Effects of exercise on gallbladder volume and motility in obese women.
Comparatively few prospective studies have investigated the relationship between physical activity and gallbladder motility, and the results are controversial. Exercise may affect gallbladder motility via neural or hormonal mechanisms. The purpose of this study was to evaluate the possible effects of aerobic exercise on gallbladder motility in a group of obese women without gallstones. Twenty-three obese women (age 41.2+/-10.3 years, body mass index 40.7+/-6.7 kg/m(2)) were included in the study. Following an overnight fast, fasting and postprandial (15, 30, 45, 60, 75, 90, 120, and 150 minute) volumes and ejection fractions were evaluated with real-time ultrasonography before exercise. For all subjects, the exercise regimen consisted of daily 45-minute walking sessions at 60-80% of maximum heart rate for 4 weeks except weekends. Gallbladder volume and ejection fraction were again evaluated after exercise. Fasting and postprandial (15, 30, 45, 60, 75, 90, 120, and 150 minute) volumes were 38.6+/- 10.9, 32.8+/- 8.8, 27.6/- 8.1, 22.7+/- 8.5, 21.4+/- 7.2, 20.8+/- 7.0, 22.8+/- 7.3, 29.6 +/- 7.0, and 36.8+/- 6.2 cm(3) before the exercise period, respectively, and 40.8+/- 18.9, 29.9+/-11.2, 25.3+/- 9.2, 22.4+/-8.5, 19.6+/-7.8, 17.7+/- 6.8, 17.8+/- 7.3, 23.1+/-10.8, and 29.0+/-14.4 cm(3) after the exercise period, respectively. Postprandial (15, 30, 45, 60, 75, 90, 120, and 150 minute) ejection fractions were 13.5+/-15.9, 27.4+/-15.4, 39.5+/-20.0, 43.2+/-16.7, 44.3+/-17.3, 37.5 +/- 23.5, 23.5 +/-25.1, and 5.5+/- 21.6% before the exercise period, respectively, and 22.6+/- 20.1, 34.6+/-14.5, 42.0+/-13.6, 49.2+/-12.6, 53.1+/-14.1, 52.6+/-16.1, 43.6+/-17.0, and 29.2+/- 26.5% after exercise, respectively. After the exercise period, the 75, 90, 120, and 150 minute volumes were lower (p< 0.05, p< 0.05, p< 0.05, p< 0.01) and the 90, 120, and 150 minute ejection fractions were higher than before exercise (p< 0.05, p < 0.05, p< 0.01). Our study showed that exercise decreased late-phase postprandial gallbladder volume and increased late-phase postprandial gallbladder motility in these obese women.


Synthesis, cytotoxic activities and proposed mode of binding of a series of bis([(9-oxo-9,10-dihydroacridine-4-carbonyl)amino]alkyl) alkylamines.
A series of bis([(9-oxo-9,10-dihydroacridine-4-carbonyl)amino]alkyl) alkylamines have been prepared and their antiproliferative properties have been tested against HT-29 cell lines. Compounds 6b and 6d showed an interesting cytotoxic profile and were subjected to further cytotoxic evaluation, DNA binding properties and molecular modelling studies. The evaluation of the cytotoxic activity of compounds 6b and 6d against pairs of cisplatin-sensitive and -resistant ovarian tumour cells shows that both compounds may be endowed with interesting antitumour properties because they are able to circumvent cisplatin resistance in A2780cisR, CH1cisR and Pam 212-ras tumour cells. On the other hand, DNA binding data indicate that compounds 6b and 6d are able to intercalate stronger than acridine within the double helix. Both compounds displace ethidium bromide with an efficiency ten times higher than acridine from several linear double-stranded DNAs and induce 43 degrees unwinding in supercoiled pBR322 DNA while acridine unwinds pBR322 DNA by only 24 degrees. Altogether these data indicate that the significant conformational changes induced by compounds 6b and 6d in the double helix are due to a bis-intercalative DNA binding mode. We propose that binding to DNA through bisintercalation might be at least in part responsible for the remarkable cytotoxic properties of these acridine derivatives. The complex of 6b with d(GCGCGC)(2) in the four possible orientations that the ligand can adopt when binding to the DNA hexamer have been modelled and subjected to molecular dynamics simulations with the aim of evaluating the binding preferences of this bisintercalating agent into the DNA molecule. The predictions suggest that 6b binds to d(GCGCGC)(2) with a parallel orientation of the chromophores relative to each other and with a preference for binding through the minor groove of the hexamer. The possible relevance of these findings to the process of bisintercalation and the antitumour profile of these compounds is discussed in this paper.


PAIR: polymorphic Alu insertion recognition.
Alu polymorphisms are some of the most common polymorphisms in the genome, yet few methods have been developed for their detection. We present algorithms to discover Alu polymorphisms using paired-end high throughput sequencing data from multiple individuals. We consider the problem of identifying sites containing polymorphic Alu insertions. We give efficient and practical algorithms that detect polymorphic Alus, both those that are inserted with respect to the reference genome and those that are deleted. The algorithms have a linear time complexity and can be run on a standard desktop machine in a very short amount of time on top of the output of tools standard for sequencing analysis. In our simulated dataset we are able to locate 98.1% of Alus inserted with respect to the reference and 97.7% of Alus deleted, our simulations also show an excellent correlations between the deletions detected in parents and children. We further run our algorithms on publicly available data from the 1000 genomes project and find several thousand Alu polymorphisms in each individual.


The role of DNA repair in brain related disease pathology.
Oxidative DNA damage is implicated in brain aging, neurodegeneration and neurological diseases. Damage can be created by normal cellular metabolism, which accumulates with age, or by acute cellular stress conditions which create bursts of oxidative damage. Brain cells have a particularly high basal level of metabolic activity and use distinct oxidative damage repair mechanisms to remove oxidative damage from DNA and dNTP pools. Accumulation of this damage in the background of a functional DNA repair response is associated with normal aging, but defective repair in brain cells can contribute to neurological dysfunction. Emerging research strongly associates three common neurodegenerative conditions, Alzheimer's, Parkinson's and stroke, with defects in the ability to repair chronic or acute oxidative damage in neurons. This review explores the current knowledge of the role of oxidative damage repair in preserving brain function and highlights the emerging models and methods being used to advance our knowledge of the pathology of neurodegenerative disease.


Temozolomide treatment outcomes and immunotherapy efficacy in brain tumor.
Glioblastoma (GBM) has a survival rate of around 2 years with aggressive current standard of care. While other tumors have responded favorably to trials combining immunotherapy and chemotherapy, GBM remains uniformly deadly with minimal increases in overall survival. GBM differ from others due to being isolated behind the blood brain barrier, increased heterogeneity and mutational burden, and immunosuppression from the brain environment and tumor itself. We have reviewed clinical and preclinical studies investigating how different doses (dose intense (DI) and metronomic) and timing of immunotherapy following TMZ treatment can eradicate tumor cells, alter tumor mutational burden, and change immune cells. Recent clinical trials with standard of care (SoC), DI and metronomic TMZ regimes are no able to completely eradicate GBM. Elevated TMZ levels in DI treatment can overcome MGMT resistance but may result in hypermutation of surviving tumor cells. Higher levels of TMZ will also generate a higher degree of lymphopenia compared to SoC and metronomic regimes in preclinical studies. The different levels of lymphopenia and tumor eradication discussed in this review suggest possible beneficial pairings between immunotherapy and TMZ treatment. Treatments resulting in profound lymphopenia will allow for expansion of vaccine specific T cells or of CAT T cells. Clinical and preclinical studies are currently comparing different combinations of TMZ and immunotherapy timing to treat GBM through a balance between tumor killing and immune cell expansion. More frequent immune monitoring time points in ongoing clinical trials are crucial for further development of these combinations.


The influence of medical abortion compared with surgical abortion on subsequent pregnancy outcome.
Seven prospective cohort studies (12484 cases) were included in this review of the respective effects on the next pregnancy of medical and surgical abortion in early pregnancy. The incidence of miscarriage and postpartum hemorrhage was significantly lower in the pregnancy following a medical abortion. No other significant differences were found. With respect to the outcome of the next pregnancy, first-trimester medical abortions may thus be safer than the surgical option.


Information to the relatives of people with ostomies: is it satisfactory and adequate?
The aim of this study was to evaluate how relatives of patients with an ostomy rated the various aspects of care, how they perceived the quality of the care provided, and how they ranked their involvement in the care. Patients' satisfaction was also sought, particularly their perception of relatives' involvement. Descriptive cross-sectional. The study comprised a colostomy group (32 pairs) and an ileostomy group (28 pairs). All patients attended a stoma outpatient clinic. Quality of care was assessed using the identity-oriented dimension of the validated questionnaire Qualityof Care from the Patient's Perspective. Questionnaires were mailed to patients and their relatives. Relatives and patients in both study groups considered most topics covered by the questionnaire to be important. Half of the patients with an ileostomy and their relatives and approximately 30% of those in the colostomy group were dissatisfied with the information they received, however. Moreover, a greater proportion (41-89%) of the patients were unhappy with the opportunities they were offered to participate in the decision-making process. Patients with an ileostomy and their relatives tended to be more dissatisfied with the quality of care than the colostomy group, but the difference was not statistically significant. The topics covered by the questionnaire were considered important to both patients and their relatives. Information and counseling offered by the ET nurses and the colorectal surgeons were judged to be unsatisfactory, indicating the need for frequently assessing and improving general standards of quality of care.


