The rate of protein secretion dictates the temporal dynamics of flagellar gene expression.
Flagellar gene expression is temporally regulated in response to the assembly state of the growing flagellum. The key mechanism for enforcing this temporal hierarchy in Salmonella enterica serovar Typhimurium is the sigma(28)-FlgM checkpoint, which couples the expression of the late flagellar (P(class3)) genes to the completion of the hook-basal body. This checkpoint is triggered when FlgM is secreted from the cell. In addition to the sigma(28)-FlgM checkpoint, a number of other regulatory mechanisms respond to the secretion of late proteins. In this work, we examined how middle (P(class2)) and late (P(class3)) gene expression is affected by late protein secretion. Dynamic analysis of flagellar gene expression identified a novel mechanism where induction of P(class2) activity is delayed either when late protein secretion is abolished or when late protein secretion is increased. Using a number of different approaches, we were able to show that this mechanism did not involve any known flagellar regulator. Furthermore, the changes in P(class2) activity were not correlated with the associated changes in P(class3) activity, which was found to be proportional to late protein secretion rates. Our data indicate that both P(class2) and P(class3) promoters are continuously regulated in response to assembly and late protein secretion rates. These results suggest that flagellar regulation is more complex than previously thought.


Barriers to retinopathy screening in youth and young adults with type 1 diabetes.
Early detection of diabetic retinopathy (DR) is imperative; however, adherence to screening guidelines is poor. We hypothesized that youth and young adults with type 1 diabetes (T1D) who met American Diabetes Association criteria for recommended DR screening at the time of the study (10 years old or greater with diabetes duration of 5 years or more) would report multiple barriers to screening and that targeted barriers and subpopulations could be identified to improve access to care. 271 youth aged 10 to 26 years with T1D of at least 5 years duration were recruited from clinic, diabetes camp, and a diabetes conference and completed a patient-reported questionnaire. 113 (41.7%) reported at least one barrier to DR screening, with missed school and work being the most common (20.7%). Older participants (P = 0.007) and those with a longer diabetes duration (P = 0.018) were more likely to report barriers to screening. Recruitment location, sex, race and ethnicity, HbA1c, insulin regimen, and clinic visit frequency were not associated with reporting at least one barrier. Slightly less than two-thirds (62.1%) of participants who responded (n = 235 out of 271) adhered to recommended screening guidelines of the time and reported having an eye exam within the past year, 24.7% 12-23 months ago, 9.8% 2 years ago or more, and 3.4% had never had a DR exam. As older patients and those with longer duration of diabetes are more likely to have DR, targeted interventions to address barriers to care, such as, missed school and work should be implemented in these groups.


Toxicological problems with the REDY system.
Dialysate from the REDY dialysis system was examined for toxic elements, special attention being paid to the content of zirconium and aluminium. Also investigated was the concentration of formaldehyde in the rinsing fluid of three consecutive washings. The amount of zirconium and aluminium found in the dialysate was negligible. The concentration of formaldehyde was alarmingly high after two consecutive washings, a considerable amount (less than 50 mg) still remaining after three washings. It is recommended that at least three consecutive washings be performed, and that, if possible, formaldehyde be substituted by another antiseptic. Of special interest was the finding of a very high concentration of boron in the dialysate. It is suggested that this metal, which is a potentially toxic substance, may emanate from the patient. It is concluded that use of the REDY system carries no obvious toxicological risk.


Bifunctional and Self-Supported NiFeP-Layer-Coated NiP Rods for Electrochemical Water Splitting in Alkaline Solution.
Designing efficient and robust nonprecious metal-based electrocatalysts for overall water electrolysis, which is mainly limited by the oxygen evolution reaction (OER), for hydrogen production remains a major challenge for the hydrogen economy. In this work, a bimetallic NiFeP catalyst is coated on nickel phosphide rods grown on nickel foam (NiFeP@NiP@NF). This self-supported and interfacially connected electrode structure is favorable for mass transfer and reducing electrical resistance during electrocatalysis. The preparation of NiFeP@NiP@NF is optimized in terms of (i) the coprecipitation time of the NiFe Prussian blue analogue layer that serves as phosphides precursor and (ii) the phosphidation temperature. The optimized sample exhibits excellent OER performance delivering current densities of 10 and 100 mA cm-2 at low overpotentials of 227 and 252 mV in 1.0 M KOH, respectively, and maintaining 10 mA cm-2 for more than 120 h without obvious degradation. Moreover, it can also be operated as a hydrogen evolution electrocatalyst, requiring an overpotential of 105 mV at 10 mA cm-2 in the same medium. Thus, the as-prepared material was tentatively utilized as a bifunctional electrocatalyst in a symmetric electrolyzer, requiring a voltage bias of 1.57 V to afford 10 mA cm-2 in 1.0 M KOH, while exhibiting outstanding stability.


HIV in older Americans: an epidemiologic perspective.
The elderly population is increasing as baby boomers are beginning to approach retirement. People 65 years of age or older already constitute approximately one eighth of the U.S. population; this proportion is expected to double in the next 50 years. Older Americans have their own population-specific health challenges, such as Alzheimer's disease, osteoporosis, adult-onset diabetes, prostate cancer, menopause, and hypertension. Human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome (AIDS) are seldom discussed within this community. Prevention, counseling, testing, and education efforts are not being directed their way. In addition, few practitioners are experts both in HIV and health problems associated with aging, resulting in misdiagnosis, especially in the early stages when AIDS symptoms such as fatigue, weight loss, night sweats, and diminished appetite are dismissed as part of the aging process. Very few HIV-related social support services have been aimed at the needs of the elderly, perhaps because older Americans are not suspected to be sexually active or are assumed to be in a monogamous, heterosexual relationship. Older Americans are not suspected of drug use. Yet many are sexually active, often demonstrating risky sexual behavior, such as dispensing with the use of condoms; and the isolation that frequently accompanies old age can lead to alcoholism and injectable drug use. This article examines methods suggested in the literature both in terms of primary and secondary prevention of HIV/AIDS in older Americans. The cost of these efforts is enumerated, and organizations who gear their efforts in reaching and educating older Americans regarding their risks are described.


The effect of chloride-containing potassium supplements on chloride titrator estimates of dietary sodium intake.
To examine the effect of chloride-containing potassium supplements on chloride titrator estimates of dietary sodium intake, we gave normal subjects diet containing 10, 100, or 200 mEq/d sodium in random order either as such, or supplemented with one of two potassium supplements. One regimen consisted of potassium 45 mEq/d with 12 mEq/d chloride and 33 mEq/d of citrate and gluconate; the other contained 48 mEq/d potassium and 48mEq/d chloride. Increased potassium intake with either supplemented regimen resulted in increased 24-hour potassium excretion, which was manifested in only the diurnal collections. Increased chloride intake resulted in increased urinary chloride excretion both during the day and at night. At all chloride intakes, urinary sodium and chloride excretion were highly correlated. The 48 mEq/d chloride intake generated a relationship with the same slope but with a different intercept from the other two regimens. The highest chloride intake resulted in a greater chloride titrator reading; however, the relationship was sufficiently predictable that adjustments in interpretation could be easily made. We conclude that if daily potassium chloride intake is known, chloride titrators continue to be reliable tools for estimating dietary sodium intake.


Randomized placebo-controlled trial assessing a treatment strategy consisting of pravastatin, vitamin E, and homocysteine lowering on plasma asymmetric dimethylarginine concentration in mild to moderate CKD.
Chronic kidney disease (CKD) is associated with an increased incidence of cardiovascular disease (CVD). The Anti-oxidant Therapy In Chronic Renal Insufficiency (ATIC) Study showed that a multistep treatment strategy improved carotid intima-media thickness, endothelial function, and microalbuminuria in patients with stages 2 to 4 CKD. Increased plasma concentrations of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, have been linked to greater CVD risk in patients with CKD. The aim of this study is to assess effects of the multistep intervention on plasma ADMA concentrations in the ATIC Study. Secondary analysis of a randomized double-blind placebo-controlled trial. 93 patients with creatinine clearance of 15 to 70 mL/min/1.73 m(2) (according to the Cockcroft-Gault equation) from 7 outpatient clinics in Amsterdam, The Netherlands. The treatment group received sequential treatment consisting of pravastatin, 40 mg/d. After 6 months, vitamin E, 300 mg/d, was added, and after another 6 months, homocysteine-lowering therapy (folic acid, 5 mg/d; pyridoxine, 100 mg/d; and vitamin B(12), 1 mg/d, all in 1 tablet) were added and continued for another year. The control group received matching placebos. Plasma ADMA levels. 36 participants (77%) in the treatment group and 38 (83%) in the placebo group completed the study. Mean ADMA and symmetric dimethylarginine concentrations in the total study population were 0.53 +/- 0.07 (SD) and 1.14 +/- 0.46 mumol/L, respectively. After 24 months, there was no overall effect of the treatment strategy on ADMA concentrations (beta = -0.006; P = 0.27). Analysis of separate treatment effects suggested that vitamin E significantly decreased ADMA levels by 4% in the treatment group compared with the placebo group (multiple adjusted P = 0.02). The study was a secondary analysis, power calculation was based on the primary end point of carotid intima-media thickness, mean plasma ADMA levels were relatively low. Overall, a multistep treatment strategy consisting of pravastatin, vitamin E, and B vitamins had no effect on plasma ADMA levels in a stage 2 to 4 CKD population. This suggests that the beneficial effects of the intervention were not mediated by changes in ADMA levels. Possible ADMA-lowering effects of vitamin E deserve further attention.


Axillobifemoral Bypass Graft: A Student Dissection Experience.
As first-year medical students, we were excited, but nervous, to start the anatomy course. We were prepared to dedicate ourselves to the physical demands of dissection, and the hours of memorizing names and relations of countless anatomic features. We expected to leave the anatomy course with a comprehensive understanding of the human body that we would apply to our future studies and careers. We were not prepared, however, for the experience we had with our cadaver, Lucy.* Lucy was a small woman, but as we learned, she had endured a lot, physically and medically, in her 83 years of life. She had a pacemaker. She had coronary artery disease and a triple bypass procedure. She also had severe peripheral artery disease and had undergone at least one extraordinary surgical graft procedure to maintain blood flow into her lower extremities. The surprise of discovering a small piece of an axillobifemoral bypass graft and then continuing to uncover it, region by region, throughout the anatomy course, brought our dissection experience and our connection to Lucy to a more profound level than we could ever have anticipated. *The name Lucy was chosen as a pseudonym to protect the identity of the cadaver.


