Cooperative RecA clustering: the key to efficient homology searching.
The mechanism by which pre-synaptic RecA nucleoprotein filaments efficiently locate sequence homology across genomic DNA remains unclear. Here, using atomic force microscopy, we directly investigate the intermediates of the RecA-mediated homologous recombination process and find it to be highly cooperative, involving multiple phases. Initially, the process is dominated by a rapid 'association' phase, where multiple filaments interact on the same dsDNA simultaneously. This cooperative nature is reconciled by the observation of localized dense clusters of pre-synaptic filaments interacting with the observed dsDNA molecules. This confinement of reactive species within the vicinity of the dsDNA, is likely to play an important role in ensuring that a high interaction rate between the nucleoprotein filaments and the dsDNA can be achieved. This is followed by a slower 'resolution' phase, where the synaptic joints either locate sequence homology and progress to a post-synaptic joint, or dissociate from the dsDNA. Surprisingly, the number of simultaneous synaptic joints decreases rapidly after saturation of the dsDNA population, suggesting a reduction in interaction activity of the RecA filaments. We find that the time-scale of this decay is in line with the time-scale of the dispersion of the RecA filament clusters, further emphasising the important role this cooperative phenomena may play in the RecA-facilitated homology search.


2-(Dibromo-meth-yl)benzoic acid.
In the crystal structure of the title compound, C(8)H(6)Br(2)O(2), the carboxyl groups are involved in pairs of O-H⋯O hydrogen bonds, which link the mol-ecules into inversion dimers.


Clonal GCB Cells Support Angioimmunoblastic T-cell Lymphoma Tumorigenesis.
Germinal center B (GCB) cells provide a niche to support the development of angioimmunoblastic T-cell lymphoma.


Ileo-ileal intussusception in the newborn. Report of a radiologically diagnosed case.
Ileo-Ileal intussusception was demonstrated preoperatively in a newborn infant by gastrografin enema with deliberate reflux of the contrast material into the small bowel. An intraluminal filling defect and stretching of the mucosal folds were demonstrated. The indications and proper use of contrast enemas are discussed.


The Medical Treatment of Vitiligo: An Historical Review.
Discolorations of the skin, such as vitiligo, were recognized thousands of years ago. White spots caused by vitiligo and other disorders have caused significant social opprobrium to those disfigured by these pigmentary disorders, throughout history and still in the present day. Treatments have been desperately sought with only partial success. Recent advances suggest that vitiligo and other pigmentary disorders might soon be curable.


The effect of osmium postfixation and uranyl and lead staining on the ultrastructure of young enamel in the rat incisor.
Enamel crystallites are electron opaque without osmium or heavy metal staining and give a crystalline electron diffraction pattern. Since the opacity and diffraction pattern are abolished from ultrathin sections of young enamel by floating on distilled water (Bishop and Warshawsky, 1982), the possibility that aqueous staining may also remove crystallites was tested. In addition, the effect of osmium postfixation on crystallite structure was examined. Rat incisors fixed by perfusion with a mixture of aldehydes were either nonosmicated or osmicated prior to dehydration. Incisor segments in the region of inner enamel secretion were embedded in the same Epon block to ensure reliable comparison. Osmicated enamel was more intensely stained with toluidine blue and more electron opaque than nonosmicated enamel. No other structural differences were seen. However, crystallites in osmicated enamel were more resistant to grid demineralization and electron beam damage. Routine staining was done by floating sections on solutions of uranyl acetate and lead citrate; sections were also floated on similar solutions from which the heavy metals were omitted. These solutions removed the electron opaque crystallites from the youngest enamel. Stained sections showed electron opaque crystallite-like structures similar to unstained enamel. When sections that were extracted by the solutions from which the metals were omitted were restained, they appeared identical to routinely stained enamel. It was concluded that staining of young enamel removes the crystallites and reveals only the organic matrix.


Effect of beet necrotic yellow vein virus RNA composition on transmission by Polymyxa betae.
Beet necrotic yellow vein virus (BNYVV) is naturally transmitted by the soil-borne fungus Polymyxa betae and usually remains confined to the roots of infected sugarbeets. In naturally infected sugarbeets the virion RNA always consists of four components which are uniform in size in different isolates but when BNYVV is propagated by mechanical inoculation to leaves of Chenopodium quinoa the two smallest RNA components, RNA-3 and -4, may undergo deletion or disappear from the isolate, suggesting that they are only essential for the natural mode of infection. To test this hypothesis, several C. quinoa isolates of BNYVV with different RNA-3 and -4 contents have been retransmitted to sugarbeet root via P. betae. The results show that the two isolates containing no detectable full-length RNA-3 and -4 are poorly transmitted and that cases of successful infection are associated with the reappearance of full-length RNA-3 and -4.


Costs of individuals with disabilities and the elderly in Pennsylvania.
In 2000, an estimated 4,420 children (33 per 1,000 births) were born with a disability in Pennsylvania. In addition, more than 1.8 million Medicare enrollees (age 65 and older) were residents of the state. Selected estimated costs were developed for these two populations at state and county levels.


[Unusual progression of a case of moyamoya (author's transl)].
Angiographic follow-up of a case of moyamoya after three years revealed the appearance of arteriovenous anastomosis between the middle meningeal artery and the sigmoid sinus.


Transcriptional regulation of the intercellular adhesion molecule-1 gene by proinflammatory cytokines in human astrocytes.
Intercellular adhesion molecule-1 (ICAM-1) expression is upregulated by cytokines such as tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), and interferon-gamma (IFN-gamma) in numerous cell types including the astrocyte, which functions as an immunoregulatory cell within the central nervous system. We investigated the mechanism by which ICAM-1 is transcriptionally regulated by proinflammatory cytokines in human fetal astrocytes. TNF-alpha and IL-1beta enhanced ICAM-1 expression at both the mRNA and protein levels, while IFN-gamma had a modest enhancing effect. However, a synergistic response was noted when IFN-gamma was added with either TNF-alpha or IL-1beta. Using human ICAM-1 deletion constructs and linker scanning mutants, we determined that the NF-kappaB element (-186 bp region) is critical for both TNF-alpha- and IL-1beta-mediated ICAM-1 expression, while the IFN-gamma activation sequence (GAS) element at -75 bp region is important for IFN-gamma stimulation. The synergistic effect between TNF-alpha and IFN-gamma is dependent on both NF-kappaB and GAS elements. Upon TNF-alpha and IL-1beta stimulation, p65 homodimers and p65/p50 heterodimers bind to the NF-kappaB site, and STAT-1alpha homodimers bind to the GAS element upon IFN-gamma stimulation. Transient transfection assays demonstrated that overexpression of the p65 protein transactivated the promoter activity of an ICAM-1 reporter construct, while p50 overexpression inhibited, in a dose-dependent manner, p65-mediated ICAM-1 expression. These data collectively suggest that in human astrocytes, the p65 homodimer is responsible for ICAM-1 upregulation upon TNF-alpha or IL-1beta stimulation, and that IFN-gamma enhancement of ICAM-1 involves activation of STAT-1alpha homodimers.


The Role of Cardiovascular MRI in Cardio-Oncology.
"Cardiac imaging is an essential tool in the field of cardio-oncology. Cardiovascular magnetic resonance (CMR) stands out for its accuracy, reproducibility, and ability to provide tissue characterization. These attributes are particularly helpful in screening and diagnosing cardiotoxicity, infiltrative disease, and inflammatory cardiac disease. The ability of CMR to detect subtle changes in cardiac function and tissue composition has made it a useful tool for understanding the pathophysiology of cardiotoxicity. Because of these unique features, CMR is gaining prominence in both the clinical and research aspects of cardio-oncology."


Smoking cessation counseling in women with genital intraepithelial neoplasia.
Cigarette smoking is a risk factor for cervical, vaginal, vulvar, and anal dysplasia. We will study the prevalence of cigarette smoking in patients with genital dysplasia and effect of counseling on smoking cessation. All patients with genital dysplasia were screened for smoking history. One clinician provided smoking cessation counseling using the US Department of Health 5 A's technique: ask patients about their smoking status, advise smokers to quit, assess their readiness to quit, assist with their smoking cessation effort, and arrange for follow-up visits. Patients were informed on how smoking may cause worsening of genital dysplasia and increased risk of progression to cancer. Each patient received 2 counseling sessions, but no pharmacological or psychological interventions. Smoking cessation was evaluated by patient self-report via phone or during clinic visits. From January 2007 to December 2010, 344 patients were referred to our gynecologic oncology clinic for evaluation of genital dysplasia. Patients who were smokers (n=125, 36%) were counseled to cease smoking in 2 counseling sessions, with 100% compliance for attendance. At study analysis (July 2011), 83 patients still smoke and 40 patients quit smoking (smoking cessation rate of 32%). Caucasian patients (P=.0013) and patients with vulvar dyplasia (P=.411) seemed to smoke more than other races and patients with cervical/vaginal dysplasia respectively. Smoking cessation counseling for the genital dysplasia patients who smoked was associated with smoking cessation in 32% of the patients.


Forskolin decreases sensitivity of brain adenylate cyclase to inhibition by 2',5'-dideoxyadenosine.
The effects of forskolin on the sensitivity of adenylate cyclase to 'P'-site-mediated inhibition were studied. Stimulation of crude and purified preparations of adenylate cyclase by forskolin led to decreased sensitivity to inhibition by 2',5' dideoxyadenosine with enzyme from rat and bovine brain. This is in contrast with the enhancement of P-site sensitivity induced by calmodulin, divalent cations, and stable GTP analogs and is in contrast with behavior seen with enzyme from liver and S49 cyc membranes. The effect of forskolin on P-site sensitivity of the brain adenylate cyclase was not dependent on the presence of G-proteins or calmodulin. It was not the consequence of proteolysis nor was it due to an obvious artifact in the assay procedures. This distinct behavior of the brain enzyme is most likely due to a structural difference in the catalytic subunit.


The complementary role of sonography and arteriography in the evaluation of the atheromatous abdominal aorta.
Sonography was performed on 41 patients, 24 of whom were suspected of having abdominal aortic aneurysms and 17 of whom had symptomatic peripheral vascular disease. The accuracy of sonography in the diagnosis of aneurysms of the abdominal aorta was evaluated, and the instances in which angioggraphy contributed to the management of these patients was defined. Sonography is adequate for the diagnosis and management of many aneurysms of the abdominal aorta. Aortography is necessary when: (1) an inadequate study has been obtained, (2) the iliac arteries are not visualized, (3) renal or mesenteric artery involvement is suspected, (4) multiple or lobulated aneurysms are found, or (5) the aorta is very tortuous.


