Enhanced responsiveness of cardiac vagal chemosensitive endings to bradykinin in heart failure.
There is good evidence that the cardiopulmonary and arterial baroreflexes are blunted in chronic heart failure (HF). Other evidence, however, suggests that the cardiac chemoreflex is enhanced during HF. In the present study, we sought to determine whether HF alters the sensitivity of cardiac vagal chemosensitive endings to bradykinin (BK), an endogenous mediator that activates ventricular C fiber afferents. We measured the activity of cardiac vagal single fibers and compared the afferent responses to left atrial injections of BK and capsaicin in sham-operated and pacing-induced HF dogs. The capsaicin-sensitive endings did not respond to changes in cardiac pressures evoked by vascular snares and were C fiber endings (0.8-2.1 m/s). Most were located in the left heart. There was no difference in rate or pattern of resting discharge of the cardiac vagal fibers between HF and sham groups (1.5 +/- 0.5 vs. 1.3 +/- 0.3 impulses/s, respectively). The afferent response to BK (0.001-1 microgram/kg), but not capsaicin (1-10 micrograms/kg), was greater in HF compared with sham dogs. Captopril (2 mg/kg i.v.) significantly enhanced resting discharge (P < 0.05) from cardiac chemosensitive vagal afferents in HF but not sham dogs. The afferent response to BK in both groups was significantly (P < 0.05) and similarly enhanced. Indomethacin (5 mg/kg i.v.) significantly inhibited resting discharge (P < 0.05) and nearly abolished the afferent responses to lower doses of BK in HF, but did not affect resting discharge and less effectively attenuated responses to BK in sham dogs. Responses to capsaicin did not differ between HF and sham animals. From these results, we conclude that 1) resting discharge from cardiac vagal chemosensitive endings is not altered in HF, 2) these vagal endings exhibit an enhanced sensitivity to exogenous BK but not to capsaicin in the HF state, 3) angiotensin-converting enzyme activity inhibits resting discharge from these afferents in HF, and 4) the cyclooxygenase system contributes to the enhanced BK responsiveness of cardiac chemosensitive endings in HF.


Female gender doubles pre-hospital delay times for patients experiencing ST segment elevation myocardial infarction in Saudi Arabia.
Pre-hospital delay has a significant impact on patients' mortality and morbidity in ST segment elevation myocardial infarction (STEMI). Internationally many factors including female gender have been implicated, but no research has been conducted in Arab cultures. We aimed to explore the factors contributing to pre-hospital delay among female STEMI patients in Saudi Arabia. This sequential, explanatory mixed methods study comprised a consecutive sample of 311 patients, presenting with STEMI to three hospitals in Riyadh, from March 2011-August 2011. Of these, 189 patients (36 females) were eligible and interviewed using the Response to Symptoms Questionnaire. A purposive sample of 18 patients (9 females) then participated in qualitative interviews that were taped and transcribed prior to thematic analysis. The median pre-hospital delay for males was 5 h and 12.9 h for females (p<0.002). Standard multiple regression determined female gender as the strongest predictor of transfer delay-from decision to seek help to hospital arrival. Qualitative analysis produced five gender-related themes: (a) women require a male relative's permission to seek medical help; (b) women cannot travel to hospital unless accompanied by a male relative; (c) women prioritise family responsibilities over seeking help; (d) women lack knowledge of myocardial infarction (MI) symptoms and treatment; and (e) perception that women should not attract attention. This study provides new insight into how cultural factors increase pre-hospital delay for women within Saudi Arabia. While the quantitative data demonstrates that women experience much longer delays, the qualitative interviews confirm that cultural factors are implicated. Further research is urgently required.


Low prefrontal perfusion linked to depression symptoms in methadone-maintained opiate-dependent patients.
Clinically depressed patients without substance use disorders, compared to controls, exhibit significantly lower resting regional cerebral blood flow (rCBF) in the prefrontal cortex (PFC). In this study, we examined the link between resting rCBF in the PFC and current depressive symptoms in methadone-maintained opiate-dependent (MM) patients with or without major depression. Arterial spin labeled perfusion fMRI at 3 Tesla was used to measure resting rCBF in 21 MM patients. Perfusion data were analyzed using SPM2. The relationship between Beck Depression Inventory (BDI) score and resting rCBF was examined in a single regression analysis. The BDI scores ranged between 0 and 18 (m=7.0, S.D.=4.8), and 30% of the sample had mild to moderate depression symptoms according to BDI scores. A negative correlation was observed between BDI scores and relative rCBF in the bilateral ventrolateral prefrontal cortex, and middle frontal gyri. The inverse relationship between prefrontal paralimbic rCBF and depression scores suggests a link between reduced fronto-limbic activity and depressive symptoms in MM patients. A significant subgroup of opiate-dependent patients has clinical or sub-clinical depression that is often undetected; our data identify brain substrates of depression symptoms that may also be a potential marker of relapse in this population. Treatment strategies targeting these brain regions may improve outcomes in depressed substance abusers.


Phylogenetic analysis of the small subunit ribosomal RNA of Marteilia refringens validates the existence of phylum Paramyxea (Desportes and Perkins, 1990).
Marteilia refringens is recognized as one of the most significant pathogens of bivalve molluscs. The nucleotide sequence of the small subunit ribosomal RNA gene of Marteilia refringens is used to elucidate the phylogenetic position of the phylum Paramyxea. Genomic DNA was extracted from sporangia of Marteilia, purified from infected blue mussels, Mytilus edulis, and flat oysters, Ostrea edulis. The sequences obtained from Marteilia species purified from both oysters and mussels were identical. The sequence identity was confirmed by in situ hybridization using a DNA probe targeted to a variable region of the ribosomal DNA. The small subunit ribosomal RNA gene sequence of M. refringens is very different from all known sequences of eukaryotic organisms, including those of myxosporeans and haplosporeans. Therefore, the phylum Paramyxea should continue to be recognized as an independent eukaryotic phylum.


Epigallocatechin-3-gallate is absorbed but extensively glucuronidated following oral administration to mice.
Epigallocatechin-3-gallate (EGCG), the most abundant catechin in green tea (Camellia sinensis), has shown cancer preventive activity in animal models. The bioavailability of EGCG in the most commonly used animal species, mice, is poorly understood. Moreover, the pharmacokinetic parameters of EGCG have not been reported previously in mice. Here we report that after administration of EGCG intravenously at 21.8 micro mol/kg or intragastrically at 163.8 micro mol/kg, the peak plasma levels of EGCG in male CF-1 mice were 2.7 +/- 0.7 and 0.28 +/- 0.08 micro mol/L, respectively. EGCG was present mainly (50-90%) as the glucuronide. The plasma bioavailability of EGCG after intragastric administration was higher than previously reported in rats (26.5 +/- 7.5% vs. 1.6 +/- 0.6%). The conjugated EGCG displayed a shorter t(1/2) (82.8-211.5 vs 804.9-1102.3 min) than unconjugated EGCG (P < 0.01, Student's t test). EGCG was present in the unconjugated form in the lung, prostate and other tissues at levels of 0.31-3.56 nmol/g after intravenous administration. Although intragastric administration resulted in lower levels in most tissues compared with intravenous administration (e.g., 0.006 +/- 0.004 vs. 2.66 +/- 1.0 nmol/g in the lung), the levels in the small intestine and colon were high at 45.2 +/- 13.5 and 7.86 +/- 2.4 nmol/g, respectively. This is the first report of the pharmacokinetic parameters of EGCG in mice. Such information provides a basis for understanding the bioavailability of EGCG in mice and should aid in understanding the cancer preventive activity of EGCG.


Supervised tractogram filtering using Geometric Deep Learning.
A tractogram is a virtual representation of the brain white matter. It is composed of millions of virtual fibers, encoded as 3D polylines, which approximate the white matter axonal pathways. To date, tractograms are the most accurate white matter representation and thus are used for tasks like presurgical planning and investigations of neuroplasticity, brain disorders, or brain networks. However, it is a well-known issue that a large portion of tractogram fibers is not anatomically plausible and can be considered artifacts of the tracking procedure. With Verifyber, we tackle the problem of filtering out such non-plausible fibers using a novel fully-supervised learning approach. Differently from other approaches based on signal reconstruction and/or brain topology regularization, we guide our method with the existing anatomical knowledge of the white matter. Using tractograms annotated according to anatomical principles, we train our model, Verifyber, to classify fibers as either anatomically plausible or non-plausible. The proposed Verifyber model is an original Geometric Deep Learning method that can deal with variable size fibers, while being invariant to fiber orientation. Our model considers each fiber as a graph of points, and by learning features of the edges between consecutive points via the proposed sequence Edge Convolution, it can capture the underlying anatomical properties. The output filtering results highly accurate and robust across an extensive set of experiments, and fast; with a 12GB GPU, filtering a tractogram of 1M fibers requires less than a minute.


Theory application by school-based occupational therapists.
Recent literature indicates that there is an inconsistent use of theory to guide clinical actions by occupational therapists, including those working in pediatrics. The purpose of this study was to describe school-based therapists' theory application by collecting information about what frames of reference they used and why. Of the 72 school-based therapists in the mid-Atlantic states who agreed to respond to a questionnaire, 51 (70.8%) returned the questionnaire. Information about demographics, what frames of reference were used, and why they were used was obtained from the questionnaire. Respondents reported using a multitheoretical approach, with sensory integration theory and neurodevelopmental theory being the predominate frames of reference applied but not the only ones used. The frames of reference were used on the basis of several factors, including the children's needs and the respondent's education. Formal and continuing education seems to have a great effect on school-based occupational therapists as they develop their personal conceptual frameworks.


