Impact of mitigating interventions and temperature on the instantaneous reproduction number in the COVID-19 pandemic among 30 US metropolitan areas.
After more than six months into the coronavirus disease (COVID-19) pandemic, as of August 10, 2020, over 734,664 people had died worldwide. The current study aims to evaluate how mitigating interventions affected the epidemic process in the 30 largest metropolitan areas in the US and whether temperature played a role in the epidemic process. Publicly available data for the time series of COVID-19 cases and deaths and weather were analyzed at the metropolitan level. The time-varying reproductive numbers (Rt) based on retrospective moving average were used to explore the trends. Student t-tests were used to compare temperature and peak Rt cross-sectionally. We found that virus transmissibility, measured by instantaneous reproduction number (Rt), had declined since the end of March for all areas and almost all of them reached a Rt of 1 or below after April 15, 2020. The timing of the main decline was concurrent with the implementation of mitigating interventions. However, the Rts remained around 1 for most areas since then and there were some small and short rebounds in some areas, suggesting a persistent epidemic in those areas when interventions were relaxed. Cities with warm temperature also tended to have a lower peak Rt than that of cities with cold temperature. However, they were not statistically significant and large geographic variations existed. Aggressive interventions might have mitigated the current pandemic of COVID-19, while temperature might have weak effects on the virus transmission. We may need to prepare for a possible return of the coronavirus outbreak.


Large, Tunable, and Reversible pH Changes by Merocyanine Photoacids.
Molecular photoswitches capable of generating precise pH changes will allow pH-dependent processes to be controlled remotely and noninvasively with light. We introduce a series of new merocyanine photoswitches, which deliver reversible bulk pH changes up to 3.2 pH units (pH 6.5 to pH 3.3) upon irradiation with 450 nm light, displaying tunable and predictable timescales for thermal recovery. We present models to show that the key parameters for optimizing the bulk pH changes are measurable: the solubility of the photoswitch, the acidity of the merocyanine form, the thermal equilibrium position between the spiropyran and the merocyanine isomers, and the increased acidity under visible light irradiation. Using ultrafast transient absorption spectroscopy, we determined the quantum yields for the ring-closing reaction and found that the lifetimes of the transient cis-merocyanine isomers ranged from 30 to 550 ns. Quantum yields did not appear to be a limitation for bulk pH switching. The models we present use experimentally determined parameters and are, in principle, able to predict the change in pH obtained for any related merocyanine photoacid.


Limited efficacy of universal leucodepletion in reducing the incidence of febrile nonhaemolytic reactions in red cell transfusions.
This article demonstrates a 62% reduction in the number of febrile nonhaemolytic transfusion reactions (FNHTRs) and 50% reduction in febrile reaction rate associated with red cell transfusions following graded introduction of universal leucodepletion. Though this is a statistically significant reduction (P = 0.009), it shows limited efficacy in abrogating this complication. We also found a reduction in the proportion of cases of FNHTRs with lymphocytotoxic antibodies over the period studied from 54% in 1998, 28% in 1999 to 23% in 2000. This corresponds to a relative increase in the number of febrile reactions without human leucocyte antigen (HLA) antibodies following full implementation of universal leucodepletion, as the total number of reported reactions actually fell considerably during the period. The increase in the number of cases without HLA antibodies was directly proportional to the increase in the number of leucodepleted units used.


An exploratory descriptive cohort study of 90-day prognosis after acute ischaemic stroke with mechanical thrombectomy.
To evaluate the relationship between nursing assessment findings at discharge and acute ischaemic stroke (AIS) patient prognosis after mechanical thrombectomy (MT). We analysed the characteristics of 144 AIS patients with MT treatment admitted to a university affiliated teaching hospital in Chengdu, Sichuan Province China, from January 2020 to December 2020. The modified Rankin Scale (mRS) score was used to assess outcomes 90-days after discharge. Exploratory analyses were undertaken using IBM SPSS Statistics (Version 26.0). At 90-days, 47.9% (n = 69) had a good prognosis (mRS ≤ 2) including 22.2% (n = 32) fully recovered patients. There were 5 (3.5%) deceased patients and 48.6% (n = 70) of patients had a poor prognosis (mRS ≥ 3). In univariate analysis, clinical prognosis correlated with the need for inpatient endotracheal intubation (p = 0.02), nasogastric tube (p < 0.001), indwelling urinary catheter (p < 0.001), central venous catheter (p = 0.03), health knowledge needs of pressure injury prevention (p = 0.03), National Institute of Health Stroke Scale (NIHSS) score (p < 0.001) and Activities of Daily Living (ADL) score (p < 0.001) at the time of discharge from hospital. The average hospitalization time of the 144 patients was 12[IQR, 9-25] days, and the average cost of hospitalization was $Y$21291.93 (SD 9165.01). Almost half of the surviving patients had a poor prognosis. In our country, this surgery and rehabilitation impose a significant financial burden that needs to be addressed. However, the longer length of hospital stay and higher costs at discharge may be contributing factors to worse outcomes. The outcomes of comprehensive nursing assessment of the patients, including nursing needs, activities of daily living, and neurological function, can predict their outcome. We recommend a comprehensive nursing assessment at discharge that predicts patient outcomes and can be used for subsequent targeted interventions. The prognosis of patients with acute ischaemic stroke after mechanical thrombectomy is poor, and the financial burden needs to be considered.


MC4R rs17782313 gene polymorphism was associated with glycated hemoglobin independently of its effect on BMI in Japanese: the Shimane COHRE study.
Type 2 diabetes (T2D) is among the leading public health problems in Japan, and glycated hemoglobin (HbA1c) can be used to screen the population for T2D. Gene polymorphisms, known to be associated with obesity, may predispose individuals to T2D. Rs17782313 the melanocortin 4 receptor (MC4R) has shown one of the strongest associations with body mass index (BMI). We conducted a study to investigate whether rs17782313 (TT versus TC + CC) was associated with HbA1c. We conducted a cross-sectional study including 1142 Japanese adults (446 men: 64.9 ± 14.4 years and 696 women: 66.7 ± 12.3 years). MC4R rs17782313 was genotyped using fast real-time polymerase chain reaction. TC + CC genotype group showed significantly greater BMI (p = 0.039) and HbA1c (p = 0.001) than TT genotype group after adjustment for gender, age and, for HbA1c, BMI. Further analysis using linear regression analysis confirmed that the effect of MC4R rs17782313 on HbA1c (β = 0.08; p = 0.003) was independent of the effect age, gender, BMI, low density lipoprotein cholesterol, homeostasis model assessment of insulin resistance and of beta cell function. This significant independent association was similarly noticed in non-obese (β = 2.82; p = 0.005) subgroups. MC4R rs17782313 was associated with obesity and could confer a certain susceptibility to T2D that could be independent of its pro-obesity effect.


Inactivation of serine:glyoxylate and glutamate:glyoxylate aminotransferases from tobacco leaves by glyoxylate in the presence of ammonium ion.
Serine:glyoxylate and glutamate:glyoxylate aminotransferases (SGAT and GGAT), which catalyze the formation of glycine from glyoxylate during photorespiration, have been purified >300-fold from tobacco leaf extracts. Incubation with glyoxylate in the absence of amino acid substrate resulted in the time- and concentration-dependent inhibition of the partially purified enzymes. The second order rate constants for glyoxylate inhibition were 1.25 and 0.175 per millimolar per minute for SGAT and GGAT, respectively. The enzymes of highest specific activity were not inhibited by 5 millimolar glyoxylate alone but when 1 millimolar NH(4) (+) was added to 1 millimolar glyoxylate for 10 min in the absence of amino donor, SGAT was irreversibly inhibited more than 50%. GGAT was inhibited 50% in 10 minutes by 15 millimolar NH(4) (+) and 1 millimolar glyoxylate. By itself, NH(4) (+) was a reversible inhibitor; SGAT and GGAT were inhibited 50% at 6 millimolar and 50 millimolar, respectively. The irreversible inhibition occurred only with glyoxylate and NH(4) (+) added together; oxalate, formate, acetaldehyde, pyruvate, hydroxypyruvate, and alpha-ketoglutarate did not inhibit either in the presence or absence of NH(4) (+). Glyoxylate and NH(4) (+) could form a carbinolamine which is a serine analog and might bind irreversibly to the enzymes. Under conditions in vivo in which reassimilation of NH(4) (+) is reduced or blocked, the activity of SGAT may be inhibited and if glyoxylate is available, as in leaf peroxisomes, irreversible inhibition may occur.


Metal-coordinated sub-10 nm membranes for water purification.
Ultrathin membranes with potentially high permeability are urgently demanded in water purification. However, their facile, controllable fabrication remains a grand challenge. Herein, we demonstrate a metal-coordinated approach towards defect-free and robust membranes with sub-10 nm thickness. Phytic acid, a natural strong electron donor, is assembled with metal ion-based electron acceptors to fabricate metal-organophosphate membranes (MOPMs) in aqueous solution. Metal ions with higher binding energy or ionization potential such as Fe3+ and Zr4+ can generate defect-free structure while MOPM-Fe3+ with superhydrophilicity is preferred. The membrane thickness is minimized to 8 nm by varying the ligand concentration and the pore structure of MOPM-Fe3+ is regulated by varying the Fe3+ content. The membrane with optimized MOPM-Fe3+ composition exhibits prominent water permeance (109.8 L m-2 h-1 bar-1) with dye rejections above 95% and superior stability. This strong-coordination assembly may enlighten the development of ultrathin high-performance membranes.