Insulin and extremity muscle mass in overweight and obese women.
Obesity disproportionately affects women, especially those of African descent, and is associated with increases in both fat and muscle masses. Although increased extremity muscle mass may be compensatory to fat mass load, we propose that elevated insulin levels resulting from diminished insulin sensitivity may additionally contribute to extremity muscle mass in overweight or obese women. The following measurements were performed in 197 non-diabetic women (57% black, 35% white; age 46±11 years (mean±s.d.), body mass index (BMI) range 25.0-57.7 kg m(-2)): dual-energy X-ray absorptiometry for fat and extremity muscle masses; exercise performance by duration and peak oxygen consumption (VO2 peak) during graded treadmill exercise; fasting insulin and, in 183 subjects, insulin sensitivity index (SI) calculated from the minimal model. SI (range 0.5-14.1 l mU(-1 )min(-1)) was negatively, and fasting insulin (range 1.9-35.6 μU ml(-1)) positively associated with extremity muscle mass (both P<0.001), independent of age and height. Sixty-seven percent of women completed 6 months of participation in a weight loss and exercise program: we found a significant association between reduction in fasting insulin and a decrease in extremity muscle mass (P=0.038), independent of reduction in fat mass or improvement in exercise performance by VO2 peak and exercise duration, and without association with change in SI or interaction by race. Hyperinsulinemia in overweight or obese women is associated with increased extremity muscle mass, which is partially reversible with reduction in fasting insulin concentration, consistent with the stimulatory effects of insulin on skeletal muscle.


Illiteracy and the incidence of Alzheimer's disease in the Yonchon County survey, Korea.
This study aims to establish the incidence rates of Alzheimer's disease (AD) and to understand the relations between illiteracy and AD in the Korean Yonchon survey cohort. A community-based, dementia-free cohort of 966 people aged 65 years and older was followed up for an average of 5.4 +/- 1.60 years to detect incident AD cases using a two-phase procedure. Age-specific incidence rates were calculated using a person-years approach with Poisson distribution confidence intervals. Data were analyzed using the Cox proportional hazards model to find the hazard ratio of illiteracy. The participating percentage of the survivors was 86.4% and 74 subjects were diagnosed with AD. Incidence rates per 1000 person-years were 20.99 (95% CI 16.48 to 26.35) for AD. The hazard ratio of illiteracy was 1.78 (95% CI 1.08 to 2.93) adjusted for age, sex, educational level. AD developed more rapidly with aging in the illiterate group than in the literate group. Illiteracy is associated with a higher risk of AD and the risk increases with age.


Networks of Adversity in Childhood and Adolescence and Their Relationship to Adult Mental Health.
Adverse experiences before the age of eighteen are common and include diverse events ranging from sexual abuse to parental divorce. These stressful experiences have been linked to physical and mental health issues. Previous research has focused mainly on childhood adversity, such as experiences in the family environment. Little consideration has been given to adversities that may be particularly harmful in adolescence. To understand adolescents' adverse experiences, this project used data from the Avon Longitudinal Study of Parents and Children (ALSPAC, total N = 14,901, N ≈ 1,200 - 10,000 per measure). We modelled interrelations of adversities in childhood (1-11 years) and adolescence (11-23 years) and examined adversity clusters using network analysis. We found two similar clusters in the childhood and adolescence networks: (1) direct abuse and (2) adverse family factors. We identified a third cluster of (3) educational and social adversities for adolescence. For both age groups, emotional abuse in the family environment was closely linked to mental health in early adulthood and most adversities were linked with depression in early adulthood. In adolescence, housing and academic issues and abuse by a romantic partner were particularly central to the network of adversities. Thus, we found commonalities and differences in the relevance of adverse experiences at different developmental stages. These findings highlight the need to develop age-dependent frameworks for adversity research and policymaking.


Determining the involvement of two aminopeptidase Ns in the resistance of Plutella xylostella to the Bt toxin Cry1Ac: cloning and study of in vitro function.
The cloning, expression in vitro, and characterization of two aminopeptidase Ns (APN5s and APN2s) isolated from the midgut of Cry1Ac-resistant (R) and susceptible (S) strains of Plutella xylostella larvae are presented in this paper. The deduced amino acid sequences of APN5s included C-terminal GPI-modification sites, the gluzincin aminopeptidase motif GATEN, and three N-glycosylated sites; those of APN2s had no GPI-modification sites, had gluzincin aminopeptidase motif GAMEN, and had four N-glycosylated sites. O-glycosylated sites were not predicted for either APN. Because APN2R and APN2S cDNAs contained the same nucleotides, only full-length cDNAs encoding APN5R and APN5S were expressed in Trichoplusia ni cells. Far-Western blotting showed that the expressed receptor APN5 bound to the Cry1Ac toxin. An enzyme-specific activity experiment also showed that APN5 genes were expressed in T. ni cells. ELISA revealed no differences in the binding of expression proteins from the resistant and susceptible strain with Cry1Ac.


Impact of a continuing medical education meeting on the use and timing of urgent cancer referrals among general practitioners - a before-after study.
Detection of cancer in general practice is challenging because symptoms are diverse. Even so-called alarm symptoms have low positive predictive values of cancer. Nevertheless, appropriate referral is crucial. As 85% of cancer patients initiate their cancer diagnostic pathway in general practice, a Continuing Medical Education meeting (CME-M) in early cancer diagnosis was launched in Denmark in 2012. We aimed to investigate the effect of the CME-M on the primary care interval, patient contacts with general practice and use of urgent cancer referrals. A before-after study was conducted in the Central Denmark Region included 396 general practices, which were assigned to one of eight geographical clusters. Practices were invited to participate in the CME-M with three-week intervals between clusters. Based on register data, we calculated urgent referral rates and patient contacts with general practice before referral. Information about primary care intervals was collected by requesting general practitioners to complete a one-page form for each urgent referral during an 8-month period around the time of the CME-Ms. CME-M practices were compared with non-participating reference practices by analysing before-after differences. Forty percent of all practices participated in the CME-M. There was a statistically significant reduction in the number of total contacts with general practice from urgently referred patients in the month preceding the referral and an increase in the proportion of patients who waited 14 days or more in general practice from the reported date of symptom presentation to the referral date from before to after the CME-M in the CME-M group compared to the reference group. We found a reduced number of total patient contacts with general practice within the month preceding an urgent referral and an increase in the reported primary care intervals of urgently referred patients in the CME-M group. The trend towards higher urgent referral rates and longer primary care intervals may suggest raised awareness of unspecific cancer symptoms, which could cause the GP to register an earlier date of first symptom presentation. The standardised CME-M may contribute to optimising the timing and the use of urgent cancer referral. NCT02069470 on ClinicalTrials.gov. Retrospectively registered, 1/29/2014.


No Clear Evidence for the Effect of Low-Level Laser Treatment on Orthodontically Induced Inflammatory Root Resorption: More Human Clinical Studies Are Needed.
Influence of low-level laser therapy on orthodontically induced inflammatory root resorption. A systematic review. Michelogiannakis D, l-Shammery D, Akram Z, Rossouw PE, Javed F, Romanos GE. Arch Oral Biol 2019;100:1-13. The authors reported that this article did not receive any specific grants from funding agencies in the public, commercial, or nonprofit sectors. Systematic review.


Avoiding deformity in proximal tibial nailing: risk factors, deformity rules, tips, and tricks.
Malalignment is one of the most common problems linked to nailing of proximal tibial fractures. This review will cover technical aspects of intramedullary nailing and will help explain the various risk factors. Deformity rules aid in identifying the likely deformity and help to develop management strategies. Various tools and techniques are discussed which can help optimize the outcome. Therapeutic Level V.


Distribution, Characteristics, and Management of Older Patients With Valvular Heart Disease in China: China-DVD Study.
The epidemiology and management of valvular heart disease (VHD) have changed with economic development and population aging in China in recent decades. This study sought to understand the distribution, etiology, and presentation and assess the current practice and outcomes of older patients with VHD in China. The authors conducted the first nationwide survey of older patients with VHD between September and December 2016 from 69 hospitals in 28 provinces and municipalities throughout China. Hospitalized patients over 60 years of age with moderate-to-severe VHD, infective endocarditis, or previous valvular intervention were consecutively enrolled. Of 8,929 patients (median age of 69 years, 47.5% female), 8227 (92.1%) had native VHD. Mitral regurgitation was the most prevalent single VHD (26.9% of native VHD), followed by tricuspid regurgitation (16.5%), aortic regurgitation (10.6%), aortic stenosis (5.1%), and mitral stenosis (3.1%). Degenerative (37.2%), functional (21.8%), and rheumatic (15.0%) etiologies were the 3 most common causes. Among symptomatic patients with severe VHD, 37.3% underwent valvular intervention. The intervention rates decreased significantly with age across all types of VHD (P trend < 0.01). Valvular surgery covered 93.7% of interventions. The overall 1-year survival rate was 74.4% (95% CI: 63.4%-85.4%). This study provides a unique national insight into the contemporary spectrum and management of older VHD patients in China. With the increase in the health care demand, more resources and efforts are required for early detection, effective intervention, and targeting innovation on advanced therapeutic techniques and devices to improve the outcomes.


Changes in platelet free Ca2+ concentration after chronic digoxin treatment.
Cell Na+ and Ca2+ concentrations control each other by various mechanisms. In excitable cells from various origins, Ca2+ extrusion from the cell and its entry are dependent for a large part on the activity of the Na+, Ca2+-countertransport system. Cytosolic free Ca2+ concentration is also controlled by the Na+-H+ exchange activity. To analyze the changes in cytosolic Ca2+ concentration accompanying the reduction of the membrane Na+ gradient, cytosolic free Ca2+ concentration ([Ca2+]i) was measured by fluorescent dyes in platelets and erythrocytes from healthy subjects, before and during digoxin treatment (0.25 mg/day for 6 days). [Ca2+]i was increased in platelets from 169 +/- 30 to 321 +/- 61 nmol/l (n = 7, P less than 0.02) and unchanged in erythrocytes (121 +/- 6 and 104 +/- 7 nmol/l). This increase in platelet [Ca2+]i was not accompanied by a change in serotonin content (5.43 +/- 0.67 vs 5.49 +/- 0.61 10(-7) mol per 10(11) cells) and could not be reproduced by in vitro addition of 10(-4) mol/l ouabain (198 +/- 33 vs 186 +/- 73 nmol/l). The enhanced [Ca2+]i in platelets is thus not a short-term consequence of a reduced membrane Na+ gradient, but reflects either the overload of intracellular Ca2+ stores or an enhanced in vivo stimulation by hormones or neurotransmitters.