Membrane-associated proteins of ejaculated sperm from Morada Nova rams.
The objective was to describe the profile of membrane proteins from sperm of tropically adapted Morada Nova rams (N = 5). Samples from protein-enriched fractions of ejaculated sperm (containing 400 μg of protein) were separated by two-dimensional electrophoresis and respective maps analyzed using PDQuest software (version 7.3.0; Bio-Rad). Proteins were identified using tandem mass spectrometry. Also, membrane proteins were incubated with antibodies against binder of sperm protein (BSP) 1 and bodhesin 2 (Bdh-2), components of vesicular gland secretion. For membrane proteins of ejaculated sperm, an average of 133 ± 4.6 spots were detected per gel, of which, 107 spots were consistently present on all gels. Sixty-eight spots and 37 proteins were identified using mass spectrometry, corresponding to 71.6% of the intensity of all spots detected. Three major spots identified as ram seminal vesicle protein (RSVP) 14 represented approximately 30% of the intensity of all spots. Two of the most intense spots in the gel reacted against anti-BSP1, at 14 kDa. In addition, four low molecular weight spots reacted with anti-Bdh-2 antibodies. Proteins RSVP and Bdh-2 belong to the BSP and spermadhesin families, respectively, and were previously reported as major components of ram seminal proteins. Additional proteins identified in the sperm membrane two-dimensional maps included alpha-2-heparan sulfate-glycoprotein, plasma glutamate carboxypeptidase, arylsulfatase A, cathelicidin, heat shock protein 70 kDa, angiotensin-converting enzyme, leucine aminopeptidase, and clusterin. Some proteins were present as multiple isoforms, such as tubulin (12), alpha-2-heparan sulfate-glycoprotein (5), ATP synthase (5), Bdh-2 (4) and RSVP14 (3). Based on gene ontology analysis, the most common biological processes associated with the membrane proteins were cellular processes (34%), response to stimulus (14%), and metabolic processes (11%). Binding (37%) and catalytic activity (32%) corresponded to the most frequent molecular functions for those proteins. In conclusion, we identified a diverse cohort of components of membrane proteins in ram sperm. Major proteins previously reported in seminal plasma, such as RSVP14 and Bdh-2, were also extracted from sperm membranes. Knowledge of sperm proteins is crucial for elucidating mechanisms underlying their association with sperm function.


Insulin's regulation of c-fos gene transcription in hepatoma cells.
In H4IIE rat hepatoma cells insulin interacts with its receptors to induce DNA synthesis and promote cell division. However, the postreceptor events that lead to DNA synthesis and cell division have not been well characterized. Previous studies indicate that insulin can regulate the expression of several genes in H4 cells. One of these genes is the proto-oncogene c-fos, a cellular gene whose deregulation has been implicated in the process of cellular differentiation and division. In the present work insulin is shown to regulate cellular c-fos mRNA accumulation and the transcription rate of the c-fos gene. Insulin caused a rapid, dose-dependent increase in the cytoplasmic concentration of c-fos mRNA which was maximal by 30 min. Preceding this, a more rapid 6-8 fold increase in transcription of the c-fos gene was observed. Induction of transcription was apparent following only 5 min of insulin addition. This is the most rapid effect of insulin yet demonstrated on the induction of gene expression. Protein synthesis inhibitors (cycloheximide, anisomycin) also induced the transcription of the c-fos gene. However, they stimulated a much greater increase in transcription than did insulin, and followed a different time course of action. The addition of insulin in combination with a protein synthesis inhibitor resulted in no greater increase in c-fos transcription than did the addition of a protein synthesis inhibitor alone. The nonadditivity of H4 cell c-fos gene expression may indicate a similar mode of action by insulin and protein synthesis inhibitors.


Transcriptomic analysis of glutamate-induced HT22 neurotoxicity as a model for screening anti-Alzheimer's drugs.
Glutamate-induced neurotoxicity in the HT22 mouse hippocampal neuronal cell line has been recognized as a valuable cell model for the study of neurotoxicity associated with neurodegenerative diseases including Alzheimer's disease (AD). However, the relevance of this cell model for AD pathogenesis and preclinical drug screening remains to be more elucidated. While there is increasing use of this cell model in a number of studies, relatively little is known about its underlying molecular signatures in relation to AD. Here, our RNA sequencing study provides the first transcriptomic and network analyses of HT22 cells following glutamate exposure. Several differentially expressed genes (DEGs) and their relationships specific to AD were identified. Additionally, the usefulness of this cell model as a drug screening system was assessed by determining the expression of those AD-associated DEGs in response to two medicinal plant extracts, Acanthus ebracteatus and Streblus asper, that have been previously shown to be protective in this cell model. In summary, the present study reports newly identified AD-specific molecular signatures in glutamate-injured HT22 cells, suggesting that this cell can be a valuable model system for the screening and evaluation of new anti-AD agents, particularly from natural products.


Expression of normal sequence pathogenic proteins for neurodegenerative disease contributes to disease risk: 'permissive templating' as a general mechanism underlying neurodegeneration.
Loci underlying autosomal dominant forms of most neurodegenerative disease have been identified: prion mutations cause Gerstmann Straussler syndrome and hereditary Creutzfeldt-Jakob disease, tau mutations cause autosomal dominant frontal temporal dementia and alpha-synuclein mutations cause autosomal dominant Parkinson's disease. In these cases, the pathogenic mutation is in the protein that is deposited in the diseased tissue and the whole protein is deposited. In Alzheimer's disease, mutations in amyloid precursor protein or in the presenilins cause autosomal dominant disease. These are the substrate and proteases responsible for the production of the deposited peptide Abeta. Thus, in all the cases, the mutations lead to the disease by a mechanism that involves the deposition process. Furthermore, sporadic forms of all these diseases are predisposed by genetic variability at the same loci, implying that the quantity of the normal protein influences the risk of this form of disease. These results show that the amount of pathogenic protein expression is a key factor in determining disease initiation. Recent work on transgenic models of these diseases is consistent with the view that there are two stages of pathogenesis: a concentration-dependent formation of a pathogenic protein oligomer followed by aggregation on to this oligomeric template by a process that is less dependent on the concentration of the protein.


Dimensions of physical frailty and cognitive function in older adults with amnestic mild cognitive impairment.
The objective of this study was to examine relationships between dimensions of physical frailty and severity of cognitive impairment in older adults with amnestic mild cognitive impairment (aMCI). The prevalence of physical frailty dimensions including slow gait speed, low physical activity, and low grip strength was examined among 201 sedentary older adults with aMCI. Associations between dimensions of physical frailty and severity of cognitive impairment, as measured with the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) and individual dimensions of cognitive function were examined using multiple linear regression models. Greater than 50% of participants met physical frailty criteria on dimensions of slow gait speed, low physical activity and low grip strength. Slower gait speed was associated with elevated severity of cognitive impairment. Both gait speed and physical activity were associated with individual dimensions cognitive function. Dimensions of physical frailty, particularly gait speed, were associated with severity of cognitive impairment, after adjusting for age, sex and age-related factors. Further studies are needed to investigate mechanisms and early intervention strategies that assist older adults with aMCI to maintain function and independence.


Experimental high-velocity missile head injury.
A standardized experimental high-velocity penetrating head-injury model has been produced in which pathological lesions were observed, not only in the wound track but at sites more remote from the track in the hypothalamus, brain stem and cerebellum. Diffuse subarachnoid haemorrhage was common and intraventricular haemorrhage was a constant feature. Other constant histological abnormalities were:L 1. Perivascular "ring' haemorrhages. 2. Perivascular haemorrhage with a surrounding zone of decreased staining intensity. 3. Perivascular increased staining intensity. 4. Areas of decreased staining intensity apparently dissociated from areas of haemorrhage. The pathogenesis of the perivascular lesions is discussed and preliminary studies suggest that these may be the site of early oedema. The implications of this experiment for military surgery and for ballistic protection of the head are discussed.


A narrative review of maternal physical activity during labour and its effects upon length of first stage.
Women in western countries generally lie semi-recumbent during first stage of labour, when perhaps it is more natural to move around. Consequently carers are unaware of what constitutes instinctive behaviours and their outcomes. With this in mind, a structured narrative review of the literature identified what prior research has shown about the impact of maternal movement upon length of first stage; results are ambiguous, with 11 studies reporting no alteration to length and 7 reporting shortening. These studies fail to adequately detail time spent mobilising and what in fact constituted walking, squatting, upright, lying lateral, supine or semi-recumbent, and their direct effects upon progress of first stage. Advancements in knowledge are required to progress understanding about maternal activity during labour and its outcomes.


Resistance among urinary tract pathogens collected in Europe during 2018.
Escherichia coli, Klebsiella pneumoniae and Proteus mirabilis are urinary tract infection (UTI) pathogens and extended spectrum β-lactamase (ESBL)-producing pathogens exhibit co-resistance to oral fluoroquinolones (FQ) and trimethoprim-sulphamethoxazole (TMP-SMX). This study assessed the prevalence of ESBL phenotypes and co-resistance to FQ and TMP-SMX. In total, 766 E. coli, 260 K. pneumoniae and 104 P. mirabilis from UTIs in 18 countries were evaluated for susceptibility in the SENTRY surveillance programme, and results interpreted using EUCAST criteria. E. coli, K. pneumoniae and P. mirabilis accounted for 57.1%, 11.3% and 7.8%, respectively, of the isolates. Among E. coli, resistance to levofloxacin and TMP-SMX ranged from 21.8% to 32.7% for all isolates increasing to 66.5-67.0% among those with a ESBL phenotype (17.9% of all UTI E. coli from Europe were ESBL phenotypes). In contrast, all E. coli were susceptible to meropenem. For K. pneumoniae, resistance rates for levofloxacin and TMP-SMX were 32.2-40.0% increasing to 69.1-78.6% for ESBL phenotypes. Meropenem was the most active agent, with 7.7% resistance. Among P. mirabilis resistance to levofloxacin and TMP-SMX was 26-38.5% and increased to 100% for ESBL phenotypes. No meropenem-resistant P. mirabilis were reported. High co-resistance rates were observed for oral antibiotics among ESBL phenotypes raising concerns regarding empiric use of FQ and TMP-SMX for treating resistant UTIs outside of the hospital. In contrast, intravenous carbapenems retain activity against resistant UTI pathogens. New oral options with the spectrum of the carbapenems would address an unmet need for managing resistant UTIs.


NLRP3 inflammasome activation promotes liver inflammation and fibrosis in experimental biliary atresia.
Biliary atresia (BA) is characterized by a progressive fibroinflammatory cholangiopathy in early infants with unknown etiology. Although innate immune disorder is involved in its mechanism, role of NLRP3 inflammasome in BA remains largely undefined. To explore the role of NLRP3 inflammasome in BA. The expressions of NLRP3 inflammasome-related genes were determined in BA patients. Role of NLRP3 inflammasome was evaluated using MCC950 in experimental BA. Furthermore, gadolinium chloride, a macrophage scavenger, was applied to validate the inflammasome's cellular localization. Finally, the effects of NLRP3 inflammasome activation on liver fibrosis were explored in vivo and vitro in experimental BA. The components of NLRP3 inflammasome were up-regulated in BA patients. Inflammasome-related genes showed positively correlated with liver inflammation and fibrosis in BA patients. In experimental BA, inflammasome-related genes were up-regulated, and their expressions were inhibited by MCC950, which promoted mice growth, protected liver function, alleviated obstructive jaundice, inhibited liver inflammation, and reduced serum IL-1β level. NLRP3 inflammasome was expressed in macrophages, and macrophage elimination exerted the same protective roles as MCC950 did in BA. Additionally, NLRP3 inflammasome activation promoted liver fibrosis in experimental BA. NLRP3 inflammasome activation in macrophages promoted liver inflammation and fibrosis in experimental BA.


