Prevalence of and Risk Factors for Extrapyramidal Side Effects of Antipsychotics: Results From the National FACE-SZ Cohort.
Extrapyramidal side effects (EPS) have been identified as a complication of antipsychotic treatment. Previous meta-analyses have investigated EPS prevalence and risk factors in randomized clinical trials with highly selected patients, but studies in real-world schizophrenia are missing. To examine the prevalence and clinical correlates associated with EPS in a nonselected national multicenter sample of stabilized patients with schizophrenia. Between 2010 and 2016, patients suffering from schizophrenia (DSM-IV-TR criteria) were recruited through the FondaMental Academic Centers of Expertise for Schizophrenia (FACE-SZ) network and data were collected during a comprehensive 1-day-long standardized evaluation. The Simpson-Angus Scale and the Abnormal Involuntary Movement Scale were used to assess drug-induced parkinsonism (DIP) and tardive dyskinesia, respectively. The overall prevalence of DIP and tardive dyskinesia was 13.2% and 8.3%, respectively, in this community-dwelling sample of 674 patients. DIP was associated with negative symptoms (Positive and Negative Syndrome Scale [PANSS] subscore) (adjusted odds ratio [aOR] = 1.102, P < .001), first-generation antipsychotic prescription (aOR = 2.038, P = .047), and anticholinergic drug administration (aOR = 2.103, P = .017) independently of sex, age, disorganization (PANSS disorganized factor), and antipsychotic polytherapy. Tardive dyskinesia was associated with PANSS disorganized factor (aOR = 1.103, P = .049) independently of sex, age, negative symptoms, excitation, first-generation antipsychotic prescription, and benzodiazepine and anticholinergic drug administration. Our results indicate the high prevalence of EPS in a nonselected community-dwelling clinically stable sample of outpatients with schizophrenia. In the monitoring of antipsychotic treatment, EPS should be systematically evaluated, especially when negative symptoms and disorganization or cognitive alteration are present. Monotherapy with a second-generation antipsychotic should be preferentially initiated for patients with these side effects.


Characterization of the Escherichia coli O59 and O155 O-antigen gene clusters: the atypical wzx genes are evolutionary related.
O-antigens are highly polymorphic. The genes specifically involved in O-antigen synthesis are generally grouped together on the chromosome as a gene cluster. In Escherichia coli, the O-antigen gene clusters are characteristically located between the housekeeping genes galF and gnd. In this study, the O-antigen gene clusters of E. coli O59 and E. coli O155 were sequenced. The former was found to contain genes for GDP-mannose synthesis, glycosyltransferase genes and the O-antigen polymerase gene (wzy), while the latter contained only glycosyltransferase genes and wzy. O unit flippase genes (wzx) were found immediately downstream of the gnd gene, in the region between the gnd and hisI genes in these two strains. This atypical location of wzx has not been reported before, and furthermore these two genes complemented in trans despite the fact that different O-antigen structures are present in E. coli O59 and O155. A putative acetyltransferase gene was found downstream of wzx in both strains. Comparison of the region between gnd and hisI revealed that the wzx and acetyltransferase genes are closely related between E. coli O59 and O155, indicating that the two gene clusters arose recently from a common ancestor. This work provides further evidence for the O-antigen gene cluster having formed gradually, and selection pressure will eventually bring O-antigen genes into a single cluster. Genes specific for E. coli O59 and O155, respectively, were also identified.


Case-control study of anaemia among middle-aged and elderly women in three rural areas of China.
To propose a feasible suggestion to reduce the high prevalence of anaemia in middle-aged and elderly women by investigating risk factors, particularly nutritional factors, and analysing the effect on anaemia in three different rural areas of China. A case-control study. Three counties of China. Women aged 50-75 years in the three counties. Adjusted OR (95% CI) of anaemia associated with diet, lifestyle and blood biochemical indices. Compared with controls, women with anaemia had lower body mass index (22.1 (3.2) kg/m(2) vs 23.2 (3.5) kg/m(2); p<0.001), a higher experience of shortage of food (45.0% vs 36.5%; p<0.001), less soy food intake (0.5 (0.3, 26.7) g/day vs 5.6 (0.4, 27.8) g/day; p<0.048), lower serum iron (13.4 (5.4) μmol/L vs 16.4 (5.7) μmol/L; p<0.001), lower ferritin (109.6 (85.6) ng/mL vs 131.0 (92.0) ng/mL; p<0.001), lower transferrin saturation levels (22.5 (9.5)% vs 26.8 (9.6)%; p<0.001) and higher levels of free erythrocyte protoporphyrin (42.4 (21.2) μg/dL vs 39.6 (17.8) μg/dL; p<0.001). Anaemia was significantly associated with BMI(OR=0.90, 95% CI (0.87 to 0.92)), food shortage experience (OR=1.39, 95% CI (1.15 to 1.69)), total protein (OR=0.66, 95%CI (0.54 to 0.80)), Albumin (OR=0.72, 95%CI (0.59 to 0.87)) in univariate analysis. Multivariate analysis showed that body mass index, experience of food shortage, total protein and albumin were independently related to anaemia. Among middle-aged and elderly women in rural China, the nutrition status of anaemic cases is far below that of controls. Lower body mass index and a greater experience of food shortage are closely related to anaemia. Improving the blood protein status by consuming protein-sufficient foods such as soy food is a feasible approach for elderly anaemic women. Further research is needed on the effect of chronic inflammation and infectious disease on anaemia in elderly women in rural China.


Virion assembly defect of polyomavirus hr-t mutants: underphosphorylation of major capsid protein VP1 before viral DNA encapsidation.
The major capsid protein of polyomavirus, VP1, was separated into at least four subspecies by isoelectric focusing. One of these subspecies was selectively extracted from purified virions by mild treatment with sodium dodecyl sulfate, leaving a 140S particle enriched in the other three forms. The two most acidic subspecies were labeled in vivo with [32P]phosphate, and these subspecies are among those identified as being deficient in nontransforming host range (hr-t) mutant virus nonpermissive infection of NIH3T3 cells. Quantitation of VP1 phosphorylation revealed that hr-t mutant virus VP1 is phosphorylated to about 40 to 50% the level of the wild type in NIH3T3 cells, and two-dimensional phosphoamino acid analysis suggested that threonine phosphorylation was affected more than serine phosphorylation. Two results indicate that the VP1 modifications occur before and independent of virus assembly: modified subspecies were detected during wild-type infection within a 2-min pulse-label with [32S]methionine, and VP1 modifications of temperature-sensitive VP1 mutants were the same at both restrictive and permissive temperatures for virus assembly. We conclude that most VP1 modification occurs before viral DNA encapsidation, and that one defect in hr-t mutant virus assembly is in VP1 phosphorylation, primarily affecting threonine.


Screening anti-HIV Chinese materia medica with HIV and equine infectious anemic virus reverse transcriptase.
The inhibitory activities of human immunodeficiency virus reverse transcriptase (HIV-RT) inhibitors PFA and Suramin against HIV-RT and equine infectious anemic virus reverse transcriptase (EIAV-RT) were studied in this paper. The 50% inhibitory concentration (IC50) of HIV-RT and EIAV-RT treated by PFA and Suramin were 0.2 mumol, 9.8 mumol and 17 mumol, 19.9 mumol, respectively. More than thirty Chinese medicines, including recipes, herbs, extracts of traditional materia medica and isolated compounds were tested using HIV-RT and EIAV-RT as target enzymes. It was found that 5 crude extracts such as Rhizoma Polygoni Cuspidati, and Radix Notoginseng, 7 isolated compounds like Flavone of Ramulus Visci, Flavone of Ajuga Decumbens Thumb, and Aristolochic acid, as well as the extract of the complex prescription Xiao Chai Hu Tang have shown various inhibitory actions on these two enzymes. The activities of the two enzymes were comparable, but HIV-RT was more sensitive, suggesting that HIV-RT can be used as index for the screening of anti-aids drugs.


[Alteration of serum interleukin-1 receptor antagonist and interleukin-6 levels after surgical injury].
The aim of the study was to investigate alterations in systemic production of interleukin 1 receptor antagonist (IL-1Ra) and interleukin 6 (IL-6) following major abdominal surgery in oncologic patients and in patients after minor surgical trauma who had undergone open cholecystectomy (OC). Studies were carried out in 30 patients. The concentrations of IL-1Ra in oncologic patients (865 +/- 1021 pg/ml) before operation were significantly higher (p = 0.042) in comparison with OC group (466.16 +/- 389 pg/ml). There was a significant (p = 0.017) increase in the IL-1Ra level to 2735 +/- 1943 pg/ml on day 1 after major surgery and the IL-1Ra level remained significantly elevated until the day 10. The IL-1Ra values were significantly increased on day 1 after OC (843.93 +/- 627 pg/ml, p = 0.001) and remained significantly (p = 0.02) elevated until the 10 postoperative day. The IL-1Ra serum concentrations were significantly higher on day 1 to 10 after major surgery with complications compared with patients after OC and uneventful postoperative course. The preoperative concentrations of IL-6 in oncologic patients was 24.9 +/- 64 pg/ml and in OC patients 8.35 +/- 14 pg/ml. The level of IL-6 on the day 1 after the major operations was ten times higher (268.38 +/- 330 pg/ml, p = 0.002) and remained significantly elevated over the ten days period. The highest concentration of IL-6 was observed in oncologic patients with severe complications (384.7 +/- 484 pg/ml). The significantly lower level of IL-6 (p = 0.009) was seen after OC in patients with uneventful postoperative course (50.6 +/- 53 pg/ml on the 1st postoperative day) as compared to major surgery. We conclude that elevated serum concentrations of IL-1Ra and IL-6 on the day 1 following surgery represent early sensitive markers of the extent of surgical trauma. The monitoring of changes in IL-1Ra and IL-6 blood levels may be useful in early recognising of pathological response to surgical trauma in oncologic patients after major surgery with increased risk of the development severe complications.


The prevalence of methicillin-resistant Staphylococcus aureus colonization in feedlot cattle.
Methicillin-resistant Staphylococcus aureus (MRSA) is an important human pathogen and recent evidence has implicated food animals in the epidemiology of human infections in some regions. While the role of food in MRSA transmission and human health relevance are unclear, MRSA can be found in retail meat products internationally, including beef, yet there has been minimal investigation of MRSA in beef cattle. This study involved screening feedlot cattle for nasal and gastrointestinal colonization with MRSA shortly before the time of slaughter. Methicillin-resistant S. aureus was not isolated from any of 491 nasal swabs and 488 faecal samples. This finding is in contrast to studies that have isolated MRSA from retail beef in Canada, performed in the same laboratory using comparable culture techniques. The reason for this discrepancy is unclear but it demonstrates that further study of MRSA in livestock as well as slaughter, processing and retail environments is needed to elucidate the epidemiology of MRSA contamination of meat.


