Factors associated with time to availability for cases reported to population-based cancer registries.
Population-based cancer registries provide an excellent source of data for cancer surveillance and research. However, delays in reporting and processing can affect the accuracy of incidence rates and the availability of cases for research. This study was designed to describe factors related to delays in availability of cancer cases for epidemiologic analysis. We identified all cancer cases diagnosed in 2000 and reported to the California Cancer Registry by August 2004. We analyzed factors associated with time to availability, defined as the time from diagnosis until the time the case was available for research. A total of 137,270 cancer cases were reported during the study period. The median time to availability for all cases was 382 days. Forty-five percent of cases were available within the first 12 months and 96% were available within 24 months after diagnosis. Cases reported by hospitals had the shortest time to availability (373 days) followed by doctors' offices and laboratories. Melanoma and prostate cancers had longer times to be available than other types of cancer. Time to availability varied by geographic region, but differences by age, gender, race and stage at diagnosis were minimal or non-significant. Strategies are needed to improve timeliness without sacrificing quality and completeness.


A simple model of recurrent epidemics.
A cellular automaton conceived as a simple model of disease spreading is investigated. We show that the steady-state of the model is described by a spatial organization of the infectious individuals on fronts and undamped temporal oscillations in the number of infectious individuals. This behaviour is observed both for a deterministic and a stochastic input of susceptible individuals, hence showing that recurrent epidemic behaviour can be persistent without any external forcing. The simplicity of the model suggests that such spatio--temporal behaviour can be obtained from nothing, but a direct transmission mechanism between nearest neighbors provided some mechanism for the introduction of new susceptible individuals, e.g., loss of immunity is present.


Association Between Nitric Oxide, Oxidative Stress, Eryptosis, Red Blood Cell Microparticles, and Vascular Function in Sickle Cell Anemia.
Chronic hemolysis, enhanced oxidative stress, and decreased nitric oxide (NO) bioavailability promote vasculopathy in sickle cell anemia (SCA). Oxidative stress and NO are known to modulate eryptosis in healthy red blood cells (RBCs); however, their role in SCA eryptosis and their impact on the genesis of RBC-derived microparticles (RBC-MPs) remains poorly described. RBC-MPs could play a role in vascular dysfunction in SCA. The aims of this study were to evaluate the roles of oxidative stress and NO in eryptosis and RBC-MPs release, and to determine whether RBC-MPs could be involved in vascular dysfunction in SCA. Markers of eryptosis and oxidative stress, plasma RBC-MPs concentration and arterial stiffness were compared between SCA and healthy (AA) individuals. In-vitro experiments were performed to test: 1) the effects of oxidative stress (antioxidant: n-acetylcysteine (NAC); pro-oxidant: cumene hydroperoxide) and NO (NO donor: sodium nitroprusside (SNP); NO-synthase inhibitor (L-NIO)) on eryptosis, RBC deformability and RBC-MP genesis; 2) the effects of SCA/AA-RBC-MPs on human aortic endothelial cell (HAEC) inflammatory phenotype and TLR4 pathway. Eryptosis, RBC-MPs, oxidative stress and arterial stiffness were increased in SCA. NAC increased RBC deformability and decreased eryptosis and RBC-MPs release, while cumene did the opposite. SNP increased RBC deformability and limited eryptosis, but had no effect on RBC-MPs. L-NIO did not affect these parameters. Arterial stiffness was correlated with RBC-MPs concentration in SCA. RBC-MPs isolated directly from SCA blood increased adhesion molecules expression and the production of cytokines by HAEC compared to those isolated from AA blood. TLR4 inhibition alleviated these effects. Our data show that oxidative stress could promote eryptosis and the release of RBC-MPs that are potentially involved in macrovascular dysfunction in SCA.


Ameobal pathogen mimivirus infects macrophages through phagocytosis.
Mimivirus, or Acanthamoeba polyphaga mimivirus (APMV), a giant double-stranded DNA virus that grows in amoeba, was identified for the first time in 2003. Entry by phagocytosis within amoeba has been suggested but not demonstrated. We demonstrate here that APMV was internalized by macrophages but not by non-phagocytic cells, leading to productive APMV replication. Clathrin- and caveolin-mediated endocytosis pathways, as well as degradative endosome-mediated endocytosis, were not used by APMV to invade macrophages. Ultrastructural analysis showed that protrusions were formed around the entering virus, suggesting that macropinocytosis or phagocytosis was involved in APMV entry. Reorganization of the actin cytoskeleton and activation of phosphatidylinositol 3-kinases were required for APMV entry. Blocking macropinocytosis and the lack of APMV colocalization with rabankyrin-5 showed that macropinocytosis was not involved in viral entry. Overexpression of a dominant-negative form of dynamin-II, a regulator of phagocytosis, inhibited APMV entry. Altogether, our data demonstrated that APMV enters macrophages through phagocytosis, a new pathway for virus entry in cells. This reinforces the paradigm that intra-amoebal pathogens have the potential to infect macrophages.


[Politics and power in gerontological nursing in Brazil].
The objective of the present study was to identify the politic activities implemented by gerontological nursing in Brazil in the period spanning 1970 to 1996, which aimed at making it an effective specialty in elderly care. This descriptive-qualitative study was performed using a historical approach, using thematic oral history. Fourteen nurses, pioneers in the field, took part in the study. The following categories were identified: 1) Political organization of the field; and 2) Relationship between the field and the State. Results identified the following examples of political activities: traveling throughout Brazil, aimed at getting researchers interested in the theme; creating the Scientific Department of Gerontological Nursing; and assuming an effective participation in the creation of public policies in the country. The specialty is aware of the political relevance for its construction and has been making efforts to achieve recognition as a field of knowledge within the multidisciplinary team of elderly care.


Intracerebral calcification in systemic sclerosis.
Advanced cerebrovascular wall calcification was recently observed at autopsy in 2 patients with systemic sclerosis. To further investigate this issue, we conducted a prospective CT study of scleroderma patients to detect intracerebral calcification. Thirty-seven consecutive patients with systemic sclerosis underwent unenhanced brain CT. Images were blindly interpreted, together with those of 2 age-matched (+/-1 year) and sex-matched control subjects per patient. Intracerebral calcification was found in 12 patients (32.4%) and 7 controls (9.5%) (P=0.006). Among the patients, intracerebral calcification was associated with the duration of Raynaud's phenomenon (P=0.005) and not with age (P=0.086). Intracerebral calcification is closely associated with scleroderma, which suggests that scleroderma causes primary cerebrovascular changes.


Development of a carbon dot and methylene blue NIR-emitting FLIM-FRET pair in niosomes for controlled ROS generation.
Non-ionic surfactant vesicular systems (niosomes) are structurally similar to lipid vesicles, differing only in the bilayer composition. Herein we report a unique method to generate reactive oxygen species (ROS) utilizing a FLIM-FRET technique involving niosome-trapped yellow emissive carbon dots (YCDs) and methylene blue (MB) in aqueous medium under neutral conditions. Niosomes are biologically important because of their good stability and extremely low toxicity. Fluorescent CDs, emitting in the higher wavelengths on visible light excitation, are of incredible importance in bio-imaging and optoelectronics. Hence, we prepared nitrogen-containing YCDs from a single precursor, o-phenylenediamine, and explained their detailed photophysics upon incorporation into the niosomal bilayer. The YCDs are polarity sensitive, and are rotationally restricted in niosomes, which increases their fluorescence quantum yield from 29% (in water) to 91%. These YCDs are tactically employed to develop a near infrared (NIR) FRET pair with methylene blue (MB), which is a very well-known type-I and type-II photosensitizer. This FRET pair, which emits in the NIR region, is found to be an ideal system to generate ROS by excitation in the lower visible wavelengths. Interestingly, the ROS production by MB from the dissolved oxygen is enhanced inside the niosomes. The donor and the acceptor moieties in this unique NIR-emitting FRET pair display an unprecedented 300 nm Stokes shift. The findings could be influential in bio-imaging in the NIR region evading cellular autofluorescence and the controllably generated ROS can be further applied as a potential photodynamic therapeutic agent.


Antigenic variation of Campylobacter flagella.
Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of flagella dissociated from strains of Campylobacter coli and Campylobacter jejuni belonging to the heat-labile serogroup LIO 8 showed that some strains were capable of producing flagellin subunits of two different molecular weights (MrS), 59,500 and 61,500. Immunoelectron microscopy of cultures of the type strain of this serogroup, C. coli VC167, showed the presence of two flagellum filaments of different antigenic specificity. Epitopes on the surface of one of these flagella bound antibodies in LIO 8 typing antiserum, and Western blotting (immunoblotting) and immunoprecipitation showed that the flagellum was composed of flagellin of Mr 61,500. The other flagellum antigenic type did not bind LIO 8 antibodies but did possess serospecific epitopes which bound a second polyclonal antiserum, LAH2. This second antigenic flagellum type was composed of the Mr 59,500 flagellin. Cells producing either of the flagellum antigenic types serotyped as LIO 8, indicating that flagella composed of the Mr 61,500 flagellin do not carry the serological determinants for this serogroup. The ability of C. coli VC167 to produce these flagella of different subunit MrS was shown to represent a bidirectional antigenic variation. When measured in culture medium, the phase 1-to-phase 2 transition occurred at a rate of approximately 2.0 x 10(-5) per cell per generation, and the phase 2-to-phase 1 transition occurred at a rate of 1.2 x 10(-6) per cell per generation.


Clinical activity and safety of the anti-PD-1 monoclonal antibody dostarlimab for patients with recurrent or advanced dMMR endometrial cancer.
This document provides a short summary of the GARNET trial which was published in JAMA Oncology in October 2020. At the end of this document, there are links to websites where you can find more information about this study. The trial enrolled adult participants with advanced solid tumors. This report is restricted to patients with a particular type of endometrial cancer that has a deficient mismatch repair (dMMR) status. Patients received a trial treatment called dostarlimab (also known by the brand name Jemperli). In the US, dostarlimab is approved as a single therapy in adult patients with dMMR recurrent or advanced endometrial cancer that has progressed on or after platinum-based chemotherapy. In the EU, dostarlimab is approved as a single therapy in adult patients with recurrent or advanced dMMR/microsatellite instability-high (MSI-H) endometrial cancer that has progressed on or after treatment with a platinum-containing regimen. The GARNET trial looked at dostarlimab given intravenously to patients with dMMR endometrial cancer from 7 countries. The trial showed that dostarlimab was successful in shrinking the tumor in 42% of these patients. In general, the percentage of participants who experienced medical problems (referred to as side effects) was low and within expectations for this type of treatment. ClinicalTrials.gov NCT number: NCT02715284. To read the full Plain Language Summary of this article, click on the View Article button above and download the PDF. Link to original article here.


