Bioelectrical Impedance Phase Angle and Morbidity and Mortality in Critically Ill Children.
Nutrition markers may be useful for diagnosis and monitoring and, also, as additional indicators of estimating death risk. We tested the association of body composition indicators (mid-upper arm circumference and phase angle) with pediatric intensive care unit (PICU) length of stay and mortality in critically ill pediatric patients. Data from children aged 2 months-18 years were collected, and bioelectrical impedance was performed to obtain phase angle. Severity was evaluated by scoring the Pediatric Index of Mortality. Descriptive statistics were reported for nominal variables. Receiver operating characteristic curve was used to analyze the association of phase angle with 30-day mortality and to find the best cutoff. Survival probabilities and PICU length of stay were estimated using the Kaplan-Meier method. We evaluated 247 children with a median age of 4.8 years whose main cause of admission was sepsis. Survival curves showed higher survival in patients with phase angle >2.8° compared with patients with phase angle ≤2.8° (P < .0001). Kaplan-Meier time-to-event analysis showed that children with lower phase angle values were more likely to remain in the PICU (hazard ratio, 1.84; P = .003). Lower survival was also observed in patients who presented mid-upper arm circumference values ≤5th percentile (P < .03). Mid-upper arm circumference and phase angle were associated with mortality and morbidity in critically ill children, suggesting that these parameters may be useful not only for nutrition diagnosis and monitoring, but also as an additional indicator in estimating prognosis.


Charge levels in programmable pacemakers.
The method of calculation of charge in one series of programmable pacemakers is described. Accurate charge tables are constructed and examples of their use are given. With the tables the margin between the threshold and the pacemaker setting can be more precisely determined and consequently, at least in some cases, it can be reduced for greater pacemaker longevity.


Simultaneous determination of LH activity in blood serum of sheep during three synchronized oestrous cycles by Bio and Ria method.
LH activity has been in 6 Merino sheep by means of the biological (Bio) and radioimmunological (RIA) test during three subsequent synchronized oestrous cycles. The vaginal sponges were impregnated with 30 mg chlormadinone acetate. The results obtained by the two afore mentioned methods are similar. Oestrous appeared in the average within 96 hours after removal of the sponges. The first increase of LH activity (Bio) was found to occur within 48--72 hours after removal of the sponges (270--400 IU/100 ml serum), the second increase within 15--16 days (450-570 IU/100 ml) and the third within further 16 days (390--590 IU/100 ml serum). The values obtained in the first oestrous cycle by RIA showed an LH peak within 62--110 hours after removal of the sponges (75--90 ng/ml in the second oestrous cycle 86--135 ng/ml and in the third one 58--60 ng/ml serum. In three animals no LH peak could be observed during the first, second or third oestrous cycle. The failure to prove LH peaks in three sheep during different phases of the oestrous cycles is explained by the fact that the synchronization led to heat which, however, did not result in fertile ovulation.


Breast lymphoma: imaging findings of 32 tumors in 27 patients.
To retrospectively evaluate the imaging findings of breast lymphomas in patients who had undergone mammography, ultrasonography (US), magnetic resonance (MR) imaging, or combined positron emission tomography (PET)/computed tomography (CT) scanning. The institutional review board approved this HIPAA-compliant study and waived informed consent. Twenty-seven women who had been diagnosed with breast lymphoma (32 tumors) and had undergone preoperative imaging were identified from the surgical pathology database (mean age, 51 years; median, 55 years; range, 19-78 years at time of diagnosis). Two radiologists reviewed the mammographic, US, and MR images. One nuclear medicine physician reviewed the PET/CT scans. All available pathologic specimens were reviewed by a hematologic pathologist. The mean tumor size at diagnosis was 2.9 cm (range, 1-5 cm). Seventeen tumors manifested with a palpable mass, two with diffuse enlargement of the breast, and 13 were asymptomatic. Twenty-two women underwent mammography; 24, US; one, MR imaging; and 10, PET/CT scanning. Mammograms of 25 tumors showed a noncalcified mass in 19, global asymmetry in four, focal asymmetry in one, and no abnormality in one. US of 29 tumors showed a mass in 26 and diffuse architectural distortion in three. Masses typically were irregular, hypoechoic, and hypervascular and demonstrated indistinct margins or an echogenic boundary. Dynamic contrast material-enhanced MR imaging of one tumor showed an intensely and heterogeneously enhancing mass with rapid enhancement and washout characteristics. PET/CT scans of 13 tumors showed intense diffuse hypermetabolism in 12 and response to therapy in all 12 tumors. The imaging findings reported in this study should alert the radiologist to a possible diagnosis of breast lymphoma.


Safe and Effective Prophylaxis with Bimonthly Intravenous Pentamidine in the Pediatric Hematopoietic Stem Cell Transplant Population.
Without prophylaxis, Pneumocystis jiroveci pneumonia (PCP) develops in 5%-15% of pediatric hematopoietic stem cell transplant (HCT) patients with mortality above 50%. Trimethoprim-sulfamethoxazole is a standard PCP prophylaxis; pentamidine is frequently used as second-line prophylaxis because of trimethoprim-sulfamethoxazole's potential for cytopenias. Monthly intravenous (IV) pentamidine has variable efficacy with PCP infection rates of 0%-10% in pediatric patients, and higher breakthrough rates in those younger than 2 years. We hypothesized that bimonthly (twice monthly) pentamidine might have equivalent safety and improved efficacy; therefore, we conducted a retrospective analysis of bimonthly pentamidine PCP prophylaxis. We retrospectively reviewed records of all pediatric HCT patients who received bimonthly IV pentamidine between December 2006 and June 2013, and collected data regarding demographics, clinical course, prophylaxis rationale, laboratory values and adverse events. Between December 2006 and June 2013, 111 pediatric HCT patients received bimonthly IV pentamidine (574 doses, 8758 patient-days); 31 patients were younger than 2 years at initiation. In the majority (53% of courses), pentamidine was initiated because of cytopenias. Fourteen patients (12.6% of patients, 2.4% of doses) experienced a side-effect prompting discontinuation, including 3 patients with infusion-related hypotension/anaphylaxis and 3 with acute pancreatic dysfunction. No patients [0% (95% confidence interval: 0-3.2)] developed PCP during or after bimonthly IV pentamidine prophylaxis. Bimonthly IV pentamidine for PCP prophylaxis in the HCT pediatric population has comparable safety to monthly IV pentamidine and was highly effective, including in the very young. Bimonthly IV pentamidine should be considered in pediatric patients as second-line PCP prophylaxis.


Autobiographical memory in multiple sclerosis.
Studies have consistently found that patients with multiple sclerosis (MS) are impaired on tests of anterograde memory, but the status of remote memory in MS remains unclear. To better understand remote memory in MS we administered the Autobiographical Memory Interview (AMI) to 44 MS patients and 19 normal controls matched for age, education, and gender. Additionally, a shortened version of the Famous Faces Test, a test of recall of past U.S. presidents, and a 14-word learning list were administered. Patients performed significantly lower than controls on the learning list and Famous Faces Test, but not on recall of past presidents. On the AMI, patients were significantly impaired on recall of semantic but not of episodic memories. These results indicate that MS patients exhibit retrograde amnesia that cannot be attributed to anterograde memory deficits or lack of exposure to task-relevant information.


Rural-urban health care provider disparities in Alaska and New Mexico.
Compared to their urban counterparts, rural residents face numerous disparities in obtaining health care, including limited access to care providers. We assessed disparities in provider availability in rural versus urban Alaska and New Mexico, with emphasis on professionals likely to provide mental health care. Using lists of licenses, we categorized physical and mental health care providers into rural versus urban and calculated rural versus urban disparity ratios. Rural residents had significantly less access to health care providers and discrepancies grew with level of required provider education and specialization. Addressing disparities via creative strategies is crucial to improving rural care delivery.


The moderating role of housing quality on concentrated poverty and asthma-related emergency department visits among Hispanics/Latinos.
Rates of asthma-related emergency department visits have been shown to vary significantly by place (i.e. neighborhood) and race/ethnicity. The moderating factors of asthmatic events among Hispanic/Latino-specific populations are known to a much lesser degree. To assess the extent to which housing moderates the effect of poverty on Hispanic/Latino-specific asthma-related emergency department (ED) visits at an ecological level. Using data from the Office of Statewide Health Planning and Development (OSHPD) and the 2016-2017 U.S. Census, a cross-sectional ecological analysis at the census tract-level was conducted. Crosswalk files from the U.S. Department of Housing and Urban Development were used to associate zip codes to census tracts. Negative binomial regression was used to estimate rate ratios. The effect of poverty on asthma-related ED visits was significantly moderated by the median year of housing structures built. The effect of mid-level poverty (RR = 1.57, 95% CI 1.27, 1.95) and high-level poverty (RR = 1.47, 95% CI 1.22, 1.78) in comparison to low-level poverty, was significantly greater among census tracts with housing built prior to 1965 in comparison to census tract with housing built between 1965 and 2020. Communities with older housing structures tend to be associated with increased Hispanic/Latino ED visits apart from affluent communities.


Structural characterization of a chain termination mutant of human serum albumin.
Mutant forms of human serum albumin have been detected on the basis of their abnormal electrophoretic mobility which is either faster or slower than that of normal albumin. In the present work we have studied the structure of a slow variant, referred to as albumin Ge/Ct, in order to define the cause of its genetic abnormality. The protein was isolated from the serum of a young healthy woman homozygous for the variant. Analysis of CNBr fragments by isoelectric focusing allowed us to localize the mutation to the COOH-terminal region of the molecule (residues 549-585). This fragment was isolated on a preparative scale and subjected to tryptic digestion. All tryptic peptides were purified by reverse-phase high performance liquid chromatography and characterized. Sequential analysis of three abnormal peptides revealed that albumin Ge/Ct has a shortened chain with the following COOH-terminal sequence: Leu-Val-Ala-Ala-Ser-Lys580-Leu-Pro. The presence of an additional lysine residue accounts for the electrophoretic behavior of the variant. It is likely that the variant may be caused by a single base deletion in the structural gene, a Cyt in mRNA codon 580, and the consequent shift in reading frame.


