Intervention versus a conservative approach in the management of TRAP sequence: a systematic review.
In the management of twin reversed arterial perfusion (TRAP) sequence, we wished to (i) determine if intervention is better than a conservative approach and (ii) assess if any of the apparent adverse prognostic indicators could guide intervention. A systematic review was conducted between 1994 and 2014. Data extracted were inspected for heterogeneity. Overall rates and confidence intervals (CIs) for each prognostic factor were calculated. Where there were comparative data, the odds ratio (OR) was calculated. Twenty-six studies were included in the review. When all cases were considered, intervention either by cord occlusion or by ablation conferred a better survival rate compared with conservative management (OR=2.22, 95% CI 1.23-4.01, heterogeneity I2=37%, P=0.008). This difference was greater in the presence of one or more poor prognostic features (OR=8.58, 95% CI 1.47-49.96, heterogeneity I2=0%, P=0.02). Survival was better using ablative techniques compared to cord occlusion (OR=9.84, 95% CI 1.56-62.00, heterogeneity I2=0%, P=0.01). Intervention either by cord occlusion or by ablation confers a better survival rate compared to conservative management. This appears more compelling if there are one or more poor prognostic features. Ablative techniques are superior to cord occlusion. There were insufficient data to determine which poor prognostic features should guide management.


APE chemotherapy for children with relapsed Hodgkin disease: a Pediatric Oncology Group trial.
MOPP (mechlorethamine, vincristine, procarbazine, prednisone) and ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) are effective therapies for Hodgkin disease (HD) that may cause long-term toxicities in children. APE (cytosine arabinoside, cisplatin, etoposide) is a non-cross-resistant regimen with limited toxicities. We evaluated this regimen for patients with recurrent or refractory disease. Patients with recurrent Hodgkin disease who were <or=21 years of age and had previously received standard alkylating agent and doxorubicin-based therapy, were treated with APE chemotherapy (cytosine arabinoside 750 mg/m(2), cisplatin 15 mg/m(2), etoposide 20 mg/m(2)) every 12 hr, administered three or four times per cycle. Response, Event-free survival (EFS), and overall survival (OS) were assessed. Thirty-one patients in first (n = 25) or second (n = 6) relapse of Hodgkin disease were eligible and evaluable. APE chemotherapy was well-tolerated, with the major toxicity consisting of short duration, grade 3/4 hematopoietic toxicity. The CR/PR response rate was 68% (42% CR, 26% PR). Allowing subsequent stem cell transplantation in some patients, 4-year EFS and OS were 27% +/- 8% and 49% +/- 9%, with 8-year EFS and OS of 23% +/- 9% and 34% +/- 10%. APE is an efficacious regimen with minimal toxicity. Novel regimens are necessary to: (1) re-induce remission, (2) treat newly diagnosed patients, and (3) augment therapy in patients with slow response to standard regimens. This regimen had minimal toxicity and an excellent response rate that facilitated long term survival, often in conjunction with transplantation. The Children's Oncology Group is using a similar regimen to augment therapy for slow responders on a current Hodgkin disease trial.


Effect of pregnancy on left ventricular motion (twist) in women with aortic stenosis.
The combination of fixed outflow obstruction from aortic stenosis (AS) and the hemodynamic changes of pregnancy increased the risk of maternal or fetal deterioration. Left ventricular (LV) response in patients with AS to the hemodynamic changes of pregnancy has not been examined. We studied and compared myocardial mechanics with echocardiography in 3 groups of 10 women each, including (1) pregnant with bicuspid aortic valve (BAV; peak aortic gradient 59 +/-7 mm Hg, aortic valve area 0.9 +/- 0.04 cm2), (2) pregnant without BAV, and (3) nonpregnant, healthy volunteer. Measurements in the pregnant BAV group were made on 3 occasions, within a year before pregnancy (baseline), in the antepartum period, and at least 6 weeks postpartum. Tissue tracking ultrasound was used to assess longitudinal strain and LV twist. During pregnancy, peak AS gradient rose from 59 +/- 7 to 70 +/- 9 mm Hg (p = 0.004) whereas valve area remained unchanged 0.9 +/- 0.04 to 0.8 +/- 0.04 cm2 (p = 0.48) as compared with baseline (before pregnancy). Overall, in all patients, there was no significant change in the longitudinal strain (-22 +/- 1, -21 +/- 0.6, -20 +/- 0.6 percent, p = 0.21)] at baseline, during pregnancy, or after pregnancy, respectively. Patients with AS had a higher baseline LV twist compared with both control groups (5.4 +/- 0.3, pregnant, with AS; 4.1 +/- 0.8, pregnant, without AS; 3.6 +/- 0.3, nonpregnant volunteer; expressed in degrees; p = 0.023). Additionally, all but 2 patients had a significant increase in LV twist during pregnancy compared with baseline. These 2 women had symptomatic deterioration requiring urgent aortic balloon valvuloplasty. Postpartum, in all AS patients, LV twist returned to antepartum values. In conclusion, we found that LV twist was significantly increased in women with congenital AS. During pregnancy, LV twist further increased in the antepartum period, except in those women who experienced functional deterioration.


Pemphigus.
Pemphigus is an autoimmune blistering disorder. Paradoxically intact blisters are rarely seen as the superficial blister is so fragile. The disease is frequently fatal if untreated. Pemphigus is an ideal model for autoimmunity as the antigen has been characterized and the antibody demonstrated to be pathogenic.


Topic Analysis of Nursing Research Using Co-Word Analysis.
Nursing is one of the most important areas of medical sciences whose developments including its scientific publications can influence health care. Therefore, the aim of this study was to investigate nursing articles published from 2013 to 2018, and to provide a comprehensive view of common topical clusters in this research area. In this practical research, bibliometrics method and co-word analysis technique are used. The study population included all the articles in nursing area indexed in Web of Science from 2013 to 2018. The bibliometrics software, including BibExcel, UCINET, and SPSS was used to analyze the data. Results indicated that the most frequently used nursing words in nursing research articles were "Quality of life," "Aged," "Education," and "Nursing." Moreover, the pairs such as "Anxiety-Depression", "Education, Nursing-Students, Nursing" and "Depression--Quality of life" were the most frequent co-occurrences. The use of hierarchical clustering led to the formation of seven topical clusters in Nursing: "Nursing care for the Aged," "Self-care," "Physical, emotional, and social support, "Mother and child health," "Preventing nursing care," "Nursing profession Research," and "Quality of nursing care." The growth of nursing scientific productions is an indicative of the importance of this subject area in healthcare services; however, there is no balanced growth in various subjects.


The Impact of an Incidental Dose on Axillary Tumor Control and Toxicity in Localized Breast Cancer: A Retrospective Analysis.
The dosimetric analysis of the incidental axillary dose delivered to axillary lymph node levels I-III by different techniques of whole breast irradiation and the analysis of prognostic factors of axillary recurrence of breast cancer. We perform a retrospective analysis that includes 171 patients with localized breast carcinoma irradiated at Centre Paul Strauss. To be included in the study, patients had to have a histological confirmation of breast cancer diagnosis, surgical treatment without axillary lymph node dissection (ALND), whole breast irradiation without axillary irradiation by a specific field, and a treatment plan available. Three patients had lymph node recurrence. There was no significant correlation between the maximal or mean dose delivered at the three axillary levels and the risk of axillary lymph node recurrence. There was no significant correlation between the irradiation technique and the risk of axillary lymph node recurrence. Two patients, both in the HT group, had lymphoedema. There was significantly more lymphoedema in the HT group than in the ST and IMRT groups (p < 0.048). The mean dose in level II was significantly higher in the group of patients with lymphoedema (3.45 Gy (1.08; 9.62) vs. 23.4 Gy (23.1; 23.6)) (p < 0.02). The irradiation technique has an influence on the incidental dose delivered to the axillary area, but has no influence on the risk of axillary recurrence. The risk of lymphoedema could be related to the use of HT and the mean dose delivered at level II.


The use of lateral V-Y advancement flaps for fingertip reconstruction.
An operation is described that is based on anatomical studies showing the pattern of the fibrous septa and neurovascular bundles of the distal phalanx. Lateral V-Y advancement flaps are outlined with the dorsal incisions going sharply to the bone. With palmar retraction of each flap, dense fibrous bands on its underside are sharply divided. The palmar incision is made through skin only. The nerves, vessels, and adipose tissue of this pedicle are preserved while the fibrous septa are carefully divided. This technique permits 10 to 14 mm advancement of each flap. Complete division of the dorsal pedicle permits great mobility of the flap without functionally diminishing circulation or innervation. This procedure is particularly useful in traumatic fingertip amputations with the palmar and transverse oblique deformities. Elective remodeling of irregular fingertips has also been aided by this operation.


Nandrolone decanoate increases the volume but not the length of the proximal and distal convoluted tubules of the mouse kidney.
Anabolic androgenic steroids are widely used by athletes for increasing their muscle mass. These drugs are also used by some patients with chronic renal disease. But the effect of these drugs on the renal structure has received less attention. To investigate which parts of the kidney are affected by these drugs, mice kidneys were studied stereologically after injection of nandrolone decanoate (ND), an anabolic androgenic steroid. The treated group received nandrolone decanoate intraperitoneally (solved in olive oil) in doses of 3mg/kg of body weight and administered in one, two and three doses, respectively, in the first, second and third week of treatment. The mice in the control group received an olive oil solution. One week after the last injection, the mice were anaesthetized and their kidney removed. The analysis of data revealed that the weight of kidney was increased approximately 30% (p < or = 0.006) and its volume increased approximately 25% (p < or = 0.02) in ND treated mice in comparison with the control group. The volume of the cortex increased in ND treated animals approximately 44% (p < or = 0.006). Proximal convoluted tubules (PCT) and distal convoluted tubules (DCT) volume increased approximately 25% (p < or = 0.02) and approximately 68% (p < or = 0.02) in ND treated mice. The volume of glomeruli, other ducts, connective tissues, vessels and the length of PCT, DCT, collecting and Henle's ducts and vessels did not show significant differences. ND can increase the volume of the renal cortex and its two main parts, i.e. PCT and DCT in mice.


