake (Comp. Biochem. Physiol. A Comp. Physiol. 58: 413-419, 1977.) and W. A. Calder and E. J. Braun (Am. J. Physiol. 244 (Regulatory Integrative Comp. Physiol. 13): R601-R606, 1983.) have predicted that urine concentrating ability of mammals should decline with increasing body mass (M, in kg) as M-0.08. Edwards (29), on the other hand, speculated that concentrating ability should be independent of body mass. Using information compiled from the literature for 245 species of mammals, I examined the scaling of urine concentrating ability with body mass. Maximum urine concentration (Uosm, in mosmol/kgH2O) declined exponentially with body mass as Uosm = 2,564 M-0.097, and generally only the smallest species (less than 400 g) could produce urine with an osmolality greater than 4,000 mosmol/kgH2O. Medullary thickness (MT, in mm) and, therefore, the length of the loop of Henle, increased with body mass as MT = 8.147 M0.129. The thickness of the medulla relative to the size of the kidney (RMT), however, declined with body size (RMT = 5.408 M-0.108). The relative thickness of the medulla accounted for only 59% of the variability among species in concentrating ability, indicating that there are other morphological or physiological factors that significantly influence urine concentrating ability.


Identification of sub-groups in acutely ill elderly patients with delirium: a cluster analysis.
Delirium is a serious neuropsychiatric syndrome affecting mainly elderly participants with acute medical diseases. The pathophysiology of delirium remains poorly understood as it involves complex dynamic interactions between a diversity of risk factors. Exploring how etiological factors interact with each other can clarify the pathophysiological mechanisms and facilitate the early identification of this syndrome. The aim of this study was to explore how different risk factors co-occur in medically ill elderly patients with delirium with cluster analysis and identify clinically meaningful sub-groups in this population. A cross-sectional study was developed. Ninety-nine elderly inpatients admitted to acute medical wards diagnosed with delirium during hospitalization were selected. For each patient sociodemographic characteristics, acute and chronic medical conditions, laboratory parameters, and current medication were collected. The cluster analysis extracted three distinct subgroups of participants with delirium. Patients in cluster 1 (n = 28) had higher rates of medication with anticholinergic proprieties. Cluster 2 (n = 29) included participants with cardiac and pulmonary comorbidities associated with both chronic and acute reduction of blood flow and/or oxygenation to the brain. Cluster 3 (n = 42 patients) comprised patients with simultaneous deregulation of different organs/systems, such as electrolytic disturbances, metabolic disturbances, and acute renal failure. Known predisposing factors of delirium, such as age and pre-existing dementia, were similar between groups. The results reveal different patterns of clinical characteristics in elderly patients with delirium. This is relevant to clinical care of acute medically ill patients and suggests that different pathways are implicated in delirium pathophysiology.


Emotional recognition in autism spectrum conditions from voices and faces.
The present study reports on a new vocal emotion recognition task and assesses whether people with autism spectrum conditions (ASC) perform differently from typically developed individuals on tests of emotional identification from both the face and the voice. The new test of vocal emotion contained trials in which the vocal emotion of the sentence were congruent, incongruent, or neutral with respect to the semantic content. We also included a condition in which there was no semantic content (an 'mmm' was uttered using an emotional tone). Performance was compared between 11 adults with ASC and 14 typically developed adults. Identification of emotion from sentences in which the vocal emotion and the meaning of sentence were congruent was similar in people with ASC and a typically developed comparison group. However, the comparison group was more accurate at identifying the emotion in the voice from incongruent and neutral trials, and also from trials with no semantic content. The results of the vocal emotion task were correlated with performance on a face emotion recognition task. In decoding emotion from spoken utterances, individuals with ASC relied more on verbal semantics than did typically developed individuals, presumably as a strategy to compensate for their difficulties in using prosodic cues to recognize emotions.


Incorporation of axonally transported glycoproteins into axolemma during nerve regeneration.
The insertion of axonally transported fucosyl glycoproteins into the axolemma of regenerating nerve sprouts was examined in rat sciatic motor axons at intervals after nerve crush. [(3)H]Fucose was injected into the lumbar ventral horns and the nerves were removed at intervals between 1 and 14 d after labeling. To follow the fate of the "pulse- labeled" glycoproteins, we examined the nerves by correlative radiometric and EM radioautographic approaches. The results showed, first, that rapidly transported [(3)H]fucosyl glycoproteins were inserted into the axolemma of regenerating sprouts as well as parent axons. At 1 d after delivery, in addition to the substantial mobile fraction of radioactivity still undergoing bidirectional transport within the axon, a fraction of label was already associated with the axolemma. Insertion of labeled glycoproteins into the sprout axolemma appeared to occur all along the length of the regenerating sprouts, not just in sprout terminals. Once inserted, labeled glycoproteins did not undergo extensive redistribution, nor did they appear in sprout regions that formed (as a result of continued outgrowth) after their insertion. The amount of radioactivity in the regenerating nerves decreased with time, in part as a result of removal of transported label by retrograde transport. By 7-14 d after labeling, radioautography showed that almost all the remaining radioactivity was associated with axolemma. The regenerating sprouts retained increased amounts of labeled glycoproteins; 7 or 14 d after labeling, the regenerating sprouts had over twice as much of radioactivity as comparable lengths of control nerves or parent axons. One role of fast axonal transport in nerve regeneration is the contribution to the regenerating sprout of glycoproteins inserted into the axolemma; these membrane elements are added both during longitudinal outgrowth and during lateral growth and maturation of the sprout.


Murine dendritic cells loaded in vitro with soluble protein prime cytotoxic T lymphocytes against tumor antigen in vivo.
The priming of an immune response against a major histocompatibility complex class I-restricted antigen expressed by nonhematopoietic cells involves the transfer of that antigen to a host bone marrow-derived antigen presenting cell (APC) for presentation to CD8+ T lymphocytes. Dendritic cells (DC), as bone marrow-derived APC, are first candidates for presentation of tumor-associated antigens (TAA). The aim of this study was to see whether DC are able to prime in vivo antigen-specific cytotoxic T lymphocytes after exposure to a soluble protein antigen in vitro. Lacking a well-defined murine TAA, we took advantage of beta-galactosidase (beta-gal)-transduced tumor cell lines as a model in which beta-gal operationally functions as TAA. For in vivo priming both a DC line, transduced or not transduced with the gene coding for murine GM-CSF, and fresh bone marrow-derived DC (bm-DC), loaded in vitro with soluble beta-gal, were used. Priming with either granulocyte macrophage colony-stimulating factor-transduced DC line or fresh bm-DC but not with untransduced DC line generated CTL able to lyse beta-gal-transfected target cells. Furthermore, GM-CSF was necessary for the DC line to efficiently present soluble beta-gal as an H-2Ld-restricted peptide to a beta-gal-specific CTL clone. Data also show that a long-lasting immunity against tumor challenge can be induced using beta-gal-pulsed bm-DC as vaccine. These results indicate that effector cells can be recruited and activated in vivo by antigen-pulsed DC, providing an efficient immune reaction against tumors.


Incidence of skin breakdown and higher amputation after transmetatarsal amputation: implications for rehabilitation.
The purpose of this study of patients with transmetatarsal amputation (TMA) is to describe multiple patient characteristics, including the incidence of subsequent skin breakdown and higher amputation, that may influence rehabilitation treatment and outcomes. Data were gathered on all patients having a TMA at this facility between April 1989 and September 1993. One hundred twenty TMAs were performed on 107 patients with a mean age of 62.4 +/- 13.8 years. There were 55 men and 52 women. Thirteen patients (12%) had a bilateral TMA. Twenty-nine patients (27%) developed skin breakdown. Of these, 48% occurred within the first 3 months after surgery. Thirty patients (28%) required a higher amputation. Of these, 60% occurred in the first month after TMA. In addition, this group of patients had a high incidence of diabetes mellitus (77%), hypertension (54%), electrocardiogram (EKG) abnormalities (60%), congestive heart failure (22%), and prior ipsilateral vascular surgery (51%). These results indicate that patients with TMA often present with a complicated medical condition and that they are at high risk of skin breakdown or higher amputation, especially in the first 3 months after surgery. The investigators conclude that patients with TMA may benefit from a rehabilitation program emphasizing protection of the residuum during their return to functional activities. Additional research is needed to determine optimal acute and long-term rehabilitation of patients with TMA.


Regulation of iron homeostasis in anemia of chronic disease and iron deficiency anemia: diagnostic and therapeutic implications.
The anemia of chronic disease (ACD) is characterized by macrophage iron retention induced by cytokines and the master regulator hepcidin. Hepcidin controls cellular iron efflux on binding to the iron export protein ferroportin. Many patients, however, present with both ACD and iron deficiency anemia (ACD/IDA), the latter resulting from chronic blood loss. We used a rat model of ACD resulting from chronic arthritis and mimicked ACD/IDA by additional phlebotomy to define differing iron-regulatory pathways. Iron retention during inflammation occurs in macrophages and the spleen, but not in the liver. In rats and humans with ACD, serum hepcidin concentrations are elevated, which is paralleled by reduced duodenal and macrophage expression of ferroportin. Individuals with ACD/IDA have significantly lower hepcidin levels than ACD subjects, and ACD/IDA persons, in contrast to ACD subjects, were able to absorb dietary iron from the gut and to mobilize iron from macrophages. Circulating hepcidin levels affect iron traffic in ACD and ACD/IDA and are more responsive to the erythropoietic demands for iron than to inflammation. Hepcidin determination may aid to differentiate between ACD and ACD/IDA and in selecting appropriate therapy for these patients.


