Experience of the biggest School of Medicine in Mexico during the COVID-19 pandemic.
This article was migrated. The article was marked as recommended. The coronavirus 19 disease (COVID-19) pandemic affected virtually all activities worldwide. One of them was education, especially Health Sciences. In the world, many medical schools ceased their face-to-face activities and implemented institutional reorganization actions. According to their characteristics and possibilities, institutions adopted different strategies and tools to continue providing their services online during this health crisis. These situations implied enormous challenges, especially for specific regions, such as Latin America. This article exposes a quick overview of the pandemic experience at the biggest Mexican School of Medicine (UNAM School of Medicine): forecasting, reorganization, actions, challenges, and learnings. Among the most challenging situations experienced were: effective communication strategies; resistance to migrating from face-to-face activities to remote activities; technological development; students and teachers training to implement work and study in virtual spaces; students digital gap; internet and computers access; construction and application of online evaluations; online evaluation of practical skills, and the impossibility of maintaining students in clinical clerkships given the pandemic risks. UNAM School of Medicine reorganized to provide integral care to its community, but it also participated in tasks for Mexico's health and other countries' health benefits. We had a great amount of work, reorganization efforts, and creativity resulting in efficient innovations and new projects. This health crisis showed the best in our community. Actions will remain along the pandemic period and a progressive reincorporation to in-place activities at the end of the health crisis. Some strategies, such as remote activities within teaching, learning, work, evaluation, and research, will be maintained. When this situation ends, we will hopefully have learned and applied those new experiences to improve our School of Medicine, transitioning into a more robust, more united, and enriched community after the crisis caused by this pandemic.


Gene profiling studies in the neonatal ovine lung show enhancing effects of VEGF on the immune response.
Preterm and young neonates have an increased predisposition to respiratory distress syndrome (RDS) associated with an immature development of lung surfactant. Glucocorticoids (GCs) are the major immunomodulatory agents used to increase lung development and reduce the mortality and morbidity of preterm infants with RDS. However, their safety remains uncertain, and the precise mechanisms by which they improve lung function are unclear. In previous studies, we found that vascular endothelial growth factor (VEGF) enhances the innate immune response by respiratory epithelial cells, causes a monocytic infiltration into the lung, and reduces the severity of infection by respiratory syncytial virus (RSV), a respiratory pathogen known to affect preterm infants at a high prevalence. The purpose of this study is to measure the effects of VEGF administration on local immune responses in neonatal lambs, as the ovine lung is well suited for comparison to the human lung, due to similarities in alveolar development, immune responses, and RSV susceptibility. We hypothesized that VEGF induces the expression of genes necessary for host immune responses. We analyzed global gene expression profiles in the lungs of neonate lambs treated with VEGF by real-time qPCR. We report that VEGF induced the expression of chemokines (IL-8, RANTES, MCP-1), cytokines (IFN-gamma, IL-6, TNF-alpha, GMCSF), Toll-like receptor (TLR)-4, complement family members (C3, CFB, CFH) and collectins (SP-A, SP-D). These results suggest that VEGF can regulate local immune gene expression in vivo and should be further explored as a potential exogenous therapy for various lung diseases.


[Risk factors, treatment organization and quality indicators for chronic obstructive pulmonary disease in primary care settings: Dutch experience].
Chronic obstructive pulmonary disease (COPD), usually in advanced stages, is associated with high mortality, being the third leading cause of death worldwide. In the Netherlands, care delivery to patients with COPD has become a focus of the regional medical community, since the COPD death rates in this country are higher than the European Union average. However, between 2011 and 2021, the number of people with COPD (under follow-u by general practitioners) decreased. The experience of this country is interesting, as a large set of measures to improve the situation has been developed and implemented in this region. The purpose of the study was to analyze the experience of the Netherlands in organizing medical care for COPD in primary care settings. The search for scientific literature sources was carried out using the PubMed database and Google system. The search time horizon equaled to 5 years. In the Netherlands, in the system of care delivery to patients with COPD, primary care settings are heavily burdened. The article summarizes approaches to identify COPD risk factors, summarizes current clinical recommendations as of December 2022, and highlights findings of the study on medical digital platforms with the potential to organize continuous monitoring of patients. The paper exemplifies criteria for assessing the treatment quality in specialized care settings, including primary care. It is assumed that the most effective measure to further improve efficacy of COPD treatment is the introduction of remote digital medical devices. A possible integration of the updated standards and quality indicators into digital services will further strengthen the concept of continuous automated remote monitoring of COPD patients. Evidence-based selection and introduction of effective digital solutions into current practice will improve quality of care delivery to patients.


Microaneurysm formation rate as a predictive marker for progression to clinically significant macular edema in nonproliferative diabetic retinopathy.
To evaluate the predictive value of microaneurysm (MA) formation rate concerning the development of clinically significant macular edema (CSME) in patients with mild-to-moderate nonproliferative diabetic retinopathy as evaluated by an automated analysis of central field fundus 30° photographs. Two hundred and eighty-seven eyes were included in the study. Photographs obtained at Day 0, at 6, and 12 months were analyzed using the RetmarkerDR software (Critical Health SA) in a masked manner, and the MA formation rate was documented. A threshold of a calculated MA formation rate of 2 or more was chosen to consider a patient "positive." The ability to predict CSME development was then calculated for a period of up to 5 years. HbA1c values, blood pressure, or duration of diabetes were also evaluated. The study population consisted of 89 male and 59 female patients with a mean age of 57.6 years, a mean HbA1c of 7.8, and a mean duration of diabetes of 12.3 years. Forty-seven of 287 eyes (16.4%) developed CSME during follow-up. An increased MA formation rate of >2 MA was clearly associated with development of CSME. Using the automated analysis and a threshold of 2 or more new MA, the authors were able to identify 70.2% of the eyes that developed CSME during follow-up ("true positive") and using a threshold of up to 2 new MA, 71.7% of the patients that did not develop CSME ("true negative"). No significant differences concerning baseline and 1-year HbA1c levels within patient eyes that developed CSME compared with patient eyes below or over the calculated threshold of 2 MA (P = 0.554 and P = 0.890, respectively) were seen. The positive and negative predictive value was calculated to be 33% versus 92.5%, sensitivity was 70%, and specificity was 72%. Using the RetmarkerDR software, the authors were able to identify patients with higher risk to develop CSME during follow-up using a threshold of 2 or more MA formation rate. Together with the high negative predictive value, the automated analysis may help to determine the individual risk of a patient to develop sight-threatening complications related to diabetic retinopathy and schedule individual screening intervals.


A new gene involved in the transport-dependent metabolism of phosphatidylserine, PSTB2/PDR17, shares sequence similarity with the gene encoding the phosphatidylinositol/phosphatidylcholine transfer protein, SEC14.
A new yeast strain, designated pstB2, that is defective in the conversion of nascent phosphatidylserine (PtdSer) to phosphatidylethanolamine (PtdEtn) by PtdSer decarboxylase 2, has been isolated. The pstB2 strain requires ethanolamine for growth. Incubation of cells with [(3)H]serine followed by analysis of the aminoglycerophospholipids demonstrates a 50% increase in the labeling of PtdSer and a 72% decrease in PtdEtn formation in the mutant relative to the parental strain. The PSTB2 gene was isolated by complementation, and it restores ethanolamine prototrophy and corrects the defective lipid metabolism of the pstB2 strain. The PSTB2 gene is allelic to the pleiotropic drug resistance gene, PDR17, and is homologous to SEC14, which encodes a phosphatidylinositol/phosphatidylcholine transfer protein. The protein, PstB2p, displays phosphatidylinositol but not PtdSer transfer activity, and its overexpression causes suppression of sec14 mutants. However, overexpression of the SEC14 gene fails to suppress the conditional lethality of pstB2 strains. The transport-dependent metabolism of PtdSer to PtdEtn occurs in permeabilized wild type yeast but is dramatically reduced in permeabilized pstB2 strains. Fractionation of permeabilized cells demonstrates that the pstB2 strain accumulates nascent PtdSer in the Golgi apparatus and a novel light membrane fraction, consistent with a defect in lipid transport processes that control substrate access to PtdSer decarboxylase 2.


Bladder cancer screening among primary aluminum production workers in Quebec.
We evaluated a cytology screening program, offered by a large aluminum producer after the discovery of an excess of bladder cancer due to occupational exposure to coal-tar-pitch volatiles, in terms of early detection and survival, based on information in the public domain. From January 1970 through June 1986, 79 cases of bladder cancer were identified in this cohort of aluminum workers aged 65 years or younger. By the end of 1986, 36 had died, with bladder cancer as the primary cause of death for 53%. Cases diagnosed after the screening program was introduced in 1980 were compared with those diagnosed earlier. In cases diagnosed after 1980, the proportion identified at early stages was higher (77% v 67%) and survival seemed improved but the differences were not statistically significant. Although these results do not encourage an optimistic view of screening effectiveness in this population, the limits inherent in the present study make it impossible to draw any firm conclusion. Studies restricted to public domain information do not appear to have sufficient data to evaluate workplace screening programs.


Ontogeny of swimming speed, schooling behaviour and jellyfish avoidance by Japanese anchovy Engraulis japonicus.
The ontogeny of swimming speed, schooling behaviour and jellyfish avoidance was studied in hatchery-reared Japanese anchovy Engraulis japonicus to compare its life-history strategy with two other common pelagic fishes, jack mackerel Trachurus japonicus and chub mackerel Scomber japonicus. Cruise swimming speed of E. japonicus increased allometrically from 1·4 to 3·9 standard length (L(S) ) per s (L(S) s(-1) ) from early larval to metamorphosing stage. Burst swimming speed also increased from 6·1 to 28 L(S) s(-1) in these stages. Cruise speed was inferior to that of S. japonicus, as was burst speed to that of T. japonicus. Engraulis japonicus larvae were highly vulnerable to predation by moon jellyfish Aurelia aurita and were readily eaten until they reached 23 mm L(S) , but not at 26 mm L(S) . Schooling behaviour (indicated by parallel swimming) started at c. 17 mm L(S) . Average distance to the nearest neighbour was shorter than values reported in other pelagic fishes. The relatively low predator avoidance capability of E. japonicus may be compensated for by their transparent and thus less conspicuous body, in addition to their early maturation and high fecundity.