Current state and future perspective of drug repurposing in malignant glioma.
Malignant gliomas are still extremely difficult to treat because complete surgical resection is biologically not feasible due to the invasive nature of these diseases and the proximity of tumors to functionally sensitive areas. Moreover, adjuvant therapies are facing a strong therapeutic resistance since the central nervous system is a highly protected environment and the tumor cells display a vast intra-tumoral genetic and epigenetic variation. As a consequence, new therapeutics are urgently needed but the process of developing novel compounds that finally reach clinical application is highly time-consuming and expensive. Drug repurposing is an approach to facilitate and accelerate the discovery of new cancer treatments. In malignant glioma, like in other cancers, pre-existing physiological pathways that regulate cell growth, cell death or cell migration are dysregulated causing malignant transformation. A wide variety of drugs are clinically used to treat non-cancerous diseases interfering with these malignancy-associated pathways. Repurposed drugs have key advantages: They already have approval for clinical use by national regulatory authorities. Moreover, they are for the most part inexpensive and their side effect and safety profiles are well characterized. In this work, we provide an overview on current repurposing strategies for the treatment of malignant glioma.


Mapping of the Wnt/β-catenin/TCF response elements in the human versican promoter.
Versican, a chondroitin sulfate proteoglycan, is one of the main components of the extracellular matrix and is considered to be crucial to several key cellular processes involved in development and disease. There is differential temporal and spatial expression of versican by multiple cell types and in different developmental and pathological timeframes. In order to fully appreciate the functional roles of versican as it relates to changing patterns of expression in development and disease, an in-depth knowledge of versican's biosynthetic processing is necessary. We have recently shown that β-catenin/T-cell factor (TCF) complex formation at the versican promoter site is essential for activation of versican transcription. The transcriptional activator β-catenin is the key mediator of the canonical Wnt signaling pathway. However, β-catenin does not itself bind DNA and thus functions via interaction with TCF/Lymphoid-enhancing factor (LEF) transcription factors. These proteins contain a high-mobility group (HMG) box that binds DNA in a sequence-specific manner. Thus, in the case of active Wnt signaling, β-catenin activates, in cooperation with proteins of the TCF/LEF family, the expression of a wide variety of target genes. The goal of this chapter is to describe the techniques used to elucidate the transcriptional control of versican by the β-catenin/TCF response elements in its promoter site and to demonstrate how this signaling may be assayed experimentally. These approaches provide insight into the transcriptional regulation of the versican gene and provide the basis for the identification of novel Wnt/β-catenin/TCF-regulated genes that are part of the signaling machinery regulating early embryogenesis, neoplasia, and cardiovascular remodeling.


Prevalence and geographical distribution of Escherichia coli O157 in India: a 10-year survey.
Escherichia coli colonizes the human gastrointestinal tract and produces a variety of diseases. Escherichia coli O157 is one of the most important pathogenic strains reported from food-borne illnesses leading to enterohemorrhagic colitis. The National Salmonella and Escherichia Centre is a national reference centre for Salmonella and Escherichia for India; it receives samples from research laboratories, hospitals and institutions for serological identification. The present study is an epidemiological survey of E. coli O157 in different regions of India. The data are based on samples received from humans, food items, animals and the environment. A total of 17 093 isolates cultured from samples were received during the 10-year period of which 5678 were from human sources. Thirty (0.5%) human samples were positive for E. coli O157. A significantly high percentage of E. coli O157 were isolated from meat (0.9%, 13/1376), milk and milk products (1.8%, 10/553), seafood (8.4%, 16/190) and water (1.6%, 8/486). The isolates were found to be distributed among domestic and wild animals, and the maximum number of isolates of E. coli O157 was detected in samples received from coastal belt areas. Escherichia coli O157 is widely distributed among humans and animals, food and environment in different geographical regions of India.


CART variance stabilization and regularization for high-throughput genomic data.
mRNA expression data obtained from high-throughput DNA microarrays exhibit strong departures from homogeneity of variances. Often a complex relationship between mean expression value and variance is seen. Variance stabilization of such data is crucial for many types of statistical analyses, while regularization of variances (pooling of information) can greatly improve overall accuracy of test statistics. A Classification and Regression Tree (CART) procedure is introduced for variance stabilization as well as regularization. The CART procedure adaptively clusters genes by variances. Using both local and cluster wide information leads to improved estimation of population variances which improves test statistics. Whereas making use of cluster wide information allows for variance stabilization of data. Sufficient details for our CART procedure are given so that the interested reader can program the method for themselves. The algorithm is also accessible within the Java software package BAMarray(TM), which is freely available to non-commercial users at www.bamarray.com. firstname.lastname@example.com.


Experiences of patients and next of kin on informed consent process for emergency surgery in two Urban university teaching hospitals in Uganda: a comparative cross sectional study.
Informed consent for emergency surgery is a process in which a patient or their next of kin must make quick decisions required for surgery in a life-threatening situation or surgery that may have life-altering outcomes. The objective of the study was to describe patients and their next of kin experiences and factors influencing the informed consent process in two urban university teaching hospitals in Uganda. A cross-sectional survey involving patients who underwent emergency surgery and their next of kin was conducted in two tertiary care hospitals; one public and one private-not-for profit institution. A questionnaire was administered to collect sociodemographic information, type of Surgery that was done, how informed consent was obtained and experiences and expectations from the informed consent process. Univariate and multivariate analyses of the variables was done. We collected data from 210 patients from a public hospital and 170 from a private-not-for profit hospital. Overall, most patients did not have the risks of the surgery communicated to them (79.7%), were not given alternative options (87.6%) and had no opportunity to ask questions (57.4%). Patients at the private institution had 3.35 times the odds of expecting the consent form to be explained to them than those at the public institution. Patients at the public hospital had 0.12 times the odds of preferring to have consent administered by a nurse than patients at the private institution OR 0.12 (0.05-0.29, p < 0.001). Patients in the public institution had 0.18 times the odds of preferring to have consent administered by a doctor than patients in the private institution OR 0.18 (0.08-0.45, p < 0.001). Patients in both public and private institutions are not informed about the risks of surgery, alternative options and are not given the opportunity to ask questions. Interpretation of the findings of this study on patient preferences on who administered consent though statistically significant were inconclusive due to the responses not being mutually exclusive.


Food, feeding rates and assimilation in woodland snails.
Analyses of the faeces of seven species of woodland, litterdwelling snails (Marpessa laminata, Clausilia bidentata, Oxychilus cellarius, O. alliarius, Discus rotundatus, Arianta arbustorum and Hygromia striolata), showed that all feed predominently on higher plant material, be it living or dead. H. striolata and A. arbustorum took more chlorophyll-containing plant material than the other species, D. rotundatus had a significant amount of fungus in its faeces, while the faeces of O. cellarius and O. alliarius contained significant amounts of animal material.The consumption and assimilation of a variety of foods by molluscs was studied in the laboratory using an ash-ratio technique, which had been shown to give similar results to those obtained by the standard gravimetric technique. The assimilation efficiency of the molluscs was found to be temperature independent, but ingestion rates and absolute assimilation rates were temperature dependent. The assimilation efficiency of D. rotundatus on living plant material (three field layer species) was 44.8±4.43% that of H. striolata (Urtica dioica) was 52.4±8.78% while O. cellarius and H. aspersa (on Lactuca sativa) had assimilation efficiencies of 70.2±4.40% and 53.50±6.04% respectively. The results fall within the range shown by other invertebrate groups. The assimilation efficiency of D. rotundatus on leaf litter (a mean of 49.1±1.88% on five litter types) was higher than that shown by other invertebrates, probably due to the presence of gut polysaccharidases. The assimilation on dead earthworm as animal material (86.9±2.53% with O. alliarius and 78.6±6.73% with D. rotundatus) was in the range of true carnivores. Consumption rates were more variable; Urtica dioica, amongst living material, was eaten in greatest quantity; Acer pseudoplatanus, Castanea sativa and Quercus robur litter were eaten in greater quantity than Fagus sylvatica and Carpinus betulus. Consumption was examined in terms of percentage body weight.


The association between allergy and diabetes in the Canadian population: implications for the Th1-Th2 hypothesis.
T-lymphocytes may preferentially differentiate towards a Th1 subtype, which is thought to be involved in the autoimmune aspects of diabetes, or a Th2 subtype, which is thought to mediate allergic disease. The activation of one subtype is thought to inhibit the other. To determine if diabetes is less common among those with allergic disease, consistent with the postulated TH1/Th2 paradigm, we used data from the 2000-2001 Canadian Community Health Survey of those at least 12 years of age from 125,159 households. Diabetes requiring insulin was reported in 1% whether or not allergies were reported. The crude odds ratio between diabetes and allergies for the entire population was 1.06 (95% confidence interval (CI): 0.90, 1.24). Adjusted for household size, number of bedrooms, immigrant status, income adequacy, educational level, smoking status, alcohol drinking status, regular exercise, and age, there was a positive association between allergy and diabetes with an odds ratio of 1.25 (95% CI: 1.06, 1.49). These results do not provide evidence for the existence of the Th1/Th2 paradigm as a determinant of disease patterns in the general population.


Lessons learned from clinical trials of exercise and physical activity in people with MS - guidance for improving the quality of future research.
The body of research on exercise and physical activity among persons with multiple sclerosis(MS) has expanded rapidly in quantity, but not necessarily quality, over the past 20+ years. There is evidence for beneficial effects of exercise and physical activity on immune cells and neurotrophic factors, brain structure and function, walking and cognitive performance, fatigue, depression, and pain, and quality of life among persons with MS. Nevertheless, there is heterogeneity in the outcomes of exercise and physical activity, and a recognition of substantial challenges for improving the effectiveness of those behaviors in MS. To move the field forward, members of the National MS Society physical wellness research working-group pooled collective experiences for identifying challenges, logistic complexities, and opportunities for researchers in designing and conducting interventions of exercise and physical activity among persons with MS. We examined the scope of our experiences and identified collective "lessons learned" regarding the behaviors themselves; study design features and stage of research; study setting, safety, and sample selection; and implementation of randomized controlled trials(RCTs) and treatment fidelity. This paper provides a resource that can inform researchers, particularly new investigators or established investigators transitioning into MS, on conducting high-quality RCTs on exercise and physical activity in MS.


Treatment of recurrent, multiloculated, obstructive hydrocephalus with suprahepatic peritoneal catheter placement.
The suprahepatic space represents a potential reservoir for cerebrospinal fluid absorption and becomes critical when extensive abdominal adhesions prevent passage of a peritoneal shunt catheter toward the pelvis. We present a patient with refractory hydrocephalus in which a multishunt system with drainage into the suprahepatic space was ultimately successful in decompressing the patient's trapped ventricular spaces.