Biocompatible Magnetic Fluids of Co-Doped Iron Oxide Nanoparticles with Tunable Magnetic Properties.
Magnetite (Fe3O4) particles with a diameter around 10 nm have a very low coercivity (Hc) and relative remnant magnetization (Mr/Ms), which is unfavorable for magnetic fluid hyperthermia. In contrast, cobalt ferrite (CoFe2O4) particles of the same size have a very high Hc and Mr/Ms, which is magnetically too hard to obtain suitable specific heating power (SHP) in hyperthermia. For the optimization of the magnetic properties, the Fe2+ ions of magnetite were substituted by Co2+ step by step, which results in a Co doped iron oxide inverse spinel with an adjustable Fe2+ substitution degree in the full range of pure iron oxide up to pure cobalt ferrite. The obtained magnetic nanoparticles were characterized regarding their structural and magnetic properties as well as their cell toxicity. The pure iron oxide particles showed an average size of 8 nm, which increased up to 12 nm for the cobalt ferrite. For ferrofluids containing the prepared particles, only a limited dependence of Hc and Mr/Ms on the Co content in the particles was found, which confirms a stable dispersion of the particles within the ferrofluid. For dry particles, a strong correlation between the Co content and the resulting Hc and Mr/Ms was detected. For small substitution degrees, only a slight increase in Hc was found for the increasing Co content, whereas for a substitution of more than 10% of the Fe atoms by Co, a strong linear increase in Hc and Mr/Ms was obtained. Mössbauer spectroscopy revealed predominantly Fe3+ in all samples, while also verifying an ordered magnetic structure with a low to moderate surface spin canting. Relative spectral areas of Mössbauer subspectra indicated a mainly random distribution of Co2+ ions rather than the more pronounced octahedral site-preference of bulk CoFe2O4. Cell vitality studies confirmed no increased toxicity of the Co-doped iron oxide nanoparticles compared to the pure iron oxide ones. Magnetic heating performance was confirmed to be a function of coercivity as well. The here presented non-toxic magnetic nanoparticle system enables the tuning of the magnetic properties of the particles without a remarkable change in particles size. The found heating performance is suitable for magnetic hyperthermia application.


The mechanism of organophosphorus pesticide-induced inhibition of cytolytic activity of killer cells.
The main toxicity of organophosphorus pesticides (OPs) is neurotoxicity, which is caused by the inhibition of acetylcholinesterase. OPs also affect immune responses including effects on antibody production, IL-2 production, T cell proliferation, decrease of CD5 cells, and increase of CD26 cells and autoantibodies. However, there have been few papers investigating the mechanism of OP-induced inhibition of cytolytic activity of killer cells. This study reviews the new mechanism of OP-induced inhibition of activities of natural killer (NK), lymphokine-activated killer (LAK) and cytotoxic T lymphocytes (CTL). NK, LAK and CTL induce cell death in tumor or virus-infected target cells by two main mechanisms. The first mechanism is direct release of cytolytic granules that contain perforin, granzymes, and granulysin by exocytosis to kill target cells, which is called the granule exocytosis pathway. The second mechanism is mediated by the Fas ligand (Fas-L)/Fas pathway. To date, it has been reported that OPs inhibit NK, LAK and CTL activities by at least the following three mechanisms: 1) OPs impair the granule exocytosis pathway of NK, LAK and CTL cells by inhibiting the activity of granzymes, and by decreasing the intracellular level of perforin, granzyme A and granulysin, which was mediated by inducing degranulation of NK cells and by inhibiting the transcript of mRNA of perforin, granzyme A and granulysin; 2) OPs impair the FasL/Fas pathway of NK, LAK and CTL cells, as investigated by using perforin-knockout mice, in which the granule exocytosis pathway of NK cells does not function and only the FasL/Fas pathway remains functional; 3) OPs induce apoptosis of immune cells.


Economic and livestock health impacts of birds on dairies: Evidence from a survey of Washington dairy operators.
The survey described in this research paper aimed to investigate the economic and health impacts of birds on dairies. Birds are common pests on dairies, consuming and contaminating feed intended for cattle. As a result, dairy operators experience increased feed costs and increased pathogen and disease risk. We surveyed dairy operators attending the 2017 Washington Dairy Conference to examine the impact of birds on dairies in Washington State. Dairy operators reported feed losses valued at $55 per cow resulting in annual losses totaling $5.5 million in the Western region of the state and $9.2 million in the Eastern region of the state. Shooting was the most commonly used bird management method and European starlings (Sternus vulgaris) were the most frequently implicated species statewide. Bird abundance greater than 10,000 birds per day was associated with larger herd size and with self-reported presence of Johne's disease and Salmonella.


Reduction of shock-induced gastric damage by a nitric oxide-releasing aspirin derivative: role of neutrophils.
The gastric damage associated with hemorrhagic shock appears to occur, at least in part, through neutrophil-dependent mechanisms. Nitric oxide (NO)-releasing derivatives of aspirin have been shown to spare the gastrointestinal tract of injury. As NO can inhibit neutrophil adherence, it is possible that such a derivative of aspirin (NCX-4016) would exert inhibitory effects on neutrophil adherence and therefore be capable of protecting the stomach against shock-induced gastric damage. This hypothesis was tested in this study. Oral administration of NCX-4016 or glyceryl trinitrate or depletion of circulating neutrophils with antineutrophil serum significantly reduced the extent of gastric damage induced by hemorrhagic shock, whereas aspirin had no effect. NCX-4016 and antineutrophil serum pretreatment resulted in significant preservation of gastric blood flow during the shock period. Moreover, NCX-4016, but not aspirin, was capable of inhibiting N-formyl-Met-Leu-Phe-induced leukocyte adherence to postcapillary mesenteric venules. These results suggest that an NO-releasing aspirin derivative reduces the susceptibility of the stomach to shock-induced damage through inhibitory effects on neutrophil adherence to the vascular endothelium.


Disparities in access to breast care nurses for breast surgeons: a National Breast Cancer Audit survey.
The involvement of a breast care nurse (BCN) in breast cancer treatment can improve the physical and psychological outcomes and provide the continuity of care and better information about the disease and treatment process. This survey examined the current status of BCNs access to determine the extent and how BCNs were accessed by breast surgeons across Australia and New Zealand in different geographical settings or health service sectors. The survey was disseminated in December 2006. Response rate was 91%. The results show that the majority of Australian and New Zealand breast surgeons either work with a BCN in their practice or can access a BCN outside their practice. Patients are more likely to have access to a BCN immediately after diagnosis while around a third of practices have access to a BCN more than once, usually "after diagnosis" and "after surgery". More public practices have direct access to a BCN than private practices, particularly in the metropolitan and regional areas while access to BCN is poor in rural public and private practices. The difference in overall access, either in the practice or external access (Yes or No but can access a BCN), to a BCN between public and private practices is smaller. Access to a BCN was best in metropolitan public practices and worst in rural private practices with one quarter rural private practices had no access to a BCN and no rural patients can access a BCN more than once in private practice. The results of this survey demonstrated some evidence of disparity in access to a BCN which needs to be reduced through more attention and/or extra resources in this area.


Chiropractic referral: the views of a group of conventional medical practitioners with an interest in unconventional therapies.
To identify, from a list of conditions prepared by leaders in the Australian chiropractic profession, disorders that medical practitioners regard as suitable for referral for chiropractic care. A descriptive study in which eight hundred and twenty (820) medical practitioners with an interest in "unconventional" interventions were invited to respond to a mailed questionnaire. Medical practitioners with a demonstrable interest in at least one form of nonconventional therapy were surveyed. Seven hundred and ninety-six medical practitioners who subscribe to a professional organization committed to "alternative" nutritional approaches in health care were sent mail. Twenty-four practitioners known to be sympathetic to chiropractic were also included. The response rate was 28%. Medical respondents who refer to chiropractors more frequently consider a larger number of conditions suitable for chiropractic care than those who never refer. Referral of patients with visceral disorders enjoys relatively little support, especially among practitioners who never actually use chiropractic referral as an intervention option. Analysis of perceptions regarding chiropractic referral of patients with headaches suggests that the perceived etiology of the symptom is a consideration in making referral decisions. Chiropractic referral for musculoskeletal care enjoys substantial support, whereas referral for chiropractic intervention in visceral conditions continues to be largely opposed by those members of the medical profession participating in this study.


Incidence of astigmatism after cataract surgery. Comparison of continuous and interrupted sutures.
In spite of the increased use of intraocular implants and contact lenses, the majority of cataract cases require spectacles after operation. Too great an amount of astigmatism will cause distortion and spoil an otherwise perfect operation. It is clear that the amount of astigmatism depends upon how the section is made and how it is sutured. In a series of cases employing different kinds of section and different methods of suturing, the postoperative astigmatism for each combination was recorded. A comparison was made between direct sutures and continuous suturing with 10.0 monofilament. Some suggestions are made as to the best method of keeping astigmatism to a minimum.


TLR9 ligand CpG-ODN applied to the injured mouse cornea elicits retinal inflammation.
During bacterial and viral infections, unmethylated CpG-DNA released by proliferating and dying microbes is recognized by toll-like receptor (TLR) 9 in host cells, initiating innate immune responses. Many corneal infections occur secondary to epithelial breaches and represent a major cause of vision impairment and blindness globally. To mimic this clinical situation, we investigated mechanisms of TLR9 ligand-induced corneal inflammation in mice after epithelial debridement. Application of CpG oligodeoxynucleotides (ODNs) resulted in neutrophil and macrophage infiltration to the cornea and loss of transparency. By 6 hours after CpG-ODN administration, TLR9 mRNA was increased in the cornea and retina. In vivo clinical examination at 24 hours revealed inflammatory infiltrates in the vitreous and retina, which were confirmed ex vivo to be neutrophils and macrophages, along with activated resident microglia. CpG-ODN-induced intraocular inflammation was abrogated in TLR9(-/-) and macrophage-depleted mice. Bone marrow reconstitution of irradiated TLR9(-/-) mice with TLR9(+/+) bone marrow led to restored corneal inflammatory responses to CpG-ODN. Fluorescein isothiocyanate-CpG-ODN rapidly penetrated the cornea and ocular media to reach the retina, where it was present within CD68(+) retinal macrophages and microglia. These data show that topically applied CpG-ODN induces intraocular inflammation owing to TLR9 activation of monocyte-lineage cells. These novel findings indicate that microbial CpG-DNA released during bacterial and/or viral keratitis can cause widespread inflammation within the eye, including the retina.


Reactions of the class II peroxidases, lignin peroxidase and Arthromyces ramosus peroxidase, with hydrogen peroxide. Catalase-like activity, compound III formation, and enzyme inactivation.
The reactions of the fungal enzymes Arthromyces ramosus peroxidase (ARP) and Phanerochaete chrysosporium lignin peroxidase (LiP) with hydrogen peroxide (H(2)O(2)) have been studied. Both enzymes exhibited catalase activity with hyperbolic H(2)O(2) concentration dependence (K(m) approximately 8-10 mm, k(cat) approximately 1-3 s(-1)). The catalase and peroxidase activities of LiP were inhibited within 10 min and those of ARP in 1 h. The inactivation constants were calculated using two independent methods; LiP, k(i) approximately 19 x 10(-3) s(-1); ARP, k(i) approximately 1.6 x 10(-3) s(-1). Compound III (oxyperoxidase) was detected as the majority species after the addition of H(2)O(2) to LiP or ARP, and its formation was accompanied by loss of enzyme activity. A reaction scheme is presented which rationalizes the turnover and inactivation of LiP and ARP with H(2)O(2). A similar model is applicable to horseradish peroxidase. The scheme links catalase and compound III forming catalytic pathways and inactivation at the level of the [compound I.H(2)O(2)] complex. Inactivation does not occur from compound III. All peroxidases studied to date are sensitive to inactivation by H(2)O(2), and it is suggested that the model will be generally applicable to peroxidases of the plant, fungal, and prokaryotic superfamily.


