Automated quantification of 18F-flutemetamol PET activity for categorizing scans as negative or positive for brain amyloid: concordance with visual image reads.
Clinical trials of the PET amyloid imaging agent (18)F-flutemetamol have used visual assessment to classify PET scans as negative or positive for brain amyloid. However, quantification provides additional information about regional and global tracer uptake and may have utility for image assessment over time and across different centers. Using postmortem brain neuritic plaque density data as a truth standard to derive a standardized uptake value ratio (SUVR) threshold, we assessed a fully automated quantification method comparing visual and quantitative scan categorizations. We also compared the histopathology-derived SUVR threshold with one derived from healthy controls. Data from 345 consenting subjects enrolled in 8 prior clinical trials of (18)F-flutemetamol injection were used. We grouped subjects into 3 cohorts: an autopsy cohort (n = 68) comprising terminally ill patients with postmortem confirmation of brain amyloid status; a test cohort (n = 172) comprising 33 patients with clinically probable Alzheimer disease, 80 patients with mild cognitive impairment, and 59 healthy volunteers; and a healthy cohort of 105 volunteers, used to define a reference range for SUVR. Visual image categorizations for comparison were from a previous study. A fully automated PET-only quantification method was used to compute regional neocortical SUVRs that were combined into a single composite SUVR. An SUVR threshold for classifying scans as positive or negative was derived by ranking the PET scans from the autopsy cohort based on their composite SUVR and comparing data with the standard of truth based on postmortem brain amyloid status for subjects in the autopsy cohort. The derived threshold was used to categorize the 172 scans in the test cohort as negative or positive, and results were compared with categorization using visual assessment. Different reference and composite region definitions were assessed. Threshold levels were also compared with corresponding thresholds derived from the healthy group. Automated quantification (using pons as the reference region) demonstrated 91% sensitivity and 88% specificity and gave 3 false-positive and 4 false-negative scans. All 3 false-positive cases were either borderline-normal by standard of truth or had moderate to heavy cortical diffuse plaque burden. In the test cohort, the concordance between quantitative and visual read categorization ranged from 97.1% to 99.4% depending on the selection of reference and composite regions. The threshold derived from the healthy group was close to the histopathology-derived threshold. Categorization of (18)F-flutemetamol amyloid imaging data using an automated PET-only quantification method showed good agreement with histopathologic classification of neuritic plaque density and a strong concordance with visual read results.


A population-based study on uveitis in juvenile rheumatoid arthritis.
To obtain information on the occurrence and characteristics of uveitis in a population-based survey of patients with juvenile rheumatoid arthritis (JRA). The subjects in this study were entitled, under the nationwide sickness insurance scheme, to receive specially reimbursed medication for JRA in 5 of the 21 central hospital districts in Finland (population base about 270,000 children < 16 years of age) in 1980, 1985 and 1990. A total of 114 incident cases (34 boys and 80 girls) satisfied the criteria for JRA. Uveitis was diagnosed in 18 of these patients (16%). The mean age of uveitis patients at the diagnosis of JRA was 6.8 years (median 5.4 years) and the mean interval from the diagnosis of JRA to the detection of uveitis was 2.9 years. Silent (asymptomatic) anterior uveitis was found in 4 boys and 11 girls and acute anterior uveitis in 2 boys. One girl had marginal corneal ulceration with mild anterior uveitis. Uveitis was chronic (> 6 months) in 9 cases. Uveal inflammation was most severe in the 3 children whose uveitis was detected at the time of the diagnosis of JRA. The study provides population-based information on the occurrence and characteristics of uveitis associated with JRA.


On the use of effective core potentials in the calculation of magnetic properties, such as magnetizabilites and magnetic shieldings.
State-of-the art effective core potentials (ECPs) that replace electrons of inner atomic cores involve non-local potentials. If such an effective core potential is added to the Hamiltonian of a system in a magnetic field, the resulting Hamiltonian is not gauge invariant. This means, magnetic properties such as magnetisabilities and magnetic shieldings (or magnetic susceptibilities and nuclear magnetic resonance chemical shifts) calculated with different gauge origins are different even for exact solutions of the Schrödinger equation. It is possible to restore gauge invariance of the Hamiltonian by adding magnetic field dependent terms arising from the effective core potential. Numerical calculations on atomic and diatomic model systems (potassium mono-cation and potassium dimer) clearly demonstrate that the standard effective core potential Hamiltonian violates gauge invariance, and this affects the calculation of magnetisabilities more strongly than the calculation of magnetic shieldings. The modified magnetic field dependent effective core potential Hamiltonian is gauge invariant, and therefore it is the correct starting point for distributed gauge origin methods. The formalism for gauge including atomic orbitals (GIAO) and individual gauge for localized orbitals methods is worked out. ECP GIAO results for the potassium dimer are presented. The new method performs much better than a previous ECP GIAO implementation that did not account for the non-locality of the potential. For magnetic shieldings, deviations are clearly seen, but they amount to few ppm only. For magnetisabilities, our new ECP GIAO implementation is a major improvement, as demonstrated by the comparison of all-electron and ECP results.


Pharmacokinetics of prednisone and prednisolone at steady state in the rabbit.
A range (approximately 0.2-2.0 micrograms/min/kg) of constant rate iv infusions of prednisolone (as the phosphate ester) was administered to five rabbits either singly or as two consecutive infusions, and then again at about the same rates of infusion as part of multiple infusion studies. Prednisone (as the succinate) was also infused at three different infusion rates (range, 1.5-15 micrograms/min/kg) to four of the five rabbits. Plasma concentrations of prednisolone and prednisone at steady state were measured by HPLC. The binding of prednisone and prednisolone in plasma was measured by equilibrium dialysis. The multiple infusion studies demonstrated that the nonlinearity in plasma clearance of prednisolone could not be attributed to any time-dependent effect. The average plasma clearance of prednisolone increased by 250% when its rate of infusion was increased 10-fold. The ranges of clearance values at low and high rates of infusion were 2.51-4.08 and 6.08-10.98 ml/min/kg, respectively. The binding of prednisolone in plasma was found to be concentration dependent. At the lower rates of infusions, the clearance of unbound prednisolone appeared to increase on increasing its rate of infusion but remained relatively constant thereafter (greater than 1.0 microgram/min/kg). The ranges of unbound plasma prednisolone clearance at low and high rates of infusions were 30.3-67.7 and 50.6-110.2 ml/min/kg, respectively. The percentage of unbound prednisone increased on increasing the total plasma prednisone concentration (ranges at low and high concentrations of prednisone were 15.5-33.7 and 32.3-47.6%).(ABSTRACT TRUNCATED AT 250 WORDS)


Assessment of evaluation of transference support and training impact on the work of nurses.
to assess the impact of the Training Course on Prevention and Treatment of PU, in width and depth; to observe and analyze the variables of transference support of training, offered by the organization and to verify the existence of the relationship between transference support and training impact. this was a quantitative study, in which data were collected through the application of Likert-type instruments, conducted with 75 nurses participating in a training at a hospital organization in São Paulo city. Data were analyzed statistically. there was a positive impact in width and depth, and the variables of transference support were strongly related to the impact, and situational factors of support were the main predictors of impact. the results pointed toward pathways to redirect the practice of instructional actions in the work environment of individuals in the study scenario and in similar situations that occur in organizations.


The basolateral expression of mUT-A3 in the mouse kidney.
Facilitative UT-A urea transporters play a central role in the urinary concentrating mechanism. There are three major UT-A isoforms found in the mouse kidney: mUT-A1, mUT-A2, and mUT-A3. The major aim of this study was to identify the location and function of mUT-A3. UT-A proteins were investigated using three novel mouse UT-A-targeted antibodies: ML446, MQ2, and ML194. ML446 detected mUT-A1 and mUT-A3. ML194 detected mUT-A1 and mUT-A2. Importantly, MQ2 was found to be selective for mUT-A3. MQ2 detected a 45- to 65-kDa signal in the mouse kidney inner medulla, which was deglycosylated to a 40-kDa protein band. Immunolocalization studies showed that mUT-A3 was strongly detected in the papillary tip, mainly in the basolateral regions of inner medullary collecting duct (IMCD) cells. Immunoblotting of subcellular fractions of inner medullary protein suggested that in mouse kidney mUT-A3 was present in plasma membranes. Consistent with this, immunoelectron microscopy demonstrated that mUT-A3 was predominantly localized at the basal plasma membrane domains of the IMCD cells in mouse kidney. Heterologous expression of mUT-A3-enhanced green fluorescent protein in Madin-Darby canine kidney cells showed that the protein localized to the basolateral membrane. In conclusion, our study indicates that mUT-A3 is a basolateral membrane transporter expressed in IMCD cells.


Formal modelling of toll like receptor 4 and JAK/STAT signalling pathways: insight into the roles of SOCS-1, interferon-β and proinflammatory cytokines in sepsis.
Sepsis is one of the major causes of human morbidity and results in a considerable number of deaths each year. Lipopolysaccharide-induced sepsis has been associated with TLR4 signalling pathway which in collaboration with the JAK/STAT signalling regulate endotoxemia and inflammation. However, during sepsis our immune system cannot maintain a balance of cytokine levels and results in multiple organ damage and eventual death. Different opinions have been made in previous studies about the expression patterns and the role of proinflammatory cytokines in sepsis that attracted our attention towards qualitative properties of TLR4 and JAK/STAT signalling pathways using computer-aided studies. René Thomas' formalism was used to model septic and non-septic dynamics of TLR4 and JAK/STAT signalling. Comparisons among dynamics were made by intervening or removing the specific interactions among entities. Among our predictions, recurrent induction of proinflammatory cytokines with subsequent downregulation was found as the basic characteristic of septic model. This characteristic was found in agreement with previous experimental studies, which implicate that inflammation is followed by immunomodulation in septic patients. Moreover, intervention in downregulation of proinflammatory cytokines by SOCS-1 was found desirable to boost the immune responses. On the other hand, interventions either in TLR4 or transcriptional elements such as NFκB and STAT were found effective in the downregulation of immune responses. Whereas, IFN-β and SOCS-1 mediated downregulation at different levels of signalling were found to be associated with variations in the levels of proinflammatory cytokines. However, these predictions need to be further validated using wet laboratory experimental studies to further explore the roles of inhibitors such as SOCS-1 and IFN-β, which may alter the levels of proinflammatory cytokines at different stages of sepsis.


