Bilirubin mediated oxidative stress involves antioxidant response activation via Nrf2 pathway.
Unconjugated bilirubin (UCB) is responsible for neonatal jaundice and high level of free bilirubin (Bf) can lead to kernicterus. Previous studies suggest that oxidative stress is a critical component of UCB-induced neurotoxicity. The Nrf2 pathway is a powerful sensor for cellular redox state and is activated directly by oxidative stress and/or indirectly by stress response protein kinases. Activated Nrf2 translocates to nucleus, binds to Antioxidant Response Element (ARE), and enhances the up-regulation of cytoprotective genes that mediate cell survival. The aim of the present study was to investigate the role of Nrf2 pathway in cell response to bilirubin mediated oxidative stress in the neuroblastoma SH-SY5Y cell line. Cells exposed to a toxic concentration of UCB (140 nM Bf) showed an increased intracellular ROS levels and enhanced nuclear accumulation of Nrf2 protein. UCB stimulated transcriptional induction of ARE-GFP reporter gene and induced mRNA expression of multiple antioxidant response genes as: xCT, Gly1, γGCL-m, γGCL-c, HO-1, NQO1, FTH, ME1, and ATF3. Nrf2 siRNA decreased UCB induced mRNA expression of HO1 (75%), NQO1 (54%), and FTH (40%). The Nrf2-related HO-1 induction was reduced to 60% in cells pre-treated with antioxidant (NAC) or specific signaling pathway inhibitors for PKC, P38α and MEK1/2 (80, 40 and 25%, respectively). In conclusion, we demonstrated that SH-SY5Y cells undergo an adaptive response against UCB-mediated oxidative stress by activation of multiple antioxidant response, in part through Nrf2 pathway.


Effect of altered oligosaccharide structure on the cell surface number, distribution and turnover of the high molecular weight acidic glycoproteins of CHO cells.
The influence of altered carbohydrate structure on the surface number, distribution and turnover of plasma membrane glycoproteins has been studied in Chinese hamster ovary (CHO) cells by comparing three lines that are resistant to the cytotoxic effects of wheat germ agglutinin (WGA) with parental CHO cells. The glycoproteins investigated were members of a group of high molecular weight acidic glycoproteins (HMWAG). On parental cells these represent the major surface components that become labelled by lactoperoxidase-catalysed iodination. They are the only plasma membrane glycoproteins that bind WGA. The mutant lines also possess iodinatable surface polypeptides of high molecular weight, but these were less acidic and electrophoretically less diffuse than those from parental cells. These polypeptides in general did not bind [125I]WGA when two-dimensional polyacrylamide gels were overlaid with iodinated lectin. Mutant cells treated with fluorescein-conjugated WGA showed low surface fluorescence. However, the nuclear envelope and a small region in the perinuclear zone fluoresced strongly. Together, these results confirm that the surface glycoproteins of mutant cells had altered carbohydrate structure. Mouse antiserum prepared against the HMWAG, however, bound equally effectively to the mutant lines as to the parental lines. Indirect immunofluorescence experiments showed that the HMWAG had a fairly uniform distribution over the surface, and that internalization induced by second antibody occurred at a similar rate and in a similar manner in all lines, including the mutants. Electron microscopic observations using immunoperoxidase procedures confirmed the similarities in glycoprotein distribution on mutant and parental cells. Two mouse monoclonal antibodies raised against the HMWAG also revealed no difference in the number or topography of surface glycoproteins. Finally, the half-lives of several HMWAG in a parental and a mutant line (15B) maintained on low-serum medium were compared by means of a 125I/131I double-label technique. Half-lives of HMWAG from the former averaged 12 h and from the latter 11 h. It is concluded that the lack of complex termini on oligosaccharides of this particular group of CHO plasma membrane glycoproteins has no effect on their number, distribution or turnover.


The neural basis of impulsive discounting in pathological gamblers.
Pathological gambling is thought to result from a shift of balance between two competing neurobiological mechanisms: on the one hand the reward system involved in the regulation of the urge to get rewards and on the other hand the top-down control system. Fifteen pathological gamblers (PG) and fifteen healthy controls (HC) were studied in an event-related functional magnetic resonance imaging experiment where participants had to choose either a smaller, but immediately available monetary reward (SIR) or a larger delayed reward (LDR). We examined contrasts between LDR and SIR decisions. Additionally, we contrasted choices near the individual indifference point (indifferent decisions) and clear SIR or LDR choices (sure decisions). Behavioral data confirmed former results of steeper discount rates in PG. Contrasting choices of LDR vs. SIR showed widespread bilateral activations in PG, including postcentral gyrus, thalamus, superior/medial frontal gyrus and cingulate gyrus, whereas HC demonstrated only focal left-sided pre/postcentral activity. Forgoing an immediate reward thus recruits a widespread brain network including typical control areas. Indifferent vs. sure decisions were associated with widespread activation in PG, including the bilateral fronto-parietal cortex, insula, anterior cingulate gyrus, and striatum, whereas in HC, only bilateral frontal cortex and insula were activated. The reverse contrast demonstrated more activity for sure decisions in the cingulate gyrus, insula, and medial frontal gyrus in HC, whereas PG showed inferior parietal and superior temporal activity. The present study demonstrates that pathological gambling is associated with a shift in the interplay between a prefrontal-parietal control network and a brain network involved in immediate reward consumption.


Antagonistic effects of laminin and fibronectin on the expression of the myogenic phenotype.
Skeletal myoblasts from fetal muscle respond adversely to fibronectin and laminin substrata: when primary mouse skeletal myoblasts are plated onto laminin, more myosin and desmin-positive myoblasts (myo+ cells) develop than on plates coated with fibronectin or collagen. In clonal cultures virtually all cells differentiate into postmitotic, fusion-capable myo + myoblasts on laminin after 3 days. In contrast, on fibronectin, the majority of the cells becomes myosin- and desmin-negative, partially due to proliferation of undifferentiated myoblast precursor cells, partially due to dedifferentiation or modulation of myoblasts into fibroblast-like myo- cells. Loss of the myogenic phenotype on fibronectin was also observed in cloned mouse myoblasts and in cultures of a differentiating mouse satellite cell line, MM14Dy, confirming that the appearance of desmin-negative cells is a result of myoblast modulation and not due simply to overgrowth by muscle fibroblasts. In the light of other effects of laminin on myoblasts, such as the stimulation of migration, differentiation and proliferation, our findings are consistent with the notion that laminin and fibronectin may be counteracting factors in the control of muscle differentiation.


Inflammation and disintegration of intestinal villi in an experimental model for Vibrio parahaemolyticus-induced diarrhea.
Vibrio parahaemolyticus is a leading cause of seafood-borne gastroenteritis in many parts of the world, but there is limited knowledge of the pathogenesis of V. parahaemolyticus-induced diarrhea. The absence of an oral infection-based small animal model to study V. parahaemolyticus intestinal colonization and disease has constrained analyses of the course of infection and the factors that mediate it. Here, we demonstrate that infant rabbits oro-gastrically inoculated with V. parahaemolyticus develop severe diarrhea and enteritis, the main clinical and pathologic manifestations of disease in infected individuals. The pathogen principally colonizes the distal small intestine, and this colonization is dependent upon type III secretion system 2. The distal small intestine is also the major site of V. parahaemolyticus-induced tissue damage, reduced epithelial barrier function, and inflammation, suggesting that disease in this region of the gastrointestinal tract accounts for most of the diarrhea that accompanies V. parahaemolyticus infection. Infection appears to proceed through a characteristic sequence of steps that includes remarkable elongation of microvilli and the formation of V. parahaemolyticus-filled cavities within the epithelial surface, and culminates in villus disruption. Both depletion of epithelial cell cytoplasm and epithelial cell extrusion contribute to formation of the cavities in the epithelial surface. V. parahaemolyticus also induces proliferation of epithelial cells and recruitment of inflammatory cells, both of which occur before wide-spread damage to the epithelium is evident. Collectively, our findings suggest that V. parahaemolyticus damages the host intestine and elicits disease via previously undescribed processes and mechanisms.


Direct fabrication of graphene on SiO2 enabled by thin film stress engineering.
We demonstrate direct production of graphene on SiO2 by CVD growth of graphene at the interface between a Ni film and the SiO2 substrate, followed by dry mechanical delamination of the Ni using adhesive tape. This result is enabled by understanding of the competition between stress evolution and microstructure development upon annealing of the Ni prior to the graphene growth step. When the Ni film remains adherent after graphene growth, the balance between residual stress and adhesion governs the ability to mechanically remove the Ni after the CVD process. In this study the graphene on SiO2 comprises micron-scale domains, ranging from monolayer to multilayer. The graphene has >90% coverage across centimeter-scale dimensions, limited by the size of our CVD chamber. Further engineering of the Ni film microstructure and stress state could enable manufacturing of highly uniform interfacial graphene followed by clean mechanical delamination over practically indefinite dimensions. Moreover, our findings suggest that preferential adhesion can enable production of 2-D materials directly on application-relevant substrates. This is attractive compared to transfer methods, which can cause mechanical damage and leave residues behind.


Leaving colorectal polyps in place can be achieved with high accuracy using blue light imaging (BLI).
A negative predictive value of more than 90% is proposed by the American Society of Gastrointestinal Endoscopy Preservation and Incorporation of Valuable Endoscopic Innovations (PIVI) statement for a new technology in order to leave distal diminutive colorectal polyps in place without resection. To our knowledge, no prior prospective study has yet evaluated the feasibility of the most recently introduced blue light imaging (BLI) system for real-time endoscopic prediction of polyp histology for the specific endpoint of leaving hyperplastic polyps in place. Prospective assessment of real-time prediction of colorectal polyps by using BLI. In total, 177 consecutive patients undergoing screening or surveillance colonoscopy were included. Colorectal polyps were evaluated in real-time by using high-definition endoscopy and the BLI technology without optical magnification. Before resection, the endoscopist described each polyp according to size, shape and surface characteristics (pit and vascular pattern, colour and depression), and histology was predicted with a level of confidence (high or low). Histology was predicted with high confidence in 92.5% of polyps. Sensitivity of BLI for prediction of adenomatous histology was 92.68%, with a specificity and accuracy of 94.87 and 93.75%, respectively. Following the recommendation of the PIVI statement, positive and negative predictive values were calculated with values of 95 and 92.5%, respectively. Prediction of surveillance based on both US and European guidelines was correctly predicted in 91% of patients. The most recently introduced BLI technology is accurate enough to leave distal colorectal polyps in place without resection. BLI also allowed for assignment of postpolypectomy surveillance intervals. This approach therefore has the potential to reduce costs and risks associated with the redundant removal of diminutive colorectal polyps.