Recombinant human erythropoietin protects the myocardium from ischemia-reperfusion injury and promotes beneficial remodeling.
Erythropoietin (EPO), originally identified for its critical hormonal role in promoting erythrocyte survival and differentiation, is a member of the large and diverse cytokine superfamily. Recent studies have identified multiple paracrineautocrine functions of EPO that coordinate local responses to injury by maintaining vascular autoregulation and attenuating both primary (apoptotic) and secondary (inflammatory) causes of cell death. Experimental evidence also supports a role for EPO in repair and regeneration after brain and spinal cord injury, including the recruitment of stem cells into the region of damage. Tissue expression of the EPO receptor is widespread, especially during development, and includes the heart. However, it is currently unknown as to whether EPO plays a physiological function in adult myocardial tissue. We have assessed the potential protective role of EPO in vitro with adult rat cardiomyocytes, and in vivo in a rat model of myocardial infarction with reperfusion. The results show that EPO markedly prevents the apoptosis of cultured adult rat myocardiocytes subjected to 28 h of hypoxia (approximately 3% normal oxygen). Additional studies employing a rat model of coronary ischemia-reperfusion showed that the administration of recombinant human EPO (5,000 units/kg of body weight; i.p. daily for 7 days) reduces cardiomyocyte loss by approximately 50%, an extent sufficient to normalize hemodynamic function within 1 week after reperfusion. These observations not only suggest a potential therapeutic role for recombinant human EPO in the treatment of myocardial ischemia and infarction by preventing apoptosis and attenuating postinfarct deterioration in hemodynamic function, but also predict that EPO is likely a tissue-protective cytokine in other organs as well.


Real-time three-dimensional echocardiography: technological gadget or clinical tool?
The complex anatomy of cardiac structures requires three-dimensional spatial orientation of images for a better understanding of structure and function, thereby improving image interpretation. Real-time three-dimensional echocardiography is a recently developed technique based on the design of an ultrasound transducer with a matrix array that rapidly acquires image data in a pyramidal volume. The simultaneous display of multiple tomographic images allows three-dimensional perspective and the anatomically correct examination of any structure within the volumetric image. As a consequence, it is less operator-dependent and hence more reproducible. Dedicated software systems and technologies are based on high-performance computers designed for graphic handling of three-dimensional images by providing possibilities beyond those obtainable with echocardiography. This methodology allows simultaneous display of multiple superimposed planes in an interactive manner as well as a quantitative assessment of cardiac volumes and ventricular mass in a three-dimensional format without a pre-established assumption of cardiac chamber geometry. In addition, myocardial contraction and/or perfusion abnormalities are clearly identified. Finally, real-time three-dimensional colour Doppler flow mapping enables complete visualisation of the regurgitant jet and new ways of assessing regurgitant lesion severity. Thus, this technique expands the abilities of non-invasive cardiology and may open new doors for the evaluation of cardiac diseases. In this article, current and future clinical applications of real-time three-dimensional echocardiography are reviewed.


The relationship among cardiovascular risk factors, diet patterns, alcohol consumption, and ethnicity among women aged 50 years and older.
Cardiovascular disease (CVD) is the leading cause of death among women of all races and ethnicities. The risk of developing the disease is greater in postmenopausal women. The purpose of this study was to use cluster analysis to examine diet patterns and to examine the association between diet patterns and the presence of major cardiovascular disease risk factors. Data from the cross-sectional National Health and Nutrition Examination Survey (NHANES) 2001-2002 were used. Women aged 50 years and older were included (n=1,313). The following major CVD risk factors were examined: being overweight or obese (body mass index >24.9), having elevated systolic blood pressure (>120 mm Hg), and having low levels of high-density lipoprotein cholesterol (<50 mg/dL [<1.30 mmol/L]). Dietary patterns were derived by cluster analysis using data from a 24-hour dietary recall. Odds Ratios (ORs) and 95% confidence intervals (CIs) were calculated using logistic regression to determine the probability of having a risk factor according to diet pattern while accounting for race/ethnicity, physical activity, age, and smoking. Cluster analysis generated six nonoverlapping diet patterns labeled: Pasta and Yellow Vegetables; Sweets; Beef, Starches, Fruits, and Milk; Frozen Meals, Burritos, and Pizza; Meat Dishes; and Soft Drinks and Poultry. The majority of the women were grouped in the Sweets diet pattern. Factors associated with adequate levels of high-density lipoprotein cholesterol included being non-Hispanic African American (OR 0.59, 95% CI 0.44 to 0.81; P<0.0001), alcohol consumption (OR 0.76, 95% CI 0.69 to 0.84; P<0.0001), and being assigned to the Sweets diet pattern (OR 0.27, 95% CI 0.14 to 0.50; P<0.0001) or Meat dishes diet pattern (OR 0.94, 95% CI 0.54 to 1.65; P<0.0075). The Sweets pattern was also associated with having normal systolic blood pressure levels (OR 0.51, 95% CI 0.34 to 0.76; P<0.0001). Individuals grouped in the Beef, Starches, and Milk diet pattern were more likely to have an adequate body mass index (OR 0.42, 95% CI 0.23 to 0.77; P<0.0032). Significant associations between dietary patterns and major CVD risk factors were observed. Food and nutrition professionals can use this information to assess unhealthful food choices observed in the dietary patterns to guide nutrition recommendations and help reduce the incidence of CVD risk factors. Future research should aim to evaluate dietary intake via complementary methods (ie, dietary patterns and nutrient assessment) to better understand diet-disease relationships.


Cervicovaginal cytology in the detection of recurrence after cervical cancer treatment.
To evaluate the utility of liquid-based cytology in detecting recurrent cervical cancer among treated cervical cancer patients. A retrospective multi-institution study identified patients treated for cervical cancer from January 1, 2000, to November 1, 2009, through local cancer registries and patient databases. Patients were excluded if they lacked follow-up or treatment data. In all, 4,167 cytology results from 929 women were identified. Of these, 626 (15%) Pap test results from 312 (34%) women were abnormal, including 296 atypical squamous cells of undetermined significance (ASC-US; 47%); 179 low-grade squamous intraepithelial lesions (LSIL; 29%), 59 atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesions (ASC-H; 9%); 55 high-grade squamous intraepithelial lesions (HSIL; 9%); 14 atypical glandular cells (2%), and 23 favor neoplasia (4%). Abnormal Pap test results led to 201 colposcopies in 135 women. Only 45 women had cervical intraepithelial neoplasia (CIN) 2 or worse, 25 had CIN 3, and 12 had cancer. Only 5 of 475 (1%) women with ASC-US or LSIL had CIN 3. Cancer recurred in 147 women, with 12 (8.1%) detected by Pap test; all but one had Pap test results of ASC-H or worse. One patient with ASC-US and human papillomavirus had a visible lesion on return for assessment 2 months after Pap testing. Colposcopy for cytology less than HSIL without a visible lesion on examination did not detect any recurrence or CIN 3. When stratified by stage and institution, patients treated with radiation had a higher risk of abnormal Pap test results (P<.001). A third of cervical cancer survivors will have abnormal cytology during follow-up, but in the absence of a visible lesion, those with ASC-US or LSIL can be followed without colposcopy unless abnormalities persist. Women with ASC-H, HSIL, and similar abnormalities deserve colposcopy. II.


When individual behaviour matters: homogeneous and network models in epidemiology.
Heterogeneity in host contact patterns profoundly shapes population-level disease dynamics. Many epidemiological models make simplifying assumptions about the patterns of disease-causing interactions among hosts. In particular, homogeneous-mixing models assume that all hosts have identical rates of disease-causing contacts. In recent years, several network-based approaches have been developed to explicitly model heterogeneity in host contact patterns. Here, we use a network perspective to quantify the extent to which real populations depart from the homogeneous-mixing assumption, in terms of both the underlying network structure and the resulting epidemiological dynamics. We find that human contact patterns are indeed more heterogeneous than assumed by homogeneous-mixing models, but are not as variable as some have speculated. We then evaluate a variety of methodologies for incorporating contact heterogeneity, including network-based models and several modifications to the simple SIR compartmental model. We conclude that the homogeneous-mixing compartmental model is appropriate when host populations are nearly homogeneous, and can be modified effectively for a few classes of non-homogeneous networks. In general, however, network models are more intuitive and accurate for predicting disease spread through heterogeneous host populations.


The effect of distance on short-term outcomes in a regionalized, publicly funded bariatric surgery model.
While high-volume Centers of Excellence (COE) for bariatric surgery may have improved clinical outcomes, their disparate distribution results in longer travel distances for patients. The purpose of this study was to investigate effect of distance from COE on outcomes and readmission. This was a retrospective study of all adults, aged 18 years or older, receiving bariatric surgery from April 2009 to March 2012 in the province of Ontario. Main outcomes included 30-day complication rates and readmission. Multivariable logistic regression was used to examine the impact of distance from patients' primary residence to their bariatric COE on patient outcomes and readmissions. Five thousand and seven patients were identified, two-thirds residing within 100 km of a COE with a mean distance of 117.2 km. The majority of patients did not reside within a Local Integrated Health Network (LHIN) that contained a COE, while 18.3% of patients lived in rural areas. Using multivariable adjustment, for every 10 km increase from the COE where surgery was performed, the Odds Ratio (OR) for complications was 1.00 [95% Confidence Interval (CI) 0.99-1.01; P = 0.747]. Additionally, both residing in a LHIN without a COE, OR 1.10 (95% CI 0.87-1.40; P = 0.434), and rural status, OR 0.97 (95% CI 0.77-1.23; P = 0.821) showed no increase in risk of complication. Similarly, further distances did not influence rate of readmission, OR 0.99 (95% CI 0.98-1.00; P = 0.077) nor did rural status OR 1.31 (95% CI 0.97-1.76; P = 0.076). The COE model, where a few centers in high population areas service a large geographic region, is adequate in ensuring patients that live further away receive appropriate short-term care.


