Girth measurement is not a reliable investigation for the detection of intra-abdominal fluid.
Routine measurement of abdominal girth after suspected trauma is still recommended as a predictor of intraperitoneal bleeding but there is little evidence to support its accuracy. Girth measurements were taken on 12 recumbent adult patients by independent observers and repeated after infusion of 550 ml aliquots of dialysate to a maximum of 2000 ml. Girth increase per 500 ml infusion varied from -0.46 cm to 2.1 cm (mean 0.84 +/- 0.65 SD) giving a range in excess of 2.5 cm. In some cases the girth decreased after a further 500 ml infusion. A change in patient position altered the girth at a constant volume by 1.32 cm (+/- 0.75 SD). Observer error was low at 0.33 cm (+/- 0.35 SD). These results preclude girth as a reliable clinical indicator of intraperitoneal haemorrhage.


Effectiveness of COVID-19 vaccine mandates in raising vaccination rates among the elderly and general population in Europe: Controlled interrupted time series analysis.
During the COVID-19 pandemic, three European countries (Austria, Greece, Italy) announced and/or implemented mandatory COVID-19 vaccination for high-risk groups in the general population. Besides the ethical justification for this policy, it is important to assess and quantify the effectiveness of the mandate in raising vaccination rates. Controlled interrupted time series analysis of first-dose vaccination rates in the targeted age groups (Greece: ≥60 years; Italy: ≥50 years) relative to a control group (Greece: 50-59 years; Italy: 25-49 years) between week 35/2021 and week 50/2022. For Austria an uncontrolled analysis was performed, as the vaccine mandate targeted all adults ≥18 years. Announcement of mandatory vaccination substantially increased vaccination rates in the targeted age groups compared to control in both Greece (RR = 4.36, 95 % CI: 3.57-5.32) and Italy (RR = 2.90, 95 % CI: 2.37-3.56), an effect which persisted throughout the study period. There were 176,428 (95 % CI: 164,097-187,226) mandate-attributable first-dose vaccinations in Greece and 316,192 (95 % CI: 282,467-346,678) in Italy, most of which occurred before the mandate came into effect. In Austria no discernible increase in vaccination rates was observed after the announcement of mandatory vaccination. At the end of the study period, 9.5 % of ≥60 year-olds in Greece, 4.9 % of ≥50 year-olds in Italy and 13.8 % of ≥18 year-olds in Austria remained unvaccinated. In Greece and Italy - though not in Austria - simple announcement of a vaccine mandate rapidly increased COVID-19 vaccination rates in the targeted age groups, without fully closing the vaccination gap. Mandatory vaccination appears to effectively target complacency but not vaccine hesitancy, and its public health benefits need to be weighted against possible detrimental effects on confidence and trust.


Rapid pathogen-induced apoptosis: a mechanism used by dendritic cells to limit intracellular replication of Legionella pneumophila.
Dendritic cells (DCs) are specialized phagocytes that internalize exogenous antigens and microbes at peripheral sites, and then migrate to lymphatic organs to display foreign peptides to naïve T cells. There are several examples where DCs have been shown to be more efficient at restricting the intracellular replication of pathogens compared to macrophages, a property that could prevent DCs from enhancing pathogen dissemination. To understand DC responses to pathogens, we investigated the mechanisms by which mouse DCs are able to restrict replication of the intracellular pathogen Legionella pneumophila. We show that both DCs and macrophages have the ability to interfere with L. pneumophila replication through a cell death pathway mediated by caspase-1 and Naip5. L. pneumophila that avoided Naip5-dependent responses, however, showed robust replication in macrophages but remained unable to replicate in DCs. Apoptotic cell death mediated by caspase-3 was found to occur much earlier in DCs following infection by L. pneumophila compared to macrophages infected similarly. Eliminating the pro-apoptotic proteins Bax and Bak or overproducing the anti-apoptotic protein Bcl-2 were both found to restore L. pneumophila replication in DCs. Thus, DCs have a microbial response pathway that rapidly activates apoptosis to limit pathogen replication.


Evaluating the added values of regional climate modeling over China at different resolutions.
Previous studies have suggested that dynamical downscaling to global climate models can produce improved climate simulations at regional and local scales. However, the expensive computational requirements of dynamical downscaling inevitably add a limit to the spatial resolution of the resulting regional climate simulations. In order to find a balance between computational requirements and simulation improvements, it is extremely important to investigate how the spatial resolution of regional climate simulation affects the added values of dynamical downscaling; yet, it is still not well understood. Therefore, in this study, we conduct long-term climate simulations for the entire country of China with the PRECIS regional climate model at two different spatial resolutions (i.e., 25 and 50 km). The purpose is to evaluate whether a fine-resolution model simulation, given its considerable requirements for computational resources, would add more valuable information for understanding regional climatology than a coarse-resolution model simulation. Our results show that the PRECIS can reasonably reproduce the spatial distribution of seasonal and monthly mean temperature and precipitation over the most of regions in China. However, in the process of downscaling, RCM with higher resolution cannot always produce more accurate output. In regard to precipitation simulations, compared with the host GCM, it is difficult to determine exactly a homogeneous improvement of performance in downscaling, both in terms of spatial patterns as well as magnitude of errors. For interannual variability, variations in temperature are closer to observation than precipitation and the high-resolution R25 has better skills over the northwest than R50. Moreover, except for the west, it is shown that PRECIS is able to better reproduce the probability distribution function of precipitation and some impact-relevant indices such as the number of consecutive wet days and simple precipitation intensity index in spatial distribution.


[Biomedical research in Revista de Biologia Tropical].
The contributions published in Revista de Biología Tropical in the area of Biomedical Sciences are reviewed in terms of number of contributions and scope of research subjects. Biomedical Sciences, particularly Parasitology and Microbiology, constituted the predominant subject in the Revista during the first decade, reflecting the intense research environment at the School of Microbiology of the University of Costa Rica and at Hospital San Juan de Dios. The relative weight of Biomedicine in the following decades diminished, due to the outstanding increment in publications in Biological Sciences; however, the absolute number of contributions in Biomedical Sciences remained constant throughout the last decades, with around 80 contributions per decade. In spite of the predominance of Parasitology as the main biomedical subject, the last decades have witnessed the emergence of new areas of interest in the Revista, such as Pharmacology of natural products, Toxinology, especially related to snake venoms, and Human Genetics. This retrospective analysis evidences that Biomedical Sciences, particularly those related to Tropical Medicine, were a fundamental component during the first years of Revista de Biología Tropical, and have maintained a significant presence in the scientific output of this journal, the most relevant scientific publication in biological sciences in Central America.


A realistic three dimensional FEM of the human head.
A realistic three-dimensional finite element model (FEM) of the human head has been developed. Separate layers for the scalp, skull, cerebrospinal fluid (CSF) and brain were modelled. Hexahedral elements, a special master matrix assembly technique and an iterative successive over-relaxation (SOR) solution scheme were employed. This approach enabled rapid modelling with minimal memory requirements, which makes this method practical if used for electrical impedance tomography (EIT) or source localization inverse problems. Compared to scalp electrodes, subdural voltage sensing electrodes were three to four times more sensitive close to an oedema or source region, if it was peripheral, but this decreased to 30%-40% for central oedema or source regions. Scalp current injecting electrodes are preferable, since the maximum allowable current is 10 times larger than that of the subdural ones. The distance of voltage sensing electrodes from a region to be imaged highly affects sensitivity, so depth electrodes will be more sensitive, provided that they are close to the region of interest. Finally, the electrode size has significant effects on the input or transfer impedance.


Cone-beam CT for radiotherapy applications.
Clinical implementation of cone-beam tomography has been hampered by the lack of two-dimensional electronic x-ray detectors that can encompass the full width of the body. We encountered the undersized detector problem in our development of a cone-beam CT system for radiotherapy applications. In order to mitigate the problem, we developed an algorithm which permits an increased reconstruction volume to be imaged using a detector of a given size. We describe the algorithm and report on its implementation using a radiotherapy simulator configured with a digital fluorography unit.


[Resistance of uropathogenic strains of Escherichia coli in pregnant women and other women in generative ages in comparison with antibiotics consumption in Zagreb].
To compare resistance of uropathogenic strains of Escherichia coli (UPEC) to antibiotics in women in generative ages and pregnant women during two year period (2004 and 2008) in Zagreb, and comparison of resistance and the consumption of antibiotics. The standard disk-diffusion method was used for sensitivity testing to 16 different antibiotics. Data on antibiotic utilization were used to calculate the number of defined daily doses (DDD) and DDD per 1000 inhabitants using Anatomical-Therapeutic-Chemical/DDD methodology. Data on antibiotic consumption during pregnancy were collected using a questionnaire filled in by 893 women after delivery. During 2004 resistance of UPEC to antimicrobial drugs was not different in pregnant and in non-pregnant women, with the exception of amoxicillin and nitrofurantoin, with statistically higher resistance in pregnant women (p < 0.01). Four years later the statistically higher resistance to norfloxacin was observed in non-pregnant women (p < 0.01). Comparing the resistance in 2004 and 2008, in the both groups of women a statistically significant decrease of resistance to cefalexin and nitrofurantoin was detected (p < 0.01). Outpatient utilization of antimicrobial drugs in Zagreb increased significantly, from 32 to 39 DDD/1000 inhabitants per day. The most used antibiotic was co-amoxiclav, and its utilization increased from 9.6 to 12.2 DDD/1000/day. Amoxicillin and co-amoxiclav were used during pregnancy by 9.6% interviewed women. The observed significant decrease of resistance to cefalexin makes that antibiotic the drug of choice for treatment of urinary tract infections in women in generative ages, and together with coamoxiclav can be administered in pregnancy. Constant monitoring of urinary tract pathogens resistance to antimicrobial agents ensures the effectiveness of empirical therapy, whose versatile use is limited due the potentially harmful effects of antimicrobial drugs on fetus.


