Predicting fear and perceived health during the COVID-19 pandemic using machine learning: A cross-national longitudinal study.
During medical pandemics, protective behaviors need to be motivated by effective communication, where finding predictors of fear and perceived health is of critical importance. The varying trajectories of the COVID-19 pandemic in different countries afford the opportunity to assess the unique influence of 'macro-level' environmental factors and 'micro-level' psychological variables on both fear and perceived health. Here, we investigate predictors of fear and perceived health using machine learning as lockdown restrictions in response to the COVID-19 pandemic were introduced in Austria, Spain, Poland and Czech Republic. Over a seven-week period, 533 participants completed weekly self-report surveys which measured the target variables subjective fear of the virus and perceived health, in addition to potential predictive variables related to psychological factors, social factors, perceived vulnerability to disease (PVD), and economic circumstances. Viral spread, mortality and governmental responses were further included in the analysis as potential environmental predictors. Results revealed that our models could accurately predict fear of the virus (accounting for approximately 23% of the variance) using predictive factors such as worrying about shortages in food supplies and perceived vulnerability to disease (PVD), where interestingly, environmental factors such as spread of the virus and governmental restrictions did not contribute to this prediction. Furthermore, our results revealed that perceived health could be predicted using PVD, physical exercise, attachment anxiety and age as input features, albeit with smaller effect sizes. Taken together, our results emphasize the importance of 'micro-level' psychological factors, as opposed to 'macro-level' environmental factors, when predicting fear and perceived health, and offer a starting point for more extensive research on the influences of pathogen threat and governmental restrictions on the psychology of fear and health.


Bioinspired Supercharging of Photoredox Catalysis for Applications in Energy and Chemical Manufacturing.
For more than a decade, photoredox catalysis has been demonstrating that when photoactive catalysts are irradiated with visible light, reactions occur under milder, cheaper, and environmentally friendlier conditions. Furthermore, this methodology allows for the activation of abundant chemicals into valuable products through novel mechanisms that are otherwise inaccessible. The photoredox approach, however, has been primarily used for pharmaceutical applications, where its implementation has been highly effective, but typically with a more rudimentary understanding of the mechanisms involved in these transformations. From a global perspective, the manufacture of everyday chemicals by the chemical industry as a whole currently accounts for 10% of total global energy consumption and generates 7% of the world's greenhouse gases annually. In this context, the Bio-Inspired Light-Escalated Chemistry (BioLEC) Energy Frontier Research Center (EFRC) was founded to supercharge the photoredox approach for applications in chemical manufacturing aimed at reducing its energy consumption and emissions burden, by using bioinspired schemes to harvest multiple electrons to drive endothermically uphill chemical reactions. The Center comprises a diverse group of researchers with expertise that includes synthetic chemistry, biophysics, physical chemistry, and engineering. The team works together to gain a deeper understanding of the mechanistic details of photoredox reactions while amplifying the applications of these light-driven methodologies.In this Account, we review some of the major advances in understanding, approach, and applicability made possible by this collaborative Center. Combining sophisticated spectroscopic tools and photophysics tactics with enhanced photoredox reactions has led to the development of novel techniques and reactivities that greatly expand the field and its capabilities. The Account is intended to highlight how the interplay between disciplines can have a major impact and facilitate the advance of the field. For example, techniques such as time-resolved dielectric loss (TRDL) and pulse radiolysis are providing mechanistic insights not previously available. Hypothesis-driven photocatalyst design thus led to broadening of the scope of several existing transformations. Moreover, bioconjugation approaches and the implementation of triplet-triplet annihilation mechanisms created new avenues for the exploration of reactivities. Lastly, our multidisciplinary approach to tackling real-world problems has inspired the development of efficient methods for the depolymerization of lignin and artificial polymers.


Evaluation of the efficacy of the modified bluegrass appliance in cessation of thumb-sucking habit: an in vivo study with 12 months follow-up.
Blue grass appliance, also known as habit correction roller has gained universal attention and acceptance to correct thumb sucking habit. The present study utilizes the modified bluegrass appliance that was fabricated with an inexpensive acrylic roller to lower the cost of treatment and make it more affordable for the patients in developing countries. The purpose of this study was to evaluate the efficacy of the modified bluegrass appliance in cessation of thumb-sucking habit. Forty children aged 4-14 years visiting our department for the treatment of thumb sucking habit were selected. A modified bluegrass appliance having an acrylic roller was used along with the positive reinforcement. The patients were followed-up after two weeks of appliance placement and then monthly for twelve months. The various factors like need of reinsertion, discomfort caused due to improper placement or distortion, and/or breakages of the appliance following insertion were evaluated. The cessation of the thumb sucking habit was determined by the patient and/or parental/legal guardian confirmation and disappearance of the callous formation on the thumb. However, the total treatment time was determined when the appliance was removed. Of the total 33 patients included in the final analysis, the treatment was successful in 32 (97%) of the patients. The treatment time for the cessation of habit was ≤ 4 weeks in 13 (40.6 %) patients and 5-20 weeks in 50% of the subjects. Conversely, in 2 (6.3%) of the patients the habit ceased after 21-24 weeks and in 1 (3.1%) patients it took 25-28 weeks for the habit to cease. The appliance had to be reinserted during the treatment in 5 (15.7%) out of the total 32 patients. The total treatment time for the cessation of thumb-sucking habit with modified bluegrass appliance was ≤24 weeks in 17 (53.1%) patients, 25-36 weeks in 34.4% and 37-48 weeks for the 12.5% subjects. The modified bluegrass appliance was found to be highly comfortable and cost saving for the patients and very much successful in eliminating the habit within a short period of time without any complications.


Long-term prostate cancer survivors with low socioeconomic status reported worse mental health-related quality of life in a population-based study.
To explore whether socioeconomic status (SES) was associated with health-related quality of life (HRQL) and health care use among long-term prostate cancer survivors. Through urologists in the Comprehensive Cancer Center South, all 5- to 10-year prostate cancer survivors known in the Eindhoven Cancer Registry without disease progression were invited to complete the 36-item Short Form Health Survey (SF-36), the Expanded Prostate Cancer Index, and the Dutch sexual activities module. Multivariate linear regression assessed the effect of SES (based on home value and household income) on HRQL and health care use. Five-hundred eighty-four patients (response rate 81%) were included. Survivors with a low SES exhibited lower mental SF-36 scores (6-16 points on a 0-100 scale), independent of sociodemographic and clinical characteristics (P < .05), and hardly any differences in physical SF-36 subscales, sexual function, and urinary and bowel function and bother. Presence of serious comorbidity had a stronger predictive value for HRQL than SES. Health care use did not seem to be associated with SES. Prostate cancer survivors with a low SES exhibited a worse mental but not physical HRQL than those with a higher SES. Long-term health outcomes of patients with low SES may be maximized by paying extra attention to comorbid conditions.


A cell-cycle independent role for p21 in regulating synovial fibroblast migration in rheumatoid arthritis.
Rheumatoid arthritis (RA) is characterized by synovial hyperplasia and destruction of cartilage and bone. The fibroblast-like synoviocyte (FLS) population is central to the development of pannus by migrating into cartilage and bone. We demonstrated previously that expression of the cell cycle inhibitor p21 is significantly reduced in RA synovial lining, particularly in the FLS. The aim of this study was to determine whether reduced expression of p21 in FLS could alter the migratory behavior of these cells. FLS were isolated from mice deficient in p21 (p21(-/-)) and were examined with respect to growth and migration. p21(-/-) and wild-type (WT) FLS were compared with respect to migration towards chemoattractants found in RA synovial fluid in the presence and absence of cell cycle inhibitors. Restoration of p21 expression was accomplished using adenoviral infection. As anticipated from the loss of a cell cycle inhibitor, p21(-/-) FLS grow more rapidly than WT FLS. In examining migration towards biologically relevant RA synovial fluid, p21(-/-) FLS display a marked increase (3.1-fold; p < 0.05) in migration compared to WT cells. Moreover, this effect is independent of the cell cycle since chemical inhibitors that block the cell cycle have no effect on migration. In contrast, p21 is required to repress migration as restoration of p21 expression in p21(-/-) FLS reverses this effect. Taken together, these data suggest that p21 plays a novel role in normal FLS, namely to repress migration. Loss of p21 expression that occurs in RA FLS may contribute to excessive invasion and subsequent joint destruction.


Spectroscopic and computational studies of the ATP:corrinoid adenosyltransferase (CobA) from Salmonella enterica: insights into the mechanism of adenosylcobalamin biosynthesis.
CobA from Salmonella enterica is a member of an enzymatic system responsible for the de novo biosynthesis of adenosylcobalamin (AdoCbl), catalyzing the formation of the essential Co-C bond by transferring the adenosyl group from a molecule of ATP to a transient Co(1+)corrinoid species generated in the enzyme active site. A particularly fascinating aspect of this reaction is that the flavodoxin in vivo reducing agent that serves as the electron donor to CobA possesses a reduction potential that is considerably more positive than that of the Co(2+/1+) couple of the corrinoid substrate. To explore how CobA may overcome this challenge, we have employed electronic absorption, magnetic circular dichroism, and electron paramagnetic resonance (EPR) spectroscopies to probe the interaction between Co(3+)- and Co(2+)corrinoids and the enzyme active site. Our data reveal that while Co(3+)corrinoids interact only weakly with CobA, Co(2+)corrinoids undergo partial conversion to a new paramagnetic species that can be obtained in nearly quantitative yield when CobA is preincubated with the co-substrate ATP. This "activated" species is characterized by a distinct set of ligand field transitions in the near-IR spectral region and EPR parameters that are unprecedented for Co(2+)corrinoids. Analysis of these data on the basis of qualitative spectral correlations and density functional theory computations reveals that this unique Co(2+)corrinoid species possesses an essentially square-planar Co(2+) center that lacks any significant axial bonding interactions. Possible implications of these findings for the mechanism of Co(2+) --> Co(1+) reduction employed by CobA and Co-C bond-forming enzymes in general are explored.