Patients' perceptions of individualized care: evaluating psychometric properties and results of the individualized care scale.
Health-care organizations aim to provide patient-centred care, yet measurement of this aspect of care quality remains a challenge.This cross-sectional study investigated the reliability and validity of the bipartite Individualized Care Scale (ICSA, ICS-B) in a Canadian hip and knee arthroplasty population. Internal consistency of the ICS-A and ICS-B was high; however, factorial validity was not fully supported. Twenty-five percent of participants provided additional open-ended comments to describe individual perceptions, needs, and suggestions, noting that the Likert-scale approach required them to aggregate their feedback about rather than share their perceptions of individual nurses.The findings indicate that it is important to patients to be able to share their individual stories when evaluating nursing care. Future qualitative studies should examine the nurse perspective on the provision of patient-centred care, including investigation of systems and process-related features that foster or hinder more individualized care.


Evolutionary dynamics of tag mediated cooperation with multilevel selection.
Understanding the conditions and dynamics that produce cooperation in evolving systems remains a fundamental goal of evolutionary theory. Significant progress has been made in determining the conditions that support cooperation in simple models, but the evolutionary dynamics that lead from noncooperative conditions to cooperation are still poorly understood. And, in more complex models, even the conditions that support cooperation are not well defined. In this paper we study the dynamics of the evolution of cooperation in both a simple tag-mediated cooperation model and in a more complex version of the same system in which there is multilevel competition--competition between both individuals and populations of individuals. The results show that the inclusion of multilevel competition has both quantitative effects (increasing the frequency and duration of the periods of cooperation) and qualitative effects (introducing a new stable state) on the evolutionary dynamics of cooperation.


Translocation of the brain-type glucose transporter largely accounts for insulin stimulation of glucose transport in BC3H-1 myocytes.
Insulin-stimulated glucose transport was examined in BC3H-1 myocytes. Insulin treatment lead to a 2.7 +/- 0.3-fold increase in the rate of deoxyglucose transport and, under the same conditions, a 2.1 +/- 0.1-fold increase in the amount of the brain-type glucose transporter (GLUT 1) at the cell surface. It has been shown that some insulin-responsive tissues express a second, immunologically distinct, transporter, namely GLUT 4. We report here that BC3H-1 myocytes and C2 and G8 myotubes express only GLUT 1; in contrast, rat soleus muscle and heart express 3-4 times higher levels of GLUT 4 than GLUT 1. Thus translocation of GLUT 1 can account for most, if not all, of the insulin stimulation of glucose transport in BC3H-1 myocytes. On the other, hand, neither BC3H-1 myocytes nor the other muscle-cell lines are adequate as models for the study of insulin regulation of glucose transport in muscle tissue.


Effects of oral testosterone undecanoate therapy on bone mineral density and body composition in 322 aging men with symptomatic testosterone deficiency: a 1-year, randomized, placebo-controlled, dose-ranging study.
We investigated the effects of oral testosterone undecanoate (TU) on bone mineral density (BMD), lean body mass (LBM) and body fat mass (BFM) in aging men with symptomatic testosterone deficiency (TD). Three hundred twenty-two men ≥50 years with TD symptoms and calculated free testosterone <0.26 nmol/L participated in a multicenter, double-blind, placebo-controlled trial. Patients were randomized to placebo, oral TU 80 mg/d, oral TU 160 mg/d, or oral TU 240 mg/d, administered as divided doses with normal meals. BMD of the hip and lumbar spine were evaluated by dual energy X-ray absorptiometry (DEXA), and body composition (LBM and BFM) by whole body DEXA. Oral TU significantly increased BMD at Month 12 at the lumbar spine (240 mg/d), total hip (240 mg/d), and trochanter and intertrochanter (160 and 240 mg/d) compared with placebo. Oral TU significantly increased LBM at Months 6 and 12 for all oral TU groups compared with placebo. BFM significantly decreased at Month 6 (all oral TU groups) and Month 12 (160 mg/d) compared with placebo. The effects on BMD and body composition showed a clear dose response. Treatment with oral TU led to improvement in BMD, LBM and BFM in aging men with symptomatic TD.


Perforated gastrointestinal ulcers presenting as acute respiratory distress.
Dyspnea is one of the most common complaints facing the emergency medicine physician. Some of the gastrointestinal causes of dyspnea are self-limited and not life-threatening, yet others are, and early diagnosis and treatment are crucial. In this article we presented one of these life-threatening conditions through a clinical description of a patient presenting with acute respiratory distress that was finally diagnosed to be the result of a perforated gastric ulcer. An emergent thoracotomy revealed a small ulcer with perforation in the fundus of the stomach. The patient was transferred after the operation to the intensive care unit and after a prolonged hospitalization discharged home. Biopsies taken from the ulcer showed diffuse inflammation, with no evidence of microorganisms or malignancy. Perforation of gastric and duodenal ulcers is a rare yet existing cause of dyspnea and respiratory failure and should be kept in mind by the emergency physician, especially when other more common causes are ruled out.


Basic fibroblast growth factor maintains calcium homeostasis and granulosa cell viability by stimulating calcium efflux via a PKC delta-dependent pathway.
Previous studies have demonstrated that basic fibroblast growth factor prevents granulosa cell apoptosis. The following six observations provide insight into the mechanism by which basic fibroblast growth factor mediates its antiapoptotic action. First, loading granulosa cells with 1,2 bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid, an intracellular calcium chelator, prevented apoptosis when granulosa cells were deprived of basic fibroblast growth factor. Second, treatment with thapsigargin, an agent known to increase intracellular free calcium, induced granulosa cell apoptosis even in the presence of basic fibroblast growth factor. Third, an activator of PKC mimicked, whereas PKC inhibitors blocked, basic fibroblast growth factor's antiapoptotic action. Fourth, continuous basic fibroblast growth factor exposure maintained relatively constant levels of intracellular free calcium, and a PKC inhibitor induced a sustained 2- to 3-fold increase in intracellular free calcium. Fifth, granulosa cells, as well as spontaneously immortalized granulosa cells, were shown to express PKC delta, -lambda, and -zeta. Finally, the PKC delta-specific inhibitor, rottlerin, blocked basic fibroblast growth factor's antiapoptotic action in granulosa cells and spontaneously immortalized granulosa cells. These studies suggest that basic fibroblast growth factor regulates intracellular free calcium through a PKC delta-dependent mechanism and that a sustained increase in intracellular free calcium is sufficient to induce and is required for granulosa cell apoptosis. Additional studies demonstrated that in spontaneously immortalized granulosa cells, basic fibroblast growth factor increased PKC delta activity by 60% within 2.5 min compared with serum-free control levels. Rottlerin attenuated basic fibroblast growth factor's ability to stimulate PKC delta activity and to maintain intracellular free calcium. Further, intracellular free calcium levels in spontaneously immortalized granulosa cells transfected with a PKC delta antibody in the presence of basic fibroblast growth factor were 2-fold higher than those spontaneously immortalized granulosa cells transfected with IgG. Similarly, transfecting spontaneously immortalized granulosa cells with a specific PKC delta-substrate increased intracellular free calcium compared with spontaneously immortalized granulosa cells transfected with a specific substrate for PKC epsilon. Moreover, basic fibroblast growth factor increased and rottlerin attenuated (45)Ca efflux by 50% compared with that in basic fibroblast growth factor-treated cells. Finally, an inhibitor of the plasma membrane calciumadenosine triphosphatase pump suppressed (45)Ca efflux, elevated intracellular free calcium, and induced apoptosis. Collectively, these studies demonstrate that basic fibroblast growth factor activates PKC delta, which, in turn, stimulates calcium efflux, accounting in part for basic fibroblast growth factor's ability to maintain calcium homeostasis and, ultimately, granulosa cell viability.


Oesophagoscopy, biopsy, and acid perfusion test in diagnosis of "reflux oesophagitis".
The results of fibreoptic endoscopy have been assessed retrospectively in 71 patients referred for consideration of the oesophagus as the possible or probable cause of their symptoms. Gross endoscopic abnormality was uncommon but friability of the mucosa was seen in about half of the patients with typical symptoms of "reflux-pain" and a quarter of those without. The combination of radiological reflux and endoscopic abnormality--that is, true reflux oesophagitis--was seen in only a third of the patients with typical symptoms though much less commonly in those with atypical symptoms. Histological abnormality was common but did not relate well to symptom pattern. The results of the acid perfusion test were significantly related to symptom pattern though overlap was observed between the two symptomatic groups. Six of these patients had had or were awaiting surgery to correct reflux and they all had uniformly positive findings. This study confirms the value of the acid perfusion test in clarifying the diagnosis of reflux pain, espcially if the symptoms are difficult to assess. Endoscopy and biopsy added little further information of diagnostic value and could probably be reserved for the small minority of patients who have special problems such as blood loss or dysphagia or where clarification of a radiological lesion is required.


UV mutagenesis in Salmonella typhimurium is umuDC dependent despite the presence of samAB.
We investigated the role of the umuDC and samAB operons in the UV mutability of Salmonella typhimurium. umuDC is located on the chromosome, whereas samAB resides on the virulence plasmid pSLT. Using allele replacement and plasmid curing techniques, we found that UV mutability was eliminated when any of three different umuDC alleles (umuD1, umuC1, or umuD1 umuC1) were on the chromosome even when samAB was present. We conclude that samAB normally does not complement umuDC function in S. typhimurium.


The cytologic diagnosis of adenocarcinoma in situ of the cervix uteri and related lesions. I. Adenocarcinoma in situ.
Seventy cases of histologically confirmed adenocarcinoma in situ (AIS) of the cervix uteri have been predicted in this laboratory using cytologic criteria, which are illustrated in this paper. The architectural features that were of primary diagnostic importance included an exfoliation pattern consisting of sheets of cells and tissue fragments in the form of cellular strips and rosettes. Nuclear criteria allowed the distinction of AIS into well-differentiated and poorly differentiated types. The former showed nuclear enlargement, an oval nuclear shape, hyperchromasia and moderate-to-coarse granularity as usual features. In the latter, nuclear enlargement was even greater, with an oval-to-round shape, prominent nucleoli and chromatin that was usually only finely granular. Variant patterns of AIS included endocervical, endometrioid and intestinal subtypes, each with characteristic cytologic appearances that correspond closely with their histologic appearances. The evolution of the description of AIS reveals a range of precursor lesions that may match the range of invasive adenocarcinomas originating in the cervix. This suggests that invasive adenocarcinoma of the cervix uteri could be preventable as is its more common squamous counterpart.