Whole brain radiation therapy does not improve the overall survival of EGFR-mutant NSCLC patients with leptomeningeal metastasis.
Leptomeningeal metastasis (LM) is a devastating and terminal complication of advanced non-small-cell lung cancer (NSCLC), especially in patients harboring epidermal growth factor receptor (EGFR) mutations. The role of whole brain radiation therapy (WBRT) in the treatment of EGFR-mutant NSCLC patients with LM is not conclusive. Therefore, we conducted a retrospective study to evaluate the therapeutic effect of WBRT in this setting. EGFR-mutant NSCLC patients with LM, who had previously received treatment at the Shandong Cancer Hospital and Institute from July 2014 to March 2018 were reviewed retrospectively. LM was diagnosed by positive CSF cytology and/or leptomeningeal-enhanced magnetic resonance imaging (MRI). Survival was estimated using the Kaplan-Meier method. In total, 51 EGFR-mutated NSCLC patients with LM were eligible for analysis, subdivided into 26 in the WBRT group and 25 in the non-WBRT group. No significant differences were observed in intracranial ORR (15.4% vs. 16%, p = 0.952) and DCR (34.7% vs. 28%, p = 0.611) between the two groups. The median iPFSLM and OSLM for the entire cohort were 3.3 months (95% CI: 2.77-3.83) and 12.6 months (95% CI: 9.66-15.54), respectively. No difference in iPFSLM was observed between the WBRT and non-WBRT groups (median 3.9 vs. 2.8 months; HR = 0.506, p = 0.052). The median OSLM was 13.6 months in the WBRT group, compared with 5.7 months in the non-WBRT group (HR = 0.454, p = 0.022). Multivariate analyses of OSLM showed that KPS ≥ 80 at the time of LM diagnosis (HR = 0.428, 95% CI: 0.19-0.94; p = 0.034) and the administration of EGFR-TKIs (HR = 0.258, 95% CI: 0.11-0.58; p = 0.001) were independent predictors of survival, but WBRT (HR = 0.49, 95% CI: 0.24-1.01; p = 0.54) was not. Toxicities associated with WBRT or other treatment were rare. For EGFR-mutated NSCLC patients with LM, WBRT did not improve intracranial treatment response and survival statistically.


Review of LDL-C Lowering with Focus on New and Emerging Agents.
Identify the benefits and limitations of statin therapy as a treatment option for lowering LDL-C. Intensify treatment in appropriate patients or refer for intensification. Describe the safety and efficacy of ezetimibe, bempedoic acid, PCSK9 inhibitors, LDL apheresis. Describe the safety and efficacy of medications in late-stage development or under review by the FDA for LDL-C reduction.


Testing intestinal permeability in rats with burns and administration of early enteral nutrition.
Damaged intestinal mucosa in patients with extensive burns is one of the causes of the development of SIRS and MOFS. No unequivocal method has been established so far for assessment of the extent of damage of the intestinal mucosa. In the presented work the authors focus their attention on assessment of intestinal permeability in rats with burns. As their experimental method they used the lactulose-mannitol test (LAMA test). The animals were subjected to a deep burn with an extent of 20% body surface (TBSA). Then the LAMA test was performed 24, 48 and 72 hours after the burn. The rats were divided into groups: the first with a burn without enteral nutrition, the second with a burn and polymeric enteral nutrition and the last with oligomeric enteral nutrition. From the conclusions it is evident that a burn extending over 20% TBSA causes in the laboratory rat to experience impaired intestinal permeability. The work did not prove a significant difference between groups with and without enteral nutrition. Due to its simplicity speed, repeatability and high yield the LAMA test is a method which can be used in patients with burns in departments for the treatment of burns.


Lack of functional wolframin causes drop in plasmalemmal sodium-calcium exchanger type 1 expression at early stage in rat model of Wolfram syndrome.
In previously introduced rat model of Wolfram syndrome, we have shown that in cardiac myocytes lacking functional wolframin protein the calcium transients and contractile response are significantly changed. Therefore, in this model, we evaluated protein and mRNA expression levels of following proteins involved in cardiac myocytes calcium homeostasis: the ryanodine receptor type 2, calsequestrin type 2, the junctophilin type 2 and plasmalemmal sodium-calcium exchanger type 1 (NCX1). For NCX1 we detected a significant decrease in expression both on protein and mRNA level. Thus, beyond its impact on endoplasmic reticulum stress, calcium, and mitochondria, wolframin influences processes in the myocyte plasma membrane.


Short-Term Effects of Global Pelvic Manipulation on Knee Joint Position Sense in Asymptomatic Participants: A Double-Blind Randomized Controlled Trial.
The purpose of this study was to evaluate short-term effects of the global pelvic manipulation (GPM) on knee joint position sense (JPS). This randomized, controlled double-blind trial included 26 asymptomatic participants (X¯± 25.3; standard deviation ± 4.4 years) who were randomly allocated into 2 groups. Sixteen participants were allocated into the experimental group, in which GPM was performed, and the rest of the participants (n = 10) were included in the control group, which received sham ultrasound therapy. Each participant attended 1 session only, and the evaluations were assessed pretreatment and 5 minutes posttreatment through an isokinetic dynamometer (Biodex Medical Systems), in which the data regarding knee JPS ipsilateral to the manipulated sacroiliac joint were collected. Mann-Whitney and Wilcoxon tests were used, with a 95% significance level. There were no statistically significant differences between the groups concerning active and passive JPS at 30° and 60° (P > .05). The results showed a lack of significant differences between the moments in both groups (P > .05). This investigation demonstrated that GPM, with high-velocity low-amplitude thrust, has no effect on knee JPS, suggesting that this manipulative technique does not have a relative effect on muscle spindles and Golgi tendon organ activation in asymptomatic participants.


Reliability and validity of the youth asset survey: an update.
Improve and expand an existing youth asset scale. Consisted of seven steps: (1) review of poorer-performing items and constructs, (2) literature review for relevant new asset constructs/items, (3) review of revised instrument by panel of experts, (4) qualitative review through focus group research, (5) pilot-test of instrument, (6) evaluation of the performance of the instrument in a longitudinal study, and (7) conduct of test-retest analysis. Youth (N = 1111) recruited through canvassing of randomly selected census tracts and blocks. Youth Asset Survey (YAS). Factor analysis was conducted on 50% of the baseline data and repeated on the second half of the baseline data. Correlations were computed for the test-retest analysis. Following modifications to the YAS based upon qualitative research, the survey was administered to youth (mean age, 14.3 years; 53% female; 39% white, 28% Hispanic, 23% African-American, 9% other). Cronbach alpha = .55-.92. A majority (27 of 34) of alpha > or = .65. All items loaded on one construct at alpha > or = .40. The final results yielded 17 constructs assessed via 61 items. Spearman correlations and intraclass correlations ranged from .60 to .82 and .58 to .87, respectively. The results generally suggest that the expanded YAS is a reliable and valid measure of assets.


Discovery of highly potent DENV NS2B-NS3 covalent inhibitors containing a phenoxymethylphenyl residue.
Dengue virus (DENV) has developed rapidly in the past few decades and has been becoming the most widespread arbovirus in the world. The vital role of NS2B-NS3 in virus replication and maturation of relevant proteins makes it the most promising target for anti-DENV drug discovery, although none of NS2B-NS3 inhibitors have been approved for the market so far. In this study, potent NS2B-NS3 covalent inhibitors were discovered via chemical modification of a published covalent inhibitor WSL-01 (IC50 = 129 nM), yielding promising analogs WSL-75 and WSL-84 (IC50 = 24.8 nM and IC50 = 32.89 nM, respectively) with more than 10-fold increased enzymatic activities compared to the lead compound, and no evident cellular toxicity was observed. Further comprehensive structure-activity relationship analysis through covalent docking and molecular dynamics simulation provides informative understanding of the binding modes of covalent inhibitors targeting NS2B-NS3, which would be beneficial for novel NS2B-NS3 inhibitory development.


Mucosal AIDS vaccines.
Debates are still being waged over what is the best strategy for developing a potent AIDS vaccine. All the obvious approaches to making AIDS vaccines have been tried in the past two decades without much success. It is clear that new thinking and a revision of prevailing dogmas needs to be in place if we really want a vaccine. Conventional envelope-based antibody-inducing vaccines do not appear to hold promise, and broadly-neutralizing antibodies are now being searched as an alternative to the failed approach with subunit vaccines. The current consensus is that cellular immune responses, especially those mediated by CD8 cytotoxic/suppressor (CTL) and CD4 helper T lymphocytes, are needed to control HIV. Vaccines capable of inducing cell-mediated responses are, therefore, considered critical for controlling the spread of HIV. DNA-based vaccines triggering CTL reaction are currently thought to be an answer, but will they fulfill the promise? In the following paragraphs, a critical assessment of the state of the art will be provided in an attempt to analyze what we know and still don't know. The focus of this review is primarily on mucosal vaccines-a relatively new area in AIDS research. The update on V-1 Immunitor, the first mucosal AIDS vaccine available commercially, is provided within this context. Some of the reviewed concepts may be disputable, but without departure from the uninspiring consensus no substantial progress in the AIDS vaccine field can be envisioned.


Dietary factors related to physical fitness among navy shipboard men.
Abstract This study examines the relationship between habitual dietary practices and performance on the physical readiness test required of active duty Navy personnel. Participants were 1,013 men (mean age = 26.2 years) stationed aboard nine Navy ships. The men completed a self-report survey of lifestyle and dietary habits and were evaluated on four tests of physical fitness: 1.5-mile Run, Sit-ups, Sit-reach, and Percent Body Fat. A standardized Overall Fitness score was also computed for each person. Results indicated that the participants tended to skip breakfast, ingest moderate amounts of caffeine, and favor a high-fat, low-fiber diet. Fitness scores were associated with a number of dietary variables, including caffeine intake, between-meal snacking, and overeating (all negatively related to fitness, p <.01), and having a general "nutrition orientation" (positively related to fitness, p <.001). The relationships were confounded by the influence of age, exercise, and smoking, but even after controlling for these, diet was a significant predictor of fitness (p <.001).


A comparative study of p53 gene mutations, protein accumulation, and response to cisplatin-based chemotherapy in advanced ovarian carcinoma.
The p53 protein is a multifunctional transcriptional regulator involved in cellular response to DNA damage and has been implicated as a putative determinant of sensitivity of tumor cells to cytotoxic agents. Since the p53 gene becomes inactivated in over one-half of advanced ovarian carcinoma, in this study we have examined the relationships between p53 gene alterations, p53 immunoreactivity, and response to cisplatin-based chemotherapy in ovarian cancer patients. All patients had advanced (FIGO stage III or IV) ovarian carcinoma and, with one exception, were untreated at the time of collection of tumor specimens. After initial debulking surgery, patients received high-dose cisplatin therapy. Tumor samples were analyzed for p53 gene mutations and for p53 protein accumulation, and the findings were correlated with tumor responsiveness. Of the 33 tumors examined, p53 gene mutations were found in 20 cases, including 15 missense mutations, 2 deletions, 2 nonsense mutations, and a base substitution at splice site. Twenty tumors showed positive immunostaining for p53. Only missense mutations were associated with positive immunostaining. In addition, p53 overexpression was detected in five tumors in the absence of mutations. Most (12 of 14) of the missense mutations associated with p53 protein stabilization were found refractory to therapy, as well as tumors overexpressing wild-type p53 (4 of 5). A significant correlation has been found between p53 accumulation, type of mutation (i.e., missense mutations), and pathological response to cisplatin-based therapy. In conclusion, the present results are consistent with a role of p53 as a determinant of chemosensitivity of ovarian carcinoma.


