Pyruvate kinase isozymes in various tissues of rat, and increase of spleen-type pyruvate kinase in liver by injecting chromatins from spleen and tumor.
Pyruvate kinase [EC 184.108.40.206] in various tissues of rats was separable into seven kinds of pI-isozymes by isoelectric separation with Ampholine carrier ampholytes; pI 5.4-isozyme, pI 5.6-isozyme, pI 6.2-isozyme (2 kinds), pI 6.6-isozyme, pI 7.4-isozyme, and pI 7.8-isozyme. Some of these pI-isozymes contained bound fructose 1,6-diphosphate (FDP). The bound FDP was completely dissociated when the pI-isozymes were salted out with ammonium sulfate. In the FDP-free form, pyruvate kinase was classified into three types, liver-type (type L) of pI 6.2, muscle-type (type M) of pI 7.4, and spleen-type (type M2) of pI 7.8. The liver-type isoenzyme had two kinds of FDP-binding sites; the pI 5.6-isozyme and pI 5.4-isozyme were obtained when one and two kinds of sites were bound with FDP, respectively. The association and dissociation of FDP at both sites were reversible in the presence and absence of 0.15 M KC1 (high ionic strength). The muscle-type isoenzyme had no FDP-binding site. The spleen-type isoenzyme had two kinds of FDP-binding sites, like the liver-type isoenzyme. When the ionic strength of solutions containing the enzyme and FDP was sufficiently low, one and two kinds of the sites could bind with FDP, converting the enzyme into pI 6.6-isozyme and pI 6.2-isozyme, respectively. FDP bound with one kind of site (the 2nd site) was easily dissociable, but FDP bound with the other kind of site (the 1st site) was not. Provided that the 1st site carried bound FDP, the 2nd site was associable at high ionic strength. The liver-type isoenzyme free of FDP and the spleen-type isoenzyme bound with FDP at both sites had similar pI values of 6.2 and were not separable by isoelectric separation. Some properties of these pI-isozymes were compared. When Rhodamine sarcoma was transplanted in rats, the content of spleen-type isoenzyme in the livers increased. When rats were injected with chromatin prepared from either Rhodamine sarcoma or spleen, the content of spleen-type isoenzyme in the livers again increased. This was not observed on the injection of chromatin prepared from liver, indicating that the factor capable of controlling the gene expression was present in chromatins of sarcoma and spleen but barely or not at all in chromatin of liver.


Period Prevalence of COVID-19 and Influenza Symptoms in 2022 Among Adults in Jazan, Saudi Arabia.
Seasonal influenza and the circulating new variants of coronavirus disease 2019 (COVID-19) were predicted to increase the risk of developing respiratory symptoms in 2022. The objective of this study was to estimate the period prevalence of respiratory symptoms associated with COVID-19 and influenza among adults in 2022. This cross-sectional study targeted adults in Jazan, Saudi Arabia. Data collection was performed in February 2023 and utilized an online approach. The assessment was performed via a self-administered questionnaire, which measured demographics, vaccination practices against COVID-19 and influenza, and the occurrence of respiratory symptoms in 2022. This study involved 625 participants, 65% of whom were women with a mean age of 23 years. Only 80 participants (13%) reported receiving the influenza vaccine in 2022. The most frequently reported symptoms were headache (55%), sore throat (43.7%), and fever (43%). Nearly 34% were diagnosed with influenza, 17% were diagnosed with COVID-19, and 8% reported coinfection of both diseases. Sixty-one percent reported the occurrence of symptoms more than once in 2022. The presence of a higher frequency of respiratory symptoms was associated with gender, age, social status, employment, asthma, and obesity (P < 0.05). A majority of the participants reported multiple occurrences of respiratory symptoms in 2022. The uptake of the influenza vaccine was low in the same year, suggesting a need for a targeted approach to enhance vaccination rates among vulnerable groups.


Localization of soft modes at the depinning transition.
We characterize the soft modes of the dynamical matrix at the depinning transition, and compare the matrix with the properties of the Anderson model (and long-range generalizations). The density of states at the edge of the spectrum displays a universal linear tail, different from the Lifshitz tails. The eigenvectors are instead very similar in the two matrix ensembles. We focus on the ground state (soft mode), which represents the epicenter of avalanche instabilities. We expect it to be localized in all finite dimensions, and make a clear connection between its localization length and the Larkin length of the depinning model. In the fully connected model, we show that the weak-strong pinning transition coincides with a peculiar localization transition of the ground state.


Apraxia, mechanical problem solving and semantic knowledge: contributions to object usage in corticobasal degeneration.
To investigate the nature of the apraxia in corticobasal degeneration (CBD) five patients with CBD and five matched controls were compared on tests of: i) meaningless and symbolic gesture production, ii) a battery of semantic tasks based on 20 everyday items (involving naming and picture-picture matching according to semantic attributes, matching gestures-to-objects, object usage from name and with the real object) and iii) a novel tool test of mechanical problem solving. All five patients showed severe impairment in the production of meaningless and symbolic gestures from command, and by imitation, and were also impaired when using real objects. Deficits were not, however, restricted to action production: four were unable to match gestures to objects and all five showed impairment in the selection and usage of novel tools in the mechanical problem solving task. Surprising was the finding of an additional semantic knowledge breakdown in three cases, two of whom were markedly anomic. The apraxia in CBD is, therefore, multifactorial. There is profound breakdown in the organisation and co-ordination of motor programming. In addition, patients show central deficits in action knowledge and mechanical problem solving, which has been linked to parietal lobe pathology. General semantic memory may also be affected in CBD in some cases and this may then contribute to impaired object usage. This combination of more than one deficit relevant for object use may explain why CBD patients are far more disabled by their dyspraxia in everyday life than any other patient group.


Serum prostatic acid phosphatase (PAP): monoclonal enzyme-linked immunoassay compared to polyclonal radioimmunoassay.
A new enzyme linked immunosorbent assay (ELISA) kit which utilizes a monoclonal antibody against prostatic acid phosphatase (PAP) was compared with current radioimmunoassay (RIA) methodology which uses a polyclonal antibody. Both assays are double antibody immunoassays with the major difference being the method of antibody preparation. A study of intrarun precision using control material showed an average within run coefficient of variation (CV) percent as 7.0 percent and 6.9 percent for ELISA and RIA, respectively, while between run CV percent averaged 11.1 percent and 11.5 percent, respectively. Thus, precision results compare similarly between the two assays. The specificity showed significantly different results. Patterns of correlation between the two methods indicate differing specificities of the primary antibodies. The values for ELISA were greater than RIA for control sera and patient samples when values fell outside the reference range; however, RIA values exceeded ELISA values with patient samples which fell within the reference ranges as provided by each manufacturer. Therefore, there exists a question of specificity of antibody employed in each of the two assays. The PAP antigen is prepared from two different sources for each kit. The ELISA manufacturer prepares antigen from seminal fluid and RIA manufacturer prepares antigen from normal human prostate. The question of specificity may be influenced by: (1) source of antigen used in immunizing animals and (2) monoclonal versus polyclonal means of producing antibody.


The plaque-removing efficacy of a finger brush (I-Brush).
The purpose of the present study was to test the effectiveness of a finger toothbrush (I-Brush) in removing plaque compared with a flat-trimmed manual toothbrush. For this study, 37 subjects were selected, without previous experience of the use of the I-Brush. Each subject received a finger brush (I-Brush), a manual toothbrush (Butler GUM 311), two written brushing instructions for both types of brushes, and a brush calendar. Subjects were given a period of 3 weeks to become familiar with the two types of brushes. During this period, the subjects were instructed to use the two types of brushes on alternate days. The brush calendar helped as a reminder and served to ensure compliance. No instructions regarding brushing time or frequency of brushing were given to the subjects, except that they should conform to their usual oral habits. After 3 weeks, all subjects were asked to abstain from oral hygiene procedures for 48 h prior to the experiment. In this experiment, the amount of dental plaque was scored by a trained examiner. The examiner (N.A.M.R.) used the modified Silness & Loe (1964) plaque index at six sites per tooth. After scoring, each subject received a new finger brush and a new manual toothbrush. The subjects brushed according to a split mouth protocol. Two contra-lateral quadrants were chosen randomly and were brushed with one randomly chosen brush and the two opposing contra-lateral quadrants with the alternate brush. The brushing was performed under supervision in front of a mirror. The available time for brushing was 2 min. for the entire dentition. Finally, the remaining plaque was scored again. The overall reduction in plaque was 79% for the manual toothbrush and 62% for the finger brush. The plaque removing efficacy of the finger brush was poorest at the approximal vestibular surfaces (55% plaque reduction) compared with the manual toothbrush (77% plaque reduction). The plaque reduction of the finger brush is not an acceptable alternative to the use of a regular manual toothbrush.


International Classification of Functioning, Disability and Health categories explored for self-rated participation in Swedish adolescents and adults with a mild intellectual disability.
To explore internal consistency and correlations between perceived ability, performance and perceived importance in a preliminary selection of self-reported items representing the activity/participation component of the International Classification of Functioning, Disability and Health (ICF). Structured interview study. Fifty-five Swedish adolescents and adults with a mild intellectual disability. Questions about perceived ability, performance and perceived importance were asked on the basis of a 3-grade Likert-scale regarding each of 68 items representing the 9 ICF domains of activity/participation. Internal consistency for perceived ability (Cronbach's alpha for all 68 items): 0.95 (values for each domain varied between 0.57 and 0.85), for performance: 0.86 (between 0.27 and 0.66), for perceived importance: 0.84 (between 0.27 and 0.68). Seventy-two percent of the items showed correlations >0.5 (mean=0.59) for performance vs perceived importance, 41% >0.5 (mean=0.47) for perceived ability vs performance and 12% >0.5 (mean=0.28) for perceived ability vs perceived importance. Measures of performance and perceived importance may have to be based primarily on their estimated clinical relevance for describing aspects of the ICF participation concept. With a clinimetric approach, parts of the studied items and domains may be used to investigate factors related to different patterns and levels of participation, and outcomes of rehabilitation.


