Serum cystatin C and indices of lung function in elderly Chinese men with chronic obstructive pulmonary disease.
The aim of this cross-sectional case-control study was to determine the relationship between serum cystatin C (sCysC) levels and lung function in elderly male patients with chronic obstructive pulmonary disease (COPD). This study included 251 Chinese men (age ≥ 65 years) who were divided into COPD (n = 129) and non-COPD (n = 122) groups. Participants underwent lung function and laboratory testing, including measurement of sCysC levels. Relationships between sCysC concentration and indices of lung function were assessed by multiple regression analysis. Participants in the COPD group displayed higher sCysC concentrations (P = 0.041) and lower lung function (P < 0.001) compared to participants in the non-COPD group. Multiple linear regression analyses revealed that the reciprocal of the sCysC concentration (1/sCysC) was positively associated with the predicted forced expiratory volume in 1 s in all subjects (β = 0.156, P = 0.009). The findings indicate that high sCysC levels were directly associated with decreased lung function in elderly Chinese men with COPD. High sCysC concentration may be a potential indicator of impaired lung function, and its application may improve the diagnosis and assessment of COPD severity in elderly male patients.


Translational and functional oncogenomics. From cancer-oriented genomic screenings to new diagnostic tools and improved cancer treatment.
We present here an experimental pipeline for the systematic identification and functional characterization of genes with high potential diagnostic and therapeutic value in human cancer. Complementary competences and resources have been brought together in the TRANSFOG Consortium to reach the following integrated research objectives: 1) execution of cancer-oriented genomic screenings on tumor tissues and experimental models and merging of the results to generate a prioritized panel of candidate genes involved in cancer progression and metastasis; 2) setup of systems for high-throughput delivery of full-length cDNAs, for gain-of-function analysis of the prioritized candidate genes; 3) collection of vectors and oligonucleotides for systematic, RNA interference-mediated down-regulation of the candidate genes; 4) adaptation of existing cell-based and model organism assays to a systematic analysis of gain and loss of function of the candidate genes, for identification and preliminary validation of novel potential therapeutic targets; 5) proteomic analysis of signal transduction and protein-protein interaction for better dissection of aberrant cancer signaling pathways; 6) validation of the diagnostic potential of the identified cancer genes towards the clinical use of diagnostic molecular signatures; 7) generation of a shared informatics platform for data handling and gene functional annotation. The results of the first three years of activity of the TRANSFOG Consortium are also briefly presented and discussed.


Patient and public involvement in the development of clinical practice guidelines: a scoping review.
Organisations that develop clinical practice guidelines (CPGs) encourage involvement of patients and the publics in their development, however, there are no standard methodologies for doing so. To examine how CPGs report patient and public involvement (PPI), we conducted a scoping review of the evidence addressing the following four questions: (1) who are the patients and publics involved in developing the CPG?; (2) from where and how are the patients and publics recruited?; (3) at what stage in the CPG development process are the patients and publics involved? and (4) how do the patients and publics contribute their views? We also extracted data on the use of PPI reporting checklists by the included studies. We used the methodology developed by Arksey and O'Malley and refined by the Joanna Briggs Institute. We searched PubMed, Embase, CINAHL and PsycINFO, websites of national guideline bodies from the UK, Canada, Australia and the USA, and conducted a forward citation search. No language, date or participant demographics restrictions were applied. Data were synthesised narratively. We included 47 studies addressing 1 or more of the 4 questions. All included studies reported who the patient and publics involved (PPI members) were, and several studies reported PPI members from different groups. Patients were reported in 43/47 studies, advocates were reported in 22/47 studies, patients and advocates reported in 17/47 studies, and general public reported in 2/47 studies. Thirty-four studies reported from where the patients and publics were recruited, with patient groups being the most common (20/34). Stage of involvement was reported by 42/47 studies, most commonly at question identification (26/42) and draft review (18/42) stages. Forty-two studies reported how the patients contributed, most commonly via group meetings (18/42) or individual interviews. Ten studies cited or used a reporting checklist to report findings. Our scoping review has revealed knowledge gaps to inform future research in several ways: replication, terminology and inclusion. First, no standard approach to PPI in CPG development could be inferred from the research. Second, inconsistent terminology to describe patients and publics reduces clarity around which patients and publics have been involved in developing CPGs. Finally, the under-representation of research describing PPI in the development of screening, as opposed to treatment, CPGs warrants further attention.


[Determination of Ca, Mg, K, P, Na, Zn, Fe and F in bone with microwave digest].
Microwave digest technique is widely applied in the analytical chemistry field. Comparing with traditional sample digestion method, i.e. wet digest or dry digest. microwave technique is simple, rapid, little contaminative and saves reagent, digests completely. Elements in the bone such as Ca, Mg, P, K, Na, Fe, Zn and F are determined by atomic absorption spectrometry. Their recovery ratio is 66.4%-110.9%, variation coefficient is 0.32%-7.61% except fluorine and phosphor.


How Home Delivery of Antiretroviral Drugs Ensured Uninterrupted HIV Treatment During COVID-19: Experiences From Indonesia, Laos, Nepal, and Nigeria.
Faced with the coronavirus disease (COVID-19) pandemic, governments worldwide instituted lockdowns to curtail virus spread. Health facility closures and travel restrictions disrupted access to antiretroviral (ARV) therapy for people living with HIV. This report describes how HIV programs in Indonesia, Laos, Nepal, and Nigeria supported treatment continuation by introducing home delivery of ARVs. Staff supporting the programs provided accounts of when and how decisions were taken to support ARV home delivery. They captured programmatic information about home delivery implementation using an intervention documentation tool. The 4 country experiences revealed lessons learned about factors favoring successful expansion of ARV home delivery. Three of the countries relied on existing networks of community health workers for ARV delivery; the fourth country, Indonesia, relied on a private sector courier service. Across the 4 countries, between 19% and 51% of eligible clients were served by home delivery. The experiences showed that ARV home delivery is feasible and acceptable to health service providers, clients, and other stakeholders. Essential to success was rapid mobilization of stakeholders who led the design of the home delivery mechanisms and provided leadership support of the service innovations. Timely service adaptation was made possible by pre-existing differentiated models of care supportive of community-based ARV provision by outreach workers. Home delivery models prioritized protection of client confidentiality and prevention measures for COVID-19. Sustainability of the innovation depends on reinforcement of the commodity management infrastructure and investment in financing mechanisms. Home delivery of ARVs is a feasible client-centered approach to be included among the options for decentralized drug distribution. It serves as a measure for expanding access to care both when access to health services is disrupted and under routine circumstances.


[Role of sinusoidal cells in the morphogenesis of alcoholic liver cirrhosis].
49 liver biopsies in alcoholic liver damage (fibrosis, chronic persisting hepatitis, cirrhosis) are studied on semithin sections electron microscopically and morphometrically. Morphological varieties of hepatocytes and sinusoidal cells are revealed as well as some rules in their proportions. Domination of stellate reticulo-endotheliocytes with a high secretory and phagocyte activity correlates with high adaptive properties of hepatocytes and transformation of lipocytes into fibroblast-like cells without development of intralobular fibrosis. If nonactive variant of the stellate reticulo-endotheliocytes prevails, the number of damaged hepatocytes and fibroblast-like lipocytes increases, intralobular fibrosis becomes pronounced resulting in hepatocyte death. Role of sinusoidal cells in realization of alcoholic cirrhosis morphogenesis is discussed.


Screening for Corynebacterium diphtheriae and Corynebacterium ulcerans in patients with upper respiratory tract infections 2007-2008: a multicentre European study.
Diphtheria is now rare in most European countries but, when cases do arise, the case fatality rate is high (5-10%). Because few countries continue to routinely screen for the causative organisms of diphtheria, the extent to which they are circulating amongst different European populations is largely unknown. During 2007-2008, ten European countries each screened between 968 and 8551 throat swabs from patients with upper respiratory tract infections. Six toxigenic strains of Corynebacterium diphtheriae were identified: two from symptomatic patients in Latvia (the country with the highest reported incidence of diphtheria in the European Union) and four from Lithuania (two cases, two carriers); the last reported case of diphtheria in Lithuania was in 2002. Carriage rates of non-toxigenic organisms ranged from 0 (Bulgaria, Finland, Greece, Ireland, Italy) to 4.0 per 1000 (95% CI 2.0-7.1) in Turkey. A total of 28 non-toxigenic strains were identified during the study (26 C. diphtheriae, one Corynebacterium ulcerans, one Corynebacterium pseudotuberculosis). The non-toxigenic C. ulcerans strain was isolated from the UK, the country with the highest reported incidence of cases due to C. ulcerans. Of the eleven ribotypes detected, Cluj was seen most frequently in the non-toxigenic isolates and, amongst toxigenic isolates, the major epidemic clone, Sankt-Petersburg, is still in circulation. Isolation of toxigenic C. diphtheriae and non-toxigenic C. diphtheriae and C. ulcerans in highly-vaccinated populations highlights the need to maintain microbiological surveillance, laboratory expertise and an awareness of these organisms amongst public health specialists, microbiologists and clinicians.


Nifedipine and acute myocardial infarction.
In consideration of the results of experimental studies indicating that nifedipine, a vasodilating calcium antagonist with little inotropic or electrophysiological effects, increases coronary flow to both normal and ischemic zones potentially rendering protection of ischemic myocardium as well as the results of clinical studies in patients with angina pectoris, this pilot study was carried out in patients with acute myocardial infarction to evaluate the clinical, hemodynamic and electrophysiological responses. Nifedipine was administered sublingually in a dosage of 10 mg initially, after an interval of 1 to 1.5 hours and thereafter to maintain the pressure at the level prevailing after three hours. As compared with a control group, the frequency of ventricular dysrhythmia as well as the frequency of complex dysrhythmias in the 17 treated patients were similar (mean 313 vs. 325 PVCs/24 hours; and 5.9 vs. 3.6 episodes respectively in treated and controls). No patient developed evidence of second or third degree AV block. Systemic vascular resistance fell from 1661 to 1283 dyne . s . cm-5 and cardiac index increased from 3.2 to 3.59 l/min/m2 at one hour. Arterial pressure decreased from 146/93 to 131/88 mm Hg. Pulmonary artery pressure remained unchanged in five patients and decreased by more than 3 mm Hg in four. Thus, in patients with acute myocardial infarction nifedipine decreases systemic resistance and, provided preload is not substantially reduced, increases cardiac output. Neither an exacerbation of chest pain nor an increase in ventricular dysrhythmia was observed. Extensive clinical investigation will be needed to definitively characterize effects of nifedipine on infarct size, coronary flow and prognosis of patients with acute myocardial infarction.


