Minor components of a multi-envelope HIV vaccine are recognized by type-specific T-helper cells.
HIV has thus far evaded control by vaccines, in part due to the high diversity among viral isolates. To effectively target HIV diversity, we propose that multi-envelope HIV vaccines should be designed. We hypothesize that minor components of complex envelope cocktail vaccines can be immunogenic and can thus elicit unique T-cell responses. To test our hypothesis, we first defined unique T-helper cell determinants on 1007 (clade B) and UG92005 (UG, clade D) gp140 envelope proteins delivered by DNA vaccination. Peptide-specific T-helper cell responses were then used as markers for type-specific immune activity. Results showed that type-specific responses could indeed be generated when an envelope protein was represented as only 1 part per 100 of the total vaccine. We also found that type-specific T-helper cell responses were elicited and sustained toward an envelope that appeared only once within a sequential prime/boost/boost regimen. Our results illustrate the flexibility and durability of immune responses toward individual components of mixed envelope vaccines and encourage the continued development of vaccine cocktails for the control of HIV.


Differential degradation of full-length and cleaved ataxin-7 fragments in a novel stable inducible SCA7 model.
Spinocerebellar ataxia type 7 (SCA7) is one of nine neurodegenerative disorders caused by expanded polyglutamine repeats, and a common toxic gain-of-function mechanism has been proposed. Proteolytic cleavage of several polyglutamine proteins has been identified and suggested to modulate the polyglutamine toxicity. In this study, we show that full-length and cleaved fragments of the SCA7 disease protein ataxin-7 (ATXN7) are differentially degraded. We found that the ubiquitin-proteosome system (UPS) was essential for the degradation of full-length endogenous ATXN7 or transgenic full-length ATXN7 with a normal or expanded glutamine repeat in both HEK 293T and stable PC12 cells. However, a similar contribution by UPS and autophagy was found for the degradation of proteolytically cleaved ATXN7 fragments. Furthermore, in our novel stable inducible PC12 model, induction of mutant ATXN7 expression resulted in toxicity and this toxicity was worsened by inhibition of either UPS or autophagy. In contrast, pharmacological activation of autophagy could ameliorate the ATXN7-induced toxicity. Based on our findings, we propose that both UPS and autophagy are important for the reduction of mutant ataxin-7-induced toxicity, and enhancing ATXN7 clearance through autophagy could be used as a potential therapeutic strategy in SCA7.


Factors Associated with Matching into Surgical Specialties.
The United States medical education system has a vested interest in understanding medical student specialty choice. The purpose of this study is to identify the demographic, educational, lifestyle preference, and other factors associated with matching into surgical specialties. An annual survey was given to students at the University of Iowa Carver College of Medicine from 2013-2019. 456 medical students were eligible to participate and 374 completed at least one survey. Surveys were distributed 5 times; M1, M2, M3, and M4 years and after the residency match process. Logistic regression was used to estimate the association between various factors and the likelihood of matching into a surgical specialty. Exposure to surgical fields, through a family member practicing surgery (aOR = 3.21), mentorship (aOR = 2.78), or research (aOR = 2.96) increase the likelihood of matching into a surgical specialty. Married students are less likely to pursue surgical specialties (aOR = 0.246). White students interested in surgery in their first two years of medical school were more likely (aOR = 6.472) to match into surgery than non-White students also interested in surgery (aOR = 0.155). Factors associated with an increased likelihood of matching into surgical specialties include having surgical mentors, performing surgical research, and having family members in surgical specialties. Of the students interested in surgery early in medical school, being of Caucasian ethnicity is associated with higher rates of matching into surgery. Students who are married without children are less likely to enter a surgical field.


Diverse expression patterns of LIM-homeodomain transcription factors (LIM-HDs) in mammalian inner ear development.
LIM-homeodomain transcription factors (LIM-HDs) are essential in tissue patterning and differentiation. But their expression patterns in the inner ear are largely unknown. Here we report on a study of twelve LIM-HDs, by their tempo-spatial patterns that imply distinct yet overlapping roles, in the developing mouse inner ear. Expression of Lmx1a and Isl1 begins in the otocyst stage, with Lmx1a exclusively in the non-sensory and Isl1 in the prosensory epithelia. The second wave of expression at E12.5 includes Lhx3, 5, 9, Isl2, and Lmx1b in the differentiating sensory epithelia with cellular specificities. With the exception of Lmx1a and Lhx3, all LIM-HDs are expressed in ganglion neurons. Expression of multiple LIM-HDs within a cell type suggests their redundant function.


Serum concentrations of an aflatoxin-albumin adduct in the National Health and Nutrition Examination Survey (NHANES) 1999-2000.
During 1998, weather conditions in the United States favored the growth of Aspergillus species leading to widespread contamination of Midwestern and Southern corn with hepatotoxic and hepatocarcinogenic aflatoxins. We designed a study to provide the first national prevalence estimate of aflatoxin exposure using the National Health and Nutrition Examination Survey (NHANES), a representative cross-sectional survey of the noninstitutionalized civilian population of the US. Isotope dilution liquid chromatography-tandem mass spectrometry was used to quantitate serum concentrations of aflatoxin B1-lysine in a one-third random subset of participants from NHANES 1999-2000. About 1% of the U.S. population had detectable levels (≥0.02μg/l) of aflatoxin B1-lysine. Of those with detectable levels, the geometric mean (95% confidence interval) was 0.038 (0.024-0.060) μg/l (equivalent to 0.842 (0.530-1.34) pg/mg albumin). The highest value was 0.2μg/l (4.43pg/mg albumin). Based on liver function biomarkers, there was no evidence of increased liver dysfunction in these persons. During a time when exposure to aflatoxins in food products might have been expected to be increased, we identified few exposed persons. Although none of the subgroup analyses provided reliable estimates due to high relative standard errors, they suggested that additional targeted surveillance may be warranted.


The behavioral effects of serotonin synthesis inhibition and quisqualic acid induced lesions of the nucleus basalis magnocellularis in rats.
1. To investigate the role of the cholinergic and serotonergic systems in the regulation of cognitive functions, the effects of concurrent lesioning of nucleus basalis magnocellularis (NB) with quisqualic acid (quis) and inhibition of brain serotonin synthesis by systemic p-chlorophenylalanine (PCPA) treatment on passive avoidance (PA) retention and water maze (WM) spatial navigation performance were studied in rats. 2. Quis NB lesioning induced a marked reduction (-62%) in frontal cortical choline-acetyltransferase activity, impaired retention of PA, and slightly and transiently impaired acquisition of WM spatial navigation. 3. PCPA (400 mg/kg/day x 3, i.p.) treatment depleted frontal cortical concentrations of both serotonin (82% depletion) and its major metabolite 5-HIAA (90% depletion) and slightly affected the noradrenergic and dopaminergic systems. PCPA treatment alone had no effect on WM or PA behavior, but potentiated the PA retention deficit and slightly aggravated the WM deficit in rats subjected to quis NB lesioning. 4. The present results further support the view that serotonergic and NB neurons interact in the regulation of cognitive functions.


Clostridioides difficile: Sometimes It Pays To Be Difficult.
In this issue of Cell Host & Microbe, publications from Bushman et al. (2020) and Knippel et al. (2020) outline elements of host epithelial damage or inflammation that Clostridioides difficile subverts, enabling continued growth. These mechanisms provide insight into how this important pathogen influences the gut environment to promote its metabolic strategy during infection.


Comparison and identification of metabolic profiling of bicyclol in rats, dogs and humans in vitro and in vivo.
Bicyclol, a novel hepatoprotective agent, has been widely used to treat chronic viral hepatitis and drug-induced liver injury (DILI). However, its metabolic characteristics remains to be explored, especially in humans. The current study aimed to identify major metabolites and specific metabolizing enzymes involved in bicyclol metabolism in vitro and in vivo using high performance liquid chromatography coupled with Q-Exactive orbitrap mass spectrometry (HPLC-Q-Exactive Orbitrap/MS). After incubation with liver microsomes and oral administration to rats, dogs and humans, a total of nine metabolites of bicyclol were identified including M1 (methyl ester hydrolysate product), M2-M3 (demethylated bicyclol), M4-M5 (demethoxy or dehydroxymethyl bicyclol), M6 (glucuronidated bicyclol) and M7-M9 (glucuronide conjugates of metabolites). Among these metabolites, M2 and M3 were the major phase I metabolites mainly mediated by CYP2C19 and CYP3A4, while M6 was the dominant phase II metabolite primarily catalyzed by UGT2B4. In this study, species-related metabolic difference among rats, dogs and humans were observed. In humans and dogs, M6 (glucuronidated bicyclol) was the most abundant circulating metabolite (higher than the parent drug) in the blood after oral administration, while the parent drug was the highest in rats. M4 and M5 were rats-specific metabolites whereas M1 and M9 were absent in dogs in vivo. The metabolism of bicyclol was demonstrated as demethylation and glucuronidation mediated by multiple drug metabolizing enzymes in different species. Our findings systematically elucidated the metabolic sites and routes of bicyclol in human for the first time, which may be helpful for rational combined application in clinic and further study of metabolites-related efficacy or toxicity.


A prospective observational study of recall of discomfort on tracheal extubation after general anaesthesia.
Tracheal extubation is a critical stage in the management of general anaesthesia during which serious complications may occur. Immediately before extubation, patients often exhibit signs that suggest that they are awake and experiencing discomfort. There is concern that patients may retain such memories of the extubation process. However, previous studies have not examined patient recall of extubation in detail. We therefore investigated the frequency of recall of discomfort during extubation, as well as first orientation to place, and other recollections upon emerging from general anaesthesia. In a prospective observational study, 818 patients were interviewed during routine post-anaesthesia rounds on the day after general anaesthesia. The primary outcome was the proportion of patients recalling discomfort during extubation. The secondary outcome was the location of orientation to place upon emerging from general anaesthesia. Recall of discomfort during extubation was uncommon, at 1.1% (n=9; 95% confidence interval [CI]: 0.5-2.1%). Only 3.1% of patients recalled the extubation process at all (n=25; 95% CI: 2.0-4.5%). The first orientation to place was most commonly in transit to a ward, in 41% of cases (n=337; 95% CI: 38-45%). Recall of discomfort during extubation appears to be rare, and the great majority of patients may not retain any memory of the extubation process. This information may be used to reassure patients and guide extubation practices for anaesthetists. UMIN Clinical Trials Registry (UMIN000046136).


