Routine postoperative intensive care unit admission after colorectal cancer surgery for the elderly patient reduces postoperative morbidity and mortality.
Older colorectal cancer (CRC) patients are at increased risk of postoperative morbidity and mortality. Routine postoperative overnight intensive care unit (ICU) admission might reduce this risk. This study aimed to examine the effect of routine overnight ICU admission after CRC surgery on postoperative adverse outcomes and costs in patients aged 80 years or older. Patients aged 80 years or older who underwent CRC surgery in our centre were included in this observational cohort study. All patients in the period 2014-2017 with routine overnight ICU admission were assigned to the ICU cohort; all patients in the period 2009-2013 were assigned to the non-ICU cohort. Multivariable logistic regression was performed to compare the primary composite end-point (30-day mortality, serious complications and readmission) between the groups. Cost data from the literature were used to perform a cost analysis. A total of 242 patients were included, 125 in the ICU cohort and 117 in the non-ICU cohort. Routine overnight ICU admission was associated with a reduced risk of the composite end-point (OR 0.44, 95% CI 0.22-0.87, P = 0.02) after adjusting for important confounders. In the ICU cohort 28% of patients experienced ICU events requiring intervention; this was not associated with postoperative morbidity or mortality. The 9% reduction in the incidence of serious complications in the ICU cohort is sufficient to offset the additional costs of routine overnight ICU admission. Routine overnight ICU admission after CRC surgery in patients aged 80 years and older is associated with reduced risk of postoperative mortality and morbidity and seems to be cost-effective.


Glycemic control in the prevention of diabetic complications.
The relationship between abnormal circulating glucose levels and the development of long-term diabetic complications became apparent soon after the introduction of insulin 70 years ago and the avoidance of early death due to ketoacidosis. Classic observational studies by Pirart described the relationship between increased glycosuria and the ultimate development of diabetic retinopathy, nephropathy, and neuropathy. Nonetheless, it required the findings of randomized, controlled clinical trials to finally and definitively establish the relationship between glucose control and microvascular diabetic complications. With the publication of the Diabetes Control and Complications Trial, the Kumomoto Trial, and the United Kingdom Prospective Diabetes Study, the impact of glycemic control in the development of microvascular complications was confirmed. Our understanding of the pathophysiology of diabetes--particularly, the dysmetabolic changes seen in type 2 diabetes--includes abnormalities in lipid metabolism, fuel flux, and endothelial function. Diabetes control, therefore, can no longer be viewed exclusively as glucose management. Rather, a more global approach is necessary to minimize risks of both microvascular and macrovascular complications. This article explores data supporting a variety of interventions that have been shown to reduce morbidity and mortality associated with long-standing diabetes mellitus. In addition to acknowledging the relationship between complications and diabetic metabolic abnormalities, this article presents a health economics perspective by examining the cost-effectiveness and health utility of these interventions.


Detectability of artificial marginal bone lesions as a function of lesion depth. A comparison between subtraction radiography and conventional radiographic technique.
Subtraction of serially obtained standardized radiographs of the marginal periodontal bone offers possibilities for an increased detectability of small bony changes compared to conventional radiography. In this study, the depth of artificially induced bone lesions in the alveolar crest was assessed by means of 125I absorptiometry. The results served as reference values when a series of radiographs containing lesions of various depths was interpreted by 10 examiners. Both conventional radiographs and subtraction images made from the conventional radiographs after digitization were interpreted. The ROC-curve technique was used to evaluate the two techniques. A close to perfect accuracy was found at a lesion depth corresponding to 0.49 mm of compact bone using the subtraction technique. A similar degree of accuracy was not reached for the conventional technique until the lesions were approximately 3 times deeper.


Efficacy of anatomical prostheses in primary glenohumeral osteoarthritis.
More than 32.8% of the over-60s suffer from shoulder osteoarthritis. For advanced osteoarthritis, arthroplasty is the treatment of choice. Current systems have moved on from the first shoulder prosthesis implanted by Neer in 1974, thanks to the use of adaptable modular systems. The aim of this study was to investigate the effectiveness of anatomical shoulder replacements in 30 cases of primary glenohumeral osteoarthritis through clinical and radiographic follow-up for a mean of 5 years. All implants were total cemented prostheses. Preoperative investigations included a clinical examination, conventional X-rays and CT. The Constant-Murley scale was used to evaluate the results; the mean score increased from 21.4 preoperative to 69.8 postoperative (p<0.05). In patients aged under 50, the increase in the mean postoperative Constant Score and ROM was greater than for the sample as a whole. The following complications were encountered: 2 postoperative radial nerve paralyses, resolving in 3 months, 2 cases of glenoid loosening, 1 periprosthetic fracture and 3 cases of pain and stiffness. The results led us to conclude that anatomical prostheses are effective in the treatment of severe primary glenohumeral arthropathy.


Widespread protein lysine acetylation in gut microbiome and its alterations in patients with Crohn's disease.
Lysine acetylation (Kac), an abundant post-translational modification (PTM) in prokaryotes, regulates various microbial metabolic pathways. However, no studies have examined protein Kac at the microbiome level, and it remains unknown whether Kac level is altered in patient microbiomes. Herein, we use a peptide immuno-affinity enrichment strategy coupled with mass spectrometry to characterize protein Kac in the microbiome, which successfully identifies 35,200 Kac peptides from microbial or human proteins in gut microbiome samples. We demonstrate that Kac is widely distributed in gut microbial metabolic pathways, including anaerobic fermentation to generate short-chain fatty acids. Applying to the analyses of microbiomes of patients with Crohn's disease identifies 52 host and 136 microbial protein Kac sites that are differentially abundant in disease versus controls. This microbiome-wide acetylomic approach aids in advancing functional microbiome research.


High incidence of severe influenza among individuals over 50 years of age.
Age-specific epidemiological data on asymptomatic, symptomatic, and severe infections are essential for public health policies on combating influenza. In this study, we incorporated data on microbiologically confirmed infections and seroprevalence to comprehensively describe the epidemiology of pandemic H1N1 2009 influenza. Seroprevalence was determined from 1,795 random serum samples collected in our hospital in January 2007 (before the first wave of the pandemic) and March 2010 (after the second wave). Data on microbiologically confirmed infection and severe cases were obtained from the Centre for Health Protection in Hong Kong. Severe cases were most common in the 51- to 60-year-old age group. The microbiologically confirmed incidence rate was highest for children aged ≤10 years and dropped sharply for the adult population (ρ = -1.0; P < 0.01), but the incidence rate for severe disease was highest for the 51- to 60-year-old age group. For the 51- to 60-year-old age group, the seroprevalence was similar to that for the younger age groups, but the proportion of severe cases relative to seroprevalence was significantly higher than that for 11- to 50-year-old age groups. As judged from the percentage of specimens positive for other respiratory viruses compared with that for pandemic H1N1 virus, the impact of symptomatic disease due to pandemic H1N1 virus was higher than that for other respiratory viruses in people aged ≤50 years. In conclusion, the 51- to 60-year-old age group, which had the highest overall incidence and the highest rate of severe disease but is currently not considered by the World Health Organization to be an at-risk group, should be prioritized for influenza vaccination in areas where universal influenza vaccination is not practiced.


Activated EGFR and PDGFR internalize in separate vesicles and downstream AKT and ERK1/2 signaling are differentially impacted by cholesterol depletion.
The interplay between membrane subregions and receptor tyrosine kinases (RTK) will influence signaling in both normal and pathological RTK conditions. In this study, epidermal growth factor receptor (EGFR) and platelet-derived growth factor receptor β (PDGFR-β) internalizations were investigated by immunofluorescent microscopy following simultaneous treatment with EGF and PDGF-BB. We found that the two receptors utilize separate routes of internalization, which merges in a common perinuclear endosomal compartment after 45 min of stimulation. This is further strengthened when contrasting the recruitment of either EGFR or PDGFR-β to either clathrin or caveolin-1: PDGFR-β dissociates from caveolin-1 upon stimulation, and engages clathrin, whilst an increased recruitment of EGFR, to both clathrin and caveolin-1, was observed upon EGF stimulation. The association between EGFR and caveolin-1 is supported by the observation that EGFR was localized in lipid raft associated fractions, whereas PDGFR-β was not. We also found that disruption of lipid rafts using MβCD led to an increased EGFR dimerization and phosphorylation in response to ligand, as well as a dramatic decrease in AKT- and a smaller but robust decrease in ERK1/2 phosphorylation. This suggest that lipid rafts may be important to effectively connect the EGFR with downstream proteins to facilitate signaling. Our data implies that cholesterol depletion of the plasma membrane affect the signaling of EGFR and PDGFRβ differently.


Controlled Pore Generation in Single-Layer Graphene Oxide for Membrane Desalination.
Nanoporous graphene was proposed as an efficient material for reverse osmosis water desalination membranes because it allows water molecules to pass at high flux while rejecting hydrated salt ions. Nevertheless, from an experimental point of view it is still difficult to control the pore size. A scalable method to generate pores is urgently required for the diffusion of this technology. We propose, by theoretical calculations, an innovative and scalable strategy to better control the dimension of the pores in graphene-based membranes by reduction of single-layer graphene oxide (GO). The latter is first annealed at a controlled mild temperature to induce the aggregation of its randomly distributed oxygen-containing functional groups into small nanometric clusters. The layer then undergoes a high-temperature reducing treatment that causes the desorption of the functional groups along with carbon removal only in the oxidized areas, producing subnanometric pores while leaving unchanged the remaining pristine graphene areas.


Microglia in epilepsy.
Epilepsy is one of most common chronic neurological disorders, and the antiseizure medications developed by targeting neurocentric mechanisms have not effectively reduced the proportion of patients with drug-resistant epilepsy. Further exploration of the cellular or molecular mechanism of epilepsy is expected to provide new options for treatment. Recently, more and more researches focus on brain network components other than neurons, among which microglia have attracted much attention for their diverse biological functions. As the resident immune cells of the central nervous system, microglia have highly plastic transcription, morphology and functional characteristics, which can change dynamically in a context-dependent manner during the progression of epilepsy. In the pathogenesis of epilepsy, highly reactive microglia interact with other components in the epileptogenic network by performing crucial functions such as secretion of soluble factors and phagocytosis, thus continuously reshaping the landscape of the epileptic brain microenvironment. Indeed, microglia appear to be both pro-epileptic and anti-epileptic under the different spatiotemporal contexts of disease, rendering interventions targeting microglia biologically complex and challenging. This comprehensive review critically summarizes the pathophysiological role of microglia in epileptic brain homeostasis alterations and explores potential therapeutic or modulatory targets for epilepsy targeting microglia.