Conserved Double Translation Initiation Site for Δ160p53 Protein Hints at Isoform's Key Role in Mammalian Physiology.
p53 is the most commonly mutated gene in human cancers. Two fundamental reasons for this are its long protein isoforms protect from cancer, while its shorter C-terminal isoforms can support cancer and metastasis. Previously, we have shown that the Δ160p53 protein isoform enhances survival and the invasive character of cancer cells. Here, we identified a translation initiation site nine codons downstream of codon 160-the known initiation codon for the translation of Δ160p53-that is recognized by the translation machinery. When translation failed to initiate from AUG160 due to mutation, it initiated from AUG169 instead, producing similar levels of a similar protein, Δ169p53, which promoted cell survival as efficiently as Δ160p53 following DNA damage. Interestingly, almost all mammalian species with an orthologue to human AUG160 also possess one for AUG169, while none of the non-mammalian species lacking AUG160 have AUG169, even if that region of the p53 gene is well conserved. In view of our findings, we do not believe that Δ169p53 acts as a different p53 protein isoform; instead, we propose that the double translation initiation site strengthens the translation of these products with a critical role in cell homeostasis. Future studies will help verify if this is a more general mechanism for the expression of essential proteins in mammals.


Analyses of direct and indirect impacts of a positive list system on pharmaceutical R&D investments.
The South Korean government recently enacted a Positive List System (PLS) as a major change of the national formulary listing system and reimbursed prices for pharmaceutical products. Regardless of the primary goal of the PLS, its implementation might have spillover effects by influencing the pharmaceutical industry's research and development (R&D), potentially leading to a variety of responses by firms in relation to their R&D activities. We investigated the spillover effect of the PLS on R&D investments of the pharmaceutical industry in Korea through both direct and indirect channels, examining the influence of the PLS on sales profit and cash flow. Data from 9 years (5 before and 4 after PLS implementation) were drawn from the financial statements of firms whose stocks were exchanged in 2 official stock markets in Korea (526 firms) and additional pharmaceutical firms whose financial performance was officially audited by external reviewers (263 firms). Longitudinal analyses were conducted, using the panel nature of the data to control for permanent unobserved firm heterogeneity. Our results showed that the PLS was directly associated with R&D investments. In contrast, its indirect impacts stemming from the influence on sales profit and cash flow were minimal and statistically nonsignificant. The gross impact of the PLS on R&D investments increased moving further from the enactment year; R&D investments were reduced by 18.3% to 25.8% in 2009-2010 (compared with before PLS implementation) in the firm fixed-effects model. We also found that such negative direct and gross impacts of the PLS on R&D investments were significant only in firms without newly developed chemical entities. Considering the gross negative impact of the PLS on R&D investments of pharmaceutical firms and the heterogeneous response of these firms by the R&D activities, governmental efforts of cost-containment may need to consider the spillover impact of the PLS on pharmaceutical innovation.


Control of Pecan Weevil With Microbial Biopesticides.
The pecan weevil, Curculio caryae (Horn) (Coleoptera: Curculionidae), is a key pest of pecans Carya illinoinensis ([Wangenh.] K. Koch) (Fagales: Juglandaceae). Control recommendations rely on broad spectrum chemical insecticides. Due to regulatory and environmental concerns, effective alternatives for C. caryae control must be sought for pecan production in conventional and organic systems. We explored the use of microbial biopesticides for control of C. caryae in Georgia pecan orchards. Three experiments were conducted. The first investigated an integrated microbial control approach in an organic system at two locations. Three microbial agents, Grandevo (based on byproducts of the bacterium Chromobacterium subtsugae Martin, Gundersen-Rindal, Blackburn & Buyer), the entomopathogenic nematode Steinernema carpocapsae (Weiser), and entomopathogenic fungus Beauveria bassiana (Balsamo) Vuillemin, were applied to each treatment plot (0.6 ha) at different times during the season. A second experiment compared the effects of S. carpocapsae and B. bassiana applied as single treatments relative to application of both agents (at different times); survival of C. caryae was assessed approximately 11 mo after larvae were added to pots sunk in an organic pecan orchard. In a conventional orchard (with 1.0 ha plots), the third experiment compared Grandevo applications to a commonly used regime of chemical insecticides (carbaryl alternated with a pyrethroid). All experiments were repeated in consecutive years. The combined pest management tactic (experiment 1) reduced C. caryae infestation relative to non-treated control plots in both locations in 2014 and one of the two locations in 2015 (the other location had less than 1% infestation). In experiment 2, no differences among combined microbial treatments, single-applied microbial treatments or different numbers of application were observed, yet all microbial treatments reduced C. caryae survival relative to the control. In the third experiment, both Grandevo and standard chemical insecticide applications resulted in lower weevil infestation than the control (both years) and there was no difference between the insecticide treatments in 2014 although the chemical insecticide regime had slightly lower infestation in 2015. These results provide evidence that microbial biopesticides can substantially reduce pecan weevil infestations in organic and nonorganic systems.


Clinical application of surface-linked liposomal antigens.
The potential usefulness of surface-linked liposomal antigens for application to vaccine development was investigated. During the course of this investigation, a significant difference was observed in the recognition of liposomal antigens by antigen-presenting cells (APCs) between liposomes with different lipid components, and this difference was closely correlated with the adjuvant activity of liposomes. In addition to this "quantitative" difference between liposomes with differential lipid components, a "qualitative" difference (i.e., a differential ability to induce cross-presentation) was also observed between liposomes with different lipid components. Although the precise mechanism underlying this difference is currently unclear, the significant difference in membrane mobility observed between these liposomes might affect their ability to induce cross-presentation. Thus, surface-linked liposomal antigens may be applicable for the development of vaccines with minimal allergic side effects and for a novel protocol of allergen immunotherapy. In addition, by utilizing their ability to induce cross-presentation, surface-linked liposomal antigens could be used to develop virus vaccines that induce a cytotoxic T-cell (CTL) response, as well as tumor vaccine preparations that present tumor antigens to APCs and induce effective antitumor responses. These data suggest that differential lipid components in liposomes lead to differential processing and presentation of liposomal antigens in APCs.


Subcortical arteriosclerotic encephalopathy (Binswanger's disease).
Subcortical arteriosclerotic encephalopathy is a chronic vascular dementia with hydrocephalus characterized clinically by: (i) subacute focal neurological deficit; (ii) acute strokes; (iii) dementia; (iv) motor signs and pseudobulbar palsy; (v) hydrocephalus; (vi) persistent hypertension and systemic vascular disease; and (vii) a lengthy course. The pathogenesis is most probably ischaemic change related to subacute hypertensive encephalopathy. The pathological changes include severe central nervous system disease characterized by loss of white matter with gliosis, and arterial and arteriolar sclerosis of small penetrating cerebral blood vessels. The differential diagnosis includes vascular pseudobulbar palsy, multi-infarct dementia and senile dementia (Alzheimer's disease). Treatment includes blood pressure control as well as management of other factors known to affect vascular disease (diabetes mellitus).


Shifting Participatory Design Approaches for Increased Resilience.
OCCUPATIONAL APPLICATIONSSocial distancing restrictions imposed by the global outbreak of COVID-19 exposed vulnerabilities in traditional User-Centered Design processes. This paper presents a shift in methodological thinking and deployment of participatory processes toward a more dynamic and resilient approach of user-centered design in a multi-year joint academia-industry design project. We moved beyond an overreliance on resource-intensive formal discrete events - such as in-person design workshops, focus groups, or traditional field studies and observations - toward including more continuous inputs to create a more sustainable and fluid approach within a living lab ecosystem. User-centered data collection methods were organized in a framework across three dimensions of interaction: 1) Communication; 2) Timing; and 3) Presence. Expanding methodological options along these differing dimensions increased opportunities for more diversified inputs and sample recruitment, while increasing overall data and design feedback collected. Lowering participation and knowledge sharing thresholds enabled more continuous, inclusive involvement of key stakeholders throughout design processes.


DNA damage by lipid peroxidation products: implications in cancer, inflammation and autoimmunity.
Oxidative stress and lipid peroxidation (LPO) induced by inflammation, excess metal storage and excess caloric intake cause generalized DNA damage, producing genotoxic and mutagenic effects. The consequent deregulation of cell homeostasis is implicated in the pathogenesis of a number of malignancies and degenerative diseases. Reactive aldehydes produced by LPO, such as malondialdehyde, acrolein, crotonaldehyde and 4-hydroxy-2-nonenal, react with DNA bases, generating promutagenic exocyclic DNA adducts, which likely contribute to the mutagenic and carcinogenic effects associated with oxidative stress-induced LPO. However, reactive aldehydes, when added to tumor cells, can exert an anticancerous effect. They act, analogously to other chemotherapeutic drugs, by forming DNA adducts and, in this way, they drive the tumor cells toward apoptosis. The aldehyde-DNA adducts, which can be observed during inflammation, play an important role by inducing epigenetic changes which, in turn, can modulate the inflammatory process. The pathogenic role of the adducts formed by the products of LPO with biological macromolecules in the breaking of immunological tolerance to self antigens and in the development of autoimmunity has been supported by a wealth of evidence. The instrumental role of the adducts of reactive LPO products with self protein antigens in the sensitization of autoreactive cells to the respective unmodified proteins and in the intermolecular spreading of the autoimmune responses to aldehyde-modified and native DNA is well documented. In contrast, further investigation is required in order to establish whether the formation of adducts of LPO products with DNA might incite substantial immune responsivity and might be instrumental for the spreading of the immunological responses from aldehyde-modified DNA to native DNA and similarly modified, unmodified and/or structurally analogous self protein antigens, thus leading to autoimmunity.