Second-Harmonic Scattering as a Probe of Structural Correlations in Liquids.
Second-harmonic scattering experiments of water and other bulk molecular liquids have long been assumed to be insensitive to interactions between the molecules. The measured intensity is generally thought to arise from incoherent scattering due to individual molecules. We introduce a method to compute the second-harmonic scattering pattern of molecular liquids directly from atomistic computer simulations, which takes into account the coherent terms. We apply this approach to large-scale molecular dynamics simulations of liquid water, where we show that nanosecond second-harmonic scattering experiments contain a coherent contribution arising from radial and angular correlations on a length scale of ≲1 nm, much shorter than had been recently hypothesized ( Shelton , D. P. J. Chem. Phys. 2014 , 141 ). By combining structural correlations from simulations with experimental data ( Shelton , D. P. J. Chem. Phys. 2014 , 141 ), we can also extract an effective molecular hyperpolarizability in the liquid phase. This work demonstrates that second-harmonic scattering experiments and atomistic simulations can be used in synergy to investigate the structure of complex liquids, solutions, and biomembranes, including the intrinsic intermolecular correlations.


Bacterial resistance to beta-lactam antibiotics.
The historical development of antibiotic resistance, mechanisms of resistance, classification schemes for beta-lactamases, the clinical relevance of resistance, and approaches to overcoming resistance are reviewed. The promise of eradication of infectious diseases has not been fulfilled, in great part owing to the emergence of antibiotic-resistant organisms. Although genes for bacterial resistance may have existed before the clinical use of antibiotics, selection of new resistant strains is driven by the widespread use of antimicrobials in humans and animals. The most commonly prescribed antimicrobials in the United States are the beta-lactam antibiotics, and the most common mechanism of bacterial resistance to these agents is inactivation by beta-lactamase. The clinical and economic consequences of therapeutic failure and relapse--extended hospital stays, increased morbidity and mortality, and the use of potentially more toxic and costly antimicrobial agents--require new strategies to prevent the spread of resistant organisms and to limit future resistance.


PDAM: A Panoptic-Level Feature Alignment Framework for Unsupervised Domain Adaptive Instance Segmentation in Microscopy Images.
In this work, we present an unsupervised domain adaptation (UDA) method, named Panoptic Domain Adaptive Mask R-CNN (PDAM), for unsupervised instance segmentation in microscopy images. Since there currently lack methods particularly for UDA instance segmentation, we first design a Domain Adaptive Mask R-CNN (DAM) as the baseline, with cross-domain feature alignment at the image and instance levels. In addition to the image- and instance-level domain discrepancy, there also exists domain bias at the semantic level in the contextual information. Next, we, therefore, design a semantic segmentation branch with a domain discriminator to bridge the domain gap at the contextual level. By integrating the semantic- and instance-level feature adaptation, our method aligns the cross-domain features at the panoptic level. Third, we propose a task re-weighting mechanism to assign trade-off weights for the detection and segmentation loss functions. The task re-weighting mechanism solves the domain bias issue by alleviating the task learning for some iterations when the features contain source-specific factors. Furthermore, we design a feature similarity maximization mechanism to facilitate instance-level feature adaptation from the perspective of representational learning. Different from the typical feature alignment methods, our feature similarity maximization mechanism separates the domain-invariant and domain-specific features by enlarging their feature distribution dependency. Experimental results on three UDA instance segmentation scenarios with five datasets demonstrate the effectiveness of our proposed PDAM method, which outperforms state-of-the-art UDA methods by a large margin.


Northwestern China: a place to learn more on oesophageal cancer. Part one: behavioural and environmental risk factors.
Oesophageal squamous cell carcinoma (OSCC) remains a public health problem in many countries, especially in emerging and developing countries. Epidemiology of OSCC is characterized by marked differences in prevalence between countries/regions/ethnical groups. The highest incidence in the world is reached by populations living in specific areas of northwestern Xinjiang, China where age-adjusted mortality may reach 150 of 100 000. In fact, there are also marked differences among the various geographical areas and the various ethnic groups within the region, which suggests specific risk factors. Behavioural factors include those factors which are common to all 'high-risk populations', such as tobacco smoking and alcohol drinking. However, the very unusual sex ratio (1.2 : 1.0) and young age range of OSCC occurrence suggests the involvement of additional early risk factors shared by males and females, and which are different from those studied in other 'high-risk' areas of the world, including China, such as LinXian area. These include drinking very hot and salted tea, boiled with milk; a diet rich in meat, especially salted, dry and/or smoked meat, and dairy products; and a diet poor in fresh fruit and vegetables. The combination of hot drinks (such as milk, tea and soups) and high-degree spirit drinks, and hard food (bread, meat and cheese), together with poor oral hygiene and tooth loss, is likely to add mechanical injury of the oesophagus to other factors linked to climate characteristics of the area (drought) and dietary habits, which promote a sodium and nitrosamine-rich diet. Association of early and severe hypertension in the same populations at high risk of OSCC might likely raise more attention. Human papilloma virus (HPV) infection, and especially HPV 16/18 E6/E7, with gene mutations and association with p53 overexpression, may contribute to the extremely high incidence of OSCC observed in Xinjiang, and could be accessible to prevention. Infection may especially be a crucial additional factor in the Uygur population in which not only HPV infection but also infection with other oncogenic viruses, such as HHV8, are highly prevalent. Genetic polymorphism might interact with viruses and/or viral products to promote carcinogenesis. These observations in northwestern China suggest that usually neglected factors, such as sodium excess and viral infection, could be taken into more account when studying OSCC risk factors in other parts of the world, especially Europe.


Is device-based total and domain-specific sedentary behaviour associated with psychological distress in Flemish workers?
There is increasing interest in the association between psychological distress and time spent in sedentary behaviour (e.g. sitting), a highly prevalent behaviour in modern society. The limited evidence is mixed and mainly based on studies using self-reported sedentary time. Few studies have investigated device-based total sedentary time in its association with distress. None, however, have examined device-based domain-specific sedentary time in relation to psychological distress. The aim of this study was to investigate whether device-based total and domain-specific sedentary behaviour were associated with psychological distress. Flemish employees (n = 401; 20-64 years; 42.6% male; 83.6% had a 'physically active occupation') of seven organizations in service and production sectors participated. Sedentary behaviour (exposure) was assessed by two Axivity AX3 accelerometers (one placed on the thigh and one placed between the shoulders) for two to four consecutive working days. Based on diary completion, domain-specific sedentary behaviour (leisure vs. work) was assessed. The 12-item General Health Questionnaire was used to assess psychological distress (outcome). Adjusted hierarchical multiple regression models were conducted to report on the associations between total and domain-specific sedentary behaviour and psychological distress. About 35% of the sample had high levels of distress and average total sedentary time was 7.2 h/day. Device-based total sedentary behaviour [B = -0.009, 95% confidence interval (CI), -0.087 to 0.068], leisure-time (B = 0.001, 95% CI, -0.017 to 0.018) and work-related (B = 0.004, 95% CI, -0.006 to 0.015) sedentary behaviour were not significantly associated with psychological distress. This cross-sectional study examining the association between device-based total and domain-specific sedentary behaviour and psychological distress among employees showed a lack of significant findings.


Multiples of multiple: Case series of mirror aneurysms and review of literature.
Mirror aneurysms are a rare subtype of multiple aneurysms, located in identical or adjacent arterial segment bilaterally. We report a case series of 3 such patients amongst whom one of them had 3 sets of mirror aneurysms and the other patient had 2 sets of mirror aneurysm on the same arterial segment which has not been reported till date. A retrospective analysis of 3 patients with incidentally detected multiple mirror aneurysms, who were treated with microsurgical clipping and coiling, was conducted. A systematic search was performed using the PUBMED database and relevant articles were reviewed with particular attention to incidence, associated conditions, risk factors and management strategies. Written informed consent was obtained from all of the patients for publication of this case report and accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal on request. This research work has been reported in line with the PROCESS criteria (Agha et al., 2018). All the 3 patients were females with incidentally detected multiple mirror aneurysms. All the 3 patients were known Hypertensives. All the aneurysms were successfully clipped by a multistage, bilateral craniotomy except the one in the cavernous ICA, for which an endovascular procedure is planned. All of them had an uneventful postoperative course with the CT angiogram showing obliteration of all the clipped aneurysms except the one in the cavernous ICA. Multiple mirror aneurysms represent a rare occurrence of a diverse pathology. Both these described types of cases have not been reported so far in the literature. The treatment strategy for mirror aneurysms should be determined individually based on the location, size, and morphology of the aneurysms, as well as, on the clinical manifestations of each patient.


A Clinical Study to Assess the Efficacy and Safety of MP-AzeFlu Nasal Spray in Comparison to Commercially Available Azelastine Hydrochloride and Fluticasone Propionate Nasal Sprays in Chinese Volunteers with Allergic Rhinitis.
The objective of the present study was to evaluate the efficacy and safety of MP-AzeFlu nasal spray in comparison to commercially available azelastine hydrochloride and fluticasone propionate sprays in Chinese patients with moderate-to-severe allergic rhinitis (AR). We conducted a 14-day multicenter, randomized, double-blind, active controlled prospective clinical study in adult and adolescent patients with AR, who had moderate-to-severe symptoms. The primary efficacy endpoint was the change from baseline in combined 12-h reflective total nasal symptom score (rTNSS) (morning [AM] + afternoon [PM]). The safety profile of the study medications was assessed through the recording, reporting, and analysis of baseline medical conditions, adverse events (AEs), vital signs, and focused nasal examination. Three hundred patients per treatment group were randomized, which led to a total sample size estimation of 900 patients. MP-AzeFlu group showed significantly higher symptom reduction for the entire 2-week treatment period in rTNSS when compared with the AZE group (LS mean difference: - 1.96; 95% CI: - 2.53, - 1.39; p < 0.0001), or the FLU group (LS mean difference: - 0.98; 95% CI: - 1.55, - 0.41; p = 0.0007). The results of adult RQLQ showed improvement in QoL in all treatment groups. Except for dysgeusia (bitter taste) that was reported by more patients (13 [4.3%]) in the MP-AzeFlu group, the incidence of all other TEAEs in the MP-AzeFlu group was comparable or even lower than in other treatment groups. MP-AzeFlu, when administered as one spray per nostril twice daily for 14 days, alleviated AR symptoms in Chinese patients with moderate-to-severe AR. Clinicaltrials.gov; NCT03599791, Registered June 29, 2018, retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT03599791 .