Eliminating canine rabies: the role of public-private partnerships.
Canine rabies has been eliminated from industrialized countries, but infected dogs remain the principal source of human infections in the developing world. Despite the availability of effective tools for prevention and post-exposure prophylaxis, canine rabies inflicts a heavy burden on the poorest people of Africa, Asia and Latin America, resulting in more than 60,000 deaths each year. Public-private partnerships offer a new approach to the challenge of eliminating canine rabies in the developing world, by bringing together stakeholders to share responsibilities and reduce costs. The leading partnership for rabies control, the Partners for Rabies Prevention, is an informal international group that includes representatives of major health organizations (WHO, PAHO, FAO, OIE), the European Commission, universities, nongovernmental organizations, the human and animal health industries, and private global health institutions. This article describes how the Partners for Rabies Prevention is working toward the global elimination of canine rabies. It forms part of a symposium in Antiviral Research on the elimination of canine rabies.


Cardiovascular effects of selective agonists and antagonists of histamine H3 receptors in the anaesthetized rat.
The cardiovascular responses to a series of selective histamine H3 receptor agonists, (R) alpha-methylhistamine, imetit and immepip and selective antagonists, thioperamide, clobenpropit and clophenpropit, were studied in anaesthetized rats. At 0.003-1 mumol/kg i.v. doses, H3 agonists failed to produce any significant change in the basal blood pressure and heart rate. Larger doses of (R) alpha-methylhistamine increased the blood pressure and heart rate and higher doses of imetit caused vasodepressor responses and reduced heart rate, whereas immepip proved virtually inactive. While (R) alpha-methylhistamine-induced effects were not blocked by histamine H1-, H2- and H3-receptor antagonists, they were however reduced by idazoxan and propranolol, which indicates that the mechanisms involved are adrenergic. The effects induced by imetit are not related to histamine H3 receptors but are mediated by indirect (via 5HT3 receptors) cholinergic mechanisms, since these effects were prevented by 1 mg/kg i.v. atropine and by 0.1 mg/kg i.v. ondansetron. Similarly, the H3 antagonists per se failed to change basal cardiovascular function up to 10 mumol/kg i.v. and only at 30 mumol/kg i.v. were marked decreases observed in the blood pressure and heart rate with a significant reduction in the effects of noradrenaline. These data indicate that in anaesthetized rats, histamine H3 receptor activation or blockade has no effect on basal cardiovascular function. The effects recorded after the administration of large doses of (R) alpha-methylhistamine and imetit are clearly unrelated to histamine H3 receptors and should be taken into account when using these compounds as H3 ligands for "in vivo" experiments.


Effects of sleep duration and sleep quality on prevalence of type 2 diabetes mellitus: A 5-year follow-up study in China.
To explore the interactions of sleep quality and sleep duration on the development of type 2 diabetes mellitus (DM2) in Chinese adults. We randomly selected 11,842 Chinese subjects from the Xuzhou community of China and obtained self-reported quality and duration of sleep by questionnaire. DM2 was assessed by fasting blood glucose. Sleep quality was categorized as good, common, or poor. Sleep duration was measured by average hours of sleep per night. We evaluated interaction, relative excess risk of interaction (RERI), the attributable proportion (AP), and the synergy index (S) using a logistic regression model. The relative risk for the development of DM2 was higher in subjects with short sleep duration (1.67 [1.34-2.16]) or poor sleep quality (1.91 [1.31-2.74]) or long sleep duration (1.45 [1.02-1.77]). DM2 occurred more frequently with poor sleep quality combined with short sleep duration (odds ratio: 6.21; 95% confidence interval (CI): 2.78-11.81). RERI, AP, and S values (and their 95% CI) were 3.99 (1.41-7.76), 0.64 (0.45-0.76), and 5.15 (3.74-7.89) for the interaction between poor sleep quality and short sleep duration. In subjects with poor sleep quality combined with long sleep duration, the RERI, AP, and S values (and 95% CI) were 0.13 (-0.19 to 0.66), 0.07 (-0.35 to 0.18), and 1.19 (0.85-2.11). Interactions between poor sleep quality and short sleep duration were additive. Preventive measures should focus on short sleep duration and poor sleep quality.


Role of cAMP receptor protein in phenotype and stress tolerance in Salmonella enterica serovar Typhimurium.
Salmonella enterica serovar Typhimurium (S. Typhimurium) is exposed to biotic and abiotic stresses. The survival of Salmonella in nature depends on the global regulators like cAMP receptor protein (CRP). The role of CRP in the phenotypic characteristics and stress tolerance was elucidated in S. Typhimurium using a crp gene null mutant (Δcrp). A 1.6-fold decrease in the cell size, a two-fold reduction in the colony size, and a 3.5-fold decrease in motility were observed in the Δcrp compared with the S. Typhimurium wild-type (WT). H2 S production on selective media was affected in the Δcrp. The utilisation of d-mannose, d-glycerol and d-mannitol was completely affected, whereas that of d-galactose and d-fructose was partially affected. The utilisation of d-arabinose was induced in the Δcrp. The growth rate of the Δcrp in Luria Bertani medium was unaffected. However, in the glucose-containing minimal medium, the growth rate of the Δcrp was reduced by 1.5-fold compared with the WT. The Δcrp was able to utilise ethanolamine as the sole carbon source similar to the WT. The Δcrp was more tolerant to heat and oxidative stress. Overexpression of heat and oxidative stress-related genes was observed in the Δcrp in the stationary phase. The Δcrp was less tolerant to radiation stress compared with the WT. The current findings decisively establish the CRP protein as a global regulator. The CRP affects multiple phenotypes, carbon metabolism and stress physiology of S. Typhimurium.


Mitigating driver distraction with retrospective and concurrent feedback.
An experiment was conducted to assess the effects of retrospective and combined retrospective and concurrent feedback on driver performance and engagement in distracting activities. A previous study conducted by the authors showed that concurrent (or real time) feedback can help drivers better modulate their distracting activities. However, research also shows that concurrent feedback can pose additional distractions due to the limited time and resources available during driving. Retrospective feedback, which is presented at the end of a trip (i.e., post-drive), can include additional information on safety critical situations during a trip and help the driver learn safe driving habits. A driving simulator study was conducted with 48 participants and 3 conditions: retrospective feedback, combined feedback (both retrospective and concurrent), and no feedback (baseline case). The feedback conditions (retrospective and combined) resulted in faster response to lead vehicle braking events as depicted by shorter accelerator release times. Moreover, combined feedback also resulted in longer glances to the road. The results suggest that both feedback types have potential to improve immediate driving performance and driver engagement in distractions. Combined feedback holds the most promise for mitigating the effects of distraction from in-vehicle information systems.


Postmortem inspection for neurosurgery: a training model for endoscopic dissection technique.
In 63 specimens, 74 aneurysms, and five other lesions, postmortem microsurgical and endoscopic inspection (PMI) was done. This work not only allowed for safe pathoanatomic findings, but moreover showed characteristics of a training method developed according to a model with clear standards. PMI gives training in: 1. Understanding of pathoanatomic topography and syntopy. 2. Analysis of imaging findings. 3. Analysis of approaches (approach planning). 4. Paraendoscopic methods (video surgery). 5. Clipping training. 6. Analyzing the ergonomy of the setting and instrumentation. In the series presented, aneurysms were the focus of attention. Postmortem inspection trains nearly all manipulative and cognitive abilities necessary for operative management of this difficult lesion. The acceptance and applicability of this method for resident training must be evaluated in the future.


The role of hsa_circ_0008945 in juvenile-onset systemic lupus erythematosus.
circular RNAs (circRNAs) play a crucial role in many physiological and pathological processes including juvenile-onset systemic lupus erythematosus (JSLE). The aim of this study is to investigate the role of circRNA hsa_circ_0008945 in JSLE and evaluate its significance as diagnosing biomarker. RT-qPCR was applied to detect the level of circ_0008945 in JSLE and controls. The Spearman correlation test assessed the correlation between circ_0008945 and clinical variables. The receiver operating characteristic (ROC) curve was calculated for evaluating the diagnostic value. Overexpression or knockdown of circ_0008945 in primary peripheral blood mononuclear cells (PBMCs) was performed to further examine its function in apoptosis. RT-qPCR revealed that there were significantly higher levels of hsa_circ_0008945 in PMBCs from JSLE patients (p < 0.001) compared to healthy controls. In addition, there were significant associations between hsa_circ_0008945 level and the level of C3, C4, anti-ds DNA, IgG, CRP and ESR (p < 0.05) but not associated with the level of Ig A and Ig M. ROC curve of the circ_0008945 showed that the AUC was 0.790 and it may potentially be used as a novel biomarker for the diagnosis of JSLE. The results showed that overexpression of circ-0008945 increased the apoptosis of PBMCs while knockdown of circ-0008945 by siRNA decreased the apoptosis of PBMCs, supporting that circ-0008945 promoted the apoptosis in PBMCs and contributed to the pathogenesis of JSLE. The role of circ_0008945 was first investigated in JSLE and proposed herein their possible contribution to the pathogenesis of JSLE. This study provides not only novel insight into the pathological mechanisms but also the potential value as a useful biomarker for JSLE.


Psychiatrists in their eyes: Children's drawings of what a psychiatrist looks like.
Drawings can be used as an important tool to measure children's perception and emotions. Using a qualitative design, we asked a group of 24 school children (10 boys and 14 girls) aged 11-12 to draw their impressions of psychiatrists. In the majority of drawings, psychiatrists were portrayed as a friendly or kind figure. The art work was analysed by the coordinator of the Arts Initiative in Mental Health, Niamh O'Connor. Psychiatrists were portrayed positively by this group of young people. This reflects a strong influence of the media on children's perception.


Computerized diagnosis: implications for clinical education.
The advent of the small computer as a basic clinical tool will have a significant impact on clinical practice and medical training. The application of probability theory to clinical diagnosis has led to the development of several practical diagnostic programs which run on small computers. Expert systems--interactive programs which function as 'electronic consultants'--have now been successfully developed for a number of clinical situations. Experience with two of these, INTERNIST/CADUCEUS and MYCIN, has provided insight into problems and prospects for expert systems in medicine. Less complex programs, particularly those employing clinical prediction rules, and expert system shells, seem well suited for clinical environments. Although computerized medical diagnosis holds great promise as an aid to clinicians, its success will largely be determined by the quality of the information that clinicians provide for analysis. A brief review of the status of bedside diagnosis reveals that data-gathering strategies and techniques must be better understood. In order to take full advantage of computer programs for diagnosis, basic diagnostic skills must be more heavily emphasized in clinical training.