Risk factors associated with albuminuria in Kuwaiti adults with type 2 diabetes.
There are no available data about the factors associated with diabetic nephropathy (DN) in Kuwaiti individuals with type 2 diabetes. This study was conducted on 154 consecutive Kuwaiti adults with type 2 diabetes who attended the diabetic out-patient clinic at Al-Sabah Hospital to determine the factors associated with albuminuria among them. Albuminuria was considered to be present if the urinary albumin:creatinine ratio test or 24-h collection was positive on two occasions. There were 102 (66.2%) women and 52 (33.8%) men, with a mean age of 49.1 ± 10.1 years and a median duration of diabetes for 6 years. Hypertension was found in 60.8% of the patients and 16.3% had an HbA 1c <7%. Albuminuria was found in 43.5% of the patients. The prevalence of microalbuminuria and macroalbuminuria was 27.3% and 16.2%, respectively. In the univariate analysis, the factors that were significantly associated with albuminuria were hypertension - both systolic and diastolic blood pressure levels, HbA 1c , retinopathy, duration of diabetes, and modality of treatment. Multiple logistic regression analysis indicated that hyper-tension was the main independent risk factor associated with albuminuria (OR 4.1, 95% CI 1.1- 15.0; P = 0.03). In conclusion, although albuminuria is common among Kuwaiti adults with type 2 diabetes, the prevalence is lower than that reported for other populations in spite of the poor glycemic control and the high prevalence of hypertension. Factors associated with albuminuria appear to be similar to other populations, and hypertension was the most independent factor. Early recognition and treatment of hypertension is an important strategy to prevent or delay DN as well as cardiovascular morbidity and mortality. A population-based study is warranted to confirm these findings and to search for genetic linkage for the development of DN.


Fatty acid sensing in the gut and the hypothalamus: in vivo and in vitro perspectives.
The ability to properly sense both ingested and circulating nutrients is crucial for the maintenance of metabolic homeostasis. As such, both the gastrointestinal tract and the hypothalamus have demonstrated the capacity to sense and effectively respond to nutrients, such as fatty acids, to control food intake and glucose production to regulate energy and glucose homeostasis. In modern, Westernized societies, obesity and diabetes rates continue to rise unabated, due in part to an increase in highly palatable high-fat diet consumption. Thus, our understanding in the ability of the body to successfully monitor lipids is more vital than ever. This review details the current understanding of both the gut and the brain, specifically the hypothalamus, in sensing fatty acids. Highlighting both in vivo and in vitro studies, we explore some of the mechanisms upon which different fatty acids activate enteroendocrine and neural lipid-sensing signaling mechanisms to subsequently lower food intake and glucose production to ultimately regulate metabolic homeostasis. A better understanding of these lipid-sensing pathways could lay the groundwork for successful pharmacological targets for the treatment of obesity and diabetes.


Atrial Fibrillation, Stroke, and Silent Cerebrovascular Disease: A Population-based MRI Study.
Atrial fibrillation (AF) has been associated with cognitive decline and dementia. However, the mechanisms behind these associations are not clear. Examination of cerebrovascular pathology on MRI may shed light on how AF affects the brain. This study aimed to determine whether AF is associated with a broad range of cerebrovascular diseases beyond the well-known association with symptomatic stroke, including silent infarcts and markers of small vessel disease, i.e., cerebral microbleeds (CMBs), white matter hyperintensities (WMHs), and lacunes, in a population-based sample of 70-year-olds. Data were obtained from the Gothenburg H70 Birth Cohort Studies, in which individuals are invited based on birthdate. This study has a cross-sectional design and includes individuals born in 1944 who underwent structural brain MRI in 2014 to 2017. AF diagnoses were based on self-report, ECG, and register data. Symptomatic stroke was based on self-report, proxy interviews, and register data. Brain infarcts and CMBs were assessed by a radiologist. WMH volumes were measured on fluid-attenuated inversion recovery images with the Lesion Segmentation Tool. Multivariable logistic regression was used to study the association between AF and infarcts/CMBs, and multivariable linear regression was used to study the association between AF and WMHs. A total of 776 individuals were included, and 65 (8.4%) had AF. AF was associated with symptomatic stroke (odds ratio [OR] 4.5, 95% confidence interval [CI] 2.1-9.5) and MRI findings of large infarcts (OR 5.0, 95% CI 1.5-15.9), lacunes (OR 2.7, 95% CI 1.2-5.6), and silent brain infarcts (OR 3.5; 95% CI 1.6-7.4). Among those with symptomatic stroke, individuals with AF had larger WMH volumes (0.0137 mL/total intracranial volume [TIV], 95% CI 0.0074-0.0252) compared to those without AF (0.0043 mL/TIV, 95% CI 0.0029-0.0064). There was no association between AF and WMH volumes among those without symptomatic stroke. In addition, AF was associated to CMBs in the frontal lobe. AF was associated with a broad range of cerebrovascular pathologies. Further research is needed to establish whether cerebrovascular MRI markers can be added to current treatment guidelines to further personalize anticoagulant treatment in patients with AF and to further characterize the pathogenetic processes underlying the associations between AF and cerebrovascular diseases, as well as dementia.


Recognition and repair of the slipped rectus muscle.
Since the first description of the slipped muscle as a complication of strabismus surgery in 1979, the distinctions between it and the lost muscle have become blurred both in the literature and in general understanding. Sixtytwo slipped muscles in 52 consecutive patients were reviewed in an effort to more fully describe this Important and often unrecognized entity. The range of clinical presentation of slipped muscle is large: from the immediate large postoperative over- or undercorrection with absent duction, to the gradual moderate deviation with subtly reduced excursion. The auctions provided by the slipped muscles ranged from complete absence to almost normal, with an average of 19° excursion beyond the midline. At surgery, recognizing the empty muscle capsule attached to the sclera with the tendon slipped posteriorly within it is imperative for its repair. Recognition is facilitated by suspecting it from clinical findings. Correction of the motility defect requires advancement of the muscle tissue and not just its empty capsule. Slippage can probably be prevented by using a surgical technique, which firmly locks the suture to the tendon and not just to the muscle capsule.


Intraruminal infusion of propionate alters feeding behavior and decreases energy intake of lactating dairy cows.
The dose-response effects of intraruminal infusion of propionate on feeding behavior of lactating dairy cows were evaluated with eight ruminally cannulated Holstein cows past peak lactation. Treatments were mixtures of propionic acid and acetic acid containing propionic acid at eight different concentrations in Experiment 1, and mixtures of sodium propionate and sodium acetate containing sodium propionate at 4 different concentrations in Experiment 2. Experimental designs were an 8 x 8 and duplicated 4 x 4 Latin squares, respectively, for Experiments 1 and 2. Treatment solutions were infused into the rumen continuously for 14 h at a rate of 16.7 and 25 mmol/min, respectively, for Experiments 1 and 2. Infusion started 2 h before feeding and ended 12 h after feeding; feeding behavior was monitored for 12 h after feeding using a computerized data acquisition system. Total metabolizable energy (ME) intake was calculated by adding the energy of infusates to dietary energy intake. In both experiments, as the proportion of propionate of the infusates increased, total ME intake and dry matter intake decreased linearly. As infusion of propionate increased, meal size tended (P < 0.09) to decrease linearly and intermeal interval tended (P < 0.07) to increase linearly in Experiment 1; meal size decreased linearly and number of meal bouts tended (P < 0.08) to decrease linearly in Experiment 2. These observations indicate that the reduction in dietary energy intake from propionate infusion was greater than the energy supplied from infusates, and that propionate plays an important role in feed intake regulation by affecting both satiety and hunger.


Plasmodium falciparum: protein antigens identified by analysis of serum samples from vaccinated Aotus monkeys.
Serum samples from Aotus trivirgatus subsp. griseimembra monkeys obtained at different stages of a vaccination experiment were analyzed for total antibody titer to Plasmodium falciparum and were used for identifying protective antigens of the human malaria parasite. Total malarial antibody titers were higher in serum samples from protected monkeys (vaccinated with antigen in an adjuvant) than in those from unprotected monkeys (vaccinated with either antigen or adjuvant only). Parasite proteins were labeled with [3H]isoleucine, solubilized with nonionic detergent, and reacted with immune Aotus sera. Immunoprecipitates obtained were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and fluorography. Thirteen protein antigen bands in the molecular weight range 73,000 to 180,000 were resolved. Serum samples obtained from protected Aotus monkeys reacted more intensely with these proteins than samples from unprotected monkeys did. Evidence is presented that the protective antigen is not a single, normally nonimmunogenic, protein that is recognized only in protected monkeys. Rather, the present data indicate that a heightened immune response to multiple proteins correlated with in vivo protection to P. falciparum in Aotus monkeys. This finding may have a significant bearing on strategies for the development of a human P. falciparum vaccine.


Modeling signal propagation in the human cochlea.
The level-dependent component of the latency of human auditory brainstem responses (ABR) to tonebursts decreases by about 38% for every 20-dB increase in stimulus level over a wide range of both frequency and level [Neely, Norton, Gorga, and Jesteadt (1998). J. Acoust. Soc. Am. 31, 87-97]. This level-dependence has now been simulated in an active, nonlinear, transmission-line model of cochlear mechanics combined with an adaptation stage. The micromechanics in this model are similar to previous models except that a dual role is proposed for the tectorial membrane (TM): (1) passive sharpening the tuning of sensory-cell inputs (relative to basilar-membrane vibrations) and (2) providing an optimal phase shift (relative to basilar-membrane vibrations) of outer-hair-cell feedback forces, so that amplification is restricted to a limited range of frequencies. The adaptation stage, which represents synaptic adaptation of neural signals, contributes to the latency level-dependence more at low frequencies than at high frequencies. Compression in this model spans the range of audible sound levels with a compression ratio of about 2:1. With further development, the proposed model of cochlear micromechanics could be useful both (1) as a front-end to functional models of the auditory system and (2) as a foundation for understanding the physiological basis of cochlear amplification.