Computational Methods for Tracking, Quantitative Assessment, and Visualization of C. elegans Locomotory Behavior.
The nematode Caenorhabditis elegans provides a unique opportunity to interrogate the neural basis of behavior at single neuron resolution. In C. elegans, neural circuits that control behaviors can be formulated based on its complete neural connection map, and easily assessed by applying advanced genetic tools that allow for modulation in the activity of specific neurons. Importantly, C. elegans exhibits several elaborate behaviors that can be empirically quantified and analyzed, thus providing a means to assess the contribution of specific neural circuits to behavioral output. Particularly, locomotory behavior can be recorded and analyzed with computational and mathematical tools. Here, we describe a robust single worm-tracking system, which is based on the open-source Python programming language, and an analysis system, which implements path-related algorithms. Our tracking system was designed to accommodate worms that explore a large area with frequent turns and reversals at high speeds. As a proof of principle, we used our tracker to record the movements of wild-type animals that were freshly removed from abundant bacterial food, and determined how wild-type animals change locomotory behavior over a long period of time. Consistent with previous findings, we observed that wild-type animals show a transition from area-restricted local search to global search over time. Intriguingly, we found that wild-type animals initially exhibit short, random movements interrupted by infrequent long trajectories. This movement pattern often coincides with local/global search behavior, and visually resembles Lévy flight search, a search behavior conserved across species. Our mathematical analysis showed that while most of the animals exhibited Brownian walks, approximately 20% of the animals exhibited Lévy flights, indicating that C. elegans can use Lévy flights for efficient food search. In summary, our tracker and analysis software will help analyze the neural basis of the alteration and transition of C. elegans locomotory behavior in a food-deprived condition.


Botulinum neurotoxin A promotes functional recovery after peripheral nerve injury by increasing regeneration of myelinated fibers.
The injection of safe doses of botulinum neurotoxin A (BoNT/A) have been reported to be useful for the treatment of neuropathic pain, but it is still unknown how functional recovery is induced after peripheral nerve injury. We evaluated the effects of intranerve application of BoNT/A, on regeneration and sensorimotor functional recovery in partial and complete peripheral nerve injuries in the mouse. After sciatic nerve crush (SNC) and intranerve delivery of BoNT/A (15pg), axonal regeneration was measured by nerve pinch test at different days. Regeneration of myelinated and unmyelinated fibers was assessed by immunohistochemical double labeling for NF200/GAP43 and CGRP/GAP43. S100 was used as Schwann cells marker. Medial footpad skin reinnervation was assessed by PGP staining. Motor functions were assessed by means of nerve conduction tests. In other mice groups, nerve conduction tests were performed also after chronic constriction injury (CCI) of the sciatic nerve and intraplantar injection of BoNT/A (15pg). In SNC mice, BoNT/A increased the rate of axonal regeneration. The advantage of regrowing myelinated axons after BoNT/A injection was evidenced by longer NF200+ nerve profiles and confirmed by nerve histology. We observed also a higher expression of S100 in the distal portion of BoNT/A-injected regenerated nerves. In CCI mice, BoNT/A induced an increase in reinnervation of gastrocnemius and plantar muscles. These results show that a low dose of BoNT/A, insufficient to produce muscular dysfunction, conversely speeds up sensorimotor recovery by stimulating myelinated axonal regeneration, and points out its application as a multipotent treatment for peripheral neuropathies.


Prostaglandin E2 inhibits sodium transport in rabbit cortical collecting duct by increasing intracellular calcium.
The mechanism by which prostaglandin E2 (PGE2) inhibits sodium absorption (JNa) in the rabbit cortical collecting duct (CCD) was explored. PGE2 activates at least three signaling mechanisms in the CCD: (a) by itself PGE2 increases cAMP generation (b) PGE2 also inhibits vasopressin-stimulated cAMP accumulation, and (c) PGE2 raises intracellular calcium([Ca++]i). We tested the contribution of these signaling pathways to PGE2's effect on Na+ absorption, measuring 22Na flux (JNa) and [Ca++]i (using fura-2) in microperfused rabbit CCDs. In control studies PGE2 reduced JNa from 28.2 +/- 3.4 to 15.6 +/- 2.6 pmol.mm-1.min-1. Lowering bath calcium from 2.4 to 45 nM did not by itself alter JNa but in this setting PGE2 failed to inhibit JNa (28.6 +/- 5.4 to 38.5 +/- 4.0). In separate tubules, PGE2 raised [Ca++]i in a spike-like fashion followed by a sustained elevation. However, in 45 nM bath Ca++, PGE2 failed to produce a sustained [Ca++]i elevation. While pretreatment of CCDs with pertussis toxin blocked PGE2 inhibition of vasopressin-stimulated water permeability, it did not block the effect of PGE2 on JNa. To see if cAMP generation contributes to the effect of PGE2 on JNa, we tested the effect of exogenous cAMP, (8-chlorophenylthio(CPT)cAMP) on JNa. 0.1 mM 8-CPTcAMP reduced JNa from 35.75 +/- 2.3 to 21.6 +/- 2.2. However, the addition of PGE2 further blunted JNa to 15.9 +/- 1.3. In CCDs pretreated with indomethacin, 8-CPTcAMP did not significantly decrease JNa 33.6 +/- 2.8 vs. 28.4 +/- 2. However, superimposed PGE2 reduced JNa to 19.0 +/- 3.0. We conclude that PGE2 inhibits sodium transport predominantly by increasing intracellular calcium. This action is not mediated by a pertussis toxin-sensitive G protein. Finally, cAMP, through a cyclooxygenase-dependent mechanism, also inhibits CCD JNa and may contribute to the effects of PGE2 on JNa in the rabbit CCD.


How Migration Status Shapes Susceptibility of Individuals' Loneliness to Social Isolation.
Objectives: Our research provides competing hypotheses and empirical evidence how associations between objectively social isolation and subjective loneliness differ between host populations, migrants, and refugees. Methods: The analysis uses data of 25,171 participants from a random sample of the German population (SOEP v.35). We estimate regression models for the host population, migrants, and refugees and test five hypotheses on the association between social isolation and loneliness using a Bayesian approach in a multiverse framework. Results: We find the strongest relative support for an increased need for social inclusion among refugees, indicated by a higher Bayes factor compared to the hosts and migrants. However, all theoretically developed hypotheses perform poorly in explaining the major pattern in our data: The association of social isolation and loneliness is persistently lower for migrants (0.15 SD-0.29 SD), with similar sizes of associations for refugees and the host population (0.38 SD-0.67 SD). Conclusion: The migration history must be actively considered in health service provision and support programs to better cater to the needs of the different groups.


Control of Chemical Reaction Pathways by Light-Matter Coupling.
Because plasmonic metal nanostructures combine strong light absorption with catalytically active surfaces, they have become platforms for the light-assisted catalysis of chemical reactions. The enhancement of reaction rates by plasmonic excitation has been extensively discussed. This review focuses on a less discussed aspect: the induction of new reaction pathways by light excitation. Through commentary on seminal reports, we describe the principles behind the optical modulation of chemical reactivity and selectivity on plasmonic metal nanostructures. Central to these phenomena are excited charge carriers generated by plasmonic excitation, which modify the energy landscape available to surface reactive species and unlock pathways not conventionally available in thermal catalysis. Photogenerated carriers can trigger bond dissociation or desorption in an adsorbate-selective manner, drive charge transfer and multielectron redox reactions, and generate radical intermediates. Through one or more of these mechanisms, a specific pathway becomes favored under light. By improved control over these mechanisms, light-assisted catalysis can be transformational for chemical synthesis and energy conversion.


Infectious bursal disease (Gumboro disease).
Infectious bursal disease (IBD) (Gumboro disease) has been described throughout the world, and the socio-economic significance of the disease is considerable world-wide. Various forms of the disease have been described, but typing remains unclear, since antigenic and pathotypic criteria are used indiscriminately, and the true incidence of different types is difficult to determine. Moreover, the infection, when not fatal, leads to a degree of immunosuppression which is often difficult to measure. Finally, the control measures used are subject to variations, and seldom follow a specific or standardised plan. In the context of expanding international trade, the authors provide an overview of existing knowledge on the subject to enhance available information on the epidemiology of IBD, the identification of reliable viral markers for diagnosis, and the implementation of specific control measures to ensure a global and co-ordinated approach to the disease.


Cryo-electron microscope tomography to study axonemal organization.
Cilia and flagella are important organelles that perform both motile and sensory functions. For more than half a century, electron microscopy has provided crucial insights into the fundamental architecture and function of these organelles, such as the characteristic [9+2] microtubule arrangement of the axoneme or the dynein-driven microtubule sliding as the basis of motility. However, we are just starting to explore the molecular organization and mechanisms that drive and regulate axonemal bending. Recently, electron tomography (ET) of rapidly frozen, that is, life-like preserved specimen, has emerged as a cutting-edge technique that provides three-dimensional (3D) views of cellular structures. Cryo-ET and subtomogram averaging has provided high-resolution 3D images of intact flagella and axonemes, allowing us to discover new structures and gain a better understanding of their molecular organization. This chapter provides an overview of the principles of cryo-preservation, ET, and tomographic averaging, and it highlights both strengths and limitations of combining these methods to study axonemal organization. The chapter gives a comprehensive overview of the major technical steps involved in cryo-ET and 3D averaging, and explains successful strategies to generate structural data of the axoneme with 3 to 4nm resolution. Basic equipment requirements, available software packages and how to use them, as well as common problems, artifacts and future challenges are discussed. The chapter is addressed to both scientists who already use or consider using cryo-tomography of cilia and flagella, as well as researchers who would like to learn more about the process and how to "read" these new 3D images.


[Lhermitte-Duclos disease. Apropos of a case].
The authors report a case of dysplastic gangliocytoma of the cerebellum (Lhermitte-Duclos disease). This woman's first neurosurgical admission was in 1970 at the age of 15 years. Hydrocephalus related to aqueduct-stenosis was diagnosed and a ventriculo atrial shunt was inserted. Ten years later, she underwent partial resection of a third ventricle tumor which was identified as a pilocytic astrocytoma. In 1986, computerized tomography revealed a non-enhancing left cerebellar mass lesion. Surgical excision was performed, and pathological examination disclosed dysplastic gangliocytoma of the cerebellum.