Structural and enzymatic insights into species-specific resistance to schistosome parasite drug therapy.
The antischistosomal prodrug oxamniquine is activated by a sulfotransferase (SULT) in the parasitic flatworm Schistosoma mansoni. Of the three main human schistosome species, only S. mansoni is sensitive to oxamniquine therapy despite the presence of SULT orthologs in Schistosoma hematobium and Schistosoma japonicum The reason for this species-specific drug action has remained a mystery for decades. Here we present the crystal structures of S. hematobium and S. japonicum SULTs, including S. hematobium SULT in complex with oxamniquine. We also examined the activity of the three enzymes in vitro; surprisingly, all three are active toward oxamniquine, yet we observed differences in catalytic efficiency that implicate kinetics as the determinant for species-specific toxicity. These results provide guidance for designing oxamniquine derivatives to treat infection caused by all species of schistosome to combat emerging resistance to current therapy.


Hong Kong nurses' perceptions of and participation in continuing nursing education.
As medical technologies change, practicing nurses need to update their knowledge and skills to ensure quality health care for patients and to minimize possible health hazards in the workplace. This article describes a study that explored Hong Kong hospital nurses' perceptions of and participation in continuing nursing education. It found that Hong Kong nurses participate actively in continuing education out of a sense of professional responsibility and personal interest. However, consistent with findings from other studies, the major factors hindering nurses' participation are finances, family commitments, and time.


Heparin versus 0.9% sodium chloride intermittent flushing for prevention of occlusion in central venous catheters in adults.
Heparin intermittent flushing is a standard practice in the maintenance of patency in central venous catheters. However, we could find no systematic review examining its effectiveness and safety. To assess the effectiveness of intermittent flushing with heparin versus 0.9% sodium chloride (normal saline) solution in adults with central venous catheters in terms of prevention of occlusion and overall benefits versus harms. The Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator searched the Specialised Register (last searched December 2013) and the Cochrane Central Register of Controlled Trials (CENTRAL) (2013, Issue 11). Searches were also carried out in MEDLINE, EMBASE, CINAHL and clinical trials databases (December 2013). Randomised controlled trials (RCTs) in adults 18 years of age and older with a central venous catheter (CVC) in which intermittent flushing with heparin (any dose with or without other drugs) was compared with 0.9% normal saline were included. No restriction on language was applied. Two review authors independently selected trials, assessed trial quality and extracted data. Trial authors were contacted to retrieve additional information, when necessary. Six eligible studies with a total of 1433 participants were included. The heparin concentrations used in these studies were very different (10-5000 IU/mL), and follow-up varied from 20 days to 180 days. The overall risk of bias in the studies was low. The quality of the evidence ranged from very low to moderate for the main outcomes (occlusion of CVC, duration of catheter patency, CVC-related sepsis, mortality and haemorrhage at any site).Combined findings from three trials in which the unit of analysis was the catheter suggest that heparin was associated with reduced CVC occlusion rates (risk ratio (RR) 0.53, 95% confidence interval (CI) 0.29 to 0.94). However, no clear evidence of a similar effect was found when the results of two studies in which the unit of analysis was the participant were combined (RR 0.21, 95% CI 0.03 to 1.70), nor when findings were derived from one study, which considered total line accesses (RR 1.08, 95% CI 0.84 to 1.40). Furthermore, results for other estimated effects were found to be imprecise and compatible with benefit and harm: catheter duration in days (mean difference (MD) 0.41, 95% CI -1.29 to 2.12), CVC-related thrombosis (RR 1.22, 95% CI 0.74 to 1.99), CVC-related sepsis (RR 1.02, 95% CI 0.34 to 3.03), mortality (RR 0.77, 95% CI 0.45 to 1.32) and haemorrhage at any site (RR 1.37, 95% CI 0.49 to 3.85). We found no conclusive evidence of important differences when heparin intermittent flushing was compared with 0.9% normal saline flushing for central venous catheter maintenance in terms of efficacy or safety. As heparin is more expensive than normal saline, our findings challenge its continued use in CVC flushing outside the context of clinical trials.


[Seroprevalence of Hepatitis C Virus (HCV) in patients of the Regional Viral Reference Laboratory (Maracaibo, Venezuela)].
Collect and analyze information regarding seroprevalence of Hepatitis C Virus (HCV) in a population of 722 patients that visited the Regional Viral Reference Laboratory (Maracaibo, Venezuela) during the years 2000-2003. An immunoenzymatic test INNOTEST HCV Ab IV of Innogenetics was used to evaluate the presence of IgG type antibodies against the Hepatitis C Virus (HCV) in the serum of the patients studied. Results obtained with respect to seroprevalence and other epidemiological variables, were organized and analyzed using SPSS 10.0 (Chicago, USA) and Origin Pro 7.5 (Northampton, USA) software. A seroprevalence of 2.63% (19,322) was found, higher than that reported in Venezuela for the general population (0.9%) and other groups. The infection was more frequent in men than in women. The most common symptoms in the infected patients were jaundice and cephalalgia (31.58%). The data reported shall update previous research in the zone and indicates the need to develop epidemiological control for Hepatitis C Virus (HCV) in the State of Zulia.


Cardiac muscle ultrastructure and cyclic AMP reactions to altered gravity conditions.
Morphological and biochemical analyses of heart muscle of rats subjected to microgravity on Spacelab 3 (SL-3) flight and rats born and reared under increased gravity (1.7 G) conditions were compared with 1-G controls. Electronmicroscopic studies showed an increase in the number of lipid droplets and in areas of glycogen storage. Distribution changes of microtubules and cytoskeletal elements from both SL-3 and 1.7-G groups were observed. The high Km cyclic AMP phosphodiesterase activity was lower (P less than 0.05) in SL-3 heart muscle, and low Km activity was lower in 1.7-G males but was unaltered in females. Cyclic AMP-dependent protein kinase (cA-PK) activity was decreased in subcellular fractions of heart muscle of SL-3 animals. Recompartmentalization of cA-PK activity occurred in particulate tissue fraction of 1.7-G animals (70.3% of total for 1.7 G vs. 35.9% for controls). Phosphorylation of endogenous low-mobility proteins increased in SL-3 heart-soluble fractions. Photoaffinity labeling (18 h, 4 degrees C) decreased in type II cA-PK regulatory (R) subunits in both SL-3 and in 1.7-G male heart tissue particulate fractions. The 1.7-G female heart R subunit distribution did not differ from controls. These findings indicate that in heart muscle altered gravity conditions influenced physiological reactions similar to catecholamine-induced receptor-mediated hormonal responses.


Gender, aging, and the economics of "active aging": Setting a new research agenda.
The world is aging, and the percentages of older people are on a dramatic ascent. This dramatic demographic aging of human society is not gender neutral; it is mostly about older women. One of the key policy approaches to address the aging revolution is known as "active aging," crystalized by the WHO in 2002 by three pillars: participation, health, and security. The active aging policy has financial and economic aspects and affects both men and women. However, as argued in this article, a gender-based approach has not been adopted within the existing active aging framework. Therefore, a new gender-specific research agenda is needed, one that focuses on an interrelation between gender and different economic aspects of "active aging" from international, comparative, cultural, and longitudinal perspectives.


Loss of Mir146b with aging contributes to inflammation and mitochondrial dysfunction in thioglycollate-elicited peritoneal macrophages.
Macrophages undergo programmatic changes with age, leading to altered cytokine polarization and immune dysfunction, shifting these critical immune cells from protective sentinels to disease promoters. The molecular mechanisms underlying macrophage inflammaging are poorly understood. Using an unbiased RNA sequencing (RNA-seq) approach, we identified Mir146b as a microRNA whose expression progressively and unidirectionally declined with age in thioglycollate-elicited murine macrophages. Mir146b deficiency led to altered macrophage cytokine expression and reduced mitochondrial metabolic activity, two hallmarks of cellular aging. Single-cell RNA-seq identified patterns of altered inflammation and interferon gamma signaling in Mir146b-deficient macrophages. Identification of Mir146b as a potential regulator of macrophage aging provides novel insights into immune dysfunction associated with aging.


COVID-19, Australia: Epidemiology Report 13 (Reporting week to 23:59 AEST 26 April 2020).
Confirmed cases in Australia notified up to 26 April 2020: notifications = 6,711; deaths = 77. The reduction in international travel and domestic movement, social distancing measures and public health action have likely slowed the spread of COVID-19 in Australia. Notifications in Australia remain predominantly among people with recent overseas travel, with some locally-acquired cases being detected. Most locally-acquired cases can be linked back to a confirmed case, with a small portion unable to be epidemiologically linked to another case. The ratio of overseas-acquired cases to locally-acquired cases varies by jurisdiction. The crude case fatality rate (CFR) in Australia remains low (1.1%) compared to the World Health Organization's globally-reported rate (6.9%) and to other comparable high-income countries such as the United States of America (5.1%) and the United Kingdom (13.7%). The lower CFR in Australia is likely reflective of high case ascertainment including detection of mild cases. High case ascertainment and prompt identification of contacts enables an effective public health response and a reduction of disease transmission. Internationally, cases continue to increase. The rates of increase have started to slow in several regions, although it is too soon to tell whether this trend will be sustained. Interpretation of international epidemiology should be conducted with caution as it differs from country to country depending not only on the disease dynamics, but also on differences in case detection, testing and implemented public health measures.


A Novel Potassium-Ion-Based Dual-Ion Battery.
In this work, combining both advantages of potassium-ion batteries and dual-ion batteries, a novel potassium-ion-based dual-ion battery (named as K-DIB) system is developed based on a potassium-ion electrolyte, using metal foil (Sn, Pb, K, or Na) as anode and expanded graphite as cathode. When using Sn foil as the anode, the K-DIB presents a high reversible capacity of 66 mAh g-1 at a current density of 50 mA g-1 over the voltage window of 3.0-5.0 V, and exhibits excellent long-term cycling performance with 93% capacity retention for 300 cycles. Moreover, as the Sn foil simultaneously acts as the anode material and the current collector, dead load and dead volume of the battery can be greatly reduced, thus the energy density of the K-DIB is further improved. It delivers a high energy density of 155 Wh kg-1 at a power density of 116 W kg-1 , which is comparable with commercial lithium-ion batteries. Thus, with the advantages of environmentally friendly, cost effective, and high energy density, this K-DIB shows attractive potential for future energy storage application.