Increased maternal hCG concentrations in early in vitro pregnancy with elevated basal FSH.
To investigate factors that influence maternal hCG concentration in early pregnancy and the relationship between hCG concentration in early pregnancy and basal FSH (bFSH) level. Retrospective cohort study. Reproductive medical center. In total, 482 women aged 22 to 38 years with elevated basal FSH (> 10 IU/L) and who experienced a single live birth after in vitro fertilization-embryo transfer were selected. These 482 women were age-matched with an equal number of women with normal basal FSH (≤10 IU/L) who also experienced a single live birth. None. HCG concentration. The hCG concentrations on Day 14 and Day 21 were 560.46 (363.63-842.52) IU/L and 9862.00 (6512.25-14029.50) IU/L, respectively, in the elevated bFSH group, and these values were significantly increased compared with the normal bFSH group. After adjusting for confounding factors, the concentrations of maternal hCG on Day 14 and Day 21 were significantly associated with basal FSH. In addition, crude linear regression analysis demonstrated that hCG concentrations increased as the basal serum levels of FSH increased. Elevated basal FSH has implications for the interpretation of hCG concentrations in early pregnancy after in vitro fertilization-embryo transfer (IVF-ET) that led to a single live birth.


Hormones in amniotic fluid.
With increasing use of amniocentesis for high-risk pregnancies, measurement of amniotic fluid hormone levels could prove to be a pratical value. Protein steroid hormones as well as prostaglandins in amniotic fluid are reviewed. The source and entry of each hormone, their concentrations, and their possible physiologic role in pregnancy are discussed. Changes in the level of hormones in amniotic fluid or pregnancies with complications jeopardizing fetal well-being are referred to, and their significance is discussed. Since amniotic fluid is close to the myometrium, changes in some amniotic fluid hormones might be responsible for or associated with the onset of labor.


Hemorrhagic Descemet's membrane detachment after viscocanalostomy.
We report a case of hemorrhagic detachment of Descemet's membrane after viscocanalostomy. A 60-year-old man with pseudoexfoliative glaucoma had an uneventful viscocanalostomy in the right eye. On the first postoperative day, a 5.0 mm x 5.0 mm Descemet's membrane detachment was present in the superior nasal quadrant. The space between Descemet's membrane and the stroma was filled with a hemorrhage. The hemorrhage resorbed by 6 months postoperatively, and Descemet's membrane completely reattached without surgical manipulation. The final visual acuity dropped from 20/40 to 20/100, final intraocular pressure was 20 mm Hg with 1 medication, and a paracentral fibrinoid scar persisted 18 months after surgery. Hemorrhagic detachment of Descemet's membrane can cause visual acuity deterioration and should be recognized as a rare complication of viscocanalostomy.


The prevalence and clinical course of shoulder injury related to vaccine administration (SIRVA) after COVID-19 vaccines in Dutch hospital workers.
Shoulder Injury Related to Vaccine Administration (SIRVA) is a rare disorder characterized by persistent shoulder pain and limited range of motion presenting within 48 h after vaccine administration. With the widespread distribution of the COVID-19 vaccine, the incidence of SIRVA is expected to rise. This sudden rise in vaccine administration presents an ideal opportunity to estimate the prevalence of SIRVA and to better characterize SIRVA. This study aims to investigate the prevalence of SIRVA following COVID-19 vaccine administration among hospital workers in the Netherlands. A questionnaire was sent to all hospital workers from a single non-academic hospital in the Netherlands. Respondents who had active SIRVA complaints were invited for an outpatient orthopaedic clinic assessment. Data was collected on participant characteristics and physical examination including assessment of active and passive range of motion (ROM). An ultrasound was performed to identify potential abnormalities. 32 out of 981 (3.3%) respondents reported shoulder pain with limited ROM occurring within 48 h after vaccine administration lasting for at least 7 days. Of these 32 respondents with SIRVA, 18 (56.2%) still reported active symptoms at the time of the survey. Clinical examination of 13 (72.2%) respondents with active SIRVA complaints showed limited glenohumeral ROM, limitations in activities of daily living and injection site pain. Twelve out of thirteen (92.3%) respondents with active SIRVA complaints showed abnormalities of the soft-tissue of the shoulder on ultrasound. Physiotherapy was the most common treatment modality for persistent SIRVA complaints (38.9%). The prevalence of SIRVA is estimated at 3% in the adult working population. Signs and symptoms of SIRVA are variable in severity, localization and timing. Soft-tissue abnormalities is the most common clinical sign. This study contributes to clinician's knowledge on SIRVA, aiding in early recognition and treatment, which are imperative for prevention of persistent and severe shoulder pathology.


Efficiency of desensitizing materials in xerostomic patients with head and neck cancer: a comparative clinical study.
To assess the clinical effectiveness of four desensitizing materials in patients who are xerostomic due to radiotherapy for head and neck cancer (HNC) in comparison to a healthy group with normal salivation. The study was conducted as a split-mouth randomized clinical trial. Forty HNC patients (group A) and 46 healthy patients (group B) suffering from dentin hypersensitivity (DH) were included. Salivary flow was determined through a scialometric test. Hypersensitivity was assessed with air stimulus and tactile stimulus. The materials used as desensitizing agents were Vertise Flow, Universal Dentin Sealant, Clearfil Protect Bond, and Flor-Opal Varnish. The response was recorded before application of the materials, immediately after, and at 1 week, 4 weeks, and 12 weeks. Salivary flow rates in groups A/B were 0.15/0.53 mL/min (unstimulated) and 0.54/1.27 mL/min (stimulated), respectively. In group A, 100 hypersensitive teeth were included. Application of the desensitizing agents significantly decreased the hypersensitivity immediately and throughout the 4-week follow-up (p < 0.001). However, after the 12-week timepoint, a loss of efficacy was detected in all agents (p = 0.131). In group B, 116 hypersensitive teeth were included. The materials performed a more stable action, although a loss of effectiveness was detected at 12-week control (p = 0.297). The efficiency of the desensitizing agents after the first application was similar in both groups. In the radiated group, this effect lasted for shorter periods than in healthy controls. HNC patients with hyposalivation may be a new risk group for DH.


Characterization of the first complete chloroplast genome of Amaranthus hybridus (Caryophyllales: Amaranthaceae) with phylogenetic implications.
In the present study, the complete chloroplast genome of Amaranthus hybridus was sequenced and assembled. The complete chloroplast genome of Amaranthus hybridus is 150,709 in size, with the GC content of 36.56%. The chloroplast genome of Amaranthus hybridus contained 86 protein-coding genes (PCGs), eight ribosomal RNA (rRNA) genes, and 37 transfer RNA (tRNA) genes. Phylogenetic analysis based on combined chloroplast gene dataset indicated that the Amaranthus hybridus exhibited a close relationship with A. hypochondriacus and A. caudatus.


CT based lung density correction verification with in vivo dosimetry using diodes.
In vivo dose measurements with diodes are easy to perform. The first aim of our study was to show whether diode measurements of the patient exit doses are precise enough for verifying inhomogeneity corrections used for treatment planning. The second aim was to assess the precision of the modified Batho Law inhomogeneity correction of the CadPlan treatment planning system. For this purpose, entrance and lait doses were measured in the thoracic region of 115 patients. Diode measurements were sufficiently precise to verify the density corrections predicted by the treatment planning system (< 0.5% of ICRU dose). The measured doses were compared with calculations of the CadPlan treatment planning system. The mean deviation of the exit dose calculations within the measurements error was zero. The present results show that measurements of exit dose even in a small number of patients are sufficient to identify systematic errors in the dose calculation.


IL-1 Receptor-1 on Vglut2 + neurons in the hippocampus is critical for neuronal and behavioral sensitization after repeated social stress.
Myriad findings connect stress and inflammation to mood disorders. Social defeat in mice promotes the convergence of neuronal, central inflammatory (microglia), and peripheral immune (monocytes) pathways causing anxiety, social avoidance, and "stress-sensitization." Stress-sensitization results in augmented inflammation and the recurrence of anxiety after re-exposure to social stress. Different cell compartments, including neurons, may be uniquely sensitized by social defeat-induced interleukin-1 (IL-1) signaling. Therefore, the aim of this study was to determine if glutamatergic neuronal IL-1 receptor signaling was essential in promoting stress-sensitization after social defeat. Here, wild-type (IL-1R1+/+) mice and mice with IL-1 receptor-1 deleted selectively in glutamatergic neurons (Vglut2-IL-1R1-/-) were stress-sensitized by social defeat (6-cycles) and then exposed to acute defeat (1-cycle) at day 30. Acute defeat-induced neuronal activation (ΔFosB and phospo-CREB) in the hippocampus of stress-sensitized mice was dependent on neuronal IL-1R1. Moreover, acute defeat-induced social withdrawal and working memory impairment in stress-sensitized mice were also dependent on neuronal IL-1R1. To address region and time dependency, an AAV2-IL-1 receptor antagonist construct was administered into the hippocampus after sensitization, but prior to acute defeat at day 30. Although stress-sensitized mice had increased hippocampal pCREB and decreased working memory after stress re-exposure, these events were not influenced by AAV2-IL-1 receptor antagonist. Hippocampal ΔFosB induction and corresponding social withdrawal in stress-sensitized mice after stress re-exposure were prevented by the AAV2-IL-1 receptor antagonist. Collectively, IL-1 signaling in glutamatergic neurons of the hippocampus was essential in neuronal-sensitization after social defeat and the recall of social withdrawal.


Effect of educational outreach to nurses on tuberculosis case detection and primary care of respiratory illness: pragmatic cluster randomised controlled trial.
To develop and implement an educational outreach programme for the integrated case management of priority respiratory diseases (practical approach to lung health in South Africa; PALSA) and to evaluate its effects on respiratory care and detection of tuberculosis among adults attending primary care clinics. Pragmatic cluster randomised controlled trial, with clinics as the unit of randomisation. 40 primary care clinics, staffed by nurse practitioners, in the Free State province, South Africa. 1999 patients aged 15 or over with cough or difficult breathing (1000 in intervention clinics, 999 in control clinics). Between two and six educational outreach sessions delivered to nurse practitioners by usual trainers from the health department. The emphasis was on key messages drawn from the customised clinical practice guideline for the outreach programme, with illustrative support materials. Sputum screening for tuberculosis, tuberculosis case detection, inhaled corticosteroid prescriptions for obstructive lung disease, and antibiotic prescriptions for respiratory tract infections. All clinics and almost all patients (92.8%, 1856/1999) completed the trial. Although sputum testing for tuberculosis was similar between the groups (22.6% in outreach group v 19.3% in control group; odds ratio 1.22, 95% confidence interval 0.83 to 1.80), the case detection of tuberculosis was higher in the outreach group (6.4% v 3.8%; 1.72, 1.04 to 2.85). Prescriptions for inhaled corticosteroids were also higher (13.7% v 7.7%; 1.90, 1.14 to 3.18) but the number of antibiotic prescriptions was similar (39.7% v 39.4%; 1.01, 0.74 to 1.38). Combining educational outreach with integrated case management provides a promising model for improving quality of care and control of priority respiratory diseases, without extra staff, in resource poor settings. Current controlled trials ISRCTN13438073.