The non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) impairs late reconsolidation of passive avoidance learning in the day-old chick.
Both NMDA and non-NMDA receptors participate in the consolidation of passive avoidance learning (PAL) in the day-old chick. NMDA antagonists have also been implicated in reconsolidation processes following reminder-trials. In this study, we examined the effect of administering 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), a non-NMDA receptor antagonist, on reconsolidation following memory reactivation. New Hampshire x White leghorn cockerels were trained using a modified version of the PAL task. When CNQX was administered 20 min following a reminder trial, a retention deficit was detected at 90 min, but this had resolved by 24 h following the reminder. The parameters of the reconsolidation deficit were similar to those induced by CNQX injections post-training with the exception of their transience. This finding suggests that the action of non-NMDA receptors may perform a similar role in both consolidation and reconsolidation processes.


Gramicidin D enhances the antibacterial activity of fluoride.
Fluoride is a toxic anion found in many natural environments. One of the major bacterial defenses against fluoride is the cell envelope, which limits passage of the membrane-impermeant fluoride anion. Accordingly, compounds that enhance the permeability of bacterial membranes to fluoride should also enhance fluoride toxicity. In this study, we demonstrate that the pore-forming antibiotic gramicidin D increases fluoride uptake in Bacillus subtilis and that the antibacterial activity of this compound is potentiated by fluoride. Polymyxin B, another membrane-targeting antibiotic with a different mechanism of action, shows no such improvement. These results, along with previous findings, indicate that certain compounds that destabilize bacterial cell envelopes can enhance the toxicity of fluoride.


The effect of conditioning regimen and prescribed medications on hyposalivation in haematopoietic cell transplantation (HCT) patients: an 18-month prospective longitudinal study.
Haematopoietic cell transplantation (HCT) preceded by a conditioning regimen is an established treatment option for (non)malignant haematologic disorders. We aim to describe the development of hyposalivation over time in HCT recipients, and determine risk indicators. A multi-centre prospective longitudinal observational study was conducted. Unstimulated (UWS) and stimulated (SWS) whole saliva was collected before HCT, early post-HCT, and after 3, 6, 12, and 18 months. The effect of type of transplantation (allogeneic vs autologous) and intensity (full vs reduced) of the conditioning regimen on hyposalivation (UWS < 0.2 mL/min; SWS < 0.7 mL/min) was explored. A total of 125 HCT recipients were included. More than half of the patients had hyposalivation early post-HCT; a quarter still had hyposalivation after 12 months. The conditioning intensity was a risk indicator in the development of hyposalivation of both UWS (OR: 3.9, 95% CI: 1.6-10.6) and SWS (OR: 8.2, 95% CI: 2.9-24.6). After 3 and 12 months, this effect was not statistically significant anymore. Hyposalivation affects the majority of patients early post-HCT. The conditioning intensity and the type of transplantation were significant risk indicators in the development of hyposalivation. The number of prescribed medications, total body irradiation as part of the conditioning regimen and oral mucosal graft-versus-host disease did not influence hyposalivation significantly. Because of the high prevalence of hyposalivation, HCT recipients will have an increased risk of oral complications. It might be reasonable to plan additional check-ups in the dental practice and consider additional preventive strategies.


Prostate cancer prevention with 5-alpha reductase inhibitors: concepts and controversies.
We review the concepts surrounding prostate cancer prevention strategies with 5-alpha reductase inhibitors (5-ARIs) and the controversies associated with their use. Updated data have shown no increased risk of death from the diagnosis of higher risk cancer; however, 5-ARIs remain controversial and not approved for prostate cancer prevention. The main theme of the review identifies the success of reducing insignificant prostate cancer and the controversy with the increased association of higher risk prostate cancer by approximately 20%. The reduction was shown to be most significant reduction in low-grade prostate cancer. The initial concern about 5-ARI use was that it could potentially increase high-risk prostate cancer leading to higher mortality in those men. Higher mortality has not been seen in follow-up data; however, 5-ARIs continue to have a black box warning and are not approved for prostate cancer prevention.


A trial of the effects of soya-bean flour and soya-bean saponins on plasma lipids, faecal bile acids and neutral sterols in hypercholesterolaemic men.
1. The hypothesis that soya-bean saponins, by binding bile salts in the gastrointestinal lumen, are responsible for some of the plasma-cholesterol-lowering effect of soya-bean preparations, was tested. In a double-blind crossover study 50 g soya-bean flour/d, containing either 22 or 4 g saponins/kg (adjusted by ethanol extraction) was incorporated in biscuits as a substitute for biscuits or bread into the diet of ten outpatient hypercholesterolaemic men over two consecutive 4-week study periods. The diet was monitored to ensure constancy, saponin-rich foods excluded, faeces collected for bile acid and neutral sterol analysis, and blood taken for plasma lipoprotein lipid analysis. 2. Neither diet had any effect on cholesterol in any plasma lipoprotein fraction, on fasting plasma triglyceride, or on faecal bile acids and neutral sterols. 3. These results suggested that soya-bean saponins are not responsible for the hypocholesterolaemic effect of soya-bean products.


A FRET-based Protein Kinase Assay Using Phos-tag-modified Quantum Dots and Fluorophore-labeled Peptides.
We have developed a novel FRET-based assay to monitor protein kinase activity using quantum dots (QDs) and fluorophore-labeled substrate peptides. To develop a FRET-based protein kinase assay, it is important to consider the phosphate group recognition strategy and to ensure that the FRET pairs are close enough because the FRET efficiency is highly dependent on the distance between the FRET pairs. Here, we incorporated a phos-tag, which captures phosphate groups strongly and selectively, into a protein kinase assay to recognize phosphorylation. Our detection system was composed of phos-tag-modified QDs and Cy5-labeled substrate peptides. Because the phos-tags capture phosphate groups by forming dinuclear complexes, the Cy5-labeled substrate peptides are captured by the phos-tags on the QD surface upon protein kinase-mediated phosphorylation, which induces FRET from the QDs to Cy5 because of the approximation of Cy5 to the QDs. On the basis of the difference of this FRET efficiency, we successfully measured protein kinase A activity, which demonstrated the feasibility of our assay.


Integrin targeting for tumor optical imaging.
Optical imaging has emerged as a powerful modality for studying molecular recognitions and molecular imaging in a noninvasive, sensitive, and real-time way. Some advantages of optical imaging include cost-effectiveness, convenience, and non-ionization safety as well as complementation with other imaging modalities such as positron emission tomography (PET), single-photon emission computed tomography (SPECT), and magnetic resonance imaging (MRI). Over the past decade, considerable advances have been made in tumor optical imaging by targeting integrin receptors in preclinical studies. This review has emphasized the construction and evaluation of diverse integrin targeting agents for optical imaging of tumors in mouse models. They mainly include some near-infrared fluorescent dye-RGD peptide conjugates, their multivalent analogs, and nanoparticle conjugates for targeting integrin αvβ3. Some compounds targeting other integrin subtypes such as α4β1 and α3 for tumor optical imaging have also been included. Both in vitro and in vivo studies have revealed some promising integrin-targeting optical agents which have further enhanced our understanding of integrin expression and targeting in cancer biology as well as related anticancer drug discovery. Especially, some integrin-targeted multifunctional optical agents including nanoparticle-based optical agents can multiplex optical imaging with other imaging modalities and targeted therapy, serving as an attractive type of theranostics for simultaneous imaging and targeted therapy. Continued efforts to discover and develop novel, innovative integrin-based optical agents with improved targeting specificity and imaging sensitivity hold great promises for improving cancer early detection, diagnosis, and targeted therapy in clinic.


Halopolyspora alba gen. nov., sp. nov., isolated from sediment.
A novel halophilic, filamentous actinomycete, designated strain AFM 10251(T), was isolated from a sediment sample collected from the Dead Sea, Israel. The isolate grew with 10-35% multi-salts, and did not grow without NaCl or MgCl2. The isolate formed a white aerial mycelium, and long chains of arthrospores with more than 10 spores per chain. The spores were spherical or oval with warty surfaces, and sterile mycelium was present between individual spores. The isolate contained meso-diaminopimelic acid and a small proportion of LL-diaminopimelic acid as cell-wall diamino acids, and galactose and arabinose as whole-cell sugars. The major menaquinone was MK-9(H4). The polar lipids were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol and three unknown phospholipids. Major fatty acids were iso-C(16 : 0), iso-C(17 : 0), iso-C(15 : 0) and anteiso-C(17 : 0). The DNA G+C content of strain AFM 10251(T) was 66.7 mol%. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain AFM 10251(T) and the genus Actinopolyspora formed a distinct lineage. Analysis of the secondary structures of variable areas of the 16S rRNA gene showed that strain AFM 10251(T) was different from all recognized species of the genus Actinopolyspora and members of the family Pseudonocardiaceae. Analysis of the signature nucleotides of the 16S rRNA gene showed that strain AFM 10251(T) and Actinopolyspora halophila formed a single group, but with base pair differences at positions 127 : 234 and 183 : 194. On the basis of analysis of chemical and molecular characteristics, strain AFM 10251(T) is considered to represent a novel species of a new genus in the family Actinopolysporaceae, for which the name Halopolyspora alba gen. nov., sp. nov. is proposed. The type strain of Halopolyspora alba is AFM 10251(T) ( = DSM 45976(T) = CGMCC 4.7114(T)).


Suppression of the c-Jun N-terminal kinase pathway by 17beta-estradiol can preserve human islet functional mass from proinflammatory cytokine-induced destruction.
The c-Jun N-terminal kinase (JNK) activation occurs after islet isolation, oxidative stress, and proinflammatory cytokine (PIC) exposure to beta-cells. Previous studies demonstrated that 17beta-estradiol modulates the activity of JNK; therefore we assessed the effects of 17beta-estradiol on JNK activation on islet survival and function after transplantation. Isolated human pancreatic islets were incubated with PIC and 17beta-estradiol. Viability was analyzed by a colorimetric assay, islet mass by DNA content, JNK activity by Western blots, AP-1 nuclear activity with a promoter-Luciferase AP-1 responsive construct, and c-Fos, Jun-D, and ATF-2 nuclear activities by an enzyme-linked immunosorbent assay. Islet functionality was evaluated after transplantation in streptozotocin-induced diabetic NOD-SCID mice. The 17beta-estradiol enhanced islet viability and islet mass after exposure to PIC. A significant reduction in JNK activation occurred in islets treated with 17beta-estradiol, compared with controls, an effect partially dependent on estrogen receptors. The 17beta-estradiol induced a significant reduction in nuclear AP-1, c-fos, Jun-D, and ATF-2 activities. Animals that received 17beta-estradiol-treated islets had better islet functionality compared with saline solution-treated controls. The 17beta-estradiol improved isolated human pancreatic islets survival after PIC exposure by inhibition of JNK. These effects were associated with reduction in JNK targets, including the nuclear activities of transcription factors AP-1, c-Jun, c-Fos, Jun-D and ATF-2, involved in apoptosis in beta-cells. The 17beta-estradiol therapy may improve the results in clinical transplantation.