Analgesic effects of rosemary essential oil and its interactions with codeine and paracetamol in mice.
The use of herbal medicinal products in the management of pain has been increasing steadily in recent years, often in combination with conventional analgesics, which can induce significant interactions. In traditional medicine, rosemary was used as mild analgesic, for relieving renal colic pain and dysmenorrhea. The aim of our study was to examine analgesic effects of rosemary essential oil and its pharmacodynamic interactions with codeine and paracetamol in mice. The identification and quantification of chemical constituents of the essential oil isolated from air-dried aerial parts of rosemary were carried out by GC/FID and GC/MS. The hot plate test was performed on NMRI mice by placing them individually on hot plate and assessing their response to the thermal stimulus. In this research, we identified 29 chemical compounds of the studied rosemary essential oil, and the main constituents were 1,8-cineole, camphor, and α-pinene. Administration of investigated essential oil increased significantly the latency time of animal response to heat-induced pain between 20th and 50th minute of the test, when compared to saline-treated group. Rosemary essential oil in the dose of 20 mg/kg was shown to be more efficient than in the dose of 10 mg/kg, in combinations with both codeine and paracetamol. Our findings support the use of rosemary in the management of pain and indicate a therapeutic potential of rosemary essential oil in combination with analgesic drugs. The mechanisms involved in analgesic effects of rosemary essential oil and the potential influence on cytochromes and drug metabolism should be more in-depth investigated.


Food Insecurity and Mental Health among Venezuelan Migrants and Refugees Living in Peru: Secondary Data Analysis of a Cross-Sectional Survey.
The objective of this study was to analyze the association between food insecurity and mental health in Venezuelan migrants and refugees residing in Peru using data from the Survey Directed at the Venezuelan Population Residing in the Country (ENPOVE) conducted in 2022. The analysis included 7739 Venezuelan adults. The presence of mental health problems was self-reported, and household food insecurity was measured using the Food Insecurity Experience Scale. The study found that 4 out of 10 participants lived in households with moderate to severe food insecurity, and around 10% reported experiencing some mental health problem in the last month. The study identified a positive association between living in households with moderate to severe food insecurity and having some mental health problem compared to living in households without food insecurity. The findings suggest that food insecurity is a common problem among the Venezuelan migrant population residing in Peru, and measures are required to address this problem and mitigate its consequences on mental health and other health problems. The study highlights the need for international organizations to provide assistance and support to these populations and ensure adequate and sustainable follow-up of food insecurity at the national level. It is also necessary to implement early detection tests for mental health problems in the migrant population, especially in individuals exposed to food insecurity. This study provides relevant evidence for addressing public health in the Venezuelan migrant population residing in Peru.


Prison hospice and pastoral care services in California.
Hospice at the California Medical Facility (CMF) Vacaville dates back to the mid-1980s, when the acquired immune deficiency syndrome (AIDS) epidemic began to be felt throughout California's Department of Corrections. Vacaville has served for decades as the principal location for delivering health services to California's incarcerated men. Informal hospice-like services were inspired by Elisabeth Kubler-Ross and through inmate and community calls for more humane care for dying inmates. By 1990, efforts to formally establish a hospice were under way. In 1996, a 17-bed, state-licensed hospice began caring for dying inmates. An interdisciplinary team plans and delivers the care, meeting weekly to admit and review patients. The Pastoral Care Services (PCS) inmate volunteer program, with more than 50 trained participants, provides care and comfort to dying patients in hospice and to ill patients on the general medicine service. PCS volunteers perform many duties, including sitting vigil with actively dying inmates. Inmates enrolling in hospice have to forgo further curative therapy, consent to the program in writing, and have a 6-month or less survival prognosis; patients are not required to have a do-not-resuscitate (DNR) order, but are encouraged to consider one. Training for physicians, staff and PCS volunteers is provided by the University of California, Davis faculty of the West Coast Center for Palliative Education. Bereavement services are provided for PCS volunteers, other inmate "family" and staff. Family and friends of the deceased in the free community are followed by phone, mail, and primarily through referral to resources in their local area.


Diaphragm plication following phrenic nerve injury: a comparison of paediatric and adult patients.
A study was undertaken to evaluate whether adults differ from children in the indications and outcome of diaphragmatic plication following phrenic nerve injury. A retrospective study was performed of 21 patients, 10 below the age of 5 and 11 older than 37 years. The indication for surgery for all the children was failure to wean from ventilatory support. The indications for surgery in the adult group were ventilator dependency (n=4) and symptomatic dyspnoea (n=7). All patients had at least one imaging study confirming diaphragmatic paralysis. The American Thoracic Society (ATS) dyspnoea scale, pulmonary function tests, and quantitative pulmonary perfusion scans were used as evaluation parameters. At surgery the diaphragm was centrally plicated. One child died immediately after surgery due to irreversible heart failure and two children died within 2 months of surgery from ongoing complications of their original condition. These three patients were considered as selection failures. Seven children were weaned from ventilatory support within a median of 4 days (range 2-140). Only one of four ventilated adults was successfully weaned. Seven adults who underwent surgery for chronic symptoms had a marked subjective improvement of 2-3 levels in the ATS dyspnoea scale. Pulmonary function studies in the seven symptomatic adults showed a 40% improvement above baseline. Severely asymmetrical perfusion scans reverted to a normal pattern after plication. Diaphragmatic plication offers a significant benefit to children with diaphragmatic paralysis and should be performed early to facilitate weaning from mechanical ventilation. While plication is of limited benefit in weaning ventilated adults, it results in significant subjective and objective lifetime improvement in non-ventilated symptomatic adults.


The Patient-Centered Medical Home as a Community-based Strategy.
Increasing attention has been devoted to the important role that primary care will play in improving population health. One innovation, the patient-centered medical home (PCMH), aims to unite a variety of professionals with patients in the prevention and treatment of illness. Although patient perspectives are critical to this model, this article questions whether the PCMH in practice is truly community-based. That is, do physicians, planners, and other health care professionals take seriously the value of integrating local knowledge into medical care? The argument presented is that community-based philosophy contains a foundational principle that the perspectives of health care practitioners and community members must be integrated. Although many proponents of the PCMH aim to offer patient-centered and sustainable health care, focusing on this philosophical shift will ensure that services are organized by communities in collaboration with health care professionals.


[Relationship between lipid peroxidase and superoxide dismutase in bronchoalveolar lavage fluid and pulmonary qi deficiency syndrome].
Investigating the levels of lipid peroxidase (LPO) and superoxide dismutase (SOD) in serum, bronchoalveolar lavage fluid (BALF) and alveolar macrophage (AM) were determined in 40 chronic bronchitis patients with Pulmonary Qi Deficiency (PQD) Syndrome and 36 normal subjects. Results showed: (1) No significant differences were found between PQD syndrome and normal subjects on serum SOD or LPO levels. (2) Patients with PQD Syndrome. LPO level in BALF was significantly higher, and SOD significantly lower, when compared with normal subjects. (3) Through correlation analysis, it was found in BALF that SOD level was markedly correlated with AM, while LPO was significantly correlated with neutrophil. In short, SOD and LPO in BALF play an important role in the development of the PQD Syndrome, and are good indications in evaluating the PQD Syndrome.


Pseudo-single domain colloidal superparamagnetic nanoparticles designed at a physiologically tolerable AC magnetic field for clinically safe hyperthermia.
Magnetic nanofluid hyperthermia (MNFH) with pure superparamagnetic nanoparticles (P-SPNPs) has drawn a huge attraction for cancer treatment modality. However, the low intrinsic loss power (ILP) and attributable degraded-biocompatibility resulting from the use of a heavy dose of P-SPNP agents as well as low heat induction efficiency in biologically safe AC magnetic field (HAC,safe) are challenging for clinical applications. Here, we report an innovatively designed pseudo-single domain-SPNP (PSD-SPNP), which has the same translational advantages as that of conventional P-SPNPs but generates significantly enhanced ILP at HAC,safe. According to the analyzed results, the optimized effective relaxation time, τeff, and magnetic out-of-phase susceptibility, χ'', precisely determined by the particle size at the specific frequency of HAC,safe are the main reasons for the significantly enhanced ILP. Additionally, in vivo MNFH studies with colloidal PSD-SPNPs strongly demonstrated that it can be a promising agent for clinically safe MNFH application with high efficacy.


The incidence of cerebral amyloid angiopathy in surgically treated intracranial hemorrhage in the Chinese population.
Despite being widely accepted as an important cause of spontaneous intracranial hemorrhage (ICH), cerebral amyloid angiopathy (CAA) has seldom been studied in the Chinese population. The current study aims to investigate the incidence and features of CAA in surgically treated ICH patients in China. From May 2006 to April 2011, 974 patients admitted to 71 hospitals throughout China for acute spontaneous ICH were studied. Craniotomy for hematoma evacuation was performed. Brain tissue from the superficial side of the suspected residual hematoma cavity, as well as from the cortex and subcortex, was obtained. Congo Red stain and β-amyloid immunohistochemistry were used for the diagnosis. Each case was assigned a pathological severity score. Of the 974 involved patients, 37.7% were identified with CAA of different degrees. CAA had positive correlation with age and was independent of sex. Most patients had mild CAA with only the superficial vessels involved in lobes instead of the basal ganglia; the patients ≥65 years had more severe pathological score of CAA than those <65 years and had more lobes and cerebellum involved than the latter. More than one third of the surgically treated Chinese ICH patients may have CAA of different degrees.


Eight-year follow-up of resurfacing hemiarthroplasty for advanced glenohumeral osteoarthritis following total acromionectomy.
Total acromionectomy is now a largely historical procedure due to a number of biomechanical sequelae caused by defunctioning of the deltoid, although its overall effect on joint kinematics is uncertain. This presents a challenge when considering arthroplasty for subsequent glenohumeral arthritis. We report on successful management of such a case, treated with resurfacing hemiarthroplasty 57 years following acromionectomy. The patient continues to enjoy excellent functional outcome of the shoulder at 8 years after arthroplasty.