Magnetic resonance imaging of pediatric spinal dysraphism.
Thirty pediatric patients with spinal dysraphism were studied with magnetic resonance imaging. A variety of dysraphic anomalies were visualized, including syringohydromyelia, tethered cord, widened spinal canal, meningomyelocele, lipomyelomeningocele, lipomeningocele, intraspinal lipoma, congenital dermal sinus tract, and scoliosis. In 29 of 30 cases, MRI diagnostically visualized spinal cord and dysraphic anatomy. A combination of T1-weighted sagittal and axial imaging planes provided the most complete visualization. In specific cases, T2-weighted examinations were useful in demonstrating likely regions of inflammation bordering infected sinus tracts. MRI demonstrates a wide variety of dysraphic spinal anomalies and effectively screens children for occult spinal dysraphism.


TGF-beta1 up-regulates transglutaminase two and fibronectin in dermal fibroblasts: a possible mechanism for the stabilization of tissue inflammation.
Transglutaminase (TGase) has been reported to stabilize tissue inflammation via the mediation of the polymerization of extracellular matrix proteins. A set of cytokines has been implicated in wound healing processes in the dermis. This study was undertaken in order to evaluate the effects of these cytokines on the expression of TGase 2 in human dermal fibroblasts (hDFs), in that TGase 2 is known to be the principal TGase in the dermis. In Western blot analysis, TGF-beta1 (1 ng/ml) treatment was found to steadily up-regulate TGase 2 expression for up to 7 days. However, such increases were not observed when the cells were treated with IL-1beta, IL-2, and TNF-alpha. In the enzyme assay, total TGase activities were closely related to the levels of TGase 2 expression. TGase 2 mRNA expression was up-regulated as the result of TGF-beta treatment in competitive RT-PCR. In the denatured SDS-PAGE, TGF-beta1 treatment resulted in marked induction of an approximately 220 kDa protein, which was revealed to be a fibronectin (FN) via western immunoblotting with an anti-FN antibody. Next, when the hDFs were treated with TGF-beta1 (1 ng/ml), FN expression was induced beginning at the third day after treatment. The immunoprecipitants generated by anti-FN antibody were positive for the anti-TGase 2 antibody, and the immune complexes were identified at molecular weights of 92 kDa. Collectively, TGF-beta1 stimulates the polymerization of FN via the action of TGase 2, which is supposed to to be an important mechanism in the stabilization of the inflammatory dermis.


China's energy consumption and green economy efficiency: an empirical research based on the threshold effect.
Using the panel data of China's provinces from 2005 to 2016, the paper adopts the ultra-efficiency model to measure the green economy efficiency of each province. Then, the paper used the panel threshold model to study the impact of science and technological input on the green economy efficiency with the energy consumption intensity as a threshold variable. The results show that the green economy efficiency in China's provinces is low and is in a downward trend. When the energy consumption intensity is the threshold variable, the single-threshold effect is significant. When the energy consumption intensity is lower than the threshold value, the impact of science and technological input on green economic efficiency is not significant, and the energy consumption intensity has a significant impact on green economic efficiency with science and technological input and energy consumption intensity as the core explanatory variables and with energy consumption intensity as the threshold variable. When the energy consumption intensity crosses the threshold value, the impact of science and technological input and energy consumption intensity on green economic efficiency becomes significant. According to the above empirical results, this paper proposes corresponding countermeasures and suggestions.


Self-serving reward and punishment: evidence from the laboratory.
Reward for altruism and punishment for selfishness are crucial components for the maintenance of society. Past studies have provided strong evidence that people are willing to incur costs to punish selfish behaviors and to reward altruistic behaviors, but how their willingness to do so depends on their relationship with the individuals conducting the anti-social or pro-social behaviors is much less explored. To probe into this question, we devised a three-stage experiment that combined a revised dictator game and third-party reward or punishment. We employed two payoff frameworks, alignment and conflict, and analyzed how third-party's willingness to reward and punish differed when their interests were either aligned or in conflict with the first-party under observation. We found that due to considerations for personal interests, third-party's reward and punishment levels deviated from what was deemed "legitimate" by society, that is, the level of reward and punishment that enhances society's intrinsic motivations to comply with social norms and act pro-socially. When an anti-social behavior was observed, third-party punished less severely under the alignment framework than under the conflict framework; when a pro-social behavior was observed, third-party demonstrated self-serving reward under the alignment framework, but they rewarded altruistically under the conflict framework. These findings provided evidence for third-party's self-serving reward and punishment.


Theoretical prediction of the gel electrophoretic retardation changes due to point mutations in a tract of SV40 DNA.
The changes of gel electrophoretic retardation due to single base substitutions in a 173 bp fragment of Sv40 DNA were predicted by using a theoretical model based on conformational energy calculations. As described in previous papers, this model allows successful prediction of the gel electrophoretic retardation of synthetic as well as natural DNAs reported in literature. The experimental retardations related to 195 point-mutated DNAs were reproduced with a standard deviation of 0.05 comparable with the experimental one of 0.04. This result, which represents a very critical test for the proposed model, indicates that DNA superstructures can be satisfactorily predicted on the simple physical basis of the integration of the nearest-neighbour perturbations in the dinucleotide steps. Thus, cooperative effects appear, in the majority of cases investigated, to play a second order role.


Hydrogen-bonded self-assemblies in a polychlorotriphenylmethyl radical derivative substituted with six meta-carboxylic acid groups.
The synthesis, self assembly and magnetic properties of a polychlorotriphenylmethyl radical, substituted with six meta-carboxylic groups, are reported showing that radical-radical hydrogen bonds in the solid state yield to very weak intermolecular ferromagnetic interactions.


FIT-based risk-stratification model effectively screens colorectal neoplasia and early-onset colorectal cancer in Chinese population: a nationwide multicenter prospective study.
No fully validated risk-stratification strategies have been established in China where colonoscopies resources are limited. We aimed to develop and validate a fecal immunochemical test (FIT)-based risk-stratification model for colorectal neoplasia (CN); 10,164 individuals were recruited from 175 centers nationwide and were randomly allocated to the derivation (n = 6776) or validation cohort (n = 3388). Multivariate logistic analyses were performed to develop the National Colorectal Polyp Care (NCPC) score, which formed the risk-stratification model along with FIT. The NCPC score was developed from eight independent predicting factors and divided into three levels: low risk (LR 0-14), intermediate risk (IR 15-17), and high risk (HR 18-28). Individuals with IR or HR of NCPC score or FIT+ were classified as increased-risk individuals in the risk-stratification model and were recommended for colonoscopy. The IR/HR of NCPC score showed a higher prevalence of CNs (21.8%/32.8% vs. 11.0%, P < 0.001) and ACNs (4.3%/9.2% vs. 2.0%, P < 0.001) than LR, which was also confirmed in the validation cohort. Similar relative risks and predictive performances were demonstrated between non-specific gastrointestinal symptoms (NSGS) and asymptomatic cohort. The risk-stratification model identified 73.5% CN, 82.6% ACN, and 93.6% CRC when guiding 52.7% individuals to receive colonoscopy and identified 55.8% early-onset ACNs and 72.7% early-onset CRCs with only 25.6% young individuals receiving colonoscopy. The risk-stratification model showed a good risk-stratification ability for CN and early-onset CRCs in Chinese population, including individuals with NSGS and young age.


The effect of tricyclic antidepressants on stress-induced heart rate changes in panic disorder patients.
Eight panic disorder patients participated in a double-blind placebo-controlled infusion study designed to induce panic-anxiety in the laboratory both before and after treatment with tricyclic antidepressants. Pre-infusion heart rates for the first infusion were significantly higher than baseline both before and after treatment. The delta increase in pre-infusion heart rates from baseline and the ratios of pre-infusion heart rates to baseline values were not significantly different between before and after treatment conditions indicating similar levels of arousal during the two pre-infusion periods, while the pre-infusion anxiety ratings after treatment were significantly lower.


Diagnostic accuracy of content-based dermatoscopic image retrieval with deep classification features.
Automated classification of medical images through neural networks can reach high accuracy rates but lacks interpretability. To compare the diagnostic accuracy obtained by using content-based image retrieval (CBIR) to retrieve visually similar dermatoscopic images with corresponding disease labels against predictions made by a neural network. A neural network was trained to predict disease classes on dermatoscopic images from three retrospectively collected image datasets containing 888, 2750 and 16 691 images, respectively. Diagnosis predictions were made based on the most commonly occurring diagnosis in visually similar images, or based on the top-1 class prediction of the softmax output from the network. Outcome measures were area under the receiver operating characteristic curve (AUC) for predicting a malignant lesion, multiclass-accuracy and mean average precision (mAP), measured on unseen test images of the corresponding dataset. In all three datasets the skin cancer predictions from CBIR (evaluating the 16 most similar images) showed AUC values similar to softmax predictions (0·842, 0·806 and 0·852 vs. 0·830, 0·810 and 0·847, respectively; P > 0·99 for all). Similarly, the multiclass-accuracy of CBIR was comparable with softmax predictions. Compared with softmax predictions, networks trained for detecting only three classes performed better on a dataset with eight classes when using CBIR (mAP 0·184 vs. 0·368 and 0·198 vs. 0·403, respectively). Presenting visually similar images based on features from a neural network shows comparable accuracy with the softmax probability-based diagnoses of convolutional neural networks. CBIR may be more helpful than a softmax classifier in improving diagnostic accuracy of clinicians in a routine clinical setting.