Delivery of RANKL-Binding Peptide OP3-4 Promotes BMP-2-Induced Maxillary Bone Regeneration.
Although bone morphogenetic protein 2 (BMP-2) is known to stimulate osteogenesis, there is evidence that high doses of BMP-2 can lead to side effects, including inflammation and carcinogenesis. The supplementation of other bone-augmenting agents is considered helpful in preventing such side effects by reducing the amount of BMP-2 required to obtain a sufficient amount of bone. We recently showed that a receptor activator of nuclear factor κB ligand (RANKL)-binding peptide promotes osteoblast differentiation. In the present study, we aimed to investigate whether OP3-4, a RANKL-binding peptide, promotes BMP-2-induced bone formation in the murine maxilla using an injectable gelatin hydrogel (GH) carrier. A GH carrier containing OP3-4 with BMP-2 was subperiosteally injected into the murine maxillary right diastema between the incisor and the first molar. The mice were sacrificed 28 d after the injections. The local bone formation in the OP3-4-BMP-2-injected group was analyzed in comparison to the carrier-injected, BMP-2-injected, and control-peptide-BMP-2-injected groups. The GH carrier containing OP3-4 with BMP-2 enlarged the radio-opaque area and increased the bone mineral content and density in the radiological analyses in comparison to the other experimental groups. Interestingly, fluorescence-based histological analyses revealed that the mineralization had started from the outside, then proceeded inward, suggesting that the size of the newly formed bone had already been set before calcification started and that the effects of OP3-4 might be involved in accelerating the early steps of osteogenesis. Actually, OP3-4 enhanced the BMP-2-induced 5-bromo-2'-deoxyuridine (BrdU)-positive cell numbers at the injected site on day 7 and the expression of Runx2 and Col1a1, which are early osteogenic cell markers, on day 10 after the subperiosteal injections. In summary, we demonstrated, for the first time, that the application of OP3-4 by subperiosteal injection promoted BMP-2-induced bone formation, which could lead to the development of an easy and noninvasive means of promoting alveolar ridge formation.


Discharged rehabilitation patients: impact of follow-up surveillance by a friendly visitor.
The period after hospital discharge is the most critical for rehabilitation patients returning to a community setting. A friendly visitor surveillance program using nonprofessional volunteers was designed to monitor treatment regimen compliance by alerting medical professionals of impending crises among discharged rehabilitation patients. A randomized experimental design was used to evaluate the impact of 1 year of program exposure on rehospitalization, service use, and psychosocial outcomes experienced by 142 patients. Patients were randomized into 3 groups: friendly visitors (FV) and biannual nursing visits; biannual nursing (RN) visits only; and controls (CON). Over 1/3 of the sample was rehospitalized at least once during the 1-year impact period, yet no differences were found across experimental groups nor patients' diagnostic category. No meaningful pattern of significant differences between the groups was observed at the p less than 0.1 probability level in any of the other outcome areas. The need to alert the medical system of impending patient problems occurred rarely, suggesting that existing informal support systems and regular use of medical services may be sufficient to monitor rehabilitation patients' progress.


Functional macroautophagy induction by influenza A virus without a contribution to major histocompatibility complex class II-restricted presentation.
Major histocompatibility complex (MHC) class II-presented peptides can be derived from both exogenous (extracellular) and endogenous (biosynthesized) sources of antigen. Although several endogenous antigen-processing pathways have been reported, little is known about their relative contributions to global CD4(+) T cell responses against complex antigens. Using influenza virus for this purpose, we assessed the role of macroautophagy, a process in which cytosolic proteins are delivered to the lysosome by de novo vesicle formation and membrane fusion. Influenza infection triggered productive macroautophagy, and autophagy-dependent presentation was readily observed with model antigens that naturally traffic to the autophagosome. Furthermore, treatments that enhance or inhibit macroautophagy modulated the level of presentation from these model antigens. However, validated enzyme-linked immunospot (ELISpot) assays of influenza-specific CD4(+) T cells from infected mice using a variety of antigen-presenting cells, including primary dendritic cells, revealed no detectable macroautophagy-dependent component. In contrast, the contribution of proteasome-dependent endogenous antigen processing to the global influenza CD4(+) response was readily appreciated. The contribution of macroautophagy to the MHC class II-restricted response may vary depending upon the pathogen.


Effects of zhongfeng cutong moxibustion on motor function and corticospinal tract in the patients with motor dysfunction during the recovery period of cerebral infarction.
To observe the effects of zhongfeng cutong moxibustion (moxibustion therapy for unblocking and treating stroke) on the motor function and the structure of corticospinal tract (CST) in the patients with motor dysfunction during the recovery period of cerebral infarction, and to explore the central mechanism of this moxibustion therapy for improving the motor function. Fifty patients with motor dysfunction during the recovery period of cerebral infarction were randomly divided into an observation group (25 cases, 1 case dropped out) and a control group (25 cases, 1 case dropped out). The patients in both groups underwent the conventional basic treatment. In the control group, acupuncture was applied to Baihui (GV 20) and Shuigou (GV 26), as well as Chize (LU 5), Neiguan (PC 6), Weizhong (BL 40) and Sanyinjiao (SP 6) etc. on the affected side. Besides the intervention of the control group, in the observation group, zhongfeng cutong moxibustion therapy was combined at Baihui (GV 20), Shenque (CV 8) and bilateral Zusanli (ST 36). Both acupuncture and moxibustion therapies were delivered once daily, 5 times a week, for 2 weeks. The scores of Fugl-Meyer assessment scale (FMA) and National Institutes of Health stroke scale (NIHSS) were compared between the two groups before and after treatment. The diffusion tensor imaging technique was used to observe the fractional anisotropy (FA) of CST at the bilateral whole segment, the cerebral cortex, the posterior limb of the internal capsule and the cerebral peduncle before and after treatment in the two groups. The scores of the upper and the lower limbs of FMA, as well as the total FMA score swere increased after treatment when compared with those before treatment in the two groups (P<0.05), the upper limb FMA score and the total FMA score in the observation group were higher than those in the control group (P<0.05), and NIHSS scores of the two groups were dropped compared with those before treatment (P<0.01). FA of CST at the bilateral sides of the posterior limb of the internal capsule and the whole segment on the focal side was improved in comparison with that before treatment in the observation group (P<0.05), and FA of CST at the healthy side of the whole segment was higher than that before treatment in the control group (P<0.05). Zhongfeng cutong moxibustion improves motor function and reduces neurological deficits in the patients with motor dysfunction during the recovery period of cerebral infarction, which may be related to enhancing the remodeling of white matter fiber bundles in the corticospinal tract on the focal side of the whole segment and the bilateral posterior limb of the internal capsule.


Effects of aging on biological motion discrimination.
Previous studies have shown that older subjects have difficulties discriminating the walking direction of point-light walkers. In two experiments, we investigated the underlying cause in further detail. In Experiment 1, subjects had to discriminate the walking direction of upright and inverted point-light walkers in a cloud of randomly moving dots. In general, older subjects performed less accurately and showed an increased inversion effect. Nevertheless, they were as accurate as young subjects for upright walkers during training, in which no noise was added to the display. These results indicate that older subjects are less able to extract relevant information from noisy displays. In Experiment 2, subjects discriminated the walking direction of scrambled walkers that primarily contained local motion information, random-position walkers that primarily contained global form information, and normal point-light walkers that contained both kinds of information. Both age groups performed at chance when no global form information was present in the display but were equally accurate for walkers that only contained global form information. However, when both local motion and global form information were present in the display, older subjects were less accurate then younger subjects. Older subjects again exhibited an increased inversion effect. These results indicate that both older and younger subjects rely more on global form than local motion to discriminate the direction of point-light walkers. Also, older subjects seem to have difficulties integrating global form and local motion information as efficiently as younger subjects.


A controlled study of serum anti-locus ceruleus antibodies in REM sleep behavior disorder.
The newly identified association of human nonnarcoleptic rapid eye movement (REM) sleep behavior disorder (RBD) with human leukocyte antigen (HLA) DQw1 class II genes raises the possibility that RBD may arise from autoimmune mechanisms. Two recent case reports involving postmortem brain stem histochemical analyses in elderly males with RBD identified severe monoaminergic cell loss in the locus ceruleus (LC). Thus, we designed a study to detect anti-LC antibodies in RBD. Ten Caucasian males (mean age, 66 years) with polygraphically confirmed RBD (n = 5, idiopathic RBD: n = 5, RBD with Parkinson's disease), but without narcolepsy, idiopathic hypersomnia, or autoimmune disease, were recruited for this study, along with 10 Caucasian male controls (mean age, 63 years) without a history of sleep disorder or autoimmune disease. In a blinded design, sera from the RBD patients and their controls were tested against human LC and other brainstem neurons. Brainstem tissue was obtained from autopsies of neurologically normal individuals. The presence of anti-LC antibodies was examined using immunohistochemistry on brainstem sections. Sections incubated with sera from normal individuals and sera from patients with paraneoplastic antineuronal antibodies (anti-Hu and anti-Ri) were used as controls. No reactivity with LC or any other brainstem area was identified with sera from either RBD patients or their controls, or from the other group of normal individuals. In contrast, sera from patients with paraneoplastic anti-Hu and anti-Ri antibodies reacted strongly with nuclei of LC and other brainstem neurons, sparing the nucleoli, and reacted to a lesser extent with the cytoplasm of these neurons. Therefore, it is unlikely that human RBD is associated with anti-LC antibodies. However, an autoimmune process in RBD has not been excluded by this study.


Cardiac involvement in muscular dystrophies: molecular mechanisms.
In this review, we draw attention to the multiple mechanisms responsible for the pathogenesis of cardiomyopathies in patients with muscular dystrophies. More than one single mechanism is likely to be involved in the development of skeletal and cardiac muscle pathology even when there is a single protein defect. The best example is dystrophin deficiency, in which increased sarcolemmal permeability following eccentric exercise, reduced force generation, and abnormal signaling are all likely to contribute to the progressive muscle damage observed. In other conditions, such as the sarcoglycanopathies, a protein deficiency both in the striated cardiomyocte and the vascular smooth muscle appears to play a significant role. An entirely different mechanism of disease is likely in defects of nuclear envelope proteins, although the precise pathogenesis of this group of conditions is still not clear. Differences between the organization of skeletal and cardiac muscle protein complex are also only starting to emerge and will very likely be the focus of future research.