No evidence of enteroviruses in the intestine of patients with type 1 diabetes.
The purpose of this study was to investigate whether the gut mucosa is a reservoir for enterovirus persistence in patients with type 1 diabetes. Small intestine biopsy samples from 25 individuals at different stages of type 1 diabetes, 21 control individuals and 27 individuals with coeliac disease were analysed for the presence of enterovirus RNA by using both radioactive in-situ hybridisation and real-time RT-PCR and for the presence of enterovirus proteins by immunostaining with antibodies against VP1 and VP4-2-3 capsid proteins and virus polymerase. Lymphocytic enteropathy and serum anti-VP1 antibodies were also evaluated at the time of biopsy. Moreover, high-throughput sequencing was performed to identify viral transcripts or genomes. Enterovirus was not detected by in-situ hybridisation or RT-PCR in any of the individuals tested. Immunohistology revealed a few stained cells in the intestinal epithelium in a low number of individuals, with no difference between diabetic and non-diabetic individuals. Levels of serum IgG against VP1 did not differ between control individuals and those with diabetes or coeliac disease and no evidence of diabetes-related lymphocytic enteropathy was detected. High-throughput sequencing did not reveal specific enterovirus sequences in the gut mucosa of individuals with type 1 diabetes. Prolonged/persistent enterovirus infections in gut mucosa are not common in patients with type 1 diabetes.


Education to address medical error--a role for high fidelity patient simulation.
To describe and evaluate a simulation based course that emphasizes the role of teamwork in the management of both crises and errors. The course allowed participants to experience and manage simulated crises. Emphasis was placed on important error management strategies such as communication, leadership and delegation of workload. A computerized mannequin that is physiologically and pharmacologically responsive was used to run life-like crisis scenarios. The scenarios were videotaped and reviewed during a debriefing discussion after each crisis. Scenarios were alternated with tutorials that addressed error management, communication and medico-legal issues. Participants evaluated the courses using 5-point Likert scales and free comments. In 1999 and 2000, 172 participants (34% of New Zealand anaesthetists) attended one of these courses. Evaluation forms were received from 151 participants (88%). The global evaluations had median scores of 4 or 5 and all respondents would recommend the course to others. The responses from 50 participants indicated that the course should be repeated at least every two years. New Zealand anaesthetists found this an acceptable and useful form of training. Teamwork is an effective strategy in crisis management and error reduction and is worthy of consideration within the broader context of medical education.


Community based participatory research of breastfeeding disparities in African American women.
OBJECTIVE: Lack of support for breastfeeding mothers has been consistently identified in the literature as a barrier for breastfeeding across racial and ethnic groups. Using a community-based participatory approach, academic and community-based partners conducted an iterative process to assess barriers, facilitators and potential mediating interventions for breastfeeding in the African-American community in Durham, North Carolina. METHODS: Eight focus groups were conducted with African-American mothers, fathers and grandmothers. Researchers transcribed and coded each focus group and analyzed using Atlas ti. 5.2. Patterns and themes that emerged informed the development of community stakeholder interviews; 41 interviews were conducted with community representatives. These findings informed the development of a support group pilot intervention. The pilot support groups were evaluated for increase in knowledge of attendees. RESULTS: Focus group and community interviews indicate that African Americans may disproportionately experience inadequate support for breastfeeding. This lack of support was reported in the home, the workplace, among peers, and from healthcare providers. The pilot support groups resulted in increased knowledge of breastfeeding among group participants OR=3.6 (95% CI: 2.5, 5.2). CONCLUSIONS: The findings from this research underscore the importance of a multi-level approach to breastfeeding support for African American women to address breastfeeding disparities.


[Change of zero-stress state of portal vein in the rat during the pathogenesis of intrahepatic portal hypertension].
A model of intrahepatic portal hypertension was established in SD rats by injection of carbon tetrachloride (CCl4). By observing the opening angle of the portal vein, the zero-stress state of the portal veins was studied at different time during the pathogenesis of intrahepatic portal hypertension. After CCl4 injection, the opening angles of the portal veins were increased, in the tenth week, they were much greater than those in the corresponding controls (P<0.05). The results suggest that during the pathogenesis of portal hypertension, unequal remodeling exists in the portal veins to change its biomechanical properties, and the residual stress and strain of the portal veins in portal hypertensive rats are greater than those in normal controls.


[A new imaging FTIR spectroradiometer].
According to the characteristic of single-element detector and non-imaging spectroradiometer, a new imaging FTIR spectroradiometer system was developed for spectral data acquisition This system is composed of a spectroradiometer, a synchronous controller and a scanning device. Using the data interface of spectroradiometer, spectral radiometric calibration can be achieved for the system. The image resolution is 500 x 500 pixels, spectral range is 667-5000 cm(-1), spectral resolution is 1 cm(-1), and space Field of view is 150 degrees, Instant Field of View is 0.3 degrees. Experiments were held for actual data acquisition and data analysis was made. The analysis result indicates that the proposed system is adequate for non-realtime imaging spectral data acquisition


Evaluating phylogenetic informativeness as a predictor of phylogenetic signal for metazoan, fungal, and mammalian phylogenomic data sets.
Phylogenetic research is often stymied by selection of a marker that leads to poor phylogenetic resolution despite considerable cost and effort. Profiles of phylogenetic informativeness provide a quantitative measure for prioritizing gene sampling to resolve branching order in a particular epoch. To evaluate the utility of these profiles, we analyzed phylogenomic data sets from metazoans, fungi, and mammals, thus encompassing diverse time scales and taxonomic groups. We also evaluated the utility of profiles created based on simulated data sets. We found that genes selected via their informativeness dramatically outperformed haphazard sampling of markers. Furthermore, our analyses demonstrate that the original phylogenetic informativeness method can be extended to trees with more than four taxa. Thus, although the method currently predicts phylogenetic signal without specifically accounting for the misleading effects of stochastic noise, it is robust to the effects of homoplasy. The phylogenetic informativeness rankings obtained will allow other researchers to select advantageous genes for future studies within these clades, maximizing return on effort and investment. Genes identified might also yield efficient experimental designs for phylogenetic inference for many sister clades and outgroup taxa that are closely related to the diverse groups of organisms analyzed.


How do internal medicine residency programs evaluate their resident float experiences?
We surveyed the nation's internal medicine residency training program directors to determine the range and frequency of existing methods by which float experiences are evaluated. We sent questionnaires to the program directors of all 396 internal medicine residency training program sites in the country. Information requested included program characteristics, months devoted to float experiences in each year of training, and the location and purpose of the rotation. Program directors were also asked to choose among descriptors characterizing the evaluative process. There were 139 responding programs (39%), 134 with data that could be aggregated. Responding programs were similar to all programs nationally in the distributions of size and university sponsorship. Overall, 76% of programs employed a night float for any period of time, and 71% currently had one, on average for 6.7 years. Mean months of float experience during residency was 2.4 months, significantly longer in programs that were not university based. Float experiences were evaluated in 89% of those programs who employed them, with ten different methods reported. University-based programs were significantly less likely to use chart review as a method of evaluation, but no other differences in methodology were significant. Float rotations are common among internal medicine residency training programs. Evaluative methods vary, but one or more are applied in the vast majority of programs.


[Tuberculosis cutis colliquativa in lymph node tuberculosis].
We report on the case of a 75-year-old woman patient with tuberculosis colliquativa cutis (scrofuloderma). The skin lesions had developed from a cervical lymph node tuberculosis. The diagnosis was made by culturing biopsied skin and underlying lymph node. Under a triple drug regimen the skin lesions cleared within 2 months. Lymph nodes appeared to be normal after 6 months. Diagnostic and therapeutic approaches to scrofuloderma and cervical lymph node tuberculosis are discussed.


Ultrasound: an extension of clinical examination.
To study the impact the use of portable ultrasound can have for the benefit of the patients when used by doctors other than radiologist, in this case surgeons. Ultrasound performed by surgeons in the pre-operative, operative and post-operative period was studied. Patients presenting to the Hospital with acute abdomen was subjected to ultrasound. They were either pre-operative or post-operative patients. Five patients were scanned intraoperatively. The impact of these scans to the patients as well as the clinicians was studied. This is an ongoing study and preliminary results of the scans show two pre-operative diagnosis of acute appendicular collection and one acute hydronephrosis. In the operation room, ultrasound was done on 5 cases. On three occasions, it was to locate renal stones so that it could be extracted with ease. On two of the case, it was t to confirm the adequacy of common bile duct exploration thereby allowing primary closure of the common bile duct. Post-operatively, it was used in four cases of which in two cases post-operative hemorrhage were detected timely within hours. In the other two cases, the surgical team was assured that the patient's complaint was not surgically related. Ultrasound should be an extension of the clinical examination when indicated and all clinicians should be proficient in its use in their respective fields.


Docosahexaenoic acid induces proteasome-dependent degradation of beta-catenin, down-regulation of survivin and apoptosis in human colorectal cancer cells not expressing COX-2.
n-3 Polyunsaturated fatty acids have been shown to powerfully inhibit the growth of colon cancer cells, mainly acting as pro-apoptotic agents through inhibition of cycloxygenase-2 (COX-2) expression. Since dysregulation of beta-catenin expression is frequently found at early stage of colorectal carcinogenesis, we analyzed whether docosahexaenoic acid (DHA) may modify the expression of beta-catenin in colon cancer cells (SW480 and HCT116) over-expressing this protein, but lacking COX-2. Futhermore, we investigated if alterations in beta-catenin expression may be associated with apoptosis induction. Treatment of cells with increasing concentrations of DHA induced a dose- and time-dependent inhibition of beta-catenin protein expression which, however, was not accompanied by modifications in beta-catenin transcription. Conversely, the proteasomal inhibitors MG132 and lactacystin prevented DHA-induced beta-catenin decrease, suggesting that DHA may regulate the proteasomal degradation of beta-catenin. The reduced levels of beta-catenin were accompanied by decreased translocation of beta-catenin into the nucleus, where it acts as a transcription factor in concert with T-Cell Factor (TCF). DHA, at the same range of concentrations, was also able to induce apoptosis by a caspase-3-dependent mechanism and to cause a dose- and time-dependent decrease of survivin, an apoptosis inhibitor undetectable in normal tissues and expressed in colorectal cancer through TCF-beta-catenin stimulation. Several other proteins regulated by the TCF-beta-catenin pathway and involved in regulation of tumor growth were down-regulated by DHA, including peroxisome proliferator-activated receptor-delta, membrane type 1 (MT1)-matrix metalloproteinase (MMP), MMP-7 and vascular endothelial growth factor. The present study, thus, raises the possibility that DHA may exert pro-apoptotic and antitumoral effects through proteasomal regulation of beta-catenin levels and alterations in the expression of TCF-beta-catenin target genes.