Sex-specific foraging behaviour in a seabird with reversed sexual dimorphism: the red-footed booby.
Most hypotheses attempting to explain the evolution of reversed sexual dimorphism (RSD) assume that size-related differences in foraging ability are of prime importance, but the studies on sex-specific differences in foraging behaviour remain scarce. We compare the foraging behaviour of males and females in a seabird species with a RSD by using several miniaturised activity and telemetry loggers. In red-footed boobies males are 5% smaller and 15% lighter than females, but have a longer tail than females. Both sexes spend similar time on the nest while incubating or brooding. When foraging at sea, males and females spend similar time foraging in oceanic waters, forage in similar areas, spend similar proportion of their foraging trip in flight, and feed on similar prey-flying fishes and flying squids-of similar size. However, compared to males, females range farther during incubation (85 km vs. 50 km), and furthermore feed mostly at the extremity of their foraging trip, whereas males actively forage throughout the trip. Males are much more active than females, landing and diving more often. During the study period, males lost mass, whereas females showed no significant changes. These results indicate that males and females of the red-footed boobies differ in several aspects in their foraging behaviour. Although some differences found in the study may be the direct result of the larger size of females, that is, the slightly higher speeds and deeper depths attained by females, others indicate clearly different foraging strategies between the sexes. The smaller size and longer tail of males confer them a higher agility, and could allow them to occupy a foraging niche different from that of females. The higher foraging effort of males related to its different foraging strategy is probably at the origin of the rapid mass loss of males during the breeding period. These results suggest that foraging differences are probably the reason for the differential breeding investment observed in boobies, and are likely to be involved in the evolution and maintenance of RSD.


Gemcitabine-induced respiratory failure associated with elevated erythrocyte sedimentation rate (ESR).
Gemcitabine is a newer pyrimidine analog used for the treatment of solid tumors. Though generally considered safe, it can cause pulmonary toxicity, which is generally mild and reversible. The purpose of this publication is to document a case of adult respiratory distress syndrome (ARDS) caused by Gemcitabine administration. The patient was noticed to have the extreme elevation of erythrocyte sedimentation rate (ESR) (> 100 mm/h) at the time of diagnosis. We observed excellent response to the corticosteroids. The ESR trended back to normal after the resolution of her symptoms thereby suggesting the utility of monitoring ESR in the diagnosis and management of Gemcitabine-induced pulmonary toxicity.


New challenges and opportunities in the management of brain metastases in patients with ErbB2-positive metastatic breast cancer.
The introduction of trastuzumab for the treatment of tumors that overexpress ErbB2 (also known as HER2) has contributed significantly to recent improvements in systemic therapy for advanced breast cancer. The advances in systemic therapy have highlighted an increasing prevalence of central nervous system involvement in patients with ErbB2-positive breast cancer and a consequent need for new treatment options for brain metastases. Just as ErbB2-targeted systemic therapy has given rise to this challenge, so too could targeted therapy represent an opportunity to meet it. This Review considers the potential for targeted therapy to facilitate effective management of brain metastases in patients with ErbB2-positive breast cancer, and discusses in particular the data currently available in this setting for lapatinib, an orally available small-molecule tyrosine kinase inhibitor of ErbB1 and ErbB2.


Folding and inserting silicone intraocular lens implants.
A two-forceps system for folding and inserting silicone lens implants and the method for using them is described. Other methods and instruments currently available are reviewed, and requirements for folding and inserting silicone intraocular lenses are discussed.


Cloning and characterization of the fur gene from Moraxella bovis.
A homologue of the ferric uptake regulator gene (fur) was isolated from Moraxella bovis by degenerate polymerase chain reaction and cloning. Fur protein of M. bovis exhibited 72.1% amino acid identity with Acinetobacter calcoaceticus Fur. Western blot analysis showed a decrease of Fur expression in response to sufficient-iron conditions compared with deficient-iron conditions. An electrophoretic mobility-shift assay indicated that Fur protein binds to DNA fragments containing a putative Fur-box derived from the upstream region of the M. bovis fur gene. Fur of M. bovis may regulate the expression of iron transport systems in response to iron limitation in the environment.


A systematic review of transcatheter aortic valve implantation via carotid artery access.
The carotid artery is a novel access route for transcatheter aortic valve implantation (TAVI). This may represent a viable alternative in patients unsuitable for TAVI via traditional transfemoral access, up to 20%, as well as other access routes such as subclavian, transapical and aortic. This systematic review summarises the current evidence for its safety and feasibility. A systematic review was conducted as per the Preferred Reporting Instructions for Systematic Reviews and Meta-analysis (PRISMA) guidelines using five electronic databases. 16 studies were identified, including three prospective cohort studies, one retrospective cohort study, three case series and eight case reports. Data on 74 patients (mean age 76.9years) was extracted including pre-operative work-up, technical procedure details and outcomes. This found 1 intraoperative death, 2 further deaths within 30days, two incidences of transient ischaemic attack, no incidences of stroke, myocardial infarction, carotid access site complications or infection, 1 patient required new dialysis and 1 patient had an intraoperative dissection which resolved. Follow-up from 30days to 1year showed symptomatic improvement and echocardiographic improvement in line with those seen in transfemoral TAVI. The available data on TAVI via carotid access demonstrate technical feasibility with comparable outcomes to other traditional access routes. A low number of patients, heterogeneous clinical endpoints and relatively short follow-up periods limit formal meta-analysis and firmer conclusions. For patients in which other access routes are impossible, TAVI via carotid access represents a viable and potentially crucial alternative in patients who might otherwise be untreatable.


Coronary vasospasm induced by painful compression of the brachial artery following coronary angiography.
We report the occurrence of coronary vasospasm following forceful compression of the brachial artery after coronary angiography.


Metastable two-component gel-exploring the gel-crystal interface.
This paper reports a two-component system in which molecular recognition rapidly leads to the formation of a homogeneous fibrillar gel that, over a period of hours, aggregates via fibre-fibre interactions to yield microcrystals--providing insight into the relationship between nanoscale gels and microscale crystals.


Impaired gluconeogenesis in extensively injured patients with gram-negative bacteremia.
Glucose kinetics and gluconeogenic precursors were studied in burned patients with or without gram-negative bacteremia. Gram-negative sepsis in burned patients impairs the increased rate of hepatic glucose production which characteristically occurs after thermal injury.


Nickel sulfate-specific suppressor T cells induced by nickel sulfate in drinking water.
Suppressor T cell function was studied in nickel sulfate (NiSO4) delayed type hypersensitivity (DTH). NiSO4 in drinking water administered orally to normal mice for 10 weeks elicited no significant footpad swelling. However, after drinking water for 7 weeks, suppression of footpad swelling response was not detected. Suppression of footpad swelling response was mediated by CD4-8+ T cells. However, these suppressor T cells did not overcome CD4+8- helper T cells by co-transfer to recipient mice. Unresponsiveness to NiSO4 by oral administration of antigen was due to suppressor T cells.


Syndecan-2.
The members of the Syndecan family of heparan sulfate proteoglycans play diverse roles in cell adhesion and cell communication by serving as co-receptors for both cell-signaling and extracellular matrix molecules. Syndecan-2 has been implicated in the formation of specialized membrane domains and functions as a direct link between the extracellular environment and the organization of the cortical cytoplasm. Recent studies have shown that syndecan-2 is required for angiogenesis, possibly by serving as a co-receptor for vascular endothelial growth factor, and cell-to-cell signaling during development of left-right asymmetry. This unique combination of activities suggests that syndecan-2 can function as a potential drug target for the development of multi-functional, anti-cancer therapeutics.


{Mu-N,N'-bis[2-(dimethylamino)ethyl]oxamidato(2-)-kappa(6)N,N',O':N'',N''',O}bis[(2,2'-bipyridine-kappa2N,N')copper(II)] bis(perchlorate).
In the crystal structure of the title complex, [Cu(2)(C(10)H(20)N(4)O(2))(C(10)H(8)N(2))(2)](ClO(4))(2), the deprotonated dmaeoxd(2-) ligand {H(2)dmaeoxd is N,N'-bis[2-(dimethylamino)ethyl]oxamide} occupies an inversion centre at the mid-point of the central C-C bond and is thus in a trans conformation. The two Cu(II) atoms are located in slightly distorted square-based pyramidal environments. The binuclear units interact with each other via pi-pi interactions to form a one-dimensional chain extending in the c direction.


Sperm DNA fragmentation and base oxidation.
Sperm DNA damage has been shown to be a valuable diagnostic and prognostic biomarker for male infertility and assisted reproductive treatment (ART) outcome. It is linked to every fertility checkpoint from reduced fertilization rates, lower embryo quality and pregnancy rates to higher rates of spontaneous miscarriage and childhood diseases. It is more robust than conventional semen parameters.The aim of this chapter is to provide an overview of current laboratory tests and relationships between sperm DNA damage and clinical outcomes. The conclusion is that sperm DNA damage is an important indicator of semen quality, and its routine use in the fertility clinic would improve ART success rates.


Research on the Mechanism of Qushi Huayu Decoction in the Intervention of Nonalcoholic Fatty Liver Disease Based on Network Pharmacology and Molecular Docking Technology.
To use network pharmacology and molecular docking technology in predicting the main active ingredients and targets of Qushi Huayu Decoction (QHD) treatment in Nonalcoholic Fatty Liver Disease (NAFLD) and explore the potential mechanisms of its multi-component-multi-target-multi-pathway. The main chemical components of QHD were searched using traditional Chinese medicine system pharmacology technology platform (TCMSP) and PubChem database. The main chemical components of the prescription were ADMET screened by the ACD/Labs software. The main active ingredient was screened by 60% oral bioavailability, and 60% of "bad" ingredients were removed from the drug-like group. Swiss Target Prediction, the SEA, and HitPick systems were sequentially used to search for the target of each active ingredient, and a network map of the QHD's target of the active ingredient was constructed. Genome annotation database platforms (GeneCards, OMIM, and DisGeNET) were used to predict action targets related to fatty liver disease. "Drug-Disease-Target" network diagram could be visualized with the help of Cytoscape (3.7.1) software. UniProt and STRING database platforms were used to build a protein interaction network. The KEGG signal pathway and DAVID platform were analyzed for biological process enrichment. A total of 128 active ingredients and 275 corresponding targets in QHD were discovered through screening. 55 key target targets and 27 important signaling pathways were screened, such as the cancer pathway, P13K-AKT signaling pathway, PPAR signaling pathway, and other related signaling pathways. The present study revealed the material basis of QHD and discussed the pharmacological mechanism of QHD in fatty liver, thus providing a scientific basis for the clinical application and experimental research of QHD in the future.