Analysis of the HSV-1 strain 17 DNA polymerase gene reveals the expression of four different classes of pol transcripts.
We have investigated the structure and the expression of transcripts of the HSV-1 strain 17 DNA polymerase gene (pol) by various mapping methods including cDNA cloning. The majority of mature pol transcripts is strictly colinear with the pol gene. But additionally, pol cDNAs show a defined heterogeneity in respect to their 5'-terminal regions and can be divided into four classes with characteristic differences; (i) class 1 represents the major transcript (pol-R1) with initiation at HSV-1 positions 62,605-62,610, (ii) class 2 initiates about 70 bp downstream, (iii) class 3 is generated by splicing the short open reading frame (SORF) to a 5'-truncated part of the long open reading frame (LORF) which results in a partially different coding potential, and (iv) class 4 starts 120 bp upstream of the major initiation site in the central part of the origin of replication (oriL). S1 and Exo VII nuclease and RNase protection assays as well as primer extension analyses confirm the classification regarding the genuine structure of pol mRNAs and the differential usage of transcriptional start sites. Furthermore, the transcript classes can be distinguished from each other by their kinetics of appearance/disappearance in the cytoplasm: The first transcription of the pol gene is indicated by the predominant presence of class 2 and class 4 mRNAs at 2 hr postinfection (h.p.i.), followed by an increase of class 1 transcripts up to 4 h.p.i. and a parallel decrease of class 2 mRNAs. These data suggest that expression of the pol gene is finely regulated already at the transcriptional and/or posttranscriptional level prior to the translation of pol mRNAs.


Influence of tooth preparation taper and cement type on recementation strength of complete metal crowns.
Clinical studies have shown that lack of retention is one of the major causes of fixed dental prosthesis failure. The purpose of this study was to determine the relationship between the convergence angle of a complete metal crown tooth preparation and the recementation strength for restorations cemented with conventional and adhesive cements. One hundred twenty artificial crowns were cast for standardized complete metal crown tooth preparations accomplished with the use of a milling machine on extracted human teeth. Three different tapers, 5, 12, and 25 degrees, were used (n=40). The crowns in each group were subdivided into 4 subgroups (n=10) according to the luting cement: zinc phosphate cement (Fleck's), glass ionomer cement (Ketac-Cem), and adhesive resin cements (Panavia 21 and C&B-Metabond). Retention was evaluated by measuring the tensile force required to dislodge the crowns from the tooth preparations in a universal testing machine. Subsequently, the tooth preparations were scraped clean and polished with prophylaxis paste, and the intaglio surfaces of the artificial crowns were ultrasonically cleaned and airborne-particle abraded with 50-mum aluminum oxide powder prior to recementation. The data were analyzed with 3-way repeated-measures ANOVA and Tukey's HSD test (alpha=.05). Analysis of measurements disclosed a significant difference for taper and luting cement (P<.001); however, their interaction was not significant. Also, there was a statistically significant difference between the retention of the first cementation and the second cementation (P<.001). However, the interaction was not significant with taper or cement. Regardless of the taper used, Panavia 21 cement exhibited the highest mean initial retention, but the difference was not significantly different from the recementation retentive strength. Tooth preparation taper and type of luting cement had a direct effect on the recementation strength of complete metal crowns.


Performance Characteristics of TOP5 Versus NOT-TOP5 Races in Female Professional Cycling.
Maximal mean power output (MMP) is commonly used to describe the demands and performances of races in professional male cycling. In the female professional cyclist domain, however, there is limited knowledge regarding MMPs in races. Therefore, this study aimed to describe MMPs in female professional cycling races while investigating differences between TOP5 and NOT-TOP5 races. Race data (N = 1324) were collected from 14 professional female cyclists between 2013 and 2019. Races were categorized as TOP5 or NOT-TOP5. The MMPs were consequently determined over a range of different time frames (5 s to 60 min). To provide these MMPs with additional context, 2 factors were determined: when these MMPs were attained in a race (based on duration and kilojoules spent [kJspent·kg-1]) and these MMPs relative to the cyclist's season's best MMP (MMP%best). Short-duration power outputs (≤1 min) were higher in TOP5 races compared with NOT-TOP5 races. In addition, the timing (both duration and kJspent·kg-1) of all MMPs was later and after more workload in the race in TOP5 compared with NOT-TOP5 races. In contrast, no difference in MMP%best was noted between TOP5 and NOT-TOP5 races. TOP5 races in female cycling are presented with higher short-duration MMPs (≤1 min) when compared with NOT-TOP5 races, and cyclists were able to reach a higher percentage of their seasonal best MMP when they were able to finish TOP5. In addition, these MMPs are performed later and after more kJspent·kg-1 in TOP5 versus NOT-TOP5 races, which confirms the importance of "fatigue resistance" in professional (female) cycling.


Critical incident stress intervention after loss of an air ambulance: two-year follow up.
Following an air ambulance crash with five fatalities, critical incident stress debriefing (CISD) was provided for involved paramedics, physicians, and nurses. A study was conducted to evaluate the long-term effects of a critical incident with critical incident stress debriefing according to the Mitchell model. Six months following the incident, empirically designed questionnaires were mailed to all transport paramedics and directly involved medical staff, and a random sample of both nurses from the dispatch/receiving institution and paramedics from around the province. Twenty-four months post-incident, all members of the transport paramedics completed the Impact of Events Scale and the General Health Questionnaires. There were no differences between groups on any scores, except for disturbed sleep patterns, bad dreams, and the need for personal counseling being greater among transport paramedics at one day. There was no correlation between how well the deceased individuals were known, amount of debriefing, and symptom severity. A trend was seen for those with pre-existing stress management routines to have less severe symptoms at six months (p = 0.07). At two years, 16% of transport paramedics still had significant abnormal behavior. CISD did not appear to affect the severity of stress symptoms, whereas having pre-existing stress management strategies may. These findings give justification for proceeding to a randomized, controlled trial of different levels of critical incident stress intervention.


The epidemiology of fatigue and depression: a French primary-care study.
The prevalence of fatigue as a presenting complaint and as a symptom is evaluated in French general practice patients. The data for a sample of 3784 persons 18-64 years-of-age who were seen by 367 general practitioners were examined for fatigue as a presenting complaint, diagnosis, and reported symptoms of persistent fatigue. Gender, age, and socio-professional category were considered as potential risk correlates. At least one of the symptoms of persistent fatigue was reported by 41.2% of the patients, but only 7.6% had presented with fatigue to the doctor. Women reported more symptoms of fatigue than men, but they were only slightly more likely to present with, or be diagnosed with fatigue; women were more frequently diagnosed with depression. There was a strong relationship between the symptoms of depression as measured by the Center for Epidemiologic Studies-Depression Scale (CES-D) and fatigue, but fatigue was neither sensitive nor specific for the diagnosis of depression. Age and fatigue as a presenting complaint and diagnosis were strongly associated for men. After adjusting for sex and age, we found that lower social classes were less likely to be diagnosed as fatigued, though they were more likely to report symptoms of fatigue.


Reaction times and electromechanical delay in reactions of increasing and decreasing force.
The purpose of this study was to compare reaction times and electromechanical delay between reactions to increase force from rest and reactions to decrease force from an active state in the quadriceps femoris of healthy young adults. Force, position, and electromyographic data were recorded from 35 subjects reacting to a forced knee-flexion perturbation. Electromechanical delay was assessed through cross-correlation of the filtered EMG and force data. Reaction time to increase force (M= 159.9 msec., 95% CI= 149.9-169.9 msec.) was significantly longer than RT to decrease force (M= 124.4 msec., 95% CI= 118.7-130.1 msec.). This difference was partially caused by a difference in electromechanical delay (RT to increase force electromechanical delay was 63 msec., 95% CI=60-67 msec., greater than the RT to decrease force electromechanical delay of 49 msec., 95% CI=46-52 msec.). This difference in reaction time could be important in identifying and interpreting physiologically meaningful changes in muscle force and in intermuscular coordination during movement.


[Preventive medicine in geriatrics].
This paper gives a summary of check-up and preventive recommendations for elderly. It concerns screening, vaccination, chemoprophylaxy, and counseling. It is mainly based on the recommendations of the U.S. Preventive Services Task Force. It approaches the screening of hypertension, visual and auditive impairment, breast, colorectal, cervical, prostate cancers, about dyslipidemia, depression, osteoporosis, vaccination against influenza, pneumococcal infection, and chemoprophylaxy by estrogen, raloxifene, acetylsalicylic acid. There is also counseling in the prevention of falls, exercises, and diet. This summary underlines the multiple recent changes compared with the 1996 recommendations.


The nasal valves: changes in anatomy and physiology in normal subjects.
There is confusion in the literature concerning the physiology and pathology of the nasal valve, and some debate as to whether there is one valve or two. In an attempt to clarify these uncertainties we have measured nasal function by assessing nasal minimum cross-sectional area, inspiratory resistance and peak inspiratory flow under baseline conditions and after the application of a topical vasoconstrictor. These measurements were then repeated following the application of external and internal nasal splints. Whatever test was employed the results showed that vasoconstriction tended to be the most potent stimulus which changed nasal function producing significant expansion of the minimum cross-sectional area, a decrease in inspiratory resistance and an increase in peak inspiratory flow. External splints also increased the minimal cross sectional area but they had no effect on inspiratory resistance or on the tendency of the vestibular rim to collapse at high inspiratory flow rates. The tendency for lower lateral cartilage collapse was, however, prevented by internal splintage using alar dilators. The results of this study suggest that there is an internal valve at the nasal isthmus where the principal alterations in airway patency follow changes in mucosal congestion, and a mobile external valve where airflow is limited by the tendency of the alar cartilages to collapse. These should be considered as separate entities with differing pathophysiology and these differences should be taken into account when treating patients with airway obstruction due to pathology at these sites.


USB-driven microfluidic chips on printed circuit boards.
A technology is presented to fabricate a microfluidic chip in which the microchannels and the microelectrodes of sensors are integrated directly into the copper sheet on a printed circuit board. Then, we demonstrate an application of the generation of oil-in-water and water-in-oil emulsion droplets on this microfluidic chip driven by a USB interface, and the droplet size is detected by the microelectrodes on the downstream microchannel. The integration of the microfluidic chip is improved by the direct connection of the channels to the microelectrodes of the driving unit and of the sensors on the same substrate, and it is a promising way to integrate microfluidics into a more complex micro electrical-mechanical system (MEMS).