Improving recruitment to clinical trials during pregnancy: A mixed methods investigation.
To identify reasons underlying women's refusal to participate in a pregnancy trial and to identify ways of increasing recruitment. Mixed methods study using a questionnaire and qualitative interviews. A questionnaire asking them to indicate reasons for their decision was completed by 296 pregnant women who declined to participate in one of two trials of nutritional supplementation in a large teaching hospital in southern England. Qualitative interview data were collected from two samples of pregnant women: 1) 30 women who declined to participate in a trial but completed the questionnaire; and 2) 44 women who participated in a trial. Questionnaire data from pregnant women who declined to participate suggested the major barriers to participation were study requirements, including taking study medication, having a bone scan or blood tests, or being too busy. Thematic analysis of interview data identified differences in self-efficacy and levels of trust in medical research between participants and decliners. Participants believed that the research would cause no harm, while decliners felt they or their unborn child would be at risk. When faced with potential obstacles, participants found ways around them while decliners felt they were insurmountable. Recruitment methods for pregnancy trials should focus on building women's trust in the trial, and on enhancing women's self-efficacy so they feel able to meet trial requirements. Suggestions for building trust include investing time in open, honest discussion of the risks and benefits of participation, improving visibility of the research team, testimonials from previous participants and advertising study safety and ethical conduct. Self-efficacy can be enhanced by training research staff in empowering styles of communication enabling women to feel heard and supported to problem-solve. These strategies could be implemented relatively easily into pregnancy trial protocols, and their effectiveness tested through their impact on recruitment rates.


Acidosis activation of the proton-sensing GPR4 receptor stimulates vascular endothelial cell inflammatory responses revealed by transcriptome analysis.
Acidic tissue microenvironment commonly exists in inflammatory diseases, tumors, ischemic organs, sickle cell disease, and many other pathological conditions due to hypoxia, glycolytic cell metabolism and deficient blood perfusion. However, the molecular mechanisms by which cells sense and respond to the acidic microenvironment are not well understood. GPR4 is a proton-sensing receptor expressed in endothelial cells and other cell types. The receptor is fully activated by acidic extracellular pH but exhibits lesser activity at the physiological pH 7.4 and minimal activity at more alkaline pH. To delineate the function and signaling pathways of GPR4 activation by acidosis in endothelial cells, we compared the global gene expression of the acidosis response in primary human umbilical vein endothelial cells (HUVEC) with varying level of GPR4. The results demonstrated that acidosis activation of GPR4 in HUVEC substantially increased the expression of a number of inflammatory genes such as chemokines, cytokines, adhesion molecules, NF-κB pathway genes, and prostaglandin-endoperoxidase synthase 2 (PTGS2 or COX-2) and stress response genes such as ATF3 and DDIT3 (CHOP). Similar GPR4-mediated acidosis induction of the inflammatory genes was also noted in other types of endothelial cells including human lung microvascular endothelial cells and pulmonary artery endothelial cells. Further analyses indicated that the NF-κB pathway was important for the acidosis/GPR4-induced inflammatory gene expression. Moreover, acidosis activation of GPR4 increased the adhesion of HUVEC to U937 monocytic cells under a flow condition. Importantly, treatment with a recently identified GPR4 antagonist significantly reduced the acidosis/GPR4-mediated endothelial cell inflammatory response. Taken together, these results show that activation of GPR4 by acidosis stimulates the expression of a wide range of inflammatory genes in endothelial cells. Such inflammatory response can be suppressed by GPR4 small molecule inhibitors and hold potential therapeutic value.


Update on drugs used to treat endocrine diseases in small animals.
Drug therapy for the endocrine system is implemented to replace a hormone deficiency or to prevent or reduce the formation or effects of excess hormone. Treatment of endocrine disorders covers diseases of the pituitary, adrenal, parathyroid, and thyroid glands as well as the endocrine pancreas. This article focuses on new therapies currently available for specific diseases. Administration of trilostane for treatment of hyperadrenocorticism and use of insulin glargine, protamine zinc insulin (PZI), and porcine Lente insulin for diabetes mellitus are discussed. In addition, transdermal methimazole therapy for treatment of feline hyperthyroidism and administration of progestins for pituitary dwarfism are considered.


Three-dimensional laser microvision.
A three-dimensional (3-D) optical imaging system offering high resolution in all three dimensions, requiring minimum manipulation and capable of real-time operation, is presented. The system derives its capabilities from use of the superstructure grating laser source in the implementation of a laser step frequency radar for depth information acquisition. A synthetic aperture radar technique was also used to further enhance its lateral resolution as well as extend the depth of focus. High-speed operation was made possible by a dual computer system consisting of a host and a remote microcomputer supported by a dual-channel Small Computer System Interface parallel data transfer system. The system is capable of operating near real time. The 3-D display of a tunneling diode, a microwave integrated circuit, and a see-through image taken by the system operating near real time are included. The depth resolution is 40 mum; lateral resolution with a synthetic aperture approach is a fraction of a micrometer and that without it is approximately 10 mum.


Water immersion: does it enhance recovery from exercise?
To assess the effect that postexercise immersion in water has on subsequent exercise performance. A literary search and review of water-immersion and performance studies was conducted. Seven articles were examined. In 2, significant benefits to performance were observed. Those 2 articles revealed a small to large effect on jump performance and isometric strength. PRACTICAL APPLICATION AND CONCLUSIONS: It is possible that water immersion might improve recovery from plyometric or muscle-damaging exercise. Such a statement needs to be verified, however, because of the scarcity of research on water immersion as a recovery strategy.


Common-path interferometer for frequency-domain optical coherence tomography.
A Michelson-type spectral interferometer that uses a common beam path for the reference and the sample arms is described. This optical arrangement is more compact and stable than the more commonly used dual-arm interferometer and is well suited for frequency-domain optical coherence tomography of biological samples. With a 16-bit CCD camera, the instrument has sufficient dynamic range and resolution for imaging to depths of 2 mm in scattering biological materials. Images obtained with this spectral interferometer are presented, including cross-sectional images in a Xenopus laevis tadpole.


Antimicrobial activity of organometallic isonicotinyl and pyrazinyl ferrocenyl-derived complexes.
Isonicotinyl and pyrazinyl ferrocenyl-derived complexes were prepared using various hydrazides and ferrocenyl aldehydes. Three heterobimetallic complexes were also synthesized from the Schiff base-derived isonicotinyl ferrocene complex using various platinum group metal dimers based on ruthenium, rhodium and iridium. All complexes were evaluated in vitro for antimycobacterial and antiparasitic activity. Against Mycobacterium tuberculosis H37Rv, the platinum group metal complexes showed glycerol-dependent antimycobacterial activity. The antiplasmodial activities against the NF54 chloroquine-sensitive strain of Plasmodium falciparum of some compounds were moderate, while some complexes also showed promising activity against Trichomonas vaginalis. Incorporation of the ferrocenyl-salicylaldimine moiety resulted in enhanced antimicrobial activity compared to the non-ferrocenyl compound in some cases. The bimetallic iridium-ferrocene isonicotinyl complex exhibited superior antitrichomonal activity relative to its organic counterpart, isoniazid. Furthermore, all these compounds, when screened on several normal flora bacteria of humans, showed no effect on the microbiome, emphasizing the selection of these compounds for these pathogens. The promising antimicrobial activities of the complexes thus supports incorporation of ferrocene as part of existing antimicrobial therapies in order to alter their biological activities favorably.


Intervertebral reaction force prediction using an enhanced assembly of OpenSim models.
OpenSim offers a valuable approach to investigating otherwise difficult to assess yet important biomechanical parameters such as joint reaction forces. Although the range of available models in the public repository is continually increasing, there currently exists no OpenSim model for the computation of intervertebral joint reactions during flexion and lifting tasks. The current work combines and improves elements of existing models to develop an enhanced model of the upper body and lumbar spine. Models of the upper body with extremities, neck and head were combined with an improved version of a lumbar spine from the model repository. Translational motion was enabled for each lumbar vertebrae with six controllable degrees of freedom. Motion segment stiffness was implemented at lumbar levels and mass properties were assigned throughout the model. Moreover, body coordinate frames of the spine were modified to allow straightforward variation of sagittal alignment and to simplify interpretation of results. Evaluation of model predictions for level L1-L2, L3-L4 and L4-L5 in various postures of forward flexion and moderate lifting (8 kg) revealed an agreement within 10% to experimental studies and model-based computational analyses. However, in an extended posture or during lifting of heavier loads (20 kg), computed joint reactions differed substantially from reported in vivo measures using instrumented implants. We conclude that agreement between the model and available experimental data was good in view of limitations of both the model and the validation datasets. The presented model is useful in that it permits computation of realistic lumbar spine joint reaction forces during flexion and moderate lifting tasks. The model and corresponding documentation are now available in the online OpenSim repository.