In vitro cultivation of infective larvae of Dirofilaria immitis.
Infective larvae (L3) of Dirofilaria immitis were cultivated in various synthetic media. L3 obtained from Aedes aegypti mosquitoes by mass dissection were inoculated into the media, viz: RPMI 1640 medium with 10 per cent human AB serum (medium-A); Tc-199 medium with organic acids, sugars of Grace's insect medium and 10 per cent foetal calf serum (FCS) (medium-B); and Grace's insect medium with 10 per cent FCS (medium-C). Maximum survival of 26 days was found in medium 'A'. Approximately 80 per cent healthy larvae moulted after 72 hours. They increased in size from an initial average length of 1050 microns and 25 microns width to an average 1600 microns length and 35 microns width. Blunting and rounding of anterior ends were conspicuous.


Two new species of the genus Chilobrachys (Araneae, Theraphosidae) from China.
Two new species of the genus Chilobrachys Karsh, 1892 are described from China: Chilobrachysdominus Lin & Li, sp. nov. from Yunnan and C.jinchengi Lin & Li, sp. nov. from Tibet. Photos and a morphological description of the new species are given. The type specimens of the new species are deposited in the Institute of Zoology, Chinese Academy (IZCAS) in Beijing.


Lipoedematous scalp: is there an association with fatty infiltration of the parotid?
Lipoedematous scalp (LS) is an extremely rare condition characterised by a soft and boggy consistency in the scalp due to an increased layer of subcutaneous tissue.In this report, we present a case of LS in a 64-year-old Indian woman. Clinical examination revealed only vague boggy lumpiness involving the whole of occipital scalp extending to parietal scalp. MRI scalp showed diffuse fatty infiltration of the scalp, particularly at the posterior parietal and occipital convexity extending to both lateral aspects of the cranium, with homogeneous signal in keeping with fat. Incidentally MRI also found diffuse fatty infiltration of the parotids.The aethiopathogenesis of LS is still unknown, however it is believed that the hormone leptin could be the key hormone in the dysregulation of fat deposition and distribution. This case report highlights the subtle features with which these cases can present and explores the literature on reported cases of LS.


Minimum prevalence of latex hypersensitivity in health care workers.
Health care workers (HCW) have been shown to be at significant risk for developing latex allergy. Natural rubber latex hypersensitivity has been reported in 2.9 to 17% of health care workers in previously published studies. This study describes the prevalence of latex hypersensitivity in a large cohort of medical center employees. A screening questionnaire was distributed to 1967 employees in six job categories exposed to latex, and 1331 questionnaires were returned (68%) between March and November 1995. Skin and serologic testing was performed on 156 volunteers. Of the 1331 HCWs who completed the screening questionnaire, 290 (21.8%) self-reported contact dermatitis to latex, 67 (5.0%) self-reported urticaria to latex, 163 (12.2%) self-reported rhinoconjunctivitis to latex, and 17 (1.3%) self-reported asthmatic symptoms to latex. Of the total population of 1967 employees, 38 (1.9%) were either skin test or blood test positive and 30 (1.5%) of these 38 were symptomatic around latex. This study suggests a minimum prevalence of IgE-mediated hypersensitivity to latex of 1.5% among medical center employees. Our reported prevalence figures are lower than previously reported, reflecting, in part, reporting methods using a denominator more consistent with the total population at risk. Our study also illustrates the pitfall of relying on self-reporting in making the diagnosis of latex allergy.


Listening to the Patient: Women Veterans' Insights About Health Care Needs, Access, and Quality in Rural Areas.
Many work to ensure that women veterans receive appropriate and timely health care, yet the needs of those living in rural areas are often ignored. This is a critical oversight given the multitude of reports documenting rural access problems and health disparities. Lacking this, we are unable to plan for and evaluate appropriate care for this specific group. In this project, we spoke with rural women veterans to document service needs and quality of care from their perspective. Rural women veterans' views about health care access and quality were ascertained in a series of five, semistructured focus groups (n = 35) and completion of a demographic questionnaire. Content analysis documented focus-group themes. Participants said that local dental, mental health, and gender-specific care options were needed, as well as alternative healing options. Community-based support for women veterans and interaction with female peers were absent. Participants' support for telehealth was mixed, as were requests for gender-specific care. Personal experiences in the military impacted participants' current service utilization. Action by both Veterans Affairs and the local community is vital to improving the health of women veterans. Service planning should consider additional Veterans Affairs contracts, mobile health vans, peer support, and enhanced outreach.


Human receptor for measles virus (CD46) enhances nitric oxide production and restricts virus replication in mouse macrophages by modulating production of alpha/beta interferon.
Complement regulatory protein CD46 is a human cell receptor for measles virus (MV). In this study, we investigated why mouse macrophages expressing human CD46 restricted MV replication and produced higher levels of nitric oxide (NO) in response to MV and gamma interferon (IFN-gamma). Treatment of MV-infected CD46-expressing mouse macrophages with antibodies against IFN-alpha/beta blocked NO production. Antibodies against IFN-alpha/beta also inhibited the augmenting effect of MV on IFN-gamma-induced NO production in CD46-expressing mouse macrophages. These antibodies did not affect NO production induced by IFN-gamma alone. These data suggest that MV enhances NO production in CD46-expressing mouse macrophages through action of IFN-alpha/beta. Mouse macrophages expressing a human CD46 mutant lacking the cytoplasmic domains were highly susceptible to MV. These cells produced much lower levels of NO and IFN-alpha/beta upon infection by MV, suggesting the CD46 cytoplasmic domains enhanced IFN-alpha/beta production. When mouse macrophages expressing tailless human CD46 were exposed to culture medium from MV-infected mouse macrophages expressing intact human CD46, viral protein synthesis and development of cytopathic effects were suppressed. Pretreating the added culture medium with antibodies against IFN-alpha/beta abrogated these antiviral effects. Taken together, these findings suggest that expression of human CD46 in mouse macrophages enhances production of IFN-alpha/beta in response to MV infection, and IFN-alpha/beta synergizes with IFN-gamma to enhance NO production and restrict viral protein synthesis and virus replication. This novel function of human CD46 in mouse macrophages requires the CD46 cytoplasmic domains.


VMA21 deficiency causes an autophagic myopathy by compromising V-ATPase activity and lysosomal acidification.
X-linked myopathy with excessive autophagy (XMEA) is a childhood-onset disease characterized by progressive vacuolation and atrophy of skeletal muscle. We show that XMEA is caused by hypomorphic alleles of the VMA21 gene, that VMA21 is the diverged human ortholog of the yeast Vma21p protein, and that like Vma21p it is an essential assembly chaperone of the V-ATPase, the principal mammalian proton pump complex. Decreased VMA21 raises lysosomal pH, which reduces lysosomal degradative ability and blocks autophagy. This reduces cellular free amino acids, which upregulates the mTOR pathway and mTOR-dependent macroautophagy, resulting in proliferation of large and ineffective autolysosomes that engulf sections of cytoplasm, merge together, and vacuolate the cell. Our results uncover macroautophagic overcompensation leading to cell vacuolation and tissue atrophy as a mechanism of disease.


The Suppressor of fused gene encodes a novel PEST protein involved in Drosophila segment polarity establishment.
Suppressor of fused, Su(fu), was identified as a semi-dominant suppressor of the putative serine/threonine kinase encoded by the segment polarity gene fused in Drosophila melanogaster. The amorphic Su(fu) mutation is viable, shows a maternal effect and displays no phenotype by itself. Su(fu) mutations are often found associated to karmoisin (kar) mutations but two complementation groups can be clearly identified. By using a differential hybridization screening method, we have cloned the Su(fu) region and identified chromosomal rearrangements associated with Su(fu) mutations. Two classes of cDNAs with similar developmental patterns, including a maternal contribution, are detectable in the region. Transformation experiments clearly assigned the Su(fu)+ function to one of these transcription units while the other one can be most likely assigned to the kar+ function. Surprisingly the 5' end of the kar RNA mapped within the 3' untranslated region of the Su(fu) transcribed sequence. The Su(fu) gene encodes a 53-kD protein, which contains a PEST sequence and shows no significant homologies with known proteins. Genetic analysis shows that proper development requires a fine tuning of the genetic doses of fu and Su(fu) both maternally and zygotically. These results, together with previous genetic and molecular data, suggest that fused and Suppressor of fused could act through a competitive posttraductionnal modification of a common target in the hedgehog signaling pathway.


Network topology of a potential energy landscape: a static scale-free network.
Here we analyze the topology of the network formed by the minima and transition states on the potential energy landscape of small clusters. We find that this network has both a small-world and scale-free character. In contrast to other scale-free networks, where the topology results from the dynamics of the network growth, the potential energy landscape is a static entity. Therefore, a fundamentally different organizing principle underlies this behavior: The potential energy landscape is highly heterogeneous with the low-energy minima having large basins of attraction and acting as the highly connected hubs in the network.


Human adenovirus 5-vectored Plasmodium falciparum NMRC-M3V-Ad-PfCA vaccine encoding CSP and AMA1 is safe, well-tolerated and immunogenic but does not protect against controlled human malaria infection.
In a prior study, a DNA prime / adenovirus boost vaccine (DNA/Ad) expressing P. falciparum circumsporozoite protein (CSP) and apical membrane antigen-1 (AMA1) (NMRC-M3V-D/Ad-PfCA Vaccine) induced 27% protection against controlled human malaria infection (CHMI). To investigate the contribution of DNA priming, we tested the efficacy of adenovirus vaccine alone (NMRC-M3V-Ad-PfCA ) in a Phase 1 clinical trial. The regimen was a single intramuscular injection with two non-replicating human serotype 5 adenovectors encoding CSP and AMA1, respectively. One x 10 (10) particle units of each construct were combined prior to administration. The regimen was safe and well-tolerated. Four weeks later, 18 study subjects received P. falciparum CHMI administered by mosquito bite. None were fully protected although one showed delayed onset of parasitemia. Antibody responses were low, with geometric mean CSP ELISA titer of 381 (range<50-1626) and AMA1 ELISA of 4.95 µg/mL (range 0.2-38). Summed ex vivo IFN-γ ELISpot responses to overlapping peptides were robust, with geometric mean spot forming cells/million peripheral blood mononuclear cells [sfc/m] for CSP of 273 (range 38-2550) and for AMA1 of 1303 (range 435-4594). CD4+ and CD8+ T cell IFN-γ responses to CSP were positive by flow cytometry in 25% and 56% of the research subjects, respectively, and to AMA1 in 94% and 100%, respectively. In contrast to DNA/Ad, Ad alone did not protect against CHMI despite inducing broad, cell-mediated immunity, indicating that DNA priming is required for protection by the adenovirus-vectored vaccine. ClinicalTrials.gov Identifier: NCT00392015.