In vivo behavior of peptide-specific T cells during mucosal tolerance induction: antigen introduced through the mucosa of the conjunctiva elicits prolonged antigen-specific T cell priming followed by anergy.
The mucosa of the conjunctiva is an important site of entry for environmental Ags as well as Ags emanating from the eye itself. However, very little is known about T cell recognition of Ag introduced through this important mucosal site. We have characterized the in vivo process of CD4 T cell recognition of Ag delivered via the conjunctival mucosa. Application of soluble OVA to the conjunctiva of BALB/c mice induced potent T cell tolerance. APC-presenting OVA peptide in vivo was only found in the submandibular lymph node and not in other lymph nodes, spleen, or nasal-associated lymphoid tissue. Similarly, in TCR transgenic DO11. 10 adoptive transfer mice, OVA-specific CD4+ T cell clonal expansion was only observed in the submandibular lymph node following conjunctival application of peptide. These experiments thus define a highly specific lymphatic drainage pathway from the conjunctiva. OVA-specific T cell clonal expansion peaked at day 3 following initiation of daily OVA administration and gradually declined during the 10-day treatment period, but remained elevated compared with nontreated adoptive transfer mice. During this period, the T cells expressed activation markers, and proliferated and secreted IL-2 in vitro in response to OVA stimulation. In contrast, these cells were unable to clonally expand in vivo, or proliferate in vitro following a subsequent OVA/CFA immunization. These results suggest that Ag applied to a mucosal site can be efficiently presented in a local draining lymph node, resulting in initial T cell priming and clonal expansion, followed by T cell anergy.


Couple-focused human immunodeficiency virus prevention for young Latino parents: randomized clinical trial of efficacy and sustainability.
To evaluate the efficacy and sustainability of a couple-focused human immunodeficiency virus (HIV) prevention intervention in reducing unprotected sex and increasing intent to use condoms and knowledge about AIDS. Randomized controlled trial. Urban community settings in Southern California. Primarily Latino couples (168 couples; 336 individuals) who were aged 14 to 25 years, English or Spanish speaking, and coparenting a child at least 3 months of age. A 12-hour theory-based, couple-focused HIV prevention program culturally tailored for young Latino parents, with emphasis on family protection, skill building, and issues related to gender and power. The 1½-hour control condition provided basic HIV-AIDS information. Primary outcome measures included self-report of condom use during the past 3 months; secondary, intent to use condoms and knowledge about AIDS. The HIV prevention intervention reduced the proportion of unprotected sex episodes (odds ratio, 0.87 per month from baseline to 6 months; 95% confidence interval [CI], 0.82-0.93) and increased intent to use condoms (slope increase, 0.20; 95% CI, 0.04-0.37) at the 6-month follow-up; however, these effects were not sustained at 12 months. Knowledge about AIDS was increased in both groups from baseline to 6 months (slope estimate, 0.57; 95% CI, 0.47-0.67) and was maintained in the intervention group only through 12 months. Female participants in both groups had higher intent to use condoms and knowledge about AIDS than male participants (P ≤ .01). The couple-focused HIV prevention intervention reduced risky sexual behaviors and improved intent to use condoms among young Latino parents at the 6-month evaluation. A maintenance program is needed to improve the sustainability of effects over time.


Combined exposure to lifting and psychosocial strain at work and adverse pregnancy outcomes-A study in the Danish National Birth Cohort.
Previous studies have investigated physical and psychosocial job exposures separately in relation to foetal growth. We therefore investigated if occupational lifting and psychosocial job strain interact to affect foetal growth and gestational length. We hypothesised that heavy lifting and high job strain would increase the risk of impacted foetal growth (small or large for gestational age) and preterm birth. The cohort included 47,582 pregnancies from the Danish National Birth Cohort (1996-2002), where the woman was pregnant at 22 gestational weeks (GW), expected one child and worked ≥30 hours/week. Information on occupational lifting and psychosocial job strain was derived from an interview (16±3.0 GW). Data to calculate small and large for gestational age (SGA/LGA) and gestational length was retrieved from the Medical Birth Register. Interaction between lifting and job strain (Karasek's model) was analysed by multinomial logistic regression. Overall, the adjusted regression analysis showed statistically significant interaction between lifting and job strain for SGA and LGA. For each additional 250 kg lifted/day, high strain women (high Demand/low Control) had increased odds of giving birth to a LGA-child (OR = 1.15; 95% CI 1.06-1.26), whereas women in the active group (high Demand/high Control) had increased odds of giving birth to a SGA child (OR = 1.12; 95% CI 1.03-1.23). When women lifting ≤1000 kg/day were excluded in the sensitivity analyses the interaction between lifting and job strain became insignificant. No interaction of lifting and job strain was found for gestational length. The main findings may give some support to our hypothesis, as lifting in combination high with job strain increased the risk of giving birth to a LGA child. This finding was, however, not supported in the sensitivity analysis and no association of the interaction was found relative to gestational length.


Design of the sex hormones and physical exercise (SHAPE) study.
Physical activity has been associated with a decreased risk for breast cancer. The biological mechanism(s) underlying the association between physical activity and breast cancer is not clear. Most prominent hypothesis is that physical activity may protect against breast cancer through reduced lifetime exposure to endogenous hormones either direct, or indirect by preventing overweight and abdominal adiposity. In order to get more insight in the causal pathway between physical activity and breast cancer risk, we designed the Sex Hormones and Physical Exercise (SHAPE) study. Purpose of SHAPE study is to examine the effects of a 1-year moderate-to-vigorous intensity exercise programme on endogenous hormone levels associated with breast cancer among sedentary postmenopausal women and whether the amount of total body fat or abdominal fat mediates the effects. In the SHAPE study, 189 sedentary postmenopausal women, aged 50-69 years, are randomly allocated to an intervention or a control group. The intervention consists of an 1-year moderate-to-vigorous intensity aerobic and strength training exercise programme. Participants allocated to the control group are requested to retain their habitual exercise pattern. Primary study parameters measured at baseline, at four months and at 12 months are: serum concentrations of endogenous estrogens, endogenous androgens, sex hormone binding globuline and insuline. Other study parameters include: amount of total and abdominal fat, weight, BMI, body fat distribution, physical fitness, blood pressure and lifestyle factors. This study will contribute to the body of evidence relating physical activity and breast cancer risk and will provide insight into possible mechanisms through which physical activity might be associated with reduced risk of breast cancer in postmenopausal women.


Factors of the Kaingang culture which influence care for the older adult: the view of the health professional.
to describe the health professionals' perception in relation to the factors of the Kaingang culture which influence the undertaking of healthcare practices with the elders in this ethnic group. descriptive research with a qualitative approach, grounded in the ethnographic method, undertaken with ten health professionals who work in the Indigenous Territory in Faxinal, in the Brazilian state of Paraná. The data was collected in the period November 2010 to February 2012 through interviews and participant observation, and was analyzed in the light of the Transcultural Nursing Theory. evidence was found that the Kaingang culture has a strong influence on the professional care for the older adult, principally due to the cultural strangeness of certain customs, aspects which limit the health care for such older adults being listed. knowledge of the influences on the care can contribute to the forming of a framework of information relevant to the professional in the provision of care for the Kaingang older adults.


Thiolation of symmetrical and unsymmetrical diketopiperazines.
The introduction of sulfur units into a variety of symmetrical and unsymmetrical diketopiperazines (DKPs) is described. We investigated different thiolation methods utilizing several bases and electrophilic sulfur reagents, leading to monomethylthio-, bis(methylthio)-, and epithio-DKPs. Their formation proceeded diastereoselectively, facilitating the application in total syntheses of many thiodiketopiperazine (TDKP) natural products. Furthermore, possible side reactions as well as mechanistic studies and stereochemical structural assignments of the obtained products are given.


Metformin in the management of diabetes during pregnancy and lactation.
This review explores the current place of metformin in the management of gestational diabetes (GDM) and type 2 diabetes during pregnancy and lactation. The rationale and basic pharmacology of metformin usage in pregnancy is discussed along with the evidence from observational and randomized controlled trials in women with GDM or overt diabetes. There seems to be adequate evidence of efficacy and short-term safety of metformin in relation to maternal and neonatal outcomes in GDM, with possible benefits related to lower maternal weight gain and lower risk of neonatal hypoglycemia and macrosomia. Additionally, metformin offers the advantages of oral administration, convenience, less cost and greater acceptability. Metformin may, therefore, be considered in milder forms of GDM where glycemic goals are not attained by lifestyle modification. However, failure rate is likely to be higher in those with an earlier diagnosis of GDM, higher blood glucose, higher body mass index (BMI) or previous history of GDM, and insulin remains the cornerstone of pharmacological treatment in such cases. The use of metformin in type 2 diabetes has been assessed in observational and small randomized trials. Metformin monotherapy in women with overt diabetes is highly unlikely to achieve glycemic targets. Hence, the use should be restricted as adjunct to insulin and may be considered in women with high insulin dose requirements or rapid weight gain. There is clearly a need for more clinical trials to assess the effect of combined insulin plus metformin therapy in pregnancy with type 2 diabetes. Additionally, there is a paucity of data on long-term effects in offspring exposed to metformin in utero. It is imperative to further explore its impact on offspring as metformin has significant transplacental transfer and has the potential to impact the programming of the epigenome. Therefore, caution must be exercised when prescribing metformin in pregnant women. More research is clearly needed before metformin can be considered as standard of care in the management of diabetes during pregnancy.


Graded Replacement of Carbohydrate-Rich Breakfast Products with Dairy Products: Effects on Postprandial Aminoacidemia, Glycemic Control, Bone Metabolism, and Satiety.
Postprandial metabolic responses following dairy consumption have mostly been studied using stand-alone dairy products or milk-derived nutrients. Assessing the impact of ingesting dairy products as part of a common breakfast on postprandial aminoacidemia, glycemic control, markers of bone metabolism, and satiety. In this randomized, cross-over study, 20 healthy young males and females consumed on three separated occasions an iso-energetic breakfast containing no dairy (NO-D), one dairy (ONE-D) or two dairy (TWO-D) products. Postprandial concentrations of amino acids, glucose, insulin, glucagon-like peptide-1 (GLP-1), calcium, parathyroid hormone (PTH), and markers of bone formation (P1NP) and resorption (CTX-I) were measured before and up to 300 minutes after initiating the breakfast, along with VAS-scales to assess satiety. Plasma essential and branched-chained amino acids availability (expressed as total area under the curve (tAUC)) increased in a dose-dependent manner (P<0.05 for all comparisons). Plasma glucose tAUCs were lower in ONE-D and TWO-D compared to NO-D (P<0.05 for both comparisons). Plasma GLP-1 tAUC increased in a dose-dependent manner (P<0.05 for all comparisons), while no differences were observed in plasma insulin tAUC between conditions (P>0.05 for all comparisons). Serum calcium tAUCs were higher in ONE-D and TWO-D when compared to NO-D (P<0.05 for both comparisons), along with lower PTH tAUCs in ONE-D and TWO-D when compared to NO-D (P=0.001 for both comparisons). In accordance, serum CTX-I concentrations were lower in the late postprandial period in ONE-D and TWO-D vs NO-D (P<0.01 for both comparisons). No differences were observed in P1NP tAUCs between conditions (P>0.05). The tAUCs for satiety were higher in TWO-D compared with NO-D and ONE-D (P<0.05 for both comparisons). Iso-energetic replacement of a carbohydrate-rich breakfast component with one serving of dairy improves postprandial amino acid availability, glycemic control, and bone metabolism. Adding a second serving of dairy in lieu of carbohydrates augments postprandial amino acid and GLP-1 concentrations, while further promoting satiety. ISRCTN13531586 (https://doi.org/10.1186/ISRCTN13531586).