Effectiveness of two coronavirus disease 2019 (COVID-19) vaccines (viral vector and inactivated viral vaccine) against severe acute respiratory coronavirus virus 2 (SARS-CoV-2) infection in a cohort of healthcare workers.
We investigated real-world vaccine effectiveness for Oxford-AstraZeneca (ChAdOx1) and CoronaVac against laboratory-confirmed severe acute respiratory coronavirus virus 2 (SARS-CoV-2) infection among healthcare workers (HCWs). We conducted a retrospective cohort study among HCWs (aged ≥18 years) working in a private healthcare system in Brazil between January 1, 2021 and August 3, 2021, to assess vaccine effectiveness. We calculated vaccine effectiveness as 1 - rate ratio (RR), with RR determined by adjusting Poisson models with the occurrence of SARS-CoV-2 infection as the outcome and the vaccination status as the main variable. We used the logarithmic link function and simple models adjusting for sex, age, and job types. In total, 13,813 HCWs met the inclusion criteria for this analysis. Among them, 6,385 (46.2%) received the CoronaVac vaccine, 5,916 (42.8%) received the ChAdOx1 vaccine, and 1,512 (11.0%) were not vaccinated. Overall, COVID-19 occurred in 6% of unvaccinated HCWs, 3% of HCWs who received 2 doses of CoronaVac vaccine, and 0.7% of HCWs who received 2 doses of ChAdOx1 vaccine (P < .001). In the adjusted analyses, the estimated vaccine effectiveness rates were 51.3% for CoronaVac, and 88.1% for ChAdOx1 vaccine. Both vaccines reduced the number of hospitalizations, the length of hospital stay, and the need for mechanical ventilation. In addition, 19 SARS-CoV-2 samples from 19 HCWs were screened for mutations of interest. Of 19 samples, 18 were the γ (gamma) variant. Although both COVID-19 vaccines (viral vector and inactivated virus) can significantly prevent COVID-19 among HCWs, CoronaVac was much less effective. The COVID-19 vaccines were also effective against the dominant γ variant.


Diagnostic Accuracy of Next Generation Sequencing Panel using Circulating Tumor DNA in Patients with Advanced Non-Small Cell Lung Cancer: A Systematic Review and Meta-Analysis.
Until now, no meta-analysis has been published to evaluate the diagnostic performance of next-generation sequencing (NGS) panel using circulating tumor (ctDNA) in patients with advanced non-small cell lung cancer (aNSCLC). The aim of the study was to carry out a systematic review and a meta-analysis in order to determine the accuracy of NGS of ctDNA to detect six oncogenic driver alterations: epidermal growth factor receptor (EGFR); anaplastic lymphoma kinase (ALK); ROS proto-oncogene 1, receptor tyrosine kinase (ROS-1); serine/threonine-protein kinase B-RAF (BRAF); RET proto-oncogene (RET); and MET proto-oncogene, receptor tyrosine kinase (MET) exon 14 in patients with aNSCLC. MEDLINE/PubMed, Cochrane Library, Latin American and Caribbean Health Sciences Literature (LILACS), and Centre for Reviews and Dissemination databases and articles obtained from other sources were searched for relevant studies that evaluate the accuracy (sensitivity and specificity) of NGS using ctDNA in patients with aNSCLC. The studies were eligible when NGS of ctDNA was compared with tissue tests to detect at least one of the six oncogenic driver alterations. Diagnostic measures (sensitivity and specificity) were pooled with a bivariate diagnostic random effect. All statistical analyses were performed with software R, v.4.0.0. Ten studies were eligible for data extraction. The overall pooled estimates of sensitivity and specificity were 0.766 (95% CI: 0.678-0.835); 0.999 (95% CI: 0.990-1.000), respectively. The analysis has demonstrated that the NGS panel using ctDNA has a high accuracy to identify the six actionable oncogenic driver alterations in patients with aNSCLC. Therefore, it can be considered a reliable alternative to guide the patients with aNSCLC to the right treatment who cannot undergo an invasive procedure or have insufficient tissue material for molecular tests.


The Chironomidae (Diptera) of Svalbard and Jan Mayen.
Non-biting midges of the fly family Chironomidae are extremely abundant and diverse in Arctic regions and are essential components of Arctic ecosystems. Modern identification tools based on documented records of Arctic chironomid species are therefore important for ecological research and environmental monitoring in the region. Here, we provide an updated review of the chironomid fauna of the Svalbard archipelago and the island of Jan Mayen, Norway. Our results show that a total of 73 species distributed across 24 genera in four subfamilies are known from these areas. Our review treats 109 taxa, including nomina dubia and misidentifications. It includes morphological identification keys to all known species as well as photographs of most taxa and DNA barcodes of 66 species. Taxonomic remarks are given for selected taxa, including previous misidentifications and erroneous records. Chironomus islandicus, Tvetenia bavarica, Limnophyes schnelli, Metriocnemus brusti and Metriocnemus fuscipes as well as the genera Allocladius, Corynoneura and Bryophaenocladius are reported from Svalbard for the first time, while Procladius (Holotanypus) frigidus, Stictochironomus psilopterus, Chaetocladius incertus, Orthocladius (Orthocladius) mixtus and Smittia longicosta, previously considered as junior synonyms or nomina dubia, are revived as valid species based on examination of type material or literature. Twenty species within eleven genera are introduced with interim names. Metriocnemus similis is regarded as a junior synonym of Metriocnemus ursinus, and Smittia incerta, Smittia flexinervis and Smittia spitzbergensis are regarded as nomina dubia. Valid taxa no longer considered as part of the Svalbard fauna are Parochlus kiefferi, Arctopelopia barbitarsis, Procladius (Holotanypus) crassinervis, Diamesa lindrothi, Diamesa incallida, Diamesa lundstromi, Chironomus hyperboreus, Sergentia coracina, Camptocladius stercorarius, Chaetocladius dissipatus, Chaetocladius dentiforceps, Chaetocladius laminatus, Chaetocladius perennis, Cricotopus (Cricotopus) humeralis, Cricotopus (Cricotopus) polaris, Hydrosmittia ruttneri, Limnophyes edwardsi, Metriocnemus picipes, Metriocnemus tristellus, Orthocladius (Eudactylocladius) gelidus, Orthocladius (Euorthocladius) thienemanni, Orthocladius (Orthocladius) obumbratus, Orthocladius (Orthocladius) rhyacobius, Paralimnophyes, Paraphaenocladius impensus, Psectrocladius (Monopsectrocladius) calcaratus, Psectrocladius (Psectrocladius) psilopterus, Psectrocladius (Psectrocladius) ventricosus, Smittia lasiophthalma, Smittia lasiops and Zalutschia tatrica.


Expression Levels of PIWI-interacting RNA, piR-823, Are Deregulated in Tumor Tissue, Blood Serum and Urine of Patients with Renal Cell Carcinoma.
Renal cell carcinoma (RCC) is the most common neoplasm of adult kidney accounting for about 3% of adult malignancies. P-Element induced wimpy testis (PIWI)-interacting RNAs (piRNAs) are a new class of naturally occurring, short non-coding RNAs involved in silencing of transposable elements and in sequence-specific chromatin modifications. There were preliminary data published indicating that piR-823 expression is deregulated in circulating tumor cells and tumor tissue in gastric and kidney cancer, respectively. In our study, we analyzed piR-823 levels in 588 biological specimens: tumor tissue (N=153), adjacent renal parenchyma (N=121), blood serum (N=178) and urine (N=20) of patients undergoing nephrectomy for RCC; and in blood serum (N=101) and urine (N=15) of matched healthy controls. Expression levels of piR-823 were determined in all biological specimens by quantitative real-time polymerase chain reaction, compared in patients and controls, and correlated with clinicopathological features of RCC. We identified a significant down-regulation of piR-823 in tumor tissue [p<0.0001, area under the curve (AUC)=0.7945]. On the contrary in blood serum and urine, the expression of piR-823 was significantly higher in patients with RCC compared to healthy individuals (p=0.0005, AUC=0.6264 and p=0.0157, AUC=0.7433, respectively). We further observed higher levels of piR-823 in tumor tissue to be associated with shorter disease-free survival of patients (p=0.0186) and a trend for higher piR-823 levels in serum to be associated with advanced clinical stages of RCC (p=0.0691). There were no other significant associations of piR-823 levels in any type of biological specimen with clinicopathological features of RCC. piR-823 is down-regulated in tumor tissue, but positively correlated with worse outcome, indicating its complex role in RCC pathogenesis. In blood serum, piR-823 is up-regulated, but with unsatisfactory analytical performance. Preliminary data indicate the promising diagnostic utility of urinary piR-823 in patients with RCC.


Asymmetric severe skeletal Class II division 1 patient with temporomandibular joint disorder treated with zygomatic anchorage devices and Ni-Ti alloy wires.
To describe the orthodontic treatment of a nongrowing 30-year-old woman with asymmetric severe skeletal Class II malocclusions (asymmetric Angle Class II), large overjet (16 mm), large overbite (8 mm), two congenitally missing mandibular incisors (presenting a deciduous anterior tooth), and signs and symptoms of temporomandibular joint disorder (TMD). We used novel improved super-elastic Ni-Ti alloy wires (ISWs) combined with Ni-Ti alloy coil springs, power hooks, and a zygomatic implant as reinforced anchorage to provide a constant and continuous mild force to the dentition. We successfully distalized maxillary molars, premolars, and retracted anterior teeth and corrected the asymmetric Angle Class II molar relationship using this system of zygomatic anchorage in conjunction with ISWs, Ni-Ti alloy open-coil springs, and crimpable power hook. The maxillary molars were distalized, and postero-occlusal relationships were improved to achieve Class I canine and molar relationships on both sides. Intrusion of the upper molars made the mandibular plane close. Ideal overbite and overjet relationships were established. Facial esthetics were improved with decreased upper and lower lip protrusion, and no symptoms of TMD were observed after treatment. The orthodontic treatment described here is a promising anchorage technique alternative to traditional techniques to improve severe skeletal Class II with TMD.


Inclusion of Pediatric-Specific Indications and Procedures in the New ACR MRI Accreditation Program.
MRI equipment with its complex instrumentation and adaptable software applications is vulnerable to technical and image quality problems, and maintaining quality assurance is essential. Accreditation of MRI centers by the ACR has become a routine practice for radiology departments and imaging centers across the country. In its prior format, the ACR MRI Accreditation Program had examination anatomic modules designed primarily to measure quality and validate MR performance primarily in adult imaging practices. In an effort to more closely meet the specific imaging requirements of pediatric patients, an ad hoc MR accreditation committee was created under the ACR Commission on Pediatric Imaging. The committee, consisting of ACR members from five children's hospitals, was tasked with creating suggested revisions to the anatomic modules and helping develop pediatric-specific studies that could be adopted into the ACR MRI Accreditation Program. Updated ACR MRI accreditation anatomic modules incorporating the ad hoc committee's recommendations were released by ACR in May 2017. This article highlights the recommendations made by the ad hoc committee. The revised modules should allow pediatric imaging centers to achieve ACR MRI accreditation for all anatomic modules and will underscore best imaging practices for patients of all ages.