Vesico-vaginal and recto-vaginal fistulae.
In a series of 1138 patients with vesico-vaginal and/or recto-vaginal fistulae, the main cause in the developing world was obstructed labour, and in the developed world was surgery and/or malignancy. Most repairs were performed by a vaginal approach; there was dedicated nursing care; 85% were cured at the first attempt. In the developing world, prevention will require improved access to good obstetric care.


Lipopolysaccharide-induced inhibition of scavenger receptor expression in human monocyte-macrophages is mediated through tumor necrosis factor-alpha.
The exposure of mononuclear cells to LPS results in a variety of cellular alterations including changes in the expression of various membrane receptors. In human monocyte-macrophages the development of the scavenger receptor, which mediates the uptake and internalization of chemically modified proteins, was suppressed by 100 ng/ml of LPS, concomitant with a reduction in receptor mRNA. Removal of LPS from the media resulted in a rapid increase in scavenger-receptor activity and mRNA that was further enhanced by macrophage-CSF and granulocyte/macrophage-CSF. However, neither macrophage-CSF nor granulocyte/macrophage-CSF could overcome the suppression of scavenger-receptor activity in the presence of LPS. The LPS-induced suppression of the scavenger receptor could be overcome by the co-addition of neutralizing antibody to TNF-alpha. TNF-alpha added to human monocyte-macrophages in the absence of LPS suppressed scavenger receptor activity to the same extent as did LPS. In contrast, the co-addition of LPS and neutralizing antibodies to either IFN-gamma or to IL-1 beta did not overcome the inhibitory effects of LPS on scavenger receptor activity. We conclude that the LPS-induced suppression of the scavenger receptor is mediated primarily through TNF-alpha.


Herpes Simplex Virus 1 Small Noncoding RNAs 1 and 2 Activate the Herpesvirus Entry Mediator Promoter.
Herpes simplex virus 1 (HSV-1) latency-associated transcript (LAT) plays a significant role in efficient establishment of latency and reactivation. LAT has antiapoptotic activity and downregulates expression of components of the type I interferon pathway. LAT also specifically activates expression of the herpesvirus entry mediator (HVEM), one of seven known receptors used by HSV-1 for cell entry that is crucial for latency and reactivation. However, the mechanism by which LAT regulates HVEM expression is not known. LAT has two small noncoding RNAs (sncRNAs) that are not microRNAs (miRNAs), within its 1.5-kb stable transcript, which also have antiapoptotic activity. These sncRNAs may encode short peptides, but experimental evidence is lacking. Here, we demonstrate that these two sncRNAs control HVEM expression by activating its promoter. Both sncRNAs are required for wild-type (WT) levels of activation of HVEM, and sncRNA1 is more important in HVEM activation than sncRNA2. Disruption of a putative start codon in sncRNA1 and sncRNA2 sequences reduced HVEM promoter activity, suggesting that sncRNAs encode a protein. However, we did not detect peptide binding using two chromatin immunoprecipitation (ChIP) approaches, and a web-based algorithm predicts low probability that the putative peptides bind to DNA. In addition, computational modeling predicts that sncRNA molecules bind with high affinity to the HVEM promoter, and deletion of these binding sites to sncRNA1, sncRNA2, or both reduced HVEM promoter activity. Together, our data suggest that sncRNAs exert their function as RNA molecules, not as proteins, and we provide a model for the predicted binding affinities and binding sites of sncRNA1 and sncRNA2 in the HVEM promoter. IMPORTANCE HSV-1 causes recurrent ocular infections, which is the leading cause of corneal scarring and blindness. Corneal scarring is caused by the host immune response to repeated reactivation events. LAT functions by regulating latency and reactivation, in part by inhibiting apoptosis and activating HVEM expression. However, the mechanism used by LAT to control HVEM expression is unclear. Here, we demonstrate that two sncRNAs within the 1.5-kb LAT transcript activate HVEM expression by binding to two regions of its promoter. Interfering with these interactions may reduce latency and thereby eye disease associated with reactivation.


Necrotizing myopathy with pipestem capillaries and minimal cellular infiltration: a case associated with cutaneous signs of dermatomyositis.
In 1991, Emslie-Smith and Engel described a distinct form of idiopathic inflammatory myopathy they called "necrotizing myopathy with pipestem capillaries, microvascular deposition of the complement membrane attack complex (MAC) and minimal cellular infiltration." We describe a patient with exercise-dependent painful myopathy related to a necrotizing myopathy with pipestem capillaries in whom mild cutaneous signs of dermatomyositis were detected 7 years after onset and who subsequently developed multiple cerebral infarcts.


The nutrition support team: surviving and thriving in an era of reform.
Nutrition support teams today are being buffeted by the winds of change in the health care system. With the emphasis shifting from whether to deliver care to how to do so and to how much that care will cost, nutrition support professionals must stay attuned to their institution's needs--and be prepared to adapt to those needs. This article reviews the types of data collection necessary for teams to remain solid as well as offering tips from experts about ways to harness, and even capitalize on, the changes.


Enhanced killing effect on 5-bromodeoxyuridine labelled bacteriophage T1 by monoenergetic synchrotron X-ray at the energy of bromine K-shell absorption edge.
5-Bromo-2'-deoxyuridine labelled bacteriophage T1 was irradiated with monoenergetic X-rays obtained from synchroton radiation with the energies at 13.51 keV and 12.40 keV, just above and below the K-shell absorption edge (13.41 keV) of bromine, respectively. Phage samples were irradiated under three conditions, wet N2 gas, dry N2 gas and in vacuum, with water contents (g H2O/g sample) of 60, 2.6 and 0%. At 12.40 keV the D0 in kGy were 1.1 ("wet"), 1.9 ("dry") and 2.5 ("vacuum") for the Br-labelled phages and 1.6 ("wet"), 2.4 ("dry") and 6.2 ("vacuum") for unlabelled phages. The results clearly demonstrated that the X-ray sensitivities decreased with decrease in water contents. Br-enhancement ratios, ER = D0 (unlabelled)/D0 (Br-labelled), varied from 1.4 ("wet", 12.40 keV) to 2.5 ("vacuum", 13.51 keV). Auger enhancements which were defined by energy-dependent enhancement factor, Fen = [ER(13.51 keV)-ER(12.40 keV)]/ER(12.40 keV), were 0.09 +/- 0.09, 0.29 +/- 0.07 and 0.02 +/- 0.03 under "wet", "dry" and "vacuum" conditions, respectively. The change in Auger enhancement under "dry" condition in comparison with "wet" condition could be explained due to less of water. However the Auger enhancement decreased sharply under "vacuum" condition as the water content was zero. The reason for the sharp decrease in Auger enhancement under "vacuum" condition is difficult to understand. A possible explanation is discussed in the text.


Noncovalent interaction of 5,10,15,20-tetrakis(4-N-methylpyridyl)porphyrin with Cucurbit[7]uril: a supramolecular architecture.
Noncovalent interaction of two water-soluble synthetic macromolecules, Cucurbit[7]uril (CB7) and 5,10,15,20-tetrakis(4- N-methylpyridyl)porphyrin (TMPyP), has been studied from the viewpoint of organizing them through supramolecular interactions and thereby modulating their functional activities. Steady-state and time-resolved fluorescence measurements along with NMR results establish that CB7 crowns the N-methylpyridyl group of the TMPyP in a 1:4 stoichiometry. The overall binding constant was evaluated to be approximately 4.5 x 10 (19) M (-4). The high binding affinity, promoting a stable and extendable molecular assembly in aqueous solution, could open new frontiers in the design and synthesis of higher-order supramolecular structures with photofunctional moieties and project their utility in therapeutic applications.


Effects of Vacuum Impregnation with Sucrose Solution on Mango Tissue.
The influences of vacuum impregnation (VI) on the tissue of mango cubes during atmospheric immersion in sucrose solution were investigated. Results showed that VI effectively facilitated water loss (WL) and sugar gain (SG) during the 300min immersion process, with increases of 20.59% and 31.26%, respectively. A pectin solubilization/degradation phenomenon was observed in the immersion process. The intercellular space and cross section area in the VI-treated mango tissue increased immediately after being released to atmospheric pressure. And it was noted that after experiencing shrinkage-relaxation period twice in the 300 min immersion process, the size of VI-treated mango cells recovered to the original level of fresh ones. Major variations in WL, protopectin content, water soluble pectin content, firmness and microstructure of mango cubes appeared within the first 60 min. In addition, the firmness of mango cubes was positively correlated with the protopectin content (P < 0.01), but negatively correlated with WL and the water soluble pectin content (P < 0.01), indicating that WL and degradation of protopectin contributed greatly to the loss of firmness.


Risk Factors for Recurrence After Pterygium Surgery: An Image Analysis Study.
To determine the risk factors related to recurrence of pterygium using automated image analysis. This study included 149 eyes of 149 patients who underwent pterygium excision and limbal-conjunctival autograft. Demographic variables including age and sex were collected. Image analysis was performed using anterior segment photographs taken preoperatively to measure relative length (horizontal length of pterygium invading cornea/horizontal corneal diameter), relative width (width of pterygium invading cornea/vertical corneal diameter), relative area (RA; area of pterygium invading cornea/total corneal area), and vascularity index (VI; degree of vascularity). In all patients, recurrence of pterygium was determined at 1 year after surgery. Association between these factors and recurrence rate was evaluated with univariate and multivariate analyses. Recurrence at 1 year was reported in 18.8% (28/149) of the patients. Univariate analysis showed that relative length (P = 0.001), relative width (P = 0.031), relative area (P = 0.009), and VI (P < 0.001) were significantly associated with increased risk of recurrence, whereas age and sex had no significant association with recurrence. In multivariate analysis, only VI (P < 0.001) had significant correlation with recurrence. Patients with VI ≥30 had significantly higher recurrence rate than those with VI <30 (33.3% vs. 8.1%, P < 0.001). Increased vascularity was associated with a higher risk of recurrence. Quantification of vascularity using automated image analysis might be useful in predicting the risk of recurrence.