Robust and durable aberrative and absorptive phantom for therapeutic ultrasound applications.
Phase aberration induced by soft tissue inhomogeneities often complicates high-intensity focused ultrasound (HIFU) therapies by distorting the field and, previously, we designed and fabricated a bilayer gel phantom to reproducibly mimic that effect. A surface pattern containing size scales relevant to inhomogeneities of a porcine body wall was introduced between gel materials with fat- and muscle-like acoustic properties-ballistic and polyvinyl alcohol gels. Here, the phantom design was refined to achieve relevant values of ultrasound absorption and scattering and make it more robust, facilitating frequent handling and use in various experimental arrangements. The fidelity of the interfacial surface of the fabricated phantom to the design was confirmed by three-dimensional ultrasound imaging. The HIFU field distortions-displacement of the focus, enlargement of the focal region, and reduction of focal pressure-produced by the phantom were characterized using hydrophone measurements with a 1.5 MHz 256-element HIFU array and found to be similar to those induced by an ex vivo porcine body wall. A phase correction approach was used to mitigate the aberration effect on nonlinear focal waveforms and enable boiling histotripsy treatments through the phantom or body wall. The refined phantom represents a practical tool to explore HIFU therapy systems capabilities.


Comparative sequential morphological analyses during in vitro chondrogenesis and osteogenesis of mesenchymal stem cells embedded in collagen gels.
Chondrogenesis and osteogenesis during fetal development and postnatal growth constitute one of the most interesting and complicated subjects in biology. In this study, bone marrow mesenchymal stem cells (MSCs) were embedded in collagen gel, cultured in chondrogenic or osteogenic medium, and compared morphologically during chondrogenic and osteogenic differentiation sequentially by light and electron microscopy and immunohistochemical examination. Before induction, the MSCs were dispersed and round in the collagen gel. At day 1, MSCs with a large number of short processes produced extracellular fibers whose immunoreactivity was positive for collagen type I. At day 3, the shape of MSCs changed from round to elongated. Gap junctions positive for connexin 43 were also observed. At day 7, remarkable morphological differences were first observed during chondrogenesis and osteogenesis. The shape of MSCs changed to polygonal without cell processes during chondrogenesis, while MSCs remained spindle shaped with long processes during osteogenesis. Concurrently, collagen type II during chondrogenesis and osteocalcin during osteogenesis were first detected. At day 21, chondrogenesis and osteogenesis of the MSC/collagen composite further progressed, respectively. In vitro chondrogenesis and osteogenesis using an MSC/collagen composite clarified the morphological differences.


The adenylate cyclase system and prostaglandin production in human decidua parietalis.
We studied the beta-adrenergic system in the human decidua and its effect on prostaglandin E2 and F2a release from dispersed decidual cells in culture. Beta-adrenergic receptors in decidual membranes were partially characterized using (+)[125I]HYP. Specific binding was demonstrated with maximum binding capacity (Bmax) of 70 +/- 10.6 fmol/mg and an affinity (KD) of 20.85 +/- 1.86 pmol. cAMP dependent phosphoproteins in decidual cytosol were also identified. Two phosphoproteins of M(r) 42,000 and 22,000 were seen in all preparations. Three others (M(r) 39,000, 23,000 and 21,000) were identified in only some of the preparations. Phosphoproteins of similar M(r) to those seen in cytosol prepared from decidual homogenates were also identified in cytosol of cultured decidual cells. Phosphorylation of the 42,000 M(r) and 22,000 M(r) proteins was maximal (3.04 +/- 0.35-fold and 5.7 +/- 0.68-fold) with 10(-6) M cAMP. Cultured decidual cells produced prostaglandin E2 and F2a which increased in a dose-dependent manner in response to dbcAMP, forskolin or isoproterenol. The decidua contains an intact beta-adrenergic system that, when activated, is capable of phosphorylating specific proteins and modulating prostaglandin release.


Medical students and drugs: further neuropsychological and use pattern considerations.
Drug use patterns of 134 freshman medical students were surveyed. Ninety-four percent reported experience with alcohol, 72% with marijuana, 24% with hallucinogens or stimulants, and 7% with opiates. Persons who reported use of the least socially sanctioned substances (hallucinogens, stimulants, opiates) were a subgroup of marijuana users, whereas marijuana experienced students were a subgroup of alcohol users. Increasing marijuana use appears to be associated with increased alcohol consumption. Twenty-five students who had never used marijuana and 26 students who had used it on 50 or more occasions were compared on three neuropsychological tests: Tactual Performance Test, Minnesota Perceptuo-Diagnostic Test, and the Hutt Adaptation of the Bender Gestalt Test. There were no neuropsychological differences between marijuana experienced and marijuana naive subjects. The methodological difficulties in studying the long-term cerebral effects of marijuana are discussed.


Diltiazem enhances and flunarizine inhibits nimodipine's antiseizure effects.
The dihydropyridine calcium channel antagonist, nimodipine has antiepileptic and anticonvulsive properties that are thought to be mediated through neuronal calcium channel blockade. The dihydropyridine binding site can be positively and negatively allosterically regulated by the benzothiazepines and the phenylalkylamines/piperazines, respectively. We investigated this binding interaction at the physiologic level by examining the effects of diltiazem (a benzothiazepine) and flunarizine (a piperazine) on the antiseizure activity of nimodipine. Seizures were induced with pentylenetetrazole in awake rats with chronically implanted EEG electrodes. Calcium channel antagonists were administered intracerebroventricularly 30 min after pentylenetetrazole at doses given at 15 min intervals. Diltiazem and flunarizine alone lacked antiseizure properties. The calculated ED50 values for nimodipine were: nimodipine alone = 135 micrograms; nimodipine + diltiazem (100 micrograms) = 67 micrograms. Nimodipine + flunarizine (10 micrograms) completely suppressed nimodipine's antiseizure activity. These findings may reflect the interaction observed among these agents at binding sites associated with the calcium channel and supports the idea that dihydropyridines mediate their antiseizure actions through neuronal calcium channel antagonism.


In vitro studies of the hemolytic activity of microemulsions in human erythrocytes.
Hemolytic activity in human erythrocytes as alternative to in vivo testing was used as a potential screening method to evaluate irritant potential of microemulsions for possible application in pharmaceutical and cosmetic formulations. Microemulsions were prepared by mixing surfactants and oil and slowly titrating the mixtures with aliquots of phosphate buffer saline or water. All microemulsions were characterized by dynamic light scattering to determine both the mean droplet size and droplet distribution. Microemulsion droplet size decreased as aqueous component increased. No differences in droplet size were observed between formulations containing phosphate buffered saline or water. The hemolytic activity was measured photometrically by the RBC assay, based in the cell membrane lysis, to estimate the potential irritation of both surfactants and microemulsions selected with water or PBS as aqueous component. The most hemolytic microemulsions corresponded to those containing the surfactant Labrasol, with or without butyl lactate, and no differences were found between the hemolytic activity between these components and microemulsions containing them. The highest hemolytic activity of microemulsions in this study may be attributed to the excipient used in the formulations. We should avoid the use of high amounts of Labrasol and butyl lactate in microemulsions because they may be potential irritants.


Smooth muscle cell sarcolemma. Purification and properties of plasma membranes from the rat uterus.
A membrane fraction with sarcolemmal properties was purified from the smooth muscle layers (myometrium) of rat uterus by successive differential and equilibrium centrifugation in sucrose. The putative sarcolemmal fraction was identified by iodination with [125I]iodosulfanilic acid, had an equilibrium density of 1.15, and was enriched in enzyme activities usually associated with the plasma membrane including 5'-nucleotidase (EC 220.127.116.11) and (Na+ + K+) ATPase (EC 184.108.40.206). These membranes were free of mitochondrial or nuclear membrane contamination, suggesting the relative enrichment of sarcolemmal membranes in the fraction. Proteins of the membranes were heterogeneous with respect to molecular weight, but only a few were labelled when intact muscle was radioiodinated. Uniform resistance of sarcolemmal proteins to trypsin digestion and salt extraction suggested many are tightly bound or intrinsic membrane proteins and was a further indication of the homogeneity of membranes in this fraction.


Successful heart transplantation in a patient with Ivemark syndrome combined with situs inversus, single atrium and ventricle after total cavo-pulmonary connection.
Heart transplantation represents a valuable therapeutical option for patients with congenital heart disease and end-stage heart failure. We report the case of a young adult patient with a situs inversus and additional complex congenital malformations of the heart who underwent several prior palliative interventions, a biventricular repair being impossible. Orthotopic cardiac transplantation with several technical modifications was performed successfully at the age of 19 years.


Association between the Ser128Arg variant of the E-selectin and risk of coronary artery disease in the central China.
The E-selectin mediates the interaction of activated endothelial cells with leukocytes and plays a fundamental role in the pathogenesis of coronary atherosclerosis. It has been suggested that a S/R (Ser128Arg) polymorphism of E-selectin might be associated with the predisposition to coronary artery disease (CAD). Our purpose was to determine whether this S/R polymorphism influences the risk of CAD in Chinese patients. We studied the human E-selectin gene polymorphism in a Chinese population by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). This polymorphism was determined in 248 CAD patients and in 256 control subjects. Frequencies of the SS, SR, and RR genotypes were found as 86.7%, 13.3%, and 0.0% in CAD patients and 93.8%, 6.2%, and 0.0% in control subjects, respectively. Frequency of the R allele was higher among CAD patients compared to controls(6.7% vs. 3.1%). However, either the genotype or the allele distribution of Ser128Arg polymorphism of E-selectin was statistically significantly different between the two groups (P<0.05). The odds ratio for the risk of CAD associated with the R allele was 2.21 (CI95%:1.20-4.07). These results suggest that the SR genotype of the E-selectin gene polymorphism in codon 128 is a genetic factor that may determine an individual's susceptibility for CAD in Chinese.


Identifying the Molecular Orientation and Clusters in the Liquid-Vapor Interface of 1-Propanol by Time-Delayed Mass Spectrometry.
Structural inhomogeneity of the liquid-vapor interface, such as the spatial orientation of molecular specific groups and the non-uniform distribution of hydrogen-bonded (HB) clusters, is crucial for understanding the physicochemical processes therein. Although the molecular orientation at the outermost layer was authenticated, to date, direct experimental evidence of the in situ existence of different-sized HB clusters, as a long-standing theoretical argument, is still lacking. Here we report time-delayed electron-impact tandem mass spectrometry, and its powerful ability to identify the local structures of the liquid-vapor interface of 1-propanol is demonstrated not only by mapping the molecular orientations both in the outermost layer and in the subsurface but also by validating the existence of the HB molecular dimers in the subsurface by detecting their protonated ions. We further distinguish two different sources of the protonated dimer: the gas-phase protonation of the neutral dimer that evaporates in advance and the time-lag evaporation of the protonated dimer produced in the subsurface. This methodology is a brand-new way to explore the microstructures and the electron-driven chemical reactions in different local regions of the liquid-vapor interface.


