[The application and therapeutic effects of immunodepressant for Crohn's disease].
To investigate the therapeutic effect of immunodepressant on Crohn's disease (CD). 105 patients with CD were collected from 1983 to 2006 in Peking Union Medical College Hospital. All of their clinical manifestations and therapeutic results were analyzed retrospectively. (1) The application of immunodepressant was significantly increased after the year of 2000 (34.7% vs 3.0%, P = 0.000). (2) The application of immunodepressant and the clinical features of these patients were as follows: 1) The number of patients with moderate to severe CD were more than that with mild CD in those using immunodepressant (28.9% vs 0). 2) The use of immunodepressant was not related with the diseased site of CD, because there were no difference among the groups with lesion in small intestine (20.0%), colon (27.3%) and ileocolon (27.1%), P =0.726. 3) The serum albumin level of CD patients using immunodepressant was significantly lower than that of those not using (31.9 g/L vs 35.1 g/L, P = 0.047). 4) The use of immunodepressant did not decrease the incidence of operative treatment (38.5% vs 50.0%, P= 0.320). (3) The rate of remission in 19 CD patients using azathioprine is 68.4% (13/19) and the percentage of neutrophil in the group with relief was lower than that without relief (0.76 vs 0.65, P = 0.032). Immunodepressant is playing more important role in the treatment of CD. The patients with moderate and severe CD with as well as lower serum albumin should be treated with immunodepressant as early as possible. Whether immunodepressant is necessary or not is not decided by the diseased site. CD patients with higher percentage of neutrophil have less therapeutic effect than those with lower.


Nitric oxide is involved in brassinosteroid-induced alternative respiratory pathway in Nicotiana benthamiana seedlings' response to salt stress.
Recent studies reported that brassinosteroids (BRs) can induce plant tolerance to different environmental stresses via the nitric oxide (NO) signaling pathway. Previous reports have indicated that alternative oxidase (AOX) plays an important role in plants under various stresses. The mechanisms governing how NO is involved as a signal molecule which connects BR with AOX in regulating stress tolerance are still unknown. Recently, we found that Nicotiana benthamiana seedlings which were pretreated with BR have more tolerance to salt stress, accompanied with an increase of CN-resistant respiration. Our results suggested that pretreatment with 0.1 μM brassinolide (BL, the most active brassinosteroid) alleviated salt-induced oxidative damage and increased the NbAOX1 transcript level. Application of 2-(4-carboxyphenyl)-4,4,5,5-tetramethyl-imidazoline-1-1-oxyl-3-oxide (cPTIO, an NO scavenger) or virus-induced gene silencing of nitrate reductase (NR) and nitric oxide synthase (NOS)-like enzyme compromised the BRs-induced alternative respiratory pathway. Furthermore, pretreatment with specific chemical inhibitors of NR and NOS or gene silencing experiments decreased plant resistance to salt stress which also compromised BRs-induced salt stress tolerance. In conclusion, NO is involved in BRs-induced AOX capability which plays essential roles in salt tolerance in N. benthamiana seedlings.


Conjunctival Lesions; a Histopathologic Review in Fars Province, Iran.
To determine the prevalence of various types of conjunctival lesions, at a tertiary ophthalmic center in Fars Province, South of Iran. Histopathologic slides and medical records of conjunctival lesions submitted to the pathology department of Khalili Hospital, Shiraz, Iran were reviewed from April, 2009 to July, 2013. The histopathologic diagnoses were categorized into benign, pre-malignant, and malignant lesions. The prevalence of various types of conjunctival lesions was calculated. Histologic sections of 631 conjunctival lesions were reviewed. Benign lesions were most prevalent (81.8%), followed by premalignant (10.8%) and malignant (7.4%) lesions. Pterygia were the most common benign lesions (69.2%), intraepithelial dysplasia constituted most cases of premalignant lesions (94.1%), and squamous cell carcinoma was the most frequent malignant lesion (93.6%). Benign lesions were the most common type of lesions in all age groups, however the prevalence of malignant lesions increased significantly with age (P < 0.001). Benign lesions were the most common conjunctival lesions with pterygia on top of the list, while intraepithelial neoplasia and squamous cell carcinoma were the most common premalignant and malignant lesions, respectively. Conjunctival malignant lesions were more prevalent with older age.


[Replacement of the knee-joint (author's transl)].
Survey of methods. In first part new classification of prostheses. Discussion of some biomechanical problems, mainly on hinge-prosthesis which can only be compromises for various periods. Replacement to be considered only for elderly or very old patients, when conservative treatment offers no chances, other operations are not promising or have failed, arthrodeses cannot be done and pain and loss of function are severe. Indications for hinge- and slide-prostheses are given. In the second part two statistics of results from the literature are discussed and experience with 130 own cases using own model is described. Infection occurred in 3 cases where removal of prosthesis had to be done. Examples of the need for reversal operations are given.


HYPOVENTILATION, CYANOSIS AND POLYCYTHEMIA IN A THIN MAN.
A lack of respiratory centrogenic drive of undetermined origin is a rare cause of cyanosis. In this condition, voluntary hyperventilation restores arterial oxygen saturation to normal. Secondary changes consist of polycythemia, somnolence, headache and right heart failure. The present report of a 43-year-old thin man with idiopathic alveolar hypoventilation is combined with a review of 12 similar patients reported by others. His resting oxygen saturation increased from 60% to 98% with hyperventilation. The pulmonary artery pressure was 68/26 mm. Hg and cardiac output 12.3 l./min. Death resulted from pulmonary infarction, and no specific abnormalities were found in the brain.


Water vulnerability to pesticide contamination in a Brazilian semiarid watershed.
This study aimed to prepare an inventory of the main active ingredients of pesticides and estimate the risk of pollution of groundwater and surface water resources in a Brazilian semiarid basin. The inventory was prepared using data from government agency databases. The contamination risk estimate was obtained using the GOSS index, Groundwater Ubiquity Score (GUS), Groundwater Screening Index (GSI), Leachability Index (LIX), US Environmental Protection Agency (USEPA) criteria, Leaching Index (LEACH), and Relative Leaching Potential Index (RLPI). The inventory identified 57 active ingredients commercialized under a well-defined chemical class. Most of these (51.5%) belong to the very dangerous class, while 43.6% belong to the moderately toxic class. The GOSS model showed that 23.7% of the active ingredients have a low potential, 50.85% have a moderate potential, and 13.56% have a high potential for surface water contamination, with its transport being associated with the sediment. The GUS index indicates a low potential for groundwater contamination. However, the GSI points to a high potential for water contamination, the USEPA criteria for a possible contamination of groundwater, and, according to the LIX, most of the pollutants do so by leaching. The information provided contributes to the management of xenobiotic compounds in arid and semiarid basins, adding to the water security effort by providing tools for the assessment of potential pesticide pollution. Integr Environ Assess Manag 2023;19:804-816. © 2022 SETAC.


What are the Specifics of Abdominal Wall Surgery in Cirrhotic Patients.
The risk of developing an abdominal wall hernia is high in the cirrhotic patient, due to the association of ascites, hypoalbuminemia and amyotrophy in connection with undernutrition frequently associated with cirrhosis. Thus, almost 20% of cirrhotic patients develop an umbilical hernia. Parietal surgery is more at risk in cirrhotic patients and its indications must be discussed on a case-by-case basis. The objective of this work was to review the entire literature on wall surgery in order to best define the surgical indications and the specifics of their management. The bibliographic research was done on Pubmed over the period from January 1995 to December 2019, using French and English as publication languages. The keywords retained were "hernia" [Mesh] and "liver cirrhosis" [Mesh]. In an elective situation, preoperative ascites control is recommended. A parietal prosthesis can be used, even in the case of uninfected ascites, preferably in the retromuscular position. Laparoscopy should be used with caution, due to the bleeding risk. No recommendation can be made on the use of prophylactic intra-abdominal drainage. The literature data do not allow the trans-jugular route portosystemic shunt recommendation, nor the use of a peritoneal-vesical pump to decrease the volume of ascites before parietal surgery in cirrhotic patients.


Interleukin-37: A crucial cytokine with multiple roles in disease and potentially clinical therapy.
Interleukin (IL)-37, a new IL-1 family member, has received increasing attention in recent years. In the past decade, it has been determined that IL-37 is expressed in various normal cells and tissues and is regulated by inflammatory stimuli and pro-cytokines via different signal transduction pathways. Recently, it has been found that IL-37 is expressed in a variety of cancers, chronic inflammatory and autoimmune disorders, and exerts anti-inflammatory effects. Moreover, a growing body of literature demonstrates that IL-37 plays a vital role in inhibiting both innate and adaptive immune responses as well as inflammatory reactions. In addition, IL-37 may prove to be a new and potentially useful target for effective cytokine therapy. Further evidence is needed to clarify in more detail the effects of IL-37 in experimental and clinical studies. Based on an extensive summary of published data, the aim of this review is to outline the current knowledge of IL-37, including the location, structure, expression, regulation and function, as well as the potential clinical applications of this cytokine.


HIV-1 envelope protein gp120 modulation of glutamate effects on cortical neuronal synapses: implications for HIV-1-associated neuropathogenesis.
Despite the introduction of combined antiretroviral therapy (cART) HIV-1 virus persists in the brain in a latent or restricted manner and viral proteins, such as gp120, continue to play a significant disease-inciting role. Gp120 is known to interact with N-methyl-D-aspartate (NMDA) receptors (NMDARs) resulting in neuronal injury. Glutamate is the main excitatory neurotransmitter in the brain and plays an important role in cognitive function and dysregulation of excitatory synaptic transmission impairs neurocognition. It is our hypothesis that gp120 may alter synaptic function via modulating glutamate function from a physiological molecule to a pathophysiological substance. To test this hypothesis, we studied the modulatory effects of gp120 and glutamate on NMDAR-mediated spontaneous excitatory postsynaptic current (sEPSCNMDAR) and dynamic dendritic spine changes in rat cortical neuronal cultures. Our results revealed that gp120 and glutamate each, at low concentrations, had no significant effects on sEPSCNMDAR and dendritic spines, but increased sEPSCNMDAR frequency, decreased numbers of dendritic spines when tested in combination. The observed effects were blocked by either a CXCR4 blocker or an NMDAR antagonist, indicating the involvements of chemokine receptor CXCR4 and NMDARs in gp120 modulation of glutamate effects. These results may imply a potential mechanism for HIV-1-associated neuropathogenesis in the cART era.