N-Degradomic Analysis Reveals a Proteolytic Network Processing the Podocyte Cytoskeleton.
Regulated intracellular proteostasis, controlled in part by proteolysis, is essential in maintaining the integrity of podocytes and the glomerular filtration barrier of the kidney. We applied a novel proteomics technology that enables proteome-wide identification, mapping, and quantification of protein N-termini to comprehensively characterize cleaved podocyte proteins in the glomerulus in vivo We found evidence that defined proteolytic cleavage results in various proteoforms of important podocyte proteins, including those of podocin, nephrin, neph1, α-actinin-4, and vimentin. Quantitative mapping of N-termini demonstrated perturbation of protease action during podocyte injury in vitro, including diminished proteolysis of α-actinin-4. Differentially regulated protease substrates comprised cytoskeletal proteins as well as intermediate filaments. Determination of preferential protease motifs during podocyte damage indicated activation of caspase proteases and inhibition of arginine-specific proteases. Several proteolytic processes were clearly site-specific, were conserved across species, and could be confirmed by differential migration behavior of protein fragments in gel electrophoresis. Some of the proteolytic changes discovered in vitro also occurred in two in vivo models of podocyte damage (WT1 heterozygous knockout mice and puromycin aminonucleoside-treated rats). Thus, we provide direct and systems-level evidence that the slit diaphragm and podocyte cytoskeleton are regulated targets of proteolytic modification, which is altered upon podocyte damage.


Correlates of osteoporosis among Jewish and Arab women aged 45-74 in Israel: national women's health interview survey.
To determine the prevalence and correlates of osteoporosis among middle-aged and elderly Jewish and Arab women in Israel. A cross-sectional study on a random sample of Israeli women, carried out through telephone interviews. Questions included physician-diagnosed osteoporosis, demographic and lifestyle variables, medical conditions, and present and past use of estrogen-containing medications. Body mass index (BMI) was calculated from reported height and weight. A national population-based survey conducted from March through August 1998. A national random sample of 888 women aged 45-74. The overall prevalence of self-reported osteoporosis was estimated at 13.7%. The rates increased abruptly from about 5.8% at ages 45-59 to 19.6% at ages 60-64, and reached 27.7% at ages 70-74. Between ages 45-59, the rates were higher among Arab women, whereas in the older group they were higher among Jewish women. There was a marked increase following menopause. After adjustment for potential confounders, at ages 45-59, osteoporosis was positively associated with menopause and BMI, whereas at ages 60-74, it was positively associated with age and family history of osteoporosis, and negatively associated with BMI. The prevalence of physician-diagnosed osteoporosis in Israel among women aged 45-74 is estimated to be 13.7%, which is similar to that for the United States. The association of osteoporosis with risk factors is age-dependent, and in particular, age-BMI interaction on osteoporosis requires further investigation.


HSV serologic testing for pregnant women: willingness to be tested and factors affecting testing.
This prospective study was undertaken to evaluate pregnant women's willingness to undergo HSV type-specific serologic testing and factors affecting willingness in an obstetrics/gynecology ambulatory unit. At prenatal Visit 1, pregnant women (n = 303) with no history of HSV-2 were tested for HSV-1/HSV-2 before and after they received counseling on genital and neonatal herpes. In both the Unwilling Subgroup and the group that changed from being willing to being unwilling, the most common reasons for choosing not to be tested were not being at risk for genital herpes, being tested is too personal, and concern about what will be done with the results. Of the 134 participants in the Willing/Tested Subgroup, 27 (20%) were HSV-2 seropositive and 81 (60%) were HSV-1 seropositive. Conclusions. These results support the feasibility of HSV serologic testing and counseling in pregnant women.


Effects of Feeding Corn-lablab Bean Mixture Silages on Nutrient Apparent Digestibility and Performance of Dairy Cows.
This study estimated the fermentation characteristics and nutrient value of corn-lablab bean mixture silages relative to corn silages. The effects of feeding corn-lablab bean mixture silages on nutrient apparent digestibility and milk production of dairy cows in northern China were also investigated. Three ruminally cannulated Holstein cows were used to determine the ruminal digestion kinetics and ruminal nutrient degradability of corn silage and corn-lablab bean mixture silages. Sixty lactating Holstein cows were randomly divided into two groups of 30 cows each. Two diets were formulated with a 59:41 forage: concentrate ratio. Corn silage and corn-lablab bean mixture silages constituted 39.3% of the forage in each diet, with Chinese wildrye hay constituting the remaining 60.7%. Corn-lablab bean mixture silages had higher lactic acid, acetic acid, dry matter (DM), crude protein (CP), ash, Ca, ether extract concentrations and ruminal nutrient degradability than monoculture corn silage (p<0.05). Neutral detergent fiber (NDF) and acid detergent fiber (ADF) concentrations of corn-lablab bean mixture silages were lower than those of corn silage (p<0.05). The digestibility of DM, CP, NDF, and ADF for cows fed corn-lablab bean mixture silages was higher than for those fed corn silage (p<0.05). Feeding corn-lablab bean mixture silages increased milk yield and milk protein of dairy cows when compared with feeding corn silage (p<0.05). The economic benefit for cow fed corn-lablab bean mixture silages was 8.43 yuan/day/cow higher than that for that fed corn silage. In conclusion, corn-lablab bean mixture improved the fermentation characteristics and nutrient value of silage compared with monoculture corn. In this study, feeding corn-lablab bean mixture silages increased milk yield, milk protein and nutrient apparent digestibility of dairy cows compared with corn silage in northern China.


Residual hepatocellular carcinoma after oxaliplatin treatment has increased metastatic potential in a nude mouse model and is attenuated by Songyou Yin.
The opposite effects of chemotherapy, which enhance the malignancy of treated cancers such as hepatocellular carcinoma (HCC), are not well understood. We investigated this phenomenon and corresponding mechanisms to develop a novel approach for improving chemotherapy efficacy in HCC. Human hepatocellular carcinoma cell lines HepG2 (with low metastatic potential) and MHCC97L (with moderate metastatic potential) were used for the in vitro study. An orthotopic nude mouse model of human HCC was developed using MHCC97L cells. We then assessed the metastatic potential of surviving tumor cells after in vitro and in vivo oxaliplatin treatment. The molecular changes in surviving tumor cells were evaluated by western blot, immunofluorescence, and immunohistochemistry. The Chinese herbal extract Songyou Yin (composed of five herbs) was investigated in vivo to explore its effect on the metastatic potential of oxaliplatin-treated cancer cells. MHCC97L and HepG2 cells surviving oxaliplatin treatment showed enhanced migration and invasion in vitro. Residual HCC after in vivo oxaliplatin treatment demonstrated significantly increased metastasis to the lung (10/12 vs. 3/12) when re-inoculated into the livers of new recipient nude mice. Molecular changes consistent with epithelial-mesenchymal transition (EMT) were observed in oxaliplatin-treated tumor tissues and verified by in vitro experiments. The Chinese herbal extract Songyou Yin (4.2 and 8.4 g/kg) attenuated EMT and inhibited the enhanced metastatic potential of residual HCC in nude mice (6/15 vs. 13/15 and 3/15 vs. 13/15, respectively). The surviving HCC after oxaliplatin treatment underwent EMT and demonstrated increased metastatic potential. Attenuation of EMT by Songyou Yin may improve the efficacy of chemotherapy in HCC.


[Considering advantages of dynamical omentopancreatostomy in the treatment of necrotic pancreatitis].
While application of dynamical omentopancreatopexy for the treatment of necrotic pancreatitis there were noted the purulent and visceral complications frequency lowering from 3.34 in every patient--while the closed interventions usage down to 2.02 and of mortality--from 57.2 down to 33% accordingly.


TLR9 expression in glioma tissues correlated to glioma progression and the prognosis of GBM patients.
Our study aims to evaluate the expression of TLR9 in glioma tissues, examine the association between TLR9 expression, clinicopathological variables, and glioma patient outcome, we further characterized the direct effects of TLR9 agonist CpG ODN upon the proliferation and invasion of glioma cells in vitro. RT-PCR and immunofluorescence were used to determine the expression of TLR9 in glioma cell lines and clinical glioma samples. Tissue microarry and immunohistochemistry were applied to evaluated TLR9 expression in 292 newly diagnosed glioma and 13 non-neoplastic brain tissues. We further investigated the effect of CpG ODN on the proliferation and invasion of glioma cells in vitro with MTT assays and matrigel transwell assay respectively. RT-PCR showed that TLR9 expressed in all the glioma samples and glioma cell lines we examined. The tissue array analysis indicated that TLR9 expression is correlated with malignancy of glioma (p < 0.01). Multivariate Cox regression analysis revealed that TLR9 expression is an independent prognostic factor for PFS of GBM patients (P = 0.026). TLR9 agonist CpG ODN has no significant effect on glioma proliferation, but matrigel transwell analysis showed that TLR9 agonist CpG ODN can significantly enhance glioma invasion in vitro. Our data indicated that TLR9 expression increases according to the histopathological grade of glioma, and the TLR9 expression level is related to the PFS of GBM patients. In addition, our findings warrant caution in the directly injection of TLR9 agonist CpG ODN into glioma tissues for the glioma immunotherapy.


Optimizing Outcomes in Cardiac Rehabilitation: The Importance of Exercise Intensity.
Exercise based cardiac rehabilitation (CR) is recognized internationally as a class 1 clinical practice recommendation for patients with select cardiovascular diseases and heart failure with reduced ejection fraction. Over the past decade, several meta-analyses have generated debate regarding the effectiveness of exercise-based CR for reducing all-cause and cardiovascular mortality. A common theme highlighted in these meta-analyses is the heterogeneity and/or lack of detail regarding exercise prescription methodology within CR programs. Currently there is no international consensus on exercise prescription for CR, and exercise intensity recommendations vary considerably between countries from light-moderate intensity to moderate intensity to moderate-vigorous intensity. As cardiorespiratory fitness [peak oxygen uptake (VO2peak)] is a strong predictor of mortality in patients with coronary heart disease and heart failure, exercise prescription that optimizes improvement in cardiorespiratory fitness and exercise capacity is a critical consideration for the efficacy of CR programming. This review will examine the evidence for prescribing higher-intensity aerobic exercise in CR, including the role of high-intensity interval training. This discussion will highlight the beneficial physiological adaptations to pulmonary, cardiac, vascular, and skeletal muscle systems associated with moderate-vigorous exercise training in patients with coronary heart disease and heart failure. Moreover, this review will propose how varying interval exercise protocols (such as short-duration or long-duration interval training) and exercise progression models may influence central and peripheral physiological adaptations. Importantly, a key focus of this review is to provide clinically-relevant recommendations and strategies to optimize prescription of exercise intensity while maximizing safety in patients attending CR programs.