Asymmetric effects of loss and gain of a floral trait on pollinator preference.
Shifts in pollination syndromes involve coordinated changes in multiple floral traits. This raises the question of how plants can cope with rapid changes in pollinator availability by the slow process of accumulation of mutations in multiple genes. Here we study the transition from bee to hawkmoth pollination in the genus Petunia. Interspecific crosses followed by single locus introgressions were used to recreate putative intermediate evolutionary stages in the evolution of moth pollination. The effect of the loss/gain of petal color was asymmetric: it had no influence on the established pollinator but enhanced visitation by the new pollinator. Therefore, shifts in pollination syndromes may proceed through intermediate stages of reduced specialization and consequently enhanced reproductive assurance. The loss of petal color in moth-pollinated Petunia involves null mutations in a single regulatory gene, An2. Such simple genetic changes may be sufficiently rapid and frequent to ensure survival during pollinator failure.


Perforated leiomyosarcoma of Meckel's diverticulum. Case report.
A case of perforated leiomyosarcoma of Meckel's diverticulum causing acute abdomen is described. In the available literature only 58 cases of leiomyosarcoma at this site have been reported, with three perforations.


Anatomical considerations of fascial release in ulnar nerve transposition: a concept revisited.
Surgical transposition of the ulnar nerve to alleviate entrapment may cause otherwise normal structures to become new sources of nerve compression. Recurrent or persistent neuropathy after anterior transposition is commonly attributable to a new distal compression. The authors sought to clarify the anatomical relationship of the ulnar nerve to the common aponeurosis of the humeral head of the flexor carpi ulnaris (FCU) and flexor digitorum superficialis (FDS) muscles following anterior transposition of the nerve. The intermuscular septa of the proximal forearm were explored in 26 fresh cadaveric specimens. The fibrous septa and common aponeurotic insertions of the flexor-pronator muscle mass were evaluated in relation to the ulnar nerve, with particular attention to the effect of transposition upon the nerve in this region. An intermuscular aponeurosis associated with the FCU and FDS muscles was present in all specimens. Transposition consistently resulted in angulation of the nerve during elbow flexion when this fascial septum was not released. The proximal site at which the nerve began to traverse this fascial structure was found to be an average of 3.9 cm (SD 0.7 cm) from the medial epicondyle. The common aponeurosis encountered between the FDS and FCU muscles represents a potential site of posttransposition entrapment, which may account for a subset of failed anterior transpositions. Exploration of this region with release of this structure is recommended to provide an unconstrained distal course for a transposed ulnar nerve.


Isoleucine increases muscle mass through promoting myogenesis and intramyocellular fat deposition.
Isoleucine (Ile), as a branched-chain amino acid (BCAA), has a vital role in regulating body weight and muscle protein synthesis. However, the regulatory effect of Ile on muscle mass under high-fat diet (HFD) conditions and intramyocellular lipid deposition remains largely unclear. In this study, a feeding experiment with HFD with or without 25 g L-1 Ile was performed using 32 wild male C57BL/6J mice randomly divided into two groups. The results showed that Ile significantly increased both muscle and fat mass, as well as causing insulin resistance and meanwhile upregulating the levels of key adipogenic and myogenic proteins. More importantly, Ile damaged the mitochondrial function by vacuolation, swelling and cristae fracture in the gastrocnemius (GAS) and tibialis anterior (TA) with downregulation of mitochondrial function-related genes. Furthermore, Ile promoted myogenesis and more lipid droplet accumulation in myotubes. Compared with the control, the protein levels of myosin heavy chain (MyHC), myoblast determination protein 1 (MyoD), myogenin (MyoG), peroxisome proliferator-activated receptor gamma (PPARg) and fatty acid synthase (FAS) were upregulated in the Ile group, whereas the protein levels of adipose triglyceride lipase (ATGL) and lipoprotein lipase (LPL) were downregulated. Collectively, Ile increased muscle mass through myogenesis and intramyocellular lipid deposition. Our findings provide a new perspective for not only improving the lean juiciness of farm animals by increasing intramyocellular lipid accumulation, but also modulating myopathies under obesity.


Impact of basal ganglia damage after successful endovascular recanalization for acute ischemic stroke involving lenticulostriate arteries.
Regional ischemic vulnerability of the brain reportedly differs between the cortex and basal ganglia and has been poorly assessed in the setting of endovascular mechanical thrombectomy. This study was conducted to determine the fate of an ischemic basal ganglia and its contribution to the clinical outcome after successful endovascular recanalization for acute ischemic stroke with large vessel occlusion involving the lenticulostriate arteries. Clinical and radiological findings were retrospectively analyzed in consecutive patients with acute ischemic stroke characterized by large vessel occlusion involving the lenticulostriate arteries. Mechanical thrombectomy was performed in all patients using a stent retriever. The fate of ischemic basal ganglia based on location (lentiform nucleus, caudate nucleus, and internal capsule) and insular cortex was assessed according to the Alberta Stroke Programme Early CT Score (ASPECTS). Of 170 patients with large intracranial vessel occlusion who achieved successful endovascular recanalization, defined as a thrombolysis in cerebral infarction grade of ≥ 2B, involvement of the lenticulostriate arteries was seen in 55 patients (internal carotid artery, n = 35; proximal middle cerebral artery, n = 20). Preoperative infarction was detected in the lentiform nucleus (66.7%), internal capsule (11.1%), and caudate nucleus (33.3%), all of which showed secondary advancement despite successful recanalization (85.4%, 27.3%, and 54.5%, respectively; p < 0.05). Lenticulostriate arteries with a lateral proximal and/or medial proximal origin significantly affected the development of mature infarction in the lentiform nucleus. Postoperative hemorrhagic transformation was detected in 25 of 55 patients, mostly in the lentiform nucleus. Involvement of insular ribbon infarction was significantly high in patients with hemorrhagic transformation in the basal ganglia. Age, initial National Institutes of Health Stroke Scale (NIHSS) score, initial ASPECTS, postoperative ASPECTS, postoperative infarction in the insular ribbon, and lesions in the middle cerebral artery area (M1-M6) were significantly different between patients with good and poor modified Rankin Scale scores. Interestingly, no differences were detected in postoperative infarction or hemorrhagic transformation in the basal ganglia. Multivariate analysis showed that only age (p = 0.02, OR 0.88) and the initial NIHSS score (p = 0.01, OR 0.86) independently affected favorable clinical outcomes. The basal ganglia are vulnerable and readily develop secondary infarction and hemorrhagic transformation despite successful recanalization. However, this does not have a significant impact on the clinical outcome of acute ischemic stroke with large vessel occlusion involving the lenticulostriate arteries.


Collagen IV of basement membranes: IV. Adaptive mechanism of collagen IV scaffold assembly in Drosophila.
Collagen IV is an essential structural protein in all metazoans. It provides a scaffold for the assembly of basement membranes, a specialized form of extracellular matrix, which anchors and signals cells and provides microscale tensile strength. Defective scaffolds cause basement membrane destabilization and tissue dysfunction. Scaffolds are composed of α-chains that coassemble into triple-helical protomers of distinct chain compositions, which in turn oligomerize into supramolecular scaffolds. Chloride ions mediate the oligomerization via NC1 trimeric domains, forming an NC1 hexamer at the protomer-protomer interface. The chloride concentration-"chloride pressure"-on the outside of cells is a primordial innovation that drives the assembly and dynamic stabilization of collagen IV scaffolds. However, a Cl-independent mechanism is operative in Ctenophora, Ecdysozoa, and Rotifera, which suggests evolutionary adaptations to environmental or tissue conditions. An understanding of these exceptions, such as the example of Drosophila, could shed light on the fundamentals of how NC1 trimers direct the oligomerization of protomers into scaffolds. Here, we investigated the NC1 assembly of Drosophila. We solved the crystal structure of the NC1 hexamer, determined the chain composition of protomers, and found that Drosophila adapted an evolutionarily unique mechanism of scaffold assembly that requires divalent cations. By studying the Drosophila case we highlighted the mechanistic role of chloride pressure for maintaining functionality of the NC1 domain in humans. Moreover, we discovered that the NC1 trimers encode information for homing protomers to distant tissue locations, providing clues for the development of protein replacement therapy for collagen IV genetic diseases.


Some types of exercise are more effective than others in people with chronic low back pain: a network meta-analysis.
What are the effects of specific types of exercise treatments on pain intensity and functional limitation outcomes for adults with chronic low back pain? Systematic review with network meta-analysis of randomised controlled trials. Adults with non-specific low back pain for ≥ 12 weeks. Exercise treatments prescribed or planned by a health professional that involved conducting specific activities, postures and/or movements with a goal to improve low back pain outcomes. Pain intensity (eg, visual analogue scale or numerical rating scale) and back-related functional limitations (eg, Roland Morris Disability Questionnaire or Oswestry Disability Index), each standardised to range from 0 to 100. This review included 217 randomised controlled trials with 20,969 participants and 507 treatment groups. Most exercise types were more effective than minimal treatment for pain and functional limitation outcomes. Network meta-analysis results were compatible with moderate to clinically important treatment effects for Pilates, McKenzie therapy, and functional restoration (pain only) and flexibility exercises (function only) compared with minimal treatment, other effective treatments and other exercise types. The estimated mean differences for these exercise types compared with minimal treatment ranged from -15 to -19 for pain and from -10 to -12 for functional limitation. This review found evidence that Pilates, McKenzie therapy and functional restoration were more effective than other types of exercise treatment for reducing pain intensity and functional limitations. Nevertheless, people with chronic low back pain should be encouraged to perform the exercise that they enjoy to promote adherence. DOI:10.1002/14651858.CD009790.