[Factors Affecting Adherence to Adjuvant Endocrine Therapy in Japanese Patients with Breast Cancer-An Observational Study].
The purpose of this study was to investigate adherence to adjuvant endocrine therapy (ET) and the factors affecting demotivation and motivation to continue adjuvant ET. In patients with hormone receptor-positive breast cancer in Japan, an online survey was conducted from June to July 2021 to investigate the treatment effects, side effects, concerns about side effects(for demotivation only), convenience of hospital visits, treatment duration, concerns about recurrence/progression, treatment cost, support from healthcare professionals, and support from family, the patient association, and peers(for motivation only). According to the responses from 263 patients, the most common factor affecting demotivation to continue adjuvant ET was the burden of side effects, and the most common factor affecting motivation to continue adjuvant ET was concerns about recurrence/progression. Continuous relief of the burden of side effects from the early stage of treatment, and mental support for concerns about recurrence/progression, as well as explaining and promoting the risks and benefits of continuing treatment, are considered to lead to motivation to continue adjuvant ET(Fig. 1: Summary of this survey).


In Support of Universal Admission Testing for SARS-CoV-2 During Significant Community Transmission.
Many hospitals have stopped or are considering stopping universal admission testing for SARS-CoV-2. We discuss reasons why admission testing should still be part of a layered system to prevent hospital-acquired SARS-CoV-2 infections during times of significant community transmission. These include the morbidity of SARS-CoV-2 in vulnerable patients, the predominant contribution of presymptomatic and asymptomatic people to transmission, the high rate of transmission between patients in shared rooms, and data suggesting surveillance testing is associated with fewer nosocomial infections. Preferences of diverse patient populations, particularly the hardest hit communities, should be surveyed and used to inform prevention measures. Hospitals' ethical responsibility to protect patients from serious infections should predominate over concerns about costs, labor, and inconvenience. We call for more rigorous data on the incidence and morbidity of nosocomial SARS-CoV-2 infections and more research to help determine when to start, stop, and restart universal admission testing and other prevention measures.


Interventions to Educate Family Physicians to Change Test Ordering: Systematic Review of Randomized Controlled Trials.
The purpose is to systematically review randomised controlled trials (RCTs) to change family physicians' laboratory test-ordering. We searched 15 electronic databases (no language/date limitations). We identified 29 RCTs (4,111 physicians, 175,563 patients). Six studies specifically focused on reducing unnecessary tests, 23 on increasing screening tests. Using Cochrane methodology 48.5% of studies were low risk-of-bias for randomisation, 7% concealment of randomisation, 17% blinding of participants/personnel, 21% blinding outcome assessors, 27.5% attrition, 93% selective reporting. Only six studies were low risk for both randomisation and attrition. Twelve studies performed a power computation, three an intention-to-treat analysis and 13 statistically controlled clustering. Unweighted averages were computed to compare intervention/control groups for tests assessed by >5 studies. The results were that fourteen studies assessed lipids (average 10% more tests than control), 14 diabetes (average 8% > control), 5 cervical smears, 2 INR, one each thyroid, fecal occult-blood, cotinine, throat-swabs, testing after prescribing, and urine-cultures. Six studies aimed to decrease test groups (average decrease 18%), and two to increase test groups. Intervention strategies: one study used education (no change): two feedback (one 5% increase, one 27% desired decrease); eight education + feedback (average increase in desired direction >control 4.9%), ten system change (average increase 14.9%), one system change + feedback (increases 5-44%), three education + system change (average increase 6%), three education + system change + feedback (average 7.7% increase), one delayed testing. The conclusions are that only six RCTs were assessed at low risk of bias from both randomisation and attrition. Nevertheless, despite methodological shortcomings studies that found large changes (e.g. >20%) probably obtained real change.


Hsa_circ_0009910: oncogenic circular RNA targets microRNA-145 in ovarian cancer cells.
Circular RNAs (circRNAs) correlate with cancer cell phenotypes. Particularly, circRNAs mediate the cancer process as microRNAs (miRNAs) sponges. This study was to ascertain the roles of hsa_circ_0009910 in phenotypic aspects of ovarian cancer cells. Mantel-Cox test was performed to analyze the correlation between hsa_circ_0009910 and survival outcomes of ovarian cancer. Minigene reporter was constructed and small interfering-RNA was designed for constructing hsa_circ_0009910-dysregulated and miR-145-upregulated cells identified by qRT-PCR. Proliferative and motile activities were monitored by CCK and Transwell. Western blot was applied for quantification of cyclin D1, CDK4, CDK6, MMP-2, MMP-9, IκBα, p65, Notch1, Hes1, and Hes5. miRNAs targets were predicted using a bioinformatics tool and confirmed using qRT-PCR and Dual-Luciferase reporter assay. Hsa_circ_0009910 was correlated with the poor prognosis of ovarian cancer patients. The ovarian cancer cell phenotypes were promoted by hsa_circ_0009910 while repressed by silencing hsa_circ_0009910. Hsa_circ_0009910 silence was responsible for the upregulation of the predicted miRNAs targets. Thereinto, miR-145 was confirmed as a miRNA target and negatively regulated by hsa_circ_0009910. miR-145 nullified the biological function of hsa_circ_0009910 in the proliferative and motile phenotypes, and the active status of NF-κB and Notch. Hsa_circ_0009910, representing unfavorable prognosis, induced proliferative and motile phenotypes by suppressing miR-145 in ovarian cancer cells.


Engraftment, migration and differentiation of neural stem cells in the rat spinal cord following contusion injury.
Spinal cord injury is a devastating injury that impacts drastically on the victim's quality of life. Stem cells have been proposed as a therapeutic strategy. Neural stem (NS) cells have been harvested from embryonic mouse forebrain and cultured as adherent cells. These NS cells express markers of neurogenic radial glia. Mouse NS cells expressing green fluorescent protein (GFP) were transplanted into immunosupressed rat spinal cords following moderate contusion injury at T9. Animals were left for 2 and 6 weeks then spinal cords were fixed, cryosectioned and analyzed. Stereologic methods were used to estimate the volume and cellular environment of the lesions. Engraftment, migration and differentiation of NS cells were also examined. NS cells integrated well into host tissue and appeared to migrate toward the lesion site. They expressed markers of neurons, astrocytes and oligodendrocytes at 2 weeks post-transplantation and markers of neurons and astrocytes at the 6-week time-point. NS cells appeared to have a similar morphologic phenotype to radial glia, in particular at the pial surface. Although no functional recovery was observed using the Basso Beattie Bresnahan (BBB) locomotor rating scale, NS cells are a potential cellular therapy for treatment of injured spinal cord. They may be used as delivery vehicles for therapeutic proteins because they show an ability to migrate toward the site of a lesion. They may also be used to replace lost or damaged neurons and oligodendrocytes.


Mitogen-activated protein kinase (MEK) inhibitors to treat melanoma alone or in combination with other kinase inhibitors.
Malignant melanoma (MM) is an aggressive disease with a rapidly rising incidence due to neoplasm of melanocytes. Molecular targeted therapies have demonstrated lower toxicity and improved overall survival versus conventional therapies of MM. The revealing of mutations in the BRAF/MEK/ERK pathway has led to the development of BRAF inhibitors such as vemurafenib and dabrafenib for the treatment of cutaneous MM. Though, progression of resistance to these agents has prompted attempts to target downstream proteins in this pathway. Trametinib, a MEK1/2 inhibitor, was approved in 2013 for the treatment of BRAF V600E/K mutation-positive unresectable or metastatic cutaneous melanoma patients. Areas covered: The aim of the current review is to present an update on the role of MEK in progressive melanomas and summarize latest results of clinical studies with innovative MEK inhibitors and/or combined approaches with other kinase inhibitors such as BRAF inhibitors in the treatment of MM. Expert opinion: Two combined treatments (i.e. trametinib plus dabrafenib and vemurafenib plus cobimetinib) target two different kinases in the BRAF/MEK/ERK pathway. The simultaneous prohibition of both MEK and BRAF is associated with more durable response rate than BRAF monotherapy and can overcome acquired resistance.


Nationwide surveillance of drug-resistant tuberculosis in The Netherlands: rates, risk factors and treatment outcome.
The Netherlands, 1993 and 1994. To determine 1) rates of drug resistance in relation to nationality and country of birth, 2) risk factors for drug resistance, 3) treatment outcome of drug-resistant cases, and 4) rates of primary and acquired drug resistance. Retrospective study of all cases notified with bacillary tuberculosis in The Netherlands in 1993 and 1994. Drug resistance to one or more drugs was reported in 268 (14.6%) of all 1836 cases, of whom 203 (76%) were foreign born. In Dutch patients rates of isoniazid (H) (2.9%) and streptomycin resistance (3.6%) were lower than in foreign patients (8.6% and 10.6% respectively, P < 0.001). Multidrug (H and rifampicin [R]) resistance was reported in 0.5% of Dutch-born and 1.4% of foreign cases (P = 0.055). Rates of acquired resistance to H (11.4%) and HR (5.7%) were higher than rates of primary resistance to these drugs (5.2% and 0.7% respectively, P < 0.05), but the number of retreatment cases was low (6.8% of all cases). Drug resistance was associated with immigration but not with drug use, homelessness or human immunodeficiency virus (HIV) co-infection. One fifth (20%) of drug-resistant cases was diagnosed by active case finding. Treatment outcome in sensitive and resistant cases was compared. These findings suggest that drug resistance is imported, but it is unclear to what extent drug resistance among foreigners has been transmitted or created in The Netherlands. Drug resistance data should be monitored in Dutch and foreign patients separately.


Self- and peer assessment may not be an accurate measure of PBL tutorial process.
Universidade Cidade de São Paulo adopted a problem-based learning (PBL) strategy as the predominant method for teaching and learning medicine. Self-, peer- and tutor marks of the educational process are taken into account as part of the final grade, which also includes assessment of content. This study compared the different perspectives (and grades) of evaluators during tutorials with first year medical students, from 2004 to 2007 (n = 349), from seven semesters. The tutorial evaluation method was comprised of the students' self assessment (SA) (10%), tutor assessment (TA) (80%) and peer assessment (PA) (10%) to calculate a final educational process grade for each tutorial. We compared these three grades from each tutorial for seven semesters using ANOVA and a post hoc test. A total of 349 students participated with 199 (57%) women and 150 (42%) men. The SA and PA scores were consistently greater than the TA scores. Moreover, the SA and PA groups did not show statistical difference in any semester evaluated, while both differed from tutor assessment in all semesters (Kruskal-Wallis, Dunn's test). The Spearman rank order showed significant (p < 0.0001) and positive correlation for the SA and PA groups (r = 0.806); this was not observed when we compared TA with PA (r = 0.456) or TA with SA (r = 0.376). Peer- and self-assessment marks might be reliable but not valid for PBL tutorial process, especially if these assessments are used for summative assessment, composing the final grade. This article suggests reconsideration of the use of summative assessment for self-evaluation in PBL tutorials.