Is There a Role for Color Doppler Ultrasonography in Acute Cholecystitis?
The aim of this study was to evaluate the utility of the Pulsatility Index (PI) of the right hepatic artery, measured by color Doppler sonography, in the diagnosis of acute cholecystitis. Seventy-five subjects were included in this study and divided into three groups, each consisting of 25 subjects: the cholecystitis group, the asymptomatic cholelithiasis group, and normal controls. Patients with acute cholecystitis fulfilled all the diagnostic criteria as stated in the latest Tokyo Guidelines. In all patients, the right hepatic artery was detected by color Doppler ultrasound and the PI was measured. Patients with acute cholecystitis were found to have significantly higher PI values compared to both normal controls and cholelithiasis patients. Regression analysis revealed a significant positive correlation between the PI and the cholecystitis outcome. Measurement of PI by color Doppler ultrasound represents a useful aid in the diagnostic process of acute cholecystitis. More studies are needed before this method is incorporated in the relevant guidelines.


Improvement of bit error rate and page alignment in the holographic data storage system by using the structural similarity method.
Although widely recognized as a promising candidate for the next generation of data storage devices, holographic data storage systems (HDSS) incur adverse effects such as noise, misalignment, and aberration. Therefore, based on the structural similarity (SSIM) concept, this work presents a more accurate locating approach than the gray level weighting method (GLWM). Three case studies demonstrate the effectiveness of the proposed approach. Case 1 focuses on achieving a high performance of a Fourier lens in HDSS, Cases 2 and 3 replace the Fourier lens with a normal lens to decrease the quality of the HDSS, and Case 3 demonstrates the feasibility of a defocus system in the worst-case scenario. Moreover, the bit error rate (BER) is evaluated in several average matrices extended from the located position. Experimental results demonstrate that the proposed SSIM method renders a more accurate centering and a lower BER, lower BER of 2 dB than those of the GLWM in Cases 1 and 2, and BER of 1.5 dB in Case 3.


The technical reliability and biotemporal stability of cerebrospinal fluid biomarkers for profiling multiple pathophysiologies in Alzheimer's disease.
Alzheimer's disease (AD) is a complex neurodegenerative disease driven by multiple interacting pathophysiological processes that ultimately results in synaptic loss, neuronal death, and dementia. We implemented a fit-for-purpose modeled approach to qualify a broad selection of commercially available immunoassays and evaluate the biotemporal stability of analytes across five pathophysiological domains of interest in AD, including core amyloid-β (Aβ) and tau AD biomarkers, neurodegeneration, inflammation/immune modulation, neurovascular injury, and metabolism/oxidative stress. Paired baseline and eight-week CSFs from twenty participants in a clinical drug trial for mild cognitive impairment (MCI) or mild dementia due to AD were used to evaluate sensitivity, intra-assay precision, inter-assay replicability, and eight-week biotemporal stability for sixty unique analytes measured with commercially available single- and multi-plex ELISA assays. Coefficients of variation (CV) were calculated, and intraclass correlation and Wilcoxon signed rank tests were applied. We identified 32 biomarker candidates with good to excellent performance characteristics according to assay technical performance and CSF analyte biotemporal stability cut-off criteria. These included: 1) the core AD biomarkers Aβ1-42, Aβ1-40, Aβ1-38, and total tau; 2) non-Aβ, non-tau neurodegeneration markers NfL and FABP3; 3) inflammation/immune modulation markers IL-6, IL-7, IL-8, IL-12/23p40, IL-15, IL-16, MCP-1, MDC, MIP-1β, and YKL-40; 4) neurovascular markers Flt-1, ICAM-1, MMP-1, MMP-2, MMP-3, MMP-10, PlGF, VCAM-1, VEGF, VEGF-C, and VEGF-D; and 5) metabolism/oxidative stress markers 24-OHC, adiponectin, leptin, soluble insulin receptor, and 8-OHdG. Assays for these CSF analytes demonstrate consistent sensitivity, reliability, and biotemporally stability for use in a multiple pathophysiological CSF biomarker panel to profile AD. Their qualification enables further investigation for use in AD diagnosis, staging and progression, disease mechanism profiling, and clinical trials.


Genistein improves inflammatory response and colonic function through NF-κB signal in DSS-induced colonic injury.
This study aimed to investigate the protective potential of genistein in dextran sulfate sodium (DSS)-induced colonic injury in vitro and in vivo models. The results showed that DSS exposure caused growth suppression, colonic injury, inflammation, and barrier dysfunction in mice. Dietary genistein alleviated DSS-caused colonic injury via reducing colonic weight, rectal bleeding, and diarrhea ratio. Meanwhile, genistein reduced colonic inflammatory response via downregulating cytokines expression and improved colonic permeability and barrier in DSS-challenged mice. In Caco-2 cells, genistein improved cell viability and cellular permeability and inhibited DSS-induced activation of TLR4/NF-κB signal. In conclusion, genistein alleviated DSS-caused colonic injury, inflammation, and gut dysfunction, which might be associated with the TLR4/NF-κB signal.


Inhibition of premature labor in sheep by a combined treatment of nimesulide, a prostaglandin synthase type 2 inhibitor, and atosiban, an oxytocin receptor antagonist.
The aim of this study was to compare the effects of the selective prostaglandin synthase type 2 inhibitor nimesulide, alone or in combination with the oxytocin receptor antagonist atosiban, on the progression of glucocorticoid-induced premature labor in sheep. Effects on circulating maternal and fetal prostaglandin concentrations and on fetal well-being were also examined. Premature labor was induced in ewes with long-term catheterized fetuses by infusion of dexamethasone (1 mg/d) starting at 138 +/- 1 days' gestation. Ewes also received an infusion of either nimesulide and atosiban (20.0 and 4.12 mg/kg per day, respectively; n = 5), nimesulide alone (20.0 mg/kg per day; n = 5), or vehicle only (n = 9). Plasma 13,14-dihydro-15-keto-prostaglandin F(2)(alpha) and prostaglandin E(2) concentrations were measured before and during infusions in plasma samples obtained from the maternal and fetal carotid arteries and the utero-ovarian vein. No fetuses from ewes treated with nimesulide and atosiban were delivered during treatment. These animals were killed electively 98.0 +/- 6.8 hours after the commencement of dexamethasone induction. This was significantly longer than the delivery times for those ewes treated with nimesulide alone (71.2 +/- 3.9 hours; n = 5) and for vehicle-treated ewes (51.4 +/- 1.7 hours; n = 9). Both maternal and fetal plasma 13, 14-dihydro-15-keto-prostaglandin F(2alpha) and prostaglandin E(2) concentrations in nimesulide and atosiban-treated ewes and in nimesulide-treated ewes decreased during treatment. In contrast, vehicle-treated ewes showed a significant increase in maternal and fetal plasma 13,14-dihydro-15-keto-prostaglandin F(2alpha) and prostaglandin E(2) concentrations during dexamethasone induction. Uterine electromyographic activity observed in nimesulide and atosiban-treated ewes was significantly suppressed with respect to activities in both vehicle- and nimesulide-treated ewes during the treatment period. All fetuses were alive at delivery or scheduled death. These results indicate that the combination of an inhibitor of prostaglandin endoperoxidase H synthase type 2 with an oxytocin receptor antagonist is more effective in inhibition of preterm labor than is treatment with a prostaglandin endoperoxidase H synthase type 2 inhibitor alone. The clinical use of atosiban to prevent the oxytocin-stimulated increase in uterine activity associated with labor in combination with nimesulide may permit reduction of the dose of nimesulide used to a level that has minimal impact on fetal well-being.


Lower Cambrian vendobionts from China and early diploblast evolution.
Ediacaran assemblages immediately predate the Cambrian explosion of metazoans and should have played a crucial role in this radiation. Their wider relationships, however, have remained refractory and difficult to integrate with early metazoan phylogeny. Here, we describe a frondlike fossil, Stromatoveris (S. psygmoglena sp. nov.), from the Lower Cambrian Chengjiang Lagerstätte (Yunnan, China) that is strikingly similar to Ediacaran vendobionts. The exquisite preservation reveals closely spaced branches, probably ciliated, that appear to represent precursors of the diagnostic comb rows of ctenophores. Therefore, this finding has important implications for the early evolution of this phylum and related diploblasts, some of which independently evolved a frondose habit.


Peel-and-stick: fabricating thin film solar cell on universal substrates.
Fabrication of thin-film solar cells (TFSCs) on substrates other than Si and glass has been challenging because these nonconventional substrates are not suitable for the current TFSC fabrication processes due to poor surface flatness and low tolerance to high temperature and chemical processing. Here, we report a new peel-and-stick process that circumvents these fabrication challenges by peeling off the fully fabricated TFSCs from the original Si wafer and attaching TFSCs to virtually any substrates regardless of materials, flatness and rigidness. With the peel-and-stick process, we integrated hydrogenated amorphous silicon (a-Si:H) TFSCs on paper, plastics, cell phone and building windows while maintaining the original 7.5% efficiency. The new peel-and-stick process enables further reduction of the cost and weight for TFSCs and endows TFSCs with flexibility and attachability for broader application areas. We believe that the peel-and-stick process can be applied to thin film electronics as well.


