A de novo chromosomal abnormality in Cri du Chat syndrome.
To find the length and location of the deletions in the short arm of chromosome 5 in one case of Cri du Chat syndrome using oligo array comparative genomic hybridization. Metaphase chromosomes were prepared from peripheral blood lymphocyte cultures using standard cytogenetic protocols. Chromosomal analysis was done in G-banded metaphases. Oligo array comparative genomic hybridization and fluorescence in situ hybridization were performed by the commercially available kits. Oligonucleotide array comparative genomic hybridization (CGH) analysis revealed a 23.263 Mb deletion at region 5p14.2-->qter, combined with a duplication of 14.602 Mb in size in the area 12p13.1-->pter. Chromosomal aberrations were confirmed by fluorescence in situ hybridization. The male neonate with Cri du Chat syndrome had an unbalanced translocation which was inherited from his father who was a balanced carrier with a karyotype 46, XY, t (5; 12) (p14.2; p13.1). This report shows the clinical utility of the oligonucleotide array in the detection of submicroscopic chromosomal aberrations, thus improving the molecular diagnosis of Cri du Chat syndrome.


Association Between Clinical Depression, Anxiety, and Chronic Pain in the Active Duty Army Personnel.
Chronic pain is highly prevalent among soldiers leading to costly impacts on disability and readiness. Depression and anxiety (D&A) are frequently comorbid with chronic pain, but previous studies tend to focus on reporting the odds of co-occurrence. The aim of this study was to examine the association of properly diagnosed D&A disorders on chronic pain indicators among active duty soldiers. Data were drawn from the intake assessments of 203 soldiers seen at an Interdisciplinary Pain Management Center. The Diagnostic and Statistical Manual of Mental Disorders-5 diagnostic criteria and the D&A subscales of the Patient Health Questionnaire were used to identify patients who met criteria for clinical depression or anxiety. Of the 203 patients, 129 met neither depression nor anxiety criteria (No D&A), 12 met clinical depression criteria only, 16 met clinical anxiety only, and 46 showed coexisting D&A disorders. The D&A and No D&A groups were compared using validated measures to assess the pain intensity rating and pain effect on well-being, physical functioning, and catastrophizing tendency. Data were analyzed using descriptive statistics and independent samples t-test analyses. Significant differences were found between the D&A and No D&A groups on all pain-related measures (all Ps < .001). Patients in the D&A group reported higher average intensity of pain (6.11 versus 5.05) and greater effect of pain on activity (6.91 versus 5.37), sleep (7.20 versus 4.90), emotional state (7.74 versus 4.47), and stress (8.13 versus 4.78). Depression and anxiety patients also reported higher pain-catastrophizing tendency (38.56 versus 18.50) and greater physical disability (18.20 versus 12.22). Soldiers who have chronic pain with coexisting D&A disorders experience a greater degree of perceived negative impacts. Consequently, attentiveness to proper diagnosis and treatment of coexisting clinical mood disorders is an essential step in fully addressing chronic pain management.


Chemical (neo)glycosylation of biological drugs.
Biological drugs, specifically proteins and peptides, are a privileged class of medicinal agents and are characterized with high specificity and high potency of therapeutic activity. However, biologics are fragile and require special care during storage, and are often modified to optimize their pharmacokinetics in terms of proteolytic stability and blood residence half-life. In this review, we showcase glycosylation as a method to optimize biologics for storage and application. Specifically, we focus on chemical glycosylation as an approach to modify biological drugs. We present case studies that illustrate the success of this methodology and specifically address the highly important question: does connectivity within the glycoconjugate have to be native or not? We then present the innovative methods of chemical glycosylation of biologics and specifically highlight the emerging and established protecting group-free methodologies of glycosylation. We discuss thermodynamic origins of protein stabilization via glycosylation, and analyze in detail stabilization in terms of proteolytic stability, aggregation upon storage and/or heat treatment. Finally, we present a case study of protein modification using sialic acid-containing glycans to avoid hepatic clearance of biological drugs. This review aims to spur interest in chemical glycosylation as a facile, powerful tool to optimize proteins and peptides as medicinal agents.


Challenges in Crohn's Disease Management after Gastrointestinal Cancer Diagnosis.
Crohn's disease (CD) is a chronic inflammatory bowel disease with a progressive course, potentially affecting the entire gastrointestinal tract from mouth to anus. Several studies have shown an increased risk of both intestinal and extra-intestinal cancer in patients with CD, due to long-standing transmural inflammation and damage accumulation. The similarity of symptoms among CD, its related complications and the de novo onset of gastrointestinal cancer raises difficulties in the differential diagnosis. In addition, once a cancer diagnosis in CD patients is made, selecting the appropriate treatment can be particularly challenging. Indeed, both surgical and oncological treatments are not always the same as that of the general population, due to the inflammatory context of the gastrointestinal tract and the potential exacerbation of gastrointestinal symptoms of patients with CD; moreover, the overlap of the neoplastic disease could lead to adjustments in the pharmacological treatment of the underlying CD, especially with regard to immunosuppressive drugs. For these reasons, a case-by-case analysis in a multidisciplinary approach is often appropriate for the best diagnostic and therapeutic evaluation of patients with CD after gastrointestinal cancer onset.


Blood Pressure May Be Associated with Arterial Collateralization in Anterior Circulation Ischemic Stroke before Acute Reperfusion Therapy.
Leptomeningeal collaterals maintain arterial perfusion in acute arterial occlusion but may fluctuate subject to arterial blood pressure (ABP). We aim to investigate the relationship between ABP and collaterals as assessed by computer tomography (CT) perfusion in acute ischemic stroke. We retrospectively analyzed acute anterior circulation ischemic stroke patients with CT perfusion from 2009 to 2014. Collateral status using relative filling time delay (rFTD) determined by time delay of collateral-derived contrast opacification within the Sylvian fissure, from 0 seconds to unlimited count. The data were analyzed by zero-inflated negative binomial regression model including an appropriate interaction examining in the model in terms of occlusion location and onset-to-CT time (OCT). Two hundred and seventy patients were included. We found that increment of 10 mm Hg in BP, the odds that a patient would have rFTD equal to 0 seconds increased by 27.9% in systolic BP (SBP) (p=0.001), by 73.9% in diastolic BP (DBP) (p<0.001) and by 68.5% in mean BP (MBP) (p<0.001). For patients with rFTD not necessarily equal to 0 seconds, every 10 mm Hg increase in BP, there was a 7% decrease in expected count of seconds for rFTD in SBP (p=0.002), 10% decrease for rFTD in DBP and 11% decrease for rFTD in MBP. The arterial occlusion location and OCT showed no significant interaction in the BP-rFTD relationship (p>0.05). In acute ischemic stroke, higher ABP is possibly associated with improved leptomeningeal collaterals as identified by decreased rFTD.


Circumferential resection margin as a prognostic marker in the modern multidisciplinary management of rectal cancer.
A positive circumferential resection margin has been associated with a high risk of local recurrence and a decrease in survival in patients who have rectal cancer. The purpose of this study was to analyze the involvement of circumferential resection margin in local recurrence and survival in a multidisciplinary population-based setting by using tailored oncological therapy and surgery with total mesorectal excision. Data were collected in a prospective database and retrospectively analyzed. Between 1996 and 2009, 448 patients with rectal cancer underwent a curative bowel resection. Population-based data were collected at a single institution in the county of Västmanland, Sweden. Preoperative radiotherapy was delivered to 334 patients (74%); it was delivered to 35 patients (8%) concomitantly with preoperative chemotherapy. In 70 patients (16%), en bloc resections of the prostate and vagina were performed. Intraoperative perforations were seen in 7 patients (1.6%). The mesorectal fascia was assessed as complete in 117/118 cases. In 32 cases (7%), the circumferential resection margin was 1 mm or less. After a median follow-up of 68 months, 5 (1.1%) patients developed a local recurrence; one of them had circumferential resection margin involvement. The 5-year overall survival was 77%. In the multivariate analysis, the circumferential resection margin was not an independent factor for disease-free survival. Mesorectal fascia was not assessed before 2007. The findings might be explained by a type II error but, from a clinical perspective, enough patients were included to motivate the conclusion of the study. Circumferential resection margin is an important measurement in rectal cancer pathology, but the correlation to local recurrence is much less than previously stated, probably because of oncological treatment and surgery that respects the mesorectal fascia and, when required, en bloc resections. Circumferential resection margin should not be used as a prognostic marker in the modern multidisciplinary management of rectal cancer.


[Sporulation in Bacillus licheniformis strains that do not synthesize bacitracin and serine exo- and endoproteases].
Sporulation and synthesis of bacitracin, a peptide antibiotic and serine exoproteases and endoproteases were studied in 6 strains of Bacillus licheniformis at various periods of cultivation in sporulation media. Thermostable spores in all the strains were shown to form in the absence of both the exogenic and endogenic antibiotic and proteases. It was suggested that bacitracin and the serine proteases were not specific regulators of sporogenesis in B. licheniformis and their biological function under the natural conditions included, respectively, the antibiotic action and hydrolysis of proteins and peptides of the environment and cells.


Cdk2-dependent phosphorylation of the NF-Y transcription factor and its involvement in the p53-p21 signaling pathway.
Recent studies have suggested that the NF-Y transcription factor is involved in transcription repression of the cell cycle regulatory genes in a response to p53 induction or DNA damage. Here we demonstrate the cdk2-dependent phosphorylation of NF-Y and its involvement in transcription repression by the p53-p21 signaling pathway. Cdk2 phosphorylates two serine residues near the DNA-binding domain of the YA subunit of NF-Y. Cyclin A-cdk2 appears to associate with NF-Y both in vitro and in vivo. Furthermore, YA protein is phosphorylated in parallel with a cell cycle-dependent activation of cdk2 kinase and cyclin A expression. YA phosphorylation is unnecessary for heterotrimer formation with the YB-YC dimer. However, NF-Y containing a phosphorylation-deficient mutant form of YA, YA-aa, has its DNA binding activity impaired. Consistently, YA-aa inhibits transcription activation of a NF-Y target promoter, cdc2, by cdk2. These results facilitate the elucidation of the regulatory mechanisms of cell cycle progression involving the p21-cdk2-NF-Y signaling pathway.