Survivin gene expression in chronic liver disease and hepatocellular carcinoma.
Survivin is an oncofetal protein involved both in cell death and cell cycle regulation. Survivin is undetectable or found at very low levels in normal differentiated tissues whereas increased expression has been observed in several human malignancies, including lung, colon and liver cancer. The aim of this study was to evaluate the diagnostic and clinical significance of Survivin expression in hepatocellular carcinoma and non-neoplastic liver tissues in a series of surgical patients. Survivin mRNA levels were quantitated by real time RT-PCR in 25 patients. Survivin mRNA was documented in all liver tissues with significantly higher levels in neoplastic specimens (p=0.01). In non-neoplastic liver tissue, Survivin levels were correlated with activity score of chronic liver disease. Increased Survivin levels were correlated with high tumor grade (p=0.05) and vascular invasion (p= 0.005). Tumor recurrences were more frequent in patients with high Survivin levels, although the difference did not reach statistical significance. Low levels of Survivin mRNA are present in normal and in non-neoplastic liver tissue. In hepatocellular carcinomas, high levels of Survivin are associated with aggressive tumor features. The prognostic significance of quantitative Survivin evaluation requires further studies.


FlexAID: Revisiting Docking on Non-Native-Complex Structures.
Small-molecule protein docking is an essential tool in drug design and to understand molecular recognition. In the present work we introduce FlexAID, a small-molecule docking algorithm that accounts for target side-chain flexibility and utilizes a soft scoring function, i.e. one that is not highly dependent on specific geometric criteria, based on surface complementarity. The pairwise energy parameters were derived from a large dataset of true positive poses and negative decoys from the PDBbind database through an iterative process using Monte Carlo simulations. The prediction of binding poses is tested using the widely used Astex dataset as well as the HAP2 dataset, while performance in virtual screening is evaluated using a subset of the DUD dataset. We compare FlexAID to AutoDock Vina, FlexX, and rDock in an extensive number of scenarios to understand the strengths and limitations of the different programs as well as to reported results for Glide, GOLD, and DOCK6 where applicable. The most relevant among these scenarios is that of docking on flexible non-native-complex structures where as is the case in reality, the target conformation in the bound form is not known a priori. We demonstrate that FlexAID, unlike other programs, is robust against increasing structural variability. FlexAID obtains equivalent sampling success as GOLD and performs better than AutoDock Vina or FlexX in all scenarios against non-native-complex structures. FlexAID is better than rDock when there is at least one critical side-chain movement required upon ligand binding. In virtual screening, FlexAID results are lower on average than those of AutoDock Vina and rDock. The higher accuracy in flexible targets where critical movements are required, intuitive PyMOL-integrated graphical user interface and free source code as well as precompiled executables for Windows, Linux, and Mac OS make FlexAID a welcome addition to the arsenal of existing small-molecule protein docking methods.


[Advances on gene therapy for USH2A exon 13 related inherited retinal dystrophy].
Biallelic pathogenic variants in the USH2A gene result in Usher syndrome type Ⅱ and non-syndromic retinitis pigmentosa, both of which entail the progressive loss of photoreceptors leading to blindness. The cDNA of the USH2A gene is extensive, consisting of 15 606 base pairs, rendering it impractical for delivery via adeno-associated virus vectors for gene replacement therapy. Notably, exon 13 has emerged as a focal point for therapeutic intervention, given its predilection for harboring the most pathogenic variants within USH2A. Recent intervention studies targeting USH2A exon 13 through the utilization of antisense oligonucleotides, genome editing, and RNA editing approaches have exhibited promising therapeutic potential. This paper provides a comprehensive overview of the molecular mechanisms, outcome data, and the challenges associated with the application of these interventions in this domain.


Association of COVID-19 Infection and Acute Mesenteric Ischemia.
COVID-19 is an infectious disease that is considered to be a thromboinflammatory disorder. The study was aimed to determine the prevalence of COVID-19 in patients with acute mesenteric ischemia (AMI) and the outcomes of surgical treatment in relation to COVID-19. A total of 140 patients were included in this multicentric study divided into two groups: the test group (n=65) consisted of cases of AMI detected during the COVID-19 pandemic and the control group (n=65) consisted of cases of AMI detected before the pandemic. Test group patients were classified as COVID-positive (COVID+), or COVID-negative (COVID-) if they tested positive, respectively negative test for COVID-19 on admission. Primary outcomes were: prevalence of COVID-19 infection among test group patients, association between COVID-19 infection and inoperability, and between COVID-19 and treatment outcome. Secondary outcomes were association between each blood parameter and inoperability and treatment outcome. There were no statistically significant differences between inoperability and COVID-19 positivity on admission, overall mortality between the control group and the test group and overall mortality between COVID+ and COVID- patients, as well as among those patients that have been surgically treated (p>0.05). There were statistically significant differences between serum amylase levels (p=0.034), and serum LDH levels (p=0.0382) and inoperability, between serum LDH levels and postoperative mortality (p=0.0151), and overall mortality (p=0.00163). High level of LDH and serum pancreatic amylase are associated with a higher rate of inoperability and a higher postoperative and overall mortality rate. COVID-19 does not seem to independently influence the treatment outcome of AMI.


Nucleotide sequence of cloned cDNA coding for pumpkin 11-S globulin beta subunit.
cDNA coding for preproglobulin beta, a precursor protein of 11-S globulin beta subunit, was cloned and the nucleotide sequence has been determined. The sequence covers the whole coding region (1440 base pairs) with 5' and 3' noncoding region (30 and 214 base pairs, respectively). The deduced amino acid sequence of preproglobulin beta consists of a 21-amino-acid N-terminal signal peptide, preceding the acidic gamma polypeptide region (275 amino acids) and the subsequent basic delta region (184 amino acids). The site for post-translational cleavage of the precursor polypeptide to make the gamma and delta chains is estimated to be located between the asparagine-glycine residues. The N-terminal amino acid of the gamma chain of mature 11-S globulin beta subunit was reported to be blocked by 5-oxoproline (pyroglutamic acid) [Ohmiya et al. (1980) Plant Cell Physiol. 21, 157-167]. It was shown that the blocked N-terminal amino acid is coded as a glutamine residue. The derived amino acid sequence was also compared with those of precursor proteins of other 11-S globulins such as soybean glycinin, cotton beta globulin, pea legumin and rape 11-S globulin by dot matrix analysis.


Biological responses to trauma and the development of intrusive memories: an analog study with the trauma film paradigm.
Evidence suggests that previous trauma reduces the cortisol response to subsequent stressors. We examined the relation of this response to intrusive memory, and the potential moderating roles of sympathetic reactions. Pre-existing trauma-related factors and the cardiac defense response were assessed before 58 healthy participants viewed a trauma film. Salivary cortisol and alpha-amylase (sAA) were collected pre-, peri- and post-film. Intrusive memories about the film were recorded for a week. Cortisol increased whereas sAA decreased after the film. Those with more recent traumatic experiences and greater subclinical PTSD symptoms had lower cortisol concentration post-film. Lower cortisol levels predicted greater vividness of intrusions. Positive correlations between cortisol and the frequency of intrusion were only present among individuals with more sympathetic activations. These findings suggest the contribution of insufficient cortisol secretion to over-consolidation of traumatic memory, and highlight the variation attributable to individual differences and different memory characteristics.


A retrogen strategy for presentation of an intracellular tumor antigen as an exogenous antigen by dendritic cells induces potent antitumor T helper and CTL responses.
Induction of an effective antitumor response requires CD4+ helper T (Th) cells to recognize antigens on the same dendritic cells (DCs) that cross-present CTL antigens. Such cross-presentation is difficult to achieve by current tumor vaccine strategies. Here, we develop a novel "Retrogen" strategy for DCs to efficiently cross-present an intracellular tumor antigen, MAGE-3, to both MHC class I and MHC class II in a cognate manner. Specifically, the MAGE-3 gene was linked to a leader sequence at its NH2 terminus for secretion and to a cell-binding domain at its COOH terminus for receptor-mediated internalization. DCs transduced with the modified MAGE-3 gene produced and secreted MAGE-3 proteins, which were efficiently taken up by DCs via receptor-mediated internalization and presented as exogenous antigens to class I and class II molecules. Immunization of mice with the transduced DCs expressing the MAGE-3 fusion protein, termed "Retrogen" for its retrograde transport/internalization after secretion, efficiently induced all arms of the adaptive antitumor immune responses. Thus, this retrogen strategy of using a unifying mechanism for DCs to cross-present an intracellular tumor antigen in a cognate manner could be generally used to improve the efficacy of tumor vaccines and immunotherapies.


Left ventricular volumes during exercise in endurance athletes assessed by contrast echocardiography.
The objective was to assess left ventricular (LV) volumes at rest and during upright submaximal exercise in endurance athletes to see whether changes in heart volume could explain the large predicted increase in cardiac output in endurance athletes. Contrast echocardiography was used to assess changes in LV volumes during upright bicycle exercise in 24 healthy male endurance athletes. Maximal oxygen uptake and oxygen pulse were measured by using cardiopulmonary exercise testing. From rest to exercise at a heart rate of 160 beats min(-1) end-diastolic volume increased by 18% (P < 0.001) and end-systolic volume decreased by 21% (P = 0.002). Stroke volume showed an almost linear increase during exercise (45% increase, P < 0.001). The increase in end-diastolic volume contributed to 73% of the increase in stroke volume. No significant differences were observed between stroke volume calculated from LV volumes with contrast echocardiography and stroke volume calculated from oxygen pulse at heart rates of 130 and 160 beats min(-1). Using the linear regression equation between oxygen uptake and cardiac output assessed by echocardiography during exercise (r=0.87, P=0.002), cardiac output at maximal exercise was estimated at 33 +/- 3 L min(-1), with an estimated increase in stroke volume by 69% from rest to maximal exercise. By using contrast echocardiography, a large increase in stroke volume in endurance athletes could be explained by an almost linear increase in end-diastolic volume and an initial small decrease in end-systolic volume during incremental upright exercise.