In vivo autofluorescence spectroscopy of oral premalignant and malignant lesions: distortion of fluorescence intensity by submucous fibrosis.
To test whether autofluorescence spectroscopy can be used for the diagnosis of oral neoplasia in a high-risk population, we characterized the in vivo autofluorescence spectra from oral submucous fibrosis (OSF) lesions and oral premalignant and malignant lesions in both OSF and non-OSF patients. Autofluorescence emission spectra were measured under the excitation wavelength of 330 nm, using a Xenon lamp-based fluorospectrometer coupled to a handheld optical fiber probe. Autofluorescence spectroscopies were analyzed among patients with OSF lesions, and oral lesions of epithelial hyperkeratosis (EH), epithelial dysplasia (ED), and squamous cell carcinomas (SCC) and normal oral mucosa (NOM) of healthy volunteers. We found that the most intensely autofluorescence emission peaks occurred at 380 nm and 460 nm. For comparing the spectral patterns among different groups of oral lesions and NOM, ratios of the area under the spectrum of 460+/-10 nm to that under the spectrum of 380+/-10 nm (denoted as A(460+/-10nm)/A(380+/-10nm)) were calculated. The mean ratio values increased gradually from OSF to NOM, to EH and ED, and to SCC. The ANOVA test showed significant differences in the ratio value among all categories of samples (P<0.01). On the other hand, we found that EH, ED, and SCC lesions on OSF patients had distorted autofluorescence intensity. The mean ratio values of EH, ED, and SCC between non-OSF and OSF patients show significant differences. Furthermore, an ANOVA test showed NOM is not distinguishable from EH and ED lesions on oral fibrotic mucosa (P>0.05). Autofluorescence spectroscopy can be used to diagnose EH, ED, and SCC lesions in non-OSF patients but not in OSF patients.


Cognitive mechanisms influence the relationship between social anxiety and depression among college students.
Social anxiety and depression are commonly comorbid and cause significant impairment in college students. Past research suggests that both poor attentional control and increased rumination are related to these disorders and independently mediate their relationship. Theory suggests that social anxiety loads working memory, thus decreasing attentional control, which influences rumination and depression. The current study aimed to investigate the potential combined influence of attention control and rumination on social anxiety and depression. Participants: Participants (80) were recruited from a large Midwestern university in September 2017. Methods: Participants completed questionnaires regarding social anxiety, attentional control, rumination, and depression and data were analyzed using bias-corrected bootstrapping analyses. Results: Results demonstrate a significant indirect relationship between social anxiety and depression through attentional control and rumination. Conclusions: Results indicated that college students with social anxiety may be at risk for depression due to decreased attentional control and increased rumination. Clinical implications are discussed.


The lymphatic vascular system: secondary or primary?
It has generally been accepted that the blood vascular system is primary and the lymphatic vascular system secondary. Diseases of the blood vascular system are the leading cause for mortality and morbidity in developed nations. In contrast, lymphedema is seldom life-threatening and can generally be well-managed by combined physiotherapy. During ontogeny, the blood vessels and the heart develop much earlier than the lymphatic vessels. However, there is growing evidence that the first vascular system occurring during ontogeny and phylogeny has lymphatic functions. Defense mechanisms are crucial for all organisms irrespective of their size. Macrophages precede the emergence of erythrocytes during ontogeny, and their circulation in the hemolymphatic (more accurately, lymphohematic) system of insects, which do not possess erythrocytes, shows that the lymphatic function is primary whereas the nutritive function is secondary, needed only in larger organisms. In molluscs and arthropods, which have an open vascular system, hemocyanin has both oxygen transporting and defense functions. In vertebrates, the early blood vessels have structural characteristics of lymphatics and express the lymphendothelial receptor flt-4 (Vascular Endothelial Growth Factor Receptor-3). Later, flt-4 becomes restricted to the definitive lymphatics, which are either formed from the primary vessels or from mesodermal lymphangioblasts. The primary lymphatic function has become overruled by the nutritive function in blood vessels of larger animals. The circular movement of cells is driven by a blood heart, which, however, is not an unique organ. Lymph hearts are present in lower vertebrates, still develop transiently in birds, and are vestigial in the contractile lymphangion which "circulates" immune cells. We conclude that the definitive lymphatics are perhaps secondary in mammals, but the blood vascular system seems to develop on the basis of an ancestral lymphatic system with lymph hearts.


Identification of the haematopoietic stem cell niche and control of the niche size.
Haematopoietic stem cells (HSCs) are a subset of bone marrow cells that are capable of self-renewal and of forming all types of blood cells (multi-potential). However, the HSC 'niche'--the in vivo regulatory microenvironment where HSCs reside--and the mechanisms involved in controlling the number of adult HSCs remain largely unknown. The bone morphogenetic protein (BMP) signal has an essential role in inducing haematopoietic tissue during embryogenesis. We investigated the roles of the BMP signalling pathway in regulating adult HSC development in vivo by analysing mutant mice with conditional inactivation of BMP receptor type IA (BMPRIA). Here we show that an increase in the number of spindle-shaped N-cadherin+CD45- osteoblastic (SNO) cells correlates with an increase in the number of HSCs. The long-term HSCs are found attached to SNO cells. Two adherens junction molecules, N-cadherin and beta-catenin, are asymmetrically localized between the SNO cells and the long-term HSCs. We conclude that SNO cells lining the bone surface function as a key component of the niche to support HSCs, and that BMP signalling through BMPRIA controls the number of HSCs by regulating niche size.


Impact of COVID-19 Pandemic on Hidradenitis Suppurativa Patients: a Cross-Sectional Study From Tertiary Referral Hospital.
Hidradenitis suppurativa (HS) is a chronic, disabling skin disorder which is characterized by recurrent attacks of nodule, abscess, sinus tract formation and scarring. Oral/topical antibiotics, oral retinoids and TNF-alpha inhibitors are used for the treatment of HS. In the present study, we aimed to determine the prevalence of coronavirus disease 2019 (COVID-19) real-time polymerase chain reaction (real-time PCR) positivity and the presence of COVID-19 related symptoms in relation to the age, gender, body mass index, disease duration, treatment used for HS, treatment duration and smoking. We conducted a comparative, cross-sectional study of 178 patients diagnosed with HS in a referral hospital. Age, gender, smoking status, body mass index, treatment modalities used for HS, the presence of COVID-19 related symptoms, history of close contact to a person with COVID-19 and COVID-19 real time-PCR results were determined by a telephone questionnaire. Sixty-three patients were female, whereas 115 patients were male. During COVID-19 pandemic, 94 out of 178 patients had COVID-19 related symptoms; COVID-19 real time-PCR test was performed in 109 (61.2%) patients. Thirty (27.5%) cases tested positive for COVID-19 whereas 79 (72.5%) tested negative. Patients having COVID-19 related symptoms were shown to have statistically significantly higher mean age compared to the ones who did not have any symptoms (P = 0.031). No statistically significant relationship was found COVID-19 real time-PCR positivity and the type of treatment administered for HS when categorized as tumor necrosis factor-alpha inhibitor, oral retinoid, topical antibiotic and oral antibiotic group (P > 0.05).


Academic Performance and Lifestyle Behaviors in Australian School Children: A Cluster Analysis.
Poor academic performance has been linked with particular lifestyle behaviors, such as unhealthy diet, short sleep duration, high screen time, and low physical activity. However, little is known about how lifestyle behavior patterns (or combinations of behaviors) contribute to children's academic performance. We aimed to compare academic performance across clusters of children with common lifestyle behavior patterns. We clustered participants (Australian children aged 9-11 years, n = 284) into four mutually exclusive groups of distinct lifestyle behavior patterns, using the following lifestyle behaviors as cluster inputs: light, moderate, and vigorous physical activity; sedentary behavior and sleep, derived from 24-hour accelerometry; self-reported screen time and diet. Differences in academic performance (measured by a nationally administered standardized test) were detected across the clusters, with scores being lowest in the Junk Food Screenies cluster (unhealthy diet/high screen time) and highest in the Sitters cluster (high nonscreen sedentary behavior/low physical activity). These findings suggest that reduction in screen time and an improved diet may contribute positively to academic performance. While children with high nonscreen sedentary time performed better academically in this study, they also accumulated low levels of physical activity. This warrants further investigation, given the known physical and mental benefits of physical activity.


Effect of interval training programme on pulse pressure in the management of hypertension: a randomized controlled trial.
Pulse pressure (PP), might be a stronger determinants of cardiovascular risk. To investigate the effect of interval training program on PP in subjects with hypertension. Two hundred and forty five male patients with mild to moderate (Systolic Blood Pressure [SBP] between 140-179 & Diastolic Blood Pressure [DBP] between 90-109 mmHg) essential hypertension were age-matched and grouped into exercise and control groups. The exercise (work: rest ratio of 1:1) groups involved in an 8-weeks interval training programs of between 45-60 minutes, at intensities of 60-79% of HR max (maximum heart rate), while the control group remained sedentary during this period. SBP, DBP, VO2max and PP were assessed. Findings of the study revealed significant correlation between PP and blood pressure; correlation of PP with SBP was much stronger (95% variance). Also, there was significant effect of the exercise training program on SBP, DBP and PP. Changes in VO2max also negatively correlated with changes in PP (r= -.285) at p<0.05. Moderate intensity interval training programs is effective in the non-pharmacological management of hypertension and may prevent cardiovascular event through the down regulation of PP in hypertension.