Comparative Analysis of Type I Keratin Expression By Nail Consistency: An Immunohistochemistry Study.
The nail plate is one of the essential structures of the nail apparatus and is highly keratinized, making it difficult to handle this tissue experimentally. Different types of nail consistency were identified by applying distal pressure to the nail plate. To analyze the relationship between the keratins expressed in the nail plate and nail consistency, we chose a sample of 32 adult individuals (age 49.81±3.21 y) with the same number of each sex, who had a similar percentage of nail consistency types (56.25% hard consistency nails and 43.75% soft consistency nails). Immunohistochemical analyses showed that hard consistency nails contain more keratin 17 than soft consistency nails (P=0.026). These novel results allow nail consistency to be defined by the differential expression of keratins in the nail plate, and have potential clinical implications for the diagnosis of possible nail disorders and/or systemic disease.


Accelerated atherosclerosis in a cardiac transplant patient.
A cardiac transplant patient with rapidly progressive graft atherosclerosis is described. This case demonstrates the accelerated nature of this disease and problems in diagnosis, as well as an unexpected and previously unreported lack of sensitivity of exercise thallium scintigraphy in its investigation. This case also gives further support to the practice of routinely and frequently obtaining coronary arteriograms in the management of these patients.


Laparoscopic repair of abdominal hernias using an ePTFE patch--a modification of a previously described technique.
A variety of laparoscopic procedures for the repair of abdominal wall hernias have been described. The repair described in this paper represents a modification and improvement of one approach. Our technique employs an Origin Tacker (Origin Medsystems, Inc, Menlo Park, CA) and a Gore suture passer (W. L. Gore, Flagstaff, AZ) to secure an expanded polytetrafluoroethylene (ePTFE) patch, (DualMesh, W. L. Gore, Flagstaff, AZ) to the anterior abdominal wall. This approach simplifies the repair by minimizing the number of steps required to secure the ePTFE graft to the anterior abdominal. We have found this to be a safe and reliable technique that may be used in the laparoscopic repair of ventral, umbilical, or inguinal hernias.


Adolescent-Parent Relationships and Communication: Consequences for Pregnancy Knowledge and Family Planning Service Awareness.
We explore three dimensions of parent-adolescent relationships (sexual and reproductive health (SRH) communications, connectedness, and parental monitoring) from the perspective of young adolescents as they relate to pregnancy knowledge and family planning service awareness in four diverse geographic areas ranging from low to high income settings and stratified by sex. Analyses utilized baseline data from four Global Early Adolescent Study sites (Shanghai, China; Kinshasa, Democratic Republic of the Congo; Denpasar and Semarang, Indonesia; and New Orleans, United States). Multiple linear regressions were conducted to assess the relationships between key characteristics of parent-adolescent relationships and pregnancy knowledge. Multiple logistic regressions were also conducted to assess relationships between key characteristics of parent-adolescent relationships and family planning service awareness. Across all four sites, communication with a parent about SRH matters was significantly associated with increased pregnancy knowledge among female respondents. Further, girls in Shanghai and New Orleans and boys in Kinshasa who had ever communicated with a parent about SRH matters were significantly more likely to know where to get condoms. Finally, girls who communicated with a parent about any SRH matter were significantly more likely to know where to get other forms of contraception across all four study sites. Findings strongly support the importance of SRH communications between young adolescents and their parents. Our findings also suggest that while parental connectedness and monitoring are beneficial they are not replacements for quality parent-adolescent communications about SRH issues that begin early in adolescence before sexual intercourse is initiated.


Uveal vascular bed in health and disease: uveal vascular bed anatomy. Paper 1 of 2.
The uveal vascular bed is the largest vascular system in the eye and has a role in supplying almost every tissue in the eyeball. This makes it the most important ocular vascular system. This is an up-to-date review of the literature of the entire uveal vascular bed in health based on detailed anatomy of the posterior ciliary arteries (PCAs), anterior ciliary arteries, cilioretinal arteries, and vortex veins. Although postmortem injection cast preparations gave us useful information on the morphology of the choroidal vascular bed; in vivo studies showed that they misled us for centuries about the in vivo situation. According to the postmortem cast studies, the uveal vascular bed has no segmental distribution, the uveal vessels anastomose freely with one another, there are inter-arterial and arteriovenous anastomoses in the choroid, and the choriocapillaris form a freely communicating and an uninterrupted vascular bed in the entire choroid.


Fluorescent Mechanism-Based Probe for Aerobic Flavin-Dependent Enzyme Activity.
Diversity in non-ribosomal peptide and polyketide secondary metabolism is facilitated by interactions between biosynthetic domains with discrete monomer loading and their cognate tailoring enzymes, such as oxidation or halogenation enzymes. The cooperation between peptidyl carrier proteins and flavin-dependent enzymes offers a specialized strategy for monomer selectivity for oxidization of small molecules from within a complex cellular milieu. In an effort to study this process, we have developed fluorescent probes to selectively label aerobic flavin-dependent enzymes. Here we report the preparation and implementation of these tools to label oxidase, monooxygenase, and halogenase flavin-dependent enzymes.


Monoclonal antibody to DNA containing thymine glycol.
Exposure of DNA to ionizing or near ultraviolet radiation modifies thymine to form ring-saturated products. One of the major products formed is 5,6-dihydroxy-5,6-dihydrothymine (thymine glycol). Thymine glycol can also be selectively formed by oxidizing DNA with OsO4. We have isolated hybrids that produce monoclonal antibodies against thymine glycol by fusing mouse myeloma cells (P3X63-Ag8-6.5.3) with spleen cells from BALB/c mice immunized with OsO4-oxidized poly(dT) complexed with methylated bovine serum albumin. This report describes the characterization of the antibody from one hybridoma using a competitive enzyme-linked immunosorbent assay (ELISA). The antibody reacted with both single- and double-stranded DNA treated with OsO4, and with OsO4-treated poly(dA-dT) and poly(dT); it did not crossreact with unmodified or apurinic DNA. It also reacted with DNA treated with H2O2 or with gamma-rays at doses as low as 250 rad. We were able to detect 2 fmoles of thymine glycol in OsO4-treated DNA and could quantitate 1 thymine glycol per 220 000 thymines. Using the antibody and the ELISA, the formation and removal of thymine glycol was examined in cultures of African green monkey cells irradiated with 25 krad of gamma-rays. The antibody reactive sites produced by irradiation (8.5 per 10(6) thymines) were efficiently removed from the cellular DNA.


A CAD/CAM system for the production of metal copings for porcelain-fused-to-metal restorations.
A computer-aided design and manufacture system for the production of metal copings for porcelain-fused-to-metal restorations is described and evaluated. The three stages of production: digitizing, mathematical processing, and milling are described, with emphasis on the system's ability to produce metal copings for both single-unit and multiple-unit restorations. Evaluation of the marginal fit of the produced copings demonstrates the potential for clinically acceptable results.


Transitory behaviors in diffusively coupled nonlinear oscillators.
We study collective behaviors of diffusively coupled oscillators which exhibit out-of-phase synchrony for the case of weakly interacting two oscillators. In large populations of such oscillators interacting via one-dimensionally nearest neighbor couplings, there appear various collective behaviors depending on the coupling strength, regardless of the number of oscillators. Among others, we focus on an intermittent behavior consisting of the all-synchronized state, a weakly chaotic state and some sorts of metachronal waves. Here, a metachronal wave means a wave with orderly phase shifts of oscillations. Such phase shifts are produced by the dephasing interaction which produces the out-of-phase synchronized states in two coupled oscillators. We also show that the abovementioned intermittent behavior can be interpreted as in-out intermittency where two saddles on an invariant subspace, the all-synchronized state and one of the metachronal waves play an important role.


Studies of DNA dumbbells. V. A DNA triplex formed between a 28 base-pair DNA dumbbell substrate and a 16 base linear single strand.
CD spectra and melting curves were collected for a 28 base-pair DNA fragment in the form of a DNA dumbbell (linked on both ends by T4 single-strand loops) and the same DNA sequence in the linear form (without end loops). The central 16 base pairs (bp) of the 28-bp duplex region is the poly(pu) sequence: 5'-AGGAAGGAGGAAAGAG-3'. Mixtures of the dumbbell and linear DNAs with the 16-base single-strand sequence 5'-TCCTTCCTCCTTTCTC-3' were also prepared and studied. At 22 degrees C, CD measurements of the mixtures in 950 mM NaCl, 10 mM sodium acetate, 1 mM EDTA, pH 5.5, at a duplex concentration of 1.8 microM, provided evidence for triplex formation. Spectroscopic features of the triplexes formed with either a dumbbell or linear substrate were quite similar. Melting curves of the duplex molecules alone and in mixtures with the third strand were collected as a function of duplex concentration from 0.16 to 2.15 microM. Melting curves of the dumbbell alone and mixtures with the third strand were entirely independent of DNA concentration. In contrast, melting curves of the linear duplex alone or mixed with the third strand were concentration dependent. At identical duplex concentrations, the dumbbell alone melts approximately 20 degrees C higher than the linear duplex. The curve of the linear duplex displayed a significant pretransition probably due to end fraying. On melting curves of mixtures of the dumbbell or linear duplex with the third strand, a low temperature transition with much lower relative hyperchromicity change (approximately 5%) was observed. This transition was attributed to the melting of a new molecular species, e.g., the triplex formed between the duplex and single-strand DNA molecules. In the case of the dumbbell/single-strand mixture, these melting transitions of the triplex and the dumbbell were entirely resolvable. In contrast, the melting transitions of the linear duplex and the triplex overlapped, thereby preventing their clear distinction. To analyze the data, a three-state equilibrium model is presented. The analysis utilizes differences in relative absorbance vs temperature curves of dumbbells (or linear molecules) alone and in mixtures with the third strand.(ABSTRACT TRUNCATED AT 400 WORDS)


The pertussis hypothesis: Bordetella pertussis colonization in the etiology of asthma and diseases of allergic sensitization.
Decades of peer reviewed evidence demonstrate that: 1)Bordetellapertussisand pertussis toxin are potent adjuvants, inducing asthma and allergic sensitization in animal models of human disease, 2)Bordetella pertussisoften colonizes the human nasopharynx, and is well documented in highly pertussis-vaccinated populations and 3) in children, a history of whooping cough increases the risk of asthma and allergic sensitization disease. We build on these observations with six case studies and offer a pertussis-based explanation for the rapid rise in allergic disease in former East Germany following the fall of the Berlin Wall; the current asthma, peanut allergy, and anaphylaxis epidemics in the United States; the correlation between the risk of asthma and gross national income per capita by country; the lower risk of asthma and allergy in children raised on farms; and the reduced risk of atopy with increased family size and later sibling birth order. To organize the evidence for the pertussis hypothesis, we apply the Bradford Hill criteria to the association between Bordetella pertussisand asthma and allergicsensitization disease. We propose that, contrary to conventional wisdom that nasopharyngealBordetella pertussiscolonizing infections are harmless, subclinicalBordetella pertussiscolonization is an important cause of asthma and diseases of allergic sensitization.