State dependent activity in monkey visual cortex. I. Single cell activity in V1 and V4 on visual tasks.
This study examined the extent to which the responses of single cells in the striate cortex (V1) and the extrastriate cortex (V4) of the alert rhesus monkey are modulated by visual stimuli whose relevance in a behavioral task is varied. The animal had to detect the repetition of a visual pattern (i.e. detect similarity), preceded by a randomized number of alternations between two different patterns. The responses produced by the last, reward contingent stimulus were compared with responses obtained to that same stimulus earlier in the sequence. Modulatory effects in V1 were moderate: 31% of the cells (63 of 200) showed response increments of 20% or more to the last, reward contingent stimulus. In V4 the effects were much more pronounced: 72% of the cells (110 of 154) showed modulatory effects of more than 20%. In V4 but not in V1 orientation tuning curves showed a significant narrowing as well as a peak response increment to the behaviorally salient stimulus, suggesting a feature specific mechanism associated with the detection of similarity. Although a response decrement was observed in many cells during the repeated alternations, this effect was significantly smaller than the modulation produced by the detection of similarity. Controls included the presentation of novel stimuli during the presentation sequence which did not produce an enhanced response. It is hypothesized that the feature specific effects reported here are produced by higher order feedback systems.


Using an Adenosine Triphosphate Bioluminescent Assay to Determine Effective Antibiotic Combinations against Carbapenem-Resistant Gram Negative Bacteria within 24 Hours.
Current in vitro combination testing methods involve enumeration by bacterial plating, which is labor-intensive and time-consuming. Measurement of bioluminescence, released when bacterial adenosine triphosphate binds to firefly luciferin-luciferase, has been proposed as a surrogate for bacterial counts. We developed an ATP bioluminescent combination testing assay with a rapid turnaround time of 24h to determine effective antibiotic combinations. 100 strains of carbapenem-resistant (CR) GNB [30 Acinetobacter baumannii (AB), 30 Pseudomonas aeruginosa (PA) and 40 Klebsiella pneumoniae (KP)] were used. Bacterial suspensions (105 CFU/ml) were added to 96-well plates containing clinically achievable concentrations of multiple single and two-antibiotic combinations. At 24h, the luminescence intensity of each well was measured. Receiver operator characteristic curves were plotted to determine optimal luminescence threshold (TRLU) to discriminate between inhibitory/non-inhibitory combinations when compared to viable plating. The unweighted accuracy (UA) [(sensitivity + specificity)/2] of TRLU values was determined. External validation was further done using 50 additional CR-GNB. Predictive accuracies of TRLU were high for when all antibiotic combinations and species were collectively analyzed (TRLU = 0.81, UA = 89%). When individual thresholds for each species were determined, UA remained high. Predictive accuracy was highest for KP (TRLU = 0.81, UA = 91%), and lowest for AB (TRLU = 0.83, UA = 87%). Upon external validation, high overall accuracy (91%) was observed. The assay distinguished inhibitory/non-inhibitory combinations with UA of 80%, 94% and 93% for AB, PA and KP respectively. We developed an assay that is robust at identifying useful combinations with a rapid turn-around time of 24h, and may be employed to guide the timely selection of effective antibiotic combinations.


Valve-sparing operations after Ross procedure: a single-center experience.
The Ross procedure has demonstrated excellent long-term results, with restoration of life-expectancy in patients with severe aortic valve dysfunction. However, reintervention after Ross can occur, and herein we describe our center's experience with redo surgery after previous Ross procedures. We searched our prospective database for aortic valve-repair and recruited all adult (≥18 years) patients who have undergone valve-sparing root replacements (VSRRs) and/or aortic valve-repair after Ross procedure between July 2001 and July 2022. Univariable logistic regression analysis was performed to identify variables affecting early mortality. Survival, freedom-from-valve-reintervention and freedom-from-aortic regurgitation (AR) grade ≥3 were analyzed with the Kaplan-Meier method. A total of 63 patients were recruited for this study. Indication for reoperation after Ross was aortic aneurysm without AR in 17 (27%), aortic aneurysm with AR in 27 (43%), and isolated AR in 19 (30%) patients. Median follow-up time was 7.82 years. The majority of patients (76%) had undergone the free root technique during their index Ross operation. Cumulative survival, after redo surgery following Ross, was 98.4% [95% confidence interval (CI): 89.3-99.8%] at 1 year, 96.3% (95% CI: 88.2-98.3%) at 5 years, and 92.4% (95% CI: 87.1-98.0%) at 10 years. Freedom-from-reoperation on the aortic valve at 1 year was 98.4% (95% CI: 97.0-99.8%), at 5 years was 96.7% (95% CI: 87.6-99.0%), and 79.7% (95% CI: 71.1-88.3%) at 10 years. Long-term survival after redo surgery following the Ross operation is excellent. The data support our aggressive valve-sparing approach after Ross.


[Two cases of pneumocephalus following noninvasive continuous positive airway ventilation after transsphenoidal neurosurgery].
The early use of continuous positive airway pressure ventilation has been shown to be effective and is recommended for patients with obstructive sleep apnea. The complications of continuous positive airway pressure ventilation are not well described. We report two cases of pneumocephalus following the use of continuous positive airway pressure ventilation after transsphenoidal surgery. One patient had an obstructive sleep apnea and the other suffered acute respiratory failure. In both cases, pneumocephalus caused major morbidity and required specific treatment and prolonged considerably hospital stay. Based on these observations we believe new precautions in the use of noninvasive continuous positive airway pressure ventilation should be recommended.


High prevalence of a linear valve-like structure on CT at the pulmonary artery terminus of patent ductus arteriosus in adult patients, mimicking endarteritis.
A linear valve-like structure at the pulmonary artery terminus is identified on CT in some patients with patent ductus arteriosus (PDA) and can potentially be mistaken for endarteritis. The purpose of this study was to evaluate the differences in CT features between adult patients with PDA and a linear structure and those without. We retrospectively evaluated ECG-gated cardiac CT of 38 patients with PDA dividing them into two groups [patients with linear symmetrical valve-like structure (group1, n = 16), and those without (group 2, n = 22)]. We analyzed CT findings of the PDA including length, minimal and maximal diameter, presence of calcification, and PDA type, comparing the two subgroups. The authors also investigated the prevalence of endarteritis. There was no difference in CT findings between the two groups in the prevalence of calcification and length, and minimal and maximal diameter of PDA. Notably the linear valve-like structure was only identified in type 1 PDA (cone-shaped PDA) (p = 0.04), while there were variable types of PDA in group 2. There was only one case of endarteritis as a complication of PDA in group 1. In contrast to a linear valve-like structure, asymmetrical nodular thickening was noted in the patient with endarteritis on CT overlying the pre-existing linear valve-like structure at the pulmonary end of PDA. A linear valve-like structure is frequently identified at the pulmonary end in type 1 PDA. This CT finding should not be mistaken for endarteritis in the absence of other clinical evidence.


Transversus abdominis plane block: a cadaveric and radiological evaluation.
The abdominal wall is a significant source of pain after abdominal surgery. Anterior abdominal wall analgesia may assist in improving postoperative analgesia. We have recently described a novel approach to block the abdominal wall neural afferents via the bilateral lumbar triangles of Petit, which we have termed a transversus abdominis plane block. The clinical efficacy of the transversus abdominis plane block has recently been demonstrated in a randomized controlled clinical trial of adults undergoing abdominal surgery. After institutional review board approval, anatomic studies were conducted to determine the deposition and spread of methylene blue injected into the transversus abdominis plane via the triangles of Petit. Computerized tomographic and magnetic resonance imaging studies were then conducted in volunteers to ascertain the deposition and time course of spread of solution within the transversus abdominis fascial plane in vivo. Cadaveric studies demonstrated that the injection of methylene blue via the triangle of Petit using the "double pop" technique results in reliable deposition into the transversus abdominis plane. In volunteers, the injection of local anesthetic and contrast produced a reliable sensory block, and demonstrated deposition throughout the transversus abdominis plane. The sensory block produced by lidocaine 0.5% extended from T7 to L1, and receded over 4 to 6 hours, and this finding was supported by magnetic resonance imaging studies that showed a gradual reduction in contrast in the transversus abdominis plane over time. These findings define the anatomic characteristics of the transversus abdominis plane block, and underline the clinical potential of this novel block.


A voxel-by-voxel parametric fMRI study of motor mental rotation: hemispheric specialization and gender differences in neural processing efficiency.
Differences between men and women in brain size, cognitive performance and lateralization of brain activation have been perennial and controversial issues. Here we show that in a motor mental rotation task where women and men performed equally well, the slope of the functional magnetic resonance imaging (fMRI) blood oxygenation level dependent (BOLD) signal per degree of mental rotation was overall 2.4x higher in men than in women. This was attributed to the much more inefficient engagement (i.e. higher slopes) of the right hemisphere by men (mainly the frontal lobe). These findings indicate that women process information much more efficiently than men, which could offset smaller brain size.


Experimental human exposure to ethylene glycol monomethyl ether.
The uptake of EGME and the urinary excretion of its major metabolite (MAA) was studied in seven male volunteers during experimental exposure to EGME at rest. The exposure concentration was set at 16 mg/m3, the present Threshold Limit Value. A high retention (0.76) remained unchanged during the 4-h exposure period. In combination with a constant pulmonary ventilation and a fixed exposure concentration this resulted in an uptake rate that showed no significant variation in time. The total amount of EGME inhaled corresponded to a dose of only 0.25 mg/kg. During and up to 120 h after the start of the exposure, MAA was detected in the urine. The elimination half-life was on average 77.1 h. The total amount of MAA excreted was calculated by extrapolation and averaged 85.5% of the inhaled EGME. The pharmacokinetic data are compared with those obtained from other human exposure studies to ethylene glycol ethers (EGEE and EGBE).