Multifunctional IgG/IgM antibodies and cellular cytotoxicity are elicited by the full-length MSP1 SumayaVac-1 malaria vaccine.
Radical control of malaria likely requires a vaccine that targets both the asymptomatic liver stages and the disease-causing blood stages of the human malaria parasite Plasmodium falciparum. While substantial progress has been made towards liver stage vaccines, the development of a blood stage vaccine is lagging behind. We have recently conducted a first-in-human clinical trial to evaluate the safety and immunogenicity of the recombinant, full-length merozoite surface protein 1 (MSP1FL) formulated with GLA-SE as adjuvant. Here, we show that the vaccine, termed SumayaVac-1, elicited both a humoral and cellular immune response as well as a recall T cell memory. The induced IgG and IgM antibodies were able to stimulate various Fc-mediated effector mechanisms associated with protection against malaria, including phagocytosis, release of reactive oxygen species, production of IFN-γ as well as complement activation and fixation. The multifunctional activity of the humoral immune response remained for at least 6 months after vaccination and was comparable to that of naturally acquired anti-MSP1 antibodies from semi-immune adults from Kenya. We further present evidence of SumayaVac-1 eliciting a recallable cellular cytotoxicity by IFN-γ producing CD8+ T cells. Our study revitalizes MSP1FL as a relevant blood stage vaccine candidate and warrants further evaluation of SumayaVac-1 in a phase II efficacy trial.


Effect of hCG administration on Day 7 post-mating on accessory corpus luteum development and progesterone concentration in llamas.
A high embryo loss rate has been reported in llamas. As strategies that lead to an increase in plasma progesterone (P4) concentration might improve fertility, the aim of the present study was to evaluate if the administration of hCG on Day 7 post-mating is useful to develop an accessory corpus luteum (CL), increasing plasma P4 concentration. Twenty (n = 20) female llamas, ranging between 5 and 10 years of age and four (n = 4) males of proven fertility, ranging between 8 and 10 years of age were included in the study. Accessory CL developed in all treated llamas after hCG administration and plasma P4 concentration was significantly greater in treated than in control females (P˂0.0001). The diameter and vascularization of the original CL were not affected by treatment in pregnant llamas. However, in treated non-pregnant llamas, corpus luteum diameter was greater than in the control group from Day 14 post-mating until the end of the study (P˂0.001). In treated llamas, the accessory CL was detected throughout the study in pregnant and non-pregnant females, but its vascularization started to decrease around Day 16 post-mating in non-pregnant animals (P˂0.05). In conclusion, hCG treatment on Day 7 post mating was useful to induce an accessory CL and increase plasma P4 concentration in llamas. Thus, this treatment could be considered as a useful strategy to improve pregnancy rates in llama herds.


Activating receptor KIR2DS2 bound to HLA-C1 reveals the novel recognition features of activating receptor.
Killer cell immunoglobulin-like receptors (KIRs) are important receptors for regulating the killing of virus-infected or cancer cells of natural killer (NK) cells. KIR2DS2 can recognize peptides derived from hepatitis C virus (HCV) or global flaviviruses (such as dengue and Zika) presented by HLA-C*0102 to activate NK cells, and has shown promising results when used for cancer immunotherapy. Here, we present the complex structure of KIR2DS2 with HLA-C*0102 at a resolution of 2·5Å. Our structure reveals that KIR2DS2 can bind with HLA-C*0102 and HLA-A*1101 in two different directions. Moreover, Tyr45 (in activating receptor KIR2DS2) and Phe45 (in inhibitory KIRs) distinguish the two different binding models and binding affinity between activating KIRs and inhibitory KIRs. The conserved 'AT' motif of the peptide mediates recognition and determines the peptide specificity of recognition. These structural characteristics shed light on how KIRs activate NK cells and can provide a molecular basis for immunotherapy by NK cells.


The Impact of the COVID-19 Pandemic on Intimate Partner Violence Advocates and Agencies.
Relatively few studies have considered the impact of the COVID-19 pandemic on intimate partner violence (IPV) advocates or the agencies where they work. In this study, based on United States IPV advocates' experiences working with survivors during the COVID-19 pandemic, we conducted interviews to explore: 1) personal challenges and resilience working as IPV advocates during the COVID-19 pandemic; 2) how agencies adapted to the pandemic to support IPV survivors and advocates; and 3) specific needs and challenges of culturally-specific agencies. We conducted semi-structured interviews with 53 IPV advocates from June to November 2020. Participants were included if they worked directly with survivors, identified as an IPV advocate, worked at a US-based agency, and spoke and understood English. We created a sampling matrix to ensure adequate representation from IPV advocates serving survivors from communities which have been marginalized. Interviews were conducted through a virtual platform by a trained member of the research team. We used an inductive thematic analysis approach, with weekly coding meetings to resolve discrepancies in coding. Five themes emerged from the data: 1) IPV advocates described how working as an IPV advocate during the COVID-19 pandemic impacted them personally; 2) agencies developed new methods of addressing IPV advocates' needs; 3) agencies developed new solutions to address pandemic-related client needs; 4) transitioning advocacy work to virtual formats created challenges but also opportunities and; 5) pandemic limitations and impacts compounded pre-pandemic challenges for culturally specific agencies. IPV advocates are frontline workers who have played essential roles in adjusting services to meet survivor needs during the COVID-19 pandemic while simultaneously coping with pandemic impacts on themselves and their agencies. Developing inter-agency collaborations and promoting advocates' safety and wellbeing during future public health crises will help support IPV survivors.


Lymphoid enhancer factor interacts with GATA-3 and controls its function in T helper type 2 cells.
GATA-3 is the master transcription factor for T helper 2 (Th2) cell differentiation and is critical for the expression of Th2 cytokines. Little is known, however, about the nature of the functional molecular complexes of GATA-3. We identified a high-mobility group (HMG)-box type transcription factor, lymphoid enhancer factor 1 (LEF-1), in the GATA-3 complex present in Th2 cells using a Flag-calmodulin-binding peptide (CBP)-tag based proteomics method. The interaction between GATA-3 and LEF-1 was confirmed by co-immunoprecipitation experiments using LEF-1-introduced T-cell lineage TG40 cells. The HMG-box domain of LEF-1 and two zinc finger domains of GATA-3 were found to be important for the physical association. The introduction of LEF-1 into developing Th2 cells resulted in the suppression of Th2 cytokine production. The suppression was significantly lower in the cells into which a HMG-box-deleted LEF-1 mutant was introduced. Moreover, LEF-1 inhibited the binding activity of GATA-3 to the interleukin (IL)-5 promoter. These results suggest that LEF-1 is involved in the GATA-3 complex, while also regulating the GATA-3 function, such as the induction of Th2 cytokine expression via the inhibition of the DNA-binding activity of GATA-3.


Spatial organization of a desert rodent community: food addition and species removal.
From 1977 through 1983 we conducted experiments on a desert rodent community where supplemental seeds were added or certain rodent species and ants were removed from 0.25-ha fenced plots in a Chihuahuan Desert site in southeastern Arizona, USA. In this paper we examine the patterns of microhabitat use relative to vegetative cover by 11 rodent species. The results show that: i) removal of the largest seed-eating species, Dipodomys spectabilis, produced the most pervasive and dramatic shifts in microhabitat use by the remaining rodent species; ii) adding seeds or removing ants had little effect on the spatial use of microhabitats by rodents in this community; and iii) non-granivores were just as likely as granivores to shift microhabitat use when other granivores were removed. We believe these results indicate that both food and foraging microsites are limited but the relegation of subdominant species to lesspreferred microhabitats by the large Dipodomys spectabilis is the major factor underlying the spatial organization of this community. Results also demonstrate that strong interactions among species increase the probability that pathways of indirect interactions through intermediary species are important; these complex linkages may include species that overlap little in food preferences.


Lowering urinary oxalate excretion to decrease calcium oxalate stone disease.
Dietary modifications should be considered as a first line approach in the treatment of idiopathic calcium oxalate nephrolithiasis. The amounts of oxalate and calcium consumed in the diet are significant factors in the development of the disease due to their impact on urinary oxalate excretion. There are a number of strategies that can be employed to reduce oxalate excretion. The consumption of oxalate-rich foods should be avoided and calcium intake adjusted to 1000-1200 mg/day. To encourage compliance it should be emphasized to patients that they be vigilant with this diet as a deviation in any meal or snack could potentially result in significant stone growth. The evidence underlying these two modifications is outlined and other strategies to reduce urinary oxalate excretion are reviewed.


Description of a New Clade within Subtype 1 of Betaarterivirus suid 1 Causing Severe Outbreaks in Spain.
This report describes 28 genome sequences from a new clade within subtype 1 of Betaarterivirus suid 1, formerly known as porcine reproductive and respiratory syndrome virus 1. All share a potential recombinant pattern, with a highly pathogenic Italian strain as the putative major parental sequence and three other possible parents.


Should you repeat mismatch repair testing in cases of tumour recurrence? An evaluation of repeat mismatch repair testing by the use of immunohistochemistry in recurrent tumours of the gastrointestinal and gynaecological tracts.
The role of mismatch repair (MMR) testing has evolved from identifying Lynch syndrome patients to predicting response to immune checkpoint inhibitors. This has led to requests from clinicians to retest recurrences of MMR-proficient primary tumours in the hope that the recurrence may show a different MMR status and qualify the patient for treatment. We aimed to determine whether repeat testing is warranted. We evaluated recurrent tumours (local recurrences or metastases) from 137 patients with MMR-proficient primary tumours of the gastrointestinal and gynaecological tracts. The local recurrences and metastases all occurred at least 30 days after resection of the primary tumour. We used a combination of a tissue microarray and whole slide staining to perform immunohistochemistry (IHC) for PMS2, MLH1, MSH2, and MSH6, and compared the results with the MMR status of the primary tumour. Three of 137 (2%) initially showed a discordant staining pattern. However, further investigation showed that these discordances were attributable to some of the known pitfalls associated with MMR IHC interpretation - post-radiotherapy loss of MSH6 expression and subclonal loss of MLH1 staining. We did not identify any cases with a genuine discordance in MMR status. We conclude that repeat MMR IHC testing of recurrences is not warranted, as MMR status does not change relative to that of the primary tumour.