[German adaptation of the "Activities-Specific Balance Confidence (ABC) scale" for the assessment of falls-related self-efficacy].
The present study investigates the psychometric properties and the factorial structure of the German adaptation of the Activities-Specific Balance Confidence (ABC) scale (Powell & Myers, 1995) for the evaluation of falls-related self-efficacy in community-dwelling older adults. The German adaptation of the ABC using a forward-backward procedure was administered to 113 older adults (age 68.9+/-8.5 years). The following internationally accepted instruments were used for validation: The Short Form Health Survey SF 36, the Geriatric Depression Scale (GDS), the Trail Making Test and the Letter Number Sequencing Test, and motor tests (balance, strength, mobility). The internal consistency (0.91-0.95) as well as the test-retest reliability of the subscales was excellent (0.94-0.98). The correlation coefficients with the validation instruments ranged between 0.33 and 0.58. Significant differences in the ABC-D scores were found in older adults with and without falls. Older adults with a recent fall history scored lower on the ABC-D than older adults without a recent fall history. To conclude, the German version of the ABC has properties analogous to the original English version and is apparently useful in assessing falls-related self-efficacy.


The minimum required muscle force for a sit-to-stand task.
The purpose of this study was to reveal the minimum required muscle force for a sit-to-stand task. Combining experimental procedures and computational processing, movements of various sit-to-stand patterns were obtained. Muscle forces and activations during a movement were calculated with an inverse dynamics method and a static numerical optimization method. The required muscle force for each movement was calculated with peak muscle activation, muscle physiological cross sectional area and specific tension. The robustness of the results was quantitatively evaluated with sensitivity analyses. From the results, a distinct threshold was found for the total required muscle force of the hip and knee extensors. Specifically, two findings were revealed: (1) the total force of hip and knee extensors is appropriate as the index of minimum required muscle force for a sit-to-stand task and (2) the minimum required total force is within the range of 35.3-49.2 N/kg. A muscle is not mechanically independent from other muscles, since each muscle has some synergetic or antagonistic muscles. This means that the mechanical threshold of one muscle varies with the force exertion abilities of other muscles and cannot be evaluated independently. At the same time, some kinds of mechanical threshold necessarily exist in the sit-to-stand task, since a muscle force is an only force to drive the body and people cannot stand up from a chair without muscles. These indicate that the existence of the distinct threshold in the result of the total required muscle force is reasonable.


[Hepatitis associated cryoglobulinemia].
Cryoglobulins are immunoglobulins that precipitate at temperatures below 37 degrees C. Clinically cryoglobulinemia is manifested in a variety of symptoms on different organs. The most important clinical symptoms are fatigue, peripheral neuropathy and vasculitis associated skin lesions. Pathophysiologically cryoglobulinemia is based on a disturbed immunocascade with an elevated B-cell-activity. Often a cryoglobulinemia progresses smoothly to a Non-Hodgkin-Lymphoma. The main activator of a cryoglobulinemia is a Hepatitis C virus infection. Other causes for developing a cryoglobulinemia are rheumatological and haematological diseases. In the past cryoglubulinemia has predominantly been treated with plasmapheresis and immunosuppression, nowadays antiviral strategies are becoming more important. Cases of rapid worsening under therapy with interferon alpha have also been reported. A promising new option is the use of rituximab.


Effect of ketamine, an NMDA receptor inhibitor, in acute and chronic orofacial pain.
We examined the analgesic effect of racemic ketamine and its 2 enantiomers in 16 female patients (age: 20-29 years) suffering acute pain after oral surgery and in 7 female patients (age: 42-79 years) suffering chronic neuropathic orofacial pain. All 3 forms of ketamine consistently relieved postoperative pain, (S)-ketamine being 4 times more potent than (R)-ketamine. The analgesic effect was maximal 5 min after i.m. injection and lasted for about 30 min. The 7 patients with neuropathic pain received ketamine at one or several occasions. Four patients (age: 54-79 years) who had suffered pain for more than 5 years did not experience an analgesic effect, whereas 3 patients (age: 42-53 years) who had suffered pain for less than 3 years reported pain relief lasting from 24 h to 3 days. The individual type of response did not depend on the form of ketamine used. The mental side effects were qualitatively similar for the 3 forms of ketamine. Relative to the analgesic effect (S)-ketamine caused more disturbing side effects than did (R)-ketamine. The mean serum concentration of each form of ketamine at the time of maximal effect was close to the approximate Kd value for PCP site occupancy by that particular form. This is in concert with the hypothesis that the effect of ketamine on acute nociceptive pain is due to N-methyl-D-aspartate (NMDA) receptor inhibition and adds to the evidence that NMDA receptors are important for the perception of acute, nociceptive pain in humans.(ABSTRACT TRUNCATED AT 250 WORDS)


A New Monotypic Genus from the American Southwest to accommodate Semiothisa kuschea (Geometridae: Ennominae).
The monotypic Metrica new genus is described for Metrica kuschea (Guedet, 1939) new combination. The genus is placed in the tribe Ennomini Duponchel and hypothesized to be most closely related to a Neotropical species of Isochromodes Warren. Adult morphology, including male and female genitalia are illustrated, and molecular data supporting the transfer of Semiothisa kuschea (Macariini Guene) to the Ennomini are presented.


Immunogenicity of a Plasmodium vivax vaccine based on the duffy binding protein formulated using adjuvants compatible for use in humans.
The invasion of reticulocytes by Plasmodium vivax merozoites is dependent on the interaction of the Plasmodium vivax Duffy Binding Protein (PvDBP) with the Duffy antigen receptor for chemokines (DARC). The N-terminal cysteine-rich region II of PvDBP (PvDBPII), which binds DARC, is a leading P. vivax malaria vaccine candidate. Here, we have evaluated the immunogenicity of recombinant PvDBPII formulated with the adjuvants Matrix-M and GLA-SE in mice. Analysis of the antibody responses revealed comparable ELISA recognition titres as well as similar recognition of native PvDBP in P. vivax schizonts by immunofluorescence assay. Moreover, antibodies elicited by the two adjuvant formulations had similar functional properties such as avidity, isotype profile and inhibition of PvDBPII-DARC binding. Furthermore, the anti-PvDBPII antibodies were able to block the interaction of DARC with the homologous PvDBPII SalI allele as well as the heterologous PvDBPII PvW1 allele from a Thai clinical isolate that is used for controlled human malaria infections (CHMI). The cross-reactivity of these antibodies with PvW1 suggest that immunization with the PvDBPII SalI strain should neutralize reticulocyte invasion by the challenge P. vivax strain PvW1.


Lesions found at foot trimming of dairy goats: Baseline data for comparing lesions and locomotion scoring.
Data on the foot lesions of housed dairy goats, especially those that are not lame, is sparse. In this study, visits were made to four farms for whole herd locomotion scoring after milking and to observe routine foot trimming. During trimming, the amount of trimming required for each hoof was recorded, alongside the presence of lesions. The process was repeated at the next routine foot trim on three of the four farms (on Farm 1 whole herd locomotion scoring after milking was not feasible). Across both visits, 3445 locomotion scores were recorded, alongside 3850 trimming and lesion records. There were large differences between farms and visits in the proportion of lame goats (6.7 to 25.5%) and in the proportion of goats which needed a substantial trim of all four feet (15.1-33.1%). Hoof lesions were observed in 65.5% of trimmed goats. We defined lesions by their site and presence of separation and/or granuloma, with white line separation being the most commonly recorded lesion (41.5% of goats). On all visits on the three farms which were locomotion scored, the number of goats recorded as lame was lower than the number observed with white line lesions, but the relative proportion ranged from 17% to 95.4%. Separations were much more common than granulomas, as granulomas were usually accompanied by separation. Toe lesions were much more likely to be associated with granulomas than white line lesions, with 91.5% of toe separations having granulomas but only 10.6% of white line separations. This study provides useful baseline data for comparing lesions and locomotion scoring between goat herds but also identifies areas where we need more data and more consensus.


ACPS: An accurate bioinformatics tool for precision-based anti-cancer peptide generation via omics data.
The anti-cancer targets play a crucial role in the signaling processes of cells, and therefore, it becomes nearly impossible to engage these targets without affecting the native cellular function. Thus, an approach has been taken to develop an anti-cancer Scanner (ACPS) tool aimed toward the recognition of anti-cancer marks in the form of peptides. The proposed ACPS tool allows fast fingerprinting of the anti-cancer targets having extreme significance in the current bioinformatics research. There already exist some tools that offer these features on a single platform; however, the performance of ACPS was compared with the preexisting online tools and was observed that ACPS offers greater than 95% accuracy that is comparatively much higher. The anti-cancer marked sequences of proteins supplied by the operators are scanned against the anti-cancer target datasets via ACPS and provide precision-based anti-cancer peptides. The proposed tool has been contrived in PERL programming language, and this tool is the extended version of A-CaMP codes, which are highly scalable having an extensible application in cancer biology with robust coding architecture. The availability of tools like ACPS will greatly benefit researchers in the field of oncology and structure-based drug design.


Sumoylation, a post-translational regulatory process in plants.
The reversible conjugation of the small ubiquitin-related modifier (SUMO) peptide to protein substrates (sumoylation) is emerging as a major post-translational regulatory process in animals and other eukaryotes, including plants. Database annotation, and genetic and biochemical analyses indicate that components of the SUMO conjugation and deconjugation systems are conserved in plants such as Arabidopsis, rice, tomato, and Medicago. Specifically, Arabidopsis AtSUMO1/2 and SUMO E2 conjugation enzyme AtSCE1a are implicated in abscisic acid (ABA) responses and the ubiquitin-like SUMO protease 1 (ULP1) AtESD4 in flowering time regulation. The AtSIZ1 SUMO E3 ligase functions in phosphate starvation responses, cold tolerance, basal thermotolerance, salicylic acid (SA)-dependent pathogen defense, and flowering time regulation. Following is a brief overview of the current understanding of SUMO conjugation and deconjugation determinants, and biological processes that are regulated in plants.