Comparative analysis of foliar epidermal anatomical traits and their taxonomic relevance in Lilium pumilum, L. brownii, and L. davidi.
The anatomical traits of plant species are essential for taxonomic analyses and evolutionary evaluations. Clarifying the anatomical characteristics of the foliar epidermis in three distinct Lilium species L. pumilum Delile, L. brownii F.E.Br. ex Miellez and L. davidii Duch. ex Elwes were studied in this article. The objective is to assess the taxonomic relevance of these characteristics and their potential as indicators of species divergence within the genus Lilium. Plant samples were gathered in Gansu, China, from numerous populations of each species that represented a range of climatic and ecological factors. A microscopic analysis employing thin slices and peel mounts was done to assess the stomatal density and dimensions. Significant interpopulation differences in stomatal features were found in the results, offering potential opportunities for taxonomic discrimination. The species differ in qualitative and quantitative characters to differentiate the three species. The links between the observed anatomical characteristics and species classification within the Lilium genus were clarified for the three studied species. In the end, this research advances knowledge of Lilium taxonomy, aids in conservation efforts, and deepens awareness of the general patterns of plant variety. RESEARCH HIGHLIGHTS: Epidermal Traits Aid Taxonomy: Cell shape, arrangement, and structures aid Lilium Identification. Cuticle Reveals Taxonomic Clues: Thickness, composition, and structure inform classification. Micromorphology for Species ID: Cell shape, wax, and striations differentiate Lilium species.


Target antigens for antibodies and complement at the cell surface of RSV-transformed fibroblasts.
Using cells transformed by Rous sarcoma virus (RSV), an RNA tumour virus whose genetic and structural composition is fully known, the virus-induced surface antigens acting as targets for antibodies and complement were studied. Among the virus structural proteins, only the envelope antigen gp85, but not the core group-specific proteins or reverse transcriptase, were able to mediate immune lysis in the 51Cr-release assay. The group-specific antigenic determinants of gp85 were predominantly involved. The virus-induced cell surface antigen (VCSA), specific for transformation, was the only other molecule effective. Since different cells express either of these antigens, further support is given to the non-identity of virus structural antigens and VCSA.


Esophageal tissue engineering.
Esophageal tissue engineering is still in an early state, and ideal methods have not been developed. Since the beginning of the 20th century, advances have been made in the materials that can be used to produce an esophageal substitute. Three approaches to scaffold-based tissue engineering have yielded good results. The first development concerned non-absorbable constructs based on silicone and collagen. The need to remove the silicone tube is the main disadvantage of this material. Polymeric absorbable scaffolds have been used since the 1990s. The main polymeric material used is poly (glycolic) acid combined with collagen. The problem of stenosis remains prevalent in most studies using an absorbable construct. Finally, decellularized scaffolds have been used since 2000. The promises of this new approach are unfulfilled. Indeed, stenosis occurs when the esophageal defect is circumferential regardless of the scaffold materials. Cell supplementation can decrease the rate of stenosis, but the type(s) of cells and their roles have not been defined. Finally, esophageal tissue engineering cannot provide a functional esophageal substitute, and further development is necessary prior to conducting human clinical studies.


Definition and Clinical Significance of the Monoclonal Gammopathy of Undetermined Significance-Like Phenotype in Patients With Monoclonal Gammopathies.
The existence of patients with multiple myeloma (MM) and light-chain (AL) amyloidosis who present with a monoclonal gammopathy of undetermined significance (MGUS)-like phenotype has been hypothesized, but methods to identify this subgroup are not standardized and its clinical significance is not properly validated. An algorithm to identify patients having MGUS-like phenotype was developed on the basis of the percentages of total bone marrow (BM) plasma cells (PC) and of clonal PC within the BM PC compartment, determined at diagnosis using flow cytometry in 548 patients with MGUS and 2,011 patients with active MM. The clinical significance of the algorithm was tested and validated in 488 patients with smoldering MM, 3,870 patients with active MM and 211 patients with AL amyloidosis. Patients with smoldering MM with MGUS-like phenotype showed significantly lower rates of disease progression (4.5% and 0% at 2 years in two independent series). There were no statistically significant differences in time to progression between treatment versus observation in these patients. In active newly diagnosed MM, MGUS-like phenotype retained independent prognostic value in multivariate analyses of progression-free survival (PFS; hazard ratio [HR], 0.49; P = .001) and overall survival (OS; HR, 0.56; P = .039), together with International Staging System, lactate dehydrogenase, cytogenetic risk, transplant eligibility, and complete remission status. Transplant-eligible patients with active MM with MGUS-like phenotype showed PFS and OS rates at 5 years of 79% and 96%, respectively. In this subgroup, there were no differences in PFS and OS according to complete remission and measurable residual disease status. Application of the algorithm in two independent series of patients with AL predicted for different survival. We developed an open-access algorithm for the identification of MGUS-like patients with distinct clinical outcomes. This phenotypic classification could become part of the diagnostic workup of MM and AL amyloidosis.


Growth hormone-binding protein: II. Studies in pygmies and normal statured subjects.
The serum concentrations of a specific GH-binding protein, derived from the GH receptor, were assayed in sera from 62 African pygmies and 101 normal statured controls. Samples were assayed in the absence and presence of excess GH using 2 separatory procedures. Interassay variability for samples was corrected by a standard reference pool of sera from adults assayed with all unknown samples. Results were expressed as specific binding relative to this standard. The mean percent relative specific binding for GH increased with age in normal-statured controls throughout childhood and adolescence. Relative specific binding for GH was 37.0 +/- 2.0% (mean +/- SEM) in control subjects between the ages of 1-5 yr (mean age, 2.9 yr) and increased progressively to 93.0 +/- 7.0% in young adults (mean age, 23 yr). The relative specific binding of GH by serum from pygmies did not exceed 30.1 +/- 3.4% of the control adult standard at any age period (P less than 0.001), and there was no progressive age-related increase in binding. The decrease from normal binding was minimal in pygmies during childhood (29%), but the decrease from normal was 60-70% in adolescents and adults. Thus, short stature in pygmies probably results not from an absolute deficiency of GH receptors per se, as in Laron dwarfism, but from a failure of cellular GH receptors to increase in a normal manner. This is most compatible with a change in regulating expression of the GH receptor gene, rather than a structural defect in the coding sequence of the GH receptor gene.


[Forensic-biochemical indices of serum amilase and cholinesterase activity in lethal poisoning with heroin].
The examination of the activity of serum amilase and cholinesterase in the blood from subjects who had died of heroin poisoning showed significant elevation of such activity. These findings allow experts to use the activity of the above enzymes as effective markers in detection of narcotic drugs in cadaveric blood, opiate narcotics, in particular.


Provisional restorations (Part 2).
This chapter will emphasise the need to: 1) Provide a provisional restoration following tooth preparation to protect the pulp; secure positional stability, function and aesthetics; and maintain gingival health; 2) Consider using long-term provisional restorations to assess aesthetic, occlusal and periodontal changes before embarking on definitive restorations; 3) Distinguish between preparations for conventional and adhesive restorations when providing provisional restorations; 4) Determine in advance the type of provisional restorations and materials to be used, ideally, while treatment planning; 5) Be aware of materials for making provisional restorations and how to control potential hazards; and 6) Make provisional restorations to a high standard to ensure a predictable restorative outcome.


Capacity of quantum erasure channel assisted by backwards classical communication.
We present a communication protocol for the erasure channel assisted by backward classical communication, which achieves a significantly better rate than the best prior result. In addition, we prove an upper bound for the capacity of the channel. The upper bound is smaller than the capacity of the erasure channel when it is assisted by two-way classical communication. Thus, we prove the separation between quantum capacities assisted by backward classical communication and two-way classical communication.


CARDIO-RENAL METABOLIC SYNDROME AND PRO-INFLAMMATORY FACTORS: THE DIFFERENTIAL EFFECTS OF DIETARY CARBOHYDRATE AND FAT.
We aimed to evaluate whether a high carbohydrate or a high fat diet differs in alteration of the inflammatory and metabolic risk factors in cardio-renal metabolic syndrome in rats. Twelve male Wister rats were randomly divided into two groups: one received diet 1 standard pellet rat diet (D1) containing 10% fat, 50% carbohydrate, 25% protein and another group received diet 2 (D2) containing 59% fat, 30% carbohydrate and 11% protein for 16 weeks. Weight was recorded weekly. FSG and insulin levels were measured using an enzymatic spectrophotometric and a standard ELISA kit respectively. Inflammatory parameters including TGF-β, MCP-1, TNF-α, IL-1β, IL-6 in the renal and cardiac tissues of rats were evaluated by ELISA technique. Food intake in D1 and D2 groups increased in the study period, however food intake in D2 group was significantly higher compared with D1 group. FSG, HOMA and TG concentrations in D2 group were significantly higher compared to D1 group. Moreover, TGF-β and MCP-1 concentrations in the renal tissues of D2 group and TNF-α in the cardiac tissues of D1 group were significantly higher compared with D1 group (P<0.05). Positive associations between IL-1β and TG and between HOMA, FSG with TGF-β and MCP-1 in the renal tissue of animals were also identified.


Functional Capacity and Levels of Physical Activity in Aging: A 3-Year Follow-up.
Over the last decades, the world elderly population has increased exponentially and this tendency will continue during the coming years; from 2000 to 2050, people over 60 will double and those over 80 will quadruple. Loss of independence occurs as people age due to mobility restrictions, frailty, and decreased functional fitness and cognitive abilities. Evidence has shown that appropriate programs and policies contribute to keep older adults healthy and independent over time. The purpose of this chapter is to report the results of our 3-year follow-up study designed to characterize functional physical fitness in a sample of Portuguese community-dwelling older adults to propose a set of functional parameters that decline the most. We studied a group of 43 elderly people, aged 60 and over. Variables assessed on the participants were anthropometric measurements, functional capacity with the Senior Fitness Test battery (muscle strength, aerobic endurance, flexibility, agility, and dynamic balance), handgrip strength, levels of physical activity, and balance. Three years after the first assessment, a second assessment of the same variables was conducted. We analyzed what were the variables that, for this group, were related with a healthier aging and the relation with different physical activity levels. Our study showed that the distance covered in 6-min walk test and handgrip strength seem to explain a great amount of variability on functional variables that have changed on this period (68% of balance, lower and upper functional strength, respectively) and the active participants showed less decrements with aging in anthropometric and functional variables than those inactive or insufficiently active (p < 0.05). Greater importance should be given to prescription of exercise targeting older adults and, specifically, walking and manual activities should be given more attention as components of a community exercise program.


