French Society of Cardiology guidelines on exercise tests (part 2): Indications for exercise tests in cardiac diseases.
The exercise test is performed routinely in cardiology; its main indication is the diagnosis of myocardial ischemia, evaluated along with the subject's pretest probability and cardiovascular risk level. Other criteria, such as analysis of repolarization, must be taken into consideration during the interpretation of an exercise test, to improve its predictive value. An exercise test is also indicated for many other cardiac diseases (e.g. rhythm and conduction disorders, severe asymptomatic aortic stenosis, hypertrophic cardiomyopathy, peripheral artery disease, hypertension). Moreover, an exercise test may be indicated for specific populations (women, the elderly, patients with diabetes mellitus, patients in a preoperative context, asymptomatic patients and patients with congenital heart defects). Some cardiac diseases (such as chronic heart failure or arterial pulmonary hypertension) require a cardiopulmonary exercise test. Finally, an exercise test or a cardiopulmonary exercise test is indicated to prescribe a cardiac rehabilitation programme, adapted to the patient.


Antithyroid drugs inhibit thyroid hormone receptor-mediated transcription.
Methimazole (MMI) and propylthiouracil (PTU) are widely used as antithyroid drugs (ATDs) for the treatment of Graves' disease. Both MMI and PTU reduce thyroid hormone levels by several mechanisms, including inhibition of thyroid hormone synthesis and secretion. In addition, PTU decreases 5'-deiodination of T(4) in peripheral tissues. ATDs may also interfere with T(3) binding to nuclear thyroid hormone receptors (TRs). However, the effect of ATDs on the transcriptional activities of T(3) mediated by TRs has not been studied. The present study was undertaken to determine whether ATDs have an effect on the gene transcription regulated by T(3) and TRs in vitro. Transient gene expression experiments and GH secretion assays were performed. To elucidate possible mechanisms of the antagonistic action of ATDs, the interaction between TR and nuclear cofactors was examined. In the transient gene expression experiments, both MMI and PTU significantly suppressed transcriptional activities mediated by the TR and T(3) in a dose-dependent manner. In mammalian two-hybrid assays, both drugs recruited one of the nuclear corepressors, nuclear receptor corepressor, to the TR in the absence of T(3). In addition, PTU dissociated nuclear coactivators, such as steroid receptor coactivator-1 and glucocorticoid receptor interacting protein-1, from the TR in the presence of T(3). Finally, MMI decreased the GH release that was stimulated by T(3). ATDs inhibit T(3) action by recruitment of transcriptional corepressors and/or dissociation of coactivators. This is the first report to show that ATDs can modulate T(3) action at the transcriptional level.


Variability in the benzodiazepine response of serotonin 5-HT1A receptor null mice displaying anxiety-like phenotype: evidence for genetic modifiers in the 5-HT-mediated regulation of GABA(A) receptors.
Benzodiazepines (BZs) acting as modulators of GABA(A) receptors (GABA(A)Rs) are an important group of drugs for the treatment of anxiety disorders. However, a large inter-individual variation in BZ sensitivity occurs in the human population with some anxiety disorder patients exhibiting diminished sensitivity to BZ and reduced density of GABA(A)Rs. The mechanism underlying BZ treatment resistance is not known, and it is not possible to predict whether an anxiety patient will respond to BZ. 5-hydroxytryptamine1A receptor (5-HT1AR) null mice (R-/-) on the Swiss-Webster (SW) background reproduce several features of BZ-resistant anxiety; they exhibit anxiety-related behaviors, do not respond to BZ, have reduced BZ binding, and have decreased expression of the major GABA(A)R subunits alpha1 and alpha2. Here, we show that R-/- mice on the C57Bl6 (B6) background also have anxiety phenotype, but they respond to BZ and have normal GABA(A)R subunit expression. This indicates that the 5-HT1AR-mediated regulation of GABA(A)R alpha subunit expression is subject to genetic modification. Hybrid SW/B6-R-/- mice also exhibit BZ-resistant anxiety, suggesting that SW mice carry a genetic modifier, which mediates the effect of the 5-HT1AR on the expression of GABA(A)Ralpha subunits. In addition, we show that this genetic interaction in SW mice operates early in postnatal life to influence the expression of GABA(A)R alpha subunits at the transcriptional level. These data indicate that BZ-resistant anxiety results from a developmental arrest of GABA(A)R expression in SW-R-/- mice, and a similar mechanism may be responsible for the BZ insensitivity of some anxiety patients.


The development of curvature in the porcine radioulna.
Long bone curvature in animal limbs has long been a subject of interest and much work has explored why long bones should be curved. However, the 'when' and 'how' of curvature development is poorly understood. It has been shown that the rat tibia fails to attain its normal curvature if the action of muscles is removed early in life, but it is not clear if this is because the curvature fails to develop or if the bone becomes straighter without the action of muscles. No studies have examined the development of bone curvature in a normally developing quadruped, so this study tracks the course of curvature formation in the radioulna in a series of growing pigs. We also histologically examined the epiphyseal growth plates of these bones to determine if they contribute to the formation of curvature. In all three epiphyseal plates examined, the proliferative zone is thicker and more densely populated with chondrocytes on the cranial (convex) side than the caudal (concave) side. Frost's chondral modelling theory would suggest that the cranial side of the bone is under more compression than the caudal side, and we conclude that this is due to the action of triceps extending the elbow by pulling on the olecranon process. These results support the idea that bone curvature is an adaptation to habitual loading, where longitudinal loads acting on the curved bone cause bending strains that counter the bending resulting from the habitual muscle action.


Identification of Vibrio hollisae associated with severe gastroenteritis after consumption of raw oysters.
Vibrio hollisae was recovered from the stool culture of a 40-year-old female hospitalized for severe abdominal cramping, vomiting, fever, and watery diarrhea. She had consumed two dozen raw oysters 5 days prior. There was only a single colony on thiosulfate-citrate-bile salts-sucrose-agar, and definitive identification required conventional test media with 1% NaCl.


Effect of 4 % chlorhexidine on cord colonization among hospital and community births in India: a randomized controlled study.
Infections are the single most important cause of neonatal mortality in developing countries. Results from trials in Asia evaluating the effect of chlorhexidine on neonatal mortality have been encouraging but limited data are available on the impact of cord cleansing on bacterial colonization. Further, no data from facility deliveries and impact with time is available. This pilot study was aimed to evaluate the impact of 4 % commercially prepared chlorhexidine on cord colonization and density of colonization among newborns in India. Three hundred twenty-six newborns (hospital-247; community-79) were enrolled within 24 h of birth and randomly assigned to one of three groups: chlorhexidine, placebo or dry cord care. Umbilical swabs were collected at baseline, 2- and 48- hours after intervention application. At baseline, growth positivity (any bacterial growth) was 20 % (50 of 247 swabs) and 81 % (64 of 79 swabs) among hospital and community born neonates, respectively. In both settings, chlorhexidine compared to placebo and dry cord care, reduced colonization following 2- and 48-hour post application. Chlorhexidine significantly reduced 48-hour post application colony counts in comparison to placebo [Hospital: mean difference = -1.01; 95 % CI: -1.72, -0.30 Community: mean difference = -1.76; 95 % CI: -2.60, -0.93] and dry cord care [Hospital: mean difference = -1.16; 95 % CI: -1.93, -0.39 Community: mean difference = -2.23; 95 % CI: -3.18, -1.29]. Differences were similar for gram-positive and gram-negative bacteria. Cord cleansing with 4 % chlorhexidine soon after birth reduced colonization as well as density of colonization significantly; however this pilot study does not address the impact of chlorhexidine on mortality. The control preparation neither increased or decreased colonization. clinicaltrials.gov: NCT01528852, Registered February 7, 2012.


[Echocardiographic evaluation of pulmonary artery flow parameters in patients with chronic pulmonary disease].
This study aimed at comparing the Doppler echocardiographic artery blood flow parameters in patients with and without chronic obstructive pulmonary disease (COPD), and estimating an effect of the present degree of airway obstruction on systolic functioning of the right ventricle. The study included 28 patients with COPD, and 22 patients without COPD constituting a control group. Pulmonary functional tests have been performed with the use of body plethysmography. Doppler echocardiographic assessment of the pulmonary artery flow included a measurements the acceleration time (AcT), and right ventricular ejection time (RVET). Both AcT and RVET have been corrected for the heart rate. Corrected AcT shorter than 100 ms has been considered specific for the pulmonary hypertension (PH). AcT in the studied group of patients ranged from 67 ms to 143 ms (mean 106 +/- 21), and has been significantly shorter than that in the control group. However, no correlation between body plethysmographic findings and echocardiographic measurements has been found in COPD patients. Echocardiography is a sensitive technique detecting PH. As spirometric findings do not predict development of the cor pulmonale, Doppler echocardiographic evaluation of the blood flow in pulmonary artery may serve as a screening test.