[Congenital sternal cleft].
Congenital sternal cleft is a rare malformation. Little more than one hundred cases have been published, and rarely more than two cases are published in a single publication. We present five new cases that show the entire spectrum of defects. They were 3 males and 2 females. Age range between 1 day and 5 years of age. There were 2 supraxiphoid clefts (SC), 2 gladiolar defects and 1 xiphoid cleft. We evaluate the demographics, associated malformations, mode of treatments and results. The SC were not associated to congenital herat malformations, but with a many other malformative spectrum (anterior cervical web, hemangiomatosis, CNS malformations, coloboma and pectus excavatum). The two females had SC and were operated on the 24th and 30th days of age. The first one developed a superior vena cava síndrome for a few days after surgery and a moderate pectus excavatum that did not required surgery. A midline cervical web was also surgically repaired at 10 years of age. The second patient with SC was treated with interferon alfa-2a and local infiltration of corticosteroid for treatment of hemangiomatosis. Both patients had excellent final results (follow up 11 and 5 years respectively). Gladiolar clefts were observed durign surgical repair of congenital Herat malformations (ventricular septal defect and partial anomalous of pulmonary venous draninage). They were repaired by direct closure of the defect. The patient with the xiphoid cleft had associaed a Cantrell pentalogy. He died 4 days after operation because of extreme prematurity and pulmonary vascular hypertenion. 1) We have observed five new cases of sternal cleft. 2) Each anatomical variety had their own mode of presentation, a different malformative spectrum and clinical evolution that are based on a distinct embryonic origin. 3) Excluding the xiphoid clefts, the long term surviving is 100%, but they are associated with a great variety of other congenital defects.


Knockdown and Mortality of Five Stored Product Beetle Species After Short Exposures of Thiamethoxam.
Laboratory bioassays were conducted to evaluate the effectiveness of thiamethoxam, against five major stored-grain beetle species, the lesser grain borer, Rhyzopertha dominica (F.), the rice weevil, Sitophilus oryzae (L.), the confused flour beetle, Tribolium confusum Jacquelin du Val, the larger grain borer, Prostephanus truncatus (Horn), and the sawtoothed grain beetle, Oryzaephilus surinamensis (L.). Adults of the above species were exposed on wheat (or maize in the case of P. truncatus) treated with thiamethoxam at 0.1, 1, and 10 ppm for 0, 2, 4, 6, 8, 16, 40, 72, and 96 h. After each of these intervals, mortality was recorded (immediate mortality) and the surviving individuals were transferred in untreated wheat (or maize), where mortality was recorded again 7 d later (delayed mortality). During both immediate and delayed mortality counts, the number of adults that were knocked down was also recorded. Immediate mortality was low in all exposures, with the exception of the highest dose rate and after 72-96 h. At these conditions, during this interval, most of the surviving individuals were knocked down. Delayed mortality was further increased with the increase of dose and the initial exposure, but knockdown was extremely low, with the exception of P. truncatus. The results of the present work show that O. surinamensis was the least susceptible species, while P. truncatus was the most susceptible. These findings show that, despite the increased mortality, recovery after short exposures is likely for all species tested here. In this regard, partially treated areas on which the insects are exposed only for short intervals may reduce thiamethoxam efficacy.


Functionalized single-walled carbon nanotubes: cellular uptake, biodistribution and applications in drug delivery.
The unique properties of single-walled carbon nanotubes (SWNTs) enable them to play important roles in many fields. One of their functional roles is to transport cargo into cell. SWNTs are able to traverse amphipathic cell membranes due to their large surface area, flexible interactions with cargo, customizable dimensions, and surface chemistry. The cargoes delivered by SWNTs include peptides, proteins, nucleic acids, as well as drug molecules for therapeutic purpose. The drug delivery functions of SWNTs have been explored over the past decade. Many breakthrough studies have shown the high specificity and potency of functionalized SWNT-based drug delivery systems for the treatment of cancers and other diseases. In this review, we discuss different aspects of drug delivery by functionalized SWNT carriers, diving into the cellular uptake mechanisms, biodistribution of the delivery system, and safety concerns on degradation of the carriers. We emphasize the delivery of several common drugs to highlight the recent achievements of SWNT-based drug delivery.


Effect of chronic NG-nitro-L-arginine methyl ester (L-NAME) on blood pressure and renal function in conscious uninephrectomized spontaneously hypertensive rats.
We have studied during 30 days the effect of a low dose of NG-nitro-L-arginine methyl ester (1 mg.kg-1.day-1 in drinking water) in the presence of D- or L-arginine (1 mg.kg-1.day-1 in drinking water) in comparison with D- or L-arginine alone on blood pressure and renal function in conscious uninephrectomized female spontaneously hypertensive rats. At the end of the study, there was a significant increase in systolic blood pressure in the NG-nitro-L-arginine methyl ester + D-arginine group (307 +/- 6 mmHg (1 mmHg = 133.3 Pa), n = 14, p < 0.05) in comparison with NG-nitro-L-arginine methyl ester + L-arginine (281 +/- 6 mmHg, n = 14), L-arginine (262 +/- 5 mmHg, n = 13), and D-arginine (258 +/- 7 mmHg, n = 12) groups. There were no changes in diuresis, proteinuria, or sodium and potassium excretion between differently treated animals during this study. These results suggest that in uninephrectomized female spontaneously hypertensive rats, after 1 month blockade of NO synthesis with a low dose of NG-nitro-L-arginine methyl ester, vasculature is under tonic control by NO and it is not correlated with renal dysfunction.


Outcome of esophageal cancer in the elderly - systematic review of the literature.
As the population ages, the number of elderly patients with esophageal cancer increases. Esophageal cancer has a poor prognosis and is associated with decreased life quality. To review the literature about the outcome of esophageal cancer in patients over 65. Articles published between January 2006 and November 2016 in the PubMed/Medline and ResearchGate databases were reviewed. Nineteen retrospective studies were included. Six thousand seven hundred and twenty-nine patients over 65 were analyzed. Thirty-day mortality ranges from 3.2% to 8.1%. Overall 5-year survival rates range from 0% to 49.2%, and the median survival rate ranges from 9.6 to 108.2 months. The incidence of complications in the surgery group ranges from 27% to 69%. Chemoradiotherapy grade ≥ 3 toxicity was observed in 22-36% of patients. Chronological age seems to have little influence on outcome of esophageal cancer. Open esophagectomy seems to be the mainstay of treatment for patients with esophageal cancer, regardless of age. There is still high mortality and morbidity involved in this procedure. To reduce them, some less invasive methods are being trialed.


Selection of Differential Isolates of Magnaporthe oryzae for Postulation of Blast Resistance Genes.
A set of differential isolates of Magnaporthe oryzae is needed for the postulation of blast resistance genes in numerous rice varieties and breeding materials. In this study, the pathotypes of 1,377 M. oryzae isolates from different regions of China were determined by inoculating detached rice leaves of 24 monogenic lines. Among them, 25 isolates were selected as differential isolates based on the following characteristics: they had distinct responses on the monogenic lines, contained the minimum number of avirulence genes, were stable in pathogenicity and conidiation during consecutive culture, were consistent colony growth rate, and, together, could differentiate combinations of the 24 major blast resistance genes. Seedlings of rice cultivars were inoculated with this differential set of isolates to postulate whether they contain 1 or more than 1 of the 24 blast resistance genes. The results were consistent with those from polymerase chain reaction analysis of target resistance genes. Establishment of a standard set of differential isolates will facilitate breeding for blast resistance and improved management of rice blast disease.


Occupational Safety and Health Equity Impacts of Artificial Intelligence: A Scoping Review.
Artificial intelligence (AI) has the potential to either reduce or exacerbate occupational safety and health (OSH) inequities in the workplace, and its impact will be mediated by numerous factors. This paper anticipates challenges to ensuring that the OSH benefits of technological advances are equitably distributed among social groups, industries, job arrangements, and geographical regions. A scoping review was completed to summarize the recent literature on AI's role in promoting OSH equity. The scoping review was designed around three concepts: artificial intelligence, OSH, and health equity. Scoping results revealed 113 articles relevant for inclusion. The ways in which AI presents barriers and facilitators to OSH equity are outlined along with priority focus areas and best practices in reducing OSH disparities and knowledge gaps. The scoping review uncovered priority focus areas. In conclusion, AI's role in OSH equity is vastly understudied. An urgent need exists for multidisciplinary research that addresses where and how AI is being adopted and evaluated and how its use is affecting OSH across industries, wage categories, and sociodemographic groups. OSH professionals can play a significant role in identifying strategies that ensure the benefits of AI in promoting workforce health and wellbeing are equitably distributed.


Fixation devices for whole-body 18F-FDG PET/CT: patient perspectives and technical aspects.
To evaluate the use of a fixation device in whole-body postiron emission tomography/computed tomography (PET/CT). Two hundred and thirty patients were prospectively included over a period of 3 months. Different single-phase and multiphase contrast-enhanced PET/CT protocols were used for whole-body examination. An unforced expiration state was applied as breathing protocol for CT examination. Patients were placed on a deflating device (1.0 m x 1.5 m) with arms elevated but supported in order to prevent full extension in shoulders and elbows providing comfortable positioning. Image quality was assessed by means of alignment of the liver quantitatively on co-registered PET/CT images. After the examination, patients were asked to complete a survey on subjective sensations such as pain in different body regions (yes/no). They were asked to give a final evaluation for the whole-body PET/CT examination (comfortable/not comfortable). Additionally, a control group (n=30) was assessed without the aid of additional devices. Examination protocols using the device showed minor misalignment of 5 mm. Different protocols did not reveal significant differences in misalignment. When comparing the control group misalignment was significantly higher with approx. 7 mm. The majority (75%) evaluated the positioning as comfortable despite 46% of the patients in this group feeling more or less severe pain in at least one body region. For controls, misalignment was slightly higher whereas only 39% found the positioning comfortable (chi(2)=13.03; P<0.0005) and 61% reported pain (NS). Both the technical aspects and patient evaluations favour the use of the vacuum device in whole-body PET/CT examinations. In particular, in time consuming protocols using multiphase CT examination the fixation device leads to excellent co-registration quality and patient compliance.