Simulation of the effects of seasonally varying pumping on intraborehole flow and the vulnerability of public-supply wells to contamination.
Public-supply wells with long screens in alluvial aquifers can produce waters of differing quality from different depths. Seasonal changes in quality are linked to seasonal changes in pumping rates that influence the distribution of flow into the well screens under pumping conditions and the magnitude and direction of intraborehole flow within the wells under ambient conditions. Groundwater flow and transport simulations with MODFLOW and MT3DMS were developed to quantify the effects of changes in average seasonal pumping rates on intraborehole flow and water quality at two long-screened, public-supply wells, in Albuquerque, New Mexico and Modesto, California, where widespread pumping has altered groundwater flow patterns. Simulation results indicate that both wells produce water requiring additional treatment to maintain potable quality in winter when groundwater withdrawals are reduced because less water is derived from parts of the aquifer that contain water requiring less treatment. Simulation results indicate that the water quality at both wells could be improved by increasing average winter-pumping rates to induce more lateral flow from parts of the aquifer that contain better quality water. Arsenic-bearing water produced by the Albuquerque well could be reduced from 55% to 45% by doubling average winter-pumping rate, while nitrate- and uranium-bearing water produced by the Modesto well could be reduced from 95% to 65% by nearly tripling the average winter-pumping rate. Higher average winter-pumping rates would also reduce the volume of intraborehole flow within both wells and prevent the exchange of poor quality water between shallow and deep parts of both aquifers.


Snakebite in Australia: a practical approach to diagnosis and treatment.
Snakebite is a potential medical emergency and must receive high-priority assessment and treatment, even in patients who initially appear well. Patients should be treated in hospitals with onsite laboratory facilities, appropriate antivenom stocks and a clinician capable of treating complications such as anaphylaxis. All patients with suspected snakebite should be admitted to a suitable clinical unit, such as an emergency short-stay unit, for at least 12 hours after the bite. Serial blood testing (activated partial thromboplastin time, international normalised ratio and creatine kinase level) and neurological examinations should be done for all patients. Most snakebites will not result in significant envenoming and do not require antivenom. Antivenom should be administered as soon as there is evidence of envenoming. Evidence of systemic envenoming includes venom-induced consumption coagulopathy, sudden collapse, myotoxicity, neurotoxicity, thrombotic microangiopathy and renal impairment. Venomous snake groups each cause a characteristic clinical syndrome, which can be used in combination with local geographical distribution information to determine the probable snake involved and appropriate antivenom to use. The Snake Venom Detection Kit may assist in regions where the range of possible snakes is too broad to allow the use of monovalent antivenoms. When the snake identification remains unclear, two monovalent antivenoms (eg, brown snake and tiger snake antivenom) that cover possible snakes, or a polyvalent antivenom, can be used. One vial of the relevant antivenom is sufficient to bind all circulating venom. However, recovery may be delayed as many clinical and laboratory effects of venom are not immediately reversible. For expert advice on envenoming, contact the National Poisons Information Centre on 13 11 26.


Identification of XRCC1 Arg399Gln and XRCC3 Thr241Met Polymorphisms in a Turkish Population and Their Association with the Risk of Chronic Lymphocytic Leukemia.
DNA repair systems are essential for cellular functions. Defects due to sequence variations in DNA repair genes can lead severe failure of cell functions and causing many cancer types including leukemia. The aim of this study was to investigate the relationship between XRCC1 Arg399Gln and XRCC3 Thr241Met polymorphisms and susceptibility to chronic lymphocytic leukemia (CLL) in Turkish patients. In addition, genotype distribution of these polymorphisms was compared with other populations. The frequencies of Arg399Gln and Thr241Met single nucleotide polymorphisms were studied in 25 CLL patients and 30 healthy individuals. Single nucleotide polymorphisms were genotyped by PCR-RFLP method. The genotype and allele frequencies of Arg399Gln and Thr241Met polymorphisms were not statistically different between the CLL patients and control group. The allelic frequency similarities were found between Turkish and Brazilian populations for Arg399Gln polymorphism. On the other hand, similarities were found between Turkish and other Caucasian populations for Thr241Met polymorphism. Marked differences were observed between American African versus Turkish and Chinese versus Turkish populations for Arg399Gln and Thr241Met polymorphisms respectively. These results indicate that Arg399Gln and Thr241Met polymorphisms were not associated with the development of CLL in Turkish population and ethnic differences is one of the most important factor for allele frequency differences.


Local Effect of Ballistic Fragments Embedded Along the Carotid Sheath of a Porcine Animal Model.
Energized ballistic fragments from improvised explosive devices were the most common cause of injury to coalition service personnel during conflicts in Iraq and Afghanistan. Surgical excision of retained fragments is not routinely performed unless there is a concern for injury to vital structures. However, no clear guidelines dictate when or if a fragment should be removed, reflecting a lack of objective evidence of their long-term effects. Using a porcine model, we aimed to evaluate changes to the carotid artery produced by retained fragments over time. Institutional Animal Care and Use Committee approval for all experiments was obtained before commencement of the study. Eighteen female swine (mean mass 62.0 ± 3.4 kg) were randomized into three study groups corresponding to the time of survival after implantation of ballistic fragments: 1, 6, and 12 weeks. Two animals from each group were randomly assigned to have one of the three different fragments implanted within the right carotid sheath in zones 1-3 of the neck. The left carotid served as the control. The vascular flow rate and arterial diameter were measured at each level before implantation and again after the survival interval. Baseline and interval angiograms were performed to identify gross vascular changes. No abnormalities were identified on baseline or interval angiograms. No significant difference was found when the baseline was compared to interval measurements or when compared to the control side for all gross and physiological measures at 1 and 6 weeks (P = .053-.855). After 12 weeks, the flow and diameter changed significantly (P < .001-.03), but this significant change was found in both the control and affected carotid. The lack of significant gross anatomical and physiological changes at 6 weeks postimplantation lends evidence toward the current policy that early removal of retained ballistic fragments around cervical vessels is not required. Changes were significant after 12 weeks which suggest that surveillance may be required; however, such changes could be explained by physiological animal growth.


Alteration in Bacterial Culture After Treatment With Topical Mupirocin for Recalcitrant Chronic Rhinosinusitis.
Topical mupirocin therapy is used to treat symptomatic chronic sinusitis (CRS). However, the potential adverse impact of this therapy on the sinus microbiota has not been well quantified. To determine changes in microbiologic culture results before and after topical mupirocin therapy in patients with CRS with medically and surgically refractory disease. We performed a retrospective medical chart review for 22 consecutive adults evaluated and treated between January 1, 2012, and January 1, 2014, at an otolaryngology-rhinology clinic at a regional academic medical center. The patients were 14 men and 8 women, who had undergone functional endoscopic sinus surgery for CRS, and in whom sinus aspirate cultures were performed before and after topical mupirocin therapy for symptomatic disease. Analyses were performed in April 2014. Patients underwent treatment with saline sinus rinse, with the addition of mupirocin, for at least 1 week. Bacterial isolates from sinus aspirate culture. The patients included 14 men and 8 women, 18 to 75 years old, who underwent a mean of 1.9 functional endoscopic sinus surgical procedures. The mean (range) duration of mupirocin therapy was 6 (2-12) weeks. Before mupirocin therapy, cultures from symptomatic patients (14 men and 8 women, ages 18-75 years) revealed common bacteria implicated in CRS, which are characteristically gram-positive. After mupirocin therapy, cultures from symptomatic patients shifted significantly: 19 were gram-positive vs 3 gram-negative before treatment; 9 were gram-positive vs 13 gram-negative after treatment (P = .004), with increased growth of pathogenic gram-negative bacteria and Corynebacterium. These data present evidence supporting the distinct abrogation of culturable sinus bacteria after mupirocin rinses, identifying a shift toward increased pathogenic bacteria. Consideration of healthy host microbiome and immune dysfunction should guide future treatment considerations.


The Requirement of Glycoprotein C for Interindividual Spread Is Functionally Conserved within the Alphaherpesvirus Genus (Mardivirus), but Not the Host (Gallid).
Marek's disease (MD) in chickens is caused by Gallid alphaherpesvirus 2, better known as MD herpesvirus (MDV). Current vaccines do not block interindividual spread from chicken-to-chicken, therefore, understanding MDV interindividual spread provides important information for the development of potential therapies to protect against MD, while also providing a natural host to study herpesvirus dissemination. It has long been thought that glycoprotein C (gC) of alphaherpesviruses evolved with their host based on their ability to bind and inhibit complement in a species-selective manner. Here, we tested the functional importance of gC during interindividual spread and host specificity using the natural model system of MDV in chickens through classical compensation experiments. By exchanging MDV gC with another chicken alphaherpesvirus (Gallid alphaherpesvirus 1 or infectious laryngotracheitis virus; ILTV) gC, we determined that ILTV gC could not compensate for MDV gC during interindividual spread. In contrast, exchanging turkey herpesvirus (Meleagrid alphaherpesvirus 1 or HVT) gC could compensate for chicken MDV gC. Both ILTV and MDV are Gallid alphaherpesviruses; however, ILTV is a member of the Iltovirus genus, while MDV is classified as a Mardivirus along with HVT. These results suggest that gC is functionally conserved based on the virus genera (Mardivirus vs. Iltovirus) and not the host (Gallid vs. Meleagrid).