Interleukin-22 mediates early host defense against Rhizomucor pusilluscan pathogens.
In recent years, the fungal infectious disease zygomycosis has increased in incidence worldwide, especially among the immunodeficient population. Despite the rates of zygomycosis-related death and deformation being very high, the mechanism(s) by which the fungal pathogens cause these severe manifestations remain unknown. Using the associated Rhizomucor variabilis species, which can selectively induce cutaneous zygomycosis in otherwise healthy individuals, we investigated the host mechanisms of infection-related responses, including cytokine and chemokine expression as well as contributions of particular T cell subsets. siRNA specifically targeting IL-22,IL-17 and IFN-γ were used to down-regulate expression of those molecules. In mouse models of infection, IL-22 was implicated in development of Rhizomucor spp.-induced skin lesions. In cultured human peripheral blood monocytes, R. pusilluscan, which is often found in immunodeficient patients, induced the production of IL-22, while R. variabilis did not. Moreover, Rhizomucor spp.-induced secretion of Il-22 from CCR6(+)CCR4(+)CCR10(+) cells was down-regulated by knockdown of IL-22 related signaling receptors, RORC and ARH. Our data strongly suggest that avoidance of IL-22 may be one mechanism by which mucor species produce morbidity and mortality in infected individuals.


Formation of new chromosomes as a virulence mechanism in yeast Candida glabrata.
In eukaryotes, the number and rough organization of chromosomes is well preserved within isolates of the same species. Novel chromosomes and loss of chromosomes are infrequent and usually associated with pathological events. Here, we analyzed 40 pathogenic isolates of a haploid and asexual yeast, Candida glabrata, for their genome structure and stability. This organism has recently become the second most prevalent yeast pathogen in humans. Although the gene sequences were well conserved among different strains, their chromosome structures differed drastically. The most frequent events reshaping chromosomes were translocations of chromosomal arms. However, also larger segmental duplications were frequent and occasionally we observed novel chromosomes. Apparently, this yeast can generate a new chromosome by duplication of chromosome segments carrying a centromere and subsequently adding novel telomeric ends. We show that the observed genome plasticity is connected with antifungal drug resistance and it is likely an advantage in the human body, where environmental conditions fluctuate a lot.


Results of a tri-national online survey on the current status of sports injury prevention among members of the German-Speaking Orthopaedic Sports Medicine Society (GOTS).
To assess the current opinions and state of knowledge in primary sports injury prevention among members of the German-Speaking Society for Orthopaedic and Traumatologic Sports Medicine (GOTS). On 21 August 2019, a web-based questionnaire was sent to the members of the tri-national society GOTS (Austria, Germany and Switzerland). The survey was online until 21 November 2019 and included twenty-two questions, which were divided into five sections: 1) general importance of prevention (n = 4), 2) specifications of the study population (n = 3), 3) implementation of prevention (n = 8), 4) improvement opportunities in prevention (n = 4) and 5) future research areas (n = 3). A total of 272 participants completed the survey, representing a total survey participation of 17.7 % of all members. The study population consisted of orthopaedic surgeons (55 % with surgical and 21 % with non-operative orientation), medical students (10 %), physical therapists (8 %) and sports scientists (4 %). Ninety-four percent of all participants stated that they considered the importance of sports injury prevention to be "very high" (68 %) or "high" (26 %). However, almost 70 % of all participants stated that they spend less than one hour per week on injury prevention work. The term "prevention" was clearly defined and practicable for only 40 %, understandable but difficult to implement for 51 %, and unclear and difficult to implement for 9 % of the participants. Seventy-two percent of respondents were aware of existing prevention programs such as "Stop-X" or "FIFA 11 +", whereas 28 % of participants were uninformed regarding these programs. A strong divergence was identified between participants' perception of the importance of sports injury prevention and the existing implementation of preventive measures. Future funding of prevention programs, expansion of research strategies for injury prevention and better financial reimbursement are of utmost importance.


[Experimental latency of scrapie].
BALB/c mice infected with the scrapie agent without apparent symptoms of the disease for 12 to 14 months after inoculation were examined by virological and histological methods. Changes in the central nervous system characteristic of the pathohistological picture of scrapie were detected in two out of 66 mice. Intracerebral challenge of mice with the examined material from these animals did not result in disease. Scrapie superinfection of animals inoculated previously but not falling ill revealed a similar susceptibility to infection in these animals in comparison with 2-3-week-old intact mice. Basing on their findings and published data, the authors discuss the problem of latent infection in transmission spongiform encephalopathies and its possible contribution to the epidemic process.


Expression of human immunodeficiency virus antigen (HIV-Ag) in serum and cerebrospinal fluid during acute and chronic infection.
Human immunodeficiency virus antigen (HIV-Ag) was detected in the serum of most adult (13/16) and paediatric (6/6) AIDS patients and rarely in the serum of symptomless seropositive controls (1/13). It was present in the cerebrospinal fluid (CSF) of all 5 children and most (5/9) adults with AIDS-related encephalopathy, but not in the CSF of 13 symptomless seropositive controls, of whom 8 had antibody in the CSF. A longitudinal study of 1 of the controls with antibody in the CSF showed that HIV-Ag in CSF was present transiently before the occurrence of antibody in the CSF. In serial samples of serum from 35 men who seroconverted HIV-Ag was detected in 11 persons--in 5 before seroconversion and in 6 after. 3 of the 6 who became antigenaemic after seroconversion remained so for the rest of the follow-up. AIDS was diagnosed in 1 patient, 3 months after HIV-Ag was first detected in serum and 6 months after seroconversion. The findings suggest that HIV-Ag appears early and transiently in primary HIV infection. Antibody production follows, after which HIV-Ag may disappear. Its persistence or reappearance seems to correlate with clinical, immunological, and neurological deterioration.


Prevalence of drooling in children with cerebral palsy attending special schools.
Prevalence of drooling in children with cerebral palsy (CP) and its severity across dental age (i.e. children with primary, mixed, and permanent dentitions) was investigated. One hundred and sixty children and adolescents (91 males, 69 females; mean age 10 years 10 months, SD 4 years 2 months; range 4 to 18 years) with CP who attended special schools were involved in this study. Sixty eight per cent of participants had spastic CP with the majority (45%) diagnosed as having quadriplegia. Presence or absence of drooling was determined by direct observation of the participants. Other data, such as age, sex, learning disability, and type of CP were collected using questionnaires. Results showed 93 of 160 children (58%) with CP had a drooling condition and of these 53 (33%) had severe drooling. It was found that the degree of drooling decreased as the child's dental age increased. Prevalence of drooling in children with primary dentition was found to be 75% as compared with 43% of those with permanent dentition, although this difference was not statistically significant. It was concluded that any invasive treatment to reduce drooling should, perhaps, be postponed until the child's oromusculature has matured.


Effect of magnesium on the function of the rabbit corpus cavernosum.
Contraction and relaxation of the smooth muscle, including the corpus cavernosum, are mediated by changes in the intracellular concentration of calcium. Since magnesium modulates the movement of calcium, it can modify the function of the erectile tissue. We designed this study to investigate the effects of magnesium in doses ranging from 5 to 30 mM on the function of the rabbit corpus cavernosum in vitro. The resting tension of tissue strips was significantly reduced by exposure to a solution high in magnesium (5-30 mM). The contractile response to field stimulation under resting conditions, and the contraction to phenylephrine, were significantly decreased by magnesium (5-30 mM). There were no differences in the contractile strength of the corpus cavernosum to KCl. Although the relaxation induced by field stimulation under preincubation with 200 microM phenylephrine was abolished in the presence of 30 mM magnesium, there were no differences at a concentration of 5 mM or of 10 mM magnesium. The relaxation induced by sodium nitroprusside under precontraction with 200 microM phenylephrine was further increased by magnesium dose dependently. A high concentration of magnesium (30 mM) enhanced both bethanechol-induced and ATP-induced relaxations under precontraction with phenylephrine. Our study demonstrated that magnesium reduced the receptor-mediated contraction of the rabbit corpus cavernosum and enhanced the relaxation of this tissue induced by sodium nitroprusside, bethanechol, and ATP.


STAT3 enhances intracellular Fas-mediated apoptotic signals in HHUA human endometrial epithelial cells.
Several endometrial signal transducer and activator of transcription 3 (STAT3)-activating cytokines are reported to be essential for blastocyst implantation, with inhibition of STAT3 activation in the endometrium also reported to prevent implantation. To investigate STAT3 signals in endometrial epithelial cells, the activation and inactivation effects of STAT3 signals were examined in the human endometrial epithelial cell line HHUA, which is thought to retain many of the intracellular signaling pathways found in normal human endometrial epithelial cells. Five STAT3-activating cytokines, IL-11, IL-10, LIF, oncostatin M and leptin, enhanced the Fas-mediated apoptosis of the HHUA cells without any increase in cell surface Fas antigen expression. STAT3 siRNA transfection suppressed STAT3 expression in HHUA cells and significantly inhibited Fas-mediated cell death. These results indicate that intracellular apoptotic signals in HHUA cells are constitutively activated and regulated by STAT3-mediated signals. This apoptosis-promoting effect of STAT3 in HHUA cells is completely different from many previous reports demonstrating anti-apoptotic effects by STAT3 activation. The STAT3 signals in HHUA cells may be specific to the human endometrial epithelial cell lineage in the regulation of blastocyst implantation.


Optokinetic stimulation induces illusory movement of both out-of-the-body and on-the-body hand-held visual objects.
The coding of body part location may depend upon both visual and proprioceptive information, and allows targets to be localized with respect to the body. The present study investigates the interaction between visual and proprioceptive localization systems under conditions of multisensory conflict induced by optokinetic stimulation (OKS). Healthy subjects were asked to estimate the apparent motion speed of a visual target (LED) that could be located either in the extrapersonal space (visual encoding only, V), or at the same distance, but stuck on the subject's right index finger-tip (visual and proprioceptive encoding, V-P). Additionally, the multisensory condition was performed with the index finger kept in position both passively (V-P passive) and actively (V-P active). Results showed that the visual stimulus was always perceived to move, irrespective of its out- or on-the-body location. Moreover, this apparent motion speed varied consistently with the speed of the moving OKS background in all conditions. Surprisingly, no differences were found between V-P active and V-P passive conditions in the speed of apparent motion. The persistence of the visual illusion during the active posture maintenance reveals a novel condition in which vision totally dominates over proprioceptive information, suggesting that the hand-held visual stimulus was perceived as a purely visual, external object despite its contact with the hand.