Sex bias and dosage compensation in the zebra finch versus chicken genomes: general and specialized patterns among birds.
We compared global patterns of gene expression between two bird species, the chicken and zebra finch, with regard to sex bias of autosomal versus Z chromosome genes, dosage compensation, and evolution of sex bias. Both species appear to lack a Z chromosome-wide mechanism of dosage compensation, because both have a similar pattern of significantly higher expression of Z genes in males relative to females. Unlike the chicken Z chromosome, which has female-specific expression of the noncoding RNA MHM (male hypermethylated) and acetylation of histone 4 lysine 16 (H4K16) near MHM, the zebra finch Z chromosome appears to lack the MHM sequence and acetylation of H4K16. The zebra finch also does not show the reduced male-to-female (M:F) ratio of gene expression near MHM similar to that found in the chicken. Although the M:F ratios of Z chromosome gene expression are similar across tissues and ages within each species, they differ between the two species. Z genes showing the greatest species difference in M:F ratio were concentrated near the MHM region of the chicken Z chromosome. This study shows that the zebra finch differs from the chicken because it lacks a specialized region of greater dosage compensation along the Z chromosome, and shows other differences in sex bias. These patterns suggest that different avian taxa may have evolved specific compensatory mechanisms.


Exercise Dependence and Body Image Concerns Amongst Group Fitness Instructors: A Self-Determination Theory Approach.
Despite the fact that group fitness instructors serve as significant role models with potentially great impact on class participants' motivation for exercise, they are a very under-researched group. The aim of this study was therefore to examine group fitness instructors' motivational regulations for exercise, and how these motivational regulations can predict symptoms of exercise dependence and body image concerns. Group fitness instructors from the largest fitness companies in Norway (n = 837, response rate: 57%) completed an online survey with reference to the Situational Motivation Scale (SIMS), the Exercise Dependence Scale (EDS), the Eating Disorders Inventory subscales drive for thinness (EDI-DT) and body dissatisfaction (EDI-BD), and their weekly amount of exercise and instruction. The instructors scored high on identified regulation and intrinsic regulation for exercise. EDS total score was positively correlated with all SIMS subscales and weekly instruction was positively correlated with Intrinsic regulation. Multiple hierarchical regression analyses found that both self-determined motivational regulations as well as external regulation positively predicted their EDS score. External regulation positively predicted EDI-DT, and EDI-BD. Group fitness instructors seem highly intrinsically motivated for exercise, which is hypothesized to have a positive impact on group fitness class participants. High self-determined exercise behavior does not seem to buffer against symptoms of exercise dependence within this specific population. There is a need for awareness of group fitness instructors who show high exercise dependency scores due to the link to body image concerns, amotivation and external regulated motivation.


Multimodal repertoire analysis unveils B cell biology in immune-mediated diseases.
Despite the involvement of B cells in the pathogenesis of immune-mediated diseases (IMDs), biological mechanisms underlying their function are scarcely understood. To overcome this gap, here we constructed and investigated a large-scale repertoire catalogue of five B cell subsets of patients with IMDs. We mapped B cell receptor regions from RNA sequencing data of sorted B cell subsets. Our dataset consisted of 595 donors under IMDs and health. We characterised the repertoire features from various aspects, including their association with immune cell transcriptomes and clinical features and their response to belimumab treatment. Heavy-chain complementarity-determining region 3 (CDR-H3) length among naïve B cells was shortened among autoimmune diseases. Strong negative correlation between interferon signature strength and CDR-H3 length was observed in naïve B cells and suggested the role for interferon in premature B cell development. VDJ gene usage was skewed especially in plasmablasts and unswitched-memory B cells of patients with systemic lupus erythematosus (SLE). We developed a scoring system to quantify this skewing, and it positively correlated with peripheral helper T cell transcriptomic signatures and negatively correlated with the amount of somatic hyper mutations in plasmablasts, suggesting the association of extrafollicular pathway. Further, this skewing led to high usage of IGHV4-34 gene with 9G4 idiotypes in unswitched-memory B cells, which showed a prominent positive correlation with disease activity in SLE. Gene usage skewing in unswitched-memory B cells was ameliorated after belimumab treatment. Our multimodal repertoire analysis enabled us the system-level understanding of B cell abnormality in diseases.


Lysosomal degradation of alpha 2u-globulin and alpha 2u-globulin-xenobiotic conjugates.
A diverse group of chemicals cause a male rat-specific nephrotoxicity in which alpha 2u-globulin accumulates in renal lysosomes. It has been suggested that these chemicals bind to the protein and decrease its degradation by lysosomal proteinases. To test this hypothesis, the lysosomal degradation of native alpha 2u-globulin and that to which d-limonene, d-limonene-1,2-oxide, isophorone, 1,4-dichlorobenzene, and 2,5-dichlorophenol were bound was studied. alpha 2u-Globulin was purified from male rat urine, and male rat renal cortical lysosomes, isolated by differential centrifugation, served as the proteolytic enzyme source. Pepstatin, an inhibitor of aspartic acid proteinases, and leupeptin, an inhibitor of cysteine proteinases, reduced alpha 2u-globulin degradation to 28 +/- 8 and 17 +/- 5% of control, respectively, whereas addition of both inhibitors decreased alpha 2u-globulin degradation to 8 +/- 1% of control values. These results indicate that both classes of endopeptidases are important in the degradation of alpha 2u-globulin. Under the incubation conditions used, 30% of native alpha 2u-globulin was degraded in a 4-hr period. Conjugates of the protein were made for in vitro binding experiments. Binding of d-limonene and 1,4-dichlorobenzene to alpha 2u-globulin did not alter the degradation of the protein, whereas binding of d-limonene-1,2-oxide, 2.5-dichlorophenol, and isophorone decreased alpha 2u-globulin degradation by 33%. These results indicate that not all chemicals which have been shown to bind in vivo to alpha 2u-globulin alter the in vitro lysosomal degradation of the protein. However, in all cases, one metabolite of each hyaline droplet inducer did alter degradation of alpha 2u-globulin, suggesting that a decrease in lysosomal degradation is involved in the accumulation of this protein in male rat kidney lysosomes.


The association between habitual physical activity and cigarette cravings, and influence of smokers' characteristics in disadvantaged smokers not ready to quit.
Habitual physical activity (PA) may have an important role in suppressing cigarette cravings. Systematic reviews show a strong acute effect of bouts of PA on reducing cigarette cravings, and it may be that these effects accumulate. The aim was to investigate the relationship between habitual levels of PA and cigarette cravings in disadvantaged smokers not ready to quit by examining baseline cross-sectional data from the Exercise Assisted Reduction then Stop smoking study (EARS). A series of linear regression models were applied to investigate the relationship between habitual PA and cigarette cravings and to identify additional predictors of cigarette cravings. The analyses were extended by including interaction terms with PA to identify potential moderators of the relationship between PA and cravings. A higher level of moderate intensity PA was associated with lower cravings (p = 0.033). Additional predictors were the mood and physical symptoms scale (p = 0.007; higher scores were associated with higher cravings) and alcohol consumption (p = 0.002; higher consumption was associated with lower cravings). In addition, a moderation effect of alcohol consumption was found; at higher levels of alcohol consumption, higher PA was significantly associated with higher cravings (p = 0.023). Overall, participation in regular PA is associated with reduced cigarette cravings; among those with heavy alcohol consumption, this participation is associated with higher cravings. These exploratory analyses suggest that further research into the relationship between PA, alcohol consumption and cigarette cravings is needed.


The microbiology of minimally processed fresh fruits and vegetables.
Minimally processed fresh (MPF) fruits and vegetables are good media for growth of microorganisms. They have been involved in outbreaks because of the consumption of products contaminated by pathogens. They are also sensitive to various spoilage microorganisms such as pectinolytic bacteria, saprophytic Gram-negative bacteria, lactic acid bacteria, and yeasts. Contamination of MPF fruits and vegetables occurs at every stage of the food chain, from cultivation to processing. Polluted environments during cultivation or poor hygienic conditions in processing increase the risk of contamination with foodborne pathogens. Although MPF fruits and vegetables may harbor psychrotrophic microorganisms such as fluorescent pseudomonads or Listeria monocytogenes, good control of refrigeration temperature limits growth of spoilage and pathogenic microorganisms. Modified atmospheres are often efficient to maintain or improve visual organoleptic quality of MPF fruits and vegetables, but their effects on microorganisms are inconsistent. Chemical disinfection can partially reduce the initial bacterial contamination; irradiation seems to be more efficient. The applications of legislations and quality assurance systems to control contamination, survival, and growth of foodborne pathogens in MPF fruits and vegetables are discussed.


[Evaluation of the effectiveness of the calcaneal spurs radiotherapy].
The radiotherapy results of 46 calcaneal spurs were analysed. Patients were irradiated using fraction dose of 1.0 Gy, 1.5 Gy or 2.0 Gy up to total dose of 2.0-22.5 Gy. All patients previously had chronic pain in the plantar region influencing possibility of walking and not reacting for conventional treatment. Whole group was periodically controlled after the treatment completion. The mean follow-up period was 12.5 months. The complete pain relief was observed in 9% cases one month after treatment and in 52% during the last control. The lack of analgetic effect was noted only in 3% cases as well one month after the treatment as during the last examination. Performed statistical analysis showed only inverse significant correlation between degree of pain relief six months after the treatment and duration of symptoms. Obtained results allow to form conclusion that radiotherapy of calcaneal spurs is easy, effective and safe way of analgetic treatment giving good results after low fraction and total delivered doses and that its efficacy depends on symptoms duration what is correlated to disease stage.


In situ structure and organization of the influenza C virus surface glycoprotein.
The lipid-enveloped influenza C virus contains a single surface glycoprotein, the haemagglutinin-esterase-fusion (HEF) protein, that mediates receptor binding, receptor destruction, and membrane fusion at the low pH of the endosome. Here we apply electron cryotomography and subtomogram averaging to describe the structural basis for hexagonal lattice formation by HEF on the viral surface. The conformation of the glycoprotein in situ is distinct from the structure of the isolated trimeric ectodomain, showing that a splaying of the membrane distal domains is required to mediate contacts that form the lattice. The splaying of these domains is also coupled to changes in the structure of the stem region which is involved in membrane fusion, thereby linking HEF's membrane fusion conformation with its assembly on the virus surface. The glycoprotein lattice can form independent of other virion components but we show a major role for the matrix layer in particle formation.