Electrochemical luminescence-based homogeneous immunoassay.
Aromatic hydrocarbon such as pyrene capable of generating electrochemical luminescence was employed as a label of immunoassay. Pyrene labeled antigen generated luminescence upon electrolytic reduction, while the luminescence decreased remarkably in the presence of antibody. The labeled antigen (constant) and free antigen were competitively reacted to the constant amount of antibody. The luminescence was correlated to the antigen concentration as little as 10(-6)M antigen. The proposed method is a very unique immunochemical technique which requires no BF separation.


Impact of Obesity and Visceral Fat on Mortality in Hematopoietic Stem Cell Transplantation.
Many studies have shown the importance of body composition parameters, muscle, and fat mass, evaluated by several methods in hematopoietic stem cell transplantation (HSCT) outcomes. Ultrasound (US) is an efficient and low-cost method to evaluate body composition, even though there have not been many studies in HSCT. Our goal was to investigate the muscle, visceral fat (VF), and echogenicity before HSCT and after engraftment, evaluated by US and its association with outcomes. All adult patients with hematological malignances admitted for HSCT autologous and allogeneic were eligible to enter this prospective study. Their thigh muscle thickness, VF, and echogenicity were evaluated by US on the first day of hospitalization (baseline) and after engraftment (15-25 days post-HSCT). We evaluated 50 patients; 42% were male and 58% had undergone allogeneic HSCT. Most patients were <55 years old (68%) and had normal body mass index (50%). We found a significant reduction of right and left muscle thickness (P < .001) and echogenicity (P = .002) after engraftment compared with baseline. Our elderly patients had significantly bigger right-thigh muscle thickness (P = .02) and more VF (P = .009). The following data were higher in obese patients: right and left muscle thickness (P < .001), VF (P = .003), and echogenicity (P = .04). Death in the first 100 days had a positive association with obesity (P = 0.001) and VF (P = .002). VF was the only variable independent of HSCT type and age in mortality risk. Obesity and VF had an important impact in mortality. US could be a useful tool and strategy for evaluating body composition in HSCT patients.


Is Infection an Independent Risk Factor for Venous Thromboembolism? A Population-Based, Case-Control Study.
The independent association of recent infection with venous thromboembolism is uncertain. The study aims were to test both overall infection (site unspecified) and specific infection sites as potential risk factors for deep vein thrombosis and pulmonary embolism adjusting for other known venous thromboembolism factors. By using Rochester Epidemiology Project resources, we identified all Olmsted County, Minnesota, residents with objectively diagnosed incident deep vein thrombosis or pulmonary embolism over the 13-year period 1988 to 2000 (cases; n = 1303) and 1 to 2 residents without venous thromboembolism matched to each case on age, sex, and incident venous thromboembolism date (controls; n = 1494). Using conditional logistic regression, we tested recent infection and infection site(s) for an association with venous thromboembolism, adjusting for body mass index, smoking, current/recent hospitalization with/without surgery, nursing home confinement, active cancer, trauma/fracture, leg paresis, prior superficial vein thrombosis, transvenous catheter/pacemaker, ischemic heart disease, congestive heart failure, chronic lung or renal disease, serious liver disease, asthma, diabetes mellitus, hormone therapy, and pregnancy/postpartum. A total of 513 cases (39.4%) and 189 controls (12.7%) had an infection in the previous 92 days (odds ratio, 4.5; 95% confidence interval, 3.6-5.5; P < .0001). In a multivariable analysis adjusting for common venous thromboembolism risk factors, pneumonia and symptomatic urinary tract, oral, intra-abdominal, and systemic bloodstream infections were associated with significantly increased odds of venous thromboembolism. Infection as a whole and specific infection sites in particular are independent risk factors for venous thromboembolism and should be considered as potential indications for venous thromboembolism prophylaxis.


Developing a risk/cost framework for routing truck movements of hazardous materials.
As the United States continues to increase its dependence on industrial technologies which require hazardous materials and generate hazardous wastes, concern is mounting over the safe transport of hazardous cargo. It is estimated that 1.5 billion tons of hazardous cargo are moved through the nation's transportation systems (excluding pipeline), with truck as the primary mode of transport. Because of the dynamic nature of exposure to the population and environment associated with the transport of hazardous cargo, it is important to develop an accurate representation of this type of transport risk, and to structure a framework for designating a permanent set of shipping routes based on optimizing across risks and costs. This paper describes a methodology which has been developed that incorporates risk and cost into a framework for optimizing the routing of truck movements of hazardous materials. Considerable attention is focused on the risk estimation part of this process, as this is a subject of much uncertainty and of considerable significance to policymakers. The resulting methodology is applied in a regional setting to illustrate its use as an analysis tool. Enhancements to the model structure and extensions beyond the truck routing problem are also discussed.


A case of cerebral astroblastoma with rhabdoid features: a cytological, histological, and immunohistochemical study.
Astroblastoma is a rare neuroepithelial neoplasm of unknown origin, usually occurring in children and young adults. Here we report a case of astroblastoma with uncommon features in an 18-year-old female. The tumor was a well-circumscribed cystic and solid mass with marked gadolinium enhancement in the right frontal lobe. Cytological examination showed polarized monopolar cells with diminished cohesiveness. Tumor cells possessed eccentric round to oval nuclei with abundant eosinophilic cytoplasm, sometimes having cytoplasmic processes. Histopathologically, the tumor showed perivascular pseudorosettes with prominent vascular sclerosis. Foam cells were frequently infiltrated around blood vessels and among tumor cells. In some areas, a solid growth pattern of plump tumor cells with abundant inclusion-like eosinophilic cytoplasm showing rhabdoid appearance was observed. The immunohistochemical study revealed strong and diffuse positivity for vimentin and epithelial membrane antigen. Tumor cells were focally positive for glial fibrillary acidic protein and cytokeratin AE1/AE3. Nuclear immunoreactivity for INI1 protein was evident. The Ki-67 labeling index was 10.8%. This tumor was finally diagnosed as low-grade astroblastoma and the patient had no evidence of recurrence without postoperative radiotherapy or chemotherapy during the last 6 months of follow-up. This report describes novel cytological, histopathological, and immunohistochemical features of the rare tumor.


Catalytic functionalization of unactivated primary C-H bonds directed by an alcohol.
New synthetic methods for the catalytic functionalization of C-H bonds have the potential to revolutionize the synthesis of complex molecules. However, the realization of this synthetic potential requires the ability to functionalize selectively one C-H bond in a compound containing many such bonds and an array of functional groups. The site-selective functionalization of aliphatic C-H bonds is one of the greatest challenges that must be met for C-H bond functionalization to be used widely in complex-molecule synthesis, and processes catalysed by transition-metals provide the opportunity to control selectivity. Current methods for catalytic, aliphatic C-H bond functionalization typically rely on the presence of one inherently reactive C-H bond, or on installation and subsequent removal of directing groups that are not components of the desired molecule. To overcome these limitations, we sought catalysts and reagents that would facilitate aliphatic C-H bond functionalization at a single site, with chemoselectivity derived from the properties of the catalyst and site-selectivity directed by common functional groups contained in both the reactant and the desired product. Here we show that the combination of an iridium-phenanthroline catalyst and a dihydridosilane reagent leads to the site-selective γ-functionalization of primary C-H bonds controlled by a hydroxyl group, the most common functional group in natural products. The scope of the reaction encompasses alcohols and ketones bearing many substitution patterns and auxiliary functional groups; this broad scope suggests that this methodology will be suitable for the site-selective and diastereoselective functionalization of complex natural products.


The first phase of nocturnal sleep in mentally retarded children.
The first phase of sleep observed in 104 mentally retarded children (from 3 months to 8 years of age) was studied throughout nocturnal sleep, and the following results were obtained. In 4 out of 104 subjects, REM sleep onset was observed, and in the remaining 100 subjects NREM sleep onset was found at the first wakefulness-sleep transition of the night. Following awakenings (lasting 4 min or more) during the night, 170 (51.7%) out of a total of 329 samples were REM sleep onset, and 159 (48.3%) showed NREM sleep onset. The phases of sleep onset and those following awakenings evidenced no correlation between the frequency of NREM sleep onset and DQ or clinical EEG, whereas a positive correlation was found between the frequency of NREM sleep onset and age.


Molecular characterization of a thioredoxin h gene (HbTRX1) from Hevea brasiliensis showing differential expression in latex between self-rooting juvenile clones and donor clones.
The cDNA code of thioredoxin h, designated as HbTRX1, was isolated from Hevea brasiliensis by rapid amplification of cDNA ends. HbTRX1 contained a 542-bp open reading frame encoding 123 amino acids. The deduced HbTRX1 protein showing high identity to thioredoxin h of other plant species was predicted to possess the conserved catalytic site WCXPC. Semiquantitative reverse transcription-polymerase chain reaction analysis revealed that HbTRX1 was constitutively expressed in all tested tissues. HbTRX1 transcripts accumulated at relatively low levels in the flower, somatic embryo, and leaves, while HbTRX1 transcripts accumulated at relatively high levels in the callus and latex. The HbTRX1 transcript was expressed at different levels, with higher levels in self-rooting juvenile clones than in their donor clones. HbTRX1 was expressed in Escherichia coli, and its activity was demonstrated using the dithiothreitol-dependent insulin assay. This work provides a basis for studying the biological function of thioredoxin h in rubber tree.


Seagrass beds acting as a trap of microplastics - Emerging hotspot in the coastal region?
Microplastics is an emerging environmental problem in the world. However, presence and fate of microplastics in seagrass meadows are barely known. In this study, the abundance and diversity of microplastic from Enhalus acodoides vegetated sites and bare sites were quantified and characterized in Xincun bay and Li'an bay, Hainan, China. Microplastics ranged from 80.0 to 884.5 particles per kg of dry sediment, and fibers were the dominant shape. The most frequent colors of microplastics were blue, transparent and black. The dominant size of microplastics was in the range of 125-250 μm. And the seagrass sediments were enriched in microplastics 2.1 and 2.9 times for Xincun bay and Li'an bay, respectively. The trap effect of seagrass was non-selective regarding the shape, color and size of microplastics. High anthropogenic pollution and poor beach management may contribute to higher concentrations of microplastics in Li'an bay.