[Protective effect of rutin against lipopolysaccharide-induced acute lung injury in mice].
To investigate the protective effect of rutin against acute lung injury induced by lipopolysaccharide (LPS). Thirty C57BL/6 mice were randomly divided into control group, LPS-induced acute lung injury model group and treatment (LPS+Rutin) group. The pathological changes of the lung tissue were observed microscopically on paraffin sections with HE staining, and the lung wet/dry weight ratio was measured. The levels of TNF-α and IL-1β in the bronchoalveolar lavage fluid (BALF) were measured with ELISA, and the expressions of α-ENaC were detected with RT-PCR and Western blotting. Pathological examination of the lung tissue revealed distinct inflammation, congestion and edema in the model group. The mice in the treatment group showed significantly milder lung injuries than those in the model group. Compared with the control group, the model group showed significantly increased lung wet/dry ratio and contents of TNF-α and IL-1β in BALF but lowered expressions of α-ENaC mRNA and protein. Compared with the model group, rutin treatment significantly decreased the lung wet/dry ratio and TNF-α and IL-1β levels in the BALF and increased the expressions of α-ENaC mRNA and protein. Rutin can inhibit the pulmonary inflammation and increase the expression of alveolar epithelial sodium channel protein to alleviate LPS-induced acute lung injury in mice.


A statherin and calcium enriched layer at the air interface of human parotid saliva.
Parotid saliva placed in 35-mm-diameter tissue culture dishes developed increasing surface viscoelasticity at the interface with air. A surface layer became visible with time, and was collected and analysed by protein electrophoresis which indicated that a single protein (pI 4.2; molecular mass approx. 6 kDa) predominated. Western blot analysis demonstrated that the major protein band reacted with an antiserum directed against the C-terminal of the calcium-binding salivary protein statherin. Matrix-assisted laser-desorption ionization-time-of-flight MS analysis gave a molecular mass of 5380 Da for the protein, corresponding to the molecular mass of statherin. Staining of film protein in electrophoresis gels was compared with statherin synthesized on a solid phase, and the mean statherin content of film formed from 1 ml of parotid saliva was measured as 7 nmol. The mean calcium content of the surface layer was 250 nmol. Surface rheology was greatly decreased in the presence of EDTA, whereas surface tension of saliva was unaffected by calcium chelation, suggesting that protein accumulated at the surface was unaffected. The results suggest that a layer rich in statherin forms at the interface of saliva and air, and that the surface rheology developed is dependent upon protein interactions mediated by calcium. The surface layer may enhance the function of saliva as a protective layer on the mucosal surfaces and teeth.


Ovarian cancer specific kallikrein profile in effusions.
Kallikreins belong to the serine protease family and their roles as cancer associated markers have been proposed. However, a comprehensive and parallel analysis of different secreted kallikreins in ovarian cancer has not been performed. This study was undertaken to profile the secreted kallikreins in cancer effusion supernatants. We applied ELISA to measure the protein levels of nine kallikreins (4-8, 10, 11, 13, and 14) in a total of 221 effusion supernatants obtained from ovarian cancer, benign non-neoplastic diseases and a variety of other neoplastic diseases. Our results demonstrated that ovarian cancer effusions contained higher levels of all kallikreins analyzed except kallikrein 4, as compared to benign effusions (p<0.0005) and other cancer types (p<0.03). Unsupervised principal component analyses demonstrated a unique cluster of ovarian cancer samples which were distinct from benign effusions and other cancer groups based on measurements of secreted kallikreins 5-8, 10, 11, 13 and 14. Supervised combinations of the eight kallikreins achieved areas under ROC curve of 0.994 and 0.961 in separating ovarian cancer from benign effusion groups and other cancer groups, respectively. Among kallikreins, kallikreins 6, 7, 8, and 10 showed the highest statistical power in distinguishing ovarian cancer from benign controls and other cancer groups and these kallikreins could diagnose false negative cases based on cytology. The above findings indicate that kallikreins 6, 7, 8 and 10 are the four most specific secreted kallikreins in ovarian cancer. These kallikreins may have clinical implications in the differential diagnosis of ovarian carcinoma from benign diseases and other cancer types.


Blocking of stimuli and the free recall and subjective organization of EMR adolescents.
Number of unrelated stimulus items presented consistently and spatially grouped (1, 3, or 5) was studied in a multitrial free recall experiment with EMR adolescents. This blocking was effective in (a) improving recall from recently presented items, (b) increasing subjective organization, and (c) leading to the formation of stable clusterable output groups. Some evidence suggested that overall recall also increased as a result of the consistent and simultaneous presentation. Discussion of the results emphasized that for a retarded population the relationship between organization and recall may not be strong unless intensive strategy training is employed.


The Patient Health Questionnaire depression screener in spinal cord injury.
Although depression is not inevitable following spinal cord injury/dysfunction (SCI/D), it can have a negative impact on rehabilitation. Evidence-based assessment of depression utilizing self-report instruments, such as the Patient Health Questionnaire-9 (PHQ-9), is considered good clinical practice. Although the PHQ-9 has been studied in individuals with SCI/D, little is known about the clinical utility of the Patient Health Questionnaire-2 (PHQ-2). Traditional cutoff scores for the PHQ-2 were examined to explore their operating characteristics as related to PHQ-9 results. Archival data were collected for 116 Veterans with SCI/D who completed the PHQ-2 and PHQ-9 as one component of their routine, comprehensive SCI annual evaluation at a Veterans Affairs Medical Center. Logistic regressions were performed to determine the impact of different cutoff scores for the PHQ-2 on the likelihood that participants would endorse clinically significant levels of depressive symptoms on the PHQ-9 (≥10). Using a cutoff score of 3 or greater correctly classified 94.8% of the cases, outperforming the other cutoff scores. A cutoff score of 3 or greater had a sensitivity of 83.3% and specificity of 97.8%, and yielded a positive predictive value of 90.9% and a negative predictive value of 95.7%. The PHQ-2 shows promise as a clinically useful screener in the community-residing SCI/D population. Findings regarding the presence of suicidal ideation emphasize the importance of routine screening for depressive symptomatology in the SCI/D population. Future research should investigate the role of the PHQ-2 in clinical decision-making and treatment monitoring.


Factors Affecting User's Behavioral Intention and Use of a Mobile-Phone-Delivered Cognitive Behavioral Therapy for Insomnia: A Small-Scale UTAUT Analysis.
A mobile app could be a powerful medium for providing individual support for cognitive behavioral therapy (CBT), as well as facilitating therapy adherence. Little is known about factors that may explain the acceptance and uptake of such applications. This study, therefore, examines factors from an extended version of the Unified Theory of Acceptance and Use of Technology (UTAUT2) model to explain variation between people's behavioral intention to use a CBT for insomnia (CBT-I) app and their use-behavior. The model includes eight aspects of behavioral intention: performance expectancy, effort expectancy, social influence, self-efficacy, trust, hedonic motivation, anxiety, and facilitating conditions, and investigates further the influence of the behavioral intention and facilitating conditions on app-usage behavior. Data were gathered from a field trial involving people (n = 89) with relatively mild insomnia using a CBT-I app. The analysis applied the Partial Least Squares-Structural Equation Modeling method. The results found that performance expectancy, effort expectancy, social influence, self-efficacy, trust, and facilitating conditions all explained part of the variation in behavioral intention, but not beyond the explanation provided by hedonic motivation, which accounted for R2 = 0.61. Both behavioral intention and facilitating conditions could explain the use-behavior (R2 = 0.32). We anticipate that the findings will help researchers and developers to focus on: (1) users' positive feelings about the app as this was an indicator of their acceptance of the mobile app and usage; and (2) the availability of resources and support as this also correlated with the technology use.


Type I and II positive allosteric modulators differentially modulate agonist-induced up-regulation of α7 nicotinic acetylcholine receptors.
Long-term treatment with nicotine or selective α7 nicotinic acetylcholine receptor (nAChR) agonists increases the number of α7 nAChRs and this up-regulation may be involved in the mechanism underlying the sustained procognitive effect of these compounds. Here, we investigate the influence of type I and II α7 nAChR positive allosteric modulators (PAMs) on agonist-induced α7 nAChR up-regulation. We show that the type II PAMs, PNU-120596 (10 μM) or TQS (1 and 10 μM), inhibit up-regulation, as measured by protein levels, induced by the α7 nAChR agonist A-582941 (10 nM or 10 μM), in SH-EP1 cells stably expressing human α7 nAChR, whereas the type I PAMs AVL-3288 or NS1738 do not. Contrarily, neither type I nor II PAMs affect 10 μM nicotine-induced receptor up-regulation, suggesting that nicotine and A-582941 induce up-regulation through different mechanisms. We further show in vivo that 3 mg/kg PNU-120596 inhibits up-regulation of the α7 nAChR induced by 10 mg/kg A-582941, as measured by [(125)I]-bungarotoxin autoradiography, whereas 1 mg/kg AVL-3288 does not. Given that type II PAMs decrease desensitization of the receptor, whereas type I PAMs do not, these results suggest that receptor desensitization is involved in A-582941-induced up-regulation. Our results are the first to show an in vivo difference between type I and II α7 nAChR PAMs, and demonstrate an agonist-dependent effect of type II PAMs occurring on a much longer time scale than previously appreciated. Furthermore, our data suggest that nicotine and A-582941 induce up-regulation through different mechanisms, and that this confers differential sensitivity to the effects of α7 nAChR PAMs. These results may have implications for the clinical development of α7 nAChR PAMs.


Repeated exposures to cobalt or chromate on the hands of patients with hand eczema and contact allergy to that metal.
The present study aimed at evaluating the effects of daily repeated exposures to low cobalt or chromate concentrations on the hands of patients with hand eczema and cobalt or chromate allergy. For 2 weeks, the patients immersed a finger for 10 min daily into the appropriate metal salt solution in water. During the 1st week, this was a 10 or 50 mg/l cobalt concentration or a 10 mg/l chromate concentration, and, during the 2nd week, a 100 or 200 mg/l cobalt concentration or a 100 mg/l chromate concentration. This regimen elicited a flare of hand eczema only in the chromate-exposed chromate-sensitive patients. During the exposure period, accumulation of cobalt or chromate in the nail was demonstrated. Standardization of chemical methods of quantification of skin exposure to allergens, combined with experimental exposure studies in patients with specific contact allergy, will increase the possibility of providing evidence-based medicine in the area of allergic contact dermatitis in the future.


Laboratory pilot scale study for H2S removal from biogas in an anoxic biotrickling filter.
The purpose of this laboratory pilot scale study at the Wastewater Technology Centre (WTC), Environment Canada, Burlington, ON was to investigate the anaerobic biological removal of H2S from biogas under real-time operating conditions. Biogas produced in a 538 litre pilot anaerobic digester was continuously fed into a 12 litre biotrickling filter containing plastic fibres as packing bed media. The process was monitored for several months. The biogas flowrate and H2S concentration ranged between 10 to 70 L/h and 1,000 to 4,000 ppmv respectively over the course of the test period. Nitrate-rich wastewater from a pilot scale sequencing batch reactor effluent was used as the nutritive solution for the biotrickling filter. The paper presents the influence of several operational parameters such as biogas flowrate, hydrogen sulphide concentration and composition of nutrient solution on process performance. To date, our results show H2S removal rates up to 100% without adverse effects on the methane concentration of the biogas. No system deterioration was observed over long term operation. This non-conventional technology is very promising and could be considered for full scale applications.