Cell-permeable transgelin-2 as a potent therapeutic for dendritic cell-based cancer immunotherapy.
Transgelin-2 is a 22 kDa actin-binding protein that has been proposed to act as an oncogenic factor, capable of contributing to tumorigenesis in a wide range of human malignancies. However, little is known whether this tiny protein also plays an important role in immunity, thereby keeping body from the cancer development and metastasis. Here, we investigated the functions of transgelin-2 in dendritic cell (DC) immunity. Further, we investigated whether the non-viral transduction of cell-permeable transgelin-2 peptide potentially enhance DC-based cancer immunotherapy. To understand the functions of transgelin-2 in DCs, we utilized bone marrow-derived DCs (BMDCs) purified from transgelin-2 knockout (Tagln2-/-) mice. To observe the dynamic cellular mechanism of transgelin-2, we utilized confocal microscopy and flow cytometry. To monitor DC migration and cognate T-DC interaction in vivo, we used intravital two-photon microscopy. For the solid and metastasis tumor models, OVA+ B16F10 melanoma were inoculated into the C57BL/6 mice via intravenously (i.v.) and subcutaneously (s.c.), respectively. OTI TCR T cells were used for the adoptive transfer experiments. Cell-permeable, de-ubiquitinated recombinant transgelin-2 was purified from Escherichia coli and applied for DC-based adoptive immunotherapy. We found that transgelin-2 is remarkably expressed in BMDCs during maturation and lipopolysaccharide activation, suggesting that this protein plays a role in DC-based immunity. Although Tagln2-/- BMDCs exhibited no changes in maturation, they showed significant defects in their abilities to home to draining lymph nodes (LNs) and prime T cells to produce antigen-specific T cell clones, and these changes were associated with a failure to suppress tumor growth and metastasis of OVA+ B16F10 melanoma cells in mice. Tagln2-/- BMDCs had defects in filopodia-like membrane protrusion and podosome formation due to the attenuation of the signals that modulate actin remodeling in vitro and formed short, unstable contacts with cognate CD4+ T cells in vivo. Strikingly, non-viral transduction of cell-permeable, de-ubiquitinated recombinant transgelin-2 potentiated DC functions to suppress tumor growth and metastasis. This work demonstrates that transgelin-2 is an essential protein for both cancer and immunity. Therefore, transgelin-2 can act as a double-edged sword depending on how we apply this protein to cancer therapy. Engineering and clinical application of this protein may unveil a new era in DC-based cancer immunotherapy. Our findings indicate that cell-permeable transgelin-2 have a potential clinical value as a cancer immunotherapy based on DCs.


Calcium-Sensing Receptor Gene Polymorphisms (CASRV1 and CASRV2) and the Physical Activity Level of Men in Lower Silesia, Poland.
Calcium-sensing receptors (CASR) are a dimeric family of C-class G-protein-coupled receptors that play a crucial role in bone and mineral metabolism by regulating parathyroid hormone (PTH) secretion, skeletal development, and urinary Ca2+ excretion. Genetic factors mainly impact bone mineral density (BMD). However, many variable factors may affect bone health, including physical activity. The aim of our study was to investigate the potential associations between calcium-sensing receptor gene polymorphisms (CASRV1 and CASRV2) and the level of physical activity in adult males from Lower Silesia, a region in the south of Poland. A total of 428 adult male inhabitants of Lower Silesia were included in the study. Their physical activity was evaluated using the International Physical Activity Questionnaire. The CASRV1 (rs 1801725, G>T, A986S) and CASRV2 (rs 761486, T>G, non-coding region) polymorphisms were determined using polymerase chain reaction (PCR) and mini-sequencing. The polymorphisms were identified with GeneScan software ver. 3.1.2. We did not observe any statistically significant differences between the total energy expenditure (total MET) and the CASRV1 and CASRV2 polymorphisms. We did not find any association between the level of physical activity and the frequency of genotypes at the polymorphic locus of the calcium-sensing receptor genes CASRV1 and CASRV2. We found that the number of hours the subjects spent in a sitting position was unrelated to the genotypes at the polymorphic locus of the calcium-sensing receptor gene CASRV1. Based on our studies, we concluded that there were no associations between CASR and physical activity in the men inhabiting Lower Silesia in Poland. Our results do not suggest any influence of the assessed genetic factors in the population variability of the level of physical activity of adults.


Effect of tetanic stimulation on subsequent train-of-four responses at various levels of vecuronium-induced neuromuscular block.
Tetanic stimulation influences subsequent neuromuscular responses. In addition, the tetanus-induced changes in neuromuscular responses differ according to the level of neuromuscular block at which tetanic stimulation is delivered. We studied the tetanus-induced effect on subsequent train-of-four (TOF) responses at various levels of vecuronium-induced neuromuscular block in 45 anaesthetized patients. Tetanic stimulation was applied when a twitch height of T1 returned to 25%, 50% and 75% of its control twitch height (T0) (groups 1, 2 and 3, respectively) after administration of vecuronium 0.1 mg kg-1. Maximum post-tetanic percentage increases in TOF responses in groups 1, 2 and 3 were 257 (SD 119)%, 107 (75)% and 68 (54)% for T1/T0 (P < 0.001 for group 1 vs 2; P < 0.001 for group 1 vs 3) and 535 (259)%, 421 (213)% and 292 (171)% for T4/T1 (P < 0.01 for group 1 vs 3), respectively. Durations of post-tetanic increases in TOF responses in groups 1, 2, and 3 were 52 (19) s, 37 (14) s and 32 (13) s for T1/T0 (P < 0.05 for group 1 vs 2; P < 0.01 for group 1 vs 3) and 53 (17) s, 46 (15) s and 35 (12) s for T4/T1 (P < 0.05 for group 1 vs 3), respectively. These data suggest that the tetanus-induced effect on subsequent TOF is more apparent and lasts longer at greater degrees than at lesser degrees of neuromuscular block.


The extracytoplasmic function sigma factor σS protects against both intracellular and extracytoplasmic stresses in Staphylococcus aureus.
Previously we identified a novel component of the Staphylococcus aureus regulatory network, an extracytoplasmic function σ-factor, σ(S), involved in stress response and disease causation. Here we present additional characterization of σ(S), demonstrating a role for it in protection against DNA damage, cell wall disruption, and interaction with components of the innate immune system. Promoter mapping reveals the existence of three unique sigS start sites, one of which appears to be subject to autoregulation. Transcriptional profiling revealed that sigS expression remains low in a number of S. aureus wild types but is upregulated in the highly mutated strain RN4220. Further analysis demonstrates that sigS expression is inducible upon exposure to a variety of chemical stressors that elicit DNA damage, including methyl methanesulfonate and ciprofloxacin, as well as those that disrupt cell wall stability, such as ampicillin and oxacillin. Significantly, expression of sigS is highly induced during growth in serum and upon phagocytosis by RAW 264.7 murine macrophage-like cells. Phenotypically, σ(S) mutants display sensitivity to a broad range of DNA-damaging agents and cell wall-targeting antibiotics. Furthermore, the survivability of σ(S) mutants is strongly impacted during challenge by components of the innate immune system. Collectively, our data suggest that σ(S) likely serves dual functions within the S. aureus cell, protecting against both cytoplasmic and extracytoplasmic stresses. This further argues for its important, and perhaps novel, role in the S. aureus stress and virulence responses.


omega-Aga-I: a presynaptic calcium channel antagonist from venom of the funnel web spider, Agelenopsis aperta.
Spider venoms are proving to be important sources of specific ion channel toxins. Venom of Agelenopsis aperta, a funnel web spider, contains a class of polypeptide toxins which blocks neuromuscular synapses at nanomolar concentrations. Detailed physiological analyses of block caused by one of these toxins, omega-Aga-I, show that it suppresses transmitter release at insect and frog neuromuscular junctions and blocks calcium spikes in insect neuronal cell bodies. omega-Aga-I may define a binding site on neuronal calcium channels which is common to both vertebrates and invertebrates.


Subnormal activation of phagocytes by complement in chronic inflammatory bowel disease? Neutrophil chemotaxis to complement split product C5a.
The capacity of circulating phagocytes for activation by complement was investigated in consecutive, untreated cases of chronic inflammatory bowel disease. The major complement derived chemotactic factor, C5a, served as chemoattractant in dose response studies of neutrophil chemotaxis. A similar, significantly decreased sensitivity and peak response was revealed in patients with Crohn's disease and ulcerative colitis. This subnormal function of neutrophils could be shown even in cases of complete clinical remission. Chemotactic response to casein and spontaneous motility was within the normal range showing an unaffected basic cell function of neutrophils in the patients. The study shows a dysfunction of phagocytic cells, related to potentially important phlogistic mediators, in chronic inflammatory bowel disease.


Obesity and incidence of cancer: a large cohort study of over 145,000 adults in Austria.
We investigated the relation of overweight and obesity with cancer in a population-based cohort of more than 145 000 Austrian adults over an average of 9.9 years. Incident cancers (n=6241) were identified through the state cancer registry. Using Cox proportional-hazards models adjusted for smoking and occupation, increases in relative body weight in men were associated with colon cancer (hazard rate (HR) ratio 2.48; 95% confidence interval (CI): 1.15, 5.39 for body mass index (BMI) > or =35 kg m(-2)) and pancreatic cancer (HR 2.34, 95% CI: 1.17, 4.66 for BMI>30 kg m(-2)) compared to participants with normal weight (BMI 18.5-24.9 kg m(-2)). In women, there was a weak positive association between increasing BMI and all cancers combined, and strong associations with non-Hodgkin's lymphomas (HR 2.86, 95% CI: 1.49, 5.49 for BMI> or =30 kg m(-2)) and cancers of the uterine corpus (HR 3.93, 95% CI: 2.35, 6.56 for BMI> or =35 kg m(-2)). Incidence of breast cancer was positively associated with high BMI only after age 65 years. These findings provide further evidence that overweight is associated with the incidence of several types of cancer.


The association between diabetes and hypertension with the number and extent of weight cycles determined from 6 million participants.
The purpose of this study was to elucidate the association between weight cycling and clinical outcomes such as type 2 diabetes and hypertension with differential effects of baseline age and obesity. Nationwide data from 6,132,569 healthy adults who underwent five or more health screenings between 2002 and 2011 were analyzed and followed until December 2019 for type 2 diabetes and hypertension. Weight cycling was defined as a change in body weight followed by another change in the opposite direction. Through the Cox proportional hazards model, the number and degree of weight cycles were positively associated with increased risk of type 2 diabetes and hypertension. The hazard ratios (HRs) of weight cycling for type 2 diabetes and hypertension were as high as 1.263 (1.213-1.315) and 1.175 (1.144-1.207) at two or more weight cycles of 10% of body weight (BW), respectively. The association was stronger for females, individuals with normal body weight/BMI, and older individuals. Weight cycling was significantly associated with an increased risk of adverse health outcomes and was stronger in individuals with normal BMI and females, indicating that these people should be informed about the potential risk of weight cycling.