Navigating features: a topologically informed chart of electromyographic features space.
The success of biological signal pattern recognition depends crucially on the selection of relevant features. Across signal and imaging modalities, a large number of features have been proposed, leading to feature redundancy and the need for optimal feature set identification. A further complication is that, due to the inherent biological variability, even the same classification problem on different datasets can display variations in the respective optimal sets, casting doubts on the generalizability of relevant features. Here, we approach this problem by leveraging topological tools to create charts of features spaces. These charts highlight feature sub-groups that encode similar information (and their respective similarities) allowing for a principled and interpretable choice of features for classification and analysis. Using multiple electromyographic (EMG) datasets as a case study, we use this feature chart to identify functional groups among 58 state-of-the-art EMG features, and to show that they generalize across three different forearm EMG datasets obtained from able-bodied subjects during hand and finger contractions. We find that these groups describe meaningful non-redundant information, succinctly recapitulating information about different regions of feature space. We then recommend representative features from each group based on maximum class separability, robustness and minimum complexity.


Predicting adaptive behavior in the environment from central nervous system dynamics.
To generate adaptive behavior, the nervous system is coupled to the environment. The coupling constrains the dynamical properties that the nervous system and the environment must have relative to each other if adaptive behavior is to be produced. In previous computational studies, such constraints have been used to evolve controllers or artificial agents to perform a behavioral task in a given environment. Often, however, we already know the controller, the real nervous system, and its dynamics. Here we propose that the constraints can also be used to solve the inverse problem--to predict from the dynamics of the nervous system the environment to which they are adapted, and so reconstruct the production of the adaptive behavior by the entire coupled system. We illustrate how this can be done in the feeding system of the sea slug Aplysia. At the core of this system is a central pattern generator (CPG) that, with dynamics on both fast and slow time scales, integrates incoming sensory stimuli to produce ingestive and egestive motor programs. We run models embodying these CPG dynamics--in effect, autonomous Aplysia agents--in various feeding environments and analyze the performance of the entire system in a realistic feeding task. We find that the dynamics of the system are tuned for optimal performance in a narrow range of environments that correspond well to those that Aplysia encounter in the wild. In these environments, the slow CPG dynamics implement efficient ingestion of edible seaweed strips with minimal sensory information about them. The fast dynamics then implement a switch to a different behavioral mode in which the system ignores the sensory information completely and follows an internal "goal," emergent from the dynamics, to egest again a strip that proves to be inedible. Key predictions of this reconstruction are confirmed in real feeding animals.


Effectiveness of camera traps for quantifying daytime and nighttime visitation by vertebrate pollinators.
Identification of pollen vectors is a fundamental objective of pollination biology. The foraging and social behavior of these pollinators has profound effects on plant mating, making quantification of their behavior critical for understanding the ecological and evolutionary consequences of different pollinators for the plants they visit. However, accurate quantification of visitation may be problematic, especially for shy animals and/or when the temporal and spatial scale of observation desired is large. Sophisticated heat- and movement-triggered motion-sensor cameras ("camera trapping") provide new, underutilized tools to address these challenges. However, to date, there has been no rigorous evaluation of the sampling considerations needed for using camera trapping in pollination research.We measured the effectiveness of camera trapping for identifying vertebrate visitors and quantifying their visitation rates and foraging behavior on Banksia menziesii (Proteaceae). Multiple still cameras (Reconyx HC 500) and a video camera (Little Acorn LTL5210A) were deployed.From 2,753 recorded visits by vertebrates, we identified five species of nectarivorous honeyeater (Meliphagidae) and the honey possum (Tarsipedidae), with significant variation in the species composition of visitors among inflorescences. Species of floral visitor showed significant variation in their time of peak activity, duration of visits, and numbers of flowers probed per visit. Where multiple cameras were deployed on individual inflorescences, effectiveness of individual still cameras varied from 15% to 86% of all recorded visits. Methodological issues and solutions, and the future uses of camera traps in pollination biology, are discussed. Conclusions and wider implications: Motion-triggered cameras are promising tools for the quantification of vertebrate visitation and some aspects of behavior on flowers. However, researchers need to be mindful of the variation in effectiveness of individual camera traps in detecting animals. Pollinator studies using camera traps are in their infancy, and the full potential of this developing technology is yet to be realized.


Immunomodulatory effects of allogeneic blood transfusions: clinical manifestations and mechanisms.
Recognition that allogeneic transfusion associated immunomodulation can increase morbidity in allogeneically transfused individuals has become a major concern for those involved in transfusion medicine. However, whether allogeneic blood transfusions predispose recipients to increased risk for cancer recurrence or to bacterial infections is still unproven. In contrast, data from studies in experimental animal models suggest that allogeneic blood transfusion associated immunomodulation is an immunologically mediated biological effect which is associated primarily with the infusion of allogeneic leukocytes. Moreover, the available experimental animal data suggest that pre-storage leukoreduction, as opposed to post-storage leukodepletion, is effective in ameliorating this tumor growth-enhancing effect of allogeneic blood. While considerable data have accumulated in an attempt to unravel the mechanism of the immunomodulatory effect of allogeneic blood transfusions, the precise mechanism of this effect has not yet been elucidated.


Macrophage death and defective inflammation resolution in atherosclerosis.
A key event in atherosclerosis is a maladaptive inflammatory response to subendothelial lipoproteins. A crucial aspect of this response is a failure to resolve inflammation, which normally involves the suppression of inflammatory cell influx, effective clearance of apoptotic cells and promotion of inflammatory cell egress. Defects in these processes promote the progression of atherosclerotic lesions into dangerous plaques, which can trigger atherothrombotic vascular disease, the leading cause of death in industrialized societies. In this Review I provide an overview of these concepts, with a focus on macrophage death and defective apoptotic cell clearance, and discuss new therapeutic strategies designed to boost inflammation resolution in atherosclerosis.


Propagation phasor approach for holographic image reconstruction.
To achieve high-resolution and wide field-of-view, digital holographic imaging techniques need to tackle two major challenges: phase recovery and spatial undersampling. Previously, these challenges were separately addressed using phase retrieval and pixel super-resolution algorithms, which utilize the diversity of different imaging parameters. Although existing holographic imaging methods can achieve large space-bandwidth-products by performing pixel super-resolution and phase retrieval sequentially, they require large amounts of data, which might be a limitation in high-speed or cost-effective imaging applications. Here we report a propagation phasor approach, which for the first time combines phase retrieval and pixel super-resolution into a unified mathematical framework and enables the synthesis of new holographic image reconstruction methods with significantly improved data efficiency. In this approach, twin image and spatial aliasing signals, along with other digital artifacts, are interpreted as noise terms that are modulated by phasors that analytically depend on the lateral displacement between hologram and sensor planes, sample-to-sensor distance, wavelength, and the illumination angle. Compared to previous holographic reconstruction techniques, this new framework results in five- to seven-fold reduced number of raw measurements, while still achieving a competitive resolution and space-bandwidth-product. We also demonstrated the success of this approach by imaging biological specimens including Papanicolaou and blood smears.


Cutaneous basophil hypersensitivity. II. A light and electron microscopic description.
Delayed onset erythematous skin reactions elicited in guinea pigs early in the course of sensitization with azobenzenearsonate-protein conjugates or with protein antigens in incomplete Freund's adjuvant or in saline were found to have a characteristic morphology which sets them apart from delayed hypersensitivity and the classic antibody mediated reactions. The principle feature was massive dermal infiltration with basophilic leukocytes. Mononuclear cells of several types including activated and small lymphocytes, monocytes, macrophages, and blast cells were also present. Such reactions have in the past been designated Jones-Mote hypersensitivity, but we prefer the descriptive term cutaneous basophil hypersensitivity (CBH) for the reasons given. Occasional basophils extruded their granules, and individual granules, retaining their characteristic ultrastructure, were commonly seen in the interstitium. However, intercellular junctions between endothelial cells were closed except during cell emigration and there was no morphologic evidence of an histamine-like effect. The majority of basophils, moreover, did not degranulate but underwent nuclear pyknosis and cytoplasmic degeneration and were phagocytosed by macrophages. Phagocytosed basophil granules retained their ultrastructure. Skin tests performed at late intervals after sensitization had a different time course and morphology. Animals sensitized with protein antigens in complete Freund's adjuvant developed delayed hypersensitivity; however, reactions elicited in such animals at early (but not late) intervals after sensitization contained a prominent basophil component. We interpret such reactions to be a mixture of delayed hypersensitivity and cutaneous basophil hypersensitivity. The function of the basophil in CBH and its relation to the mononuclear cells which accompany it are unknown, and various possibilities are discussed. We conclude that cutaneous basophil hypersensitivity is a distinct immunologic and morphologic entity, occurring early in the course of sensitization with protein antigens incorporated in any of several vehicles. The mechanism of the reaction is presently unknown, and a general hypothesis to explain its pathogenesis has been proposed.