Biomechanical evaluation of meniscal repair systems: a comparison of the Meniscal Viper Repair System, the vertical mattress FasT-Fix Device, and vertical mattress ethibond sutures.
The biomechanical characteristics of the Meniscal Viper Repair System have not been previously studied. Comparable meniscal lesion fixation standards will exist among the Meniscal Viper Repair System, the vertical FasT-Fix device, and vertical mattress sutures. Controlled laboratory study. Porcine menisci (3 groups of 7 menisci each) were repaired using different devices. A servohydraulic device cycled each construct between 5 N and 50 N for 500 cycles before load to failure (5 mm/min). Group differences were evaluated with 1-way analysis of variance and Tukey post hoc tests. During cyclic testing, the vertical mattress suture group (2.3 +/- 0.2 mm) showed less mean displacement than did the vertical FasT-Fix or the Viper system groups (3.9 +/- 0.7 mm and 3.9 +/- 0.5 mm, respectively); the vertical mattress suture group (21.8 +/- 2 N/mm) also displayed superior mean stiffness to the vertical FasT-Fix or the Viper system groups (13.2 +/- 2 N/mm and 13.1 +/- 1.8 N/mm, respectively). During load-to-failure testing, the vertical FasT-Fix group (145.9 +/- 9 N) withstood greater mean loads than did the Viper system group (111.2 +/- 30 N), but it did not differ significantly from loads withstood by the vertical mattress suture group (133.4 +/- 10 N). The Viper system and vertical FasT-Fix groups (14.6 +/- 2 N/mm and 12.1 +/- 1 N/mm, respectively) displayed superior mean stiffness to the vertical mattress suture group (9.8 +/- 0.5 N/mm) during load-to-failure testing. Standard vertical mattress sutures provided superior fixation during cyclic loading compared with the 2 all-inside methods of suture fixation, suggesting a potential for better meniscal lesion healing with vertical mattress sutures when confronted with the stresses associated with early, progressive rehabilitation activities. Stronger sutures and less meniscal segment purchase in tears located 3 to 4 mm from the periphery may contribute to the failure of the Viper repair system.


Plasma 25-hydroxyvitamin D and the inflammatory response in canine cancer.
Decreased circulating 25-hydroxyvitamin D (25[OH]D) and increased inflammatory marker concentrations have been reported separately in canine cancer. Correlations between the two exist in humans, but little work has examined links in dogs. This study aimed to determine plasma 25(OH)D and inflammatory marker concentrations in healthy dogs and dogs with cancer and to assess correlations in each group. Newly diagnosed dogs with B-cell lymphoma (B-cell, n = 25), T-cell lymphoma (T-cell, n = 9), osteosarcoma (OSA, n = 21), and mast cell tumour (MCT, n = 26) presenting to a tertiary oncology centre, and healthy dogs (n = 25), were enrolled. Plasma samples were analysed for 25(OH)D, C-reactive protein (CRP), haptoglobin (HP), serum amyloid A (SAA), alpha-1-acid glycoprotein (AAG), and 13 chemokines and cytokines. Dogs with B-cell had decreased plasma 25(OH)D (P = .03), and increased plasma CRP, AAG, HP, KC-like and MCP-1 concentrations (P < =.001, .011, <.001, .013 and .009, respectively) compared with healthy dogs. Plasma CRP, HP and SAA concentrations were increased in dogs with OSA compared with healthy dogs (P = .001, .010 and .027, respectively). No differences were noted in dogs with T-cell and MCT. Negative correlations were observed between plasma 25(OH)D concentrations and: AAG concentrations in dogs with T-cell (Rs = -0.817, P = .007); GM-CSF concentrations (Rs = -0.569, P = .007) in dogs with OSA; and IL-7 concentrations (Rs = -0.548, P = .010) in dogs with OSA. Decreased 25(OH)D concentrations and increased concentrations of multiple inflammatory markers were observed in B-cell patients, supporting an association between 25(OH)D and inflammation. The cross-sectional study design meant the timing of changes could not be determined. Prospective cohort studies are warranted.


Self-Harm and Suicidality in US College Students: Associations with Emotional Exhaustion versus Multiple Psychiatric Symptoms.
This study aimed at describing self-harm and suicidality (SHS) in relation to unobserved heterogeneous groups of college students based on their psychiatric symptoms. SHS of each latent class were examined by race/ethnicity to inform risk factors relevant to subgroups of U.S. college population. The participants (N = 42,779) were drawn from the Spring 2017 American College Health Association-National College Health Assessment II (ACHA-NCHA II) Reference Group. Latent class analysis (LCA) was conducted based on participants' reports of past-year psychiatric symptoms. The reported SHS were examined by the latent class of students and their race/ethnicity. LCA identified two latent classes: The Emotional Exhaustion (EE) class and the Multiple Psychiatric Symptoms (MPS) class. Within the EE class, Black students were at the greatest risk for exhibiting suicide intent and attempted suicide. Within the MPS class, Multiracial students showed the highest odds of self-harm and suicidal intent, and Black students showed the highest odds of attempted suicide, followed by Asians/Pacific Islanders. The findings were based on a cross-sectional dataset that did not inform the temporal relations of psychiatric symptoms and SHS. Utilizing a person-centered latent class analysis, this study revealed that Black students were of the greatest concern for SHS among those who reported only common symptoms of emotional exhaustion. The findings highlight the importance of developing preventive and remedial models that address unique risk factors and mental health needs for various subgroups of U.S. college population.


5-tert-butyl-N-pyrazol-4-yl-4,5,6,7-tetrahydrobenzo[d]isoxazole-3-carboxamide derivatives as novel potent inhibitors of Mycobacterium tuberculosis pantothenate synthetase: initiating a quest for new antitubercular drugs.
Pantothenate synthetase (PS) is one of the potential new antimicrobial targets that may also be useful for the treatment of the nonreplicating persistent forms of Mycobacterium tuberculosis. In this Letter we present a series of 5- tert-butyl- N-pyrazol-4-yl-4,5,6,7-tetrahydrobenzo[ d]isoxazole-3-carboxamide derivatives as novel potent Mycobacterium tuberculosis PS inhibitors, their in silico molecular design, synthesis, and inhibitory activity.


Short-term and long-term effects of major depressive disorder subtypes on obesity markers and impact of sex on these associations.
Only a few studies with conflicting results have examined the effects of sex on the prospective association between depression and subsequent obesity. (1) To simultaneously assess the associations of the subtypes (atypical, melancholic, unspecified) of major depressive disorder (MDD) measured at baseline and subtypes of major depressive episodes (MDE) that emerged during a 5.5-year follow-up with changes in obesity markers (body mass index, waist circumference, fat mass) during this follow-up, and (2) to test the effect of sex on these associations. Data from CoLaus|PsyCoLaus, a population-based cohort study including 2702 participants (50.1% women, mean age 49.6 years). Criteria for mental disorders were elicited using semi-structured interviews. History of atypical MDD at baseline was associated with a steeper increase in BMI and waist circumference, whereas atypical MDE during follow-up was associated with a steeper increase in the three studied obesity markers. Melancholic MDD at baseline was associated with a steeper increase in BMI. Several significant interactions with sex were found indicating higher increase in fat mass in men than in women following melancholic MDD reported at baseline, higher decrease in BMI and fat mass in women than in men related to melancholic MDE emerging during follow-up and higher increase in waist circumference in men than in women following unspecified MDD reported at baseline. Urban sample which may not be representative for the whole population. Our results further advocate for the specific need of a thorough monitoring of obesity markers in patients with atypical MDD and suggest less favorable obesity marker changes mainly related to melancholic MDE in men.


Sequence classification with side effect machines evolved via ring optimization.
The explosion of available sequence data necessitates the development of sophisticated machine learning tools with which to analyze them. This study introduces a sequence-learning technology called side effect machines. It also applies a model of evolution which simulates the evolution of a ring species to the training of the side effect machines. A comparison is done between side effect machines evolved in the ring structure and side effect machines evolved using a standard evolutionary algorithm based on tournament selection. At the core of the training of side effect machines is a nearest neighbor classifier. A parameter study was performed to investigate the impact of the division of training data into examples for nearest neighbor assessment and training cases. The parameter study demonstrates that parameter setting is important in the baseline runs but had little impact in the ring-optimization runs. The ring optimization technique was also found to exhibit improved and also more reliable training performance. Side effect machines are tested on two types of synthetic data, one based on GC-content and the other checking for the ability of side effect machines to recognize an embedded motif. Three types of biological data are used, a data set with different types of immune-system genes, a data set with normal and retro-virally derived human genomic sequence, and standard and nonstandard initiation regions from the cytochrome-oxidase subunit one in the mitochondrial genome.


Maximum energy assimilation rates in the Djungarian hamster (Phodopus sungorus).
Physiological limits to energy budgets were estimated in Djungarian hamsters (Phodopus sungorus) using food balance and respirometric methods. The summer acclimatized, reproductively inactive hamsters could balance their energy budget at-2° C, assimilating 91.1 kJ·animal-1· day-1 after gradual cold acclimation, whereas non-acclimated hamsters showed negative energy balance assimilating only 54.4 kJ·animal-1·day-1. At the same ambient temperature, multiparous females (although neither pregnant nor lactating at the time) maintained positive energy balance assimilating 81.6 kJ·animal-1·day-1. Hamsters are capable of rapid adjustments of their maximum assimilation rates to meet their current energy demands, but only up to the value of about 3.5xBMR. It is concluded, that the actual energy budgets of small mammals keep, all the time, fairly near the upper physiological limit, with body reserves ready to buffer short-term oscillations.


In Vitro Modeling of Human Brain Arteriovenous Malformation for Endovascular Simulation and Flow Analysis.
Current in vitro models for human brain arteriovenous malformation (AVM) analyzing the efficacy of embolic materials or flow conditions are limited by a lack of realistic anatomic features of complex AVM nidus. The purpose of this study was to evaluate a newly developed in vitro AVM model for embolic material testing, preclinical training, and flow analysis. Three-dimensional (3D) images of the AVM nidus were extracted from 3D rotational angiography from a patient. Inner vascular mold was printed using a 3D printer, coated with polydimethylsiloxanes, and then was removed by acetone, leaving a hollow AVM model. Injections of liquid embolic material and 4-dimensional (4D) flow magnetic resonance imaging (MRI) were performed using the AVM models. Additionally, computational fluid dynamics analysis was performed to examine the flow volume rate as compared with 4D flow MRI. The manufacture of 3D in vitro AVM models delivers a realistic representation of human nidus vasculature and complexity derived from patients. The injection of liquid embolic agents performed in the in vitro model successfully replicated real-life treatment conditions. The model simulated the plug and push technique before penetration of the liquid embolic material into the AVM nidus. The 4D flow MRI results were comparable to computational fluid dynamics analysis. An in vitro human brain AVM model with realistic geometric complexities of nidus was successfully created using 3D printing technology. This AVM model offers a useful tool for training of embolization techniques and analysis of hemodynamics analysis, and development of new devices and materials.