Loss of the DnaK-DnaJ-GrpE chaperone system among the Aquificales.
The DnaK-DnaJ-GrpE (KJE) chaperone system functions at the fulcrum of protein homeostasis in bacteria. It interacts both with nascent polypeptides and with proteins that have become unfolded, either funneling its clients toward the native state or ushering misfolded proteins into degradation. In line with its key role in protein folding, KJE has been considered an essential building block for a minimal bacterial genome and common to all bacteria. In this study, I present a rigorous survey of 1,233 bacterial genomes, which reveals that the entire KJE system is uniquely absent from two members of the order Aquificales, Desulfurobacterium thermolithotrophum, and Thermovibrio ammonificans. The absence of KJE from these free-living bacteria is surprising, particularly in light of the finding that individual losses of grpE and dnaJ are restricted to obligate endosymbionts with highly reduced genomes, whereas dnaK has never been lost in isolation. Examining protein features diagnostic of DnaK substrates in Escherichia coli, radical changes in protein solubility emerge as a likely precondition for the loss of KJE. Both D. thermolithotrophum and T. ammonificans grow under strictly anaerobic conditions at temperatures in excess of 70°C, reminiscent of hyperthermophilic archaea, which--unlike their mesophilic cousins--also lack KJE. I suggest that high temperature promotes the evolution of high intrinsic protein solubility on a proteome-wide scale and thereby creates conditions under which KJE can be lost. However, the shift in solubility is common to all Aquificales and hence not sufficient to explain the restricted incidence of KJE loss.


A polymorphism in the tumor suppressor p53 affects aging and longevity in mouse models.
Tumor suppressor p53 prevents early death due to cancer development. However, the role of p53 in aging process and longevity has not been well-established. In humans, single nucleotide polymorphism (SNP) with either arginine (R72) or proline (P72) at codon 72 influences p53 activity; the P72 allele has a weaker p53 activity and function in tumor suppression. Here, employing a mouse model with knock-in of human TP53 gene carrying codon 72 SNP, we found that despite increased cancer risk, P72 mice that escape tumor development display a longer lifespan than R72 mice. Further, P72 mice have a delayed development of aging-associated phenotypes compared with R72 mice. Mechanistically, P72 mice can better retain the self-renewal function of stem/progenitor cells compared with R72 mice during aging. This study provides direct genetic evidence demonstrating that p53 codon 72 SNP directly impacts aging and longevity, which supports a role of p53 in regulation of longevity.


Returning to Stimulants in Children with Treatment Resistant ADHD: A Case Series.
To present a case series of children retrialed on stimulants after initial poor stimulant responses given the paucity of information on the usefulness of this strategy. Health records from an ADHD medication service were obtained for six children who: (i) were medication naïve at service entry; (ii) had trials of at least one stimulant from each stimulant class; (iii) subsequently received a non-stimulant ADHD medication; and, (iv) were then retried on stimulants. Initial stimulant discontinuation was a function of adverse effects and/or limited symptom improvement. Minimal response and/or adverse effects to non-stimulants contributed to the decision to retry stimulants. Final ADHD symptom ratings by parents and teachers were significantly better than baseline for this cohort. Three were discharged on stimulants, two as monotherapy. Further study is required to develop evidence-based treatment algorithms for treatment resistant ADHD. Retrying a stimulant may be one option.


Pain Catastrophizing and Function In Individuals With Chronic Musculoskeletal Pain: A Systematic Review and Meta-Analysis.
Pain catastrophizing (PC) is the most consistent psychosocial factor predicting of adjustment to chronic pain and may contribute to the development and long-term maintenance of chronic pain. The aim of this review was systematically review and critically appraise the concurrent and longitudinal associations between PC and both pain intensity and disability in individuals with chronic musculoskeletal pain (CMP). An electronic search of PubMed, Scopus, AMED, CINAHL, PsycINFO, and PubPsych databases, as well as gray literature, was undertaken from inception until September 2018. Cross-sectional and longitudinal studies reporting on the associations between measures of PC, pain intensity, and disability were selected for review. A total of 85 observational studies (92% cross-sectional) were included, with a total sample of 13,628 participants with CMP. Very low-quality evidence (based on the GRADE criteria) indicated that higher levels of PC were often, but not always, significantly associated with and prospectively predicted both chronic pain intensity and disability. Heterogeneity was large after conducting multiple meta-analyses. Despite the very low quality of the available evidence, the general consistency of the findings highlights the potential role that PC may play in delaying recovery from CMP. Research that uses higher quality study designs and procedures would allow for more definitive conclusions regarding the impact of PC on pain and function.


Persistence of racial disparities in advance care plan documents among nursing home residents.
This paper analyzes the association between race and the presence of advance care plan documents (living wills, do not resuscitate (DNR) orders, and do not hospitalize (DNH) orders) in nursing home residents. We conducted secondary analysis of publicly available survey data from the 1996 Medical Expenditure Panel Survey-Nursing Home Component, a nationally representative survey of nursing home residents in the United States. There were 3,747 participants in the survey, weighted to represent 1.56 million nursing home residents in the United States. We found that 20% of U.S. nursing home residents in 1996 had documentation of living wills, 48% had DNR orders, and 4% had DNH orders. African Americans are about one-third as likely as Caucasians to have living wills and one-fifth as likely as Caucasians to have DNR orders; Hispanics are about one-third as likely as Caucasians to have DNR orders and just as likely as Caucasians to have living wills. In conclusion, we found that the presence of advance care plans is related to race, even after controlling for health and other demographic factors. These findings call attention to an area where further research is needed to determine whether residents' (and their families') preferences are being elicited and documented.


Characterization of the morphonuclear features and DNA ploidy of prostatic disease.
The relationship between several morphonuclear parameters related to nuclear densitometry (DNA content and ploidy), and the chromatin pattern of Feulgen-stained nuclei is confronted to the histopathological grading of 39 prostatic samples obtained from surgical adenomatous or transurethral resection. We use a SAMBA 200 cell image processor with software allowing for the setting up of preliminary data banks that enable carrying out an objective and reproducible grading of unknown cases obtained from core biopsies of fine-needle aspirations. The present approach must be validated prospectively on a large series of cases in order to create an expert system for diagnosing such fine-needle aspirations from prostate.


Burden of rotavirus in India--is rotavirus vaccine an answer to it?
Rotavirus is currently by far the most common cause of severe diarrhea in infants and young children worldwide and of diarrheal deaths in developing countries. Worldwide Rotavirus is responsible for 611,000 childhood deaths out of which more than 80% occur in low-income countries. The resistance of rotavirus to commonly used disinfectants and ineffectiveness of oral rehydration therapy due to severe vomiting indicates that if an effective vaccine is the preferred option. WHO has recommended inclusion of rotavirus vaccine in the National Schedules where under 5 mortality due to diarrheal diseases is ≥ 10%. Currently two vaccines are available against rotavirus. Rotarix (GlaxoSmithKline) is a monovalent vaccine recommended to be orally administered in two doses at 6-12 weeks. Rota Teq (Merck) is a pentavalent vaccine recommended to be orally administered in three doses starting at 6-12 weeks of age. Serodiversity of rotavirus in India and its regional variation favor either a monovalent vaccine that can induce heterotypic immunity or a polyvalent vaccine incorporating majority of serotypes prevalent in the country. However, the efficacy of available rotavirus vaccines is less in low-income countries. Both the candidate vaccines when coadministered with OPV, immune response to first dose of these vaccines is reduced. However, immune responses to subsequent rotavirus vaccine doses are not affected. In view of this, WHO recommends three doses of either vaccine to be given to children in developing countries to produce the optimum response. Indigenous vaccine, 116E (Bharat Biotech) based on human rotavirus of serotype G9P [11] is still under Phase 2 trials. Another multivalent vaccine is being developed by Shantha Biotechnics in India. The cost effectiveness of the three dose schedule of the available and the rsults of the field trials of the indigenous vaccines should be assessed before inclusion of rotavirus vaccine in the National Immunization Schedule.


Surgical reconstruction of the foramen tympanicum: What is known and how we do it.
Defects affecting the anterior wall of the tympanal bone can result from trauma, infection, neoplasm or previous local surgery. An anatomic variation, namely the persistence of the foramen tympanicum, can also be encountered. When symptomatic, surgical reconstruction may be indicated. The aim of this study was to identify the surgical treatments of symptomatic foramen tympanicum found in the literature and detail our innovative reconstruction technique. A bibliographic research was conducted in PubMed database in March 2020, without time limitation. Papers dealing with surgical management of a foramen tympanicum were included. Data collected were the publication date, the number of patients, their age and gender, the symptoms and the surgical treatment performed. We report, in addition, the case of a symptomatic persistent foramen tympanicum in a 30-year-old man with a follow-up of 18-months. A total of 17 studies (n=23 patients) were included for analysis. The main reconstruction techniques were, in equal proportion, cartilage graft (30%) and insertion of a titanium mesh (30%). We carried out an iliac crest bone graft using a preauricular approach on a patient suffering from chronic tinnitus and fullness in the left ear resulting from a persistent foramen tympanicum, confirmed by clinical and radiological examinations. It allowed the complete resolution of symptoms and no complication such as temporomandibular ankylosis occurred. Based on the review of the literature, we believe this technique has the advantage of providing durable reconstruction thanks to osseointegration.


History of Newcastle disease in South Africa.
Poultry production in South Africa, a so-called developing country, may be seen as a gradient between two extremes with highly integrated commercial enterprises with world-class facilities on one hand and unimproved rural chickens kept by households and subsistence farmers on the other. Although vaccination against Newcastle disease is widely applied to control this devastating infection, epizootics continue to occur. Since the first official diagnosis in 1945, through the sporadic outbreaks of the 1950s and early 1960s, to serious epizootics caused by genotype VIII (late 1960s-2000), genotype VIIb (1993-1999), genotype VIId (2003-2012) and most recently genotype VIIh (2013 to present), South Africa's encounters with exotic Newcastle disease follow global trends. Importation - probably illegal - of infected poultry, poultry products or exotic birds and illegal swill dumping are likely routes of entry. Once the commercial sector is affected, the disease spreads rapidly within the region via transportation routes. Each outbreak genotype persisted for about a decade and displaced its predecessor.