Antibacterial, ester-free monomers: Polymerization kinetics, mechanical properties, biocompatibility and anti-biofilm activity.
Quaternary ammonium (QA) methacrylate monomers have been extensively investigated and demonstrate excellent antibacterial properties. However, the presence of ester bonds makes them prone to degradation in the oral cavity. In this study, ester-free QA monomers based on meth-acrylamides were synthesized and screened for polymerization kinetics, mechanical properties and antibacterial effects. Tertiary quaternary ammonium acrylamides (AM) and methacrylamides (MAM) with alkyl side chain lengths of 9 and 14 carbons (C9 and C14) were synthesized and incorporated at 10 wt% into experimental composites based on BisGMA:TEGDMA (1:1), camphorquinone/ethyl-4-dimethylaminobenzoate (0.2/0.8 wt%) and 70 wt% barium glass fillers. Analogous methacrylate versions (MA) were used as controls. Degree of conversion (DC) and rate of polymerization (RP) during photoactivation (800 mW/cm2) were followed in real-time with near-IR. Flexural Strength (FS) and Modulus (E) were measured on 2 × 2 × 25 mm bars in 3-point bending after 24 h dry storage and 7-day storage in water at 37 °C. Antimicrobial properties and biofilm adhesion (fouling) were evaluated by bioluminescence (Luciferase Assay) and biofilm removal by water spray microjet impingement test, respectively. Cytotoxicity was assessed by MTT assay on dental pulp stem cells (DPSC). Data were analyzed with one-way ANOVA/Tukey's test (α = 0.05). DC was similar for all groups tested (∼70%). Both MAMs and C14-AM presented significantly lower RP. Under dry conditions, FS (110-120 MPa) and E (8-9 GPa) were similar for all groups. After water storage, all materials presented FS/E similar to the control, except for C14-AM (for FS) and C14-MAM (for E), which were lower. All C14 versions were strongly antibacterial, decreasing the titer counts of biofilm by more than two orders of magnitude in comparison to the control. C9 monomers did not present significant antibacterial nor antifouling properties. And biofilms had approximately equivalent adhesion on the C9 composites as on the control. Cytotoxicity did not show significant differences between the MA and AM versions and the control group. C14-QA monomers based on methacrylates and meth-acrylamides present strong antibacterial properties, and in general, similar conversion/mechanical properties compared to the methacrylate control. This work demonstrates the viability of methacrylamides and acrylamides as potential components in dental restorative materials with antimicrobial properties. The use of ester-free polymerizable functionalities has the potential of improving the degradation resistance of these materials long-term. The use of (meth)acrylamides did not interfere with the antimicrobial potential of quaternary ammonium-based materials.


Serum soluble endothelial-cell specific adhesion molecules in children with insulin-dependent diabetes mellitus.
Endothelial-cell specific adhesion molecules are reported to be elevated in patients with diabetes mellitus and related to diabetic vascular complications. We studied serum concentrations of soluble intercellular adhesion molecule-1 (sICAM-1), vascular cell adhesion molecule-1 (sVCAM-1), endothelial-leukocyte adhesion molecule (sE-selectin) in 30 healthy children and 35 children with type 1 diabetes without symptomatic vascular complications. sE-selectin levels were higher in diabetics than in controls (p < 0.001). sVCAM-1 and sICAM-1 levels were not different between the groups (p > 0.05). In seven newly diagnosed diabetics with ketoacidosis, concentrations of these molecules were not different before and after one month of insulin therapy (p > 0.05). In the combined group, only sE-selectin was correlated positively with serum glucose, HbA1c (r = 0.3, p < 0.05 for both) and negatively with C-peptide levels (r = -0.4, p < 0.05). In diabetic children without symptomatic vascular complications, sE-selectin but not sICAM and sVCAM levels was elevated; this finding might reflect ongoing endothelial-cell activation rather than endothelial damage.


The associations of serum n-6 polyunsaturated fatty acids with serum C-reactive protein in men: the Kuopio Ischaemic Heart Disease Risk Factor Study.
There are concerns that high intake of n-6 polyunsaturated fatty acids (PUFA) may promote inflammation, because the end-product of n-6 PUFA metabolism, arachidonic acid, is a precursor for pro-inflammatory eicosanoids. Our aim was to investigate cross-sectional associations of the serum n-6 PUFAs, objective biomarkers for exposure, with serum high-sensitivity C-reactive protein (CRP), a key inflammation marker. The study included 1287 generally healthy men aged 42-60 years from the population-based Kuopio Ischaemic Heart Disease Risk Factor Study, examined in 1984-1989. ANCOVA and logistic regression were used for analyses. In the multivariable-adjusted analyses, both serum total n-6 PUFA and linoleic acid, the predominant n-6 PUFA, were associated with lower CRP. The mean CRP concentrations in quartiles of linoleic acid were 1.86, 1.51, 1.53, and 1.37 mg/L (P-trend = 0.001). The odds ratio for elevated CRP (>3 mg/L) in the highest vs. the lowest quartile was 0.47 (95% confidence interval (CI) 0.25-0.87, P-trend = 0.01). Arachidonic acid or the mainly endogenously produced n-6 PUFAs, gamma-linolenic acid and dihomo-gamma-linolenic acid, were not associated with higher CRP, either. Age, body mass index, or serum long-chain n-3 PUFA concentration did not modify the associations (P-interactions > 0.14). Serum n-6 PUFAs were not associated with increased inflammation in men. In contrast, the main n-6 PUFA linoleic acid had a strong inverse association with the key inflammation marker, CRP.


Total Knee Arthroplasty in the Ambulatory Surgery Center Setting: Best Practices for Cost Containment and Clinical Care Delivery.
As the current population continues to increase in age, so does the degeneration of the musculoskeletal system and the development of knee osteoarthritis. Total knee arthroplasty (TKA) will be the treatment of choice when it comes to improving physical function and decreasing pain associated with osteoarthritis of the knee. The global push for more cost-effective healthcare services has led to new models of care and payment delivery methods such as performing TKA in the ambulatory surgery center (ASC) setting. With deeply invasive surgical procedures such as TKA being done in the ASC setting, orthopaedic nurses must be mindful of best practices that will promote quality and safety while considering the importance of using current evidence to guide nursing practice when promoting appropriate patient selection and effective patient education of self-management of postoperative care pertaining to TKA being performed in the ASC setting. This is critical to consider during a time when financial profits in the ASC setting may take a front seat to the delivery of high-quality and safe patient care.


An Autoimmune Response Signature Associated with the Development of Triple-Negative Breast Cancer Reflects Disease Pathogenesis.
The repertoire of antigens associated with the development of an autoimmune response in breast cancer has relevance to detection and treatment strategies. We have investigated the occurrence of autoantibodies associated with the development of triple-negative breast cancer (TNBC) in the before diagnosis setting and in samples collected at the time of diagnosis of TNBC. Lysate arrays containing protein fractions from the TNBC MDA-MB-231 cell line were hybridized with TNBC plasmas from the Women's Health Initiative cohort, collected before clinical diagnosis and with plasmas from matched controls. An immune response directed against spliceosome and glycolysis proteins was observed with case plasmas as previously reported in estrogen receptor(+) breast cancer. Importantly, autoantibodies directed against networks involving BRCA1, TP53, and cytokeratin proteins associated with a mesenchymal/basal phenotype were distinct to TNBC before diagnosis samples. Concordant autoantibody findings were observed with mouse plasma samples collected before occurrence of palpable tumors from a C3(1)-T triple negative mouse model. Plasma samples collected at the time of diagnosis of stage II TNBC and from matched healthy controls were subjected to proteomic analysis by mass spectrometry to identify Ig-bound proteins yielding a predominance of cytokeratins, including several associated with a mesenchymal/basal phenotype among cases compared with controls. Our data provide evidence indicative of a dynamic repertoire of antigens associated with a humoral immune response reflecting disease pathogenesis in TNBC.


[Hormonal disorders in patients with chronic pyelonephritis with nephrosclerosis and kidney failure].
Blood plasma content was studied of hydrocortisone, parathyroid hormone (PTH) and calcitonin in patients with chronic pyelonephritis (ChP) using methods of radioimmunologic and immunoenzymatic analyses. ChP patients had marked alterations of blood plasma levels of hydrocortisone, PTH and calcytonin, with the reduced levels of hydrocortisone and hypercalcitoninamia being noted during the early stages of nephrosclerosis. It is suggested that hydrocortisone and calcitonin content in blood of ChP patients might be used as indicators of state of the endocrine mechanisms controlling the renal connective tissue metabolism during the early stages of nephrosclerosis. The above measure will also be helpful in the assessment of activity of the sclerotic process in the kidneys, prognosis of the outcome of the medical condition, and development of treatment options of adequate pathogenetic therapy.


Immunological monitoring for prediction of clinical response to antitumor vaccine therapy.
Immunotherapy has shown promising results in a variety of cancers, including melanoma. However, the responses to therapy are usually heterogeneous, and understanding the factors affecting clinical outcome is still not achieved. Here, we show that immunological monitoring of the vaccine therapy for melanoma patients may help to predict the clinical course of the disease. We studied cytokine profile of cellular Th1 (IL-2, IL-12, IFN-γ) and humoral Th2 (IL-4, IL-10) immune response, vascular endothelial growth factor (VEGFA), transforming growth factor-β 2 (TGF-β 2), S100 protein (S100A1B and S100BB), adhesion molecule CD44 and serum cytokines β2-microglobulin to analyze different peripheral blood mononuclear cell subpopuations of patients treated with dendritic vaccines and/or cyclophosphamide in melanoma patients in the course of adjuvant treatment. The obtained data indicate predominance of cellular immunity in the first adjuvant group of patients with durable time to progression and shift to humoral with low cellular immunity in patients with short-term period to progression (increased levels of IL-4 and IL- 10). Beta-2 microglobulin was differentially expressed in adjuvant subgroups: its higher levels correlated with shorter progression-free survival and the total follow-up time. Immunoregulatory index was overall higher in patients with disease progression compared to the group of patients with no signs of disease progression.


Airway compromise due to angiotensin-converting enzyme inhibitor-induced angioedema: clinical experience at a large community teaching hospital.
To evaluate the incidence of airway compromise, clinical presentation and morbidity of angiotensin-converting enzyme inhibitor (ACEI)-related angioedema (AE). A retrospective chart review was conducted of all patients admitted to our hospital between 1996 and 2001 with the diagnosis of AE. A total of 70 charts on which a diagnosis of AE had been entered were reviewed. Of those, 45 patients (64%) had AE that was thought to be related to ACEI therapy. Of those 45 patients, 29 were women. The mean age was 62 years, and 41 (91%) were African-American. The duration of ACEI therapy before presentation varied from 1 day to 5 years postingestion. Twenty-one of 32 patients presented within 2 months of the initiation of therapy. The mean duration between the onset of symptoms and presentation to the hospital was 9 h. Lip and tongue swelling was seen in all patients. Pulmonary manifestations were noted in 17 of 45 patients (38%) [dyspnea 17 of 17 patients; stridor/respiratory failure, 5 of 17 patients; cough, 2 of 17 patients]. Dysphagia was noted in 9 of 45 patients, drooling of saliva in 8 of 45 patients, and pruritus in 6 of 45 patients. Ten of 45 patients had a history of AE. In five of those patients (50%), ACEI use was a presumed cause of the AE for the current hospital admission. Eighteen of 45 (40%) patients required ICU admission. The mean ICU length of stay was 2.2 days. Five of 45 patients required endotracheal intubation. The mean time spent receiving ventilation was 2.2 days. Discontinuation of the initiating agent and supportive care were the keys to therapy. All of our patients responded to supportive management, and there was no mortality. Sixty-four percent of patients in this series had AE due to receiving an ACEI. The majority of the patients were African-American women. Most patients presented within 2 months of starting to receive the drug, although longer durations of therapy were not uncommon. Lip and tongue swelling was the most common airway manifestation. Based on our observations, the discontinuation of ACEI therapy and supportive management are the recommended approaches to therapy to prevent an untoward outcome.