Pinocytosis of poly (alpha, beta-(N-2-hydroxyethyl))-DL-aspartamide and a tyramine derivative by rat visceral yolk sacs cultured in vitro. Ability of phenolic residues to enhance the rate of pinocytic capture of a macromolecule.
Incorporation of 20% tyramine residues into its structure greatly increased the rate of pinocytosis of poly(alpha, beta-(N-2-hydroxyethyl))-DL-aspartamide (PHEA) by rat visceral yolk sacs cultured in vitro. Both the parent macromolecule and the tyramine derivative (PHEA-tyramine) were captured by adsorptive pinocytosis, the higher affinity of the derivative for the yolk sac plasma membrane being responsible for its greater rate of capture. Using 125I-labelled PHEA-tyramine, the relationship between substrate concentration and rate of capture was determined, it was also shown that following internalization, the PHEA-tyramine linkage is resistant to intracellular hydrolysis. Fluorescence micrographs were consistent with capture of both substrates being by pinocytosis and illustrated the highly efficient concentration of the tyramine derivative by yolk sac endodermal cells.


Real-life effectiveness of transitioning from paliperidone palmitate 1-monthly to paliperidone palmitate 3-monthly long-acting injectable formulation.
Non-adherence to antipsychotics in schizophrenia is associated with an increased risk of psychotic relapse and hospitalization, a risk that is reduced with the use of long-acting injectable (LAI) antipsychotics. Randomized clinical trials (RCTs) have demonstrated the efficacy of paliperidone palmitate 3-monthly (PP3M) for psychotic relapse prevention in schizophrenia, but it remains poorly documented among individuals treated in real-life settings who can benefit the most out of LAIs. The objective of this study was to evaluate the effectiveness of PP3M in relapse prevention among patients with schizophrenia. This is a multicentre retrospective study conducted in four outpatients' clinics across Canada. All consecutive patients with a main diagnosis of schizophrenia who initiated PP3M between June 2016 and March 2020 were included. The primary outcome was psychotic relapse, defined using broad and clinically relevant criteria. Among 178 consecutive patients who were switched to PP3M, the 12-month relapse rate was 18.5% and the relapse-free survival probability was 0.788 (95% confidence interval [CI] = 0.725-0.856). Comorbid diagnoses of personality disorders and substance use disorders were associated with hazard rates (HRs) of 3.6 (95% CI = 1.8-7.3, p < 0.001) and 3.1 (95% CI = 1.6-6.2), respectively. Increased psychopathology severity was associated with an increased likelihood of relapse, while having a job or being in school was protective. These findings reinforce the necessity of conducting research in patients with comorbid psychiatric disorders who are typically underrepresented in RCTs, yet overrepresented in real-life settings, in order to better inform and guide clinical practice.


Image Pretreatment Tools II: Normalization Techniques for 2-DE and 2-D DIGE.
Gel electrophoresis is usually applied to identify different protein expression profiles in biological samples (e.g., control vs. pathological, control vs. treated). Information about the effect to be investigated (a pathology, a drug, a ripening effect, etc.) is however generally confounded with experimental variability that is quite large in 2-DE and may arise from small variations in the sample preparation, reagents, sample loading, electrophoretic conditions, staining and image acquisition. Obtaining valid quantitative estimates of protein abundances in each map, before the differential analysis, is therefore fundamental to provide robust candidate biomarkers. Normalization procedures are applied to reduce experimental noise and make the images comparable, improving the accuracy of differential analysis. Certainly, they may deeply influence the final results, and to this respect they have to be applied with care. Here, the most widespread normalization procedures are described both for what regards the applications to 2-DE and 2D Difference Gel-electrophoresis (2-D DIGE) maps.


Impact of Neoadjuvant Chemotherapy on Pathologic Response in Patients With Upper Tract Urothelial Carcinoma Undergoing Extirpative Surgery.
Neoadjuvant chemotherapy (NAC) has been increasingly adopted in the management of high-grade upper tract urothelial carcinoma (UTUC), largely extrapolating from level I evidence in urothelial carcinoma of the bladder. Studies examining pathologic outcomes in patients with UTUC receiving NAC are mostly limited to retrospective, single-center studies with limited sample size, with results of a phase II trial recently presented. Hypothesizing that NAC is associated with improved pathologic response (PR), we compared pathologic outcomes in patients with high-grade UTUC who did and did not receive NAC before extirpative surgery. A total of 6174 patients with nonmetastatic, high-grade UTUC who underwent extirpative surgery from 2006 to 2014 were identified from the National Cancer Database. Patients were stratified by NAC status. PR was defined as pathologic stage less than clinical stage. Univariate and multivariable logistic regression analysis was employed to identify predictors of PR. Two hundred sixty (4.2%) patients received NAC. A higher incidence of PR was observed in patients receiving NAC (25.2% vs. 1.8%; P < .001), with complete PR observed in 6.1% of patients receiving NAC and 0.4% of patients undergoing surgery alone. NAC (odds ratio [OR], 19.8; 95% confidence interval [CI], 11.8-33.5), nonwhite race (OR, 3.2; 95% CI, 1.7-6.3), and ureteral tumor location (OR, 1.6; 95% CI, 1.02-2.6) were independently associated with PR. Examining a large national cancer registry, we observed a higher incidence of PR in patients with UTUC receiving NAC, validating findings of prior studies. Our findings support consideration of NAC in high grade UTUC. Prospective trials will better define the impact of NAC on pathologic and survival outcomes.


Cement augmentation of the proximal humerus internal locking system in elderly patients: a multicenter randomized controlled trial.
Cement augmentation of the proximal humerus internal locking system (PHILOS) screws might reduce complication rates in osteoporotic bones. This study compared the risk of mechanical failure during the first year after PHILOS™ treatment of proximal humerus fractures (PHF) without (control group) and with (augmented group) screw augmentation. Secondary objectives were to report shoulder functions, quality of life (QoL), adverse events (AEs), and reoperation rates. This multicenter randomized trial enrolled patients aged ≥ 65 years with displaced/unstable PHF from eight European centers. Randomization was performed during surgery through sealed opaque envelopes. Mechanical failures were assessed by two independent reviewers via radiographs, shoulder function by Quick DASH, SPADI, and Constant Murley scores, and QoL by EQ-5D. Follow-ups were planned at postoperative 6 weeks, 3, 6, and 12 months. The preliminary analysis of 6-week radiographs of the first 59 enrolled patients suggested a mechanical failure rate lower than expected and the difference between groups was too small to be detected by the planned sample size of 144. The trial was prematurely terminated after 67 patients had been enrolled: 34 (27 eligible) in the control group and 33 (29 eligible) in the augmented group. Follow-ups were performed as planned. Nine patients had mechanical failures and the failure rates (95% CI) were: augmented group, 16.1% (5.5; 33.7); control group, 14.8% (4.2; 33.7); the relative risk (95% CI) for the augmented group was 1.09 (0.32; 3.65) compared to the control group (p = 1.000). No statistically significant differences in shoulder function, QoL, and AEs were observed between study groups at 1 year. Nine patients (15.8%) underwent a revision. Due to premature termination, the study was underpowered. A larger study will be necessary to determine if cement augmentation lowers the risk of mechanical failure rate.


[Dementia Screening and Test Psychology in German General and Specialist Practices under Conditions of the Corona Pandemic].
To analyse changes in frequencies of test psychology examinations (TPE) relevant to detect change in dementia diagnosis in general (GP) and neuropsychiatric (NP) practices during the Covid 19 pandemic. Cross-sectional study analysis comparing the number of patients aged ≥ 70 with at least one TPE in 908 GP and 107 NP-practices in 2018-2019 (prepandemic) and 2020-2021 (pandemic) using descriptive statisics and correlations. While there was a large decrease in TPE between 2018-2019 and 2020-2021 (- 18.4%) conducted in NP-practices, it remained stable in GP-practices (+ 2.6%). In both GP and NP, there was a strong correlation between the number of patients tested and newly diagnosed with dementia. TPE in performing in GP practices appears less susceptible to a pandemic-related decline in the provision compared to NP practices. Further research is needed to reveal the reasons for these differences.


Effects of spinal segmental flexion and extension exercises on spinal flexibility.
We considered spinal segmental movement exercise that voluntarily control local muscles as a convenient treatment to correct the trunk muscle recruitment pattern in individuals with global muscle overactivity. The purpose of this study was to verify the effects of segmental flexion and extension movements of the spine and overall flexion and extension movements of the spinal column on the flexibility of the spinal column among healthy university students who had completed a day of lectures and had a certain load on their lower back as a preliminary step to applying the exercise to low back pain patients with a broken trunk muscle recruitment pattern. The subjects performed trunk flexion/extension exercises that required segmental control of the spine (segmental movement) and trunk flexion/extension exercises that do not require segmental control of the spine (total movement) in the chair position. As an evaluation task, finger floor distance (FFD) and muscle tension of the hamstrings were evaluated before and after exercise intervention. There was no significant difference in the FFD value and the passive pressure before the intervention between the two exercises. FFD decreased significantly after the intervention compared to that before, and passive pressure did not change in both motor tasks. The FFD change amount of segmental movement was significantly larger than that of total movement. (P < 0.01). It has been suggested that segmental spinal movements improve spinal mobility and may reduce global muscle tension.


Pharmacokinetic behavior of doxycycline after intramuscular injection in sheep.
To determine the pharmacokinetics of a commercial formulation of doxycycline hyclate after IM administration of a single dose to sheep. 11 healthy domestic sheep. For each sheep, doxycycline was administered as a single dose of 20 mg/kg, IM. Blood samples were obtained prior to and for 84 hours after doxycycline administration. Plasma concentrations of doxycycline were determined via high-performance liquid chromatography with UV detection. Pharmacokinetic data were analyzed with noncompartmental methods. Mean ± SD values for pharmacokinetic parameters included maximum plasma concentration (2.792 ± 0.791 μg/mL), time to reach maximum plasma concentration (0.856 ± 0.472 hours), mean residence time (91.1 ± 40.78 hours), elimination half-life (77.88 ± 28.45 hours), and area under the curve (65.67 ± 9.877 μg•h/mL). Results indicated that doxycycline had prolonged absorption and elimination in sheep after IM administration. A daily dose of 20 mg/kg would be sufficient to reach effective plasma concentrations against Chlamydia spp (minimum inhibitory concentration, 0.008 to 0.031 μg/mL) and Staphylococcus aureus (minimum inhibitory concentration, 0.12 μg/mL). Doxycycline administered IM could be an option for therapeutic use in sheep, although further studies are needed.