Microsporidian polar tube proteins: highly divergent but closely linked genes encode PTP1 and PTP2 in members of the evolutionarily distant Antonospora and Encephalitozoon groups.
The spore polar tube is a unique organelle required for cell invasion by fungi-related microsporidian parasites. Two major polar tube proteins (PTP1 and PTP2) are encoded by two tandemly arranged genes in Encephalitozoon species. A look at Antonospora (Nosema) locustae contigs (http://jbpc.mbl.edu/Nosema/Contigs/) revealed significant conservation in the order and orientation of various genes, despite high sequence divergence features, when comparing with Encephalitozoon cuniculi complete genome. This syntenic relationship between distantly related Encephalitozoon and Antonospora genera has been successfully exploited to identify ptp1 and ptp2 genes in two insect-infecting species assigned to the Antonospora clade (A. locustae and Paranosema grylli). Targeting of respective proteins to the polar tube was demonstrated through immunolocalization experiments with antibodies raised against recombinant proteins. Both PTPs were extracted from spores with 100mM dithiothreitol. Evidence for PTP1 mannosylation was obtained in studied species, supporting a key role of PTP1 in interactions with host cell surface.


Flow resistance in mechanically ventilated patients with severe neurological injury.
In 5 mechanically ventilated patients with severe neurological injury (SNI), we measured the respiratory system's flow resistance (Rrs) over a range of inspiratory flows between 0.2 to 2 L/s, at inflation volumes (delta V) ranging from 0.1 to 1 L. Under baseline ventilatory conditions (V = 1 L/s; delta V = 0.95 L), we also partitioned Rrs into airway resistance (Raw) and the additional resistance offered by the tissues of the lung and chest wall (delta Rrs). At all inflation volumes, Rrs decreased hyperbolically with increasing flow but was higher than in normal anesthetized paralyzed subjects (N). At V of 1 L/s and delta V of 0.5 L, Rrs was significantly greater in SNI than in N (7.7 +/- 1.5 v 4.2 +/- 0.5 cm H2O/L/s; P < .01). This discrepancy was due to higher Raw in SNI. Indeed, at V of 1 L/s, Raw (mean +/- SEM) was significantly higher in SNI than in N (4.0 +/- 0.9 v 2.4 +/- 0.2 cm H2O/L/s; P < .001), whereas delta Rrs did not differ significantly. The increased Raw in SNI was due to the fact that these patients were therapeutically hyperventilated (PaCO2 = 30.4 +/- 4.2 mm Hg) and as a result their airways were bronchoconstricted. We conclude that in the intensive care unit setting, hyperventilated patients with severe neurological injury can not be considered to be adequate controls in terms of Rrs and Raw, because hypocapnia induces an increase of Raw and consequently also in Rrs (= Raw+delta Rrs).


A study of meconium staining and meconium aspiration syndrome in a maternity hospital.
To determine the incidence of meconiumstaining and meconium aspiration syndrome in a maternity hospital in Colombo and to evolve a suitable protocol for management. A prospective study of 366 meconium stained babies delivered during 1988. Castle Street Hospital for Women, Colombo. 113 babies developed the 'meconium aspiration syndrome' and 16 of them died.


Identifying Breast Cancer Distant Recurrences from Electronic Health Records Using Machine Learning.
Accurately identifying distant recurrences in breast cancer from the Electronic Health Records (EHR) is important for both clinical care and secondary analysis. Although multiple applications have been developed for computational phenotyping in breast cancer, distant recurrence identification still relies heavily on manual chart review. In this study, we aim to develop a model that identifies distant recurrences in breast cancer using clinical narratives and structured data from EHR. We applied MetaMap to extract features from clinical narratives and also retrieved structured clinical data from EHR. Using these features, we trained a support vector machine model to identify distant recurrences in breast cancer patients. We trained the model using 1,396 double-annotated subjects and validated the model using 599 double-annotated subjects. In addition, we validated the model on a set of 4,904 single-annotated subjects as a generalization test. In the held-out test and generalization test, we obtained F-measure scores of 0.78 and 0.74, area under curve (AUC) scores of 0.95 and 0.93, respectively. To explore the representation learning utility of deep neural networks, we designed multiple convolutional neural networks and multilayer neural networks to identify distant recurrences. Using the same test set and generalizability test set, we obtained F-measure scores of 0.79 ± 0.02 and 0.74 ± 0.004, AUC scores of 0.95 ± 0.002 and 0.95 ± 0.01, respectively. Our model can accurately and efficiently identify distant recurrences in breast cancer by combining features extracted from unstructured clinical narratives and structured clinical data.


Genotype and phenotype heterogeneity in perrault syndrome.
The hallmarks of Perrault syndrome are progressive sensorineural hearing loss and ovarian dysgenesis, but the disorder is both clinically and genetically heterogenous. We report a 15-year-old girl with gonadal dysgenesis, unilateral sensorineural deafness, cataracts in both eyes, and Marfanoid body proportions diagnosed Perrault syndrome. We detected 14 single nucleotide variations including 2 homozygous missense change of c.317G>A (p.Arg106His) and c.1675A>G (p.Ile559Val) in HSD17B4. No significant mutation in HARS2 and PSMC3IP, and gene copy number variant were found as the cause of Perrault syndrome. Mutations in HARS2, HSD17B4, and PSMC3IP genes do not explain Perrault syndrome in our patient, indicating that other critical genes remain to be identified.


Spanish population data and forensic usefulness of a novel Y-STR set (DYS437, DYS438, DYS439, DYS460, DYS461, GATA A10, GATA C4, GATA H4).
DNA typing of 8 recently described STRs on the Y chromosome was carried out by means of 2 multiplex amplification reactions for 134 unrelated males from Cantabria, a region in northern Spain. Multiplex 1 included loci DYS460 (GATA A7.1), GATA A10, GATA H4 and DYS439; multiplex 2 included DYS461 (GATA A7.2), GATA C4, DYS437 and DYS438. Haplotype diversity was found to be 99.36%, similar to that obtained with the standard 9-STR set ("minimal haplotype") of the European Y-user group (99.35%). The 13-locus haplotype resulting from the combination of the standard minimal haplotype and the 4-locus multiplex 1 showed a 99.89% diversity. Further inclusion of the 4 loci in multiplex 2 resulted in a haplotype diversity of 99.93%. The combination of the "minimal haplotype" and the multiplex 1 in the present study may be an efficient way of increasing the power of discrimination in forensic cases.


Pilot data of serum proteins from children with autism spectrum disorders.
Protein profiles of 13 serum samples from children with autism spectrum disorders (ASD) and 11 serum samples from healthy volunteers was obtained using panoramic ultra-high resolution mass spectrometry. The analysis of measurements was performed using the proteomics search engine. We identified a group of 74 proteins which we term a "protein fingerprint" specific for serum samples collected from children with autism. Components of the protein fingerprint are involved in hemostasis maintenance including biological regulation, the response to stimulus, regulation of metabolism, and proteins of the immune system.


Unreliability of home blood pressure measurement and the effect of a patient-oriented intervention.
Home blood pressure (BP) measurement (HBPM) is recommended for the diagnosis and follow-up of high BP. It is unclear how this aspect of BP monitoring has evolved over the years and whether interventions could influence patient adherence to HBPM guidelines. After a questionnaire-based cross-sectional study performed in 2010, a passive, multimodal intervention, focused on improving adherence to HBPM guidelines, was implemented. A second study was conducted in 2014 to measure its effect. In 2010 and 2014, 1010 and 1005 patients, respectively, completed the questionnaire. In 2010 and 2014, 82% and 84% of patients, respectively, self-measured their BP. Reporting of HBPM and adherence to recommended procedures was suboptimal. Only 34.0% of patients in 2010 and 31.7% in 2014 brought > 80% of their measurements to their doctor. Only 49.6% in 2010 and 52.9% in 2014 prepared > 80% of the time for HBPM. Only 48.1% in 2010 and 52.1% in 2014 rested for 5 minutes > 80% of the time before HBPM. Only 15% of patients in 2010 and 18% in 2014 were defined as sufficiently compliant with all HBPM procedures. Paired analysis of a subset of 535 patients who participated in the 2010 and 2014 studies showed no clinically significant differences in reliability between the 2 surveys. Adherence to HBPM guidelines was suboptimal in 2010 and still is in 2014 despite a passive, multimodal intervention. Active training in HBPM procedures should be studied. Greater automation could improve HBPM reliability.


RETIRED: Tension-free vaginal tape (TVT) procedure.
This document has been archived because it contains outdated information. It should not be consulted for clinical use, but for historical research only. Please visit the journal website for the most recent guidelines.


Blood pressure and cognitive function in an African-American and a Caucasian-American sample: the Maine-Syracuse Study.
The primary purpose of this study was to examine associations between indices of blood pressure (BP) and cognitive function for African-American participants in the Maine-Syracuse Longitudinal Study (MSLS). Corresponding data for the Caucasian-American MSLS participants were included to provide a basis for comparison. Interactions of age with BP indices were also assessed in relation to cognitive function. Data were drawn from the baseline MSLS questionnaires, medical interviews and examinations, Wechsler Adult Intelligence Scale subtests, and measurements of BP for 1563 participants, of whom 147 were African American. Multiple linear regression analyses were employed to examine the relationship between several BP predictors and cognitive outcomes with statistical adjustment for demographic, psychosocial, and cardiovascular risk factors. Significant inverse associations between BP indices and cognitive performance were obtained for both racial cohorts but were generally of higher magnitude for the African-American cohort. Interactions of BP with age were not obtained for any of the cognitive test scores. Elevations in BP are associated with poorer cognitive function for African-American and Caucasian-American cohorts. These associations are similar for younger and older participants.