[Early rheumatoid arthritis].
Rheumatoid arthritis (RA) is chronic joint disease which if untreated leads to permanent structural damage and disability. Early diagnosis and therapy are the main requests for good clinical practice. Early diagnosis tools include specific clinical assesment, serological, immunogenetic and radiological evaluation. Disease activity score is cornerstone in clinical assesment, rheumatoid factor and anti-cyclic citrullinated peptide antibodies (anti-CCP) are very specific serological parameters. The shared epitope containing HLA-DRB1* alleles represent the most significant genetic risk for RA. Magnetic resonance and ultrasound imaging are very sensitive methods in early phase of disease.


Influence of a modified Nd:YAG laser treatment outside the visual axis on the morphology of Elschnig pearls.
To observe changes in posterior capsule opacification (PCO) after Nd:YAG treatment with and without opening the posterior lens capsule. This prospective randomized study included patients with regeneratory PCO. In substudy 1, a small low-energy Nd:YAG capsulotomy was performed (MiniYAG). In substudy 2, a low-energy Nd:YAG laser treatment without opening the lens capsule was performed (GentleYAG). Concerning analysis, in both substudies, the posterior capsule was divided into 4 quadrants and the quadrant where the Nd:YAG laser treatment was performed was randomly allocated. Change in PCO was analyzed using retroillumination images objectively (AQUA score: 0-10). In total, 27 eyes of 25 patients were used for this study. In substudy 1, the mean amount of PCO (AQUA score) for the entire posterior capsule decreased significantly (p < 0.05, ANOVA) from 5.2 (SD: 1.6) before to 4.0 (SD: 1.9) immediately after the MiniYAG. In substudy 2, the mean amount of PCO (AQUA score) for the entire posterior capsule analyzed before and immediately after the GentleYAG was 5.1 (SD: 2.4) and 5.2 (SD: 2.3), respectively. Performing a MiniYAG led to a significant PCO reduction. Gentle polishing of the posterior capsule resulted in a relevant reduction of PCO in one third of the patients.


Chemical structure of the core region of Escherichia coli J-5 lipopolysaccharide.
The lipopolysaccharide of Escherichia coli J-5 was sequentially de-O-acylated, dephosphorylated, reduced, de-N-acylated, and N-acetylated. The products were separated by high-performance anion-exchange chromatography into a nonasaccharide (1), two octasaccharides (2, 3), and a heptasaccharide (4). Compositional analysis, methylation analysis, and NMR spectroscopy revealed the structures of the products as: alpha-D-GlcpNAc-(1-7)-L-alpha-D-Hepp-(1-7)-[alpha-D-Glcp-(1-3)-]-L -alpha-D- Hepp-(1-3)-R1, (1) L-alpha-D-Hepp-(1-7)-[alpha-D-Glcp-(1-3)-]-L-alpha-D-Hepp-(1 -3)-R1, (2) alpha-D-GlcpNAc-(1-7)-L-alpha-D-Hepp-(1-7)-[alpha-D-Glcp-(1-3)-]-L -alpha-D- Hepp-(1-3)-R2, (3) alpha-D-Glcp-(1-3)-L-alpha-D-Hepp-(1-3)-R1, (4) in which 1R is L-alpha-D-Hepp-(1-5)-[alpha-Kdop-(2-4)-]-alpha-Kdop-(2 -6)- beta-D-GlcpNAc-(1-6)-D-GlcN-Acol, and 2R is L-alpha-D-Hepp-(1-5)-alpha-Kdop-(2-6)-beta-D-GlcpNAc-(1-6 )-D- GlcNAcol (LD-Hep, L-glycero-D-manno-heptose; Kdo, 3-deoxy-D-manno-octulopyranosonic acid; GlcNAcol, 2-acetamido-2-deoxy-glucitol). Fast-atom-bombardment mass spectrometry of de-O-acylated and dephosphorylated lipopolysaccharide showed that the isolated oligosaccharides represented the complete carbohydrate moiety of the lipopolysaccharide, and indicated that the non-reducing terminal D-GlcN residue in lipopolysaccharide was present as the free base.


Analysis of the efficacy and safety of new oral anticoagulant drugs in the secondary stroke prevention in patients with AF: single center experience based on 311 patients.
According to the performed trials, an introduction of the new oral anticoagulant drugs (NOAC) in the chronic anticoagulation in patients with non-valvular AF (NVAF) is an interesting treatment option. In addition to the encouraging results of the randomized controlled trials the efficacy of this treatment modality in the real-world clinical settings should also be confirmed. In the article, the two-year single center experience with NOACs in the secondary prevention of cerebral stroke in patients with NVAF and previous ischemic stroke was presented. The objective of the study was to evaluate the efficacy, safety and tolerability of the NOACs in the secondary stroke prevention in patients with NVAF. Three hundred eleven patients (M/F 98/213) with NVAF (mean age 62.22 years [41-85]) on NOAC in secondary prevention of cardiogenic stroke, were enrolled into a prospective study. All of them started the therapy during the acute period of cerebral ischemia from III to IX day after the stroke onset. The estimated risk of stroke was based on the CHA2DS2VASc and the risk of hemorrhage on the basis of HAS-BLED scale. Patients underwent a long-term follow-up within the period from 12 to 24 months after initiation of NOAC therapy (mean follow up 18.6 months). 230 patients were treated by the means of rivaroxaban, in 78 patients dabigatran was administered and 1 patient received apixaban. The rate of stroke recurrence, bleeding as well as the drug intolerance were evaluated. Ischemic stroke during NOAC treatment was diagnosed in 6 patients (1.92%); TIA was observed in 3 cases (0.96%). Hemorrhagic complications during follow-up were recorded in 29 patients (9.32%), of which 3 patients had major bleedings (0,96%): intracranial bleeding (1), bleeding from the genital tract (1) and from the urinary tract (1). There were no deaths caused by bleeding associated with the use of medications, 1 patient died after ischemic stroke when taking NOACs. In 59 patients (18.97%) NOAC therapy was discontinued in the course of follow-up, mostly because of bleeding (29 patients) or renal function worsening (10 patients). There were no significant differences in the efficacy and safety between the groups on selective factor II inhibitor (dabigatran) or factor Xa inhibitor (rivaroxaban). Clinical application of NOAC in a real-world clinical setting results in the treatment profile of high efficacy and acceptable safety for patients with non-valvular AF and stroke.


Upper extremity deep venous thrombosis after port insertion: What are the risk factors?
Totally implantable venous access devices (ports) are widely used, especially for cancer chemotherapy. Although their use has been associated with upper extremity deep venous thrombosis, the risk factors of upper extremity deep venous thrombosis in patients with a port are not studied adequately. The Healthcare Cost and Utilization Project's Florida State Ambulatory Surgery and Services Database was queried between 2007 and 2011 for patients who underwent outpatient port insertion, identified by Current Procedural Terminology code. Patients were followed in the State Ambulatory Surgery and Services Database, State Inpatient Database, and State Emergency Department Database for upper extremity deep venous thrombosis occurrence. The cohort was divided into a test cohort and a validation cohort based on the year of port placement. A multivariable logistic regression model was developed to identify risk factors for upper extremity deep venous thrombosis in patients with a port. The model then was tested on the validation cohort. Of the 51,049 patients in the derivation cohort, 926 (1.81%) developed an upper extremity deep venous thrombosis. On multivariate analysis, independently significant predictors of upper extremity deep venous thrombosis included age <65 years (odds ratio = 1.22), Elixhauser score of 1 to 2 compared with zero (odds ratio = 1.17), end-stage renal disease (versus no kidney disease; odds ratio = 2.63), history of any deep venous thrombosis (odds ratio = 1.77), all-cause 30-day revisit (odds ratio = 2.36), African American race (versus white; odds ratio = 1.86), and other nonwhite races (odds ratio = 1.35). Additionally, compared with genitourinary malignancies, patients with gastrointestinal (odds ratio = 1.55), metastatic (odds ratio = 1.76), and lung cancers (odds ratio = 1.68) had greater risks of developing an upper extremity deep venous thrombosis. This study identified major risk factors of upper extremity deep venous thrombosis. Further studies are needed to evaluate the appropriateness of thromboprophylaxis in patients at greater risk of upper extremity deep venous thrombosis.


Affect lability predicts occurrence of suicidal ideation in bipolar patients: a two-year prospective study.
The aim of our study was to investigate, in bipolar patients, whether affect lability was associated with suicidal ideation incidence during 2-year follow-up, and which subtype of affect lability was associated with suicidal ideation. A total of 319 euthymic or mildly depressed bipolar outpatients recruited in the French FondaMental Advanced Centres of Expertise for Bipolar Disorder were divided into two subgroups according to the occurrence of suicidal ideation during a 2-year follow-up. Affect lability was assessed by the French version of the Affect Lability Scale. Bipolar patients with high affect lability were more likely to report suicidal ideation during follow-up, even after adjustment for age, study level, rapid cycling, current depression level, anxiety disorder, and lifetime history SA (OR = 2.47; 95% CI [1.15-5.30], P = 0.01). The risk of suicidal ideation increased with the level of affect lability. More specifically, the propensity to switch from neutral to elation affect, from anxious to depressive affect (or inversely), and from neutral to anger affect predicted suicidal ideation. Reducing affective lability could become a new therapeutic target of suicidal prevention in bipolar disorder.


Agglutinins to Coxiella burnetii and Brucella spp, with particular reference to Brucella canis, in wild animals of southern Texas.
The prevalence of agglutinins to Coxiella burnetii and Brucella spp, particularly Brucella canis, was determined in 269 wild animals (14 species) in southern Texas. Serologic evidence of coxiellosis and brucellosis, including B canis infection, was shown for coyotes, raccoons, opossums, badgers, jackrabbits, and feral hogs. Using the microagglutination test, the seroprevalence of C burnetii, phases I and II (titer greater than or equal to 4) was 4.1 and 27.9%, respectively. For brucella agglutinins, prevalence rates were 7.1, 8.9, and 6.7%, as determined by the brucellosis card test, the rapid slide agglutination test, and the salt 2-mercaptoethanol tube agglutination (titer greater than or equal to 50) test, respectively.