Primary squamous cell carcinoma of the thyroid diagnosed as anaplastic carcinoma: failure in fine-needle aspiration cytology?
A case of primary squamous-cell carcinoma (SCC) of the thyroid which had been initially diagnosed as an anaplastic carcinoma (ATC) is described: female, 73 years old, with a fast-growing cervical nodule on the left side and hoarseness for 3 months. Ultrasonography showed a 4.5 cm solid nodule. FNA was compatible with poorly differentiated carcinoma with immunoreactivity for AE1/AE3, EMA. Thyroidectomy was performed. Histopathological examination showed a nonencapsulated tumor. Immunohistochemistry disclosed positivity for AE1/AE3, p53,p63, and Ki67. The diagnosis was ATC. A second opinion reported tumor consisting of squamous cells, with intense inflammatory infiltrate both in tumor and in the adjacent thyroid, with final diagnosis of SCC, associated with Hashimoto thyroiditis. No other primary focus of SCC was found. Patient has shown a 48-month survival period. Clinically, primary SCCs of the thyroid and ATCs are similar. The distinction is often difficult particularly when based on the cytological analysis of FNA material.


Formation of the inner ear during embryonic and larval development of the cichlid fish (Oreochromis mossambicus).
The vertebrate inner ear comprises mineralized elements, namely the otoliths (fishes) or the otoconia (mammals). These elements serve vestibular and auditory functions. The formation of otoconia and otoliths is described as a stepwise process, and in fish, it is generally divided into an aggregation of the otolith primordia from precursor particles and then a growth process that continues throughout life. This study was undertaken to investigate the complex transition between these two steps. Therefore, we investigated the developmental profiles of several inner ear structural and calcium-binding proteins during the complete embryonic and larval development of the cichlid fish Oreochromis mossambicus in parallel with the morphology of inner ear and especially otoliths. We show that the formation of otoliths is a highly regulated temporal and spatial process which takes place throughout embryonic and larval development. Based on our data we defined eight phases of otolith differentiation from the primordia to the mature otolith.


Investigation of autistic traits through strategic decision-making in games with adaptive agents.
Autism Spectrum Disorders are characterized by difficulties in communicating and cooperating with other people. Impairment in Theory of Mind (ToM), the ability to infer what another person is thinking, may contribute to these social deficits. The present study assesses the relationship between autistic traits and decision-making in a socioeconomic game environment that measures ToM and cooperation. We quantified participant strategy during game play with computer agents that simulated aspects of ToM or fixed strategy agents with static behaviors or heuristics. Individuals with higher Autism Quotient (AQ) scores cooperated less than subjects with low AQ scores with the ToM agents. In contrast, subjects with higher AQ scores cooperated more with fixed strategy agents. Additionally, subjects with higher AQ scores spent more time than low AQ subjects signaling cooperative intent in games with fixed strategy agents while spending less time signaling cooperation with adaptive agents, indicating a preference toward systemizing behaviors in the face of uncertainty. We conclude that individuals with high levels of autistic traits are less likely to utilize ToM as a cognitive strategy, even when it is beneficial, to achieve a desired outcome.


Relapsing Candida parapsilosis Endocarditis With Septic Embolization: A Case Report.
Candida endocarditis is a rare infection that is becoming an emerging and growing health concern, especially among risk groups such as the elderly and the immunosuppressed. It is associated with high morbidity and mortality. Dilemmas about Candida endocarditis treatment are still around, particularly about the treatment options and their duration. We report a case of Candida parapsilosis prosthetic valve endocarditis with septic embolisms. An elderly male patient with a biological prosthetic valve presented with fever and constitutional symptoms. Abdominal computed tomography (CT) showed an area suggestive of splenic emboli. Transesophageal echocardiography showed a vegetation attaching to the prosthetic valve. Due to several comorbidities, he was not considered a candidate for surgical treatment. He was treated with antifungal drugs (liposomal amphotericin B and caspofungin) and was discharged with per os fluconazole. Later he presented with evidence of lumbar spondylodiscitis due to septic embolization and relapsing fungemia with multidrug-resistant isolates was documented. Unfortunately, the patient outcome was ill-fated and he died in hospital due to sepsis-related to the candidemia and also nosocomial urinary sepsis. Here, we illustrate the complexity of diagnosing and managing fungal endocarditis due to its complications and poor prognosis.


Human Trypanosoma evansi infection linked to a lack of apolipoprotein L-I.
Humans have innate immunity against Trypanosoma brucei brucei that is known to involve apolipoprotein L-I (APOL1). Recently, a case of T. evansi infection in a human was identified in India. We investigated whether the APOL1 pathway was involved in this occurrence. The serum of the infected patient was found to have no trypanolytic activity, and the finding was linked to the lack of APOL1, which was due to frameshift mutations in both APOL1 alleles. Trypanolytic activity was restored by the addition of recombinant APOL1. The lack of APOL1 explained the patient's infection with T. evansi.


Treatment of 4-5 year old patients with cleft lip and cleft palate in Tawanchai center.
The occurrence of Cleft Lip/Palate condition in Thailand reaches a rate of 2.49% of child births, with estimates of 800 new cases per year in the Northeastern region. The healthcare process emphasizes interdisciplinary teamwork at each stage of the planning of treatment and services with the primary goal of achieving patient satisfaction and ability to live normally in society. The first 5 years are particularly important, with a focus on quality of care and ability to adapt to the environment before entering school. To study the treatment of patients with cleft lip and palate in Tawanchai center in the 4-5 year age range. A retrospective study of the clinical records was led, concerning the 123 cleft lip and cleft palate patients aged 4-5 years under treatment in Tawanchai center, Srinagarind Hospital. Data was collected during three months from October to December 2011, using the admission records of the interdisciplinary team. Percentages and mean values were calculated from these data. 120 of the 123 patients were operated, giving a ratio of 97.56%. 108 cases were under government universal health coverage regime, corresponding to 87.80% of cases. 74 cases (60.16%) presented both cleft lip and palate condition, and an average of 5-night stay in hospital per person. Medical services by the interdisciplinary team were provided as follows: (1) of 30 patients with cleft lip aged 3-4 months, 30 (100%) received pre and post-surgery care counseling, 29 (96.67%) received surgery; (2) of 19 patients with cleft palate aged 10-18 months, 17 (89.47%) received treatment information, pre and postsurgery counseling and were operated according to the protocols; (3) of 74 patients with cleft lip and palate, 53 (71.62%) received counseling for pre and post-surgery care for lip repair at the age of 3-4 months, 52 (70.27%) were operated following the protocols, while at the age of 10-18 months 63 patients (85.14%) received treatment information, pre and postsurgery care counseling, and surgical intervention for palate repair. Results of cleft lip and palate continuous treatment by interdisciplinary team in Tawanchai center for patients aged 4-5 years are reported. The highest percentage of patients to follow the treatment protocol, with pre and post-surgery care counseling and surgical intervention was achieved for cleft lip only cases, followed by cleft palate cases. Patients with both cleft lip and palate condition achieved the lowest percentage. In all cases, patients accepted within the center were treated at an 85.39% rate.


Assessment of temporal variation and sources of PCBs in the sediments of Mediterranean Sea, Mersin Bay, Turkey.
Information on temporal distribution of polychlorinated biphenyls (PCBs) in the coastal sediments of Mediterranean Sea, Mersin was compiled using data published between 1980 and 2009, and the present study. The first congener specific PCB results from the region yield concentration levels of Σ(41)PCBs in sediments ranging from 0.61 to 1.04 ng g(-1). Sediment profiles show penta-, hexa- and hepta-chlorobiphenyls, specifically, #149 and 153 as the most abundant congeners in all samples. Comparison of total PCB concentrations over time suggests no recent PCB input to the region. Using congener specific PCB data for the region, identity and contribution of PCB sources were also predicted using a chemical mass balance -based (CMB) receptor model. The CMB model identified Aroclor 1260 to be the major PCB source in coastal sediments. The potential sources for the PCBs were briefly discussed in terms of their use in various industrial applications.


An image feature-based approach to automatically find images for application to clinical decision support.
The illustrations in biomedical publications often provide useful information in aiding clinicians' decisions when full text searching is performed to find evidence in support of a clinical decision. In this research, image analysis and classification techniques are explored to automatically extract information for differentiating specific modalities to characterize illustrations in biomedical publications, which may assist in the evidence finding process. Global, histogram-based, and texture image illustration features were compared to basis function luminance histogram correlation features for modality-based discrimination over a set of 742 manually annotated images by modality (radiological, photo, etc.) selected from the 2004-2005 issues of the British Journal of Oral and Maxillofacial Surgery. Using a mean shifting supervised clustering technique, automatic modality-based discrimination results as high as 95.57% were obtained using the basis function features. These results compared favorably to other feature categories examined. The experimental results show that image-based features, particularly correlation-based features, can provide useful modality discrimination information.