Mediation of glucolipotoxicity in INS-1 rat insulinoma cells by small heterodimer partner interacting leucine zipper protein (SMILE).
Sustained elevations of glucose and free fatty acid concentration have deleterious effects on pancreatic beta cell function. One of the hallmarks of such glucolipotoxicity is a reduction in insulin gene expression, resulting from decreased insulin promoter activity. Sterol regulatory element binding protein-1c (SREBP-1c), a lipogenic transcription factor, is related to the development of beta cell dysfunction caused by elevated concentrations of glucose and free fatty acid. Small heterodimer partner (SHP) interacting leucine zipper protein (SMILE), also known as Zhangfei, is a novel protein which interacts with SHP that mediates glucotoxicity in INS-1 rat insulinoma cells. Treatment of INS-1 cells with high concentrations of glucose and palmitate increased SREBP-1c and SMILE expression, and decreased insulin gene expression. Adenovirus-mediated overexpression of SREBP-1c in INS-1 cells induced SMILE expression. Moreover, adenovirus-mediated overexpression of SMILE (Ad-SMILE) in INS-1 cells impaired glucose-stimulated insulin secretion as well as insulin gene expression. Ad-SMILE overexpression also inhibited the expression of beta-cell enriched transcription factors including pancreatic duodenal homeobox factor-1, beta cell E box transactivator 2 and RIPE3b1/MafA, in INS-1 cells. Finally, in COS-1 cells, expression of SMILE inhibited the insulin promoter activity induced by these same beta-cell enriched transcription factors. These results collectively suggest that SMILE plays an important role in the development of beta cell dysfunction induced by glucolipotoxicity.


Adults with Loeys-Dietz syndrome and vascular Ehlers-Danlos syndrome: A cross-sectional study of life satisfaction.
To explore life satisfaction among adults with Loeys-Dietz and those with vascular Ehlers-Danlos syndrome. Postal survey in 2018. Persons with molecularly verified Loeys-Dietz syndrome or vascular Ehlers-Danlos syndrome were recruited through the National Resource Centre for Rare Disorders in Norway. The study used the Life Satisfaction Questionnaire 11, Hospital Anxiety and Depression Scale, Fatigue Severity Scale, and questions about physical activity and disease burden. Descriptive statistics were conducted with Bonferroni corrections. The response rate was 74%, 52 participants, age range 18-68 years, and 58% were women. Only half of the participants were satisfied with their lives as a whole. Participants reported dissatisfaction with vocation, somatic health, and sexual life in particular. Participants with vascular Ehlers-Danlos syndrome (n = 18) were satisfied with more areas of life than those with Loeys-Dietz syndrome (n = 34). Low overall satisfaction was significantly associated with severe fatigue (p = 0.002) and symptoms of anxiety (p = 0.001). This study provides important information about living with Loeys-Dietz syndrome and vascular Ehlers-Danlos syndrome. Future studies should identify factors that reduce/increase life satisfaction. Professionals in welfare systems need more information about the unique challenges of living with these diagnoses. Guidelines for research and clinical measurements of life satisfaction should be updated.


First Detection and Characterization of Hepatitis E Virus in Sewage Samples in Cameroon.
Hepatitis E virus (HEV) represents an important public health concern in many developing countries, including Africa. Transmission of HEV to humans by contaminated drinking water is the most important mode of transmission in low- and middle-income countries. This study aimed to assess the presence of HEV in the environment in Cameroon through molecular analysis of sewage samples. Retrospectively, a total of 157 sewage samples collected between January 2018 and December 2019 were randomly selected and analyzed by molecular techniques to detect and characterize the HEV followed by sequencing and phylogenetic analysis. Three samples (1.9%) collected from North, Far North, and Adamawa regions were positive by real-time reverse transcription polymerization chain reaction. Among these, 2 samples were positive for HEV ribonucleic acid by nested reverse transcription polymerization chain reaction and only one yielded a good sequencing product. Phylogenetic analysis of this unique HEV strain showed that this HEV strain belonged to genotype 3, subtype 3a, and clustered with swine HEV strains from Cameroon, Argentina, and the USA. This study provides preliminary data on the circulation of HEV in wastewater in Cameroon. Further studies will be needed to assess the overall situation in Cameroon.


Does Geographical Bias Impact the Match for General Surgery Residents?
As the competitiveness of applicants for general surgery residency grows, it is becoming challenging for programs to differentiate qualified candidates with a genuine interest in matching at their institution. The purpose of this study was to examine geographic trends in the general surgery match in order to elicit regional biases and optimize applicant interview selection strategies. In this single-center retrospective study, geographical information regarding birth place, college, medical school, and final match institution for general surgery residency applicants was examined. This study was set at the University of Cincinnati College of Medicine. All general surgery residency applicants interviewing at our institution between 2015-2017 were included. Academic variables and geographical information were collected for all applicants in the cohort. Statistical analyses were performed using chi-square and logistic regression techniques to determine any association between geography and match outcomes. Of 198 applicants included in the analysis, approximately 25% matched at an institution located in the same state as their medical school. Total 75% of applicants matched at a residency program located less than 640 miles away from either their birth place, college, or medical school, while only 15% matched at an institution located over 1000 miles away and 4% matched over 2000 miles away. When examining applicant characteristics, there were no significant differences in gender, clerkship grade, United States Medical Licensing Exam scores, Alpha Omega Alpha Honor Society membership, or quality of recommendation letters between applicants who matched in the lowest and highest quartiles of distance to final residency program location. A significant proportion of general surgery applicants matched at institutions located in a region near either their birth place, college, or medical school. Given the limited number of interviews able to be offered by institutions and the associated opportunity costs, general surgery programs should consider regional biases when evaluating residency applicants.


Cost-Utility Analysis of Extending Public Health Insurance Coverage to Include Diabetic Retinopathy Screening by Optometrists.
Diabetic retinopathy (DR) is one of the leading causes of vision loss and blindness in Canada. Eye examinations play an important role in early detection. However, DR screening by optometrists is not always universally covered by public or private health insurance plans. This study assessed whether expanding public health coverage to include diabetic eye examinations for retinopathy by optometrists is cost-effective from the perspective of the health care system. We conducted a cost-utility analysis of extended coverage for diabetic eye examinations in Prince Edward Island to include examinations by optometrists, not currently publicly covered. We used a Markov chain to simulate disease burden based on eye examination rates and DR progression over a 30-year time horizon. Results were presented as an incremental cost per quality-adjusted life year (QALY) gained. A series of one-way and probabilistic sensitivity analyses were performed. Extending public health coverage to eye examinations by optometrists was associated with higher costs ($9,908,543.32) and improved QALYs (156,862.44), over 30 years, resulting in an incremental cost-effectiveness ratio of $1668.43/QALY gained. Sensitivity analysis showed that the most influential determinants of the results were the cost of optometric screening and selected utility scores. At the commonly used threshold of $50,000/QALY, the probability that the new policy was cost-effective was 99.99%. Extending public health coverage to eye examinations by optometrists is cost-effective based on a commonly used threshold of $50,000/QALY. Findings from this study can inform the decision to expand public-insured optometric services for patients with diabetes.


Coronary vasospasm-induced acute coronary syndrome complicated by life-threatening cardiac arrhythmias in patients without hemodynamically significant coronary artery disease.
Coronary vasospasm-induced electrical and mechanical complications in patients with acute coronary syndrome and no hemodynamically significant coronary artery disease are rarely reported. A total of 733 consecutive patients with acute coronary syndrome admitted to our hospital who subsequently underwent coronary angiography at our institution were enrolled. Patients who had documented complete atrioventricular block or ventricular fibrillation, no evidence of hemodynamically significant coronary artery disease on coronary angiogram, and no other (non-coronary) cardiac abnormalities were included. Patients were followed for subsequent cardiac events and mortality. Over a 6-year period at our institution, acute coronary syndrome complicated by life-threatening cardiac arrhythmias developed in six patients who had no hemodynamically significant coronary artery disease with corresponding intra-coronary ergonovine provocative coronary vasospasm. Acute myocardial infarction was diagnosed in five of these patients and variant angina pectoris in one. Complete atrioventricular block was the most common complication in these cases, followed by cardiogenic shock with or without right ventricular infarction, ventricular fibrillation, and severe sinus arrest. These complications were corrected with intravenous fluid, intravenous atropine or cardiac defibrillation. During a median follow-up period of 26 months, none of the patients expired or suffered nonfatal reinfarction. Two individuals who did not stop smoking during follow-up developed recurrent angina after self-discontinuation of calcium antagonists. Coronary vasospasm can be a cause of life-threatening cardiac arrhythmias in patients with acute coronary syndrome and no hemodynamically significant coronary artery disease. Coronary angiography with/without intra-coronary ergonovine testing is necessary in acute coronary syndrome patients to identify the underlying pathology and establish appropriate treatment in these cases.


Comparing Cerebellar tDCS and Cerebellar tACS in Neurodegenerative Ataxias Using Wearable Sensors: A Randomized, Double-Blind, Sham-Controlled, Triple-Crossover Trial.
Cerebellar transcranial direct current stimulation (tDCS) represents a promising therapeutic approach for both motor and cognitive symptoms in neurodegenerative ataxias. Recently, transcranial alternating current stimulation (tACS) was also demonstrated to modulate cerebellar excitability by neuronal entrainment. To compare the effectiveness of cerebellar tDCS vs. cerebellar tACS in patients with neurodegenerative ataxia, we performed a double-blind, randomized, sham controlled, triple cross-over trial with cerebellar tDCS, cerebellar tACS or sham stimulation in twenty-six participants with neurodegenerative ataxia. Before entering the study, each participant underwent motor assessment with wearable sensors considering gait cadence (steps/minute), turn velocity (degrees/second) and turn duration (seconds), and a clinical evaluation with the scale for the Assessment and Rating of Ataxia (SARA) and the International Cooperative Ataxia Rating Scale (ICARS). After each intervention, participants underwent the same clinical assessment along with cerebellar inhibition (CBI) measurement, a marker of cerebellar activity. The gait cadence, turn velocity, SARA, and ICARS significantly improved after both tDCS and tACS, compared to sham stimulation (all p<0.010). Comparable effects were observed for CBI (p<0.001). Overall, tDCS significantly outperformed tACS on clinical scales and CBI (p<0.01). A significant correlation between changes of wearable sensors parameters from baseline and changes of clinical scales and CBI scores was detected. Cerebellar tDCS and cerebellar tACS are effective in ameliorating symptoms of neurodegenerative ataxias, with the former being more beneficial than the latter. Wearable sensors may serve as rater-unbiased outcome measures in future clinical trials. ClinicalTrial.gov Identifier: NCT05621200.