High-Mr glycoprotein profiles in human milk serum and fat-globule membrane.
Gradient-polyacrylamide-gel electrophoresis of human milk serum separated three high-Mr glycoprotein bands. The properties of the components corresponding to the three bands (tentatively termed 'Components C, B and A' in their order of migration) were compared by staining with four monoclonal antibodies and lectins. Components B and C both reacted with the four antibodies, but Component A did not. Components B and C were stained with peanut (Arachis hypogaea) agglutinin (PNA) and wheat (Triticum)-germ agglutinin (WGA), Component A being stained with soya-bean (Glycine max) agglutinin as well as PNA and WGA. These results suggest that Components B and C were related molecules, whereas Component A was markedly different from them. The reactivities of Components B and C were the same as those of PAS-0, a high-Mr periodate/Schiff (PAS)-positive glycoprotein previously isolated from human milk fat-globule membrane (MFGM). Component C, whose electrophoretic mobility was the same as PAS-0, could have been a soluble form of PAS-0. A high-Mr glycoprotein having the same properties as Component A was also observed in MFGM. The amino acid composition of the isolated Component A was significantly different from that of Component C and PAS-0, high threonine and serine contents being characteristic of Component A. The carbohydrate content of Component A was 65-80%, and was much higher than that of Component C and PAS-0. Fucose, galactose, N-acetylglucosamine, N-acetylgalactosamine and sialic acid were each detected as constituent sugars of Component A. Component A represents, therefore, a new high-Mr glycoprotein species in human milk serum and MFGM. Since these glycoproteins were high-Mr mucin-like glycoproteins, the names 'HM glycoprotein-A' and 'HM glycoprotein-C' were proposed for Component A and Component C (PAS-O) respectively.


Radiotherapy planning: PET/CT scanner performances in the definition of gross tumour volume and clinical target volume.
Positron emission tomography is the most advanced scintigraphic imaging technology and can be employed in the planning of radiation therapy (RT). The aim of this study was to evaluate the possible role of fused images (anatomical CT and functional FDG-PET), acquired with a dedicated PET/CT scanner, in delineating gross tumour volume (GTV) and clinical target volume (CTV) in selected patients and thus in facilitating RT planning. Twenty-eight patients were examined, 24 with lung cancer (17 non-small cell and seven small cell) and four with non-Hodgkin's lymphoma in the head and neck region. All patients underwent a whole-body PET scan after a CT scan. The CT images provided morphological volumetric information, and in a second step, the corresponding PET images were overlaid to define the effective target volume. The images were exported off-line via an internal network to an RT simulator. Three patient were excluded from the study owing to change in the disease stage subsequent to the PET/CT study. Among the remaining 25 patients, PET significantly altered the GTV or CTV in 11 (44%) . In five of these 11 cases there was a reduction in GTV or CTV, while in six there was an increase in GTV or CTV. FDG-PET is a highly sensitive imaging modality that offers better visualisation of local and locoregional tumour extension. This study confirmed that co-registration of CT data and FDG-PET images may lead to significant modifications of RT planning and patient management.


Driven molecular dynamics studies of the shared proton motion in the H5O2+·Ar cluster: the effect of argon tagging and deuteration on vibrational spectra.
We report IR spectra of H5O2(+) and H5O2(+)·Ar and their deuterium isotopologues using ab initio molecular dynamics. The trajectories were propagated as microcanonical (NVE) ensembles at energies corresponding to temperatures 50 and 100 K. The potential energy surface is calculated on-the-fly at the MP2/aug-cc-pVDZ level of theory. The calculations show that adding an argon atom to H5O2(+) introduces symmetry breaking in the Zundel core ion, causes blueshift in the shared proton vibration by about 200 cm(-1), and leads to the splitting of the OH stretch vibrations into four bands. Driven molecular dynamics (DMD) method is used to assign the spectrum by coupling the dipole moment to an external electric field oscillating at frequency ω. The broad feature at 1100 cm(-1) in the H5O2(+)·Ar spectrum is ascribed to the large amplitude shared proton vibration coupled with torsion and wag modes. MD MP2 simulations predict the H/D redshift in the shared proton vibration and water bending vibration to be about 280 and 460 cm(-1), respectively, in good agreement with experimental observations.


Establishing a Cancer Registry in a Resource-Constrained Region: Process Experience From Ghana.
In a review of cancer incidence across continents (GLOBOCAN 2012), data sources from Ghana were classified as Frequencies, the lowest classification for inclusion, signifying the worst data quality for inclusion in the analysis. Recognizing this deficiency, the establishment of a population-based cancer registry was proposed as part of a broader cancer control plan. The registry was examined under the following headings: policy, data source, and administrative structure; external support and training; and definition of geographic coverage. The registry was set up based on the Ghana policy document on the strategy for cancer control. The paradigm shift ensured subscription to one data collection software (CanReg 5) in the country. The current approach consists of trained registrars based in the registry who conduct active data abstraction at the departments and units of the hospital and pathologic services. To ensure good governance, an administrative structure was created, including an advisory board, a technical committee, and registry staff. External support for the establishment of the Accra Cancer Registry has come mainly from Stanford University and the African Cancer Registry Network, in collaboration with the University of Ghana. Unlike previous attempts, this registry has a well-defined population made up of nine municipal districts. The Accra Cancer Registry was established as a result of the lessons learned from failed previous attempts and aim to provide a model for setting up other cancer registries in Ghana. It will eventually be the focal point where all the national data can be collated.


[The second cycle in nursing. A project of historical continuity].
The year 2000 broke out with a controversial and accelerated debate about a Licentiate for Nursing, a project which has been developing since the beginning of the nineties as a result of a series of demands and projects presented earlier on. In this article, Marta Durán, a well-known prestigious professional who is playing an important, leading role in this whole process, presents the academic and disciplinary benchmarks which, in her opinion and based on a rigorous, well-founded position, should be those which enable us to select a model that covers the expectations opened up by this project. The issue is dealt with from the following perspectives: the context of human and social development and the academic proposal for the development of nursing.


Aspirin, but Not Tirofiban Displays Protective Effects in Endotoxin Induced Lung Injury.
Treatment of acute lung injury (ALI) remains an unsolved problem in intensive care medicine. Recruitment of neutrophils into the lungs, regarded as a key mechanism in progression of ALI, depends on signaling between neutrophils and platelets. Consequently we explored the effect of platelet-targeted aspirin and tirofiban treatment in endotoxin induced acute lung injury. C57Bl/6 mice were exposed to aerosolized LPS (500μg/ml) for 30min and treated with Aspirin (100μg/g bodyweight via intraperitoneal injection, 30 min before or 1 hour after LPS inhalation) or Tirofiban (0.5μg/ g bodyweight via tail vein injection 30 min before or 1 hour after LPS inhalation). The count of alveolar, interstitial, and intravascular neutrophils was assessed 4h later by flow cytometry. Lung permeability changes were assessed by FITC-dextran clearance and protein content in the BAL fluid. Aspirin both before and after LPS inhalation reduced neutrophil influx into the lung and lung permeability indicating the protective role of Aspirin in ALI. Tirofiban, however, did not alter neutrophil recruitment after LPS inhalation. Release of platelet-derived chemokines CCL5 and PF4 and neutrophil extracellular traps was reduced by Aspirin but not by Tirofiban. Aspirin, but not Tirofiban reduces neutrophil recruitment and displays protective effects during endotoxin induced lung injury.


[Prenatal and postnatal development of Sertoli cells in rams].
The morphological picture of Sertoli cells was studied in view of development. The testicular tissue of rams was studied from the 80th to the 140th day of intrauterine development and the testes of ram-lambs were studied from the 1st to the 40th day from birth; further, the testes were studied in adult rams. The development and differentiation of Sertoli cell precursors were examined, including their change into differentiated mature Sertoli cells. The electron-microscopic picture of these cells was described with special emphasis on those morphological changes in cells which are closely related with their functional activity during the development of the testes. The findings obtained so far in this field are incomplete and concern mainly laboratory animals and man. The results of the study extend the theoretical knowledge in the fields of histology, embryology, physiology, endocrinology and andrology. At the same time, they may serve as starting material for the study of the control of spermatogenesis under experimental conditions.


Construction of a Bcl-2-shRNA expression vector and its effect on the mitochondrial apoptosis pathway in SW982 cells.
Apoptosis is considered to serve an important role in the pathogenesis of rheumatoid arthritis. The aim of the present study was to construct Bcl-2-short hairpin (sh)RNA expression vectors and transfect them into human synovial sarcoma SW982 cells, in order to screen for an effective interference sequence and analyze the effects of this interference on the expression levels of Bcl-2 and other molecules associated with the mitochondrial apoptosis pathway. Three different shRNAs (Bcl-2-sh1, 2 and 3) were designed according to the human Bcl-2 mRNA target sequence and were transformed into competent DH5α Escherichia coli cells following the construction of an expression vector, which was then transfected into SW982 cells. SW982 cells were grouped into a control group (transfected with a negative control shRNA), and Bcl-2-sh1, Bcl-2-sh2 and Bcl-2-sh3 groups (transfected with Bcl-2-sh1, 2 and 3, respectively). The expression levels of Bcl-2 mRNA were detected using reverse transcription-quantitative PCR (RT-qPCR). Bcl-2-sh1 was identified as the most effective shRNA sequence for interference, and was used for subsequent experiments. The mRNA and protein expression levels of Bcl-2, Bax, CytC and Caspase-3 were detected in SW982 cells by RT-qPCR and western blotting at various time-points (48 and 72 h) following transfection with Bcl-2-sh1, in order to observe the effectiveness of this interference. Compared with the control group, the expression levels of Bcl-2 were decreased, while those of Bax, CytC and Caspase-3 were increased in Bcl-2-sh1-transfected cells (P<0.01). The interference effect was greater at 48 h than at 72 h. In summary, an effective shRNA sequence (Bcl-2-sh1) targeting the Bcl-2 gene was identified from three candidates, and was demonstrated to significantly interfere with the expression of Bcl-2, Bax, CytC and Caspase-3 when transfected into SW982 cells. The interference effect of Bcl-2-sh1 was more pronounced at 48 h than at 72 h post-transfection.