Decreased Risk of Esophageal Adenocarcinoma After Gastric Bypass Surgery in a Cohort Study From 3 Nordic Countries.
The objective of this study was to test the hypothesis that bariatric surgery decreases the risk of esophageal and cardia adenocarcinoma. Obesity is strongly associated with esophageal adenocarcinoma and moderately with cardia adenocarcinoma, but whether weight loss prevents these tumors is unknown. This population-based cohort study included patients with an obesity diagnosis in Sweden, Finland, or Denmark. Participants were divided into a bariatric surgery group and a nonoperated group. The incidence of esophageal and cardia adenocarcinoma (ECA) was first compared with the corresponding background population by calculating standardized incidence ratios (SIR) with 95% CIs. Second, the bariatric surgery group and the nonoperated group were compared using multivariable Cox regression, providing hazard ratios (HR) with 95% CI, adjusted for sex, age, comorbidity, calendar year, and country. Among 748,932 participants with an obesity diagnosis, 91,731 underwent bariatric surgery, predominantly gastric bypass (n=70,176; 76.5%). The SIRs of ECA decreased over time after gastric bypass, from SIR=2.2 (95% CI, 0.9-4.3) after 2 to 5 years to SIR=0.6 (95% CI, <0.1-3.6) after 10 to 40 years. Gastric bypass patients were also at a decreased risk of ECA compared with nonoperated patients with obesity [adjusted HR=0.6, 95% CI, 0.4-1.0 (0.98)], with decreasing point estimates over time. Gastric bypass was followed by a strongly decreased adjusted risk of esophageal adenocarcinoma (HR=0.3, 95% CI, 0.1-0.8) but not of cardia adenocarcinoma (HR=0.9, 95% CI, 0.5-1.6), when analyzed separately. There were no consistent associations between other bariatric procedures (mainly gastroplasty, gastric banding, sleeve gastrectomy, and biliopancreatic diversion) and ECA. Gastric bypass surgery may counteract the development of esophageal adenocarcinoma in morbidly obese individuals.


Assessment of HIV-1 patient recruitability in the Republic of Guinea-Bissau using African versus North American hematology and biochemistry reference intervals.
Hematology and biochemistry reference intervals have been derived from healthy, HIV-negative populations to guide clinical trials worldwide. However, it is less clear how such values may be applied to clinical trials involving HIV-infected individuals. We show that contradictory interpretations about patient recruitability are reached when applying African versus North American reference intervals to an HIV-1 cohort in Guinea-Bissau. These observations underscore the need to question non-African guidelines in the context of HIV intervention clinical trials in Africa.


Dahuang Danshen Decoction Inhibits Pancreatic Fibrosis by Regulating Oxidative Stress and Endoplasmic Reticulum Stress.
In Traditional Chinese Medicine (TCM), Dahuang Danshen decoction (DD) is used to treat pancreatic fibrosis. Pancreatic fibrosis is a typical manifestation of chronic pancreatitis (CP), which affects the digestive system. The therapeutic mechanisms of DD in pancreatic fibrosis are unclear. This study aimed to investigate the regulatory mechanisms of DD on oxidative stress and endoplasmic reticulum stress in CP. Experimental rats were intraperitoneally injected with 500 mg/kg BW of diethyldithiocarbamate (DDC) twice a week for six weeks to induce CP. At the same time, DD was administered orally at daily doses of 1.37 g/kg BW, 2.74 g/kg BW, and 5.48 g/kg BW to evaluate its treatment effects on CP. After all treatments, pancreatic tissues were harvested and subjected to H&E staining. Transmission electron microscopy (TEM) was also performed to show the endoplasmic reticulum structure in the pancreatic tissues. Immunohistochemistry was used to detect the α-SMA expression level in the pancreatic tissues. Metabolomics analysis of the serum and proteomics analysis of the pancreatic tissues were performed to reveal the changes of endogenous metabolites and proteins, respectively. Concentrations of GSH, MDA, SOD, ROS, col-1, and col-3 were determined using corresponding kits. The western blotting method was used to determine the protein levels of Keap-1, HO-1, NQO1, Nrf2, GRP, JNK, and caspase 12. The pancreatic mRNA levels of NQO1, GPX1, HO-1, GST-π, GRP, JNK, and caspase 12 were also determined by quantitative PCR. The interactions between TCM components and Keap-1 were investigated by molecular docking modeling. The pathohistological results demonstrated that DD could ameliorate DDC-induced CP in vivo, indicated by reduction of α-SMA, col-1, col-3, TNF-α, and IL-6. DD increased serum levels of GSH and SOD but reduced pancreatic ROS. DD decreased cytoplasmic Keap-1 and increased Nrf2 nuclear localization. Correspondingly, DD increased the expression levels of Nrf2 downstream antioxidant genes NQO1, GPX1, HO-1, and GST-π. DD also decreased ERS hallmarks caspase 12 cleavage and GRP expression. Eventually, DD inhibited PSC activation by reducing JNK phosphorylation and MMK-3/p38 expression. Molecular docking analysis showed that salvianolic acid B and emodin had a good binding affinity toward Keap-1. These results demonstrated that DD could ameliorate the oxidative and endoplasmic reticulum stress through releasing Nrf2 from Keap-1 binding and inducing the downstream antioxidant enzymes. As a result, DD could thwart pancreatic fibrosis by inhibiting PSCs activation, which was induced by OS and ERS through JNK and MMK3/p38 pathways.


Theoretical analysis of thermal damage in biological tissues caused by laser irradiation.
A bioheat transfer approach is proposed to study thermal damage in biological tissues caused by laser radiation. The laser light propagation in the tissue is first solved by using a robust seven-flux model in cylindrical coordinate system. The resulting spatial distribution of the absorbed laser energy is incorporated into the bioheat transfer equation for solving temperature response. Thermal damage to the tissue is assessed by the extent of denatured protein using a rate process equation. It is found that for the tissue studied, a significant protein denaturation process would take place when temperature exceeds about 53 degrees C. The effects of laser power, exposure time and beam size as well as the tissue absorption and scattering coefficients on the thermal damage process are examined and discussed. The laser conditions that cause irreversible damage to the tissue are also identified.


Visual Health Analysis of Print Advertising Graphic Design Based on Image Segmentation and Few-Shot Learning.
Graphics innovation must adapt to the changing trends of the times in order to stay ahead of the curve. This article investigates the use of graphic vision in print advertising design, using image segmentation as a starting point and examines the current state of visual innovation in print advertising graphic design and its various expressions and applications. A series of homogeneous regions are generated and outlined using an image segmentation algorithm based on adaptive local threshold. The user then paints different colors on the area sets that make up the various targets. Finally, the image segmentation is completed by merging the color mark region sets. Automatic extraction of the initial curve of an active contour model, construction of an active contour model based on saliency and level set solution, automatic selection of training samples when a classifier is used for image segmentation, and so on are all problems that this method effectively solves. Experiments show that this algorithm not only satisfies users' demands for more intuitive input and more accurate interactive image segmentation results but also enables multiregion and multitarget image segmentation with ease.


Clinical outcome of confluent laser photoablation for retinopathy of prematurity.
During the past decade, laser photoablation has supplanted cryotherapy as the standard treatment for threshold retinopathy of prematurity (ROP). We evaluated the progression and the complication rate in a cohort of infants with threshold ROP treated with a confluent technique. We retrospectively studied 47 patients with ROP (91 eyes), treated with confluent diode laser photoablation. Four main outcomes were evaluated: (1) the rate of progression, (2) the frequency of laser retreatment, (3) postoperative complications, and (4) postoperative refractive error. A mean of 1943 +/- 912 laser burns were administered in a confluent pattern to 91 eyes with threshold ROP. Progression to stage 4 or 5 disease occurred in 13 of 29 eyes (44.8%) with zone I and posterior zone II and in 2 of 51 eyes (3.9%) with anterior zone II ROP (P =.01). Eyes with anterior zone II ROP that received more than or equal to 2000 burns progressed more than those that received fewer than 2000 burns. Only 1 eye (1%) needed a supplemental laser treatment. Postoperative complications included corneal edema (2.3%), anterior segment ischemia (2.3%), vitreous hemorrhage (7.9%), posterior synechiae (2.3%), cataract (4.9%), and macular ectopia (12%). The mean spherical equivalent at the last follow-up was -4.52 +/- 5.63 D. In our series, infants received more laser burns than infants reported in the literature receiving scatter or near-confluent treatment. While confluent treatment almost eliminated supplemental treatment, it was associated with a similar rate of progression and complications as has been reported with other patterns of laser treatment.


Twenty-five year history of the journal Psicothema.
There is a growing interest in evaluating the contents of scientific Psychology journals and therefore, to mark the twenty-fifth anniversary of Psicothema, we aim to provide an insight into its historical evolution. The objective of this study was to carry out a bibliometric analysis of the articles published from 1989 to 2012, in order to provide information regarding different parameters related to production and quality. The data analysed were the evolution of the articles throughout the analysed period, languages of publication, index of authorship, countries according to author affiliation, subject matter, the ten most cited articles, Top Ten journals in which Psicothema is most cited, and the evolution of the Impact Factor, amongst others. A total of 2,163 articles were analysed, of which the majority (96.16%) are original articles, published in Spanish (80.07%) and with predominantly two authors (28.34%). The journal has published work by authors from 32 different countries according to their affiliation. The results support the multidisciplinary character of the journal and a positive and constant evolution towards the advance in Psychology.