Gamma tropomyosin gene products are required for embryonic development.
The actin filament system is essential for many cellular functions, including shape, motility, cytokinesis, intracellular trafficking, and tissue organization. Tropomyosins (Tms) are rod-like components of most actin filaments that differentially affect their stability and flexibility. The Tm gene family consists of four genes, alphaTm, betaTm, gammaTm (Tm5 NM, where "NM" indicates "nonmuscle"), and deltaTm (Tm4). Multiple isoforms of the Tm family are generated by alternative splicing of three of these genes, and their expression is highly regulated. Extensive spatial and temporal sorting of Tm isoforms into different cellular compartments has been shown to occur in several cell types. We have addressed the function of the low-molecular-weight Tms encoded by the gammaTm gene by eliminating the corresponding amino-terminal coding sequences from this gene. Heterozygous mice were generated, and subsequent intercrossing of the F1 pups did not result in any viable homozygous knockouts. Genotype analysis of day 2.5 morulae also failed to detect any homozygous knockouts. We have failed in our attempts to delete the second allele and generate in vitro double-knockout cells, although 51 clones displayed homologous recombination back into the originally targeted locus. We therefore conclude that low-molecular-weight products from the gammaTm gene are essential for both embryonic development and cell survival.


[A family with the EEC syndrome (ectrodactily, ectodermal dysplasia clefting syndrome): clinical variability and genetic counseling].
In a family with segregation of EEC-Syndrome we observed five children--two girls and three males--(two of them dizygotic twins) affected by very various phenotypes of the syndrome. The ocular symptomatology was represented by agenesis or stenosis of lacrimal ducts: two children were operated, the other suffered from frequent inflammations. The study of the family suggest an autosomic dominant heredity with defect of penetrance on the father.


Parental investment related to social systems in microtines.
Laboratory offspring of wild-caught voles Clethrionomys glareolus and Microtus agrestis, bred for 1 year under constant conditions, were examined with regard to sex ratios and weights at weaning and at 2 months of age. C. glareolus exhibits female territoriality and M. agrestis male territoriality in summer. The adults die away in late summer-autumn. Early-summer young mature in the year of birth but late-summer young do not reach maturity until the following year. C. glareolus young showed a male bias in early summer and a female bias in late summer. Conditions were the opposite but less clear in M. agrestis. C. glareolus males grew comparatively faster than M. agrestis males and showed a markedly higher early summer male: female weight ratio at 2 months of age. Maternal investment thus appears clearly related to the social system; the sex with the largest number and highest quality of young was that which was not limited in number by territoriality. However, the investment depended also on the time until maturation of the young.


The levels and relations of prostaglandins in pregnant and non-pregnant tumor-bearing mice.
Tissue levels of prostaglandins PGE1, PGE2, PGF1 alpha and PGF2 alpha were determined in muscle tissues of pregnant, and in tumor tissue of pregnant tumor-bearing female syngeneic Balb/c mice bearing a transplanted methylcholanthrene-induced fibrosarcoma. Tests were done on the 7th, 10th, and 15th days of tumor growth/pregnancy using a thin-layer chromatography method. The results showed significantly increased levels of prostaglandins in tumor-bearing animals as well as in pregnant tumor-bearing hosts when compared to controls. Changes in the levels of PGE1 in pregnant mice were the most prominent among all prostaglandins tested. In these animals, the mutual relations between prostaglandin subclasses were not affected. In tumor-bearing mice, especially those which were pregnant, the inversion of prostaglandins of the E series was observed. Tumor changed the levels of the E series prostaglandins in favour of PGE2. However, it did not change the relation between those of the F series. The levels of PGE2 were more expressed in pregnant tumor-bearing hosts than in their non-pregnant counterparts. This has led us to the conclusion that, besides the malignant tumor, the pregnancy itself also potentiates immunosuppression. Blocking of PGE2 production in tumor-bearing animals might have potential therapeutic implications.


L-2-oxothiazolidine-4-carboxylate protects cultured endothelial cells against hyperoxia-induced injury.
When bovine pulmonary artery endothelial monolayers were exposed to hyperoxia (95% O2 and 5% Co2), they responded by selectively elevating the intracellular concentration of glutathione without affecting the activities of glutathione peroxidase or glutathione reductase, L-2-Oxothiazolidine-4-carboxylate, an intracellular cysteine-delivering agent, further enhanced the intracellular concentration of glutathione in oxygen-exposed endothelial cells and protected them from the lethal effect of hyperoxia. In contrast, buthionine sulfoximine, a potent inhibitor of gamma-glutamylcysteine synthetase, reduced the glutathione concentration and rendered the cells more sensitive to the toxic effect of oxygen. Both L-2-oxothiazolidine-4-carboxylate and buthionine sulfoximine had no effect on the activities of glutathione peroxidase or glutathione reductase. Our results suggest that L-2-oxothiazolidine-4-carboxylate may have the potential of preventing oxygen toxicity.


An international survey and modified Delphi process revealed editors' perceptions, training needs, and ratings of competency-related statements for the development of core competencies for scientific editors of biomedical journals.
Background: Scientific editors (i.e., those who make decisions on the content and policies of a journal) have a central role in the editorial process at biomedical journals. However, very little is known about the training needs of these editors or what competencies are required to perform effectively in this role. Methods: We conducted a survey of perceptions and training needs among scientific editors from major editorial organizations around the world, followed by a modified Delphi process in which we invited the same scientific editors to rate the importance of competency-related statements obtained from a previous scoping review. Results: A total of 148 participants completed the survey of perceptions and training needs. At least 80% of participants agreed on six of the 38 skill and expertise-related statements presented to them as being important or very important to their role as scientific editors. At least 80% agreed on three of the 38 statements as necessary skills they perceived themselves as possessing (well or very well). The top five items on participants' list of top training needs were training in statistics, research methods, publication ethics, recruiting and dealing with peer reviewers, and indexing of journals. The three rounds of the Delphi were completed by 83, 83, and 73 participants, respectively, which ultimately produced a list of 23 "highly rated" competency-related statements and another 86 "included" items. Conclusion: Both the survey and the modified Delphi process will be critical for understanding knowledge and training gaps among scientific editors when designing curriculum around core competencies in the future.


Effects of neurotrophins on human bronchial smooth muscle cell migration and matrix metalloproteinase-9 secretion.
The neurotrophins nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophin-3 (NT-3) have been found to be upregulated in inflammatory pulmonary diseases, including asthma. The functional role for the neurotrophins in the airways is still not known, but it has been proposed that neurotrophins induce airway hyperreactivity and tissue remodeling. Bronchial smooth muscle cells have been suggested to be involved in the remodeling process through their capacity to proliferate, migrate, and secrete inflammatory mediators and matrix metalloproteinases (MMPs). Therefore, we studied the effect of NGF, BDNF, and NT-3 on human bronchial smooth muscle cell (HBSMC) migration and MMP-2 and MMP-9 secretion. Immunocytochemistry studies showed that HBSMCs expressed the neurotrophin receptors TrkA, TrkB, and TrkC. BDNF, NT-3, and NGF increased MMP-9, but not MMP-2, secretion as shown by zymography. BDNF and NT-3, but not NGF, stimulated HBSMC migration as evaluated by Boyden chamber. Taken together, our data indicate that the neurotrophins may stimulate events important for airway remodeling.


Reliability and validity of pelvic floor muscle strength assessment using the MizCure perineometer.
The purpose of this study was to clarify the reliability and validity of pelvic floor muscle (PFM) strength assessment using the MizCure perineometer in healthy women. Twenty healthy women (age 20-45 years) participated in this study. The vaginal pressure measured using the MizCure and validated Peritron perineometers were repeated during PFM contraction in the supine and standing positions. All women were evaluated twice by examiners 1 and 2. Following the measurements in the first session (Test 1), they were repeated after an interval of between 2 and 6 weeks (Test 2). Within- and between-session intra- and inter-rater reliabilities in vaginal pressure were analyzed using intraclass correlation coefficients (ICC) (1, 1) and (2, 1), respectively. Validity was assessed by Pearson's product-moment correlation coefficient and Spearman's rank correlation analysis. Within-session intra-rater reliabilities for both examiners 1 and 2 for all vaginal pressures in Tests 1 and 2 were 0.90-0.96 for both perineometers. Between-session intra-rater reliability for the MizCure was 0.72-0.79 for both positions for examiner 1, and 0.63 in the supine position and 0.80 in the standing position for examiner 2. Inter-rater reliability for Test 1 was 0.91 in the supine position and 0.87 in the standing position for the MizCure. The vaginal pressures using the MizCure and Peritron were significantly associated with the supine position (r = 0.68, P < .001) and the standing position (rs = 0.82, P < .001). MizCure perineometer is a validated tool to measure PFM strength in both supine and standing positions in healthy nulliparous women.


Mild depressive symptoms are associated with elevated C-reactive protein and proinflammatory cytokine levels during early to midgestation: a prospective pilot study.
We examined depressive symptoms, C-reactive protein (CRP), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) levels during early to-midgestation. We measured depressive symptoms on the Patient Health Questionnaire-9 (PHQ-9), and serum CRP, IL-6, and TNF-α levels twice in 27 pregnant women. After adjustment, depressive symptoms prospectively (β=0.42, p<0.05 at 16-20 weeks of gestation) and concurrently (β=0.54, p<0.01 at 7-10 weeks of gestation) predicted elevated CRP [F (2, 14)=9.20, p=0.003, R(2)=0.57 and F (3, 15)=9.08, p=0.001, R(2)=0.64, respectively]. There were similar patterns of results for TNF-α (β=0.72, p<0.01) and IL-6 levels (β=0.39, p<0.05) at 7-10 weeks of gestation [F (2,19)=8.84, p=0.002, R(2)=0.48]. Furthermore, the association between depressive symptoms at 7-10 weeks of gestation and increased IL-6 levels at 16-20 weeks of gestation approached statistical significance. We confirmed the findings with the Wilcoxon signed rank test (IL-6: Z=2.44, p=0.015; TNF-α: Z=1.94, p=0.05; CRP: approached statistical significance). These pilot data suggest that depressive symptoms may be associated with inflammatory markers during early to-midgestation.


[Influence of SO2 on the amino acid metabolism of pea seedlings].
Long-termed fumigation of pea seedlings with SO2 caused typical alterations of the concentration of free glutamate and glutamine as well as fluctuations of the activity of glutamate dehydrogenase and glutamine synthetase. Shortly after the beginning of the fumigation with low concentrations of SO2 (up to 0,3 ppm) the amount of glutamate increased. The concentration of glutamine however increases always independently of the concentration of SO2. The activity of glutamate dehydrogenase (reductive amination of α-ketoglutarate) generally increased. In roots of fumigated seedlings the effects of SO2 on the concentration of both glutamate and glutamine as well as on the activity of GDH are quite similar to those observed in shoots. Metabolic sequences derived from glutamate seem to be activated by SO2 as can be seen by the increase of the concentration of glutamine and γ-aminobutyric acid.