Discriminant analysis of serum inflammatory biomarkers which differentiate pediatric appendicitis from other acute abdominal diseases.
Other acute abdominal diseases in children can confound the signs and symptoms of appendicitis, resulting in misdiagnosis and unnecessary appendectomy. In this study, we used discriminant analysis of serum inflammatory biomarkers to determine which acute abdominal diseases could mimic appendicitis, and further analyzed these diseases based on different age groups. We prospectively collected 417 patients aged from 4 to 18 years with clinically suspected acute appendicitis in the pediatric emergency department. We selected the significantly higher serum biomarkers for appendicitis as the discriminating variables. Furthermore, we analyzed the definitive diagnoses of patients with normal appendices who could not be predicted by discriminant analysis. Patients with acute appendicitis had significantly higher leukocyte counts (p < 0.01), neutrophil counts, (p < 0.01) and C-reactive protein concentrations (p < 0.01 ) than those with normal appendices. The discriminant power of these three serum biomarkers in acute appendicitis was 76 percent. Acute abdominal diseases which mimicked appendicitis included acute gastroenteritis, nonspecific abdominal pain, urinary tract infection, and upper respiratory infection with gastrointestinal upset. Serum biomarkers may serve as helpful discriminators to predict the presence of pediatric appendicitis. But, some acute abdominal diseases mimicking appendicitis should be considered during differential diagnosis of acute appendicitis to avoid making misdiagnosis and performing unnecessary appendectomy.


Measuring participation in patients with chronic back pain-the 5-Item Pain Disability Index.
Of the three broad outcome domains of body functions and structures, activities, and participation (eg, engaging in valued social roles) outlined in the World Health Organization's (WHO) International Classification of Functioning, Disability and Health (ICF), it has been argued that participation is the most important to individuals, particularly those with chronic health problems. Yet, participation is not commonly measured in back pain research. The aim of this study was to investigate the construct validity of a modified 5-Item Pain Disability Index (PDI) score as a measure of participation in people with chronic back pain. A validation study was conducted using cross-sectional data. Participants with chronic back pain were recruited from a multidisciplinary pain center in Alberta, Canada. The outcome measure of interest is the 5-Item PDI. Each study participant was given a questionnaire package containing measures of participation, resilience, anxiety and depression, pain intensity, and pain-related disability, in addition to the PDI. The first five items of the PDI deal with social roles involving family responsibilities, recreation, social activities with friends, work, and sexual behavior, and comprised the 5-Item PDI seeking to measure participation. The last two items of the PDI deal with self-care and life support functions and were excluded. Construct validity of the 5-Item PDI as a measure of participation was examined using Pearson correlations or point-biserial correlations to test each hypothesized association. Participants were 70 people with chronic back pain and a mean age of 48.1 years. Forty-four (62.9%) were women. As hypothesized, the 5-Item PDI was associated with all measures of participation, including the Participation Assessment with Recombined Tools-Objective (r=-0.61), Late-Life Function and Disability Instrument: Disability Component (frequency: r=-0.66; limitation: r=-0.65), Work and Social Adjustment Scale (r=0.85), a global perceived participation scale (r=0.54), employment status (r=-0.30), and the Usual Activity domain of the 15D (r=0.50). The expected correlations observed indicating a moderate or strong association provided supporting evidence for the construct validity of the 5-Item PDI as a measure of participation. The Oswestry Disability Index and the 5-Item PDI were also strongly correlated (r=0.70). The 5-Item PDI was associated to a lesser degree with depressive symptoms and resilience, as measured by the Hospital Anxiety and Depression Scale (HADS) (r=0.25) and the Connor-Davidson Resilience Scale (r=-0.28), as would be expected. No statistically significant association was found between the 5-Item PDI and the HADS Anxiety score. It is important that outcome measures of participation are included in back pain research to gauge the effects of painful spinal conditions and interventions on maintaining valued social roles. A simple, concise measure would be very useful for this purpose in clinical and research settings. The results of this study support the construct validity of the 5-Item PDI as a brief measure of participation in people with chronic back pain. These findings are likely most applicable to those with chronic back pain attending pain clinics and other tertiary centers for care.


An Eight-Residue Deletion in Escherichia coli FabG Causes Temperature-Sensitive Growth and Lipid Synthesis Plus Resistance to the Calmodulin Inhibitor Trifluoperazine.
FabG performs the NADPH-dependent reduction of β-keto acyl-acyl carrier protein substrates in the elongation cycle of fatty acid synthesis. We report the characterization of a temperature-sensitive mutation (fabGΔ8) in Escherichia colifabG that results from an in-frame 8-amino-acid residue deletion in the α6/α7 subdomain. This region forms part of one of the two dimerization interfaces of this tetrameric enzyme and is reported to undergo significant conformational changes upon cofactor binding, which define the entrance to the active-site cleft. The activity of the mutant enzyme is extremely thermolabile and is deficient in forming homodimers at nonpermissive temperatures with a corresponding decrease in fatty acid synthesis both in vivo and in vitro Surprisingly, the fabGΔ8 strain reverts to temperature resistance at a rate reminiscent of that of a point mutant with intragenic pseudorevertants located either on the 2-fold axes of symmetry or at the mouth of the active-site cleft. The fabGΔ8 mutation also confers resistance to the calmodulin inhibitor trifluoperazine and renders the enzyme extremely sensitive to Ca2+in vitro We also observed a significant alteration in the lipid A fatty acid composition of fabGΔ8 strains but only in an lpxC background, probably due to alterations in the permeability of the outer membrane. These observations provide insights into the structural dynamics of FabG and hint at yet another point of regulation between fatty acid and lipid A biosynthesis.IMPORTANCE Membrane lipid homeostasis and its plasticity in a variety of environments are essential for bacterial survival. Since lipid biosynthesis in bacteria and plants is fundamentally distinct from that in animals, it is an ideal target for the development of antibacterial therapeutics. FabG, the subject of this study, catalyzes the first cofactor-dependent reduction in this pathway and is active only as a tetramer. This study examines the interactions responsible for tetramerization through the biochemical characterization of a novel temperature-sensitive mutation caused by a short deletion in an important helix-turn-helix motif. The mutant strain has altered phospholipid and lipid A compositions and is resistant to trifluoperazine, an inhibitor of mammalian calmodulin. Understanding its structural dynamics and its influence on lipid A synthesis also allows us to explore lipid homeostasis as a mechanism for antibiotic resistance.


Quantitative relationship between sensitivity to beta-lactam antibiotics and beta-lactamase production in gram-negative bacteria--I. Steady-state treatment.
A simple graphical method is proposed to decide whether a decreased sensitivity to beta-lactam antibiotics can be explained by the sole increase of beta-lactamase production or if other factors such as outer membrane permeability or target sensitivity must also be involved. The parameters which are necessary for the analysis can easily be measured: the relative amounts of beta-lactamase produced by the various strains; the Km of the enzyme for the various beta-lactams under study and the susceptibility of each strain to the same antibiotics, measured as MIC values.


Patterns of oral and pharyngeal cancer incidence in New South Wales, Australia.
Incidence and mortality rates for oral and pharyngeal cancers have been reported to be increasing in Europe and the United States, with particularly large increases in mortality in central and eastern Europe. Such increases have been noted to be birth cohort-based, primarily affecting young and middle-aged men. In this report oral and pharyngeal cancer incidence data from New South Wales, Australia has been analysed for the period 1972-90. Although an increase in the incidence of oral and pharyngeal cancer occurred during the mid-1970s and early 1980s, it did not continue. This pattern is consistent with Australian trends in per capita consumption of tobacco, alcohol, fruit and vegetables. Individual regions within metropolitan Sydney showed substantial geographical variation with age-specific rates of oral and pharyngeal cancers (combined) in middle-aged men being at least three times higher in the city of Sydney than in New South Wales as a whole. Given the preventable nature of the disease, such high rates need not occur.


Skeletal lesions in palmar-plantar pustulosis.
In four women low-grade spondylitis-arthritis-osteitis coincided with palmar-plantar pustulosis. Both conditions are believed to be aseptic and part of a common immuno-defect reaction.


Oral epidemiological examination - protocol: the National Study of Adult Oral Health 2017-18.
The National Study of Adult Oral Health (NSAOH) 2017-18 aimed to collect data on population oral health status of the Australian adult population. This complex nation-wide project required reliable data collection procedures. The NSAOH 2017-18 Oral Epidemiological Examination Protocol has been developed based on internationally accepted examination procedures. Examiners have been trained and calibrated in using the protocol. Details of the clinical examination components are provided. Examiner reliability has been tested and presented.


Structured exercises to prevent lower limb injuries in young handball players.
To investigate the effect of a structured warm-up program in reducing the occurrence of knee and ankle injuries in teenage handball players. Block randomized controlled trial with a sample size designed to achieve 90% power with [alpha] = 5% to detect a relative risk (RR) reduction of 50%. Clubs within the randomization blocks were matched by region, playing level, and number and sex of players. Norwegian Handball Federation clubs in the 16-year and 17-year divisions during the 2002 to 2003 season. Clubs in the division were invited to participate in the study before the season (n = 123 clubs recruited; 85% of the 145 invited clubs). After 3 clubs were excluded or dropped out, 1837 eligible players (uninjured at baseline) aged 15 to 17 years (86% young women) were included in the analysis. Coaches of the intervention group clubs (958 players) were instructed in exercises to improve awareness and control of knees and ankles during standing, running, cutting, jumping, and landing. The program comprised exercises with the ball, including the use of the wobble board and balance mat, for warm-up, technique, balance, and strength. Players were to spend 4 to 5 minutes on each group of exercises for a total of 15 to 20 minutes at the first 15 training sessions and thereafter once per week. Coaches recorded attendance and details of the sessions on standard forms. Coaches of the control group clubs (879 players) were asked to continue with their usual training methods and to record types and volume of exercises used. The primary outcome measure was an acute injury to the knee or ankle during a match or training session that required the player to have medical attention or miss part of the next session. Secondary outcomes were any injury to the lower limbs, injuries overall, and injuries to the upper limb. Injuries were recorded by physiotherapists blinded to group assignment who were in contact with the coaches at least every month. The physiotherapists interviewed injured players in person or by telephone as soon as possible (range, 1 day to 4 months). During the season 262 players (14%) were injured at least once (241 acute and 57 overuse injuries). In intention-to-treat analysis, the intervention group had lower risks than the control group of acute knee or ankle injuries (RR, 0.53; 95% CI, 0.35-0.81), lower limb injuries (RR, 0.51; CI, 0.36-0.73), any injury (RR, 0.49; CI, 0.36-0.68), and upper limb injuries (RR, 0.37; CI, 0.20-0.69). Rate ratios for moderate and major injuries (absence from play for 8 to > or =21 days) were lower for the intervention group for all injuries (P < 0.001) and for acute knee or ankle injuries (P < or = 0.03). Fewer players in the intervention group had > or =2 injuries. Risk of injury did not differ for young men and women. Crossovers to the other intervention occurred in 13% of the intervention clubs (noncompliance with the training program) and 22% of the control clubs (use of similar preventive exercises to the intervention group). The rate of acute knee and ankle injuries and all injuries to young handball players was reduced by half by a structured program designed to improve knee and ankle control during play.