Beta-blockade in heart failure: a comparison of carvedilol with metoprolol.
This study was performed to compare the long-term clinical efficacy of treatment with metoprolol versus carvedilol in patients with chronic heart failure. Beta-adrenergic blockade is of proven value in chronic heart failure. Metoprolol, a selective beta-blocker, is widely used, but recent trials suggest carvedilol, a nonselective beta-blocker with alpha-1-receptor antagonist activity and antioxidant activities, is also effective. It is uncertain, however, if these additional properties of carvedilol provide further clinical benefit compared with metoprolol. In this randomized double-blind control trial, 51 patients with chronic heart failure and mean left ventricular (LV) ejection fraction of 26% +/- 1.8% were randomly assigned treatment with metoprolol 50 mg twice daily or carvedilol 25 mg twice daily in addition to standard therapy after a four-week dose titration period for a total of 12 weeks. Response was assessed by a quality of life questionnaire, New York Heart Association class, exercise capacity (6-min walk test), radionucleotide ventriculography for LV ejection fraction, two-dimensional echocardiography measurement of LV dimensions and diastolic filling and 24-h electrocardiograph monitoring to assess heart rate variability. Both carvedilol and metoprolol produced highly significant improvement in symptoms (p < 0.001), exercise capacity (p < 0.05) and LV ejection fraction (p < 0.001), and there were no significant differences between the two drugs. Carvedilol had a significantly greater effect on sitting and standing blood pressure, LV end-diastolic dimension and normalized the mitral E wave deceleration time. Both metoprolol and carvedilol were equally effective in improving symptoms, quality of life, exercise capacity and LV ejection fraction, although carvedilol lowers blood pressure more than metoprolol.


Birds of a Feather Laugh Together: An Investigation of Humour Style Similarity in Married Couples.
The present research investigated the degree of similarity in humour styles between spouses as assessed with the Humour Styles Questionnaire (HSQ). Furthermore, self-esteem was investigated as a potential moderator of partner humour style similarity. A sample of 116 heterosexual, married couples independently completed questionnaires assessing self-reported humour styles across the 32 item HSQ, as well as global self-esteem. Results indicated that there is significant positive association between the humour styles of married partners. This association was moderated by individual self-esteem. Specifically, participants with high self-esteem were found to have greater humour style similarity with their partners. Similarity was also greater for positive compared to negative types of humour. Implications for the use of dyadic data in investigating the roles of humour within couples are discussed.


Microbiome-functionality in anaerobic digesters: A critical review.
Microbially driven anaerobic digestion (AD) processes are of immense interest due to their role in the biovalorization of biowastes into renewable energy resources. The function-versatile microbiome, interspecies syntrophic interactions, and trophic-level metabolic pathways are important microbial components of AD. However, the lack of a comprehensive understanding of the process hampers efforts to improve AD efficiency. This study presents a holistic review of research on the microbial and metabolic "black box" of AD processes. Recent research on microbiology, functional traits, and metabolic pathways in AD, as well as the responses of functional microbiota and metabolic capabilities to optimization strategies are reviewed. The diverse ecophysiological traits and cooperation/competition interactions of the functional guilds and the biomanipulation of microbial ecology to generate valuable products other than methane during AD are outlined. The results show that AD communities prioritize cooperation to improve functional redundancy, and the dominance of specific microbes can be explained by thermodynamics, resource allocation models, and metabolic division of labor during cross-feeding. In addition, the multi-omics approaches used to decipher the ecological principles of AD consortia are summarized in detail. Lastly, future microbial research and engineering applications of AD are proposed. This review presents an in-depth understanding of microbiome-functionality mechanisms of AD and provides critical guidance for the directional and efficient bioconversion of biowastes into methane and other valuable products.


Radioactive Iodine in Differentiated Thyroid Carcinoma: A Systematic AGREE II Clinical Practice Guideline Appraisal.
Identify and appraise clinical practice guidelines (CPGs) for radioactive iodine (RAI) indications in differentiated thyroid carcinoma (DTC), and the treatment for radioactive iodine refractory (RAI-R) DTC using the Appraisal of Guidelines for Research and Evaluation II tool. MEDLINE (Pubmed), Ovid (EMBASE), and Scopus. A systematic literature search was conducted to identify CPGs addressing RAI in DTC. CPGs were appraised by 4 independent reviewers in 6 distinct areas of quality. Scaled domain scores were subsequently calculated for each domain. Intraclass correlation coefficients were calculated for each domain to assess interrater reliability. Sixteen guidelines were found addressing RAI indications for DTC. Of these 16, 9 also addressed the treatment of RAI-R DTC. A further 6 unique guidelines were identified that exclusively address RAI-R DTC, bringing the total number of guidelines to 22. The American Thyroid Association (ATA) guidelines for adult thyroid cancer were the highest scoring with a mean score of 83.5%. Two guidelines scored >60% in 5 or more domains, qualifying as "high" quality: ATA and British Thyroid Association. The highest scoring domain was domain 4: clarity of presentation (80.4%) while the lowest scoring domain was domain 5: applicability (38.6%). Of the 22 guidelines identified, only two were "high quality." CPGs exclusively addressing the treatment of RAI-R DTC were weak with most guidelines scoring in the "low" quality range. This report reveals an unmet need for rigorously developed guidelines addressing indications for RAI in DTC, as well as the treatment for RAI-R DTC.


Ambrisentan, an endothelin receptor type A-selective antagonist, inhibits cancer cell migration, invasion, and metastasis.
Several studies reported a central role of the endothelin type A receptor (ETAR) in tumor progression leading to the formation of metastasis. Here, we investigated the in vitro and in vivo anti-tumor effects of the FDA-approved ETAR antagonist, Ambrisentan, which is currently used to treat patients with pulmonary arterial hypertension. In vitro, Ambrisentan inhibited both spontaneous and induced migration/invasion capacity of different tumor cells (COLO-357 metastatic pancreatic adenocarcinoma, OvCar3 ovarian carcinoma, MDA-MB-231 breast adenocarcinoma, and HL-60 promyelocytic leukemia). Whole transcriptome analysis using RNAseq indicated Ambrisentan's inhibitory effects on the whole transcriptome of resting and PAR2-activated COLO-357 cells, which tended to normalize to an unstimulated profile. Finally, in a pre-clinical murine model of metastatic breast cancer, treatment with Ambrisentan was effective in decreasing metastasis into the lungs and liver. Importantly, this was associated with a significant enhancement in animal survival. Taken together, our work suggests a new therapeutic application for Ambrisentan in the treatment of cancer metastasis.


Open-Label Single-Arm Phase II Trial of Sorafenib Therapy with Drug-eluting Bead Transarterial Chemoembolization in Patients with Unresectable Hepatocellular Carcinoma: Clinical Results.
To determine the efficacy of combined continuous sorafenib therapy and drug-eluting bead (DEB) transarterial chemoembolization (TACE) in patients with unresectable hepatocellular carcinoma (HCC). This study was conducted in accordance with the principles of the Declaration of Helsinki, and all patients provided written informed consent prior to enrollment. Inclusion criteria included unresectable HCC, a treatment naïve status, an Eastern Cooperative Oncology Group score of 0-1, and a Child-Pugh score of A-B7. Continuous sorafenib therapy (400 mg twice daily) was started 1 week before the first round of DEB TACE, which was performed in 6-week cycles. Up to four rounds of DEB TACE therapy were allowed on demand within 6 months. The primary end point was safety. Secondary end points were time to progression (TTP), response rate, and overall survival (OS) and were stratified by the Barcelona Clinic Liver Cancer (BCLC) stage and the duration of sorafenib therapy. OS was assessed with Kaplan-Meier estimates, and the Mantel-Cox log-rank test was used to determine differences in survival. A two-sided P value of less than .05 was considered to indicate a significant difference. The study was approved by the Johns Hopkins institutional review board and remained open from March 2009 to January 2012. Fifty patients--of whom 76% were male, 92% had a Child-Pugh score of A, and 62% had BCLC stage C disease--underwent a median of three cycles of therapy. The 6-month disease control rate (defined as complete response plus partial response plus stable disease) was 94% according to the response evaluation criteria in solid tumors. Median TTP and OS were 13.9 and 20.4 months, respectively, and 81% of toxicities were grades 1-2. There was one death that was possibly treatment related. Combined continuous sorafenib therapy and on-demand DEB TACE provided excellent local disease control and did not lead to multiplicative toxicities. Long-term administration of sorafenib therapy in combination with DEB TACE may have a survival benefit in patients with advanced HCC.


Radiographic classification of ankle injuries.
The initial ankle radiographs of 144 patients with ankle injuries were used to predict the total extent of ankle injury. Using the operative, clinical and radiographic findings, each injury was then classified according to the Lauge-Hansen system. Three patterns of lateral mallecolar fracture were unique to specific mechanisms of injury, with transverse fractures occurring in supination-adduction injuries, spiral fractures in supination lateral rotation injuries, and bending fractures in pronation abduction injuries. Vertical medial mallecolar fractures occurred only with supination-adduction injuries. Oblique and transverse medial malleolar fractures were not characteristic of a particular mechanism of injury. The complete extent of injury was accurately determined by the ankle radiographs in all but four patients. In these, the deltoid ligament tears could not be predicted by the radiographic findings.


Opposite effects of dextrans substituted with sulfhydryls or mercury on tumor growth.
Macromolecular dextrans carrying substituents terminated by sulfhydryl groups or terminated by aromatic amines effectively inhibit the growth of a fibrosarcoma and of a mammary adenocarcinoma in a syngeneic mouse model. These compounds have no or very low toxicity to animals and are nontoxic to fibrosarcoma cells in vitro. Small-molecular-weight compounds carrying the same substituents as the above dextrans are without any effect on the growth of these tumors. A dextran substituted with mercury-containing side chains is growth promoting for the same fibrosarcoma in mice at doses which are nontoxic for these animals. However, the mercury-containing compound is toxic to fibrosarcoma cells in vitro. It is hypothesized that these nonpermeating macromolecules do not directly influence the tumor cells in animals but modulate the natural system of defense against tumors; cells of that system are stimulated or poisoned by the substituted dextrans.