Freshly fractured crystalline silica induces activator protein-1 activation through ERKs and p38 MAPK.
The transcription factor activator protein-1 (AP-1) reportedly plays an important role in the induction of neoplastic transformation and multiple genes involved in cell proliferation, differentiation, and inflammation. To investigate the mechanisms of silica-induced carcinogenesis, AP-1-luciferase reporter transgenic mice were used as an in vivo model, whereas the JB6 mouse epidermal cell line and a rat lung epithelial cell line were employed as in vitro models to study the effects of silica at the molecular level. Freshly fractured silica caused an 8-fold increase in AP-1 activity in JB6 cells and a 2.5-fold increase in rat lung epithelial cells. The induction of AP-1 activity in cultured cell lines was time- and dose-dependent. Intratracheal administration of silica was also able to induce AP-1 transactivation in transgenic mice. AP-1 activation was first observed at 2 days after silica administration and reached its maximum at 3 days post-exposure of the mice to silica. The signal transduction pathways for AP-1 activation were also investigated using these cell lines. The results demonstrate that freshly fractured silica stimulates mitogen-activated protein kinase (MAPK) family members, as determined by the phosphorylation of p38 MAPK and extracellular signal-regulated protein kinases (ERKs). Inhibition of ERKs with PD98059 or of p38 with SB203580 significantly inhibited silica-induced AP-1 activation. These findings demonstrate for the first time that freshly fractured silica induces AP-1 activation, which may be mediated through p38 MAPK and ERK pathways. Unraveling the complex mechanisms associated with these events may provide insights into the initiation and progression of silica-induced carcinogenesis.


Substituent effect on the dynamics of the inclusion complex formation between protoberberine alkaloids and cucurbit[7]uril.
The kinetics of entry into and exit from the cavity of cucurbit[7]uril (CB7) was studied by the stopped-flow method in water at various temperatures using pharmaceutically important natural isoquinoline alkaloids as guest compounds. The rate constant of the alkaloid-CB7 complex dissociation was separately determined exploiting the very strong competitive binding of the 1-adamantylammonium cation to CB7. The enthalpy and entropy of activation for the release of berberine from CB7 were significantly lower than those found in the case of the other alkaloids, suggesting different dissociation dynamics. CB7 initially moved from the energetically most stable position encompassing the isoquinoline moiety of berberine to the smaller benzodioxole part, which could leave the macrocycle with less structural distortion. Despite the same thermodynamic parameters of berberine and palmatine inclusion, the latter compound was encapsulated in and set free from CB7 much slower due to the more substantial steric hindrance. The most rapid entry into CB7 and the most exothermic binding were found for epiberberine and coptisine, the alkaloids substituted with the less spacious dioxole ring on their isoquinoline moiety.


The Cervical Dysplasia Worksheet: A Longitudinal Map of Cervical Dysplasia Cytology and Histology Tests and Procedures.
Our objectives were to describe the Cervical Dysplasia Worksheet (CDW), provide evidence of its feasibility to view patient cervical dysplasia results over time, and evaluate patient attitudes toward the tool in the setting of abnormal result follow-up. The CDW augments the ASCCP guidelines for managing abnormal cervical cancer screenings by visually depicting cervical cytological and histological history along a color gradient showing severity. We evaluated tool feasibility by graphing a retrospectively reviewed convenience sample of patient data. A cross-sectional evaluation of the tool was then performed to assess patient attitudes in the setting of either dysplasia or colposcopy clinic. Patients had their data graphed on the CDW and explained to them before their clinical encounter. They then gave general comments about the tool and filled out a short evaluation survey. The large majority of retrospective patient data (N = 167) fit well within the CDW with roughly 20% requiring space for additional comments. Among the 30 patients who participated in our evaluation, almost all agreed (n = 29, 96.7%) that the tool helped them understand their history and results and that they would use the tool in the future. The CDW is a novel tool to display a patient's cervical dysplasia history to visualize treatment and future care while enhancing patient-provider communication. Patient evaluation of the tool was largely positive, and suggestions will be taken into consideration for future modification. Further evaluation of the CDW among healthcare providers is needed to analyze its efficacy in the clinical setting.


Prospective pilot evaluation of the effectiveness and cost-utility of a 'health first' case management service for long-term Incapacity Benefit recipients.
In line with the NICE guidance, an NHS-commissioned case management intervention was provided for individuals receiving Incapacity Benefit payments for ≥3 years in the North East of England. The intervention aimed to improve the health of the participants. A total of 131 participants receiving the intervention were compared over 9 months with a (non-equivalent) comparison group of 229 receiving Incapacity Benefit payments and usual care. Health was measured using EQ-5D, EQ-VAS, SF-8, HADS and the Nordic Musculoskeletal questionnaire. Socio-demographic and health behaviour data were also collected. Fixed-effects linear models with correlated errors were used to compare health changes between groups over time. A preliminary cost-utility analysis was also conducted. The comparison group measures of health were stable over time. Starting from comparatively poor initial levels, case-management group generic (EQ5D, EQ-VAS) and mental health (HADS-A, HADS-D and SF8-MCS) measures improved within 6 months to similar levels found in the comparison group. Musculoskeletal (Nordic 2) and health behaviours did not improve. Tentative estimates of cost-utility suggest an intervention cost in the region of £16 700-£23 500 per QALY. Case management interventions may improve the health of Incapacity Benefit recipients. Further research is required to help confirm these pilot findings.


A monoclonal antibody specific to Müller cells and selective synaptic sites in the retina.
We have produced a monoclonal antibody which stains the Müller cells in the region of the photoreceptors, nerve terminals surrounding the horizontal cells, and nerve terminals in the inner plexiform layer in carp, goldfish, and white perch retinas. Electron microscopy showed that the staining in the outer and inner retina was confined to Müller cells and presynaptic terminals, respectively. In the teleost brain, the antibody stained only the optic tectum and efferent fibers from the stratum album centrale. Biochemical characterization by immunoblotting showed that this monoclonal antibody recognizes an approximately 70-kD molecule in both whole retina and brain homogenates, suggesting that the antibody recognizes an identical molecule. No staining was noted in the spleen or the liver. This monoclonal antibody appears to be specific to a molecule common to the Müller cells and presynaptic terminals in the teleost retina, and although it is present in other parts of the central nervous system, it is confined to the visual pathway.


Aptamer selection in a porous hydrogel.
The process of nucleic acid aptamer selection can be quite laborious and fraught with artifacts. In a work published in Nature Biotechnology, Singh et al. describe an approach that should allow more facile aptamer selection.


Severe traumatic brain injury.
Although adherence to traumatic brain injury (TBI) guidelines has been associated with improved patient outcomes, guideline adherence remains suboptimal in practice. With neurologists becoming increasingly involved in specialized neurointensive care units and in the care of patients with severe TBI, familiarization with these guidelines is essential. Intracranial monitoring of different physiologic variables has increased in the past few years. Intracranial pressure (ICP)-driven therapy has been replaced by ICP-cerebral perfusion pressure (CPP)-driven therapy. More recently, the importance of brain oxygen optimization in addition to ICP-CPP has been recognized, and clinical trials are underway to study the effect of this approach. Surgical management of patients with TBI is also evolving rapidly with further studies on decompressive craniectomy. These are significant advances to improve TBI outcomes. This article summarizes the routine monitoring of patients with severe TBI and offers insight into some novel physiologic monitoring devices available. The guidelines for management of patients with severe TBI are summarized along with outcome measures.


Culturally-consistent diet among individuals of Mexican descent at the US-Mexico border is associated with sleep duration and snoring.
Existing studies show that consuming food consistent with one's culture reduces cardiometabolic risk. However, few studies have assessed whether these dietary choices influence sleep health. Accordingly, this study assessed how Mexican food consumption by individuals of Mexican descent residing at the US-Mexico border, was associated with various measures of sleep, after accounting for acculturation. Data were provided by 100 adults between the ages of 18-60, in the city of Nogales, AZ. Questionnaires were provided in either Spanish or English. Acculturation was assessed with the Acculturation Scale for Mexican-Americans (ARSMA-II), with an additional question, asking how often "my family cooks Mexican foods." Frequency of cooking Mexican food was coded as either "yes" or "no." Sleep was assessed, using validated measures that include the Insomnia Severity Index (ISI), the Epworth Sleepiness Scale (ESS), the Pittsburgh Sleep Quality Index (PSQI), and sleep duration with the item "how many hours of actual sleep did you get at night?" Regression models estimated the associations between sleep health variables as outcomes and consumption of Mexican food as the independent variable. Covariates included age, sex, and acculturation scores. Parental education level was also included, as an indicator of childhood socioeconomic status and since food culture likely involves parents. We found that among individuals who identified as Mexican-Americans who consumed culturally-consistent foods, was associated with, on average, 1.41 more hours of sleep (95% CI 0.19, 2.62; p = 0.024) and were less likely to report snoring (OR: 0.25; 95% CI 0.07, 0.93; p = 0.039). Consuming Mexican food was not associated with sleep quality, insomnia severity or sleepiness. Individuals of Mexican descent residing at the US-Mexico border who regularly consumed Mexican food, reported more sleep and less snoring. Mexican acculturation has been shown previously to improve sleep health. This is likely due to consumption of a culturally- consistent diet. Future studies should examine the role of acculturation in sleep health, dietary choices, and subsequent cardiometabolic risk.


Characterization of binding sites for [3H]spiroperidol.
Experiments were designed to investigate the biochemical properties of binding sites for [3H]spiroperidol ([3H]SPD) solubilized from canine caudate and to define the effect of detergent on the binding of the radioligand. Extraction of canine caudate with 0.75-1.0% digitonin was found to generate the maximum yield of binding sites for [3H]SPD while minimizing extraction of membrane proteins. Although binding sites were solubilized with 1.0% digitonin, a 10-fold reduction in detergent concentration was necessary to achieve maximal binding of [3H]SPD. The rank order of affinity for agonists and antagonists was consistent with the pharmacologic properties of the D2 subtype of the dopamine receptor. However, the binding of antagonists was found to be complex. Studies with some preparations of pooled canine caudate resulted in competition curves for the D2-selective antagonists domperidone and sulpiride that best fit a single-site model. Other preparations exhibited biphasic inhibition curves with these antagonists. The class of binding sites for [3H]SPD with low affinity for D2-selective antagonists constituted as much as 30-40% of the binding sites. Enrichment of solubilized binding sites for [3H]SPD was achieved by size exclusion HPLC followed by adsorption to DEAE-Sephadex and elution with buffer of increasing ionic strength. Enrichment of binding sites was accompanied by a decrease in the affinity of solubilized sites for [3H]SPD.