Clinical features and outcome of patients with apical hypertrophic cardiomyopathy in Taiwan.
The aim of this study was to analyze clinical characteristics and the outcome of patients with apical hypertrophic cardiomyopathy (ApHCM) followed in a Taiwan tertiary referral medical center. ApHCM is regarded as a subgroup of nonobstructive HCM that occurs largely in Japanese patients. The clinical features, gender differences and prognosis of the disease in Taiwan are poorly understood. A retrospective cohort study with 40 patients was performed. Diagnosis was based on the demonstration of left ventricular hypertrophy by echocardiography. Clinical features, cardiovascular morbidity and mortality were analyzed. Multiple logistic regression was used to adjust for potential confounding factors. Among 40 patients, males predominated with a percentage of 75%. The female patients obviously had later onset of presentation (mean age +/- SD, 62.2 +/- 5.7 vs. 54.1 +/- 11.4 years; p = 0.038). During a mean follow-up of 72.2 +/- 60.1 months, there was no mortality. However, 13 patients (32.5%) had one or more major cardiovascular morbidities, the most frequent being syncope or near syncope (15%) and ischemic stroke-associated atrial fibrillation (10%). In a multivariate analysis, left atrial enlargement (odds ratio 5.85, 95% CI 1.15-29.40; p = 0.034) was the only predictor of cardiovascular morbidity. Patients with ApHCM in Taiwan have a benign clinical course without association with sudden death and cardiovascular mortality. Left atrial enlargement was the only identified predictor of cardiovascular morbidity


Microbial Communities of Polymetallic Deposits' Acidic Ecosystems of Continental Climatic Zone With High Temperature Contrasts.
Acid mine drainage (AMD) systems are globally widespread and are an important source of metal pollution in riverine and coastal systems. Microbial AMD communities have been extensively studied for their ability to thrive under extremely acidic conditions and for their immense contribution to the dissolution of metal ores. However, little is known on microbial inhabitants of AMD systems subjected to extremely contrasting continental seasonal temperature patterns as opposed to maritime climate zones, experiencing much weaker annual temperature variations. Here, we investigated three types of AMD sites in Eastern Transbaikalia (Russia). In this region, all surface water bodies undergo a deep and long (up to 6 months) freezing, with seasonal temperatures varying between -33 and +24°C, which starkly contrasts the common well-studied AMD environments. We sampled acidic pit lake (Sherlovaya Gora site) located in the area of a polymetallic deposit, acidic drainage water from Bugdaya gold-molybdenum-tungsten deposit and Ulan-Bulak natural acidic spring. These systems showed the abundance of bacteria-derived reads mostly affiliated with Actinobacteria, Acidobacteria, Alpha- and Gammaproteobacteria, chloroplasts, Chloroflexi, Bacteroidetes, and Firmicutes. Furthermore, candidate taxa "Ca. Saccharibacteria" (previously known as TM7), "Ca. Parcubacteria" (OD1) and WPS-2 were represented in substantial quantities (10-20%). Heterotrophy and iron redox cycling can be considered as central processes of carbon and energy flow for majority of detected bacterial taxa. Archaea were detected in low numbers, with Terrestrial Miscellaneous Euryarchaeal Group (TMEG), to be most abundant (3%) in acidic spring Ulan-Bulak. Composition of these communities was found to be typical in comparison to other AMD sites; however, certain groups (as Ignavibacteriae) could be specifically associated with this area. This study provides insight into the microbial diversity patterns in acidic ecosystems formed in areas of polymetallic deposits in extreme continental climate zone with contrasting temperature parameters.


Acute and chronic HBV infection in central Argentina: High frequency of sub-genotype F1b, low detection of clinically relevant mutations and first evidence of HDV.
Genomic analysis of hepatitis B virus (HBV) identifies phylogenetic variants, which may lead to distinct biological and clinical behaviors. The satellite hepatitis D virus (HDV) may also influence clinical outcomes in patients with hepatitis B. The aim of this study was to investigate HBV genetic variants, including clinically relevant mutations, and HDV infection in acute and chronic hepatitis B patients in central Argentina. A total of 217 adult HBV infected patients [acute (AHB): n = 79; chronic (CHB): n = 138] were studied; 67 were HBV/human immunodeficiency virus (HIV) coinfected. Clinical and demographic data were obtained from medical records. Serological markers were determined. Molecular detection of HBV and HDV was carried out by RT-Nested PCR, followed by sequencing and phylogenetic analysis. Overall, genotype (gt) F [sub-genotype (sgt) F1b] was the most frequently found. In AHB patients, the gts/sgts found were: F1b (74.7%) > A2 (13.9%) > F4 (7.6%) > C (2.5%) > A1 (1.3%). Among CHB patients: F1b (39.1%) > A2 (23.9%) > F4 (18.2%) > D (9.4%) > C and F6 (3.6% each) > A1, A3 and B2 (0.7% each). The distribution of sgt A2 and gt D was significantly different between HBV mono and HBV/HIV coinfected patients [A2: 15.9% vs. 35.7% (p < 0.05), respectively and D: 14.6% vs. 1.8% (p < 0.05), respectively]. Mutation frequency in basal core promoter/pre-Core (BCP/pC) region was 35.5% (77/217) [AHB: 20.3% (16/79), CHB: 44.2% (61/138)]. In the open reading frame (ORF) S, mutations associated with vaccine escape and diagnostic failure were detected in 7.8% of the sequences (17/217) [AHB: 3.8% (3/79), CHB: 10.1% (14/138)]. ORF-P amino acid substitutions associated with antiviral resistance were detected in 3.2% of the samples (7/217) [AHB: 1.3% (1/79), CHB 4.3%, (6/138)]. The anti-HDV seropositivity was 5.2% (4/77); one sample could be sequenced, belonging to gt HDV-1 associated with sgt HBV-D3. We detected an increase in the circulation of genotype F in Central Argentina, particularly among AHB patients, suggesting transmission advantages over the other genotypes. A low rate of mutations was detected, especially those with antiviral resistance implications, which is an encouraging result. The evidence of HDV circulation in our region, reported for the first time, alerts the health system for its search and diagnosis.


Circadian rhythm of exocrine pancreatic secretion in rats: major and minor cycles.
The circadian variations of exocrine pancreatic secretion were studied in conscious rats provided with pancreatic, biliary, duodenal, and peritoneal cannulas and kept in restraint cages under controlled conditions, with a regular 12-h light cycle. Rats were divided into fed and fasted groups, and experiments were performed separately. During a 4-day post-surgical recovery period, rats were fed ad libitum. During the experiment, fed rats had free access to food and water. Food, but not water, was denied fasted rats 10 h before the experiment and for its 48-h duration. During the experiment, pancreatic juice was continuously collected for 4 and 2 days from fed and fasted rats, respectively. Every 30 min, a 20-microliters aliquot of sampled pancreatic juice was removed for total protein, amylase, and chymotrypsinogen assays. The remainder was mixed with bile collected simultaneously, and the mixture was recirculated into the duodenum. Over the 4- and 2-day periods there was a clear circadian rhythm of 24-h duration; for all measured parameters, secretory rates increased in the dark period and decreased during the light period. This major circadian rhythm was unexpectedly found to be superimposed on by a remarkably constant neurosecretory-like minor cycle of 2-h duration present in both fed and fasted states. The amplitude of the minor cycle was diminished by fasting. The outputs of fluid, total protein, and amylase were found to be only modestly correlated with each other, whereas chymotrypsinogen output was virtually completely independent of the others. The results suggest that the spontaneous major increase of exocrine pancreatic secretion in the dark was at least partially independent of food intake.(ABSTRACT TRUNCATED AT 250 WORDS)


Purification of a nuclear protein (receptor binding factor-1) associated with the chromatin acceptor sites for the avian oviduct progesterone receptor.
The specific high affinity binding of the avian oviduct progesterone receptor (PR) to target cell nuclei and chromatin has been shown to involve DNA complexed with specific chromatin acceptor proteins. One of these chromatin acceptor proteins has been partially purified and found to be a small hydrophobic protein with a broad pI of 5.0-6.0 [Goldberger and Spelsberg (1988), Biochem. 27, 2103-2109]. Using western immunoblots with anti-RBF-1 polyclonal antibodies to monitor the purification, a 10 kD candidate acceptor protein, termed the Receptor Binding Factor-1 (RBF-1), has been purified to apparent homogeneity. RBF-1 has an amino acid composition consistent with a hydrophobic protein having an acidic pI and a unique N-terminal sequence. Two-dimensional polyacrylamide gel electrophoresis and high-performance capillary electrophoresis support the purity of a protein congruent to 10 kD in size, having an acidic pI, but with evidence of several differently charged isoforms. Phosphatase treatment provides evidence that charge heterogeneity may result from variable phosphorylation states. A role of this factor as a candidate "acceptor protein" in the chromatin acceptor sites for the avian oviduct PR is proposed.


The rhythm of protein synthesis does not depend on oscillations of ATP level.
A rhythm of the [3H]leucine incorporation rate with a period of about one hour (circahoralian rhythm) has been found in rat hepatocytes grown in vitro as a monolayer and in liver organ culture. The periodicity of the incorporation rate remained after correction for changes in leucine pool size. A similar periodicity of the leucine incorporation rate was detected in a cell-free system prepared from rat hepatocytes. We have also found circahoralian oscillations of the ATP level and similar oscillations of the leucine tRNA aminoacylation rate in a hepatocyte monolayer. The addition of 1 mM ADP to the culture resulted in a considerable increase in the ATP level in the cells, but the rhythm of protein synthesis was retained under these conditions. The conclusion that there is a flexible association between changes in the ATP and GTP levels on the one hand, and oscillations of the protein synthesis rate on the other, is also supported by experiments with a cell-free system, in which the rhythm of protein synthesis rate was observed in the presence of excess ATP and GTP. We propose an hypothesis to explain the fractal pattern of circahoralian metabolic rhythms.