Casimir force and its effects on pull-in instability modelled using molecular dynamics simulations.
We present a new methodology to incorporate the Casimir forces within the molecular dynamics (MD) framework. At atomistic scales, the potential energy between two particles arising due to the Casimir effect can be represented as U(r ij ) = C/r 7. Incorporating the Casimir effect in MD simulations requires the knowledge of C, a problem hitherto unsolved. We overcome this by equating the total potential energy contributions due to each atomistic pair with the potential energy of continuum scale interacting bodies having similar geometries. After having identified the functional form of C, standard MD simulations are augmented with the potential energy contribution due to pairwise Casimir interactions. The developed framework is used to study effects of the Casimir force on the pull-in instability of rectangular and hollow cylindrical shaped deformable electrodes separated by a small distance from a fixed substrate electrode. Our MD results for pull-instability qualitatively agree with the previously reported analytical results but are quantitatively different. The effect of using longer-ranged Casimir forces in a constant temperature environment on the pull-in behaviour has also been studied.


Planning treatment of the rheumatoid hand.
A detailed assessment of the patient as a whole is an essential pre-requisite to the successful planning and execution of surgical treatment of the rheumatoid hand. In particular the decision whether or not to operate must emerge from a careful weighing of the severity of the patient's symptoms, signs and physical disability against the benefits which are likely to accrue from surgical treatment assessed in relation to the patient's own individual requirements. The author presents his personal reflections on the relative merits of the commonly used surgical procedures with reference to their ability to relieve pain, restore function, achieve cosmetic improvement, and prevent further damage, while at the same time carrying minimal risk of further damage to the already impaired function of the hand. Finally, the philosophy which should govern the surgeon - patient relationship during the management of a chronic progressive disease is examined. That it is absolutely essential to establish a sound rapport from early in the surgical programme is strongly emphasised. Some guidelines as to the design of the programme are also provided.


Possible relationship of proliferative enteritis in pigs and hamsters.
Three- to six-week-old hamsters were orally inoculated with broths containing one of the following cultures: Campylobacter mucosalis; C. hyointestinalis; C. coli; C. jejuni, all of porcine proliferative enteritis origin, or else C. jejuni of hamster origin. Hamsters given the last of those organisms were shown to have colonisation of their intestines by C. jejuni and 36 of 40 developed an acute enteritis. Mild hyperplasia of enterocytes in ileal crypts was evident in one hamster 2 days after it was given C. coli. No other lesions were detected. Further 3-week-old hamsters were orally inoculated with homogenised intestinal mucosa collected from 4 pigs (A-D) affected by proliferative enteritis. Lesions of proliferative enteritis were detected in 7 of 41 hamsters necropsied 10-21 days after being dosed with mucosas B or D. Marked hyperplasia of ileal enterocytes, associated with numerous intracellular Campylobacter-like organisms, were invariably detected in experimentally affected hamsters. No particular Campylobacter sp. was consistently isolated. None of the controls had demonstrable lesions. The results suggested that cross-species transmission of proliferative enteritis was possible from pigs to hamsters. Therefore a common initiating or aetiological agent may be present. No specific organism was identified as filling this role by inoculation of hamsters with pure cultures.


Global Association of Cause-specific Mortality between the Major Gastrointestinal Cancers and Parkinson's Disease for the First Two Decades of the New Millennium.
Parkinson's disease (PD) and gastrointestinal (GI) cancers are both "age-related diseases" sharing several environmental risk factors, but possess opposite underlying biological mechanisms. Aim of this study was to evaluate the correlations between GI cancers and PD using national cause-specific mortality data of 183 countries extracted from the Global Health Observatory database. The association between PD- and GI cancers- (i.e. esophagus cancer, EC; stomach cancer, SC; colorectal cancer, CRC; liver cancer, LC and pancreatic cancer, PC) specific mortality on the country level was evaluated using Spearman correlation and logistic regression analysis. A global increase in mortality from 2000 to 2019 was observed in PD, CRC and PC, whereas in EC, SC and LC it decreased. We see the consistent diminishment of correlation intensities between PD and GI cancer mortalities from 2000 to 2019 as a positive development. In 2019, PD inversely correlated with CRC (rs = -0.39) and PC (rs = -0.40, all P < 0.001) but not with EC and SC. Of note, an exceptionally positive correlation of PD with LC (rs = 0.26, P < 0.001) and its two hepatitis B and C virus-associated subtypes was revealed. Logistic regression analysis further determined that PD associated negatively with CRC (OR = 0.25) and PC (OR = 0.21, both P < 0.001), but positively with LC (OR = 2.27, P = 0.007). Consequently, future research aiming to unravel the functional biological link between neurodegeneration, hepatitis and tumor development holds great potential for developing novel therapeutics.


Probability of mortality of critically ill cancer patients at 72 h of intensive care unit (ICU) management.
To develop and validate a model for probability of hospital mortality for cancer patients at 72 h of intensive care unit (ICU) management. This is an inception cohort study performed at four ICUs of academic medical centers in the United States. Defined continuous and categorical variables were collected on consecutive patients with cancer admitted to the ICU. A preliminary model was developed from 827 patients and then validated on an additional 415 patients. Multiple logistic regression modeling was used to develop the models, which were subsequently evaluated for discrimination and calibration. The main outcome measure is in-hospital death. A probability of mortality model, which incorporates ten discrete categorical variables, was developed and validated. All variables were collected at 72 h of ICU care. Variables included evidence of disease progression, performance status before hospitalization, heart rate >100 beats/min, Glasgow coma score </=5, mechanical ventilation, arterial oxygen pressure/fractional inspiratory oxygen ( PaO(2)/FiO(2)) ratio <250, platelets <100 k/ micro l, serum bicarbonate (HCO(3))<20 mEq/l, blood urea nitrogen (BUN) >40 mg/dl, and a urine output of <150 ml for any 8 h in the previous 24 h. The p values for the fit of the preliminary and validation models were 0.535 and 0.354 respectively, and the areas under the receiver operating characteristic (ROC) curves were 0.809 and 0.820. We report a multivariable logistic regression model to estimate the probability of hospital mortality in critically ill cancer patients at 72 h of ICU care. The model is comprised of ten unambiguous and readily available variables. When used in conjunction with clinical judgment, this model should improve discussions about goals of care of these patients. Additional validation in a community hospital setting is warranted.


Isolation, culture and identification of pulmonary arterial smooth muscle cells from rat distal pulmonary arteries.
The culture of pulmonary arterial smooth muscle cells (PASMCs) is one of the most powerful tools for exploring the mechanisms of pulmonary hypertension (PH). Both pulmonary vasoconstriction and remodeling occur predominantly in distal pulmonary arteries (PA). In this study, we provide our detailed and standardized protocol for easy isolation and culture of PASMCs from rat distal PA to supply every investigator with a simple, economical and useful method in studying PH. The protocol can be divided into four stages: isolation of distal PA, isolation of cells, growth in culture and passage of cells. Rat distal PASMCs were characterized by morphological activity and by immunostaining for smooth muscle α-actin and smooth muscle myosin heavy chain, but not for CD90/Thy-1 or von Willebrand factor. Furthermore, functional assessments were performed, confirming the presence of voltage-dependent Ca2+ channels and physiological characteristic of response to hypoxia. In conclusion, we have developed a detailed and simple protocol for obtaining rat distal PASMCs. These PASMCs exhibit features consistent with vascular smooth muscle cells, and they could subsequently be used to further explore the pathophysiological mechanisms of PH.


Regulation of pancreatic duct cell differentiation by phosphatidylinositol-3 kinase.
We have previously demonstrated that the phosphatidylinositol-3 kinase (PI3K)/Akt signaling is essential for pancreatic regeneration after partial pancreatectomy in mice. In the present study, we examined a role of PI3K/Akt signaling for pancreatic duct cell differentiation into insulin-producing cells. Epithelial-like cells were isolated from mouse pancreas and confirmed to be positive for a duct cell marker cytokeratin-20 (CK-20) but negative for insulin. Incubation of these cells with epidermal growth factor, exhibited a gradual increase in Akt phosphorylation and expression of pancreatic duodenal homeobox-1 (PDX-1), a regulator of beta-cell differentiation. Three weeks later, these CK-20-positive cells were noted to express insulin as determined by immunofluorescent double-staining. Akt phosphorylation, PDX-1 expression, and insulin production were effectively reduced by blocking the PI3K/Akt pathway using siRNA to the p85alpha regulatory subunit of PI3K. Our results demonstrate that PI3K/Akt activation has a critical role for pancreatic duct cell differentiation into insulin-producing cells.


A deep learning system for automated kidney stone detection and volumetric segmentation on noncontrast CT scans.
Early detection and size quantification of renal calculi are important for optimizing treatment and preventing severe kidney stone disease. Prior work has shown that volumetric measurements of kidney stones are more informative and reproducible than linear measurements. Deep learning-based systems that use abdominal noncontrast computed tomography (CT) scans may assist in detection and reduce workload by removing the need for manual stone volume measurement. Prior to this work, no such system had been developed for use on noisy low-dose CT or tested on a large-scale external dataset. We used a dataset of 91 CT colonography (CTC) scans with manually marked kidney stones combined with 89 CTC scans without kidney stones. To compare with a prior work half the data was used for training and half for testing. A set of CTC scans from 6185 patients from a separate institution with patient-level labels were used as an external validation set. A 3D U-Net model was employed to segment the kidneys, followed by gradient-based anisotropic denoising, thresholding, and region growing. A 13 layer convolutional neural network classifier was then applied to distinguish kidney stones from false positive regions. The system achieved a sensitivity of 0.86 at 0.5 false positives per scan on a challenging test set of low-dose CT with many small stones, an improvement over an earlier work that obtained a sensitivity of 0.52. The stone volume measurements correlated well with manual measurements ( r 2 = 0.95 $r^2 = 0.95$ ). For patient-level classification, the system achieved an area under the receiver-operating characteristic of 0.95 on an external validation set (sensitivity = 0.88, specificity = 0.91 at the Youden point). A common cause of false positives were small atherosclerotic plaques in the renal sinus that simulated kidney stones. Our deep-learning-based system showed improvements over a previously developed system that did not use deep learning, with even higher performance on an external validation set.


Technical considerations using a composite graft for aortic root replacement.
We performed modified aortic root replacement using a composite graft in seven patients over a 7-year-period. Six patients underwent emergency surgery for acute aortic dissection and one patient underwent elective surgery for an aortic aneurysm. To make the composite graft, we chose an artificial valve that was 1 mm larger than the graft, and when performing the proximal anastomosis, we sutured only the graft edge using the horizontal mattress suture technique, applying an additional running suture for reinforcement. The button technique was routinely used for coronary reattachment. To assess hemostasis of the aortic proximal and coronary suture line, cardioplegia was injected via the left atrial vent, which enabled us to confirm hemostasis before performing the distal anastomosis. Blood loss and the need for blood transfusion were minimized by this modified technique. None of the six survivors has required reoperation during 7-year period. Our technique of aortic root replacement based on a composite graft with some operative modifications seems to be safe and reliable, resulting in a satisfactory outcome.