Effects of activation of protein kinase C on the agonist-induced stimulation and inhibition of cyclic AMP formation in intact human platelets.
Jakobs, Bauer & Watanabe [(1985) Eur. J. Biochem. 151, 425-430] reported that treatment of platelets with phorbol 12-myristate 13-acetate (PMA) prevented GTP- and agonist-induced inhibition of adenylate cyclase in membranes from the platelets. This was attributed to the phosphorylation of the inhibitory guanine nucleotide-binding protein (Gi) by protein kinase C. In the present study, the effects of PMA on cyclic [3H]AMP formation and protein phosphorylation were studied in intact human platelets labelled with [3H]adenine and [32P]Pi. Incubation mixtures contained indomethacin to block prostaglandin synthesis, phosphocreatine and creatine kinase to remove ADP released from the platelets, and 3-isobutyl-1-methylxanthine to inhibit cyclic AMP phosphodiesterases. Under these conditions, PMA partially inhibited the initial formation of cyclic [3H]AMP induced by prostaglandin E1 (PGE1), but later enhanced cyclic [3H]AMP accumulation by blocking the slow decrease in activation of adenylate cyclase that follows addition of PGE1. PMA had more marked and exclusively inhibitory effects on cyclic [3H]AMP formation induced by prostaglandin D2 and also inhibited the action of forskolin. Adrenaline, high thrombin concentrations and, in the absence of phosphocreatine and creatine kinase, ADP inhibited cyclic [3H]AMP formation induced by PGE1. The actions of adrenaline and thrombin were attenuated by PMA, but that of ADP was little affected, suggesting differences in the mechanisms by which these agonists inhibit adenylate cyclase. sn-1,2-Dioctanoylglycerol (diC8) had effects similar to those of PMA. The actions of increasing concentrations of PMA or diC8 on the modulation of cyclic [3H]AMP formation by PGE1 or adrenaline correlated with intracellular protein kinase C activity, as determined by 32P incorporation into the 47 kDa substrate of the enzyme. Parallel increases in phosphorylation of 20 kDa and 39-41 kDa proteins were also observed. Platelet-activating factor, [Arg8]vasopressin and low thrombin concentrations, all of which inhibit adenylate cyclase in isolated platelet membranes, did not affect cyclic [3H]AMP formation in intact platelets. However, the activation of protein kinase C by these agonists was insufficient to account for their failure to inhibit cyclic [3H]AMP formation. Moreover, high thrombin concentrations simultaneously activated protein kinase C and inhibited cyclic [3H]AMP formation. The results show that, in the intact platelet, the predominant effects of activation of protein kinase C on adenylate cyclase activity are inhibitory, suggesting actions additional to inactivation of Gi.


Selective location of palisaded myofibroblastoma with amianthoid fibres.
The occurrence of a palisaded myofibroblastoma with amianthoid fibres in the left inguinal lymph node of a 51 year old man prompted an investigation of the factors underlying its exclusive location. The antigen profile was characterised which confirmed the homogeneous expression of vimentin and smooth muscle actin as well as the lack of desmin. Use of monoclonal antibodies to check for a differential distribution of myofibroblasts and the putative cell of origin of palisaded myofibroblastoma showed that inguinal lymph nodes have abundant vimentin and actin positive cells and desmin negative cells. This suggests that the selective occurrence of myofibroblastoma is related to the nodal microenvironment, providing a source of available and potentially proliferating myofibroblasts. Mast cells abounded in this lesion, particularly around amianthoid fibres, as well as in pelvic and inguinal lymph nodes. In view of the known role of mast cells in interstitial matrix degradation it is postulated that the core of amianthoid fibres represents degraded interstitial matrix, analogous to the sclerotic areas commonly found in the above mentioned lymph node groups, while the peripheral spokes, so peculiar to this entity, are the result of vimentin and smooth muscle actin, directly shed by proliferating myofibroblasts.


High rate of return to sport in adolescent athletes following anterior shoulder stabilisation: a systematic review.
Traumatic anterior shoulder instability remains common for the adolescent athletes. To perform a systematic review on the outcomes and return to sport (RTS) following Bankart repair in adolescent athletes. A systematic review using the Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines was conducted of studies reporting outcomes following open and/or arthroscopic Bankart repair using modern suture anchors following traumatic anterior shoulder dislocations in adolescent patients (ages 10-19 years). Quality assessment was evaluated with ROBINS-I and MINORS instruments. The outcomes analysed included RTS, timetable to unrestricted activity, recurrent instability and revision surgery. This systematic review identified 11 studies comprising 461 adolescent athletes with a mean age of 15.7 years (range, 11-19 years) and an average follow-up of 48.8 months (range, 22-85.2 months). A total of 392 patients (400 shoulders) underwent arthroscopic Bankart repair, while the remaining 69 patients (69 shoulders) underwent an open procedure. The average MINORS score was 9.6 for non-comparative studies and 17 for comparative studies. ROBINS-I revealed six studies to have a moderate risk of bias, while the remaining five studies presented serious risk of bias. There was an overall 81.5% rate of RTS to preinjury levels of athletic competition at an average of 5.3 months following Bankart repair for traumatic anterior shoulder instability. The overall total mean incidence of recurrent instability was 18.5%, while the mean incidence of revision surgery was 12.1%. Contact athletes had a 31.1% and 13% rate of recurrence and revision surgery, respectively. In comparison, collision athletes were shown to have a 10.4% and 1.4% incidence of recurrent instability and revision surgery, respectively. Adolescent athletes who undergo Bankart repair for traumatic anterior shoulder instability have an 81.5% rate of RTS to preinjury levels of play at an average of 5 months following surgery. The overall total mean incidence of recurrent instability in the adolescent population is 18.5%, while the mean incidence of revision surgery is 12.1%. The results of anterior shoulder stabilisation in contact athletes is much less predictable, with higher reported rates of recurrent instability and revision surgery. Level IV.


Association between Leukoaraiosis and Symptomatic Intracranial Large Artery Stenoses and Occlusions: the Chinese Intracranial Atherosclerosis (CICAS) Study.
Leukoaraiosis (LA) is frequently found in ischemic stroke patients, especially when those patients have intracranial atherosclerosis (ICAS). However, previous studies regarding an association of LA with cerebral large artery atherosclerosis showed conflicting results, and the relationship of LA with ICAS is uncertain. This study aimed to explore the association between LA and cerebral large artery atherosclerosis in Chinese patients with cerebral ischemia. Data were derived from the Chinese Intracranial Atherosclerosis (CICAS) study. Patients diagnosed with an ischemic stroke or transient ischemic attack (TIA) within 7 days of symptom onset were included. The analysis of magnetic resonance imaging (MRI) focused on severity of LA in periventricular and deep white matter; type of cerebral large artery stenosis; and the number, severity, and distribution of ICAS lesions. ICAS was defined as an occlusion or more than 50% stenosis of intracranial vessels on magnetic resonance angiography. Among 2420 patients included, distinct LA was observed in 898 (37.11%) patients, and the rate of LA increased significantly with an increased number of risk factors. Multivariate analysis revealed that LA was independently associated with ICAS (odds ratio [OR], 1.388; 95% confidence interval [CI], 1.132-1.702; P=0.0016). In the subgroup analysis of ICAS, LA was more frequently observed in multiple lesions (OR, 1.342; 95% CI, 1.060-1.699; P=0.0146), occlusive lesions (OR, 1.554; 95% CI, 1.214-1.998; P=0.0005), and lesions in the posterior circulation (OR, 1.360; 95% CI, 1.003-1.846; P=0.0481). In this nationwide prospective study, LA was associated with symptomatic ICAS, patients with multiple ICAS lesions, occlusive lesions, and atherosclerotic lesions in the posterior circulation were more likely to coexist with LA.


PKR inhibitor protects spinal cord injury through mitigating endoplasmic reticulum stress and pyroptosis.
The goal of the study was to reveal the regulatory role of protein kinase R (PKR) in spinal cord injury (SCI), a devasting disorder of the neurological system, and to elucidate its potential mechanism. The established animal and cellular models of SCI were treated by the PKR inhibitor C12. Histological injury and tissue apoptosis were assessed via H&E staining and TUNEL assays, respectively. Basso-Beattie-Bresnahan (BBB) scoring as well as forelimb grip strength tests were employed to evaluate functional recovery. The production of ROS and cytokines were appraised via their related commercial kits. Western blot and immunofluorescence assay were used to examine protein expression. CCK-8 method was used to assay cell activity. Co-immunoprecipitation assay was conducted to measure the affinity of PKR with STAT1. PKR expression was enhanced following SCI, and the PKR inhibitor C16 mitigated histological injury, cell apoptosis and water content in spinal cord, and improved function recovery following SCI. Meanwhile, C16 attenuated ER stress, pyroptosis, NLRP3 inflammasome and inflammation in mice with SCI and in BV-2 cells challenged with LPS. Additionally, PKR interacted with STAT1 in BV-2 cells, and STAT1 knockdown inhibited ER stress, pyroptosis and inflammation in BV-2 cells challenged with LPS. The protective role of C16 in BV-2 cells exposed to LPS were partly abolished by STAT1 overexpression. PKR inhibition might be a prospective effective approach to attenuating SCI and accelerating function recovery through modulating microglial pyroptosis and ER stress.


The effect of hippocampal subfield damage on rapid temporal integration through statistical learning and associative inference.
The hippocampus (HPC) supports integration of information across time, often indexed by associative inference (AI) and statistical learning (SL) tasks. In AI, an indirect association between stimuli that never appeared together is inferred, whereas SL involves learning item relationships by extracting regularities across experiences. A recent model of hippocampal function (Schapiro et al., 2017) proposes that the HPC can support temporal integration in both paradigms through its two distinct pathways. We tested this models' predictions in four patients with varying degrees of bilateral HPC damage and matched healthy controls, with two patients with complementary damage to either the monosynaptic or trisynaptic pathway. During AI, participants studied overlapping paired associates (AB, BC) and their memory was tested for premise pairs (AB) and for inferred pairs (AC). During SL, participants passively viewed a continuous picture sequence that contained an underlying structure of triplets that later had to be recognized. Binomial distributions were used to calculate above chance performance at the individual level. For AI, patients with focal HPC damage were impaired at inference, but could correctly infer pairs above chance once premise pair acquisition was equated to controls. However, the patient with HPC and cortical damage showed severe impairment at recalling premise and inferred pairs, regardless of accounting for premise pair performance. For SL, none of the patients performed above chance, but notably neither did most controls. Associative inference of indirect relationships can be intact with HPC damage to either hippocampal pathways or the HPC more broadly, provided premise pairs can first be formed. Inference may remain intact through residual HPC tissue supporting premise pair acquisition, and/or through extra-hippocampal structures supporting inference at retrieval. Clear conclusions about hippocampal contributions to SL are precluded by low performance in controls, which we caution is not dissimilar to previous amnesic studies using the same task. This complicates interpretations, therefore common use of a reliable task is needed before conclusions can be drawn about the necessity of hippocampal contributions to SL.