3D Quasi-Static Ultrasound Elastography With Plane Wave In Vivo.
In biological tissue, an increase in elasticity is often a marker of abnormalities. Techniques such as quasi-static ultrasound elastography have been developed to assess the strain distribution in soft tissues in two dimensions using a quasi-static compression. However, as abnormalities can exhibit very heterogeneous shapes, a three dimensional approach would be necessary to accurately measure their volume and remove operator dependency. Acquisition of volumes at high rates is also critical to performing real-time imaging with a simple freehand compression. In this study, we developed for the first time a 3D quasi-static ultrasound elastography method with plane waves that estimates axial strain distribution in vivo in entire volumes at high volume rate. Acquisitions were performed with a 2D matrix array probe of 2.5MHz frequency and 256 elements. Plane waves were emitted at a volume rate of 100 volumes/s during a continuous motorized and freehand compression. 3D B-mode volumes and 3D cumulative axial strain volumes were successfully estimated in inclusion phantoms and in ex vivo canine liver before and after a high intensity focused ultrasound ablation. We also demonstrated the in vivo feasibility of the method using freehand compression on the calf muscle of a human volunteer and were able to retrieve 3D axial strain volume at a high volume rate depicting the differences in stiffness of the two muscles which compose the calf muscle. 3D ultrasound quasi-static elastography with plane waves could become an important technique for the imaging of the elasticity in human bodies in three dimensions using simple freehand scanning.


Silencing of NADPH-dependent oxidoreductase genes (yqhD and dkgA) in furfural-resistant ethanologenic Escherichia coli.
Low concentrations of furfural are formed as a side product during the dilute acid hydrolysis of hemicellulose. Growth is inhibited by exposure to furfural but resumes after the complete reduction of furfural to the less toxic furfuryl alcohol. Growth-based selection was used to isolate a furfural-resistant mutant of ethanologenic Escherichia coli LY180, designated strain EMFR9. Based on mRNA expression levels in the parent and mutant in response to furfural challenge, genes encoding 12 oxidoreductases were found to vary by more than twofold (eight were higher in EMFR9; four were higher in the parent). All 12 genes were cloned. When expressed from plasmids, none of the eight genes in the first group increased furfural tolerance in the parent (LY180). Expression of three of the silenced genes (yqhD, dkgA, and yqfA) in EMFR9 was found to decrease furfural tolerance compared to that in the parent. Purified enzymes encoded by yqhD and dkgA were shown to have NADPH-dependent furfural reductase activity. Both exhibited low K(m) values for NADPH (8 microM and 23 microM, respectively), similar to those of biosynthetic reactions. Furfural reductase activity was not associated with yqfA. Deleting yqhD and dkgA in the parent (LY180) increased furfural tolerance, but not to the same extent observed in the mutant EMFR9. Together, these results suggest that the process of reducing furfural by using an enzyme with a low K(m) for NADPH rather than a direct inhibitory action is the primary cause for growth inhibition by low concentrations of furfural.


Advanced considerations in organ donors.
The rising need for lung transplantation over recent years has not paralleled the availability of suitable lung allografts. The number of lung transplantations performed each year in the United States remains limited by an inadequate supply of suitable donors as well as low donor utilization rates. While several methods have been proposed for increasing the donor pool, there is considerable disparity between acceptance and utilization of these practices among transplant centers. In this review article, we explore various approaches for enhancing donor selection and expanding the donor pool. We discuss the use of "extended criteria" donors including high risk groups such as drug overdose donors, and we examine the role of techniques in donor assessment and selection such as the use of computed tomography for accurate size matching. We review topics in donor management such as the establishment of specialized donor care facilities and the implementation of lung-focused resuscitation protocols, and we discuss advancements in donor procurement such as the utilization of local procurement teams. We also review barriers to donation, such as variability in organ procurement organization (OPO) consent practices, as well as patient-specific factors such as religious or cultural beliefs. Addressing these aspects of donor evaluation, management, and accessibility is essential in maximizing the number of lungs available for transplantation within the existing donor pool.


Mortality Risk and Its Association with Geriatric Domain Deficits in Older Outpatients: The Amsterdam Ageing Cohort.
In older patients, life expectancy is determined by a complex interaction of multiple geriatric domains. A comprehensive geriatric assessment (CGA) captures different geriatric domains. Yet, if and how components of the CGA are related to mortality in an outpatient geriatric setting is unknown. In the Amsterdam Ageing Cohort, we therefore studied distribution and accumulation of geriatric domain deficits in relation to mortality. All patients received a CGA as part of standard care, independent of referral reason. We summarized deficits on the CGA, using predefined cutoffs, in 5 geriatric domains: somatic, mental, nutritional, physical, and social domain. Information on mortality was obtained from the Dutch municipal register. We used age- and sex-adjusted Cox proportional hazards analyses to relate the separate domains and accumulation of impaired domains to overall mortality. From the 1,055 geriatric outpatients (53% female; age 79 ± 7 years), 172 patients (16%) had died after 1.7 ± 1.1 years. In 626 patients (59%), 3 or more domains were impaired. All domains were independently associated with mortality, with the highest hazard for the somatic domain (HR 3.7 [1.7-8.0]) and the lowest hazard for the mental domain (HR 1.5 [1.1-12.0]). In addition, accumulation of impaired domains showed a gradually increased mortality risk, ranging from HR 2.2 (0.8-6.1) for 2 domains to HR 9.6 (3.7-24.7) for all 5 domains impaired. This study provides evidence that impairment in multiple geriatric domains is highly prevalent and independently and cumulatively associated with mortality in an outpatient geriatric setting.


Neuropathology of the limbic system.
The history and development of the fanciful terminology concerning the structures of the limbic system are discussed. The diseases involving the limbic system are divided into three groups; (1) diseases in which the limbic system is more or less selectively involved, such as limbic encephalitis, herpes simplex encephalitis, cerebral confusions by the falx and tentorium, and internal herniations through the falx and tentorium; (2) diseases in which the limbic system is predominantly involved, such as arhinencephalia, holoprosencephaly, cyst of cavum septi pellucidi, Pick's disease, Alzheimer's disease, hippocampal sclerosis, and vascular diseases of the hippocampal formation; and (3) diseases in which the limbic system is randomly involved, such as various types of neoplasms and vascular and inflammatory lesions. The relationship between destructive lesions of the hippocampus and memory also is emphasized.


Expression of the Evi-1 zinc finger gene in 32Dc13 myeloid cells blocks granulocytic differentiation in response to granulocyte colony-stimulating factor.
Expression of the Evi-1 gene is frequently activated in murine myeloid leukemias by retroviral insertions immediately 5' or 90 kb 5' of the gene. The Evi-1 gene product is a nuclear, DNA-binding zinc finger protein of 145 kDa. On the basis of the properties of the myeloid cell lines in which the Evi-1 gene is activated, it has been hypothesized that its expression blocks normal differentiation. To explore this proposed role, we have constructed a retrovirus vector containing the gene and examined its effects on an interleukin-3-dependent myeloid cell line that differentiates in response to granulocyte colony-stimulating factor (G-CSF). Expression of the Evi-1 gene in these cells did not alter the normal growth factor requirements of the cells. However, expression of the Evi-1 gene blocked the ability of the cells to express myeloperoxidase and to terminally differentiate to granulocytes in response to G-CSF. This effect was not due to altered expression of the G-CSF receptor or to changes in the initial responses of the cells to G-CSF. These results support the hypothesis that the inappropriate expression of the Evi-1 gene in myeloid cells interferes with the ability of the cells to terminally differentiate.


Upscaling, integration and electrical characterization of molecular junctions.
The ultimate target of molecular electronics is to combine different types of functional molecules into integrated circuits, preferably through an autonomous self-assembly process. Charge transport through self-assembled monolayers has been investigated previously, but problems remain with reliability, stability and yield, preventing further progress in the integration of discrete molecular junctions. Here we present a technology to simultaneously fabricate over 20,000 molecular junctions-each consisting of a gold bottom electrode, a self-assembled alkanethiol monolayer, a conducting polymer layer and a gold top electrode-on a single 150-mm wafer. Their integration is demonstrated in strings where up to 200 junctions are connected in series with a yield of unity. The statistical analysis on these molecular junctions, for which the processing parameters were varied and the influence on the junction resistance was measured, allows for the tentative interpretation that the perpendicular electrical transport through these monolayer junctions is factorized.


Development and Biological Characterization of a Novel Selective TrkA Agonist with Neuroprotective Properties against Amyloid Toxicity.
Neurotrophins are growth factors that exert important neuroprotective effects by preventing neuronal death and synaptic loss. Nerve Growth Factor (NGF) acts through the activation of its high-affinity, pro-survival TrkA and low-affinity, pro-apoptotic p75NTR receptors. NGF has been shown to slow or prevent neurodegenerative signals in Alzheimer's Disease (AD) progression. However, its low bioavailability and its blood-brain-barrier impermeability limit the use of NGF as a potential therapeutic agent against AD. Based on our previous findings on synthetic dehydroepiandrosterone derivatives, we identified a novel NGF mimetic, named ENT-A013, which selectively activates TrkA and exerts neuroprotective, anti-amyloid-β actions. We now report the chemical synthesis, in silico modelling, metabolic stability, CYP-mediated reaction phenotyping and biological characterization of ENT-A013 under physiological and neurodegenerative conditions. We show that ENT-A013 selectively activates the TrkA receptor and its downstream kinases Akt and Erk1/2 in PC12 cells, protecting these cells from serum deprivation-induced cell death. Moreover, ENT-A013 promotes survival of primary Dorsal Root Ganglion (DRG) neurons upon NGF withdrawal and protects hippocampal neurons against Amyloid β-induced apoptosis and synaptic loss. Furthermore, this neurotrophin mimetic partially restores LTP impairment. In conclusion, ENT-A013 represents a promising new lead molecule for developing therapeutics against neurodegenerative disorders, such as Alzheimer's Disease, selectively targeting TrkA-mediated pro-survival signals.


Automated on-line preconcentration of palladium on different sorbents and its determination in environmental samples.
The determination of noble metals in environmental samples is of increasing importance. Palladium is often employed as a catalyst in chemical industry and is also used with platinum and rhodium in motor car catalytic converters which might cause environmental pollution problems. Two different sorbents for palladium preconcentration in different samples were investigated: silica gel functionalized with 1,5-bis(di-2-pyridyl)methylene tbiocarbohydrazide (DPTH-gel) and [1,5-Bis(2-pyridyl)-3-sulphophenyI methylene thiocarbonohydrazide (PSTH) immobilised on an anion-exchange resin (Dowex lx8-200)]. The sorbents were tested in a micro-column, placed in the auto-sampler arm, at the flow rate 2.8 mL min(-1). Elution was performed with 4 M HCl and 4 M HNO3, respectively. Satisfactory results were obtained for two sorbents.