[Mutagenic and DNA-damaging effect of potassium bichromate in Escherichia coli cells].
Mutagenic effects and DNA degradation in Escherichia coli cells treated with potassium bichromate were studied in this work. It is estimated that events taking place in cells treated with the mutagen are controlled by recB recC and sbcB gene products. The method for sedimentation analysis has revealed DNA degradation. The use of the impulse label of 3H-thymidine made it possible to detect DNA breaks in the daughter strands. This effect of potassium bichromate on DNA degradation is, possibly, connected with mutagenic repair.


A new Moenkhausia (Actinopterygii: Characiformes: Characidae) from the upper rio Negro basin, Brazil.
A new species of Moenkhausia is described from the upper rio Negro basin, Amazonas, Brazil. The new species is distinguished from all congeners, except M. agnesae, by presenting a color pattern characterized by the presence of two irregularly-shaped humeral blotches, and the presence of dark longitudinal stripes on the dorsal portion of the body. The new species can be readily separated from M. agnesae by presenting longitudinal stripes straight and more conspicuous dorsally, humeral blotches contacting each other, 2-3 tricuspid maxillary teeth, 32-35 lateral-line scales, and length of maxilla 45.3-51.0% in head length.


Juveniles' Miranda comprehension: Understanding, appreciation, and totality of circumstances factors.
This study examined juvenile justice-involved youths' understanding and appreciation of the Miranda warnings' rights to silence and legal counsel using the Miranda Rights Comprehension Instruments (Goldstein, Zelle, & Grisso, 2012). It also examined the relationships between totality of circumstances factors and understanding and appreciation of rights. Data were collected from 183 youths (140 boys) in pre- and postadjudication facilities in 2 states. Overall, youths demonstrated greater difficulty on measures of appreciation than understanding, with particular deficits in their abilities to comprehend the abstract concept of the right to silence. Results varied slightly by instrument, highlighting the importance of a multimodal assessment of these complex abilities. Examination of totality of circumstances factors identified relationships between some factors (e.g., age, verbal IQ, academic achievement) and Miranda comprehension, but revealed that other factors (e.g., gender, number of previous arrests) were not significantly related to Miranda understanding or appreciation. The findings support a nuanced conceptualization of Miranda rights comprehension that acknowledges the complexity of understanding and appreciating the warnings. Empirical analyses also support the continued use of some totality of circumstances factors and abandonment of others. Findings underscore the necessity of multimodal assessment and interpretation when conducting capacity to waive Miranda rights evaluations.


[Small irregular pulmonary radiological anomalies seen in coal miners in the Lorraine region].
Amongst the pulmonary radiological abnormalities more or less suggestive of pneumoconiosis seen in 1 044 miners from Lorraine, there were 976 cases of typical pneumoconiosis: 154 "P.M.F." forms and 890 forms with small round opacities. In the other 68 cases, hence in a proportion of 1 in 15, the X-ray appearance consisted of small irregular opacities which have only been introduced by the I.L.O. into the international nomenclature on pneumoconiosis since 1968 (symbols: s, t, u, according to their size). These forms with small irregular abnormalities are associated with obstructive spirographic ventilatory disorders and a decrease in CO transfer (steady-state) on average greater than those seen in forms with classical round opacities. Age is greater and tobacco consumption higher, but long exposure to pneumoconiosis risk (26.9 years, on average) must also be taken into consideration in interpreting the singular prevalence of


Association between abdominal and general obesity and respiratory symptoms, asthma and COPD. Results from the RHINE study.
Previous studies on the association between abdominal and general obesity and respiratory disease have provided conflicting results. We aimed to explore the associations of abdominal obesity with respiratory symptoms, asthma, and chronic obstructive pulmonary disease independently from general obesity in women and men. This cross-sectional study was based on the Respiratory Health in Northern Europe (RHINE) III questionnaire (n = 12 290) conducted in 2010-2012. Abdominal obesity was self-measured waist circumference using a sex-specific standard cut-off point: ≥102 cm in males and ≥88 cm in females. General obesity was defined as self-reported BMI ≥30.0 kg/m2. There were 4261 subjects (63% women) with abdominal obesity and 1837 subjects (50% women) with general obesity. Both abdominal and general obesity was independent of each other and associated with respiratory symptoms (odds ratio (OR) from 1.25 to 2.00)). Asthma was significantly associated with abdominal and general obesity in women, OR (95% CI) 1.56 (1.30-1.87) and 1.95 (1.56-2.43), respectively, but not in men, OR 1.22 (0.97-3.17) and 1.28 (0.97-1.68) respectively. A similar sex difference was found for self-reported chronic obstructive pulmonary disease. General and abdominal obesity were independent factors associated with respiratory symptoms in adults. Asthma and chronic obstructive pulmonary disease were independently linked to abdominal and general obesity in women but not men.


Polymorphism of TLR5 rs5744174 is associated with disease progression in Chinese patients with chronic HBV infection.
Toll-like receptors (TLRs) play a crucial role in innate and adaptive immunity, protecting the host from viral pathogens. Studies have implicated that TLR5 is associated with various diseases such as autoimmune and inflammation related diseases. However, little is known about the relationship between TLR5 and hepatitis B virus (HBV) infection. We studied the effect of TLR5 gene polymorphisms on susceptibility to and disease progression of chronic hepatitis B (CHB) infection in Chinese. Blood samples were taken from 636 patients with CHB, HBV-related liver cirrhosis (LC) or hepatocellular carcinoma (HCC) and 273 controls. Polymorphisms of TLR5 (1775A>G rs2072493 and 1846T>C rs5744174) were analyzed by PCR-based sequencing. No difference in genotypic and allelic frequencies of TLR5 rs2072493 and rs5744174 was observed between patients and controls. Significant difference was found in frequency of TLR5 rs5744174 TT genotype between men with CHB and LC (p = 0.035). Frequency of TT genotype of TLR5 rs5744174 in patients positive for HBeAg was increased from 53.2% in patients with CHB to 74.1% in those with HCC (p = 0.024). Our results indicate that in Chinese genetic variation of TLR5 may be not a determinant of susceptibility to HBV-related diseases but may play a role in development of HBV-related severe liver diseases.


IBM, Elsevier Science, and academic freedom.
Elsevier Science refused to publish a study of IBM workers that IBM sought to keep from public view. Occupational and environmental health (OEH) suffers from the absence of a level playing field on which science can thrive. Industry pays for a substantial portion of OEH research. Studies done by private consulting firms or academic institutions may be published if the results suit the sponsoring companies, or they may be censored. OEH journals often reflect the dominance of industry influence on research in the papers they publish, sometimes withdrawing or modifying papers in line with industry and advertising agendas. Although such practices are widely recognized, no fundamental change is supported by government and industry or by professional organizations.


Immunoinformatics study to search epitopes of spike glycoprotein from SARS-CoV-2 as potential vaccine.
The Coronavirus disease named COVID-19 is caused by the virus reported in 2019 first identified in China. The cases of this disease have increased and as of June 1st, 2020 there are more than 216 countries affected. Pharmacological treatments have been proposed based on the resemblance of the HIV virus. With regard to prevention there is no vaccine, thus, we proposed to explore the spike protein due to its presence on the viral surface, and it also contains the putative viral entry receptor as well as the fusion peptide (important in the genome release). In this work we have employed In Silico techniques such as immunoinformatics tools which permit the identification of potential immunogenic regions on the viral surface (spike glycoprotein). From these analyses, we identified four epitopes E332-370, E627-651, E440-464 and E694-715 that accomplish essential features such as promiscuity, conservation grade, exposure and universality, and they also form stable complexes with MHCII molecule. We suggest that these epitopes could generate a specific immune response, and thus, they could be used for future applications such as the design of new epitope vaccines against the SARS-CoV-2.Communicated by Ramaswamy H. Sarma.


Temperature dependence of the hydrophobic hydration and interaction of simple solutes: an examination of five popular water models.
We examine five different popular rigid water models (SPC, SPCE, TIP3P, TIP4P, and TIP5P) using molecular dynamics simulations in order to investigate the hydrophobic hydration and interaction of apolar Lennard-Jones solutes as a function of temperature in the range between 275 and 375 K along the 0.1 MPa isobar. For all investigated models and state points we calculate the excess chemical potential for the noble gases and methane employing the Widom particle insertion technique. All water models exhibit too small hydration entropies, but show a clear hierarchy. TIP3P shows poorest agreement with experiment, whereas TIP5P is closest to the experimental data at lower temperatures and SPCE is closest at higher temperatures. As a first approximation, this behavior can be rationalized as a temperature shift with respect to the solvation behavior found in real water. A rescaling procedure inspired by the information theory model of Hummer et al. [Chem. Phys. 258, 349 (2000)] suggests that the different solubility curves for the different models and real water can be largely explained on the basis of the different density curves at constant pressure. In addition, the models that give a good representation of the water structure at ambient conditions (TIP5P, SPCE, and TIP4P) show considerably better agreement with the experimental data than the ones which exhibit less structured O-O correlation functions (SPC and TIP3P). In the second part of the paper we calculate the hydrophobic interaction between xenon particles directly from a series of 60 ns simulation runs. We find that the temperature dependence of the association is to a large extent related to the strength of the solvation entropy. Nevertheless, differences between the models seem to require a more detailed molecular picture. The TIP5P model shows by far the strongest temperature dependence. The suggested density rescaling is also applied to the chemical potential in the xenon-xenon contact-pair configuration, indicating the presence of a temperature where the hydrophobic interaction turns into purely repulsive. The predicted association for xenon in real water suggests the presence of a strong variation with temperature, comparable to the behavior found for TIP5P water. Comparing different water models and experimental data we conclude that a proper description of density effects is an important requirement for a water model to account correctly for the correct description of the hydrophobic effects. A water model exhibiting a density maximum at the correct temperature is desirable.