In situ S-isotope compositions of sulfate and sulfide from the 3.2 Ga Moodies Group, South Africa: A record of oxidative sulfur cycling.
Sulfate minerals are rare in the Archean rock record and largely restricted to the occurrence of barite (BaSO4 ). The origin of this barite remains controversially debated. The mass-independent fractionation of sulfur isotopes in these and other Archean sedimentary rocks suggests that photolysis of volcanic aerosols in an oxygen-poor atmosphere played an important role in their formation. Here, we report on the multiple sulfur isotopic composition of sedimentary anhydrite in the ca. 3.22 Ga Moodies Group of the Barberton Greenstone Belt, southern Africa. Anhydrite occurs, together with barite and pyrite, in regionally traceable beds that formed in fluvial settings. Variable abundances of barite versus anhydrite reflect changes in sulfate enrichment by evaporitic concentration across orders of magnitude in an arid, nearshore terrestrial environment, periodically replenished by influxes of seawater. The multiple S-isotope compositions of anhydrite and pyrite are consistent with microbial sulfate reduction. S-isotope signatures in barite suggest an additional oxidative sulfate source probably derived from continental weathering of sulfide possibly enhanced by microbial sulfur oxidation. Although depositional environments of Moodies sulfate minerals differ strongly from marine barite deposits, their sulfur isotopic composition is similar and most likely reflects a primary isotopic signature. The data indicate that a constant input of small portions of oxidized sulfur from the continents into the ocean may have contributed to the observed long-term increase in Δ33 Ssulfate values through the Paleoarchean.


Early and Late Complications in Laparoscopic Gastric Bypass: Comparative Study between Manual and Stapled Anastomosis.
The aim of this study is to evaluate the early and late complications of laparoscopic gastric bypass (GBP) with manual versus stapled gastrojejunal anastomosis. Eighty-two patients with morbid obesity and body mass index (35-56 kg/m2) who underwent GBP were divided into two groups: manual gastrojejunal anastomosis (Group 1) and stapled anastomosis (Group 2). Early and late complications were evaluated. No differences were found between both groups in age, sex, body mass index, American Society of Anesthesia classification, and comorbidity. The mean operative time was 184.8 minutes [standard deviation (SD) = 61]; 203.5 minutes (SD = 51.9) in Group 1 and 167.4 minutes (SD = 64.2) in Group 2 (P = 0.001). The average length of stay was 5.9 days (SD = 3.9) in Group 1 and 5 days (SD = 2.1) in Group 2 (P = 0.039). Early complications were recorded in 9.7 per cent of the cases, without any differences between the two groups: 12.2 per cent in Group 1 and 7.3 per cent in Group 2 (P > 0.05). Late complication rate was 8.5 per cent, significantly higher in Group 1 (14.6%) than in Group 2 (2.4%; P < 0.05). However, in the logistic regression analysis these differences were not statistically significant (OR 0.48; 95% CI 0.03-8.37; P = 0.61). In our series, the GBP with stapled gastrojejunal anastomosis has shown lower hospital length of stay and operative time than the hand-sewn anastomosis. We have not found significant differences between both groups in early complications or in the need for reoperation. Fewer late complications were found in the group of stapled anastomosis; however, this has not been confirmed in the logistic regression analysis.


Data-driven Evolution Equation Reconstruction for Parameter-Dependent Nonlinear Dynamical Systems.
When studying observations of chemical reaction dynamics, closed form equations based on a putative mechanism may not be available. Yet when sufficient data from experimental observations can be obtained, even without knowing what exactly the physical meaning of the parameter settings or recorded variables are, data-driven methods can be used to construct minimal (and in a sense, robust) realizations of the system. The approach attempts, in a sense, to circumvent physical understanding, by building intrinsic "information geometries" of the observed data, and thus enabling prediction without physical/chemical knowledge. Here we use such an approach to obtain evolution equations for a data-driven realization of the original system - in effect, allowing prediction based on the informed interrogation of the agnostically organized observation database. We illustrate the approach on observations of (a) the normal form for the cusp singularity, (b) a cusp singularity for the nonisothermal CSTR, and (c) a random invertible transformation of the nonisothermal CSTR, showing that one can predict even when the observables are not "simply explainable" physical quantities. We discuss current limitations and possible extensions of the procedure.


An ocular presentation of familial tumoral calcinosis.
This case report presents the ophthalmic features and complications of a 56-year-old Caucasian woman with familial tumoral calcinosis. She presented to our ophthalmology clinic with a 3-month history of blurring of her vision. She had been diagnosed 14 years earlier with familial tumoral calcinosis. Ophthalmological examination revealed calcific depositions on the eyelid margins, perilimbal calcific deposits and angioid streaks. An optical coherence tomography scan of the left eye revealed a choroidal neovascular membrane. Deterioration in vision occurred secondary to subretinal haemorrhage, resulting from the angioid streak. The patient was treated with a series of three intravitreal ranibizumab injections to her left eye, which led to an improvement in her visual acuity (VA). The patient is being closely followed up with monthly appointments, and to date, after 6 months of follow-up, there has been no further deterioration in her VA or reactivation of the choroidal neovascular membrane.


Individualized, home-based interactive training of cerebral palsy children delivered through the Internet.
The available health resources limit the amount of therapy that may be offered to children with cerebral palsy and the amount of training in each session may be insufficient to drive the neuroplastic changes, which are necessary for functional improvements to take place. The aim of this pilot study was to provide proof of concept that individualized and supervised interactive home-based training delivered through the internet may provide an efficient way of maintaining intensive training of children with cerebral palsy over prolonged periods. 9 children (aged 9-13 years) with cerebral palsy were included in the study. Motor, perceptual and cognitive abilities were evaluated before and after 20 weeks of home-based training delivered through the internet. The children and their families reported great enthusiasm with the training system and all experienced subjective improvements in motor abilities and self-esteem. The children on average trained for 74 hours during a 20 week period equalling just over 30 minutes per day. Significant improvements in functional muscle strength measured as the frontal and lateral step-up and sit-to-stand tests were observed. Assessment of Motor and processing skills also showed significant increases. Endurance measured as the Bruce test showed a significant improvement, whereas there was no significant change in the 6 min walking test. Balance (Romberg) was unchanged. Visual perceptual abilities increased significantly. We conclude that it is feasible to deliver interactive training of children with cerebral palsy at home through the internet and thereby ensure more intensive and longer lasting training than what is normally offered to this group.


Overexpression of the hOGG1 gene and high 8-hydroxy-2'-deoxyguanosine (8-OHdG) lyase activity in human colorectal carcinoma: regulation mechanism of the 8-OHdG level in DNA.
8-Hydroxy-2'-deoxyguanosine (8-OHdG) is one of the most abundant oxidatively modified lesions in DNA. Our previous study (Kondo et al, Free Radic. Biol. Med., 27: 401-410, 1999) revealed that human colorectal carcinoma cells are oxidatively stressed based on 8-OHdG determination. To elucidate 8-OHdG metabolism and its clinical significance in colorectal carcinoma, we studied the 8-OHdG repair system in DNA by measuring specific lyase activity and hOGG1 expression using quantitative-competitive reverse transcription-PCR. In addition, we searched for the presence of mutations and single nucleotide polymorphisms of the hOGG1 gene by single-strand conformational polymorphism and sequencing analyses. It was found that 8-OHdG-specific lyase activity and hOGG1 expression were significantly up-regulated in carcinoma, and a proportional association between 8-OHdG levels and either 8-OHdG lyase activity (r = 0.641, P < 0.05) or hOGG1 expression (r = 0.702, P < 0.05) was present. Whereas no difference was detected in the 8-OHdG level between early- and advanced-stage cancer, lyase activity (1.2-fold) and hOG1 expression (1.6-fold) were significantly increased in advanced-stage cancer. No mutation was found in the 25 tumors examined. Three kinds of single nucleotide polymor. phism were observed, including that of codon 326 (Ser/Cys) in exon 7. However, there was no correlation between any of the three polymorphic patterns and either 8-OHdG level or lyase activity. These results suggest that increased 8-OHdG levels in colorectal carcinoma are attributed to increased formation and are maintained by induced 8-OHdG repair activity at appropriate high levels. Our results may offer a unique approach in the development of preventive and therapeutic interventions as well as new insights into the pathogenesis of colorectal carcinoma.


Precision Surgical Therapy for Adenocarcinoma of the Esophagus and Esophagogastric Junction.
To facilitate the initial clinical decision regarding whether to use esophagectomy alone or neoadjuvant therapy in surgical care for individual patients with adenocarcinoma of the esophagus and esophagogastric junction-information not available from randomized trials-a machine-learning analysis was performed using worldwide real-world data on patients undergoing different therapies for this rare adenocarcinoma. Using random forest technology in a sequential analysis, we (1) identified eligibility for each of four therapies among 13,365 patients: esophagectomy alone (n = 6649), neoadjuvant therapy (n = 4706), esophagectomy and adjuvant therapy (n = 998), and neoadjuvant and adjuvant therapy (n = 1022); (2) performed survival analyses incorporating interactions of patient and cancer characteristics with therapy; (3) determined optimal therapy as that predicted to maximize lifetime within 10 years (restricted mean survival time; RMST) for each patient; and (4) compared lifetime gained from optimal versus actual therapies. Actual therapy was optimal in 61% of those receiving esophagectomy alone; neoadjuvant therapy was optimal for 36% receiving neoadjuvant therapy. Many patients were predicted to benefit from postoperative adjuvant therapy. Total RMST for actual therapy received was 58,825 years. Had patients received optimal therapy, total RMST was predicted to be 62,982 years, a 7% gain. Average treatment effect for adenocarcinoma of the esophagus yields only crude evidence-based therapy guidelines. However, patient response to therapy is widely variable, and survival after data-driven predicted optimal therapy often differs from actual therapy received. Therapy must address an individual patient's cancer and clinical characteristics to provide precision surgical therapy for adenocarcinoma of the esophagus and esophagogastric junction.