Updated Adaptive Servo-Ventilation Recommendations for the 2012 AASM Guideline: "The Treatment of Central Sleep Apnea Syndromes in Adults: Practice Parameters with an Evidence-Based Literature Review and Meta-Analyses".
An update of the 2012 systematic review and meta-analyses were performed and a modified-GRADE approach was used to update the recommendation for the use of adaptive servo-ventilation (ASV) for the treatment of central sleep apnea syndrome (CSAS) related to congestive heart failure (CHF). Meta-analyses demonstrated an improvement in LVEF and a normalization of AHI in all patients. Analyses also demonstrated an increased risk of cardiac mortality in patients with an LVEF of ≤ 45% and moderate or severe CSA predominant sleep-disordered breathing. These data support a Standard level recommendation against the use of ASV to treat CHF-associated CSAS in patients with an LVEF of ≤ 45% and moderate or severe CSAS, and an Option level recommendation for the use of ASV in the treatment CHF-associated CSAS in patients with an LVEF > 45% or mild CHF-related CSAS. The application of these recommendations is limited to the target patient populations; the ultimate judgment regarding propriety of any specific care must be made by the clinician.


Aged garlic extract enhances exercise-mediated improvement of metabolic parameters in high fat diet-induced obese rats.
Aged garlic extract (AGE) is known to have a protective effect against immune system, endothelial function, oxidative stress and inflammation. We examined the effects of exercise with and without aged garlic extract administration on body weight, lipid profiles, inflammatory cytokines, and oxidative stress marker in high-fat diet (HFD)-induced obese rats. Forty-five Sprague-Dawley rats were fed either a HFD (HFD, n = 40) or a normal diet (ND, n = 5) for 6 weeks and thereafter randomized into ND (n = 5), HFD (n = 10), HFD with AGE (n = 10), HFD with Exercise (n = 10), or HFD with Exercise+AGE (n = 10) for 4 weeks. AGE groups were administered at a dose of 2.86 g/kg·body weight, orally. Exercise consisted of running 15-60 min 5 days/week with gradually increasing intensity. AGE (P < 0.01), Exercise, and Exercise+AGE (P < 0.001) attenuated body weight gain and food efficiency ratio compared to HFD. Visceral fat and liver weight gain were attenuated (P < 0.05) with all three interventions with a greater effect on visceral fat in the Exercise+AGE than AGE (P < 0.001). In reducing visceral fat (P < 0.001), epididymal fat (P < 0.01) and liver weight (P < 0.001), Exercise+AGE was effective, but exercise showed a stronger suppressive effect than AGE. Exercise+AGE showed further additive effects on reducing visceral fat and liver weight (P < 0.001). AGE significantly attenuated the increase in total cholesterol and low-density lipoprotein-cholesterol compared with HFD (P < 0.05). Exercise+AGE attenuated the increase in triglycerides compared with HFD (P < 0.05). Exercise group significantly decrease in C-reactive protein (P < 0.001). These results suggest that AGE supplementation and exercise alone have anti-obesity, cholesterol lowering, and anti-inflammatory effects, but the combined intervention is more effective in reducing weight gain and triglycerides levels than either intervention alone.


ST2 and galectin-3 as novel biomarkers for the prediction of future cardiovascular disease risk in preeclampsia.
The aim of this study was to investigate known cardiovascular disease (CVD) risk biomarkers galectin-3 (Gal-3) and human stromelysin-2 (ST2) levels in preeclampsia (PE) and normotensive pregnancies. A case-control study was conducted in a teaching and research hospital. We performed data analysis involving 45 pregnant women with PE and gestational week (GW) matched 35 normotensive pregnant women. The Gal-3 and ST2 levels were determined by using ELISA kit. Gal-3 values did not differ statistically between PE and control groups (535.1 ng/mL vs. 615.2 ng/mL) (p> .05). ST2 value in the PE group was statistically significantly lower than the control group (33.3 pg/mL vs. PE, 54.5 pg/mL, p ˂ .05). >34 GW patients (late-onset PE) had statistically significantly lower Gal-3 values than the ≤34 GW patients (early-onset PE) (507.1 ng/mL vs. 769.6 ng/mL, p ˂ .05). Late-onset PE patients had significantly lower ST2 values than early-onset patients (26.4 pg/mL vs. 57.9 pg/mL, p ˂ .05). We assume that low Gal-3 values in early-onset PE show a higher risk of cardiac fibrosis although both early and late-onset PE patients had an increased CVD risk later in life. We found the superiority of ST2 levels to Gal-3 levels in PE pregnancies for CVD risk assessment.Impact StatementWhat is already known about this subject? Preeclampsia (PE) in pregnancy is a known risk factor for future cardiovascular disease (CVD) and is also associated with increased mortality from ischaemic heart disease later in life. Studies that investigate patients with a higher risk for CVD in PE pregnancies are lacking.What do the results of this study add? We found different levels of two novel cardiac markers with PE and normotensive pregnancies, and also with early and late-onset PE pregnancies.What are the implications of these findings for clinical practice and/or further research? Different adaptive responses from patients during PE pregnancies via altered levels of cardiac markers could help clinicians to identify women with a higher risk of CVD.


Human papillomavirus genotype specificity of hybrid capture 2.
Hybrid Capture 2 (hc2), a clinical test for carcinogenic human papillomavirus (HPV) DNA, has proven to be a sensitive but only modestly specific predictor of cervical precancer and cancer risk. Some of its nonspecificity for clinical end points can be ascribed to cross-reactivity with noncarcinogenic HPV genotypes. However, the reference genotyping tests that have been used for these comparisons are also imperfect. We therefore sought to describe further the HPV genotype specificity of hc2 by comparing the hc2 results to paired results from two related PGMY09/11 L1 primer-based HPV genotyping assays: Linear Array (LA) and its prototype predecessor, the line blot assay (LBA). LA and LBA results were considered separately and combined (detection by either assay or both assays) for 37 individual HPV genotypes and HPV risk group categories (carcinogenic HPV > noncarcinogenic HPV > negative). Baseline specimens from 3,179 of 3,488 (91.5%) women referred to ALTS (a clinical trial to evaluate the management strategies for women with atypical squamous cells of undetermined significance [ASCUS] or low-grade squamous intraepithelial lesions) because of an ASCUS Papanicolaou smear were tested by all three assays. Among single-genotype infections with genotypes targeted by hc2 as detected by either PCR assay, HPV genotype 35 (HPV35) (86.4%), HPV56 (84.2%), and HPV58 (76.9%) were the most likely to test positive by hc2. Among single-genotype infections with genotypes not targeted by hc2 as detected by either assay, HPV82 (80.0%), HPV66 (60.0%) (recently classified as carcinogenic), HPV70 (59.1%), and HPV67 (56.3%) were the most likely to test positive by hc2. Among women who tested negative for carcinogenic HPV by both PCR tests and were positive for noncarcinogenic HPV by either test, 28% of women were hc2 positive. Conversely, 7.8% of all hc2-positive results in this population were due to cross-reactivity of hc2 with untargeted, noncarcinogenic HPV genotypes. In conclusion, hc2 cross-reacts with certain untargeted, noncarcinogenic HPV genotypes that are phylogenetically related to the targeted genotypes, but the degree of cross-reactivity may be less than previously reported.


Soil transmitted parasites in Qualyobia Governorate.
The study determined the relation between prevalence of intestinal parasites and soil-transmitted parasites among households in Shiblanga representing a rural area of Qualyobia Governorate and Benha City representing an urban area of the same Governorate. The effect of soil's type on the intensity of parasites and to provide guidance on the prevention and control of soil transmitted parasitic infections for future studies in this field. This study was conducted at Benha City and Shiblanga village representing the urban and rural areas of Qualyobia Governorate. Geoparasites were investigated in-doors, around houses, in the fields and the streets from both areas. One hundred soil samples from Benha city and one hundred soil samples from Shiblanga village were collected .each hundred soil samples was collected in the form of: 25 samples from the fields, 25 samples in-indoor yards, 25 samples the streets, 25 samples around houses. Approximately 200 g soil was collected in plastic bags at 2-10 cm depth from different parts. Stool samples from households in same areas were collected after taken oral consent. All soil samples were screened for parasites using different parasitological methods (Zinc sulphate flotation, ether sédimentation technique, modified Baerman's apparatus and modified Berlese technique). All stool samples were examined using direct smear, formalinether concentration techniques for detection of helminthes eggs, and modified acid-fast staining for detection of protozoa. The results showed that 86/200 soil samples were contaminated with different parasites, the prevalence rate of 43%. Soil samples from Shiblanga village showed higher level of parasitic contamination (56%) and Benha city showed a lower level of contamination by different parasites (30%). Soil samples obtained from Manshiet El-Nour district, Benha revealed the highest level of parasitic contamination. While, in Shiblanga, El-Mansheya district revealed the highest level of parasitic contamination. Clay soil was the most type of soil contaminated by hel-minthes.The10 houses out of 50 houses had the same parasites in the soil and in stool of their households, 8 houses in Shiblinga village and 2 houses in Benha city.


Knowledge of pathologically versus clinically negative lymph nodes is associated with reduced use of radioactive iodine post-thyroidectomy for low-risk papillary thyroid cancer.
Cervical lymph node metastases are common in papillary thyroid cancer (PTC). Clinically negative lymph nodes confer uncertainty about true lymph node status, potentially prompting empiric postoperative radioactive iodine (RAI) administration even in low-risk patients. We examined the association of clinically (cN0) versus pathologically negative (pN0) lymph nodes with utilization of RAI for low-risk PTC. Using the National Cancer Database 1998-2011, adults with PTC who underwent total thyroidectomy for Stage I/II tumors 1-4 cm were evaluated for receipt of RAI based on cN0 versus pN0 status. Cut-point analysis was conducted to determine the number of pN0 nodes associated with the greatest decrease in the odds of receipt of RAI. Survival models and multivariate analyses predicting RAI use were conducted separately for all patients and patients <45 years. 64,980 patients met study criteria; 39,778 (61.2 %) were cN0 versus 25,202 (38.8 %) pN0. Patients with pN0 nodes were more likely to have negative surgical margins and multifocal disease (all p < 0.001). The mean negative nodes reported in surgical pathology specimens was 4; ≥5 pathologically negative lymph nodes provided the best cut-point associated with reduced RAI administration (OR 0.91, CI 0.85-0.97). After multivariable adjustment, pN0 patients with ≥5 nodes examined were less likely to receive RAI compared to cN0 patients across all ages (OR 0.89, p < 0.001) and for patients aged <45 years (0R 0.86, p = 0.001). Patients with <5 pN0 nodes did not differ in RAI use compared to cN0 controls. Unadjusted survival was improved for pN0 versus cN0 patients across all ages (p < 0.001), but not for patients <45 years (p = 0.11); adjusted survival for all ages did not differ (p = 0.13). Pathological confirmation of negative lymph nodes in patients with PTC appears to influence the decision to administer postoperative RAI if ≥5 negative lymph nodes are removed. It is possible that fewer excised lymph nodes may be viewed by clinicians as incidentally resected and thus may suboptimally represent the true nodal status of the central neck. Further research is warranted to determine if there is an optimal number of lymph nodes that should be resected to standardize pathological diagnosis.