In vitro effect of cyclosporin A on immunoglobulin production and concanavalin A induced suppression in primary biliary cirrhosis.
The in vitro effect of Cyclosporin A on the regulation of immunoglobulin production was investigated in 16 patients with primary biliary cirrhosis. A significant improvement in concanavalin A induced suppression of IgG and IgM producing cells was observed after prior incubation of mononuclear cells with 300 ng/ml Cyclosporin A for 30 minutes. No effect was seen on spontaneous or pokeweed mitogen induced immunoglobulin production, nor on con A induced suppression if Cyclosporin A was added after 24 hours. Incubation of mononuclear cells with a variable dose of Cyclosporin A showed an effect only at 250-500 ng/ml. Higher and lower doses had no effect. This dose dependent effect of Cyclosporin A is likely to be related to a differential inhibitory effect on T helper and T suppressor cells and may underlie the clinical benefit being observed in current clinical trials.


Sucrase-isomaltase is an adenosine 3',5'-cyclic monophosphate-dependent epithelial chloride channel.
We previously isolated a monoclonal antibody against a Necturus gallbladder epitope that blocks native adenosine 3',5'-cyclic monophosphate (cAMP)-dependent chloride channels in intestine, gallbladder, urinary bladder, and airway epithelia in various animals. Using this antibody, we purified a 200-kilodalton protein that, when reconstituted in lipid bilayers, forms 9-pS chloride channels that are blocked by the antibody. Amino acid sequencing of the purified protein showed strong homology to rabbit sucrase-isomaltase, an abundant intestinal enzyme. Western blot analysis of the in vitro-translated sucrase-isomaltase was indistinguishable from that of the protein used in the lipid bilayer studies. Expression of this protein in Chinese hamster ovary cells and in Xenopus laevis oocytes yielded cAMP-dependent chloride currents that in the latter system were blocked by the antibody. Because the monoclonal antibody blocks cAMP-dependent currents in epithelia as well as those produced both by the reconstituted and by the heterologously expressed protein, sucrase-isomaltase is a cAMP-dependent epithelial chloride channel. Thus an enzyme that can also function as an ion channel has been described for the first time.


Expression evolution facilitated the convergent neofunctionalization of a sodium channel gene.
Ion channels have played a substantial role in the evolution of novel traits across all of the domains of life. A fascinating example of a novel adaptation is the convergent evolution of electric organs in the Mormyroid and Gymnotiform electric fishes. The regulated currents that flow through ion channels directly generate the electrical signals which have evolved in these fish. Here, we investigated how the expression evolution of two sodium channel paralogs (Scn4aa and Scn4ab) influenced their convergent molecular evolution following the teleost-specific whole-genome duplication. We developed a reliable assay to accurately measure the expression stoichiometry of these genes and used this technique to analyze relative expression of the duplicate genes in a phylogenetic context. We found that before a major shift in expression from skeletal muscle and neofunctionalization in the muscle-derived electric organ, Scn4aa was first downregulated in the ancestors of both electric lineages. This indicates that underlying the convergent evolution of this gene, there was a greater propensity toward neofunctionalization due to its decreased expression relative to its paralog Scn4ab. We investigated another derived muscle tissue, the sonic organ of Porichthys notatus, and show that, as in the electric fishes, Scn4aa again shows a radical shift in expression away from the ancestral muscle cells into the evolutionarily novel muscle-derived tissue. This study presents evidence that expression downregulation facilitates neofunctionalization after gene duplication, a pattern that may often set the stage for novel trait evolution after gene duplication.


Cerebral lateralisation of first and second languages in bilinguals assessed using functional transcranial Doppler ultrasound.
Background: Lateralised representation of language in monolinguals is a well-established finding, but the situation is much less clear when there is more than one language. Studies to date have identified a number of factors that might influence the brain organisation of language in bilinguals. These include proficiency, age of acquisition and exposure to the second language. The question as to whether the cerebral lateralisation of first and second languages are the same or different is as yet unresolved. Methods: We used functional transcranial Doppler sonography (FTCD) to measure cerebral lateralisation in the first and second languages in 26 high proficiency bilinguals with German or French as their first language (L1) and English as their second language (L2). FTCD was used to measure task-dependent blood flow velocity changes in the left and right middle cerebral arteries during word generation cued by single letters. Language history measures and handedness were assessed through self-report questionnaires. Results:The majority of participants were significantly left lateralised for both L1 and L2, with no significant difference in the size of asymmetry indices between L1 and L2. Asymmetry indices for L1 and L2 were not related to language history, such as proficiency of the L2. Conclusion: In highly proficient bilinguals, there is strong concordance for cerebral lateralisation of first and second languages.


Inserting chromosome 18 into pancreatic cancer cells switches them to a dormant metastatic phenotype.
We demonstrated previously that restoration of chromosome 18 suppressed growth of pancreatic cancer cells in vitro, as well as that of tumors inoculated into nude mice. We also demonstrated that loss of 18q was associated with poor prognosis. Hence there is the possibility that the 18q arm harbors a gene(s) implicated in tumor progression and/or metastasis. In this study, we evaluated the effect of restoring chromosome 18 on metastasis in a few human pancreatic cancer cell lines with and without inactivation of SMAD4. After microcell-mediated chromosome 18 transfer, hybrid cells showed more than a 10-fold weaker metastatic ability than corresponding parental cells; mice injected with 1.25 x 10(6)/250 micro l hybrid clones via tail vein had less than one-tenth of the number of macroscopic metastases in the lung when compared with the control cells. Microscopic examination confirmed the decrease in the number of metastatic lesions. After inoculation of hybrid cells, more than 80% of the high-power fields showed no micrometastases, contrasting with their abundance after using the parental cells. Hybrid cells restored maspin expression irrespective of SMAD4 status in corresponding parental cells. On the other hand, significantly lower vascular endothelial growth factor and matrix metalloproteinase 2 secretion was observed by measuring levels in the conditioned media (CM); the averages were 22% and 20%, respectively. Angiogenesis assays using in vivo Matrigel plugs demonstrated that less neovascularization was observed in nude mice with hybrid cells than with corresponding parental cells. When cells were treated with CM from hybrids, the migration of human umbilical vascular endothelial cells was decreased, but it was partially restored with anti-vascular endothelial growth factor neutralizing antibody, as compared with CM from parental cells. These data represent the first functional evidence suggesting that chromosome 18q encodes a gene that strongly suppresses metastatic activity, possibly through dormancy.


Differential effects of protein kinase C-eta on apoptosis versus senescence.
Protein kinase C-eta (PKCη) is considered an anti-apoptotic kinase, which promotes cell survival and chemoresistance in several cancers, including breast cancer. We have recently shown that PKCη positively regulates the anti-apoptotic protein Mcl-1 in breast cancer cells, and depletion of PKCη induced proteasomal degradation of Mcl-1. We therefore examined if depletion of PKCη would enhance cellular sensitivity to chemotherapeutic agents. Silencing of PKCη by siRNA attenuated apoptosis induced by doxorubicin and paclitaxel in both MCF-7 and T47D breast cancer cells. While silencing of Mcl-1 caused a substantial increase in apoptosis induced by doxorubicin, the combined knockdown of PKCη and Mcl-1 was less effective. Depletion of PKCη also caused an increase in the abundance of the cell cycle inhibitor p27 and a decrease in the clonogenic survival of MCF-7 and T47D cells. PKCη knockdown was associated with an increase in senescence-associated β-galactosidase (SA-β-gal) activity but this increase was attenuated by knockdown of p27. The suppression of doxorubicin-induced apoptosis by PKCη knockdown was partially relieved when p27 was depleted. Since loss of proliferative capacity during senescence could cause resistance to chemotherapeutic drugs, our results suggest that PKCη knockdown inhibits apoptosis by inducing p27-mediated senescence.


Relationships among food and contact signals in experimental group-living young of tegenaria atrica
Relationships between the quantity of diet, and group vs. individual rearing toward ontogenesis on degree of cannibalism and cuticular lipid profile of young Tegenaria atrica Araneae, Agelenidae were studied. Ad libitum diet increases the development rate and decreases cannibalism between conspecifics compared to a reduced diet. Individually reared young on the two diets showed no quantitative differences in cuticular lipid profile, but differences were observed in individual vs. group rearing modes. The ad libitum-fed grouped young spiders had notably increased quantities of palmitic acid, 13,17-,11,17-, and 9,17-dimethylhentriacontane, methyl oleate, and n-heptatriacontane over the reduced diet, cannibalistic group. Arch. Copyright 1999 Wiley-Liss, Inc.


[Platelet functional status in patients with gastric cancer at combined treatment stages].
Platelets are active cells that excrete various humoral factors that contribute to thrombogenesis and inflammation. The investigation was undertaken to study induced platelet aggregation in patients with gastric cancer at combined treatment stages and to evaluate the impact of intraoperative radiotherapy (IOR). The study covered patients with gastric cancer (GC). Group 1 included Stage III GC patients who had undergone elective radical surgery; Group 2 comprised Stage III GC patients who had radical surgery with a session of IOR; Group 3 consisted of Stage IV GC patients who had undergone palliative surgery or explorative laparotomy. Induced platelet aggregation were explored from the BIOLA aggregometer (Russia) readings before, 30 minutes, 1, 3, 5, 7, and 14 days after surgery. Adenosine phosphate, adrenaline, collagen were used as inducers. It is concluded that there is a need for postoperative laboratory control and correction of platelet activity. In GC patients operated on with IOR, platelet activity should be monitored for at least 2 weeks after surgery.


False-positive flag of WBC and change of mean platelet volume (MPV) caused by K3-EDTA on the DxH 900 hematology analyzer.
During the evaluation of the DxH 900 hematology analyzer (Beckman Coulter, Miami, FL), we noted that some patient samples produced a false positive white blood cell (WBC) flag, neutrophil blasts (NE-blast), despite the absence of abnormal cells. We investigated whether storage time or anticoagulants such as K2- or K3-ethylenediaminetetraacetic acid (EDTA) would affect complete blood count (CBC) tests on the DxH 900. Sixty-four whole blood samples were collected in K3-EDTA tubes, and 44 were simultaneously drawn in K2-EDTA tubes. Samples were tested at the following two intervals: within 30 min of collection (0 min) and after an additional 30 min of roller-mixing at room temperature (30 min). WBC differential dataplots in 0-min K3-EDTA tubes showed a mixed cell population between lymphocytes and neutrophils in 22 patients presenting the NE-blast flag. All 22 samples revealed normal WBC differential dataplots after 30 min of roller-mixing. The significantly lower mean neutrophil volume in specimens of 0-min K3-EDTA tubes than those of 0-min K2-EDTA, 30-min K2-EDTA and 30-min K3-EDTA tubes appear to be the cause of the false flag. Unlike blood cell counts, mean platelet volume (MPV) was significantly higher at 30 min using both EDTA tubes than that at 0 min. In conclusion, K3-EDTA can produce a false positive flag, NE-blast, on the DxH 900. MPV increases over time irrespective of EDTA salt type.