The radiology corner: the small bowel in immunoglobulin deficiency syndromes.
Recent advances in immunology have permitted recognition of a group of patients who have gastrointestinal manifestations as part of an immunoglobulin deficency syndrome. Such immunoglobulin deficiency may be primary or may be secondary to a variety of diseases. We have classified and described the small bowel roentgen features associated with the various immunoglobulin deficiency syndromes as follows: 1. the sprue pattern, as seen in hypogammaglobulinemic sprue and in Ig-A deficient sprue; 2. multiple nodular defects; 3. inflammatory changes secondary to giardiasis, associated with immune deficiency diseases; 4. thickening of the small intestinal folds, as seen in the plasma cell dyscrasias, lymphoma, intestinal lymphangiectasia and amyloidosis.


Promoter-wide hypermethylation of the ribosomal RNA gene promoter in the suicide brain.
Alterations in gene expression in the suicide brain have been reported and for several genes DNA methylation as an epigenetic regulator is thought to play a role. rRNA genes, that encode ribosomal RNA, are the backbone of the protein synthesis machinery and levels of rRNA gene promoter methylation determine rRNA transcription. We test here by sodium bisulfite mapping of the rRNA promoter and quantitative real-time PCR of rRNA expression the hypothesis that epigenetic differences in critical loci in the brain are involved in the pathophysiology of suicide. Suicide subjects in this study were selected for a history of early childhood neglect/abuse, which is associated with decreased hippocampal volume and cognitive impairments. rRNA was significantly hypermethylated throughout the promoter and 5' regulatory region in the brain of suicide subjects, consistent with reduced rRNA expression in the hippocampus. This difference in rRNA methylation was not evident in the cerebellum and occurred in the absence of genome-wide changes in methylation, as assessed by nearest neighbor. This is the first study to show aberrant regulation of the protein synthesis machinery in the suicide brain. The data implicate the epigenetic modulation of rRNA in the pathophysiology of suicide.


The in vivo gene expression signature of oxidative stress.
How higher organisms respond to elevated oxidative stress in vivo is poorly understood. Therefore, we measured oxidative stress parameters and gene expression alterations (Affymetrix arrays) in the liver caused by elevated reactive oxygen species induced in vivo by diquat or by genetic ablation of the major antioxidant enzymes CuZn-superoxide dismutase (Sod1) and glutathione peroxidase-1 (Gpx1). Diquat (50 mg/kg) treatment resulted in a significant increase in oxidative damage within 3-6 h in wild-type mice without any lethality. In contrast, treatment of Sod1(-/-) or Gpx1(-/-) mice with a similar concentration of diquat resulted in a significant increase in oxidative damage within an hour of treatment and was lethal, i.e., these mice are extremely sensitive to the oxidative stress generated by diquat. The expression response to elevated oxidative stress in vivo does not involve an upregulation of classic antioxidant genes, although long-term oxidative stress in Sod1(-/-) mice leads to a significant upregulation of thiol antioxidants (e.g., Mt1, Srxn1, Gclc, Txnrd1), which appears to be mediated by the redox-sensitive transcription factor Nrf2. The main finding of our study is that the common response to elevated oxidative stress with diquat treatment in wild-type, Gpx1(-/-), and Sod1(-/-) mice and in untreated Sod1(-/-) mice is an upregulation of p53 target genes (p21, Gdf15, Plk3, Atf3, Trp53inp1, Ddit4, Gadd45a, Btg2, Ndrg1). A retrospective comparison with previous studies shows that induction of these p53 target genes is a conserved expression response to oxidative stress, in vivo and in vitro, in different species and different cells/organs.


Cancer and autoimmunity: autoimmune and rheumatic features in patients with malignancies.
To review the autoimmune and rheumatic manifestations of patients with malignancy. A Medline search of all published papers using keywords related to malignancies, autoimmunity, rheumatic diseases, and paraneoplastic syndromes. Patients with malignant diseases may develop autoimmune phenomena and rheumatic diseases as a result of (a) generation of autoantibodies against various autoantigens, including oncoproteins (P185, 1-myc, c-myc, c-myb), tumour suppression genes (P53), proliferation associated antigens (cyclin A, B1, D1, E; CENP-F; CDK, U3-RNP), onconeural antigens (Hu, Yo, Ri, Tr), cancer/testis antigens (MAGE, GAGE, BAGE, SSX, ESO, SCP, CT7), and rheumatic disease associated antigens (RNP, Sm). The clinical significance of the various autoantibodies is not clear. Anti-oncoprotein and anti-tumour suppression gene antigens are detected before the diagnosis of the cancer or in the early stages of the malignant disease, suggesting a potential diagnostic or prognostic role. Anti-onconeural antibodies are pathogenic and are associated with specific clinical neurological syndromes (anti-Hu syndrome and others). (b) Paraneoplastic syndromes, a wide range of clinical syndromes, including classic autoimmune rheumatic diseases that develop among patients with cancer. (c) Rheumatism after chemotherapy, a clinical entity characterised by the development of musculoskeletal symptoms after combination chemotherapy for malignancy. Autoimmune and rheumatic features are not rare among patients with malignancies. They are the result of various diverse mechanisms and occasionally they may be associated with serious clinical entities.


Engineering NK-92 Cell by Upregulating CXCR2 and IL-2 Via CRISPR-Cas9 Improves Its Antitumor Effects as Cellular Immunotherapy for Human Colon Cancer.
Natural killer (NK) cells have shown good application prospects in adoptive cellular immunotherapy against cancer. However, due to its insufficient infiltration and low activity, the therapeutic effect of infused NK cells has been limited in solid tumors, such as colorectal cancer. It has been proved that tumor-produced chemokines regulate the migration of NK cells expressing corresponding chemokine receptors, and cytokines could enhance the antitumor activity of NK cells. In this study, we innovatively upregulated the expression of chemokine receptor CXC chemokine receptor 2 (CXCR2) and cytokine interleukin (IL)-2 on NK-92 cells using CRISPR-Cas9 gene-editing technology. We demonstrated that overexpressing CXCR2 and IL-2 promotes NK-92 cells to increasingly transfer into tumor sites and achieve stronger cell-killing and proliferation activity. Moreover, the inhibitory effects of gene-edited NK-92 cells on the growth of human colon cancer in vivo were also improved. The tumor burden of tumor-bearing mice was reduced, and their survival time was significantly prolonged. Gene-editing modification NK cells are expected to become a novel and promising tumor treatment strategy.


A meta-analysis of the relationship among impaired taste and treatment, treatment type, and tumor site in head and neck cancer treatment survivors
To understand how taste impairment caused by head and neck cancer treatment changes over time or varies with treatment site or type. Ovid MEDLINE® database was searched for reports of health-related quality of life (HRQOL) in head and neck cancer treatment survivors (HNCTS), which included taste function in a HRQOL instrument from 1946-2013. Eligible studies compared taste scores from baseline to post-treatment, using two treatment types or two cancer sites. 247 reports were identified; 19 were suitable for meta-analysis. A series of dichotomous meta-analyses were conducted using comprehensive meta-analysis software .PRESENTATION OF FINDINGS: Taste scores were statistically significantly worse after treatment; the summary effect for the standard measure difference between pretreatment and post-treatment taste scores was 0.353 (p < 0.001). Patients treated with radiation therapy (RT) reported statistically significant worse taste function post-treatment than those who received no RT; the summary effect for the standard mean differences in taste scores was 0.77 (p = 0.001). Differences in tumor site were not significant. Taste dysfunction is a long-term complication for HNCTS, and nurses should screen survivors for this sensory dysfunction.


Triboelectric and Piezoelectric Nanogenerators for Self-Powered Healthcare Monitoring Devices: Operating Principles, Challenges, and Perspectives.
The internet of medical things (IoMT) is used for the acquisition, processing, transmission, and storage of medical data of patients. The medical information of each patient can be monitored by hospitals, family members, or medical centers, providing real-time data on the health condition of patients. However, the IoMT requires monitoring healthcare devices with features such as being lightweight, having a long lifetime, wearability, flexibility, safe behavior, and a stable electrical performance. For the continuous monitoring of the medical signals of patients, these devices need energy sources with a long lifetime and stable response. For this challenge, conventional batteries have disadvantages due to their limited-service time, considerable weight, and toxic materials. A replacement alternative to conventional batteries can be achieved for piezoelectric and triboelectric nanogenerators. These nanogenerators can convert green energy from various environmental sources (e.g., biomechanical energy, wind, and mechanical vibrations) into electrical energy. Generally, these nanogenerators have simple transduction mechanisms, uncomplicated manufacturing processes, are lightweight, have a long lifetime, and provide high output electrical performance. Thus, the piezoelectric and triboelectric nanogenerators could power future medical devices that monitor and process vital signs of patients. Herein, we review the working principle, materials, fabrication processes, and signal processing components of piezoelectric and triboelectric nanogenerators with potential medical applications. In addition, we discuss the main components and output electrical performance of various nanogenerators applied to the medical sector. Finally, the challenges and perspectives of the design, materials and fabrication process, signal processing, and reliability of nanogenerators are included.


Oestrogenicity of prenylflavonoids from hops: activation of pro-oestrogens by intestinal bacteria.
For many centuries, hops (Humulus lupulus L.) have been used as essential ingredient in beers, providing the typical bitterness and hoppy flavour. However, the last few years the plant has gained increasing attention as a source of prenylflavonoids and in 1999, 8-prenylnaringenin (8-PN) was identified as the most potent phyto-oestrogen known so far. Hop extracts are therefore now marketed to reduce menopausal complaints. However, 8-PN concentrations in hops are very low, and variable efficiency of these extracts was observed. Yet, hops also contain isoxanthohumol (IX) in much higher amounts (IX/8-PN ratio in hop extracts is typically 10-20). This article reviews our recent findings on how the human intestinal microbiota may activate IX. Depending on inter-individual differences in the intestinal transformation potential, this conversion could easily increase the 8-PN exposure 10-fold. The variability in efficacy of hop extracts may therefore be explained by variable intestinal metabolism. Based on this scientific knowledge, an innovative strategy was developed to decrease this variability. First, Eubacterium limosum, capable of rapidly metabolizing all IX into 8-PN, was isolated from the complex intestinal ecosystem. This bacterium was then used to develop a new generation of hop products with increased reliability in effect. This strategy involves the use of the bacterium as probiotic, in which the bacterium is administered in combination with the original hop extract. This leads to efficient intestinal 8-PN production, also in individuals who originally did not harbour the appropriate bacteria. The findings presented in this review can therefore be considered as a typical example that good insight in the specific metabolic potential of complex microbial communities and individual bacterial species may offer important opportunities for the management and modulation of the microbial organization towards a certain metabolic function.