Angled BIO-RSA (bony-increased offset-reverse shoulder arthroplasty): a solution for the management of glenoid bone loss and erosion.
Glenoid deficiency and erosion (excessive retroversion/inclination) must be corrected in reverse shoulder arthroplasty (RSA) to avoid prosthetic notching or instability and to maximize function, range of motion, and prosthesis longevity. This study reports the results of RSA with an angled, autologous glenoid graft harvested from the humerus (angled BIO-RSA). A trapezoidal bone graft, harvested from the humeral head and fixed with a long-post baseplate and screws, was used to compensate for residual glenoid bone loss/erosion. For simple to moderate (<25°) glenoid defects, standardized instrumentation combined with some eccentric reaming (<15°) was used to reconstruct the glenoid and obtain neutral implant alignment. For severe (>25°) and complex (multiplanar) glenoid bone defects, patient-specific grafts and guides were used after 3-dimensional planning. Patients were reviewed with minimum 2 years of follow-up. Mean follow-up was 36 months (range, 24-81 months). Preoperative and postoperative measurements of inclination and version were performed in the plane of the scapula on computed tomography images. The study included 54 patients (41 women, 13 men; mean 73 years old). Fifteen patients had combined vertical and horizontal glenoid bone deficiency. Among E2/E3 glenoids, inclination improved from 37° (range, 14° to 84°) to 10.2° (range -28° to 36°, P < .001). Among B2/C glenoids, retroversion improved from -21° (range, -49° to 0°) to -10.6° (-32° to 4°, P = .06). Complete radiographic incorporation of the graft occurred in 94% (51 of 54). Complications included infection in 1 and clinical aseptic baseplate loosening in 2. Mild notching occurred in 25% (13 of 51) of patients. Constant-Murley and Subjective Shoulder Value assessments increased from 31 to 68 and from 30% to 83%, respectively (P < .001). Angled BIO-RSA predictably corrects glenoid deficiency, including severe (>25°) multiplanar deformity. Graft incorporation is predictable. Advantages of using an autograftharvested in situ include bone stock augmentation, lateralization, low donor-site morbidity, low relative cost, and flexibility needed to simultaneously correct posterior and superior glenoid defects.


The WISEWOMAN projects: lessons learned from three states.
The WISEWOMAN program provides chronic disease risk factor screening, lifestyle interventions, and referrals to financially disadvantaged women who participate in the National Breast and Cervical Cancer Early Detection Program (NBCCEDP). Three states (Arizona, Massachusetts, and North Carolina) participated in Phase One (1995-1998). Using a case study approach, we reviewed documents and conducted telephone interviews to compare the three projects' design and execution. The interviews, carried out in mid-2002, involved a convenience sample of project coordinators, project directors, researchers, and one CDC project officer (n = 9). Many providers were overwhelmed by WISEWOMAN's research component and disliked its lack of flexibility. Researchers emphasized that high-quality evaluation requires resources and attention. Informants described the challenges of integrating WISEWOMAN with state BCCEDP programs that are in varying development stages and recommended changes in organizational culture and provider practices. Regarding implementation, informants emphasized the need for adequate and appropriate planning, buy-in, training, professional support, and outreach. Our sample also noted that WISEWOMAN projects tend to be labor intensive. WISEWOMAN projects face challenges of integrating clinical and lifestyle interventions, reaching beyond a focus on individuals, marshaling substantial resources, and introducing complex interventions into stretched healthcare environments. The three Phase One projects were deemed successful in reaching underserved women, developing a more comprehensive women's health model, strengthening linkages to primary healthcare, experimenting with innovative behavioral interventions, and tapping into women's roles as social support providers and family/community gatekeepers.


Therapeutic variability in adult minimal change disease and focal segmental glomerulosclerosis.
Variability in the management of glomerulonephritis may negatively impact efficacy and safety. However, there are little/no data on actual variability in the treatment of minimal change disease (MCD)/focal segmental glomerulosclerosis (FSGS) in adults. We assessed Spanish practice patterns for the management of adult nephrotic syndrome due to MCD or FSGS. The absence of reasonably good evidence on treatment for a disease often increases the variability substantially. Identification of evidence-practice gaps is the first necessary step in the knowledge-to-action cyclical process. We aim to analyse the real clinical practice in adults in hospitals in Spain and compare this with the recently released Kidney Disease: Improving Global Outcomes clinical practice guideline for glomerulonephritis. Participating centres were required to include all adult patients (age >18 years) with a biopsy-proven diagnosis of MCD or FSGS from 2007 to 2011. Exclusion criteria included the diagnosis of secondary nephropathy. We studied 119 Caucasian patients with biopsy-proven MCD (n = 71) or FSGS (n = 48) from 13 Spanish hospitals. Of these patients, 102 received immunosuppressive treatment and 17 conservative treatment. The initial treatment was steroids, except in one patient in which mycophenolate mofetil was used. In all patients, the steroids were given as a single daily dose. The mean duration of steroid treatment at initial high doses was 8.7 ± 13.2 weeks and the mean global duration was 38 ± 32 weeks. The duration of initial high-dose steroids was <4 weeks in 41% of patients and >16 weeks in 10.5% of patients. We did find a weak and negative correlation between the duration of whole steroid treatment in the first episode and the number of the later relapses (r = -0.24, P = 0.023). There were 98 relapses and they were more frequent in MCD than in FSGs patients (2.10 ± 1.6 versus 1.56 ± 1.2; P = 0.09). The chosen treatment was mainly steroids (95%). Only seven relapses were treated with another drug as a first-line treatment: two relapses were treated with mycophenolate and five relapses were treated with anticalcineurinics. A second-line treatment was needed in 29 patients (24.4%), and the most frequent drugs were the calcineurin inhibitors (55%), followed by mycophenolate mofetil (31%). Although cyclophosphamide is the recommended treatment, it was used in only 14% of the patients. We found variation from the guidelines in the duration of initial and tapered steroid therapy, in the medical criteria for classifying a steroid-resistant condition and in the chosen treatment for the second-line treatment. All nephrologists started with a daily dose of steroids as the first-line treatment. The most frequently used steroid-sparing drug was calcineurin inhibitors. Cyclophosphamide use was much lower than expected.


Cryogenic X-ray diffraction microscopy for biological samples.
X-ray diffraction microscopy (XDM) is well suited for nondestructive, high-resolution biological imaging, especially for thick samples, with the high penetration power of x rays and without limitations imposed by a lens. We developed nonvacuum, cryogenic (cryo-) XDM with hard x rays at 8 keV and report the first frozen-hydrated imaging by XDM. By preserving samples in amorphous ice, the risk of artifacts associated with dehydration or chemical fixation is avoided, ensuring the imaging condition closest to their natural state. The reconstruction shows internal structures of intact D. radiodurans bacteria in their natural contrast.


Heparin and antithrombin III levels during cardiopulmonary bypass: correlation with subclinical plasma coagulation.
The anticoagulant effect of heparin in the milieu of altered antithrombin III levels was investigated in adult (n = 7) and pediatric (n = 14) patients undergoing open heart operations. The pediatric patients were subdivided into a control group (n = 8) and an antithrombin III group (n = 6), which received 1,000 units of antithrombin III. The reduction in antithrombin III levels during cardiopulmonary bypass was obvious in patients of all ages, showing a greater reduction (although not statistically significant) in the pediatric patients. However, the antithrombin III group patients maintained their preoperative levels of antithrombin III. The elevated fibrinopeptide A levels in pediatric and adult control group patients suggested that considerable subclinical plasma coagulation occurred during open heart operations, especially during the normothermic period of cardiopulmonary bypass and after the administration of protamine. Antithrombin III levels in the children were the most predictive (r = -0.58; p < 0.001) for production of fibrinopeptide A during moderate hypothermic cardiopulmonary bypass, but the heparin levels were most predictive (r = -0.57, p < 0.03) in the adults. This result may be related to the different actions of heparin when antithrombin III levels are reduced. Supplementation with antithrombin III succeeded in suppressing the activation of the coagulation cascade and resulted in no statistical change in fibrinopeptide A levels at any time. We conclude that heparin and (in some patients) antithrombin III levels are important variables for the inhibition of fibrin formation and the possible preservation of coagulation proteins.


[Studies on imipenem/cilastatin sodium in the perinatal period].
Pharmacokinetic, bacteriological and clinical studies of imipenem/cilastatin sodium (IPM/CS) were carried out in the perinatal period, and the results obtained are summarized as follows: Effects of IPM on bacterial growth curves of Staphylococcus aureus (sensitive and resistant strains) and Escherichia coli (sensitive strains) in amniotic fluid were determined. The bactericidal effects of IPM increased in amniotic fluid and remarkable increases against resistant strains were demonstrated. IPM and CS were detected promptly after intravenous drip infusion to pregnant women, and reached peak levels shortly after administration in maternal plasma. Placental penetration of IPM and CS to the fetus was favorable. After intravenous drip infusion of 500 mg/500 mg of IPM/CS, drug concentrations in the umbilical cord plasma and the amniotic fluid exceeded MICs against main pathogenic organisms. Clinically, IPM/CS was effective in the treatment of perinatal infections without any side effect. The above results demonstrated that IPM/CS is a clinically useful antibiotic for the prophylaxis and the treatment of perinatal infections.