Increased sodium intake correlates with greater use of antihypertensive agents by subjects with chronic kidney disease.
Hypertension is a common disease in patients with chronic kidney disease (CKD) and predisposes to heart disease, stroke, and progression of renal failure. In the general population, sodium restriction has been shown to improve blood pressure (BP) control, but this is not widely recommended in CKD patients. The aim of this study was to assess the sodium balance in a CKD clinic and its effect on BP management. We retrospectively reviewed charts from June 1998 through to June 2003 and included all patients with an estimated glomerular filtration rate (GFR) of <30 mL/min who completed a 24-h urine collection for sodium. Patients were divided into tertiles based upon their 24-h sodium excretion and analyzed by ANOVA. We included 141 CKD patients who had a mean (+/- SE) sodium excretion of 145.7 +/- 4.7 mmol/day. There were a significantly greater number of antihypertensive agents used with increasing sodium excretion (2.00 +/- 0.16, 2.61 +/- 0.20, and 2.77 +/- 0.19 medications, respectively for each tertile; P = .01). This difference was even more prominent when only those patients with a GFR <or=15 mL/min (n = 77) were examined (1.69 +/- 0.19, 2.52 +/- 0.27, and 3.08 +/- 0.26 medications, respectively; P = .001). Control of BP was equivalent in all groups. Multivariable analysis revealed sodium excretion (P = .00005) and age (P = .007) to be significantly associated with use of antihypertensive medication. We have demonstrated that increased sodium intake is associated with an increased number of antihypertensive medications to achieve comparable BP control in a population with CKD.


The effect of vasopressin infusion on glucose metabolism in man.
Studies on intact animals and isolated rat hepatocytes have shown that arginine vasopression (AVP) stimulates glycogen phosphorylase to break down glycogen and raise plasma glucose concentrations. Since no similar work has been performed on healthy human adults, the effect of moderate (25 pmol/min) and high (75 pmol/min) dose AVP infusion on plasma glucose, intermediary metabolites, glucose kinetics, and circulating glucagon and insulin concentrations was investigated. After AVP infusion, plasma glucose rose from 4.9 +/- 0.1 to a peak of 5.7 +/- 0.2 mmol/l (P less than 0.001), but no changes in blood lactate, pyruvate, alanine, glycerol or 3-hydroxybutyrate concentrations were observed. The glucose rise was accounted for entirely by an increase in the rate of appearance of glucose from 11.19 +/- 0.43 to 13.38 +/- 0.63 mu mol/kg/min (P less than 0.001). Infusion of AVP also increased plasma glucagon concentrations from 38 +/- 8 to 79 +/- 20 pg/l (P less than 0.01). The hyperglycaemic effect of AVP may be mediated solely by stimulation of glucagon release, but we cannot exclude direct stimulation of glycogen phosphorylase activity.


Evaluating the relationships of hypoglycaemia and HbA1c with screening-detected diabetes distress in type 1 diabetes.
To explore the relationship between diabetes distress, glucose control and awareness of hypoglycaemia in adults with type 1 diabetes. We performed a cross-sectional study using data collected from 280 consecutive type 1 diabetes patients who used a routine clinic consultation tool that recorded HbA1c, hypoglycaemia awareness (measured using the Gold score) and diabetes distress (measured using the Diabetes Distress Scale 2 [DDS2]). We assessed correlations between DDS2 and HbA1c and DDS2 and Gold score and performed an ordinal regression analysis to identify factors contributing to distress. Diabetes distress was significantly correlated with HbA1c (r = .319, P < .001) and Gold score (r = .258, P < .001) independently and with synergistic effect. Female gender was also associated with diabetes distress, while age, BMI, duration of diabetes, severity of complications and use of CSII pumps were not. Occurrence of severe hypoglycaemia (SH) episodes increased with Gold score in a linear manner throughout the scale. This study has identified new evidence of a significant, independent relationship between diabetes distress measured by the DDS2 and reduced awareness of hypoglycaemia in people with type 1 diabetes. It also demonstrates that diabetes distress is significantly associated with HbA1c and female gender independently. The DDS2 identifies distress associated with both hypo- and hyperglycaemia and can be a useful creening tool. Additionally, the occurrence of SH increases with increasing Gold score.


Temporal associations between problematic use of the internet and self-stigma among people with substance use disorders: A cross-lagged model across one year.
Self-stigma is a common experience for people with substance use disorders (SUDs). Understanding factors associated with self-stigma may aid in intervention development. This study investigated the reciprocal relationship between three types of problematic use of the internet [PUI; i.e. problematic use of social media (PUSM), problematic smartphone use (PSPU), and problematic gaming (PG)] and self-stigma among people with SUDs. This longitudinal study involved five waves of a survey given to individuals with SUDs in Taiwan. A total of 319 participants (85% male), with a mean age of 42.2 years (SD = 8.9), were recruited. The Smartphone Application-Based Addiction Scale, Bergen Social Media Addiction Scale, Internet Gaming Disorder-Short Form, and Self-Stigma Scale-Short Form were used. No significant associations between PUI and self-stigma were found in early waves (i.e., Waves 1 and 2). The earliest significant finding was identified between Wave 2 PSPU (smartphone) and Wave 3 self-stigma. Additionally, Wave 3 PSPU (smartphone) and PG (gaming) were associated with Wave 4 self-stigma, and Wave 4 PSPU (smartphone), PG (gaming), and PUSM (social media) were associated with Wave 5 self-stigma. Therefore, all three types of PUI (internet) may elevate self-stigma at different time points for individuals with SUDs. However, the reciprocal effects between self-stigma and PUI (internet) only occurred in PUSM (social media) at a later stage (i.e., from Wave 4 to Wave 5). In conclusion, people with SUDs who have PUI (internet) are at increased likelihood of developing more self-stigma, which may then increase subsequent PUSM (social media), forming a vicious cycle.


Metal Concentrations in Eurasian Eagle Owl Pellets as a Function of Reproductive Variables in Korea.
Eight metals were analyzed in the pellet of Eurasian eagle owls (Bubo bubo) breeding in Korea: Paju, Ganghwa, Gimpo, and Sihwa, Gyeonggi-do (N = 15, respectively). Except for cadmium (Cd), concentrations of all metals differed among sites (ANOVA, p < 0.001); Sihwa had relatively higher metal concentrations compared with other sites. Clutch size did not differ among the four sites. However, Sihwa had the greatest nesting success and number of fledglings (per hatchlings and laid egg) and highest mean weight of diet. Lead concentrations in the pellets were generally lower than the excrements of various birds worldwide. We suggest that all metal concentrations in pellets do not negatively affect the reproduction of Eurasian eagle owls, and food supply at Sihwa seems likely more important to breeding success than metal contamination.


Toxicity of a male contraceptive, gossypol, in mammalian cell cultures.
Gossypol, a substance extracted from cotton plants, is a potential male contraceptive. Although human users reported only mild or no side effects, our study found gossypol to be cytotoxic to cultured mammalian cells. A dose dependent decrease in the number of viable cells and mitotic index was demonstrated with both Chinese hamster ovary (CHO) cells and human lymphocytes after the cultures received treatment of gossypol for various durations. Cellular DNA, RNA, and protein synthetic activities were reduced in the presence of gossypol. However, gossypol did not seem to induce chromosome breakage or polyploidy.


Interpretation of Mismatch Repair Protein Immunohistochemistry in Endometrial Carcinoma Should Consider Both Lynch Syndrome Screening and Immunotherapy Susceptibility: An Illustrative Case Report.
We present an instructive case of FIGO grade 1 endometrioid endometrial carcinoma with a biphasic morphology, corresponding to subclonal loss of mismatch repair proteins (MMRP) MLH1 and PMS2 by immunohistochemistry and subclonal microsatellite instability. A pulmonary metastasis represented only the tumor component with retention of MMRPs. This case illustrates the need for pathologists to recognize and report heterogenous expression of MMRPs in endometrial carcinoma, to consider tumor heterogeneity when selecting foci for molecular studies, and to re-evaluate MMRP expression in tumor metastases, when clinically indicated. These considerations are particularly important as the relevance of MMRP expression in endometrial cancer expands beyond Lynch syndrome screening, into a new role as a predictive marker for immunotherapy.


Optimization of immobilization conditions of Bacillus atrophaeus FSHM2 lipase on maleic copolymer coated amine-modified graphene oxide nanosheets and its application for valeric acid esterification.
The thermoalkalophilic lipase from Bacillus atrophaeus (BaL) was immobilized onto amine-functionalized graphene oxide nanosheets coated with the poly (maleic anhydride-alt-1-octadecene) copolymer (GO-NH2-PMAO) and activated with glutaraldehyde as spacer arm through interfacial activation and subsequent multipoint covalent attachment. Experimental design method was applied for optimization of immobilization conditions including GO-NH2-PMAO concentration, buffer concentration, pH, sonication time, enzyme concentration, glutaraldehyde concentration, time, and temperature. The optimum specific activity of the immobilized BaL (105.95 ± 2.37 U/mg) reached at 5 mg/mL for GO-NH2-PMAO, 25 mM of buffer, pH 6.0, 60 min sonication time, 100 mM glutaraldehyde, 60 U/mL of enzyme, and 4 h of immobilization time at 25 °C, which was very close to the predicted amount (106.08 ± 1.42 U/mg). Maximum immobilization yield (81.35%) and efficiency (277.63%) were determined in optimal immobilization conditions. The obtained results clearly indicated that the immobilized BaL exhibited better stability at extreme temperature and pH than the free BaL. At temperature of 90 °C and pH 11, more than 90% of the initial activity of the immobilized BaL was retained. Furthermore, the immobilized BaL retained about 90% of its initial activity after 10 days of storage and 6 cycles of application. The esterification studies showed that maximum bioconversion of valeric acid to pentyl valerate using the free BaL (34.5%) and the immobilized BaL (96.3%) occurred in the xylene medium after 48 h of incubation at 60 °C. Therefore, the BaL immobilized on GO-NH2-PMAO was introduced as an effective biocatalyst to synthesize green apple flavour ester.


Applications of Artificial Intelligence in Breast Imaging.
Artificial intelligence (AI) technology shows promise in breast imaging to improve both interpretive and noninterpretive tasks. AI-based screening triage may help identify normal examinations and AI-based computer-aided detection (AI-CAD) may increase cancer detection and reduce false positives. Risk assessment, quality assurance, and other workflow tasks may also be streamlined. AI adoption will depend on robust evidence of improved quality, increased efficiency, and cost-effectiveness. Reliance on AI will likely proceed through stages and will involve careful attention to its limitations to prevent overconfidence in its application.