Retention of a time pressure heuristic in a target identification task.
S. Rice and D. Keller (2009) previously reported that participants who were put under time pressure tended to comply more with a diagnostic aid than participants who were not put under time pressure. The present study investigates whether or not learning the benefits of this time pressure heuristic carries over to a second session. Seventy-two New Mexico State University students performed a simulated target-detection task, assisted by a 95% reliable diagnostic aid. Participants were exposed to the following conditions, which were composed of two sessions: speeded-speeded, unspeeded-speeded, speeded-unspeeded, or unspeeded-unspeeded. Results showed that participants who completed the speeded condition for Session 1 performed just as well in the 2nd session regardless of whether or not they were put under time pressure. Participants found that complying with the aid was beneficial to overall performance and continued to comply in a 2nd session even when allowed more time to overrule the aid.


Terephthalate salts of dipositive cations.
The crystal structures of M(C(8)H(4)O(4))(H(2)O)(2), M = Mg, Mn, Fe and Co, have been determined by applying Monte Carlo simulated annealing techniques to synchrotron powder diffraction data and refined by the Rietveld method using both synchrotron and laboratory powder data. These isostructural compounds crystallize in the monoclinic space group C2/c, with 18.2734 (9) <or= a <or= 18.7213 (13), 6.5186 (13) <or= b <or= 6.5960 (4), 7.2968 <or= c <or= 7.4034 (6) A, 98.653 (2) <or= beta <or= 99.675 (1) degrees and Z = 4. The structure consists of alternating layers (perpendicular to a) of terephthalate anions and octahedrally coordinated metal cations. The octahedra are isolated; each carboxylate bridges two metal cations. The equatorial metal coordination consists of four terephthalate O atoms and there are two axial water molecules. Both water-molecule H atoms participate in normal-strength hydrogen bonds to carboxylate O atoms. Quantum chemical calculations (using CASTEP) were used to determine the H-atom positions and analyze the hydrogen bonding and the metal coordination. Both the atomic charges and the M-O bond-overlap populations indicate that, despite the fact that these compounds are isostructural, the metal-terephthalate bonding is different. The bonding in the Mg complex is essentially ionic, while the M-O bonds in the Mn, Fe and Co complexes have significant covalent character. Comparison of a new Rietveld refinement of the structure of copper(II) terephthalate trihydrate with the reported single-crystal structure provides an opportunity to assess the accuracy and precision that can be expected from structures of aromatic carboxylates determined using X-ray powder data. The average difference between the bond distances in the two structures is 0.03 A and the average difference in bond angles is only 1.1 degrees.


[2 cases of gastric mucosa-associated lymphoid tissue lymphoma presenting as a submucosal tumor-like lesion].
Gastric mucosa-associated lymphoid tissue (MALT) lymphoma is the most common form of primary extranodal lymphomas. In most cases, it is developed as multifocal and mucosal lesions, and its initial diagnosis is made by biopsy of suspicious lesions on endoscopy. However, when gastric MALT lymphoma afflict submucosal site without typical mucosal lesion, further procedures are necessary for diagnosis, such as endoscopic mucosal resection and endoscopic ultrasonography. We recently experienced two cases of submucosal tumor-like gastric MALT lymphoma. Both cases were without any mucosal lesion. One case was confirmed by endoscopic mucosal resection, and the latter was by wedge resection. Treatment modalities included endoscopic mucosal resection, surgery, H. pylori eradication, and/or chemotherapy. Both cases achieved complete remission until our 18 months' and 16 months' follow up.


The advances of genetics research on Hirschsprung's disease.
Hirschsprung's disease (HSCR) is a rare and complex congenital disorder characterized by the absence of the enteric neurons in lower digestive tract with an incidence of 1/5 000. Affected infant usually suffer from severe constipation with megacolon and distended abdomen, and face long-term complications even after surgery. In the last 2 decades, great efforts and progresses have been made in understanding the genetics and molecular biological mechanisms that underlie HSCR. However, only a small fraction of the genetic risk can be explained by the identified mutations in the previously established genes. To search novel genetic alterations, new study designs with advanced technologies such as genome/exome-wide association studies (GWASs/EWASs) and next generation sequencing (NGS) on target genes or whole genome/exome, were applied to HSCR. In this review, we summaries the current development of the genetics researches on HSCR based on GWASs/EWASs and NGS, focusing on the newly discovered variants and genes, and their potential roles in HSCR pathogenesis.


Circular on early marriage, March 1988.
This Circular calls on government at all levels in Hunan, China, to summon the departments concerned thoroughly to investigate the problem of early child-bearing so that they can do a good job in managing the problems of unregistered cohabiting and of unmarried mothers. The Circular recommends that: "It is necessary to criticize and educate, and even punish by discipline, those parents who connive with their sons and daughters in practicing unregistered cohabiting." It also states the following: "It is necessary to keep a strict check on registry personnel who do not carry out their duties properly. Those who violate laws and discipline, engage in malpractices for selfish ends, and practice bribery and corruption, resulting in early marriage and child-bearing, must be dealt with strictly. Legal sanctions must be enforced against those who break the law."


The impact of different GFR estimating equations on the prevalence of CKD and risk groups in a Southeast Asian cohort using the new KDIGO guidelines.
Recently, the Kidney Disease: Improving Global Outcomes (KDIGO) group recommended that patients with CKD should be assigned to stages and composite relative risk groups according to GFR (G) and proteinuria (A) criteria. Asians have among the highest rates of ESRD in the world, but establishing the prevalence and prognosis CKD is a problem for Asian populations since there is no consensus on the best GFR estimating (eGFR) equation. We studied the effects of the choice of new Asian and Caucasian eGFR equations on CKD prevalence, stage distribution, and risk categorization using the new KDIGO classification. The prevalence of CKD and composite relative risk groups defined by eGFR from with Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI); standard (S) or Chinese(C) MDRD; Japanese CKD-EPI (J-EPI), Thai GFR (T-GFR) equations were compared in a Thai cohort (n = 5526) There was a 7 fold difference in CKD3-5 prevalence between J-EPI and the other Asian eGFR formulae. CKD3-5 prevalence with S-MDRD and CKD-EPI were 2 - 3 folds higher than T-GFR or C-MDRD. The concordance with CKD-EPI to diagnose CKD3-5 was over 90% for T-GFR or C-MDRD, but they only assigned the same CKD stage in 50% of the time. The choice of equation also caused large variations in each composite risk groups especially those with mildly increased risks. Different equations can lead to a reversal of male: female ratios. The variability of different equations is most apparent in older subjects. Stage G3aA1 increased with age and accounted for a large proportion of the differences in CKD3-5 between CKD-EPI, S-MDRD and C-MDRD. CKD prevalence, sex ratios, and KDIGO composite risk groupings varied widely depending on the equation used. More studies are needed to define the best equation for Asian populations.


Corrected QT interval prolongation in anthracycline-treated survivors of childhood cancer.
Comprehensive cardiac evaluations are currently recommended for all anthracycline-treated patients to detect subclinical cardiac failure. A screening test is needed that would easily and inexpensively identify patients who are at risk for late cardiac decompensation. We routinely reviewed the ECG and echocardiogram (ECHO) results of 52 of 56 anthracycline-treated long-term survivors of childhood cancer who had received > or = 100 mg/m2 of ANTH (ANTH = 1 mg/m2 of doxorubicin), and who were not in clinical heart failure. Exercise testing was performed in eight patients with a corrected QT interval (QTc) of > or = 0.43. Zero of 15 patients (without chest radiation) who received less than 300 mg/m2 of ANTH versus six of 22 who received > or = 300 mg/m2 of ANTH had a QTc > or = 0.43 (P = .03). Three of 15 patients (with chest radiation) who received less than 300 mg/m2 of ANTH versus 12 of 22 who received > or = 300 mg/m2 of ANTH had a QTc > or = 0.43 (P = .03). For all patients (including those with chest radiotherapy), zero of 19 who received less than 300 mg/m2 of ANTH versus eight of 33 who received > or = 300 mg/m2 of ANTH had a QTc of > or = 0.45 (P = .025). Three of 19 who received less than 300 mg/m2 of ANTH versus 19 of 33 who received > or = 300 mg/m2 of ANTH had a QTc of > or = 0.43 (P = .003). One patient had decreased fractional shortening (FS) and QTc prolongation. Cardiac decompensation (with a FS of 24%) occurred with propranolol in a patient with previously normal FS but prolonged QTc. With exercise, the QTc became further prolonged in all four patients with a QTc of 0.44 to 0.46 and in two of four patients with a QTc of 0.43. Prolongation of the QTc, a measure of myocardial repolarization, may reflect injury to myocardial cells. QTc prolongation may be predictive of an increased risk of late cardiac decompensation. If the utility of the QTc measure is confirmed, screening for evidence of myocardial damage can be easily and inexpensively performed by oncologists and primary caretakers.


Cholinergic agonists inhibit HMGB1 release and improve survival in experimental sepsis.
Physiological anti-inflammatory mechanisms can potentially be exploited for the treatment of inflammatory disorders. Here we report that the neurotransmitter acetylcholine inhibits HMGB1 release from human macrophages by signaling through a nicotinic acetylcholine receptor. Nicotine, a selective cholinergic agonist, is more efficient than acetylcholine and inhibits HMGB1 release induced by either endotoxin or tumor necrosis factor-alpha (TNF-alpha). Nicotinic stimulation prevents activation of the NF-kappaB pathway and inhibits HMGB1 secretion through a specific 'nicotinic anti-inflammatory pathway' that requires the alpha7 nicotinic acetylcholine receptor (alpha7nAChR). In vivo, treatment with nicotine attenuates serum HMGB1 levels and improves survival in experimental models of sepsis, even when treatment is started after the onset of the disease. These results reveal acetylcholine as the first known physiological inhibitor of HMGB1 release from human macrophages and suggest that selective nicotinic agonists for the alpha7nAChR might have therapeutic potential for the treatment of sepsis.


Methodological review of treatments for nonparaphilic hypersexual behavior.
Research on nonparaphilic hypersexual behavior has increased in recent years. In the present article, the authors conducted a methodological review of empirical studies that evaluated a treatment for nonparaphilic hypersexual behavior. The authors reviewed several characteristics of the extant studies, including the participants, research designs, treatments evaluated, assessment of nonparaphilic hypersexual behavior, and outcomes. Despite several attempts to explore treatments aimed at attenuating the symptoms of nonparaphilic hypersexual behavior, the findings from this review indicate that much of the outcome research in the field contains significant methodological limitations. The authors conclude by offering recommendations to enhance future outcome research among investigators working with hypersexual populations.