A prototype mobile application for triaging dental emergencies.
Evidence suggests that dental emergencies are likely to occur when preferred care is less accessible. Communication barriers often exist that cause patients to receive suboptimal treatment or experience discomfort for extended lengths of time. Furthermore, limitations in the conventional approach for managing dental emergencies prevent dentists from receiving critical information before patient visits. The authors developed a mobile application to mediate the uncertainty of dental emergencies. The development and study consisted of a needs analysis and quality assessment of intraoral images captured by smartphones, prototype development, refining the prototype through usability inspection methods, and formative evaluation through usability testing with prospective users. The developed application successfully guided all users through a series of questions designed to capture clinically meaningful data by using familiar smartphone functions. All participants were able to complete a report within 4 minutes, and all clinical information was comprehended by the users. Patient-provided information accompanied by high-resolution images may help dentists substantially in predicting urgency or preparing necessary treatment resources. The results illustrate the feasibility of patients using smartphone applications to report dental emergencies. This technology allows dentists to assess care remotely when direct patient contact is less practical. This study's results demonstrate that patients can use mobile applications to transmit clinical data to their dentists and suggest the possibility of expanding the use of mobile applications to enhance access to routine and emergency dental care. The authors addressed how to enable patients to communicate emergency needs directly to a dentist while obviating patient emergency department visits.


Predictors of compliance with short-term treatment among patients with back pain.
Great efforts have been made to find effective treatments for back pain. Nevertheless, the effectiveness of a particular treatment can depend on patient compliance. The objective of this study was to prospectively investigate whether patients' demographic factors, clinical factors, external barriers in following the treatment, and perceptions of disability, quality of life, depression, and control over health were predictive of compliance with a physical therapy program carried out with patients with low back pain. This was an exploratory prospective cohort study that was carried out in New York City during 1999. All study participants answered a questionnaire at the initial clinical evaluation by a physical therapist and were followed during the treatment. The study assessed compliance with the three treatment regimens that were prescribed for every patient: attending scheduled physical therapy sessions, following a program of home exercises, and watching back-education videotapes. Depending on the individual patient, the planned treatment program could last from 2 to 6 weeks. The study employed a battery of instruments to measure patient characteristics that included perceived functional limitations, perceived quality of life, depression, and their beliefs about their health. Student's t tests and chi-square tests were used to determine if non- and low-compliant patients differed significantly from high-compliant patients. Logistic regression was used to estimate adjusted odds ratios expressing the association of selected variables with compliance. We found that 51% of the patients were either noncompliant or low-compliant overall with the low back pain treatment program. There were differences in compliance behavior among the three treatment regimens, with compliance being highest for watching the back-education videotapes and lowest for doing the home exercises. Poor compliance overall was positively associated with the expectation of barriers in following the proposed treatment, with comorbidity, and with longer duration of treatment in this program. The findings of our study indicate that patient compliance with back pain treatment is a serious and complex problem. Nevertheless, while this study was only an exploratory one, we believe that the results of this study can be used by care providers to identify patients likely to become noncompliant and also by researchers to plan specific studies on the effectiveness of treatment programs for patients with low back pain.


Serum cathepsin S is associated with decreased insulin sensitivity and the development of type 2 diabetes in a community-based cohort of elderly men.
To investigate associations between serum cathepsin S, impaired insulin sensitivity, defective insulin secretion, and diabetes risk in a community-based sample of elderly men without diabetes. Serum cathepsin S, insulin sensitivity (euglycemic-hyperinsulinemic clamp), and insulin secretion (early insulin response during an oral glucose tolerance test) were measured in 905 participants of the Uppsala Longitudinal Study of Adult Men (mean age, 71 years). Thirty participants developed diabetes during 6 years of follow-up. After adjustment for age, anthropometric variables, and inflammatory markers, higher cathepsin S was associated with decreased insulin sensitivity (regression coefficient per SD increase -0.09 [95% CI -0.14 to -0.04], P = 0.001), but no association with early insulin response was found. Moreover, higher cathepsin S was associated with a higher risk for developing diabetes (odds ratio per SD increase 1.48 [1.08-2.01], P = 0.01). Cathepsin S activity appears to be involved in the early dysregulation of glucose and insulin metabolism.


Influence of age and HLA type on interferon-gamma (IFN-gamma) responses to a naturally occurring polymorphic epitope of Plasmodium falciparum liver stage antigen-1 (LSA-1).
Antigenic polymorphism and HLA restriction may limit the immunogenicity of a subunit vaccine against liver-stage Plasmodium falciparum. We examined 59 clinical isolates and five laboratory clones of P. falciparum for polymorphism in the N- and C-terminal regions of LSA-1, evaluated binding of the corresponding peptides to selected HLA class I alleles, and measured IFN-gamma responses in residents of a malaria-endemic area of Papua New Guinea where HLA-A*1101, -24, -B13, and -B40 are the most common class I alleles. LSA-1 polymorphism was limited to a single non-synonymous mutation encoding serine (S), proline (P), or threonine (T) at amino acid 85. Nine-mer 84-92 peptides with S, T, or P at the primary anchor position bound differentially to HLA-A11, -A2, and -B7. IFN-gamma ELISPOT responses increased with age in malaria-exposed subjects: 14-16% and 30-36% of 2-5- and 6-54-year-olds, respectively, had > or =10 IFN-gamma-secreting cells/106 peripheral blood mononuclear cells when stimulated with at least one peptide variant (P<0.05). IFN-gamma responses to all three peptides were also greater for older than younger individuals. No children < 3 years old had lymphocytes that responded to all three 84-92 peptides, whereas 45% of adults (mean age 48 years) had aggregated IFN-gamma responses. These data support the notion that age-related cumulative exposure to P. falciparum increases the frequency of IFN-gamma responses to polymorphic epitopes of liver-stage antigens such as LSA-1.


Motor imagery training improves balance and mobility outcomes in older adults: a systematic review.
Does motor imagery training improve measures of balance, mobility and falls in older adults without a neurological condition? Systematic review and meta-analysis of randomised controlled trials. Adults aged at least 60 years and without a neurological condition. Three or more sessions of motor imagery training. The primary outcomes were balance measures (such as single leg stance and Berg Balance scale) and mobility measures (such as gait speed and the Timed Up and Go test). Falls were a secondary outcome measure. Risk of bias was evaluated using the PEDro Scale, and overall quality of evidence was assessed using the Grades of Research, Assessment, Development and Evaluation (GRADE) approach. Twelve trials including 356 participants were included in the systematic review and 10 trials (316 participants) were included in the meta-analyses. All trials included either apparently healthy participants or older adults after orthopaedic surgery. There was evidence that motor imagery training can significantly improve balance (SMD 1.03, 95% CI 0.25 to 1.82), gait speed (MD 0.13 m/s, 95% CI 0.04 to 0.22) and Timed Up and Go (MD 1.64 seconds, 95% CI 0.79 to 2.49) in older adults; however, the quality of evidence was very low to low. No data regarding falls were identified. Motor imagery training improves balance and mobility in older adults who do not have a neurological condition. These results suggest that motor imagery training could be an adjunct to standard physiotherapy care in older adults, although it is unclear whether or not the effects are clinically worthwhile. PROSPERO CRD42017069954.


Cyberbullying: its nature and impact in secondary school pupils.
Cyberbullying describes bullying using mobile phones and the internet. Most previous studies have focused on the prevalence of text message and email bullying. Two surveys with pupils aged 11-16 years: (1) 92 pupils from 14 schools, supplemented by focus groups; (2) 533 pupils from 5 schools, to assess the generalisability of findings from the first study, and investigate relationships of cyberbullying to general internet use. Both studies differentiated cyberbullying inside and outside of school, and 7 media of cyberbullying. Both studies found cyberbullying less frequent than traditional bullying, but appreciable, and reported more outside of school than inside. Phone call and text message bullying were most prevalent, with instant messaging bullying in the second study; their impact was perceived as comparable to traditional bullying. Mobile phone/video clip bullying, while rarer, was perceived to have more negative impact. Age and gender differences varied between the two studies. Study 1 found that most cyberbullying was done by one or a few students, usually from the same year group. It often just lasted about a week, but sometimes much longer. The second study found that being a cybervictim, but not a cyberbully, correlated with internet use; many cybervictims were traditional 'bully-victims'. Pupils recommended blocking/avoiding messages, and telling someone, as the best coping strategies; but many cybervictims had told nobody about it. Cyberbullying is an important new kind of bullying, with some different characteristics from traditional bullying. Much happens outside school. Implications for research and practical action are discussed.


How often is genital yeast infection sexually transmitted?
We analysed data from a computer-based bank of clinical records of patients seen in a clinic for sexually transmitted diseases over a three-year period to investigate the association between genital yeast infections and sexually transmitted diseases (STDs). We classified STDs as primary and secondary syphilis; gonorrhoea; lymphogranuloma venereum; trichomoniasis; scabies; pediculosis; genital herpes; warts; and molluscum contagiosum. Of a total of 2984 disease episodes among women, 1054 (35-3%) included yeast infections, whereas only 382 (6-9%) of 5501 episodes in heterosexual men were associated with yeast infections, We found a significant association between yeast infection and STD and non-specific genital infection (non-specific urethritis (NSU) and procitis in men, and female contacts of men with NSU), which suggested that yeast infection was sexually acquired in 414 out of 1054 disease episodes in women (39%) and 110 out of 382 episodes in heterosexual men (29%). We conclude that sexually active patients with genital yeast infections should be screened for other STDs particularly non-specific genital infection.