Laser treatment for retinopathy of prematurity through the incubator wall.
In this era of early treatment for retinopathy of prematurity, sick infants who develop aggressive diseases or remain oxygen and temperature dependent may be treated while they are inside the incubator itself, thus avoiding unnecessary delays. This article describes the treatment of eight infants with retinopathy of prematurity who were dependent on an incubator by using a laser indirect ophthalmoscope delivery system through the slanting transparent wall of the incubator. In this series, which is the largest to date, the relative advantages and disadvantages of the procedure are discussed.


The effects of 5-hydroxy-5(4'-chlorophenyl)-2, 3-dihydro-5H-imidazo (2, 1-a) isoindole (mazindol, SaH 42-548) on the metabolism of brain norepinephrine.
Mazindol, 5-hydroxy-5-(4'-chlorophenyl)-i, 3-dihydro-5H-imidazo-(2, 1-a) isoindole, has demonstrated anorexic activity and other pharmacological responses which suggest alterations in brain norepinephrine metabolism. Studies of the effects of mazindol on neuronal uptake and/or release of norepinephrine showed that mazindol, when given before cerebral intraventricular injection of 3-H-norepinephrine by a mechanism that increases 3-H-normetanephrine synthesis via catechol-O-methyl-transferase and provided no significant effect on deamination of the catecholamine. Studies designed to measure norepinephrine release showed that mazindol (in contrast to d-amphetamine) did not cause release of 3-H-norepinephrine from neuronal stores. Furthermore, mazindol did not inhibit norepinephrine synthesis, whereas d-amphetamine did. The effect of d-amphetamine on norepinephrine release and synthesis may be more important than effects on uptake of this catecholamine. In contrast, mazindol appears to produce its primary effect on norepinephrine metabolism by inhibition of neuronal uptake mechanism.


Communication for HIV/AIDS prevention in Kenya: social-cultural considerations.
The acquired immune deficiency syndrome (AIDS) epidemic is spreading fast in Africa in spite of the various efforts and resources put in place to prevent it. In Kenya, reproductive health programs have used the mass media and other communication interventions to inform and educate the public about the disease and to promote behavior change and healthy sexual practices. This effort has led to a discrepancy between awareness and behavioral change among people of reproductive age. In this article I examine the discrepancy in Kenya from a communications perspective addressing social cultural and related factors contributing to the lack of change in behavior and sexual practices. I draw on the theoretical framework of Grunig's model of excellence in communication, the importance of understanding and relationship building between programs and their stakeholders. Data were gathered qualitatively using focus groups and in-depth interviews among men and women in rural Kenya. Key findings indicate that although awareness of sexually transmitted diseases (STDs) including human immunodeficiency virus (HIV)/AIDS is high in Kenya, a majority of the population, particularly those in the rural communities, lack understanding of the communicated messages. They also lack the knowledge of other ways of transmitting HIV particularly among those not sexually involved. Cultural beliefs, values, norms, and myths have played a role in the rapidly increasing epidemic in the rural communities and yet HIV/AIDS communication programs have not addressed these factors adequately. I conclude that successful behavior change communication must include strategies that focus on increasing understanding of the communicated messages and understanding of the audience through application of appropriate methodologies. Building a relationship with the audience or stakeholders through dialogues and two-way symmetrical communication contributes toward this understanding and the maintenance of the newly adopted behaviors and practices.


A Molecular Phylogenetic Study of the Tribe Corallineae (Corallinales, Rhodophyta) with an Assessment of Genus-Level Taxonomic Features and Descriptions of Novel Genera.
A multigene phylogeny using COI-5P (mitochondrial cytochrome c oxidase subunit 1), psbA (PSII reaction center protein D1), and EF2 (elongation factor 2) sequence data for members of the tribe Corallineae was constructed to assess generic boundaries. We determined that traditional reliance on conceptacle position as an indicator of generic affinities in the Corallineae is not supported and taxonomic changes are required. We found that species currently assigned to Pseudolithophyllum muricatum resolved within the Corallineae in all analyses. This is the first record of crustose members in the subfamily Corallinoideae. Further-more, the genus Serraticardia was polyphyletic; we propose to synonomize Serraticardia with Corallina, transfer the type species S. maxima to Corallina (C. maxima (Yendo) comb. nov.), and describe the new genus Johansenia for S. macmillanii (J. macmillanii (Yendo) comb. nov.). Our molecular data also indicate that species in the genus Marginisporum have evolutionary affinities among species of Corallina and these genera should also be synonymized. This necessitates the combinations C. aberrans (Yendo) comb. nov. for M. aberrans (Yendo) Johansen & Chihara, C. crassissima (Yendo) comb. nov. for M. crassissimum (Yendo) Ganesan, and C. declinata (Yendo) comb. nov. for M. declinata (Yendo) Ganesan. Corallina elongata was divergent from all other members of Corallina and is transferred to a new genus, Ellisolandia (E. elongata (J. Ellis & Solander) comb. nov). In addition, COI-5P and internal transcribed spacer (ITS) data combined with morphological characters were used to establish that rather than the four Corallina species recognized in Canada, there are nine.


Sentinel hospital-based surveillance for assessment of burden of rotavirus gastroenteritis in children in Pakistan.
To determine the burden and molecular epidemiology of rotavirus gastroenteritis in children hospitalized with severe acute watery diarrhea in Pakistan prior to introduction of rotavirus vaccine. A cross-sectional study was carried out over a period of two years from 2006 - 2008 at five sentinel hospitals in the cities of Karachi, Lahore, Rawalpindi, and Peshawar. Stool samples collected from children under five years of age hospitalized with severe acute watery diarrhea were tested for rotavirus antigen via enzyme immunoassay (EIA) (IDEA REF K6020 Oxoid Ltd (Ely), Cambridge, United Kingdom). A subset of EIA positive stool samples were further processed for genotyping. 6679 children were enrolled and stool specimens of 2039 (30.5%) were positive for rotavirus. Rotavirus positivity ranged from 16.3% to 39.4% in the 5 hospitals with highest positivity in Lahore. 1241 (61%) of all rotavirus cases were in infants under one year of age. Among the strains examined for G-serotypes, the occurrence of G1, G2, G9 and G4 strains was found to be 28%, 24%, 14% and 13%, respectively. Among P-types, the most commonly occurring strains were P6 (31.5%) followed by P8 (20%) and P4 (12%). Prevalent rotavirus genotype in hospitalized children of severe diarrhea were G1P[8] 11.6% (69/593), followed by G2P[4] 10.4% (62/593), and G4P[6] 10.1% (60/593). Approximately one third of children hospitalized with severe gastroenteritis in urban centers in Pakistan have rotavirus. Introduction of rotavirus vaccine in Pakistan's national immunization program could prevent many severe episodes and diarrheal deaths.


Two-photon imaging of blood flow in the rat cortex.
Cerebral blood flow plays a central role in maintaining homeostasis in the brain, and its dysfunction leads to pathological conditions such as stroke. Moreover, understanding the dynamics of blood flow is central to the interpretation of data from imaging modalities--such as intrinsic optical signaling and functional magnetic resonance imaging--that rely on changes in cerebral blood flow and oxygen level to infer changes in the underlying neural activity. Recent advances in imaging techniques have allowed detailed studies of blood flow in vivo at high spatial and temporal resolutions. We discuss techniques to accurately measure cerebral blood flow at the level of individual blood vessels using two-photon laser-scanning microscopy. By directing the scanning laser along a user-defined path, it is possible to measure red blood cell (RBC) velocity and vessel diameter across multiple vessels simultaneously. The combination of these measurements permits accurate assessment of total flux with sufficient time resolution to measure fast modulations in flux, such as those caused by heartbeat, as well as slower signals caused by vasomotion and hemodynamic responses to stimulus. Here, we discuss general techniques for animal preparation and measurement of blood flow with two-photon microscopy. We incorporate extensions to existing methods to accurately acquire flux data simultaneously across multiple vessels in a single trial. Central to these measurements is the ability to generate scan paths that smoothly connect user-defined lines of interest while maintaining high accuracy of the scan path.


Evolution of a Project to Improve Inpatient-to-Outpatient Dermatology Care Transitions: Mixed Methods Evaluation.
In-hospital dermatological care has shifted from dedicated dermatology wards to consultation services, and some consulted patients may require postdischarge follow-up in outpatient dermatology. Safe and timely care transitions from inpatient-to-outpatient specialty care are critical for patient health, but communication around these transitions can be disjointed, and workflows can be complex. In this 3-phase quality improvement effort, we developed and evaluated an intervention that leveraged an electronic health record (EHR) feature, known as SmartPhrase, to enable a new workflow to improve transitions from inpatient care to outpatient dermatology. Phase 1 (February-March 2021) included interviews with patients and process mapping with key stakeholders to identify gaps and inform an intervention: a SmartPhrase table and associated workflow to promote collection of patient information needed for scheduling follow-up and closed-loop communication between dermatology and scheduling teams. In phase 2 (April-May 2021), semistructured interviews-with dermatologists (n=5), dermatology residents (n=5), and schedulers (n=6)-identified pain points and refinements. In phase 3, the intervention was evaluated by triangulating data from these interviews with measured changes in scheduling efficiency, visit completion, and messaging volume preimplementation (January-February 2021) and postimplementation (April-May 2021). Preintervention pain points included unclear workflow for care transitions, limited patient input in follow-up planning, multiple messaging channels (eg, EHR based, email, and phone messages), and time-inefficient patient tracking. The intervention addressed most pain points; interviewees reported the intervention was easy to adopt and improved scheduling efficiency, workload, and patient involvement. More visits were completed within the desired timeframe of 14 days after discharge during the postimplementation period (21/47, 45%) than the preimplementation period (28/41, 68%; P=.03). The messaging workload also decreased from 88 scheduling-related messages sent for 25 patients before implementation to 30 messages for 8 patients after implementation. Inpatient-to-outpatient specialty care transitions are complex and involve multiple stakeholders, thus requiring multifaceted solutions. With deliberate evaluation, broad stakeholder input, and iteration, we designed and implemented a successful solution using a standard EHR feature, SmartPhrase, integrated into a standardized workflow to improve the timeliness of posthospital specialty care and reduce workload.