The medicinal leech and its use in plastic surgery: a possible cause for infection.
Recent interest in the use of the medicinal leech (Hirudo medicinalis) in microsurgical practice prompted us to undertake a bacteriological study. Aeromonas hydrophila was consistently cultured from 9 leeches that we examined. This organism is pathogenic to man and we consider that there is a significant risk of infection, particularly in those procedures where the vascularity of the tissues is compromised. There are several pharmacological preparations which have similar properties to the secretion of the medicinal leech and we submit that these non-infective preparations may be worthy of investigation.


Proust and perversion: some clinical and theoretical considerations.
Relationships may be perserve without"normal" sexuality being replaced by deviant acts and fantasies. The link between perversion and genital sexuality can be loosened without the term becoming inapplicable. Moreover perversions manifest themselves in almost any idiosyncratic form, just like defences. Next to a seemingly not for perverse aim and object, split-off fantasies and acts exist, which form the condition for the "normal" genital sexual relationship. Such a fantasy may be the idea that one's partner has a secret homosexual adventure like in Proust's novel. It can be the need to be unfaithful, or the fantasy of having two lovers instead of one husband, as in the examples given. Perversions can be understood as regulators of self-esteem, and defence against (pre)oedipal conflict. Proust, an expert on perversion and the pre-oedipal, gives us insight into its development, and manifestations: in the mother-child relationship, in love life, in social life and as a sexual perversion in the strict sense of the term. We go into some detail regarding what he tells us about the sado-masochistic fantasies in a love relationship, where paradox seems to be another word for perversion. This is followed by three clinical examples of perverted relationships between partners, with safeguarding of genital aim and object. Perversion seems still more pervasive, more enigmatic and difficult to delineate than in Freud's time.


Regression of tricuspid regurgitation after two-stage arterial switch operation for failing systemic ventricle after atrial inversion operation.
The cases of five patients with previous Senning (n = 4) or Mustard (n = 1) operations and failing systemic ventricles in whom banding of the pulmonary artery was performed as an interim step toward an arterial switch procedure are reported. The rise in the ratio of left to right mean systolic ventricular pressure, from 0.35 before operation to 0.90 during operation and 0.80 on the first postoperative day, caused a shift of the ventricular septum from a leftward to a midline or nearly midline position. This shift was associated with a reduction of tricuspid regurgitation. At a median interval of 5.1 months after pulmonary artery banding, the mean left ventricular posterior wall thickness had increased to 8.2 mm, versus 5 mm before operation, and the mean left ventricular myocardial mass index had increased to 90 gm/m2, versus 55.6 gm/m2 before operation. After the arterial switch operation, which was performed in four patients, the tricuspid regurgitation decreased to a trivial amount (n = 1) or disappeared completely (n = 3).


Posttraumatic Chondrocyte Apoptosis in the Murine Xiphoid.
To demonstrate posttraumatic chondrocyte apoptosis in the murine xiphoid after a crush-type injury and to ultimately determine the pathway (i.e., intrinsic or extrinsic) by which chondrocytes undergo apoptosis in response to mechanical injury. The xiphoids of adult female wild-type mice were injured with the use of a modified Kelly clamp. Postinjury xiphoid cartilage was analyzed via 3 well-described independent means of assessing apoptosis in chondrocytes: hematoxylin and eosin staining, terminal deoxynucleotidyl transferase dUTP nick end labeling assay, and activated caspase-3 staining. Injured specimens contained many chondrocytes with evidence of apoptosis, which is characterized by cell shrinkage, chromatin condensation, nuclear fragmentation, and the liberation of apoptotic bodies. There was a statistically significant increase in the number of chondrocytes undergoing apoptosis in the injured specimens as compared with the uninjured specimens. Chondrocytes can be stimulated to undergo apoptosis as a result of mechanical injury. These experiments involving predominantly cartilaginous murine xiphoid in vivo establish a baseline for future investigations that employ the genetic and therapeutic modulation of chondrocyte apoptosis in response to mechanical injury.


Diagnostic evaluation of cats with seizure disorders: 30 cases (1991-1993).
To investigate causes of seizure disorders in cats. Case series. 30 cats referred to the Ontario Veterinary College for recurrent seizures. Signalment and seizure pattern were evaluated. Diagnostic procedures included physical, neurologic, and fundic examinations; CBC; serum biochemical analyses, including determination of pre- and postprandial bile acid concentrations; urinalysis; serologic assays for FeLV and feline immunodeficiency virus, feline infectious peritonitis, and Toxoplasma gondii, magnetic resonance imaging of the brain; CSF analysis; and neuropathologic examination of euthanatized cats and of surgical biopsy specimens. All cats were found to have structural brain diseases; nonsuppurative meningoencephalitis of unknown cause was found in 14 cats, feline ischemic encephalopathy in 6, meningioma in 2, polycythemia vera with secondary brain lesions in 2, posttraumatic epilepsy in 1, and cerebral abscess in 1. A definitive diagnosis could not be reached in 4 cats. The most common cause of seizures in cats is structural brain disease. Structural brain lesions often can be detected on the basis of seizure pattern and results of neurologic examination. Cerebrospinal fluid analysis and brain imaging are essential to determine the cause of these lesions. Causes of seizures found in the cats of this study differ from those reported to be the most common. Nonsuppurative meningoencephalitis of unknown origin appears to be a frequent cause of neurologic disorders in cats, including seizure disorders. Feline ischemic encephalopathy appears to exist in a milder form than the classic disease and may be a common cause of seizures in cats.


Four-Dimensional Magnetic Resonance Imaging Assessment of Intracranial Aneurysms: A State-of-the-Art Review.
Treatment of unruptured intracranial aneurysms can reduce the risk of subarachnoid hemorrhage and its associated morbidity and mortality. However, current methods to predict the risk of rupture and optimize treatment strategies for intracranial aneurysms are limited. Assessment of intra-aneurysmal flow using 4-dimensional magnetic resonance imaging (4D MRI) is a novel tool that could be used to guide therapy. A systematic search of the literature was performed to provide a state-of-the-art review on 4D MRI assessment of unruptured intracranial aneurysms. A total of 18 studies were available for review. Eccentric flow on 4D MRI is associated with a greater aspect ratio and peak wall shear stress (WSS). WSS, vorticity, and peak velocity are greater in saccular than fusiform aneurysms. Unstable aneurysms are associated with greater WSS, peak wall stress, and flow jet angle and may exhibit wall enhancement. In comparison to computational fluid dynamics (CFD), 4D MRI has a lower spatial resolution and reports lower WSS and velocity magnitudes, but these parameters equalize when spatial resolution is matched. 4D MRI demonstrates the intra-aneurysmal hemodynamic changes associated with flow diversion, including significantly decreased flow velocity. Thus, 4D MRI is a novel, noninvasive imaging tool used for the evaluation of hemodynamics within intracranial aneurysms. Hemodynamic indices derived from 4D MRI appear to correlate well with the simulated (CFD) values and may be used to measure the success of endovascular therapies and risk factors for aneurysm growth and rupture.


Remarkable enantioselectivity enhancement of the extractors with nonaxial chirality in liquid-liquid extraction of underivatized amino acids by introducing t-butyl group.
A class of carbonyl extractors, (R)-3, (R)-4, and (R)-5, with nonaxial chirality containing asymmetric carbons has been synthesized and studied for their efficiencies in enantioselective liquid-liquid extraction for underivatized amino acids. The bulky t-butyl ketone extractors, (R)-4 and (R)-5, showed the stereoselectivities ranging 5.4-9.4 of l/d ratio much better than those of the aldehyde extractor, (R)-3, ranging 2.4-5.2. The imine formation rates and yields of the t-butyl ketones were not significantly affected by their bulkiness and even in the absence of resonance-assisted hydrogen bond. This work confirms that a bulky t-butyl ketone can be a good choice in the development of an extractor not only with axial chirality but also with nonaxial chirality for the enantioselective extraction of unprotected amino acids.


Evolutionary sequence analysis of complete eukaryote genomes.
Gene duplication and gene loss during the evolution of eukaryotes have hindered attempts to estimate phylogenies and divergence times of species. Although current methods that identify clusters of orthologous genes in complete genomes have helped to investigate gene function and gene content, they have not been optimized for evolutionary sequence analyses requiring strict orthology and complete gene matrices. Here we adopt a relatively simple and fast genome comparison approach designed to assemble orthologs for evolutionary analysis. Our approach identifies single-copy genes representing only species divergences (panorthologs) in order to minimize potential errors caused by gene duplication. We apply this approach to complete sets of proteins from published eukaryote genomes specifically for phylogeny and time estimation. Despite the conservative criterion used, 753 panorthologs (proteins) were identified for evolutionary analysis with four genomes, resulting in a single alignment of 287,000 amino acids. With this data set, we estimate that the divergence between deuterostomes and arthropods took place in the Precambrian, approximately 400 million years before the first appearance of animals in the fossil record. Additional analyses were performed with seven, 12, and 15 eukaryote genomes resulting in similar divergence time estimates and phylogenies. Our results with available eukaryote genomes agree with previous results using conventional methods of sequence data assembly from genomes. They show that large sequence data sets can be generated relatively quickly and efficiently for evolutionary analyses of complete genomes.