The recognition and characterisation of Finnish Clostridium difficile isolates resembling PCR-ribotype 027.
To characterise and compare twenty-eight Finnish Clostridium difficile RT027-like isolates, selected based on the presence of 18 bp deletion in the tcdC gene and toxin gene profile (A, B, binary), with eleven RT027 isolates from different Finnish geographical areas and time periods. Twenty-eight C. difficile RT027-like isolates and 11 RT027 comparative strains were characterised by capillary-electrophoresis (CE) ribotyping, multi-locus variable tandem-repeats analysis (MLVA), multi-locus sequence typing (MLST), and sequencing of tcdC and gyrA gene fragments. Susceptibility to moxifloxacin was determined by E-test. Of 28 RT027-like isolates, seven RTs (016, 034, 075, 080, 153, 176 and 328), three WEBRIBO types (411, 475, AI-78) and three new profiles (F1-F3) were identified. MLVA revealed six clonal complexes (RTs 016, 027, 176 and F3). MLST showed eleven sequence types (1, 41, 47, 67, 95, 191,192, 223, 229, 264 and new ST). Twenty-two isolates (RTs 016, 080, 176, 328, F1, F2, F3 and WRTAI-78) carried Δ117 in the tcdC gene. Isolates of RTs 016, 027 and 176 were moxifloxacin resistant and harboured Thr82Ile in the GyrA. Our results show a high diversity within 28 Finnish RT027-like C. difficile isolates, with twelve CE-ribotyping profiles and eleven STs. MLVA revealed the regional spread of RTs 016, 027, 176 and F3. The presence of Δ117 in the tcdC gene in eight non-027 RTs highlights the importance of careful interpretation of the results from molecular systems targeting this site in the genome of C. difficile and the need of strain typing for epidemiological purposes.


Examining normative values using the Cambridge neuropsychological test automated battery and developmental traits of executive functions among elementary school-aged children in Japan.
The Cambridge Neuropsychological Test Automated Battery (CANTAB) is a computerized and child-friendly neuropsychological assessment battery that includes subtests aimed at evaluating some aspects of executive functions. Using the CANTAB, this study aims to establish normative values based on the aspects of executive functions among school-aged children in Japan. The participants included 234 children (135 boys and 99 girls aged 6-12 years) enrolled in regular classes, without any clinical records of developmental disorders or educational support. The participants were grouped according to age (6-7, 8-9, and 10-12 years). Four CANTAB subtests, including spatial working memory (SWM) to assess spatial working memory, Stockings of Cambridge (SOC) to evaluate planning, intra/extradimensional set shift (IED) to evaluate attentional set shifting and flexibility, and stop signal task (SST) to evaluate inhibition, were administered to each participant. The results showed that performance in all the CANTAB subtests administered changed with age. Among the subtests, compared with performances in the SOC and IED, those in the SWM and SST improved earlier, thereby indicating that spatial working memory and inhibition develop earlier than planning as well as attentional set shifting and flexibility. Additionally, in the SST subtest, girls made fewer errors than boys did in the 6-7 years group. This study presents normative data of four CANTAB subtests according to age and sex among school-aged children in Japan. We expect that the findings will be used to develop effective tools for the early detection of and support for children with executive dysfunction.


Influence of environmental variability on phylogenetic diversity and trait diversity within Calligonum communities.
Since phylogenetic data provide the evolutionary history of the species and traits are the result of adaptation to the environmental conditions, joint analysis of these two aspects and ecological data may illuminate that how ecological processes affect the evolution of species and assembly of communities. In this study, we compared the community structure of sibling communities in order to illuminate the influence of environmental variability. We chose different Calligonum communities as research subjects which grow in active sand dunes and stabilized sand fields. Our results show that species which co-occurred in C. rubicundum community have greater phylogenetic evenness compared to species in other communities where co-occurring plants had similar traits. Soil variability might legitimately explain this result. Based on the similarity between the pattern of trait diversity and the pattern of phylogenetic diversity, we inferred that the evolution of traits is conservative and species of all but C. rubicundum communities are under more intense selection pressure.


Thyroid-induced changes in the growth of the liver, kidney, and diaphragm of neonatal rats.
Eu-, hypo- and hyper-thyroid rats were studied 12 days postpartum. Hypothyroidism was induced by administering propylthiouracil (PTU) via the mother's drinking water between late gestation and throughout lactation. This procedure effectively blocked the normal early postnatal surge of T3 and T4. In contrast, hyperthyroidism was induced in the young pups by daily injections of T4 from day 3 postpartum. The effects of these experimental manipulations of thyroid status on the rates of protein turnover and growth of the liver, kidney, and diaphragm were studied and compared with measurements made on appropriate euthyroid control tissues. Tissue rates of protein synthesis were decreased in response to hypothyroidism with consequent growth retardation of all three tissues and the whole animal. In contrast, the three body tissues responded very differently to the induction of hyperthyroidism. Hepatic rates of protein synthesis and growth were completely unaffected by thyroid excess. The response of the diaphragm was essentially the reverse of that seen with hypothyroidism, i.e., the enhanced rates of protein synthesis and protein degradation leading to muscle hypertrophy. The rates of protein turnover in the kidney were also increased, but unlike the diaphragm the net result was renal atrophy. Clearly, thyroid hormones influence the normal rapid growth of the neonate and its individual tissues. However, beyond a certain concentration the threshold of responsiveness to these hormones seems to vary between individual tissues.


Kinetics of fibronectin release from fibroblasts in response to 12-O-tetradecanoylphorbol-13-acetate and retinoic acid.
We have studied the effects of the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) and its in vivo and in vitro antagonist retinoic acid (RA) on the synthesis and release of a major extracellular glycoprotein, fibronectin (FN), in human lung fibroblasts (HLF). The studies reported here investigate the question of whether the increased amounts of FN released by TPA treatment are cell-surface derived or require de novo synthesis of FN. Untransformed HLF continuously released FN into the medium. Addition of TPA rapidly enhanced this release of FN into the culture medium, as shown with enzyme-linked immunosorbent assay. RA, given simultaneously with TPA, prevented the increased release and resulted in a normal FN accumulation in the medium. RA alone did not influence FN release. To study the effect of TPA or RA on synthesis rates of FN, HLF were labeled metabolically: FN synthesis rates with or without TPA, RA, or with TPA and RA were similar, as judged by assaying cell-layer-associated and medium [3H]FN. Pre-existing (unlabeled) FN accumulated in the medium as a result of TPA treatment at a time when newly synthesized (labeled) FN was still intracellular. Cycloheximide, in concentrations which inhibited protein synthesis by 95%, did not prevent but only reduced the normal FN release, nor did it prevent the effect of TPA at this reduced level. We conclude that phorbol ester action and RA counteraction on the release of FN takes place on a cell-surface target; that FN which is released into the medium by TPA is derived from pre-existing FN; that RA specifically antagonizes TPA action. No protein synthesis is required to release FN, to mediate enhanced FN release by TPA, or to counteract the enhanced release by RA.


IL233, A Novel IL-2 and IL-33 Hybrid Cytokine, Ameliorates Renal Injury.
CD4+Foxp3+ regulatory T cells (Tregs) protect the kidney during AKI. We previously found that IL-2, which is critical for Treg homeostasis, upregulates the IL-33 receptor (ST2) on CD4+ T cells, thus we hypothesized that IL-2 and IL-33 cooperate to enhance Treg function. We found that a major subset of Tregs in mice express ST2, and coinjection of IL-2 and IL-33 increased the number of Tregs in lymphoid organs and protected mice from ischemia-reperfusion injury (IRI) more efficiently than either cytokine alone. Accordingly, we generated a novel hybrid cytokine (IL233) bearing the activities of IL-2 and IL-33 for efficient targeting to Tregs. IL233 treatment increased the number of Tregs in blood and spleen and prevented IRI more efficiently than a mixture of IL-2 and IL-33. Injection of IL233 also increased the numbers of Tregs in renal compartments. Moreover, IL233-treated mice had fewer splenic Tregs and more Tregs in kidneys after IRI. In vitro, splenic Tregs from IL233-treated mice suppressed CD4+ T cell proliferation better than Tregs from saline-treated controls. IL233 treatment also improved the ability of isolated Tregs to inhibit IRI in adoptive transfer experiments and protected mice from cisplatin- and doxorubicin-induced nephrotoxic injury. Finally, treatment with IL233 increased the proportion of ST2-bearing innate lymphoid cells (ILC2) in blood and kidneys, and adoptive transfer of ILC2 also protected mice from IRI. Thus, the novel IL233 hybrid cytokine, which utilizes the cooperation of IL-2 and IL-33 to enhance Treg- and ILC2-mediated protection from AKI, bears strong therapeutic potential.


Toward improving student motivation and performance in introductory programming learning by Scratch: The role of achievement emotions.
This study investigated the differences in programming novices' intrinsic motivation and performance within a Scratch-based programming learning environment using a pretest-posttest intervention design. Specifically, this study aimed to examine what and how achievement emotions were aroused to impact learners' academic success during Scratch implementation processes by employing regression analyses. One hundred and seventy-two undergraduates (Mage = 20.44, SDage = 1.09, 55.8% female) were voluntarily recruited to participate in a Scratch-based instruction workshop during a 6-week period. The workshop was structured with regard to preparation, Scratch-based programming learning and projects, and assessment activities and questionnaire implemented both before the instructional period and after the workshop. The results suggested that the Scratch-based intervention significantly increased students' overall motivation and examination performance. Concerning achievement emotions, the outcome emotion of hopelessness first negatively predicted students' motivation and performance. Anxiety then replaced hopelessness as a negative predictor, while enjoyment was the strongest predictor of motives and performance. Taking eight emotions together, the arousal of activity and outcome emotions within visual programming environments facilitated students' emotion dynamics that impacted motivation and performance. The discussion and contributions concerning the mechanism behind the effectiveness of visualization and the emotion-performance relationship are presented herein.