Rate my data: quantifying the value of ecological data for the development of models of the terrestrial carbon cycle.
Primarily driven by concern about rising levels of atmospheric CO2, ecologists and earth system scientists are collecting vast amounts of data related to the carbon cycle. These measurements are generally time consuming and expensive to make, and, unfortunately, we live in an era where research funding is increasingly hard to come by. Thus, important questions are: "Which data streams provide the most valuable information?" and "How much data do we need?" These questions are relevant not only for model developers, who need observational data to improve, constrain, and test their models, but also for experimentalists and those designing ecological observation networks. Here we address these questions using a model-data fusion approach. We constrain a process-oriented, forest ecosystem C cycle model with 17 different data streams from the Harvard Forest (Massachusetts, USA). We iteratively rank each data source according to its contribution to reducing model uncertainty. Results show the importance of some measurements commonly unavailable to carbon-cycle modelers, such as estimates of turnover times from different carbon pools. Surprisingly, many data sources are relatively redundant in the presence of others and do not lead to a significant improvement in model performance. A few select data sources lead to the largest reduction in parameter-based model uncertainty. Projections of future carbon cycling were poorly constrained when only hourly net-ecosystem-exchange measurements were used to inform the model. They were well constrained, however, with only 5 of the 17 data streams, even though many individual parameters are not constrained. The approach taken here should stimulate further cooperation between modelers and measurement teams and may be useful in the context of setting research priorities and allocating research funds.


Spontaneous broken-symmetry insulator and metals in tetralayer rhombohedral graphene.
Interactions among charge carriers in graphene can lead to the spontaneous breaking of multiple degeneracies. When increasing the number of graphene layers following rhombohedral stacking, the dominant role of Coulomb interactions becomes pronounced due to the significant reduction in kinetic energy. In this study, we employ phonon-polariton-assisted near-field infrared imaging to determine the stacking orders of tetralayer graphene devices. Through quantum transport measurements, we observe a range of spontaneous broken-symmetry states and their transitions, which can be finely tuned by carrier density n and electric displacement field D. Specifically, we observe a layer-antiferromagnetic insulator at n = D = 0 with a gap of approximately 15 meV. Increasing D allows for a continuous phase transition from a layer-antiferromagnetic insulator to a layer-polarized insulator. By simultaneously tuning n and D, we observe isospin-polarized metals, including spin-valley-polarized and spin-polarized metals. These transitions are associated with changes in the Fermi surface topology and are consistent with the Stoner criteria. Our findings highlight the efficient fabrication of specially stacked multilayer graphene devices and demonstrate that crystalline multilayer graphene is an ideal platform for investigating a wide range of broken symmetries driven by Coulomb interactions.


Estimating the state of the COVID-19 epidemic in France using a model with memory.
In this paper, we use a deterministic epidemic model with memory to estimate the state of the COVID-19 epidemic in France, from early March until mid-December 2020. Our model is in the SEIR class, which means that when a susceptible individual (S) becomes infected, he/she is first exposed (E), i.e. not yet contagious. Then he/she becomes infectious (I) for a certain length of time, during which he/she may infect susceptible individuals around him/her, and finally becomes removed (R), that is, either immune or dead. The specificity of our model is that it assumes a very general probability distribution for the pair of exposed and infectious periods. The law of large numbers limit of such a model is a model with memory (the future evolution of the model depends not only upon its present state, but also upon its past). We present theoretical results linking the (unobserved) parameters of the model to various quantities which are more easily measured during the early stages of an epidemic. We then apply these results to estimate the state of the COVID-19 epidemic in France, using available information on the infection fatality ratio and on the distribution of the exposed and infectious periods. Using the hospital data published daily by Santé Publique France, we gather some information on the delay between infection and hospital admission, intensive care unit (ICU) admission and hospital deaths, and on the proportion of people who have been infected up to the end of 2020.


Spontaneous diabetes mellitus in the BB/W rat. Effects of glucocorticoids, cyclosporin-A, and antiserum to rat lymphocytes.
Combination immunosuppression therapy with long-acting glucocorticoids, cyclosporin-A, and antiserum to rat lymphocytes (ALS) reduced the severity of spontaneous diabetes among BioBreeding/Worcester rats and decreased the frequency of diabetes in susceptible littermates. Combination therapy with glucocorticoids and three injections of ALS reversed hyperglycemia in a significant number of acutely diabetic animals. These results strengthen the hypothesis that autoimmunity plays a role in the pathogenesis of diabetes in these animals and increase our understanding of the requirements of treatment protocols for the prevention and cure of this spontaneous syndrome.


New elastographic classification of breast lesions during and after compression.
Proposal for the classification of breast masses through ultrasound elastography in order to differentiate benign and malignant lesions with histological correlation. 188 patients enrolled for percutaneous biopsy of 228 breast lesions. Elastography was performed and interpreted according to criteria created by the authors, with scores varying from 1 to 4 based on elasticity of images obtained upon release of compression. These results were compared with the histological results; elasticity scores of 1 and 2 were considered benign, a score of 3 as probably benign, and 4 as suspicious for malignancy. Positive predictive value, specificity, and diagnostic accuracy have been calculated. The results were evaluated using Fisher's exact test and the analysis of the receiver operating characteristic (ROC) curve to determine the association with the histological results, and diagnostic accuracy of the proposed classification. The positive predictive value, specificity, and diagnostic accuracy of the scores were 76.5%, 95.9%, and 94.7%, respectively. Of 228 lesions tested, 26 tests yielded true positive results; 8 yielded false positive results; 190 true negative results; and 4 false negative results. There was association with the histological results by the Fisher method (P < 0.05) and an excellent area below the ROC curve of 0.954 (confidence range of 95%, 0.925-0.982). The classification by elastography proposed by the authors can be used as an important tool combined with ultrasonographic studies for differentiating benign and malignant lesions of the breast.


Alternative tobacco product use and smoking cessation among homeless youth in los angeles county.
Approximately 70% of homeless youth smoke cigarettes, but their use of alternative tobacco products (ATPs) is unknown. This paper reports on ATP use among past-month smokers in Los Angeles County, including whether it differs by demographic characteristics, homelessness severity, past-year quit attempts, and readiness to quit smoking. Given the growing popularity of e-cigarettes, we also report on perceptions of harm and reasons for using this product. We surveyed 292 unaccompanied homeless youth who were randomly sampled from street sites. Participants had smoked at least 100 cigarettes during their lifetime and 1 cigarette during the past month. Seventy-two percent of youth reported past-month ATP use (e-cigarettes = 51%; little cigars/cigarillos = 46%; hookah = 31%; other smokeless tobacco product = 24%; chewing tobacco/moist snuff = 19%). Current ATP use was unrelated to most demographic characteristics or having a past-year quit attempt. However, youth who planned to quit smoking in the next 30 days were significantly less likely to report current use of hookahs, other smokeless tobacco products, or e-cigarettes. Among lifetime e-cigarette users, the most common reasons for use included not having to go outside to smoke (38%) and being able to deal with situations or places where they cannot smoke (36%); it was less common to report using e-cigarettes to quit smoking (17%-18%). Dual use of ATPs among homeless youth smokers is common and is more likely among those who have no immediate plans to quit smoking. Effective and easily disseminable strategies for reducing all forms of tobacco use among homeless youth are urgently needed.


Validation of Diagnostic and Performance Characteristics of the Wireless Motility Capsule in Patients With Suspected Gastroparesis.
It is a challenge to make a diagnosis of gastroparesis. There is good agreement in results from wireless motility capsule (WMC) analysis and gastric emptying scintigraphy (GES), but the diagnostic yield of WMC is unclear and the accuracy of this method has not been validated. We compared the performance characteristics of WMC vs GES in assessing gastric emptying in patients with suspected gastroparesis. We performed a prospective study of 167 subjects with gastroparesis (53 with diabetes and 114 without) at 10 centers, from 2013 through 2016. Subjects were assessed simultaneously by GES and with a WMC to measure gastric emptying and regional transit. Delayed gastric emptying by GES was defined as more than 10% meal retention at 4 hrs whereas delayed gastric emptying by WMC was defined as more than 5 hrs for passage of the capsule into the duodenum; a severe delay in gastric emptying was defined as a gastric emptying time of more than 12 hrs by WMC or more than 35% retention at 4 hrs by GES. Rapid gastric emptying was defined as less than 38% meal retention at 1 hr based on by GES or gastric emptying times less than 1:45 hrs by WMC. We compared diagnostic and performance characteristics of GES vs WMC. Delayed gastric emptying was detected in a higher proportion of subjects by WMC (34.6%) than by GES (24.5%) (P=.009). Overall agreement in results between methods was 75.7% (kappa=0.42). In subjects without diabetes, the WMC detected a higher proportion of subjects with delayed gastric emptying (33.3%) than GES (17.1%) (P < .001). A higher proportion of subjects with diabetes had delayed gastric emptying detected by GES (41.7%) compared with non-diabetic subjects (17.1%) (P=.002). Severe delays in gastric emptying were observed in a higher proportion of subjects by WMC (13.8%) than by GES (6.9%) (P = .02). Rapid gastric emptying was detected in a higher proportion of subjects by GES (13.8%) than by WMC (3.3%) (P < .001). Regional and generalized transit abnormalities were observed in 61.8% subjects and only detected by WMC. Although there is agreement in analysis of gastric emptying by GES vs WMC, WMC provides higher diagnostic yield than GES. WMC detects delayed gastric emptying more frequently than GES and identifies extra-gastric transit abnormalities. Diabetic vs non-diabetic subjects have different results from GES vs WMC. These findings could affect management of patients with suspected gastroparesis. ClinicalTrials.gov no: NCT02022826.


Tumor-intrinsic determinants of immunogenic cell death modalities.
The immune system can recognize tumor cells to mount antigen-specific T cell response. Central to the establishment of T cell-mediated adaptive immunity are the inflammatory events that facilitate antigen presentation by stimulating the expression of MHC and costimulatory molecules and the secretion of pro-inflammatory cytokines. Such inflammatory events can be triggered upon cytotoxic treatments that induce immunogenic cancer cell death modalities. However, cancers have acquired a plethora of mechanisms to subvert, or to hide from, host-encoded immunosurveillance. Here, we discuss how tumor intrinsic oncogenic factors subvert desirable intratumoral inflammation by suppressing immunogenic cell death.