Rapid diagnostic test of Campylobacter pylori infection in patients of gastritis, duodenal ulcer and gastric ulcer. A study of 100 cases.
Campylobacter pylori has been cultured from 85-90% of antral biopsies of patients of gastritis, duodenal ulcer and gastric ulcer at different centres in the world. It has been now firmly implicated in the aetiology of active gastritis as well as suspected to cause repeated recurrences of peptic ulcers. However, the organism is very fastidious and is difficult to grow by standard culture methods as a result of which low positivity is often obtained even in well equipped centres. The rapid biopsy urease test for the diagnosis of C pylori infection, in which the biopsy is directly cultured in a solid medium containing urea, is a very simple test. A change in colour indicates the growth of the organism. This test is 100% specific and 98% sensitive. We performed this test in 100 patients; 93 of gastritis, 6 of DU and 1 of GU during a three month period. 87 of 93 cases of gastritis (90%) and all 6 cases of DU (100%) were positive. The single case of gastric ulcer was negative. Treatment of C pylori positive cases showed that they responded poorly to 4 weeks therapy with tinidazole; 33% were cured after 2 weeks of 1.5 g amoxycillin daily, but all responded when the therapy was continued for 4 weeks.


High volume, low volume, or pills, which way should we go? a review of bowel preparation for colonoscopy.
Colorectal cancer (CRC) is the second leading cause of adult cancer-related deaths in the United States. Colonoscopy is the gold standard for CRC screening. Adequate bowel preparation prior to colonoscopy is essential for good visualization, which results in higher polyp detection rates and shorter procedural times. Achieving adequate preparation prior to colonoscopy is accomplished approximately 75% of the time. This review covers current recommendations and recent updates in bowel preparation for colonoscopy. Split-dose bowel preparation is recommended, but recent studies show that same day, low-volume preparations are noninferior. Low-volume polyethylene glycol with electrolytes + ascorbic acid can achieve high-quality bowel preparation and 1-day, low-residue diets prior to colonoscopy, particularly prepackaged low-residue diets, can lead to better outcomes. Utilizing visual aids and artificial intelligence in the form of smartphone applications and quality prediction systems can also lead to higher rates of bowel preparation adequacy. An individualized approach should be used to decide on the best preparation option for patients. Lower volume, same day preparations are available and lead to better patient tolerability and compliance, along with less stringent precolonoscopy diets. Smartphone applications and artificial intelligence will allow us to better educate and guide patients with regards to following preparation instructions.


The endocannabinoid system as a target for novel anxiolytic drugs.
The endocannabinoid (eCB) system has attracted attention for its role in various behavioral and brain functions, and as a therapeutic target in neuropsychiatric disease states, including anxiety disorders and other conditions resulting from dysfunctional responses to stress. In this mini-review, we highlight components of the eCB system that offer potential 'druggable' targets for new anxiolytic medications, emphasizing some of the less well-discussed options. We discuss how selectively amplifying eCBs recruitment by interfering with eCB-degradation, via fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL), has been linked to reductions in anxiety-like behaviors in rodents and variation in human anxiety symptoms. We also discuss a non-canonical route to regulate eCB degradation that involves interfering with cyclooxygenase-2 (COX-2). Next, we discuss approaches to targeting eCB receptor-signaling in ways that do not involve the cannabinoid receptor subtype 1 (CB1R); by targeting the CB2R subtype and the transient receptor potential vanilloid type 1 (TRPV1). Finally, we review evidence that cannabidiol (CBD), while representing a less specific pharmacological approach, may be another way to modulate eCBs and interacting neurotransmitter systems to alleviate anxiety. Taken together, these various approaches provide a range of plausible paths to developing novel compounds that could prove useful for treating trauma-related and anxiety disorders.


Genotype-environment interactions of spontaneous mutations for vegetative fitness in the human pathogenic fungus Cryptococcus neoformans.
Spontaneous mutation is the ultimate source of all genetic variation. By interacting with environmental factors, genetic variation determines the phenotype and fitness of individuals in natural populations. However, except in a few model organisms, relatively little is known about the patterns of genotype-environment interactions of spontaneous mutations. Here I examine the rates of spontaneous mutation and the patterns of genotype-environment interaction of mutations affecting vegetative growth in the human fungal pathogen Cryptococcus neoformans. Eight mutation accumulation (MA) lines were established from a single clone on the nutrient-rich medium YEPD for each of two temperatures, 25 degrees and 37 degrees. Cells from generations 100, 200, 400, and 600 for each of the 16 MA lines were stored and assayed for vegetative growth rates under each of four conditions: (i) 25 degrees on SD (a synthetic dextrose minimal medium); (ii) 25 degrees on YEPD; (iii) 37 degrees on SD; and (iv) 37 degrees on YEPD. Both MA conditions and assay environments for vegetative growth showed significant influence on the estimates of genomic mutation rates, average effect per mutation, and mutational heritability. Significant genotype-environment interactions were detected among the newly accumulated spontaneous mutations. Overall, clones from MA lines maintained at 37 degrees showed less decline in vegetative fitness than those maintained at 25 degrees. The result suggests that a high-temperature environment might be very important for the maintenance of the ability to grow at a high temperature. Results from comparisons between clinical and environmental samples of C. neoformans were consistent with laboratory experimental population analyses. This study calls into question our long-standing view that warm-blooded mammals were only occasional and accidental hosts of this human fungal pathogen.


A defect in the activities of Δ and Δ desaturases and pro-resolution bioactive lipids in the pathobiology of non-alcoholic fatty liver disease.
Non-alcoholic fatty liver disease (NAFLD) is a low-grade systemic inflammatory condition, since liver and adipose tissue tumor necrosis factor-α (TNF-α) and TNF receptor 1 transcripts and serum TNF-α levels are increased and IL-6(-/-) mice are less prone to NAFLD. Fatty liver damage caused by high-fat diets is associated with the generation of pro-inflammatory prostaglandin E(2) (PGE(2)). A decrease in the levels of arachidonic acid (AA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and the usefulness of EPA and DHA both in the prevention and management of NAFLD has been reported. AA, EPA and DHA and their anti-inflammatory products lipoxins (LXs), resolvins and protectins suppress IL-6 and TNF-α and PGE(2) production. These results suggest that the activities of Δ(6) and Δ(5) desaturases are reduced in NAFLD and hence, the dietary essential fatty acids, linoleic acid (LA) and α-linolenic acid (ALA) are not metabolized to their long-chain products AA, EPA and DHA, the precursors of anti-inflammatory molecules, LXs, resolvins and protectins that could pre vent NAFLD. This suggests that an imbalance between pro- and anti-inflammatory bioactive lipids contribute to NAFLD. Hence, it is proposed that plasma and tissue levels of AA, EPA, DHA and LXs, resolvins and protectins could be used as predictors and prognostic biomarkers of NAFLD. It is suggested that the synthesis and use of more stable analogues of LXs, resolvins and protectins need to be explored in the prevention and management of NAFLD.


The impact of eculizumab on routine complement assays.
Eculizumab (ECU) blocks complement C5 cleavage, preventing the formation of C5a and the cytolytic effects of the membrane attack complex. The presence of ECU in blood impacts routine complement tests used to monitor treatment. Residual serum samples with normal total complement (CH50) and residual citrate plasma with normal PT/APTT were spiked with ECU at varied concentrations ranging from 25 to 600 μg/mL. In addition, seventy-one samples from patients on ECU were obtained. Artificial and patient samples were analyzed for CH50 and C5 function (Wako Diagnostics), C5 concentration (Quidel), AH50 (Wieslab ELISA) and sMAC (Quidel). ECU concentration was measured by mass spectrometry for all patients. Complement blockage by ECU was evident in spiked artificial samples. At 25 μg/mL ECU, partial complement blockage was observed in CH50, AH50 and C5 function in serum. Complete blockage defined by undetectable AH50 (<10%) occurred at 100 μg/mL ECU. C5 concentrations remained the same regardless of ECU. sMAC results stayed around 81% of baseline in serum and 47% in citrate plasma with 50μg/mL ECU. Patient samples had ECU ranging from <5 to 1220 μg/mL. In all patients with ECU >100 μg/mL, C5 function was <29 U/mL. The spiked sera and patient samples showed complement blockage with CH50, AH50 and C5 function assays when ECU >100 μg/mL. CH50, AH50 or C5 function assays can serve as indicators for the pharmacodynamic effects of eculizumab. Allied to ECU concentration, laboratory studies may be helpful to tailor therapy.


Overview of the clinical development of rituximab: first monoclonal antibody approved for the treatment of lymphoma.
Rituximab (Rituxan; IDEC Pharmaceuticals, San Diego, CA, and Genentech, Inc, San Francisco, CA) is a genetically engineered monoclonal antibody for the treatment of non-Hodgkin's lymphoma. This chimeric mouse/human, immunoglobulin GI kappa anti-CD20 antibody mediates complement-dependent cell lysis and antibody-dependent cellular cytotoxicity. It also has been shown to sensitize chemoresistant human lymphoma cell lines and to induce apoptosis. It was approved by the Food and Drug Administration on November 26, 1997, for the indication of relapsed or refractory, CD-20 positive, B-cell, low-grade or follicular non-Hodgkin's lymphoma Rituximab is the first monoclonal antibody approved for the treatment of cancer and the first single agent approved specifically for therapy of a lymphoma. The recommended dose is rituximab 375 mg/m2 intravenously weekly x4 infusions. Treatment is well tolerated and outpatient therapy is feasible. Adverse events are mostly grades I and 2, occurring primarily with the first infusion. In a phase II single-agent clinical trial, the overall response rate was 50%, with a median time to progression in responders of 10.2 months. In a larger multicenter trial involving 166 patients, the overall response rate was 48% with 6% complete and 42% partial responses. Median time to progression for responders was 13.2 months and median duration of response was 11.6 months. A 40% response rate has been observed on re-treatment with rituximab. Activity also has been seen in patients with bulky disease. Combination studies have been performed with interferon, cyclophosphamide/doxorubicin/vincristine/prednisone, and radioimmunotherapy. Rituximab, the first monoclonal antibody approved for the treatment of cancer, is safe and effective in treating patients with relapsed or refractory, CD-20 positive, B-cell, low-grade or follicular non-Hodgkin's lymphoma.