Modification of receptor-mediated inhibition of adenylate cyclase in NG108-15 neuroblastoma X glioma cells by n-ethylmaleimide.
Previous studies with membranes from rat heart (Mol. Pharmacol. 21: 570-580, 1982) and human platelets (J. Biol. Chem. 257: 2829-2833, 1982) have suggested that inhibition of adenylate cyclase by occupation of hormone receptors is blocked by pretreatment of membranes with relatively low concentrations of N-ethylmaleimide (NEM). Using membranes derived from NG108-15 neuroblastoma X glioma cells as a model system, we have examined the effect of NEM on the interaction of three inhibitory receptors with adenylate cyclase. Pretreatment of membranes with 100 to 216 microM NEM resulted in a loss of the capacity of agonists to inhibit adenylate cyclase through muscarinic cholinergic and opiate receptors and a loss of GTP-sensitive high-affinity binding of agonists to both of these receptors. Under the same conditions, stimulation of adenylate cyclase by prostaglandin E1 was unchanged. In contrast to the total loss of capacity to inhibit adenylate cyclase by muscarinic and opiate receptor activation, the inhibition of adenylate cyclase by activation of alpha-2 adrenergic receptors was only partially blocked by maximally effective concentrations of NEM. Similarly, GTP-sensitive high-affinity binding of epinephrine to alpha-2 receptors still occurred in NEM (316 microM)-treated membranes. Whereas only a decrease in the efficacy of muscarinic and opiate receptor agonists for inhibition of adenylate cyclase occurred as a result of NEM treatment, pretreatment of membranes with 316 microM NEM resulted in a 30-fold decrease in the potency of epinephrine for inhibition of adenylate cyclase.(ABSTRACT TRUNCATED AT 250 WORDS)


Cytotoxicity of Neisseria gonorrhoeae for human peripheral blood phagocytes.
The toxicity of gonococci [strain BS4 (agar)] for human peripheral blood polymorphonuclear phagocytes, infected in vitro, was assessed by light microscopic examination of Giemsa stained cell deposits of polymorphonuclear phagocytes which had ingested these bacteria. The cytotoxicity elicited by viable gonococci, assessed by percentage lysis and concomitant reduction in the number of polymorphonuclear phagocytes increased as the ratio of gonococci to phagocytes in the original suspension mixture was raised. Pretreatment of viable gonococci with antiserum raised to whole organisms increased the cytotoxic effect produced by the organisms. Killed (heat or UV irradiation) gonococci caused little or no cytotoxicity, even when the organisms were pretreated with specific antiserum. Hence, the lysis of polymorphonuclear phagocytes appears to be caused by a factor or factors produced by viable gonococci and not by LPS per se.


Improving day surgery rates of anterior cruciate ligament reconstruction surgery in surgical units not dedicated to performing day surgery: A retrospective observational cohort study.
Current guidance advises that at least 90% of anterior cruciate ligament reconstructions are performed as day-case operations. Same-day surgery rates achieved by surgical units have significant clinical and financial implications. The primary aim of this multi-centre study was to determine the rate of admission and causes for admissions in patients undergoing anterior cruciate ligament reconstruction. Patient documentations were studied for those who underwent an elective anterior cruciate ligament reconstruction between January 2015 and April 2019. Contributing factors related to admission length were investigated and included patient age, gender, body mass index (BMI), operating surgeon, operating hospital, American Society of Anaesthesiology (ASA) grade, and position of the patient on the operating list. Both univariate and multivariate analysis were conducted using the STATA/IC 16.1 statistical package. The day surgery rate of anterior cruciate ligament reconstructions were 52% (50/95). Patients positioned later on the operating list were more likely to be admitted post-operatively (OR, 4.49; P = .002; 95% CI, 1.72-11.69) and this was the only factor associated with admission. A large majority of admitted patients (95.6%) were admitted without a clinical cause and were otherwise safe for same-day discharge. The day surgery rate for ACL reconstruction remains low, despite an extremely low complication rate. Reconfiguration of the operating lists and positioning anterior cruciate ligament reconstructions earlier in the day will likely increase the same-day discharge rate and reduce associated costs.


Ancillary findings on CT pulmonary angiograms and abnormalities on chest radiographs in patients in whom pulmonary embolism was excluded.
To determine whether chest radiographs identify some abnormalities not shown as ancillary findings on computed tomography(CT) pulmonary angiograms of patients in whom pulmonary embolism (PE) was excluded. This was a retrospective study of reports of negative 64-detector CT pulmonary angiograms and chest radiographs. Among 332 patients with no PE, pulmonary parenchymal disease was shown in 60 (18%) only on standard chest radiographs, and pleural or pericardial disease was shown in 17 (5%) only on chest radiographs. Skeletal abnormalities were reported more frequently on standard chest radiographs, lymph nodes more frequently on CT angiograms. Some abnormalities on chest radiographs of patients in whom PE is excluded may not be described as ancillary findings on CT pulmonary angiograms. This suggests a need for ancillary findings on CT pulmonary angiograms to be described systematically. At present, however, plain chest radiographs in some patients show ancillary findings not reported on CT angiograms. [corrected].


Medical confidentiality: legal and ethical aspects in Greece.
Respect for confidentiality is firmly established in codes of ethics and law. Medical care and the patients' trust depend on the ability of the doctors to maintain confidentiality. Without a guarantee of confidentiality, many patients would want to avoid seeking medical assistance The principle of confidentiality, however, is not absolute and may be overridden by public interests. On some occasions (birth, death, infectious disease) there is a legal obligation on the part of the doctor to disclose but only to the appropriate authorities. Permissible disclosure can be granted by the patients' consent, for example, for the purpose of insurance they may wish to take out. Moreover, there are some ambivalent situations (such as criminal acts, or notification of sexual partner in case of a patient with AIDS) for which Greek law does not include relevant provisions, and the Codes of Medical Ethics do not offer clear guidelines. Therefore, the Greek doctor is called to estimate the situation and assume full responsibility for his decision. Finally, new considerations have arisen in the context of the recent advances in the field of telemedicine and electronic archiving. The paper discusses the current situation and legislation in Greece.


Relapses and recurrences of basal cell face carcinomas.
To evaluate factors related to oncological follow-up of basal cell face carcinomas it was carried out the analysis of a series of cases. Four hundred sixty-five patients with 834 basal cell face carcinomas were evaluated; 3,1% presented recurrences. There was 14.7% of recurrence in incompletely excised tumors against 2.3% of the tumors with clear margins. Recurrences were more prevalent on the nose. Relapse rates showed a cumulative risk. These findings reinforce the importance of oncological follow-up after surgery of basal cell carcinoma.


Leu-1+ (CD5+) B cells. A major lymphoid subpopulation in human fetal spleen: phenotypic and functional studies.
Examination of the cell surface phenotype of fetal splenic lymphocytes demonstrated a major, novel subpopulation of B cells that co-express Leu-1 (CD5) in addition to B cell differentiation antigens (Leu-1+ B cells). These cells are similar to some conventional B cells in that they express HLA-DR, Leu-12, and B1, as well as both immunoglobulin (Ig) M and IgD. They comprise 40 to 60% of total splenic B cells in the fetus but are infrequent in fetal liver and adult spleen. Fetal Leu-1+ B cells do not respond to pokeweed mitogen with either proliferation or Ig secretion, and in contrast to the murine counterpart, Ly-1 B cells, they do not constitutively produce Ig. Leu-1+ B cells were incapable of augmenting Ig production of Leu-1- B cells when suboptimal numbers of T cells were present; however, they did require the presence of T cells to secrete antibody. They do not cap either the CD5 protein or surface Ig. These cells are a unique subpopulation of fetal splenic B cells that do not function as conventional B cells. Their role in the humoral immune response is unknown. They may represent the normal stage of B cell development, which is reflected in the phenotype of B cell CLL cells.


Microperfusion study of proximal tubule bicarbonate transport in maleic acid-induced renal tubular acidosis.
Microperfusion studies were carried out in rats to examine the abnormality in proximal tubule HCO3- transport caused by maleic acid administration. Permeability of the proximal tubule to HCO-3 was measured by perfusing proximal tubules with a HCO3- -free low-buffer isotonic equilibrium solution containing acetazolamide after plasma [HCO3-] had been raised by intravenous NaHCO3 infusion. Insulin recovery in the collected perfusate was approximately 100% in control and maleic acid-treated rats. CO2 influx measured by microcalorimetry was not significantly different in control vs. maleic acid-treated rats. Thus maleic acid did not cause increased permeability of the proximal tubule to either inulin or HCO3-. In a second group of experiments, proximal tubule fluid and HCO3- efflux were measured in paired-reperfusion experiments before and after maleic acid administration. The perfusion fluid contained 25 mM HCO3- and 120 mM Cl-. HCO3- absorption was inhibited 25% (79 pmol/min), Na+ was inhibited 22% (164 pmol/min), and Cl- absorption (calculated as the anion gap) by 85 pmol/min. [HCO3-] in the collected perfusate rose significantly after maleic acid, presumably accompanied by a fall in [Cl-]. The observations indicate that proximal renal tubular acidosis (RTA) induced by maleic acid is characterized by impaired lumen-to-blood transport of sodium bicarbonate and chloride but not by increased backflux. Based on previously demonstrated effects of maleic acid on mitochondrial energy metabolism and cellular ATP levels, we postulate that the principal transport abnormality is impaired basolateral membrane active sodium transport, leading to a secondary reduction in brush border Na+-H+ exchange.(ABSTRACT TRUNCATED AT 250 WORDS)


Sperm storage, internal fertilization, and embryonic dispersal in vent and seep tubeworms (Polychaeta: Siboglinidae: Vestimentifera).
Vestimentiferan tubeworms are ecologically important members of deep-sea chemosynthetic communities, including hydrothermal vents and cold seeps. Some are community dominants and others are primary colonists of new vent sites; they include some of the longest living and fastest growing marine invertebrates. Their mechanisms of propagation, dispersal, and genetic exchange have been widely discussed. Direct sperm transfer from males to females has been documented in one species, Ridgeia piscesae, but others are known to discharge what are apparently primary oocytes. Brooding of embryos has never been observed in any vestimentiferan. These observations have led to the supposition that fertilization might be external in most species. Here we report sperm storage at the posterior end of the oviduct in five species, including tubeworms from both vents and seeps. We show experimentally that most eggs are inseminated internally, that fertilization rate is typically lower than 100%, that meiosis is completed after eggs are released from the female, and that the dispersal phase includes the entire embryonic period.


[Etiology of influenza according to the data of serological diagnostics in hospital patients in St. Petersburg at the period of 1968 - 2000].
The specific features of the etiology of influenza in children and adults at the period of the simultaneous circulation of two subtypes of influenza virus A, according to the results in the hemagglutination-inhibition reaction in 261,490 influenza and ARD patients hospitalized in St. Petersburg in the course of 32 years, were analyzed. The results of serological diagnostics was shown to correspond to the data of the identification of influenza viruses in Russia and all over the world. At the period of epidemics diseases caused by the main infective agents of the epidemics were detected in 11.0% - 51.0% of cases and by concomitant infective agents, in 0.6% - 12.4% of cases. After the reappearance of influenza virus A(H1N1) in circulation higher frequency of mixed forms of infection and the presence of competition between the subtypes of influenza virus A was noted. In young children a decrease in differences in the proportion of influenza cases, caused by the main and concomitant infective agents, as well as between the detection of influenza in epidemic and in summer periods, was registered.