Spo13 regulates cohesin cleavage.
A key aspect of meiotic chromosome segregation is that cohesin, the protein complex that holds sister chromatids together, dissociates from chromosome arms during meiosis I and from centromeric regions during meiosis II. The budding yeast protein Spo13 plays a key role in preventing centromeric cohesin from being lost during meiosis I. We have determined the molecular basis for the metaphase arrest obtained when SPO13 is overexpressed during the mitotic cell cycle. Overexpression of SPO13 inhibits anaphase onset by at least two mechanisms. First, Spo13 causes a transient delay in degradation of the anaphase inhibitor Pds1. Second, Spo13 inhibits cleavage of the cohesin subunit Scc1/Mcd1 or its meiosis-specific homolog, Rec8, by the separase Esp1. The finding that Spo13 did not prevent cleavage of another Esp1 substrate, Slk19, suggests that overexpression of SPO13 is sufficient to prevent cohesin cleavage by protecting specific substrates from separase activity.


DaVIE: Database for the Visualization and Integration of Epigenetic data.
One of the challenges in the analysis of large data sets, particularly in a population-based setting, is the ability to perform comparisons across projects. This has to be done in such a way that the integrity of each individual project is maintained, while ensuring that the data are comparable across projects. These issues are beginning to be observed in human DNA methylation studies, as the Illumina 450k platform and next generation sequencing-based assays grow in popularity and decrease in price. This increase in productivity is enabling new insights into epigenetics, but also requires the development of pipelines and software capable of handling the large volumes of data. The specific problems inherent in creating a platform for the storage, comparison, integration, and visualization of DNA methylation data include data storage, algorithm efficiency and ability to interpret the results to derive biological meaning from them. Databases provide a ready-made solution to these issues, but as yet no tools exist that that leverage these advantages while providing an intuitive user interface for interpreting results in a genomic context. We have addressed this void by integrating a database to store DNA methylation data with a web interface to query and visualize the database and a set of libraries for more complex analysis. The resulting platform is called DaVIE: Database for the Visualization and Integration of Epigenetics data. DaVIE can use data culled from a variety of sources, and the web interface includes the ability to group samples by sub-type, compare multiple projects and visualize genomic features in relation to sites of interest. We have used DaVIE to identify patterns of DNA methylation in specific projects and across different projects, identify outlier samples, and cross-check differentially methylated CpG sites identified in specific projects across large numbers of samples. A demonstration server has been setup using GEO data at http://echelon.cmmt.ubc.ca/dbaccess/, with login "guest" and password "guest." Groups may download and install their own version of the server following the instructions on the project's wiki.


Embryo implantation after assisted reproductive procedures and maternal thrombophilia.
Women undergoing assisted reproductive procedures, such as in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI), fail to achieve pregnancy in approximately 70% of cases. Postulating that among the possible causes of failure of embryo implantation might be an impairment of the uteroplacental circulation due to hypercoagulability in the mother, we investigated the association between thrombophilia and failure to achieve pregnancy after IVF or ICSI. A case-control study was carried out in 234 women undergoing IVF or ICSI and in 234 women who, in the same period, conceived naturally. Thrombophilia due to mutations in genes encoding coagulation factor V (G1691A), prothrombin (G20210A), methylene-tetrahydrofolate reductase (C677T) and the presence of antiphospholipid antibodies was searched for. The prevalence of factor V, prothrombin and methylene-tetrahydrofolate reductase mutations was similar in the 162 women who failed to achieve pregnancy after IVF or ICSI and in control women (5% and 2% for factor V G1691A, odd ratio 2.4, 95% CI 0.8-7.4; 3% and 6% for prothrombin G20210A, odds ratio 0.5, 95% CI 0.2-1.5; 19% and 20% for homozygous methylene-tetrahydrofolate reductase C677T, odds ratio 1.0, 95% CI 0.6-1.6). Nor was any association found when women who failed to achieve pregnancy were divided according to the total number of assisted reproductive procedures, age, type of procedure and cause of infertility. Antiphospholipid antibodies were not detected in any of the women. This study provides no evidence for an association between maternal thrombophilia and failure to achieve pregnancy after assisted reproductive procedures. Routine anticoagulant treatment in women undergoing assisted reproductive procedures is not warranted.


Identification of small molecules uncoupling the Notch::Jagged interaction through an integrated high-throughput screening.
Notch signaling plays an important role in several cellular functions including growth, differentiation, cell fate determination and stemness. Increased Notch activity has been linked to several types of cancers. Activation of Notch signaling is triggered by the interaction of Notch receptors (Notch1-4) with 5 different ligands (Jagged1-2 and Dll1-3-4) expressed on the neighbouring cells. Currently, indirect approaches to inhibit Notch signalling are based on the inhibition of the key step of Notch activation catalyzed by the γ-Secretase and thereby affect several different γ-Secretase substrates; conversely direct strategies get advantage of antibody-based drugs. The evidence that Jagged-mediated Notch activation plays a key role in cancer cell biology and the interplay with the surrounding microenvironment prompted us to develop a strategy to directly inhibit Notch activation by uncoupling its interaction with the Jagged, using an unprecedented approach based on small molecules. We set-up a screening strategy based on: protein::protein docking of crystallographic structures of Notch1 with Jagged1; comparative modelling of the Notch2:Jagged2 complex, based on the Notch1::Jagged1 complex; in silico high-throughput screening directed to Notch2 interaction surface of a virtual chemical library containing a large variety of molecules commercially available. The predicted pharmacological activity of the selected compounds was validated in vitro by a gene reporter and a viability assay. This approach led to the successful identification of two candidates with different anti-proliferative potency and efficacy. This represents the first step towards the rational identification of candidate molecules for the development of entirely novel drugs directed to inhibit Notch signaling in cancer.


Laparoscopic Nissen fundoplication during gastrostomy tube placement and noninvasive ventilation may improve survival in type I and severe type II spinal muscular atrophy.
Progressive respiratory muscle weakness with bulbar involvement is the main cause of morbidity and mortality in type I and severe type II spinal muscular atrophy. Noninvasive positive pressure ventilation techniques coupled with laparoscopic gastrointestinal procedures may allow for improved morbidity and mortality. The authors present a series of 7 spinal muscular atrophy patients (6 type I and 1 severe type II) who successfully underwent laparoscopic gastrostomy tube insertion coupled with Nissen fundoplication and early postoperative extubation using noninvasive positive pressure ventilation techniques. The authors measured the length of survival and the frequencies of pneumonia and hospitalization before and after surgery as outcomes of these new surgical and medical interventions. All 7 patients had respiratory symptoms (unmanageable oropharyngeal secretions, cough, pneumonia), difficulty feeding, and weight loss. Six patients had documented reflux via diagnostic testing preoperatively. Five patients were on noninvasive positive pressure ventilation and other supportive respiratory therapies prior to surgery. All 7 patients survived the procedures. By August 2006, 5 patients with type I and 1 with severe type II spinal muscular atrophy were alive and medically stable at home 1.5 months to 41 months post-op. One patient with type I expired approximately 5 months post-op due to obstructive apnea. This case series demonstrates that laparoscopic gastrostomy tube placement coupled with Nissen fundoplication and noninvasive positive pressure ventilation can be successfully used as a treatment option to allow for early postoperative extubation and to optimize quality of life in type I and severe type II spinal muscular atrophy patients.


regulation of the invasion and metastasis of human glioma cells by polypeptide N-acetylgalactosaminyltransferase 2.
Polypeptide, N-acetylgalactosaminyltransferase 2 (ppGalNAc-T2), is a member of the ppGalNAcT family which is the initial glycosyltransferase in O-glycan synthesis. Our previous studies have demonstrated that ppGalNAc-T2 plays a vital role in the process of tumor emergence and development. In this study, we aimed to determine whether ppGalNAc-T2 is correlated with the invasion and metastasis of human glioma cells. PpGalNAc-T2 sense vectors and interference vectors constructed in our laboratory were successfully transfected into SHG44 and U251 cells, which were observed through fluorescence microscopy, RT-PCR and western blot analysis. The metastasis of U251 cells was determined using a wound healing assay, and ppGalNAc-T2 was found to inhibit cell migration. By RT-PCR, glioma cell invasion assay showed that the expression of MMP-2 was increased in ppGalNAc-T2-knockdown cells, while the expression of MMP-9 and TGF-β1 was decreased in ppGalNAc-T2-overexpressing cells at the mRNA level. Meanwhile, the expression of TIMP-2 at the mRNA level was contrary to MMP-2. In summary, our findings indicate that ppGalNAc-T2 plays a poten-tial role in glioma cell migration and invasion, suggesting a new molecular therapeutic target for human malignant glioma treatment.


The paediatric emergency ward--do mothers want to stay?
The attitudes of parents towards staying with their children in the medical emergency ward at the Red Cross War Memorial Children's Hospital, Cape Town, are reported on. A randomly selected sample of 80 parents or caretakers attending children in the ward were interviewed. The interviews were semi-structured and included open-ended questions. Data were recorded on interview schedules. Of the respondents, 96% wanted to stay with their acutely ill children, although 20% of these were anxious about the effect of this on events at home or at work. Based on the finding that mothers want to stay, even in view of difficulties regarding the situation at home and at work, improved facilities for parents should receive high priority. Recommendations arising from the study include the provision of more comfortable sleeping accommodation for parents, availability of refreshments on a 24-hour basis and provision of a regular supply of books and magazines to the ward.