Heart and Nervous System Pathology in Compound Heterozygous Friedreich Ataxia.
In a small percentage of patients with Friedreich ataxia (FA), the pathogenic mutation is compound heterozygous, consisting of a guanine-adenine-adenine (GAA) trinucleotide repeat expansion in one allele, and a deletion, point mutation, or insertion in the other. In 2 cases of compound heterozygous FA, the GAA expansion was inherited from the mother, and deletions from the father. Compound heterozygous FA patient 1, an 11-year-old boy (GAA, 896/c.11_12TCdel), had ataxia, chorea, cardiomyopathy, and diabetes mellitus. Compound heterozygous FA patient 2, a 28-year-old man (GAA, 744/exon 5 del), had ataxia, cardiomyopathy, and diabetes mellitus. Microscopy showed cardiomyocyte hypertrophy, iron-positive inclusions, and disrupted intercalated discs. The cardiac lesions were similar to those in age-matched homozygous FA patients with cardiomyopathy and diabetes mellitus (boy, 10, GAA 1016/1016; woman, 25, GAA 800/1100). The neuropathology was also similar and included hypoplasia of spinal cord and dorsal root ganglia, loss of large axons in dorsal roots, and atrophy of the dentate nucleus (DN). Frataxin levels in heart and DN of all 4 FA cases were at or below the detection limits of the enzyme-linked immunosorbent assay (≤10 ng/g wet weight) (normal DN: 126 ± 43 ng/g; normal heart: 266 ± 92 ng/g). The pathologic phenotype in homozygous and compound heterozygous FA is determined by residual frataxin levels rather than unique mutations.


Twenty-one additional cases of familial renal glucosuria: absence of genetic heterogeneity, high prevalence of private mutations and further evidence of volume depletion.
Familial renal glucosuria (FRG) is a rare renal tubular disorder caused by mutations within the SLC5A2 gene. It is characterized by persistent glucosuria in the absence of hyperglycaemia and any other signs of generalized tubular dysfunction. In small series of patients previously reported, the molecular and phenotypic findings in FRG families, including first hints of extracellular volume depletion and activation of the renin-angiotensin-aldosterone system induced by natriuresis, have been described. We have now extended this analysis to another 21 consecutive cases from 17 pedigrees, including 11 cases with severe glucose excretion. Mutation analysis was performed by direct sequencing of the genomic coding segments of the SLC5A2 gene. In two cases with severe glucosuria, basal plasma renin activity and serum aldosterone concentrations were determined. Within the 17 pedigrees, we have identified a total of 20 different SLC5A2 mutations. Fifteen have not been previously reported. In all glucosuric individuals tested, at least one SLC5A2 mutation could be identified. Heterozygous individuals were found to have only mild glucose excretion whereas homozygous or compound heterozygous patients had severe glucosuria, ranging from 10 to 86.5 g/1.73 m(2)/24 h. In two patients of the latter group, basal plasma renin activity and serum aldosterone concentration were determined and found to be raised to an average of 4.6-fold and 3.1-fold of the upper limit of the normal range, respectively. Discussion. The identification of at least one mutated allele in every affected individual in this cohort of 17 consecutively investigated families strongly suggests that genetic heterogeneity is not prevalent in FRG. Although 5 of the detected alleles have been described previously, 15 are novel, confirming that most mutations in FRG are private. Our finding of an activation of compensatory mechanisms for salt loss may warrant more detailed studies of long-term hormonal and metabolic imbalances in patients with FRG.


Mathematical model of an avian urine concentrating mechanism.
A mathematical model was used to investigate how concentrated urine is produced within the medullary cones of the quail kidney. Model simulations were consistent with a concentrating mechanism based on single-solute countercurrent multiplication and on NaCl cycling from ascending to descending limbs of loops of Henle. The model predicted a urine-to-plasma (U/P) osmolality ratio of approximately 2.26, a value consistent with maximum avian U/P osmolality ratios. Active NaCl transport from descending limb prebend thick segments contributed 70% of concentrating capability. NaCl entry and water extraction provided 80 and 20%, respectively, of the concentrating effect in descending limb flow. Parameter studies indicated that urine osmolality is sensitive to the rate of fluid entry into descending limbs and collecting ducts at the cone base. Parameter studies also indicated that the energetic cost of concentrating urine is sensitive to loop of Henle population as a function of medullary depth: as the fraction of loops reaching the cone tip increased above anatomic values, urine osmolality increased only marginally, and, ultimately, urine osmolality decreased.


Non-surgical extraction of right atrial mass by AngioVac aspiration device under fluoroscopic and transesophageal echocardiographic guidance.
Right-sided cardiac masses are commonly encountered. We present a challenging case of a right atrial thrombus in a patient who had a high surgical risk for open removal. AngioVac aspiration device, under transesophageal echocardiography (TEE) and fluoroscopy guidance, was successfully used to remove the thrombus. The patient tolerated the procedure well and was discharged home. Our case confirms the safety and efficacy of this procedure for treatment of unwanted intracardiac and intravascular masses in patients who are not candidates for conventional therapies of surgery or thrombolytics.


Prevalence and correlates of successful transfer from pediatric to adult health care among a cohort of young adults with complex congenital heart defects.
More than 85% of children born today with chronic medical conditions will live to adulthood, and many should transfer from pediatric to adult health care. The numbers of adults with congenital heart defects (CHDs) are increasing rapidly. Current guidelines recommend that just over half of adult CHD patients should be seen every 12 to 24 months by a cardiologist with specific CHD expertise at a regional CHD center, because they are at risk for serious complications (eg, reoperation and/or arrhythmias) and premature mortality. The present study aimed to determine the percent of young adults with CHDs who successfully transferred from pediatric to adult care and examine correlates of successful transfer. Cross-sectional study with prevalence data from an entire cohort. All patients (n = 360) aged 19 to 21 years with complex CHDs who, according to current practice guidelines, should be seen annually at a specialized adult CHD center were identified from the database of the cardiology program at the Hospital for Sick Children in Toronto, Canada, a pediatric tertiary care center. Of these patients, 234 completed measures about health beliefs, health behaviors, and medical care since age 18 years. All 15 specialized adult CHD centers in Canada formed the Canadian Adult Congenital Heart (CACH) Network. Attendance for at least 1 follow-up appointment at a CACH center before the age of 22 years was ascertained for all eligible patients. Attendance at a CACH center provides a clear criterion for successful transfer. In the total cohort, 47% (95% confidence interval [CI]: 42-52) had transferred successfully to adult care. There was no difference in rates of successful transfer between patients consenting to complete questionnaires (48%) and those who declined (47%). More than one quarter (27%) of the patients reported having had no cardiac appointments since 18 years. In multivariate analyses of the entire cohort, successful transfer was significantly associated with more pediatric cardiovascular surgeries (odds ratio [OR]: 2.47; 95% CI: 1.40-4.37), older age at last visit to the Hospital for Sick Children (OR: 1.29; 95% CI: 1.10-1.51), and documented recommendations in the medical chart for follow-up at a CACH center. In multivariate analyses of the patients completing questionnaires, successful transfer was significantly related to documented recommendations and patient beliefs that adult CHD care should be at a CACH center (OR: 3.64; 95% CI: 1.34-9.90). Comorbid conditions (OR: 3.13; 95% CI: 1.13-8.67), not using substances (eg, binge drinking; OR: 0.18; 95% CI: 0.07-0.50), using dental antibiotic prophylaxis (OR: 4.23; 95% CI: 1.48-12.06), and attending cardiac appointments without parents or siblings (OR: 6.59; 95% CI: 1.61-27.00) also correlated with successful transfer. This is the first study to document the percent of young adults with a chronic illness who successfully transfer to adult care in a timely manner. Patients were from an entire birth cohort from the largest pediatric cardiac center in Canada, and outcome data were obtained on all eligible patients. Similar data should be obtained for other chronic illnesses. There is need for considerable improvement in the numbers of young adults with CHDs who successfully transfer to adult care. At-risk adolescents with CHDs should begin the transition process before their teens, should be educated in the importance of antibiotic prophylaxis, should be contacted if a follow-up appointment is missed, and should be directed to a specific CHD cardiologist or program, with the planned timing being stated explicitly. Adult care needs to be discussed in the pediatric setting, and patients must acquire appropriate beliefs about adult care well before transfer. Developmentally appropriate, staged discussions involving the patient, with and without parents, throughout adolescence may help patients acquire these beliefs and an understanding of the need for ongoing care. Improved continuity of pediatric care and provision of clear details for adult follow-up might be sufficient to cause substantive improvements in successful transfer. An understanding of why patients drop out of pediatric care may be needed to improve the continuity of care throughout adolescence. Almost one quarter of the patients believed adult care should be somewhere other than at a CACH center despite opposite recommendations. For these patients, a single discussion of adult care during the final pediatric visit may be too little, too late. In addition to earlier discussions, multiple mechanisms such as referral letters and transition clinics are needed. Similarly, patients engaging in multiple risky or poor health behaviors such as substance use may need more intensive programs to make substantial changes in these behaviors, which hopefully would lead to successful transfer. Overall, these data support the view that transition to adult care (a planned process of discussing and preparing for transfer to an adult health center) is important and should begin well before patients are transferred. The future health of adults with chronic conditions may depend on our ability to make these changes.