Activation of the sympathetic nervous system mediates hypophagic and anxiety-like effects of CB₁ receptor blockade.
Complex interactions between periphery and the brain regulate food intake in mammals. Cannabinoid type-1 (CB1) receptor antagonists are potent hypophagic agents, but the sites where this acute action is exerted and the underlying mechanisms are not fully elucidated. To dissect the mechanisms underlying the hypophagic effect of CB1 receptor blockade, we combined the acute injection of the CB1 receptor antagonist rimonabant with the use of conditional CB1-knockout mice, as well as with pharmacological modulation of different central and peripheral circuits. Fasting/refeeding experiments revealed that CB1 receptor signaling in many specific brain neurons is dispensable for the acute hypophagic effects of rimonabant. CB1 receptor antagonist-induced hypophagia was fully abolished by peripheral blockade of β-adrenergic transmission, suggesting that this effect is mediated by increased activity of the sympathetic nervous system. Consistently, we found that rimonabant increases gastrointestinal metabolism via increased peripheral β-adrenergic receptor signaling in peripheral organs, including the gastrointestinal tract. Blockade of both visceral afferents and glutamatergic transmission in the nucleus tractus solitarii abolished rimonabant-induced hypophagia. Importantly, these mechanisms were specifically triggered by lipid-deprivation, revealing a nutrient-specific component acutely regulated by CB1 receptor blockade. Finally, peripheral blockade of sympathetic neurotransmission also blunted central effects of CB1 receptor blockade, such as fear responses and anxiety-like behaviors. These data demonstrate that, independently of their site of origin, important effects of CB1 receptor blockade are expressed via activation of peripheral sympathetic activity. Thus, CB1 receptors modulate bidirectional circuits between the periphery and the brain to regulate feeding and other behaviors.


Antibiotic Usage After Procalcitonin-Guided Therapy Algorithm Implementation In A Burn Intensive Care Unit.
The study investigated antibiotic utilization after the implementation of a procalcitonin (PCT)-guided antibiotic algorithm in the burn intensive care unit (BICU) to minimize antibiotic exposure appropriately. An algorithm established the ordering of an initial procalcitonin level, an additional level following 48 hours post-admission, and upon suspicion of sepsis. The primary endpoint was the percent of days on antibiotics in the BICU. Secondary endpoints were the percent of patients reinitiated on antibiotics, length of BICU and hospital stay, and 30-day mortality. Desirability of Outcome Ranking (DOOR) and Response Adjusted for Duration of Antibiotic Risk (RADAR) methodology aided in antibiotic usage evaluation. The retrospective and prospective phases involved five and seven patients in the final analysis, respectively. The median percent of days on antibiotics in the BICU was 33.3% versus 14.3% in the retrospective and prospective phases, respectively (p=0.222). Secondary outcomes evaluated were percent of patients reinitiated on antibiotics at 80.0% versus 28.6% (p=0.242), the median length of BICU stay at 38 days versus 31 days (p=0.465), the median duration of hospital stay at 39 days versus 37 days (p=0.624) and 30-day mortality of one versus zero cases (p=0.417) in the retrospective and prospective group, respectively. The probability of better DOOR with a PCT-guided antibiotic algorithm versus the control group was 95.7% (95% CI, 81.4-99.5%). The benefit of a PCT-guided antibiotic algorithm implementation cannot be determined based on the small sample size producing a lack of internal validity. Future studies warrant utilizing DOOR/RADAR to evaluate antibiotic stewardship strategies in the burn patient population.


Prevalence and Risk Factors for Acute Postoperative Pain After Elective Orthopedic and General Surgery at a Tertiary Referral Hospital in Tanzania.
In Africa, postoperative pain management is still a major problem with a prevalence of postoperative pain in up to 95.2% of the patients. There are little data on the prevalence and potential risk factors for postoperative pain in Tanzania. Therefore, we aimed to investigate these at Kilimanjaro Christian Medical Centre in Northern Tanzania. Our goal is to optimize pain management. A prospective cohort study was carried out from December 2016 to April 2017. Patients ≥18 years admitted for elective general or orthopedic surgery were included in the study. Demographic data were collected during a pre-operative visit, and pain was assessed with a numerical rating scale (NRS 0-10) at 4, 24, 36 and 48 hours postoperatively. A NRS >3 was considered as moderate to severe postoperative pain. Potential risk factors for postoperative pain were identified using univariate and multivariable binary logistic regression analyses. A total of 281 patients were included in the study. The prevalence of postoperative pain was 61%, 73%, 67% and 58% at 4, 24, 36 and 48 hours after surgery, respectively. Pethidine was the most frequently prescribed analgesic for postoperative pain management (85.1%) in the first 24 hours postoperatively; only 1% received paracetamol or diclofenac, and 13% received tramadol. In the multivariable model, general anesthesia and intra-operative analgesia (OR = 3.70, 95% CI 1.70-8.04) were significant risk factors for postoperative pain. Pain is still inadequately managed at Kilimanjaro Christian Medical Centre leading to a high prevalence (73% on the first day after surgery) of reported postoperative pain in this study. It reflects the need for adequate postoperative analgesia, especially in low- and middle-income countries. Further research identifying risk factors in larger cohorts can be performed if adequate analgesia is given.


What is the utility of biomarkers for assessing the pathophysiology of hip osteoarthritis? A systematic review.
Innovations in biologics offer great promise in the treatment of patients with orthopaedic conditions and in advancing our ability to monitor underlying disease pathophysiology. Our understanding of the pathophysiology of hip osteoarthritis (OA) has improved significantly in the last decade. Femoroacetabular impingement (FAI) and hip dysplasia are increasingly recognized and treated as forms of prearthritic hip disease, yet the inability of radiographic and MR imaging to identify patients before the onset of irreversible articular cartilage injury limits their use for early diagnosis and treatment of patients with these conditions. Molecular biomarkers, as objectively measureable indicators of the pathophysiology of hip OA, have the potential to improve diagnosis, disease staging, and prognosis of hip OA and prearthritic hip disease. Although research into molecular biomarkers of hip OA has been conducted, investigations in prearthritic hip disease have only recently begun. The purpose of our review was to assess the use of molecular biomarkers in the pathophysiology of hip OA, including (1) diagnosis; (2) disease staging; and (3) prognosis. We additionally aimed to summarize the available literature investigating the use of biomarkers in (4) prearthritic hip disease, including FAI and hip dysplasia. We conducted a systematic review of molecular biomarkers associated with hip OA or prearthritic hip disease by searching four major electronic databases for keywords "hip", "osteoarthritis", "biomarker", and all synonyms. The search terms "femoroacetabular impingement" and "hip dysplasia" were also included. The biologic source of biomarkers was limited to serum, plasma, urine, and synovial fluid. The literature search yielded a total of 2740 results. Forty studies met all criteria and were included in our review. Studies were categorized regarding their relevance to (1) diagnosis; (2) disease staging; (3) prognosis; and/or (4) prearthritic hip disease. Biomarker studies were characterized as relevant to diagnosis (16 studies), disease staging (15 studies), prognosis (11 studies), and prearthritic hip disease (three studies). Sixteen different biomarkers demonstrated associations relevant to the diagnosis of hip OA, 16 biomarkers demonstrated similar associations for disease staging, and six for prognosis. Six biomarkers seemed to be the most promising, demonstrating associations with hip OA in multiple studies, including: urinary level of type II collagen telopeptide (n = 5 studies), serum cartilage oligomeric protein (n = 4 studies), and serum C-reactive protein (n = 4 studies). Only three studies investigated the role of biomarkers in prearthritic hip disease, including two in FAI and one in unspecified etiology of pain. There were no studies about biomarkers in hip dysplasia. Molecular biomarkers are increasingly investigated for their use in evaluating the pathophysiology of hip OA, but less so for prearthritic hip disease. Several biomarkers have demonstrated significant associations with hip OA across multiple studies. Further validation of these biomarkers is needed to assess their clinical use and potential application to prearthritic hip disease.


Orphanin FQ, but not dynorphin A, accelerates colonic transit in rats.
The endogenous opiate receptor-like 1 ligand, orphanin FQ (OFQ), which structurally resembles dynorphin A, has been identified. We investigated the mechanism of action of OFQ in the colon and compared it with that of dynorphin A in vivo. Colonic contractions were recorded via miniature force transducers implanted on the serosal surface of the rat colon. Intravenous administration of OFQ (0.01-3 nmol/kg) induced contractions in the rat colon in a dose-dependent manner. Colonic contractions induced by OFQ were not affected by extrinsic denervation but abolished by tetrodotoxin. Continuous infusion of OFQ (1 nmol x kg(-1) x min(-1)) and dynorphin A (100 nmol x kg(-1) x min(-1)) induced similar phasic contractions in the proximal colon. However, the contractile activity induced by the 2 peptides differed significantly in the mid and distal colon. Giant contractions induced by OFQ infusion migrated from the mid to distal colon. In contrast, dynorphin A evoked simultaneous contractions throughout the entire colon, which did not migrate aborally. Subcutaneous administration of OFQ (1-3 nmol/kg) accelerated colonic transit, whereas dynorphin A (30-100 nmol/kg) delayed colonic transit. The results show that OFQ accelerates colonic transit by promoting migrating colonic contractions in rats.


Asymptomatic, isolated tubercular splenic abscess, in an immunocompetent person.
Tubercular splenic abscess in an immunocompetent person, especially when the patient is without any symptoms, is a rare clinical entity. We report a case of isolated tubercular splenic abscess in a 38-year-old asymptomatic healthy female and emphasize the importance of careful smear examination. The patient had come to the hospital for repair of vaginal vault prolapse. Her abdominal ultra sonography showed normal sized spleen with hypoechoic areas suggesting abscess. Fine needle aspiration of splenic lesion revealed tubercle bacilli on Ziehl Neelsen stain. The organisms also grew on culture. The splenic lesions cleared after six months of treatment with anti tubercular drugs at our Directly Observed Treatment centre under Revised National TB Control Programme. The patient was operated successfully for vault prolapse one year later.


Ultrafast nonlinear optical properties of thin-solid DNA film and their application as a saturable absorber in femtosecond mode-locked fiber laser.
A new extraordinary application of deoxyribonucleic acid (DNA) thin-solid-film was experimentally explored in the field of ultrafast nonlinear photonics. Optical transmission was investigated in both linear and nonlinear regimes for two types of DNA thin-solid-films made from DNA in aqueous solution and DNA-cetyltrimethylammonium chloride (CTMA) in an organic solvent. Z-scan measurements revealed a high third-order nonlinearity with n2 exceeding 10-9 at a wavelength of 1570 nm, for a nonlinarity about five orders of magnitude larger than that of silica. We also demonstrated ultrafast saturable absorption (SA) with a modulation depth of 0.43%. DNA thin solid films were successfully deposited on a side-polished optical fiber, providing an efficient evanescent wave interaction. We built an organic-inorganic hybrid all-fiber ring laser using DNA film as an ultrafast SA and using Erbium-doped fiber as an efficient optical gain medium. Stable transform-limited femtosecond soliton pulses were generated with full width half maxima of 417 fs for DNA and 323 fs for DNA-CTMA thin-solid-film SAs. The average output power was 4.20 mW for DNA and 5.46 mW for DNA-CTMA. Detailed conditions for DNA solid film preparation, dispersion control in the laser cavity and subsequent characteristics of soliton pulses are discussed, to confirm unique nonlinear optical applications of DNA thin-solid-film.