Intestinal flora and human health.
There is a growing interest in intestinal flora and human health and disease. The intestines of humans contain 100 trillion viable bacteria. These live bacteria, which make up 30% of the faecal mass, are known as the intestinal flora. There are two kinds of bacteria in the intestinal flora, beneficial and harmful. In healthy subjects, they are well balanced and beneficial bacteria dominate. Beneficial bacteria play useful roles in the aspects of nutrition and prevention of disease. They produce essential nutrients such as vitamins and organic acids, which are absorbed from the intestines and utilised by the gut epithelium and by vital organs such as the liver. Organic acids also suppress the growth of pathogens in the intestines.Other intestinal bacteria produce substances that are harmful to the host, such as putrefactive products, toxins and carcinogenic substances. When harmful bacteria dominate in the intestines, essential nutrients are not produced and the level of harmful substances rises. These substances may not have an immediate detrimental effect on the host but they are thought to be contributing factors to ageing, promoting cancer, liver and kidney disease, hypertension and arteriosclerosis, and reduced immunity. Little is known regarding which intestinal bacteria are responsible for these effects. A number of factors can change the balance of intestinal flora in favour of harmful bacteria. These include peristalsis disorders, surgical operations of stomach or small intestine, liver or kidney diseases, pernicious anaemia, cancer, radiation or antibiotic therapies, immune disorders, emotional stress, poor diet and ageing. However, more importantly, the normal balance of intestinal flora may be maintained, or restored to a normal from an unbalanced state, by oral bacterio-therapy or by a well balanced diet. Oral bacterio-therapy using intestinal strains of lactic acid bacteria, such as lactobacillus and bifidobacteria, can restore normal intestinal balance and produce beneficial effects. Benefits include suppression of intestinal putrification so as to reduce constipation and other geriatric diseases; prevention and treatment of diarrhoea including antibiotic-associated diarrhoea; stimulation of the immune system; and increased resistance to infection.


Wearing an Inflatable Vest Alters Muscle Activation and Trunk Angle While Paddling a Surfboard.
Low back pain is a commonly reported problem among recreational surfers. Some individuals report that wearing a vest with an inflatable bladder that alters trunk angle may help to alleviate pain. The purpose of this study was to determine whether such a vest has an effect on muscle activation and extension of the lower back. Twelve recreational surfers completed 12 paddling trials at 1.1 m/s in a swim flume on both a shortboard and a longboard on 2 separate days. Three conditions of no vest, vest uninflated, and vest inflated were presented to participants in random order. Surface EMG and trunk angle were acquired via wireless sensors placed over the right erector spinae, mid-trapezius, upper trapezius, and latissimus dorsi. Wearing the inflated vest affected muscle activation: erector spinae and mid-trapezius demonstrated a significant decrease in activation relative to wearing no vest (12% and 18% respectively, p < .05). Trunk extension was also significantly reduced when the vest was inflated (18% reduction, p < .05). Results were similar for both the short and longboard, though this effect was greater while paddling the larger board. These results suggest that a properly inflated vest can alter trunk extension and muscle activity while paddling a surfboard in water.


Hierarchical mean-field model describing relaxation in a small-world network.
This Brief Report presents the hierarchical reaction-diffusion partial differential equations (PDE) system, which reproduces a mean-square displacement and a density relaxation process corresponding to the anomalous diffusion on a small-world network. These results are confirmed by the comparison with the known direct numerical simulations.


A clinical trial to assess the efficacy of sanguinarine-zinc mouthrinse (Veadent) compared with chlorhexidine mouthrinse (Corsodyl).
A single-blind crossover study was used to compare the ability of a 0.2% chlorhexidine mouthrinse (Corsodyl) with a sanguinarine-zinc mouthrinse (Veadent) to inhibit plaque and gingivitis. 14 volunteers starting with plaque-free mouths and optimal gingival health, rinsed with the preparations over two 19-day periods whilst refraining from all other oral hygiene procedures. At days 8, 15 and 19 of the trial, Corsodyl was significantly more effective at inhibiting both plaque and gingivitis. The findings of this study would suggest that the Veadent mouthrinse would at most only have a limited rôle as an inhibitor of plaque and gingivitis.


Re-establishing ataxin-2 downregulates translation of mutant ataxin-3 and alleviates Machado-Joseph disease.
Machado-Joseph disease is a progressive neurodegenerative disorder associated with the polyQ-expanded ataxin-3 (encoded by ATXN3), for which no therapy is available. With the aim of clarifying the mechanism of neurodegeneration, we hypothesized that the abnormally long polyQ tract would interact aberrantly with ataxin-2 (encoded by ATXN2), another polyQ protein whose function has recently been linked to translational regulation. Using patient's samples and cellular and animal's models we found that in Machado-Joseph disease: (i) ataxin-2 levels are reduced; and (ii) its subcellular localization is changed towards the nucleus. Restoring ataxin-2 levels by lentiviral-mediated overexpression: (i) reduced mutant ataxin-3 levels; and (ii) rescued behaviour defects and neuropathology in a transgenic mouse model of Machado-Joseph disease. Conversely (i) mutating the ataxin-2 motif that enables binding to its natural interactor and translation activator poly(A)-binding protein; or (ii) overexpressing poly(A)-binding protein, had opposite effects, increasing mutant ataxin-3 translation and aggregation. This work suggests that in Machado-Joseph disease, mutant ataxin-3 drives an abnormal reduction of ataxin-2 levels, which overactivates poly(A)-binding protein, increases translation of mutant ataxin-3 and other proteins and aggravates Machado-Joseph disease. Re-establishment of ataxin-2 levels reduces mutant ataxin-3 and alleviates Machado-Joseph disease pathogenesis opening a new avenue for therapeutic intervention in this and potentially other polyQ disorders.


Coenzyme Q10 supplementation therapy for 2 children with proteinuria renal disease and ADCK4 mutation: Case reports and literature review.
Mitochondrial nephropathy has a poor prognosis and often progresses to the end-stage renal disease. Renal pathology often is focal segmental glomerulosclerosis (FSGS) and does not respond to steroid therapy or immunosuppressive therapy. Some patients are benefited from the therapy of coenzyme Q10, which affect the synthesis pathway of coenzyme Q10. Herein, we report 2 cases of children with proteinuria renal disease with ADCK4 mutation. Proteinuria renal disease with ADCK4 mutation. Compound heterozygous mutation in ADCK4 gene were detected with next-generation sequencing and confirmed by Sanger sequencing. Both of the patients were given coenzyme Q10 supplementation therapy. The first patient showed a decreased proteinuria after coenzyme Q10 supplementation therapy, while the other was not improved. Based on the cases we reported and from the literature, recognition of ADCK4 mutation through early and accurate genetic screening could be helpful in avoiding unnecessary toxicities and in preventing complications arising in mitochondrial nephropathy.


Optical coherence tomography based angiography [Invited].
Optical coherence tomography (OCT)-based angiography (OCTA) provides in vivo, three-dimensional vascular information by the use of flowing red blood cells as intrinsic contrast agents, enabling the visualization of functional vessel networks within microcirculatory tissue beds non-invasively, without a need of dye injection. Because of these attributes, OCTA has been rapidly translated to clinical ophthalmology within a short period of time in the development. Various OCTA algorithms have been developed to detect the functional micro-vasculatures in vivo by utilizing different components of OCT signals, including phase-signal-based OCTA, intensity-signal-based OCTA and complex-signal-based OCTA. All these algorithms have shown, in one way or another, their clinical values in revealing micro-vasculatures in biological tissues in vivo, identifying abnormal vascular networks or vessel impairment zones in retinal and skin pathologies, detecting vessel patterns and angiogenesis in eyes with age-related macular degeneration and in skin and brain with tumors, and monitoring responses to hypoxia in the brain tissue. The purpose of this paper is to provide a technical oriented overview of the OCTA developments and their potential pre-clinical and clinical applications, and to shed some lights on its future perspectives. Because of its clinical translation to ophthalmology, this review intentionally places a slightly more weight on ophthalmic OCT angiography.


Regression of glomerulosclerosis in response to transient treatment with angiotensin II blockers is attenuated by blockade of matrix metalloproteinase-2.
Understanding mechanisms that contribute to the regression of glomerulosclerosis is important for developing new strategies to treat chronic kidney disease. We reported that transient high-dose treatment with an angiotensin receptor blocker causes regression of renal arteriolar hypertrophy and hypertension in spontaneously hypertensive rats. To extend those findings to another form of kidney disease, we examined the short- and long-term effects of transient high-dose angiotensin receptor blocker treatment in a mouse model of adriamycin-induced glomerulosclerosis. A 2-week course of candesartan caused a dose-dependent regression of established glomerulosclerotic lesions sustained for over 6 months following cessation of treatment. Highly sensitive in situ zymography and activity assays showed that glomerular matrix metalloproteinase (MMP)-2 activity was increased after high-dose angiotensin blocker therapy. Treatment of cultured podocytes with candesartan resulted in an increase in MMP-2 activity. The regression of glomerulosclerosis was partially attenuated in mice pretreated with the MMP inhibitor doxycycline, as well as in MMP-2 knockout mice. Our results suggest that transient high-dose angiotensin receptor blocker treatment effectively induced sustained regression of glomerulosclerosis by a mechanism mediated, in part, by changes in MMP-2 activity.


[Physical exploration and morbidity of pelvic members in the diabetic patient type 2].
to determine the prevalence of the physical exploration and morbidity on pelvic members in the type 2 diabetic patient. cross-sectional study; 189 files of diabetic family medicine patients were analyzed. The sample was considered with the formula of proportions for a finite population. Sampling units were chosen by convenience and they were taken up again from each one of the family medicine physician's offices. Sociodemographic variables, pathologies, time of evolution of diabetes, glycemic control and consultations along a year were studied. Physical explorations were made and signs explored by the physicians. Descriptive statistic for the analysis of data was used. average age 58.89 years (CI 95 %, 57.1-60.7); women predominated with 61.9 % (CI 95 %, 55.0-68.8), mean time of evolution 10.60 years ± 7.29. In 74.1 % some sign in pelvic members was explored, and in 14.3 % some added problem was detected. Of these, 9 % suffered from onychomycosis. physical exploration of pelvic members it is not to be performed in all type 2 diabetic patients.