Pouchitis: pathophysiology and treatment.
Pouchitis is a potential complication after proctocolectomy and restorative ileoanal anastomosis. It is more frequent in UC than in familial polyposis. Little is known about the etiopathology of pouchitis. Risk factors include the presence of extraintestinal manifestations, primary sclerosing cholangitis, cessation of smoking, and previous course of disease. A host of pathophysiological pathways have been identified as potential mechanisms of pouchitis, which include inflammatory mediators, adhesion molecules, oxygen radical species, p-ANCA, and short-chain fatty acids. The microflora in the pouch may also be an important factor in causing inflammation. The risk of developing cancer in cases of pouchitis has not been established as clearly as in those of UC. Particular attention should be paid to patients who have remaining anorectal mucosa after pouch construction. Experience in the treatment of chronic relapsing and chronic refractory pouchitis is limited. The continuation of conventional anti-inflammatory treatment is successful only in a small percentage of patients. New biological response-modifying therapies which target novel immunoregulatory molecules in IBD will also have impact on the systemic and topical treatment of pouchitis.


Multilocular adenomatoid tumor of the ovary: ultrasonographic findings.
We report the sonographic findings of a rare benign ovarian tumor in a 69-year-old woman. Transvaginal ultrasonography showed a cystic multilocular lesion with a vascularized central solid portion of the left ovary. Surgery revealed an adenomatoid tumor. Adenomatoid tumors are benign lesions of mesothelial origin, usually solid in nature and rarely located in the ovaries. (c) 2005 Wiley Periodicals, Inc. J Clin Ultrasound 33:233-236, 2005.


Decomposable quantum-dots/DNA nanosphere for rapid and ultrasensitive detection of extracellular respiring bacteria.
Extracellular respiring bacteria (ERB) are a group of bacteria capable of transferring electrons to extracellular acceptors and have important application in environmental remediation. In this study, a decomposable quantum-dots (QDs)/DNA nanosphere probe was developed for rapid and ultrasensitive detection of ERB. The QDs/DNA nanosphere was self-assembled from QDs-streptavidin conjugate (QDs-SA) and Y-shaped DNA nanostructure that is constructed based on toehold-mediated strand displacement. It can release numerous fluorescent QDs-SA in immunomagnetic separation (IMS)-based immunoassay via simple biotin displacement, which remarkably amplifies the signal of antigen-antibody recognizing event. This QDs/DNA-nanosphere-based IMS-fluorescent immunoassay is ultrasensitive for model ERB Shewanella oneidensis, showing a wide detection range between 1.0 cfu/mL and 1.0 × 108 cfu/mL with a low detection limit of 1.37 cfu/mL. Moreover, the proposed IMS-fluorescent immunoassay exhibits high specificity, acceptable reproducibility and stability. Furthermore, the proposed method shows acceptable recovery (92.4-101.4%) for detection of S. oneidensis spiked in river water samples. The proposed IMS-fluorescent immunoassay advances an intelligent strategy for rapid and ultrasensitive quantitation of low-abundance analyte and thus holds promising potential in food, medical and environmental applications.


Polycystic ovary syndrome: Implications of measurement of plasma aldosterone, renin activity and progesterone.
A positive correlation between aldosterone, inflammatory parameters, blood pressure and metabolic abnormalities in polycystic ovary syndrome (PCOS) has been reported in the early estrogenic phase. The aim of the study was to measure plasma aldosterone, plasma renin activity (PRA) and progesterone on the 21st day of the cycle, in women with PCOS and to consider the interrelationships between these hormones. Sixty-six consecutive normal BMI women with PCOS (median age 24 years, range 21-28 years) and 53 age- and body mass index-matched healthy controls were enrolled in the study. Aldosterone, aldosterone/PRA ratio (ARR) and Homeostasis Model Assessment (HOMA) index were significantly higher (p<0.0001) in PCOS women than controls. Positive correlations were found in PCOS but not in controls between (i) progesterone and aldosterone, (ii) aldosterone and PRA, (iii) PRA and progesterone. Mean blood pressures were within the normal range but significantly higher in PCOS than controls. The increase of plasma aldosterone, ARR and blood pressure in PCOS compared with controls is consistent with an increased mineralocorticoid effector mechanism in PCOS; prolonged therapy with spironolactone could counteract both the hyperandrogenism and reduce future cardiovascular risk.


Characterization of solution-phase and gas-phase reactions in on-line electrochemistry-thermospray tandem mass spectrometry.
Electrochemistry was used on-line with high-performance liquid chromatography-thermospray tandem mass spectrometry to provide insight into the solution-phase decomposition reactions of electrochemically generated oxidation products. Products formed during electrooxidation were monitored as the electrode potential was varied. The solution reactions which follow the initial electron transfer at the electrode are affected by the vaporizer tip temperature of the thermospray probe and the composition of the thermospray buffer. Either hydrolysis or ammonolysis reactions of the initial electrochemical oxidation products can occur with pH 7 ammonium acetate buffer. Both the electrochemically generated and the synthesized disulfide of 6-thiopurine decompose under thermospray conditions to produce 6-thiopurine and purine-6-sulfinate. Solution-phase studies indicate that nucleophilic and electrophilic substitution reactions with purine-6-sulfinate result in the formation of purine, adenine, and hypoxanthine. Products were identified and characterized by tandem mass spectrometry. This work shows the first example of high-performance liquid chromatography used on-line with electrochemistry to separate stable oxidation products prior to analysis by thermospray tandem mass spectrometry. In addition, solution-phase and gas-phase studies with methylamine show that the site of the nucleophilic and electrophilic reactions is probably inside the thermospray probe. Most importantly, these results also show that the on-line combination of electrochemistry with thermospray tandem mass spectrometry provides valuable information about redox and associated chemical reactions of biological molecules such as the structures of intermediates or products as well as providing insight into reaction pathways.


Context-dependent substitution models for circular DNA.
The most general context-dependent Markov substitution process, where each substitution event involves only one site and substitution rates depend on the whole sequence, is presented for the first time. The focus is on circular DNA sequences, where the problem of specifying the behaviour of the first and last sites in a linear sequence does not arise. Important special cases include (1) the established models where each site behaves independently, (2) models which are increasingly applied to non-coding DNA, where each site depends on only the immediate neighbouring sites, and (3) models where each site depends on two closest neighbours on both sides, such as the codon models. These special cases are classified and illustrated by published models. It is shown that the existing codon substitution models mix up the mutation and selection processes, rendering the substitution rates challenging to interpret. The classification suggests the study of a more interpretable codon model, where the mutation and selection processes are clearly delineated. Furthermore, this model allows a natural accommodation of possibly different selection pressures in overlapping reading frames, which may contribute to furthering the understanding of viral diseases. Also included are brief discussions on the stationary distribution of a context-dependent substitution process and a simple recipe for simulating it on a computer.


Severe HIV-1 encephalitis and development of cerebral non-Hodgkin lymphoma in a patient with persistent strong HIV-1 replication in the brain despite potent HAART -- case report and review of the literature.
A 39 year old patient with HIV-1 infection, who was asymptomatic without antiretroviral therapy (HAART) for ten years, developed severe encephalopathy. Despite therapy with a four drug antiretroviral combination regimen including two protease-inhibitors (PI), plasma viral load could not be suppressed sufficiently with persistence of low level viremia of 3.08-3.40 log copies/ml, even after addition of two other antiretroviral drugs. On therapy the patient showed improvement of clinical symptoms, however with severe persisting cognitive deficits. Repeated parallel measurements of viral load showed a far higher viremia in the cerebrospinal fluid than in the plasma. Resistance testing provided no evidence of relevant PI-mutations and analysis of protease inhibitor levels demonstrated good plasma levels. 17 months after start of HAART, the patient developed a cerebral Non-Hodgkin lymphoma, leading to his death despite radiation therapy. There has been a dramatic reduction in the prevalence of HIV-1 associated CNS events in the post-HAART era. Nevertheless, subgroups of patients are infected with neurotropic viral variants which could cause progressive neurological pathology as they can not be reached sufficiently by the available drugs. These patients require the development of new drugs that achieve a better penetration into the brain.


BODY IMAGE IN CHILDHOOD: AN INTEGRATIVE LITERATURE REVIEW.
To analyse the scientific literature regarding the evaluation of body image in children through an integrative literature review. An intersection of the keywords "body image" AND "child" was conducted in Scopus, Medline and Virtual Health Library (BVS - Biblioteca Virtual de Saúde) databases. The electronic search was based on studies published from January 2013 to January 2016, in order to verify the most current investigations on the subject. Exclusion criteria were: articles in duplicate; no available summaries; not empirical; not assessing any component of body image; the sample did not consider the target age of this research (0 to 12 years old) and/or considered clinical populations; besides articles not fully available. 7,681 references were identified, and, after the exclusion criteria were implemented, 33 studies were analysed. Results showed that the perceptual and attitudinal dimensions focusing on body dissatisfaction were explored, mainly evaluated by silhouette scales. Intervention programs were developed internationally to prevent negative body image in children. The studies included in this review evaluated specific aspects of body image in children, especially body perception and body dissatisfaction. The creation of specific tools for children to evaluate body image is recommended to promote the psychosocial well being of individuals throughout human development.


[Surgical management of peripheral nerves after extremity loss].
After limb loss, it is the surgeon's task to provide the patient with a pain-free and resilient residual limb. Particularly in the upper extremity, there is an additional functional aspect, as appropriate muscle signals are needed to control myoelectric prostheses. Surgical management of peripheral nerves within the residual limb plays a central role both in terms of pain treatment as well as functional human-machine interfacing. The presentation of current surgical procedures for dealing with peripheral nerves after limb amputation. A literature search is carried out regarding the surgical prophylaxis and therapy of neuroma and phantom limb pain, as well as techniques to improve the functional interface between residual limb and prosthesis. Practical recommendations are formulated based on relevant literature, as well as the experiences of the authors. There is a large number of different surgical techniques, particularly for the management of painful neuromas. Of the conventional methods, intramuscular implantation of the terminal nerves is commonly used with good results. Newer techniques such as targeted muscle reinnervation (TMR) and the regenerative peripheral nerve interface (RPNI) aim for the first time to provide functional end organs to the nerve even after amputation. In addition to the improved control of myoelectric prostheses, these methods further show excellent results for treatment and prevention of neuroma and phantom limb pain.