Complex Stability and an Irrevertible Transition Reverted by Peptide and Fibroblasts in a Dynamic Model of Innate Immunity.
We here apply a control analysis and various types of stability analysis to an in silico model of innate immunity that addresses the management of inflammation by a therapeutic peptide. Motivation is the observation, both in silico and in experiments, that this therapy is not robust. Our modeling results demonstrate how (1) the biological phenomena of acute and chronic modes of inflammation may reflect an inherently complex bistability with an irrevertible flip between the two modes, (2) the chronic mode of the model has stable, sometimes unique, steady states, while its acute-mode steady states are stable but not unique, (3) as witnessed by TNF levels, acute inflammation is controlled by multiple processes, whereas its chronic-mode inflammation is only controlled by TNF synthesis and washout, (4) only when the antigen load is close to the acute mode's flipping point, many processes impact very strongly on cells and cytokines, (5) there is no antigen exposure level below which reduction of the antigen load alone initiates a flip back to the acute mode, and (6) adding healthy fibroblasts makes the transition from acute to chronic inflammation revertible, although (7) there is a window of antigen load where such a therapy cannot be effective. This suggests that triple therapies may be essential to overcome chronic inflammation. These may comprise (1) anti-immunoglobulin light chain peptides, (2) a temporarily reduced antigen load, and (3a) fibroblast repopulation or (3b) stem cell strategies.


Voucher-based contingent reinforcement of smoking abstinence among methadone-maintained patients: a pilot study.
This study evaluated the efficacy of a contingency management (CM) intervention to promote smoking cessation in methadone-maintained patients. Twenty participants, randomized into contingent (n=10) or noncontingent (n=10) experimental conditions, completed the 14-day study. Abstinence was determined using breath carbon monoxide and urine cotinine levels. Contingent participants received voucher-based incentives for biochemical evidence of smoking abstinence. Noncontingent participants earned vouchers independent of smoking status. Contingent participants achieved significantly more smoking abstinence and longer durations of continuous smoking abstinence than did noncontingent participants. These results support the potential efficacy of using voucher-based CM to promote smoking cessation among methadone-maintained patients.


Intravenous Immunoglobulin Administration Significantly Increases BKPyV Genotype-Specific Neutralizing Antibody Titers in Kidney Transplant Recipients.
BK polyomavirus (BKPyV)-associated nephropathy (BKPyVAN) is one of the major causes of kidney graft dysfunction, and there are no BKPyV-specific antiviral therapies available. BKPyV neutralizing antibodies (NAbs) play key roles in protecting against BKPyV replication and represent a potential therapeutic or preventive strategy. In this study, we evaluated NAb titers in intravenous immunoglobulin (i.v. Ig) preparations and in kidney transplant recipients (KTR) before and after i.v. Ig administration. NAb titers directed against major BKPyV genotypes were measured using a BKPyV pseudovirion system. Thirty-three KTR receiving high (1 g/kg of body weight/day; n = 17) or low (0.4 g/kg/day; n = 16) i.v. Ig doses were included. Median NAb titers in i.v. Ig preparations ranged from 5.9 log10 50% inhibitory concentration (IC50) for genotype I to 4.1 log10 IC50 for genotype IV. A mean of 90% of patients (range, 88% to 100%) displaying low or negative BKPyV NAb titers against genotype I reached 4 log10 IC50 after the first i.v. Ig administration. This value was reached by a mean of 44% (range, 13% to 83%) and 19% (range, 0% to 38%) of patients against genotype II and genotype IV, respectively. The benefit of i.v. Ig administration persisted until the following course of treatment (day 22 ± 7 days) for genotypes I and II, and no cumulative effect was observed through the three doses. Our findings demonstrate that i.v. Ig administration results in a significant increase in BKPyV NAb titers in KTR. These in vitro and in vivo pharmacokinetic data provide the rationale for a proof-of-concept study investigating the efficacy of i.v. Ig for the prevention of BKPyV infection in KTR.


Long-term ethanol consumption and macrocytosis: diagnostic and pathogenic implications.
Although excessive alcohol consumption is known to elevate the mean cell volume (MCV) of erythrocytes, the relationships among the intensity of ethanol exposure, the generation of abnormal red blood cell indices, and the underlying pathogenic mechanisms have remained unclear. The authors examined 105 alcoholics with a wide range of ethanol consumption (40-500 g of ethanol/day), 62 moderate drinkers (mean consumption 1-40 g/day), and 24 abstainers, who underwent detailed interviews, measurements of blood cell counts, markers of liver status, and circulating antibodies against ethanol-derived protein modifications. Follow-up information was collected from healthy volunteers with detailed records on drinking habits. Data from the NORIP project for laboratory parameters in apparently healthy moderate drinkers or abstainers (n = 845) were used for reference interval comparisons. The highest MCV (P < 0.001) and mean cell hemoglobin (MCH) (P < 0.01) occurred in the alcoholics. However, the values in the moderate drinkers also responded to ethanol intake such that the upper normal limit for MCV based on the data from moderate drinkers was 98 fl, as compared with 96 fl from abstainers. Follow-up cases with carefully registered drinking habits showed parallel changes in MCV and ethanol intake. Anti-adduct IgA and IgM against acetaldehyde-induced protein modifications were elevated in 94% and 64% of patients with high MCV, respectively, the former being significantly less frequent in the alcoholics with normal MCV (63%) (P < 0.05). The data indicate dose-related responses in red blood indices upon chronic ethanol consumption, which may also be reflected in reference intervals for hematological parameters in health care. Generation of immune responses against acetaldehyde-modified erythrocyte proteins may be associated with the appearance of such abnormalities.


The eighth American college of chest physicians guidelines on venous thromboembolism prevention: implications for hospital prophylaxis strategies.
Venous thromboembolism (VTE) is the most common potentially preventable form of hospital-related mortality. It presents as a major healthcare burden, affecting both medical and surgical patients. The prevention of VTE has been identified as one of the most important in-hospital safety practices in the US. VTE guideline recommendations provide a framework for clinical practice and guide VTE prophylaxis policies. Guidelines produced by the American College of Chest Physicians (ACCP) are considered to be the 'gold standard' in VTE prevention, diagnosis and management, and have been updated. A number of differences exist between the new 2008 ACCP guidelines on VTE prevention and the previous version published in 2004. There are variations regarding VTE prevention, including new and stronger evidence-based recommendations for several indications and agents. The updated guidelines give a strong recommendation that every hospital develop a VTE prevention policy, which is particularly important given the current international drive to reduce the incidence of VTE. A formal hospital policy should help improve compliance with appropriate VTE prophylaxis strategies. The ACCP guidelines form a basis for improving patient safety at a time of public reporting of quality of care, hospital accreditation, national standards of care, and pay for performance initiatives. In this review, changes in recommendations for VTE prevention in the 2008 ACCP guidelines compared with the previous edition in 2004 are outlined. In addition, outstanding areas of debate are discussed and the role of the 2008 ACCP guidelines in the context of the new VTE performance measures analyzed.


Gallic acid induces G1 phase arrest and apoptosis of triple-negative breast cancer cell MDA-MB-231 via p38 mitogen-activated protein kinase/p21/p27 axis.
Gallic acid (GA) possesses potential antitumoral activity on different types of malignancies. In this study, we aimed to explore the antitumoral effects of GA on triple-negative breast cancer (TNBC) cells, the breast cancer cells showing resistance to hormonal therapy or HER2 receptor targeting therapy. We observed that GA treatment significantly decreased the cell viability of human TNBC cell line MDA-MB-231 and HS578T in a dose-dependent manner. In addition, GA exerted a relative lower cytotoxicity on noncancer breast fibroblast MCF-10F. Next, we analyzed the changes of cell-cycle distribution in response to GA treatment and found that GA led to an increase of G0/G1 and sub-G1 phase ratio in MDA-MB-231 cells. We further explored the crucial mediators controlling cell cycle and inducing apoptotic signaling, and the findings showed that GA downregulated cyclin D1/CDK4 and cyclin E/CDK2, upregulated p21and p27, and induced activation of caspase-9 and caspase-3. In addition, we demonstrated that p38 mitogen-activated protein kinase was involved in the GA-mediated cell-cycle arrest and apoptosis. Collectively, our findings indicate that GA inhibits the cell viability of TNBC cells, which may attribute to the G1 phase arrest and cellular apoptosis via p38 mitogen-activated protein kinase/p21/p27 axis. Thus, we suggest that GA could be beneficial to TNBC treatment.


Adult neurobehavioral alterations in male and female mice following developmental exposure to paracetamol (acetaminophen): characterization of a critical period.
Paracetamol (acetaminophen) is a widely used non-prescription drug with analgesic and antipyretic properties. Among pregnant women and young children, paracetamol is one of the most frequently used drugs and is considered the first-choice treatment for pain and/or fever. Recent findings in both human and animal studies have shown associations between paracetamol intake during brain development and adverse behavioral outcomes later in life. The present study was undertaken to investigate if the induction of these effects depend on when the exposure occurs during a critical period of brain development and if male and female mice are equally affected. Mice of both sexes were exposed to two doses of paracetamol (30 + 30 mg kg-1 , 4 h apart) on postnatal days (PND) 3, 10 or 19. Spontaneous behavior, when introduced to a new home environment, was observed at the age of 2 months. We show that adverse effects on adult behavior and cognitive function occurred in both male and female mice exposed to paracetamol on PND 3 and 10, but not when exposed on PND 19. These neurodevelopmental time points in mice correspond to the beginning of the third trimester of pregnancy and the time around birth in humans, supporting existing human data. Considering that paracetamol is the first choice treatment for pain and/or fever during pregnancy and early life, these results may be of great importance for future research and, ultimately, for clinical practice. Copyright © 2017 John Wiley & Sons, Ltd.


OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY IN PATIENTS WITH RETINITIS PIGMENTOSA.
To evaluate the correlation between the flow density measured by optical coherence tomography angiography and functional parameters in patients with retinitis pigmentosa. Twenty eyes of 20 patients with retinitis pigmentosa and 21 eyes of 21 healthy subjects were prospectively included in this study. Optical coherence tomography angiography was performed using RTVue XR Avanti with AngioVue (Optovue Inc). The macula was imaged with a 6 × 6-mm scan, whereas for the optic nerve head a 4.5 × 4.5-mm scan was taken. Visual acuity, visual field parameters (mean deviation and visual field index), full-field electroretinography, and multifocal electroretinography were tested for correlation with flow density data. The flow density (whole en face) in the superficial/deep retinal OCT angiograms and in the optical coherence tomography angiography of the optic nerve head was significantly lower in the retinitis pigmentosa group when compared with the control group (P < 0.001). The flow density in the superficial retinal OCT angiogram (fovea) correlated significantly with the visual acuity (rSpearman = -0.77, P < 0.001) and the visual field parameters (visual field index: rSpearman = 0.56, P = 0.01; mean deviation: rSpearman = 0.54, P = 0.01). Patients with retinitis pigmentosa show a decreased macular and optic nerve head perfusion compared with healthy subjects. The flow density measured using optical coherence tomography angiography correlated with subjective and objective functional parameters.


The ClpX chaperone controls autolytic splitting of Staphylococcus aureus daughter cells, but is bypassed by β-lactam antibiotics or inhibitors of WTA biosynthesis.
β-lactam antibiotics interfere with cross-linking of the bacterial cell wall, but the killing mechanism of this important class of antibiotics is not fully understood. Serendipitously we found that sub-lethal doses of β-lactams rescue growth and prevent spontaneous lysis of Staphylococcus aureus mutants lacking the widely conserved chaperone ClpX, and we reasoned that a better understanding of the clpX phenotypes could provide novel insights into the downstream effects of β-lactam binding to the PBP targets. Super-resolution imaging revealed that clpX cells display aberrant septum synthesis, and initiate daughter cell separation prior to septum completion at 30°C, but not at 37°C, demonstrating that ClpX becomes critical for coordinating the S. aureus cell cycle as the temperature decreases. FtsZ localization and dynamics were not affected in the absence of ClpX, suggesting that ClpX affects septum formation and autolytic activation downstream of Z-ring formation. Interestingly, oxacillin antagonized the septum progression defects of clpX cells and prevented lysis of prematurely splitting clpX cells. Strikingly, inhibitors of wall teichoic acid (WTA) biosynthesis that work synergistically with β-lactams to kill MRSA synthesis also rescued growth of the clpX mutant, as did genetic inactivation of the gene encoding the septal autolysin, Sle1. Taken together, our data support a model in which Sle1 causes premature splitting and lysis of clpX daughter cells unless Sle1-dependent lysis is antagonized by β-lactams or by inhibiting an early step in WTA biosynthesis. The finding that β-lactams and inhibitors of WTA biosynthesis specifically prevent lysis of a mutant with dysregulated autolytic activity lends support to the idea that PBPs and WTA biosynthesis play an important role in coordinating cell division with autolytic splitting of daughter cells, and that β-lactams do not kill S. aureus simply by weakening the cell wall.


Dental bur fragments causing metal artifacts on MR images.
Our purpose was to define the role of dental bur fragments in producing metal artifacts on MR images. Dental prosthetic reconstructions were made for two dogs. The two lower second premolars were prepared for full-cast crowns by using a diamond bur. The crown margin was placed subgingivally on the right side (1 mm below the free gingival margin) and at the same level as the free gingival margin on the left side. After 1 week, full-cast crowns were cemented in place. MR imaging was performed 7 days later. Metal artifacts appeared in both second premolar regions of the mandible on MR images, with the right side, in which the crown margin was positioned subgingivally, displaying a larger signal distortion than the left side. After removal of the crown, the artifact remained on the right. On histopathologic examination, bur fragments were detected in the gingiva, more on the right than on the left. X-ray fluorescent element analysis showed iron in the gingival tissue containing bur fragments. Distortion of MR images was considered to be attributable in part to the damage of the gingiva and in part to the presence of dental bur fragments.


Association of the plasma and tissue riboflavin levels with C20orf54 expression in cervical lesions and its relationship to HPV16 infection.
Riboflavin deficiency can cause a variety of metabolic problems that lead to skin and mucosal disorders. Limited evidence suggests that high intake of riboflavin may reduce overall risks of cancer. However, association of this deficiency with cervical cancer and precancerous lesions are still not definitively known. In this study, we characterized the relationship between plasma and tissue riboflavin levels and C20orf54 protein expression in patients with cervical intraepithelial neoplasia (CIN) and cervical squamous cell carcinoma (CSCC) as well as the relationship of these levels with human papillomavirus virus 16, 18 (HPV16/18) infections. High-performance liquid chromatography (HPLC) was used to measure blood riboflavin levels in patients with CIN and CSCC, and an enzyme-linked immunosorbent assay (ELISA) was used to determine tissue riboflavin levels in patients with CSCC and matched normal mucous epithelia. The expression of C20orf54 in fresh CSCC and matched tissues were detected by qRT-PCR and western blot, respectively. And it was further confirmed by immunohistochemistry (IHC) with formalin-fixed, paraffin-embedded CIN and CSCC. An HPV genotyping chip was used to analyze HPV infection and typing. The results showed that patients with CIN and CSCC had decreased plasma riboflavin levels as compared with normal controls. There was also significantly decreased riboflavin in tissues from CSCC patients, when compared with normal cervical epithelia. C20orf54 expression were significantly up-regulated in CSCC compared to matched control on both mRNA and protein level. Tissue riboflavin levels were significantly lower in HPV16/18 positive tissue compared with HPV16/18-negative tissue, and an inverse association was found between tissue riboflavin levels and C20orf54 mRNA and protein expression in CSCC. Additionally, C20orf54 was significantly correlated with tumor stages. In conclusion, C20orf54 tend to play a protective role in Uyghur cervical carcinogenesis of which modulating riboflavin absorption, and it is also related with HPV infection.


Prognostic factors and the therapeutic strategy for patients with bone metastasis from differentiated thyroid carcinoma.
The treatment of bone metastasis in association with thyroid cancer represents a difficult challenge. Given the paucity of patients with bone metastasis and the difficulty of treating this disease, few studies have investigated the clinical features and prognostic factors of bone metastasis from differentiated thyroid cancer. During the 31-year-period from 1976 to 2006, a total of 1,398 patients underwent initial thyroidectomy at Cancer Institute Hospital for differentiated thyroid carcinomas, including standard papillary thyroid carcinoma, papillary microcarcinoma (primary tumor diameter < or =1.0 cm), and follicular thyroid carcinoma. Among these, 25 (2%) patients displayed bone metastasis at initial presentation (synchronous) and 27 patients showed bone metastasis during follow-up (metachronous). The records for these 52 patients were reviewed retrospectively to identify prognostic factors and analyze treatment strategies. Univariate analysis for disease-specific survival indicated metachronous bone metastasis and the presence of distant metastasis at sites other than bone as indicators of significantly worse prognosis. The type of cancer (papillary thyroid carcinoma versus follicular thyroid carcinoma) was not a significant indicator of prognosis; however, patients with papillary microcarcinoma showed significantly worse survival than patients with standard papillary and follicular thyroid carcinoma. A significant survival advantage was observed among patients who underwent radioactive iodine therapy, and better prognosis seemed to be obtained with greater doses of radioactive iodine. Operative resection of metastatic bone lesions also seemed to be associated with better prognosis. A multivariate analysis for disease-specific survival identified the coexistence of distant metastasis at sites other than bone as the only independent variable indicative of poor prognosis. In the absence of definitive, effective treatments for this disease, radioactive iodine therapy combined with resection of bone metastasis, wherever possible, seems to represent the most potent therapy available. Although bone metastasis is a strong sign of poor prognosis, early detection and administration of appropriate therapy using radioactive iodine seems likely to improve the survival rate and quality of life in patients with bone metastasis from differentiated thyroid carcinoma.


Interneuron- and GABA(A) receptor-specific inhibitory synaptic plasticity in cerebellar Purkinje cells.
Inhibitory synaptic plasticity is important for shaping both neuronal excitability and network activity. Here we investigate the input and GABA(A) receptor subunit specificity of inhibitory synaptic plasticity by studying cerebellar interneuron-Purkinje cell (PC) synapses. Depolarizing PCs initiated a long-lasting increase in GABA-mediated synaptic currents. By stimulating individual interneurons, this plasticity was observed at somatodendritic basket cell synapses, but not at distal dendritic stellate cell synapses. Basket cell synapses predominantly express β2-subunit-containing GABA(A) receptors; deletion of the β2-subunit ablates this plasticity, demonstrating its reliance on GABA(A) receptor subunit composition. The increase in synaptic currents is dependent upon an increase in newly synthesized cell surface synaptic GABA(A) receptors and is abolished by preventing CaMKII phosphorylation of GABA(A) receptors. Our results reveal a novel GABA(A) receptor subunit- and input-specific form of inhibitory synaptic plasticity that regulates the temporal firing pattern of the principal output cells of the cerebellum.


Regression approaches in the test-negative study design for assessment of influenza vaccine effectiveness.
Influenza vaccination is the most practical means available for preventing influenza virus infection and is widely used in many countries. Because vaccine components and circulating strains frequently change, it is important to continually monitor vaccine effectiveness (VE). The test-negative design is frequently used to estimate VE. In this design, patients meeting the same clinical case definition are recruited and tested for influenza; those who test positive are the cases and those who test negative form the comparison group. When determining VE in these studies, the typical approach has been to use logistic regression, adjusting for potential confounders. Because vaccine coverage and influenza incidence change throughout the season, time is included among these confounders. While most studies use unconditional logistic regression, adjusting for time, an alternative approach is to use conditional logistic regression, matching on time. Here, we used simulation data to examine the potential for both regression approaches to permit accurate and robust estimates of VE. In situations where vaccine coverage changed during the influenza season, the conditional model and unconditional models adjusting for categorical week and using a spline function for week provided more accurate estimates. We illustrated the two approaches on data from a test-negative study of influenza VE against hospitalization in children in Hong Kong which resulted in the conditional logistic regression model providing the best fit to the data.