Integrated genetic and genomic approach in the SingaporeTranslational and Clinical Research in Psychosis Study: an overview.
Schizophrenia is a severe mental disorder with onset frequently in adolescence and followed by a chronic and disabling course. Although the exact pathophysiology of this devastating disorder has not been clearly elucidated, a large part of it has been attributed to genetic influences. This article seeks to provide an overview on what our group has embarked on--to elucidate genetic risk factors for schizophrenia within the Chinese ethnic group. We plan to conduct an integrated approach to interrogate comprehensively the genome from different angles and in stages. The first stage involves a genome-wide association study of 1000 cases of schizophrenia-control pairs, with a follow-up replication study in another 1000 cases of schizophrenia and in 1000 controls, and combination analyses with groups from other places including China and Hong Kong. Other than the genome-wide association study, gene sequencing for purported candidate genes and copy number variation analysis will be performed. Neurocognitive intermediate phenotypes will be employed to deconstruct the complex schizophrenia phenotype in a bid to improve association findings. Promising leads from longitudinal gene and protein expression in ultra-high-risk subjects who develop psychosis and schizophrenia (in a parallel study) will be followed up as candidate genes and sequenced in the genetic analysis. Functional analysis forms the last stage of this integrated approach. This integrated genetic and genomic approach will hopefully help in further characterizing and deepening our understanding of molecular pathophysiological mechanisms underlying schizophrenia.


Preparation of Thin Films Containing Modified Hydroxyapatite Particles and Phospholipids (DPPC) for Improved Properties of Biomaterials.
The main aims of thin biofilm synthesis are to either achieve a new form to promote the transport of drugs in oral delivery systems or as a coating to improve the biocompatibility of the implant's surface. In this study, the Langmuir monolayer technique was employed to obtain films containing Mg-doped hydroxyapatite with 0.5%, 1.0%, and 1.5% Mg(II). The obtained modified HA particles were analysed via the FT-IR, XRD, DLS, and SEM methods. It was shown that the modified hydroxyapatite particles were able to form thin films at the air/water interface. BAM microscopy was employed to characterized the morphology of these films. In the next step, the mixed films were prepared using phospholipid (DPPC) molecules and modified hydroxyapatite particles (HA-Mg(II)). We expected that the presence of phospholipids (DPPC) in thin films improved the biocompatibility of the preparing films, while adding HA-Mg(II) particles will promote antibacterial properties and enhance osteogenesis processes. The films were prepared in two ways: (1) by mixing DPPC and HA-Mg (II) and spreading this solution onto the subphase, or (2) by forming DPPC films, dropping the HA-Mg (II) dispersion onto the phospholipid monolayer. Based on the obtained π-A isotherms, the surface parameters of the achieved thin films were estimated. It was observed that the HA-Mg(II) films can be stabilized with phospholipid molecules, and a more stable structure was obtained from films synthesied via method (2).


Duodenal Aspirates for Small Intestine Bacterial Overgrowth: Yield, PPIs, and Outcomes after Treatment at a Tertiary Academic Medical Center.
Duodenal aspirates are not commonly collected, but they can be easily used in detection of small intestinal bacterial overgrowth (SIBO). Proton pump inhibitor (PPI) use has been proposed to contribute to the development of SIBO. We aimed to determine the yield of SIBO-positive cultures detected in duodenal aspirates, the relationship between SIBO and PPI use, and the clinical outcomes of patients identified by this method. In a retrospective study, we analyzed electronic medical records from 1263 consecutive patients undergoing upper endoscopy at a tertiary medical center. Aspirates were collected thought out the third and fourth portions of the duodenum, and cultures were considered to be positive for SIBO if they produced more than 100,000 cfu/mL. Culture analysis of duodenal aspirates identified SIBO in one-third of patients. A significantly higher percentage of patients with SIBO use PPIs than patients without SIBO, indicating a possible association. Similar proportions of patients with SIBO improved whether or not they received antibiotic treatment, calling into question the use of this expensive therapy for this disorder.


Evaluation of Intratumoral and Intertumoral Heterogeneity of MET Protein Expression in Gastric Cancer.
Tumor heterogeneity of a target molecule could contribute to failure of the targeted therapy. We investigated the heterogeneity of MET expression within same primary gastric cancer (GC) and between primary and corresponding secondary GC lesions using immunohistochemistry (IHC). Intratumoral heterogeneity was defined as discordant MET status among 3 tissue microarray cores (3 different areas of same tumor). IHC 3+ was considered positive for MET overexpression. MET overexpression was observed in 2.7% (50/1869) of all examined cores and 5.3% (33/623) of primary GCs. When we compared MET IHC results between 3 cores from each tumor, intratumoral heterogeneity was identified (65.0% in total 623 cases; 84.4% in 480 cases with any staining intensity; 84.9% in 251 cases with moderate to strong intensity; 90.9% in 33 cases with strong intensity). Of 33 MET-overexpressed GCs, the average proportion of strongly stained area was 19.6% in the whole sections. Of 269 cases with primary GC and regional lymph node metastasis, 17 (6.3%) showed MET positivity in which 9 (52.9%) were discordant (negative conversion). In 123 cases with primary and corresponding local recurrent/distant metastatic GC, 3 (2.4%) showed MET positivity in which 2 (66.7%) were discordant (positive conversion). In the survival analysis, MET IHC 3+ in lymph node metastases was an independent negative prognostic factor for overall survival. We found that MET overexpression is uncommon and highly heterogeneous in GC. This severe heterogeneity of MET status should be considered in tissue sampling and development of biomarkers for anti-MET therapy.


Turkey muscle acylphosphatase: purification and comparative studies.
Turkey muscle acylphosphatase is strongly bound to anti-(horse muscle acylphosphatase ) antibodies covalently linked to an agarose resin. This permits use of an affinity chromatography step in the purification, which increased the final yield and allowed us to isolate three different molecular forms of the enzyme. Form 1 is a mixed disulfide between the polypeptide chain and glutathione; form 3 is an S-S dimer of the polypeptide chain present in form 1, while form 2, present in a very low amount, consists of a polypeptide chain quite similar in aminoacid composition to that found in form 1. The three molecular forms show very similar kinetic parameters. The comparison of these molecular forms with those isolated from horse muscle showed similar kinetic properties but different structural features.


iMAgery focused psychological therapy for persecutory delusions in PSychosis (iMAPS): a multiple baseline experimental case series.
Many people with psychosis experience persecutory delusions and report negative schematic beliefs and intrusive mental images which may be maintaining factors for psychotic symptoms. This study examined the feasibility and acceptability of a new psychological therapy targeting schemas and images (iMAPS therapy). The study used a randomised multiple baseline design. Participants with first episode psychosis were randomised using a multiple baseline design with 2-5 assessments. Six sessions of therapy, consisting of a combination of imagery techniques and imagery rescripting techniques, was used. In each session, participants completed a Mental Imagery in Psychosis Questionnaire (MIPQ) and imagery interview. Mood and delusional beliefs (PSYRATS) were also measured at each session. Five participants with first episode psychosis completed the baseline visits and attended all therapy sessions. One participant declined the final assessment. Results demonstrated significant reductions in negative schematic beliefs, delusions, imagery distress and other measures of schema (YSQ, SMI). Although multiple baseline randomisation strengthens the study, it lacked a control arm and blind assessments. iMAPS appears a feasible and acceptable treatment for psychosis, and further evaluation is indicated.


Design of a standard Iranian protocol of Intravenous thrombolysis with tissue plasminogen activator: A national project.
Standard protocols should be established for treating eligible stroke patients with tissue plasminogen activator (TPA) (recommendation class I, level of evidence B). The Iranian standard protocol of Intravenous Thrombolysis with recombinant Tissue Plasminogen Activator (IVTTPA) is the best possible and easy to use method for performing intravenous thrombolysis in Iran. This protocol overcomes problems and limitations of IVTTPA in Iran. The protocol achieves the best selection criteria and assessment method of IVTTPA for our residents and neurologists. This protocol was provided in Persian language and could be easily downloaded from Google site by writing Thrombolysis and Iran in Persian.


Alpine treeline ecotone stasis in the face of recent climate change and disturbance by fire.
How species respond to climate change will depend on biological characteristics, species physiological limits, traits (such as dispersal), and interactions with disturbance. We examine multi-decadal shifts in the distribution of trees at the alpine treeline in response to regional warming and repeated disturbance by fire in the Victorian Alps, south-east Australia. Alpine treelines are composed of Eucalyptus pauciflora subsp. niphophila (Snow Gum, Myrtaceae) species. The location and basal girth of all trees and saplings were recorded across treelines at four mountains in 2002 and 2018. We quantify changes in treeline position (sapling recruitment above treeline) over time in relation to warming and disturbance by fire, and examine changes in stand structure below treeline (stand density, size class analyses). Short-distance advance of the treeline occurred between 2002 and 2018, but was largely restricted to areas that were unburned during this period. No saplings were seen above treeline after two fires, despite evidence that saplings were common pre-fire. Below treeline, subalpine woodland stands were largely resilient to fire; trees resprouted from lignotubers. However, small trees were reduced in number in woodlands when burned twice within a decade. Population dynamics at the alpine treeline were responsive to recent climate change, but other factors (e.g. disturbance) are crucial to understand recruitment trends. Establishment of saplings above treeline was largely restricted to unburned areas. These results indicate fire is a strong demographic filter on treeline dynamics; there is a clear need to frame alpine treeline establishment processes beyond just being a response to climate warming. Long lag periods in treeline change may be expected where recurrent disturbance is a feature of the landscape.


The Moral Obligation of Nurse Leaders:: COVID-19.
The international pandemic of COVID-19 is unprecedented. Nurse leaders play a pivotal role in balancing the needs of their staff with the needs of the patients. Maintaining one's moral compass during critical decision times is of the utmost importance. They do so to minimize the negative impact and maximize success for all key stakeholders and avoid moral distress. Transparent communication that is truthful, mindful, and relevant is only one of the competencies necessary to accomplish this. This article explores these challenges and offers some suggestions on staying resilient and upholding one's moral obligations.