Characterisation of the mechanical and fracture properties of a uni-weave carbon fibre/epoxy non-crimp fabric composite.
A complete database of the mechanical properties of an epoxy polymer reinforced with uni-weave carbon fibre non-crimp fabric (NCF) is established. In-plane and through-the-thickness tests were performed on unidirectional laminates under normal loading and shear loading. The response under cyclic shear loading was also measured. The material has been characterised in terms of stiffness, strength, and failure features for the different loading cases. The critical energy release rates associated with different failure modes in the material were measured from interlaminar and translaminar fracture toughness tests. The stress-strain data of the tensile, compressive, and shear test specimens are included. The load-deflection data for all fracture toughness tests are also included. The database can be used in the development and validation of analytical and numerical models of fibre reinforced plastics (FRPs), in particular FRPs with NCF reinforcements.


Design features and baseline characteristics of the LIPID (Long-Term Intervention with Pravastatin in Ischemic Disease) Study: a randomized trial in patients with previous acute myocardial infarction and/or unstable angina pectoris.
LIPID is a multicenter, double-blind, randomized, placebo-controlled trial comparing the effects of pravastatin, 40 mg/day, with placebo, given for > or = 5 years, in patients aged 31 to 75 years with a total cholesterol level at baseline of 4.0 to 7.0 mmol/L (155 to 270 mg/dl), and with a history of acute myocardial infarction (AMI) or hospitalization for unstable angina pectoris (UAP). Each group receives dietary advice according to National Heart Foundation guidelines. Individual care of each patient is otherwise left to the discretion of the patient's usual doctor. The study has a primary outcome of coronary mortality, and is designed to detect an 18% reduction with 80% power. From April 1990 to September 1992, 11,106 patients were registered, and following the run-in phase, 9,014 were randomized: 5,754 (64%) after a qualifying event of AMI and 3,260 (36%) after hospitalization for UAP. The randomized population includes relatively large numbers in subgroups not assessed reliably in earlier trials: 1,511 women, 3,516 patients aged > or = 65 years, 777 diabetics, and 3,829 patients with serum cholesterol < or = 5.5 mmol/L (213 mg/dl) at baseline. With a projected 700 fatal coronary events, the trial should be able to detect important reductions in coronary mortality and contribute substantially to prospective meta-analyses to detect effects on total mortality. The spectrum of patients being assessed will improve the reliability of evidence for the benefits and risks of cholesterol-lowering therapies in patients with lower cholesterol levels and in other important subgroups.


Sociodemographic and Economic Factors in Outcomes of Tube Shunts for Neovascular Glaucoma.
Few studies have analyzed associations between sociodemographic factors and neovascular glaucoma (NVG) outcomes. To determine the potential impact of sociodemographic and economic factors on the NVG tube shunt surgery outcomes. Retrospective, single-center, comparative case series. Consecutive patients who underwent tube shunt surgery for NVG and had ≥6 months of follow-up. Regional average adjusted gross income (AGI) was determined by cross-referencing self-reported residential zip codes with average AGI per zip code supplied by the Internal Revenue Service. Two groups were created: (1) lower-income: individuals from neighborhoods with the lowest 10% of AGI (near the United States poverty line), (2) higher-income: the remaining 90% of individuals. Visual acuity (VA), intraocular pressure (IOP), and glaucoma medication number at 6 months and the most recent visit. The mean annual AGI in the higher-income group (130 patients) was $69,596 ± 39,700 and the lower-income group (16 patients) was $27,487 ± 1,600 (p < 0.001). Age, sex, distance to the clinic, language, and all baseline clinical variables (including VA and IOP) were comparable between groups. Lower-income was associated with non-white race (81.3 vs 52.3%; p = 0.024). At month 6, VA in the lower-income group [median: HM (20/70-NLP)] was worse than the higher-income group [median: CF (20/25-NLP)] (log MAR VA: 2.32 ± 0.8 vs 1.77 ± 1.1; p = 0.02); these trends persisted through the most recent visit (p = 0.043). Follow-up IOP and medications were similar between groups. Lower-income may be associated with worse VA outcomes following NVG tube shunt surgery. Shalaby WS, Arbabi A, Myers JS, et al. Sociodemographic and Economic Factors in Outcomes of Tube Shunts for Neovascular Glaucoma. J Curr Glaucoma Pract 2021;15(2):70-77.


Localised disease in cancer of unknown primary (CUP): the value of positron emission tomography (PET) for individual therapeutic management.
Two to four percent of cancer patients present with CUP syndrome. Median survival for localised disease is 20 and for disseminated disease, seven months. For localised disease, curative treatment is more likely and individual therapeutic strategies become more important. After conservative diagnostic procedures including MRI, the primary is detected in less than 25%. The diagnostic value of PET and its influence on therapeutic strategies was evaluated. Forty-two patients with localised CUP were investigated from 5 of 98 to 10 of 2000. The presenting site was lymph node metastasis in 34 and visceral metastasis in 8 patients. After a median of 7 (3-11) diagnostic procedures without detection of the primary, but evidence of localised disease, PET was performed with fluorine-18-fluorodeoxyglucose. In 26 of 42 patients (62%), a primary was suggested by PET and confirmed in 18 (43%). In 5 of 18 patients beyond localised disease, additional dissemination, not detected by previous diagnostic measures, was diagnosed by PET. Overall, dissemination was only detected only by PET in 16 of 42 patients (38%). In29 of 42 patients (69%), the PET result influenced selection of the definitive treatment. In CUP patients, PET has a certain impact on detection of the primary as well as of the disseminated disease. and may also have a certain impact on therapeutic management.


ICV-CRH alters stress-induced freezing behavior without affecting pain sensitivity.
Freezing is an adaptive response often induced by stressful, fear-eliciting stimuli. Three experiments with rats investigated the effects of intracerebroventricular (ICV) administration of corticotropin-releasing hormone (CRH) on freezing behavior and pain sensitivity. Experiments 1 and 3 demonstrated that ICV-CRH (300 ng) enhanced shock-elicited freezing. In Experiment 1, ICV-CRH also enhanced recovery from shock-elicited freezing, suggesting that the peptide has a biphasic effect. Experiments 2 and 3 established that CRH-induced freezing was not caused by heightened pain sensitivity. Interestingly, in Experiment 2, hot-plate exposure produced increased freezing that was attenuated by ICV-CRH. Thus, the direction of the ICV-CRH effect on freezing was found to depend on the nature of the stressor. These results suggest that endogenous CRH systems modulate stress-induced freezing.


Lipopolysaccharide upregulates the expression of corticotropin-releasing hormone via MAP kinase pathway in rat peritoneal macrophages.
The stress neuropeptide, corticotropin-releasing hormone (CRH) is expressed in peripheral tissues and inflammatory sites and is implicated in the modulation of the inflammatory response in a paracrine/ autocrine manner. However, the mechanisms by which CRH expression is regulated in peripheral immune cells are unclear. In this article, we address this question by employing primary rat peritoneal macrophages treated with lipopolysaccharide (LPS). Our results showed that CRH could be detected at the mRNA and protein levels in normal peritoneal macrophages and the levels increased significantly and reached a peak at 4 h after stimulation with 100 ng/ml LPS. Furthermore, LPS-induced CRH expression was inhibited by pretreatment with PD98059, a specific MAP kinase inhibitor, in a dose-dependent fashion in which the mRNA and protein levels of CRH was decreased by 90% and 95%, respectively. In addition, pretreatment with 50 μM SB203580, a p38 MAPK inhibitor, led to the decrease of CRH mRNA level by about 41%. Altogether, these results demonstrate that LPS significantly upregulates CRH expression through MAP kinase signaling pathway in rat peritoneal macrophages.


Pharmacological characterization of a substance P antagonist, [D-Arg1,D-Pro2,D-Trp7,9,Leu11]-substance P.
The substance P antagonist [D-Arg1,D-Pro2,D-Trp7,9,Leu11]-substance P produced parallel log dose-response curve shifts to both substance P and eledoisin on five in vitro smooth muscle preparations. The slope values of Arunlakshana-Schild plots were not significantly different from unity suggesting that it acts as a simple competitive antagonist on all five preparations with an association constant (Ka) in the range of 0.3-1.5 X 10(6)M-1. The Ka value of the antagonist was always slightly greater when tested against eledoisin than against substance P; however, this difference appears too small to suggest that these two agonists are acting on different receptor sub-types.


Recent Developments of Actuation Mechanisms for Continuum Robots: A Review.
Traditional rigid robots face significant challenges in congested and tight environments, including bulky size, maneuverability, and safety limitations. Thus, soft continuum robots, inspired by the incredible capabilities of biological appendages such as octopus arms, starfish, and worms, have shown promising performance in complex environments due to their compliance, adaptability, and safety. Different actuation techniques are implemented in soft continuum robots to achieve a smoothly bending backbone, including cable-driven actuators, pneumatic actuators, and hydraulic actuation systems. However, designing and developing efficient actuation mechanisms, motion planning approaches, and control algorithms are challenging due to the high degree of redundancy and non-linearity of soft continuum robots. This article profoundly reviews the merits and drawbacks of soft robots' actuation systems concerning their applications to provide the readers with a brief review reference to explore the recent development of soft robots' actuation mechanisms technology. Moreover, the authors have surveyed the recent review studies in controller design of continuum robots as a guidance for future applications.


Identification of cyclic peptides able to mimic the functional epitope of IgG1-Fc for human Fc gammaRI.
Identification of short, structured peptides able to mimic potently protein-protein interfaces remains a challenge in drug discovery. We report here the use of a naive cyclic peptide phage display library to identify peptide ligands able to recognize and mimic IgG1-Fc functions with Fc gammaRI. Selection by competing off binders to Fc gammaRI with IgG1 allowed the isolation of a family of peptides sharing the common consensus sequence TX(2)CXXthetaPXLLGCPhiXE (theta represents a hydrophobic residue, Phi is usually an acidic residue, and X is any residue) and able to inhibit IgG1 binding to Fc gammaRI. In soluble form, these peptides antagonize superoxide generation mediated by IgG1. In complexed form, they trigger phagocytosis and a superoxide burst. Unlike IgG, these peptides are strictly Fc gammaRI-specific among the Fc gammaRs. Molecular modeling studies suggest that these peptides can adopt 2 distinct and complementary conformers, each able to mimic the discontinuous interface contacts constituted by the Cgamma2-A and -B chains of Fc for Fc gammaRI. In addition, by covalent homodimerization, we engineered a synthetic bivalent 37-mer peptide that retains the ability to trigger effector functions. We demonstrate here that it is feasible to maintain IgG-Fc function within a small structured peptide. These peptides represent a new format for modulation of effector functions.