Health care economics is changing--the law is sure to follow.
Law is intimately related to economics. As the economic relationships in a market change, the legal landscape evolves accordingly. Even if no health care reform is enacted at the federal level, ever-increasing portions of today's managed indemnity sector will convert to plans constraining enrollee choice and seeking to deliver cost-effective care through risk-sharing relationships (both corporate and contractual) with providers. This is inevitable, given employer and federal government pricing demands, and it is changing the face of health care law. If federal reform is enacted and/or the systems adopted in Minnesota, Maryland, Washington, and Florida (to name a few) are replicated elsewhere, the legal concerns of physicians and other providers will shift even more dramatically. In this article, some of the legal fall-out from these economic developments is discussed.


The role of regulatory T cells in ovarian cancer.
Regulatory T cells (T(reg)), also termed suppressor T cells, control self-reactive T cells in the periphery, thereby conferring protection against immunologic self-destruction. While T(reg) are essential for the prevention of autoimmunity, they also inhibit immune responses against tumor antigens. This is corroborated by an increased mortality rate associated with the presence of a high number of intratumoral T(reg). Tumor infiltration by non-T(reg), on the other hand, is predictive for a substantially longer patient survival. These clinical data suggest that ovarian cancer patients can spontaneously mount effective antitumor immune responses that are undermined by T(reg)-mediated tolerization. The present article reviews clinical and experimental findings on T(reg) in ovarian cancer, with special regard to potential therapeutic implications, which may result from the existing evidence.


Prophylactic methylxanthine for prevention of apnoea in preterm infants.
Recurrent apnoea is common in preterm infants. These episodes can lead to hypoxaemia and bradycardia, which may be severe enough to require the use of positive pressure ventilation. In infants with apnoea, methylxanthine treatment has been used successfully to prevent further episodes. It is possible that prophylactic therapy given to all very preterm infants soon after birth might prevent apnoea and the need for additional ventilator support. To determine the effect of prophylactic treatment with methylxanthine on apnoea, bradycardia, episodes of hypoxaemia, use of mechanical ventilation, and morbidity in preterm infants at risk for apnoea of prematurity The standard search strategy of the Neonatal Review Group was updated in August 2010. This included searches of the Cochrane Central Register of Controlled Trials, Oxford Database of Perinatal Trials, MEDLINE, CINAHL and EMBASE. All trials using random or quasi-random patient allocation in which prophylactic methylxanthine (caffeine or theophylline) was compared with placebo or no treatment in preterm infants were eligible. The standard methods of the Cochrane Collaboration and its Neonatal Review Group were used. Three studies were eligible for inclusion in the review. Two small studies (randomising a total of 104 infants) evaluated the effect of prophylactic caffeine on short term outcomes. There were no meaningful differences between the caffeine and placebo groups in the number of infants with apnoea, bradycardia, hypoxaemic episodes, use of IPPV or side effects in either of the studies. Only two outcomes (use of IPPV and tachycardia) were common to the two studies and meta-analysis showed no substantive differences between the groups. One large trial of caffeine therapy (CAP 2006) in a heterogeneous group of infants at risk for and having apnoea of prematurity demonstrated an improved rate of survival without developmental disability at 18 to 21 months corrected age. The reports of the subgroup of infants treated with prophylactic caffeine did not demonstrate any significant differences in clinical outcomes except for a decrease in the risk of PDA ligation. The results of this review do not support the use of prophylactic caffeine for preterm infants at risk of apnoea.Any future studies need to examine the effects of prophylactic methylxanthines in preterm infants at higher risk of apnoea. This should include examination of important clinical outcomes such as need for IPPV, neonatal morbidity, length of hospital stay and long term development.


Nutrition data use and needs: Findings from an online survey of global nutrition stakeholders.
There is growing global demand for country-specific information to track nutritional status and its determinants, including intervention coverage. Periodic population-based surveys form the backbone of most national nutrition information systems. However, data on the coverage of many nutrition specific and sensitive interventions remain sparse. An online survey was administered to the international nutrition community in 2018 through relevant listservs and professional networks to characterize their use of nutrition-related indicators and data sources. Respondents were asked about their professional background, access and use of specific indicators and data sources in the previous year, and unmet data needs. Results were tabulated by respondent characteristics and χ2 tests used for statistical testing. Complete survey responses were received from 235 respondents, the majority from non-governmental organizations and research communities, and few from governments. Demographic Health Surveys (DHS) were the most frequently accessed country-specific data source and the Global Nutrition Report (GNR) was the most accessed consolidated data source, each accessed by approximately 75% of respondents. Respondents with a multi-country focus were more likely to have accessed DHS than those with a single-country focus (85% vs 60%, P < 0.001). Similarly, respondents with a multi-country focus were more likely to have accessed the GNR compared to those with a single-country focus (82% vs 66%, P < 0.05). The most commonly accessed indicators overall were the prevalence of exclusive breastfeeding (69%), child minimum dietary diversity (66%), under-5 stunting (65%), and under-5 wasting (65%). Reported data gaps included adult and household diet quality indicators (n = 32), nutrition-sensitive intervention coverage (n = 25), and infant and young child feeding promotion coverage (n = 11). Lack of data availability for the desired geographic level (82%) or demographic group of interest (82%) and out-of-date data (77%) were common data challenges experienced by respondents. The survey results highlight the continued need for high-quality, actionable nutrition data to help facilitate progress towards national and global nutrition targets.


[The radon therapy: radon inhalation spa in Kowary].
In this paper the measurements of radon-222 concentration in the air of Kowary Radon Inhalatorium in the vicinity of Jelenia Góra, Lower Silesia, Poland, performed by Radiation Protection and Radiobiology Department of National Institute of Hygiene in Warsaw, have been presented. For the measurements the integration method with the application of charcoal canisters have been used. The radon concentration was found within the very broad ranges from about 4 to 420 kBq m-3 depending of the season of the year. Basing on the radon concentration measurements during the inhalation therapy session and taking into account the equilibrium factor of 0.8 the doses to the bronchi of the patients in range from 1.2 to about 204 mSv (0.12-20.4 rem) have been assessed. The majority of patients (ca. 76%) received the doses between 115 and 204 mSv.


A cross-sectional study on oral health and dental care in intellectually able adults with autism spectrum disorder.
Autism spectrum disorder (ASD) is characterized by impairments in social interaction and communication, restricted patterns of behaviour, and unusual sensory sensitivities. The hypotheses to be tested were that adult patients with ASD have a higher caries prevalence, have more risk factors for caries development, and utilize dental health care to a lesser extent than people recruited from the normal population. Forty-seven adults with ASD, (25 men, 22 women, mean age 33 years) and of normal intelligence and 69 age- and sex-matched typical controls completed a dental examination and questionnaires on oral health, dental hygiene, dietary habits and previous contacts with dental care. Except for increased number of buccal gingival recessions, the oral health was comparable in adults with ASD and the control group. The group with ASD had less snacking, but also less frequent brushing of teeth in the mornings. The stimulated saliva secretion was lower in the ASD group, regardless of medication. Frequencies of dental care contacts were equal in both groups. The most common reason for missing a dental appointment was forgetfulness in the ASD group. Adults with ASD exhibited more gingival recessions and considerably lower saliva flow compared to healthy controls. Despite equal caries prevalence, the risk for reduced oral health due to decreased salivary flow should be taken into consideration when planning dental care for patients with ASD. Written reminders of dental appointments and written and verbal report on oral health status and oral hygiene instructions are recommended.


Role of D535 and H538 in endogenous toxicity of xenocin from Xenorhabdus nematophila.
Bacteriocins are the toxic proteins produced by bacteria under stress condition to inhibit the growth of closely related bacterial strain(s). In our earlier study, purified recombinant xenocin-immunity protein complex from Xenorhabdus nematophila showed detrimental effect on six different insect gut residing bacteria. In this study, endogenous toxicity assay with xcinA and its catalytic domain under tightly regulated ara promoter was performed. Multiple sequence alignment and homology modelling revealed six conserved amino acid residues in the catalytic domain of xenocin. Site-directed mutagenesis was performed in all the conserved residues, followed growth profile analysis of all the mutants by endogenous toxicity assay. Among the six different conserved sites in catalytic domain of xenocin, we have identified one position where mutation resulted in no measurable reduction in the endogenous toxicity (K564), three positions with measurable reduction in the endogenous toxicity (E542, H551 and R570) and two positions where mutation caused a significant reduction in the toxicity (D535 and H538). Endogenous toxicity assay is validated by in vitro RNA degradation assay. Structural integrity of purified recombinant proteins was confirmed through circular dichroism and fluorescence spectroscopy. Our results indicate that D535 and H538 act as the acid-base pair for RNA hydrolysis.


Current applications of electrotherapeutics in collagen healing.
Electrical current flow appears to be integral to the healing of collagen containing tissue, i.e., bone, cartilage, ligaments, tendons and skin. Accordingly, it is reasonable to hypothesize that externally applied electrical fields should be able to enhance healing, especially in conditions that have resisted more standard treatments. Nevertheless, applications of electrotherapeutics is challenging because the precise mechanism of action is unknown and, accordingly, there is an almost unlimited combination of stimulation parameters (e.g., type of waveform, voltage, current, phase, frequency, etc.) that can be applied to a treatment site. Presently, of the three major types of electrical stimulation, i.e., direct, and capacitive and inductive coupling, there is a growing trend toward utilization of the latter because of its efficacy and greater margin of safety. Although the mechanisms of action for enhanced healing of all three types remain elusive there is increasing evidence that electrical stimulation exerts its influence via effects at the cellular and/or molecular levels within the tissue. Utilization of electrotherapeutics has been most prevalent in bony injuries resistant to healing, but applications to severe lesions of skin and ligaments, and even to degenerative joint disease seems promising as cartilage has been shown to be more responsive than bone to applied electrical energy. We conclude that there is a clear trend toward greater orthopedic utilization of inductive stimulation and that, despite the lack of definitive guidelines relating specific parameters with specific conditions, electrotherapeutics appears to be a safe and often effective treatment for collagen containing tissues in many cases in which more standard therapies have failed.