Comparative genomic analysis of inbred rat strains reveals the existence of ancestral polymorphisms.
In an alignment of closely related genomic sequences, the existence of discordant mutation sites, which do not reflect the phylogenetic relationship of the genomes, is often observed. Although these discordant mutation sites are thought to have emerged by ancestral polymorphism or gene flow, their frequency and distribution in the genome have not yet been analyzed in detail. Using the genome sequences of all protein coding genes of 25 inbred rat strains, we analyzed the frequency and genome-wide distribution of the discordant mutation sites. From the comparison of different substrains, it was found that these loci are not substrain specific, but are common among different groups of substrains, suggesting that the discordant sites might have mainly emerged through ancestral polymorphism. It was also revealed that the discordant sites are not uniformly distributed along chromosomes, but are concentrated at certain genomic loci, such as RT1, major histocompatibility complex of rats, and olfactory receptors, indicating that genes known to be highly polymorphic tend to have more discordant sites. Our results also showed that loci with a high density of discordant sites are also rich in heterozygous variants, even though these are inbred strains.


Effect of Negative Pressure Wound Therapy vs Standard Wound Management on 12-Month Disability Among Adults With Severe Open Fracture of the Lower Limb: The WOLLF Randomized Clinical Trial.
Open fractures of the lower limb occur when a broken bone penetrates the skin. There can be major complications from these fractures, which can be life-changing. To assess the disability, rate of deep infection, and quality of life in patients with severe open fracture of the lower limb treated with negative pressure wound therapy (NPWT) vs standard wound management after the first surgical debridement of the wound. Multicenter randomized trial performed in the UK Major Trauma Network, recruiting 460 patients aged 16 years or older with a severe open fracture of the lower limb from July 2012 through December 2015. Final outcome data were collected through November 2016. Exclusions were presentation more than 72 hours after injury and inability to complete questionnaires. NPWT (n = 226) in which an open-cell solid foam or gauze was placed over the surface of the wound and connected to a suction pump, creating a partial vacuum over the dressing, vs standard dressings not involving application of negative pressure (n = 234). Disability Rating Index score (range, 0 [no disability] to 100 [completely disabled]) at 12 months was the primary outcome measure, with a minimal clinically important difference of 8 points. Secondary outcomes were complications including deep infection and quality of life (score ranged from 1 [best possible] to -0.59 [worst possible]; minimal clinically important difference, 0.08) collected at 3, 6, 9, and 12 months. Among 460 patients who were randomized (mean age, 45.3 years; 74% men), 88% (374/427) of available study participants completed the trial. There were no statistically significant differences in the patients' Disability Rating Index score at 12 months (mean score, 45.5 in the NPWT group vs 42.4 in the standard dressing group; mean difference, -3.9 [95% CI, -8.9 to 1.2]; P = .13), in the number of deep surgical site infections (16 [7.1%] in the NPWT group vs 19 [8.1%] in the standard dressing group; difference, 1.0% [95% CI, -4.2% to 6.3%]; P = .64), or in quality of life between groups (difference in EuroQol 5-dimensions questionnaire, 0.02 [95% CI, -0.05 to 0.08]; Short Form-12 Physical Component Score, 0.5 [95% CI, -3.1 to 4.1] and Mental Health Component Score, -0.4 [95% CI, -2.2 to 1.4]). Among patients with severe open fracture of the lower limb, use of NPWT compared with standard wound dressing did not improve self-rated disability at 12 months. The findings do not support this treatment for severe open fractures. isrctn.org Identifier: ISRCTN33756652.


Multiscale Self-Assembly of a Phenyl-Flanked Diketopyrrolopyrrole Derivative: A Solution-Processable Building Block for π-Conjugated Supramolecular Polymers.
We report a solution-processable π-conjugated molecular building block (denoted as PhDPP) consisting of a rigid and planar core of phenyl-flanked diketopyrrolopyrrole and "soft" branched alkoxy chains that endow the solubility in a variety of organic solvents. Intermolecular hydrogen bonding in PhDPP was revealed in nonpolar solvents above a threshold of concentration and below a critical point of temperature. The strong intermolecular interaction mainly contributed by the hydrogen-bonding and π-π interaction between PhDPP molecules promoted the formation of supramolecular polymeric structures in both solution and solid states and at interfaces. The supramolecular polymeric properties enabled solution-based processing of PhDPP under a variety of conditions into different structures including fibers and uniform thin films. The structure-property relationship that we established in the present system of PhDPP from the molecular to supramolecular level will be important to solution-process this type of H-bonding π-conjugated molecules for a variety of applications such as optoelectronic devices.


Construction and selection of the natural immune Fab antibody phage display library from patients with colorectal cancer.
To construct the natural immune Fab antibody phage display libraries of colorectal cancer and to select antibodies related with colorectal cancer. Extract total RNA from tissue of local cancer metastasis lymph nodes of patients with colorectal cancer. RT-PCR was used to amplify the heavy chain Fd and light chain kappa and the amplification products were inserted successively into the vector pComb3 to construct the human libraries of Fab antibodies. They were then panned by phage display technology. By means of Dot immunoblotting and ELISA, the libraries were identified and the Fab phage antibodies binding with antigens of colorectal cancer were selected. The amplified fragments of Fd and kappa gained by RT-PCR were about 650 bp. Fd and kappa PCR products were subsequently inserted into the vector pComb3, resulting in a recombination rate of 40% and the volume of Fab phage display library reached 1.48 x 10(6). The libraries were enriched about 120-fold by 3 cycles of adsorption-elution-multiplication (panning). Dot immunoblotting showed Fab expressions on the phage libraries and ELISA showed 5 clones of Fab phage antibodies which had binding activities with antigens of colorectal cancer. The natural immune Fab antibody phage display libraries of colorectal cancer were constructed. They could be used to select the relative antibodies of colorectal cancer.


[Study of the autonomous nervous system with heart rate spectral analysis in acute myocardial infarction].
Characterize power spectrum pattern of heart rate variability (HRV) and assessment of relative cardiac nervous system in patients with acute myocardial interaction of sympathetic and parasympathetic infarction. We also compared the spectral power with some known prognostic risk variables. Study of patients with acute myocardial infarction (AMI) and sedentary healthy subjects sex matched. 19 postinfarction patients aged 55.7 +/- 10.5 years and 19 healthy subjects controls aged 53.9 +/- 11.0. ECG signals were recorded after 15 minutes of supine rest with controlled breathing at 15 cycles/min. Signal acquisition was done at 300 samples/sec. From 512 consecutive sinus beats, we calculated the average, standard deviation, maximum and minimum values and rate between the longest and shortest R-R interval (E/I). We also calculated, after computing the fast Fourier transform, the total spectrum power, low frequency component (LF, from 0.01 to 0.15 Hz), high frequency component (HF, from 0.15 to 0.50 Hz) and its ratio (LF/HF). Thereafter, we correlated these results with radionuclide ejection fraction, duration of treadmill test, Holter ventricular premature complex and localization of infarction. The average R-R interval was 757.9 +/- 116.3 and 850.9 +/- 133.9 msec (p less than 0.05), the R-R corrected standard deviation was 15.3 +/- 6.0 and 38.2 +/- 8.5 msec (p less than 0.001) and ratio E/I was 1.13 +/- 0.06 and 1.32 +/- 0.09 (p less than 0.001) in AMI and control group, respectively. In AMI group, low frequency spectral band was very decreased (LF = 0.03 +/- 0.02 sec2) and high frequency was virtually absent (HF = 0.01 +/- 0.01 sec2) compared with control group (LF = 0.13 +/- 0.06 and HF = 0.14 +/- 0.15 sec2), p less than 0.001; ratio LF/HF was increased in AMI group. There were no significant differences between groups for normalized LF (LF%) and HF (HF%). These results showed that spectral pattern in AMI patients had very low LF and HF power density. Decreased HRV in that group was mainly due to diminished parasympathetic influence in cardiac regulation; nevertheless ratio LF/HF was increased which represents an imbalance of sympatho-vagal activity with predominance of sympathetic tone. We found poor correlation between frequency domain indices and other risk variable; best correlation was between total spectral power and radionuclide ejection fraction (r = 0.642, p less than 0.01), which could express independent prognostic value in AMI patients risk stratification.


Niche breadth of Amazonian trees increases with niche optimum across broad edaphic gradients.
Understanding how biotic interactions and environmental filtering mediated by soil properties shape plant community assembly is a major challenge in ecology, especially when studying complex and hyperdiverse ecosystems like tropical forests. To shed light on the influence of both factors, we examined how the edaphic optimum of species (their niche position) related to their edaphic range (their niche breadth) along different environmental gradients and how this translates into functional strategies. Here we tested four scenarios describing the shape of the niche breadth-niche position relationship, including one neutral scenario and three scenarios proposing different relative influences of abiotic and biotic factors on community assembly along a soil resource gradient. To do so, we used soil concentration data for five key nutrients (N, P, Ca, Mg, and K), along with accurate measurements of 14 leaf, stem, and root traits for 246 tree species inventoried in 101 plots located across Eastern (French Guiana) and Western (Peru) Amazonia. We found that species niche breadth increased linearly with species niche position along each soil nutrient gradient. This increase was associated with more resource acquisitive traits in the leaves and the roots for soil N, Ca, Mg, and K concentration, while it was negatively associated with wood density for soil P concentration. These observations agreed with one of our hypothetical scenarios in which species with resource conservation traits are confined to the most nutrient-depleted soils (abiotic filter), but they are outperformed by faster-growing species in more fertile conditions (biotic filter). Our results refine and strengthen support for niche theories of species assembly while providing an integrated approach to improving forest management policies.


A longitudinal study of maternal depression and preschool children's mental health.
The purpose of this longitudinal study was to examine the relationship between maternal depression and preschool children's mental health in a community sample. Cohort 1 (n = 97) consisted of mothers and children followed from 2 to 3 years of age. Cohort 2 (n = 97) consisted of mothers and children followed from 3 to 4 years of age. Mothers completed a self-report measure of depression twice during 1 year. The children's day care providers/nursery school teachers completed two instruments measuring the children's social competence and behavior problems at the end of the year. Maternal depression was significantly related to lower social competence and more behavior problems in the children. Although there were no significant mean differences in children's mental health scores by gender, boys of more depressed mothers were more likely to have poorer social competence and more behavior problems than girls. Item analyses suggest that the boys' behaviors may be particularly aversive for depressed mothers, increasing the likelihood that these mothers will respond to and reinforce their sons' difficult behaviors.