To cross or not to cross - thrushes at the German North Sea coast adapt flight and routing to wind conditions in autumn.
Although many aspects of passerine migration are genetically determined, routing appears to be flexibly adjusted to the conditions experienced on each individual journey. This holds especially true for routing decisions taken when confronted with large bodies of water. Once taken, these decisions can be hardly altered or revised. In this paper, we analysed stopover and routing decisions taken by three species of thrushes, blackbirds, redwings and song thrushes, at the German North Sea coast. Birds were equipped with radio-telemetry tags at stopover sites along the coast during autumn migration and subsequently tracked by an automated receiver network covering the coastline and islands of the German Bight. The thrushes resumed migration in nights with a favourable northward wind component and clear skies. About 40% of the tagged individuals have taken an offshore instead of an alongshore oriented flight route. Routing decisions were influenced by the strength of the eastward wind component with offshore oriented flights taking place primarily under weak winds or winds blowing towards the west. Thrushes that took an offshore oriented route stopped over at the coast longer than those flying alongshore. Interestingly, offshore as well as alongshore oriented flights co-occurred within single nights and under comparable weather conditions. Migratory flight and routing decisions of thrushes at the German North Sea coast are highly dependent on weather, in particular wind. Still, we found evidence that weather may not be the sole reason for individual routes taken. Physical condition, morphology or animal personality lend themselves as possible additional factors of influence. Enabling a more detailed understanding of thrush migration over and along the German North Sea, our data help to better judge risks that migratory birds are facing when en route conditions are altered, for example by artificial obstacles such as offshore wind turbines.


Glucocorticoid receptor expression in blood, but not across brain regions, reveals long-term effects of early life adversity in zebra finches.
Early-life environment can affect organisms for life on many levels. The glucocorticoid receptor (GR) gene has a pivotal role mediating organismal physiological and behavioral responses to environmental change, and is sensitive to early-life environmental conditions and epigenetic programming. Longitudinal studies require non-lethal sampling of peripheral tissues (e.g. blood), but this approach is dependent on the extent to which GR expression in peripheral tissues covaries with GR expression in central tissues. To test for the long-term effects of early life adversity on GR expression across brain and peripheral tissues, we manipulated developmental conditions of captive zebra finches (n = 45), rearing them in either benign or harsh conditions through manipulation of parental foraging costs. We measured relative GR mRNA expression in blood and five brain regions in adulthood: hippocampus, hypothalamus, amygdala, ventral striatum, and the nidopallium caudolaterale (analogous to the mammalian prefrontal cortex), using qPCR. We further tested whether GR expression was modulated by natal brood size (which affected growth), age at sampling, and sex. GR expression correlations among tissues varied widely in magnitude and direction, ranging from -0.27 to +0.80, indicating that our understanding of developmental effects on GR expression and associated phenotypes needs to be region specific rather than organism wide. A more consistent pattern was that GR expression increased with age in blood, ventral striatum and hippocampus; GR expression was independent of age in other tissues. Developmental treatment did not affect GR expression in any of the tissues measured directly, but in blood and ventral striatum of adult females we found a positive correlation between nestling mass and GR expression. Thus, GR expression in blood was affected by early life conditions as reflected in growth in adult females, a pattern also found in one brain tissue, but not ubiquitous across brain regions. These results point at sex-dependent physiological constraints during development, shaping early life effects on GR expression in females only. Further study is required to investigate whether these tissue-dependent effects more generally reflect tissue-dependent long-term effects of early life adversity. This, together with investigating the physiological consequences of GR expression levels on individual performance and coping abilities, will be fundamental towards understanding the mechanisms mediating long-term impacts of early life, and the extent to which these can be quantified through non-lethal sampling.


ITPKB and ZNF184 are associated with Parkinson's disease risk in East Asians.
A recent meta-analysis of Parkinson's disease (PD) genome-wide association studies has identified 17 novel risk loci in the European population. We aim to assess if these reported novel risk loci are similarly implicated in PD risk within the East Asian population by analyzing the reported risk single nucleotide polymorphism or proxy single nucleotide polymorphism in 14,006 East Asian samples (779 patients and 13,227 controls). We found that 9 of the 17 reported novel PD risk loci showed very similar effects in Europeans and East Asians (I2 = 0 to 10.7%), of which 2 loci ITPKB and ZNF184 were significantly associated with PD in our samples. Two of the reported risk loci, ANK2/CAMK2D and CTSB, were non-polymorphic in East Asians and therefore not implicated in PD risk in the East Asian population. Given the small effect sizes of these risk loci, further validation is needed in additional Asian samples.


Lomefloxacin versus amoxicillin in the treatment of acute exacerbations of chronic bronchitis: an Italian multicenter study.
Nine centers in Italy participated in a worldwide, multicenter study comparing the effectiveness and safety of lomefloxacin and amoxicillin in patients with acute exacerbations of chronic bronchitis caused mainly by gram-negative pathogens. The 157 enrolled patients received either 400 mg lomefloxacin once daily (n = 78) or 500 mg amoxicillin every 8 hours (n = 79) for 7-10 days. A total of 131 patients were evaluable for bacteriologic efficacy and 154 for clinical efficacy. At 2-4 days after the conclusion of treatment, the bacterial eradication rate was 84.8% for lomefloxacin-treated patients and 64.6% for amoxicillin-treated patients (p = 0.0065); the clinical success rate (cure plus improvement) for lomefloxacin was 94.7% and for amoxicillin was 83.3% (p = 0.0212). The reinfection rate was lower in the lomefloxacin group than in the amoxicillin group (3.0% vs 13.8%, p = 0.0382). Both drug regimens were well tolerated. Once-a-day treatment with 400 mg lomefloxacin was more effective than 500 mg amoxicillin three times daily for the treatment of acute exacerbations of chronic bronchitis caused by gram-negative pathogens.


The art of dissecting the function of a potassium channel.
The essential function of potassium channels is to selectively facilitate the passage of K(+) ions across the cell membrane by lowering the energy barrier that opposes this process. In this issue of Neuron, Chatelain et al. report the results from an elegant study that sheds new light on the microscopic factors that modulate the function of these important membrane channels.


Pattern separability in a random neural net with inhibitory connections.
Some interesting properties on pattern separation have been shown through researches by neural models of cerebellar cortex. It seems to us that those results are a part of the properties of pattern separation. A two layer random nerve net with inhibitory connections is given as a model of the cerebellar cortex. The model is composed of threshold elements there. A more general theory of pattern separation than those studied earlier is given, and the pattern separability of the model is considered. It is revealed that the standard deviation of threshold values of threshold elements has a great effect on the pattern separability and the control of the firing rate. The present study is also intended to investigate the pattern separability in such a case that the firing rate of input patterns are not equal, and a pattern includes the other pattern. It is assumed there that the standard deviation is small. Some properties of the degree of pattern separation are cleaned up.


Triterpenes and a triterpene glucoside from Dysoxylum cumingianum.
Six triterpenes and a triterpene glucoside were isolated from the MeOH extract of the leaves of Dysoxylum cumingianum together with three known triterpenes. Their structures were elucidated by extensive spectroscopic analyses. In cytotoxicity assays against three human cancer cell lines, including a multi-drug resistant cancer cell line (KB-C2), compounds 1, 2 and 5 demonstrated significantly enhanced cytotoxicity against KB-C2 cells in the presence of 2.5 μM colchicine, as compared with those in the absence of colchicine. This result suggested that these triterpenes might show some MDR-reversing effects.


Association between achieving textbook outcomes and better survival after laparoscopic liver resection in the anterolateral segments in patients with hepatocellular carcinoma.
The quality of surgical procedures are assessed by textbook outcomes (TO). Laparoscopic liver resection (LLR) is considered a standard treatment for hepatocellular carcinoma (HCC) in the anterolateral segments of the liver. The main objective of this study was to evaluate the factors affecting achievement of TO for LLR and its impact on survival. We conducted a retrospective cohort study of patients who underwent LLR for lesions located in the anterolateral segments (n = 309). Patients were divided into TO and non-TO group. A TO was achieved in 55.0% of patients (n = 170). In multivariable analysis, Model for End-stage Liver Disease (MELD) score ≥ 10 (odds ratio[OR] 3.076; 95% confidence interval[CI] 1.134-8.342), absence of diabetes mellitus (OR: 2.325; 95% CI: 1.227-4.407) and thrombocytopenia (OR: 2.115; 95% CI: 1.134-8.342) were independently associated with not achieving TO. The 5-year overall (82.9% vs 72.8%, P = .017) and recurrence-free (48.8% vs 35.4%; P = .036) survival rates were significantly greater in the TO group than in the non-TO group. The MELD score, thrombocytopenia, and hypoalbuminemia were independent risk factors influencing the achievement of TO. TO influences the short- and long-term outcomes after LLR for HCC.


Mapping and identification of soft corona proteins at nanoparticles and their impact on cellular association.
The current understanding of the biological identity that nanoparticles may acquire in a given biological milieu is mostly inferred from the hard component of the protein corona (HC). The composition of soft corona (SC) proteins and their biological relevance have remained elusive due to the lack of analytical separation methods. Here, we identify a set of specific corona proteins with weak interactions at silica and polystyrene nanoparticles by using an in situ click-chemistry reaction. We show that these SC proteins are present also in the HC, but are specifically enriched after the capture, suggesting that the main distinction between HC and SC is the differential binding strength of the same proteins. Interestingly, the weakly interacting proteins are revealed as modulators of nanoparticle-cell association mainly through their dynamic nature. We therefore highlight that weak interactions of proteins at nanoparticles should be considered when evaluating nano-bio interfaces.


Oncolytic herpesvirus with secretable angiostatic proteins in the treatment of human lung cancer cells.
The wild-type herpes simplex virus type 1 (HSV-1) has strong infectivity and cytolytic effect on almost all types of mammalian cells. Genetic engineering can now restrict this cytolysis to only malignant cells. G207 is an oncolytic HSV-1 vector developed based on this strategy. We used G207 as the backbone and integrated the exogenous endostatin-angiostatin fusion protein gene to generate a new vector, AE618. Marked expressions of fusion protein in A549 and H460 lung cancer cells and culture medium were found 24 hours after treatment with AE618. In comparison with the G207 treatment group, the secreted protein from H460 cells treated with AE618 significantly inhibited the growth of human umbilical vein endothelial cells (HUVEC). AE618 also significantly inhibited the growth of xenografted tumors in vivo. We propose that AE618 has the potential to be a novel anticancer agent with both oncolytic and anti-angiogenesis effects.