Recognition mechanism of Wilms' tumour suppressor protein and DNA triplets: insights from molecular dynamics simulation and free energy analysis.
The Wilms' tumour suppressor protein (WT1) plays a multifaceted role in human cancer processes. Mutations on its DNA recognition domain could lead to Denys-Drash syndrome, and alternate splicing results in insertion of the tripeptide Lys-Thr-Ser (KTS) between the third and fourth zinc fingers (ZFs), leading to changes in the DNA-binding function. However, detailed recognition mechanisms of the WT1-DNA complex have not been explored. To clarify the mutational effects upon WT1 towards DNA binding at the atomic level, molecular dynamics simulations and the molecular mechanics/Poisson Boltzmann surface area (MM/PBSA) method were employed. The simulation results indicate that mutations in ZF domains (E427Q and Q369H) may weaken the binding affinity, and the statistical analyses of the hydrogen bonds and hydrophobic interactions show that eight residues (Lys351, Arg366, Arg375, Arg376, Lys399, Arg403, Arg424 and Arg430) have a significant influence on recognition and binding to DNA. Insertion of the tripeptide KTS could form an immobilized hydrogen-bonding network with Arg403, affecting the flexibility and angle of the linker between ZF3 and ZF4, thus influencing the recognition between the protein and the DNA triplet at its 5' terminus. These results represent the first step towards a thorough characterization of the WT1 recognition mechanisms, providing a better understanding of the structure-function relationship of WT1 and its mutants.


miR-373-3p promotes lung adenocarcinoma cell proliferation via APP.
Previous studies have indicated that lung adenocarcinoma (LUAD) is one of the common human malignancies, and its incidence keeps rising. With the help of microarray technology, downregulation of miR-373-3p was observed in LUAD tissues compared with normal lung tissues. Notably, the present study demonstrated that the expression of amyloid precursor protein (APP) mRNA in LUAD tissues was overexpressed compared with adjacent tissues. Bioinformatic analysis demonstrated that miR-373-3p may interact with the 3' untranslated region of APP mRNA, and then western blot and dual-luciferase reporter gene assays were employed to verify the interaction. Finally, CCK-8 assays were used to measure the tumor-suppressing effect of miR-373-3p on A549 and it was demonstrated that overexpression of miR-373-3p may more effectively inhibit the proliferation of A549 compared with APP si-RNA. Overall, the findings suggest that miR-373-3p downregulation partly accounts for APP overexpression and leads to a promotion of cell growth in LUAD. miR-373-3p may therefore act as a valuable target in potential anticancer strategies to treat LUAD.


Benzodiazepine receptor agonists modulate thymocyte apoptosis through reduction of the mitochondrial transmembrane potential.
Peripheral-type benzodiazepines have been shown to exert immunological effects. In this study, we examined the effects of the peripheral-type benzodiazepines on murine thymocytes. Murine thymocytes that were incubated with the peripheral-type benzodiazepines underwent apoptosis associated with the collapse of mitochondrial transmembrane potential (delta psi(m)). The drugs stimulated dexamethasone- and etoposide-induced apoptosis with the enhanced collapse of delta psi(m). The central-type benzodiazepines had no effect on either the delta psi(m) or apoptosis. The reduction of delta psi(m) depended on protein synthesis and protein phosphorylation. These results suggest that the immunomodulating effect of benzodiazepines is in part due to the modulation of thymocyte apoptosis associated with the collapse of delta psi(m).


Photoswitchable Probes of Oxytocin and Vasopressin.
Oxytocin (OT) and vasopressin (VP) are related neuropeptides that regulate many biological processes. In humans, OT and VP act via four G protein-coupled receptors, OTR, V1aR, V1bR, and V2R (VPRs), which are associated with several disorders. To investigate the therapeutic potential of these receptors, particularly in the receptor-dense areas of the brain, molecular probes with a high temporal and spatial resolution are required. Such a spatiotemporal resolution can be achieved by incorporating photochromic moieties into OT and VP. Here, we report the design, synthesis, and (photo)pharmacological characterization of 12 OT- and VP-derived photoprobes using different modification strategies. Despite OT's and VP's sensitivity toward structural changes, we identified two photoprobes with good potency and photoswitch window for investigating the OTR and V1bR. These photoprobes should be of high value for producing cutting-edge photocontrollable peptide probes for the study of dynamic and kinetic receptor activation processes in specific regions of the brain.


Promoting the health, safety and welfare of adults with learning disabilities in acute care settings: a structured literature review.
To present the findings of a structured literature review that aimed to identify the influences on the health, safety and welfare of adults with learning disabilities in acute hospitals. There is increasing evidence regarding the inadequacy of care for people with learning disabilities in acute care settings. However, few studies have specifically addressed their health, safety and welfare in such contexts. Four key electronic databases (Medline; PsycINFO; British Nursing Index and archive; Cumulative Index to Nursing and Allied Health Literature) were searched for relevant literature published between 2000 and 2011. Publications assessed as meeting the inclusion criteria were retrieved in full. Data were extracted regarding methods used; primary aims of the study being reported; and key findings. Of the 3505 papers identified in the initial search, eight met the inclusion criteria. Analysis revealed six areas of influence on the health, safety and welfare of adults with learning disabilities in acute hospitals: care provision (meeting health and personal needs); communication; staff attitudes; staff knowledge; supporters; and carers (valuing their role); physical environment. We represent these six areas diagrammatically, as concentric rings. These influence on health, safety and welfare form an inner (direct) layer and an outer (indirect) layer consisting of liaison services and education/training. This new conceptualisation of influences as being multi-layered assists in the identification of similarly multi-layered improvement strategies. Adults with learning disabilities can exert their own influence on health, safety and welfare and should be supported to make decisions about their own care. More broadly they should be involved with policy development, nurse education and research. This can be achieved through inclusive approaches, for example, inviting people with learning disabilities to input into nursing curricula or to engage in research as coinvestigators.


[Should a doctor be insistence in proposing surgery for cancer?].
On a basis of a large personal experience in treatment of patients with gastro-intestinal cancer the author considers the expediency of convincing patients in surgical treatment of gastro-intestinal cancer, especially in the new social situation in Russia. Positive experience in long-term follow-up (more than 10-20 years) of patients, operated on because of cancer, is one of pro factors for such a convincing. The results of long-term follow-up (exceeding 9 and 25 years) of the patients operated on in gastro-intestinal cancer (including primary-multiple cancer); the clinical case of a patient, who was operated for several times at the period of 13 years-10 malignant tumors were removed from his body; the clinical case of a patient, who was operated in case of 3 sinchronous cancers (cancers of pancteatic head, rectum and ascending colon) illustrate the benefit of the operative intervention.


Corticotropin-Releasing Factor and Toll-Like Receptor Gene Expression Is Associated with Low-Grade Inflammation in Irritable Bowel Syndrome Patients with Depression.
The mechanism of low-grade inflammation in irritable bowel syndrome (IBS) is unclear; our research concentrates on the involvement of the corticotropin-releasing factor (CRF) and Toll-like receptor (TLR) gene expression in the process of low-grade inflammation in IBS patients with depression. This study suggests more IBS patients are presenting with the states of depression and anxiety. IBS patients with depression have shown a lower grade inflammatory response and an imbalance of the inflammatory response. CRF1, CRF2, TLR2, and TLR4 in IBS patients with depression are significantly higher than those without depression and controls. Thus, activation of the CRF-TLR associated pathways produces an inflammatory reaction, which can concurrently affect the digestive tract and the CNS and induce the corresponding digestive and psychiatric symptoms.


[Ethical dilemmas in the sharing of information in the care of HIV-infected children].
Ethical dilemmas are regularly encountered in the care of patients infected with HIV (Human Immunodeficiency Virus), especially in issues regarding professional confidentiality and shared information with the child and his/her family as well as among professional health workers. This communicable disease, which can be treated but not yet cured, leads to exclusion, due to the fear of infection, to its severity and induces stigmatisation of affected individuals. It interferes with life projects, sexuality, reproductive health, family life, projection into the future. In HIV paediatrics, practitioners regularly deal with complex situations and need to balance parental authority and children's needs/dependence, respect of patient's confidentiality and hazards to another person's health, potential negative impact of disclosing information and risks attributable to the lack of information.


Bacterial infection of endometrial stromal cells influences bovine herpesvirus 4 immediate early gene activation: a new insight into bacterial and viral interaction for uterine disease.
Experimental infection with the gamma-herpesvirus bovine herpesvirus 4 (BoHV-4) rarely establishes disease, yet BoHV-4 is commonly associated with uterine disease in cattle. Uterine disease involves co-infection with bacteria such as Escherichia coli, which stimulate the production of prostaglandin E(2) (PGE(2)) by endometrial cells. BoHV-4 replication depends on immediate early 2 (IE2) gene transactivation and, in the present study, PGE(2), E. coli or its lipopolysaccharide upregulated the IE2 gene promoter in uterine cells. Bacterial co-infection is important for BoHV-4 uterine disease.


Can a Bug in the Gut Act Like a Drug in the Brain?
Microorganisms inhabiting the gut exist in a symbiotic relationship with our bodies, performing many essential metabolic tasks for human physiology. The gut-brain axis is a bidirectional communication system integrating neural, hormonal, and immunological signaling between the gut and brain. There is strong experimental evidence from animal studies that the intestinal microbiome has an important role in the control of brain development, function, and behavior. A small number of clinical studies, mainly in healthy individuals, using probiotic formulations as an experimental probe suggest that gut bugs may indeed act like a drug and affect the brain, but much more work is needed.


Coordination and advocacy for rural elders (CARE): a model of rural case management with veterans.
To describe a pilot initiative sponsored by the Veterans Health Administration (VHA) to improve the health and community tenure of frail older veterans living in rural counties 50-100 miles from two host VHA medical centers. Veterans aged 75 and older who scored at risk of repeated hospital admission on the PRA-Plus telephone questionnaire were targeted and visited by evaluators who administered a comprehensive health questionnaire prior to being assessed at home by the Coordination and Advocacy for Rural Elders (CARE) program clinical teams. Guided by current state-of-the-art practices, the nurse-social worker teams performed in-home standardized assessments using the MDS-HC, developed patient-specific care plans, and mobilized family, community, and VHA resources to implement plans. On average, eight problems were identified for each patient, most commonly falls risk, social needs, pain, and needs related to IADL disability. As a result of initial assessment, two thirds of CARE participants received referral/linkage to formal services, more than half to medical providers. Through CARE, the VHA is learning more about the unmet needs of older rural veterans. Further development and evaluation should guide the VHA toward providing efficient, effective community-based services to all frail older veterans.


[Anaerobic microbial associations degrading aromatic amino acids].
Anaerobic microbial associations have been isolated that degrade aromatic amino acids to methane and carbon dioxide at high rates. Significant differences between the morphological, cytological, and physiological traits of cultures isolated from samples of adapted and unadapted sludge are shown. The effects of cultivation temperature, illumination, and presence of mineral nitrogen and bicarbonate in the medium upon adaptation of enrichment cultures to substrates and subsequent behavior of the anaerobic associations have been studied. Intermediate and final products of degradation of aminoaromatic compounds and the sequence of their formation in the cultures have been determined. We have also studied the effects of exogenous electron acceptors and additional carbon sources on the degradation of aminoaromatic compounds.