Antibacterial Longevity of a Novel Gallium Liquid Metal/Hydroxyapatite Composite Coating Fabricated by Plasma Spray.
Hydroxyapatite (HAp)-coated metallic implants are known for their excellent bioactivity and osteoconductivity. However, infections associated with the microstructure of the HAp coatings may lead to implant failures as well as increased morbidity and mortality. This work addresses the concerns about infections by developing novel composite coatings of HAp and gallium liquid metal (GaLM) using atmospheric plasma spray (APS) as the coating technique. Five weight percent Ga was mixed into a commercially supplied HAp powder using an orbital shaker; then, the HAp-Ga particle feedstock was coated onto Ti6Al4V substrates using the APS technique. The X-ray diffraction results indicated that Ga did not form any Ga-related phases in either the HAp-Ga powder or the respective coating. The GaLM filled the pores of the HAp coating presented both on the top surface and within the coating, especially at voids and cracks, to prevent failures of the coating at these locations. The wettability of the surface was changed from hydrophobic for the HAp coating to hydrophilic for the HAp-Ga composite coating. Finally, the HAp-Ga coating presented excellent antibacterial efficacies against both initial attachments and established biofilms generated from methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa after 18 h and 7 days of incubation in comparison to the control HAp coating. This study shows that GaLM improves the antibacterial properties of HAp-based coatings without sacrificing the beneficial properties of conventional HAp coatings. Thus, the HAp-Ga APS coating is a viable candidate for antibacterial coatings.


National Diet and Nutrition Survey data reveal a decline in folate status in the United Kingdom population between 2008 and 2019.
Folate is essential for healthy growth and development. Fortification of foods with folic acid can improve folate status and reduce risk of neural tube defects (NTD). Following concern around folate status in the United Kingdom, the United Kingdom government announced in 2021 the intention to introduce mandatory folic acid fortification. This study aimed to describe folate status in the United Kingdom population prior to the implementation of mandatory folic acid fortification of non-whole wheat (non-wholemeal) flour and to assess trends in folate status, including in females of reproductive age (FRA). Data were from the United Kingdom National Diet and Nutrition Survey Rolling Program (2008-2019), a cross-sectional, nationally representative survey of children and adults aged 1.5+ (n = 5792 with folate result). Serum folate concentration was measured by liquid chromatography tandem mass spectrometry (LC-MS/MS) and red blood cell (RBC) folate concentration by microbiological assay. Concentration data were compared against method-specific cut-offs and thresholds, and relationships were explored against demographic and lifestyle characteristics. RBC and serum folate concentration significantly decreased by ∼3 percentage points per year between 2008 and 2019 in all age/sex groups. Prevalence of deficiency (RBC folate < 305 nmol/L) was highest in children aged 11 to 18 y (17% in 2016-2019). The proportion of FRA below the cut-off for increased risk of NTD (RBC folate < 748 nmol/L) increased from 69% to 89% between 2008 and 2019. Ethnicity, smoking status, and income were significant determinants of RBC and serum folate concentrations. These data reveal a decline in population folate status in the United Kingdom between 2008 and 2019 and a high prevalence of folate deficiency. A high proportion of FRA had RBC folate concentrations below the cut-off for increased risk of NTD. These data provide information on folate status in a population not currently exposed to mandatory folic acid fortification and are essential to model and assess its impact.


Reliability and validity of depth camera 3D scanning to determine thigh volume.
Gross thigh volume is a key anthropometric variable to predict sport performance and health. Currently, it is either estimated by using the frustum method, which is prone to high inter-and intra-observer error, or using medical imaging, which is expensive and time consuming. Depth camera 3D-imaging systems offer a cheap alternative to measure thigh volume but no between-session reliability or comparison to medical imaging has been made. This experiment established between-session reliability and examined agreement with magnetic resonance imaging (MRI). Forty-eight male cyclists had their thigh volume measured by the depth camera system on two occasions to establish between-session reliability. A subset of 32 participants also had lower body MRIs, through which agreement between the depth camera system and MRI was established. The results showed low between-session variability (CV = 1.7%; Absolute Typical Error = 112 cm3) when measuring thigh volume using the depth camera system. The depth camera systematically measured gross thigh volume 32.6cm3 lower than MRI. These results suggest that depth camera 3D-imaging systems are reliable tools for measuring thigh volume and show good agreement with MRI scanners, providing a cheap and time-saving alternative to medical imaging analysis.


Effect of serum, alpha-1 acid glycoprotein, lipoproteins and albumin on human mononuclear leucocyte beta-adrenoceptors.
The effects of serum, alpha-1 acid glycoprotein (AAG), serum lipoproteins (SLP) and human serum albumin (HSA) on 3H-(-)-dihydroalprenolol (3H-(-)-DHA) binding and (-)-isoproterenol ((-)-IPR) induced cyclic AMP (cAMP) elevation in human peripheral blood mononuclear leucocytes (MNL) were investigated. The saturable binding of 3H-(-)-DHA was decomposed into two classes of binding sites with maximum binding capacity of approximately 1400 and 30000 sites/cell and with dissociation constants (Kd) of approximately 0.7 and 65 nM. Stimulation of the MNL beta-adrenoceptors by (-)-IPR caused a concentration dependent cAMP accumulation (EC50 approximately 0.2 microM) with maximum level approximately 250% above basal. For all single leucocyte preparations, 30-35 min. exposure to serum, AAG and SLP increased the number of beta-adrenoceptors with 100-200% and the maximal responsiveness to (-)-IPR with 30-90%. The presence of proteins did not change the Kd or the EC50. (-)-Alprenolol inhibited concentration dependently the serum induced increment in (-)-IPR-responsiveness. Serum, AAG and SLP did also increase the number of low affinity binding sites with 25-40% without effect on the Kd. HSA had no consistent effect on beta-adrenergic binding or stimulation. The present study shows that serum, AAG and SLP influence the number and function of MNL beta-adrenoceptors in vitro.


Phase effects owing to multilayer coatings in a two-mirror extreme-ultraviolet schwarzschild objective.
The aberrations of a multilayer-coated reflective Schwarzschild objective, which are influenced both by mirror surface profiles and by multilayer coatings, are evaluated with a phase-shifting point diffraction interferometer operating in the extreme ultraviolet. Using wave-front measurements at multiple wavelengths near 13.4 nm, we observed chromatic aberrations and wavelength-dependent transmission changes that were due to molybdenum-silicon multilayer coatings. The effects of chromatic vignetting due to limited multilayer reflection passbands on the imaging performance of the Schwarzschild optic are considered. The coating characteristics extracted from the interferometry data on the two-mirror optical system are compared with previously reported coating properties measured on individual mirror substrates.


Surgery for temporal lobe epilepsy.
Intractable epilepsy is a debilitating disease with significant associated morbidity and mortality. Uncontrolled epilepsy is socially disabling causing stigma, social exclusion, and often preventing employment. After an individual has tried and failed three or four of the standard anticonvulsants, it is very unlikely any further medications or combinations of medications will control the epilepsy. The major Neurology, Neurosurgery, and Epilepsy medical societies recommend all individuals with medically intractable epilepsy be evaluated in a comprehensive epilepsy program. In selected individuals, surgery for epilepsy has tremendous potential to cure or control intractable epilepsy. At West Virginia University Health Sciences Center, 48 individuals underwent surgery for intractable temporal lobe epilepsy over a 2.5 year period. Thirty-five (73%) of individuals were seizure free after surgery, and 96% were seizure free or significantly improved. Surgery for epilepsy has a high likelihood for success in medically intractable temporal lobe epilepsy, and is superior to medical treatment alone.


Examining risk factors for posterior migration of fusion cages following transforaminal lumbar interbody fusion: a possible limitation of unilateral pedicle screw fixation.
Because the authors encountered 4 cases of hardware migration following transforaminal lumbar interbody fusion, a retrospective study was conducted to identify factors influencing the posterior migration of fusion cages. Patients with lumbar degenerative disc disease (125 individuals; 144 disc levels) were treated using transforaminal lumbar interbody fusion and followed for 12-33 months. Medical records and pre- and postoperative radiographs were reviewed, and factors influencing the incidence of cage migration were analyzed. Postoperative cage migration was found in 4 patients at or before 3 months. Because all the cages that migrated postoperatively were bullet-shaped (Capstone), only these cages were analyzed. The analysis of preoperative radiographs revealed that higher posterior disc height ([PDH] > or = 6 mm) significantly increased the incidence of postoperative cage migration, but percent slippage, translation, range of motion, and Cobb angle did not. The incidence of cage migration in patients with unilateral fixation (3 [8.3%] of 36) was not significantly different from that in patients with bilateral fixation (1 [2.1%] of 48). Patients who had scoliotic curvature with a Cobb angle > 10 degrees when treated with unilateral fixation demonstrated a tendency to have more frequent postoperative cage migration than patients treated with bilateral fixation. To examine the influence of the height of fusion cages, a value obtained by subtracting preoperative anterior disc height (ADH) or PDH from cage height was defined as "Cage height - ADH" (or "Cage height -PDH"). The analysis revealed that the value for "Cage height -ADH" as well as "Cage height -PDH" was significantly lower in migrated levels than in nonmigrated levels, suggesting that the choice of undersized cages may increase the incidence of cage migration. The results suggest that the use of a bullet-shaped cage, higher PDH, the presence of scoliotic curvature, and undersized fusion cages are possible risk factors for cage migration. One patient with postoperative cage migration following bilateral screw fixation underwent revision surgery, and the pedicle screw fixation was found to be disrupted. Other than in this patient, cage migration occurred only in those treated by unilateral fixation. The potential for postoperative cage migration and limitations of unilateral fixation should be considered by spine surgeons.


Lead immobilization assisted by fungal decomposition of organophosphate under various pH values.
Organic phosphates (OP) account for approximately 30-90% of total soil P. However, it is too stable to be utilized by plants as available P source. Aspergillus niger (A. niger) has considerable ability to secret phytase to decompose OP. Meanwhile, mineralization of lead (Pb) is efficient to achieve its remediation. This study hence investigated Pb immobilization by A. niger assisted decomposition of OP under variable acidic environments. A. niger can survive in the acidic environment as low as pH = 1.5. However, alternation of environmental pH within 3.5-6.5 significantly changed fungal phytase secretion. In particular, weakly acidic stimulation (pH of ~5.5) increased phytase activity secreted by A. niger to 0.075 µmol/min/mL, hence elevating P release to a maximal concentration of ~20 mg/L. After Pb addition, ATR-IR and TEM results demonstrated the formation of abundant chloropyromorphite [Pb5(PO4)3Cl] mineral on the surface of mycelium at pH = 5.5. Anglesite, with a higher solubility than pyromorphite, was precipitated massively in other treatments with pH lower or higher than 5.5. This study elucidated the great potential of applying OP for Pb immobilization in contaminated water.