[Pregnancy with new coronavirus infection: clinical characteristics and placental pathological analysis of three cases].
Objective: To investigate the clinical characteristics and placental pathology of 2019-nCoV infection in pregnancy,and to evaluate intrauterine vertical transmission potential of 2019-nCoV infection. Methods: The placentas delivered from pregnant women with confirmed 2019-nCoV infection which were received in the Department of Pathology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology by February 4, 2020 were retrospectively studied. Their clinical material including placental tissue and lung CT, and laboratory results were collected, meanwhile, nucleic acid detection of 2019-nCoV of the placentas were performed by RT-PCR. Results: Three placentas delivered from pregnant women with confirmed 2019-nCoV infection, who were all in their third trimester with emergency caesarean section. All of the three patients presented with fever (one before caesarean and two in postpartum), and had no significant leukopenia and lymphopenia. Neonatal throat swabs from three newborns were tested for 2019-nCoV, and all samples were negative for the nucleic acid of 2019-nCoV. One premature infant was transferred to Department of Neonatology due to low birth weight. By the end of February 25, 2020, none of the three patients developed severe 2019-nCoV pneumonia or died(two patients had been cured and discharged, while another one had been transferred to a square cabin hospital for isolation treatment). There were various degrees of fibrin deposition inside and around the villi with local syncytial nodule increases in all three placentas. One case of placenta showed the concomitant morphology of chorionic hemangioma and another one with massive placental infarction. No pathological change of villitis and chorioamnionitis was observed in our observation of three cases. All samples from three placentas were negative for the nucleic acid of 2019-nCoV. Conclusions: The clinical characteristics of pregnant women with 2019-nCoV infection in late pregnancy are similar to those of non-pregnant patients, and no severe adverse pregnancy outcome is found in the 3 cases of our observation. Pathological study suggests that there are no morphological changes related to infection in the three placentas. Currently no evidence for intrauterine vertical transmission of 2019-nCoV is found in the three women infected by 2019-nCoV in their late pregnancy.


Rehabilitation of a partially torn distal triceps tendon after platelet rich plasma injection: a case report.
Platelet Rich Plasma (PRP) is an emerging non-surgical intervention used for the treatment of tendon and ligament pathology. Despite the growing popularity of PRP in musculoskeletal medicine, there is a paucity of research that describes appropriate rehabilitation procedures following this intervention. This case report presents the rehabilitation strategy used following a PRP injection for a patient with a partially torn distal triceps tendon who previously failed physical therapy interventions. The patient returned to light weight training and coaching activity after completing 15 visits over a 3 month period. One month after discharge, the patient reported pain-free activities of daily living and a return to previously performed gym activities. PRP presents a viable treatment option for individuals who are recalcitrant to conservative interventions yet elect to avoid more invasive surgical measures. Despite the growing popularity of PRP, a paucity of evidence exists to guide physical therapists in the rehabilitation process of these patients. The rehabilitation strategies used in a patient who had a PRP injection for a partial triceps tendon tear are outlined. Although this case report highlights a successful rehabilitation outcome, future research regarding the concomitant effects of PRP injection and rehabilitation for tendon pathology are needed. 4-Case Report.


[Biomechanics in forensic medicine].
The paper deals with the problem in the use of biomechanics in forensic and medical practice, in the application of current biomechanical progress in the experimental investigations of the workers of the Department of Forensic Medicine, I. M. Sechenov Moscow Medical Academy. The experimental and theoretical findings have permitted elaboration of a new concept of the development of intracranial lesions in brain injuries. The original studies have provided a biomechanical model of cranial injury, a comprehensive evaluation of damages caused to the passenger and the driver in the currently available cars. The ways of further development and improvement of experimental studies of biomechanical problems and their practical application are outlined.


[Tryptophan metabolism in vitiligo].
An activity of tryptophan pyrrolase was not observed in skin of healthy persons and of patients with vitiligo. Content of serotonin was similar in skin of normal persons and in skin of patients with normal pigmentation and in depigmented area. But content of serotonin in blood and excretion of anthranilic acid were decreased in the patients as compared with healthy persons. Excretion of kynurenine, 3-hydroxykynurenine, 3-hydroxyanthranilic acid, kynureninic, xanthurenic and 5-hydroxyindolyl acetic acids was increased in patients and this increase was more distinct after loading with 1-tryptophan. The data obtained suggest that kynurenine and serotonin pathways of tryptophan metabolism were intensified in vitiligo.


Low-resolution structure refinement in electron microscopy.
A real-space structure refinement method, originally developed for macromolecular X-ray crystallography, has been applied to protein structure analysis by electron microscopy (EM). This method simultaneously optimizes the fit of an atomic model to a density map and the stereo-chemical properties of the model by minimizing an energy function. The performance of this method is characterized at different resolution and signal-to-noise ratio conditions typical for EM electron density maps. A multi-resolution scheme is devised to improve the convergence of the refinement on the global energy minimum. Applications of the method to various model systems are demonstrated here. The first case is the arrangement of FlgE molecules in the helical filament of flagellar hook, in which refinement with segmented rigid bodies improves the density correlation and reduces severe van der Waals contacts among the symmetry-related subunits. The second case is a conformational analysis of the NSF AAA ATPase in which a multi-conformer model is used in the refinement to investigate the arrangement of the two ATPase domains in the molecule. The third case is a docking simulation in which the crystal structure of actin and the NOE data from NMR experiments on the dematin headpiece are combined with a low-resolution EM density map to generate an atomic model of the F-actin-dematin headpiece structure.


Diagnostic standards for occupational nasal allergy.
Based on studies of 70 outpatients having occupational nasal allergy as well as mass examinations of workers in two industries, diagnostic standards for this condition were evaluated. In practice, interviews concerning the causal relation, frequency, latent period and atopic disposition often provide suggestions, but sometimes give unreliable evidence for the basis by which to diagnose occupational nasal allergy. Both rhinoscopy and nasal smear test for eosinophilia are available, but these only distinguish allergy from non-allergy. Therefore, examinations, such as skin tests, nasal tests and determination of the IgE antibody level, using allergen extract of good quality, are necessary for a final diagnosis.


Newborn regional body composition is influenced by maternal obesity, gestational weight gain and the birthweight standard score.
This study investigated whether newborn body composition is influenced by prepregnancy obesity and gestational weight gain (GWG) and explored any associations between body composition and birthweight standard score (z-score), categorised by size for gestational age. We recruited 231 obese and 80 normal weight mothers and their newborn infants and assessed the babies' body composition using dual-energy X-ray absorptiometry. The total and abdominal fat masses of infants born to mother who were obese before pregnancy were 135 g (p < 0.001) and 18 g (p < 0.001) higher than the offspring of normal weight mothers. The infants' fat mass increased by 11 g (p < 0.001) for every kilogram of GWG. There were no associations between prepregnancy obesity and fat-free mass. The fat percentage was significantly higher in infants who were large for gestational age (15.3%) than small for gestational age (5.2%) and appropriate for gestational age (9.8%) (p < 0.001). Lower birthweight z-score was associated with a higher proportion of abdominal fat mass (p = 0.009). Infants born to obese mothers had higher fat mass at birth, with abdominal fat accumulation. Low birthweight was associated with a lower crude abdominal fat mass, but a higher proportion of total fat mass placed abdominally.


[Rationale for surgical treatment of cancer of the lower pulmonary lobe with consideration for regional metastatic spread].
Optimal extent of surgery for lung cancer is determined to a great degree by lymph drainage and regional metastases vis-a-vis tumor localization in the lobes. Data on surgical treatment of 505 cases of cancer of the lower lobe are presented. The study established such peculiarities of metastatic spread to mediastinal lymph collector as relatively frequent involvement of the lower mediastinal lymph nodes ("jumping" metastases included) and greater likelihood of spread to the superior mediastinal lymph nodes when those of radix pulmonis are involved. The latter should be interpreted as an indicator of lower lobe involvement. We established the significance of relatively worse prognosis for mediastinal lymph node involvement as well as high frequency of intrasternal recurrences of tumors located in the left lung. The prevailing evidence on partial resections of the right lung rather than lower bilobectomy and the good results of bilobectomies for stage T1-3N1-2 tumors suggest that conservative treatment might offer more advantage in managing cancer of the lower lobe of the right lung. Extended surgery entails lower incidence of intrasternal recurrence and is more effective when used to treat right-lung tumors.


Adjunctive diagnostic aids in oral cancer screening: an update.
During the past decade, several adjunctive aids have been introduced to the marketplace with the promoted goal of improving the dental practitioner's ability to screen for and identify oral premalignant and malignant lesions (OPMLs). These products include the OralCDx Brush Test, ViziLite Plus with TBlue, Microlux, VELscope Vx, Sapphire Plus, Identafi, and the DOE Oral Exam System. They are all marketed as aids for the clinician to use in addition to, not in lieu of, the accomplishment of a conventional oral examination (COE). Studies addressing the efficacy of these products when used in the general practice setting to screen for OPMLs are limited and conflicting. The ability to discriminate between truly dangerous OPML against the milieu of benign mucosal lesions remains a concern and further research is necessary to determine the true value of these products as marketed to the general practitioner. The attainment of a complete history and the accomplishment of a thorough and disciplined COE remains the foundation upon which the practitioner assesses the patient for OPMLs. Findings deemed suspicious or equivocal should be referred to an expert for further assessment or undergo immediate biopsy, while findings deemed innocuous should be re-evaluated within 2 weeks and referred to an expert for further assessment or undergo biopsy if still present.


Attenuated Total Reflection Fourier Transform Infrared Spectroscopy with Soft Independent Modeling of Class Analogy-Principal Component Analysis for Classifying Cotton Fiber Maturity Phenotypes of Cotton Population Composed of Various Genotypes.
Maturity is a major fiber trait that affects the processing and performance of cotton fiber. Rapid and accurate identification of fiber maturity phenotypes and genotypes is of importance to breeders. Previous studies showed that either conventional fiber measurements or attenuated total reflection Fourier transform infrared spectroscopy (ATR FT-IR) analysis discriminated the immature fiber (im) phenotype from the wild type (WT) mature fiber phenotype in a segregating F2 population from a cross between two upland cotton lines differing in fiber maturity. However, both conventional fiber property measurement methods and FT-IR analyses with current algorithms could not detect the subtle differences among the WT fibers composed of two different genotypes, WT homozygosity (WT-homo) and WT heterozygosity (WT-hetero). This research explored the FT-IR method, in combination with soft independent modeling of class analogy of principal component analysis (SIMCA-PCA), for the discrimination of WT fiber phenotypes consisting of two different genotypes (WT-homo and WT-hetero). The new approach enabled the detection of IR spectral intensity differences between WT-homo and WT-hetero fibers. Successful classification originated from a distinctive spectral difference in the low-wavenumber region (<700 cm-1) between WT-hetero fibers and WT-homo fibers. This observation emphasized that ATR FT-IR with a SIMCA-PCA approach would be a sensitive tool for classifying the WT fibers demonstrating minor phenotypic differences. The improved sensitivity of the infrared method may provide a way of dissecting genotype-phenotype interactions of cotton fibers rapidly and efficiently.