Parental hyperdynamic circulation predicts insulin resistance in offspring: The Tecumseh Offspring Study.
Controversy surrounds the pathogenetic mechanisms of the relationship between hyperdynamic circulation and insulin resistance. Two hundred eight children and young adults (mean age, 17.2+/-3.0 years; range, 11 to 26 years) from the Tecumseh Offspring Study whose parents had been assessed with Doppler echocardiography at the age of 34 years during the previous Tecumseh Blood Pressure Study were considered for this analysis. Offspring data were stratified according to tertiles of parental cardiac index. Parents in the top cardiac index tertile had increased heart rate (P=0.001), stroke volume (P=0.0001), left ventricular fractional shortening (P=0.02), and plasma epinephrine (P=0.02) compared with parents in the other tertiles. Body mass index (BMI) and blood pressure were similar in all groups. Offspring of parents with a high cardiac index had greater BMI (P=0.001), skinfold thickness (P=0.008), and waist/hip ratio (P=0.02), higher diastolic blood pressure (P=0.02) and plasma insulin level (P=0.001), and higher heart rate during Stroop's color test (P=0.02) than offspring of parents with a lower cardiac index. In a multivariate regression analysis, offspring BMI was predicted by parental BMI and cardiac index (P=0.0001 and 0.003, respectively). The mother-child relationship explained most of the cardiac index-BMI association. In summary, parental hyperdynamic circulation was an important predictor of overweight, abnormal fat distribution, increased blood pressure, and hyperinsulinemia in offspring. Our results illustrate the complexity of interaction between a genetic tendency and its phenotypic expression. We speculate that the degree of beta-adrenergic responsiveness may be a major determinant of the phenotypic differences between the parents and offspring found in this study.


Clinical Phenomenology and Characteristics of Centenarians in Hospice.
Little is known about the hospice experience of centenarians. As the population of centenarians is projected to increase, understanding their unique end-of-life needs will be important to inform delivery of quality end-of-life care. Our objective was to characterize the hospice experience of centenarians. A retrospective single-institution cohort study of centenarians enrolled in hospice from January 1, 2015, to December 31, 2017, was conducted to collect demographic and clinical information. Seventeen centenarians, who comprised 1.4% of hospice admissions, had an average age of 102 years, were mostly female (71%) and widowed (76%), and all caucasian. Upon hospice admission, centenarians resided in nursing (8, 47%) and assisted living (4, 24%) residencies as well as at home (4, 24%) and in senior independent living (1, 6%). Sixty percent of centenarians died in a nursing home. The most common hospice admission diagnosis was dementia (35%). Median length of stay on hospice was 41 days (range: 16-85) for 15 persons who died or discharged live. In this group of centenarians, dementia was the most common condition for hospice enrollment. Slightly less than half resided in nursing homes on admission, although death occurred most frequently in a nursing home. Centenarians were generally able to remain out of the hospital at their time of death.


Analysis of the bacterial response to Ru(CO)3Cl(Glycinate) (CORM-3) and the inactivated compound identifies the role played by the ruthenium compound and reveals sulfur-containing species as a major target of CORM-3 action.
Carbon monoxide (CO)-releasing molecules (CO-RMs) are being developed with the ultimate goal of safely utilizing the therapeutic potential of CO clinically. One such application is antimicrobial activity; therefore, we aimed to characterize and compare the effects of the CO-RM, CORM-3, and its inactivated counterpart, where all labile CO has been removed, at the transcriptomic and cellular level. We found that both compounds are able to penetrate the cell, but the inactive form is not inhibitory to bacterial growth under conditions where CORM-3 is. Transcriptomic analyses revealed that the bacterial response to inactivated CORM-3 (iCORM-3) is much lower than to the active compound and that a wide range of processes appear to be affected by CORM-3 and to a lesser extent iCORM-3, including energy metabolism, membrane transport, motility, and the metabolism of many sulfur-containing species, including cysteine and methionine. This work has demonstrated that both CORM-3 and its inactivated counterpart react with cellular functions to yield a complex response at the transcriptomic level. A full understanding of the actions of both compounds is vital to understand the toxic effects of CO-RMs. This work has furthered our understanding of how CORM-3 behaves at the cellular level and identifies the responses that occur when the host is exposed to the Ru compound as well as those that result from the released CO. This is a vital step in laying the groundwork for future development of optimized CO-RMs for eventual use in antimicrobial therapy.


A genetic map of 1,000 SSR and DArT markers in a wide barley cross.
A high-density genetic map was developed from an F1-derived doubled haploid population generated from a cross between cultivated barley (Hordeum vulgare) and the subspecies H. vulgare ssp. spontaneum. The map comprises 1,000 loci, amplified using 536 SSR (558 loci) and 442 DArT markers. Of the SSRs, 149 markers (153 loci) were derived from barley ESTs, and 7 from wheat ESTs. A high level of polymorphism ( approximately 70%) was observed, which facilitated the mapping of 197 SSRs for which genetic assignments had not been previously reported. Comparison with a published composite map showed a high level of co-linearity and telomeric coverage on all seven chromosomes. This map provides access to previously unmapped SSRs, improved genome coverage due to the integration of DArT and EST-SSRs and overcomes locus order issues of composite maps constructed from the alignment of several genetic maps.


Spinal cord herniation into pseudomeningocele after traumatic nerve root avulsion: case report and review of the literature.
We present an extremely rare case of traumatic spinal cord herniation due to a brachial plexus avulsion injury and provide a review of the literature of spinal cord herniation. Spinal cord herniation is an uncommon condition that can occur spontaneously or as a result of surgery or trauma. This condition often presents with symptoms and signs as Brown-Séquard syndrome. Traumatic pseudomeningoceles after a brachial plexus avulsion injury have been reported. But transdural herniation of the spinal cord into this pseudomeningocele is an extremely rare and poorly documented condition. There is only two reports of this condition in a thoracic case. The authors report the case of a 22-year-old man presented with a 2-year history of quadriplegia. He was involved in a motorcycle accident, 3 years prior to his presentation. Four years after the initial right brachial plexus injury, he was not able to walk independently. Magnetic resonance imaging (MRI) and computerized tomography (CT) myelography revealed a lateral pseudomeningocele arising from the right C6-7 and C7-T1 intervetebral foramen and cervical spinal cord herniation into this pseudomeningocele. The patient underwent primary closure of pseudomeningocele to prevent spinal cord reherniation. He can walk with cane and use left arm unrestrictedly at the 2-year follow-up examination. Spinal cord herniation following traumatic nerve root avulsion is extremely rare but it should be considered in the differential diagnosis of patients presenting with delayed myelopathy or Brown-Séquard syndrome.


Sex-based disparities in colorectal cancer screening.
Research suggests that recurrence and survival from colorectal cancer are worse in men than in women but the causes for this are unclear. Our aims were to (1) assess for sex differences in colorectal cancer screening (CRCS) within a large, contemporary population-based sample in California; and (2) examine the impact of income, education, and insurance status on sex differences in CRCS. Screening-eligible patients were identified from the 2007 US California Health Interview Survey. Up-to-date, CRCS was defined as fecal occult blood test within 1 year, flexible sigmoidoscopy within 5 years, or colonoscopy within 10 years. Logistic regression models were constructed to evaluate the relationship between sex and CRCS. Stratified analyses on the basis of self-reported income (low vs. high), education (≤ high school vs. > high school), and health insurance status (insured vs. uninsured) were performed to determine if sex differences in screening were modified by these parameters. In total, 11,260 men and 17,705 women were identified: mean ages were 65 and 66 years, respectively, and 63% were white in both the sexes. In the entire cohort, only two thirds of men and women reported undergoing up-to-date CRCS. Women had decreased odds of CRCS than men, after adjusting for potential confounders. Stratified analyses indicated that sex disparities in CRCS persisted among the insured, educated, and high-income earners. Women are less likely to undergo CRCS than men, but poor health care access is associated with low CRCS in both the sexes. Conventional strategies aimed at improving health care access should also include sex-specific interventions that raise awareness about preventive care to most effectively optimize CRCS.


Disentangling dynamics: group sensitivity and supervision.
In order to contextualize Altschul's interest in group dynamics we present a brief history of staff group work approaches in the UK and USA. Using case examples, the work of staff group sensitivity and group supervision is described. The difficulties of working in staff groups are highlighted and the antipathy towards group practice is discussed. It is argued that learning about conflict resolution in staff groups prepares nurses for dealing with conflicts in clinical practice. The case for re-invigorating interest in group theory and practice is presented. In presenting our reflections on staff group work, we hope not only to re-kindle the type of interest in groups that inspired Altschul but also to represent the case that it is ill conceived to attempt the work of mental health nursing without recourse to the supervisory resources of group theory, practice and support. It is through group feedback that mental health nurses and other health professionals can extend their learning about interpersonal relations, achieve quality standardization through peer feedback and reflect on practice in truly collaborative ways (Schon 1983).


[Vascular endothelium as a target for therapeutic action].
Proceeding from semi-centennial successful experience of clinical application of Actovegin in various-aetiology diseases of the vascular bed of the lower limbs, the present study was aimed at assessing interconnection between metabolic and microhaemodynamic processes in the human skin. Activation of metabolic processes was achieved by means of intravenous infusions of Actovegin and the microcirculatory processes were investigated using non-invasive methods in a total of 28 apparently healthy volunteers. The functional state of the arteriolar and venular portions of the microcirculatory bed of the skin was evaluated by means of laser Doppler flowmetry with wavelet analysis of oscillations of blood flow in the skin of the right forearm, while the parameters of the capillary blood flow were assessed by means of computer-assisted capillaroscopy in the nail bed of the 4th finger of the right hand. The known metabolic effects of Actovegin were accompanied and followed by a reliable increase in the amplitude of vasomotions within the range of the endothelial, neurogenic, and myogenic rhythms, suggesting a decrease in tonicity of the precapillary arterioles and, consequently, increased velocity of the capillary blood flow and decreased dimensions of the pericapillary zone, thus indicating improved metabolic processes in the skin. The obtained findings demonstrate close relationship between the processes of metabolism and microhaemodynamics, making it possible to suppose that amplitude activity within the range of the endothelial rhythm (0,0095-0,021 Hz) on laser Doppler flowmetry reflects not only the vasomotor but also metabolic function of the microvascular endothelium.