Solvent Vapor Annealing, Defect Analysis, and Optimization of Self-Assembly of Block Copolymers Using Machine Learning Approaches.
Self-assembly of block copolymers (BCPs) is an alternative patterning technique that promises high resolution and density multiplication with lower costs. The defectivity of the resulting nanopatterns remains too high for many applications in microelectronics and is exacerbated by small variations of processing parameters, such as film thickness, and fluctuations of solvent vapor pressure and temperature, among others. In this work, a solvent vapor annealing (SVA) flow-controlled system is combined with design of experiments (DOE) and machine learning (ML) approaches. The SVA flow-controlled system enables precise optimization of the conditions of self-assembly of the high Flory-Huggins interaction parameter (χ) hexagonal dot-array forming BCP, poly(styrene-b-dimethylsiloxane) (PS-b-PDMS). The defects within the resulting patterns at various length scales are then characterized and quantified. The results show that the defectivity of the resulting nanopatterned surfaces is highly dependent upon very small variations of the initial film thicknesses of the BCP, as well as the degree of swelling under the SVA conditions. These parameters also significantly contribute to the quality of the resulting pattern with respect to grain coarsening, as well as the formation of different macroscale phases (single and double layers and wetting layers). The results of qualitative and quantitative defect analyses are then compiled into a single figure of merit (FOM) and are mapped across the experimental parameter space using ML approaches, which enable the identification of the narrow region of optimum conditions for SVA for a given BCP. The result of these analyses is a faster and less resource intensive route toward the production of low-defectivity BCP dot arrays via rational determination of the ideal combination of processing factors. The DOE and machine learning-enabled approach is generalizable to the scale-up of self-assembly-based nanopatterning for applications in electronic microfabrication.


Food and Nutrient Intake and Nutrient Sources in 1-Year-Old Infants in Finland: A Cross-Sectional Analysis.
The infant diet has short- and long-term health consequences. Updated data regarding the dietary intake of Finnish infants are lacking. The objectives of this study were to describe infant food and nutrient intake and to identify food sources of the nutrients. Altogether, 739 healthy infants were studied. Dietary intake and breastfeeding frequency were assessed with a three-day food record at 1 year of age. Dietary intake was calculated separately for non-breastfed and breastfed infants. One-third (36%) of the infants were partially breastfed and 95% consumed mass-produced baby foods. The infants' diet consisted mainly of infant formula, dairy milk, porridges, fruit and berry foods, and meat dishes. The mean vegetable, fruit and berry consumption was 199 g/day. Most nutrient intakes were adequate except for fat, linoleic acid, vitamin D and iron from food. Mean sucrose intake, as a percentage of total energy intake (E%), was 5-6 E%. High protein intake (>20 E%) was observed in 19% of non-breastfed infants. Overall, the infants' diet was favorable since vegetable and fruit consumption was reasonably high and nutrient intake was mostly adequate. However, the fat intake was lower, and protein intake higher than recommended. Increasing the consumption of vegetable oils and reducing the intake of red meat and dairy milk may further improve the diet of 1-year-olds.


Computational comparison of CPDT to other conjugated linkers in triarylamine-based organic dyes.
The use of the cyclopentadithiophene (cpdt) fragment to chemically link electron donor and acceptor groups has become a rather common procedure to design new organic dyes with enhanced light harvesting properties. The photo-to-current efficiencies obtained by sensitized solar cells with dyes incorporating the cpdt moiety are commonly improved with respect to other similar π-fragments as separators. In many cases, the advantages of cpdt can be related to the larger extinction coefficients obtained. In this work we perform a detailed computational study of triarylamine-based organic dyes with the cyanoacrylic acid as the acceptor group and considering a variety of conjugated linkers with cpdt as the reference case. The influence of slightly different linkers and donor groups in the computed excitation energies and oscillator strengths is discussed by means of molecular geometries and frontier orbitals. The structural characteristics imposed by cpdt compared to similar conjugated bridges are responsible for its larger computed oscillator strengths. The insertion of an ethylene unit between the donor group and the linker systematically reduces the energy gap to the first excited singlet state and yields larger oscillator strengths of the optical transition. These results could be very helpful in the quest of new organic dyes with improved properties as sensitizers in Grätzel cells.


Interpersonal pathoplasticity in the course of major depression.
The identification of reliable predictors of course in major depressive disorder (MDD) has been difficult. Evidence suggests that the co-occurrence of personality pathology is associated with longer time to MDD remission. Interpersonal pathoplasticity, the mutually influencing nonetiological relationship between psychopathology and interpersonal traits, offers an avenue for examining specific personality vulnerabilities that may be associated with depressive course. This study examined 312 participants with and without a co-occurring personality disorder diagnosis who met criteria for a current MDD episode at baseline and who were followed for 10 years in the Collaborative Longitudinal Personality Disorders Study. Latent profile analysis (LPA) identified 6 interpersonal groups (extraverted, dominant, arrogant, cold, submissive, and unassuming), and circular statistical profile analysis confirmed group interpersonal distinctiveness. No significant differences between groups were found in comorbid Axis I disorders or baseline MDD severity. Chronicity and functioning analyses found significantly greater chronicity and poorer functioning in individuals with a submissive interpersonal style over 10 years. These findings support the relevance of interpersonal pathoplasticity in depressive course and that this heterogeneity has clinical significance. This study is the first to use LPA and circular profiles to examine interpersonal heterogeneity within a diagnostic group. The implications of these findings for therapeutic intervention, interpersonal functioning, and psychopathological course are discussed.


Having a Calling on Board: Effects of Calling on Job Satisfaction and Job Performance Among South Korean Newcomers.
Despite increasing research on calling, how calling functions for those experiencing transition from school to work and how their calling prior to working relates to later well-being and job outcomes has been understudied. The current study explored effects of perceiving a calling on job satisfaction and job performance, as measured at organizational entry and 2 years after organizational entry. Using a time-lagged collection of a sample of South Korean newcomers, the results based on structural equation modeling revealed that perceiving a calling was positively related to supervisor-rated job performance. Job involvement, which was measured 1 year later, fully mediated the relation between perceiving a calling and job satisfaction, but the hypothesized mediating role of job involvement on the link between perceiving a calling and job performance was not supported. We also examined moderating roles of perceived organizational support and perceived person-job fit on the relation between perceiving a calling on job involvement and found that perceived organizational support facilitated the effects of perceiving a calling on job involvement. Implications of these findings are discussed.


Crossmodal interactions of haptic and visual texture information in early sensory cortex.
Both visual and haptic information add to the perception of surface texture. While prior studies have reported crossmodal interactions of both sensory modalities at the behavioral level, neuroimaging studies primarily investigated texture perception in separate visual and haptic paradigms. These experimental designs, however, only allowed to identify overlap in both sensory processing streams but no interaction of visual and haptic texture processing. By varying texture characteristics in a bimodal task, the current study investigated how these crossmodal interactions are reflected at the cortical level. We used fMRI to compare cortical activation in response to matching versus non-matching visual-haptic texture information. We expected that passive simultaneous presentation of matching visual-haptic input would be sufficient to induce BOLD responses graded with varying texture characteristics. Since no cognitive evaluation of the stimuli was required, we expected to find changes primarily at a rather early processing stage. Our results confirmed our assumptions by showing crossmodal interactions of visual-haptic texture information in early somatosensory and visual cortex. However, the nature of the crossmodal effects was slightly different in both sensory cortices. In early visual cortex, matching visual-haptic information increased the average activation level and induced parametric BOLD signal variations with varying texture characteristics. In early somatosensory cortex only the latter was true. These results challenge the notion that visual and haptic texture information is processed independently and indicate a crossmodal interaction of sensory information already at an early cortical processing stage.


Solution structure and functional characterization of jingzhaotoxin-XI: a novel gating modifier of both potassium and sodium channels.
JZTX-XI is a peptide toxin isolated from the venom of the Chinese spider Chilobrachys jingzhao. It contains 34 residues including six cysteine residues with disulfide bridges linked in the pattern of I-IV, II-V, and III-VI. Using 3'- and 5'-RACE methods, the full-length cDNA was identified as encoding an 86-residue precursor of JZTX-XI. In the electrophysiological assay, JZTX-XI shows activity toward the Kv2.1 channel in a way similar to hanatoxin1 and SGTx1 that both the activation and the deactivation processes are affected, which is in accordance with the high sequence homology among them (over 60% identity). On the other hand, JZTX-XI also exhibits specific interaction against the Nav channels of rat cardiac myocytes with a significant reduction in the peak current and slowing of channel inactivation. The solution structure of native JZTX-XI was determined by 1H NMR methods to identify the structural basis of these specific activities. Structural comparison of JZTX-XI with other gating modifier toxins shows that they all adopt a similar surface profile, a hydrophobic patch surrounded by charged residues such as Arg or Lys, which might be a common structural factor responsible for toxin-channel interaction. JZTX-XI might be an ideal tool to further investigate how spider toxins recognize various ion channels as their targets.


Income inequality and entrepreneurship: Lessons from the 2020 COVID-19 recession.
We study entry into entrepreneurship during the COVID-19 recession of 2020 using new data from an extensive survey of more than 24,000 Spanish households, conducted between June and November 2020. We find that while the overall decline in the startup rate in 2020 was large, and of a similar magnitude as that during the Great Recession, the differential impact depending on ex ante income was starkly different. During 2020, the drop in firm entry was entirely concentrated among low- and medium-income households. We show that the entrepreneurship gap between these households and their high-income counterparts is not directly explained by social distancing, since it is mostly driven by the sectors not directly affected by lockdown measures, and it is larger among households that did not suffer a negative income shock during the pandemic. Our results instead indicate that high-income households performed relatively better during the COVID-19 recession because they had the means to exploit new business opportunities, thanks to their larger wealth and better access to external finance.


Role of MXenes in advancing soft robotics.
MXenes with their unique electronic, optical, chemical, and mechanical properties have shown great promise in soft robotics. MXene-based soft actuators have been designed to display ultrafast actuations and recovery speeds as well as angle-independent structural colors in response to vapor. Several studies have developed soft actuators by combining MXenes with other materials to mimic the movement of natural organisms. Thus, MXene-based soft actuators have the potential to revolutionize the field of soft robotics and flexible electronics (e.g., wearable devices and artificial muscles). MXene-based artificial muscles have been explored for use in kinetic soft robotics as actuators in microsystems requiring exceptional compliance. MXene-based sensors and actuators have already been developed for human-like sensors and photodetection. However, there are still challenges that need to be addressed in such applications, such as the design of stretchable and compliant robotic skins with a high-level functional integration for soft robotics. The integration of various devices, such as power sources, sensors, and actuators, into soft robotics is another crucial challenge. Despite the excellent stretchability and tensile strength of MXene-based composites, there is a vital need to develop their mechanical and electrochemical features and grant them multi-functionalities. Herein, recent developments pertaining to the applications of MXenes and their composites in soft robotics are discussed with a focus on the important challenges and future perspectives.