The Ophthalmic Knowledge Assessment Program (OKAP): a personal view.
This essay relates the historic process that led to the development of the Ophthalmic Knowledge Assessment Program (OKAP) as an established component of ophthalmic training in the U.S.A. Begun in the early 1960s as an evaluative examination for residents at the University of Florida, the first national OKAP examination took place in May 1968, with over 85% of all eye training programs participating. It was later incorporated into the Continuing Education program of the American Academy of Ophthalmology and Otolaryngology, where it prospered. Beginning January 1980 the OKAP was combined with American Board of Ophthalmology exam, thus establishing a single, unified national exam.


D3AI-Spike: A deep learning platform for predicting binding affinity between SARS-CoV-2 spike receptor binding domain with multiple amino acid mutations and human angiotensin-converting enzyme 2.
The number of SARS-CoV-2 spike Receptor Binding Domain (RBD) with multiple amino acid mutations is huge due to random mutations and combinatorial explosions, making it almost impossible to experimentally determine their binding affinities to human angiotensin-converting enzyme 2 (hACE2). Although computational prediction is an alternative way, there is still no online platform to predict the mutation effect of RBD on the hACE2 binding affinity until now. In this study, we developed a free online platform based on deep learning models, namely D3AI-Spike, for quickly predicting binding affinity between spike RBD mutants and hACE2. The models based on CNN and CNN-RNN methods have the concordance index of around 0.8. Overall, the test results of the models are in agreement with the experimental data. To further evaluate the prediction power of D3AI-Spike, we predicted and experimentally determined the binding affinity of a VUM (variants under monitoring) variant IHU (B.1.640.2), which has fourteen amino acid substitutions, including N501Y and E484K, and 9 deletions located in the spike protein. The predicted average affinity score for wild-type RBD and IHU to hACE2 are 0.483 and 0.438, while the determined Kaff values are 5.39 ± 0.38 × 107 L/mol and 1.02 ± 0.47 × 107 L/mol, respectively, demonstrating the strong predictive power of D3AI-Spike. We think D3AI-Spike will be helpful to the viral transmission prediction for the new emerging SARS-CoV-2 variants. D3AI-Spike is now available free of charge at https://www.d3pharma.com/D3Targets-2019-nCoV/D3AI-Spike/index.php.


Oligodeoxynucleotides induce brain inflammation in rats when infused intracerebroventricularly.
Antisense oligodeoxynucleotides (ODNs) can inhibit gene expression in a specific manner. However, several studies described problems with cerebral ODN application. Here, we investigated the immune effects (interleukin-6 (IL-6) release, cell invasion into cerebrospinal fluid (CSF) and brain parenchyma) of 'non-sense' randomized ODNs with different counterions (NH(4)(+), Na(+)) and modifications (with or without thioat-backbone) which were administered intracerebroventricularly for 48 h using osmotic mini-pumps in a rat model. All animals receiving ODNs showed increased IL-6 levels in the CSF as well as cell invasion into the CSF and brain parenchyma (P<0.05). However, the use of thioat-backbone and ammonium as the counterion induced the highest IL-6 levels (7210+/-1696 pg/ml, P<0.05) and the highest cell numbers in the CSF (31.6+/-15.5x10(5)/ml, P<0.05) as well as brain parenchyma (268.1+/-143.2 HIS-48+ cells/mm(2), P<0.01; and 31.3+/-10.7 OX-6+cells/mm(2), P<0.05) compared with the other groups.


Mild traumatic brain injury is associated with effect of inflammation on structural changes of default mode network in those developing chronic pain.
Mild traumatic brain injury (mTBI) has a higher prevalence (more than 50%) of developing chronic posttraumatic headache (CPTH) compared with moderate or severe TBI. However, the underlying neural mechanism for CPTH remains unclear. This study aimed to investigate the inflammation level and cortical volume changes in patients with acute PTH (APTH) and further examine their potential in identifying patients who finally developed CPTH at follow-up. Seventy-seven mTBI patients initially underwent neuropsychological measurements, 9-plex panel of serum cytokines and MRI scans within 7 days post-injury (T-1) and 54 (70.1%) of patients completed the same protocol at a 3-month follow-up (T-2). Forty-two matched healthy controls completed the same protocol at T-1 once. At baseline, mTBI patients with APTH presented significantly increased GM volume mainly in the right dorsal anterior cingulate cortex (dACC) and dorsal posterior cingulate cortex (dPCC), of which the dPCC volume can predict much worse impact of headache on patients' lives by HIT-6 (β = 0.389, P = 0.007) in acute stage. Serum levels of C-C motif chemokine ligand 2 (CCL2) were also elevated in these patients, and its effect on the impact of headache on quality of life was partially mediated by the dPCC volume (mean [SE] indirect effect, 0.088 [0.0462], 95% CI, 0.01-0.164). Longitudinal analysis showed that the dACC and dPCC volumes as well as CCL2 levels had persistently increased in patients developing CPTH 3 months postinjury. The findings suggested that structural remodelling of DMN brain regions were involved in the progression from acute to chronic PTH following mTBI, which also mediated the effect of inflammation processes on pain modulation. ClinicalTrial.gov ID: NCT02868684 ; registered 16 August 2016.


Release of the herpes simplex virus 1 protease by self cleavage is required for proper conformation of the portal vertex.
We identify an NLS within herpes simplex virus scaffold proteins that is required for optimal nuclear import of these proteins into infected or uninfected nuclei, and is sufficient to mediate nuclear import of GFP. A virus lacking this NLS replicated to titers reduced by 1000-fold, but was able to make capsids containing both scaffold and portal proteins suggesting that other functions can complement the NLS in infected cells. We also show that Vp22a, the major scaffold protein, is sufficient to mediate the incorporation of portal protein into capsids, whereas proper portal immunoreactivity in the capsid requires the larger scaffold protein pU(L)26. Finally, capsid angularization in infected cells did not require the HSV-1 protease unless full length pU(L)26 was expressed. These data suggest that the HSV-1 portal undergoes conformational changes during capsid maturation, and reveal that full length pU(L)26 is required for this conformational change.


Isolation and cytotoxic properties of a novel glycoconjugate from corms of saffron plant (Crocus sativus L.).
A novel glycoconjugate isolated from saffron corm extracts shows remarkable cytotoxic activity on cultured human cancer cells (HeLa). Its polysaccharide part represents 94.5% of the molecule, and is dominated by a 36.4% of rhamnose. The protein backbone is composed mainly of aspartic acid/asparagine, alanine, glutamic acid/glutamine, glycine and serine. HeLa cells exposed to this glycoconjugate showed swelling and local plasma membrane evaginations, suggesting that cytotoxicity is mediated by extracellular fluid uptake.


T cell epitope-containing peptides of the major dog allergen Can f 1 as candidates for allergen immunotherapy.
One prerequisite for developing peptide-based allergen immunotherapy is knowing the T cell epitopes of an allergen. In this study, human T cell reactivity against the major dog allergen Can f 1 was investigated to determine peptides suitable for immunotherapy. Seven T cell epitope regions (A-G) were found in Can f 1 with specific T cell lines and clones. The localization of the epitope regions shows similarities with those of the epitopes found in Bos d 2 and Rat n 1. On average, individuals recognized three epitopes in Can f 1. Our results suggest that seven 16-mer peptides (p15-30, p33-48, p49-64, p73-88, p107-122, p123-138, and p141-156), each from one of the epitope regions, show widespread T cell reactivity in the population studied, and they bind efficiently to seven HLA-DRB1 molecules (DRB1*0101, DRB1*0301, DRB1*0401, DRB1*0701, DRB1*1101, DRB1*1301, and DRB1*1501) predominant in Caucasian populations. Therefore, these peptides are potential candidates for immunotherapy of dog allergy.


Beta-carotene inhibits growth of human colon carcinoma cells in vitro by induction of apoptosis.
Epidemiological studies suggest that beta-carotene is able to modulate the risk of cancer. A number of in vitro studies reported that beta-carotene inhibits the growth of cancer cells; however, so far little is known about the molecular mechanisms of the antiproliferative effect of beta-carotene. Here we have investigated the effects of two beta-carotene preparations, (i) beta-carotene dissolved in tetrahydrofuran (final concentration in cell culture medium: 0.5%) and (ii) beta-carotene incorporated in a water dispersible bead form, on cultured human colon carcinoma cells HT29. The treatment of cells with beta-carotene up to 30 microM for 72 h led to a significant increase in the cellular beta-carotene concentration and formation of retinol. Beta-Carotene showed only low cytotoxicity for confluent cells tested up to 30 microM, but at dietary relevant concentrations for the intestinal tract (10, 30 microM) beta-carotene was strongly cytotoxic for growing cells and induced apoptosis in HT29 cells as assessed by the Annexin-V assay (the maximal effect was observed 15 h after treatment with beta-carotene). Exposure of cells to retinol at concentrations yielding cellular retinol levels similar to those observed by beta-carotene treatment had no antiproliferative or cytotoxic effect. Furthermore, beta-carotene did not affect the activation of the extracellular signal-regulated kinases (ERK1 and ERK2) that are essential for cellular growth. In summary, beta-carotene can inhibit growth of human colon carcinoma cells in vitro by induction of apoptosis in proliferating cells.


The management of a patient with lymphoedema of the legs.
Lymphoedema is a much under-publicised condition, yet it affects many people. Janice Bianchi and Marie Todd outline the implications of the condition and examine the treatment options of a typical case study.


Evaluation of carotid stenosis with axial high-resolution black-blood MR imaging.
High-resolution axial black-blood MR imaging (BB MRI) has been shown to be able to characterise carotid plaque morphology. The aim of this study was to explore the accuracy of this technique in quantifying the severity of carotid stenosis. A prospective study of 54 patients with symptomatic carotid disease was conducted, comparing BB MRI to the gold standard, conventional digital subtraction X-ray angiography (DSA). The BB MRI sequence was a fast-spin echo acquisition (TE = 42 ms, ETL = 24, field of view = 100 x 100 mm, slice thickness = 3.0 mm) at 1.5 T using a custom-built phased-array coil. Linear measurements of luminal and outer carotid wall diameter were made directly from the axial BB MRI slices by three independent blinded readers and stenosis was calculated according to European Carotid Surgery Trial (ECST) criteria. There was good agreement between BB MRI and DSA (intraclass correlation = 0.83). Inter-observer agreement was good (average kappa = 0.77). BB MRI was accurate for detection of severe stenosis (> or = 80%) with sensitivity and specificity of 87 and 81%, respectively. Eight cases of "DSA-defined" moderate stenosis were overestimated as severe by BB MRI and this may be related to non-circular lumens. Axial imaging with BB MRI could potentially be used to provide useful information about severity of carotid stenosis.