A Descriptive Review of the Action Mechanisms of Berberine, Quercetin and Silymarin on Insulin Resistance/Hyperinsulinemia and Cardiovascular Prevention.
Insulin resistance (IR) and the associated hyperinsulinemia are early pathophysiological changes which, if not well treated, can lead to type 2 diabetes, endothelial dysfunction and cardiovascular disease. While diabetes care is fairly well standardized, the prevention and treatment of IR lacks a single pharmaceutical approach and many lifestyle and dietary interventions have been proposed, including a wide range of food supplements. Among the most interesting and well-known natural remedies, alkaloid berberine and the flavonol quercetin have particular relevance in the literature, while silymarin-the active principle of the Silybum marianum thistle-was traditionally used for lipid metabolism disorders and to sustain liver function. This review describes the major defects of insulin signaling leading to IR and the main properties of the three mentioned natural substances, their molecular targets and synergistic action mechanisms. The actions of berberine, quercetin and silymarin are partially superimposable as remedies against reactive oxygen intermediates generated by a high-lipid diet and by NADPH oxidase, which is triggered by phagocyte activation. Furthermore, these compounds inhibit the secretion of a battery of pro-inflammatory cytokines, modulate intestinal microbiota and are especially able to control the various disorders of the insulin receptor and post-receptor signaling systems. Although most of the evidence on the effects of berberine, quercetin and silymarin in modulating insulin resistance and preventing cardiovascular disease derive from experimental studies on animals, the amount of pre-clinical knowledge strongly suggests the need to investigate the therapeutic potential of these substances in human pathology.


Comparative pathogenesis of Alkhumra hemorrhagic fever and Kyasanur forest disease viruses in a mouse model.
Kyasanur Forest disease virus (KFDV) and Alkhumra hemorrhagic fever virus (AHFV) are genetically closely-related, tick-borne flaviviruses that cause severe, often fatal disease in humans. Flaviviruses in the tick-borne encephalitis (TBE) complex typically cause neurological disease in humans whereas patients infected with KFDV and AHFV predominately present with hemorrhagic fever. A small animal model for KFDV and AHFV to study the pathogenesis and evaluate countermeasures has been lacking mostly due to the need of a high biocontainment laboratory to work with the viruses. To evaluate the utility of an existing mouse model for tick-borne flavivirus pathogenesis, we performed serial sacrifice studies in BALB/c mice infected with either KFDV strain P9605 or AHFV strain Zaki-1. Strikingly, infection with KFDV was completely lethal in mice, while AHFV caused no clinical signs of disease and no animals succumbed to infection. KFDV and high levels of pro-inflammatory cytokines were detected in the brain at later time points, but no virus was found in visceral organs; conversely, AHFV Zaki-1 and elevated levels of cytokines were found in the visceral organs at earlier time points, but were not detected in the brain. While infection with either virus caused a generalized leukopenia, only AHFV Zaki-1 induced hematologic abnormalities in infected animals. Our data suggest that KFDV P9605 may have lost its ability to cause hemorrhagic disease as the result of multiple passages in suckling mouse brains. However, likely by virtue of fewer mouse passages, AHFV Zaki-1 has retained the ability to replicate in visceral organs, cause hematologic abnormalities, and induce pro-inflammatory cytokines without causing overt disease. Given these striking differences, the use of inbred mice and the virus passage history need to be carefully considered in the interpretation of animal studies using these viruses.


Phase 2 Placebo-Controlled Trial of Two Vaccines to Prevent Ebola in Liberia.
The safety and efficacy of vaccines to prevent Ebola virus disease (EVD) were unknown when the incidence of EVD was peaking in Liberia. We initiated a randomized, placebo-controlled, phase 3 trial of the chimpanzee adenovirus 3 vaccine (ChAd3-EBO-Z) and the recombinant vesicular stomatitis virus vaccine (rVSV∆G-ZEBOV-GP) in Liberia. A phase 2 subtrial was embedded to evaluate safety and immunogenicity. Because the incidence of EVD declined in Liberia, the phase 2 component was expanded and the phase 3 component was eliminated. A total of 1500 adults underwent randomization and were followed for 12 months. The median age of the participants was 30 years; 36.6% of the participants were women. During the week after the administration of vaccine or placebo, adverse events occurred significantly more often with the active vaccines than with placebo; these events included injection-site reactions (in 28.5% of the patients in the ChAd3-EBO-Z group and 30.9% of those in the rVSV∆G-ZEBOV-GP group, as compared with 6.8% of those in the placebo group), headache (in 25.1% and 31.9%, vs. 16.9%), muscle pain (in 22.3% and 26.9%, vs. 13.3%), feverishness (in 23.9% and 30.5%, vs. 9.0%), and fatigue (in 14.0% and 15.4%, vs. 8.8%) (P<0.001 for all comparisons); these differences were not seen at 1 month. Serious adverse events within 12 months after injection were seen in 40 participants (8.0%) in the ChAd3-EBO-Z group, in 47 (9.4%) in the rVSV∆G-ZEBOV-GP group, and in 59 (11.8%) in the placebo group. By 1 month, an antibody response developed in 70.8% of the participants in the ChAd3-EBO-Z group and in 83.7% of those in the rVSV∆G-ZEBOV-GP group, as compared with 2.8% of those in the placebo group (P<0.001 for both comparisons). At 12 months, antibody responses in participants in the ChAd3-EBO-Z group (63.5%) and in those in the rVSV∆G-ZEBOV-GP group (79.5%) remained significantly greater than in those in the placebo group (6.8%, P<0.001 for both comparisons). A randomized, placebo-controlled phase 2 trial of two vaccines that was rapidly initiated and completed in Liberia showed the capability of conducting rigorous research during an outbreak. By 1 month after vaccination, the vaccines had elicited immune responses that were largely maintained through 12 months. (Funded by the National Institutes of Allergy and Infectious Diseases and the Liberian Ministry of Health; PREVAIL I ClinicalTrials.gov number, NCT02344407 .).


Classical heart rate conditioning and affective behavior: the role of the cerebellar vermis.
The involvement of the cerebellar vermis in the control of affective behaviors and in the coordination of fear-related somatic and autonomic conditioned responses is reviewed in this paper. In particular, the review focuses on the role of the midline cerebellum (vermis) on the acquisition and/or expression of classically conditioned bradycardia in the rabbit. The results of both lesioning and electrophysiological experiments indicate that the cortex of lobule III through VII is important, although not essential, in the acquisition and retention of this response, but it is not the site of its memory trace. The time course of the development of the conditioned bradycardia in neonatal rabbits is also described. The results obtained are consistent with the possibility that the expression of conditioned bradycardia may depend on the complete maturation of cerebellum. Moreover, preliminary data on the effects of the ablation of cerebellar vermis, performed at early stages of development, on the characteristics of conditioned bradycardia showed by adult rabbits are presented. These results indicate that cerebellar vermis is essential for the correct maturation of the response and that the timing of the lesion is critical for determining the characteristics of conditioned bradycardia in the adult.


Regular Black Bean Consumption Is Necessary to Sustain Improvements in Small-Artery Vascular Compliance in the Spontaneously Hypertensive Rat.
Edible legume seeds, such as lentils, have been shown to modulate the structural and functional properties of hypertensive blood vessels, however, the effects of dried beans have not been similarly evaluated. To determine whether beans could attenuate hypertension-induced vascular changes (remodeling and stiffness) in relation to their phytochemical content, spontaneously hypertensive rats (SHR) were fed diets containing black beans (BB; high phytochemical content as indicated by their dark seed coat colour) or navy (white) beans (NB; low phytochemical content) for eight weeks. An additional follow-up phase was included to determine how long the alterations in vascular properties are maintained after bean consumption is halted. Assessments included blood pressure (BP), pulse wave velocity (PWV), vessel compliance (small-artery) and morphology (large-artery), and body composition. Neither BBs nor NBs altered BP or PWV in SHR. SHR-BB demonstrated greater medial strain (which is indicative of greater elasticity) at higher intraluminal pressures (80 and 140 mmHg) compared to SHR-NB. BB consumption for 8 weeks enhanced vascular compliance compared to SHR-NB, as demonstrated by a rightward shift in the stress-strain curve, but this improvement was lost within 2 weeks after halting bean consumption. BB and NB increased lean mass after 8 weeks, but halting BB consumption increased fat mass. In conclusion, regular consumption of BBs may be appropriate as a dietary anti-hypertensive strategy via their positive actions on vascular remodeling and compliance.


Phytochemical profiles of black, red, brown, and white rice from the Camargue region of France.
Secondary metabolites in black, red, brown, and white rice grown in the Camargue region of France were investigated using HPLC-PDA-MS(2). The main compounds in black rice were anthocyanins (3.5 mg/g), with cyanidin 3-O-glucoside and peonidin 3-O-glucoside predominating, followed by flavones and flavonols (0.5 mg/g) and flavan-3-ols (0.3 mg/g), which comprised monomeric and oligomeric constituents. Significant quantities of γ-oryzanols, including 24-methylenecycloartenol, campesterol, cycloartenol, and β-sitosterol ferulates, were also detected along with lower levels of carotenoids (6.5 μg/g). Red rice was characterized by a high amount of oligomeric procyanidins (0.2 mg/g), which accounted >60% of secondary metabolite content with carotenoids and γ-oryzanol comprising 26.7%, whereas flavones, flavonols and anthocyanins were <9%. Brown and white rice contained lower quantities of phytochemicals, in the form of flavones/flavonols (21-24 μg/g) and γ-oryzanol (12.3-8.2 μg/g), together with trace levels of the carotenoids lutein and zeaxanthin. Neither anthocyanins nor procyanidins were detected in brown and white rice. By describing the profile of the heterogeneous mixture of phytochemicals present in different rice varieties, this study provides a basis for defining the potential health effects related to pigmented and nonpigmented rice consumption by humans.