Heavy metal contamination and health risk assessment for children near a large Cu-smelter in central China.
Nonferrous metallurgy is causing significant concerns due to its emissions of heavy metals into environment, degrading environmental quality, and consequently posing high risks to human health. In this study, the concentration levels of Cadmium (Cd), Copper (Cu), Lead (Pb), and Arsenic (As) were investigated in soil, crop, well water, and fish samples collected around the Daye Copper Smelter in Hubei province, China, and the potential health risks were assessed for local children. The results showed that soils near the smelter were heavily polluted by Cd, Cu, Pb, and As, with the mean concentrations of 4.87, 195.26, 92.65, and 35.84 mg/kg, respectively, which were significantly higher than the values of soil Cd (0.18 mg/kg), Cu (32.84 mg/kg), Pb (28.46 mg/kg), and As (13.65 mg/kg) in the reference area (p < 0.001). The concentrations of Cd and As in vegetable samples collected from smelter-affected area exceeded the maximum permissible level (MPL) for food in China by 82% and 39%, respectively. The concentrations of Cd and Pb in rice grain harvested from smelter-affected area were 9.35 and 1.35 times higher than the corresponding MPL, respectively. The concentrations of Cd, As, and Cu in fish muscle from smelter-affected area exceeded the national MPL by 72%, 41%, and 24% of analyzed samples, respectively. The concentrations of Cd (p < 0.05) and As (p < 0.01) in well water were significantly higher in the smelter-affected area than those in the reference area, respectively. The health risks to local children in the smelter-affected area were 30.25 times higher than the acceptable level of 1, and most of the risks were resulted from Cd (46%), As (27%) and Pb (20%). The intake of crops was a major source (78%) to health risks for local children.


Late coronary stent thrombosis complicating urologic surgery.
The current practice of withdrawing antiplatelet therapy before major surgery has been challenged by the introduction of coronary drug-eluting stents (DESs) since evidence is accumulating that a DES requires dual antiplatelet therapy for at least a year. The authors present a case demonstrating difficulty in decision-making when it comes to appropriate perioperative antiplatelet therapy. The patient experienced a coronary stent thrombosis possibly due to discontinuation of clopidogrel prior to urologic surgery.


Evaluation and evolution of apparent diffusion coefficient (ADC) in image-guided adaptive brachytherapy (IGABT) for cervical cancer.
Image-guided adaptive brachytherapy (IGABT) recently has shown excellent clinical outcomes with superior local control and less toxicity. For IGABT, T2W (T2-weighted) MRI is the gold standard. However, studies have shown that target delineation with the same results in uncertainties, poor interobserver variabilities, and low conformity indices for high-risk clinical target volume contours. In this study, we investigate the role of diffusion-weighted imaging-derived apparent diffusion coefficient (ADC) maps to aid in IGABT. We also evaluated ADC from the baseline to brachytherapy. Thirty selected patients were enrolled for this study, and two MRIs were taken at diagnosis and before brachytherapy. Patients were divided into two groups, Group 1 being patients with parametrial involvement before external beam radiotherapy and no parametrial involvement before brachytherapy. Group 2 included patients with parametrial involvement before external beam radiotherapy and persistent parametrial involvement before brachytherapy. ADC was measured at the center, edge, and 1 cm from the edge. The measured ADC increased from diagnosis to brachytherapy, and this increase was more for the patients in Group 1 than in Group 2. The mean TDadc (diagnosis ADC, center), TEadc (tumor edge ADC diagnosis), and T1cmDadc (1 cm from edge at diagnosis) were 0.884, 1.45, and 1.9 × 10-3 mm2/s, respectively. The TBadc (ADC at brachytherapy, center), TEBadc (tumor edge ADC at brachytherapy), and TE1cmBadc (1 cm from edge brachytherapy) were 1.2, 1.8, and 2.3 × 10-3 mm2/s, respectively, p-value <0.00001. No abnormal ADC was present outside the high-risk clinical target volume contours. MRI-based IGABT using T2W imaging essentially covers all functionally abnormal zones at brachytherapy. Diffusion-weighted imaging, along with ADC maps, should only be used as a supplement for target delineation.


Identification of promising CD8 and CD4 T cell epitopes for peptide vaccine formulation against SARS-CoV-2.
The novel virus "severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)" has been responsible for the worldwide pandemic causing huge devastation and deaths since December 2019. The disease caused by this virus is known as COVID-19. The present study is based on immuno-informatics approach to develop a multi-epitope-loaded peptide vaccine to combat the COVID-19 menace. Here, we have reported the 9-mer CD8 T cell epitopes and 15-mer CD4 T cell epitopes, free from glycosylation sites, belonging to three proteins, viz. surface glycoprotein, membrane glycoprotein and envelope protein of this virus. Immunogenicity, aliphatic amino acid, antigenicity and hydrophilicity scores of the predicted epitopes were estimated. In addition, other physicochemical parameters, namely net charge, Boman index and amino acid contents, were also accounted. Out of all the epitopes, three CD8 T cell epitopes viz. PDPSKPSKR, DPSKPSKRS and QTQTNSPRR and three CD4 T cell epitopes viz. ASYQTQTNSPRRARS, RIGNYKLNTDHSSSS and RYRIGNYKLNTDHSS were found to be efficient targets for raising immunity in human against this virus. With the help of our identified potent epitopes, various pharma industries might initiate efforts to incorporate those epitopes with carrier protein or adjuvant to develop a multi-epitope-loaded peptide vaccine against SARS-CoV-2. The peptide vaccines are usually cost-effective and therefore, could be administered as a preventive measure to combat the spread of this disease. Proper clinical trials must be conducted prior to the use of identified epitopes as vaccine candidates.


Evaluation of 4'-(9-acridinylamino) methanesulfon-m-anisidide (m-AMSA, NSC 249992) on human tumors in nude mice.
The nude mouse human tumor-bearing system is a useful model for studying the efficacy of new drugs against human tumors. A panel of six selected human tumor heterotransplants was used to assess the activity of m-AMSA. No effect was seen against malignant schwannoma, malignant lymphoma, liposarcoma, neuroblastoma, or malignant melanoma. A testicular carcinoma appeared to respond to m-AMSA: however, statistical evaluation demonstrated that this was not significant. No evidence was found to support the use of m-AMSA as a sensitizing agent for radiation.


Virus quantitation by transmission electron microscopy, TCID₅₀, and the role of timing virus harvesting: a case study of three animal viruses.
Quantitation of viruses is practised widely in both basic and applied virology. Infectious titration in cell cultures, the most common approach to it, is quite labour-intensive and alternative protocols are therefore sought. One of the alternatives is transmission electron microscope (TEM) quantitation using latex particles at a known concentration as a reference for counting virus particles. If virus TCID₅₀ is determined in parallel, the ratio of infectious to non-infectious virus particles may be established. This study employs such an approach to compute the number of virus particles and TCID₅₀, and establish their correlation for three viruses: Canine adenovirus 1 (CAdV-1), Feline calicivirus (FCV) and Bovine herpesvirus 1 (BoHV-1). Each of the viruses was grown in five replicates until complete cytopathology was recorded (time 0), then frozen. They were thawed, filter-sterilised and left for additional periods of 16, 32 and 48 h at 37°C. At each time point, the infectious ability of the virus was characterised by TCID50 and the number of virions quantified by TEM, in order to evaluate the influence of timing on virus harvest. The virus particle count determined by TEM did not change for any of the viruses throughout the experiment. The relationship between virus particle counts with TCID₅₀ at time 0 showed good linearity response; their ratio was almost constant. The virus particle-to-TCID₅₀ ratio varied between 146 and 426 (mean±SD: 282±103) for CAdV-1, between 36 and 79 (57±18) for FCV and between 110 and 249 (167±53) for BoHV-1. The proportion of non-infectious particles did not change throughout the experiment for either CAdV-1 or BoHV-1. However, a decrease in virus infectious ability disclosed by TCID₅₀ indicated that the fraction of non-infectious particles in FCV increased 300,000 times when time 0 and 48 h were compared. The quantitation of viruses with TEM is a simple and rapid protocol for virus quantitation but account must be taken of the type of virus and harvesting time as virus counts need not necessarily correlate with virus infectious ability.


Natural exposure and serum antibodies to house dust mite of mite-allergic children with asthma in Atlanta.
Pyroglyphid mites in house dust are important allergens associated with asthma in Europe, but comparable studies of house dust mites in the homes of patients with asthma have not been done in the United States. We examined the distribution of mites and mite allergen in the houses of 20 mite-sensitive children with asthma in Atlanta and measured IgE antibodies to mite allergens in their sera. One or more dust samples from bedding, bedroom floor, television room floor, or television room furniture from 17/20 houses contained greater than 10,000 ng of antigen P1 equivalent per gram of fine dust; amounts ranged from 280 to 230,400 ng/gm. Allergen levels were higher in dust samples from furniture and bedding than from floors. Dust samples obtained from houses in June to September had more mites and mite allergen than those houses sampled in March to April; relative humidity in the room also was higher in June to September. Mite numbers and allergen in floor and furniture samples were correlated with relative humidity in the room and were high when relative humidity was greater than 50%; antigen P1 equivalent was greater than 10,000 ng/gm in 21/39 such samples. Dermatophagoides pteronyssinus was present in all houses and dominant in 11/20. D. farinae was found in 17 houses and was dominant in six. All children studied had high IgE antibody with either D. farinae or D. pteronyssinus RAST; 16 of the 20 children also had IgE to antigen P1. It is likely that the IgE antibody responses in these 20 children with asthma were a direct result of exposure to high levels of mite allergen.(ABSTRACT TRUNCATED AT 250 WORDS)


Prognostic factors of myxofibrosarcomas: implications of margin status, tumor necrosis, and mitotic rate on survival.
Myxofibrosarcomas (MFS) are characterized by tumor progression with increased metastases after local recurrences (LR). Few series had appropriately addressed what parameters independently affect prognosis. Seventy primary localized MFS were analyzed for local recurrence-free survival (LRFS), metastasis-free survival (MeFS), and disease-specific survival (DSS). Follow-up was obtained in 61 cases. Thirty-eight males and 32 females had primary tumors ranging from 1.5 to 24 cm. Thirty and 40 tumors were superficial and deep, respectively, with 26 cases (38%) having positive margins. The 5-year LRFS-, MeFS-, and DSS-rates were 30%, 60%, and 73%. Positive margins (P = 0.0003) were the only inferior LRFS predictor. High grade (FNCLCC 2 and 3) was a negative factor of both MeFS (P = 0.0078) and DSS (P = 0.0174), and high stage (AJCC stage 3) was predictive of MeFS (P = 0.0470). However, both grading and staging were not prognostically independent. In multivariate analyses, mitoses >or=20/10 HPF (P = 0.0009, RR = 9.71) and positive margins (P = 0.0203, RR = 4.27) were independent adverse DSS predictor. However, tumor necrosis >or=10% (P = 0.0092, RR = 3.91) independently correlated with worse MeFS, together with mitoses >or=20/10 HPF (P = 0.0176, RR = 3.80) and positive margins (P = 0.0121, RR = 3.41). Margin status and histologic property both affect the prognosis of MFS. The former correlates with improved LRFS and translates into final survival benefits.