Rizatriptan: an update of its use in the management of migraine.
Rizatriptan is an orally active serotonin 5-HT(1) receptor agonist that potently and selectively binds to 5-HT(1B/1D) subtypes. Earlier clinical trials demonstrated that rizatriptan 5 or 10mg is more effective than placebo at providing pain relief and a pain-free state, relieving associated symptoms of migraine, normalising functional ability and improving patient quality of life, and showed that rizatriptan provides faster freedom from pain and reduces nausea to a greater extent than oral sumatriptan. More recently, rizatriptan 10mg was shown to be more effective than zolmitriptan 2.5mg or naratriptan 2.5mg at producing a pain-free state 2 hours postdose. Furthermore, compared with naratriptan, significantly more patients who received rizatriptan were pain free or had pain relief from 1 hour onwards. The number of patients with normal functional ability at 2 hours was significantly higher after rizatriptan than after naratriptan or zolmitriptan. Rizatriptan was also generally more effective than zolmitriptan or naratriptan at relieving migraine-associated symptoms. Rizatriptan is generally well tolerated and adverse events are usually mild and transient. The most common adverse events associated with rizatriptan in recent randomised trials were asthenia/fatigue, dizziness, somnolence and nausea. There was a trend towards a lower incidence of adverse events with rizatriptan compared with zolmitriptan (31.2 vs 38.8%). However, rizatriptan was associated with a significantly higher incidence of adverse events than naratriptan (39 vs 29%). The incidence of chest pain was similar after the administration of rizatriptan, zolmitriptan or naratriptan (2 to 4%). Rizatriptan is an effective drug for the acute treatment of moderate or severe migraine. Oral rizatriptan 5 and 10mg have shown greater efficacy than placebo in providing pain relief, an absence of pain, relief from associated symptoms, normal functional ability and an improvement in patient quality of life. Earlier results showed that rizatriptan provides faster freedom from pain and reduces nausea to a greater extent than oral sumatriptan. More recent studies have shown that rizatriptan 10mg provides faster pain relief and a higher percentage of patients with an absence of pain and normal functional ability at 2 hours than naratriptan 2.5mg or zolmitriptan 2.5mg. The efficacy of rizatriptan is retained when used in the long term and the drug is generally well tolerated. Although well designed studies comparing rizatriptan with almotriptan, eletriptan and frovatriptan would further define the position of rizatriptan, current data suggest rizatriptan should be considered as a first-line treatment option in the management of migraine.


Efficacy and safety of Tripterygium wilfordii hook F versus acitretin in moderate to severe psoriasis vulgaris: a randomized clinical trial.
Few clinical trials have evaluated the efficacy and safety of Tripterygium wilfordii Hook F (TwHF) compared with acitretin in psoriasis. We aimed to compare the efficacy and safety of TwHF compared with acitretin in the treatment of moderate to severe psoriasis vulgaris. Adults with Psoriasis Area Severity Index (PASI) score ≥ 10 and psoriasis-affected body surface area ≥ 10% were randomized into a TwHF (20 mg, 3 times a day) or acitretin group (30 mg, once a day). The treatment course lasted for 8 weeks. Patients were assessed at baseline and at 2, 4, and 8 weeks. Laboratory tests were performed at baseline, week 4, and week 8. The data were analyzed using paired samples t-test or analysis of variance (ANOVA). A total of 115 patients was enrolled (58 TwHF; 57 acitretin). The median PASI score improved in the TwHF group by 50.4% and in the acitretin group by 42.7%. There was no significant difference in median PASI improvement between two groups at 2, 4, and 8 weeks. There was also no significant difference in PASI 25, PASI 50, PASI 75, and PASI 90 response between the two groups at 2, 4, and 8 weeks. There was a significant increase in the level of aspartate transaminase and triglycerides in the TwHF group (P = 0.026 and P = 0.011, respectively). In the acitretin group, there was a significant increase in the level of alanine transaminase, cholesterol, and high-density lipoprotein (P = 0.030, P < 0.01, and P < 0.01, respectively). There was no significant difference in treatment efficacy between the TwHF and acitretin groups within 8 weeks, but there were fewer treatment-related adverse events in the TwHF group.


Epithelial lining methods in esophageal repair: a comparative study using pedicle flaps in cats.
Methods of restoring luminal lining in repair of partial-circumferential esophageal defects were evaluated to compare incidences of strictures and fistulas and quality of surface lining. In cats 50% and 67% circumferential esophageal defects were repaired by direct closure or pedicle flaps (latissimus dorsi) that were unlined (lining restored by epithelialization from wound margins) or that carried lining of normal skin (myocutaneous flaps), skin grafts, or mucosal grafts. Repairs were evaluated for esophagocutaneous fistulas, luminal stricture, flap luminal surface area, and quality of epithelial surface 6 weeks after surgery. Direct closure of 50% circumferential defects was as satisfactory as any flap repair method. Direct closure of 67% circumferential defects caused high incidences of fistulas and strictures, which were lessened by flap reconstructions. Among flap lining methods, normal skin (myocutaneous flaps) gave the lowest incidence of fistulas and strictures and the highest surface quality, but a high incidence of skin paddle loss occurred in this model. Split-thickness epithelial grafts were nearly as satisfactory as myocutaneous flaps, and less lining loss occurred. Epithelialization of unlined flaps gave the poorest results since lining was thin and often incomplete, and wound contraction produced loss of surface area and strictures. The findings are discussed from a perspective of wound healing physiology, and implications for clinical application are presented.


Becoming a guest in your own home: Home care in Sweden from the perspective of older people with multimorbidities.
To describe the meaning of the phenomenon home care from the perspective of older persons who live alone with multimorbidity. In line with worldwide changing demographics, conditions for older people in need of home care are changing. In Sweden there is a stay-in-place policy and older people are expected to live and be cared for in their own home as long as possible. Home care, instituted by different laws, is a challenge affecting the older person when the private home becomes a workplace. This study uses a qualitative design with a lifeworld approach. The study having been conducted in Sweden in 2016, the researchers interviewed 12 older persons that live alone and receive home care. Data were analysed using qualitative content analysis. The findings illustrate four sub-themes: adapting to a caring culture, feeling exposed, unable to influence care and forced relations. The overall theme reveals that older people experience a life-changing situation when receiving home care and they become a guest in their own home. Becoming older with increased needs means to disrupt one's life when one's private home becomes a public arena. The gap between an older person's rights by law and the older person's experiences of receiving home care needs to be highlighted to meet the oncoming challenges in providing a home care that includes participation of the older themselves. Only then can care be offered that enables older people to have a sense of control and experience their home as their own. The findings emphasise the need to view older people as being self-determinant and independent. Older people receiving home care need to be seen as individuals, and their entire life situation should be considered by also acknowledging the important role played by relatives and caregivers.


Prevalence of self-reported diagnosis of osteoporosis in Brazil, 2006.
To estimate the prevalence of self-reported osteoporosis (with previous medical diagnosis) and the associated risk and protection factors. A cross-sectional study was carried out, based on data from the system Vigilância de Fatores de Risco e Proteção para Doenças Crônicas por Inquérito Telefônico (VIGITEL--telephone-based surveillance of risk and protective factors for chronic diseases). A total of 54,369 individuals aged > or = 18 years living in homes served by at least one fixed telephone line in Brazilian state capitals and the Federal District in 2006 were interviewed. Estimates of osteoporosis in relation to socioeconomic and behavioral factors and the body mass index were stratified according to sex. The risk of occurrence of osteoporosis was calculated for each variable separately and through a multivariate model, taking the odds ratio to be a proxy for the prevalence ratio. The reported prevalence of osteoporosis was 4.4%, predominantly among women (7.0%) > or = 45 years of age whose marital status was not single and who were former smokers. Among men, age > 65 years, married or widowed status and sedentarism were positively associated with this outcome. Among the factors associated with osteoporosis, modifiable characteristics relating to disease prevention were highlighted, such as physical activity and smoking habits.


Pediculosis capitis and relevant factors in secondary school students of Hamadan, west of Iran.
Pediculosis capitis is a problem in children and has worldwide distribution. The aim of the present study was to determine the prevalence of pediculosis degree and its relevant factors in the secondary schools in Hamadan west of Iran. The study was carried out in two phases. A cross-sectional procedure was used to determine the prevalence of pediculosis, and the case study was done to identify the relevant factors to the infestation. Totally, 10841 secondary students were chosen and classified in accordance with the clustering sample. The prevalence of pediculosis was 1.05%. It was 1.27% among the urban student; whereas 0.05% among the rural students. About 2.3% belonged to female students, and 0.11% was pertained to the male students. The greatest amount of infestation prevalence was reported from the schools of urban areas particularly in the public schools of suburbia. Furthermore, the prevalence of infestation was more where some individuals had pediculosis previous history and suffered from head inching. It turned out to be a significant relationship between pediculosis, head itching (P<0.001) and previous history of pediculosis (P<0.001). The prevalence of pediculosis in Hamadan is low, but is more in the areas which are deprived of the access to health facilities. Therefore, there is a need for educational campaigns about danger of infection and regular mass screening at school.


A mouse model for triple-negative breast cancer tumor-initiating cells (TNBC-TICs) exhibits similar aggressive phenotype to the human disease.
Triple-negative breast cancer (TNBC) exhibit characteristics quite distinct from other kinds of breast cancer, presenting as an aggressive disease--recurring and metastasizing more often than other kinds of breast cancer, without tumor-specific treatment options and accounts for 15% of all types of breast cancer with higher percentages in premenopausal African-American and Hispanic women. The reason for this aggressive phenotype is currently the focus of intensive research. However, progress is hampered by the lack of suitable TNBC cell model systems. To understand the mechanistic basis for the aggressiveness of TNBC, we produced a stable TNBC cell line by sorting for 4T1 cells that do not express the estrogen receptor (ER), progesterone receptor (PgR) or the gene for human epidermal growth factor receptor 2 (HER2). As a control, we produced a stable triple-positive breast cancer (TPBC) cell line by transfecting 4T1 cells with rat HER2, ER and PgR genes and sorted for cells with high expression of ER and PgR by flow cytometry and high expression of the HER2 gene by Western blot analysis. We isolated tumor-initiating cells (TICs) by sorting for CD24+/CD44high/ALDH1+ cells from TNBC (TNBC-TICs) and TPBC (TPBC-TICs) stable cell lines. Limiting dilution transplantation experiments revealed that CD24+/CD44high/ALDH1+ cells derived from TNBC (TNBC-TICs) and TPBC (TPBC-TICs) were significantly more effective at repopulating the mammary glands of naïve female BALB/c mice than CD24-/CD44-/ALDH1- cells. Implantation of the TNBC-TICs resulted in significantly larger tumors, which metastasized to the lungs to a significantly greater extent than TNBC, TPBC-TICs, TPBC or parental 4T1 cells. We further demonstrated that the increased aggressiveness of TNBC-TICs correlates with the presence of high levels of mouse twenty-five kDa heat shock protein (Hsp25/mouse HspB1) and seventy-two kDa heat shock protein (Hsp72/HspA1A). Taken together, we have developed a TNBC-TICs model system based on the 4T1 cells which is a very useful metastasis model with the advantage of being able to be transplanted into immune competent recipients. Our data demonstrates that the TNBC-TICs model system could be a useful tool for studies on the pathogenesis and therapeutic treatment for TNBC.