Risk factors and long-term outcomes of elderly patients complicating with acute kidney injury after type A acute aortic dissection surgery: a retrospective study.
To identify risk factors and long-term outcomes for acute kidney injury (AKI) in elderly patients who underwent type A acute aortic dissection (TA-AAD) emergency surgeries. This retrospective study enrolled 214 consecutive patients who underwent TA-AAD emergency surgeries between January 2014 to December 2018 in Nanjing Drum Tower hospital. The diagnosis of AKI was made based on the Kidney Disease: Improving Global Outcomes definition (KDIGO) criteria. Multivariable regression analysis was performed to identify risk factors for postoperative AKI. Kaplan-Meier curves were generated to compare the long-term outcomes between patients with and without AKI complication after TA-AAD surgeries. Among all enrolled patients, 114 (53.3%) developed AKI during postoperative period. The median age of patients with or without AKI was 68.0 (64.0, 74.0) and 66.0 (62.0, 72.8) years respectively. Renal replacement therapy (RRT) was required in 43 patients (20.1%). The 30-day mortality rate was 21.5% in all enrolled patients with 26.3% in AKI group and 16.0% in non-AKI group (P=0.067) respectively. Longer mechanical ventilation duration was identified as the only independent risk factor for developing AKI by multivariable logistic regression analysis. In addition, our data suggested that the long-term cumulative survival rate was different between two groups. Postoperative AKI after TA-AAD surgeries was common and associated with worsened long-term mortality in elderly patients. Longer postoperative mechanical ventilation duration was identified as the only independent risk factor for the development of AKI.


The effect of play on immobilized children in hospital.
Organized play is not always given a high priority in the hospitalized child's total care with the result that insufficient time is allocated to its provision in the nursing care plan. The effects of such incomplete patient care are far reaching for the immobilized child in hospital. The study was designed to determine if a difference existed in the perception of time, social space and self for two groups of immobilized children in hospital. An experimental design was used. Sixty immobilized children were randomly assigned to the experimental or control group. Children in the control group were exposed to the regular ward stimuli while the experimental group participated in four periods of planned play designed to expand the child's life space. Children were interviewed following the play periods and data analysed using quantitative and qualitative analysis. Findings indicate that immobilized children exposed to planned play periods expressed more positive feelings toward themselves and significant others than the control group. As well, findings indicated that hospitalized immobilized children were in a state of waiting and increased vigilance which resulted in the dragging of time and loss of temporal integrity.


The concept of placebo.
This paper attempts to define the concept of placebo as it is used in the clinical context The author claims that X is a placebo if and only if X has such a property dp, that whenever in a therapeutic situation T a stimulus S appears, then in attending conditions A, it will cause a beneficial reaction R in the patient. Formally, the same structure may be used to define any pharmacologically active drug. The main difference between the drug and a placebo is in the range of possible substitutions for X and the property d. For the active drug there is only one possible substitution for X and property d and it can be scientifically explained why, and how the drug works. In the case of a placebo a set of possible substitutions for X and d is open, and so far it is impossible to offer any scientifically valid explanation of the action mechanism of placebo.


Mechanical determinants of nectar feeding strategy in hummingbirds: energetics, tongue morphology, and licking behavior.
To explore the mechanical determinants of feeding strategies for nectar feeders, we develop a fluid dynamical and behavioral model describing the mechanics and energetics of capillary feeding in hummingbirds. Behavioral and morphological data for Calypte and Archilochus are used to test and illustrate this model. We emphasize the important differences between capillary and suction mechanisms of fluid feeding. Model predictions of nectar intake rates and nectar volumes per lick are consistent with observed values for Calypte anna. The optimal nectar concentration maximizing rate of energy intake depends on tongue morphology and licking behavior. For hummingbirds exhibiting optimal licking behavior, the optimal nectar concentration is 35-40% sucrose for feeding on large nectar volumes. For small nectar volumes, the optimal concentration is 20-25%. The model also identifies certain tongue morphologies and licking frequencies maximizing energy intake, that are consistent with available observations on licking behavior and tongue design in nectar feeding birds. These predictions differ qualitatively from previous results for suction feeding in butterflies.The model predicts that there is a critical food canal radius above which suction feeding is superior to capillary feeding in maximizing the rate of energy intake; the tongues of most hummingbirds and sunbirds fall above this critical radius. The development of suction feeding by nectarivorous birds may be constrained by the elastic properties of their flexible tongues. Our results show that, in terms of morphology, scaling, and energetics, different mechanisms of feeding on the same food resource can lead to qualitatively different predictions about optimal design and feeding strategies.


Robust state estimation using desensitized Divided Difference Filter.
This paper develops a robust divided difference filtering approach based on the concept of Desensitized Kalman Filtering. The filters are formulated using a minimum variance cost function, augmented with a penalty function consisting of a weighted norm of the state sensitivities. Solutions are provided for first and second-order Divided Difference Filters. The resulting filters are non-minimum variance but exhibit reduced sensitivity to deviations in the assumed plant model parameters. The proposed algorithms are demonstrated using Monte Carlo simulation techniques for an induction motor state estimation problem with parameter uncertainties.


Learning home telehealth: new opportunities.
This article outlines a telehealth training program through East Carolina University. As clinicians and managers learn more about this new way to deliver services, this course provides a needed primer of this emerging field.


Biosimilars: The viewpoint of Italian patients with inflammatory bowel disease.
The viewpoint on biosimilars among patients with inflammatory bowel diseases (IBD) is largely unknown. We aimed at exploring the confidence and opinion on biosimilars among Italian patients with IBD. An anonymous, 20-item, questionnaire was sent via e-mail to all members of the Italian IBD patients' association (AMICI Onlus). Three sets of questions were formulated: 1: Characteristics of respondents; 2: The use of biologics and biosimilars in clinical practice; 3: General opinions on biologics and biosimilars. Of the 4,302 total surveys sent, there were 1,749 respondents (response rate: 40.6%). There was an equal distribution between males and females (48.3% and 51.7%, respectively), and between patients with Crohn's disease and ulcerative colitis (46.9% and 51.3%, respectively), while most of the patients were aged between 19 and 45 years and between 46 and 65 years (45.5% and 42.0%, respectively). Approximately 45% of the respondents declared to have never been informed about the existence of biosimilars. The great majority of patients (73.9%) did not know if originators and biosimilars could be considered equivalent, or if efficacy or safety of biosimilars could be lower than those of originators. Approximately half of the respondents (53.5%) had no idea that the use of low-cost biosimilars could be useful to increase the overall economic resources for the treatment of IBD. An extensive lack of knowledge and confidence in biosimilars exists among Italian patients with IBD. Efforts carried out by scientific societies and IBD patients' associations are required to overcome this issue.


Incidence and risk factors for nosocomial infections caused by fluoroquinolone-resistant Escherichia coli.
The aim of the retrospective case-control study presented here was to elucidate the incidence, risk factors, and outcomes of nosocomial infections caused by quinolone-resistant Escherichia coli (QREC). During the 3-year period studied, 51 nosocomial QREC infections were found, and the characteristics of these cases were compared with those of 102 control patients with quinolone-susceptible nosocomial infections. In the multivariate analysis, risk factors were identified as prior quinolone therapy (odds ratio [OR], 18.49; 95% confidence interval [CI], 5.53-61.82; P value <0.001), urinary tract abnormalities (OR, 6.69; 95% CI, 1.68-26.63; P=0.007), and prior therapy with other antimicrobial agents (OR, 3.57; 95% CI, 1.38-9.27; P=0.009). No difference in mortality or in length of hospital stay was found. Prudent use of quinolones, especially in patients with urinary tract abnormalities, is probably the best way to avoid an increase in the incidence of QREC infections, but further studies on interventions with restricted use of quinolones are necessary to demonstrate the effectiveness and safety of this strategy.


Frontal midline theta rhythm and mental activity.
Theta rhythm at the midline of the frontal area can be observed in normal subjects, during mental task performance, rest and sleep. Frontal midline theta rhythm (Fm theta) is a train of rhythmic waves at the frequency of 6- Hz and can be induced by various mental tasks. Fm theta is induced not only during mental tasks but also during nocturnal sleep in which it was most frequent during rapid eye movement (REM) and second most frequent during stage 1 of non-REM (NREM) sleep, and the relationship of Fm theta to dream images during sleep was found. It is concluded, therefore, that the appearance of Fm theta is related to mental activity even during sleep. Fm theta shows individual differences and is related to certain personality traits. High Fm theta groups showed the lowest anxiety score in the Manifest Anxiety Scale (MAS), the highest score in the extrovertive scale of the Maudsley Personality Inventory (MPI) and the lowest score in the neurotic scale of MPI. Low Fm theta groups showed the opposite correlation. Significant negative correlation was found between the amount of Fm theta and platelet monoamine oxidase (MAO) activity. Summarizing the above-mentioned results, it may be concluded that the appearance of Fm 0 is related to mental activity, personality traits and platelet MAO activity. Furthermore, the correlation of such markers as platelet MAO activity and Fm theta with personality traits as measured by various psychological tests may prove to be of great importance in the exploration of the biological bases of personality.


Human microsaccade cueing modulation in visual- and memory-delay saccade tasks after theta burst transcranial magnetic stimulation over the frontal eye field.
Microsaccades that occur during periods of fixation are modulated by various cognitive processes and have an impact on visual processing. A network of brain areas is involved in microsaccade generation, including the superior colliculus and frontal eye field (FEF) which are involved in modulating microsaccade rate and direction after the appearance of a visual cue (referred to as microsaccade cueing modulation). Although the neural mechanisms underlying microsaccade cueing modulations have been demonstrated in monkeys, limited research has investigated a causal role of these areas in humans. By applying continuous theta-burst transcranial magnetic stimulation (cTBS) over the right FEF and vertex, we investigated the role of human FEF in modulating microsaccade responses after the appearance of a visual target in a visual- and memory-delay saccade task. After target appearance, microsaccade rate was initially suppressed but then increased in both cTBS conditions. More importantly, in the visual-delay task, microsaccades after target appearance were directed to the ipsilateral side more often with FEF, compared to vertex stimulation. Moreover, microsaccades were directed towards the target location, then to the opposite location of the target in both tasks, with larger effects in the visual-, compared to, memory-delay task. This microsaccade direction modulation was delayed after FEF stimulation in the memory-delay task. Overall, some microsaccade cueing modulations were moderately disrupted after FEF cTBS, suggesting a causal role for involvement of the human FEF in microsaccade generation after presentation of salient stimuli.