The prevalence of depression in men who have sex with men (MSM) living with HIV: A meta-analysis of comparative and epidemiological studies.
Men who have sex with men (MSM) living with Human Immunodeficiency Virus (HIV) are more likely to suffer from depressive symptoms (depression hereafter). This is a comprehensive meta-analysis of the prevalence of depression in HIV-infected MSM. Relevant publications were systematically searched in PubMed, PsycINFO, EMBASE, Cochrane Library and Web of Science. Comparative and epidemiological studies with prevalence of depression as measured by the Center for Epidemiological Studies Depression Scale (CES-D) were included. The prevalence of depression was pooled using the random-effects model. A total of 18 studies with 7653 MSM with HIV and 3395 MSM without HIV were included in the meta-analysis. The pooled prevalence of depression in MSM living with HIV was 43% (95%CI: 32%-53%). Compared to MSM without HIV, MSM living with HIV were more likely to be depressed (OR = 1.46, 1.05-2.03). Subgroup and meta-regression analyses revealed that different CES-D cut-off values and survey year had significant moderating effects on the prevalence of depression. Depression was common in MSM living with HIV. Considering the negative effects of depression on health outcomes and wellbeing, regular screening for depression and effective treatment and interventions should be developed for this vulnerable population.


Anastomosing haemangioma of the adrenal gland: A clinicopathological series of seven cases.
Anastomosing haemangioma is a rare benign vascular neoplasm that may histologically mimic angiosarcoma. We report the largest single institution series of anastomosing haemangioma in the adrenal gland with emphasis on clinical and radiological features. Our laboratory information system was searched for a 25-year period (1999-2023), yielding seven cases confirmed as anastomosing haemangioma of the adrenal gland after pathological re-review. Clinical, radiological and pathological information was obtained from medical charts and submitting pathologists. Of a total of seven patients, four (57.1%) were men and three women, ranging in age from 37 to 75 years (mean = 61). Six of seven patients underwent adrenalectomies and one had radical nephrectomy. Tumours ranged from 0.7 to 6.4 cm (mean = 2.1 cm) and five of seven (71%) were grossly well-circumscribed. Five of seven lesions were found incidentally at imaging for other indications. All tumours were unifocal except one, which presented with multifocal disease with a concurrent adjacent retroperitoneal anastomosing haemangioma. Three of five tumours imaged with contrast enhancement were almost completely hyperenhancing with a small central non-enhancing portion, features overlapping with pheochromocytoma. One of seven tumours involved the peri-adrenal adipose tissue with a focally infiltrative pattern. There were no recurrences or metastases in six patients with available follow-up data (median = 95 months). Benign anastomosing haemangiomas of the adrenal gland tend to occur in older patients, may mimic pheochromocytoma on imaging and must be distinguished from angiosarcoma pathologically. Better awareness of this entity by pathologists, radiologists and surgeons is crucial to appropriate work-up, diagnosis and management.


Cynarin, a caffeoylquinic acid derivative in artichoke, inhibits exocytotic glutamate release from rat cortical nerve terminals (synaptosomes).
The purpose of this study was to evaluate the effect of cynarin, a caffeoylquinic acid derivative in artichoke, on glutamate release elicited by 4-aminopyridine (4-AP) in rat cortical nerve terminals (synaptosomes). We observed that cynarin decreased 4-aminopyridine-elicited glutamate release, which was prevented by the removal of external free Ca2+ with ethylene glycol bis (β-aminoethyl ether)-N,N,N,N-tetraacetic acid (EGTA) or the blockade of P/Q-type calcium channels with ω-agatoxin IVA. Molecular docking also revealed that cynarin formed a hydrogen bond with the P/Q-type Ca2+ channel, indicating a mechanism of action involving Ca2+ influx inhibition. Additionally, the inhibitory effect of cynarin on glutamate release is associated with a change in the available synaptic vesicles, as cynarin decreased 4-AP-elicited FM1-43 release or hypertonic sucrose-evoked glutamate release from synaptosomes. Furthermore, the suppression of protein kinase A (PKA) prevented the effect of cynarin on 4-AP-elicited glutamate release. 4-AP-elicited PKA and synapsin I or synaptosomal-associated protein of 25 kDa (SNAP-25) phosphorylation at PKA-specific residues were also attenuated by cynarin. Our data indicate that cynarin, through the suppression of P/Q-type Ca2+ channels, inhibits PKA activation and attenuates synapsin I and SNAP-25 phosphorylation at PKA-specific residues, thus decreasing synaptic vesicle availability and contributing to glutamate release inhibition in cerebral cortex terminals.


Mobilization for an Expanded Programme on Immunization in Somalia.
Political commitment, adequate planning, careful logistics and media preparation, and adequate supervision, coupled with house-to-house registration of vaccines, including follow-up of nonattendees, were important ingredients in accelerating and improving immunization coverage in Somalia. Satellite immunization sites with outreach teams, along with utilization of traditional birth attendants to channel mothers, are planned to ensure sustainability of achievements.


Modelling the deactivation of Escherichia coli in Nigerian soils amended with differently treated manures.
This study aimed to simulate deactivation of Escherichia coli in soils amended with cattle manure after burning, anaerobic digestion, composting, or without treatment. The Weibull survival function was used to describe deactivation of E. coli. Parameters for each treatment were determined using E. coli measurements from manure-amended soils and evaluated against measurements at different application rates. A statistically significant correlation and high coincidence between the simulated and measured values were obtained. The simulations revealed that although anaerobic digestion or burning of cattle manure effectively reduced the E. coli loads to background levels, burning retained very little nitrogen, so the ash residue was ineffective as an organic fertilizer. Anaerobic digestion was most effective at reducing E. coli levels while retaining a high proportion of N in the bioslurry residue, but the persistence of E. coli was higher than in compost. The results from this study suggest that the safest method for production of organic fertilizer would involve anaerobic digestion to reduce E. coli, followed by composting to reduce its persistence.


Abiraterone acetate: targeting persistent androgen dependence in castration-resistant prostate cancer.
Abiraterone acetate is the first second-line hormonal agent proven to improve survival in metastatic castration-resistant prostate cancer. It selectively inhibits cytochrome P450 17 (CYP17) α-hydroxylase and cytochrome17,20 (C17,20)-lyase, which are enzymes critical for androgen synthesis. Abiraterone acetate was initially approved in the United States in 2011 after demonstrating a 4-month survival benefit in docetaxel-refractory metastatic prostate cancer. The FDA recently expanded its indication for use in the pre-chemotherapy setting after it elicited significant delays in disease progression and a strong trend for increased overall survival in phase III studies. Ongoing investigations of abiraterone are evaluating its efficacy in earlier disease states, exploring its synergy in combination with other therapeutic agents, and assessing the necessity for administration of concurrent steroids and gonadal suppression. The identification and development of predictive biomarkers will optimize the incorporation of abiraterone into the management of advanced prostate cancer.


Immunofiltration assay for aflatoxin B1 based on the separation of pre-immune complexes.
A new approach for quantitative determination of AFB1 based on the separation of pre-immune complexes in the same immunoassay system has been developed. No additional step for the separation of pre-immune complexes is required. The method uses a test device for separation of pre-immune complexes from the free AFB1-enzyme conjugate by filtration through the membrane strips spotted with anti-AFB1 antibody. The bound enzyme conjugate was visualized by super-catalyzed reporter deposition (Super-CARD) signal amplification method. The measured signal intensity is directly proportional to the amount of AFB1 present in the sample. The detection limit obtained by the present method was 15 pg/ml. The data on the analytical parameters indicate that the new format of AFB1 detection in foodstuffs is reproducible, accurate and specific. The method is user friendly and does not require any costly equipment or a well-equipped laboratory.


Endovascular Treatment of Unruptured Intracranial Aneurysms by the Woven EndoBridge Device (WEB): Are There Any Aspects Influencing Aneurysm Occlusion?
The experience with Woven EndoBridge (WEB) device is still limited. The aim of this study is to discuss the efficacy of this new device, focusing on any anatomical and procedural factors influencing aneurysm occlusion. Between October 2011 and November 2016, 24 patients (10 female, 14 male) harboring 24 cerebral aneurysms treated with WEB in a single center were retrospectively reviewed. Patients underwent 6-month and 12- to 24-month (median 18 months) clinical and neuroradiologic follow-up. We evaluated whether any procedural or anatomical aspect influenced the occlusion rate. Adequate occlusion (AO) was achieved in 68% of cases at 6 months' and in 87% at 18 months' follow-up respectively. Technical difficulties occurred in 3 procedures (12.5%). No postprocedural morbidity was reported. One patient (4%) died after 1 month for reasons unrelated to the procedure. Neck size and dome-to-neck ratio were significantly associated with aneurysm occlusion (P < 0.05). AO was not associated with postoperative dual antiplatelet therapy (P > 0.99) or device compression at both first and second follow-up (P > 0.99). Immediate contrast agent stagnation was more common in aneurysms that were occluded at first (P = 0.37) and second follow-up (P = 0.24), but statistical significance was not reached. Endovascular treatment with WEB is a safe treatment for unruptured cerebral aneurysms, also resulting in a good AO rate in aneurysms that would otherwise require complex assisted coiling techniques. However, results are less favorable in cases of very large aneurysmal neck. Nevertheless, further series with larger patient populations and longer follow-up will define the role of WEB in the treatment of aneurysms.


The Solar Spectrum in the Atacama Desert.
The Atacama Desert has been pointed out as one of the places on earth where the highest surface irradiance may occur. This area is characterized by its high altitude, prevalent cloudless conditions and relatively low columns of ozone and water vapor. Aimed at the characterization of the solar spectrum in the Atacama Desert, we carried out in February-March 2015 ground-based measurements of the spectral irradiance (from the ultraviolet to the near infrared) at seven locations that ranged from the city of Antofagasta (on the southern pacific coastline) to the Chajnantor Plateau (5,100 m altitude). Our spectral measurements allowed us to retrieve the total ozone column, the precipitable water, and the aerosol properties at each location. We found that changes in these parameters, as well as the shorter optical path length at high-altitude locations, lead to significant increases in the surface irradiance with the altitude. Our measurements show that, in the range 0-5100 m altitude, surface irradiance increases with the altitude by about 27% in the infrared range, 6% in the visible range, and 20% in the ultraviolet range. Spectral measurements carried out at the Izaña Observatory (Tenerife, Spain), in Hannover (Germany) and in Santiago (Chile), were used for further comparisons.