A process framework for integrating stressor-response functions into cumulative effects models.
Stressor-response (SR) functions quantify ecological responses to natural environmental variation or anthropogenic stressors. They are also core drivers of cumulative effects (CE) models, which are increasingly recognized as essential management tools to grapple with the diffuse footprint of human impacts. Here, we provide a process framework for the identification, development, and integration of SR functions into CE models, and highlight their consequential properties, behaviour, criteria for selecting appropriate stressors and responses, and general approaches for deriving them. Management objectives (and causal effect pathways) will determine the ultimate stressor and target response variables of interest (i.e., individual growth/survival, population size, community structure, ecosystem processes), but data availability will constrain whether proxies need to be used for the target stressor or response variables. Available data and confidence in underlying mechanisms will determine whether empirical or mechanistic (theoretical) SR functions are optimal. Uncertainty in underlying SR functions is often the primary source of error in CE modelling, and monitoring outcomes through adaptive management to iteratively refine parameterization of SR functions is a key element of model application. Dealing with stressor interactions is an additional challenge, and in the absence of known or suspected interaction mechanisms, controlling main effects should remain the primary focus. Indicators of suspected interaction presence (i.e., much larger or smaller responses to stressor reduction than expected during monitoring) should be confirmed through adaptive management cycles or targeted stressor manipulations. Where possible, management decisions should selectively take advantage of interactions to strategically mitigate stressor impacts (i.e., by using antagonisms to suppress stressor impacts, and by using synergisms to efficiently reduce them).


Iatrogenic splenic injury: review of the literature and medico-legal issues.
Iatrogenic splenic injury is a recognized complication in abdominal surgery. The aim of this paper is to understand the medico-legal issues of iatrogenic splenic injuries. We performed a literature review on PubMed and Scopus using iatrogenic splenic or spleen injury and iatrogenic splenic rupture as keywords. Iatrogenic splenic injury cases were identified. Most cases were related to colonoscopy, but we also identified cases related to upper gastrointestinal procedures, colonic surgery, ERCP, left nephrectomy and/or adrenalectomy, percutaneous nephrolithotomy, vascular operations involving the abdominal aorta, gynecological operation, left lung biopsy, chest drain, very rarely spinal surgery and even cardiopulmonary resuscitation. There are several surgical procedures that can lead to a splenic injury. However, from a medico-legal point of view, it is important to assess whether the cause can be attributed to a technical error of the operator rather than being an unpredictable and unpreventable complication. It is important for the medico-legal expert to have great knowledge on iatrogenic splenic injuries because it is important to evaluate every step of the first procedure performed, how a splenic injury is produced, and whether the correct treatment for the splenic injury was administered in a judgment.


Antihyperglycemic effect of umbelliferone in streptozotocin-diabetic rats.
The present study was designed to investigate the antihyperglycemic effect of Umbelliferone (UMB) in normal and streptozotocin (STZ)-diabetic rats. Diabetes was induced in adult male albino rats of the Wistar strain, weighing 180-200 g, by administration of STZ (40 mg/kg of body weight) intraperitoneally. Diabetic rats showed an increase in levels of blood glucose and glycosylated hemoglobin (HbA(1c)) and activities of gluconeogenic enzymes such as glucose-6-phosphatase and fructose-1,6-bisphosphatase, and a decrease in levels of plasma insulin, hemoglobin (Hb), and liver glycogen and activities of glucokinase and glucose-6-phosphate dehydrogenase. Intraperitoneal administration of UMB (10, 20, and 30 mg/kg of body weight) and glibenclamide (600 micro g/kg of body weight) in 10% dimethyl sulfoxide dissolved in water, for 45 days, produced significantly decreased levels of blood glucose and HbA(1c) and activities of glucose-6-phosphatase and fructose-1,6-bisphosphatase, while elevating levels of plasma insulin, Hb, and liver glycogen and activities of glucokinase and glucose-6-phosphate dehydrogenase to near normal levels in STZ-diabetic rats when compared with normal control rats. Normal rats treated with UMB (30 mg/kg of body weight) also showed a significant effect on glycemic control. Thus, our results show that UMB at 30 mg/kg of body weight possesses a promising antihyperglycemic effect that is comparable with glibenclamide.


Electrochemistry of nanozeolite-immobilized cytochrome c in aqueous and nonaqueous solutions.
The electrochemical properties of cytochrome c (cyt c) immobilized on multilayer nanozeolite-modified electrodes have been examined in aqueous and nonaqueous solutions. Layers of Linde type-L zeolites were assembled on indium tin oxide (ITO) glass electrodes followed by the adsorption of cyt c, primarily via electrostatic interactions, onto modified ITO electrodes. The heme protein displayed a quasi-reversible response in aqueous solution with a redox potential of +324 mV (vs NHE), and the surface coverage (Gamma*) increased linearly for the first four layers and then gave a nearly constant value of 200 pmol cm(-2). On immersion of the modified electrodes in 95% (v/v) nonaqueous solutions, the redox potential decreased significantly, a decrease that originated from changes in both the enthalpy and entropy of reduction. On reimmersion of the modified electrode in buffer, the faradic response immediately returned to its original value. These results demonstrate that nanozeolites are potential stable supports for redox proteins and enzymes.


Serologic evaluation of the Mono-Chek test.
An evaluation of the Mono-Chek test shows it to be easy to read, fast and simple. In accuracy it compares favorably with the Paul-Bunnell (P-B) test and the Davidsohn modification of the Paul-Bunnell (P-B-D) test and is equal to the Mono-Spot test.


Long-term cardiovascular consequences of undiagnosed intralobar pulmonary sequestration.
We report the case of a patient with a congenital aortic valve stenosis associated with a long-term undiagnosed intralobar pulmonary sequestration. The important blood flow through the aberrant artery led to progressive congestive heart failure and severe hemoptysis at the age of 25 years. We demonstrate the regression of cardiac symptoms and left ventricular diameter after surgical resection of the sequestration.


Pulmonary surfactant phosphatidylcholines induce immunological adaptation of alveolar macrophages.
Pulmonary surfactant plays an important role in lung surface tension, defense against invading pathogens, and immune response. Furthermore, alveolar macrophages (AM) that comprise the front line of immune defense against inhaled microorganisms are covered by a layer of pulmonary fluid. Phosphatidylcholines (PCs), including unsaturated lipids such as 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), are the most prevalent phospholipids in pulmonary surfactant. POPC reacts with ozone to produce 1-palmitoyl-2-(9-oxo-nonanoyl)-sn-glycero-3-phosphocholine (PONPC), a soluble mediator that initiates an inflammatory reaction in the lungs. However, the modulatory effects of POPC and PONPC on biology and activity of AM remain inconclusive. The exposure of AM (cell line AMJ2-C11) to POPC and PONPC was not directly related to the production of inflammatory mediators. However, AM, pre-incubated with POPC or PONPC, showed enhanced response after lipopolysaccharide (LPS) stimulation, and increased the production of nitric oxide and cytokines. This phenomenon was also observed for classical-polarized macrophages (M1). This increment on the production of inflammatory mediators was not associated with macrophage polarization, but with up-regulation of Tlr4 and Myd88 gene expression, which was in accordance with the adaptation of immune cells. This observation was confirmed by the histone acetylation epigenetic pathway. In contrast to the priming effect of POPC on AM activity, a harmful immune response, induced on incubation with PONPC, improved prostaglandin E2 (PGE2) formation, resulting in diminished bacterial phagocytosis. Additionally, PONPC induced production of CXCL1/KC, which potentially mediates neutrophil recruitment and enhances tissue inflammation. These results disclosed another dynamic mechanism by which pulmonary surfactant lipids (natural or oxidized) primed macrophage activity, thus affecting lung host defense.


In situ x-ray diffraction study of polyamorphism in H2O under isothermal compression and decompression.
Amorphous-amorphous transformations in H2O have been studied under rapid isothermal compression and decompression in a diamond anvil cell together with in situ x-ray diffraction measurements using brilliant synchrotron radiation. The experimental pathways provide a density-driven approach for studying polyamorphic relations among low-, high-, and very high-density amorphs (LDA, HDA, VHDA) in a pressure range of 0-3.5 GPa at temperatures of 145-160 K. Our approach using rapid (de)compression allows for studying the polyamorphic transformations at higher temperatures than the conditions previously studied under slow (de)compression or isobaric annealing. Multiple compression-decompression cycles can be integrated with in situ x-ray measurements, thus facilitating the study of repeatability and reversibility of the polyamorphic transformations. Fast in situ x-ray diffraction measurements allow for obtaining detailed insight into the structural changes across polyamorphic transformations regarding the (dis)continuity, reversibility, and possible intermediate forms. As demonstrated at isothermal conditions of 145 K and 155 K, the polyamorphic transformations are characterized by a sharp and reversible LDA-VHDA transformation, with an HDA-like form (referred to as HDA') appearing as an intermediate state. The LDA-VHDA transformation is found to occur in two steps: a discontinuous transition between LDA and HDA' and a continuous change within HDA' involving structural reconfigurations and finally converging to VHDA.