Attenuated endothelin-1 mRNA expression with endothelin-1 receptor blockade during hypoxaemia and reoxygenation in newborn piglets.
We investigated the cause of decreased plasma endothelin-1 (ET-1) during hypoxaemia and reoxygenation in newborn piglets subjected to simultaneous blocking of the ET-1 receptors. Changes in plasma ET-1 and prepro-ET-1 mRNA expression in the main pulmonary artery and the left lower lobe in the lung were studied in 1-2-d-old piglets. Ten minutes prior to hypoxaemia, the hypoxaemia group (n = 10) was given saline, two groups (both n = 9) were given 1 and 5 mg/kg i.v. SB 217242 (an ET-1 receptor antagonist). Two groups served as normoxic controls, with and without SB 217242 5 mg/kg i.v. Hypoxaemia was induced by ventilating with 8% O2 until base excess was 20mmol/l or mean arterial blood pressure was < 20mmHg. Reoxygenation was performed for 2h with room air. During hypoxaemia, plasma ET-1 decreased in the hypoxaemia group, remained unchanged in the 1-mg group and increased in the 5-mg group. At the end of reoxygenation, plasma ET-1 was above baseline in the 1-mg and 5-mg groups. In the pulmonary artery, the hypoxaemia group showed 2- to 5-fold higher prepro-ET-1 mRNA expression compared to all the other groups (p < 0.05). There were trends for higher prepro-ET-1 mRNA expression in pulmonary tissue in the hypoxaemia group compared to the two receptor-blocking groups (p < 0.07). We conclude that hypoxaemia and reoxygenation increase prepro-ET-1 mRNA expression in the pulmonary artery in newborn piglets. These observations suggest that the half-life of ET-1 is decreased during hypoxaemia and reoxygenation in newborn piglets.


Molecular Dynamics Study of the Effect of l-Alanine Chiral Dopants on Diluted Chromonic Solutions.
Atomistic molecular dynamics simulations have been performed for disodium cromoglycate (DSCG) chromonic solutions mixed with l-alanine chiral dopants. We study the fundamental molecular mechanisms induced by low concentrations of l-alanine on diluted DSCG solutions, including their effect on the chromonic aggregates, the solvent, and sodium counterions. Simulations reveal that l-alanine molecules primarily interact with DSCG stacks establishing salt bridges between their respective ammonium and carboxylate groups. Our results demonstrate that l-alanine and sodium counterions jointly establish an intricate network of noncovalent interactions around DSCG aggregates that decreases the global electrostatic repulsion of the chromonic system. Two possible structural effects in DSCG aggregates arise from this electronic stabilization: the increment of the total number of consecutively stacked aromatic planes per DSCG aggregate (intracolumnar effect) or the partial separation reduction between neighboring DSCG columnar sections due to the simultaneous bridging of intercolumnar DSCG carboxylate sites by sodium counterions, forming sodium bridges (intercolumnar effect). Sodium bridges may be responsible for the formation of stacking faults in DSCG aggregates in the form of lateral overlap junctions. This mechanism would explain the difference between lower X-ray correlation lengths with the expected persistence length in chromonics.


Peripheral lipid oxidative stress markers are related to vascular risk factors and subcortical small vessel disease.
Subcortical white matter hyperintensities (WMH), presumed to indicate small vessel ischemic vascular disease, are found commonly in elderly individuals with and without Alzheimer's disease (AD). Oxidative stress may instigate or accelerate the development of vascular disease, and oxidative stress markers are elevated in AD. Here, we assess independent relationships between three serum lipid peroxidation markers (lipid hydroperoxides [LPH], 8-isoprostane, and 4-hydroxynonenal) and the presence of extensive subcortical WMH and/or AD. Patients were recruited from memory and stroke prevention clinics into four groups: minimal WMH, extensive WMH, AD with minimal WMH, and AD with extensive WMH. Extensive WMH, but not AD, was associated with higher serum concentrations of 8-isoprostane and LPH. Peripheral LPH concentrations mediated the effect of hypertension on deep, but not periventricular, WMH volumes. 4-hydroxynonenal was associated with hyperlipidemia and cerebral microbleeds, but not with extensive WMH or AD. We conclude that lipid peroxidation mediates hypertensive injury to the deep subcortical white matter and that peripheral blood lipid peroxidation markers indicate subcortical small vessel disease regardless of an AD diagnosis.


Endocervicosis of the bladder: report of a case and review of the current literature.
An important variety of metaplastic lesions of the urinary bladder have been reported in the medical literature up to date. Among those of Müllerian origin, endocervicosis is the most infrequent. We report a 67 years old woman who presented with a history of left flank pain and dysuria for the past 2 months. Imaging studies revealed a solid mass in the posterior bladder wall protruding into the lumen. Transurethral resection of the lesion was performed. Both pathologic examination and immunohistochemistry confirmed the diagnosis of endocervicosis. The patient was monitored with 6 months interval follow up and remains disease free 12 months post surgery.


Ambient endotoxin in PM10 and association with inflammatory activity, air pollutants, and meteorology, in Chitwan, Nepal.
Endotoxin associated with ambient PM (particulate matter) has been linked to adverse respiratory symptoms, but there have been few studies of ambient endotoxin and its association with co-pollutants and inflammation. Our aim was to measure endotoxin associated with ambient PM10 (particulate matter with aerodynamic diameter<10μm) in summer 2016 at four locations in Chitwan, Nepal, and investigate its association with meteorology, co-pollutants, and inflammatory activity. PM10 concentrations were recorded and filter paper samples were collected using E-samplers; PM1, PM2.5, black carbon (BC), methane (CH4), and carbon monoxide (CO) were also measured. The Limulus amebocyte lysate (LAL) assay was used for endotoxin quantification and the nuclear factor kappa B (NFκB) activation assay to assess inflammatory activity. The mean concentration of PM10 at the different locations ranged from 136 to 189μg/m3, and of endotoxin from 0.29 to 0.53EU/m3. Pollutant presence was positively correlated with endotoxin. Apart from relative humidity, meteorological variations had no significant impact on endotoxin concentration. NF-κB activity was negatively correlated with endotoxin concentration. To the best of our knowledge, this study provides the first measurements of ambient endotoxin associated with PM10 in Nepal. Endotoxin and co-pollutants were positively associated indicating a similar source. Endotoxin was negatively correlated with inflammatory activity as a result of a time-limited forest fire event during the sampling period. Studies of co-pollutants suggested that the higher levels of endotoxin related to biomass burning were accompanied by increased levels of anti-inflammatory agents, which suppressed the endotoxin inflammatory effect.


Growth factors and stromal matrix proteins associated with mammographic densities.
Extensive radiologically dense breast tissue is associated with a marked increase in breast cancer risk. To explore the biological basis for this association, we have examined the association of growth factors and stromal matrix proteins in breast tissue with mammographic densities. Ninety-two formalin-fixed paraffin blocks of breast tissues surrounding benign lesions were obtained, half from breasts with little or no density and half from breasts with extensive density, matched for age at biopsy. Sections were stained for cell nuclei, total collagen, the stromal matrix regulatory protein tissue metalloproteinase-3 (TIMP-3), and the growth factors, transforming growth factor-alpha and insulin-like growth factor (IGF-I). The area of immunoreactive staining was measured using quantitative microscopy. Breast tissue from subjects with extensive densities had a greater nuclear area (P = 0.007), as well as larger stained areas of total collagen (P = 0.003), TIMP-3 (P = 0.08), and IGF-I (P = 0.02) when compared with subjects with little breast density. Differences were greater for subjects less than 50 years of age. These data indicate that increased tissue cellularity, greater amounts of collagen, and increased IGF-I and TIMP-3 expression are found in tissue from mammographically dense breasts and suggest mechanisms that may mediate the associated increased risk of breast cancer.


Cortisol concentration of regrown hair and hair from a previously unshorn area in dairy cows.
This study determined cortisol concentrations in hair that had grown for one month and in hair from a previously unshorn area and examined the effects of calendar month, pregnancy and illness on hair cortisol concentrations in dairy cows. The study was conducted over a one-year period using 27 cows. Electric clippers were used to collect two hair samples per cow each month. The first sample (A sample) consisted of hair that had grown for one month in a pre-clipped area and the second sample (B sample) comprised all hair from a previously unshorn area. Liquid chromatography tandem mass-spectrometry was used for cortisol measurement. The overall mean concentrations for A and B samples did not differ. Cortisol concentrations of A samples were significantly higher in the winter (0.86±0.37pg/mg) than in the fall (0.67±0.33pg/mg). The hair cortisol concentration in A samples increased during pregnancy and the maximum concentration of 1.40±1.08pg/mg hair in the month of calving was significantly higher than the concentration measured in the first month (0.66±0.32pg/mg). The findings show that the effect of short-term stressors such as parturition on hair cortisol concentrations are more easily detected in hair that has grown for one month than in hair from a previously unshorn area.


Evaluation of extracranial-intracranial arterial bypass function by using near-infrared spectroscopy.
It has been reported that extracranial-intracranial (EC-IC) arterial bypass surgery can be useful in preventing stroke in patients with hemodynamic compromise. Little is yet known, however, regarding the extent to which the bypass contributes to maintaining adequate cerebral blood oxygenation (CBO) and its temporal changes following surgery. The authors evaluated bypass function repeatedly by using near-infrared spectroscopy (NIRS) after surgery. The authors investigated 30 patients who had undergone EC-IC bypass surgery. Single-photon emission computerized tomography revealed a decrease in regional cerebral blood flow (rCBF) and a lowered rCBF response to acetazolamide. Changes in CBO were evaluated in the sensorimotor cortex during compression of the anastomosed superficial temporal artery (STA). When decreases in oxyhemoglobin (HbO2) and total hemoglobin (Hb) concentrations were observed, the bypass was considered to have maintained CBO in the sensorimotor cortex given that decreases in HbO2 and total Hb indicate cerebral ischemic changes. The bypass maintained CBO immediately after surgery in 36.7% of patients (Group I, 11 patients) and at some time after surgery, mostly within 1 year, in 43.3% of patients (Group II, 13 patients); however, it did not maintain it throughout the follow-up period in 20% of patients (Group III, six patients). Note that the preoperative rCBF in patients in Groups I and II was lower than that in patients in Group III (p < 0.004). In fact, the preoperative rCBF predicted whether a bypass would maintain CBO at a cutoff value of 24.5 to 25 ml/100 g/min. Among Groups I and II, 18 patients demonstrated an increase in deoxyhemoglobin during STA compression. The preoperative rCBF in these cases was lower than that in the six remaining patients (p < 0.006). Note that the preoperative rCBF predicted the postoperative deoxyhemoglobin response at a cutoff value of 22.2 to 24 ml/100 g/min. The EC-IC bypass surgery can maintain CBO immediately after surgery or gradually within 1 year when the preoperative rCBF is below 24.5 to 25 ml/100 g/min. Furthermore, bypass flow plays a critical role in maintaining an adequate CBO when preoperative rCBF is below 22.2 to 24 ml/100 g/min.