Information about the US racial demographic shift triggers concerns about anti-White discrimination among the prospective White "minority".
The United States is undergoing a demographic shift in which White Americans are predicted to comprise less than 50% of the US population by mid-century. The present research examines how exposure to information about this racial shift affects perceptions of the extent to which different racial groups face discrimination. In four experiments, making the growing national racial diversity salient led White Americans to predict that Whites will face increasing discrimination in the future, compared with control information. Conversely, regardless of experimental condition, Whites estimated that discrimination against various racial minority groups will decline. Explorations of several psychological mechanisms potentially underlying the effect of the racial shift information on perceived anti-White discrimination suggested a mediating role of concerns about American culture fundamentally changing. Taken together, these findings suggest that reports about the changing national demographics enhance concerns among Whites that they will be the victims of racial discrimination in the future.


Objective cognitive impairment and subjective cognitive problems in veterans initiating psychotherapy for posttraumatic stress disorder: An exploratory study.
The prevalence of cognitive impairment in Veterans initiating an evidence-based psychotherapy (EBP) for posttraumatic stress disorder (PTSD) is not yet established and has implications for service delivery. Our objectives were to (1) describe the type, severity, and prevalence of objective cognitive impairment and subjective cognitive problems experienced by Veterans at the time they began an EBP for PTSD and (2) determine whether assessments of objective cognitive impairment and subjective cognitive problems agree. We conducted objective and subjective (self-report) cognitive assessments in a sample of 38 Veterans initiating EBP for PTSD at one Veterans Affairs Medical Center. Thirty Veterans produced valid assessments. Almost half (14/30) of the participants demonstrated objective impairment in one or more cognitive domains, primarily in the areas of learning, memory, and processing speed. Almost all (29/30) participants endorsed moderate or greater cognitive problems on at least one self-report measure. After adjustment for multiple comparisons, there were no significant correlations between objective and subjective assessments. Objective cognitive impairment and subjective cognitive problems are common in Veterans beginning an EBP for PTSD. Longitudinal research on a larger sample is warranted to better understand relationships among subjective cognitive problems, objective cognitive impairment, and PTSD treatment participation and outcomes.


Kinetics of sequential appearance of IgM and IgD on B lymphocytes in the bone marrow of the adult mouse.
The relationship between the expression of IgM, and IgD at the B-cell surface, was examined in the adult murine bone marrow. Groups of mice were injected with hydroxyurea, which prevents DNA synthesis by blocking the production of deoxyribonucleotides. The numbers of cells per femur, expressing either IgM alone or in conjunction with IgD were followed at 24 hr intervals after the drugs administration. Other mice were injected with tritiated thymidine over an 8 hr period. The appearance of radioactive label within cells expressing IgM alone or with IgD, was followed over a 5 day period. Both sets of results showed that IgM bearing cells were derived from a rapidly dividing precursor cell pool, by a process which takes more than 24 hr and does not require DNA synthesis. Cells expressing IgM and IgD together were also produced from rapidly dividing precursors. This developmental process takes more than 48 hr, does not require DNA synthesis and may go via an intermediate stage namely the cell expressing IgM alone.


Multiple independent origins of mitochondrial control region duplications in the order Psittaciformes.
Mitochondrial genomes are generally thought to be under selection for compactness, due to their small size, consistent gene content, and a lack of introns or intergenic spacers. As more animal mitochondrial genomes are fully sequenced, rearrangements and partial duplications are being identified with increasing frequency, particularly in birds (Class Aves). In this study, we investigate the evolutionary history of mitochondrial control region states within the avian order Psittaciformes (parrots and cockatoos). To this aim, we reconstructed a comprehensive multi-locus phylogeny of parrots, used PCR of three diagnostic fragments to classify the mitochondrial control region state as single or duplicated, and mapped these states onto the phylogeny. We further sequenced 44 selected species to validate these inferences of control region state. Ancestral state reconstruction using a range of weighting schemes identified six independent origins of mitochondrial control region duplications within Psittaciformes. Analysis of sequence data showed that varying levels of mitochondrial gene and tRNA homology and degradation were present within a given clade exhibiting duplications. Levels of divergence between control regions within an individual varied from 0-10.9% with the differences occurring mainly between 51 and 225 nucleotides 3' of the goose hairpin in domain I. Further investigations into the fates of duplicated mitochondrial genes, the potential costs and benefits of having a second control region, and the complex relationship between evolutionary rates, selection, and time since duplication are needed to fully explain these patterns in the mitochondrial genome.


A Rare Case of Primary Calcific Pleural Tuberculosis - A Case Report.
Tuberculosis is a highly prevalent disease in India. It has a myriad of presentations. Usually pleural tuberculosis occur secondary to pulmonary tuberculosis which can manifest as pleural effusion leading to pleural calcification. Primary pleural calcification due to tuberculosis is an extremely rare manifestation of active tuberculosis. We present a case of a 21-year-old female presenting with fever, cough, weight loss and loss of appetite who was diagnosed to have pleural calcification due to primary tuberculosis. We highlight the need to keep primary pleural tuberculosis in mind with above symptoms suggestive of active tuberculosis even when there is no underlying lung pathology.


Effect of reducing portion size at a compulsory meal on later energy intake, gut hormones, and appetite in overweight adults.
Larger portion sizes (PS) are associated with greater energy intake (EI), but little evidence exists on the appetitive effects of PS reduction. This study investigated the impact of reducing breakfast PS on subsequent EI, postprandial gastrointestinal hormone responses, and appetite ratings. In a randomized crossover design (n = 33 adults; mean BMI 29 kg/m(2) ), a compulsory breakfast was based on 25% of gender-specific estimated daily energy requirements; PS was reduced by 20% and 40%. EI was measured at an ad libitum lunch (240 min) and snack (360 min) and by weighed diet diaries until bed. Blood was sampled until lunch in 20 participants. Appetite ratings were measured using visual analogue scales. EI at lunch (control: 2,930 ± 203; 20% reduction: 2,853 ± 198; 40% reduction: 2,911 ± 179 kJ) and over the whole day except breakfast (control: 7,374 ± 361; 20% reduction: 7,566 ± 468; 40% reduction: 7,413 ± 417 kJ) did not differ. Postprandial PYY, GLP-1, GIP, insulin, and fullness profiles were lower and hunger, desire to eat, and prospective consumption higher following 40% reduction compared to control. Appetite ratings profiles, but not hormone concentrations, were associated with subsequent EI. Smaller portions at breakfast led to reductions in gastrointestinal hormone secretion but did not affect subsequent energy intake, suggesting small reductions in portion size may be a useful strategy to constrain EI.


Comparison of the wound-activated transformation of caulerpenyne by invasive and noninvasive Caulerpa species of the Mediterranean.
The invasive green alga, Caulerpa taxifolia, that has spread rapidly after its introduction into the Mediterranean and the North American Pacific, reacts to wounding by transforming its major metabolite caulerpenyne. This wound-activated reaction involves the transformation of the bis-enol acetate moiety of 1, releasing reactive 1,4-dialdehydes. The ability to perform this transformation is found also in both the noninvasive Mediterranean C. prolifera and the invasive C. racemosa. Trapping experiments, as well as transformation of the model substrate geranyl acetate, suggest that all three investigated Caulerpa spp. rely on esterases that act upon wounding of the algae by subsequently removing the three acetate residues of caulerpenyne. The resulting reactive 1,4-dialdehyde oxytoxin 2 can be identified by liquid chromatography-mass spectrometry and is unstable in the wounded tissue. Caulerpenyne transformation occurs rapidly, and severe tissue damage caused degradation of more than 50% of the stored caulerpenyne within 1 min in all three algae. Prevention of the enzymatic reaction before extraction, by shock freezing the tissue with liquid nitrogen, was used for the determination of the caulerpenyne content in intact algae. It gives about twofold higher values compared to an established methanol extraction protocol. The speed and mechanism of the wound-activated transformation, as well as the caulerpenyne content in intact tissue of invasive and noninvasive Caulerpa spp., are comparable. Thus, this enzymatic transformation, despite being fast and efficient, is likely not the key for the success of the investigated invasive species.


2b or Not 2b: Experimental Evolution of Functional Exogenous Sequences in a Plant RNA Virus.
Horizontal gene transfer (HGT) is pervasive in viruses and thought to be a key mechanism in their evolution. On the other hand, strong selective constraints against increasing genome size are an impediment for HGT, rapidly purging horizontally transferred sequences and thereby potentially hindering evolutionary innovation. Here, we explore experimentally the evolutionary fate of viruses with simulated HGT events, using the plant RNA virus Tobacco etch virus (TEV), by separately introducing two functional, exogenous sequences to its genome. One of the events simulates the acquisition of a new function though HGT of a conserved AlkB domain, responsible for the repair of alkylation or methylation damage in many organisms. The other event simulates the acquisition of a sequence that duplicates an existing function, through HGT of the 2b RNA silencing suppressor from Cucumber mosaic virus. We then evolved these two viruses, tracked the maintenance of the horizontally transferred sequences over time, and for the final virus populations, sequenced their genome and measured viral fitness. We found that the AlkB domain was rapidly purged from the TEV genome, restoring fitness to wild-type levels. Conversely, the 2b gene was stably maintained and did not have a major impact on viral fitness. Moreover, we found that 2b is functional in TEV, as it provides a replicative advantage when the RNA silencing suppression domain of HC-Pro is mutated. These observations suggest a potentially interesting role for HGT of short functional sequences in ameliorating evolutionary constraints on viruses, through the duplication of functions.