Herpes Simplex Virus Encephalitis: Atypical Presentation as a Right Middle Cerebral Artery Stroke.
Herpes simplex virus encephalitis (HSVE) is a medical emergency associated with high mortality and morbidity. Definitive diagnosis is established by history, clinical examination, neuroimaging studies, supportive electroencephalogram (EEG) findings, and cerebrospinal fluid (CSF) analysis. We report a case of HSVE presenting as a stroke mimic in a 76-year-old female with a history of atrial fibrillation on warfarin. She was admitted to our medical intensive care unit with intermittent fever, lethargy, and new onset left-sided hemiparesis. A computed tomography (CT) of the head showed a right middle cerebral artery (MCA) acute ischemic stroke with midline shift and a dense right MCA sign. Brain magnetic resonance imaging (MRI) showed evidence of acute stroke with consideration of herpes encephalitis. CSF analysis was positive for herpes simplex virus (HSV) type one. She recovered with high-dose intravenous acyclovir therapy. Our patient was a diagnostic dilemma, initially being diagnosed with an acute ischemic stroke and yet found to have HSVE, which mimicked an acute ischemic stroke. Delay in treatment may result in devastating clinical outcomes that may include severe cognitive, focal neurological deficits, persistent seizures, and even death. This case highlights the importance of a multidisciplinary approach and the need for increased awareness of an atypical presentation of HSVE among emergency physicians, neurologist, intensivists, and radiologists.


Late onset fulminant Wilson's disease: a case report and review of the literature.
Wilson's disease (WD) is an autosomal recessive inherited disorder of hepatic copper metabolism. WD can be present in different clinical conditions, with the most common ones being liver disease and neuropsychiatric disturbances. Most cases present symptoms at < 40 years of age. However, few reports exist in the literature on patients in whom the disease presented beyond this age. In this report, we present a case of late onset fulminant WD in a 58-year-old patient in whom the diagnosis was established clinically, by genetic analysis of the ATP7B gene disclosing rare mutations (G1099S and c.1707+3insT) as well as by high hepatic copper content. We also reviewed the relevant literature. The diagnosis of WD with late onset presentation is easily overlooked. The diagnostic features and the genetic background in patients with late onset WD are not different from those in patients with early onset WD, except for the age. Effective treatments for this disorder that can be fatal are available and will prevent or reverse many manifestations if the disease is discovered early.


Treatment options for acute myeloid leukemia patients aged <60 years.
Treatment of acute myeloid leukemia (AML) has changed over the last few years, after the discovery of new drugs selectively targeting AML blasts. Although 3/7 remains the standard of care for most AML patients, several new targeted agents (such as FLT3 inhibitors, CPX-351, gemtuzumab ozogamicin, BCL-2 inhibitor, and oral azacitidine), either as single agents or combined with standard chemotherapy, are approaching clinical practice, starting a new era in AML management. Moreover, emerging evidence has demonstrated that high-risk AML patients might benefit from both allogeneic stem cell transplant and maintenance therapy, providing new opportunities, as well as new challenges, for treating clinicians. In this review, we summarize available data on first-line therapy in young AML patients focusing on targeted therapies, integrating established practice with new evidence, in the effort to outline the contours of a new therapeutic paradigm, that of a "total therapy", which goes beyond obtaining complete remission.


Albertson (Alb) spectral radii and Albertson (Alb) energies of graph operation.
The sum of the absolute eigenvalues of the adjacency matrix make up graph energy. The greatest absolute eigenvalue of the adjacency matrix is represented by the spectral radius of the graph. Both molecular computing and computer science have uses for graph energies and spectral radii. The Albertson (Alb) energies and spectral radii of generalized splitting and shadow graphs constructed on any regular graph is the main focus of this study. The only thing that may be disputed is the comparison of the (Alb) energies and (Alb) spectral radii of the newly formed graphs to those of the base graph. By concentrating on splitting and shadow graph, we compute new correlations between the Alb energies and spectral radius of the new graph and the prior graph.


Comparative Genomics Uncovers the Genetic Diversity and Synthetic Biology of Secondary Metabolite Production of Trametes.
The carbohydrate-active enzyme (CAZyme) genes of Trametes contribute to polysaccharide degradation. However, the comprehensive analysis of the composition of CAZymes and the biosynthetic gene clusters (BGCs) of Trametes remain unclear. Here, we conducted comparative analysis, detected the CAZyme genes, and predicted the BGCs for nine Trametes strains. Among the 82,053 homologous clusters obtained for Trametes, we identified 8518 core genes, 60,441 accessory genes, and 13,094 specific genes. A large proportion of CAZyme genes were cataloged into glycoside hydrolases, glycosyltransferases, and carbohydrate esterases. The predicted BGCs of Trametes were divided into six strategies, and the nine Trametes strains harbored 47.78 BGCs on average. Our study revealed that Trametes exhibits an open pan-genome structure. These findings provide insights into the genetic diversity and explored the synthetic biology of secondary metabolite production for Trametes.


[Correlation of baseline serum 25-hydroxyvitamin D level with the risk of type 2 diabetes mellitus: a prospective cohort study].
To investigate the correlation of baseline serum 25(OH) D level with the risk of type 2 diabetes mellitus (T2DM) and blood glucose control in diabetic patients among the middle-aged and elderly individuals in Chengguan District of Lanzhou, Gansu Province. Residents aged 40 to 75 years in Lanzhou were selected from the "REACTION" study conducted in 2011 and had been followed up since 2014. A total of 5044 subjects with complete data from the two surveys were analyzed. Participants were divided into Q1, Q2, Q3, and Q4 subgroups based on quartiles of serum 25(OH)D level for comparison of the incidence of T2DM and blood glucose control. Baseline 25(OH)D level was not found to correlate with FPG, 2h-PG or HbA1c levels among the residents (P>0.05). The participants were followed up for a mean of 3.4±0.6 years, and compared with those in Q1 group, the participants in Q2, Q3 and Q4 groups did not show significantly lowered risk of prediabetes or diabetes regardless of glucose tolerance status. Among the patients with T2DM, the compliance rate of glycemic control after the follow-up was significantly higher than that before the follow-up (63.4% vs 60.6%), and the levels of HbA1c, FPG, and 2h-PG decreased obviously after the follow-up. But compared with Q1 group, Q2, Q3 and Q4 groups showed no significant changes in glycemic control compliance rate or levels of HbA1c, FPG and 2h-PG after the follow-up (P>0.05). There is no evidence that baseline 25(OH)D levels are associated with the risk of diabetes and blood glucose control in patients with T2DM.


Bile duct injury after laparoscopic cholecystectomy. The United States experience.
Forty series reporting experience with laparoscopic cholecystectomy in the United States from 1989 to 1995 were reviewed. A total of 114,005 cases were analyzed and 561 major bile duct injuries (0.50%) and 401 bile leaks from the cystic duct or liver bed (0.38%) were recorded. Intraoperative cholangiography (IOC) was attempted in 41.5% of the laparoscopic cholecystectomies and was successful in 82.7%. In major bile duct injuries, the common bile duct/common hepatic duct were the most frequently injured (61.1%) and only 1.4% of the patients had complete transection. When reported, most of the bile duct injuries were managed surgically with a biliary-enteric anastomosis (41.8%) or via laparotomy and t-tube or stent placement (27.5%). The long-term success rate could not be determined because of the small number of series reporting this information. The management for bile leaks usually consisted of a drainage procedure (55.3%) performed endoscopically percutaneously, or operatively. The morbidity for laparoscopic cholecystectomy, excluding bile duct injuries or leaks, was 5.4% and the overall mortality was 0.06%. It was also noted that the conversion rate to an open procedure was 2.16%. It is concluded based on this review of laparoscopic cholecystectomies that the morbidity and mortality rates are similar to open surgery. In addition, the rate of bile duct injuries and leaks is higher than in open cholecystectomy. Furthermore, bile duct injuries can be minimized by lateral retraction of the gallbladder neck and careful dissection of Calot's triangle, the cystic duct-gallbladder junction, and the cystic duct-common bile duct junction.


Confirmation of virtual unmyelinated fiber absence in hereditary sensory neuropathy type IV.
Sural nerves from two unrelated young boys were virtually without unmyelinated fibers (UFs). Small myelinated fibers (MFs) may also have been slightly reduced in number. Since no degeneration or regeneration is observed, UF absence is assumed to be congenital, due to either lack of neuron formation or to premature degeneration. The main clinical features of this inherited sensory neuropathy (previously identified by us as type IV) are the inherited nature and abnormality of nociception, of sweating, and of thermal regulation associated with mild mental retardation. Our findings confirm the congenital absence of UFs of cutaneous nerves in cases such as these and provide further evidence that this disorder has a different natural history and pathology than do the other three types of hereditary sensory neuropathy.


Silk-Based Bioinks for 3D Bioprinting.
3D bioprinting field is making remarkable progress; however, the development of critical sized engineered tissue construct is still a farfetched goal. Silk fibroin offers a promising choice for bioink material. Nature has imparted several unique structural features in silk protein to ensure spinnability by silkworms or spider. Researchers have modified the structure-property relationship by reverse engineering to further improve shear thinning behavior, high printability, cytocompatible gelation, and high structural fidelity. In this review, it is attempted to summarize the recent advancements made in the field of 3D bioprinting in context of two major sources of silk fibroin: silkworm silk and spider silk (native and recombinant). The challenges faced by current approaches in processing silk bioinks, cellular signaling pathways modulated by silk chemistry and secondary conformations, gaps in knowledge, and future directions acquired for pushing the field further toward clinic are further elaborated.


Prevention of CD40-triggered dendritic cell maturation and induction of T-cell hyporeactivity by targeting of Janus kinase 3.
Pharmacological targeting of Janus kinase 3 (JAK3) has been employed successfully to control allograft rejection and graft-vs.-host disease (GVHD). Recent evidence suggests that in addition to its involvement in common-gamma chain (cgamma) signaling of cytokine receptors, JAK3 is also engaged in the CD40 signaling pathway of peripheral blood monocytes. In this study, we assessed the consequences of JAK3 inhibition during CD40-induced maturation of myeloid dendritic cells (DCs), and tested the impact thereof on the induction of T-cell alloreactivity. Dendritic cells triggering through CD40 induced JAK3 activity, the expression of costimulatory molecules, production of IL-12, and potent allogeneic stimulatory capacity. In contrast, JAK3 inhibition with the rationally designed JAK3 inhibitor WHI-P-154 prevented these effects arresting the DCs at an immature level. Interestingly, DCs exposed to the JAK3-inhibitor during CD40-ligation induced a state of hyporeactivity in alloreactive T cells that was reversible upon exogenous IL-2 supplementation to secondary cultures. These results suggest that immunosuppressive therapies targeting the tyrosine kinase JAK3 may also affect the function of myeloid cells. This property of JAK3 inhibitors therefore represents a further level of interference, which together with the well-established suppression of cgamma signaling could be responsible for their clinical efficacy.