Attention please: evaluative priming effects in a valent/non-valent categorisation task (reply to Werner & Rothermund, 2013).
It has previously been argued (a) that automatic evaluative stimulus processing is dependent upon feature-specific attention allocation (FSAA) and (b) that evaluative priming effects can arise in the absence of dimensional overlap between the prime set and the response set. In opposition to these claims, Werner and Rothermund (2013) recently reported that they were unable to replicate the evaluative priming effect in a valent/non-valent categorisation task. In this manuscript, I report the results of a conceptual replication of the studies by Werner and Rothermund (2013). A clear-cut evaluative priming effect was found, thus supporting the initial claims about FSAA and dimensional overlap. An explanation for these divergent findings is discussed.


Implementing a routine, voluntary HIV testing program in a Massachusetts county prison.
Although U.S. prison inmates have higher rates of HIV infection than the general population, most inmates are not routinely tested for HIV infection at prison entry. The study objective was to implement a routine, voluntary HIV testing program in a Massachusetts county prison. During admission, inmates were given group HIV pre-test counseling and were subsequently offered private HIV testing. This intervention was compared to a control period during which HIV testing was provided only upon inmate or physician request. Between November 2004 and April 2005, 1,004 inmates met inclusion criteria and were offered routine, voluntary HIV testing. Of these, 734 (73.1%) accepted, 2 (0.3%) were HIV-infected, and 457 (45.5%) had been tested for HIV in the previous year. The testing rate of 73.1% was significantly increased from the rate of 18.0% (318 of 1,723) during the control period (p<0.001). Among the inmates tested for HIV in the prior year, 78.2% had received their last HIV test in the prison setting. Careful attention should be paid to prevent redundancy of testing efforts in the prison population. Implementing a routine HIV testing program among prison inmates greatly increased testing rates compared to on-request testing.


Successful treatment with plasma exchange for ANCA-negative pauci-immune crescentic glomerulonephritis with D-negative hemolytic uremic syndrome.
Co-existence of antineutrophil cytoplasmic antibody (ANCA)-negative pauci-immune crescentic glomerulonephritis (CGN) and thrombotic thrombocytopenic purpura-hemolytic uremic syndrome (TTPHUS) is extremely rare and has a poor renal prognosis. We report a 76-year-old female that had both ANCA and anti-human lysosomal membrane protein 2 (LAMP-2) antibody-negative pauci-immune CGN with D-negative HUS. She was admitted with proteinuria and worsening renal failure with massive crescent formation on renal biopsy specimens. We initiated intravenous methylprednisolone pulse therapy followed by oral prednisolone, but she still developed D-negative HUS. We then initiated plasma exchange, which achieved remission of D-negative HUS and improved renal function. To our knowledge, this is the first report of recovery from renal failure in ANCA-negative pauci-immune CGN with TTP-HUS.


Combination Therapy of Chemotherapy or Radiotherapy and the Neurokinin-1 Receptor Antagonist Aprepitant: A New Antitumor Strategy?
Although chemotherapy is predominantly used for cancer treatment, it can be ineffective and can induce serious side effects and lead to chemoresistance. It is essential to discover novel drugs that can enhance the antitumor activity and at the same time, counteract the severe side effects, of chemotherapy. The substance P (SP)/neurokinin-1 receptor (NK-1R) interaction system is known to play a key role in the pathogenesis of cancer. Studies with NK-1R antagonists (such as aprepitant) denote that the NK-1R is a potential target for the treatment of cancer. Aprepitant combined with major chemotherapeutic drugs has shown the potential to increase antitumor activity and decrease side effects. Since malignant tumor cancer cells overexpress the NK-1R, this combination therapy is a promising approach for the treatment of all kinds of cancer. Since aprepitant shows potential of being a broad-antitumor drug, the repurposing of this NK-1R antagonist as an antitumor agent is warranted. Studies pertaining to combination therapy of aprepitant/radiotherapy will also be outlined in this review. The aim of this review is to provide an update on combinational studies pertaining to chemotherapy/radiotherapy and NK-1R antagonist in cancer. This combination strategy once confirmed, might open the door to a new era in chemotherapy and radiotherapy with greater antitumor activity and fewer side effects. This treatment strategy could possibly translate into higher cure rates, better quality of life and fewer sequelae in cancer patients.


Rosmarinic Acid Exhibits Anticancer Effects via MARK4 Inhibition.
Microtubule affinity regulating kinase (MARK4) is a potential drug target for different types of cancer as it controls the early step of cell division. In this study, we have screened a series of natural compounds and finally identified rosmarinic acid (RA) as a potential inhibitor of MARK4. Molecular docking and 500 ns all-atom simulation studies suggested that RA binds to the active site pocket of MARK4, forming enough number of non-covalent interactions with critical residues and MARK4-RA complex is stable throughout the simulation trajectory. RA shows an excellent binding affinity to the MARK4 with a binding constant (K) of 107 M-1. Furthermore, RA significantly inhibits MARK4 activity (IC50 = 6.204 µM). The evaluation of enthalpy change (∆H) and entropy change (∆S) suggested that the MARK4-RA complex formation is driven by hydrogen bonding and thus complexation process is seemingly specific. The consequence of MARK4 inhibition by RA was further evaluated by cell-based tau-phosphorylation studies, which suggested that RA inhibited the phosphorylation of tau. The treatment of cancer cells with RA significantly controls cell growth and subsequently induces apoptosis. Our study provides a rationale for the therapeutic evaluation of RA and RA-based inhibitors in MARK4 associated cancers and other diseases.


Plasma Lysyl-tRNA Synthetase 1 (KARS1) as a Novel Diagnostic and Monitoring Biomarker for Colorectal Cancer.
Colorectal cancer (CRC) is one of the leading causes of world cancer deaths. To improve the survival rate of CRC, diagnosis and post-operative monitoring is necessary. Currently, biomarkers are used for CRC diagnosis and prognosis. However, these biomarkers have limitations of specificity and sensitivity. Levels of plasma lysyl-tRNA synthetase (KARS1), which was reported to be secreted from colon cancer cells by stimuli, along with other secreted aminoacyl-tRNA synthetases (ARSs), were analyzed in CRC and compared with the currently used biomarkers. The KARS1 levels of CRC patients (n = 164) plasma were shown to be higher than those of healthy volunteers (n = 32). The diagnostic values of plasma KARS1 were also evaluated by receiving operating characteristic (ROC) curve. Compared with other biomarkers and ARSs, KARS1 showed the best diagnostic value for CRC. The cancer specificity and burden correlation of plasma KARS1 level were validated using azoxymethane (AOM)/dextran sodium sulfate (DSS) model, and paired pre- and post-surgery CRC patient plasma. In the AOM/DSS model, the plasma level of KARS1 showed high correlation with number of polyps, but not for inflammation. Using paired pre- and post-surgery CRC plasma samples (n = 60), the plasma level of KARS1 was significantly decreased in post-surgery samples. Based on these evidence, KARS1, a surrogate biomarker reflecting CRC burden, can be used as a novel diagnostic and post-operative monitoring biomarker for CRC.


Scent Marks Signal Species, Sex, and Reproductive Status in Tamarins (Saguinus spp., Neotropical Primates).
Olfactory communication is an important mediator of social interactions in mammals, thought to provide information about an individual's identity and current social, reproductive, and health status. In comparison with other taxa such as carnivores and rodents, few studies have examined primate olfactory communication. Tamarins (Callitrichidae) conspicuously deposit odorous secretions, produced by specialized scent glands, in their environment. In this study, we combined behavioral and chemical data on captive cotton-top tamarins, Saguinus oedipus, and bearded emperor tamarins, S. imperator subgrisescens, to examine the role of olfactory communication in the advertisement of species, sex, and reproductive status. We observed no difference in scent-marking behavior between species; however, females marked more frequently than males, and reproductive individuals more than non-reproductive ones. In addition, tamarins predominantly used their anogenital gland when scent-marking, followed by the suprapubic gland. We collected swabs of naturally deposited tamarin anogenital scent marks, and analyzed these samples using headspace gas chromatography-mass spectrometry. Despite a limited sample size, we established differences in tamarin anogenital mark chemical composition between species, sex and reproductive status, and identified 41 compounds. The compounds identified, many of which have been reported in previous work on mammalian semiochemistry, form targets for future bioassay studies to identify semiochemicals. Our non-invasive method for collecting deposited scent marks makes it a promising method for the study of olfactory communication in scent-marking animal species, applicable to field settings and for the study of elusive animals.


Exploring the Perspectives of Preschool Teachers on Implementing Structured Motor Programs in Inclusive Classrooms.
Children with disabilities (CWD) tend to participate in fewer physical activities than typically developing children. During motor play, CWD often depend on teachers to provide direct instruction and frequent opportunities to practice motor skills, to interact with their peers, and learn new skills. To promote participation in physical activities for CWD, it is necessary to understand (a) teachers' perceptions about the importance of structured motor programs and (b) teachers' thoughts and concerns about implementing structured motor programs. The aim of this study was to understand teachers' perceptions about structured motor programs (e.g., obstacle course, bowling) and factors that may influence their motivation to implement them. Semi-structured interviews were conducted with 17 teachers who taught in inclusive preschools. Interview data were transcribed and analyzed to identify key themes. The results show that the majority of participants valued structured motor programs and were aware of the benefits of implementing such programs with preschoolers. Several teachers expressed concerns about meeting the expectations of a motor program and preschoolers' challenging behaviors during such programs. Implications for practice from this study include the need to (a) provide professional development to help teachers support preschoolers with disabilities in learning motor skills and understanding how to arrange and scaffold opportunities for children to participate in physical activities and gross motor play with their typically developing peers, and (b) create quality structured motor programs to ensure that all children have access to motor learning opportunities in inclusive preschool settings.