Halomonas radicis sp. nov., isolated from Arthrocnemum macrostachyum growing in the Odiel marshes(Spain) and emended descriptions of Halomonas xinjiangensis and Halomonas zincidurans.
Strain EAR18T was isolated as an endophyte from the roots of a halophyte plant, Arthrocnemum macrostachyum, growing in the Odiel marshes (Huelva, Spain). Cells of strain EAR18T were Gram- stain-negative, motile, non-spore-forming aerobic rods. It grew optimally on tryptic soy agar supplemented with 2.5 % NaCl (w/v), at pH 7 and 30 °C for 48 h. It tolerated NaCl from 0 to 25 % (w/v). It presented Q9 as the major quinone and C19 : 0 cyclo ω8c, summed feature 8 (C18 : 1ω7c and/or C18 : 1ω6c) and C16 : 0 as the predominant fatty acids. The polar lipid profile consisted of diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine and four unidentified phospholipids. The results of phylogenetic analysis based on 16S rRNA gene sequences revealed that strain EAR18T formed a well-supported clade with species Halomonas zincidurans B6T and Halomonas xinjiangensis TRM 0175T (similarities of 98.3 and 96.1 % respectively). Furthermore, digital DNA-DNA hybridization analysis resulted in values of 20.4 % with H. xinjiangensis TRM 0175T and 35.50 % with H. zincidurans B6T, and ANIb/ANIm results in values of 73.8 %/84.2 % with H. xinjiangensis TRM 0175T and 86.8 %/89.4 % with H. zincidurans B6T. Based on phylogeny and differential phenotypic properties in comparison with its closest related species, strain EAR18T is suggested to represent a new species in the genus Halomonas, for which the name Halomonas radicis sp. nov. is proposed. The type strain is EAR18T (=CECT 9077T=LMG 29859T). The whole genome was sequenced, and it had a total length of 4.6 Mbp and a G+C content of 64.9 mol%.


Gadolinium-oxide nanoparticles for cryogenic magnetocaloric applications.
The series of advanced nanocomposites consisting of Gd2O3 nanoparticles (NPs) embedded into periodic porous SiO2 matrix have been investigated with respect to their structural and magnetocaloric properties. By means of small angle neutron scattering and transmission electron microscopy, regular nanopores organized in the cubic or hexagonal superlattice have been documented. The pores are occupied by the NPs of progressive concentration within the nanocomposite series. All of the examined systems have exhibited extraordinarily high values of magnetic entropy change (up to 70 J kg-1 K-1) at low temperatures with the absence of thermal hysteresis, indicating their perspective utilization in cryogenic refrigeration. Profound analysis of magnetic entropy change data via scaling laws has been applied to the nanocomposite materials for the very first time. With the aid of scaling analysis, conclusions on magnetic properties and phase transition type have been made, even for the conditions unavailable in the laboratory.


Sixteen hundred years of increasing tree cover prior to modern deforestation in Southern Amazon and Central Brazilian savannas.
Tropical ecosystems are under increasing pressure from land-use change and deforestation. Changes in tropical forest cover are expected to affect carbon and water cycling with important implications for climatic stability at global scales. A major roadblock for predicting how tropical deforestation affects climate is the lack of baseline conditions (i.e., prior to human disturbance) of forest-savanna dynamics. To address this limitation, we developed a long-term analysis of forest and savanna distribution across the Amazon-Cerrado transition of central Brazil. We used soil organic carbon isotope ratios as a proxy for changes in woody vegetation cover over time in response to fluctuations in precipitation inferred from speleothem oxygen and strontium stable isotope records. Based on stable isotope signatures and radiocarbon activity of organic matter in soil profiles, we quantified the magnitude and direction of changes in forest and savanna ecosystem cover. Using changes in tree cover measured in 83 different locations for forests and savannas, we developed interpolation maps to assess the coherence of regional changes in vegetation. Our analysis reveals a broad pattern of woody vegetation expansion into savannas and densification within forests and savannas for at least the past ~1,600 years. The rates of vegetation change varied significantly among sampling locations possibly due to variation in local environmental factors that constrain primary productivity. The few instances in which tree cover declined (7.7% of all sampled profiles) were associated with savannas under dry conditions. Our results suggest a regional increase in moisture and expansion of woody vegetation prior to modern deforestation, which could help inform conservation and management efforts for climate change mitigation. We discuss the possible mechanisms driving forest expansion and densification of savannas directly (i.e., increasing precipitation) and indirectly (e.g., decreasing disturbance) and suggest future research directions that have the potential to improve climate and ecosystem models.


Parent training for young children with developmental disabilities: randomized controlled trial.
A randomized controlled trial was used to evaluate a parent training intervention for caregivers with preschool-age children with developmental disabilities. The 21 families in the experimental group received usual care plus the 12-week Incredible Years Parent Training Program with developmental delay modifications. Families in the control group (n = 23) received usual care, including early childhood education and related services. Results suggest that this parent training intervention was superior to usual care for young children with developmental delays or disabilities in reducing negative parent-child interactions and child behavior problems. Participants in the experimental group indicated high satisfaction with treatment. Additional research is necessary to document maintenance and generalization of treatment outcomes.


Plasmon-polariton modes guided by a metal film of finite width bounded by different dielectrics.
The properties of some purely bound plasmon-polariton modes guided by an asymmetric waveguide structure composed of a thin lossy metal film of finite width supported by a dielectric substrate and covered by a different dielectric superstrate are presented for what is believed to be the first time. The mode spectrum supported by these structures is quite different from the spectrum supported by corresponding asymmetric slab structures or similar finite-width symmetric waveguides. Unlike these limiting cases, the dispersion with film thickness exhibits an unusual oscillatory character that is explained by a "switching" of constituent interface modes. This mode switching is unique to asymmetric finite-width structures. Above a certain cut-off film thickness, the structure can support a long-ranging mode and its attenuation decreases very rapidly with decreasing film thickness, more so than the long-ranging mode in symmetric structures. Also, the cutoff thickness of the long-ranging mode is larger than the cutoff thickness of the long-ranging mode in the corresponding asymmetric slab waveguide, which implies that propagation along finite-width films is more sensitive to the asymmetry in the structure than propagation along a similar slab structure. Both of these results are potentially useful for the transmission and control of optical radiation.


The SH2 domain and kinase activity of JAK2 target JAK2 to centrosome and regulate cell growth and centrosome amplification.
JAK2 is cytokine-activated non-receptor tyrosine kinase. Although JAK2 is mainly localized at the plasma membrane, it is also present on the centrosome. In this study, we demonstrated that JAK2 localization to the centrosome depends on the SH2 domain and intact kinase activity. We created JAK2 mutants deficient in centrosomal localization ΔSH2, K882E and (ΔSH2, K882E). We showed that JAK2 WT clone strongly enhances cell proliferation as compared to control cells while JAK2 clones ΔSH2, K882E and (ΔSH2, K882E) proliferate slower than JAK2 WT cells. These mutant clones also progress much slower through the cell cycle as compared to JAK2 WT clone and the enhanced proliferation of JAK2 WT cells is accompanied by increased S -> G2 progression. Both the SH2 domain and the kinase activity of JAK2 play a role in prolactin-dependent activation of JAK2 substrate STAT5. We showed that JAK2 is an important regulator of centrosome function as the SH2 domain of JAK2 regulates centrosome amplification. The cells overexpressing ΔSH2 and (ΔSH2, K-E) JAK2 have almost three-fold the amplified centrosomes of WT cells. In contrast, the kinase activity of JAK2 is dispensable for centrosome amplification. Our observations provide novel insight into the role of SH2 domain and kinase activity of JAK2 in centrosome localization of JAK2 and in the regulation of cell growth and centrosome biogenesis.


Complications and adverse events of plaque brachytherapy for ocular melanoma.
Plaque brachytherapy is a well-accepted modality to manage selected cases of ocular melanoma. Although this modality provides validated oncologic and quality of life benefits, severe complications and adverse events can occur. This article reviews complications and adverse events of plaque brachytherapy, including scleral necrosis, strabismus, cataract, glaucoma, and retinopathies as well as management of these conditions. For practicing oncologists and ophthalmologists, these complications are important to understand, identify, and treat. Additionally, an understanding of common complications of brachytherapy should influence the decision of pursuing it as a treatment option.


Histologic Changes Associated With Placental Separation in Gilts Infected with Porcine Reproductive and Respiratory Syndrome Virus.
The placenta is a vital organ providing the developing fetus with nutrient and gas exchange, thermoregulation, and waste elimination necessary for fetal development, as well as producing hormones to maintain pregnancy. It is hypothesized that fetal pig death in porcine reproductive and respiratory syndrome may be attributed to pathology of the maternal-fetal interface leading to premature placental separation. This study was designed to evaluate the chronologic progression of porcine reproductive and respiratory syndrome virus (PRRSV)-induced lesions at the maternal-fetal interface, with particular focus on placental separation in experimentally challenged third-trimester gilts. Fifteen gilts were inoculated with a virulent strain of PRRSV-2 on gestation day 86 ± 0.4. On multiple days postinoculation, 3 gilts along with 1 sham-inoculated control per time point were euthanized, and uterine and fetal placental tissues corresponding to each fetus were collected for histopathologic evaluation. The presence of any fetal lesion was 23 times more likely in compromised (meconium-stained and decomposed) compared with viable fetuses ( P < .001). In PRRSV-infected gilts, endometritis was more severe than placentitis, and the severity of endometrial inflammation and vasculitis increased progressively from 2 to 14 days postinoculation. Neither placental vasculitis nor a chronologic progression in the severity of placental detachment was observed. Severe placental detachment was more frequently present in PRRSV-infected compared with noninfected samples and was most significantly associated with placental inflammation, compared with other uterine lesions, viral load, or termination day. The results of this study suggest that placental separation by itself is not sufficient to significantly compromise fetal viability in reproductive porcine reproductive and respiratory syndrome.


[Conservative treatment of the painful, stiff shoulder].
The painful respectively stiff shoulder form an important part of orthopaedic practice. The treatment of patients with such a disease is at first always conservative except acute rupture of the tendon. Recurrences and those who do not respond to therapy require surgery. This study includes 86 patients treated for the painful shoulder. The were followed up and subjected to statistical analysis to determine the success of treatment by conservative methods. Conservative methods were in 83 shoulders, what amounts to a rate of 93 percent. Our results correspond to those reported in literature.