Comparison of strain parameters in dyssynchronous heart failure between speckle tracking echocardiography vendor systems.
Although mechanical dyssynchrony parameters derived by speckle tracking echocardiography (STE) may predict response to cardiac resynchronization therapy (CRT), comparability of parameters derived with different STE vendors is unknown. In the MARC study, echocardiographic images of heart failure patients obtained before CRT implantation were prospectively analysed with vendor specific STE software (GE EchoPac and Philips QLAB) and vendor-independent software (TomTec 2DCPA). Response was defined as change in left ventricular (LV) end-systolic volume between examination before and six-months after CRT implantation. Basic longitudinal strain and mechanical dyssynchrony parameters (septal to lateral wall delay (SL-delay), septal systolic rebound stretch (SRSsept), and systolic stretch index (SSI)) were obtained from either separate septal and lateral walls, or total LV apical four chamber. Septal strain patterns were categorized in three types. The coefficient of variation and intra-class correlation coefficient (ICC) were analysed. Dyssynchrony parameters were associated with CRT response using univariate regression analysis and C-statistics. Two-hundred eleven patients were analysed. GE-cohort (n = 123): age 68 years (interquartile range (IQR): 61-73), 67% male, QRS-duration 177 ms (IQR: 160-192), LV ejection fraction: 26 ± 7%. Philips-cohort (n = 88): age 67 years (IQR: 59-74), 60% male, QRS-duration: 179 ms (IQR: 166-193), LV ejection fraction: 27 ± 8. LV derived peak strain was comparable in the GE- (GE: -7.3 ± 3.1%, TomTec: -6.4 ± 2.8%, ICC: 0.723) and Philips-cohort (Philips: -7.7 ± 2.7%, TomTec: -7.7 ± 3.3%, ICC: 0.749). SL-delay showed low ICC values (GE vs. TomTec: 0.078 and Philips vs. TomTec: 0.025). ICC's of SRSsept and SSI were higher but only weak (GE vs. TomTec: SRSsept: 0.470, SSI: 0.467) (Philips vs. QLAB: SRSsept: 0.419, SSI: 0.421). Comparability of septal strain patterns was low (Cohen's kappa, GE vs. TomTec: 0.221 and Philips vs. TomTec: 0.279). Septal strain patterns, SRSsept and SSI were associated with changes in LV end-systolic volume for all vendors. SRSsept and SSI had relative varying C-statistic values (range: 0.530-0.705) and different cut-off values between vendors. Although global longitudinal strain analysis showed fair comparability, assessment of dyssynchrony parameters was vendor specific and not applicable outside the context of the implemented platform. While the standardization taskforce took an important step for global peak strain, further standardization of STE is still warranted.


[Benign paroxysmal torticollis in childhood].
The Author describes one case of a male infant aged 12 months with recurrent short lasting episodes of torticollis, accompanied by vomiting, pallor, vacuous stare, sudden cry, without any electroencephalographical or neuroradiological alterations. At first torticollis attacks appeared with monthly frequency, afterwards they began to become less frequent and at last they disappeared at the age of about 30 months.


Novel investigational agents for the treatment of scleroderma.
The purpose of this article is to highlight novel therapies that are being used in scleroderma (SSc). Therapeutic interventions in SSc generally target at least one of three ongoing biological processes characteristic of the disease: vasculopathy, autoimmunity and tissue fibrosis. Treatment decisions in SSc are determined by the level of disease activity and the degree of specific organ involvement. Traditional therapy has primarily focused on organ-specific management without clear evidence of overall disease modification. The authors provide a review of a variety of agents, which are already used for other autoimmune diseases, that are now being used to treat active SSc skin or lung disease, including rituximab, tocilizumab and IVIG. Several agents studied in vitro and in animal models of fibrosis have shown promise, including bortezomib, LPA-1 antagonists, anti-CCN2 therapy, anti-IL-13 and thrombin antagonists. The authors also provide details on targeting intracellular molecular pathways and matricellular proteins, which is another novel area of investigation. Combination therapy may be necessary to control the complex biological network active in SSc. Most of the current evidence that suggest benefit of these agents is based on small population studies. Ultimately well-designed clinical trials are required to define the role of these agents in treating SSc.


Leukotriene B4, a mediator of inflammation present in synovial fluid in rheumatoid arthritis.
Leukotriene B4 (LTB4), generated from arachidonic acid following lipoxygenase activity by a variety of inflammatory leucocytes, has been shown to be present in synovial fluid from patients with active rheumatoid arthritis. It does not persist as such, being converted to less active metabolites. The role of LTB4 as one of the natural mediators of inflammation is discussed.


Physicochemical Characterization, Antioxidant Activity, and Phenolic Compounds of Hawthorn (Crataegus spp.) Fruits Species for Potential Use in Food Applications.
Hawthorn belongs to the Crataegus genus of the Rosaceae family and is an important medicinal plant. Due to its beneficial effects on the cardiovascular system and its antioxidant and antimicrobial activity hawthorn has recently become quite a popular herbal medicine in phytotherapy and food applications. In this study, physicochemical characterization (color parameters, pH, titratable acidity, total soluble solids, soluble carbohydrate, total carotenoid, total phenols, and flavonoid contents), antioxidant activity (by ferric-reducing antioxidant power, FRAP assay), and quantification of some individual phenolic compounds of fruits of 15 samples of different hawthorn species (Crataegus spp.) collected from different regions of Iran were investigated. According to findings, the total phenols, total flavonoid content, and antioxidant activity were in the range of 21.19-69.12 mg gallic acid equivalent (GAE)/g dry weight (dw), 2.44-6.08 mg quercetin equivalent (QUE)/g dw and 0.32-1.84 mmol Fe++/g dw, respectively. Hyperoside (0.87-2.94 mg/g dw), chlorogenic acid (0.06-1.16 mg/g dw), and isoquercetin (0.24-1.59 mg/g dw) were found to be the most abundant phenolic compounds in the extracts of hawthorn fruits. The considerable variations in the antioxidant activity and phenolic compounds of hawthorn species were demonstrated by our results. Hence, the evaluation of hawthorn genetic resources could supply precious data for screening genotypes with high bioactive contents for producing natural antioxidants and other phytochemical compounds valuable for food and pharma industries.


Whole-genome sequence-based analysis of thyroid function.
Normal thyroid function is essential for health, but its genetic architecture remains poorly understood. Here, for the heritable thyroid traits thyrotropin (TSH) and free thyroxine (FT4), we analyse whole-genome sequence data from the UK10K project (N=2,287). Using additional whole-genome sequence and deeply imputed data sets, we report meta-analysis results for common variants (MAF≥1%) associated with TSH and FT4 (N=16,335). For TSH, we identify a novel variant in SYN2 (MAF=23.5%, P=6.15 × 10(-9)) and a new independent variant in PDE8B (MAF=10.4%, P=5.94 × 10(-14)). For FT4, we report a low-frequency variant near B4GALT6/SLC25A52 (MAF=3.2%, P=1.27 × 10(-9)) tagging a rare TTR variant (MAF=0.4%, P=2.14 × 10(-11)). All common variants explain ≥20% of the variance in TSH and FT4. Analysis of rare variants (MAF<1%) using sequence kernel association testing reveals a novel association with FT4 in NRG1. Our results demonstrate that increased coverage in whole-genome sequence association studies identifies novel variants associated with thyroid function.


An oscillating reaction network with an exact closed form solution in the time domain.
Oscillatory behavior is critical to many life sustaining processes such as cell cycles, circadian rhythms, and notch signaling. Important biological functions depend on the characteristics of these oscillations (hereafter, oscillation characteristics or OCs): frequency (e.g., event timings), amplitude (e.g., signal strength), and phase (e.g., event sequencing). Numerous oscillating reaction networks have been documented or proposed. Some investigators claim that oscillations in reaction networks require nonlinear dynamics in that at least one rate law is a nonlinear function of species concentrations. No one has shown that oscillations can be produced for a reaction network with linear dynamics. Further, no one has obtained closed form solutions for the frequency, amplitude and phase of any oscillating reaction network. Finally, no one has published an algorithm for constructing oscillating reaction networks with desired OCs. This is a theoretical study that analyzes reaction networks in terms of their representation as systems of ordinary differential equations. Our contributions are: (a) construction of an oscillating, two species reaction network [two species harmonic oscillator (2SHO)] that has no nonlinearity; (b) obtaining closed form formulas that calculate frequency, amplitude, and phase in terms of the parameters of the 2SHO reaction network, something that has not been done for any published oscillating reaction network; and (c) development of an algorithm that parameterizes the 2SHO to achieve desired oscillation, a capability that has not been produced for any published oscillating reaction network. Our 2SHO demonstrates the feasibility of creating an oscillating reaction network whose dynamics are described by a system of linear differential equations. Because it is a linear system, we can derive closed form expressions for the frequency, amplitude, and phase of oscillations, something that has not been done for other published reaction networks. With these formulas, we can design 2SHO reaction networks to have desired oscillation characteristics. Finally, our sensitivity analysis suggests an approach to constructing a 2SHO for a biochemical system.


Interaction of a fluorescent acyldicholine with the nicotinic acetylcholine receptor and acetylcholinesterase.
A fluorescent acyldicholine, bis-(choline)N-[4-nitrobenzo-2-oxa-1,3-diazol-7-yl]-iminodiprop ionate (BCNI), was synthesized and its capacity to associate with acetylcholinesterase and the nicotinic acetylcholine receptor examined. The fluorescent bisquaternary diester competitively inhibits acetylcholinesterase with a Ki of 0.46 microM. Binding is accompanied by a large decrease in BCNI fluorescence and a 40% reduction in enzyme tryptophanyl fluorescence due to spectral overlap between BCNI absorption and the fluorescence emission of tryptophanyl residues on the enzyme. BCNI titrations show a stoichiometry of one site per subunit and a dissociation constant of 0.2 microM. BCNI also inhibits the initial rate of alpha-toxin binding to the membrane-associated nicotinic acetylcholine receptor and yields a protection constant (Kp) of 0.26 microM. Prior exposure of BCNI to the receptor increases the affinity of the complex, and after equilibration Kp is found to be 0.11 microM. Fluorescence titrations reveal that BCNI binds with 1:1 stoichiometry to alpha-toxin sites on the receptor with a dissociation constant of 0.22 microM. Agonists and antagonists, but not local anesthetics, compete with BCNI binding. BCNI behaves as a competitive antagonist on receptors from the snake neuromuscular junction and from BC3H-1 cells. The 4-nitrobenzo-2-oxa-1,3-diazole fluorophore in BCNI shows a hypsochromatic shift and an enhancement of quantum yield when bound to the receptor but is quenched when associated with acetylcholinesterase. Thus, despite the similarity in dissociation constants, the fluorophore exists in very different environments when bound to the two proteins.