The SCOPE-PC instrument for assessing patient safety culture in primary care: a psychometric evaluation.
Primary healthcare differs from hospitals in terms of - inter alia - organisational structure. Therefore, patient safety culture could differ between these settings. Various instruments have been developed to measure collective attitudes of personnel within a primary healthcare organisation. However, the number of valid and reliable instruments is limited. Psychometric properties of the SCOPE-Primary Care instrument were tested to examine the instrument's applicability in home care services in Belgium. A cross-sectional study was conducted by administering the SCOPE-PC questionnaire in a single home care organisation with more than 1000 employees, including nurses, midwives, healthcare assistants, diabetes educators and nursing supervisors. First, a confirmatory factor analysis was performed to test whether the observed dataset fitted to the proposed seven-factor model of the SCOPE-PC instrument. Second, Cronbach's alphas were calculated to examine internal consistency reliability. Finally, the instrument's validity was also examined. In total, 603 questionnaires were retained for further analysis, representing an overall response rate of 43.9%. Most respondents were nursing staff, followed by healthcare assistants and nursing supervisors. The results of the confirmatory factor analyses satisfied the chosen cut-offs, indicating an acceptable to good model fit. With the exception of the dimension 'organizational learning' (0.58), Cronbach's alpha scores of the SCOPE-PC scales indicated a good level of internal consistency: 'open communication and learning from error' (0.86), 'handover and teamwork' (0.78), 'adequate procedures and working conditions' (0.73), 'patient safety management' (0.81), 'support and fellowship' (0.75), and 'intention to report events (0.85). Moreover, inter-correlations between the seven dimensions as well as with the patient safety grade were moderate to good. The present study indicated that the SCOPE-Primary Care instrument has good psychometric properties for home care services in Belgium. No modifications are required to the original questionnaire in order to allow benchmarking between primary healthcare settings.


Molecularly Engineered 6FDA-Based Polyimide Membranes for Sour Natural Gas Separation.
Glassy polyimide membranes are attractive for industrial applications in sour natural gas purification. Unfortunately, the lack of fundamental understanding of relationships between polyimide chemical structures and their gas transport properties in the presence of H2 S constrains the design and engineering of advanced membranes for such challenging applications. Herein, 6FDA-based polyimide membranes with engineered structures were synthesized to tune their CO2 /CH4 and H2 S/CH4 separation performances and plasticization properties. Under ternary mixed sour gas feeds, controlling polymer chain packing and plasticization tendency of such polyimide membranes via tuning the chemical structures were found to offer better combined H2 S and CO2 removal efficiency compared to conventional polymers. Fundamental insights into structure-property relationships of 6FDA-based polyimide membranes observed in this study offer guidance for next generation membranes for sour natural gas separation.


Captopril reduced plasminogen activator inhibitor activity in patients with acute myocardial infarction.
Recent clinical trials have demonstrated that the administration of angiotensin-converting enzyme (ACE) inhibitors to patients with myocardial infarction reduces the incidence of recurrent myocardial infarction. It has also been reported that an elevated level of plasminogen activator inhibitor (PAI) appears to constitute a marker of the risk of recurrent coronary thrombosis. To determine whether the ACE inhibitor captopril reduces plasma PAI inhibitor activity, we measured changes in plasma PAI activity (IU/ml), tissue plasminogen activator (t-PA) antigen (ng/ml), and serum ACE activity (IU/L) in 14 survivors of myocardial infarction receiving captopril therapy (37.5 mg daily) and compared them with the values in 15 placebo-treated patients chosen at random. Blood sampling was performed at 07.00 h. In the captopril-treated group, serum ACE activity decreased significantly, from 14.0 +/- 0.8 to 11.5 +/- 1.2 IU/L 24 h after captopril therapy (p < 0.01), and those of PAI activity and t-PA antigen also decreased significantly-from 11.9 +/- 2.8 to 5.5 +/- 2.2 IU/ml (p < 0.02) and from 9.9 +/- 1.0 to 7.5 +/- 0.9 ng/ml (p < 0.05), respectively 48 h after captopril therapy. However, the levels of ACE activity, PAI activity, and t-PA antigen remained unchanged during the study period in the placebo group. Thus, our data indicate that the administration of captopril to patients with acute myocardial infarction may result in a reduced frequency of recurrent coronary thrombosis by increasing fibrinolytic capacity.


Evaluation of the Reliability of Cone-beam Computed Tomography Scanning and Electronic Apex Locator Measurements in Working Length Determination of Teeth with Large Periapical Lesions.
This study evaluates the endodontic working-length measurements in teeth with large periapical lesions and persistent intracanal exudate by using preexisting cone-beam computed tomography (CBCT). It compares the measurements with clinical root canal lengths determined by using 2 electronic apex locators. All patients had undergone a CBCT scan independent of the present study and needed root canal treatment of at least 1 tooth visible in the field of view. Seventy-three teeth with single roots and canals were studied. An endodontist measured each root canal length with 2 different electronic apex locators. The measurements were repeated 3 times by using a digital caliper, and the mean was recorded. This mean was compared with the root canal length as measured on CBCT sections by an oral radiologist not involved in the endodontic treatment. The CBCT measurements were taken twice for analysis of intrarater reliability. The data were statistically analyzed. There were no significant measurement differences between the methods used (P > .05). In teeth with large periapical lesions and persistent intracanal exudate, measurement of the root canal length by using CBCT was as reliable as measurements that used apex locators.


[The life cycle of Rubella Virus].
Rubella virus (RV), an infectious agent of rubella, is the sole member of the genus Rubivirus in the family of Togaviridae. RV has a positive-stranded sense RNA as a genome. A natural host of RV is limited to human, and rubella is considered to be a childhood disease in general. When woman is infected with RV during early pregnancy, her fetus may develop severe birth defects known as congenital rubella syndrome. In this review, the RV life cycle from the virus entry to budding is illustrated in comparison with those of member viruses of the genus alphavirus in the same family. The multiple functions of the RV capsid protein are also introduced.


Expressing Redundancy among Linear-Epitope Sequence Data Based on Residue-Level Physicochemical Similarity in the Context of Antigenic Cross-Reaction.
Epitope-based design of vaccines, immunotherapeutics, and immunodiagnostics is complicated by structural changes that radically alter immunological outcomes. This is obscured by expressing redundancy among linear-epitope data as fractional sequence-alignment identity, which fails to account for potentially drastic loss of binding affinity due to single-residue substitutions even where these might be considered conservative in the context of classical sequence analysis. From the perspective of immune function based on molecular recognition of epitopes, functional redundancy of epitope data (FRED) thus may be defined in a biologically more meaningful way based on residue-level physicochemical similarity in the context of antigenic cross-reaction, with functional similarity between epitopes expressed as the Shannon information entropy for differential epitope binding. Such similarity may be estimated in terms of structural differences between an immunogen epitope and an antigen epitope with reference to an idealized binding site of high complementarity to the immunogen epitope, by analogy between protein folding and ligand-receptor binding; but this underestimates potential for cross-reactivity, suggesting that epitope-binding site complementarity is typically suboptimal as regards immunologic specificity. The apparently suboptimal complementarity may reflect a tradeoff to attain optimal immune function that favors generation of immune-system components each having potential for cross-reactivity with a variety of epitopes.


Comparison of microbial contamination levels among hospital operating rooms and industrial clean rooms.
Microbial contamination in industrial clean rooms was compared quantitatively and qualitatively with that of hospital operating rooms. The number of aerobic mesophilic microorganisms which accumulated on stainless-steel strips exposed for periods up to 21 weeks to the intramural air of four operating rooms was at least 1 log higher than the accumulation on strips exposed in four clean rooms, and was essentially the same as that found in two factory areas. Volumetric air samplings showed that there were significantly higher numbers of airborne viable particles per cubic foot of air in operating rooms than in industrial clean rooms. In contrast to clean rooms, where most of the airborne contaminants were those associated with human hair, skin, and respiratory tract, the hospital operating rooms showed a very high level of microorganisms associated with dust and soil.


V2 ACHER: Visualization of complex trial data in pharmacometric analyses with covariates.
Pharmacometric models can enhance clinical decision making, with covariates exposing potential contributions to variability of subpopulation characteristics, for example, demographics or disease status. Intuitive visualization of models with multiple covariates is needed because sparsity of data in visualizations trellised by covariate values can raise concerns about the credibility of the underlying model. V2 ACHER, introduced here, is a stepwise transformation of data that can be applied to a variety of static (non-ordinary-differential-equation-based) pharmacometric analyses. This work uses four examples of increasing complexity to show how the transformation elucidates the relationship between observations and model results and how it can also be used in visual predictive checks to confirm the quality of a model. V2 ACHER facilitates consistent, intuitive, single-plot visualization of a multicovariate model with a complex data set, thereby enabling easier model communication for modelers and for cross-functional development teams and facilitating confident use in support of decisions.


Ridge count thresholding to uncover coordinated networks during onset of the Covid-19 pandemic.
In order to combat information operations (IO) and disinformation campaigns, one must look at the behaviors of the accounts pushing specific narratives and stories through social media, not at the content itself. In this work, we present a new process for extracting tweet storms and uncovering networks of accounts that are working in a coordinated fashion using ridge count thresholding (RCT). To do this, we started with a dataset of 60 million individual tweets from the early weeks of the Covid-19 pandemic. Coherent topics are extracted from this data by testing three different preprocessing pipelines and applying Orthogonal Nonnegative Matrix Factorization (ONMF). The most effective preprocessing pipeline used hashtag preclustering to downselect the total dataset to the 7 million tweets that included the top hashtags. Each topic identified by ONMF is described by a topic-tweet signal, crafted using the time stamp included in each tweet's metadata. These signals were broken down into tweet storms using RCT, which is calculated from the Dynamic Wavelet Fingerprint transform of each topic-tweet signal. Each tweet storm described a time of increased activity around a topic. Tweet storms identified in this way each represent some behavior in the underlying network. In total, we identified 39,817 total tweet storms that included about 2 million unique tweets. These tweet storms were used to identify networks of accounts that commonly co-occur within tweet storms to isolate those communities most responsible for driving narratives and pushing stories through social media. Through this process, we were able to identify 22 unique networks of accounts that were densely connected based on RCT tweet storm identification. Many of the identified networks exhibit obvious inauthentic behaviors that are potentially a part of an IO campaign.