[Changes in the pancreas structure after exposure of the body to gravitational overloads].
The aim of this study was to determine the changes in the pancreas structure after acute and chronic exposure of organism to gravitational overloads (GO). The experiments were conducted in 36 outbred albino male rats, 12 rats formed the control group. GO effect was modeled using the centrifuge; the value of the overload thus created amounted to 4,0-6,0 gravitational units. Pancreas structure was studied using histological, electron microscopic and morphometric methods. It was found that after acute exposure to GO, mainly the reactive changes were demonstrated all the pancreatic structures studied: acinocytes, endocrinocytes, blood vessels and nervous apparatus. Chronic exposure to GO resulted in both reactive modifications, similar to those described after an acute exposure, and various compensatory-adaptive and destructive changes.


Host plant volatiles synergize responses of sex pheromone-specific olfactory receptor neurons in male Helicoverpa zea.
Single-cell electrophysiological recordings were obtained from olfactory receptor neurons in antennal trichoid sensilla of male corn earworm, Helicoverpa zea. Spontaneous activity of the neuron specific for the major component ( Z)-11-hexadecenal, the conspecific female-emitted sex pheromone, was not affected by exposure to host plant volatiles. However, stimulations with binary mixtures of a threshold dosage of the pheromone component and increasing dosages of either linalool or ( Z)-3-hexenol significantly synergized the pheromone-specific neuron's firing rates compared with responses to the major pheromone component alone. Cross-adaptation studies confirmed that the enhanced impulses originated from the pheromone-component-tuned neuron. Because plant volatiles do not stimulate the pheromone-specific neuron when presented alone, the pheromone plus host odor blend would be interpreted as containing more pheromone than it actually does when processed by the pheromone-processing portion of the antennal lobe.


Cerebral blood flow velocity and cognition in children before and after adenotonsillectomy.
The goal was to determine whether amelioration of sleep-disordered breathing through adenotonsillectomy would reduce middle cerebral artery velocity in parallel with improvements in cognition and behavior. For 19 children (mean age: 6 years) with mild sleep-disordered breathing, and 14 healthy, ethnically similar and age-similar, control subjects, parents repeated the Pediatric Sleep Questionnaire an average of 12 months after adenotonsillectomy. Children with sleep-disordered breathing underwent repeated overnight measurement of mean oxyhemoglobin saturation. Neurobehavioral tests that yielded significant group differences preoperatively were readministered. Middle cerebral artery velocity measurements were repeated with blinding to sleep study and neuropsychological results, and mixed-design analyses of variance were performed. The median Pediatric Sleep Questionnaire score significantly improved postoperatively, and there was a significant increase in mean overnight oxyhemoglobin saturation. The middle cerebral artery velocity decreased in the sleep-disordered breathing group postoperatively, whereas control subjects showed a slight increase. A preoperative group difference was reduced by the postoperative assessment, which suggests normalization of middle cerebral artery velocity in those with sleep-disordered breathing. The increase in mean overnight oxyhemoglobin saturation postoperatively was associated with a reduction in middle cerebral artery velocity in a subgroup of children. A preoperative group difference in processing speed was reduced postoperatively. Similarly, a trend for a preoperative group difference in visual attention was reduced postoperatively. Executive function remained significantly worse for the children with sleep-disordered breathing, compared with control subjects, although mean postoperative scores were lower than preoperative scores. Otherwise-healthy young children with apparently mild sleep-disordered breathing have potentially reversible cerebral hemodynamic and neurobehavioral changes.


Needle in a haystack-genetic evidence confirms the expansion of the alien echinoid Diadema setosum (Echinoidea: Diadematidae) to the Mediterranean coast of Israel.
Diadema setosum (Leske, 1778), a widespread tropical echinoid and key herbivore in shallow water environments is currently expanding in the Mediterranean Sea. It was introduced by unknown means and first observed in southern Turkey in 2006. From there it spread eastwards to Lebanon (2009) and westwards to the Aegean Sea (2014). Since late 2016 sporadic sightings of black, long-spined sea urchins were reported by recreational divers from rock reefs off the Israeli coast. Numerous attempts to verify these records failed; neither did the BioBlitz Israel task force encounter any D. setosum in their campaigns. Finally, a single adult specimen was observed on June 17, 2017 in a deep rock crevice at 3.5 m depth at Gordon Beach, Tel Aviv. Although the specimen could not be recovered, spine fragments sampled were enough to genetically verify the visual underwater identification based on morphology. Sequences of COI, ATP8-Lysine, and the mitochondrial Control Region of the Israel specimen are identical to those of the specimen collected in 2006 in Turkey, unambiguously assigning the specimen to D. setosum clade b. This lends support to the hypothesis of a single introduction event and fits well with the habitat suitability and distribution model for D. setosum published recently. The more rapid and larger range extension along a south-eastern, counter-current trajectory may reflect a strong habitat preference for D. setosum in this area of the Levantine Basin as predicted by the model.


Extensive extracellular matrix depositions in active multiple sclerosis lesions.
In the central nervous system, basement membrane (BM) constituents are predominantly associated with the vasculature. However, under inflammatory conditions, the expression of BM components may alter. Here, we investigated the distribution of several BM components, including laminin, collagen type IV and heparan sulfate proteoglycans in various multiple sclerosis (MS) lesions. We observed irregular and discontinuous BMs in active lesions. Throughout active MS lesions, we found dense networks of BM proteins, which were surprisingly not associated with the cerebrovasculature. These striking parenchymal networks were not observed in chronic inactive MS lesions and brains of non-neurological controls. In addition, we studied the distribution of transforming growth factor-beta1 (TGF-beta1), since it is known as a major modulator of ECM production. Leukocytes, in particular CD68-positive macrophages, expressed high levels of TGF-beta1 and were located in close proximity to parenchymal BM deposits in the MS lesions. We postulate that these BM networks may play a role in the further recruitment of inflammatory cells and form a barrier for axonal regeneration.


Reduction of hypoxia-inducible heme oxygenase-1 in the myocardium after left ventricular mechanical support.
Left ventricular assist devices (LVAD) may improve cardiac function. The pathogenesis of this phenomenon, called 'reverse remodelling', is not completely elucidated. To examine the hypothesis that LVAD support eliminates tissue stress by reducing local hypoxia, the distribution of heme oxygenase-1 (HO-1), a stress protein inducible by hypoxia, was examined in vivo and in vitro. The immunoreactivity for HO-1 was semi-quantitatively analysed in left ventricular tissue of 23 patients (14 dilated cardiomyopathy (DCM), six ischaemic heart disease (IHD), three myocarditis/congenital heart disease) with end-stage heart failure before and after LVAD support, while two unused donor hearts served as controls. Control hearts stained almost negative for HO-1, while failing hearts showed immunoreactivity mainly in cardiomyocytes, but also in endothelial cells, some smooth muscle cells and fibroblasts. Hearts with IHD showed significantly higher HO-1 immunoreactivity than hearts with DCM or myocarditis/congenital heart disease. After LVAD support, the HO-1 content decreased significantly in the DCM and IHD group and was significantly higher in the subendocardium than in the subepicardium. In vitro, under hypoxic conditions, neonatal rat cardiomyocytes showed an increase of HO-1 protein content up to sixfold above the normal level, which returned to normal values after normoxic cultivation. Mechanical support reduces the HO-1 content of the failing heart and HO-1 is inducible in vitro under hypoxia and is reversible under normoxia. This supports the concept that restoration of cardiac normoxia by mechanical unloading, particularly in the subendocardium, may be in part responsible for the phenomenon of 'reverse remodelling'.


Nucleotide sequence conservation in paramyxoviruses; the concept of codon constellation.
The stability and conservation of the sequences of RNA viruses in the field and the high error rates measured in vitro are paradoxical. The field stability indicates that there are very strong selective constraints on sequence diversity. The nature of these constraints is discussed. Apart from constraints on variation in cis-acting RNA and the amino acid sequences of viral proteins, there are other ones relating to the presence of specific dinucleotides such CpG and UpA as well as the importance of RNA secondary structures and RNA degradation rates. Recent other constraints identified in other RNA viruses, such as effects of secondary RNA structure on protein folding or modification of cellular tRNA complements, are also discussed. Using the family Paramyxoviridae, I show that the codon usage pattern (CUP) is (i) specific for each virus species and (ii) that it is markedly different from the host - it does not vary even in vaccine viruses that have been derived by passage in a number of inappropriate host cells. The CUP might thus be an additional constraint on variation, and I propose the concept of codon constellation to indicate the informational content of the sequences of RNA molecules relating not only to stability and structure but also to the efficiency of translation of a viral mRNA resulting from the CUP and the numbers and position of rare codons.


Weight-Based PA-GPSR Protocol Improvement Method in VANET.
Vehicle Ad-hoc network (VANET) can provide technical support and solutions for the construction of intelligent and efficient transportation systems, and the routing protocol directly affects the efficiency of VANET. The rapid movement of nodes and uneven density distribution affect the routing stability and data transmission efficiency in VANET. To improve the local optimality and routing loops of the path-aware greedy perimeter stateless routing protocol (PA-GPSR) in urban sparse networks, a weight-based path-aware greedy perimeter stateless routing protocol (W-PAGPSR) is proposed. The protocol is divided into two stages. Firstly, in the routing establishment stage, the node distance, reliable node density, cumulative communication duration, and node movement direction are integrated to indicate the communication reliability of the node, and the next hop node is selected using the weight greedy forwarding strategy to achieve reliable transmission of data packets. Secondly, in the routing maintenance stage, based on the data packet delivery angle and reliable node density, the next hop node is selected for forwarding using the weight perimeter forwarding strategy to achieve routing repair. The simulation results show that compared to the greedy peripheral stateless routing protocol (GPSR), for the maximum distance-minimum angle greedy peripheral stateless routing (MM-GPSR) and PA-GPSR protocols, the packet loss rate of the protocol is reduced by an average of 24.47%, 25.02%, and 14.12%, respectively; the average end-to-end delay is reduced by an average of 48.34%, 79.96%, and 21.45%, respectively; and the network throughput is increased by an average of 47.68%, 58.39%, and 20.33%, respectively. This protocol improves network throughput while reducing the average end-to-end delay and packet loss rate.