Tanshinone IIA attenuates renal fibrosis and inflammation via altering expression of TGF-β/Smad and NF-κB signaling pathway in 5/6 nephrectomized rats.
In traditional Chinese medicine, Tanshinone IIA is used to treat chronic kidney disease (CKD). However, its biological activity and mechanism of action in renal fibrosis and inflammation are not fully identified. The current study was conducted to determine the effects of Tanshinone IIA treatment on CKD by assessing potential modulation of the TGF-β/Smad and NF-κB signaling pathway. CKD was produced in rats by 5/6 nephrectomy. They were then divided into the following groups: control (sham operation); CKD (5/6 nephrectomy); 5/6 nephrectomy+Tanshinone IIA (10mg/kg in average, once a day for 16 weeks). Serum and urine samples were obtained from animals in each group, and serum creatinine (Scr), blood urea nitrogen (BUN) levels and 24h urinary protein excretion were measured. Tissue samples from the kidney were used for morphometric studies (Masson's trichrome). The expression of fibronectin protein and collagen types I, III, IV, and TGF-β, TNF-α, CXCL-1, MCP-1, RANTES mRNA were evaluated using immunohistochemistry and RT-PCR analysis; the TGF-β/Smad and NF-κB signaling pathway was detected by immunohistochemistry and Western blot analysis. The following effects were observed in CKD rats treated with Tanshinone IIA: (1) marked improvements in Scr, and 24h urine protein excretion; (2) significant reductions in protein and mRNA levels of fibronectin, collagen III, and collagen IV and TNF-α, MCP-1, and CXCL-1; (3) significantly inhibited the TGF-β/Smad and NF-κB signaling activation. These results suggest that Tanshinone IIA suppresses renal fibrosis and inflammation via altering expression of TGF-β/Smad and NF-κB pathway in the remnant kidney, thus supporting the potential of Tanshinone IIA as a new therapeutic agent for slowing the progression of CKD.


Effects of periodic obstructive apnoeas on superior and inferior venous return in dogs.
Obstructive apnoeas could cause flow limitation to venous return, resulting in a decrease in cardiac output and a change in the distribution of flow from the upper and lower body. In 14 anaesthetized dogs, we studied the effects of obstructive apnoeas on inferior and superior vena caval flows under baseline conditions and with intra-abdominal pressure increased by approximately equal to 5 torr by binding the abdomen. During obstructive apnoeas in the two groups, respiratory rate decreased by 30% (P < 0.02) and inspiratory airway pressure decreased by approximately equal to 15 torr (P < 0.01). At baseline, the ratio of inferior to superior vena caval flow was 2.4:1 and did not change with abdominal binding or apnoeas. During apnoeas there was no change in cardiac output or in the ratio of inferior to superior vena cava flow either with baseline or abdominal binding conditions. Preservation of total inferior vena caval flow during apnoeas and cardiac output occurred, even though inspiratory flow limitation was found with the abdomen bound. We conclude: (1) there was no change in either cardiac output or the distribution of venous return during apnoeas; (2) there was substantial inspiratory/expiratory variation in venous return during obstructive apnoeas. The large inspiratory-increase in venous return may have implications for the development of pulmonary hypertension during obstructive apnoeas.


[Transient elastography accurately predicts the severity of disease in patients with chronic hepatitis B].
To evaluate the value of transient elastography (TE) for predicting severity of liver fibrosis in patients with chronic hepatitis B (CHB). A total of 969 patients with CHB was enrolled and recruited for analysis, which had been received TE scan, including 258 patients of liver biopsy, and 117 patients of gastric endoscopy. A total of 35 patients was excluded from analysis due to TE failure or unreliable TE. Liver stiffness measurement (LSM) was independently influenced by bilirubin, AST, liver fibrosis and inflammation, ultrasonic score and albumin. TE predicted Child-Pugh C, B/C, liver fibrosis S4, ≥ S3 and ≥ S2 with respective area under receiver operating characteristics curves (AUROC) 0.907 (95%CI 0.886 - 0.928), 0.920(95%CI 0.899 - 0.940), 0.871(95%CI 0.819 - 0.923), 0.852(95%CI 0.805 - 0.899) and 0.807(95%CI 0.749 - 0.865), respectively. While LSM < 32.2 kPa excluded Child-Pugh C with 99.4% probability, LSM ≥ 35.3 kPa determined Child-Pugh B/C with positive predictive value (PPV) 0.820. For compensated CHB, cut-offs of LSM 23.3, 15.2 and 10.8 kPa diagnosed cirrhosis, liver fibrosis ≥ S3 and ≥ S2 with positive likelihood ratio nearly 10.0 and PPV 0.692, 0.882 and 0.980, respectively; and cut-offs 8.8 kPa, 6.6 kPa excluded cirrhosis, liver fibrosis ≥ S3 with negative likelihood ration nearly 0.1 and negative predictive value 0.977 and 0.903, respectively. Correlation coefficient between LSM and grades of esophageal varices was only 0.180, and AUROC for TE predicting EV was of no clinical value. TE relatively make accurate prediction in the severity of liver fibrosis and classification of Child-Pugh. Patients with LSM ≥ 10.8 kPa should be considered for receiving antivirus treatment.


Potential impact of family history-based screening guidelines on the detection of early-onset colorectal cancer.
Initiating screening at an earlier age based on cancer family history is one of the primary recommended strategies for the prevention and detection of early-onset colorectal cancer (EOCRC), but data supporting the effectiveness of this approach are limited. The authors assessed the performance of family history-based guidelines for identifying individuals with EOCRC. The authors conducted a population-based, case-control study of individuals aged 40 to 49 years with (2473 individuals) and without (772 individuals) incident CRC in the Colon Cancer Family Registry from 1998 through 2007. They estimated the sensitivity and specificity of family history-based criteria jointly recommended by the American Cancer Society, the US Multi-Society Task Force on CRC, and the American College of Radiology in 2008 for early screening, and the age at which each participant could have been recommended screening initiation if these criteria had been applied. Family history-based early screening criteria were met by approximately 25% of cases (614 of 2473 cases) and 10% of controls (74 of 772 controls), with a sensitivity of 25% and a specificity of 90% for identifying EOCRC cases aged 40 to 49 years. Among 614 individuals meeting early screening criteria, 98.4% could have been recommended screening initiation at an age younger than the observed age of diagnosis. Of CRC cases aged 40 to 49 years, 1 in 4 met family history-based early screening criteria, and nearly all cases who met these criteria could have had CRC diagnosed earlier (or possibly even prevented) if earlier screening had been implemented as per family history-based guidelines. Additional strategies are needed to improve the detection and prevention of EOCRC for individuals not meeting family history criteria for early screening.


Multidetector CT imaging of pleura: comparison of two contrast infusion protocols.
Imaging of the pleura by multidetector CT (MDCT) can be challenging. There is no clear evidence or guidelines on contrast infusion parameters for imaging pleura. We compared two contrast protocols for assessing pleural pathology on MDCT. This was a prospective study in which consecutive patients with MDCT for suspected pleural disease on chest radiograph were randomised into two groups. The first group received 150 ml of intravenous contrast at a rate of 2.5 ml s(-1) and the second group received 100 ml at 2 ml s(-1). Images were acquired after a 60 s delay. Hounsfield units of the pleura, thoracic aorta, main pulmonary artery, portal vein and superior mesenteric artery were measured and analysed by two independent readers. 40 patients (20 in each group) who had pleural enhancement on MDCT were included for final analysis. The mean pleural enhancement value was 83 HU (Group A) vs 59 HU (Group B) (p = 0.0004). The mean aortic enhancement was 241 HU (A) vs 141 HU (B) (p<0.0001); main pulmonary artery enhancement was 208 HU (A) vs 139 HU (B) (p<0.0002); portal venous enhancement was 169 HU (A) vs 115 HU (B) (p<0.0001); and the superior mesenteric artery enhancement was 215 HU (A) vs 128 HU (B) (p<0.0001). Enhancement of the pleura and major vessels was significantly higher in the group receiving more contrast at a greater infusion rate. This technique of a single scan through the entire pleural surface with a delayed acquisition is promising. When pleural disease is suspected, contrast infusion protocols should be modified to achieve the best results and clinicians should be encouraged to specifically request a "pleural CT".


Enrichment of CpG island shore region hypermethylation in epigenetic breast field cancerization.
While changes in DNA methylation are known to occur early in breast carcinogenesis and the landscape of breast tumour DNA methylation is profoundly altered compared with normal tissue, there have been limited efforts to identify DNA methylation field cancerization effects in histologically normal breast tissue adjacent to tumour. Matched tumour, histologically normal tissue of the ipsilateral breast (ipsilateral-normal), and histologically normal tissue of the contralateral breast (contralateral-normal) were obtained from nine women undergoing bilateral mastectomy. Laser capture microdissection was used to select epithelial cells from normal tissue, and neoplastic cells from tumour for genome-scale measures of DNA methylation with the Illumina HumanMethylationEPIC array. We identified substantially more CpG loci that were differentially methylated between contralateral-normal and tumour (63,271 CpG loci q < 0.01), than between ipsilateral-normal and tumour (38,346 CpG loci q < 0.01). We identified differential methylation in ipsilateral-normal relative to contralateral-normal tissue (9,562 CpG loci p < 0.01). In this comparison, hypomethylated loci were significantly enriched for breast cancer-relevant transcription factor binding sites including those for ESR1, FoxA1, and GATA3 and hypermethylated loci were significantly enriched for CpG island shore regions. In addition, progression of shore hypermethylation was observed in tumours compared to matched ipsilateral normal tissue, and these alterations tracked to several well-established tumour suppressor genes. Our results indicate an epigenetic field effect in surrounding histologically normal tissue. This work offers an opportunity to focus investigations of early DNA methylation alterations in breast carcinogenesis and potentially develop epigenetic biomarkers of disease risk. DCIS: ductal carcinoma in situ; GO: gene ontology; OR: odds ratio; CI: confidence interval; TFBS: transcription factor binding site; LOLA: Locus Overlap Analysis.


[Mortality from tuberculosis in Cuba. 1902-1997].
The behavior of mortality from tuberculosis in Cuba from 1902 to 1997 was described. During the xx century, tuberculosis has been studied in various stages, but no papers reflecting its behavior in a comprehensive way have been published so far. To this end, the notifications of tuberculosis and the populations by sex, age and provinces available since 1902 in the archives of the National Statistics Division of the Ministry of Public Health were taken into consideration. The trend and the percentages of variation of the gross and specific rates were analyzed. A descending trend of mortality from tuberculosis with rates from 230.9 x 10(5), in 1902, to 0.7, in 1997, was observed. It decreased 71.7% between 1902 and 1940, 74% between 1943 and 1959, 85% between 1960 and 1978, and 0.16% between 1985 to 1991. It increased 40% from 1991 to 1994 and it decreased 30% from 1994 to 1997. Pulmonary and extrapulmonary tuberculoses descended in the same way. They were higher among females until 1940, but from 1943 on it was observed a predominance in males. The highest rates were observed in the group aged 45 and over. They have been insignificant among individuals under 15 for the last 30 years. The highest rates were reported in the capital of the country. It was concluded that the mortality rates from tuberculosis have decreased remarkably during the present century and that it should disappear as a health problem in the next 10 years.