HIV Testing With and Without a Clinical Consultation Among Men Who Have Sex With Men: A Randomized Controlled Trial.
Increasing the frequency of HIV testing among men who have sex with men (MSM) maximizes the preventive effect of antiretroviral therapy, by reducing time to diagnosis and treatment. Melbourne Sexual Health Centre, Australia. This randomized controlled trial evaluated whether access to testing, without seeing a clinician would increase testing frequency. MSM attending for HIV testing between July 2014 and April 2015 were randomized in 1:1 ratio to the intervention arm (access to HIV and syphilis testing at 300 pathology centers, without requiring consultations) or the control arm (consultation at every test), without blinding. The primary outcome was the incidence of HIV testing over 12 months. Of 443 men referred, 422 were randomized, 3 HIV positives at baseline were excluded, and 419 were analyzed. Of 208 control, 202 (97.1%) and 200 (94.8%) of 211 intervention group members were followed to 12 months. The intervention group had 453 tests in 205.6 person-years, incidence rate was 2.2 (95% confidence interval [CI]: 2.0 to 2.4) tests per year. The control group had 432 tests during 204.0 person-years, incidence rate was 2.1 (95% CI: 1.9 to 2.3) tests per year, and incidence rate ratio was 1.04 (95% CI: 0.89 to 1.2; P = 0.63). The annual rate of consultations was as follows: intervention, 1.61 (95% CI: 1.44 to 1.79); controls, 2.12 (95% CI: 1.92 to 2.33); rate ratio, 0.76 (95% CI: 0.65 to 0.88; P = 0.0001). There was no difference in quality of life scores (P = 0.61). MSM permitted HIV and syphilis testing outside of clinical consultations did not test more frequently than controls but had 24% fewer consultations, reducing service demand. ACTRN12614000760673.


Computerized Cognitive Behavioral Therapy for Treatment of Depression and Anxiety in Adolescents: Systematic Review and Meta-analysis.
Depression and anxiety are major public health concerns among adolescents. Computerized cognitive behavioral therapy (cCBT) has emerged as a potential intervention, but its efficacy in adolescents remains unestablished. This review aimed to systematically review and meta-analyze findings on the efficacy of cCBT for the treatment of adolescent depression and anxiety. Embase, PsycINFO, and Ovid MEDLINE were systematically searched for randomized controlled trials in English, which investigated the efficacy of cCBT for reducing self-reported depression or anxiety in adolescents aged 11 to 19 years. Titles, abstracts, and full texts were screened for eligibility by 2 independent researchers (TB and LC). A random-effects meta-analysis was conducted to pool the effects of cCBT on depression and anxiety symptom scores compared with the control groups. Study quality was assessed using the Cochrane Collaboration Risk of Bias tool. A total of 16 randomized controlled trials were eligible for inclusion in this review, of which 13 (81%) were included in the meta-analysis. The quality of the studies was mixed, with 5 (31%) studies rated as good overall, 2 (13%) rated as fair, and 9 (56%) rated as poor. Small but statistically significant effects of cCBT were detected, with cCBT conditions showing lower symptom scores at follow-up compared with control conditions for both anxiety (standardized mean difference -0.21, 95% CI -0.33 to -0.09; I2=36.2%) and depression (standardized mean difference -0.23, 95% CI -0.39 to -0.07; I2=59.5%). Secondary analyses suggested that cCBT may be comparable with alternative, active interventions (such as face-to-face therapy or treatment as usual). This meta-analysis reinforces the efficacy of cCBT for the treatment of anxiety and depression and is the first to examine this exclusively in adolescents. Future research could aim to identify the active components of these interventions toward optimizing their development and increasing the feasibility and acceptability of cCBT in this age group. PROSPERO CRD42019141941; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=141941.


Detection of deep venous thrombosis by scanning of 99mtechnetium-labelled red-cell venous pool.
A comparative study of 32 patients with suspected deep venous thrombosis was carried out using blood-pool radionuclide scanning and conventional x-ray phlebography. Results of the two methods showed close agreement, the sensitivity (positive correlation) of the scan being 100% and its specificity 89%. We conclude that a patient's red cells labelled with 99mtechnetium (99mTc) provide an excellent medium for this type of scanning. The technique has particular advantages in visualising the whole venous system, giving a persisting image, and obviating the need to inject into a vein of the affected limb. In view of the inherent disadvantages of contrast phlebography, 99mTc-red-cell scanning is clearly an acceptable alternative.


Impact of Physical Obstacles on the Structural and Effective Connectivity of in silico Neuronal Circuits.
Scaffolds and patterned substrates are among the most successful strategies to dictate the connectivity between neurons in culture. Here, we used numerical simulations to investigate the capacity of physical obstacles placed on a flat substrate to shape structural connectivity, and in turn collective dynamics and effective connectivity, in biologically-realistic neuronal networks. We considered μ-sized obstacles placed in mm-sized networks. Three main obstacle shapes were explored, namely crosses, circles and triangles of isosceles profile. They occupied either a small area fraction of the substrate or populated it entirely in a periodic manner. From the point of view of structure, all obstacles promoted short length-scale connections, shifted the in- and out-degree distributions toward lower values, and increased the modularity of the networks. The capacity of obstacles to shape distinct structural traits depended on their density and the ratio between axonal length and substrate diameter. For high densities, different features were triggered depending on obstacle shape, with crosses trapping axons in their vicinity and triangles funneling axons along the reverse direction of their tip. From the point of view of dynamics, obstacles reduced the capacity of networks to spontaneously activate, with triangles in turn strongly dictating the direction of activity propagation. Effective connectivity networks, inferred using transfer entropy, exhibited distinct modular traits, indicating that the presence of obstacles facilitated the formation of local effective microcircuits. Our study illustrates the potential of physical constraints to shape structural blueprints and remodel collective activity, and may guide investigations aimed at mimicking organizational traits of biological neuronal circuits.


HCV genotype distribution and possible transmission risks in Lahore, Pakistan.
To investigate the prevalence of hepatitis C virus (HCV) genotypes and their association with possible transmission routes in the general population of Lahore, as the data exclusively related to this city is limited. Complete data regarding patient's history, possible route of infection and biochemical tests was collected from the public hospital for 1364 patients. SPSS version 16 windows software was used for data analysis by univariate and multivariate techniques. Age range < or = 40 years showed high prevalence of HCV infection. HCV genotype 3a was dominant (55.9%), followed by 1a (23.6%), 4a (12.5%), 3b (3.2%), untypable (2.5%), 4b (1.2%) and mixed type (1.2%). Blood transfusion, dental surgery and barber shops were the main risk factors for HCV transmission. Genotype prevalence was independent of age (P = 0.971) and gender (P = 0.122) while risk factors showed a significant association with age (P = 0.000) and genotypes (P = 0.000). We observed an independent association of risk factors and genotype 3a, while patients with genotype 1 and 4 were mostly infected due to dental surgery blood transfusion and barber shops. Risk factors of intravenous drug use and sexual exposure were exclusively found in < or = 40 years age group. An increase in genotypes 1a and 4a suggest migration of people, possibly from Balochistan and the northern war-zone area. Government should focus on public education regarding infection routes.


Biological Activities of Red Pepper (Capsicum annuum) and Its Pungent Principle Capsaicin: A Review.
Capsaicin, the pungent alkaloid of red pepper (Capsicum annuum) has been extensively studied for its biological effects which are of pharmacological relevance. These include: cardio protective influence, antilithogenic effect, antiinflammatory, and analgesia, thermogenic influence, and beneficial effects on gastrointestinal system. Therefore, capsaicinoids may have the potential clinical value for pain relief, cancer prevention and weight loss. It has been shown that capsaicinoids are potential agonists of capsaicin receptor (TRPV1). They could exert the effects not only through the receptor-dependent pathway but also through the receptor-independent one. The involvement of neuropeptide Substance P, serotonin, and somatostatin in the pharmacological actions of capsaicin has been extensively investigated. Topical application of capsaicin is proved to alleviate pain in arthritis, postoperative neuralgia, diabetic neuropathy, psoriasis, etc. Toxicological studies on capsaicin administered by different routes are documented. Capsaicin inhibits acid secretion, stimulates alkali and mucus secretion and particularly gastric mucosal blood flow which helps in prevention and healing of gastric ulcers. Antioxidant and antiinflammatory properties of capsaicin are established in a number of studies. Chemopreventive potential of capsaicin is evidenced in cell line studies. The health beneficial hypocholesterolemic influence of capsaicin besides being cardio protective has other implications, viz., prevention of cholesterol gallstones and protection of the structural integrity of erythrocytes under conditions of hypercholesterolemia. Beneficial influences of capsaicin on gastrointestinal system include digestive stimulant action and modulation of intestinal ultrastructure so as to enhance permeability to micronutrients.


Role of physical activity and sleep duration in growth and body composition of preschool-aged children.
The impact of physical activity patterns and sleep duration on growth and body composition of preschool-aged children remains unresolved. Aims were (1) to delineate cross-sectional associations among physical activity components, sleep, total energy expenditure (TEE), and body size and composition; and (2) to determine whether physical activity components, sleep, and TEE predict 1-year changes in body size and composition in healthy preschool-aged children. Anthropometry, body composition, accelerometry, and TEE by doubly labeled water were measured at baseline; anthropometry and body composition were repeated 1 year later (n = 111). Cross-sectionally, positive associations between sedentary activity and weight and fat-free mass (FFM) (P = 0.009-0.047), and a negative association between moderate-vigorous physical activity (MVPA) and percent fat mass (FM) (P = 0.015) were observed. TEE and activity energy expenditure (AEE) were positively associated with weight, body mass index (BMI), FFM, and FM (P = 0.0001-0.046). Prospectively, TEE, AEE, physical activity level, and MVPA, but not sedentary activity, were positively associated with changes in BMI (P = 0.0001-0.051) and FFM (P = 0.0001-0.037), but not percent FM. Sleep duration inversely predicted changes in FM (P = 0.005) and percent FM (P = 0.006). Prospectively, MVPA, TEE, AEE, and physical activity level promote normal growth and accretion of FFM, whereas sleep duration inversely predicts changes in adiposity in preschool-aged children.


Acute dissecting hematoma: a complication of oral and maxillofacial surgery.
The ADH is an uncommon but potentially life-threatening bleeding complication after oral maxillofacial surgery. Prevention via adequate preoperative laboratory evaluation and meticulous mechanical hemostasis during surgery is important. In spite of these measures, cases will infrequently occur, necessitating rapid accurate diagnosis and effective therapy. Close monitoring and continual airway assessment and control are paramount. Local measures are usually effective in hemorrhage control and the use of prophylactic antibiotics is suggested.