Giant cell tumour of soft tissue--a case report.
Giant cell tumor is seen in late adolescence or in the third or fourth decade of life. It arises from epiphysis of long bones, the commonest site being the distal end of the demur and the proximal end of tibia. This paper presents a case report of giant cell tumor of soft tissue.


The use of amplified fragment length polymorphism in determining species trees at fine taxonomic levels: analysis of a medically important snake, Trimeresurus albolabris.
There are a huge number of phylogenetic studies based on mitochondrial DNA (mtDNA); however, these may represent gene trees that may not be congruent with the species tree. A solution to this problem is to include additional, independent, loci from the nuclear genome. At fine taxonomic levels, i.e. between populations and closely related species, previously suggested nuclear markers such as intron sequence data may not be appropriate. In this study we investigate the use of amplified fragment length polymorphisms (AFLP) to aid determination of the species tree for 24 specimens of a medically important snake, Trimeresurus albolabris. This is of particular importance for many venomous snakes as venom often varies intraspecifically. Five different primer combinations produced 434 bands and were analysed by constructing a phylogenetic tree using neighbour joining and principal component analysis. Results were similar across all methods and found distinct groupings. The results were compared with mtDNA data and a reconciled tree was constructed in order to determine the species tree for T. albolabris. We found that T. albolabris (sensu lato) is not monophyletic. Specimens from the Indonesian islands (except West Java) form a distinct clade and we propose elevation to species level. A specimen from Nepal is also distinct and suggests that this population also deserves specific status. We suggest that AFLPs may prove a valuable aid in determining species trees as opposed to gene trees at fine taxonomic levels and this should facilitate the incorporation of molecular data into such activities as antivenom production and conservation management.


Anesthesia information management: clinical decision support.
Perioperative informatics tools continue to be developed at a rapid pace and offer clinicians the potential to greatly enhance clinical decision making. The goal of this review is to bring the reader updates on perioperative information management and discuss future research directions in the field. Clinical decision support tools become more timely, accurate, and, in some instances, have been shown to improve patient outcomes. When correctly implemented, they are critical tools for optimization of perioperative care. Perioperative informaticians continue to test new and innovative ways to enhance the delivery of anesthesia care, improving the safety and efficacy of perioperative management. Future work will continue to refine tools to ensure that perioperative informatics provides clinicians timely and accurate feedback, with demonstrable evidence that a decision support system improves patient outcomes.


[Kinetics of the phosphorylase reaction under conditions of substrate inactivation].
Electrophoretically homogenous glycogenphosphorylase b was isolated from the Dasyatis pastinaca muscular tissue. The kinetic peculiarities of phosphorylase reaction in time were studied. It is found that the reaction rate substrate concentration real dependences are not described by the Michaelis equation. The fact of the irreversible inactivation of phosphorylase in the process of catalytic reaction is observed. It is supposed that this fact is mechanical destruction in the process of substrate splitting rather than thermoinactivation of the enzyme or its inhibition.


Abnormal heart rate variability and its application in predicting treatment efficacy in patients with chronic migraine: An exploratory study.
This study aimed to investigate the extent of autonomic nervous system dysfunction in patients with chronic migraine using heart rate variability analysis. In addition, we explored the potential association between heart rate variability and treatment outcomes in patients receiving preventive treatment. In this cross-sectional and prospective study, we compared heart rate variability profiles in 81 preventive-naïve chronic migraine patients and 58 healthy controls. In addition, treatment responses of patients, who received a 12-week treatment with flunarizine, were assessed in relation to baseline heart rate variability. We observed that chronic migraine patients had a reduced heart rate variability, signifying autonomic dysfunction in comparison to healthy controls. Furthermore, patients presenting normal heart rate variability, characterized by a standard deviation exceeding 30 milliseconds in normal-to-normal RR intervals, experienced a superior response to flunarizine treatment. This improvement was exemplified by a significantly larger reduction in monthly headache days for patients with higher heart rate variability compared to those with lower heart rate variability: -9.7 (5.9) vs. -6.2 (6.0) days (p = .026). Autonomic dysfunction occurs in chronic migraine as evaluated by heart rate variability. A preserved function is associated with a better treatment outcome to flunarizine.Trial registration: Neurologic Signatures of Chronic Pain Disorders, NCT02747940. Registered 22 April 2016, https://clinicaltrials.gov/ct2/show/NCT02747940.


Chromosomal analysis and identification based on optical tweezers and Raman spectroscopy.
The ability to identify specific chromosomes with certainty has been established by the development of several cytogenetic techniques based on staining. Here, we report the use of a new optical technique, laser tweezers and Raman spectroscopy (LTRS), to capture and manipulate chromosomes in order to obtain their spectral patterns for molecular analysis without the need for staining. The purpose of this study was to obtain Raman spectroscopy patterns for chromosomes number 1, 2, and 3 and to test if the Raman spectroscopy pattern could be used to distinguish these three chromosomes. In our experiment, optical tweezers were used to capture the individual chromosomes and the Raman spectral patterns were collected for the trapped chromosomes. Then, the captured chromosome was manipulated with the optical tweezers and moved to another chamber through a micro - channel, in which the chromosomes were G- banded for positive identification as chromosome number 1, 2, or 3. Generalized discriminate analysis (GDA) was used to compare the Raman signatures. This analysis revealed that chromosomes 1, 2, and 3 could be distinguished and identified based on their Raman spectra. Development of this approach will lead to more rapid automatic methods for chromosome analysis and identification without the use of prior staining. Moreover, the Raman spectral patterns may lend themselves to more detailed analysis of chromosomal structure than is currently available with standard staining protocols. Such analysis may some day be useful for rapid, automated screening and diagnosis for certain cancers.


Contextual priming of word meanings is stabilized over sleep.
Evidence is growing for the involvement of consolidation processes in the learning and retention of language, largely based on instances of new linguistic components (e.g., new words). Here, we assessed whether consolidation effects extend to the semantic processing of highly familiar words. The experiments were based on the word-meaning priming paradigm in which a homophone is encountered in a context that biases interpretation towards the subordinate meaning. The homophone is subsequently used in a word-association test to determine whether the priming encounter facilitates the retrieval of the primed meaning. In Experiment 1 (N = 74), we tested the resilience of priming over periods of 2 and 12 h that were spent awake or asleep, and found that sleep periods were associated with stronger subsequent priming effects. In Experiment 2 (N = 55) we tested whether the sleep benefit could be explained in terms of a lack of retroactive interference by testing participants 24 h after priming. Participants who had the priming encounter in the evening showed stronger priming effects after 24 h than participants primed in the morning, suggesting that sleep makes priming resistant to interference during the following day awake. The results suggest that consolidation effects can be found even for highly familiar linguistic materials. We interpret these findings in terms of a contextual binding account in which all language perception provides a learning opportunity, with sleep and consolidation contributing to the updating of our expectations, ready for the next day.


Recovery in the Severely Impaired Arm Post-Stroke After Mirror Therapy: A Randomized Controlled Study.
This study aimed to examine the effectiveness of mirror therapy on recovery in the severely impaired arm after stroke. Using single-blind randomized controlled design, patients with severely impaired arm within 1-month post-stroke were assigned to receive mirror therapy (n = 20) or control therapy (n = 21), 30 mins twice daily for 4 wks in addition to conventional rehabilitation. During mirror therapy and control therapy, subjects practiced similar structured exercises in both arms, except that mirror reflection of the unaffected arm was the visual feedback for mirror therapy, but mirror was absent for control therapy so that subjects could watch both arms in exercise. Fugl-Meyer Assessment and Wolf Motor Function Test were the outcome measurements. After the intervention, both mirror therapy and control therapy groups had significant arm recovery similarly in Fugl-Meyer Assessment (P = 0.867), Wolf Motor Function Test-Time (P = 0.947) and Wolf Motor Function Test-Functional Ability Scale (P = 0.676). Mirror therapy or control therapy, which involved exercises concurrently for the paretic and unaffected arms during subacute stroke, promoted similar motor recovery in the severely impaired arm.


Population Structure of Mycobacterium bovis in Germany: a Long-Term Study Using Whole-Genome Sequencing Combined with Conventional Molecular Typing Methods.
Mycobacterium bovis is the primary cause of bovine tuberculosis (bTB) and infects a wide range of domestic animal and wildlife species and humans. In Germany, bTB still emerges sporadically in cattle herds, free-ranging wildlife, diverse captive animal species, and humans. In order to understand the underlying population structure and estimate the population size fluctuation through time, we analyzed 131 M. bovis strains from animals (n = 38) and humans (n = 93) in Germany from 1999 to 2017 by whole-genome sequencing (WGS), mycobacterial interspersed repetitive-unit-variable-number tandem-repeat (MIRU-VNTR) typing, and spoligotyping. Based on WGS data analysis, 122 out of the 131 M. bovis strains were classified into 13 major clades, of which 6 contained strains from both human and animal cases and 7 only strains from human cases. Bayesian analyses suggest that the M. bovis population went through two sharp anticlimaxes, one in the middle of the 18th century and another one in the 1950s. WGS-based cluster analysis grouped 46 strains into 13 clusters ranging in size from 2 to 11 members and involving strains from distinct host types, e.g., only cattle and also mixed hosts. Animal strains of four clusters were obtained over a 9-year span, pointing toward autochthonous persistent bTB infection cycles. As expected, WGS had a higher discriminatory power than spoligotyping and MIRU-VNTR typing. In conclusion, our data confirm that WGS and suitable bioinformatics constitute the method of choice to implement prospective molecular epidemiological surveillance of M. bovis The population of M. bovis in Germany is diverse, with subtle, but existing, interactions between different host groups.