Torture vs other cruel, inhuman, and degrading treatment: is the distinction real or apparent?
After the reports of human rights abuses by the US military in Guantanamo Bay, Iraq, and Afghanistan, questions have been raised as to whether certain detention and interrogation procedures amount to torture. To examine the distinction between various forms of ill treatment and torture during captivity in terms of their relative psychological impact. A cross-sectional survey was conducted with a population-based sample of survivors of torture from Sarajevo in Bosnia and Herzegovina, Banja Luka in Republica Srpska, Rijeka in Croatia, and Belgrade in Serbia. A total of 279 survivors of torture accessed through linkage sampling in the community (Banja Luka, Sarajevo, and Rijeka) and among the members of 2 associations for war veterans and prisoners of war (Belgrade). Scores on the Semi-structured Interview for Survivors of War, Exposure to Torture Scale, Structured Clinical Interview for DSM-IV, and Clinician-Administered PTSD (posttraumatic stress disorder) Scale for DSM-IV. Psychological manipulations, humiliating treatment, exposure to aversive environmental conditions, and forced stress positions showed considerable overlap with physical torture stressors in terms of associated distress and uncontrollability. In regression analyses, physical torture did not significantly relate to posttraumatic stress disorder (odds ratio, 1.41, 95% confidence interval, 0.89-2.25) or depression (odds ratio, 1.41, 95% confidence interval, 0.71-2.78). The traumatic stress impact of torture (physical or nonphysical torture and ill treatment) seemed to be determined by perceived uncontrollability and distress associated with the stressors. Ill treatment during captivity, such as psychological manipulations, humiliating treatment, and forced stress positions, does not seem to be substantially different from physical torture in terms of the severity of mental suffering they cause, the underlying mechanism of traumatic stress, and their long-term psychological outcome. Thus, these procedures do amount to torture, thereby lending support to their prohibition by international law.


[The dietary risk factors for colorectal cancer related to meat consumption].
The integrative review is one of the methodologies used for evidence-based practice which, in this study, had the objective of surveying and synthesizing the evidence available in the literature regarding the dietary risks for colorectal cancer related to the consumption of meat. The search was made using the LILACS, MEDLINE, CINAHL, and COCHRANE Library databases, and six studies considered pertinent to the consumption of meat were found. Meta-analyses showed that there is an association between the consumption of red meat and an increased risk for colorectal cancer from 28% to 35%, whereas processed meats are associated with a rise in risk from 20% to 49%. Evidence shows that the consumption of red meat, processed meat, and total meat consumption are risk factors for developing polyps and colorectal cancer. The search did not yield any studies referring to the consumption of chicken or fish as risk factors.


An expression for backscatter factors for orthovoltage x-rays.
Backscatter factors for orthovoltage x-ray beams are fitted with the expression BSF = 1 + ms/(s + n), where s is field size and m and n are adjustable parameters. The accuracy is better than 0.5%. Good results were also obtained for Cs-137 gamma rays at depth 0.12 cm and Co-60 gamma rays at depth 0.5 cm using the same expression, which failed, however, for peak scatter factors at high x-ray energies.


Coffee improves auditory neuropathy in diabetic mice.
Coffee is a widely consumed beverage and has recently received considerable attention for its possible beneficial effects. Auditory neuropathy is a hearing disorder characterized by an abnormal auditory brainstem response. This study examined the auditory neuropathy induced by diabetes and investigated the action of coffee, trigonelline, and caffeine to determine whether they improved diabetic auditory neuropathy in mice. Auditory brainstem responses, auditory middle latency responses, and otoacoustic emissions were evaluated to assess auditory neuropathy. Coffee or trigonelline ameliorated the hearing threshold shift and delayed latency of the auditory evoked potential in diabetic neuropathy. These findings demonstrate that diabetes can produce a mouse model of auditory neuropathy and that coffee consumption potentially facilitates recovery from diabetes-induced auditory neuropathy. Furthermore, the active constituent in coffee may be trigonelline.


[Castration of roosters].
The castration of the cock is described from the topographic anatomical view. In contrast to previous authors a general narcosis is recommended, which is in accord with the relevant legislation for the prevention of cruelty to animals.


Persistent Low Toxoplasma IgG Avidity Is Common in Pregnancy: Experience from Antenatal Testing in Norway.
The parasite Toxoplasma gondii might harm the fetus if a woman is infected during pregnancy. IgG seroconversion and significant increase in IgG antibody amount in pregnancy indicates maternal infection. Presence of toxoplasma immunoglobulin M (IgM), immunoglobulin G (IgG) and low IgG avidity in a single serum sample indicates possible maternal infection, but positive toxoplasma IgM and low IgG avidity may persist for months and even years. We aimed to evaluate avidity development during pregnancy in a retrospective study. Serial blood samples from 176 pregnant women admitted to Oslo University Hospital 1993-2013 for amniocentesis because of suspected toxoplasma infection were included. Data were obtained from journals and laboratory records. The avidity method used was based on Platelia Toxo IgG assay. Mean maternal age at first serology was 29.9 years (SD 5.2, range 18-42). In 37 (21%) women only the avidity increased from low to high in < 3 months. In 139 (79%) the IgG avidity remained below the high threshold ≥ 3 months and within this group 74 (42%) women had stable low IgG avidity during the observation period. Median gestational age at first test was 10.6 weeks (range 4.6-28.7). Fetal infection was detected in four children, but none among children whose mother had stable low IgG avidity. The first antenatal toxoplasma serology should ideally be collected in early pregnancy and if stable values of toxoplasma IgM and low IgG-avidity are detected in a second sample after three to four weeks, the need for amniocentesis can be questioned.


Scattering efficiency and near field enhancement of active semiconductor plasmonic antennas at terahertz frequencies.
Terahertz plasmonic resonances in semiconductor (indium antimonide, InSb) dimer antennas are investigated theoretically. The antennas are formed by two rods separated by a small gap. We demonstrate that, with an appropriate choice of the shape and dimension of the semiconductor antennas, it is possible to obtain large electromagnetic field enhancement inside the gap. Unlike metallic antennas, the enhancement around the semiconductor plasmonics antenna can be easily adjusted by varying the concentration of free carriers, which can be achieved by optical or thermal excitation of carriers or electrical carrier injection. Such active plasmonic antennas are interesting structures for THz applications such as modulators and sensors.


Influence of misdiagnosis on the course of bipolar disorder.
It is very common that the diagnosis of bipolar disorder comes with several years of delay. This premise is supported by the fact that this diagnosis is almost always set after longitudinal monitoring of symptoms and by the fact that this disorder is often unrecognized or misdiagnosed. The aim of this study was to determine the incidence of misdiagnosed bipolar disorder and to explore its influence on the further course of the disorder. The research was provided as a naturalistic study, which included 65 bipolar patients admitted to the Hospital. We examined medical records of the first episode and five-year follow-up of the course of the disease. The average number of episodes was compared between the group with properly diagnosed first episode and the group with wrongly diagnosed first episode in the observed five-year period. T-test was used in this study, in addition to descriptive parameters, mean, median, standard deviation and coefficient of variation. In the sample over which the survey was conducted 52% of the first episodes of bipolar disorder were wrongly diagnosed. We found a statistically significant difference (t = 1.84; p < 0.05) in the number of episodes that followed the first episode between patients whose first episode was appropriately diagnosed and patients whose first episode has not been properly diagnosed. There is a high number of unrecognized and misdiagnosed bipolar disorders. Inadequate diagnosis leads to inadequate treatment of the disorder. Number of next episodes in period of follow up is statistically significantly connected with the adequacy of diagnose.


Temporomandibular joint dysfunction and flat lateral guidances: a clinical association.
Temporomandibular joint alterations have been associated with abnormal mandibular movements in the open/close cycles and in the laterotrusive border movements. The quantitative analysis of these movements could allow a better or earlier diagnosis for patients and offer some insight into the pathophysiology of the disorder. Maximum opening and mandibular laterotrusive border movements were studied and measured in a group of 165 patients with a considerable lateral deviation (equal to or greater than 5mm) in maximum opening. Movements were directly performed by the patients and recorded with a mandibular kinesiography. The slope of the lateral guidance (frontal plane projection) was measured in the first millimeters of motion and started from the maximum intercuspal position. On average, slopes were significantly flatter on the same side with the opening deviation. These slopes were significantly flatter than previously published physiologic ranges, whereas contralateral slopes were similar to normal references. The results may be explained by a correlation between the insufficient lateral protection and a temporomandibular mandibular joint dysfunction (ipsilateral low mobility).


Natural history of colonization with gram-negative multidrug-resistant organisms among hospitalized patients.
To determine the anatomic sites and natural history of colonization with gram-negative multidrug-resistant organisms (MDROs). Prospective, longitudinal cohort study. Walter Reed Army Medical Center, a 236-bed tertiary care center in Washington, DC. Deployed subjects (ie, inpatients medically evacuated from Iraq or Afghanistan) or nondeployed subjects admitted to the same hospital. Consenting patients had 6 anatomic sites cultured every 3 days for 2 weeks and then weekly. Gram-negative organisms resistant to 3 or more classes of antibiotics were considered MDROs. Isolates were genotyped using pulsed-field gel electrophoresis. Clinical data, data on antibiotic use, and clinical culture results were collected. Of 60 deployed subjects, 14 (23%) were colonized with an MDRO at admission, and 13 (22%) had incident colonization during hospitalization. The groin was the most sensitive anatomic site for detecting MDRO colonization, and all but one subject remained colonized for the duration of their hospitalization. Sixty percent of subjects with incident Acinetobacter colonization and 25% of subjects with incident Klebsiella colonization had strains that were related to those isolated from other subjects. Of 60 nondeployed subjects, 5 (8%) were colonized with an MDRO at admission; all had recent healthcare contact, and 1 nondeployed subject had an isolate related to a strain recovered from a deployed subject. Colonization with gram-negative MDROs is common among patients with war-related trauma admitted to a military hospital and also occurs among nondeployed patients with recent healthcare contact. The groin is the most sensitive anatomic site for active surveillance, and spontaneous decolonization is rare.