The pelvis after cesarean section and vaginal delivery: normal MR findings.
In postpartum women, pain and fever can indicate serious complications, such as phlegmon or abscess of the parametrium or bladder flap, ovarian vein thrombosis, or uterine dehiscence. The purpose of this study was to ascertain the MR appearance of the normal pelvis after uncomplicated cesarean section and vaginal delivery. Twenty-two patients (14 who had cesarean sections and eight who had vaginal deliveries) were imaged with a superconducting 0.35-T MR system 1-5 days after delivery. Sagittal and axial T1-weighted, proton density-weighted, and T2-weighted spin-echo images were acquired. Phase reconstruction of the axial T1-weighted sagittal images was performed to confirm flow in the ovarian veins. The ovarian veins, parametrium, bladder flap, endometrium, and uterine incision were analyzed on all images. The uterine incision was well seen in all 14 patients who had cesarean section. The signal characteristics of the incision suggested subacute hematoma within the myometrium, and no myometrial defects were seen. In all 13 patients with a low transverse incision, a hematoma of the bladder flap was seen. Patency was confirmed in the majority of ovarian veins (39/44). No evidence of parametrial edema or mass, which can be seen in abscess or phlegmon, was found in any of the 22 patients. The ovarian perivenous fat did not show edema, which can indicate acute ovarian vein thrombosis. Increased signal in the endometrial cavity was seen in all patients; the signal characteristics were similar to those of subacute hematoma, consistent with clinical findings. Normal findings of the postpartum pelvis on MR imaging are subacute hematoma in the uterine incision, bladder flap, and endometrial cavity. Patent ovarian veins are demonstrated in most (89%) cases.


Steroids administered after vacuum-assisted biopsy in the management of idiopathic granulomatous mastitis.
The aetiology and treatment options for idiopathic granulomatous mastitis (IGM) are controversial. The aim was to study the clinical and diagnostic features and discuss medical and surgical treatment for IGM in our patients. Sixty-five patients who met the histological criteria for IGM were retrospectively studied. The diagnosis of IGM was confirmed using Mammotome (an ultrasound-guided, vacuum-assisted biopsy system), core needle biopsy, quadrantectomy or segmental resection. Forty-five patients were treated with prednisolone (69.2%). Immunohistochemical (IHC) staining for immune-related antigens (CD3, CD4, CD8, CD79a, IgG, and IgM) was performed. Ultrasonography (USG) was carried out in all patients. Among them, 61 were considered to have an inflammatory mass and 15 had accompanying liquefaction. In four patients, the findings mimicked breast carcinoma (6.2%). The IHC results showed CD3, CD4, CD8 and CD79a lymphocytes diffusely distributed in the lesion. Stains for IgG and IgM were negative. Prednisolone was administered to the patients diagnosed with IGM. The success rate was 53 (81.5%) and the whole recurrence was 12 (18.5%). The median follow-up period was 12 months (range 4-42 months). The aetiology of IGM remains uncertain. The disease has no propensity for the right or left breast. It is a local autoimmune disease, involving humoral and cell-mediated immunity. Hyperprolactinaemia may play a role in some patients. Corticosteroids administered after complete removal of the IGM lesion using the Mammotome biopsy system is an effective treatment option.


Pretransplant solid organ malignancy and organ transplant candidacy: A consensus expert opinion statement.
Patients undergoing evaluation for solid organ transplantation (SOT) often have a history of malignancy. Although the cancer has been treated in these patients, the benefits of transplantation need to be balanced against the risk of tumor recurrence, especially in the setting of immunosuppression. Prior guidelines of when to transplant patients with a prior treated malignancy do not take in to account current staging, disease biology, or advances in cancer treatments. To develop contemporary recommendations, the American Society of Transplantation held a consensus workshop to perform a comprehensive review of current literature regarding cancer therapies, cancer stage-specific prognosis, the kinetics of cancer recurrence, and the limited data on the effects of immunosuppression on cancer-specific outcomes. This document contains prognosis based on contemporary treatment and transplant recommendations for breast, colorectal, anal, urological, gynecological, and nonsmall cell lung cancers. This conference and consensus documents aim to provide recommendations to assist in the evaluation of patients for SOT given a history of a pretransplant malignancy.


Responses of parasitoids to saproxylic hosts and habitat: a multi-scale study using experimental logs.
Species belonging to higher trophic levels are particularly vulnerable to habitat loss and consequential host population declines, but detection of effects depends on observation scale. We investigated the effects of habitat and host availability at multiple scales on parasitoids of early successional saproxylic beetles in middle boreal Sweden, where forestry has led to habitat fragmentation and coarse woody debris (CWD) loss. Parasitoid wasps and beetle hosts were collected from nine locations, each containing three spruce-dominated stand types (clear-cut, mature managed and unmanaged stands), using emergence traps on experimental CWD. We measured local CWD volumes and determined the availability of forests of a suitable age within the landscape. We tested parasitoid responses to stand type, CWD volume, abundance of known and probable hosts and longitude. Additionally, we tested whether parasitoids responded to the area of habitat of a suitable age within radii from 0.2 to 10 km. Stand type appeared in best-fit models for all common species, suggesting that wasps respond strongly to habitat at local scales. Longitude (largely climate) featured commonly, but CWD volume was never significant. Host abundance appeared in best-fit models for three of five common species, proving significant only for Bracon obscurator, the abundance of which correlated with that of Orthotomicus laricis at both trap and site levels. Rhimphoctona spp. also correlated significantly with its known host Tetropium castaneum at the trap level. B. obscurator responded to habitat area at scales of 0.6-1 km and Cosmophorus regius responded at radii greater than 7 km, while the larger species did not respond strongly to habitat area. The role of habitat area at greater scales thus varied greatly amongst species, but our data suggest that dispersal of these common early successional species may not be strongly restricted at the current scale of fragmentation of their boreal habitats.


[Hodgkin's disease in the Hospital General de México. Study of 309 cases].
In order to know the frequency and distribution of the histologic types of Hodgkin disease (HD) in the general Hospital of Mexico City and to compare the results with those of other countries; 96,909 surgical specimens were reviewed; 422 were of HD, from which only 309 (0.31%) could be reclassified according to the modified Rye classification, 214 (69%) were male and 95 (31%) female (M:F = 1:2.25). The mean age for the group was 26 years, for females was 30 and for males 24. The graphic for age and sex showed a unimodal curve in both sexes. The most frequent histologic type was mixed cellularity with 175 cases (56.6%), followed by the NE type with 83 (26.9%), the DL with 26 (8.4%) and finally the PL type with 25 (8.1%). In all the groups predominated the males as reported by other authors, but they reported a bimodal curve of age distribution and ours was unimodal as reported in Peru, Colombia, Uganda. The mean age is also one decade younger than in other countries, probably because almost 50% of the Mexican population are youngsters. The distribution of histologic types is similar to those of South Africa, Colombia, Uganda, Zambia and to the poor black population from USA, where the most frequent type is the mixed cellularity. The frequency of the other histologic types differs from the reports of Denmark Sweden, USA and England were the NE type predominates.(ABSTRACT TRUNCATED AT 250 WORDS)


Modeling the spread of Middle East respiratory syndrome coronavirus in Saudi Arabia.
Middle East respiratory syndrome coronavirus has been persistent in the Middle East region since 2012. Abundant scientific evidence showed that dromedary camels are the primary host of the virus. Majority of human cases (i.e., 75% or 88%) are due to human-to-human transmission, while the others are due to camel-to-human transmission. Mathematical modeling of Middle East respiratory syndrome coronavirus camel-to-camel transmission was lacking. Using the plug-and-play likelihood-based inference framework, we fitted a susceptible-exposed-infectious-recovered-susceptible model of camels to the reported human cases with a constant proportion of human cases from camels (i.e., either 25% or 12%). We considered two scenarios: (i) the transmission rate among camels is time-varying with a constant spill-over rate from camels to human or (ii) the spill-over rate is time-varying with a constant transmission rate among camels. Our estimated loss-of-immunity rate and prevalence of Middle East respiratory syndrome coronavirus infections among camels largely matched with previous serological or virological studies, shedding light on this issue. We recommended including dromedary camels in animal surveillance and control of Middle East respiratory syndrome coronavirus in Saudi Arabia which could help reduce their sporadic introductions to humans.


Furosine as a pasta quality marker: evaluation by an innovative and fast chromatographic approach.
A fast and simple high-performance liquid chromatography method suitable for determining furosine level in heat-treated food samples was developed. The analysis of furosine was performed by a novel mixed-mode column that provides multiple and simultaneous retention mechanisms including cation-exchange, anion-exchange, reversed-phase, or hydrophilic interaction. Each retention mechanism could be independently controlled by setting chromatographic conditions. Adequate retention and selectivity of polar charged furosine were achieved by adjusting mobile phase pH, buffer concentration, organic content, and ionic strength. The optimized method was successfully applied to determinate furosine in durum wheat semolina pasta samples. Furosine level in pasta may be used as a reliable marker of health and nutritional damage occurring during pasta manufacture. Indeed, a low content of furosine is generally related to high nutritional quality of food and application of mild heat treatments. A wide range of dry pasta samples, collected from both supermarkets (large-scale retail trade) and shops selling local products, were analyzed. Variable amounts of furosine, ranging from 107 to 506 mg/100 g of protein, were found in pasta samples. The proposed method allows to discriminate products submitted to different time-temperature conditions during the drying process. At the same time, it may be used to highlight potential label fraud.


Autophagy: A Promising Target for Age-related Osteoporosis.
Autophagy is a process the primary role of which is to clear up damaged cellular components such as long-lived proteins and organelles, thus participating in the conservation of different cells. Osteoporosis associated with aging is characterized by consistent changes in bone metabolism with suppression of bone formation as well as increased bone resorption. In advanced age, not only bone mass but also bone strength decrease in both sexes, resulting in an increased incidence of fractures. Clinical and animal experiments reveal that age-related bone loss is associated with many factors such as accumulation of autophagy, increased levels of reactive oxygen species, sex hormone deficiency, and high levels of endogenous glucocorticoids. Available basic and clinical studies indicate that age-associated factors can regulate autophagy. Those factors play important roles in bone remodeling and contribute to decreased bone mass and bone strength with aging. In this review, we summarize the mechanisms involved in bone metabolism related to aging and autophagy, supplying a theory for therapeutic targets to rescue bone mass and bone strength in older people.