Possible origins of cerebrovascular nerve fibers showing vasoactive intestinal polypeptide-like immunoreactivity: an immunohistochemical study in the dog.
Changes of vasoactive intestinal polypeptide-like immunoreactivity (VIP-LI) in perivascular nerve fibers of the major cerebral arteries were examined immunohistochemically in the dog. The density of cerebrovascular nerve fibers showing VIP-LI (the average number of nerve fibers with VIP-LI in a unit area of the major cerebral arteries) was estimated, by using whole-mount preparations after extirpation of the pterygopalatine, otic or superior cervical ganglion. After pterygopalatine ganglionectomy, the density was markedly decreased in major cerebral arteries of both anterior circulation (the anterior cerebral and middle cerebral arteries) and posterior circulation (the basilar, superior cerebellar, posterior cerebral and posterior communicating arteries). After otic ganglionectomy, the density was moderately reduced in the major arteries of the posterior circulation, but was not decreased in those of the anterior circulation. After superior cervical ganglionectomy, the density was decreased markedly in the major cerebral arteries of the posterior circulation, and moderately in those of the anterior circulation. The results also indicate that the pterygopalatine, otic and superior cervical ganglia supply perivascular nerve fibers showing VIP-LI to the major cerebral arteries bilaterally with an ipsilateral dominance.


Tendon biomechanical properties enhance human wrist muscle specialization.
Biomechanical properties of human wrist tendons were measured under loads predicted to be experienced by those tendons under physiological conditions. This was accomplished by measuring the architectural properties of the five prime wrist movers--extensors carpi radialis brevis (ECRB), extensor carpi radialis longus (ECRL), extensor carpi ulnaris (ECU), flexor carpi radials (FCR), flexor carpi ulnaris (FCU)--and predicting their maximum tension (P0) using a specific tension value (22.5 N cm-2. Loading the corresponding tendons to P0 resulted in significantly different strain among tendons (p < 0.01) with the largest strain observed in the FCU (3.68 +/- 0.31%) and the smallest strain observed in the ECRL (1.78 +/- 0.14%). Further, strain magnitude was significantly positively correlated with the tendon length-to-fiber length ratio of the muscle-tendon unit, a measure of the intrinsic compliance of the muscle-tendon unit. Theoretical modeling of the magnitude of muscle sarcomere shortening expected based on the measured biomechanical properties revealed a maximum sarcomere length decrease of about 0.6 micron for the FCU to a minimum of about 0.2 micron for the ECRB at P0. Thus, tendon compliance may, but does not necessarily, result in significant modification of muscle force generation. The significant variation in tendon biomechanical properties was not observed using traditional elongation-to-failure methods on the same specimens. Thus, the use of elongation-to-failure experiments for determination of tendon properties may not be reasonable when the purpose of such studies is to infer physiological function. These data indicate that muscle-tendon units show remarkable specialization and that tendon intrinsic properties accentuate the muscle architectural specialization already present.


Occurrence of secondary cystathioninuria in children with inherited metabolic disorders, liver diseases, neoplasms, cystic fibrosis and celiac disease.
Secondary cystathioninuria was found in two of 46 children suffering from tumors, leukemia, liver disease, inherited metabolic disorders, cystic fibrosis and celiac disease. Of these two patients, one had congenital biliary atresia and the other cytomegalovirus infection. Seven further children had only moderately elevated excretion of cystathionine. It is suggested that secondary cystathioninuria is uncommon in the disease investigated.


Fluorescence spectra and measurement of phylloerythrin (phytoporphyrin) in plasma from clinically healthy sheep, goats, cattle and horses.
To measure the background concentration of phylloerythrin in plasma from clinically healthy sheep, goats, cattle and horses on pasture. Blood samples were taken from 34 sheep of the Dala breed, 20 female Norwegian dairy goats, 35 Norwegian Red cows and 34 horses of different breeds. All animals were grazing green pasture when blood samples were taken. Blood samples were collected from each of four clinically healthy newborn lambs, goats, calves and foals, and pooled into one sample per species. Plasma samples were analysed for phylloerythrin by fluorescence spectroscopy, using a Perkin-Elmer LS-50B luminescence spectrometer equipped with a red-sensitive photomultiplier. The fluorescence spectra of phylloerythrin in plasma from the adult ruminants were compared with those in plasma from the neonatal ruminants, to which a known concentration of phylloerythrin had been added. Plasma obtained from the adult ruminants had spectral characteristics similar to those of phylloerythrin, namely weak emission peaks at 650 and 711 nm, when excited at 425 nm. Emission spectra obtained from plasma from the neonatal ruminants showed no fluorescence at these wavelengths. On average, 0.012 (SD 0.004), 0.06 (SD 0.04), and 0.05 (SD 0.03) micromol/l phylloerythrin were present in plasma samples from the sheep, goats, and cattle, respectively. The fluorescence spectra of plasma from the newborn foals were similar to spectra of plasma from adult horses, with weak emission at 669 nm. Small concentrations of phylloerythrin were detected in plasma from clinically healthy sheep, goats and cattle, but none could be detected in plasma from clinically healthy horses.


Arsenic concentrations in soil, water, and rice grains of rice-growing areas of Punjab, Pakistan: multivariate statistical analysis.
Arsenic (As), a class-A human carcinogen, is ubiquitously present in the earth's crust and soil and may enter the air, water, and surface environments through different natural and anthropogenic sources. In this experiment, soil, irrigation water, and rice grains were sampled from conventional rice-growing areas of Punjab, Pakistan. Soil samples were collected from 0 to 15 cm surface soil of rice growing fields, and rice grains were collected from the same field at crop maturity. Irrigation water samples were collected from the source used to irrigate the respective rice fields. Coordinates of sampling locations were noted using a global positioning system, and a locations map was made using ArcGIS. Soil samples were digested in a microwave digester using aqua regia, and plant samples were block digested using nitric acid. Arsenic concentration was determined using an inductively coupled plasma mass spectrometer coupled with an auto-sampler and integrated samples introduction system. The mean concentration of As in rice grains, soil, and water samples was found within the safe limit set by WHO except for a sample from Narowal (148.54 µg l-1) that exceeded the irrigation water standard limit, i.e., 100 µg l-1 for irrigation water. Principal component analysis was performed to reduce the multidimensional space of variables and samples. Through the calculations of estimated daily intake, it has been revealed that the As levels measured in this study would only contribute a small amount (less than 5%) of the total recommended daily intake allowance.


[Studies on the methods of extract and determination of total tannins and gallic acids of the root of Euphorbia hylonoma].
To determine total tannins and gallic acid of the root of Euphorbia hyloomla. With the gallic acid as reference, tannins and gallic acid of the root of Euphorbia hylonoma were determined by ultraviolet spectrophtometer and high performance liquid chromatography, respectively. The content of tannins of the root of Euphorbia hylonoma were determined by different extract methods, including extracted by water, 70% alcohol, acetone on supersound, the determination data were 4.375%, 7.240%, 3.958%, respectively. When used recirculation method by water, 70% alcohol, acetone, the determination data were the determination data are 3.773%, 2.503%, 1.59%, respectively. The content of gallic acid of the root was 0.047%. Content of total tannins by alcohol super sound is the highest comparing with other extract methods, this method can used in extract of total Tannins of the root of Euphorbia hylonoma.


Body shape and fluctuating asymmetry following different feeding sources and feeding time in a triatomine, Triatoma pallidipennis (Stål, 1892).
Even when an animal has a generalist diet, different food sources can impact its body shape and fluctuating asymmetry (a stress indicator; FA). To test this, we varied the food source (mammalian, avian or defibrinated mammalian blood; and control animals - ad libitum feeding) and the time of feeding (every 8 days, 45 days and ad libitum) having the Chagas triatomine vector, Triatoma pallidipennis (Stål, 1892), as a study animal which has presumable generalist feeding habits. This factorial design was applied since first instar animals until adulthood. As response variables, we measured body shape and FA in adults of both sexes, using a two-dimensional geometric morphometrics protocol. The highest variance in body shape was explained by diet (17%), followed by sex nested within diet (12%). Males had less morphological differentiation than females: females with defibrinated blood provided every 45 days differentiated more, while those that fed on mammalian blood every 8 days differed less. Distances among the averages of the FA component related to shape indicated greater distances between avian blood provided every 45 days and mammalian blood provided every 8 days, as well as between the two groups fed on avian blood (feeding every 8 and 45 days), followed by avian and defibrinated blood, both fed every 8 days. These results indicate that blood source and feeding time have significant effects on the body shape, and FA in females and both sexes. Thus, despite general feeding habits, avian blood showed a greater impact on shape and FA in triatomines. This may select for triatomines to use mammal blood rather than avian blood if they have the chance to do so.


Genistein exerts estrogen-like effects in male mouse reproductive tract.
The aim of this study was to evaluate the estrogenicity of genistein in the neonatal and adult male mouse reproductive tract. In intact adults, genistein (2.5 mg s.c./kg of body weight/day for 9 days) reduced testicular and serum testosterone concentrations, pituitary LH-content and prostate weight. In castrated adults, genistein (0.025-2.5 mg s.c./kg of body weight) increased expression of c-fos gene in prostatic urethra. In adult, neonatally estrogenized mice showing an increased estrogen sensitivity, a 10-day treatment with genistein (2.5 mg s.c./kg of body weight) induced development of squamous epithelial metaplasia in prostatic collecting ducts. Neonatally, only a very high dose of genistein (1 mg/pup per day; i.e. approximately 500 mg/kg of body weight) induced persistent structural changes, similar to those seen in mice treated neonatally with diethylstilbestrol, in the urethroprostatic complex. These results suggest that in adult males, genistein induces the typical estrogenic effects in doses comparable to those present in soy-based diets, while in neonatal animals, considerably higher doses are required to show estrogen-like activity.