Metabolic activation of 4-ipomeanol by complementary DNA-expressed human cytochromes P-450: evidence for species-specific metabolism.
4-Ipomeanol is a pulmonary toxin in cattle and rodents that is metabolically activated by cytochromes P-450 (P-450s). P-450-mediated activation of 4-ipomeanol to DNA binding metabolites was evaluated using a vaccinia virus complementary DNA expression system and an in situ DNA-binding assay. Twelve human P-450s and two rodent P-450s were expressed in human hepatoma Hep G2 cells and examined for their abilities to metabolically activate this toxin. Three forms, designated CYP1A2, CYP3A3, and CYP3A4, were able to catalyze significant production of DNA-bound metabolites of 20-, 8-, and 5-fold, respectively, above binding catalyzed by Hep G2 cells infected with wild-type vaccinia virus. These enzymes, with highest activities, are not known to be expressed in human or rodent lung. CYP2F1 and CYP4B1, two enzymes that are expressed in lung, display only modest 3- and 2-fold respective increased abilities to metabolically activate 4-ipomeanol. Two human forms were inactive and seven other human forms showed activities ranging from 0.5- to 2-fold above control level. Surprisingly, rabbit complementary DNA-expressed CYP4B1 was the most active enzyme (180-fold above control) among all P-450s tested in producing DNA-binding metabolites from this mycotoxin. These studies demonstrate a species difference in 4-ipomeanol metabolism and suggest caution when attempting to extrapolate rodent data to humans.


Chromophore Renewal and Fluorogen-Binding Tags: A Match Made to Last.
Fluorogen-binding tags, which activate the fluorescence of a specific chromophore (so-called fluorogen) upon reversible binding, have recently been proposed as a way of reducing photobleaching via fluorogen renewal. However, no generic methodology has been proposed to systematically analyze the photodamage of the fluorogen and the protein tag. Using Y-FAST (Yellow Fluorescence-activating and Absorption-Shifting Tag) as a case study we propose here a generic experimental and theoretical approach to assess how fluorogen renewal reduces the apparent photobleaching rate of a fluorogen-binding tag. Y-FAST has its apparent photobleaching rate greatly reduced by fluorogen renewal and its photostability is mainly limited by oxidation of specific residues in the protein scaffold by reactive oxygen species generated by the bound fluorogen. This study sets the groundwork for the optimization of fluorogenic systems, helping guide rational improvements to their photostability.


IL-4 as a Repurposed Biological Drug for Myocardial Infarction through Augmentation of Reparative Cardiac Macrophages: Proof-of-Concept Data in Mice.
Recent research has shown that reparative (alternatively activated or M2) macrophages play a role in repair of damaged tissues, including the infarcted hearts. Administration of IL-4 is known to augment M2 macrophages. This translational study thus aimed to investigate whether IL-4 administration is useful for the treatment of myocardial infarction. Long-acting IL-4 complex (IL-4c; recombinant IL-4 mixed with anti-IL-4 monoclonal antibody as a stabilizer) was administered after coronary artery ligation in mice. It was observed that IL-4c administration increased accumulation of CD206+F4/80+ M2-like macrophages predominantly in the injured myocardium, compared to the control. Sorted cardiac M2-like macrophages highly expressed wide-ranging tissue repair-related genes. Indeed, IL-4c administration enhanced cardiac function in association with reduced infarct size and enhanced tissue repair (strengthened connective tissue formation, improved microvascular formation and attenuated cardiomyocyte hypertrophy). Experiments using Trib1 -/- mice that had a depleted ability to develop M2 macrophages and other in-vitro studies supported that these IL-4-mediated effects were induced via M2-like macrophages. On the other hand, when administered at Day 28 post-MI, the effects of IL-4c were diminished, suggesting a time-frame for IL-4 treatment to be effective. These data represent proof-of-concept of efficacy of IL-4 treatment for acute myocardial infarction, encouraging its further development.


Biofilm formation by Staphylococcus aureus and Salmonella spp. under mono and dual-species conditions and their sensitivity to cetrimonium bromide, peracetic acid and sodium hypochlorite.
The aim of this study was evaluated the biofilm formation by Staphylococcus aureus 4E and Salmonella spp. under mono and dual-species biofilms, onto stainless steel 316 (SS) and polypropylene B (PP), and their sensitivity to cetrimonium bromide, peracetic acid and sodium hypochlorite. The biofilms were developed by immersion of the surfaces in TSB by 10 d at 37°C. The results showed that in monospecies biofilms the type of surface not affected the cellular density (p>0.05). However, in dual-species biofilms on PP the adhesion of Salmonella spp. was favored, 7.61±0.13Log10CFU/cm2, compared with monospecies biofilms onto the same surface, 5.91±0.44Log10CFU/cm2 (p<0.05). The mono and dual-species biofilms were subjected to disinfection treatments; and the most effective disinfectant was peracetic acid (3500ppm), reducing by more than 5Log10CFU/cm2, while the least effective was cetrimonium bromide. In addition, S. aureus 4E and Salmonella spp. were more resistant to the disinfectants in mono than in dual-species biofilms (p<0.05). Therefore, the interspecies interactions between S. aureus 4E and Salmonella spp. had a negative effect on the antimicrobial resistance of each microorganism, compared with the monospecies biofilms.


Antifungal Peptide P852 Effectively Controls Fusarium oxysporum, a Wilt-Causing Fungus, by Affecting the Glucose Metabolism and Amino Acid Metabolism as well as Damaging Mitochondrial Function.
Fusarium oxysporum causes wilt disease, which causes huge economic losses to a wide range of agricultural cash crops. Antifungal peptide P852 is an effective biocide. However, the mechanism of direct inhibition of pathogenic fungus needs to be explored. The proteomics and transcriptomics results showed that P852 mainly affected intracellular pathways such as glucose metabolism, amino acid metabolism, and oxidoreductase activity in F. oxysporum. P852 disrupts the intracellular oxidative equilibrium in F. oxysporum, and transmission electron microscopy observed mitochondrial swelling, disruption of membrane structure, and leakage of contents. Decreased mitochondrial membrane potential, mitochondrial cytochrome c leakage, and reduced ATP production were also detected. These results suggest that P852 is able to simultaneously inhibit intracellular metabolism and disrupt the mitochondrial function of F. oxysporum, exerting its inhibitory effects in multiple pathways together. The present study provides some insights into the multitargeted mechanism of fungus inhibition of antifungal lipopeptide substances produced by Bacillus spp.


Clinical and diagnostic findings in 20 patients with toxoplasmosis and the acquired immune deficiency syndrome.
The clinical and diagnostic findings in 20 cases of toxoplasmosis associated with the Acquired Immune Deficiency Syndrome (AIDS) were investigated in a prospective study of patients in south-east England. Individual details were recorded by a standardised questionnaire incorporating an evaluation of initial presentation, radiological findings, therapy and clinical progression. Toxoplasma serology was performed by reference assays and the presence of the parasite in tissue was sought by culture, histological examination and specific DNA detection. Clinical findings at presentation and results of radiological investigation were comparable with previously published experience from the USA. In contrast, sampling of the cerebrospinal fluid was rarely performed and was found to be of little clinical value. Examination of tissue samples was diagnostic when available, but was not performed routinely. Sulphonamide plus pyrimethamine was the treatment of choice in most cases and response to therapy was satisfactory, although a high incidence of toxicity was recorded.


[Single- and multi-unit fixed dental prostheses in relation to the occlusal system].
Occlusion concepts based on functional aspects offer more solid ground in the diagnostic process and in the treatment of (reduced) dentitions than morphologically and mechanically oriented occlusion concepts. Nevertheless, for occlusal reconstruction morphologically oriented guidelines are necessary. These guidelines are based on the border movements and positions of the mandible in the orofacial system, and on the location and modelling of the occlusal contacts in the occlusal system. The modelling of single- and multi-unit fixed dental prostheses must harmonize with the occlusal system. Moreover, an important feature is the relation of the anterior teeth which enables mutually protected occlusion. Characteristics of a healthy orofacial and occlusal system are: absence of pathology, perceived sufficient oral functions, variability inform and function, and adaptive capacity. When designing single- or multiunit fixed dental prostheses, a pragmatic starting point is to maintain the existing occlusion and the existing speech pattern unless arguments can be provided for alterations. The occlusal design should aim at optimizing oral functions, such as mandibular and occlusal stability.


Histone variant H3.3 residue S31 is essential for Xenopus gastrulation regardless of the deposition pathway.
Vertebrates exhibit specific requirements for replicative H3 and non-replicative H3.3 variants during development. To disentangle whether this involves distinct modes of deposition or unique functions once incorporated into chromatin, we combined studies in Xenopus early development with chromatin assays. Here we investigate the extent to which H3.3 mutated at residues that differ from H3.2 rescue developmental defects caused by H3.3 depletion. Regardless of the deposition pathway, only variants at residue 31-a serine that can become phosphorylated-failed to rescue endogenous H3.3 depletion. Although an alanine substitution fails to rescue H3.3 depletion, a phospho-mimic aspartate residue at position 31 rescues H3.3 function. To explore mechanisms involving H3.3 S31 phosphorylation, we identified factors attracted or repulsed by the presence of aspartate at position 31, along with modifications on neighboring residues. We propose that serine 31-phosphorylated H3.3 acts as a signaling module that stimulates the acetylation of K27, providing a chromatin state permissive to the embryonic development program.


Intestinal cells produce basement membrane proteins in vitro.
The epithelial-mesenchymal interface of the intestinal mucosa obviously plays an important role in supporting the mucosal architecture. Its significance for the process of migration and differentiation of the epithelial cells remains to be resolved. It consists of a basement membrane, the anchoring zone and the subepithelial connective tissue, the origin of which is unknown. We therefore established an in vitro model to study the development of the endodermal-mesenchymal interface of the fetal human and murine intestinal mucosa. The distribution of the interstitial collagens type I, III, VI and procollagen type III as well as the basement membrane components collagen type IV and laminin was investigated immunohistochemically in these fetal explant cultures. The cultures were also adapted to serum free culture conditions. It was evident that while laminin and collagen type IV could be detected in the primary intestinal epithelium, the formation of an authentic basement membrane required the presence of both the epithelial and the mesenchymal cells. Interstitial collagens and procollagen type III were produced exclusively by the mesenchymal cells. Basement membrane formation in vitro coincided with cytodifferentiation of the endodermal cells as betrayed by electron microscopy and the activity of brush border enzymes. In conclusion, the maturation of the endoderm and the formation of the subepithelial basement membrane require the intimate proximity of viable mesenchyme in vitro.