Pituitary-adrenal reactivity in a child psychiatric population: salivary cortisol response to stressors.
The aim of this explorative study was to investigate whether physical and psychological challenges are effective in inducing a cortisol response in psychiatric and control children, and if so whether the cortisol response can discriminate between diagnostic groups and is related to psychiatric symptoms. Fifty-two patients, including children with dysthymia, oppositional defiant disorder/conduct disorder, pervasive developmental disorder, not otherwise specified (PDDNOS) and attention deficit hyperactivity disorder, were compared to 15 healthy control children. Symptomatology was scored using the Child Behaviour Checklist. The response to both psychological and physical challenges was assessed by measuring salivary cortisol and heart rate. Physical challenge, but not psychological challenge, resulted in an overall increase in heart rate and saliva cortisol. Dysthymic and PDDNOS patients showed a diminished cortisol response, in spite of a significant increase in heart rate. These groups scored highest on the symptom factor withdrawal. Withdrawal was negatively correlated with the cortisol response. Thus, physical exercise is effective in inducing a salivary cortisol response in children. Dysthymic and PDDNOS patients have a disturbed pituitary-adrenal function in relation to physical stress, that may be associated with withdrawal.


Altered ventricular mechanics after 60 min of high-intensity endurance exercise: insights from exercise speckle-tracking echocardiography.
Transient reductions in myocardial strain coupled with cardiac-specific biomarker release have been reported after prolonged exercise (>180 min). However, it is unknown if 1) shorter-duration exercise (60 min) can perturb cardiac function or 2) if exercise-induced reductions in strain are masked by hemodynamic changes that are associated with passive recovery from exercise. Left ventricular (LV) and right ventricular global longitudinal strain (GLS), LV torsion, and high-sensitivity cardiac troponin T were measured in 15 competitive cyclists (age: 28 ± 3 yr, peak O2 uptake: 4.8 ± 0.6 l/min) before and after a 60-min high-intensity cycling race intervention (CRIT60). At both time points (pre- and post-CRIT60), strain and torsion were assessed at rest and during a standardized low-intensity exercise challenge (power output: 96 ± 8 W) in a semirecumbent position using echocardiography. During rest, hemodynamic conditions were different from pre- to post-CRIT60 (mean arterial pressure: 96 ± 1 vs. 86 ± 2 mmHg, P < 0.001), and there were no changes in strain or torsion. In contrast, during the standardized low-intensity exercise challenge, hemodynamic conditions were unchanged from pre- to post-CRIT60 (mean arterial pressure: 98 ± 1 vs. 97 ± 1 mmHg, not significant), but strain decreased (left ventricular GLS: -20.3 ± 0.5% vs. -18.5 ± 0.4%, P < 0.01; right ventricular GLS: -26.4 ± 1.6% vs. -22.4 ± 1.5%, P < 0.05), whereas LV torsion remained unchanged. Serum high-sensitivity cardiac troponin T increased by 345% after the CRIT60 (6.0 ± 0.6 vs. 20.7 ± 6.9 ng/l, P < 0.05). This study demonstrates that exercise-induced functional and biochemical cardiac perturbations are not confined to ultraendurance sporting events and transpire during exercise that is typical of day-to-day training undertaken by endurance athletes. The clinical significance of cumulative exposure to endurance exercise warrants further study.


Sexuality: advising the older patient.
The need for sexual expression continues until death. Older patients have been erroneously denied these feelings by an uninformed society. As a result, older individuals either cease to function sexually or else continue to remain active with much needless guilt. The informed and caring physician can do much to alleviate this unnecessary suffering. Education of both patients and society is needed. The normal physiologic changes that occur need to be explained, as does the possibility of alternate means of sexual expression. Of course, the moral views of the patient must be considered. If the physician is not comfortable discussing problems related to sexuality, then he must be willing to refer the patient/couple to someone who is.


A new bend-magnet beamline for scanning transmission X-ray microscopy at the Advanced Light Source.
The high brightness of the bend magnets at the Advanced Light Source has been exploited to illuminate a scanning transmission X-ray microscope (STXM). This is the first diffraction-limited scanning X-ray microscope to operate with a useful count rate on a synchrotron bend-magnet source. A simple dedicated beamline has been built covering the range of photon energy from 250 eV to 600 eV. The beamline is always available and needs little adjustment. Use of this facility is much easier than that of installations that share undulator beams. This facility provides radiation for C 1s, N 1s and O 1s near-edge X-ray absorption spectromicroscopy with STXM count rates in excess of 1 MHz and with spectral resolution typically 1:2000, limited to about 1:5000.


Falls prevention interventions for older adults with low vision: A scoping review: Étude de portée sur les interventions visant à prévenir les chutes chez les aînés ayant une basse vision.
Older adults with low vision are especially vulnerable to falls. There are no comprehensive reviews of fall prevention interventions for older adults with vision loss who live in the community. The aim of this study was to review the evidence regarding community-based falls prevention interventions that appear inclusive of and/or accessible to individuals with low vision. A scoping review was completed using the framework developed by Arksey and O'Malley, and the charted data were analyzed using sums and percentages and qualitative content analysis. Seventeen publications were selected for this review. The analysis allowed for a thorough description of the types of falls prevention interventions (multiple components, home safety/modification, tai chi, the Alexander Technique, improvement of vision through vision assessment and referral, vision/agility training, and yoga), how each intervention addresses vision impairment, and the relation of results to falls risk. Falls prevention research targeting individuals with visual impairment is limited, and the intervention approaches available may not be effective for older adults with permanent vision loss.


Does Etiology Matter? Comparative Analysis of a Singing-Enhanced Swallowing Protocol for Patients with Neurological Impairment versus Head and Neck Cancer.
Swallowing difficulties are a common complaint among patients with a variety of diseases. To address these concerns, a singing-enhanced swallowing protocol was constructed, and its differential benefits for two patient populations were investigated. Two patients with Parkinson's disease (PD) and two patients with head and neck cancer (HNC) participated in this study. Each patient participated in 30-min individual sessions of a singing-enhanced swallowing protocol two times per week for 12 weeks. Following the intervention, laryngeal diadochokinesis and quality-of-life measurements were found to be higher in all four patients. However, the Videofluoroscopic Dysphagia Scale showed this improvement was associated with different swallowing tasks for each patient group. In addition, the maximum phonation time decreased for patients with HNC, while it increased for patients with PD. The findings support the use of a singing-enhanced swallowing protocol for patients whose swallowing difficulties are due to neurological or structural impairment. In addition, the study results suggest that different intervention components should be considered depending on the etiology of the patient's swallowing difficulties.


Studies on susceptibility to infection following ionizing radiation. V. Comparison of intraperitoneal and intravenous challenge at intervals following different doses of x-radiation.
Ten week old female CF-1 mice were subjected to a single total body exposure of x-radiation in one of the following doses: 300, 400, and 500 r. At intervals thereafter, susceptibility to bacterial infection was determined by intraperitoneal challenge with graded inocula of Pseudomonas aeruginosa. Mice exposed to 400 or 500 r were also challenged by intravenous inoculation. The LD(50) of the test microorganism in each challenge was estimated from the mortality data. Exposure to 300 r caused little increase in susceptibility to this experimental infection. 400 r caused a moderate increase on the 3rd day post-irradiation with return to normal on the 17th. Leucocyte counts (geometric means) following this dose of radiation did not fall below 1200. 500 r caused a marked increase in susceptibility which lasted from the 3rd to 11th day, during which period the leucocyte counts were below 800. On the 20th day, susceptibility to infection was normal, although the geometric mean of leucocyte counts was only 2200. Comparison of mortalities resulting from equivalent inocula introduced by the two routes (intravenous and intraperitoneal) showed no difference in unirradiated mice. However, among mice irradiated with 400 or 500 r, higher mortalities resulted from intravenous inoculation. The difference was found to be due to the establishment of a small focus of infection at the site of intravenous injection as a result of leakage of a minute fraction of inoculum into the perivenous tissues of the tail. Bacterial multiplication occurred in such foci in irradiated (leucopenic) mice, but not in unirradiated mice, nor at the site of intraperitoneal inoculation even in irradiated mice.


Brain metastases treated with radiosurgery or hypofractionated stereotactic radiotherapy: outcomes and predictors of survival.
To assess treatment outcome and prognostic factors associated with prolonged survival in patients with brain metastases (BM) treated with stereotactic radiosurgery (SRS) or hypofractionated stereotactic radiotherapy (HFSRT). This study retrospectively reviewed 200 patients with 324 BM treated with one fraction (15-21 Gy) or 5-10 fractions (25-40 Gy) between January 2010 and August 2016. 26.5% of patients received whole brain radiotherapy (WBRT) and 25% initial surgery. Demographics, prognostic scales, systemic and local controls, patterns of relapse and rescue, toxicity, and cause of death were analyzed. A stratified analysis by primary tumor was done. Median overall survival (OS) was 8 months from SRS/HFSRT. Breast cancer patients had a median OS of 17 months, followed by renal (11 months), lung (8 months), colorectal (5 months), and melanoma (4 months). The univariate analysis showed improved OS in females (p 0.004), RPA I-II (p < 0.001) initial surgery (p < 0.001), absence of extracranial disease (p 0.023), and good disease control (p 0.002). There were no differences in OS or local control between SRS and HFSRT or in patients receiving WBRT. Among 44% of brain recurrences, 11% were in field. 174 patients died, 10% from confirmed intracranial progression. SRS and HSFRT are equally effective and safe for the treatment of BM, with no exceptions among different primary tumors. Disease control, surgery, age, and prognostic scales correlated with OS. However, the lack of survival benefit regarding WBRT might become logical evidence for its omission in a subset of patients.


The Role of Learning in Health Technology Assessments: An Empirical Assessment of Endovascular Aneurysm Repairs in German Hospitals.
Changes in performance due to learning may dynamically influence the results of a technology evaluation through the change in effectiveness and costs. In this study, we estimate the effect of learning using the example of two minimally invasive treatments of abdominal aortic aneurysms: endovascular aneurysm repair (EVAR) and fenestrated EVAR (fEVAR). The analysis is based on the administrative data of over 40,000 patients admitted with unruptured abdominal aortic aneurysm to more than 500 different hospitals over the years 2006 to 2013. We examine two patient outcomes, namely, in-hospital mortality and length of stay using hierarchical regression models with random effects at the hospital level. The estimated models control for patient and hospital characteristics and take learning interdependency between EVAR and fEVAR into account. In case of EVAR, we observe a significant decrease both in the in-hospital mortality and length of stay with experience accumulated at the hospital level; however, the learning curve for fEVAR in both outcomes is effectively flat. To foster the consideration of learning in health technology assessments of medical devices, a general framework for estimating learning effects is derived from the analysis. © 2017 The Authors. Health Economics published by John Wiley & Sons, Ltd.