Oxidation, tyrosine nitration and cytostasis induction in the absence of inducible nitric oxide synthase.
In the present study, we evaluated the impact of the lack of the gene for inducible nitric oxide synthase (iNOS) on oxidation, tyrosine nitration and cytotoxicity reactions triggered by immunostimulation. In mice injected with E. coli endotoxin (bacterial lipopolysaccharide, LPS, 50 mg/kg i.p.), there was a significant increase in the degree of oxidation of dihydrorhodamine 123 to rhodamine 123. This response was attenuated by inhibition of NO biosynthesis with NG-methyl-L-arginine (L-NMA, 30 mg/kg i.p.). In mice lacking functional iNOS gene (iNOS knock-out mice), the degree of the LPS-induced, L-NMA inhibitable increase in dihydrorhodamine oxidation was decreased, but not completely abolished. LPS stimulation induced a marked increase in the immunoreactivity for nitrotyrosine (an indicator of peroxynitrite formation), as measured in the aorta and lung. An L-NMA inhibitable increase in nitrotyrosine staining induced by LPS was also observed in the tissues of the iNOS knockout animals. LPS treatment induced the appearance of DNA single strand breakage and a suppression of mitochondrial respiration in peritoneal macrophages ex vivo. A significant degree of LPS-induced DNA single strand breakage and suppression of mitochondrial respiration was still observed in the peritoneal macrophages obtained from the iNOS knockout animals. Macrophages from wild-type mice stimulated with LPS and interferon-gamma suppressed the proliferation of various target cells (P815 mastocytoma, L929 fibrosarcoma and embryonic lung fibroblast cell line): this effect was abolished by in vitro treatment with L-NMA (1 mM). Macrophages from the iNOS knockout animals exhibited a reduced degree of target cell cytostatic activity. The remainder of the cytostasis in iNOS knockout macrophages was abolished by preventing cell contact and neutralizing tumor necrosis factor á. The present results demonstrate that the lack of iNOS gene does not fully abolish oxidation, tyrosine nitration and cytostatic activity in response to immunostimulation. The current findings may have implications for the development of NO-based approaches for the experimental therapy of inflammation.


Continuous neuronal ensemble control of simulated arm reaching by a human with tetraplegia.
Functional electrical stimulation (FES), the coordinated electrical activation of multiple muscles, has been used to restore arm and hand function in people with paralysis. User interfaces for such systems typically derive commands from mechanically unrelated parts of the body with retained volitional control, and are unnatural and unable to simultaneously command the various joints of the arm. Neural interface systems, based on spiking intracortical signals recorded from the arm area of motor cortex, have shown the ability to control computer cursors, robotic arms and individual muscles in intact non-human primates. Such neural interface systems may thus offer a more natural source of commands for restoring dexterous movements via FES. However, the ability to use decoded neural signals to control the complex mechanical dynamics of a reanimated human limb, rather than the kinematics of a computer mouse, has not been demonstrated. This study demonstrates the ability of an individual with long-standing tetraplegia to use cortical neuron recordings to command the real-time movements of a simulated dynamic arm. This virtual arm replicates the dynamics associated with arm mass and muscle contractile properties, as well as those of an FES feedback controller that converts user commands into the required muscle activation patterns. An individual with long-standing tetraplegia was thus able to control a virtual, two-joint, dynamic arm in real time using commands derived from an existing human intracortical interface technology. These results show the feasibility of combining such an intracortical interface with existing FES systems to provide a high-performance, natural system for restoring arm and hand function in individuals with extensive paralysis.


Thyroid hormone receptor Thra and Thrb knockout differentially affects osteoblast biology and thyroid hormone responsiveness in vitro.
Thyroid hormones (TH) are important modulators of bone remodeling and thus, thyroid diseases, in particular hyperthyroidism, are able to compromise bone quality and fracture resistance. TH actions on bone are mediated by the thyroid hormone receptors (TR) TRα1 and TRβ1, encoded by Thra and Thrb, respectively. Skeletal phenotypes of mice lacking Thra (Thra0/0 ) and Thrb (Thrb-/- ) are well-described and suggest that TRα1 is the predominant mediator of TH actions in bone. Considering that bone cells might be affected by systemic TH changes seen in these mutant mice, here we investigated the effects of TR knockout on osteoblasts exclusively at the cellular level. Primary osteoblasts obtained from Thra0/0 , Thrb-/- , and respective wildtype (WT) mice were analyzed regarding their differentiation potential, activity and TH responsiveness in vitro. Thra, but not Thrb knockout promoted differentiation and activity of early, mature and late osteoblasts as compared to respective WT cells. Interestingly, while mineralization capacity and expression of osteoblast marker genes and TH target gene Klf9 was increased by TH in WT and Thra-deficient osteoblasts, Thrb knockout mitigated the responsiveness of osteoblasts to short (48 h) and long term (10 d) TH treatment. Further, we found a low ratio of Rankl, a potent osteoclast stimulator, over osteoprotegerin, an osteoclast inhibitor, in Thrb-deficient osteoblasts and in line, supernatants obtained from Thrb-/- osteoblasts reduced numbers of primary osteoclasts in vitro. In accordance to the increased Rankl/Opg ratio in TH-treated WT osteoblasts only, supernatants from these cells, but not from TH-treated Thrb-/- osteoblasts increased the expression of Trap and Ctsk in osteoclasts, suggesting that osteoclasts are indirectly stimulated by TH via TRβ1 in osteoblasts. In conclusion, our study shows that both Thra and Thrb differentially affect activity, differentiation and TH response of osteoblasts in vitro and emphasizes the importance of TRβ1 to mediate TH actions in bone.


[ECT in autoimmune encephalitis].
In this case report, a 27-year-old male presented at a department of neurology with postherpetic anti-N-methyl-d-aspartate (NMDA) receptor autoimmune encephalitis. The patient was psychotic and exhibited symptoms of akinetic and excited catatonia. He was mechanical restrained for a total of 46 days due to violent behaviour. He was treated with olanzapine and lorazepam up to 15 mg/day without effect on catatonic and behavioural symptoms. ECT was initiated, and the patient received a total of 16 treatments. He responded well to the treatment, and the violent behaviour resolved completely after the first treatment. ECT should be considered for catatonia in anti-NMDA-receptor autoimmune encephalitis.


Reliability of MRSI brain temperature mapping at 1.5 and 3 T.
MRSI permits the non-invasive mapping of brain temperature in vivo, but information regarding its reliability is lacking. We obtained MRSI data from 31 healthy male volunteers [age range, 22-40 years; mean ± standard deviation (SD), 30.5 ± 5.0 years]. Eleven subjects (age range, 23-40 years; mean ± SD, 30.5 ± 5.2 years) were invited to receive four point-resolved spectroscopy MRSI scans on each of 3 days in both 1.5-T (TR/TE = 1000/144 ms) and 3-T (TR/TE = 1700/144 ms) clinical scanners; a further 20 subjects (age range, 22-40 years; mean ± SD, 30.5 ± 4.9 years) were scanned on a single occasion at 3 T. Data were fitted in the time domain to determine the water-N-acetylaspartate chemical shift difference, from which the temperature was estimated. Temperature data were analysed using a linear mixed effects model to determine variance components and systematic temperature changes during the scanning sessions. To characterise the effects of instrumental drift on apparent MRSI brain temperature, a temperature-controlled phantom was constructed and scanned on multiple occasions. Components of apparent in vivo temperature variability at 1.5 T/3 T caused by inter-subject (0.18/0.17 °C), inter-session (0.18/0.15 °C) and within-session (0.36/0.14 °C) effects, as well as voxel-to-voxel variation (0.59/0.54 °C), were determined. There was a brain cooling effect during in vivo MRSI of 0.10 °C [95% confidence interval (CI): -0.110, -0.094 °C; p < 0.001] and 0.051 °C (95% CI: -0.054, -0.048 °C; p < 0.001) per scan at 1.5 T and 3 T, respectively, whereas phantom measurements revealed minimal drift in apparent MRSI temperature relative to fibre-optic temperature measurements. The mean brain temperature at 3 T was weakly associated with aural (R = 0.55, p = 0.002) and oral (R = 0.62, p < 0.001) measurements of head temperature. In conclusion, the variability associated with MRSI brain temperature mapping was quantified. Repeatability was somewhat higher at 3 T than at 1.5 T, although subtle spatial and temporal variations in apparent temperature were demonstrated at both field strengths. Such data should assist in the efficient design of future clinical studies.


Statins and thrombin.
L-Mevalonic acid is the distant precursor of cholesterol, in contrast to cholesterol, L-mevalonic acid, its distant precursor gives rise to farnesyl and geranylgeranyl pyrophosphates in relatively few metabolic steps. These isoprenyl pyrophophates covalently conjugate with specific G-proteins and serve as membrane anchors enabling them to carry out their function. Although farnesyl-proteins may participate in signal transduction, geranylgeranyl-proteins (e.g., Rho GTP binding proteins) are well known to downregulate signaling pathways by inhibiting L-mevalonic acid synthesis. Such inhibitors include 3-hydroxy-3-methylglutaryl CoA reductase inhibitors, drugs (statins) and isoprenoids of dietary origins, where Rho protein activation appears to be necessary for cellular-mediated thrombin generation. Thrombin and other proteases (e.g., coagulation factor Xa, tryptase) upregulate protease-activated receptor (PAR) synthesis and PAR activation promotes synthesis and expression of other proteins [e.g., tissue factor (TF) and plasminogen activator inhibitor-1 (PAI-1)]. With the PAR-1 activating peptide SSFLRNP, we found that either cerivastatin or atorvastatin mitigated platelet stimulation in a time- and dose-dependent manner, as predicted if a statin-mediated Rho pathway is required. We also found that simvastatin decreased prothrombin fragments F1+2 in plasma from type 2 diabetics, demonstrating that statins downregulate thrombin generation. Thus, independent of cholesterol, statins and dietary isoprenoids behave as inhibitors of TF-dependent thrombin generation. Because thrombin has multiple physiological functions, the 20 pleiotropic effects reported for statins may reflect a common mechanism for downregulation of thrombin-mediated events, in particular at the cellular level.


Development of a self-report measure of unconditional positive self-regard.
The development of a measure of therapeutic change that is theoretically consistent with person-centred theory and client-centred therapy would provide a tool for the evaluation of therapeutic change that is meaningful to both clients and therapists, and that could also be applied to outcome research. The present paper reports the development of a measurement scale based on the person-centred construct of unconditional positive self-regard. A cross-sectional survey design was adopted to investigate the psychometric properties of the unconditional-positive self regard scale (UPSR). Data from 210 university students who completed the scale were subjected to principal components factor analysis in order to determine the factor structure of the scale. Comparison with theoretically similar and distinct measures was used to investigate validity, and internal reliability was assessed. Factor analysis revealed that the resulting 12-item UPSR scale is composed of two separate subscales, respectively measuring self-regard and conditionality of positive self-regard. Internal reliability of the main scale and subscales was adequate with alpha co-efficients all above .79. Comparison with other measures provides evidence supporting the validity of the new scale. Initial evidence indicates that the UPSR scale may be a potentially useful tool for the non-medicalised evaluation of therapeutic change.