Theoretical study of the fragmentation pathways of norbornane in its doubly ionized ground state.
The potential energy surface of norbornane in its dicationic singlet ground state has been investigated in detail using density functional theory along with the nonlocal hybrid and gradient-corrected Becke three-parameter Lee-Yang-Parr functional (B3LYP) and the cc-pVDZ basis set. For the sake of more quantitative insight into the chemical reactions induced by double ionization of norbornane, this study was supplemented by a calculation of basic thermodynamic state functions coupled to a focal point analysis of energy differences obtained using correlation treatments and basis sets of improving quality, enabling an extrapolation of these energy differences at the CCSD(T) level in the limit of an asymptotically complete (cc-pV infinity Z) basis set. Our results demonstrate the likelihood of an ultrafast intramolecular rearrangement of the saturated hydrocarbon cage after a sudden removal of two electrons into a kinetically metastable five-membered cyclic C5H8+-CH+-CH3 intermediate, prior to a Coulomb explosion into C5H7+=CH2 and CH3+ fragments, which might explain a tremendous rise of electron-impact (e, 2e) ionization cross sections at electron binding energies around the double-ionization threshold. The first step is straightforward and strongly exothermic (DeltaH298 = -114.0 kcal mol-1). The second step is also exothermic (DeltaH298 = -10.2 kcal mol-1) but requires an activation enthalpy (DeltaH298) of 39.7 kcal/mol. The various factors governing the structure of this intermediate, such as electrostatic interactions, inductive effects, cyclic strains, and methylenic hyperconjugation interactions, are discussed in detail.


Association Between Physical Activity, Quadriceps Muscle Performance, and Biological Characteristics of Very Old Men and Women.
The aim of the study was to evaluate the association between physical activity, knee extensors (KE) performance (ie, isometric strength and fatigability), and biological parameters (ie, muscle structural, microvascular, and metabolic properties) in healthy very old men and women. Thirty very old adults (82 ± 1 years, 15 women) performed an isometric Quadriceps Intermittent Fatigue (QIF) test for the assessment of KE maximal force, total work (index of absolute performance), and fatigability. Muscle biopsies from the vastus lateralis muscle were collected to assess muscle fibers type and morphology, microvasculature, and enzymes activity. Correlation analyses were used to investigate the relationships between physical activity (steps/day, actimetry), KE performance, and biological data for each sex separately. Men, compared to women, showed greater total work at the QIF test (44 497 ± 8 629 Ns vs 26 946 ± 4 707 Ns; p < .001). Steps per day were correlated with total work only for women (r = 0.73, p = .011). In men, steps per day were correlated with the percentage (r = 0.57, p = .033), shape factor (r = 0.75, p = .002), and capillary tortuosity of type IIX fibers (r = 0.59, p = .035). No other relevant correlations were observed for men or women between steps per day and biological parameters. Physical activity level was positively associated with the capacity of very old women to perform a fatiguing test, but not maximal force production capacity of the KE. Physical activity of very old men was not correlated with muscle performance. We suggest that very old women could be at higher risk of autonomy loss and increasing the steps per day count could provide a sufficient stimulus for adaptations in less active women.


Enamel matrix derivative promotes human periodontal ligament cell differentiation and osteoprotegerin production in vitro.
Enamel matrix derivative (EMD) has been used successfully to aid periodontal repair. We sought to elucidate the mechanism of action of EMD and hypothesized that combined exposure to EMD and parathyroid hormone (PTH), which acts anabolicly when administered intermittently, would enhance periodontal ligament cell proliferation, differentiation, and local factor production. Confluent human periodontal ligament cells were exposed to EMD continuously or to PTH(1-34) intermittently, or a combination of both. Cell number, alkaline phosphatase activity, osteocalcin, and osteoprotegerin production were determined. Continuous challenge with EMD resulted in an increase of the differentiation parameters and osteoprotegerin production, while simultaneously inhibiting proliferation. Intermittent PTH(1-34) administration exerted opposite effects. Combined administration of EMD and PTH(1-34) weakened or even nullified the effects seen for the agents alone. These results suggest that EMD promotes periodontal ligament cell differentiation and osteoprotegerin production, potentially resulting in a microenvironment supporting periodontal repair, whereas combining EMD and PTH(1-34) failed to prove beneficial in this respect.


Alterations in executive functions in inmates convicted for violent behavior: a systematic review.
The growth of the prison population and the high recidivism rates of inmates represent a major public safety problem. This systematic review explored executive functions in inmates convicted of violent behavior compared with inmates convicted of non-violent behavior and healthy controls (HCs). Systematic searches were carried out using five databases (PubMed, Scopus, Web of Science, EBSCO, and Embase) until March 6th, 2023. Following Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines, two reviewers independently performed the screening, data extraction, and risk of bias assessment of the 8 studies included. The protocol of this study was registered in Prospective Register of Systematic Reviews (PROSPERO), under registration number CRD42021252043. Consistently, inmates convicted of violent behavior exhibited a greater alteration in inhibition than inmates convicted of non-violent behavior (four out of four studies) and HCs (two out of two studies). In addition, inmates convicted of violent behavior showed greater impairments in cognitive flexibility (two out of three studies) and working memory (two out of three studies) than HCs. Although with limited evidence (only one study), they also showed worse performance in set shifting and planning than HCs. This study provides evidence of alterations in inhibition in inmates convicted of violent behavior compared to inmates convicted of non-violent behavior and HCs. Even though inmates convicted of violent behavior showed greater impairments in planning and set shifting than HCs, these findings were supported in only one study. In general, more robust evidence is needed to confirm alterations in inmates convicted due to violent behavior. These findings highlight the importance of designing and promoting specific cognitive interventions that contribute to the reintegration of inmates into society. https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021252043, identifier CRD42021252043.


The Collaborative Lipid Research Clinics Program Family Study. II. Response rates, representativeness of the sample, and stability of lipid and lipoprotein levels.
The Collaborative Family Study (1975-1978), the third phase of the Lipid Research Clinics Program Population Studies, covers 2405 probands and 15,693 of their relatives from nine North American communities. This sample was examined for participation differences across race, sex, locality, educational level, and reason for selection. The participation rates were somewhat lower for blacks, younger age groups, and subjects with lower educational levels. The probands' reason for selection into the study had little impact on the participation of probands or relatives. Moreover, based on information gathered at earlier examinations on eligible Family Study probands, the cornary risk factor profile appeared to be similar among participants and nonparticipants . The available longitudinal lipid data on probands indicated general consistency in lipid levels within subjects over short periods of time, in cholesterol even more so than in triglycerides. Among age strata, the younger subjects showed the least intrapersonal stability, especially for triglycerides.


Trametinib potentiates TRAIL-induced apoptosis via FBW7-dependent Mcl-1 degradation in colorectal cancer cells.
Trametinib is a MEK1/2 inhibitor and exerts anticancer activity against a variety of cancers. However, the effect of Trametinib on colorectal cancer (CRC) is not well understood. In the current study, our results demonstrate the ability of sub-toxic doses of Trametinib to enhance TRAIL-mediated apoptosis in CRC cells. Our findings also indicate that Trametinib and TRAIL activate caspase-dependent apoptosis in CRC cells. Moreover, Mcl-1 overexpression can reduce apoptosis in CRC cells treated with Trametinib with or without TRAIL. We further demonstrate that Trametinib degrades Mcl-1 through the proteasome pathway. In addition, GSK-3β phosphorylates Mcl-1 at S159 and promotes Mcl-1 degradation. The E3 ligase FBW7, known to polyubiquitinate Mcl-1, is involved in Trametinib-induced Mcl-1 degradation. Taken together, these results provide the first evidence that Trametinib enhances TRAIL-mediated apoptosis through FBW7-dependent Mcl-1 ubiquitination and degradation.


[Effect of human VEGF165 in vitro on proliferation of vascular endothelial cells].
To observe the effect of human VEGF165 on the proliferation of vascular endothelial cells(VECs) in vitro. VEGF165 gene was amplified by RT-PCR and cloned into eukaryotic expression plasmid pBudCE4.1. The recombinant expression plasmid pBudCE4.1/VEGF165 was identified by restriction enzyme(Hind III and BamH I) digestion analysis and confirmed by DNA sequencing. The pBudCE4.1/VEGF165 was transfected into VECs through lipofection transfection. Expression of VEGF165 was detected by Northern blot and immunocytochemical staining. The effect of expressed VEGF165 on VEC proliferation was detected by flow cytometry. Sequencing analysis revealed that the sequence of cloned VEGF165 gene was identical with that in GenBank (accession No.X62568). Restrictive enzyme digestion analysis showed that recombinant expression plasmid pBudCE4.1/tVEGF165 was constructed successfully. The expression of VEGF165 at mRNA and protein levels in the transfected VECs was demonstrated by Northern blot and immunocytochemical staining, respectively. The expressed VEGF165 notably stimulated the proliferation of VECs. pBudCE4.1/VEGF165 is successfully constructed and expressed in VECs. Expressed VEGF165 can stimulate the VEC proliferation. The present study lays the foundation for using VEGF165 gene transfection to prevent and treat vascular stenosis in transplanted organ.