Tumor necrosis factor-alpha affects growth hormone secretion by a direct pituitary interaction.
Administration of 50, 250, and 1,250 ng/kg iv of recombinant bovine tumor necrosis factor-alpha (RBTNF) did not affect basal plasma concentrations of growth hormone (GH) or thyroid-stimulating hormone in male calves. However, when administered 30 min before challenge with 1 microgram/kg iv of thyrotropin-releasing hormone (TRH), 250 ng/kg of RBTNF increased the subsequent incremental GH response. At 1,250 ng/kg of RBTNF, GH response to TRH was significantly blunted. For each dose of RBTNF administered, the incremental change in plasma thyroid-stimulating hormone following TRH was not significantly different from control. To examine direct effects of RBTNF on pituitary function, fresh bovine pituitaries were sliced into 1-mm cubes and incubated with 0 or 10(-8), 10(-9), or 10(-10) M RBTNF. Additional cultures were treated with 10(-8) or 10(-9) M GH-releasing factor or 10(-8) M TRH and 0 or 10(-8) M RBTNF. Media GH increased in cultures with 10(-10) M RBTNF and declined linearly as RBTNF concentration increased. RBTNF blocked GH release from GH-releasing factor- and TRH-challenged pituitary slices. Membranes prepared from homogenized bovine pituitaries had specific saturable binding characteristics for monomeric 125I-RBTNF. Membranes treated with 4 M MgCl2 for 10 min and washed free of Mg2+ produced Scatchard plots fit to a two-site model (high affinity site Kd = 6.6 nM), while Scatchards of non-Mg(2+)-treated membranes fit a single site (Kd = 8.9 nM). Polyacrylamide gel electrophoresis separation of 125I-RBTNF cross-linked pituitary membranes showed specific binding of monomeric 125I-RBTNF to protein components ranging in molecular weight from 19,000 to 77,000. The data suggest that RBTNF has modulatory effects on the regulation of GH secretion acting directly at the pituitary through specific receptors.


Antimicrobial potential of extracts from Stevia rebaudiana leaves against bacteria of importance in dental caries.
In recent years, the antimicrobial activity of Stevia rebaudiana Bertoni leaf extracts against a large number of microorganisms has been evaluated, but not its activity against microorganisms of importance in dental caries. The aim of this study was to evaluate the antibacterial activity of Stevia rebaudiana Bertoni leaf extracts against cariogenic bacteria. Extracts were obtained from the dried Stevia rebaudiana Bertoni leaves in hexane, methanol, ethanol, ethyl acetate and chloroform. The antimicrobial activity of the 5 extracts against 16 bacterial strains of the genera Streptococcus (n= 12) and Lactobacillus (n= 4) was evaluated by the well diffusion method. Minimal inhibitory concentrations (MIC) of the extracts in hexane, methanol, ethanol, ethyl acetate and chloroform on the 16 bacterial strains were respectively 30 mg/ml, 120 mg/ml, 120 mg/ml, 60 mg/ml and 60 mg/ml. The zones of inhibition present at the MIC were variable, ranging from 9 mm to 17.3 mm. Our results suggest that inhibition zones with a hexane extract are similar to those obtained with ethanol and methanol, but the minimal inhibitory concentration (30 mg/ml) is lower. For the four Lactobacillus species, the inhibition zones obtained between 12.3 and 17.3 mm were somewhat larger with ethyl acetate and chloroform extracts, suggesting they were the most susceptible microorganisms.


Characterizing novel thermophilic amylase producing bacteria from taptapani hot spring, odisha, India.
Amylases play a vital role in biotechnological studies and rank an important position in the world enzyme market (25% to 33%). Bioprocess method of amylase production is more effective than the other sources, since the technique is easy, cost effective, fast, and the enzymes of required properties can be procured. The current study aimed to report the characteristics of novel amylase producing bacterial strains isolated from Taptapani hot spring, Odisha, India. Bacterial strains were isolated by dilution plating method from the water samples collected from Taptapani Hot Spring, Odisha and screened for amylase production through starch hydrolysis. The bacterial isolates were identified morphologically, biochemically, and finally by 16S rDNA profiling. Based on the morphological, physiological, biochemical characteristics and the molecular characterization, the isolates SS1, SS2, and SS3 were identified as Bacillus barbaricus, Aeromonas veroni, and Stenotrophomonas maltophilia, respectively. The approximate molecular weight of enzymes from SS1, SS2, and SS3 strains were 19 kDa, 56 kDa and 49 kDa, respectively. The current report isolates, characterizes, and demonstrates the novel heat-adapted amylase-producing bacteria SS1, SS2 and SS3 from Taptapani hot spring, indicating its potentiality and stability under acidic conditions.


Enhanced signal intensity in matrix-free laser desorption ionization mass spectrometry by chemical modification of bionanostructures from diatom cell walls.
Laser desorption ionization for mass spectrometric measurements (LDI MS) is supported by nanostructured materials. This technique helps to overcome known limitations of matrix-assisted laser desorption/ionization (MALDI) and especially avoids interfering signals caused by matrix components. LDI can be supported by bionanostructures from the cell walls of diatoms. We explore how ionization efficiency can be improved by chemical modification of the cell walls. We introduce procedures to chemically modify these nanopatterned silicate structures using perfluorooctyldimethylchlorosilane or pentafluorophenylpropyldimethylchlorosilane. Using a conventional MALDI-MS instrument we compare ionization using the novel materials with that of unmodified cell walls. The functionalized bionanomaterial is comprehensively evaluated for the use in LDI MS using a broad range of analytes and two commercial drugs. Chemical modifications lead to materials that support LDI significantly better than unmodified diatom cell walls. LDI signal intensity was up to 25-fold increased using the modified preparations. No interfering signals in the lower molecular weight range down to m/z 100 were observed, demonstrating the suitability of the method for small analytes. Crude solutions of commercial drugs, such as Aspirin complex(®) and IbuHEXAL(®) could be directly investigated without additional sample preparation. Chemically modified diatom cell walls represent a powerful tool to support ionization in LDI MS. The lack of background signals in the low molecular weight region of the mass spectra allows also the investigations of small analytes.


Kruppel-like factor 2 is required for trafficking but not quiescence in postactivated T cells.
The transcription factor Kruppel-like factor 2 (KLF2) was proposed to regulate genes involved in cell cycle entry and T cell trafficking; however, the physiological role of its expression in postactivated T cells is not well defined. Previous studies suggested that the cytokines IL-2 and IL-15 differentially regulate KLF2 re-expression in postactivation T cells and that these cytokines also influence effector versus memory T cell differentiation. Using conditional and inducible KLF2-knockout model systems, we tested the specific role of KLF2 expression in activated CD8(+) T cells cultured with these cytokines. KLF2 was required for effective transcription of sphingosine-1-phosphate receptor-1 (S1P(1)) and CD62L in postactivation T cells. However, although different cytokines dramatically altered the expression of cell-cycle-related genes, endogenous KLF2 had a minimal impact. Correspondingly, KLF2-deficient T cells showed dysregulated trafficking but not altered proliferative characteristics following in vivo responses to Ag. Thus, our data help to define KLF2-dependent and -independent aspects of activated CD8(+) T cell differentiation and argue against a physiological role in cell cycle regulation.


POBASCAM, a population-based randomized controlled trial for implementation of high-risk HPV testing in cervical screening: design, methods and baseline data of 44,102 women.
Cytological cervical screening is rather inefficient because of relatively high proportions of false negative and false positive smears. To evaluate the efficiency of high-risk human papillomavirus (hrHPV) testing, by GP5+/6+ PCR-enzyme immunoassay (EIA), in conjunction with cytology (Intervention Group) to that of the classical cytology (Control Group), we initiated the Population Based Screening Study Amsterdam (POBASCAM). POBASCAM is a population-based randomized controlled trial for implementation of hrHPV testing in cervical screening. The outcome measure is the proportion of histologically confirmed > or =CIN3 lesions in each study arm up to and including the next screening round after 5 years. We present the design, methods and baseline data of POBASCAM. When, in the next 5 years, the follow-up will be completed, the data obtained will be used in model studies, including a cost-effectiveness study, to advise the Dutch Ministry of Public Health in deciding whether cervical screening should be based on combined hrHPV and cytology testing instead of cytology alone. Between January 1999 and September 2002, 44,102 women (mean age = 42.8 years; range = 29-61) that participated in the regular Dutch screening program were included in our study. In the Intervention Group the distribution of cytology and hrHPV by cytology class was as follows: normal cytology 96.6% (3.6% hrHPV positive); borderline and mild dyskaryosis (BMD) 2.5% (34.6% hrHPV positive); and moderate dyskaryosis or worse (>BMD) 0.8% (88.3% hrHPV positive), i.e., 0.4% moderate dyskaryosis (82.9% hrHPV positive), 0.3% severe dyskaryosis (92.5% hrHPV positive), 0.1% carcinoma in situ (95.2% hrHPV positive), <0.1% suspected for invasive cancer (hrHPV positive 100.0%). In the Control Group 96.5% of the women had normal cytology, 2.4% BMD and 0.8% >BMD, i.e., 0.4% moderate dyskaryosis, 0.3% severe dyskaryosis, 0.1% carcinoma in situ, <0.1% suspected for invasive cancer. The presence of hrHPV was age-dependent, decreasing from 12.0% at 29-33 years to 2.4% at 59-61 years. Among women with a positive hrHPV test, the prevalence of BMD was age-dependent ranging from 20.2% at 29-33 years to 7.8% at 54-58 years. In contrast, the risk of >BMD of 13.7% among women with a positive hrHPV test was not age-dependent. Our study indicates that large-scale hrHPV testing by GP5+/6+ PCR-EIA in the setting of population-based cervical screening is practically feasible, is accepted by both participating women and general practitioners and yields highly reproducible results.


Plasma gamma aminobutyric acid concentrations provide evidence of different mechanisms in the pathogenesis of hepatic encephalopathy in acute and chronic liver disease.
Plasma gamma aminobutyric acid (GABA) concentrations were measured using a radioreceptor assay in 24 patients with acute liver disease with and without clinical encephalopathy; 15 patients with chronic liver disease with and without clinical encephalopathy, and 16 control subjects with no evidence of liver disease or hepatic dysfunction. Plasma GABA concentrations were significantly elevated in the patients with acute liver disease and clinical encephalopathy as compared with the controls. There was a positive relationship between the clinical grade of encephalopathy, the changes in the EEG and the plasma GABA concentrations. Plasma GABA concentrations in patients with chronic liver disease did not relate to the clinical grade of encephalopathy or the changes in the EEG. It is concluded that elevated plasma GABA concentrations are in keeping with the pathogenesis of encephalopathy in acute liver disease, but not in chronic liver disease.