Synthesis of 4-vinylpyridine-divinylbenzene copolymer adsorbents for microwave-assisted desorption of benzene.
Reports on the development of polymer adsorbents for microwave-assisted desorption of nonpolar volatile organic compounds (VOCs) are rare. In this study, we synthesized macroporous polymeric adsorbents with hydrophilic methyl pyridinium units for microwave-assisted desorption of nonpolar VOCs. The benzene adsorption and desorption properties of the adsorbents were investigated under both dry and humid conditions. Under humid conditions, as the content of the hydrophilic methyl pyridinium units in the adsorbents increased from 0 to 20%, the adsorption capacity of benzene decreased from about 21 to 7 mg/g, while the desorption efficiency of benzene increased significantly from 48 to 87%. The maximum concentration of desorbate also increased significantly as the content of the hydrophilic units was increased under humid conditions. We attributed the enhanced desorption efficiency mainly to more adsorbed moisture, which indirectly allowed heating of the polymer adsorbents to higher temperatures upon irradiation with 600 W microwaves.


Constructional apraxia and visuoperceptive disabilities in relation to laterality of cerebral lesions.
The main purpose of the present study was to determine whether constructional apraxia is due to a visual perceptual disorder in right but not in left brain-damaged patients. In order to resolve this question, 36 normal controls and 73 brain-damaged patients with lesions restricted to the right (N = 30) or to the left (N = 43) cerebral hemisphere were given a graphomotor and a multiple choice version of the Benton Visual Retention Test. The graphomotor version of the V.R.T. was used as a test of constructional praxis, whereas the multiple choice version of the V.R.T. was used as a test of visual form discrimination. No difference was found between right and left brain-damaged patients with respect to incidence and severity of visuo-constructive and of visuo-perceptive disabilities. Contrary to the hypothesis, the relationship between perceptual and praxic tasks was higher in left than in right brain-damaged patients. The high level of correlation found between graphomotor and perceptual scores within the left hemispheric group was due chiefly to the poor performances obtained on both tasks by aphasic patients. These findings are interpreted as suggesting that the basis for visuoconstructive disturbances is a perceptual disorder, independently of the hemispheric side of lesion. The contrasting results of our intercorrelational study and of analogous studies reported in neuropsychological literature are interpreted as being due to sampling differences, in the absence of clearcut qualitative or quantitative differences between visuo-constructive disabilities of right and left brain-damaged patients.


Mycobacterium tuberculosis Rv1096, facilitates mycobacterial survival by modulating the NF-κB/MAPK pathway as peptidoglycan N-deacetylase.
Mycobacterium tuberculosis (Mtb) is an intracellular pathogen that can infect and replicate in macrophages. Peptidoglycan (PGN) is a major component of the mycobacterial cell wall and is recognized by host pattern recognition receptors (PRRs). Many bacteria modulate and evade the immune defenses of their hosts through PGN deacetylation. Rv1096 was previously characterized as a PGN N-deacetylase gene in Mtb. However, the underlying mechanism by which Rv1096 regulates host immune defenses during macrophage infection remains unclear. In the present study, we investigated the role of Rv1096 in evading host immunity using a recombinant M. smegmatis expressing exogenous Rv1096 and Rv1096-deleted Mtb strain H37Rv mutant. We found that Rv1096 promoted intracellular bacillary survival and inhibited the inflammatory response in M. smegmatis- or Mtb-infected macrophages. The inhibition of mycobacteria-induced inflammatory response in macrophages was at least partially due to NF-κB and MAPK activation downstream of TLR and NOD signaling pathways. Furthermore, we found that Rv1096 inhibitory effect on inflammatory response was associated with TLR2, TLR4 and NOD2. Finally, we demonstrated the PGN deacetylase activity of Rv1096 by Fourier transform IR and Rv1096 NODB deficient mutant. Our findings suggest that Rv1096 may deacetylate PGNs to evade PRRs recognition, thus protecting Mtb from host immune surveillance and clearance in macrophages.


Cultivating a communities of practice for colorectal cancer screening in northern Canada.
Knowledge management systems such as a Communities of Practice (CoP) can improve healthcare processes but are challenging in complex multidisciplinary systems, and guidance on methods to establish a CoP are needed. This case illustrates the use of early stakeholder engagement and Nominal Group Technique (NGT) to cultivate a CoP in a complex multidisciplinary system: colorectal cancer screening in northern Canada. Stakeholders in the Northwest Territories, Canada were recruited and co-designed a workshop with authors to introduce CoP concepts and identify priorities. At the workshop NGT was used to identify and prioritize gaps in process, practice, and evidence for the CoP to focus on. An anonymous polling system was used to obtain workshop participants' feedback on the process. The co-design process integrated stakeholders' perspectives in developing a workshop. Using NGT, the gap analysis identified 23 areas of focus for the CoP, among which, the highest priorities were identified: communication between clinicians and with patients, and identification of screening eligibility in the electronic medical record. Participants found the process to be useful, educational, and interesting. There was unanimous interest in moving forward with developing a CoP. A co-designed workshop and NGT were useful in laying the foundation for a CoP in a complex multidisciplinary environment. This case shows the utility of a co-designed workshop and NGT in starting a CoP: a knowledge management system that would provide critical insight into colorectal cancer screening policies for the region.


Hemagglutinins in female fish gonads: comparative investigations on perch (Perca fluviatilis) gonads of different stages of development.
Female gonads of the perch (Perca fluviatilis) in various stages of development are tested for hemagglutinin activity against human erythrocytes. Based on the different agglutination patterns obtained, and on inhibition tests with L-fucose and a mature gonad of a male perch, the appearance two different agglutinins in the course of the development of the female gonad is assumed.


Synthesis, characterization, release kinetics and toxicity profile of drug-loaded starch nanoparticles.
The current research work focuses on the medical application of the cost-effective cross-linked starch nanoparticles, for the transdermal delivery using Diclofenac sodium (DS) as a model drug. The prepared DS-cross-linked starch nanoparticles were synthesized using nanoprecipitation technique at different concentrations of sodium tripolyphosphate (STPP) in the presence of Tween 80 as a surfactant. The resultant cross-linked starch nanoparticles loaded with DS were characterized using world-class facilities such as TEM, DLS, FT-IR, XRD, and DSc. The efficiency of DS loading was also evaluated via entrapment efficiency as well as in vitro release and histopathological study on rat skin. The optimum nanoparticles formulation selected by the JMP(®) software was the formula that composed of 5% maize starch, 57.7mg DS and 0.5% STPP and 0.4% Tween 80, with particle diameter of about 21.04nm, polydispersity index of 0.2 and zeta potential of -35.3mV. It is also worth noting that this selected formula shows an average entrapment efficiency of 95.01 and sustained DS release up to 6h. The histophathological studies using the best formula on rat skin advocate the use of designed transdermal DS loaded cross-linked starch nanoparticles as it is safe and non-irritant to rat skin. The overall results indicate that, the starch nanoparticles could be considered as a good carrier for DS drug regarding the enhancement in its controlled release and successful permeation, thus, offering a promising nanoparticulate system for the transdermal delivery non-steroidal anti-inflammatory drug (NSAID).


Fibrous skeleton endocarditis: repair using Konno procedure.
Information about the surgical management of fibrous skeleton endocarditis is incomplete, as the vast majority of current literature describes the isolated repair of either the aortic or the mitral annulus, the combination rarely being addressed. Annular destruction, in the presence of endocarditis, demands extreme ingenuity for surgical treatment and cure. We describe and illustrate the Konno procedure for replacement of both infected mitral and aortic valves and repair of mycotic ventricular septal defects.


Borderzone contractile dysfunction is transiently attenuated and left ventricular structural remodeling is markedly reduced following reperfused myocardial infarction in inducible nitric oxide synthase knockout mice.
We sought to determine the effect of inducible nitric oxide synthase (iNOS) expression on regional contractile function and left ventricular (LV) remodeling after reperfused myocardial infarction (MI). Inducible nitric oxide synthase is known to contribute to global LV dysfunction after a large MI, but the mechanisms underlying this dysfunction remain unclear. We used immunohistochemistry to investigate the distribution of iNOS expression in wild-type (WT) and iNOS knockout (KO) mice early (day 1) and late (day 28) after reperfused MI. We also used serial cardiac magnetic resonance imaging at baseline and at 1, 7, and 28 days after MI to assess LV volumes, ejection fraction (EF), regional circumferential strain (E(cc)), and day 1 infarct size. At baseline, LV volumes and EF were similar between groups. Day 1 infarct size was also similar between groups. Immunohistochemistry revealed that iNOS expression was abundant throughout the heart in WT mice on day 1 after MI, particularly near the infarct borderzone. On day 7 after MI, E(cc) in KO mice was significantly improved in some borderzone sectors compared with WT. The LV volumes were significantly lower in KO mice at days 7 and 28 compared with WT. The EF on days 7 and 28 was significantly higher in KO mice compared with WT. The circumferential extent of wall thinning was also significantly reduced in KO versus WT mice at days 7 and 28. Expression of iNOS contributes importantly to post-infarction contractile dysfunction and subsequent LV remodeling, suggesting new strategies to combat heart failure resulting from large MI.


Inhibitory activity of Beauveria bassiana and Trichoderma spp. on the insect pests Xylotrechus arvicola (Coleoptera: Cerambycidae) and Acanthoscelides obtectus (Coleoptera: Chrisomelidae: Bruchinae).
Xylotrechus arvicola is an important pest in vineyards (Vitis vinifera) in the main Iberian wine-producing regions, and Acanthoscelides obtectus causes severe post-harvest losses in the common bean (Phaseolus vulgaris). Under laboratory conditions with a spray tower, the susceptibility of the immature stages of X. arvicola and A. obtectus against the entomopathogenic fungi Beauveria bassiana and four strains of Trichoderma spp. was evaluated. Both insect pests T. harzianum and B. bassiana showed a good inhibitory activity, accumulating an inhibition on the eggs of values above 85 and 82%, respectively. T. atroviride and T. citrinoviride had a lower inhibitory activity, with inhibition values of 74.1 and 73.3% respectively. These fungi can be considered a highly effective tool for the control during the immature stages of these species.