Fabrication of computationally designed scaffolds by low temperature 3D printing.
The development of artificial bone substitutes that mimic the properties of bone and simultaneously promote the desired tissue regeneration is a current issue in bone tissue engineering research. An approach to create scaffolds with such characteristics is based on the combination of novel design and additive manufacturing processes. The objective of this work is to characterize the microstructural and the mechanical properties of scaffolds developed by coupling both topology optimization and a low temperature 3D printing process. The scaffold design was obtained using a topology optimization approach to maximize the permeability with constraints on the mechanical properties. This procedure was studied to be suitable for the fabrication of a cage prototype for tibial tuberosity advancement application, which is one of the most recent and promising techniques to treat cruciate ligament rupture in dogs. The microstructural and mechanical properties of the scaffolds manufactured by reacting α/β-tricalcium phosphate with diluted phosphoric acid were then assessed experimentally and the scaffolds strength reliability was determined. The results demonstrate that the low temperature 3D printing process is a reliable option to create synthetic scaffolds with tailored properties, and when coupled with topology optimization design it can be a powerful tool for the fabrication of patient-specific bone implants.


'Super-Enrichment' Reveals Dose-Dependent Therapeutic Effects of Environmental Stimulation in a Transgenic Mouse Model of Huntington's Disease.
Huntington's disease (HD) is caused by a tandem repeat expansion and involves progressive cognitive decline, psychiatric abnormalities and motor deficits. Disease onset and progression in HD mice can be substantially delayed by a housing environment with enhanced sensorimotor and cognitive stimulation. However, the proposed benefits of environmental enrichment (EE) are always taken in the context of 'deprived' standard housing and investigation is warranted into the graded effects of enrichment. To assess if a higher level of environmental stimulation ('super-enrichment') has additional benefits compared to home-cage EE in HD mice. One group of R6/1 transgenic HD mice and wild-type (WT) littermates were home-cage enriched (EE group). A second group also had enriched home cages, but from 6 weeks of age were exposed to a large 'super-enrichment' arena (SuperE group) three times per week. A range of motor tests (open field, rotarod, clasping) were conducted from 8 weeks of age and, at the end of the experiment, grip strength was assessed and post-mortem measures were taken (brain weight, striatal volume, dopamine receptor activation and aggregate density). SuperE improved the reduction of exploration in the open field, ameliorated impaired grip strength in home-cage enriched HD mice and delayed, but did not abolish, the onset of rear-paw clasping compared to EE. SuperE increased brain weight compared to EE in HD mice and reduced striatal dopamine D1 receptor agonist-induced c-fos expression, regardless of genotype. Body weight, rotarod performance, aggregate formation and striatal volume in SuperE groups were no different compared to EE groups. The beneficial effects of sensorimotor and cognitive stimulation are graded and extend beyond merely compensating for the deprivation of standard home cages in specific motor-related phenotypes in HD. Our findings highlight the importance of environmental enrichment quality and quantity and the translational value of stimulating living conditions as experience-dependent modulators of pathogenesis in HD and other brain disorders.


The Langmuir-Hinshelwood approach for kinetic evaluation of cucurbit[7]uril-capped gold nanoparticles in the reduction of the antimicrobial nitrofurantoin.
In this work, gold nanoparticles protected by the macrocycle cucurbit[7]uril were used as a catalyst in the reduction of the hazardous antimicrobial nitrofurantoin. 4-Nitrophenol was also employed as the substrate of the reduction for comparative purposes. The kinetic data were modeled to the Langmuir-Hinshelwood equation to know the affinities of the reactants for the surface and the real kinetic constants, a comparison at the molecular level that is made for the first time. From the results, it was observed that the adsorption of nitrofurantoin was stronger than that of 4-nitrophenol whilst the kinetic constant on the surface was higher for 4-nitrophenol than for nitrofurantoin. Additionally, shifts in the nanoparticle surface plasmon band permitted insights to be obtained into the adsorption rate and strength. The reaction induction times were also investigated and were highly dependent on the borohydride concentration and, due to the higher surface affinity of nitrofurantoin compared with 4-nitrophenol, an increase in nitrofurantoin concentration increased the induction time, while a lag phase was not observed for 4-nitrophenol.


Effects of body size on the oxygen sensitivity of dragonfly flight.
One hypothesis for the small size of insects relative to vertebrates, and the existence of giant fossil insects, is that atmospheric oxygen levels constrain insect body sizes because oxygen delivery is more challenging in larger insects. This study tested this hypothesis in dragonflies by measuring the oxygen sensitivity of flight metabolic rates and behavior during hovering for 11 species of dragonflies that ranged in mass by an order of magnitude. We measured flight times and flight metabolic rates in seven oxygen concentrations ranging from 30% to 2.5% to assess the sensitivity of their flight to atmospheric oxygen. We also assessed the oxygen sensitivity of flight in low-density air (nitrogen replaced with helium) in order to increase the metabolic demands of hovering flight. Lowered atmospheric densities did induce higher flight metabolic rates. Flight behavior was more sensitive to decreasing oxygen levels than flight metabolic rate. The oxygen sensitivity of flight metabolic rates and behaviors were not correlated with body size, indicating that larger insects are able to maintain an oxygen supply-to-demand balance even during flight.


Longitudinal analysis of vertebral fracture and BMD in a Canadian cohort of adult cystic fibrosis patients.
Vertebral fractures in patients with cystic fibrosis (CF) may contribute to an accelerated decline in lung function and can be a contraindication to lung transplantation. In this study, we examined longitudinal change in bone mineral density (BMD) and the prevalence of vertebral fractures in adult CF patients, without lung-transplant, attending a Canadian specialty clinic. Retrospective chart review of all patients attending an Adult Cystic Fibrosis Clinic at Hamilton Health Sciences in Hamilton, Canada. Forty-nine of 56 adults met inclusion criteria. Chest radiographs were graded by consensus approach using Genant's semi-quantitative method to identify and grade fractured vertebrae. Dual x-ray absorptiometry (DXA) scans were also reviewed. The mean age of the cohort was 25.2 years (SD 9.4), 43% were male. The mean body mass index (BMI) was 19.8 (2.8) for males and 21.7 (5.1) for females. At baseline, the rate of at least one vertebral fracture was 16.3%; rising to 21.3% (prevalent and incident) after a 3-year follow-up. The mean BMD T-or Z-scores at baseline were -0.80 (SD 1.1) at the lumbar spine, -0.57 (SD 0.97) at the proximal femur, and -0.71 (SD 1.1) at the whole body. Over approximately 4-years, the mean percent change in BMD was -1.93% at the proximal femur and -0.73% at the lumbar spine. Approximately one in five CF patients demonstrated at least one or more vertebral fractures. Moderate declines in BMD were observed. Given the high rate of vertebral fractures noted in this cohort of adult CF patients, and the negative impact they have on compromised lung functioning, regular screening for vertebral fractures should be considered on routine chest radiographs.


[Use of myocardial scintigraphy with Tl-201 and veloergometry in patients with typical stenocardia and atypical pain syndrome].
The results of myocardial scintigraphy with 201Tl used in combination with bicycle ergometry in 19 patients with typical angina and in 41 patients with an atypical pain syndrome are reported. Possible use of a single 201Tl dose at the peak of exercise is considered. The diagnostic value of myocardial scintigraphy with 201Tl was not basically different from that of conventional bicycle ergometry in patients with typical angina, whereas in cases of an atypical pain syndrome myocardial scintigraphy had an essential advantage over bicycle ergometry, which in this case was associated with a noticeably increased number of uncertain or negative results. Total assessment of the exercise test, using both methods, was found to have a higher diagnostic value in both groups.


Improving Endoscopic Image Quality through the Use of High Dynamic Range Imaging-Like Method with Real-Time Performance.
High Dynamic Range (HDR) imaging is a digital image processing technique used to produce a wider range of brightness and color by using multiple captures of a scene taken with different exposures times. It enables capturing more details and producing a more natural-looking image with less washed-out highlights and deeper, more saturated colors. In medical endoscopy, HDR imaging enhances the visibility and clarity of images captured during endoscopy procedures. It provides enhanced visualization of subtler details in both dark cavities and bright areas, resulting in a uniformly exposed view and improved contrast among various tissue types. Standard HDR imaging methods are often complex and computationally demanding, making them unsuitable for performance-critical applications like endoscopy, where real-time performance is crucial. This paper introduces a more efficient and less complex method for achieving HDR-like image quality in real time. The method takes a high-pixel-bit-depth frame and generates multiple low-pixel-bit-depth frames and uses them to generate the high quality image. The focus of the paper is to enhance endoscopic image quality using HDR imaging, and the proposed method is demonstrated to be effective in achieving this goal with real-time performance. The method is implemented in the FPGA System-on-a-Chip (SoC) of a bronchoscope video processor system, and its effectiveness is verified through a simulated study using a phantom, which confirms the improved image quality and real-time performance.


Infusion-related reactions to rituximab: frequency, mechanisms and predictors.
Rituximab, an anti-CD20 monoclonal antibody (mAb), is indicated in the treatment of B-cell non-Hodgkin lymphomas, chronic lymphoid leukemia, and rheumatoid arthritis. The occurrence of infusion-related reactions (IRR), especially during the first infusion, is one of the main concerns of rituximab, otherwise well tolerated. Although IRR are usually mild to moderate, fatal evolutions have been reported. These reactions are not specific to rituximab and also observed with other compounds, including those recruiting effectors cells. Further studies are required to predict the frequency and severity of such reactions, to avoid life-threatening complications, especially in the first-in-human studies. Areas covered: This review reports data available to date on the occurrence of IRR induced by rituximab. Then, factors associated with IRR are described, with proposed pathogenic mechanisms of IRR. Finally, different methods to prevent and manage IRR are reported. Expert opinion: Various factors have been associated with the occurrence and severity of IRR. A predictive model of IRR is of importance to prevent life-threatening IRR or detrimental interruption of rituximab therapy. This model would combine parameters, such as the number of CD20 positive cells and NK cells (CD16 positive), together with the level of CD20 and CD16 expressions, and FCGR3Apolymorphism.