A comprehensive analysis of GATA3 expression in carcinomas of various origins with emphasis on lung carcinomas.
GATA3 is a transcription factor involved in embryogenesis of multiple human tissues and in maintaining cell differentiation and tissue homeostasis in the adult organism. GATA3 is also involved in carcinogenesis and regarded as a sensitive marker for urothelial and breast carcinomas, albeit expression in carcinomas of non-breast/urothelial origin has been frequently reported. We sought to examine the extent and intensity of GATA3 expression in various carcinomas, mainly lung, urothelial, and breast and various other primary sites. Patients with breast carcinoma (N=40), carcinoma of the urinary bladder/renal pelvis (N=40), lung carcinoma (N=110) and various other origins (N=45) were included in the study. One hundred and sixty-five patients had a primary tumor diagnosis, and 70 cases had a metastatic tumor diagnosis. Our results showed that GATA3 expression was significantly more common in carcinomas of the breast, urinary bladder and renal pelvis compared to all other origins. All primary and 93% of metastatic urinary bladder carcinomas and 94% of the primary and 80% of metastatic breast carcinomas expressed GATA3. Expression was lower in non-urothelial histology of urinary primaries and in triple negative breast carcinomas. Focal staining, mostly faint, was seen in 5.6% of the primary lung adenocarcinomas and 35% of the primary lung squamous cell carcinomas. More extensive and intense staining was seen in 3.7% of the primary lung adenocarcinomas and 12% of the primary lung squamous cell carcinomas. Expression, mostly focal was also seen in 30% of the metastatic lung carcinomas. Finally, high expression was seen in 12.5% of the other tumors (one metastatic pancreatic carcinoma, one metastatic salivary gland adenocarcinoma NOS, one metastatic squamous cell carcinoma of the skin, one primary uterine cervix serous carcinoma, and one squamous cell carcinoma of the head and neck) and focal expression was present in another 22% of them. No ideal cut-off for positivity for GATA3 staining could be identified. In conclusion our study shows that GATA3 staining has two caveats in its use: the first is that non classical histologies of urothelial carcinomas and TNBC may be negative for the marker and secondly carcinomas of various origins may show (although rarely) intense positivity.


Role of matrix metalloproteinases in renal pathophysiologies.
Matrix metalloproteinases (MMPs) are a large family of proteinases that remodel extracellular matrix (ECM) components and cleave a number of cell surface proteins. MMP activity is regulated via a number of mechanisms, including inhibition by tissue inhibitors of metalloproteinases (TIMPs). Originally thought to cleave only ECM proteins, MMP substrates are now known to include signaling molecules (growth factor receptors) and cell adhesion molecules. Recent data suggest a role for MMPs in a number of renal pathophysiologies, both acute and chronic. This review will focus on the expression and localization of MMPs and TIMPs in the kidney, as well as summarizing the current information linking these proteins to acute kidney injury, glomerulosclerosis/tubulointerstitial fibrosis, chronic allograft nephropathy, diabetic nephropathy, polycystic kidney disease, and renal cell carcinoma.


Pulmonary SPECT imaging and the stripe sign.
A patient with high clinical suspicion for pulmonary embolism underwent a diagnostic scintigraphic ventilation/perfusion scan. The planar images revealed an unmatched perfusion defect with a stripe sign in the right middle lobe. A stripe sign is the appearance of normally perfused tissue between the defect and the pleural surface suggesting a nonpleural-based abnormality. SPECT images acquired in the same study period, however, failed to demonstrate normally perfused tissue between the defect and the pleural surface. Previous studies have compared planar ventilation/perfusion studies with stripe sign perfusion defects to pulmonary angiography. The results suggest that stripe sign perfusion defects are generally not due to emboli. However, planar imaging is projectional and may miss pleural contact in some perfusion lesions depending on the projection. In the absence of SPECT data, the significance of the stripe sign may need to be reassessed.


Targeting Neurotrophins to Specific Populations of Neurons: NGF, BDNF, and NT-3 and Their Relevance for Treatment of Spinal Cord Injury.
Neurotrophins are a family of proteins that regulate neuronal survival, synaptic function, and neurotransmitter release, and elicit the plasticity and growth of axons within the adult central and peripheral nervous system. Since the 1950s, these factors have been extensively studied in traumatic injury models. Here we review several members of the classical family of neurotrophins, the receptors they bind to, and their contribution to axonal regeneration and sprouting of sensory and motor pathways after spinal cord injury (SCI). We focus on nerve growth factor (NGF), brain derived neurotrophic factor (BDNF), and neurotrophin-3 (NT-3), and their effects on populations of neurons within diverse spinal tracts. Understanding the cellular targets of neurotrophins and the responsiveness of specific neuronal populations will allow for the most efficient treatment strategies in the injured spinal cord.


Examination of Recreational and Spiritual Peyote Use Among American Indian Youth.
Some American Indians legally use hallucinogenic substances as part of religious and spiritual ceremonies. Research to date has either failed to differentiate spiritual versus recreational use or has categorized hallucinogen use in an "other drug" or "illegal drug" category. This approach could contribute to ineffectual models of prevention and treatment intervention and limit understanding of hallucinogen use in American Indian cultures. This study is a secondary data analysis of an ongoing epidemiologic and etiologic investigation of substance use among American Indian youth (N = 3,861). Two Firth logistic regression models were run with (a) spiritual peyote use and (b) recreational peyote use as the dependent variables, and grade, sex, 30-day alcohol use, 30-day marijuana use, religiosity, religious affiliation, and cultural identity as predictors, as well as a grade by sex interaction term. Grade, sex, religious affiliation, and the interaction term did not predict either recreational or spiritual peyote use. Thirty-day alcohol and marijuana use predicted both spiritual and recreational peyote use, but the effects were stronger for predicting recreational use. Religiosity and cultural identity predicted spiritual but not recreational use, such that American Indian youth who identified as more religious and identified more strongly with their culture were more likely to report using peyote for spiritual purposes. Our results suggest that current self-reported use of alcohol and/or marijuana by American Indian youth indicates an increased likelihood of using peyote. In addition, use of Firth logistic regression models proved feasible for analyzing rare events like peyote use.


Structure-function relationships in Anabaena ferredoxin/ferredoxin:NADP(+) reductase electron transfer: insights from site-directed mutagenesis, transient absorption spectroscopy and X-ray crystallography.
The interaction between reduced Anabaena ferredoxin and oxidized ferredoxin:NADP(+) reductase (FNR), which occurs during photosynthetic electron transfer (ET), has been investigated extensively in the authors' laboratories using transient and steady-state kinetic measurements and X-ray crystallography. The effect of a large number of site-specific mutations in both proteins has been assessed. Many of the mutations had little or no effect on ET kinetics. However, non-conservative mutations at three highly conserved surface sites in ferredoxin (F65, E94 and S47) caused ET rate constants to decrease by four orders of magnitude, and non-conservative mutations at three highly conserved surface sites in FNR (L76, K75 and E301) caused ET rate constants to decrease by factors of 25-150. These residues were deemed to be critical for ET. Similar mutations at several other conserved sites in the two proteins (D67 in Fd; E139, L78, K72, and R16 in FNR) caused smaller but still appreciable effects on ET rate constants. A strong correlation exists between these results and the X-ray crystal structure of an Anabaena ferredoxin/FNR complex. Thus, mutations at sites that are within the protein-protein interface or are directly involved in interprotein contacts generally show the largest kinetic effects. The implications of these results for the ET mechanism are discussed.


Age-related changes of growth hormone secretory mechanisms in the rat pituitary gland.
The mechanisms underlying the age-related decrease and increase in somatotroph responsiveness to growth hormone-releasing factor (GHRF) and somatostatin respectively were studied in rat pituitary membranes in vitro. Basal adenylate cyclase (AC) activity was similar in pituitary membranes from rats of 8 days (either sex) and male rats of 3 months, but it was almost threefold higher in membranes from male rats of 21-23 months. GHRF induced a lower percentage stimulation of AC activity in membranes from infant and old than adult rats. Somatostatin inhibited stimulation of AC induced by forskolin more effectively in membranes from adult than infant and old rats. In parallel experiments, since the tissue we used is formed by a mixed population of pituitary cells, we evaluated, for comparison, the effect on AC of neurohormones, i.e. vasoactive intestinal polypeptide (VIP) and dopamine which act primarily on lactotrophs. VIP induced a lower fold-stimulation of AC activity in membranes from infant and old than adult rats. Dopamine inhibited forskolin-induced stimulation of AC in the following rank order of magnitude: old, adult and infant rats, and was also more effective in inhibiting basal AC activity in old than in adult rats. The stimulatory and inhibitory G proteins (Gs and Gi) coupled to AC were measured indirectly by evaluating stimulatory and inhibitory effects of different concentrations of GTP on AC. GTP, at stimulatory concentrations, increased AC activity in membranes from infant and adult rats similarly whereas its effect was significantly greater in membranes from old rats.(ABSTRACT TRUNCATED AT 250 WORDS)


Pigeons presented with sequences of light flashes use behavior to count but not to time.
On randomly ordered trials, pigeons were presented with either a blue or a white key that flashed red for 200 ms at a fast (2 flashes/s), medium (1 flash/s), or slow (0.5 flashes/s) rate. The blue key signaled a fixed-interval (FI) schedule in which the first response after 20 s was reinforced, and the white key signaled a fixed-number (FN) schedule in which the first response after 20 flashes was reinforced. In Experiments 1 and 2, pigeons showed depressed responding to the flash on FI-cued trials and accelerated responding to the flash on FN-cued trials. When the response key was periodically blacked out in Experiments 3 and 4, counting but not timing was eliminated.


Genome-wide screening reveals metabolic regulation of stop-codon readthrough by cyclic AMP.
Translational fidelity is critical for microbial fitness, survival and stress responses. Much remains unknown about the genetic and environmental control of translational fidelity and its single-cell heterogeneity. In this study, we used a high-throughput fluorescence-based assay to screen a knock-out library of Escherichia coli and identified over 20 genes critical for stop-codon readthrough. Most of these identified genes were not previously known to affect translational fidelity. Intriguingly, we show that several genes controlling metabolism, including cyaA and crp, enhance stop-codon readthrough. CyaA catalyzes the synthesis of cyclic adenosine monophosphate (cAMP). Combining RNA sequencing, metabolomics and biochemical analyses, we show that deleting cyaA impairs amino acid catabolism and production of ATP, thus repressing the transcription of rRNAs and tRNAs to decrease readthrough. Single-cell analyses further show that cAMP is a major driver of heterogeneity in stop-codon readthrough and rRNA expression. Our results highlight that carbon metabolism is tightly coupled with stop-codon readthrough.