Synthesis, characterization and in vitro studies of celecoxib-loaded poly(ortho ester) nanoparticles targeted for intraocular drug delivery.
The present investigation is aimed at improving the ocular bioavailability of a poorly water soluble drug, celecoxib, to offer new options in the treatment of chronic eye diseases, such as age-related macular degeneration and diabetic retinopathy. To do so, we developed a novel formulation of drug-loaded poly(ortho ester) nanoparticles (NPs). We characterized the NPs in terms of size, morphology, controlled-release, degradation and cytocompatibity. Stable and transparent NP emulsions were prepared following a double emulsion solvent diffusion method employing poloxamer 188 as a stabilizer. Physical properties showed a narrow range size distribution of 151-164nm with spherical morphology, negative zeta potentials and remarkably high celecoxib encapsulation efficiency (98%) and loading (64%) of poly(ortho ester) NPs. Drug release followed a zero-order release by a surface erosion-controlled mechanism without any burst effect. Degradation of poly(ortho ester) NPs was observed by measuring the concentration of initial degradation product such as, lactic acid. MTT studies revealed minimal toxicity of NPs (up to 1mg/ml) toward HEK 293 cells. Poly(ortho ester) NPs were not internalized by either Müller or HEK 293 cells, which is highly desirable for a drug carrier to deliver the drugs for prolonged periods to the back of eye. These features have the potential to decrease the number of intraocular injections required to treat chronic eye diseases.


A Continuously Updated, Computationally Efficient Stress Recognition Framework Using Electroencephalogram (EEG) by Applying Online Multitask Learning Algorithms (OMTL).
Recognizing the factors that cause stress is a crucial step toward early detection of stressors. In this regard, several studies make an effort to recognize individuals' stress using an Electroencephalogram (EEG). However, current EEG-based stress recognition frameworks have several drawbacks. First, they are mostly designed to recognize individuals' stress only in a controlled laboratory environment. Second, they do not take into account the changes in the EEG signals of different subjects under the same stressors. Third, most of the current stress recognition algorithms occur in an offline setting. To address these issues, this study proposes an EEG-based stress recognition framework that takes into account each subject's brainwave patterns to train the stress recognition classifier and continuously update its classifier based on new input signals in near real-time. The proposed framework first removes EEG signal artifacts, then extracts a broad range of EEG signal features, and finally applies different online multitask learning (OMTL) algorithms to recognize individuals' stress in near real time. The proposed framework was applied on the EEG collected in two environments-first on the EEG collected in a controlled lab environment using a wired-EEG and second on the EEG collected at in the field using a wearable EEG device. The OMTL-VonNeuman method resulted in the best prediction accuracy on both datasets (71.14% on the first dataset and 77.61% on second) among all tested algorithms. The proposed stress recognition framework continuously updates its classifier and therefore contributes to stress recognition for new stressful situations that are beyond the range of predefined stressful conditions in near real time both in a controlled lab environment and at real job sites.


Children with special health care needs: Impact of health care expenditures on family financial burden.
We investigated the relationship between health care expenditures for Special Health Care Needs (SHCN) children and family perception of financial burden. Using 2005/2006 National Survey of Children with Special Health Care Needs data, a multivariate logistic regression model was used to estimate the relationship between the SHCN child's health care expenditure and perceived financial burden, while controlling for family and child characteristics. Our analysis suggests that health care expenditures for a SHCN child of $250 and more are associated with family perception of financial burden. In addition, families with lower socioeconomic status also perceived financial burden at lower level of expenditures. Members of the health care team who treat children with SHCN have an important role in understanding and assessing family financial burden as part of the care delivery to the child and the family. Our study reinforces the need to treat the whole family as the unit of care, especially when caring for children with special health care needs.


The impact of carbon nanomaterials on the development of phenanthrene catabolism in soil.
This study investigates the impact of different types of carbon nanomaterials (CNMs) namely C60, multi-walled carbon nanotubes (MWCNTs) and fullerene soot on the catabolism of (14)C-phenanthrene in soil by indigenous microorganisms. Different concentrations (0%, 0.01%, 0.1% and 1%) of the different CNMs were blended with soil spiked with 50 mg kg(-1) of (12)C-phenanthrene, and aged for 1, 25, 50 and 100 days. An increase in the concentration of MWCNT- and FS-amended soils showed a significant difference (P = 0.014) in the lag phase, maximum rates and overall extent of (14)C-phenanthrene mineralisation. Microbial cell numbers did not show an obvious trend, but it was observed that control soils had the highest population of heterotrophic and phenanthrene degrading bacteria at all time points.


Comparison of cytotoxicity between extracts of Clinacanthus nutans (Burm. f.) Lindau leaves from different locations and the induction of apoptosis by the crude methanol leaf extract in D24 human melanoma cells.
Clinacanthus nutans (Burm. f.) Lindau leaves are widely used by cancer patients and the leaf extracts possess cytotoxic and antiproliferative effects on several human cancer cell lines. However, the effect of C. nutans leaf extract on human melanoma, which is the least common but most fatal form of skin cancer and one of the most common cancers diagnosed in both sexes worldwide, is unknown. There is also limited information on whether the bioactivity of extracts differs between C. nutans leaves grown in different geographical locations with varying environmental conditions. The present study, for the first time, compared and demonstrated the cytotoxicity of the crude methanol extracts of C. nutans leaves from 11 different locations in Malaysia, Thailand and Vietnam, with diverse environmental conditions against D24 melanoma cells through WST-8 assay. The percentage of apoptotic cells following treatment with the most active extract was determined in a dose- and time-dependent manner by a cytofluorometric double staining technique. Biochemical and morphological changes in the treated and untreated cells were examined by fluorescence and transmission electron microscopy techniques, respectively, to further affirm the induction of apoptosis. The leaves of plants grown at higher elevations and lower air temperatures were more cytotoxic to the D24 melanoma cells than those grown at lower elevations and higher air temperatures, with the leaf extract from Chiang Dao, Chiang Mai, Thailand exhibited the highest cytotoxicity (24 h EC50: 0.95 mg/mL and 72 h EC50: 0.77 mg/mL). This most active crude extract induced apoptotic cell death in the D24 cells in a dose- and time-dependent manner. Typical biochemical and morphological characteristics of apoptosis were also observed in the treated D24 cells. The results, showing the cytotoxicity of C. nutans and the induction of apoptosis in D24 cells, are significant and useful to facilitate the development of C. nutans as a potential novel chemotherapeutic agent for the management of skin melanoma.


Surface immobilization of anchorage-dependent mammalian cells.
Anchorage-dependent HeLa cells were successfully cultured on two fibrous materials (A07 and R100) with porosities of 75-125 and 40 mum, void fractions of 92% and 81%, and fiber diameters of 7.6 and 10.2 mum, respectively, in 100-mL spinner flasks and 2-L stirred tank bioreactors. The matrix was formed into a fixed vertical spiral configuration. All cultures displayed rapid (< or = 2-3 h) attachment of inoculated cells (> or = 95%) to the matrix, uniform coverage of the immobilizing area with viable cells, and no significant amount of cell debris in the medium. Spinner flask cultures indicated that the denser material R100 showed better results in terms of final cell density. The growth of HeLa cells on material R100 in both culture systems was similar to that observed in tissue culture dishes (specific growth rate approximately 0.03-0.04 h(-1), maximum cell density of 8 x 10(6)-9 x 10(6) cells . mL(-1), and yields of 0.4 x 10(8) cells . mM(-1) on glucose and 2 x 10(8)-3 x 10(8) cells . mM(-1) on glutamine). Scale-up of this culture technique in a 2-L bioreactor under perfusion with pH and dissolved oxygen (DO) control yielded cell densities of up to 1.6 x 10(6) cells . mL(-1). Two other anchorage-dependent mammalian cells (ADC) known to be cultured with difficulty in roller bottles or with micro carriers were easily grown on material R100 in spinner flasks. The performance of this culture technique was compared to other ADC culture systems.


Pancreatic pseudocysts.
Improvements in imaging studies and a better understanding of the natural history of pancreatic fluid collections (PFCs) have allowed the different types to be clarified. Stratification of PFCs into subgroups should help in selecting from the increasing current available treatment options, which include percutaneous, endoscopic and surgical drainage. Percutaneous catheter drainage is safe and effective and should be the treatment of choice in poor-risk patients, and for infected pseudocysts related to acute pancreatitis. Endoscopic drainage should be the first management option in suitable pseudocysts related to chronic pancreatitis, if the necessary expertise is available. The high success rate and current low morbidity of elective open surgery mean that it is still the standard of management in this disease. Laparoscopic approaches are gaining favour, predominantly in drainage of collections in the lesser sac, and long-term data are awaited. The precise application of this modality will need to be critically compared with the low morbidity of mini-laparotomy, which is the current standard after non-operative treatment fails in these patients. It is essential to clearly stratify the different types of pancreatic pseudocysts, in particular with relation to acute or chronic pancreatitis, and perform a valid comparison of the different treatment modalities within groups. In this capacity a precise and transparent classification may provide valuable answers, in particular relating to optimal management according to pseudocyst type.


Biomechanics of the Achilles tendon.
Tendons behave viscoelastically and exhibit adaptive responses to conditions of increased loading and disuse. Strain patterns in tendons may not be uniform, as tendons show stress-shielded areas and areas subjected to compressive loading at the enthesis. These areas correspond to the sites where tendinopathic characteristics are typically seen. We review the biomechanic literature on Achilles tendon, trying to interpret it on the basis that classic inflammatory changes are not frequently seen in chronic athletic tendon conditions. Biomechanical studies show that the strains within the tendons near their insertion site are not uniform. If the material properties are similar throughout the tendon, forces transferred through the insertion site preferentially load the side of the tendon that is usually not affected initially in tendinopathy. In that case, the side affected by tendinopathy is generally 'stress shielded'. The presence of differential strains opens the possibility of alternative biomechanical explanations for the pathology found in these regions of the tendon. The traditional concept of tensile failure may not be the essential feature of the pathomechanics of insertional tendinopathy. Additional work is needed ascertain whether such principles should be incorporated in current rehabilitation.