Prevalence and genotypic identification of Cryptosporidium in free-ranging and farm-raised donkeys (Equus asinus asinus) in Xinjiang, China.
The prevalence and zoonotic potential of Cryptosporidium in donkeys is poorly understood. Here, 680 fecal specimens were collected from 178 free-ranging and 502 farmed donkeys in Xinjiang, China. Cryptosporidium was identified using PCR amplification of the small subunit of ribosomal DNA. Cryptosporidium-positive isolates were subtyped using PCR analysis of the 60 kDa glycoprotein gene (gp60). The overall prevalence of Cryptosporidium was 2.4% (16/680), with 3.2% (16/502) in farmed donkeys and 0% (0/178) in free-ranging donkeys. Cryptosporidium hominis (n = 13), C. parvum (n = 1) and Cryptosporidium horse genotype (n = 2) were identified. The C. hominis isolates belonged to two subtypes, IkA16 (n = 9) and IkA16G1 (n = 4). The subtype of C. parvum was IIdA15G1, whereas the two Cryptosporidium horse genotype isolates were of subtype VIaA15G4. The predominance of C. hominis in donkeys suggests that these animals are infected through human contact.


Robotic distal locking of intramedullary nailing: Technical description and cadaveric testing.
Interlocked intramedullary nailing is the treatment of choice for femoral shaft fractures. However, distal locking is a technically challenging part of the procedure that can result in distal femoral malrotation and high radiation exposure. We have tested a robotic procedure for robotic distal locking based on the computation of a drilling trajectory on two calibrated fluoroscopic images. Twenty distal holes were attempted in ten cadaveric femur specimens. Successful screw hole drilling was achieved at the first attempt in each of the ten specimens (20 drill holes in total). No failures were recorded. The average total number of images needed was 6.5 +/- 3.6. The average computation time was 16.5+/- 16.0 seconds. Robotic distal locking was feasible in this test and can be integrated into a fully robotic intramedullary nailing procedure.


Aortic valvuloplasty with balloon catheter in maternal-fetal emergency in adolescence.
The increase of cardiac output during pregnancy is the cause of heart failure in women with severe aortic valvular stenosis. Percutaneous aortic valvuloplasty has been associated with severe complications and short-term valvar restenosis. This case showed that percutaneous aortic valvuloplasty allowed both mother and fetus to survive after childbirth, and that postpartum treatment interruption resulted in maternal death in late postpartum care.


[Embryotoxicity of Senecionis Scandentis Hebra on in vitro cultured mouse embryos].
The purpose of this study is to evaluate the embryotoxicity of alkaloids in Senecionis Scandentis Hebra on in vitro cultured mouse embryos. Mouse whole embryo culture (WEC) was applied in this study. Post-implantation (8.5 d) mouse embryos were isolated from their mothers, and cultured in medium of immediately centrifuged serum (ICS) with different concentrations of seneciphylline (target concentrations were 100, 50, 25 and 12.5 μg x mL(-1)) or senkirkine (target concentrations were 50, 25 and 12.5 μg x mL(-1)) for 48 h. After culturing completed, the development and organic morphodifferentiation of the cultured embryos were evaluated microscopically. Treatment with seneciphylline and senkirkine had adverse effects on the development and organic morphodifferentiation of embryos. The effect also had clear dose-response. Alkaloidals in Senecionis Scandentis Hebra had embryotoxicity on cultured embryos, which indicated that pregnant people exposed to Senecionis Scandentis Hebra may get potential risk on fetus.


Differential effect of interferon on DNA synthesis, 2-deoxyglucose uptake and ornithine decarboxylase activity in 3T3 cells stimulated by polypeptide growth factors and tumor promotors.
Quiescent 3T3 cells can be stimulated to enter S by defined factors. When used in combination, three polypeptide hormones (EGF, vasopressin, and insulin), or a tumor promotor and insulin, are very effective in stimulating DNA synthesis. Like serum, the defined factors also stimulate deoxyglucose uptake and induce the synthesis of ornithine decarboxylase during G1. The second stage of deoxyglucose uptake and the induction of ornithine decarboxylase are protein synthesis-dependent events. When added with the growth factors, mouse interferon inhibits the synthesis of DNA and the induction of ornithine decarboxylase but has no effect on the uptake of deoxyglucose. Kinetic experiments comparing the effect of inhibitors of translation or transcription on induction of ornithine decarboxylase with the effect of interferon suggest that interferon may affect the synthesis of enzyme by inhibiting both transcription and translation of message. The findings provide further support for the proposition that interferon exerts a differential effect on mitogen-stimulated events events which are dependent on continuous protein synthesis.


Methadone at tapered doses for the management of opioid withdrawal.
The evidence of tapered methadone's efficacy in managing opioid withdrawal has been systematically evaluated in the previous version of this review that needs to be updated To evaluate the effectiveness of tapered methadone compared with other detoxification treatments and placebo in managing opioid withdrawal on completion of detoxification and relapse rate. We searched: Cochrane Central Register of Controlled Trials (The Cochrane Library 2012, Issue 4), PubMed (January 1966 to May 2012), EMBASE (January 1988 to May 2012), CINAHL (2003- December 2007), PsycINFO (January 1985 to December 2004), reference lists of articles. All randomised controlled trials that focused on the use of tapered methadone versus all other pharmacological detoxification treatments or placebo for the treatment of opiate withdrawal. Two review authors assessed the included studies. Any doubts about how to rate the studies were resolved by discussion with a third review author. Study quality was assessed according to the criteria indicated in the Cochrane Handbook for Systematic Reviews of Interventions. Twenty-three trials involving 2467 people were included. Comparing methadone versus any other pharmacological treatment, we observed no clinical difference between the two treatments in terms of completion of treatment, 16 studies 1381 participants, risk ratio (RR) 1.08 (95% confidence interval (CI) 0.97 to 1.21); number of participants abstinent at follow-up, three studies, 386 participants RR 0.98 (95% CI 0.70 to 1.37); degree of discomfort for withdrawal symptoms and adverse events, although it was impossible to pool data for the last two outcomes. These results were confirmed also when we considered the single comparisons: methadone with: adrenergic agonists (11 studies), other opioid agonists (eight studies), anxiolytic (two studies), paiduyangsheng (one study). Comparing methadone with placebo (two studies) more severe withdrawal and more drop-outs were found in the placebo group. The results indicate that the medications used in the included studies are similar in terms of overall effectiveness, although symptoms experienced by participants differed according to the medication used and the program adopted. Data from literature are hardly comparable; programs vary widely with regard to the assessment of outcome measures, impairing the application of meta-analysis. The studies included in this review confirm that slow tapering with temporary substitution of long- acting opioids, can reduce withdrawal severity. Nevertheless, the majority of patients relapsed to heroin use.


Comparison of early and late 68Ga-FAPI-46-PET in 33 patients with possible recurrence of pancreatic ductal adenocarcinomas.
Positron emission tomography with 68Gallium (68Ga) labeled inhibitors of fibroblast activation protein (68Ga-FAPI-PET) is a promising imaging technique for patients with recurrent pancreatic ductal adenocarcinomas (PDAC). To date, it is not clear if different acquisition timepoints for 68Ga-FAPI-PET may result in comparable imaging information and if repetitive 68Ga-FAPI-PET imaging may add diagnostic value to single timepoint acquisition for recurrent PDAC. Here we analyzed retrospectively early (20 min p.i.) and late (60 min p.i.) 68Ga-FAPI-PET imaging using FAPI-46 of 33 patients with possible recurrence of PDAC concerning detection rates and uptake over time of local recurrences, metastases, inflammatory lesions of the pancreas, cholestatic lesions of the liver and reactive tissue. 33 patients with histologically confirmed PDAC after complete or partial resection of the pancreas and possible recurrence were examined by 68Ga-FAPI-46-PET acquired 20- and 60-min post injection (p.i.) of the radiotracer. FAPI-positive lesions were classified as local recurrences, metastases, inflammatory lesions of the pancreas (ILP), cholestatic lesions of the liver and reactive tissue based on histology, PET- and CT-morphology and clinical information. Lesions were contoured, and standardized uptake values (SUVmax and SUVmean) and target-to-background ratios (TBR) were analyzed for both acquisition timepoints. In total, 152 FAPI-positive lesions (22 local relapses, 47 metastases, 26 inflammatory lesions of the pancreas, 28 reactive tissues, and 29 cholestatic lesions) were detected. Detection rates for the early and late acquisition of 68Ga-FAPI-46-PET were almost identical except cholestatic lesions, which showed a higher detection rate at early imaging. SUV parameters and TBRs of ILP significantly decreased over time. Cholestatic lesions showed a tendency towards decreasing uptake. All other types of lesions showed relatively stable uptake over time. Early and late acquisition of 68Ga-FAPI-PET results in comparable imaging information in patients with possible recurrence of PDAC. Two timepoint imaging offers additional diagnostic potential concerning differential diagnoses.


Plant structural complexity and mechanical defenses mediate predator-prey interactions in an odonate-bird system.
Habitat-forming species provide refuges for a variety of associating species; these refuges may mediate interactions between species differently depending on the functional traits of the habitat-forming species. We investigated refuge provisioning by plants with different functional traits for dragonfly and damselfly (Odonata: Anisoptera and Zygoptera) nymphs emerging from water bodies to molt into their adult stage. During this period, nymphs experience high levels of predation by birds. On the shores of a small pond, plants with mechanical defenses (e.g., thorns and prickles) and high structural complexity had higher abundances of odonate exuviae than nearby plants which lacked mechanical defenses and exhibited low structural complexity. To disentangle the relative effects of these two potentially important functional traits on nymph emergence-site preference and survival, we conducted two fully crossed factorial field experiments using artificial plants. Nymphs showed a strong preference for artificial plants with high structural complexity and to a lesser extent, mechanical defenses. Both functional traits increased nymph survival but through different mechanisms. We suggest that future investigations attempt to experimentally separate the elements contributing to structural complexity to elucidate the mechanistic underpinnings of refuge provisioning.