Enhanced Platelet Sensitivity to IGF-1 in Patients with Type 2 Diabetes Mellitus.
Diabetes mellitus is characterized by increased platelet activation which is determined by many factors including changes in the expression of membrane proteins. The aim of this study was to investigate the sensitivity of human platelets to the insulin-like growth factor (IGF) system in patients with poorly controlled type 2 diabetes mellitus (DM2). Ligand binding was analyzed using 125I-labelled IGF-1 and insulin, and relative expression of insulin-like growth factor 1 receptor (IGF-1R) and insulin receptor (IR) was evaluated by Western blotting. Platelet aggregation in the presence of IGF-1 was studied by the plate aggregometry assay. We found that platelets from DM2 patients exhibited significantly higher IGF-1 binding and upregulation of IGF-1R expression in comparison with healthy individuals. Both insulin binding and IR expression were lower in the DM2 group, but the differences with the healthy control were statistically insignificant. The potentiating effect of IGF-1 on the thrombin-induced activation of platelets was detected in both groups but was significantly more pronounced in the DM2 patients. The initial rate of platelet activation in the presence of IGF-1 positively correlated with the concentration of glycated hemoglobin. Platelets isolated from DM2 patients displayed elevated expression of the IGF-1R subunits, which might have contributed to the higher sensitivity of these cells to IGF-1 in thrombin-initiated aggregation by increasing the rate of platelet activation. However, further experiments are needed to investigate the role of IGF-1 in thrombotic complications that usually accompany diabetes.


A little knowledge: caregiver burden in schizophrenia in Malawi.
To determine the relationship between schizophrenia knowledge and burden of care among caregivers of people with schizophrenia in Mzuzu, Malawi. We recruited 90 patients and 90 caregivers to a randomized, controlled trial of group caregiver education in schizophrenia. At baseline, we administered the Family Questionnaire, which measures caregivers' knowledge of biomedical and psychosocial aspects of schizophrenia. We measured caregiver burden with the Involvement Evaluation Questionnaire. Using multivariate analysis, we examined the relationship between knowledge and burden, controlling for other patient and caregiver variables. We hypothesised that knowledge and burden would be inversely related. Caregiver burden was associated with knowledge (p = 0.001), but contrary to our hypothesis, greater knowledge was associated with greater burden. In this population, knowledge about schizophrenia was associated with higher caregiver burden. This does not prove that knowledge causes burden, but suggests that cultural factors may mediate the relationship between knowledge and burden, and that care is needed when introducing caregiver education in new cultures.


Patterns of change in selected serum chemical parameters of middle and later years.
Six serum constituents known to vary with renal function were analyzed in a probability sample of 500 persons 55 years and over, and their sex trends compared to other ages. Creatinine, BUN and alkaline phosphatase are elevated in this group whereas calcium is low and phosphorus strikingly so, especially in males. A possible explanation lies in age-related renal parenchymal changes which influence both glomerular filtration and tubular functions in ways that differ from true renal disease. These results have directed implications for geriatric diagnosis and therapy.


Effects of lufenuron treatments on the growth and development of Spodoptera frugiperda (Lepidoptera: Noctuidae).
Lufenuron is an effective benzoylurea insecticide that inhibits the synthesis of chitin and regulates the growth of insects. However, little is known about the effects of lufenuron treatment on the development of Spodoptera frugiperda (J. E. Smith). In this study, we assessed the toxicity of lufenuron on S. frugiperda and evaluated the effects of lufenuron treatment on the growth and development of S. frugiperda. The results showed that lufenuron exhibits high insecticidal activity against S. frugiperda, with the LC50 value of 0.99 mg L-1. Lufenuron treatments can significantly prolong the larval developmental duration and reduce the rates of pupation and emergence. To further explore the underlying mechanism of this observation, the expression profiles of the chitin synthase gene (SfCHS) and chitinase gene (SfCHT), two key enzyme genes involved in the molting of S. frugiperda, were determined after exposure to lufenuron for 96 h. The results of qRT-PCR demonstrated that lufenuron treatments can significantly reduce the expression of SfCHT, while the expression of SfCHS remained relatively stable. Furthermore, we found that lufenuron strongly interacted with chitinase (SfCHT) (-10.8 kcal/mol) and chitin synthase (SfCHS) (R1: -9.7 kcal/mol; R2: -10.2 kcal/mol). Our results indicated that lufenuron has significant effects on the development of S. frugiperda that might be attributed to the differential expression of SfCHT and SfCHS.


Comparative study of peroxidase-labelled IgG and anti-IgG for the detection of measles virus antigens.
The immunoperoxidase and immunoblotting techniques were used to detect measles virus antigens in nasopharyngeal samples taken from children visiting the Yaounde Health Centre (Cameroon). In order to make these diagnostic tests simpler, faster and less costly, peroxidase-labelled anti-measles IgG were prepared and compared with commercially available peroxidase-labelled mouse anti-IgG. Measles antigens were detected by immunoperoxidase and immunoblotting with the same sensitivity, no matter which type of conjugate was used. Moreover, the anti-measles IgG permitted the reduction of the duration of the test by half.


Effects of carbon sources and feeding strategies on heparosan production by Escherichia coli K5.
This work aimed to develop an optimal carbon source feeding strategy to achieve maximal production of heparosan as a precursor of bioengineered heparin by Escherichia coli K5. Glycerol gave higher heparosan titer and productivity compared to glucose. The maximum heparosan production (187 mg/L) and heparosan productivity (5.19 mg/L/h) in glycerol-defined medium were 26.4% higher than the heparosan production (148 mg/L) and heparosan productivity (4.11 mg/L/h) in glucose-defined medium. DO-stat feeding approach as compared to pH-stat feeding, exponential feeding, exponential combined with pH-stat feeding, and constant rate feeding gave the highest heparosan titer at 8.63 g/L, which was nine times that of batch culture. The obtained optimal glycerol feeding strategy may be useful for the scaling-up of microbial heparosan production.


Cancer/Testis Antigens into mitochondria: a hub between spermatogenesis, tumorigenesis and mitochondrial physiology adaptation.
Cancer/Testis Antigens (CTAs) genes are expressed only during spermatogenesis and tumorigenesis. Both processes share common specific metabolic adaptation related to energy supply, with a glucose to lactate gradient, leading to changes in mitochondrial physiology paralleling CTAs expression. In this review, we address the role of CTAs in mitochondria (mitoCTAs), by reviewing all published data, and assessing the putative localization of CTAs by screening for the presence of a mitochondrial targeting sequence (MTS). We evidenced that among the 276 CTAs, five were already shown to interfere with mitochondrial activities and 67 display a potential MTS.


Interactions between benign breast disease and other risk factors for breast cancer.
A population-based incident case-control study of breast cancer in Northern Alberta, Canada, provided an opportunity to evaluate interactions between the occurrence of benign breast disease (BBD) and other potential risk factors. Overall there was a 2-fold excess risk of breast cancer among women with BBD. This excess persisted regardless of the number of years from first biopsy for BBD to diagnosis of breast cancer, suggesting a permanent alternation in risk with BBD. Significant variations of the BBD--breast cancer association were noted with several factors. The excess risk of breast cancer among women with BBD was enhanced by having a later age at menarche, a later age at first birth, or lower parity. The usual protective effect of late age at menarche was seen only among women without BBD, and was supplanted by a 4-fold elevated risk among women with BBD. The deleterious effects of later age at first birth and nulliparity were greater among women with BBD. These patterns generally support the notion that hormonal factors mediate the relation between BBD and the development of breast cancer.


Bioelectric impedance spectroscopy underestimates fat-free mass compared to dual energy X-ray absorptiometry in incurable cancer patients.
Weight loss is frequently seen in advanced cancer. Bioelectrical impedance spectroscopy (BIS) is a convenient method for estimating body composition. We examined in a prospective, comparative study if BIS could accurately estimate fat-free mass (FFM) in cancer patients compared to dual-energy X-ray absorptiometry (DXA). The study was based on 132 consecutive incurable cancer patients with solid tumours in a University hospital outpatient clinic. Comparison of FFM from DXA and BIS with standard and revised equations. Bland-Altman plots, t-tests and linear regression analysis were used to evaluate agreement and differences between methods. BIS significantly underestimated mean FFM with 7.6+/-4.7 kg compared to DXA (P<0.001). Bias was significantly correlated to % weight loss (r=0.32), systemic inflammation as measured by C-reactive protein (r=0.29), malnutrition as assessed by low insulin-like growth factor-1 (r=-0.23) and inversely to the per cent body fat estimated by DXA (P=-0.61) and body mass index (BMI; r=-0.30). Revised BIS equations taking BMI into account reduced bias significantly but still with great individual variation. BIS by standard equations grossly underestimates FFM compared to DXA in cancer patients. This bias is related to weight loss, malnutrition and systemic inflammation. Revised equations improved FFM estimates, but with large individual variation. Thus, BIS with standard equations is not suitable to estimate FFM in patients with cachexia, inflammation and malnutrition.


α-Azido Acids in Solid-Phase Peptide Synthesis: Compatibility with Fmoc Chemistry and an Alternative Approach to the Solid Phase Synthesis of Daptomycin Analogs.
α-Azido acids have been used in solid phase peptide synthesis (SPPS) for almost 20 years. Here we report that peptides bearing an N-terminal α-azidoaspartate residue undergo elimination of an azide ion when treated with reagents that are commonly used for removing the Fmoc group during SPPS. We also report an alternative solid-phase route to the synthesis of an analog of daptomycin that uses a reduced number of α-azido amino acids and without elimination of an azide ion.


Haloperidol alters rat CNS cholinergic system: enzymatic and morphological analyses.
Chemical and morphological changes in cholinergic marker enzymes, acetylcholinesterase (AChE), and choline acetyltransferase (ChAT) of striatum, hippocampus, and cerebral cortex were studied following haloperidol treatment of rats. After short-term (7-21 days) haloperidol treatment, the levels of both enzymes (AChE and ChAT) were increased in striatum and hippocampus (greater than 25%), but not in cortex. After long-term (+40 days) haloperidol treatment, the level of AChE activity returned to control levels in all brain areas, whereas the levels of striatal and hippocampal ChAT decreased by 26% and 29%, respectively. No change in levels of both enzymes was detected after acute treatment (single dose) of haloperidol or chronic treatment with either clozapine or imipramine. Morphological analysis of cholinergic neurons and their processes using monoclonal antibody to ChAT showed two types of changes following 40 days of haloperidol treatment. First, parallel to the observed decrease in the levels of ChAT activity there was a visual decrease in the immunoreactivity in neurons as well as in their processes in striatum and hippocampus. Second, there was an apparent reduction in the size and number of stained neurons and their processes. No changes were seen in immunoreactivity after an acute treatment with haloperidol. These results indicate that the chronic haloperidol treatment in rats causes changes in central cholinergic systems that may be relevant to the pathophysiology of schizophrenia and its treatment.