Recent declines in salmon body size impact ecosystems and fisheries.
Declines in animal body sizes are widely reported and likely impact ecological interactions and ecosystem services. For harvested species subject to multiple stressors, limited understanding of the causes and consequences of size declines impedes prediction, prevention, and mitigation. We highlight widespread declines in Pacific salmon size based on 60 years of measurements from 12.5 million fish across Alaska, the last largely pristine North American salmon-producing region. Declines in salmon size, primarily resulting from shifting age structure, are associated with climate and competition at sea. Compared to salmon maturing before 1990, the reduced size of adult salmon after 2010 has potentially resulted in substantial losses to ecosystems and people; for Chinook salmon we estimated average per-fish reductions in egg production (-16%), nutrient transport (-28%), fisheries value (-21%), and meals for rural people (-26%). Downsizing of organisms is a global concern, and current trends may pose substantial risks for nature and people.


Resveratrol enhances anticancer effects of paclitaxel in HepG2 human liver cancer cells.
The aim of this in vitro study was to measure the enhanced anticancer effects of Res (resveratrol) on PA (paclitaxel) in HepG2 human liver cancer cells. The MTT (thiazolyl blue tetrazolium bromide, 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide), flow cytometry, qPCR (real-time quantitative polymerase chain reaction) and western blot assay were used for cells growth inhibitory effects, cells apoptosis (DNA content of sub-G1), mRNA and protein expressions, respectively. The 10 μg/mL of Res had no growth inhibitory effect on Nthy-ori 3-1 normal cells or HepG2 cancer cells meanwhile the 5 or 10 μg/mL of PA also had no growth inhibitory effect on Nthy-ori 3-1 normal cells. Where as PA-L (5 μg/mL) and PA-H (10 μg/mL) had the growth inhibitory effects in HepG2 cancer cells, and Res increase these growth inhibitory effects. By flow cytometry experiment, after Res (5 μg/mL) + PA-H (10 μg/mL) treatment, the HepG2 cells showed the most apoptosis in cells as compared to other treatments groups, and after additionally treated with Res, both the apoptosis cells of two concentrations PA were raised. As PA raised it also raised the mRNA and protein expressions of caspase-3, caspase-8, caspase-9, Bax (Bcl-2 assaciated X protein), p53, p21, IκB-α (inhibitor of NF-κB alpha), Fas (factor associated suicide), FasL (factor associated suicide ligand), TIMP-1 (tissue inhibitor of metalloproteinases 1), TIMP-2 (tissue inhibitor of metalloproteinases 2) and decrease Bcl-2 (B cell leukemia 2), Bcl-xL (B cell leukemia extra large), HIAP-1 (cIAP-1, cellular inhibitor of apoptosis 1), HIAP-2 (cIAP-2, cellular inhibitor of apoptosis 2), NF-κB (nuclear factor kappa B), COX-2 (cyclooxygenase 2), iNOS (inducible nitric oxide synthase), MMP-2 (metalloproteinase 2), MMP-9 (metalloproteinase 9), EGF (epidermal growth factor), EGFR (epidermal growth factor receptor), VEGF (vascular endothelial growth factor), Fit-1 (VEGFR-1, vascular endothelial growth factor receptor 1). Meanwhile, the 5 μg/mL of Res could enhance these mRNA expressions changes as compared to the control cells. From these results, we can conclude that Res could raise the anticancer effects of PA in HepG2 cells, Res could be used as a good sensitizing agent for PA.


The effectiveness of internet-based telerehabilitation among patients after total joint arthroplasty: An integrative review.
Total joint arthroplasty is one of the most commonly performed orthopaedic procedures globally. Telerehabilitation has recently been used as a supplement or an alternative to face-to-face rehabilitation services among patients after total joint arthroplasty. To synthesise the evidence on the effectiveness of internet-based telerehabilitation regarding pain relief, range of motion, physical function, health-related quality of life, self-efficacy, psychological well-being/problems, and satisfaction among patients after total joint arthroplasty. An integrative review was conducted using defined search periods, databases, and search terms. This review adopted a five-stage approach: problem identification, literature search, data evaluation, data analysis and presentation. Studies published in English and Chinese were included. The Mixed Methods Appraisal Tool was used to assess the quality of included studies. Twenty-two eligible studies with 1,179 participants were included in this review. Nineteen of them were conducted in North America, Europe and Australia, and three in China. There were 20 quantitative and two qualitative studies. Synchronous mode using videoconferencing (n = 11) was predominant in the studies between 2003 and 2017, while asynchronous mode using mobile apps (n = 7) has become the main mode since 2017. Internet-based telerehabilitation was delivered by physiotherapists in 17 studies and by nurses in three. Most of the included studies reported that, compared to face-to-face rehabilitation, internet-based telerehabilitation showed a comparable improvement in pain relief, range of motion, physical function, and health-related quality of life. Patients had a high satisfaction level. Very few studies addressed the patients' psychological well-being/problems and self-efficacy as the outcome measures. Internet-based telerehabilitation appears to be effective for and accepted by patients after total joint arthroplasty. Telerehabilitation could be delivered by nurses in collaboration with physiotherapists and surgeons as a team. The mobile app is an accessible and flexible delivery medium for telerehabilitation. Robust randomised controlled trials are warranted to enhance the quality of evidence on the effectiveness of mobile app-based telerehabilitation and nurse-delivered program. Qualitative components are suggested to be included in future research. Psychological outcomes should also be measured.


A proposed metric set for evaluation of genome assembly quality.
Quality control is essential for genome assemblies; however, a consensus has yet to be reached on what metrics should be adopted for the evaluation of assembly quality. N50 is widely used for contiguity measurement, but its effectiveness is constantly in question. Prevailing metrics for the completeness evaluation focus on gene space, yet challenging areas such as tandem repeats are commonly overlooked. Achieving correctness has become an indispensable dimension for quality control, while prevailing assembly releases lack scores reflecting this aspect. We propose a metric set with a set of statistic indexes for effective, comprehensive evaluation of assemblies and provide a score of a finished assembly for each metric, which can be utilized as a benchmark for achieving high-quality genome assemblies.


Warming-induced shifts in amphibian phenology and behavior lead to altered predator-prey dynamics.
Climate change-induced phenological variation in amphibians can disrupt time-sensitive processes such as breeding, hatching, and metamorphosis, and can consequently alter size-dependent interactions such as predation. Temperature can further alter size-dependent, predator-prey relationships through changes in species' behavior. We thus hypothesized that phenological shifts due to climate warming would alter the predator-prey dynamic in a larval amphibian community through changes in body size and behavior of both the predator and prey. We utilized an amphibian predator-prey system common to the montane wetlands of the U.S. Pacific Northwest: the long-toed salamander (Ambystoma macrodactylum) and its anuran prey, the Pacific chorus frog (Pseudacris regilla). We conducted predation trials to test if changes in predator phenology and environmental temperature influence predation success. We simulated predator phenological shifts using different size classes of the long-toed salamander representing an earlier onset of breeding while using spring temperatures corresponding to early and mid-season larval rearing conditions. Our results indicated that the predator-prey dynamic was highly dependent upon predator phenology and temperature, and both acted synergistically. Increased size asymmetry resulted in higher tadpole predation rates and tadpole tail damage. Both predators and prey altered activity and locomotor performance in warmer treatments. Consequently, behavioral modifications resulted in decreased survival rates of tadpoles in the presence of large salamander larvae. If predators shift to breed disproportionately earlier than prey due to climate warming, this has the potential to negatively impact tadpole populations in high-elevation amphibian assemblages through changes in predation rates mediated by behavior.


Temsirolimus downregulates p21 without altering cyclin D1 expression and induces autophagy and synergizes with vorinostat in mantle cell lymphoma.
To investigate the mechanisms of antiproliferative effect induced by the mammalian target of rapamycin (mTOR) inhibitor temsirolimus in mantle cell lymphoma (MCL). The antiproliferative effect of temsirolimus on three well-defined MCL cell lines was examined by the MTS assay. Induction of cell-cycle arrest, autophagy, and apoptosis were determined by fluorescence-activated cell sorting analysis. The molecular mechanisms underlining these effects were determined by Western blot. Synergy between temsirolimus and vorinostat were examined by MTS assay and the combination index was calculated. Temsirolimus has antiproliferative activity in three MCL cell lines in a dose- and time-dependent manner. Mechanistically, temsirolimus inhibited mTOR, as evidenced by inhibition of ribosomal S6 phosphorylation, and induced cell-cycle arrest in the G(0)/G(1) phase and a decrease in p21 expression without altering p27 or cyclin D1 levels. Furthermore, temsirolimus increased the number of acidic vesicular organelles and the amount of microtubule-associated protein 1 light-chain 3 processing, which are characteristic of autophagy, without induction of apoptosis. These changes were not associated with alteration in phosphorylated extracellular signal-regulated kinase (ERK), beclin-1, Bax, or Bak levels. In contrast, treatment of these cell lines with the histone deacetylase inhibitor vorinostat decreased ERK phosphorylation, activated caspase 3, and induced apoptosis. Moreover, temsirolimus synergized with submaximal concentrations of vorinostat in all MCL cell lines. This is the first report of temsirolimus-induced autophagy in MCL, and of vorinostat inhibition of ERK phosphorylation in MCL. Collectively, these data suggest that the combination of temsirolimus and vorinostat have synergistic antiproliferative activity in MCL cells by distinctively targeting apoptosis and autophagy.


Validation and evaluation of the German Brief Index of Lupus Damage (BILD)--a self-reported instrument to record damage in systemic lupus erythematosus.
Damage is a very important predictor for outcome in systemic lupus erythematosus (SLE) and should be routinely documented. Patient-reported assessments for damage are rare and neither the Lupus Damage Index Questionnaire (LDIQ) nor the Brief Index of Lupus Damage (BILD) is validated in German language. Our aim was to validate the BILD in German language and evaluate its use as a patient-administered instrument. We translated and adapted the BILD questionnaire to use it as a self-administered questionnaire for German-speaking SLE patients. It was applied to SLE outpatients at an academic centre and compared to the SLICC/SDI and other lupus outcome parameters. The German BILD showed as strong a correlation with the SLICC/SDI as the original version of the BILD and a superior correlation compared to the LDIQ. It scored significantly higher with an increase of age, disease duration or disease activity, with a lower functional status or overall health and a higher probability of receiving an incapacity pension. The German version of the BILD shows a comparable validity to the original BILD with even higher correlation to physician-reported damage even when used as a self-administered questionnaire. Hence it represents a promising instrument to survey damage in clinical routine as well as in clinical and epidemiological studies.