Does geometry matter? Effect of the ligand position in bimetallic ruthenium polypyridine siblings.
In this work, we present the preparation of a complex [(tpy)(bpy)Ru(μ-CN)Ru(py)4(OH2)](PF6)3 (tpy = 2,2',6',2''-terpyridine; bpy = 2,2'-bipyridine; py = pyridine) that combines a ruthenium chromophore linked to another ruthenium ion that bears a labile position trans to the bridge. Substitution in this position is very attractive, as it allows us to place a quencher trans to the chromophore maximizing the separation between them. This complex allowed us to prepare a family of cyanide-bridged ruthenium polypyridines of general formula [Ru(tpy)(bpy)(μ-CN)Ru(py)4(L)]2/3+ (L = Cl-, NCS-, 4-dimethylaminopyridine or acetonitrile) and compare them with the related complexes [Ru(tpy)(bpy)(μ-CN)Ru(bpy)2(L)]2/3+ where the L ligand lies cis to the bridge. The mixed-valence form of these complexes shows evidence of strong coupling between the ruthenium ions and enhanced delocalization as the redox potential of the {Ru(py)4L} fragment increases. (TD)DFT calculations reproduce very well the experimental spectra of these complexes and indicate that when L = acetonitrile, the hole in the mixed-valence complex is almost equally distributed between both ruthenium ions. For L = DMAP and NCS- the π orbitals of the ligands are mixed with dπ orbitals of the Ru ions, resulting in partial delocalization of the charge on the ligands. The latter result illustrates that the trans configuration of these complexes is well-suited to extend the interaction beyond the bridged ruthenium ions.


Selection of new health technologies for assessment aimed at informing decision making: A survey among horizon scanning systems.
Uncertainty is pervasive in decision making on new health technologies; therefore, some countries have put systems in place to support decision makers with timely information. An important, but as yet undocumented, determinant of the potential value for decision making of these so-called horizon scanning systems (HSSs) is how the most significant health technologies are selected. All thirteen member organizations of EuroScan, a collaborative network for HSSs, were surveyed and interviewed on how they prioritize technologies for assessment. The majority of HSSs directly serves a customer. Some customers actively request early assessments of new health technologies, thereby diminishing the need for priority setting for the HSSs. All systems express a concern to miss an important technology and/or to select an unimportant technology. Almost all HSSs use explicit selection criteria, but these criteria hardly ever are operationalized. The number of criteria used varies, but costs and health benefit of the technology are always taken into account. The process of reaching a final decision is implicit, undocumented in all but one system, and is based on agreement by consensus. The process of making the final decision on which technologies to assess can be improved by applying existing criteria more consistently and transparently. Current practice does not safeguard against missing an important technology. This finding is probably most important to act upon for systems with customers that do not actively request assessment of specific technologies.


Linking Mitochondrial Dysfunction to Organismal and Population Health in the Context of Environmental Pollutants: Progress and Considerations for Mitochondrial Adverse Outcome Pathways.
Mitochondria are key targets of many environmental contaminants, because specific chemicals can interact directly with mitochondrial proteins, lipids, and ribonucleic acids. These direct interactions serve as molecular initiating events that impede adenosine triphosphate production and other critical functions that mitochondria serve within the cell (e.g., calcium and metal homeostasis, apoptosis, immune signaling, redox balance). A limited but growing number of adverse outcome pathways (AOPs) have been proposed to associate mitochondrial dysfunction with effects at organismal and population levels. These pathways involve key events such as altered membrane potential, mitochondrial fission/fusion, and mitochondrial DNA damage, among others. The present critical review and analysis reveals current progress on AOPs involving mitochondrial dysfunction, and, using a network-based computational approach, identifies the localization of mitochondrial molecular initiating events and key events within multiple existing AOPs. We also present 2 case studies, the first examining the interaction between mitochondria and immunotoxicity, and the second examining the role of early mitochondrial dysfunction in the context of behavior (i.e., locomotor activity). We discuss limitations in our current understanding of mitochondrial AOPs and highlight opportunities for clarifying their details. Advancing our knowledge of key event relationships within the AOP framework will require high-throughput datasets that permit the development and testing of chemical-agnostic AOPs, as well as high-resolution research that will enhance the mechanistic testing and validation of these key event relationships. Given the wide range of chemicals that affect mitochondria, and the centrality of energy production and signaling to ecologically important outcomes such as pathogen defense, homeostasis, growth, and reproduction, a better understanding of mitochondrial AOPs is expected to play a significant, if not central, role in environmental toxicology. Environ Toxicol Chem 2019;38:1625-1634. © 2019 SETAC.


YArnhem: Co-designing a model of social and emotional wellbeing stepped care for young people of the north east Arnhem region: A development study protocol.
More Aboriginal and Torres Strait Islander young people experience high or very high levels of psychological distress compared to their non-Indigenous counterparts. This may be partly attributed to systemic barriers resulting in lower rates of help-seeking, sub-optimal identification of psychological challenges, and undertreatment. Reducing these barriers within health systems is an important factor in reducing the Social and Emotional Wellbeing (SEWB) health burden on young Aboriginal and Torres Strait Islander people. In partnership with Miwatj Health Aboriginal Corporation (Miwatj), this project will co-design an integrated youth Social and Emotional Wellbeing (SEWB) and mental health stepped care model for remote Aboriginal communities in the north east Arnhem region of the Northern Territory. A collaborative research approach using co-design methods will underpin a community-centric stepped care allocation method, to which culturally appropriate SEWB and mental health interventions and treatments are assigned. These components of the project will inform a digital platform which will facilitate access to SEWB care for young people in north east Arnhem land. This concept was co-developed in a partnership between researchers and Miwatj and builds on Miwatj's previous work to map the stepped needs of young people. The co-design of the content and features of these outputs will be facilitated through community participation and overseen by community, health, and cultural governance structures. This will ensure the solutions developed by the project are culturally responsive, fit for purpose, and will enhance self-determination while reducing systemic barriers to care.


YAP regulates the expression of Hoxa1 and Hoxc13 in mouse and human oral and skin epithelial tissues.
Yes-associated protein (YAP) is a Hippo signaling transcriptional coactivator that plays pivotal roles in stem cell proliferation, organ size control, and tumor development. The downstream targets of YAP have been shown to be highly context dependent. In this study, we used the embryonic mouse tooth germ as a tool to search for the downstream targets of YAP in ectoderm-derived tissues. Yap deficiency in the dental epithelium resulted in a small tooth germ with reduced epithelial cell proliferation. We compared the gene expression profiles of embryonic day 14.5 (E14.5) Yap conditional knockout and YAP transgenic mouse tooth germs using transcriptome sequencing (RNA-Seq) and further confirmed the differentially expressed genes using real-time PCR and in situ hybridization. We found that YAP regulates the expression of Hoxa1 and Hoxc13 in oral and dental epithelial tissues as well as in the epidermis of skin during embryonic and adult stages. Sphere formation assay suggested that Hoxa1 and Hoxc13 are functionally involved in YAP-regulated epithelial progenitor cell proliferation, and chromatin immunoprecipitation (ChIP) assay implies that YAP may regulate Hoxa1 and Hoxc13 expression through TEAD transcription factors. These results provide mechanistic insights into abnormal YAP activities in mice and humans.


Recent Advances in the Machine Learning-Based Drug-Target Interaction Prediction.
The identification of drug-target interactions is a crucial issue in drug discovery. In recent years, researchers have made great efforts on the drug-target interaction predictions, and developed databases, software and computational methods. In the paper, we review the recent advances in machine learning-based drug-target interaction prediction. First, we briefly introduce the datasets and data, and summarize features for drugs and targets which can be extracted from different data. Since drug-drug similarity and target-target similarity are important for many machine learning prediction models, we introduce how to calculate similarities based on data or features. Different machine learningbased drug-target interaction prediction methods can be proposed by using different features or information. Thus, we summarize, analyze and compare different machine learning-based prediction methods. This study provides the guide to the development of computational methods for the drug-target interaction prediction.


An HRP study of the central connections of the facial nerve in the mallard (Anas platyrhynchos L.).
The location of several facialis innervated muscles has been determined by injecting individual muscles with horseradish peroxidase. The depressors of the lower jaw are represented in the dorsal facial motor nucleus and the tongue retractor muscles in the intermediate facial motor nucleus. HRP was also directly applied to the rostral and caudal branch of the facial nerve. The afferent connections are described including two small projections to the principal sensory nucleus and n. interpolaris which were not found in birds before.


Nonequilibrium model of photon condensation.
We develop a nonequilibrium model of condensation and lasing of photons in a dye filled microcavity. We examine in detail the nature of the thermalization process induced by absorption and emission of photons by the dye molecules, and investigate when the photons are able to reach a thermal equilibrium Bose-Einstein distribution. At low temperatures, or large cavity losses, the absorption and emission rates are too small to allow the photons to reach thermal equilibrium and the behavior becomes more like that of a conventional laser.


[Dental status and treatment needs in a Vizcaya geriatric institutionalized population].
We have studied the Dental State and the Need of treatment in a population of ancients in a institucionalized regime in the province of Vizcaya. From the 565 studied individual, 300 of the were edentulate and the rest still had remanent pieces in their oral cavity. The CAOD in men was 27,86 and 29,50 in women. On average 2,83 (d.e. 1,15) teeth were pasturing but only 0,14 (d.e. 0,01) obturated teeth. Concerning to the general patology, people affected by insanity had the highest CAOD (30,45)., followed by those with Rheumatism (25,51). It existed a high level dental illness without treatment in the studied sample. The needs of treatment for dental decay were not high didn't require a complex treatment.


Deficiency of pRb family proteins and p53 in invasive urothelial tumorigenesis.
Defects in pRb tumor suppressor pathway occur in approximately 50% of the deadly muscle-invasive urothelial carcinomas in humans and urothelial carcinoma is the most prevalent epithelial cancer in long-term survivors of hereditary retinoblastomas caused by loss-of-function RB1 mutations. Here, we show that conditional inactivation of both RB1 alleles in mouse urothelium failed to accelerate urothelial proliferation. Instead, it profoundly activated the p53 pathway, leading to extensive apoptosis, and selectively induced pRb family member p107. Thus, pRb loss triggered multiple fail-safe mechanisms whereby urothelial cells evade tumorigenesis. Additional loss of p53 in pRb-deficient urothelial cells removed these p53-dependent tumor barriers, resulting in late-onset hyperplasia, umbrella cell nuclear atypia, and rare-occurring low-grade, superficial papillary bladder tumors, without eliciting invasive carcinomas. Importantly, mice deficient in both pRb and p53, but not those deficient in either protein alone, were highly susceptible to subthreshold carcinogen exposure and developed invasive urothelial carcinomas that strongly resembled the human counterparts. The invasive lesions had a marked reduction of p107 but not p130 of the pRb family. Our data provide compelling evidence, indicating that urothelium, one of the slowest cycling epithelia, is remarkably resistant to transformation by pRb or p53 deficiency; that concurrent loss of these two tumor suppressors is necessary but insufficient to initiate urothelial tumorigenesis along the invasive pathway; that p107 may play a critical role in suppressing invasive urothelial tumor formation; and that replacing/restoring the function of pRb, p107, or p53 could be explored as a potential therapeutic strategy to block urothelial tumor progression.