Cardiovascular risk factor burden in Africa and the Middle East across country income categories: a post hoc analysis of the cross-sectional Africa Middle East Cardiovascular Epidemiological (ACE) study.
A significant number of cardiovascular disease (CVD)-related deaths occur in developing countries. An increasing prevalence of CVD is associated with a change in the macro-economy of these countries. In this post hoc analysis, CVD risk factor (CVDRF) prevalence is evaluated across countries based on national income in the Africa and Middle East Region (AfME). Data from the Africa Middle East Cardiovascular Epidemiological (ACE) study were used; a cross-sectional study in 14 AfME countries (94 clinics) from July 2011-April 2012, which evaluated CVDRF prevalence in stable adult outpatients. World Bank definitions were used to classify countries as low-income (LI), lower-middle-income (LMI), upper-middle-income (UMI) or high-income (HI) countries. Four thousand three hundred seventy-eight subjects were recruited where 260 (6%), 1324 (30%), 1509 (35%) and 1285 (29%) were from LI, LMI, UMI, and HI countries, respectively. Of all the CVDRFs evaluated, almost two-thirds of the study population across the national income groups had abdominal obesity and dyslipidemia. Countries in the HI category were associated with a higher prevalence of diabetes (32%), obesity (44%) and smoking (16%). UMI and HI countries were associated with higher clustering of CVDRFs where at least one-third of subjects having four or more CVDRFs. Lower income countries had lower blood pressure control rates and lower percentages of outpatients achieving LDL-cholesterol targets. The burden of CVDRFs in stable outpatients is high across the national income categories in the AfME region, with HI countries showing a higher prevalence of CVDRFs. The high burden in lower income countries is associated with sub-optimal control of dyslipidemia and hypertension. Lowering the CVDRF burden would need specific public health actions in line with positive changes in the macro-economy of these countries. The ACE trial is registered under NCT01243138.


Significance of transiently positive enzyme-linked immunosorbent assay results in detection of Helicobacter pylori in stool samples from children.
In young children, the significance of stool samples transiently positive for Helicobacter pylori antigen is unknown. As part of a larger prospective study on enteric infections, stool samples were obtained from 323 children at two time points 3 months apart and tested for H. pylori antigen using a commercially available enzyme-linked immunosorbent assay (ELISA) test. Seminested PCR for a Helicobacter-specific 16S rRNA gene was performed on all 26 pairs reverting from positive to negative (transient positives), all 4 persistent antigen-positive pairs, and 10 randomly selected persistent antigen-negative pairs. Helicobacter species were amplified from the first stool samples of 15/26 (58%) of the transient positives and 1 (25%) of 4 persistent positives. No Helicobacter species were amplified from the 10 persistent negatives. Among the 15 amplicons from transient-positive stool, H. pylori was sequenced and identified from 12 (80%; 95% confidence interval, 52% to 96%) and other Helicobacter spp. were identified from three (Helicobacter canis, Helicobacter winghamensis, and MIT 99-5504). Four of the 15 remained positive by PCR for the second (antigen-negative) stool sample, including all 3 initially identified as non-H. pylori. Helicobacter bilis was amplified from the second sample of a persistent positive. Two of eight transient positives from whom serum was available had accompanying transient elevations in anti-H. pylori antibodies. Transiently positive stool ELISAs for H. pylori are common and represent H. pylori in the majority of cases where sequences can be obtained. A not-insignificant percentage of antigen-positive stools, however, may represent other Helicobacter species.


Formation and properties of flavoprotein-cytochrome hybrids by recombination of subunits from different species.
p-Cresol methylhydroxylases from four different pseudomonads differ in their isoelectric points and, to a lesser extent, in Mr values and substrate specificity. The enzymes from three species were isolated in homogeneous form, then resolved into their flavoprotein and cytochrome subunits, and the subunits were recombined to yield the nine possible hybrids (i.e. three intraspecies and six interspecies). The resulting flavocytochromes showed extensive similarities in steady-state kinetic parameters and in the dissociation constants of their subunits. Evidence is also presented that a fourth type of p-cresol methylhydroxylase, from Pseudomonas putida (N.C.I.B. 9869, form 'B'), the subunits of which cannot be isolated by the isoelectric focusing technique used to separate the subunits of the other flavocytochromes, nevertheless dissociates slowly at high dilution. The dissociation is reflected by a decline of catalytic activity with time. This process for the 'B' enzyme is prevented by the presence of substrate or an excess of a cytochrome subunit isolated from another enzyme species. Incubation of the dissociated subunits with p-cresol brings about extensive, albeit incomplete, re-association and regeneration of activity.


The effectiveness of community-based cycling promotion: findings from the Cycling Connecting Communities project in Sydney, Australia.
Encouraging cycling is an important way to increase physical activity in the community. The Cycling Connecting Communities (CCC) Project is a community-based cycling promotion program that included a range of community engagement and social marketing activities, such as organised bike rides and events, cycling skills courses, the distribution of cycling maps of the area and coverage in the local press. The aim of the study was to assess the effectiveness of this program designed to encourage the use of newly completed off-road cycle paths through south west Sydney, Australia. The evaluation used a quasi-experimental design that consisted of a pre- and post-intervention telephone survey (24 months apart) of a cohort of residents (n = 909) in the intervention area (n = 520) (Fairfield and Liverpool) and a socio-demographically similar comparison area (n = 389) (Bankstown). Both areas had similar bicycle infrastructure. Four bicycle counters were placed on the main bicycle paths in the intervention and comparison areas to monitor daily bicycle use before and after the intervention. The telephone survey results showed significantly greater awareness of the Cycling Connecting Communities project (13.5% vs 8.0%, p < 0.05) in the intervention area, with significantly higher rates of cycling in the intervention area (32.9%) compared with the comparison area (9.7%) amongst those aware of the project. There was a significant increase in use of bicycle paths in the intervention area (28.3% versus 16.2%, p < 0.05). These findings were confirmed by the bike count data. Despite relatively modest resources, the Cycling Connecting Communities project achieved significant increases in bicycle path use, and increased cycling in some sub-groups. However, this community based intervention with limited funding had very limited reach into the community and did not increase population cycling levels.


Pathogenesis of interstitial fibrosis in chronic purine aminonucleoside nephrosis.
A cellular and molecular approach was used to gain new insight into the pathogenesis of interstitial fibrosis in chronic purine aminonucleoside nephrosis (PAN) nephrosis. Thirty experimental rats (PAN rats) were given 15 mg/100 g body wt of i.p. PAN at time 0, followed by 4.3 mg/100 g body wt i.p. on days 20, 27 and 34; 25 control rats received i.p. saline at the same time intervals. All rats had a right unilateral nephrectomy within the first four days. Groups of control and PAN rats were killed at 21, 37, 52, 72 and 91 days. Renal sections were studied by immunofluorescence to quantitate interstitial macrophages, T lymphocytes and fibroblasts, and to characterize the deposition of the extracellular matrix (ECM) proteins (collagens I, III and IV, fibronectin and laminin) and the tissue inhibitor of the metalloproteinases (TIMP). Steady state concentrations of mRNA from the whole kidney for these ECM proteins, the metalloproteinases, TIMP, and transforming growth factor beta (TGF-beta 1) were quantitated by Northern blot analysis. Significant increases in the number of interstitial macrophages and T lymphocytes were found in the PAN rat groups compared to that in controls. All ECM proteins examined were quantitatively increased in the tubulo-interstitium of PAN rats. The pattern of distribution of some ECM proteins was also modified in experimental animals. TIMP was increased in the interstitium of PAN rats; at later times, TIMP was most prominent in sclerotic regions of the glomeruli and in tubular protein droplets. Northern blot analysis revealed increased steady-state mRNA levels for components of each of the ECM proteins, no change for the metalloproteinases--stromelysin or collagenase--and a marked increase for TIMP and TGF-beta 1 in PAN animals. The results of this study suggest that the diffuse interstitial fibrosis found in chronic PAN nephrosis results from both increased production of ECM proteins and decreased matrix degradation.


Low dose supplementation with two different marine oils does not reduce pro-inflammatory eicosanoids and cytokines in vivo.
In view of the reported potential anti-inflammatory activity of the New Zealand green lipped mussel (NZGLM), we aimed to compare the effect of low dose marine oil supplementation, from mussels and fish, in reducing blood markers of inflammation. Thirty apparently healthy males and females were recruited from the general public in Melbourne, Australia to participate in a double blind, randomised, parallel intervention study. Subjects were consuming approximately 73 mg of omega-3 long chain polyunsaturated fatty acids (n-3 LCPUFA) daily in their background diet prior to the commencement of the intervention. Subjects were randomly assigned to consume either 2 mL/day of the NZGLM oil preparation (mixed with olive oil and dl-alpha-tocopherol) or fish oil preparation (also mixed with olive oil and dl-alpha-tocopherol) for six weeks. Two mL of the oils contained 241 mg and 181 mg of n-3 LCPUFA, respectively. Neutrophil phospholipid fatty acids, serum thromboxane B2 (TXB2), stimulated monocyte production of prostaglandin E2 (PGE2), interleukin-1 beta (IL-1 beta) and tumor necrosis factor alpha (TNFalpha) were measured. During the intervention, the total intakes of n-3 LCPUFA from the background diet and the supplements were 199 mg/d and 173 mg/day for the NZGLM and FO groups, respectively. Following six weeks of supplementation, both groups showed a small, but significant increase in neutrophil phospholipid proportion of eicosapentaenoic acid. The NZGLM group also showed a significant increase in docosahexaenoic acid levels. There were no significant changes with time or treatment for TXB2, PGE2, IL-1 beta or TNFalpha. This study showed that low dose supplementation with n-3 LCPUFA from two different marine oil preparations showed no difference in inflammatory markers in this group of healthy individuals. Further studies are warranted including dose response trials and studies in populations with inflammatory conditions.