Synthesis and antimicrobial activity of certain imidazo[1,2-a]pyrimidines.
A series of 5-substituted and 5,7-disubstituted imidazo[1,2-a]pyrimidines has been prepared. The in vitro antimicrobial activity of these compounds against a variety of microorganisms is reported. 5-n-Octylaminoimidazo[1,2-a]pyrimidine exhibited significant activity against all the microorganisms studied.


A power law of cortical adaptation.
How do neural populations adapt to the time-varying statistics of sensory input? To investigate, we measured the activity of neurons in primary visual cortex adapted to different environments, each associated with a distinct probability distribution over a stimulus set. Within each environment, a stimulus sequence was generated by independently sampling form its distribution. We find that two properties of adaptation capture how the population responses to a given stimulus, viewed as vectors, are linked across environments. First, the ratio between the response magnitudes is a power law of the ratio between the stimulus probabilities. Second, the response directions are largely invariant. These rules can be used to predict how cortical populations adapt to novel, sensory environments. Finally, we show how the power law enables the cortex to preferentially signal unexpected stimuli and to adjust the metabolic cost of its sensory representation to the entropy of the environment.


Prevalence of antibodies to Rickettsiae in different regions of Serbia.
We assayed the presence of antibodies specific for Rickettsia typhi, R. akari, and R. conorii in sera of persons from several localities in Serbia with different geographic, climatic, and lifestyle characteristics. Sera from 140 patients with unclear clinical symptoms and 273 healthy persons were tested for the presence of rickettsiae-specific antibodies by indirect immunofluorescence assay. In this study, for the first time we detected the presence of rickettsiae from the spotted fever group in Serbia. We detected the presence of antibodies against R. conorii in the samples from all tested localities. The proportion of positive cases was low in the plain agricultural areas but reached up to 23% in the mountain areas. We also observed a significant number of cases positive for antibodies against R. akari. Antibodies specific for the antigens of R. typhi were detected in only 2 samples from the municipality of Pec (Kosovo region). These findings contribute to the prevalence of Rickettsia species in Southeast Europe. Our study also revealed a dramatic lack of awareness of rickettsioses among medical personnel and pointed to the need for urgent measures that would help improve the current situation in the region.


Endoscopic Ultrasound-Guided Celiac Plexus Neurolysis in Pancreatic Cancer: A Prospective Pilot Study of Safety Using 10 mL versus 20 mL Alcohol.
Background. The dose of alcohol used in EUS-CPN is not standardized. The objective was to compare the safety of 20 mL alcohol versus 10 mL alcohol during EUS-CPN for patients with pancreatic cancer-related pain. Methods. 20 patients were selected to receive 10 mL or 20 mL of alcohol during EUS-CPN. Followup was done at baseline, 24 hours, and weekly. Health-related quality of life (HRQoL) was assessed at baseline, week 2, week 4, and every 4 weeks thereafter until pain returned. Results. There were no major complications in both groups. Minor self-limited adverse effects were seen in 6 (30%) subjects and included lightheadedness in 1 (5%), transient diarrhea in 2 (10%), and transient nausea and vomiting in 3. Pain relief was similar in both groups: 80% in the 10 mL group and 100% in the 20 mL group (P = 0.21). The mean (± SD) duration of pain relief in the 10 mL and 20 mL groups was 7.9 ± 10.8 and 8.4 ± 9.2 weeks, respectively. 30% of patients in each group had complete pain relief. Conclusions. EUS-CPN using 20 mL of alcohol is safe. Similar clinical outcomes were seen in both groups. Further investigations to confirm these findings are warranted.


The effect of maternal exposure to psychosocial job strain on pregnancy outcomes and child development.
Psychological stress at work is a rising problem in Denmark. Nearly one third of the women reported in 2005 that they had difficulties completing their work tasks, and 17 % found that they had only limited or no influence on their work tasks. The corresponding numbers for 1987 were 18.3 % and 16 %, respectively. Work-related stress shortens the life expectancy and reduces the number of years without prolonged disease. For the society work-related stress amounts to more than 30,000 hospital admissions each year, half a million extra days on sick-leave for women, 500,000 contacts to general practitioners, 1600 early retirements for women, and an overuse of the health-care system. With the second highest employment rate in Europe for women - and many of them in the childbearing age - effects of psychological stress at work may extend beyond the exposed individual and affect pregnancy, birth and health of the child. Few studies on job stress relative to pregnancy have been carried out, but both animal and epidemiological studies have shown effect of exposure to stressful conditions during pregnancy and adverse effects on the offspring. The specific aims for the three studies included in this thesis were to investigate the association between maternal psychosocial job strain during pregnancy, measured as high demands and low control and the risk of: - Having a child born preterm or with low or high birth weight relative to gestational week (paper I + II) - Congenital malformations in offspring (paper III) - Asthma and atopic dermatitis in the children (paper IV). Furthermore, it was also the ambition to maximize and secure the quality of research and integrity of the data used by documenting the methods in a protocol that described the analyses before they were done and to keep transparency in the methods used following good epidemiological practices (GEP) for occupational and environmental epidemiological research. All analyses in this thesis are based on information and data from the Danish National Birth Cohort (DNBC). The cohort was established in 1994 and baseline information from the enrolled 100,418 pregnancies was gathered from 1996 to 2002. At their first antenatal visit pregnant women were invited to participate in the cohort by their general practitioner. To contribute the women had to be pregnant, have intentions of carrying the pregnancy to term, reside in Denmark and speak Danish sufficiently well to participate in telephone interviews. When enrolled the women were asked to participate in two telephone interviews during pregnancy at approximately 12-14 and 30-32 weeks of gestation and two after birth when the child was six and 18 months old and a follow-up questionnaire at age seven years. Exposure to work-related stress was assessed based on information from the first interview on two questions regarding job control and job demands. These questions were interpreted as dimensions of demands and control, and hereafter used as a proxy for the dimensions of the job strain model by Karasek. Based on their answers, the women were divided into the four job strain categories: high strain, active, passive and low strain. Gestational age at birth, birthweight and congenital malformations were extracted from the Danish Medical Birth Register. The outcome variable on asthma and atopic dermatitis were based on maternal self-reports from the fourth (child 18 months) and fifth (child seven years old) interviews/questionnaires. All studies in the thesis were based on protocols describing methods, analyses etc. prior to handling. No associations were found between exposure to high strain (high demands, low control) during pregnancy and preterm birth, small for gestational age, congenital malformations and asthma in the children when compared to women exposed to low strain (low demands, high control). A protective effect on large for gestational age was observed when exposed to high strain, suggesting an impact on the birthweight although it was not seen among the small for gestational age children. An association between high strain exposure and ever atopic dermatitis in seven-year-old children was observed, with 15% higher odds of atopic dermatitis when compared to women exposed to low strain during their pregnancy. The effects of high strain found were modest, but even modest effects might be relevant with high prevalence as with atopic dermatitis (lifetime prevalence of 15-20%). The studies included in this thesis add to the rather limited knowledge of prenatal exposure to work-related stress end health implications for the child. In the Danish work environment recommendations for women being pregnant or breastfeeding work-related stress is only mentioned very briefly. Findings from this thesis do not support rewriting in regards to risk of preterm birth, low birth weight or malformations. Results did show effects in regards to allergic diseases, but as the study is the only one of its kind, other studies are needed to replicate the findings if to reconsider the recommendations for pregnant women. Future research could benefit of validation of the use of two single-item measures of job strain compared to fully validated multi-item instruments. A shift toward more "functional endpoints" as overweight and cognitive behavioural disorders in the children could be of relevance.


Unraveling Mechanisms of Patient-Specific NRXN1 Mutations in Neuropsychiatric Diseases Using Human Induced Pluripotent Stem Cells.
Rare heterozygous deletions in the neurexin 1 (NRXN1) gene robustly increase an individual's risk of developing neurological and psychiatric disorders. However, the molecular bases by which different mutations result in different clinical presentations, with variable penetrance, are unknown. To better understand the molecular and cellular consequences of heterozygous NRXN1 mutations, Flaherty and colleagues studied how patient mutations influence the NRXN1 isoform repertoire and neuronal phenotypes using induced pluripotent stem (iPS) cells. Advancing from disease association to mechanistic insights, the authors provide insight into how patient mutations might impinge on neuronal function. This research highlights the value of iPS cells for elucidating otherwise elusive links between molecular and neuronal function. In addition, they provide further evidence of the importance of alternative splicing in the pathophysiology of neuropsychiatric diseases.


Option generation in decision making: ideation beyond memory retrieval.
According to prescriptive decision theories, the generation of options for choice is a central aspect of decision making. A too narrow representation of the problem may indeed limit the opportunity to evaluate promising options. However, despite the theoretical and applied significance of this topic, the cognitive processes underlying option generation are still unclear. In particular, while a cued recall account of option generation emphasizes the role of memory and executive control, other theoretical proposals stress the importance of ideation processes based on various search and thinking processes. Unfortunately, relevant behavioral evidence on the cognitive processes underlying option generation is scattered and inconclusive. In order to reach a better understanding, we carried out an individual-differences study employing a wide array of cognitive predictors, including measures of episodic memory, semantic memory, cognitive control, and ideation fluency. The criterion tasks consisted of three different poorly-structured decision-making scenarios, and the participants were asked to generate options to solve these problems. The main criterion variable of the study was the number of valid options generated, but also the diversity and the quality of generated options were examined. The results showed that option generation fluency and diversity in the context of ill-structured decision making are supported by ideation ability even after taking into account the effects of individual differences in several other aspects of cognitive functioning. Thus, ideation processes, possibly supported by search and thinking processes, seem to contribute to option generation beyond basic associative memory retrieval. The findings of the study also indicate that generating more options may have multifaceted consequences for choice, increasing the quality of the best option generated but decreasing the mean quality of the options in the generated set.