Analysis of the habituation-like changes in transmission in the temporodentate pathway of the rat.
Habituation-like decrements in extracellular measures of synaptic activation (population EPSP) and cell discharge (population spike) were analyzed in the dentate gyrus of the rat following repetitive low-frequency stimulation of the medial and lateral entorhinal cortex. Stimulation of either subdivision of the entorhinal projection system resulted in comparable habituation-like response decrements with similar stimulation regimens. However, habituating stimulation of one subdivision did not result in decreased responsiveness to stimulation of the other. Repetitive low-frequency stimulation or even a single pulse delivered to either subdivision did, however, result in a potentiation of granule cell discharge in response to stimulation of the other subdivision (a form of heterosynaptic potentiation). This heterosynaptic potentiation of granule cell discharge was not accompanied by any increase in the extracellular EPSP. Comparisons of the relationship between the population EPSP and population spike before and during habituating stimulation revealed changes in cell discharge in response to the habituating stimulus which could not be accounted for by changes in synaptic activation alone. The results suggest that repetitive activation of the temporodentate pathway alters granule cell output as a result of two processes, a habituation-like decrement in synaptic activation, and a potentiation of granule cell discharge as a consequence of prior activation.


Power training improves bone mineral density and fall risk for a postmenopausal woman with a history of osteoporosis and increased risk of falling: A case report.
The purpose of this case study was to assess the degree to which a 12-month power-based resistance-training program improved bone mineral density (BMD) and fall risk for a 70-year-old postmenopausal woman with osteoporosis and increased risk of falling. After an eight-week strength-development phase, we had the patient perform 44 weeks of resistance training with maximal force mobilization by instructing her to complete as many repetitions as possible during each 60-s set. We used dual-energy X-ray absorptiometry (DEXA) to assess BMD and Dynamic Gait Index (DGI) to assess fall risk before and after the intervention. Post compared to pre-training testing indicated an increase in BMD in the lumbar spine (24%) and femoral neck (29%) resulting in changes in T-score of 0.7 and 0.4 SD, respectively. Testing also revealed a seven-point change in DGI which improved her status to "safe ambulator." After a 12-month period of power training, BMD was increased and fall risk was reduced for a postmenopausal woman with osteoporosis and increased risk of falling.


Collagen Biomarkers Quantify Fibroblast Activity In Vitro and Predict Survival in Patients with Pancreatic Ductal Adenocarcinoma.
The use of novel tools to understand tumour-fibrosis in pancreatic ductal adenocarcinoma (PDAC) and novel anti-fibrotic treatments are highly needed. We established a pseudo-3D in vitro model including humane pancreatic fibroblasts (PFs) and pancreatic cancer-associated fibroblasts (CAFs) in combination with clinical collagen biomarkers, as a translational anti-fibrotic drug screening tool. Furthermore, we investigated the prognostic potential of serum collagen biomarkers in 810 patients with PDAC. PFs and CAFs were cultured in Ficoll-media. Cells were treated w/wo TGF-ß1 and the anti-fibrotic compound ALK5i. Biomarkers measuring the formation of type III (PRO-C3) and VI (PRO-C6) collagens were measured by ELISA in supernatant at days 3, 6, 9, and 12. PRO-C3 and PRO-C6, and their association with overall survival (OS), were evaluated in serum with PDAC (n = 810). PRO-C3 and PRO-C6 were upregulated in CAFs compared to PFs (p < 0.0001.). TGF-ß1 increased PRO-C3 in both PFs and CAFs (p < 0.0001). The anti-fibrotic compound ALK5i inhibited both PRO-C3 and PRO-C6 (p < 0.0001). High serum levels of PRO-C3 and PRO-C6 in patients with PDAC were associated with short OS (PRO-C3: HR = 1.48, 95%CI: 1.29-1.71, p < 0.0001 and PRO-C6: HR = 1.31, 95%CI: 1.14-1.50, p = 0.0002). PRO-C3 and PRO-C6 have the potential to be used both pre-clinically and clinically as a measure of tumor fibrosis and CAF activity.


Regional differences in sympathetic neurotransmission to cutaneous arteries in the guinea-pig isolated ear.
The effects of sympathetic nerve stimulation on different cutaneous arteries were examined in arteries isolated from guinea-pig ears, by measuring membrane potential changes in smooth muscle cells in response to electrical field stimulation. Resting membrane potential (RMP) was similar in proximal (main ear artery) and distal (3rd or 4th branch order) cutaneous arteries (mean -71 mV). Single stimuli evoked excitatory junction potentials (EJPs) in all arteries. The EJPs in proximal arteries were twice the amplitude, and the time constant of EJP decay was almost half the value, compared with distal cutaneous arteries. EJP amplitude was reduced by > 90% by suramin (30 microM) or alpha,beta,methylene-ATP (alpha,beta,m-ATP)(1 microM) in all proximal, and most distal arteries. Residual responses in distal arteries were resistant to tetrodotoxin. The N-type calcium channel blocker, omega-conotoxin GVIA (30 nM), reduced EJP amplitude by 70-100% in both proximal and distal arteries. Successive EJPs evoked by trains of stimuli at 1 to 5 Hz were depressed in amplitude in proximal arteries, but showed facilitation in distal arteries. EJP depression in proximal arteries was reversed to facilitation by the alpha2-adrenoceptor antagonist, yohimbine (30 nM). Trains of stimuli delivered at 10-20 Hz produced summation of EJPs and active membrane responses in 30% of proximal arteries. Active responses were never detected in distal arteries. Slow depolarizations following the EJPs were detected in most arteries after trains of stimuli, and were abolished by prazosin (0.3 microM) or omega-conotoxin GVIA (30 nM). The density of the perivascular plexus of axons innervating proximal arteries, demonstrated with catecholamine fluorescence histochemistry, was twice that in distal cutaneous arteries. These regional differences in sympathetic neurotransmission suggest that cutaneous vasoconstriction in response to thermoregulatory stimuli, which occurs predominantly in distal cutaneous segments, is likely to be qualitatively different from cutaneous vasoconstriction of proximal arteries in response to other physiological stimuli.


Fast Enantio- and Chemoselective Arylation of Ketones with Organoboronic Esters Enabled by Nickel/N-Heterocyclic Carbene Catalysis.
A general, efficient, highly enantio- and chemoselective N-heterocyclic carbene (NHC)/Ni-catalyzed addition of readily available and stable arylboronic esters to ketones is reported. This protocol provides unexpectedly fast access (usually 10 min) to various chiral tertiary alcohols with exceptionally broad substrate scope and excellent functional group tolerance (76 examples, up to 98 % ee). This process is orthogonal to other known Ni-mediated Suzuki-Miyaura couplings, as it tolerates aryl chlorides, fluorides, ethers, esters, amides, nitriles, and alkyl chlorides. The reaction is applied to late-stage modifications of various densely functionalized medicinally relevant molecules. Preliminary mechanistic studies suggest that a rare enantioselective η2 -coordinating activation of ketone carbonyls is involved. This cross-coupling-like mechanism is expected to enable other challenging transformations of ketones.


A new gnidiflavanone-flavonol dimer and other constituents from Gnidia apiculata.
A new 3,8''-flavanone-flavonol dimer gnidiflavanone-flavonol (1) and 10 known compounds (2-11), including four rare primula-type flavones 2-5, were isolated from the roots of Gnidia apiculata. Compounds 2-5 and 7 were reported for the first time from the plant family Thymelaeceae. Structures of the isolated compounds were established by spectroscopic data, including 1D and 2D NMR (COSY, HMBC, HSQC and ROESY) and mass spectrometry, as well as by the comparison with literature data. The crude roots extract and isolated compounds were evaluated for antimicrobial and antiplasmodial activities. Among isolated compounds, 6-hydroxyflavone (4) and 6-O-acetylflavone (4a) showed antiplasmodial activity against chloroquine-sensitive (D6) and chloroquine-resistant (W2) strains of Plasmodium falciparum.


CFD Simulation of Particle-Laden Flow in a 3D Differentially Heated Cavity Using Coarse Large Eddy Simulation.
Particulate flow in closed space is involved in many engineering applications. In this paper, the prediction of particle removal is investigated in a thermally driven 3D cavity at turbulent Rayleigh number Ra = 109 using Coarse Large Eddy Simulation (CLES). The depletion dynamics of SiO2 aerosol with aerodynamic diameters between 1.4 and 14 µm is reported in an Euler/Lagrange framework. The main focus of this work is therefore to assess the effect of the subgrid-scale motions on the prediction of the particulate flow in a buoyancy driven 3D cavity flow when the mesh resolution is coarse and below optimal LES standards. The research is motivated by the feasibility of modeling more complex particulate flows with reduced CPU cost. The cubical cavity of 0.7 m side-length is set to have a temperature difference of 39 K between the two facing cold and hot vertical walls. As a first step, the carrier fluid flow was validated by comparing the first and second-moment statistics against both previous well-resolved LES and experimental databases [Kalilainen (J. Aero Sci. 100:73-87, 2016); Dehbi (J. Aero. Sci. 103:67-82, 2017)]. First moment Eulerian statistics show a very good match with the reference data both qualitatively and quantitatively, whereas higher moments show underprediction due to the lesser spatial resolution. In a second step, six particle swarms spanning a wide range of particle Stokes numbers were computed to predict particle depletion. In particular, predictions of 1.4 and 3.5 µm particles were compared to LES and available experimental data. Particles of low inertia i.e. dp < 3.5 µm are more affected by the SGS effects, while bigger ones i.e. dp = 3.5-14 µm exhibit much less grid-dependency. Lagrangian statistics reported in both qualitative and quantitative fashions show globally a very good agreement with reference LES and experimental databases at a fraction of the CPU power needed for optimal LES.


Determining the roles of a conserved tyrosine residue in a Mip-like peptidyl-prolyl cis-trans isomerase.
The FKBP22 and the related peptidyl-prolyl cis-trans isomerases dimerize using their N-terminal domains. Conversely, their C-terminal domains possess both the substrate and inhibitor binding sites. To delineate the roles of a conserved Tyr residue at their N-terminal domains, we have studied a FKBP22 mutant that carries an Ala in place of the conserved Tyr at position 15. We have demonstrated that the Tyr 15 of FKBP22 is indispensable for preserving its dimerization ability, catalytic activity, and structure. The residue, however, little contributed to its inhibitor binding ability and stability. The mode of action of Tyr 15 has been discussed at length.