Effect modification in liver allografts with prolonged cold ischemic time.
Although prolonged cold ischemia time (PCIT) is generally associated with worse outcomes following liver transplantation, evidence suggests that some recipients and some donors might be more sensitive to PCIT than others. The purpose of this study was to identify factors that predict a higher risk of graft loss after a transplant with PCIT when compared with a similar transplant with average CIT (ACIT). 14 637 recipients reported to United Network for Organ Sharing (UNOS) in the model for end-stage liver disease (MELD) era were studied by interaction term analysis in proportional hazards models. Recipient diabetes, obesity and donor African American (AA) ethnicity were found to significantly amplify the adverse effects of PCIT. Graft loss was 1.85-fold higher in diabetic or obese PCIT recipients compared with diabetic or obese ACIT recipients, (vs. 1.17 for the same comparison in non-diabetic non-obese recipients). Similarly, graft loss was 1.80-fold higher in AA PCIT donors compared with AA ACIT donors, (vs. 1.31 for the same comparison in non-AA donors). Other factors may also exist, but current clinical practices might already mitigate the risks from those factors. As such, we recommend expanding clinical practice to include our findings, but not abandoning current judgment based on factors already perceived to amplify the adverse effects of PCIT.


Insertion of isolated insulin receptors into placental membrane vesicles.
Purified human insulin receptors were inserted into placental plasma-membrane vesicles by fusion of membranes with receptor-lysophosphatidylcholine micelles. Scatchard analysis of insulin binding showed that about 10-15% of the added receptors became inserted into the membrane. The receptor number could be increased about 3-fold, corresponding to approx. 5 pmol of receptor/mg of membrane protein. The receptors became firmly bound to the membrane, as they could not be removed by extensive wash. The insertion of exogenous receptors could be demonstrated by immunoblotting. The inserted insulin receptor had the same insulin-binding affinity as the isolated receptor and the endogenous receptor of the membrane. Insulin binding in the presence or absence of Triton X-100 revealed that more than 80% of the exogenous receptors had a right-side-out orientation. Function of the inserted receptors, as observed by insulin-stimulated autophosphorylation, could be demonstrated. About 80% of the added lysophospholipid, corresponding to approx. 160 nmol of lysophospholipid/mg of membrane protein, became integrated into the membrane and was partly metabolized to phospholipid and to non-esterified fatty acid. The method of insertion of isolated insulin receptors using the natural detergent, lysophospholipid, may be a method for insertion of receptors into intact cells, where the lysophospholipid, as in the plasma-membrane vesicles, will be acylated to phospholipid.


Upper Limb Performance in Daily Life Improves Over the First 12 Weeks Poststroke.
Background. Upper limb (UL) performance, or use, in daily life is complex and likely influenced by many factors. While the recovery trajectory of UL impairment poststroke is well documented, little is known about the recovery trajectory of sensor-measured UL performance in daily life early after stroke and the potential moderating role of psychosocial factors. Objective. To examine the recovery trajectory of UL performance within the first 12 weeks poststroke and characterize the potential moderating role of belief, confidence, and motivation on UL performance. Methods. This was a longitudinal, prospective cohort study quantifying UL performance and related psychosocial factors early after stroke. UL performance was quantified via bilateral, wrist-worn accelerometers over 5 assessment sessions for 24 hours. Belief, confidence, and motivation to use the paretic UL, and self-perceived barriers to UL recovery were quantified via survey. Change in 4 accelerometer variables and the moderating role of psychosocial factors was tested using hierarchical linear modeling. The relationship between self-perceived barriers and UL performance was tested via Spearman rank-order correlation analysis. Results. UL performance improved over the first 12 weeks after stroke. Belief, confidence, and motivation did not moderate UL performance over time. There was a negative relationship between UL performance and self-perceived barriers to UL recovery at week 2, which declined over time. Conclusions. Sensor-measured UL performance can improve early after stroke. Early after stroke, rehabilitation interventions may not need to directly target belief, confidence, and motivation but may instead focus on reducing self-perceived barriers to UL recovery.


[Laryngeal mask under total myoplegia and artificial pulmonary ventilation during laparoscopic cholecystectomies].
The problem of using a laryngeal mask (LM) under total myorelaxation and artificial pulmonary ventilation (APV) is still topical and unsolved. A hundred and forty six anesthesias for laparoscopic cholecystectomy by employing LM in 86 patients or endotracheal tube (ETT) in 60 were comparatively evaluated. Anesthesia included premedication (diazepam, dimedrol, atropine, the H2-blocking agent ranitidine), induction (ketamine, barbiturates and propofol in combination with diazepam and fentanyl; the NMBs pipecuronium bromide and succinylcholine), maintenance (N20:O2 = 2:1. Fentanyl, pipecuronium bromide), monitoring (Capnomac-Ultima (Datex), Dinamap (Criticon) and acid base balance measurements. The quantity and pH of gastric contents were examined. Methylene blue in gelatin capsules was used as a regurgitation indicator. Unlike ETT, LM caused no reactions. The hemodynamic parameters at the traumatic stages of an operation were higher in the ETT group. Smaller amount of analgetics was used in the LM group. The use of manual APV at Pinsp of < 10 cm H2O fully prevented a gas mixture from entering the stomach. Pneumoperitoneum caused increases in Et CO2, pCO2, P inspiration and decreases in breathing volume and lung compliance. The hermetic sealing of joints was 95.6-98.5% in the LM group. Regurgitation was not found in 33 patients. LM NMB and APV may be successfully and safely used in clinical practice.


Laparoscopic heminephrectomy using a new fibrin sealant powder.
To determine the ability of a hemostatic fibrin sealant powder (HFSP), delivered laparoscopically, to achieve hemostasis and seal the collecting system during laparoscopic heminephrectomy. An HFSP preparation was applied laparoscopically as a dry powder spray. Twenty-two farm pigs were randomized into two laparoscopic heminephrectomy groups: group 1 underwent conventional intracorporal suturing with vascular control (n = 11) and group 2 received HFSP application alone with regional ischemia (n = 11). Computed tomography was performed at 48 hours and again 6 weeks postoperatively. The operative findings revealed no differences between the two groups in the weight of the removed segments, mean arterial blood pressure, operating room time, estimated blood loss, or hematocrit and serum creatinine levels. The gross examination 6 weeks postoperatively found no delayed bleeding, urinoma formation, or bowel adhesions. The computed tomography findings at 48 hours postoperatively demonstrated excellent hemostasis in both groups. Urinary extravasation was detected in 8 (80%) of 10 animals in the HFSP group and 1 (9%) of 11 in the conventional group at 48 hours (P < 0.008). At the 6-week computed tomography evaluation, none of the animals showed evidence of urinoma or hematoma formation. Histopathologically, at 6 weeks, the cut surface of the kidneys in both groups had been replaced by dense scar tissue at the cortex with a sharp line of demarcation between the scar and normal kidney. HFSP greatly facilitates laparoscopic heminephrectomy by providing rapid and lasting hemostasis without suturing. Early urine extravasation was more common in the HFSP group, but no clinical, gross, or radiographic evidence of urinoma formation was seen in either group 6 weeks after surgery.


The role of spiral computed tomography and D-dimer in pulmonary embolism.
The first part of this study retrospectively compared the discriminatory power of spiral CT versus clinical findings in 112 consecutive patients referred with chest pain or dyspnoea. Spiral CT exhibited a sensitivity 91.9%; specificity 98.7%; PPV 97.1%; NPV 96.1%; accuracy 96.4%. No other test or clinical parameter had acceptable accuracy. The SimpliRED test is a latex method of estimating the level of D-dimer. The second part of this study determined that, in a similar consecutive series of patients referred for lung scintigrams, although SimpliRED tests had a NPV 95.5%, 59/126 (46.8%) consecutive were positive. However on the basis of clinical effectiveness and cost, imaging for suspected pulmonary embolism should be based on a combination of D-dimer estimation and spiral CT.


Social organization predicts nature of infant-adult interactions in two species of wild guinea pigs (Cavia aperea and Galea monasteriensis).
The authors compared interactions of infants with mothers and unfamiliar females in a novel environment in 2 caviomorph rodent species: the harem-living Cavia aperea, the probable progenitor of the domestic guinea pig; and the pair-living Galea monasteriensis. In C. aperea, interactions with mothers and unfamiliar females were largely similar; in G. monasteriensis, interactions with the mother, but not unfamiliar female, were characterized by physical closeness and sociopositive behavior. In G. monasteriensis, plasma cortisol levels were lower when with the mother than when with the unfamiliar female. Results are consistent with the species' social organizations and suggest that behavioral interactions of pups with mothers and other females in domestic guinea pigs reflect primarily the social organization of the progenitor species rather than domestication.


Systematic reviews of physical and rehabilitation medicine Cochrane contents. Part 1. Disabilities due to spinal disorders and pain syndromes in adults.
This article is the first in a series presenting the strongest published evidence for physical and rehabilitation medicine (PRM) to date coming from the Cochrane Collaboration. The intent of the series is to stimulate ideas for reviews and research in neglected areas of PRM. To systematically review the rehabilitation contents of the Cochrane Collaboration on disabilities due to spinal disorders or pain syndromes in adults. The Cochrane Database of Systematic Reviews was searched at the end of June 2013 for articles relevant for PRM about disabilities resulting from spinal disorders or pain syndromes in adults. Retrieved papers were classified according to the PRM approach: active therapies, which require active participation by patients to achieve treatment goals, and passive treatments, which rely on the application of external forces. The quality of the reviews was checked against the AMSTAR checklist. Reviews on spinal disorders or pain syndromes were found in the Cochrane Back Group (CBG) and in the Pain, Palliative and Supportive Care Group (CPPSCG). Thirty-eight (42.8%) of 89 Cochrane reviews in the CBG and 7 (2.4%) of 293 Cochrane reviews in the CPPSCG were included. All were of high quality (range, 8-11 points out of 11 on the AMSTAR checklist). The contents of the reviews are given in detail. This review presents an overview of the current evidence for PRM in the treatment of disabilities due to spinal disorders or pain syndromes in adults. Within PRM there is ample space for research in the Cochrane Collaboration and for producing original studies (randomized controlled trials [RCTs]). To apply evidence-based clinical practice, clinicians must be familiar with the current best evidence.