The composition of the maternal breastmilk microbiota influences the microbiota network structure during early infancy.
Human breastmilk (BM) is important for microbiome maturation in infants across different body sites. Streptococcus and Staphylococcus are considered universally predominant genera in the BM microbiota. However, whether the differential abundance of Streptococcus and Staphylococcus in BM can differentially affect microbiome maturation in infants remains unclear. We recruited exclusively breastfeeding mothers from among the donors of the human milk bank established at National Cheng-Kung University Hospital. The donor mothers provided 35 BM samples at three months (3 M; before introducing children to complementary feeding) and 23 BM samples at six months (6 M; after introducing children to complementary feeding) postpartum. At both time points, samples from different body sites, including nasal swabs, oral swabs and stool, were collected from the mothers and their infants. Maternal BMI was inversely associated with coagulase-negative Staphylococcus (CoNS) abundance in breastmilk. Staphylococcus caprae representation in BM CoNS showed a negative correlation with Streptococcus abundance. Network analysis revealed that infants fed Staphylococcus-dominated BM had better gut and nasal microbiota networks than infants fed Streptococcus-abundant BM during early infancy. Our work suggests that maternal metabolic status plays a crucial role in Staphylococcus/Streptococcus competition in BM, which in turn can impact the development of the infant microbiota. Our microbiota co-occurrence network analysis might serve as a helpful bioinformatic tool to monitor microbiota maturation during early infancy.


Ultrasound findings in painful spastic hip. Muscle thickness in children with cerebral palsy.
In cerebral palsy (CP), spasticity is the dominant symptom and hip pain is one of the most common secondary conditions. Aetiology is not clear. Musculoskeletal ultrasound (MSUS) is a low-cost, non-invasive imaging technique that allows assessment of structural status, dynamic imaging, and quick contralateral comparison. A retrospective case-matched-control study. To investigate associated factors with painful spastic hip and to compare ultrasound findings (focusing on muscle thickness) in children with CP vs. typically developing (TD) peers. Paediatric Rehabilitation Hospital in Mexico City, from August to November 2018. 21 children (13 male, 7 + 4.26 years) with CP, in Gross Motor Function Classification System (GMFCS) levels IV to V, with spastic hip diagnosis (cases) and 21 children age- and sex-matched (7 + 4.28 years) TD peers (controls). Sociodemographic data, CP topography, degree of spasticity, mobility arch, contractures, Visual Analog Scale (VAS), GMFCS, measurements of the volumes of eight major muscles of the hip joint and MSUS findings of both hips. All children with CP group reported chronic hip pain. Associated factors for hip pain (high VAS hip pain score) were degree of hip displacement (percentage of migration), Ashworth Level, GMFCS level V. No synovitis, bursitis or tendinopathy was found. Significant differences (p < 0.05) were found in muscle volumes in all hip muscles (right and left) except in the right and left adductor longus. Though possibly the most important issue with diminished muscle growth in CP children is the influence on their long-term function, it is likely that training routines that build muscle size may also increase muscle strength and improve function in this population. To improve the choice of treatments in this group and maintain muscle mass, longitudinal investigations of the natural history of muscular deficits in CP as well as the impact of intervention are needed.


Ternary alloy (FeCoNi) nanoparticles supported on hollow porous carbon with defects for enhanced oxygen evolution reaction.
Low-cost non-noble metal nanoparticles are promising electrocatalysts that can catalyze oxygen evolution reaction (OER). Various factors such as poor activity and stability hinder the practical applications of these materials. The electroactivity and durability of the electrocatalysts can be improved by optimizing the morphology and composition of the materials. Herein, we report the successful synthesis of hollow porous carbon (HPC) catalysts loaded with ternary alloy (FeCoNi) nanoparticles (HPC-FeCoNi) for efficient OER. HPC is firstly synthesized by a facile carbon deposition method using the hierarchical porous zeolite ZSM-5 as the hard template. Numerous defects are generated on the carbon shell during the removal of zeolite template. Subsequently, FeCoNi alloy nanoparticles are supported on HPC by a sequence of impregnation and H2 reduction processes. The synergistic effect between carbon defects and FeCoNi alloy nanoparticles endows the catalyst with an excellent OER performance (low overpotential of 219 mV; Tafel slope of 60.1 mV dec-1) in a solution of KOH (1 M). A stable potential is maintained during the continuous operation over 72 h. The designed HPC-FeCoNi presents a platform for the development of electrocatalysts that can be potentially applied for industrial OER.


Modification of wood with isopropyl glycidyl ether and its effects on decay resistance and light stability.
China fir (Cunninghamia lanceolata var. lanceolata) and maple (Acer sp.) wood were etherified with isopropyl glycidyl ether and the decay resistance and light stability of the modified wood were assessed. CP/MAS (13)C NMR and FT-IR analyses indicated that new ether bonds containing isopropyl groups formed after reacting wood with isopropyl glycidyl ether. Modified wood samples were very resistant to decay when exposed to brown-rot fungus Laetiporus sulphureus or white-rot fungus Lenzites betulina for 60 days in the soil-block test. The isopropyl glycidyl ether treatment of wood was effective in decreasing formation of phenoxyl radicals upon UV irradiation and thus protecting wood from photodiscoloration.


Knowledge about dementia in South Korean nursing students: a cross-sectional survey.
The number of individuals with dementia is increasing substantially due to South Korea's rapidly aging society. Undergraduate nursing students need to have adequate knowledge about dementia to deliver appropriate nursing services. The purpose of this study was to assess the knowledge about dementia among undergraduate nursing students. A total of 148 students ranging from freshmen to seniors at a nursing university participated in this study. Data were collected through self-reports using 12-item questionnaires with true/false responses. Knowledge levels about the general characteristics including demographic categories and dementia- related education and training were determined. Factors affecting the score of dementia knowledge were also investigated. The average score and standard deviation for knowledge about dementia were 10.26 and 1.24 out of 12 points. They had relatively low knowledge about the "prevention and treatment" and "causes" of dementia, with overall correct rate of 78.6 % and 85.4 %, respectively. Higher level of knowledge about dementia was associated with increase in grade level (p < 0.001), experience in education on dementia (p = 0.01), previous experience in caring for people with dementia during clinical practice (p < 0.001), and acquiring information on dementia (p = 0.02). Factors that influenced knowledge about dementia included grade level and experience in caring for dementia patients during clinical practice. This study showed that the level of knowledge about dementia among nursing students was reasonably good. Integrating dementia education and clinical experience into the curricula of undergraduates could improve knowledge about the causes, prevention, and treatment methods for dementia.


Compact portable sources of high-LET radiation: Validation and potential application for galactic cosmic radiation countermeasure discovery.
Implementation of a systematic program for galactic cosmic radiation (GCR) countermeasure discovery will require convenient access to ground-based space radiation analogs. The current gold standard approach for GCR simulation is to use a particle accelerator for sequential irradiation with ion beams representing different GCR components. This has limitations, particularly for studies of non-acute responses, strategies that require robotic instrumentation, or implementation of complex in vitro models that are emerging as alternatives to animal experimentation. Here we explore theoretical and practical issues relating to a different approach to provide a high-LET radiation field for space radiation countermeasure discovery, based on use of compact portable sources to generate neutron-induced charged particles. We present modeling studies showing that DD and DT neutron generators, as well as an AmBe radionuclide-based source, generate charged particles with a linear energy transfer (LET) distribution that, within a range of biological interest extending from about 10 to 200 keV/μm, resembles the LET distribution of reference GCR radiation fields experienced in a spacecraft or on the lunar surface. We also demonstrate the feasibility of using DD neutrons to induce 53BP1 DNA double-strand break repair foci in the HBEC3-KT line of human bronchial epithelial cells, which are widely used for studies of lung carcinogenesis. The neutron-induced foci are larger and more persistent than X ray-induced foci, consistent with the induction of complex, difficult-to-repair DNA damage characteristic of exposure to high-LET (>10 keV/μm) radiation. We discuss limitations of the neutron approach, including low fluence in the low LET range (<10 keV/μm) and the absence of certain long-range features of high charge and energy particle tracks. We present a concept for integration of a compact portable source with a multiplex microfluidic in vitro culture system, and we discuss a pathway for further validation of the use of compact portable sources for countermeasure discovery.


On the use of non-concurrent controls in platform trials: a scoping review.
Platform trials gained popularity during the last few years as they increase flexibility compared to multi-arm trials by allowing new experimental arms entering when the trial already started. Using a shared control group in platform trials increases the trial efficiency compared to separate trials. Because of the later entry of some of the experimental treatment arms, the shared control group includes concurrent and non-concurrent control data. For a given experimental arm, non-concurrent controls refer to patients allocated to the control arm before the arm enters the trial, while concurrent controls refer to control patients that are randomised concurrently to the experimental arm. Using non-concurrent controls can result in bias in the estimate in case of time trends if the appropriate methodology is not used and the assumptions are not met. We conducted two reviews on the use of non-concurrent controls in platform trials: one on statistical methodology and one on regulatory guidance. We broadened our searches to the use of external and historical control data. We conducted our review on the statistical methodology in 43 articles identified through a systematic search in PubMed and performed a review on regulatory guidance on the use of non-concurrent controls in 37 guidelines published on the EMA and FDA websites. Only 7/43 of the methodological articles and 4/37 guidelines focused on platform trials. With respect to the statistical methodology, in 28/43 articles, a Bayesian approach was used to incorporate external/non-concurrent controls while 7/43 used a frequentist approach and 8/43 considered both. The majority of the articles considered a method that downweights the non-concurrent control in favour of concurrent control data (34/43), using for instance meta-analytic or propensity score approaches, and 11/43 considered a modelling-based approach, using regression models to incorporate non-concurrent control data. In regulatory guidelines, the use of non-concurrent control data was considered critical but was deemed acceptable for rare diseases in 12/37 guidelines or was accepted in specific indications (12/37). Non-comparability (30/37) and bias (16/37) were raised most often as the general concerns with non-concurrent controls. Indication specific guidelines were found to be most instructive. Statistical methods for incorporating non-concurrent controls are available in the literature, either by means of methods originally proposed for the incorporation of external controls or non-concurrent controls in platform trials. Methods mainly differ with respect to how the concurrent and non-concurrent data are combined and temporary changes handled. Regulatory guidance for non-concurrent controls in platform trials are currently still limited.