Interleukin-10 signaling in somatosensory neurons controls CCL2 release and inflammatory response.
Appropriate regulation of the inflammatory response is essential for survival. Interleukin-10 (IL-10), a well-known anti-inflammatory cytokine, plays a major role in controlling inflammation. In addition to immune cells, we previously demonstrated that the IL-10 receptor (IL-10R1) is expressed in dorsal root ganglion sensory neurons. There is emerging evidence that these sensory neurons contribute to immunoregulation, and we hypothesized that IL-10 signaling in dorsal root ganglion (DRG) neurons facilitates the regulation of the inflammatory response. We showed that mice that lack IL-10R1 specifically on advillin-positive neurons have exaggerated blood nitric oxide levels, spinal microglia activation, and cytokine upregulation in the spinal cord, liver, and gut compared to wild-type (WT) counterparts in response to systemic lipopolysaccharide (LPS) injection. Lack of IL-10R1 in DRG and trigeminal ganglion (TG) neurons also increased circulating and DRG levels of proinflammatory C-C motif chemokine ligand 2 (CCL2). Interestingly, analysis of published scRNA-seq data revealed that Ccl2 and Il10ra are expressed by similar types of DRG neurons; nonpeptidergic P2X purinoceptor (P2X3R + ) neurons. In primary cultures of DRG neurons, we demonstrated that IL-10R1 inhibits the production of CCL2, but not that of the neuropeptides substance P and calcitonin-gene related peptide (CGRP). Furthermore, our data indicate that ablation of Transient receptor potential vanilloid (TRPV)1 + neurons does not impact the regulation of CCL2 production by IL-10. In conclusion, we showed that IL-10 binds to its receptor on sensory neurons to downregulate CCL2 and contribute to immunoregulation by reducing the attraction of immune cells by DRG neuron-derived CCL2. This is the first evidence that anti-inflammatory cytokines limit inflammation through direct binding to receptors on sensory neurons. Our data also add to the growing literature that sensory neurons have immunomodulatory functions.


Post-transplant methotrexate administration leads to improved curability of mice bearing a mammary tumor transplanted with marrow transduced with a mutant human dihydrofolate reductase cDNA.
To test the concept that protection of bone marrow progenitor cells via introduction of a drug resistance gene would allow larger and curative doses of chemotherapy to be administered, we used mice bearing a transplanted breast cancer as a model system. Mice bearing the E0771 tumor were treated with lethal doses of cyclophosphamide (CPA) and rescued from toxicity by administration of bone marrow transduced with a mutant dihydrofolate reductase (DHFR) cDNA (Ser-31) in a retroviral construct. Animals receiving marrow not transduced with mutant DHFR cDNA died from methotrexate (MTX) toxicity, whereas mice transduced with mutant DHFR cDNA containing marrow were able to tolerate MTX treatment post-transplant; 44% of the mice had no demonstrable tumor when sacrificed on day 52. Another control group of mice treated with CPA and transplanted but not treated with MTX post-transplant succumbed to tumor regrowth. These data provide a strong rationale for the use of drug resistance genes to protect marrow from drug toxicity because the increase in dose tolerated may result in an improved cure rate of chemosensitive tumors.


Composition and diversity patterns of megafauna discards in the deep-water shrimp trawl fishery off Brazil.
Composition and spatial diversity patterns of retained and discarded catches in the deep-water shrimp (family Aristeidae) trawling fishery off Brazil were assessed by observers on-board commercial operations in 2005 and 2006. These trawls caught 19,440 kg and 180,076 individuals of which 76·0 and 65·2%, respectively, were discarded at sea. Finfishes represented 54% of the numerical catch but were almost fully discarded (98%). Crustaceans represented 40% of the numerical catch and were mostly retained (80%). The scarlet shrimp Aristaeopsis edwardsiana comprised approximately half of the retained catch. The remainder of the retained proportion comprised mainly the red giant shrimp Aristaeomorpha foliacea, the alistado shrimp Aristeus antillensis and small quantities of Argentine hake Merluccius hubbsi and gulf hake Urophycis mystacea. Discards comprised 108 species including 72 fish species, 19 crustaceans and 10 cephalopods. The large-scaled lanternfish Neoscopelus macrolepidotus was dominant in the discards, followed by the benthopelagic fishes Monomitopus agassizii, Synagrops bellus, Dibranchus atlanticus and Gadella imberbis and various macrurid species. This fishery was restricted to a limited bathymetric range (700-800 m), where discrete megafauna assemblages exist and may have been significantly affected.


Developmental emergence of transient and persistent hippocampal events and oscillations and their association with infant seizure susceptibility.
During the second postnatal week in rats, the hippocampus exhibits a transient period of hyperexcitability. To systematically assess the relationship between the onset and end of this period and spontaneous hippocampal activity, we used silicon depth electrodes in unanaesthetized head-fixed rats from postnatal day (P)2 to P18. At all ages, hippocampal sharp waves (SPWs) were prominent in the EEG. Beginning at P6, however, marked changes in SPWs and associated oscillations were detected. SPW-related 'gamma tails' (60-100 Hz) and 'ripples' (140-200 Hz) were first observed at P6 and P7, respectively, and both oscillations persisted up to P18. Transiently, between P6 and P11, SPW duration decreased and the occurrence of SPW doublets increased. In addition, between P8 and P11, a subset of rats exhibited 'spontaneous potentiated SPWs' characterized by double polarity reversals, enhanced likelihood of gamma tails, and population spikes. Having identified a suite of transient hippocampal features consistent with a window of increased excitability, we next assessed whether electrographic seizure activity would be most easily induced during this period. To do this, kainic acid (KA; 200 ng/infusion) was infused into the hippocampus contralateral to the recording probe. KA did not induce seizure activity until P7 and reached peak effectiveness at P9. Thereafter, sensitivity to KA declined. All together, these findings provide in vivo neurophysiological support for the notion of a developmental window of heightened seizure susceptibility during the second postnatal week, and also suggest that spontaneous nonpathological hippocampal activity can be used to mark the onset and end of this period.


Does Gadolinium Deposition Lead to Metabolite Alteration in the Dentate Nucleus? An MRS Study in Patients with MS.
Repeat contrast-enhanced MR imaging exposes patients with relapsing-remitting MS to frequent administration of gadolinium-based contrast agents. We aimed to investigate the potential metabolite and neurochemical alterations of visible gadolinium deposition on unenhanced T1WI in the dentate nucleus using MRS. This prospective study was conducted in a referral university hospital from January 2020 to July 2021. The inclusion criteria for case and control groups were as follows: 1) case: patients with relapsing-remitting MS, visible gadolinium deposition in the dentate nucleus (ribbon sign), >5 contrast-enhanced MR images obtained; 2) control 1: patients with relapsing-remitting MS without visible gadolinium deposition in the dentate nucleus, >5 contrast-enhanced MR images obtained; 3) control 2: patients with relapsing-remitting MS without visible gadolinium deposition in the dentate nucleus, <5 contrast-enhanced-MR images obtained; and 4) control 3: adult healthy individuals, with no contrast-enhanced MR imaging. Dentate nucleus and pontine single-voxel 12 × 12 × 12 MRS were analyzed using short TEs. Forty participants (10 per group; 27 [67.5%] female; mean age, 35.6 [SD, 9.6] years) were enrolled. We did not detect any significant alteration in the levels of NAA and choline between the studied groups. The mean concentrations of mIns were 2.7 (SD, 0.73) (case), 1.5 (SD, 0.8) (control 1), 2.4 (SD, 1.2) (control 2), and 1.7 (SD, 1.2) (control 3) (P = .04). The mean concentration of Cr and mIns (P = .04) and the relative metabolic concentration (dentate nucleus/pons) of lipid 1.3/Cr (P = .04) were significantly higher in the case-group than in healthy individuals (controls 1-3). Further analyses compared the case group with cumulative control 1 and 2 groups and showed a significant increase in lactate (P = .02), lactate/Cr (P = .04), and Cr (dentate nucleus/pons) (P = .03) in the case group. Although elevated concentrations of Cr, lactate, mIns, and lipid in the dentate nucleus of the case group indicate a metabolic disturbance, NAA and choline levels were normal, implying no definite neuronal damage.


First-principles quantum simulations of exciton diffusion on a minimal oligothiophene chain at finite temperature.
High-dimensional multiconfigurational quantum dynamics simulations are carried out at finite temperature to simulate exciton diffusion on an oligothiophene chain, representative of a segment of the poly(3-hexylthiophene) (P3HT) polymer. The ab initio parametrized site-based Hamiltonian of Binder et al. [Phys. Rev. Lett., 2018, 120, 227401] is employed to model a 20-site system, including intra-ring and inter-ring high-frequency modes as well as torsional modes which undergo thermal fluctuations induced by an explicit harmonic oscillator bath. The system-bath dynamics is treated within the setting of a stochastic mean-field Schrödinger equation. For the 20-site excitonic system, a total of 20 Frenkel states and 248 modes are propagated using the multi-layer multi-configuration time-dependent Hartree (ML-MCTDH) method. The resulting dynamics can be interpreted in terms of the coherent motion of an exciton-polaron quasi-particle stochastically driven by torsional fluctuations. This dynamics yields a near-linear mean squared displacement (MSD) as a function of time, from which a diffusion coefficient can be deduced which increases with temperature, up to 5.7 × 10-3 cm2 s-1 at T = 300 K.


Meta-analysis of supramaximal effects in in vitro estrogenicity assays.
In scientific literature, several estrogenic compounds are reported to induce responses in vitro that are significantly higher than that of estradiol (E2). These supramaximal (SPMX) estrogenic effects do not occur consistently and seem to differ depending on the cellular models applied. This study analyzes the possible underlying causes, mechanisms, and drivers for SPMX estrogenic effects in in vitro functional assays reported in the peer-reviewed literature. For the 21 natural and industrial chemicals identified as SPMX inducers, the culture and exposure conditions varied greatly among and between the assays. Detailed information on assay characteristics, however, sometimes lacked. Diethylstilbestrol, genistein, and bisphenol A were selected to build a database. The meta-analysis revealed that the occurrence of SPMX effects could be related to a number of specific assay characteristics: (1) the type of serum used to supplement the exposure medium, (2) the end point used to quantify the estrogenic potency (endogenous or transfected), (3) the number of estrogen response elements, and (4) and the promoter's nature. An SPMX response was not reported for expression of endogenous genes, assays that used African green monkey kidney (COS-1) cell line or with chloramphenicol transferase as the reporter gene. There were no indications that solvent concentration in culture, exposure period, or cell model influenced the occurrence of an SPMX effect. It is important to understand the mechanism behind this phenomenon because in vitro assays for estrogenicity are used extensively to characterize and quantify the estrogenic potency of compounds, mixtures and environmental extracts.