Effects of histone H4 depletion on the cell cycle and transcription of Saccharomyces cerevisiae.
We have constructed a yeast strain (UKY403) in which the sole histone H4 gene is under control of the GAL1 promoter. This allows the activation of H4 mRNA synthesis on galactose and its repression on glucose. UKY403 cells, pre-synchronized in G1 with alpha-mating factor, have been used to show that glucose treatment results in the loss of approximately half the chromosomal nucleosomes. This depletion is only partially reversible when the H4 gene is reactivated on galactose. It was found that the resultant lethality manifests itself first in S phase, the period of nucleosome assembly, but leads to highly synchronous arrest in G2 and a virtually complete block in chromosomal segregation. Histone H4-depleted chromatin was analyzed for its efficiency as a template for all three RNA polymerases. Using pulse-labeling, we find no evidence for altered transcription by RNA polymerase I (25S, 18S and 5.8S rRNAs) or RNA polymerase III (5S rRNA, tRNAs). Northern blot analysis was used to measure levels of RNA polymerase II transcripts. There was little effect on the activation or repression of the CUP1 chelatin gene. While there may be some decrease in the level of certain mRNAs (e.g. HIS4, ARG4) other message levels (HIS3, TRP1) show little change upon glucose repression. Therefore, nucleosome loss certainly does not have a general effect on transcription.


Sphingosine-1-phosphate interactions in the spleen and heart reflect extent of cardiac repair in mice and failing human hearts.
Sphingosine-1-phosphate (S1P) is a bioactive mediator in inflammation. Dysregulated S1P is demonstrated as a cause of heart failure (HF). However, the time-dependent and integrative role of S1P interaction with receptors in HF is unclear after myocardial infarction (MI). In this study, the sphingolipid mediators were quantified in ischemic human hearts. We also measured the time kinetics of these mediators post-MI in murine spleen and heart as an integrative approach to understand the interaction of S1P and respective S1P receptors in the transition of acute (AHF) to chronic HF (CHF). Risk-free 8-12 wk male C57BL/6 mice were subjected to MI surgery, and MI was confirmed by echocardiography and histology. Mass spectrometry was used to quantify sphingolipids in plasma, infarcted heart, spleen of mice, and ischemic and healthy human heart. The physiological cardiac repair was observed in mice with a notable increase of S1P quantity (pmol/g) in the heart and spleen significantly reduced in patients with ischemic HF. The circulating murine S1P levels were increased during AHF and CHF despite lowered substrate in CHF. The S1PR1 receptor expression was observed to coincide with the respective S1P quantity in mice and human hearts. Furthermore, selective S1P1 agonist limited inflammatory markers CCL2 and TNF-α and accelerated reparative markers ARG-1 and YM-1 in macrophages in the presence of Kdo2-Lipid A (KLA; potent inflammatory stimulant). This report demonstrated the importance of S1P/S1PR1 signaling in physiological inflammation during cardiac repair in mice. Alteration in these axes may serve as the signs of pathological remodeling in patients with ischemia.NEW & NOTEWORTHY Previous studies indicate that sphingosine-1-phosphate (S1P) has some role in cardiovascular disease. This study adds quantitative and integrative systems-based approaches that are necessary for discovery and bedside translation. Here, we quantitated sphinganine, sphingosine, sphingosine-1-phosphate (S1P) in mice and human cardiac pathobiology. Interorgan S1P quantity and respective systems-based receptor activation suggest cardiac repair after myocardial infarction. Thus, S1P serves as a therapeutic target for cardiac protection in clinical translation.


Learning curve of fiberoptic bronchoscope-guided tracheal intubation through supraglottic airway device for pediatric airway management: a manikin study.
Although fiberoptic-guided endotracheal intubation using a supraglottic airway device (SAD) is a good alternative for the management of difficult airways, its learning curve for residents has not been evaluated in pediatric patients. We aimed to train residents using a pediatric manikin and obtain learning curves to evaluate the efficiency of the training. We conducted a single-armed prospective study with anesthesiology residents. Plain endotracheal tube (ETT) intubation guided by a fiberoptic bronchoscope through Ambu® AuraGainTM was demonstrated in a pediatric manikin to the participants before training. The procedure was divided into four steps: SAD insertion, vocal cord identification, carina identification, and ETT insertion into the trachea. The results and elapsed procedure times of each trial were recorded. The learning curves for the participants were constructed and analyzed using the cumulative sum method. All the 30 participants acquired proficiency at the end of practice between eight and 25 trials. The overall success rate for the procedure was 92.8%, and above 80% for all participants. Mean ± standard deviation procedure time was 71.3 ± 50.7 s. The 4th step accounted for 86.2% and 48.0% of the total failures and procedure time, respectively. The procedure time rapidly decreased in the 2nd trial; a modest decline was observed thereafter. Trainees can obtain proficiency for fiberoptic-guided intubation through SAD within 25 times when using pediatric manikin. Effect of the training on performance in actual clinical situation should be studied.


Molecular epidemiology of antibiotic-resistant Escherichia coli among clinical samples isolated in Azerbaijan, Iran.
The immediate emergence of resistant bacteria poses an increasingly growing problem to human society and the increasing prevalence of antibiotic resistance in Escherichia coli strains is one of the most important health problems. This study aimed to review the molecular epidemiology of drug resistance among clinical isolates of E. coli in north-west portion of Iran Azerbaijan. A complete of 219 clinical isolates of E. coli had been collected from the various clinical samples. The disk diffusion and agar dilution assays were used to determine antimicrobial susceptibility. The presence of antibiotics resistance genes was carried out by the PCR method. The highest susceptibility was shown to imipenem (3%) and fosfomycin (3%), and the most antibiotic resistance was presented to ampicillin (99%). The highest frequent ESBL gene among isolates was bla CTXM-15 in 70% followed by blaCMY-2 in 67%, and blaTEM-1 in 46%. The most common fluoroquinolone (FQ) resistance genes were oqxB (34%), followed by oqxA (25%), and qnrB (18%). The frequency of tetracycline resistance genes (tetA, tetB, tetC, and tetD) were detected in 24.8%, 31.6%, 1.8%, and 4.2%, respectively. The highest frequent genes to fosfomycin were fosA 10%, fosA3 30%, fosC 40%, and fosX 20%. The dominant founded aminoglycosides resistant genes were armA (12.96%) and npmA (4.93%). The prevalence of antibiotics resistance in the tested E. coli isolates was high in Azerbaijan, Iran and these findings showed that E. coli is one of the major drug-resistant pathogens.


Epilepsy surgery in children under 3 years.
Resective epilepsy surgery in early childhood has become an important treatment option for selected infants and children with epilepsy. We describe experience and clinical outcomes of children under 3 years undergoing epilepsy surgery at Great Ormond Street Hospital (GOSH). All children under 36 months of age who had resective surgery for the purpose of treating epilepsy within the GOSH epilepsy surgery programme were ascertained using a departmental database. Aetiology, post-operative seizure frequency, pre and post-operative cognitive function, long-term complications and re-operation rates were analysed by retrospective examination of clinical records. Forty-two children were included in our cohort with a median age at surgery of 20 months (range 3-36 months). Surgical procedures comprised 25 functional hemispherectomies, two anatomical hemispherectomies, four multilobar resections, seven lobar resections and four focal resections. 7/42 (17%, 95% CI 8-31%) children underwent re-operation. 20/42 (48%, 95% CI 33-62%) children achieved seizure freedom. 18/42 (43%, 95% CI 29-58) demonstrated an improvement in seizure frequency and no children had an increase in seizure frequency. Post-operative complications included subsequent shunt procedure in 5/25 (20%, 95% CI 9-39%) children undergoing hemispherectomy. There were no mortalities. In 23 children pre- and post-operative DQ or IQ was determinable allowing longitudinal comparison. Five children had a decrease in DQ/IQ >15 and two children had an increase DQ/IQ >15. Epilepsy surgery in children under 3 years of age offers suitable candidates a good chance of significantly improved seizure outcome which compares with rates in older cohorts.


Deactivation of alpha-chymotrypsin and alpha-chymotrypsin-CNBr-Sepharose 4B conjugates in aliphatic alcohols.
Several characterization methods have been used to study the deactivation in aliphatic alcohols of alpha-chymotrypsin and alpha-chymotrypsin-CNBr-Sepharose 4B conjugates. Active-site titration measurements, which were used to determine the amount of catalytically active enzyme, revealed appreciable differences between the deactivation kinetics of free and immobilized chymotrypsin. In all cases for the immobilized enzyme, the kinetics of active-enzyme disappearance differed significantly from first-order. Interestingly, the estimated intrinsic activity of immobilized chymotrypsin remaining active after different exposure times to 50% n-propanol solution increased somewhat as a result of exposure to alcohol. These findings were complemented by direct information, provided by EPR spectroscopy, on the effects of alcohols on the active-site configuration of spin-labeled chymotrypsin. EPR spectra of the free enzyme illustrated the appearance in different alcohol solutions of different enzyme forms with different active-site structures. EPR experiments also showed that denaturation of immobilized chymotrypsin was accompanied by unfolding of the active site that followed similar multi-step kinetics as the loss of active enzyme.