Methotrexate-treated ectopic pregnancy: beta human chorionic gonadotropin serum changes as a success predictor using a mathematical model validation.
Surgical rescue of methotrexate-treated ectopic pregnancy is necessary when tubal rupture or medical therapy failure is detected during post-therapeutic monitoring. It is known that an increased beta human chorionic gonadotropin (β-hCG) concentration is the most important factor associated with treatment failure. Therefore, we suggested that relative changes in serum β-hCG could predict a successful result of medical treatment, leading to facilitation of the decision to forgo the prospect of possible surgical rescue. A retrospective observational study of 115 patients with an ectopic pregnancy who were treated with a single dosage protocol of 50mg/m2 of methotrexate injected intramuscularly was performed at Puerta de Hierro University Hospital and Gregorio Marañón University General Hospital. Standard statistical tests were applied in order to evaluate the relative changes in β-hCG concentration between the 1st and the 4th days following methotrexate injection. Methotrexate treatment has a 95% probability to be successful if the relative change of β-hCG from the 1st to the 4th day of monitoring is within the following interval: [-1.02; 0.15]. Moreover, if the values of β-hCG-relative change from 1st to 4th day of monitoring are within [0.54; 1.2], it assures a negative result of treatment with 95% probability. Therefore, the value 0.15 (15%) of β-hCG relative change can be considered a cut-off value for a positive result to treatment. Our data support that negative β-hCG relative changes on the 4th day of treatment likely predict a successful result of methotrexate therapy, with a cut-off point of 0.15. Expectant management should be carried out in these cases if no clinical indications of surgery are presented.


Warfarin Anticoagulation and Spontaneous Pectoral Haematomas.
Warfarin is the oldest and most commonly used anticoagulant in the outpatient setting. Major bleeding events remain as the most life threatening complication of this medication. Bleeding into enclosed structures and body cavities can be fatal in acute scenarios or cause continuous exsanguination if left unnoticed. Pectoral haematomas are an unusual presentation of bleeding diathesis, and are also seldom reported in the literature. We present three cases of patients with development of spontaneous pectoral haematoma during therapy with warfarin alone or with heparin bridging in the treatment of atrial fibrillation and thromboembolism.


Lower number of modifiable risk factors was associated with reduced atrial fibrillation incidence in an 18-year prospective cohort study.
Prevention strategies for atrial fibrillation (AF) are lacking. This study aimed to identify modifiable risk factors (MRFs) and estimate their impact on AF in the midlife general population. We assessed 9049 participants who were free of prevalent AF at baseline from the Korean Genome and Epidemiology Study. Cox models with time-varying assessment of risk factors were used to identify significant MRFs for incident AF. The MRF burden was defined as the proportion of visits with MRFs during follow-up. Over a median follow-up of 13.1 years, 182 (2.01%) participants developed AF. Three MRFs, including systolic blood pressure (SBP) ≥ 140 mmHg, obesity with central obesity, and an inactive lifestyle were significantly associated with incident AF. Among participants with 3, 2, 1, and 0 MRFs at baseline, 16 (3.9%), 51 (2.5%), 90 (1.8%) and 25 (1.5%) had incident AF, respectively. Compared to participants with three MRFs, those with one or no MRFs had a decreased risk of AF (hazard ratio [95% CI] for one MRF, 0.483 [0.256-0.914]; and for no MRF, 0.291 [0.145-0.583]). A decreasing MRF burden was associated with reduced AF risk (hazard ratio [95% CI] per 10% decrease in burden for SBP ≥ 140 mmHg, 0.937 [0.880-0.997]; for obesity with central obesity, 0.942 [0.907-0.978]; for inactivity, 0.926 [0.882-0.973]). Maintaining or achieving MRF ≤ 1 was associated with decreased AF risk, suggesting that minimizing the burden of MRF might help prevent AF.


Mercury in surface sediments and benthic organisms from Guaymas Bay, east coast of the Gulf of California.
In order to know the concentration of mercury in surface sediments, macroalgae and clams from Guaymas Bay, Mexico, 20 surface sediment samples and several individuals of Codium amplivesciculatum (3), Enteromorpha clathrata (4), Gracilaria subsecundata (2), Ulva lactuca (2), Chione subrugosa (80) and Crassostrea gigas (40) were collected and their Hg concentration was measured by a cold vapor Hg analyzer, after acid digestion. In addition, granulometric analysis and quantification of total organic carbon, aluminum, iron and manganese contents in sediments were performed. A Pearsons correlation matrix was determined and, the enrichment factor, the geoaccumulation index and the biota-sediment accumulation factor were calculated. Mercury concentrations in sediments ranged from 0.3 to 2.3 microg g(-1), with the central and northern portions showing the highest values. Macroalgae had a content of Hg that oscillated from 0.058 to 0.134 microg g(-1), while the average concentrations of this metal for clams and oysters were 0.063 and 0.230 microg g(-1), respectively. A clear effect of Guaymas City and the anthropogenic activities carried out around the Guaymas Bay has been observed and the enrichment factor and the geochemical index suggest that sediments from this coastal ecosystem are moderately to strongly contaminated with Hg. However, according to the figure of the maximum human consumption of Hg per week recommended by the World Health Organization, people can ingest clams without risk to their health.


Isolation and Complete Genome Sequence of a Novel Marinobacter Phage B23.
We used the double-agar layer method to isolate a novel Marinobacter marina bacteriophage, B23, from the surface water sample of the Bohai sea of China. There is some work to better understand the phage. The result of transmission electron microscopy revealed that B23 belongs to the family Siphoviridae with a head of 80 nm in diameter and a tail of 230 nm. Microbiological characterization evidenced that phage B23 is stable at the temperatures from - 25 to 60 °C, and showed vigorous vitality at pH between 4.0 and 12.0. One-step growth experiment showed that it had a longer latent period and higher lysis efficiency. Furthermore, the complete genome of B23 was sequenced and analyzed, which consists of a 35132 bp DNA with a G + C content of 59.8% and 50 putative open reading frames. The genome was divided into five parts, consisting of DNA replication and regulation, phage packaging, phage structure, host lysis and hypothetical protein.


Effect of conjugated linoleic acid supplementation on weight loss and body fat composition in a Chinese population.
Conjugated linoleic acid (CLA) has several benefits, including body fat reduction, as proved in animals. However, the results of CLA-induced body composition alterations in humans are inconsistent, and no related data are available for Chinese populations. This study aimed to determine whether CLA affects body weight (BW) loss and body composition of overweight and obese Chinese subjects. In this randomized, double-blind, placebo-controlled trial, subjects with a body mass index (BMI) of 24 to 35 kg/m(2) randomly received 1.7 g of cis-9,trans-11 and trans-10,cis-12 CLA (n = 30) or placebo (salad oil; n = 33) in 200 mL of sterilized milk twice daily for 12 wk. Changes in body composition were determined by bioimpedance measurements. Sixty-three subjects completed the study (CLA, n = 30). After 12 wk, compared with the baseline, the BW, BMI, total fat mass, fat percentage, subcutaneous fat mass, and waist-to-hip ratio decreased in the CLA group (P < 0.05). The CLA group was stratified by BMI and gender. The BW, BMI, subcutaneous fat mass, and waist-to-hip ratio decreased in 27 subjects with a BMI ≥ 27, and these indices, except subcutaneous fat mass, were lower in female subjects. The levels of total cholesterol, triacylglycerol, low-density lipoprotein, and plasma fasting glucose increased, whereas those of high-density lipoprotein decreased after 3 mo of CLA treatment. The changes were not significantly different from the baseline values. The supplementation of CLA for 12 wk in overweight and grade I obese Chinese subjects yielded lower obesity indices, with no obvious adverse effects.


Erectile dysfunction following radiotherapy and brachytherapy for prostate cancer: pathophysiology, prevention and treatment.
Although detrimental impact on sexual function following radiotherapy (RT) and brachytherapy decreases the quality of life of prostate cancer survivors, the etiology, pathophysiology, prophylaxis and treatment of this condition has not yet been fully clarified. We reviewed the published literature in terms of etiology, treatment and possible prevention of erectile dysfunction (ED) following RT and/or brachytherapy. We have reviewed the literature through a MEDLINE search. Prostate cancer, erectile dysfunction, radiotherapy, brachytherapy, treatment and quality of life were used as keywords. Both RT and brachytherapy result in high rates of ED. Although arterial damage seems to be the main cause of ED after RT, exposure of neurovascular bundle to high levels of radiation dose has been also implicated in some studies with brachytherapy. The radiation dose received by the corpora cavernosa at the crurae of the penis may also be important in the etiology of ED. The most important predictive factor of ED following RT is the treatment modality. Intensity-modulated radiotherapy and vessel-sparing prostate radiotherapy are new techniques but those treatments may not guarantee complete preservation of the erectile function. Patients need to be correctly informed on the possible sequela of radiation-based treatments on their sexual well-being while planning their treatment. Patients should also be informed about the possible treatment modalities for ED, which may develop in due course.


Kin or Research Material? Exploring IVF Couples' Perceptions about the Human Embryo and Implications for Disposition Decisions in Norway.
In vitro fertilization (IVF) involves making embryos outside of the human body, which has spurred debate about the status of the embryo, embryo research and donation. We explore couples' perceptions about embryos and their thoughts and acceptability about various disposition decisions in Norway. Based on an ethnographic study including interviews and observations in an IVF clinic, we show that couples do not perceive their pre-implantation IVF embryos to be human lives; rather, they consider successful implantation the start of life. We suggest that this response indicates a change in the perception of the human embryo or the fertilised egg from incipient life-a viewpoint that was dominant in the discussions of embryo research in the 1980s and 1990s. We also show how this view of the pre-implantation embryo elucidates why donating embryos to research appears acceptable but donating to other infertile couples seems rather difficult. Before transfer to a woman's uterus, the embryo exists in a liminality; it is not yet human life but a living cell with potential for both research and pregnancy. When an embryo is implanted and pregnancy is confirmed, human life activates; the embryo becomes potential kin, influencing couples' struggles with donating embryos to other couples.


Two New Species and New Records of Mites of the Genus Parichoronyssus (Acari: Macronyssidae) From South American Bats (Chiroptera), With a Key to the Known Species of the Genus.
Derived from exhaustive search of mites of the genus Parichoronyssus associated with South American Bats, we found two new species associated with Phyllostomid, Emballonurid, and Noctiniolid bats: Parichoronyssus alexanderfaini n. sp. associated with Rhinophylla pumilio Peters; Parichoronyssus gettingeri n. sp. associated with Rhynchonycteris naso Wied-Newied, and Noctilio leporinus Linneo. Herein we give the description of those new species, and additionally is included several new records for Parichoronyssus from the region, as well as providing a key to the 11 species of Parichoronyssus.