Event-related brain potentials and the perception of a phonetic continuum.
Competing predictions concerning phoneme discrimination were tested by means of event-related potentials. In research on speech perception, one tradition stems from the physiology of the auditory system whereas another emphasizes categorical perception which involves a marked psychological component. The stimuli were the end points of the Finnish (i)-(y) continuum together with the intermediate boundary sound. Two of these stimuli were presented in each block of trials. One (the 'standard') had a high probability while the other (the 'deviant') was rare. The so-called mismatch negativity (MMN) component of the ERP in response to deviant stimuli showed a large amplitude and short latency when these two stimuli were pure vowels (i) and (y). When the boundary stimulus and one of the pure vowels comprised the stimulus pair, a smaller and more delayed MMN occurred. This result may be taken as support that the discrimination occurs at a basic physiological level. On the other hand, cognitive perception was reflected in the different latencies of the P3 component to (i) and (y). In sum, the results lend support to multilevel hybrid models in the explanation of vowel perception.


Preparation of Structurally Diverse Compounds from the Natural Product Lycorine.
The synthesis of a 52-member compound collection from the natural product lycorine is reported, highlighted by divergent cross-coupling and substitution strategies and an unusual ring rearrangement induced by reaction with aryne intermediates.


The influence of Aβ-dependent and independent pathways on TDP-43 proteinopathy in Alzheimer's disease: a possible connection to LATE-NC.
Alzheimer's disease (AD) is a progressive neurodegenerative disorder that results from the accumulation of plaques by cleaved Aβ42 peptides as well as neurofibrillary tangles of tau proteins. This accumulation triggers a complex cascade of cytotoxic, neuroinflammatory, and oxidative stresses that lead to neuronal death throughout the progression of the disease. Much of research in AD focused on the 2 pathologic proteins. Interestingly, another form of dementia with similar clinical manifestations of AD, but preferentially affected much older individuals, was termed as limbic-predominant age-related transactive response DNA-binding protein 43 (TDP-43) encephalopathy (LATE) and involved the cytotoxic intraneuronal deposition of phosphorylated TDP-43. TDP-43 proteinopathy was also found to be involved in AD pathology leading to the possibility that AD and LATE may share a common upstream etiology. This paper discusses the roles molecular pathways known in AD may have on influencing TDP-43 proteinopathy and the development of AD, LATE, or the 2 being comorbid with each other.


Abnormal type III fusion between lunate and triquetrum: A case report.
The lunotriquetral coalition is the fusion of the lunate and triquetral bones of the wrist and is the most frequent carpal coalition type. It is frequently asymptomatic and discovered as an incidental due to chronic wrist pain, trauma, or fracture. This case aims to present an unusual unilateral lunotriquetral coalition and clinical significance for diagnosis and treatment. In this case, we presented a 37-year-old male who exhibited with right-sided trauma and wrist pain. He was diagnosed to had a type III complete osseous lunotriquetral coalition on the right side and detected by plain radiography and CT without lytic, destructive, and sclerotic lesions. An avulsion fracture was recognized in the distal end of the right radius. A fragmented fracture was identified in the scaphoid bone, and an internal fixator extending from scaphoid bone to lunate bone. The internal fixators were observed among the lunate, capitate, and distal end of the radius bones. The plain anteroposterior, lateral radiograph and CT of the right wrist exhibited a right-sided unilateral type III osseous coalition between the lunate and triquetrum bones. Knowledge of type III complete fusion is essential to the proper diagnosis and management of this variation when a subject exhibits unexplained wrist pain, trauma, or fracture. It should be noted that plain radiographs and CT can provide an accurate diagnosis in type III complete lunotriquetral coalition without pathological evidence.


Detection and defense of active attacks for generating secret key from wireless channels in static environment.
In quasi-static or static environments, generating secret key from wireless channels is bad randomness and vulnerable to active attacks. To improve randomness of the generated secret key, singular value decomposition (SVD) techniques are used to construct equivalent wireless channels in multiple-input multiple-output (MIMO) systems. SVD techniques and private pilot are used to detect active attacks by authenticating sender based on wireless channels. To defend passive eavesdropping and active attacks, the concept of one time pad is used to encrypt wireless channels with private pilot. The proposed SKG scheme based on private pilot and SVD techniques can not only detect whether SKG suffers active attacks, but also defend man-in-the-middle attack, impersonation attack, signal injection attack, passive eavesdropping. What is more, the SKG scheme can obtain higher SKG rate and randomness than the approach via random beam-forming. Theoretical analysis and simulation results prove the above results again.


Dielectric properties of Artemia cysts at low water contents. Evidence for a percolative transition.
Cellular cysts of the crustacean Artemia provide a useful model for studies on water-dependent mechanisms in cellular function because they can undergo reversible cycles of dehydration-rehydration. We explored their dielectric behavior over the frequency range of 10 kHz to 1 MHz, at water contents between near zero and 0.5 g H2O/g dry weight (g/g). The dc conductivity and static dielectric permittivity were evaluated from electrostatic analysis of data obtained with a three-layered capacitor. Below cyst hydrations of 0.05 g/g, negligible dielectric response was observed at all frequencies. Between 0.05 and 0.25 g/g the permittivity increased sharply then reached a near plateau up to cyst hydrations close to 0.35 g/g, above which a second abrupt increase occurred. Values for the dielectric loss (tan delta) exhibited frequency-dependent peaks over the hydration range of 0.05-0.3 g/g, followed by an abrupt increase near 0.35 g/g, an hydration at which metabolism is first initiated in this system. These hydration-dependent dielectric changes are compared with previous studies on the biology and physics of this system, and evaluated by a model involving percolative ionic (likely protonic) conduction. Percolative behavior is characterized by a sharp increase in conductivity at a critical threshold of hydration (hc) according to a power law in which the exponent, t, equals 1.65 for a three-dimensional infinite lattice. For the Artemia cyst, t = 1.64 above hc = 0.35 g/g, which is in excellent agreement with theory. These results are compared to similar studies on lysozyme which also exhibits percolative behavior connected with the onset of biological function.


Task-specific ankle robotics gait training after stroke: a randomized pilot study.
An unsettled question in the use of robotics for post-stroke gait rehabilitation is whether task-specific locomotor training is more effective than targeting individual joint impairments to improve walking function. The paretic ankle is implicated in gait instability and fall risk, but is difficult to therapeutically isolate and refractory to recovery. We hypothesize that in chronic stroke, treadmill-integrated ankle robotics training is more effective to improve gait function than robotics focused on paretic ankle impairments. Participants with chronic hemiparetic gait were randomized to either six weeks of treadmill-integrated ankle robotics (n = 14) or dose-matched seated ankle robotics (n = 12) videogame training. Selected gait measures were collected at baseline, post-training, and six-week retention. Friedman, and Wilcoxon Sign Rank and Fisher's exact tests evaluated within and between group differences across time, respectively. Six weeks post-training, treadmill robotics proved more effective than seated robotics to increase walking velocity, paretic single support, paretic push-off impulse, and active dorsiflexion range of motion. Treadmill robotics durably improved gait dorsiflexion swing angle leading 6/7 initially requiring ankle braces to self-discarded them, while their unassisted paretic heel-first contacts increased from 44 % to 99.6 %, versus no change in assistive device usage (0/9) following seated robotics. Treadmill-integrated, but not seated ankle robotics training, durably improves gait biomechanics, reversing foot drop, restoring walking propulsion, and establishing safer foot landing in chronic stroke that may reduce reliance on assistive devices. These findings support a task-specific approach integrating adaptive ankle robotics with locomotor training to optimize mobility recovery. NCT01337960. https://clinicaltrials.gov/ct2/show/NCT01337960?term=NCT01337960&rank=1.


Removal of phenolic contaminants from water by in situ coated surfactant on Keggin-aluminum nanocluster and biodegradation.
Recent water treatment plants require multi-process techniques to remove contaminants from aqua media. In this study, we investigate the novel, in situ coated sodium dodecylsulphate (SDS), on kegging Al30 nanocluster as a single water treatment alternative for the removal of phenolic contaminants and suspension. FTIR, TEM-EDX and Zeta potential analysis characterized the nanocluster decoration. The resulting property was examined by emission (λ-max) of the molecular probe, the online aggregate image of fluorescence microscopy, and mixing isochrone, fat-soluble dye solubilization. The coated media was examined as nearly resembling the hydrophobicity of 1-octanol. The elemental line scanning and mapping showed different morphologies of floc depending on the SDS concentration. The material was found to follow Brownian motion to enmesh suspended particles like a ladder, and served as entrapper for small organic contaminants by the sorbed SDS aggregate, based on their log KO/W. About 85% and ≥95% removal archived for contaminants with the least and highest KO/W value, respectively. The residual solutes in the supernatant were well decomposed by using a bacterial agent. One-step removal (less footprint) and ease of operation make this approach an environmentally compatible and cost-effective alternative for the large-scale treatment process.


Effect of different storage conditions on the mycotoxin contamination of Fusarium culmorum-infected and non-infected wheat straw.
Mycotoxins are known to affect the health and performance of farm animals. In contrast to cereal grains, the straw is only rarely analysed for mycotoxins, although contaminated straw could additionally expose farm animals to mycotoxins. For this reason, two experiments were carried out to examine the effect of pre-harvest Fusarium infection (inoculation with F. culmorum) and different storage conditions on the mycotoxin concentrations in straw. In the first experiment, both the inoculated and the identically cultivated control straw were stored in rectangular bales either in a barn or outdoors for a time period of 32 weeks (farm-scale experiment). The second experiment was aimed to examine the mycotoxin concentrations during storage under controlled conditions in a temperature-controlled climatic chamber, with target dry matter contents of 86%, 82% and 78% using 1.5-l preservation jars (laboratory-scale experiment). While the concentration of deoxynivalenol and its derivates decreased in the farm-scale experiment when inoculated straw was stored outdoors, the zearalenone concentration increased within the same time period. The latter effect was also detected for the control straw. These opposite effects were probably caused by the massive water uptake during the outdoor storage. The only effect we observed in the laboratory-scale experiment with dry matter contents between 78% and 86% was a more pronounced decrease of the 3-acetyl-deoxynivalenol concentrations in the inoculated straw with increasing moisture contents.