Low myocardial protein kinase G activity in heart failure with preserved ejection fraction.
Prominent features of myocardial remodeling in heart failure with preserved ejection fraction (HFPEF) are high cardiomyocyte resting tension (F(passive)) and cardiomyocyte hypertrophy. In experimental models, both reacted favorably to raised protein kinase G (PKG) activity. The present study assessed myocardial PKG activity, its downstream effects on cardiomyocyte F(passive) and cardiomyocyte diameter, and its upstream control by cyclic guanosine monophosphate (cGMP), nitrosative/oxidative stress, and brain natriuretic peptide (BNP). To discern altered control of myocardial remodeling by PKG, HFPEF was compared with aortic stenosis and HF with reduced EF (HFREF). Patients with HFPEF (n=36), AS (n=67), and HFREF (n=43) were free of coronary artery disease. More HFPEF patients were obese (P<0.05) or had diabetes mellitus (P<0.05). Left ventricular myocardial biopsies were procured transvascularly in HFPEF and HFREF and perioperatively in aortic stenosis. F(passive) was measured in cardiomyocytes before and after PKG administration. Myocardial homogenates were used for assessment of PKG activity, cGMP concentration, proBNP-108 expression, and nitrotyrosine expression, a measure of nitrosative/oxidative stress. Additional quantitative immunohistochemical analysis was performed for PKG activity and nitrotyrosine expression. Lower PKG activity in HFPEF than in aortic stenosis (P<0.01) or HFREF (P<0.001) was associated with higher cardiomyocyte F(passive) (P<0.001) and related to lower cGMP concentration (P<0.001) and higher nitrosative/oxidative stress (P<0.05). Higher F(passive) in HFPEF was corrected by in vitro PKG administration. Low myocardial PKG activity in HFPEF was associated with raised cardiomyocyte F(passive) and was related to increased myocardial nitrosative/oxidative stress. The latter was probably induced by the high prevalence in HFPEF of metabolic comorbidities. Correction of myocardial PKG activity could be a target for specific HFPEF treatment.


Effect of acupuncture and moxibustion on intestinal flora in the rats with diarrhea-predominant irritable bowel syndrome based on 16S rDNA technique.
To explore the effect of acupuncture and moxibustion on intestinal flora in the rats with diarrhea-predominant irritable bowel syndrome (IBS-D) based on 16S rDNA technique. Ten rats were randomized from 58 SPF-grade male SD rats to be the blank group. The remained 48 rats were prepared to be IBS-D models by the modified method of acetic acid enema combined with binding tail-clip stress. Forty successfully-modeled rats were randomly divided into a model group, an acupuncture group, a moxibustion group and a western medication group, with 10 rats in each one. In the acupuncture group, the needle was inserted at bilateral "Zusanli" (ST 36) and remained for 15 min in each rat. In the moxibustion group, the suspending moxibustion was delivered at bilateral "Zusanli" (ST 36) for 15 min. The rats in the western medication group were given pinaverium bromide suspension (10 mL/kg) by intragastric administration. The above interventions were performed once daily for consecutive 14 days. The body mass and the score of fecal trait were compared before and after modeling, as well as after intervention in each group. Fecal water content, diarrhea index and colon transit time (CTT) were measured after modeling and intervention in the rats of each group separately. After intervention, the colonic morphology of rats in each group was observed, and using 16S rDNA technique, the intestinal flora was detected. After modeling, compared with the blank group, the body mass and CTT were reduced (P<0.01); fecal trait scores, fecal water contents and diarrhea index increased (P<0.01) in the other 4 groups. After intervention, the body mass and CTT of the rats decreased (P<0.01), and fecal trait score, fecal water content and diarrhea index increased (P<0.01) in the model group compared with those in the blank group. In the acupuncture group, the moxibustion group and the western medication group, when compared with the model group, the body mass and CTT were elevated (P<0.01), while fecal trait scores, fecal water contents and diarrhea index declined (P<0.01). Compared with the western medication group, fecal water content decreased in the acupuncture group and the moxibustion group (P<0.05), while CTT increased in the acupuncture group (P<0.01), the body mass increased and fecal trait score was dropped in the moxibustion group (P<0.05). The colonic mucosa structure was clear and complete, and there was no obvious inflammatory cell infiltration in the blank group. The mild interstitial edema of intestinal mucosa was presented with the infiltration of few inflammatory cells in the model group. There was the infiltration of few inflammatory cells in the mucosa of the acupuncture group, the moxibustion group and the western medication group. Compared with the blank group, the indexes of Richness, Chao1, ACE and Shannon decreased in the model group (P<0.05). Indexes of Richness, Chao1 and ACE increased in the acupuncture group and the moxibustion group (P<0.05), and the Richness index in the western medication group increased (P<0.05) when compared with those in the model group. The relative abundance of Bacteroidetes, Proteobacteria and Prevotella increased (P<0.05), and that of Firmicutes and Muribaculaceae decreased (P<0.05) in the model group compared with those in the blank group. When compared with the model group, the relative abundance of Bacteroidetes, Proteobacteria and Prevotella was reduced (P<0.05), while that of Firmicutes and Muribaculaceae increased (P<0.05) in the acupuncture group, the moxibustion group and the western medication group; and that of Actinobacteria and Bifidobacterium increased in the acupuncture group and the moxibustion group (P<0.05). Compared with the blank group, the relative abundance of lipopolysaccharide (LPS) biosynthesis was elevated (P<0.05), and that of folate biosynthesis, lipoic acid metabolism, zeatin biosynthesis, ubiquinone and other terpenoid quinone biosynthesis decreased (P<0.05) in the model group. The relative abundance of LPS biosynthesis was dropped (P<0.05), and that of folate biosynthesis, lipoic acid metabolism, zeatin biosynthesis, ubiquinone and other terpenoid quinone biosynthesis increased (P<0.05) in the acupuncture group, the moxibustion group and the western medication group compared with those of the model group. Either acupuncture or moxibustion can relieve the symptoms of IBS-D and protect intestinal mucosa, which may be associated with regulating the structure of intestinal flora and promoting nutrient metabolism and biosynthesis.


From human wrongs to universal rights: communication and feminist challenges for the promotion of women's health in the Third World.
This article argues that in the quest for global bioethics in its relation to the promotion of women's health and women's rights, the main challenge is to, first, rise above the relativist trap and second, to solve the false dilemma between individualism and collectivism. Particularly in order to improve women's position and advance their well-being in many developing countries with patriarchal cultural practices, there is an urgent need to introduce modern medicine and to share more evenly and efficiently the health care resources of the industrialized societies. This presumes that we can find a normative bioethical approach that promotes the rights of individuals without striving for cultural assimilation and disrespect. From the philosophical point of view this means that we have to overcome the debate between the rival views of justice, and rather find the shared features of the various approaches, thus diminishing the exaggerated polarizations between them. The author claims that despite its importance in women's rights protection, feminist bioethics cannot remain as a normative alternative that can replace either liberal or communitarian approaches. Instead feminism needs to be part of both liberal and communitarian ethical thinking. Communitarianism, for its part, cannot offer an alternative to either liberalism or feminism, but it can function as an essential critical balancing force within these approaches. Individualist liberalism, on the other hand, has to find its way into collective social structures and accept their maintenance, instead of exhausting itself in its attempts to lift individuals above or beyond their social contexts. All in all, the article shows that in finding the global bioethical norms the incompatibility between universalist and relativist reasoning or between individualist and collective ethical positions per se is not the main problem. Rather the problem is in our persistent tendency to believe that such an incompatibility exists. However, if we overcome the debate on whether one cultural background is superior to another, we can find a way to agree on some common norms that are based on shared values of very different traditions. Finding globally acceptable values, however, is not enough unless we pay more attention to their promotion in practice, in very different economic, social and political circumstances.


Risk of tuberculosis reactivation with rituximab therapy.
Tuberculosis (TB) is one of the world's deadliest diseases, and one-third of the world's population is infected with it. The link between antitumor necrosis factor therapy and reactivation of latent TB is well recognized. However, only limited studies have evaluated the risk of TB with rituximab, a B-cell-targeting therapeutic agent used recently for rheumatological diseases, primarily rheumatoid arthritis. Moreover, no studies have assessed this risk in TB endemic regions with a high incidence and prevalence of TB (e.g., Saudi Arabia). To examine the risk of acquiring TB or activating latent TB in adult patients with rheumatological disease who received rituximab therapy. Retrospective cohort study included 60 patients at King Faisal Specialist Hospital and Research Centre, Saudi Arabia, between October 1, 2010, and March 31, 2011. Six patients (10%) were subsequently excluded because of the treatment for latent TB (5 patients) or prior treatment for TB (1 patient). The follow-up period was 6 months for 53 patients (98.15%) and 3 months for 1 patient (1.85%). During follow-up, none of the patients received the purified protein derivative skin test while radiological studies were performed for 30 patients (55.55%). 53 patients (98.15%) had no symptoms suggestive of TB upon follow-up, and no patient experienced a TB flare-up. Rituximab can be considered a first line of therapy for the management of rheumatological diseases in the presence of the risk of TB reactivation, especially in endemic areas with a high prevalence and incidence of TB.


Signal Detection and Assessment of Herb-Drug Interactions: Saudi Food and Drug Authority Experience.
Numerous investigations on herbal medicine that have been undertaken in the past several years demonstrate the general acceptance of its safety. The Saudi Food and Drug Authority (SFDA) established the Herb-Drug Interaction (HDI) project to detect and assess potential HDIs to ensure safety. The aim is to detect safety signals and assess them based on available evidence. First, SFDA-registered herbal products (n = 30) were selected and prioritized based on commonly used herbs. Second, reported potential HDIs were retrieved from the World Health Organization global database of individual case safety reports (VigiBase), AdisInsight®, and the Natural Medicines database. We excluded drugs non-registered by SFDA and labeled interactions in the product information of SFDA, the US Food and Drug Administration (FDA), and the European Medicines Agency (EMA). Finally, a comprehensive evaluation of potential HDIs was carried out using several evidence sources: literature, global cases, local cases, and other relevant documents. The Drug Interaction Probability Scale (DIPS) scale was used to assess the probability of a causal relationship between the interacting herb and drug and the event. The search yielded 566 potential signals, and 41 had published evidence and were referred for assessment. The assessment results using DIPS were: 22 possible (53.6 %), 7 probable (17%), and 12 doubtful (29.2%) interactions. The recommendation was to include probable HDIs in the product information, including turmeric-tacrolimus, etoposide-Echinacea, Ginkgo biloba-ibuprofen, green tea-warfarin, and licorice-thiazides interactions. The HDI project assessed the screening and identification of potential HDIs. The action plan of this project can be used in post-marketing activities to identify potential drug interactions.