Spectral and photophysical studies on cruciform oligothiophenes in solution and the solid state.
The photophysical and spectroscopic properties of a new class of oligothiophene derivatives, designated as cruciform oligomers, have been investigated in solution (room and low temperature) and in the solid state (as thin films in Zeonex matrixes). The study comprises absorption, emission, and triplet-triplet absorption spectra, together with quantitative measurements of quantum yields (fluorescence, intersystem crossing, internal conversion, and singlet oxygen formation) and lifetimes. The overall data allow the determination of the rate constants for all decay processes. From these, several conclusions are drawn. First, in solution, the main deactivation channels for the compounds are the radiationless processes: S(1) --> S(0) internal conversion and S(1) --> T(1) intersystem crossing. Second, in general, in the solid state, the fluorescence quantum yields decrease relative to solution. A comparison is made with the analogous linear alpha-oligothiophenes, revealing a lower fluorescence quantum efficiency and, in contrast to the normal oligothiophenes, that internal conversion is an important channel for the deactivation of the singlet excited state. Replacement of thiophene by 1,4-phenylene units in the longer-sized cruciform oligomer increases the fluorescence efficiency. The highly efficient generation of singlet oxygen through energy transfer from the triplet state (S(Delta) approximately 1) provides support for the measured intersystem crossing quantum yields and suggests that reaction with this may be an important pathway to consider for degradation of devices produced with these compounds.


Fatal cardiac ischaemia associated with prolonged desflurane anaesthesia and administration of exogenous catecholamines.
Four cardiac ischaemic events are reported during and after prolonged anaesthesia with desflurane. We have evaluated desflurane in 21 consecutive patients undergoing advanced head and neck reconstructive surgery. Four deaths occurred which were associated with cardiac ischaemic syndromes either during or immediately after operation. All patients in the study received a similar anaesthetic. This comprised induction with propofol and maintenance with alfentanil and desflurane in oxygen-enriched air. Inotropic support (either dopamine or dobutamine in low dose, 5 micrograms.kg.min-1) was provided as part of the anaesthetic technique in all patients. Critical cardiovascular incidents were observed in each of the four patients during surgery. These were either sudden bradycardia or tachycardia associated with ST-segment electrocardiographic changes. The four patients who died had a documented past history of coronary heart disease and were classified American Society of Anesthesiologists (ASA) II or III. One patient (#2) did not survive anaesthesia and surgery and the three others died on the first, second and twelfth postoperative days. Enzyme increases (CK/CK-MB) were available in three patients and confirmed myocardial ischaemia. These cases represent an unexpected increase in the immediate postoperative mortality for these types of patients and this anaesthetic sequence.


Frequency of the functionally relevant aryl hydrocarbon receptor repressor (AhRR) Pro185Ala SNP in Papua New Guinea.
The diverse cultural and social habits of the Papua New Guinea (PNG) population include betel quid chewing and more recently smoking. The formation of DNA adducts from betel quid is mediated by the cytochrome P450 (CYP) enzymes, including CYP1A2. The tobacco smoke compounds can induce CYP1A2. The transcription factor AhR (aryl hydrocarbon receptor) is involved in the regulation of CYP1A2 expression. AhR activity is itself regulated by other transcription factors, including the aryl hydrocarbon receptor repressor (AhRR). The AhRR Pro185Ala (rs2292596; 565C>G) minor allele was recently associated with a lower AhR repressor activity, leading to a higher CYP1A2 inducibility. We investigated AhRR Pro185Ala SNP in the East Sepik populations in PNG and found a high frequency of 53.4% of the minor allele, significantly different from other Asian populations. We can hypothesize that a high frequency of the AhRR SNP can be a risk factor in the incidence of oral cancer and other neoplasias in PNG due to higher inducibility of CYP1A2. The potential role of AhRR pharmacogenetics in the risk of developing cancers associated with betel quid chewing and smoking should be addressed and clarified in future epidemiological studies in PNG.


Determination of carboxylic acid salts in pharmaceuticals by high-performance liquid chromatography after pre-column fluorogenic labelling.
2-Bromoacetyl-6-methoxynaphthalene (Br-AMN) was used as a fluorogenic labelling reagent for high-performance liquid chromatographic (HPLC) analyses of pyroglutamic acid, 4-hydroxybutyric acid and thioctic acid in pharmaceutical formulations. The reaction was carried out in aqueous medium in the presence of a cationic surfactant to obtain the direct derivatization of the salts of 4-hydroxybutyric acid and thioctic acid or in acetonitrile for pyroglutamic acid. The resulting naphthacylesters were then chromatographed under reversed-phase (C-18) conditions and detected fluorimetrically (lambda exc, 300 nm; lambda em, 460 nm). The method proved to be suitable for the sensitive and selective analysis of commercial formulations of the cited acidic drugs.


Regionalizing potential for microbial bypass flow through New Zealand soils.
Microbial breakthrough curves of 12 soils, generated by the application of dairy shed effluent followed by continuous artificial rainfall for one pore volume at 5 mm h(-1) onto large undisturbed soil cores, have been ranked as high, medium, or low potential for microbial bypass flow. The ranking is based on the position of the peak in the breakthrough curve. Knowledge of soil properties that affect microbial transport through soil gained from the microbial breakthrough curves was linked to soil classes, or to their accessory properties, of the New Zealand Soil Classification. Spatial depiction of the ratings has been achieved via the national 1:50,000 scale soil map. Soils with a drainage impediment or those with well developed soil structure have a high potential for microbial bypass flow, whereas soils from tephra and Recent Soils with less developed, porous, soil structure have a low potential for microbial bypass flow. The risk rankings should be considered as maxima because management may change some rankings.


Pro-Fibrotic CD26-Positive Fibroblasts Are Present in Greater Abundance in Breast Capsule Tissue of Irradiated Breasts.
Breast capsular contracture is a major problem following implant-based breast reconstruction, particularly in the setting of radiation therapy. Recent work has identified a fibrogenic fibroblast subpopulation characterized by CD26 surface marker expression. This work aimed to investigate the role of CD26-positive fibroblasts in the formation of breast implant capsules following radiation therapy. Breast capsule specimens were obtained from irradiated and nonirradiated breasts of 10 patients following bilateral mastectomy and unilateral irradiation at the time of expander-implant exchange, under institutional review board approval. Specimens were processed for hematoxylin and eosin staining as well as for immunohistochemistry and fluorescence activated cell sorting for CD26-positive fibroblasts. Expression of fibrotic genes and production of collagen were compared between CD26-positive, CD26-negative, and unsorted fibroblasts. Capsule specimens from irradiated breast tissue were thicker and had greater CD26-postive cells on immunofluorescence imaging and on fluorescence activated cell sorting analysis than did capsule specimens from the nonirradiated breast. Compared with CD26-negative fibroblasts, CD26-positive fibroblasts produced more collagen and had increased expression of the profibrotic genes IL8, TGF-β1, COL1A1, and TIMP4. CD26-positive fibroblasts were found in a significantly greater abundance in capsules of irradiated compared with nonirradiated breasts and demonstrated greater fibrotic potential. This fibrogenic fibroblast subpopulation may play an important role in the development of capsular contracture following irradiation, and its targeted depletion or moderation may represent a potential therapeutic option.


Using DNA methylation patterns to infer tumor ancestry.
Exactly how human tumors grow is uncertain because serial observations are impractical. One approach to reconstruct the histories of individual human cancers is to analyze the current genomic variation between its cells. The greater the variations, on average, the greater the time since the last clonal evolution cycle ("a molecular clock hypothesis"). Here we analyze passenger DNA methylation patterns from opposite sides of 12 primary human colorectal cancers (CRCs) to evaluate whether the variation (pairwise distances between epialleles) is consistent with a single clonal expansion after transformation. Data from 12 primary CRCs are compared to epigenomic data simulated under a single clonal expansion for a variety of possible growth scenarios. We find that for many different growth rates, a single clonal expansion can explain the population variation in 11 out of 12 CRCs. In eight CRCs, the cells from different glands are all equally distantly related, and cells sampled from the same tumor half appear no more closely related than cells sampled from opposite tumor halves. In these tumors, growth appears consistent with a single "symmetric" clonal expansion. In three CRCs, the variation in epigenetic distances was different between sides, but this asymmetry could be explained by a single clonal expansion with one region of a tumor having undergone more cell division than the other. The variation in one CRC was complex and inconsistent with a simple single clonal expansion. Rather than a series of clonal expansion after transformation, these results suggest that the epigenetic variation of present-day cancer cells in primary CRCs can almost always be explained by a single clonal expansion.


Isolation and characterization of the fibrin intermediate arising from cleavage of one fibrinopeptide A from fibrinogen.
The thrombin-catalyzed cleavage of N-terminal fibrinopeptide A (FPA) from the two Aalpha-chains of fibrinogen exposes aggregation sites with the critical sequence GPR located just behind FPA. It is well known that exposure of both GPR sites transforms fibrinogen into self-aggregating, fully coagulable alpha-fibrin monomers, but the fibrin precursor with one site exposed and one FPA intact has eluded description. The formation of this "alpha-profibrin" in the course of thrombin reactions and its distribution among both the aggregating and non-aggregating components of the reactions are characterized here by immunoprobing electrophoretic and gel chromatographic separations using monoclonal antibodies specific for FPA and for exposed GPR sites. These analyses show alpha-profibrin to be a non-aggregating derivative indistinguishable from fibrinogen in solutions that are rich in fibrinogen relative to dissolved fibrin. But alpha-profibrin forms soluble complexes with alpha-fibrin monomer under conditions in which it and fibrin predominate over fibrinogen. It was isolated as a complex with fibrin by gel chromatography of cryoprecipitates and then separated from the fibrin either by electrophoretic gel shifts induced with a peptide analog of the GPR aggregation site or by chromatographic gel shifts induced with monoclonal anti-FPA antibody. The weak aggregation of alpha-profibrin with itself and with fibrinogen conforms with prior indications that coupled interactions through the paired GPR sites on fibrin monomers are pivotal to their aggregation. It is suggested that alpha-profibrin may be a hypercoagulable fibrin precursor because it is converted to alpha-fibrin monomer faster than fibrinogen converts to monomer.


Insig-2, a second endoplasmic reticulum protein that binds SCAP and blocks export of sterol regulatory element-binding proteins.
This paper describes insig-2, a second protein of the endoplasmic reticulum that blocks the processing of sterol regulatory element-binding proteins (SREBPs) by binding to SCAP (SREBP cleavage-activating protein) in a sterol-regulated fashion, thus preventing it from escorting SREBPs to the Golgi. By blocking this movement, insig-2, like the previously described insig-1, prevents the proteolytic processing of SREBPs by Golgi enzymes, thereby blocking cholesterol synthesis. The sequences of human insig-1 and -2 are 59% identical. Both proteins are predicted to contain six transmembrane helices. The proteins differ functionally in two respects: (i) production of insig-1, but not insig-2, in cultured mammalian cells requires nuclear SREBPs; and (ii) at high levels of expression, insig-1, but not insig-2, can block SCAP movement in the absence of exogenous sterols. The combined actions of insig-1 and -2 permit feedback regulation of cholesterol synthesis over a wide range of sterol concentrations.