Comparing distances in mental images constructed from visual experience or verbal descriptions: the impact of survey versus route perspective.
Mental images constructed after visual examination of a spatial configuration or after processing a verbal description of that configuration have been shown to share similar properties, in particular the capacity to preserve metric information contained in the configuration represented. In the present study, we investigated the properties of mental images constructed under learning conditions resulting from the combination of a visual or a verbal mode of acquisition and a survey or route perspective. Participants memorized a virtual environment (a garden containing six objects) under one of four learning conditions: (a) viewing a map of the garden (visual-survey); (b) viewing a video presentation of a journey along the path around the garden (visual-route); (c) listening to a verbal description of the map of the garden (verbal-survey); and (d) listening to a verbal description of the journey around the garden (verbal-route). The participants were then invited to compare the distances separating objects in the garden mentally. Experiment 1, where the pairs of distances to be compared had a common starting point, revealed that the frequency of correct responses was higher, and response times were shorter when participants had learned about the environment visually rather than by a verbal description. The conditions involving a survey perspective resulted in a higher frequency of correct responses and shorter response times than those involving a route perspective. Lastly, a symbolic distance effect was obtained in the first three conditions, in that the greater the difference between the two distances being compared, the higher the frequency of correct responses, and the shorter the response times. Experiment 2, where the pairs of distances had different starting points, replicated these results, although longer response times revealed that the comparison process was more costly. Taken together, these findings support the view that mental spatial representations derived from different sources and adopting different perspectives contain genuine metric properties, except when the verbal modality and the route perspective are combined during learning.


Can the unenhanced phase be eliminated from dual-phase CT angiography for chest pain? Implications for diagnostic accuracy in acute aortic intramural hematoma.
The purposes of this study were to retrospectively assess the frequency of acute aortic intramural hematoma and evaluate whether the elimination of the unenhanced imaging acquisition series from the dual-phase MDCT angiography (CTA) protocol for chest pain might affect diagnostic accuracy in detecting intramural hematoma and justify the reduced radiation dose. From October 2006 to November 2012, 306 patients (mean age, 65.0 years) with acute chest pain underwent emergency CTA with a 64-MDCT scanner. Two experienced cardiovascular radiologists, blinded to the diagnosis, assessed the images in two different sessions in which enhanced (single-phase CTA) and combined unenhanced and contrast-enhanced (dual-phase CTA) findings were evaluated. Sensitivity, specificity, and accuracy along with 95% CIs were calculated. Surgical and pathologic diagnoses, including findings at clinical follow-up and any subsequent imaging modality, were used as reference standards. Thirty-six patients were suspected of having intramural hematoma; 16 patients underwent both surgery and transesophageal echocardiography (TEE), and the remaining 20 underwent TEE. Single-phase CTA showed a higher number of false-negative and false-positive results than dual-phase CTA. With intramural hematoma frequency of 12% (95% CI, 8.38-15.91%), sensitivity, specificity, and accuracy were 94.4% (81.3-99.3%), 99.3% (97.4-99.9%), and 98.7% (96.7-99.6%) for combined dual-phase CTA and 68.4% (51.4-82.5%), 96.3% (93.2-98.2%), and 92.8% (89.3-95.4%) for single-phase CTA. Dual-phase was significantly better than single-phase CTA with respect to sensitivity (p=0.002), specificity (p=0.008), overall accuracy (p<0.001), and interrater agreement (p=0.001). The frequency of acute aortic intramural hematoma is similar to that previously reported. The acquisition of unenhanced images during the chest pain dual-phase CTA protocol significantly improves diagnostic accuracy over single-phase CTA.


Anatomy of the Intertragic Notch of the Auricle May Protect the Ear Canal from Fluids as a Built-In Overflow Spout at an Appropriate Position.
To observe the utility of the intertragic notch during rain showers, an anatomic replica of the human auricle was studied under an artificial shower system with a video recorder. During the shower, water trickled out through the intertragic notch naturally, avoiding the ear canal. This study finds one utility of the intertragic notch may be the prevention of water flowing into the ear canal during rain showers.


Mechanical and biocompatible influences of chitosan fiber and gelatin on calcium phosphate cement.
Calcium phosphate cement (CPC) is a widely used bone substitute in the clinic; however, the low strength of CPC limits its utilization. In this study, we investigated mechanical influences of chitosan fiber combined with gelatin on CPC, and examined the biocompatibility of the new composite with rat bone marrow stromal cells. Compared to the fiber impregnated in phosphate buffered saline (80.5 MPa), our study showed that tensile strength of chitosan fiber increased 106 and 114% with the impregnation of gelatin at the mass fraction 5 and 10%, although this increase was not statistically significant. It was demonstrated by Fourier transform infrared spectroscopy that the characteristic absorption bands of chitosan were changed with the addition of gelatin. The optimal flexural strength enhancement was obtained when CPC was reinforced with fiber at volume fraction of 30% and gelatin at mass fraction of 5% (maximum: 12.31 MPa). The fiber morphology was more compact when the chitosan fibers impregnated with gelatin at mass fraction of 5 or 10% than chitosan alone. The fracture analysis showed that the new CPC-chitosan fiber-gelatin composite presented many remnants of CPC adhered to fibers. Short minimum essential medium extract test showed no cell growth inhibition after the addition of the new composite. Rat bone marrow stromal cells retain the ability to spread and grow on the composite. Our studies demonstrated that the flexural strength is greatly increased by using CPC incorporated with proper ratio of CF and gelatin. More over, the new composite demonstrated biocompatibility in vitro.


Integrative analysis of Mendelian randomization and gene expression profiles reveals a null causal relationship between adiponectin and diabetic retinopathy.
Observational studies have been conducted to investigate the correlation between adiponectin and diabetic retinopathy (DR), but no consistent relationship has been established. In this study, we employed an integrative analysis that combined Mendelian randomization (MR) and bioinformatics analyses to comprehensively explore the association between DR and adiponectin, aiming to provide a unified answer of their relationship. Using the inverse-variance weighted (IVW) method, the odd ratio (OR) of developing DR per 1 mg/dL increment in genetically predicted log-transformed adiponectin concentration was estimated to be 0.949 (P = 0.557). Other robust MR methods produced consistent results, confirming the absence of a causal effect of adiponectin on DR. Additionally, the expression levels of the six adiponectin-related genes showed no significant differences among normal controls, individuals with diabetes but without DR, and those with DR Furthermore, the biological pathways enriched by these genes were not strongly relevant to DR. At both the individual gene and pathway levels, there were no overlaps between the adiponectin-related genes and the differentially expressed genes, indicating a lack of association between adiponectin and DR based on gene expression profiles. In summary, the integrative analysis, which combined MR and bioinformatics data mining, yielded compelling evidence supporting the notion that adiponectin is not a risk factor for DR.


Regional differences in bone density of young men involved in different exercises.
In this cross-sectional, retrospective study, the bone mineral content (BMC) and density (BMD) of the whole skeleton, upper limbs, lower limbs, femoral neck, and lumbar vertebrae were measured using dual photon absorptiometry and the results compared in healthy young males involved in: weight-lifting, running, cross-training, or recreational exercises. When adjusted for body weight, the upper limb BMD was highest in those engaged solely in weight-lifting (mean 1.021, SE 0.019, and 95% CI 0.981-1.061) and lowest in runners (mean 0.908, SE 0.019 and 95% CI 0.869-0.946). These differences were significant (P = 0.0004). There were no significant differences in upper limb BMD between weight-lifters and cross-trained athletes and between runners and those engaged in recreational exercises. Significant differences in BMD were observed between weight-lifters and recreational athletes (P = 0.001) and between cross-trained athletes and runners (P = 0.03). No other significant differences were observed. These data suggest that healthy, young, adult males reporting a history of intensive weight-lifting had significantly greater bone mass of the upper limb bones than those reporting a history of non-weight-lifting exercises. These results imply a specific versus generalized effect of mechanical load on bones of the skeleton.


Hyaluronic Acid-Templated Ag Nanoparticles/Graphene Oxide Composites for Synergistic Therapy of Bacteria Infection.
Developing methods of decreasing the harm to cell and increasing the antibacterial efficiency is becoming a potential topic of medical treatments. We demonstrated a hyaluronidase-triggered photothermal platform for killing bacteria based on silver nanoparticles (AgNPs) and graphene oxide (GO). The property of the hyaluronidase (HAase)-triggered release provided excellent antibacterial activity against Staphylococcus aureus. Upon illumination of NIR light, the GO-based nanomaterials locally raised the temperature, resulting in high mortality of bacteria. The HAase-triggered AgNPs releasing approach for antibacterial allows AgNPs to be protected by hyaluronic acid (HA) template without affecting mammalian cells. The nanocomposites provided antibacterial activity against S. aureus while showing low toxicity to mammal cells. In addition, the GO-HA-AgNPs are prepared for in vivo experiments and show excellent antibacterial property in wound disinfection model.


Skeletal muscle wasting in chronic kidney disease: the emerging role of microRNAs.
Skeletal muscle wasting is a common complication of chronic kidney disease (CKD), characterized by the loss of muscle mass, strength and function, which significantly increases the risk of morbidity and mortality in this population. Numerous complications associated with declining renal function and lifestyle activate catabolic pathways and impair muscle regeneration, resulting in substantial protein wasting. Evidence suggests that increasing skeletal muscle mass improves outcomes in CKD, making this a clinically important research focus. Despite extensive research, the pathogenesis of skeletal muscle wasting is not completely understood. It is widely recognized that microRNAs (miRNAs), a family of short non-coding RNAs, are pivotal in the regulation of skeletal muscle homoeostasis, with significant roles in regulating muscle growth, regeneration and metabolism. The abnormal expression of miRNAs in skeletal muscle during disease has been well described in cellular and animal models of muscle atrophy, and in recent years, the involvement of miRNAs in the regulation of muscle atrophy in CKD has been demonstrated. As this exciting field evolves, there is emerging evidence for the involvement of miRNAs in a beneficial crosstalk system between skeletal muscle and other organs that may potentially limit the progression of CKD. In this article, we describe the pathophysiological mechanisms of muscle wasting and explore the contribution of miRNAs to the development of muscle wasting in CKD. We also discuss advances in our understanding of miRNAs in muscle-organ crosstalk and summarize miRNA-based therapeutics currently in clinical trials.