Association between greater leg length and increased incidence of colorectal cancer: the atherosclerosis risk in communities (ARIC) study.
Previous studies have reported that taller people have an increased risk of colorectal cancer (CRC). We examined the association of two height components-leg length and sitting height-with CRC risk in 14,532 individuals aged 45-64 years in the Atherosclerosis Risk in Communities study. Anthropometrics were measured at baseline (1987-1989). Incident CRC cases (n = 382) were ascertained from 1987 to 2012. Cox proportional hazards regression was used to estimate multivariable-adjusted hazard ratios for CRC and colon cancer across quintiles of sex-specific leg length and sitting height. The highest (versus the lowest) quintile of leg length was associated with a 36% greater CRC risk (p-trend = 0.04), and 51% greater colon cancer risk (p-trend = 0.01). For the top four quintiles combined, risk was increased by 34% for CRC and by 45% for colon cancer versus the lowest quintile. Total height and sitting height were not significantly associated with CRC or colon cancer risk. A small number of cases (n = 57) limited our ability to conduct subgroup analyses for rectal cancer. A positive association of leg length with CRC and colon cancer risk suggests that biological mechanisms leading to greater leg length during puberty may explain the association between taller height and CRC.


Efficacy of Pharmacologic and Cardiac Implantable Electronic Device Therapies in Patients With Heart Failure and Reduced Ejection Fraction: A Systematic Review and Network Meta-Analysis.
Background The treatment of heart failure with reduced ejection fraction has been the subject of numerous randomized controlled trials involving medications and cardiac implantable electronic device therapies. As newer effective pharmacological therapies suggest significant reductions in all-cause mortality, the role of additional device therapy in heart failure with reduced ejection fraction deserves further scrutiny. Methods A systematic review and network meta-analysis on the effect of medication and device therapies in heart failure with reduced ejection fraction on all-cause mortality was performed. Randomized controlled trials published between January 1980 and July 2017 were identified using Medline, EMBASE, and Cochrane Controlled Register of Trials databases. Pcnetmeta package in R was used to calculate treatment arm-based estimated rates, rate ratios, and probability ranks with 95% credible intervals. Results Combination therapy of ACE (angiotensin-converting enzyme) inhibitors or ARBs (angiotensin receptor blockers) with β-blockers (BBs) alone or in addition to implantable cardiac defibrillators or cardiac resynchronization therapy with defibrillators demonstrated a significant reduction of all-cause mortality when compared with placebo. By probability rank, implantable cardiac defibrillator+ACE inhibitor or ARB+BB+mineralocorticoid receptor antagonist, implantable cardiac defibrillator+ACE inhibitor or ARB+BB, and angiotensin receptor-neprilysin inhibitor+BB+mineralocorticoid receptor antagonist combination therapies have the highest probability of being ranked the best treatment. There was no significant difference in the rate of mortality when comparing angiotensin receptor-neprilysin inhibitor+BB+mineralocorticoid receptor antagonist to implantable cardiac defibrillator+optimal pharmacological combination therapy. Conclusions BB and renin-angiotensin system blockers alone or in combination with defibrillator device therapy have robust evidence for a reduction in mortality compared with placebo. The comparative efficacy of pharmacological therapy with angiotensin receptor-neprilysin inhibitors and device therapy deserves further investigation.


Baseline Understanding of Urinary Incontinence and Prolapse in New Urogynecology Patients.
Investigators sought to assess whether age was related to patient understanding of pelvic floor disorders; given studies show that increased age is associated with lower health literacy. This was a cross-sectional survey of new urogynecology patients. Enrolled participants completed a survey including demographics, history of urinary incontinence (UI) and pelvic organ prolapse symptoms and treatment, the Prolapse and Incontinence Knowledge Questionnaire (PIKQ), self-assessment of UI and prolapse knowledge, and a pelvic anatomy diagram to label. To achieve 80% power to detect a 2-point difference in PIKQ score, 33 subjects were required per age group (<65 and ≥65 years old). One hundred thirty-five of 160 new urogynecologic patients completed the survey (84% response rate). Thirty-seven participants were older than 65 years, and 98 were younger than 65 years. Total PIKQ scores (maximum, 24), the primary outcome, for the older and younger groups were 15.3 and 15.0, respectively (P = 0.7). The 2 groups self-rated UI and prolapse knowledge similarly, rating knowledge as excellent, very good, or good in 60% (P = 0.3) and 40% (P = 0.2) of subjects, respectively. Baseline patient understanding of UI and pelvic organ prolapse was low as assessed by PIKQ score and was not influenced by age.


Movement protein of tobacco mosaic virus modifies plasmodesmatal size exclusion limit.
The function of the 30-kilodalton movement protein (MP) of tobacco mosaic virus is to facilitate cell-to-cell movement of viral progeny in an infected plant. A novel method for delivering non-plasmalemma-permeable fluorescent probes to the cytosol of spongy mesophyll cells of tobacco leaves was used to study plasmodesmatal size exclusion limits in transgenic plants that express the MP gene. Movement of fluorescein isothiocyanate-labeled dextran (F-dextran) with an average molecular mass of 9400 daltons and an approximate Stokes radius of 2.4 nanometers was detected between cells of the transgenic plants, whereas the size exclusion limit for the control plants was 700 to 800 daltons. No evidence of F-dextran metabolism in the leaves of the transgenic plants was found. Thus, the tobacco mosaic virus movement protein has a direct effect on a plasmodesmatal function.


Relation Between Cardiology Follow-Up Visits, Evidence-Based Statin Prescribing, and Statin Adherence (from the Veterans Affairs Health Care System).
Statin use remains suboptimal in patients with atherosclerotic cardiovascular disease (ASCVD). We assessed whether outpatient care with a cardiology provider is associated with evidence-based statin prescription and statin adherence. We identified patients with ASCVD aged ≥18 years receiving primary care in 130 facilities and associated community-based outpatient clinics in the entire Veterans Affairs Health Care System between October 1, 2013 and September 30, 2014. Patients were divided into: (1) patients with at least 1 outpatient cardiology visit and (2) patients with no outpatient cardiology visits in the year before the index primary care visit. We assessed any- and high-intensity statin prescription adjusting for several patient- and facility-level covariates, and statin adherence using proportion of days covered (PDC). We included 1,249,061 patients with ASCVD (mean age: 71.9 years; 98.0% male). After adjusting for covariates, patients who visited a cardiology provider had greater odds of being on a statin (87.4% vs 78.4%; Odds ratio [OR] 1.25, 95% Confidence interval [CI] 1.24 to 1.26), high-intensity statin (34.5% vs 21.2%; OR: 1.21, 95% CI 1.21 to 1.22), and higher statin adherence (mean PDC 0.76 ± 0.29 vs 0.70 ± 0.34, PDC ≥0.8: 62.0% vs 57.3%; OR 1.09, 95% CI 1.09 to 1.11). A dose response relation was seen with a higher number of cardiology visits associated with a higher statin use and statin adherence. In conclusion, compared with outpatient care delivered by primary care providers alone, care delivered by a cardiology provider for patients with ASCVD is associated with a higher likelihood of guideline-based statin use and statin adherence.


Dissociation of [HCCH]2+ to H2+ and C2+: a benchmark reaction involving H migration, H-H combination, and C-H bond cleavage.
We report the formation of H2+ and C2+ from dissociation of acetylene induced by α-particle irradiation. The unusual dissociation channel [C2H2]2+ → H2+ + C2+ is unambiguously identified by measuring the time-of-flight of both fragmented ions in coincidence. Our quantum chemical calculation confirms the existence of this dissociation pathway. It shows that [HCCH]2+ is firstly populated to the 3Π excited electronic state, followed by acetylene-vinylidene isomerization, and finally the vinylidene-like intermediate dissociates to H2+ and C2+. This dissociation channel is the simplest prototypical reaction involving H migration, H-H combination, and C-H bond cleavage. The current study plays an important role for understanding the H2+/H3+ formation reactions from organic di-cations in an interstellar medium.


[Genetic Analysis, Prenatal Diagnosis and Preimplantation Genetic Diagnosis of Taiwanese Deletion β-Thalassemia].
To perform genetic analysis, prenatal diagnosis and preimplantation genetic diagnosis (PGD) in a family with a rare deletional β- thalassemia. Hematological parameters of the peripheral blood collected from all the family members were analyzed by whole blood cell analysis and capillary zone electrophoresis (CZE). Polymerase chain reaction-reverse dot blot (PCR-RDB) was used to identify 17 common β- thalassemia gene mutations, the multiplex ligation-dependent probe amplification (MLPA) and gap-polymerase chain reaction (gap-PCR) were used to identify β- globin gene cluster deletions. Chorionic villus sample or umbilical cord blood was obtained for prenatal diagnosis. Oligo-cells from blastocyst biopsy were collected for preimplantation genetic diagnosis by whole genome amplification and next generation sequencing. The proband was a carrier of Taiwanese deletion β- thalassemia, two fetuses were both thalassemia majors. The PGD results showed that 6 of 11 tested embryos could be choose for transplantation. The Taiwanese deletion is a rare type deletion of β- globin gene cluster, and it can lead to thalassemia intermedia or thalassemia major when compounded with other β- globin gene mutation. PGD is another choice for thalassemia couples.


Rupture mechanism of a thrombosed slow-growing giant aneurysm of the vertebral artery--case report.
A 76-year-old male developed left hemiparesis in July 1991. The diagnosis was thrombosed giant vertebral artery aneurysm. He showed progressive symptoms and signs of brainstem compression, but refused surgery and was followed up without treatment. He died of rupture of the aneurysm and underwent autopsy in March 1995. Histological examination of the aneurysm revealed fresh clot in the aneurysmal lumen, old thrombus surrounding the aneurysmal lumen, and more recent hemorrhage between the old thrombus and the inner aneurysmal wall. The most important histological feature was the many clefts containing fresh blood clots in the old thrombus near the wall of the distal neck. These clefts were not lined with endothelial cells, and seemed to connect the lumen of the parent artery with the most peripheral fresh hemorrhage. However, the diameter of each of these clefts is apparently not large enough to transmit the blood pressure of the parent artery. Simple dissection of the aneurysmal wall by blood flow in the lumen through many clefts in the old thrombus of the distal neck may be involved in the growth and rupture of thrombosed giant aneurysms of the vertebral artery.