Short- and Long-term Opioid Use in Patients with Oral and Oropharynx Cancer.
Opioid use and abuse is a national health care crisis, yet opioids remain the cornerstone of pain management in cancer. We sought to determine the risk of acute and chronic opioid use with head and neck squamous cell cancer (HNSCC) treatment. Retrospective population-based study. Surveillance, Epidemiology and End Results (SEER)-Medicare database from 2008 to 2011. In total, 976 nondistant metastatic oral cavity and oropharynx patients undergoing cancer-directed treatment enrolled in Medicare were included. Opiate use was the primary end point. Univariate and multivariable logistic analyses were completed to determine risk factors. Of the patients, 811 (83.1%) received an opioid prescription during the treatment period, and 150 patients (15.4%) had continued opioid prescriptions at 3 months and 68 (7.0%) at 6 months. Opioid use during treatment was associated with prescriptions prior to treatment (odds ratio [OR], 3.28; 95% confidence interval [CI], 2.11-5.12) and was least likely to be associated with radiation treatment alone (OR, 0.35; 95% CI, 0.18-0.68). Risk factors for continued opioid use at both 3 and 6 months included tobacco use (OR, 2.23; 95% CI, 1.05-4.71 and OR, 3.84; 95% CI, 1.44-10.24) and opioids prescribed prior to treatment (OR, 3.84; 95% CI, 2.45-5.91 and OR, 3.56; 95% CI, 1.95-6.50). Oxycodone prescribed as the first opioid was the least likely to lead to ongoing use at 3 and 6 months (OR, 0.33; 95% CI, 0.17-0.62 and OR, 0.26; 95% CI, 0.10-0.67). Patients with oral/oropharyngeal cancer are at a very high risk for receiving opioids as part of symptom management during treatment, and a significant portion continues use at 3 and 6 months after treatment completion.


Impact of chronically alternating light-dark cycles on circadian clock mediated expression of cancer (glioma)-related genes in the brain.
Disruption of the circadian rhythm is a risk factor for cancer, while glioma is a leading contributor to mortality worldwide. Substantial efforts are being undertaken to decrypt underlying molecular pathways. Our understanding of the mechanisms through which disrupted circadian rhythm induces glioma development and progression is incomplete. We, therefore, examined changes in the expression of glioma-related genes in the mouse brain after chronic jetlag (CJL) exposure. A total of 22 candidate tumor suppressor (n= 14) and oncogenes (n= 8) were identified and analyzed for their interaction with clock genes. Both the control and CJL groups were investigated for the expression of candidate genes in the nucleus accumbens, hippocampus, prefrontal cortex, hypothalamus, and striatum of wild type, Bmal1-/- and Cry1/2 double knockout male mice. We found significant variations in the expression of candidate tumor suppressor and oncogenes in the brain tissues after CJL treatment in the wild type, Bmal1-/- and Cry1/2 double knockout mice. In response to CJL treatment, some of the genes were regulated in the wild type, Bmal1-/- and Cry1/2 similarly. However, the expression of some of the genes indicated their association with the functional clock. Overall, our result suggests a link between CJL and gliomas risk at least partially dependent on the circadian clock. However, further studies are needed to investigate the molecular mechanism associated with CJL and gliomas.


Why genes overlap in viruses.
The genomes of most virus species have overlapping genes--two or more proteins coded for by the same nucleotide sequence. Several explanations have been proposed for the evolution of this phenomenon, and we test these by comparing the amount of gene overlap in all known virus species. We conclude that gene overlap is unlikely to have evolved as a way of compressing the genome in response to the harmful effect of mutation because RNA viruses, despite having generally higher mutation rates, have less gene overlap on average than DNA viruses of comparable genome length. However, we do find a negative relationship between overlap proportion and genome length among viruses with icosahedral capsids, but not among those with other capsid types that we consider easier to enlarge in size. Our interpretation is that a physical constraint on genome length by the capsid has led to gene overlap evolving as a mechanism for producing more proteins from the same genome length. We consider that these patterns cannot be explained by other factors, namely the possible roles of overlap in transcription regulation, generating more divergent proteins and the relationship between gene length and genome length.


[Comparison of therapeutic effects of different types of acupuncture interventions on herpes zoster in acute stage].
To compare the therapeutic effects of different types of acupuncture therapy on herpes zoster (acute stage). A total of 189 cases of acute herpes zoster outpatients and inpatients were recruited in the present multicenters (3 hospitals) randomized controlled clinical trials. They were divided into (computer-aided random allocation): basic acupuncture (n = 36), cotton moxibustion (n = 35), fire needle (n = 43), tapping-cupping (n = 39) and medication (n = 36) groups. Ashi-points (around the locus), Jiaji (EX-B 2), Zhigou (SJ 6) and Houxi (SI 3) were used in this study. For patients of the acupuncture group, the abovementioned acupoints were punctured with filiform needles (encircled needling around the affected loci) and also stimulated with electroacupuncture (EA). For patients of the cotton moxibustion group, thin defated dry cotton pieces put over the Ashi-point were ignited, 3 times altogether, followed by EA and encircled needling stimulation which were the same to those in the basic acupuncture group. Patients of the fire needle group were treated by pricking the herpes (3-5 in number) with a hot-red needle, followed by EA and encircled needling treatment. Patients of the tapping-cupping group were treated by tapping Ashi-points repeatedly with a percussopunctator and cupping over the pricked region, followed by EA and encircled needling treatment. Patients of the medication group were treated by oral administration of Valaciclovir Hydrochlordide (300 mg/time, twice a day) and vitamin B1 (10 mg/time, t. i.d.) for 10 days. The acupuncture-moxibustion treatment was given once daily for 10 days. The time of blister-occurrence cease, scab formation and decrustation was recorded, and pain degree was evaluated using visual analog scale (VAS). The therapeutic effect was assessed according to the related standards. There were no significant differences among the 5 groups in the time of blister-occurrence cease, scab formation and decrustation, and in the therapeutic effect (P > 0.05). The VAS scores of the 5 groups were decreased gradually and apparently along with the treatment (P < 0.05), suggesting a pain relief after the treatment. In comparison with the medication group, the VAS scores of the basic acupuncture group, cotton moxibustion group, fire needle group and tapping-cupping group were significantly lower from the 7th day on following the treatment (P < 0.05). Acupuncture plus encircled needling and acupuncture plus encircled needling combined with cotton-moxibustion, or with fire needle stimulation, or with tapping and cupping are effective in the treatment of herpes zoster at the acute stage, being comparable to the medication in the clinical curative effect and improvement of blisters, and better than medication in pain relief.


A high-fat diet containing lard accelerates prostate cancer progression and reduces survival rate in mice: possible contribution of adipose tissue-derived cytokines.
To examine the effects of high-fat diet (HFD) containing lard on prostate cancer development and progression and its underlying mechanisms, transgenic adenocarcinoma mouse prostate (TRAMP) and TRAMP-C2 allograft models, as well as in vitro culture models, were employed. In TRAMP mice, HFD feeding increased the incidence of poorly differentiated carcinoma and decreased that of prostatic intraepithelial neoplasia in the dorsolateral lobes of the prostate, which was accompanied by increased expression of proteins associated with proliferation and angiogenesis. HFD feeding also led to increased metastasis and decreased survival rate in TRAMP mice. In the allograft model, HFD increased solid tumor growth, the expression of proteins related to proliferation/angiogenesis, the number of lipid vacuoles in tumor tissues, and levels of several cytokines in serum and adipose tissue. In vitro results revealed that adipose tissue-conditioned media from HFD-fed mice stimulated the proliferation and migration of prostate cancer cells and angiogenesis compared to those from control-diet-fed mice. These results indicate that the increase of adipose tissue-derived soluble factors by HFD feeding plays a role in the growth and metastasis of prostate cancer via endocrine and paracrine mechanisms. These results provide evidence that a HFD containing lard increases prostate cancer development and progression, thereby reducing the survival rate.


A monoclonal antibody against the 66-kDa protein expressed in mouse spleen and thymus inhibits Ly-6A.2-dependent cell-cell adhesion.
The Ly-6 locus encodes several cell surface proteins of 10-12 kDa. Some members of this multigene family may function in cell signaling and/or cell adhesion processes. T lymphocytes overexpressing Ly-6A.2 (one member of the Ly-6 gene family) protein homotypically aggregate when cultured in vitro. Further analysis of this homotypic aggregation suggests that Ly-6A.2 participates in cell-cell adhesion. These observations indicated the presence of a Ly-6 ligand(s) on the surface of lymphoid cells. In this study we report generation of a hamster mAb, 9AB2, that blocks Ly-6A.2-dependent cell-cell adhesion. The 9AB2 Ab recognizes a 66-kDa glycoprotein with unique tissue expression. The 9AB2 mAb does not bind Ly-6A.2, but coimmunoprecipitates Ly-6A.2 molecule. Moreover, 9AB2 Ag-expressing thymocytes specifically bind to Chinese hamster ovary cells overexpressing Ly-6A.2 protein, and this binding is specifically blocked by 9AB2 and anti-Ly-6A.2 Abs. These results suggest that the 66-kDa protein recognized by 9AB2 mAb is the putative ligand for Ly-6A.2.


Nanoinformatics workshop report: Current resources, community needs, and the proposal of a collaborative framework for data sharing and information integration.
The quantity of information on nanomaterial properties and behavior continues to grow rapidly. Without a concerted effort to collect, organize and mine disparate information coming out of current research efforts, the value and effective use of this information will be limited at best. Data will not be translated to knowledge. At worst, erroneous conclusions will be drawn and future research may be misdirected. Nanoinformatics can be a powerful approach to enhance the value of global information in nanoscience and nanotechnology. Much progress has been made through grassroots efforts in nanoinformatics resulting in a multitude of resources and tools for nanoscience researchers. In 2012, the nanoinformatics community believed it was important to critically evaluate and refine currently available nanoinformatics approaches in order to best inform the science and support the future of predictive nanotechnology. The Greener Nano 2012: Nanoinformatics Tools and Resources Workshop brought together informatics groups with materials scientists active in nanoscience research to evaluate and reflect on the tools and resources that have recently emerged in support of predictive nanotechnology. The workshop goals were to establish a better understanding of current nanoinformatics approaches and to clearly define immediate and projected informatics infrastructure needs of the nanotechnology community. The theme of nanotechnology environmental health and safety (nanoEHS) was used to provide real-world, concrete examples on how informatics can be utilized to advance our knowledge and guide nanoscience. The benefit here is that the same properties that impact the performance of products could also be the properties that inform EHS. From a decision management standpoint, the dual use of such data should be considered a priority. Key outcomes include a proposed collaborative framework for data collection, data sharing and information integration.