A new osteopetrosis mutant mouse strain (ntl) with odontoma-like proliferations and lack of tooth roots.
A new spontaneous mouse mutant (ntl) with autosomal-recessive osteopetrosis was characterized. These mice formed tartrate-resistant acid phosphate (TRAP)-positive osteoclasts but their osteoclasts had no ruffled border and did not resorb bone. These mice displayed no tooth eruption or tooth root formation. Adult mutant mice developed odontoma-like proliferations near the proximal ends of the incisors. Intraperitoneal injection of progenitor cells from the liver of 16.5 days postcoitum wild-type embryos into newborn mutants rescued the osteopetrosis phenotype, indicating that the defects were intrinsic to the osteoclasts. Our findings not only provide further support for a critical role of osteoclasts in tooth eruption and tooth root development, but also suggest that the perturbation of the homeostasis of the odontogenic precursors of the incisors is primarily responsible for the development of the odontoma-like proliferations in this osteopetrosis mutant. Genetic mapping has narrowed down the location of the mutant allele to a genetic interval of 3.2 cM on mouse chromosome 17.


Quantal evoked depolarizations underlying the excitatory junction potential of the guinea-pig isolated vas deferens.
1. The effects of a putative gap junction uncoupling agent, heptanol, on the intracellularly recorded junction potentials of the guinea-pig isolated vas deferens have been investigated. 2. After the stimulation-evoked excitatory junction potentials (EJPs) had been suppressed by heptanol (2.0 mM) to undetectable levels, a different pattern of evoked activity ensued. This consisted of transient depolarizations that were similar to EJPs in being stimulus locked and in occurring at a fixed latency, but differed from EJPs in that they occurred intermittently and had considerably briefer time courses. 3. Analysis of the amplitudes and temporal parameters of the rapid residual depolarizations revealed a close similarity with spontaneous EJPs (SEJPs). There was no statistically significant difference between the rise times, time constants of decay and durations of the rapid residual depolarizations and of SEJPs. 4. Selected evoked depolarizations were virtually identical to SEJPs occurring in the same cell. Evoked depolarizations of closely similar amplitude and time course also occurred, usually within a few stimuli of each other. 5. These depolarizations appear to represent the individual quantal depolarizations that normally underlie the EJP and are therefore termed 'quantal excitatory junction potentials' (QEJPs) to distinguish them from both EJPs and SEJPs. 6. We examined the possibility that heptanol revealed QEJPs by disrupting electrical coupling between cells in the smooth muscle syncytium. Heptanol (2.0 mM) had no effect on the amplitude distribution, time courses, or the frequency of occurrence of SEJPs. Intracellular input impedance (Rin) of smooth muscle cells was left unaltered by heptanol. 7. 'Cable' potentials of the vas deferens, recorded using the partition stimulation method, also remained unchanged in the presence of heptanol. Thus, heptanol appeared not to modify syncytial electrical properties of the smooth muscle in any significant way. 8. Our observations show directly that the quantal depolarizations underlying the EJP in syncytial smooth muscle are SEJP-like events. However, no unequivocal statement can be made about the mechanism by which heptanol unmasks QEJPs from EJPs.


Morphology of immature stages of blow fly, Lucilia sinensis Aubertin (Diptera: Calliphoridae), a potential species of forensic importance.
Lucilia sinensis Aubertin (Diptera: Calliphoridae) is a blow fly species of potential forensic importance since adults are attracted to, and colonize, decomposing vertebrate remains. Blow fly larvae associated with human corpses can be useful evidence in forensic investigations; however, their use is dependent in most cases on proper species identification and availability of developmental data. For identification, morphological information on each life stage is traditionally used. We used scanning electron microscopy (SEM) to examine the ultrastructure of eggs, all instars, and puparia, of L. sinensis. The important characteristics used to differentiate L. sinensis from other species are provided. Distinctive features of the eggs are the slight widening median area extending almost the entire length. The last abdominal segment of the first instar bears elongated outer ventral tubercles along the rim of the last abdominal segment. These tubercles, as well as the well developed median and outer dorsal tubercles, are more prominent in the second and third instars. The surface integument of the tubercles is equipped with circular rows of microtrichia. Pairs of inner dorsal tubercle are absent. Each anterior spiracle is comprised of 9-12 papillae arrange in a single row in the second and third instars. As for the third instar, the dorsal spines between the first and second thoracic segments are delicate, narrow, small, and close together (as row or set). The peristigmatic tufts adjacent to the posterior spiracle of the third instar are moderately branches of short, fine hairs, but minute in puparia. In conclusion, the prominent outer ventral tubercle in all instars and puparia is a new diagnostic feature of L. sinensis and helpful in differentiating it from other Lucilia species that are forensically important. The description of immature L. sinensis in this study will be useful for forensic entomologists in countries where this species exists.


Fetal growth restriction and 18-year growth and nutritional status: Aboriginal birth cohort 1987-2007.
The main objective of the work is to compare the growth and nutritional status of Australian Aboriginal term infants born with (n = 81) and without fetal growth restriction (n = 260). A prospective birth cohort study of 341 Aboriginal babies from the Top End of the Northern Territory of Australia was recruited at birth (1987-1990) and re-examined at a mean age of 18.3 years (2006-2008) for outcome measures of growth and nutrition status. Those with growth restriction at birth were 3 cm shorter (P = 0.0026) and 9 kg lighter (P = 0.0001) with head circumferences 0.95 cm smaller (P = 0.0008) than those without growth restriction. The proportions of growth restricted participants with body mass index <18.5 kg/m(2) were significantly greater (P = 0.028), and those with BMI > 25 kg/m(2) and with fat percentage >85th percentile were significantly smaller (P = 0.012 and 0.004, respectively). In this cohort, those Aboriginal babies born smaller and lighter have remained smaller and lighter at 18 years of age. However, the highest risk of later chronic noncommunicable disease has been reported in subjects who were born small and become relatively larger in later life. The continued study of this Aboriginal birth cohort will give us an opportunity to determine if and when in later life the effects of birth weight are modified by environmental nutritional factors.


Conduction disturbances and increased atrial vulnerability in Connexin40-deficient mice analyzed by transesophageal stimulation.
Recently, it has been reported that connexin40 (Cx40) deficiency in targeted mouse mutants is associated with a prolongation of P-wave and QRS complex duration on surface electrograms. The specific effects of Cx40 deficiency on sinus node function, sinoatrial, and atrioventricular conduction properties as well as on atrial vulnerability have not yet been investigated systematically by electrophysiological analysis. Fifty-two mice (18 Cx40(+/+), 15 Cx40(+/-), and 19 Cx40(-/-) mice) were subjected to rapid atrial transesophageal stimulation after anesthesia with avertin. A significant prolongation of sinus node recovery time was noticed in Cx40(-/-) mice compared with Cx40(+/-) and Cx40(+/+) mice (287.8+/-109.0 vs 211.1+/-61.8 vs 204.4+/-60.9 ms; P<0.05). In addition, Wenckebach periodicity occurred at significantly longer atrial pacing cycle lengths in Cx40(-/-) mice than in Cx40(+/-) or Cx40(+/+) mice (93. 3+/-11.8 vs 83.9+/-9.7 vs 82.8+/-8.0 ms, P<0.05). Analysis of 27 Cx40(-/-) mice showed a significant increase in intra-atrial conduction time and atrioventricular conduction time compared with 52 Cx40(+/-) and 31 wild-type (Cx40(+/+)) mice. Furthermore, in Cx40(-/-) mice, atrial tachyarrhythmias could be induced frequently by atrial burst pacing, whereas no atrial arrhythmias were inducible in heterozygous or wild-type mice. This study demonstrates that Cx40 deficiency is associated with sinoatrial, intra-atrial, and atrioventricular conduction disturbances. In atrial myocardium of the mouse, Cx40 deficiency results in increased atrial vulnerability and might contribute to arrhythmogenesis.


Using live animal ultrasound measures of ribeye area and fat thickness in yearling Hereford bulls.
Ultrasonic measurements of fat thickness (FAT) and ribeye area (REA) were analyzed together with weight (WT), scrotal circumference (SC) and age data from 385 yearling Hereford bulls representing 45 sires. Additional variables created were 100*REA/WT (REACWT) and 365-d adjusted REA (AREA). Multiplicative age adjustment for AREA was calculated from linear regression of REA on age. Heritabilities were .45 +/- .17 for REACWT, .36 +/- .16 for WT, .12 +/- .13 for REA, .11 +/- .13 for AREA, .04 +/- .13 for FAT and .18 +/- .14 for SC. Phenotypic and genetic correlations were strongly negative for WT with REACWT. Neither AREA nor REACWT alone were considered suitable muscling variables due to their association with age, WT and FAT. Ultrasound REA measurements should be adjusted for the linear effects of age and WT and quadratic effects of FAT before being used for selection. Measurement of SC indicated a strong association with WT (r = .55) and a moderate positive genetic correlation with REA (.49 +/- .58).


Endoscopic axillary exploration and sentinel lymphadenectomy.
Minimally invasive approaches have changed the practice of surgery in several specialties. The purpose of this study was to develop a reproducible endoscopic technique for the evaluation of the axilla in breast cancer patients. A total of 23 patients with biopsy-proven breast carcinoma were enrolled. Patients were positioned in the supine position with the ipsilateral arm abducted at 90 degrees. A 1-cm skin incision was made at the superior aspect of the axilla. Dissection was carried bluntly to the lateral border of the pectoralis major. A balloon distention device was inserted into the tract and distended under endoscopic vision to create a working space. Insufflation was initiated up to a pressure of 8 mmHg. A 30 degrees laparoscope was introduced for visualization of axillary contents. One or two additional 5-mm cannulas were placed as needed under direct visualization. Manipulation of axillary contents was performed, and in 19 patients a sentinel node identification technique was applied. In all patients, using insufflation and minimal instrument dissection, the axillary vein, long thoracic, and thoracodorsal nerves were found in their usual anatomical locations. Utilizing blunt and sharp dissection, the axilla was thoroughly inspected, and individual lymph nodes were easily identified and extracted. In 11 of 19 patients, a sentinel node or blue dye was identified using isosulfan blue. There was a procedure concordance of 84%, and there were no complications. We describe a novel endoscopic technique for the evaluation of the axilla in breast cancer patients. This technique allows (a) creation of a minimally invasive working space within the axilla, (b) recognition of key axillary anatomic landmarks, and (c) instrument manipulation within the axilla to identify and extract lymph nodes, and apply the sentinel node technique. This is the first report of a minimally invasive approach to axillary exploration to employ sentinel lymph node mapping.