Diallyl trisulfide induces G2/M cell-cycle arrest and apoptosis in anaplastic thyroid carcinoma 8505C cells.
Anaplastic thyroid cancer (ATC) is the most aggressive thyroid cancer. Current approaches including surgery, chemotherapy and therapeutic drugs provide limited benefits for ATC patients. Diallyl trisulfide (DATS) has been documented as a promising anti-cancer agent for various carcinomas. However, its role in ATC tumorigenesis remained unclear. Our results showed that DATS treatment at 12.5, 25 and 50 μM decreased the viability of 8505C cells both in a time- and dose-dependent manner. The phosphorylation of H2A.X, which is a DNA damage marker, was induced by DATS both in a dose- and time-dependent manner. Moreover, DATS mediated the DNA damage through the phosphorylation of ATM but not ATR. DATS also induced G2/M cell-cycle arrest followed by the translocation of Cdc25C from the nucleus to the cytoplasm. Further results showed that DATS induced mitochondrial apoptosis in 8505C cells, evidenced by Hoechst/PI double staining, PI-Annexin V assay and western blot. Taken altogether, our findings demonstrated that DATS induced G2/M cell-cycle arrest and mitochondrial apoptosis by triggering DNA damage in ATC 8505C cells, which shed light on a novel therapeutic approach for ATC treatment.


Evaluation of palatal rugae pattern in different sagittal skeletal relationship adolescent subjects.
The purpose of this study was to evaluate the morphological structure of palatal rugae in Turkish orthodontic subjects with different sagittal skeletal malocclusions. Orthodontic dental casts of 105 patients (Class I [23 females, 12 males]; 35, Class II [18 females, 17 males]; and 35, Class III [14 females, 21 males] 10-22 years old) were analyzed for rugae patterns. Palatal rugae pattern and number, direction of rugae alignment, shape of incisive papilla were analyzed. Modified Thomas and Kotze classification was performed to analyze palatal rugae characteristics. The data were analyzed using the Kruskal-Wallis test. Wavy and curved types were the most common types of rugae pattern in all groups (Class I, Class II, Class III). As regards to the number of primary and secondary rugae on the left and right sides, there was no statistically significant difference among subjects with different skeletal malocclusions. Droplet-shaped incisive papilla was the most common form of incisive papillae among different skeletal malocclusion groups. The most common palatal rugae were direction type arranged in the horizontal direction. All rugae patterns were unique for each individual. The use of antemortem or postmortem palatal rugae records may facilitate identification of the suspects in forensic investigations by enabling facial reconstruction through skeletal malocclusions.


Hemodynamic effects of positive end-expiratory pressure during high-frequency ventilation.
We studied the intrapleural and hemodynamic effects of positive end-expiratory pressure (PEEP) during high-frequency ventilation (HFV) with a Venturi high-frequency ventilator (Bird). Ten healthy mongrel dogs were anesthetized with sodium pentobarbital, catheterized with intrapleural and thermodilution pulmonary artery lines, and subjected to oleic acid-induced pulmonary edema. A mean PEEP of 16 +/- 6 (SD) cm H2O restored venous admixture to baseline in nine animals. Both mean airway pressure (Paw) and mean intrapleural pressure (Ppl) increased significantly with each increment of PEEP during HFV. Approximately 50% of Paw was transmitted to the intrapleural space. Cardiac index (CI) decreased with increments of PEEP in spite of constant transmural central venous and pulmonary capillary wedge pressures, so that oxygen delivery decreased despite increased PaO2. Possible mechanisms of PEEP-induced depression of CI during HFV are discussed. We conclude that both hemodynamic and intrapleural effects of PEEP during HFV are similar to those during conventional mechanical ventilation.


Detection of emotional faces is modulated by the direction of eye gaze.
Emotionally expressive faces have shown enhanced detectability over neutral faces, but little is known about the effect of eye gaze on detecting the presence of emotional faces. Emotional expressions and gaze direction are both cues to the intentions of another person, and gaze direction has been shown to affect recognition accuracy and perceived intensity of emotional faces. The current study showed that fearful faces were detected more frequently with an averted gaze than with a direct gaze in an attentional blink task, whereas angry and happy faces were detected more frequently with a direct gaze than with an averted gaze. The results are in line with the shared signal hypothesis and appraisal theory and suggest that selection for awareness was based on a rapid evaluation of the intentions of another person as conveyed by their facial expression and gaze direction.


Adverse effects of antipsychotic medications.
The use of antipsychotic medications entails a difficult trade-off between the benefit of alleviating psychotic symptoms and the risk of troubling, sometimes life-shortening adverse effects. There is more variability among specific antipsychotic medications than there is between the first- and second-generation antipsychotic classes. The newer second-generation antipsychotics, especially clozapine and olanzapine, generally tend to cause more problems relating to metabolic syndrome, such as obesity and type 2 diabetes mellitus. Also, as a class, the older first-generation antipsychotics are more likely to be associated with movement disorders, but this is primarily true of medications that bind tightly to dopaminergic neuroreceptors, such as haloperidol, and less true of medications that bind weakly, such as chlorpromazine. Anticholinergic effects are especially prominent with weaker-binding first-generation antipsychotics, as well as with the second-generation antipsychotic clozapine. All antipsychotic medications are associated with an increased likelihood of sedation, sexual dysfunction, postural hypotension, cardiac arrhythmia, and sudden cardiac death. Primary care physicians should understand the individual adverse effect profiles of these medications. They should be vigilant for the occurrence of adverse effects, be willing to adjust or change medications as needed (or work with psychiatric colleagues to do so), and be prepared to treat any resulting medical sequelae.


An evaluation of the anatomical basis of the Biceps Load tests I and II for superior labral anterior and posterior (SLAP) lesions.
Both Biceps Load tests I and II rely on an increase in tension in the long head of biceps to identify a superior labral anterior and posterior (SLAP) lesion. This study aimed to evaluate the anatomical basis of Biceps Load tests I and II by measuring activity in the long head of biceps in the two clinical tests. Activity in the long head of biceps was measured in 12 healthy young participants using surface electromyography. Activity was only minimally increased in both Biceps Load I and II compared with the resting position. In the absence of convincing support for the anatomical basis of the test, investigations of diagnostic accuracy need to be replicated in order for the reported high accuracy of Biceps Load I and II tests to be supported with confidence.


[The endaural laser acupuncture of patients with cochleovestibular dysfunction].
Based on a comprehensive clinico-neurophysiological examination of 80 patients with vertebrobasilar insufficiency and 30 practically healthy subjects, a method of endaural laseropuncture of patients with cochleovestibular dysfunction was devised. It has been discovered that the endaural points of acupuncture have a high functional activity and specificity to the cochleovestibular system. The data obtained supported the appreciable therapeutic efficacy of the new treatment method.


Extracellular matrix complexity in biomarker studies: a novel assay detecting total serum tenascin-C reveals different distribution to isoform-specific assays.
Serum biomarkers are the gold standard in non-invasive disease diagnosis and have tremendous potential as prognostic and theranostic tools for patient stratification. Circulating levels of extracellular matrix molecules are gaining traction as an easily accessible means to assess tissue pathology. However, matrix molecules are large, multimodular proteins that are subject to a vast array of post-transcriptional and post-translational modifications. These modifications often occur in a tissue- and/or disease-specific manner, generating hundreds of different variants, each with distinct biological roles. Whilst this complexity can offer unique insight into disease processes, it also has the potential to confound biomarker studies. Tenascin-C is a pro-inflammatory matrix protein expressed at low levels in most healthy tissues but elevated in, and associated with the pathogenesis of, a wide range of autoimmune diseases, fibrosis, and cancer. Analysis of circulating tenascin-C has been widely explored as a disease biomarker. Hundreds of different tenascin-C isoforms can be generated by alternative splicing, and this protein is also modified by glycosylation and citrullination. Current enzyme-linked immunosorbent assays (ELISA) are used to measure serum tenascin-C using antibodies, recognising sites within domains that are alternatively spliced. These studies, therefore, report only levels of specific isoforms that contain these domains, and studies on the detection of total tenascin-C are lacking. As such, circulating tenascin-C levels may be underestimated and/or biologically relevant isoforms overlooked. We developed a highly specific and sensitive ELISA measuring total tenascin-C down to 0.78ng/ml, using antibodies that recognise sites in constitutively expressed domains. In cohorts of people with different inflammatory and musculoskeletal diseases, levels of splice-specific tenascin-C variants were lower than and distributed differently from total tenascin-C. Neither total nor splice-specific tenascin-C levels correlated with the presence of autoantibodies to citrullinated tenascin-C in rheumatoid arthritis (RA) patients. Elevated tenascin-C was not restricted to any one disease and levels were heterogeneous amongst patients with the same disease. These data confirm that its upregulation is not disease-specific, instead suggest that different molecular endotypes or disease stages exist in which pathology is associated with, or independent of, tenascin-C. This immunoassay provides a novel tool for the detection of total tenascin-C that is critical for further biomarker studies. Differences between the distribution of tenascin-C variants and total tenascin-C have implications for the interpretation of studies using isoform-targeted assays. These data highlight the importance of assay design for the detection of multimodular matrix molecules and reveal that there is still much to learn about the intriguingly complex biological roles of distinct matrix proteoforms.


scGHOST: Identifying single-cell 3D genome subcompartments.
New single-cell Hi-C (scHi-C) technologies enable probing of the genome-wide cell-to-cell variability in 3D genome organization from individual cells. Several computational methods have been developed to reveal single-cell 3D genome features based on scHi-C data, including A/B compartments, topologically-associating domains, and chromatin loops. However, no scHi-C analysis method currently exists for annotating single-cell subcompartments, which are crucial for providing a more refined view of large-scale chromosome spatial localization in single cells. Here, we present scGhost, a single-cell subcompartment annotation method based on graph embedding with constrained random walk sampling. Applications of scGhost to scHi-C data and single-cell 3D genome imaging data demonstrate the reliable identification of single-cell subcompartments and offer new insights into cell-to-cell variability of nuclear subcompartments. Using scHi-C data from the human prefrontal cortex, scGhost identifies cell type-specific subcompartments that are strongly connected to cell type-specific gene expression, suggesting the functional implications of single-cell subcompartments. Overall, scGhost is an effective new method for single-cell 3D genome subcompartment annotation based on scHi-C data for a broad range of biological contexts.