Association of serum uric acid with biventricular myocardial dysfunction in patients with type 2 diabetes mellitus.
Increased serum uric acid (SUA) is common in type 2 diabetes mellitus (T2DM) and is associated with left ventricular (LV) myocardial dysfunction. Nonetheless the association of SUA with right ventricular (RV) function in T2DM has not been studied. This study aimed to investigate the association of SUA with biventricular myocardial function in patients with T2DM. A total of 560 patients with T2DM were enrolled and divided into four groups according to sex-specific quartiles of SUA. Transthoracic echocardiography was performed and two-dimensional speckle tracking was used to measure biventricular myocardial strain, including LV global longitudinal strain (GLS), circumferential strain (CS), radial strain (RS), and RV free wall longitudinal strain (RV-FWLS). The absolute value of all biventricular strain parameters showed a stepwise decrease across SUA quartiles (all P < 0.01). In particular, LV assessment by GLS, CS and RS demonstrated that those in the 4th quartile were impaired compared with the other quartiles (all P < 0.05). Similarly, RV-FWLS of the 4th quartile was significantly impaired compared with the 1st and 2nd quartiles (all P < 0.05). The same reduction in biventricular strain across SUA quartiles was observed in patients with estimated glomerular filtration rate < or ≥60 ml/min/1.73 m2, and glycated hemoglobin < or ≥7.0% (all P < 0.05). Multivariable linear regression analysis demonstrated that higher quartile of SUA was independently associated with impaired biventricular myocardial strain (all P < 0.05). SUA was independently associated with biventricular myocardial dysfunction in asymptomatic T2DM patients, regardless of renal function or diabetic control.


The clinical and therapeutic approach to anal stenosis.
Anal stenosis is a fibrous narrowing of the anal channel. It develops, in most cases, in the aftermath of proctologic surgical procedures with extensive anoderm excision or in the presence of chronic anal inflammation in patients with Crohn Disease. However rare, this condition is thoroughly debilitating for the patients. Symptoms include constipation, pain and bleeding with defecation and a reduction of the caliber of stools. Diagnosis is essentially clinical. Prevention of postsurgical stenosis is based on a scrupulous surgical technique and on an extensive and carefully- planned follow up. Treatment is based on an initially conservative approach with regularization of stool transit through hydration, dietary fibers and bulk-forming laxatives. The role of mechanical dilatation in the treatment of AS is still debated. For severe cases and cases that are not responsive to conservative treatment we must resort to surgery. Surgical approach is tailored on the severity, position and extension. The most severe cases require anoplasty procedures with mucosal or anal flaps. KEY WORDS: Anal stenosis, Anal stricture,Proctology.


[Expression analysis of green fluorescent protein in tissues and organs in α-1,3 galactosyltransferase knockout pigs].
The pig is an ideal source to provide organs because its organ size and physiology are similar to humans. However, an acute rejection will ensue after pig-to-human xenotransplantation. The α-1,3 galactosyltransferase gene knockout (GTKO) pigs were generated in recent years, and could solve the problem of hyperacute rejection. But due to lack of reporting genes, the rejection status of cells and organs post pig-to-human xenotransplantation cannot be visualized. In this study, we introduced the enhanced green fluorescent protein (EGFP) gene driven by the CAG promoter into GTKO porcine ear fibroblasts. Then we produced transgenic pigs expressing the EGFP gene by nuclear transfer technology. Expression levels of EGFP in different tissues and organs of the cloned pig were investigated by Nightsea DFP-1 Fluorescent Protein Flashlight, fluorescence microscope and quantitative PCR assays. The results showed that the protein and transcript of EGFP were expressed in all tissues and organs of the GTKO pig, but the expression was weak in the liver and central nervous system. In conclusion, we have successfully produced the transgenic GTKO pigs expressing EGFP in all tested tissues and organs, which builds up a good basis to track transplanted cells or tissues.


[The improved method of minilaparotomy by cholecystectomy].
The new improved method of minilaparotomy by cholecystectomy is characterized by transversal cut of the abdominal wall and using a contra aperture for inserting a clamp for the gallbladder. The use of such an access was applied in 47 patients with good immediate and long-term results.


Day Surgery for Acute Appendicitis in Adults: A Prospective Series of 102 Patients.
To report the results of a consecutive series of day surgery appendectomy (DSA) for acute appendicitis. Selection criteria for DSA were as follows: body mass index<28 kg/m, white cell count <15,000/mL, C-reactive protein<30 mg/L, no radiological signs of perforation, and appendix diameter ≤10 mm. All patients with radiologically proven appendicitis and 4 or 5 criteria were proposed for DSA and prospectively included. A total of 102 patients (female=39.2%) were operated between January 1, 2013 and January 5, 2015 with a median age of 29.5 years [interquartile range (IQR), 23 to 37 y]. Diagnosis was mainly supported by computed tomographic scan (75.5%). About 60 patients (59%) were reconvened on the next morning for surgery with oral antibiotics. The median operative time was 40 minutes (IQR, 30 to 52 min), and 92 (90%) patients were discharged on day 0 after a postoperative period of 5h:12min (IQR, 4h:14min to 6h:33min). The overall median hospital length of stay was 8h:04min (IQR, 6h:46min to 10h:23min). Surgical morbidity was 6.9% (n=7), with 1.9% (n=2) major complications. DSA is a safe procedure for selected patients; it reduces the hospital length of stay without increasing morbidity.


Assessment of long-term remission in lupus nephritis patients: a retrospective analysis over 30 years.
To review the likelihood of very long-term remission in patients with biopsy-proven LN attempting to identify good prognostic features. We reviewed patients with LN whose renal biopsies showed World Health Organization (WHO) classes III, IV and V and who had a follow-up of at least 5 years between 1973 and 2008. We analysed demographic, clinical, laboratory and therapeutic parameters comparing those patients with (group A) and without (group B) 5 year remission. Of 191 LN patients followed, 105 patients met the strict inclusion criteria. Ninety-five patients were female. Mean age at diagnosis of lupus was 24.1 years (s.d. 10.7). ean age at diagnosis of LN was 28.4 years (s.d. 11.3). The mean duration of follow-up was 13.7 years (s.d. 14.1). Forty (38%) patients achieved 5 year remission, of whom 17 (16.2%) had remission for ≥15 years. The incidence of flares per year from 5 to 15 years was 7.9%; however, no flares were observed after 15 years of remission. The only distinguishing feature found in this study was the association of WHO class IV on kidney biopsy with LN progression (P = 0.03). Renal histology with WHO class IV predicted a poor long-term remission rate. Age, sex, ethnicity, serological parameters and treatment received did not predict long-term remission. Renal flares can occur up to 15 years after a patient has gone into remission.


Computerized color analysis of "xue yu" (blood stasis) in the sublingual vein using a new technology.
Computer-assisted image analyses were performed on the color of the tongues of 95 medical students to enhance the accuracy and objectivity of tongue inspections for determining blood stasis. Areas from the sublingual vein were selected and subjected to image analysis. A slide scanner was used to digitize the color slides, and the digital information was transmitted to a personal computer for subsequent feature extraction and analysis. A comparison was then made between the computerized data using Red-Green-Blue color components, and inspection with the naked eye based on the diagnostics of traditional Chinese medicine. The results obtained suggest that there are statistically significant correlations between visual analyses and the computerized normalized R value (F value; 3.397, p < 0.05). The examination of sublingual veins with the naked eye showed the validity of computer-assisted image analysis. This analysis may provide a potential solution to the demand for a sophisticated means of quantitative and qualitative observation of physiological parameters regarding blood stasis, including that for the sublingual vein.


Passive sensitization of human airways increases responsiveness to leukotriene C4.
Passive sensitization of human airways in vitro causes increased responsiveness to histamine and induces specific immunoglobulin (Ig)E-dependent contractile responsiveness to allergen. Leukotrienes (LTs) and, to a lesser extent, histamine are the major mediators of allergen-induced contraction. Since it is unclear whether passively sensitized airways are also hyperresponsive to cysteinyl leukotrienes, this study investigated the effect of passive sensitization on LTC4-, in addition to histamine- and allergen-induced contractions in vitro. Bronchial rings from nine nonatopic patients were sensitized overnight with serum containing high levels of total IgE (>250 U x mL(-1)) and allergen-specific IgE against Dermatophagoides farinae (fluorescence allergosorbent test) (FAST class > or =3). The potency (-log10 of the mediator concentration causing a half maximal response (pEC50) of histamine was significantly increased in serum-sensitized tissues compared to nonsensitized controls ((mean+/-SEM) pEC50 5.20+/-0.27 versus 5.64+/-0.18; p=0.02) and maximal contractions were enhanced (877+/-47 versus 543+/-51 mg; p<0.0001). Similarly, the potency of LTC4 was significantly increased in sensitized compared to nonsensitized bronchial rings (pEC50 9.37+/-0.20 versus 8.66+/-0.26; p=0.004); maximal contractions were also enhanced (811+/-57 versus 361+/-86 mg; p<0.0001). These data demonstrate that passive sensitization of human airways induces an increase not only in histamine but also in leukotriene responsiveness. Therefore, it might be speculated that allergen responses in sensitized airways are effected through a combination of increased mediator release from inflammatory cells and increased responsiveness of airway smooth muscle.


Supporting family carers using interative multimedia.
ACTION (Assisting Carers using Telematic Interventions to meet Older persons' Needs) is a nursing led Pan-European project (1997-2000). Its primary aim is to maintain the autonomy, independence and quality of life of frail older and disabled persons and their family carers by the application of telematic technology. This article describes the development of two multimedia programmes created as part of the ACTION project. Programme 1 'Planning ahead' helps family carers and frail older people to think about and plan for the future. Programme 2 'Break from caring' assists carers and older people to explore the range of respite care options available. Both programmes have been developed using a multimethod, user-centred approach. Preliminary evaluation data have indicated that frail older people and their carers have used the programmes to assist them when making difficult decisions such as selecting a nursing home, or exploring the use of respite care facilities.