Superior mesenteric artery syndrome: CT and ultrasonography findings.
The purpose of the study was to describe computed tomography (CT) and ultrasonography findings in superior mesenteric artery syndrome (SMAS). The study was performed on 89 CT examinations. Ultrasonography was performed on 32 and barium study was performed on four of these subjects. Group A consisted of cases with one or more of the following complaints: postprandial epigastric pain, weight loss and vomiting. Group B consisted of the remaining cases. Cases who had all of the above-mentioned clinical findings and duodenal dilatation, to-and-fro barium movement and SMA indentation in barium study were diagnosed as having SMAS. Body mass index (BMI, kg/m2) was calculated. The distance between SMA and aorta, at the location where the duodenum passes from, was measured on CT and ultrasonography. The angle between SMA and aorta was measured on ultrasonography images. Group and gender differences were analyzed with t-test, the relationship between clinical and CT findings was analyzed with Mann Whitney U test and the relations between BMI-CT and CT-ultrasonography measurements were analyzed with Pearson coefficients. Of 13 cases in Group A, 3 were diagnosed as SMAS. Eight of the cases showed gastric and/or duodenal dilatation. In 6 cases, antrum had an abnormally high location at portal hilus. In Group A, the SMA-aorta distance was 6.6 +/- 1.5 mm and the SMA-aorta angle was 18.7 +/- 10.7 degrees . In Group B, these values were 16.0 +/- 5.6 mm and 50.9 +/- 25.4 degrees , respectively (p < 0.001). Cut-off values between SMAS and Group B were 8 mm (100% sensitivity and specificity), and 22 degrees (42.8% sensitivity, 100 % specificity). CT and ultrasonography measurements (p < 0.001) and SMA-aorta distance and BMI (p=0.004) were significantly correlated. The SMA-aorta distance was significantly shorter in females (p=0.036). Gastric and/or duodenal dilatation and a diminished SMA-aorta distance have a significant correlation with clinical symptoms of SMAS that include postprandial pain, vomiting and weight loss.


Computer-generated reminders delivered on paper to healthcare professionals; effects on professional practice and health care outcomes.
Clinical practice does not always reflect best practice and evidence, partly because of unconscious acts of omission, information overload, or inaccessible information. Reminders may help clinicians overcome these problems by prompting the doctor to recall information that they already know or would be expected to know and by providing information or guidance in a more accessible and relevant format, at a particularly appropriate time. To evaluate the effects of reminders automatically generated through a computerized system and delivered on paper to healthcare professionals on processes of care (related to healthcare professionals' practice) and outcomes of care (related to patients' health condition). For this update the EPOC Trials Search Co-ordinator searched the following databases between June 11-19, 2012: The Cochrane Central Register of Controlled Trials (CENTRAL) and Cochrane Library (Economics, Methods, and Health Technology Assessment sections), Issue 6, 2012; MEDLINE, OVID (1946- ), Daily Update, and In-process; EMBASE, Ovid (1947- ); CINAHL, EbscoHost (1980- ); EPOC Specialised Register, Reference Manager, and INSPEC, Engineering Village. The authors reviewed reference lists of related reviews and studies. We included individual or cluster-randomized controlled trials (RCTs) and non-randomized controlled trials (NRCTs) that evaluated the impact of computer-generated reminders delivered on paper to healthcare professionals on processes and/or outcomes of care. Review authors working in pairs independently screened studies for eligibility and abstracted data. We contacted authors to obtain important missing information for studies that were published within the last 10 years. For each study, we extracted the primary outcome when it was defined or calculated the median effect size across all reported outcomes. We then calculated the median absolute improvement and interquartile range (IQR) in process adherence across included studies using the primary outcome or median outcome as representative outcome. In the 32 included studies, computer-generated reminders delivered on paper to healthcare professionals achieved moderate improvement in professional practices, with a median improvement of processes of care of 7.0% (IQR: 3.9% to 16.4%). Implementing reminders alone improved care by 11.2% (IQR 6.5% to 19.6%) compared with usual care, while implementing reminders in addition to another intervention improved care by 4.0% only (IQR 3.0% to 6.0%) compared with the other intervention. The quality of evidence for these comparisons was rated as moderate according to the GRADE approach. Two reminder features were associated with larger effect sizes: providing space on the reminder for provider to enter a response (median 13.7% versus 4.3% for no response, P value = 0.01) and providing an explanation of the content or advice on the reminder (median 12.0% versus 4.2% for no explanation, P value = 0.02). Median improvement in processes of care also differed according to the behaviour the reminder targeted: for instance, reminders to vaccinate improved processes of care by 13.1% (IQR 12.2% to 20.7%) compared with other targeted behaviours. In the only study that had sufficient power to detect a clinically significant effect on outcomes of care, reminders were not associated with significant improvements. There is moderate quality evidence that computer-generated reminders delivered on paper to healthcare professionals achieve moderate improvement in process of care. Two characteristics emerged as significant predictors of improvement: providing space on the reminder for a response from the clinician and providing an explanation of the reminder's content or advice. The heterogeneity of the reminder interventions included in this review also suggests that reminders can improve care in various settings under various conditions.


Monomeric Polyglutamine Structures That Evolve into Fibrils.
We investigate the solution and fibril conformations and structural transitions of the polyglutamine (polyQ) peptide, D2Q10K2 (Q10), by synergistically using UV resonance Raman (UVRR) spectroscopy and molecular dynamics (MD) simulations. We show that Q10 adopts two distinct, monomeric solution conformational states: a collapsed β-strand and a PPII-like structure that do not readily interconvert. This clearly indicates a high activation barrier in solution that prevents equilibration between these structures. Using metadynamics, we explore the conformational energy landscape of Q10 to investigate the physical origins of this high activation barrier. We develop new insights into the conformations and hydrogen bonding environments of the glutamine side chains in the PPII and β-strand-like conformations in solution. We also use the secondary structure-inducing cosolvent, acetonitrile, to investigate the conformations present in low dielectric constant solutions with decreased solvent-peptide hydrogen bonding. As the mole fraction of acetonitrile increases, Q10 converts from PPII-like structures into α-helix-like structures and β-sheet aggregates. Electron microscopy indicates that the aggregates prepared from these acetonitrile-rich solutions show morphologies similar to our previously observed polyQ fibrils. These aggregates redissolve upon the addition of water! These are the first examples of reversible fibril formation. Our monomeric Q10 peptides clearly sample broad regions of their available conformational energy landscape. The work here develops molecular-level insight into monomeric Q10 conformations and investigates the activation barriers between different monomer states and their evolution into fibrils.


Biomolecular Piezoelectric Materials: From Amino Acids to Living Tissues.
Biomolecular piezoelectric materials are considered a strong candidate material for biomedical applications due to their robust piezoelectricity, biocompatibility, and low dielectric property. The electric field has been found to affect tissue development and regeneration, and the piezoelectric properties of biological materials in the human body are known to provide electric fields by pressure. Therefore, great attention has been paid to the understanding of piezoelectricity in biological tissues and its building blocks. The aim herein is to describe the principle of piezoelectricity in biological materials from the very basic building blocks (i.e., amino acids, peptides, proteins, etc.) to highly organized tissues (i.e., bones, skin, etc.). Research progress on the piezoelectricity within various biological materials is summarized, including amino acids, peptides, proteins, and tissues. The mechanisms and origin of piezoelectricity within various biological materials are also covered.


EAACI position paper on diet diversity in pregnancy, infancy and childhood: Novel concepts and implications for studies in allergy and asthma.
To fully understand the role of diet diversity on allergy outcomes and to set standards for conducting research in this field, the European Academy of Allergy and Clinical Immunology Task Force on Diet and Immunomodulation has systematically explored the association between diet diversity and allergy outcomes. In addition, a detailed narrative review of information on diet quality and diet patterns as they pertain to allergic outcomes is presented. Overall, we recommend that infants of any risk category for allergic disease should have a diverse diet, given no evidence of harm and some potential association of benefit in the prevention of particular allergic outcomes. In order to harmonize methods for future data collection and reporting, the task force members propose relevant definitions and important factors for consideration, when measuring diet diversity in the context of allergy. Consensus was achieved on practice points through the Delphi method. It is hoped that the definitions and considerations described herein will also enable better comparison of future studies and improve mechanistic studies and pathway analysis to understand how diet diversity modulates allergic outcomes.


[Somatic and pharmacological nurse care in 2b-teams in Flanders: a cross-sectional explorative study].
In the context of the Belgian mental health care reform (project 107), 2b-teams provide care to people with a serious mental illness (smi), a population encountering regular somatic comorbidity and limited compliance with medication. Team composition and care provided by these teams is rather unclear.
 AIM: To consider the team composition and to focus on the nurses' role within Flemish 2b-teams. Also, seen from different disciplines involved, to determine the desired future nursing role.
 METHOD: A structured interview was used to discover team characteristics and fidelity to the flexible assertive community treatment (fact) model in 12 Flemish 2b-teams. With a digital survey containing 16 questions we explored the actual and desired nursing care, according to 151 nurses and medical physicians.
 RESULTS: Despite the difference in team size and composition, it was not found to be significant. Flemish team's fact model-fidelity was average. Actual care was restricted to psychosocial interventions. Regarding desired care, significant differences were found between physicians and nurses. Caregivers within outreach teams scored items significantly higher on desired care compared to actual care.
 CONCLUSION: We conclude that the team composition of Flemish 2b-team varies, with an average fact model fidelity. Team care is restricted to psychosocial interventions, while more somatic and nursing care is desired.