Lysine post-translational modifications and the cytoskeleton.
PTMs (post-translational modifications) of lysine residues have proven to be major regulators of gene expression, protein-protein interactions, and protein processing and degradation. This is of particular importance in regulating the cytoskeleton, an enormously complex system of proteins responsible for cell motility, intracellular trafficking, and maintenance of cell form and structure. The cytoskeleton is present in all cells, including eukaryotes and prokaryotes, and comprises structures such as flagella, cilia and lamellipodia which play critical roles in intracellular transport and cellular division. Cytoskeletal regulation relies on numerous multi-component assemblies. In this chapter, we focus on the regulation of the cytoskeleton by means of PTMs of lysine residues on the cytoskeletal subunits and their accessory proteins. We specifically address the three main classes of cytoskeletal proteins in eukaryotes that polymerize into filaments, including microfilaments (actin filaments), intermediate filaments and microtubules. We discuss the identification and biological importance of lysine acetylation, a regulator of all three filament types. We also review additional lysine modifications, such as ubiquitination and SUMOylation, and their role in protein regulation and processing.


Germline Cas9 expression yields highly efficient genome engineering in a major worldwide disease vector, Aedes aegypti.
The development of CRISPR/Cas9 technologies has dramatically increased the accessibility and efficiency of genome editing in many organisms. In general, in vivo germline expression of Cas9 results in substantially higher activity than embryonic injection. However, no transgenic lines expressing Cas9 have been developed for the major mosquito disease vector Aedes aegypti Here, we describe the generation of multiple stable, transgenic Ae. aegypti strains expressing Cas9 in the germline, resulting in dramatic improvements in both the consistency and efficiency of genome modifications using CRISPR. Using these strains, we disrupted numerous genes important for normal morphological development, and even generated triple mutants from a single injection. We have also managed to increase the rates of homology-directed repair by more than an order of magnitude. Given the exceptional mutagenic efficiency and specificity of the Cas9 strains we engineered, they can be used for high-throughput reverse genetic screens to help functionally annotate the Ae. aegypti genome. Additionally, these strains represent a step toward the development of novel population control technologies targeting Ae. aegypti that rely on Cas9-based gene drives.


High-speed photonically assisted analog-to-digital conversion using a continuous wave multiwavelength source and phase modulation.
A more simple photonically assisted analog-to-digital conversion system utilizing a cw multiwavelength source and phase modulation instead of a mode-locked laser is presented. The output of the cw multiwavelength source is launched into a dispersive device (such as a single-mode fiber). This fiber creates a pulse train, where the central wavelength of each pulse corresponds to a spectral line of the optical source. The pulses can then be either dispersed again to perform discrete wavelength time stretching or demultiplexed for continuous time analog-to-digital conversion. We experimentally demonstrate the operation of both time stretched and interleaved systems at 38 GHz. The potential of integrating this type of system on a monolithic chip is discussed.


Knowledge, Attitude and Practice About Coronavirus Disease (COVID-19) Pandemic and Its Psychological Impact on Students and Their Studies: A Cross-Sectional Study Among Pharmacy Students in Saudi Arabia.
Individuals' knowledge, attitude and practice towards preventive and precautionary measures of COVID-19 are essential to control the spread of the disease. Consequently, the aims of the study were to evaluate knowledge, attitude and practice of pharmacy students towards the pandemic and to assess its psychological impact on them to provide future guidance. A cross-sectional, questionnaire-based study was conducted via a web-based survey in May 2020. All pharmacy students enrolled at Unaizah College of Pharmacy, Qassim University, were invited to take part in the study. A total of 232 out of 460 students took part in the study, giving a response rate of 50.43%. The mean total knowledge score was 9.87 ± 2.04 (maximum attainable score, 12). The majority of the participants (n=163; 70.3%) believed COVID-19 is a health threat to their community in the early months of the pandemic. Moreover, the majority (93%) also believed that the lockdown at the beginning of the pandemic was necessary to contain the pandemic. Encouragingly, 86.6% reported that they did not go to any crowded places during the pandemic with more female students avoiding crowded places compared to male students (91.6% versus 78.7%, respectively, P = 0.005). The majority (91%) also reported that they were following the strategies recommended by the authorities to prevent the spread of the virus. Encouragingly, 54.3% reported that the pandemic either had no effect or just a limited effect on their studies. However, 38.5% reported that they always felt or frequently felt nervous or anxious during the pandemic. The study showed that pharmacy students had good knowledge as well as positive attitudes and good practices towards COVID-19 and the preventive measures. However, during the early months, the pandemic did have a negative psychological impact on a number of students. Consequently, proactive psychological and social support services to the students should be considered during the current and future pandemics. In addition, it is important to consider and proactively address key issues that could cause stress and anxiety among students when shifting to distance learning and assessments.


Fluoride dentifrice ingestion and fluorosis of the permanent incisors.
Fluoride dentifrice is a primary means of preventing childhood caries, but it is also an important risk factor for fluorosis. The authors examine the influence of fluoride dentifrice ingestion on fluorosis of the permanent incisors. Participants in the Iowa Fluoride Study received questionnaires at regular intervals concerning fluoride sources. The authors assessed fluorosis using the fluorosis risk index. They estimated daily fluoride ingestion from dentifrice, diet and fluoride supplements and divided the amount by kilograms of body weight. The statistical analysis related fluoride ingestion to fluorosis in the permanent incisors. In bivariate analyses, mild fluorosis was significantly related to ingestion of fluoride dentifrice at ages 24 and 36 months (P = .02 for both). After the authors adjusted for fluoride ingested from dietary sources, logistic regression showed a significant association between fluorosis and dentifrice ingestion at age 24 months (P = .04). The study results suggest that fluorosis of the permanent incisors is influenced by ingestion of fluoride dentifrice during the first three years of life. Further research is needed to assess total intake of fluoride as a risk factor for fluorosis. These results support recommendations that young children use only a pea-sized amount of dentifrice. Parents should supervise young children as they brush their teeth with fluoride dentifrice.


Personalized Video Feedback and Repeated Task Practice Improve Laparoscopic Knot-Tying Skills: Two Controlled Trials.
Compare the effect of personalized feedback (PF) vs. task demonstration (TD), both delivered via video, on laparoscopic knot-tying skills and perceived workload; and evaluate the effect of repeated practice. General surgery interns and research fellows completed four repetitions of a simulated laparoscopic knot-tying task at one-month intervals. Midway between repetitions, participants received via e-mail either a TD video (demonstration by an expert) or a PF video (video of their own performance with voiceover from a blinded senior surgeon). Each participant received at least one video per format, with sequence randomly assigned. Outcomes included performance scores and NASA Task Load Index (NASA-TLX) scores. To evaluate the effectiveness of repeated practice, scores from these trainees on a separate delayed retention test were compared against historical controls who did not have scheduled repetitions. Twenty-one trainees completed the randomized study. Mean change in performance scores was significantly greater for those receiving PF (difference = 23.1 of 150 [95% confidence interval (CI): 0, 46.2], P = .05). Perceived workload was also significantly reduced (difference = -3.0 of 20 [95% CI: -5.8, -0.3], P = .04). Compared with historical controls (N = 93), the 21 with scheduled repeated practice had higher scores on the laparoscopic knot-tying assessment two weeks after the final repetition (difference = 1.5 of 10 [95% CI: 0.2, 2.8], P = .02). Personalized video feedback improves trainees' procedural performance and perceived workload compared with a task demonstration video. Brief monthly practice sessions support skill acquisition and retention.


The top five research priorities in physician-provided pre-hospital critical care: a consensus report from a European research collaboration.
Physician-manned emergency medical teams supplement other emergency medical services in some countries. These teams are often selectively deployed to patients who are considered likely to require critical care treatment in the pre-hospital phase. The evidence base for guidelines for pre-hospital triage and immediate medical care is often poor. We used a recognised consensus methodology to define key priority areas for research within the subfield of physician-provided pre-hospital critical care. A European expert panel participated in a consensus process based upon a four-stage modified nominal group technique that included a consensus meeting. The expert panel concluded that the five most important areas for further research in the field of physician-based pre-hospital critical care were the following: Appropriate staffing and training in pre-hospital critical care and the effect on outcomes, advanced airway management in pre-hospital care, definition of time windows for key critical interventions which are indicated in the pre-hospital phase of care, the role of pre-hospital ultrasound and dispatch criteria for pre-hospital critical care services. A modified nominal group technique was successfully used by a European expert group to reach consensus on the most important research priorities in physician-provided pre-hospital critical care.