High Sensitivity of Aged Mice to Deoxynivalenol (Vomitoxin)-Induced Anorexia Corresponds to Elevated Proinflammatory Cytokine and Satiety Hormone Responses.
Deoxynivalenol (DON), a trichothecene mycotoxin that commonly contaminates cereal grains, is a public health concern because of its adverse effects on the gastrointestinal and immune systems. The objective of this study was to compare effects of DON on anorectic responses in aged (22 mos) and adult (3 mos) mice. Aged mice showed increased feed refusal with both acute i.p. (1 mg/kg and 5 mg/kg) and dietary (1, 2.5, 10 ppm) DON exposure in comparison to adult mice. In addition to greater suppression of food intake from dietary DON exposure, aged mice also exhibited greater but transient body weight suppression. When aged mice were acutely exposed to 1 mg/kg bw DON i.p., aged mice displayed elevated DON and DON3GlcA tissue levels and delayed clearance in comparison with adult mice. Acute DON exposure also elicited higher proinflammatory cytokine and satiety hormone responses in the plasma of the aged group compared with the adult group. Increased susceptibility to DON-induced anorexia in aged mice relative to adult mice suggests that advanced life stage could be a critical component in accurate human risk assessments for DON and other trichothecenes.


Follow-up investigation of asymptomatic COVID-19 cases at diagnosis in Busan, Korea.
The objective of the study was to conduct a follow-up investigation of 10 asymptomatic patients at diagnosis among the 98 confirmed coronavirus disease 2019 (COVID-19) cases reported in Busan between February 21, 2020 and March 13, 2020 to determine whether asymptomatic infection and transmission during asymptomatic period are possible. The study analyzed 10 asymptomatic, confirmed COVID-19 cases to determine whether asymptomatic infection is possible. We conducted in-depth interviews with patients and guardians; interviews with primary physicians; review of medical records and drug utilization review (DUR) reports; and base station-based location tracking. Among the 98, confirmed COVID-19 cases reported in Busan, the study analyzed 10 (10.2%) asymptomatic patients at diagnosis. The results confirmed that two (2.0%) patients reported to be asymptomatic during the initial epidemiological investigation, but turned symptomatic before diagnosis as per the in-depth interview results. Four cases (4.0%) of early detection led to confirmed diagnosis during the incubation period and presentation of symptoms after diagnosis. In addition, the remaining four patients (4.0%), having no subjective symptoms nor specific findings on chest radiography and computed tomography, remained asymptomatic until the isolation order was lifted. With regard to whether transmission during the asymptomatic period is possible, it was found that one out of 23 household contacts of the confirmed patients was identified as an additional confirmed case after coming in close contact with an index patient during the presymptomatic period. Among the 98 confirmed cases, asymptomatic infection was confirmed in four cases (4.0%). In addition, there was one additional confirmed case in which the patient was a family member who came in close contact with an index patient during the incubation period, thereby confirming that transmission during the asymptomatic period is possible. The possibility of transmission during the asymptomatic period has been confirmed; therefore, it is necessary to review the measures for expanding contact tracing that is currently being applied starting one day prior to the onset of symptoms.


Multi-scale simulation of structural heterogeneity of swift-heavy ion tracks in complex oxides.
Tracks formed by swift-heavy ion irradiation, 2.2 GeV Au, of isometric Gd2Ti2O7 pyrochlore and orthorhombic Gd2TiO5 were modeled using the thermal-spike model combined with a molecular-dynamics simulation. The thermal-spike model was used to calculate the energy dissipation over time and space. Using the time, space, and energy profile generated from the thermal-spike model, the molecular-dynamics simulations were performed to model the atomic-scale evolution of the tracks. The advantage of the combination of these two methods, which uses the output from the continuum model as an input for the atomistic model, is that it provides a means of simulating the coupling of the electronic and atomic subsystems and provides simultaneously atomic-scale detail of the track structure and morphology. The simulated internal structure of the track consists of an amorphous core and a shell of disordered, but still periodic, domains. For Gd2Ti2O7, the shell region has a disordered pyrochlore with a defect fluorite structure and is relatively thick and heterogeneous with different degrees of disordering. For Gd2TiO5, the disordered region is relatively small as compared with Gd2Ti2O7. In the simulation, 'facets', which are surfaces with definite crystallographic orientations, are apparent around the amorphous core and more evident in Gd2TiO5 along [010] than [001], suggesting an orientational dependence of the radiation response. These results show that track formation is controlled by the coupling of several complex processes, involving different degrees of amorphization, disordering, and dynamic annealing. Each of the processes depends on the mass and energy of the energetic ion, the properties of the material, and its crystallographic orientation with respect to the incident ion beam.


[Pathogenesis of autoantibodies in demyelinating disorders of the central nervous system].
Several autoantibodies in relation to central nervous system demyelinating diseases (CDD) have been reported. Among them, anti-aquaporin 4(AQP4) antibody in neuromyelitis optica (NMO) is a reliable marker for the diagnosis of NMO and the antibody is thought to be closely related to its pathogenesis. Another antibody, anti-myelin oligodendrocyte glycoprotein (MOG) antibody is recently recognized in relevance to CDD, especially in seronegative NMO. Anti-MOG antibodies are also paid attention in pediatric acute disseminated encephalomyelitis (ADEM) and optic neuritis, however the roles for the pathogenesis in these disorders are still not clear. Generally, B cells and autoantibodies are thought to have certain roles in CDD.


PI3K gamma-deficient mice have reduced levels of allergen-induced eosinophilic inflammation and airway remodeling.
In this study, we have examined the role of phosphoinositide 3 kinase gamma (PI3Kgamma), a class Ib PI3K, in contributing to airway remodeling utilizing PI3Kgamma-deficient mice exposed to chronic allergen challenge. Wild-type (WT) mice sensitized to ovalbumin (OVA) and chronically challenged with OVA for 1 mo developed significantly increased levels of eosinophilic inflammation and airway remodeling. In contrast, PI3Kgamma-deficient mice challenged with OVA had significantly reduced numbers of bronchoalveolar lavage and peribronchial eosinophils compared with WT mice. There was no significant difference in the number of bone marrow or circulating peripheral blood eosinophils when comparing WT mice and PI3Kgamma-deficient mice, suggesting that trafficking of eosinophils into the lung was reduced in PI3Kgamma-deficient mice. PI3Kgamma-deficient and WT mice had similar levels of IL-5 and eotaxin-1. The reduced eosinophil recruitment to the airway in PI3Kgamma-deficient mice challenged with OVA was associated with significantly reduced numbers of TGF-beta1+ peribronchial cells, reduced numbers of pSmad 2/3+ airway epithelial cells, and pSmad 2/3+ peribronchial cells, as well as significantly reduced levels of peribronchial fibrosis (quantitated by trichrome staining and image analysis as well as by lung collagen levels). In addition, the area of peribronchial alpha-smooth muscle staining was significantly reduced in PI3Kgamma-deficient compared with WT mice. Overall, this study demonstrates an important role for PI3Kgamma in mediating allergen-induced eosinophilic airway inflammation and airway remodeling, suggesting that PI3Kgamma may be a novel therapeutic target in asthma.


Gas-phase elemental mercury removal using ammonium chloride impregnated sargassum chars.
In this article, pyrolyzed bio-chars derived from a kind of macroalgae, sargassum, were modified by ammonium chloride (NH4Cl) impregnation, and were applied to remove Hg0 from flue gas. The characteristics of sorbents were investigated by the Brunauer-Emmett-Teller, X-ray photoelectron spectroscopy, scanning electron microscopy and ultimate and proximate analysis. The key parameters (e.g. loading value, reaction temperature and concentration of O2, NO, SO2 and water vapor), kinetics analysis and reaction mechanism of Hg0 removal were investigated. The results show that increasing loading value, reaction temperature, O2 concentration and NO concentration enhance Hg0 removal. The increase in SO2 concentration or water vapor concentration has a dual effect on Hg0 removal. The C-Cl groups and C=O groups play an important role in the process of Hg0 removal. The Hg0 removal process of modified samples meets the pseudo-second-order kinetic model.


Phytoremediation: State-of-the-art and a key role for the plant microbiome in future trends and research prospects.
Phytoremediation is increasingly adopted as a more sustainable approach for soil remediation. However, significant advances in efficiency are still necessary to attain higher levels of environmental and economic sustainability. Current interventions do not always give the expected outcomes in field settings due to an incomplete understanding of the multicomponent biological interactions. New advances in -omics are gradually implemented for studying microbial communities of polluted land in situ. This opens new perspectives for the discovery of biodegradative strains and provides us new ways of interfering with microbial communities to enhance bioremediation rates. This review presents retrospectives and future perspectives for plant microbiome studies relevant to phytoremediation, as well as some knowledge gaps in this promising research field. The implementation of phytoremediation in soil clean-up management systems is discussed, and an overview of the promoting factors that determine the growth of the phytoremediation market is given. Continuous growth is expected since elimination of contaminants from the environment is demanded. The evolution of scientific thought from a reductionist view to a more holistic approach will boost phytoremediation as an efficient and reliable phytotechnology. It is anticipated that phytoremediation will prove the most promising for organic contaminant degradation and bioenergy crop production on marginal land.


Comparative analysis of active drag using the MAD system and an assisted towing method in front crawl swimming.
The measurement of active drag in swimming is a biomechanical challenge. This research compared two systems: (i) measuring active drag (MAD) and (ii) assisted towing method (ATM). Nine intermediate-level swimmers (19.7 ± 4.4 years) completed front crawl trials with both systems during one session. The mean (95% confidence interval) active drag for the two systems, at the same maximum speed of 1.68 m/s (1.40-1.87 m/s), was significantly different (p = .002) with a 55% variation in magnitude. The mean active drag was 82.3 N (74.0-90.6 N) for the MAD system and 148.3 N (127.5-169.1 N) for the ATM system. These differences were attributed to variations in swimming style within each measurement system. The inability to measure the early catch phase and kick, along with the fixed length and depth hand place requirement within the MAD system generated a different swimming technique, when compared with the more natural free swimming ATM protocol. A benefit of the MAD system was the measurement of active drag at various speeds. Conversely, the fixed towing speed of the ATM system allowed a natural self-selected arm stroke (plus kick) and the generation of an instantaneous force-time profile.