Theories of artificial grammar learning.
Artificial grammar learning (AGL) is one of the most commonly used paradigms for the study of implicit learning and the contrast between rules, similarity, and associative learning. Despite five decades of extensive research, however, a satisfactory theoretical consensus has not been forthcoming. Theoretical accounts of AGL are reviewed, together with relevant human experimental and neuroscience data. The author concludes that satisfactory understanding of AGL requires (a) an understanding of implicit knowledge as knowledge that is not consciously activated at the time of a cognitive operation; this could be because the corresponding representations are impoverished or they cannot be concurrently supported in working memory with other representations or operations, and (b) adopting a frequency-independent view of rule knowledge and contrasting rule knowledge with specific similarity and associative learning (co-occurrence) knowledge.


The effect of hysteroscopy on the incidence of meconium aspiration in high risk obstetric patient.
Four hundred amnioscopies were performed from April to December 1984 using a 6 mm contact hysteroscope to detect the presence of intrauterine meconium on 360 high risk obstetric patients. During that eight month period, out of 400 clinic patients delivered, 25 cases of intrauterine meconium were identified. Two infants had meconium aspiration. In comparable periods of 1982 and 1983, 320-356 clinic patients were delivered. Ten-twelve infants had meconium aspiration in their respective groups. The technique of contact hysteroscopy was demonstrated to be easy to perform with few, if any, complications.


Karyometric marker features in normal-appearing glands adjacent to human colonic adenocarcinoma.
The expression of nuclear marker features in normal-appearing tissue adjacent to colonic adenocarcinoma was investigated. Formalin-fixed, paraffin-embedded tissue sections of colon from 9 patients with adenocarcinoma and from 9 normal controls were cut 4 microns thick, Feulgen stained, and measured by a cell image analysis system using a Matrox MVP-AT/NP imaging board. Thirty nuclei in the tumor region, 30 nuclei 2 mm into the histologically normal-appearing distal margin, and the same number at 5, 10, 20, and 50 mm into the margin were measured for each patient. An additional 30 nuclei were recorded from 9 patients each free from colonic disease. Nuclear features were selected to discriminate between tumor nuclei and nuclei from normal control subjects and between nuclei measured in the histologically normal-appearing margin next to the tumor and control nuclei. Eight micromorphometric measures were found to be statistically significantly different in nuclei measured in the margin site, including features describing staining density (total absorbance, average absorbance 20% below mean, average absorbance 20% above mean) chromatin texture (cooccurrence matrix, run length, and peripheral tendency) and nuclear area. The category differences are statistically highly significant.


["Released" employees of the 6th decade--a new retirement generation. Report on central results of a meeting of experts on the topic].
More and more workers and employees leave their working places and renumerated employment for good from the age of 50 onwards - by way of acknowledged incapacity to continue work due to health reasons, unemployment, forced retirement after production plants have closed down and early retirement schemes. How retirement is experienced very much depends on the living conditions encountered and on the process of transition to retirement. Acceptancy of premature retirement is of central importance - as are the opportunities of influencing by one's own decisions the age of retirement, the predictability of this event and the chances of transition through a phase of gradual re-orientation. Differentiation between those with good and very good income levels and those with only minimal financial means is imperative. Negative outcomes of the latter situation may be a feeling of total hopelessness, frictions within the family, reduction of social contacts and of out-of-door activities--a tendency to hide away in shame. To be labelled as old in too early a phase in life is not acceptable. The social status attained tends to be unclearly defined with accompanying negative effects on the self-concept as well as on the image held by others.


Conditional depletion of mast cells has no impact on the severity of experimental epidermolysis bullosa acquisita.
The role of mast cells (MCs) in autoimmunity is the matter of an intensive scientific debate. Based on observations in different MC-deficient mouse strains, MCs are considered as fundamental players in autoimmune diseases. However, most recent data suggest that the outcome of such diseases is strongly affected by the individual mouse strain used. By the use of two c-Kit mutant MC-deficient mouse strains and one c-Kit-independent strain, we here investigated the role of MCs in a systemic Ab transfer model of epidermolysis bullosa acquisita, a subepidermal autoimmune blistering skin disease characterized by autoantibodies against type VII collagen. While C57BL/6J-Kit(W-sh/W-sh) mice developed an unexpected increased blistering phenotype, no significant differences to WT controls were seen in WBB6F1 -Kit(W/W-v) or the novel Mcpt5-Cre iDTR animals. Interestingly, in a local Ab transfer model, which induces a localized disease, we showed that application of high concentrations of anti-COL7 (where COL7 is type VII collagen) Abs induced MC activation and MC-dependent edema formation that did, however, not contribute to blister induction. Our results indicate that in the autoimmune disorder epidermolysis bullosa acquisita MCs do not contribute to the immune-mediated tissue injury. Modern c-Kit mutant-independent MC-deficient mouse strains will help to further redefine the role of MCs in autoimmunity.


A Porcine Epidemic Diarrhea Virus Outbreak in One Geographic Region of the United States: Descriptive Epidemiology and Investigation of the Possibility of Airborne Virus Spread.
This study describes a spring 2013 outbreak of porcine epidemic diarrhea virus (PEDv), using data from 222 swine sites in 14 counties area in 4 contiguous states in the United States. During the outbreak, the premises-level incidence of PEDv was 40.5 percent (90/222 sites). One of the three companies from which data were collected had a lower incidence (19.5 percent) than the other two companies (41.1 and 47.2 percent). Sow sites had the highest incidence of PEDv during the outbreak (80.0 percent). Spatial analysis showed that PEDv was clustered rather than randomly distributed, which suggested that sites near a positive site had increased risk of acquiring PEDv infection. Meteorological data were used to investigate the hypothesis that PEDv was spread by air. If airborne dissemination played a role in this outbreak, we would expect the direction of disease spread to correlate with the predominant wind direction. Two methods were used to determine the direction of disease spread--linear direction mean analysis in ArcGIS and the direction test in ClusterSeer. The former method indicated PEDv spread was south to slightly southwest, and the latter indicated spread was to the southeast. The predominant wind direction during the month of the outbreak was toward the south, with some southeast and southwest winds; the strongest wind gusts were toward the southwest. These findings support the hypothesis that PEDv was spread by air. The results, however, should be interpreted cautiously because we did not have information on direct and indirect contacts between sites, such as movement of trucks, feed, pigs or people. These types of contacts should be evaluated before pathogen spread is attributed to airborne mechanisms. Although this study did not provide a definitive assessment of airborne spread of PEDv, we believe the findings justify additional research to investigate this potential mechanism of transmission.


Vegetation response to invasive Tamarix control in southwestern U.S. rivers: a collaborative study including 416 sites.
Most studies assessing vegetation response following control of invasive Tamarix trees along southwestern U.S. rivers have been small in scale (e.g., river reach), or at a regional scale but with poor spatial-temporal replication, and most have not included testing the effects of a now widely used biological control. We monitored plant composition following Tamarix control along hydrologic, soil, and climatic gradients in 244 treated and 172 reference sites across six U.S. states. This represents the largest comprehensive assessment to date on the vegetation response to the four most common Tamarix control treatments. Biocontrol by a defoliating beetle (treatment 1) reduced the abundance of Tamarix less than active removal by mechanically using hand and chain-saws (2), heavy machinery (3) or burning (4). Tamarix abundance also decreased with lower temperatures, higher precipitation, and follow-up treatments for Tamarix resprouting. Native cover generally increased over time in active Tamarix removal sites, however, the increases observed were small and was not consistently increased by active revegetation. Overall, native cover was correlated to permanent stream flow, lower grazing pressure, lower soil salinity and temperatures, and higher precipitation. Species diversity also increased where Tamarix was removed. However, Tamarix treatments, especially those generating the highest disturbance (burning and heavy machinery), also often promoted secondary invasions of exotic forbs. The abundance of hydrophytic species was much lower in treated than in reference sites, suggesting that management of southwestern U.S. rivers has focused too much on weed control, overlooking restoration of fluvial processes that provide habitat for hydrophytic and floodplain vegetation. These results can help inform future management of Tamarix-infested rivers to restore hydrogeomorphic processes, increase native biodiversity and reduce abundance of noxious species.


Metabolic engineering of lipid catabolism increases microalgal lipid accumulation without compromising growth.
Biologically derived fuels are viable alternatives to traditional fossil fuels, and microalgae are a particularly promising source, but improvements are required throughout the production process to increase productivity and reduce cost. Metabolic engineering to increase yields of biofuel-relevant lipids in these organisms without compromising growth is an important aspect of advancing economic feasibility. We report that the targeted knockdown of a multifunctional lipase/phospholipase/acyltransferase increased lipid yields without affecting growth in the diatom Thalassiosira pseudonana. Antisense-expressing knockdown strains 1A6 and 1B1 exhibited wild-type-like growth and increased lipid content under both continuous light and alternating light/dark conditions. Strains 1A6 and 1B1, respectively, contained 2.4- and 3.3-fold higher lipid content than wild-type during exponential growth, and 4.1- and 3.2-fold higher lipid content than wild-type after 40 h of silicon starvation. Analyses of fatty acids, lipid classes, and membrane stability in the transgenic strains suggest a role for this enzyme in membrane lipid turnover and lipid homeostasis. These results demonstrate that targeted metabolic manipulations can be used to increase lipid accumulation in eukaryotic microalgae without compromising growth.


Basic Physical Capability Scale: Psychometric Testing With Cognitively Impaired Older Adults.
The purpose of this study was to evaluate the reliability and validity of the Basic Physical Capability Scale when used with older adults having moderate to severe cognitive impairment and consider the utility of the measure in establishing function-focused care (FFC) goals for these individuals. The study was a secondary data analysis using data from 2 intervention studies testing FFC interventions in older adults with moderate to severe cognitive impairment in nursing homes and assisted living settings. Participants included 96 recruited from 4 assisted living facilities and 103 older adults from 4 nursing homes. There was support for validity of the measure based on construct validity and hypothesis testing, internal consistency (Cronbach's α of .79), and utility of the measure. Recommendations are provided for additional items that might help better differentiate individuals with moderate to severe cognitive impairment who are particularly high or low in basic physical capability.