Governance using the water-food-energy nexus and human-factor measures.
Household water food and energy (WFE) expenditures, reflect respective survival needs for which their resources and social welfare are inter-related. We developed a policy driven quantitative decision-making strategy (DMS) to address the domain geospatial entities' (nodes or administrative districts) of the WFE nexus, assumed to be information linked across the domain nodal-network. As investment in one of the inter-dependent nexus components may cause unexpected shock to the others, we refer to the WFE normalized expenditures product (Volume) as representing the nexus holistic measure. Volume rate conforms to Boltzman entropy suggesting directed information from high to low Volume nodes. Our hypothesis of causality-driven directional information is exemplified by a sharp price increase in wheat and rice, for U.S. and Thailand respectively, that manifests its impact on the temporal trend of Israel's administrative districts of the WFE expenditures. Welfare mass (WM) represents the node's Volume combined with its income and population density. Formulation is suggested for the nodal-network WM temporal balance where each node is scaled by a human-factor (HF) for subjective attitude and a superimposed nodal source/sink term manifesting policy decision. Our management tool is based on two sequential governance processes: one starting with historical data mapping the mean temporal nodal Volumes to single out extremes, and the second is followed by WM balance simulation predicting nodal-network outcome of policy driven targeting. In view of the proof of concept by model simulations in in our previous research, here HF extends the model and attention is devoted to emphasize how the current developed decision-making approach categorically differs from existing nexus related methods. The first governance process is exemplified demonstrating illustrations for Israel's districts. Findings show higher expenditures for water and lower for energy, and maps pointing to extremes in districts' mean temporal Volume. Illustrations of domain surfaces for that period enable assessment of relative inclination trends of the normalized Water, Food and Energy directions continuum assembled from time stations, and evolution trends for each of the WFE components.


Body mass index and outcomes from pancreatic resection: a review and meta-analysis.
There are 1.6 billion adults worldwide who are overweight, with body mass indices (BMI) between 25 and 30, while more than 400 million are obese (BMI >30). Obesity predicts the incidence of and poor outcomes from pancreatic cancer. Obesity has also been linked to surgical complications in pancreatectomy, including increased length of hospital stay, surgical infections, blood loss, and decreased survival. However, BMI's impact on many complications following pancreatectomy remains controversial. We performed a MEDLINE search of all combinations of "BMI" with "pancreatectomy," "pancreatoduodenectomy," or "pancreaticoduodenectomy." From included studies, we created pooled and weighted estimates for quantitative and qualitative outcomes. We used the PRISMA criteria to ensure this project's validity. Our primary cohort included 2,736 patients with BMI <30, 1,682 with BMI >25, and 546 with BMI between 25 and 30. Most outcomes showed no definitive differences across BMIs. Pancreatic fistula (PF) rates ranged from 4.7% to 31.0%, and four studies found multivariate association between BMI and PF (range odds ratio 1.6-4.2). Pooled analyses of PF by BMI showed significant association (p < 0.05). BMI increases the operative complexity of pancreatectomy. However, with aggressive peri- and post-operative care, increases in BMI-associated morbidity and mortality may be mitigated.


Bone Health, Pain, and Mobility: Evidence-Based Recommendations for Patients With Multiple Myeloma
About 85% of patients with multiple myeloma develop bone disease. In these patients, lytic bone lesions can cause fractures, poor circulation, blood clots, pain, poor mobility, and decreased quality of life. . This article presents consensus statements to guide nurses in the assessment and management of bone disease, pain, and mobility in patients with multiple myeloma at varying points in their disease trajectory. . Members of the International Myeloma Foundation Nurse Leadership Board reviewed previously provided recommendations, current recommendations based on literature review, and evidence-based grading. . Oncology nurses play a key role in maximizing bone health, minimizing skeletal injury, maximizing pain control, and improving quality of life in patients by enhancing patient mobility and safety. Clinician assessment accompanied by effective interventions reduces patient injury and optimizes functioning in patients with multiple myeloma.


The interaction of flavonoids with membranes: potential determinant of flavonoid antioxidant effects.
Twenty six phenolic substances including representatives of the families, flavanones, flavanols and procyanidins, flavonols, isoflavones, phenolic acids and phenylpropanones were investigated for their effects on lipid oxidation, membrane fluidity and membrane integrity. The incubation of synthetic phosphatidylcholine (PC) liposomes in the presence of these phenolics caused the following effects: (a) flavanols, their related procyanidins and flavonols were the most active preventing 2,2'-azo-bis (2,4-dimethylvaleronitrile) (AMVN)-induced 2-thiobarituric acid-reactive substances (TBARS) formation, inducing lipid ordering at the water-lipid interface, and preventing Triton X-100-induced membrane disruption; (b) all the studied compounds inhibited lipid oxidation induced by the water-soluble oxidant 2,2'-azo-bis (2-amidinopropane) (AAPH), and no family-related effects were observed. The protective effects of the studied phenolics on membranes were mainly associated to the hydrophilicity of the compounds, the degree of flavanol oligomerization, and the number of hydroxyl groups in the molecule. The present results support the hypothesis that the chemical structure of phenolics conditions their interactions with membranes. The interactions of flavonoids with the polar head groups of phospholipids, at the lipid-water interface of membranes, should be considered among the factors that contribute to their antioxidant effects.


Search for a heavy pseudoscalar boson decaying to a Z and a Higgs boson at s = 13 Te .
A search is presented for a heavy pseudoscalar boson A decaying to a Z boson and a Higgs boson with mass of 125 GeV . In the final state considered, the Higgs boson decays to a bottom quark and antiquark, and the Z boson decays either into a pair of electrons, muons, or neutrinos. The analysis is performed using a data sample corresponding to an integrated luminosity of 35.9 fb - 1 collected in 2016 by the CMS experiment at the LHC from proton-proton collisions at a center-of-mass energy of 13 Te . The data are found to be consistent with the background expectations. Exclusion limits are set in the context of two-Higgs-doublet models in the A boson mass range between 225 and 1000 GeV .


Incidence and predictors of restenosis after coronary stenting in 10 004 patients with surveillance angiography.
Systematic investigation of restenosis after percutaneous coronary intervention (PCI) with bare metal stents (BMS) or first or second generation drug eluting stents (DES) in large scale, broadly inclusive patient populations undergoing follow-up angiography represents a gap in our scientific knowledge. We investigated the incidence of angiographically proven restenosis and its predictors in patients undergoing PCI with stents. All patients undergoing successful implantation of coronary stents for de novo lesions from 1998 to 2009 and follow-up angiography at 6-8 months at two centres in Munich, Germany were eligible for inclusion. Patients with cardiogenic shock, dialysis dependent renal insufficiency or previous cardiac transplantation were excluded. Data were prospectively collected. The incidence of restenosis, defined as diameter stenosis ≥50% in the in-segment area at follow-up angiography, and its predictors were evaluated. A total of 12 094 patients met inclusion criteria. Angiographic follow-up was available for 10 004 patients (77.5%) with 15 004 treated lesions. Binary restenosis was detected in 2643 (26.4%) patients. Use of first generation DES versus BMS (OR 0.35, 95% CI 0.31 to 0.39) and second generation DES versus first generation DES (OR 0.67, 95% CI 0.58 to 0.77) were independent predictors of lower rates of restenosis. At multivariate analysis, smaller vessel size (OR 1.59, 95% CI 1.52 to 1.68, for each 0.5 mm decrease), total stented length (OR 1.27, 95% CI 1.21 to 1.33, for each 10 mm increase), complex lesion morphology (OR 1.35, 95% 1.21 to 1.51), presence of diabetes mellitus (OR 1.32, 95% 1.19 to 1.46), and history of bypass surgery (OR 1.38, 95% CI 1.20 to 1.58) were independently associated with restenosis and were similar across the spectrum of stent devices. In this large cohort of patients with angiographic surveillance we demonstrated the impact of device development on antirestenotic efficacy, with sequentially improved efficacy from BMS to first generation DES to second generation DES. Predictors of restenosis were small vessel size, increased stented length, complex lesion morphology, diabetes mellitus, and prior bypass surgery.


The epidemiology of avian herpesviruses in veterinary medicine.
There are ten avian herpesviruses, which have been isolated from eight orders. Six of these are of veterinary importance: Pacheco's parrot disease virus, pigeon herpesvirus, duck plague virus, infectious laryngotracheitis virus, herpesvirus of turkeys and Marek's disease virus. The knowledge on the epidemiology of each virus and the disease it causes is discussed. Features in common to infections with most avian herpesviruses are: infection is persistent in individuals and ubiquitous in populations; virus is shed for long periods of time after infection although in some cases erratically; infection does not necessarily result in disease and at least in some avian herpesvirus infections the incidence of disease is affected by the pathogenicity of the virus; the genetic constitution of the host and stress factors affecting the host. It is concluded that man's interference with the natural history of host species often increases the threat and incidence of disease unless preventive action is taken.


Isolation and characterization of a colonic autoantigen specifically recognized by colon tissue-bound immunoglobulin G from idiopathic ulcerative colitis.
Patients with idiopathic ulcerative colitis (UC) have a colonbound antibody (CCA-IgG) that reacts with colon tissue extracts. We have partially characterized a colonic protein that is specifically recognized by CCA-IgG. CCA-IgG was eluted from operative colon specimens from 10 patients with UC. A colon tissue-bound IgG was similarly eluted from six patients with Crohn's colitis, two with ischemic colitis, and one with diverticulitis. Purified serum IgG from patients with Crohn's disease, from normal subjects and a patient with myeloma were also used as additional controls. For detection of antigen(s), tissue extracts were prepared from 26 specimens of colon (UC, 12; Crohn's disease, 6; normal, 4; other controls, 4), 8 specimens of human normal stomach, duodenum, ileum, and liver (2 each). Tissue extracts were also prepared from rats and mice, including germ-free rat colons and rat's fetal colons. Immunorecognition of CCA-IgG to the tissue extracts was examined by affinity-column chromatography and by transblot analysis. Tissue-extracted proteins were electrophoresed in SDS-polyacrylamide gel, transferred to nitrocellulose sheet, and probed with iodinated CCA-IgG, colonic IgG from other inflammatory bowel disease patients, UC serum IgG, and control serum IgG. Although many proteins were present in colon tissue extracts, 9 of 10 CCA-IgG consistently recognized a protein of 40 kD. None of the nine IgG preparations from colon specimens of patients with Crohn's colitis and other colonic inflammatory diseases reacted with the 40-kD protein. Five of six symptomatic UC serum IgG and none of eight control serum IgG reacted with the 40-kD protein. The 40-kD protein was present in all colon specimens and it appeared to be organ specific. It was absent in mouse and rat tissues, including colon. The 40-kD protein is not actin and nor a part of the Ig molecule. These results suggest that the 40-kD protein is a colonic "autoantigen" that may initiate a specific IgG antibody response in UC.