Highlighting protein kinase CK2 movement in living cells.
Protein kinase CK2 has traditionally been described as a stable heterotetrameric complex (alpha2beta2) but new approaches that effectively capture the dynamic behavior of proteins, are bringing a new picture of this complex into focus. To track the spatio-temporal dynamics of CK2 in living cells, we fused its catalytic alpha and regulatory beta subunits with GFP and analog proteins. Beside the mostly nuclear localization of both subunits, and the identification of specific domains on each subunit that triggers their localization, the most significant finding was that the association of both CK2 subunits in a stable tetrameric holoenzyme eliminates their nuclear import (Mol Cell Biol 23: 975-987, 2003). Molecular movements of both subunits in the cytoplasm and in the nucleus were analyzed using different new and updated fluorescence imaging methods such as: fluorescence recovery after photo bleaching (FRAP), fluorescence loss in photo bleaching (FLIP), fluorescence correlation spectroscopy (FCS), and photoactivation using a biphoton microscope. These fluorescence-imaging techniques provide unprecedented ways to visualize and quantify the mobility of each individual CK2 subunit with high spatial and temporal resolution. Visualization of CK2 heterotetrameric complex formation could also be recorded using the fluorescence resonance energy transfer (FRET) technique. FRET imaging revealed that the assembling of this molecular complex can take place both in the cytoplasmic and nuclear compartments. The spatio-temporal organization of individual CK2 subunits and their dynamic behavior remain now to be correlated with the functioning of this kinase in the complex environment of the cell.


Visual information about moving objects.
A mathematical model of visual flow is presented, which could potentially account for an observer's ability to effectively interact with moving objects. The analysis demonstrates that there is visual information available to an observer about (a) a moving object's angle of approach, (b) changes in its velocity and acceleration, (c) whether its velocity and acceleration are positive or negative, (d) its time to collision with both the horizontal and vertical axes, and (e) whether it will cross the horizontal axis in front of or behind the point of observation. Several experiments are reported in which observer's sensitivity to these different aspects of visual information is examined using a variety of experimental tasks. The results suggest that human observers are highly sensitive to many abstract properties of visual stimulation, but that they are not sensitive to all of the information that is potentially available.


The Effects of Vonoprazan Fumarate on the Tacrolimus Blood Concentration in Liver Transplant Recipients.
The proton pump inhibitors were reported to affect the blood concentration of tacrolimus. Vonoprazan fumarate is a new acid suppressant with potent acid inhibitory effects. There have been no reports concerning the effect of vonoprazan on the tacrolimus blood concentration in liver transplant (LT) recipients. Eighteen living donor liver transplantation (LDLT) recipients who switched from proton pump inhibitors (PPIs) to vonoprazan between 2016 to 2018 were enrolled in this retrospective study. We investigated blood levels of tacrolimus, and liver and renal function before and after the change from PPIs to vonoprazan. The median C 0 /D of tacrolimus before conversion, 3 months after conversion, and 6 months after conversion were 2.33, 1.53, and 1.89, respectively, and there was no significant difference. Conversion from another PPI to vonoprazan was not associated with a worsening liver function. The estimated glomerular filtration rate was significantly worse after conversion. Vonoprazan can be safely administered to LT recipients receiving tacrolimus during the stable period.


[The characteristics of medical activities in families fostering disabled children].
The characteristics of medical activities in families fostering disabled children are given. The assessment is implemented according the system of specific indicators developed by the authors to determine corresponding social hygienic, medical organizational and social psychological factors. The analysis of medical activities indicators is carried out to reveal the groups of higher medical social risk and to establish the requirements in different types of medical care.


A qualitative evaluation of questions and responses from five occupational questionnaires developed to assess exposures.
Questionnaires are increasingly being used in the workplace to assess exposures to chemicals and other agents. Although the literature contains much information on questionnaire design in general, little information is available on the challenges related to questionnaires applied to the occupational setting. Questionnaires on dry cleaning workers, nurses, farmers, car mechanics, and truck drivers were administered to a total of 25 people currently performing one of these jobs. After asking each question, the interviewer probed to identify the difficulties the respondents had in answering the questions. Overall, the respondents were able to answer the questions. Problems were found, however, with particular questions that reduced the effectiveness of the questionnaire. These included the use of unclear terms, questions open to multiple interpretations, difficult computational requirements (e.g., asking for averages for highly variable tasks), ineffective transitions between topics, and overlapping response categories. This type of testing is a crucial part of questionnaire development and can be used to effectively identify potential problems with questions and, therefore, improve them to enhance collection of higher-quality data for assessments of occupational exposures.


Long-term outcome of patients treated with antithyroid drugs, radioactive iodine or surgery for persistent or relapsed Graves' disease.
The aim of this study was to compare long-term mortality, morbidity, and cumulative healthcare costs between antithyroid drugs, radioactive iodine, and surgical treatment for patients with persistent or relapsed Graves' disease. Data on patients with persistent or relapsed Graves' disease between 2006 and 2018 were retrieved from the Hong Kong Hospital Authority. Hazard ratios (HRs) estimated by Cox proportional hazards regression models were used to compare the risks of all-cause mortality, cardiovascular disease, atrial fibrillation, psychological disease, Graves' ophthalmopathy, and cancer across treatment groups. The 10-year healthcare cost and change in co-morbidity status were also estimated. Over a median follow-up of 79 months (22 636 person-years), a total of 3443 patients (antithyroid drug 2294, radioactive iodine 755, surgery 394) were analysed. Compared with antithyroid drug treatment, surgery was associated with significantly lower risks of all-cause mortality (HR 0.40, 95 per cent c.i. 0.36 to 0.45), cardiovascular disease (HR 0.54, 0.48 to 0.60), atrial fibrillation (HR 0.11, 0.09 to 0.14), psychological disease (HR 0.85, 0.79 to 0.92), Graves' ophthalmopathy (HR 0.09, 0.08 to 0.10), and cancer (HR 0.56, 0.50 to 0.63). Patients who underwent surgery also had a lower risk of all outcome events than those in the radioactive iodine group. The 10-year direct cumulative healthcare cost was €14 754 for surgery compared with €17 390 for antithyroid drugs, and €17 918 for the radioactive iodine group. Patients who underwent surgery for persistent or relapsed Graves' disease had lower risks of all-cause mortality and analysed morbidities. The 10-year cumulative healthcare cost in the surgery group was lowest among the three treatment alternatives.


Efficient and clean photoreduction of CO(2) to CO by enzyme-modified TiO(2) nanoparticles using visible light.
A hybrid enzyme-nanoparticle system is described for achieving clean reduction of CO(2) to CO using visible light as the energy source. An aqueous dispersion of TiO(2) nanoparticles modified by attachment of carbon monoxide dehydrogenase (CODH) and a Ru photosensitizer produces CO at a rate of 250 mumol of CO (g of TiO(2))(-1) h(-1) when illuminated with visible light at pH 6 and 20 degrees C.


[Cleft lip, maxilla and palate treatment by Dr. Talmant's team in Nantes].
Over the last 30 years, our private cleft lip and palate team has developed an increasing activity based on the Victor Veau's concept: "All the structures are present and only deformed". Our goal is to achieve an anatomical and fully functional repair in every fields with the first operation. A few recent refinements have improved our primary procedures: intravelar veloplasty; simultaneous lengthening of the columella and primary lip repair in bilateral clefts; nasal retainer for the 3 or 4 first postoperative months allowing the establishment of a nasal breathing mode at once. Our timing has been the same over the last 21 years if we except that we currently perform the gingivoperiosteoplasty between 4 and 5 years of age so that the width and the relationships of the maxillary arch are normal at the time of the mixed dentition. The timing is the same in uni and bilateral clefts. No preoperative orthopedics. At 6 months of age, nasolabial repair and closure of the soft palate with intravelar veloplasty. At 18 months of age, anatomical closure of the residual cleft of the bony palate in two planes without vomer flap or denuded bone. Between 4 and 5 years of age, after a short orthopedic treatment, closure of the alveolar cleft by a gingivoperiosteoplasty with iliac bone graft. From 6 years of age we start the orthodontic treatment. The current evolution allows to think that only few late corrections will be necessary.


Sex differences in neuroanatomical and clinical correlations in schizophrenia.
The purpose of this study was to investigate sex differences in relationships between brain and behavior in schizophrenia. Frontal lobe, temporal lobe, and whole brain volumes were obtained from magnetic resonance images of 91 patients with schizophrenia (54 men and 37 women) and 114 healthy comparison subjects (62 men and 52 women). Four independent symptom scales, based on the following symptom clusters, were derived from clinical data: negative, disorganization, Schneiderian hallucinations-delusions, and suspicion-hostility. Regression analyses incorporating the four clinical scales and neuroanatomical volumes were performed to investigate possible interactions between brain region and sex. Significant interactive effects of sex and frontal lobe volume were found in regression analyses of the disorganization and suspicion-hostility symptom scales. In men, higher frontal lobe volume was associated with milder severity of disorganization but was not correlated with severity of suspicion-hostility. In women, higher frontal lobe volume was associated with more severe disorganization as well as more severe suspicion-hostility. No associations were found between brain volume and severity of negative or Schneiderian symptoms. Differences between male and female patients were observed in the relationships between frontal lobe volume and two of the four clinical dimensions examined. These findings suggest that aspects of the neuropathological basis for some symptoms of schizophrenia may be sexually dimorphic.


Decreased serotonin transporter binding in unaffected relatives of manic depressive patients.
There are numerous reports of decreased binding to platelet serotonin transporter (5-HTT) in depression, suggesting that it might be considered a trait marker of depression. To further investigate whether reduced 5-HTT function could be an endophenotype in manic depressive illness, we looked for abnormalities of platelet 5-HTT among subjects who are potential carriers of genetic vulnerability to manic depressive illness (MDI). Blood samples were obtained from 20 unaffected relatives from families with at least two individuals with bipolar disorder and from 19 control participants. Plasma 5-HIAA, platelet 5-HT, and [3H] imipramine binding were measured. Unaffected relatives manifested lower platelet 5-HTT function than control participants as revealed both by reduced number and diminished affinity of imipramine binding sites and diminished platelet 5-HT content. These preliminary results suggest that reduced 5-HTT function could be considered a trait marker or an endophenotype in MDI.