Dances of Death: macabre mirrors of an unequal society.
Between 1400 and 1800, Dances of Death were a popular art form depicting a metaphorical encounter between Death and representatives of a stratified human society. We review the thematic development of Dances of Death and study the development of social critique. We first assembled a full catalogue of all Dances of Death created between 1400 and 1800. We then analyzed patterns of spatiotemporal diffusion and made an in-depth hermeneutic study of the combined texts and images of a carefully selected set of 20 Dances of Death, comparing four distinct periods (1425-1525, 1525-1600, 1600-1650, and 1650-1800). We identified more than 500 Dances of Death. It was only in its first stage of development, coinciding with the Pre-Reformation (1425-1525), that social critique was very prominent. This was represented in four forms: explicit references to social (in) equality, to failures of the authorities, and to emancipated farmers, and a general social realism. In later phases social critique largely disappeared and was replaced by religious themes. Dances of Death provide historical context to current analyses and debates of social inequalities in health. They remind us of the stubbornness of these inequalities, which despite progress in material well-being are still very much with us today.


Grading movement strength by changes in firing intensity versus recruitment of spinal interneurons.
Animals can produce movements of widely varying speed and strength by changing the recruitment of motoneurons according to the well-known size principle. Much less is known about patterns of recruitment in the spinal interneurons that control motoneurons because of the difficulties of monitoring activity simultaneously in multiple interneurons of an identified class. Here we use electrophysiology in combination with in vivo calcium imaging of groups of identified excitatory spinal interneurons in larval zebrafish to explore how they are recruited during different forms of the escape response that fish use to avoid predators. Our evidence indicates that escape movements are graded largely by differences in the level of activity within an active pool of interneurons rather than by the recruitment of an inactive subset.


Does shivering thermogenesis enhance the individual's ability to maintain rectal temperature during immersion in cold water?
Shivering thermogenesis may enable individuals to maintain rectal temperature during acute cold exposure. This data analysis revisited this hypothesis and compared previously published data with unpublished data from our laboratory on those subjects that were terminated from cold water immersion early because of a reduction in rectal temperature (T(re)) - 35 degrees C. T(re), mean skin temperature (T(sk)), and oxygen uptake (VO2) were recorded at 5, 30, 60, and 90 min of immersion and were used to calculate 3delta readings for each exposure, that is, deltaT(30) minus T5, T60 minus T(30), and T(90) minus T(60). Single group t-tests were used to examine differences in deltaT(re), deltaT(sk), and deltaVO2 between the published data (PD) group and the individual subjects who were terminated early (TE) at each of three water temperatures (18 degrees C, 22 degrees C, 26 degrees C). For deltaVO2 the TE subjects were dichotomized by fatness (low percent fat, 8%-12%; or high percent fat, 18%-22%) to account for the VO2 differences between these groups (i.e., fatness) during cold water immersion. deltaT(re) was significantly (p < 0.05) decreased in TE subjects compared with PD subjects at all timepoints for 18 degrees C and 26 degrees C. At 22 degrees C, the TE subject exhibited a significantly greater (p < 0.05) decrease in deltaT(re) than the PD group at 90 min of immersion only. No significant (p > 0.05) differences in deltaT(sk) between the PD and TE groups were detected for any of the exposure temperatures over all time points. No difference (p > 0.05) between PD subjects and TE subjects for deltaVO2 was exhibited at any time point at any temperature. It appears that with respect to the TE group, elevations in VO2 were comparable to the PD group, but the TE group was unable to maintain T(re) during cold water immersion. In conclusion, from these data it appears that shivering thermogenesis does in part enhance the individual's ability to maintain T(re); however, as evidenced in the TE group, it also appears that the alterations in shivering thermogenesis for certain individuals may not be great enough to offset heat loss.


Colonic carcinoid metastatic to the breast.
Metastatic tumors of the breast are uncommon. Breast metastases from nonmammary malignant neoplasms are rare, accounting for approximately 2% of all breast tumors. We report the case of an ileal carcinoid tumor metastatic to the breast 10 years after the initial diagnosis. A 53-year-old woman presented to our clinic with a palpable breast lump. The mammogram was nonspecific. A lumpectomy was performed that, on frozen section, showed a neoplastic lesion. Permanent sections showed that the tumor was composed of sheets of small uniform cells divided into lobules by delicate vascular septa. Immunohistochemical analysis showed that the lesional cells were strongly positive to the neuroendocrine marker panel of antibodies: chromogranin A, neuron-specific enolase, synaptophysin, serotonin, and low-molecular-weight keratin. The lesional cells were negative to cytokeratins 7 and 20, estrogen and progesterone receptors, carcinoembryonic antigen, and c-Erb-B2 antibodies. The presence of pleomorphic neurosecretory-type granules within the cytoplasm of the tumor cells by ultrastructural analysis strongly suggested a metastatic lesion from a midgut carcinoid. A detailed review of the patient's medical records confirmed a right hemicolectomy for an ileal carcinoid with lymph node and omental metastases that had been performed elsewhere 10 years earlier. A detailed pathologic analysis of this lesion by light microscopy, along with histochemical, immunohistochemical, and ultrastructural analyses, aided in confirming the metastatic nature of the current breast lesion.


Identification of IgG3-specific epitope that remedies problem in diagnostic IgG subclass determination due to human genetic variation.
There are four subtypes of human IgG with different effector functions. Quantifying the relative amount of each IgG subtype is important for laboratory diagnosis in multiple settings. However, in an evolving landscape of the appreciation of human variability and the need for precision/personalised laboratory diagnosis, it has also been shown that there are numerous natural variants of IgG subtypes, with at least 29 having been described. It has recently been reported that commercially available polyclonal antisera to IgG3 cross react with variants of other IgG subtypes, while available monoclonal anti-IgG3 have a blind-spot for the IgG3-04 variant. Herein, we report that IgG3-04 contains an epitope in common with all known IgG3 variants and absent in other subtypes. A novel monoclonal anti-IgG3 is described that is specific to IgG3 but without any blind-spots for known IgG3 variants, providing a remedy to the problem of genetic variability of IgG3.


Tuning the Cross-Linking Density and Cross-Linker in Core Cross-Linked Polymeric Micelles and Its Effects on the Particle Stability in Human Blood Plasma and Mice.
Core cross-linked polymeric micelles (CCPMs) are designed to improve the therapeutic profile of hydrophobic drugs, reduce or completely avoid protein corona formation, and offer prolonged circulation times, a prerequisite for passive or active targeting. In this study, we tuned the CCPM stability by using bifunctional or trifunctional cross-linkers and varying the cross-linkable polymer block length. For CCPMs, amphiphilic thiol-reactive polypept(o)ides of polysarcosine-block-poly(S-ethylsulfonyl-l-cysteine) [pSar-b-pCys(SO2Et)] were employed. While the pCys(SO2Et) chain lengths varied from Xn = 17 to 30, bivalent (derivatives of dihydrolipoic acid) and trivalent (sarcosine/cysteine pentapeptide) cross-linkers have been applied. Asymmetrical flow field-flow fraction (AF4) displayed the absence of aggregates in human plasma, yet for non-cross-linked PM and CCPMs cross-linked with dihydrolipoic acid at [pCys(SO2Et)]17, increasing the cross-linking density or the pCys(SO2Et) chain lengths led to stable CCPMs. Interestingly, circulation time and biodistribution in mice of non-cross-linked and bivalently cross-linked CCPMs are comparable, while the trivalent peptide cross-linkers enhance the circulation half-life from 11 to 19 h.


Maternal vascular lesions in pre-eclampsia and intrauterine growth retardation: light microscopy and immunofluorescence.
Placental bed biopsies were performed during caesarean section in a series of 137 patients. Analysis of the morphological findings confirms that vascular physiological changes were reduced in pre-eclampsia and in normotensive intrauterine growth retardation. In pre-eclampsia, acute atherosis in the decidual segments of uteroplacental arteries was a prominent feature. Intimal thickenings of the myometrial segments of the uteromaternal arteries were also noted. Normotensive intrauterine growth retardation cases were characterized by intimal thickenings of the myometrial segments of the uteroplacental arteries. Immunofluorescent investigations have demonstrated that the deep vascular stenoses were not associated with immunoglobulin deposition while in distal arterial segments displaying acute atherosis a positive immunofluorescence for IgG and fibrin and, more irregularly, for C'3 and IgM could be noted. These findings lead us to suggest that an immunological mechanism may be involved in the pathogenesis of acute atherosis.


Comparative growth analysis of capsulated (Vi+) and acapsulated (Vi-) Salmonella typhi isolates in human blood.
Salmonella enterica serovar Typhi (S. Typhi) is a human restricted pathogen. It biosynthesizes a virulence capsular polysaccharide named as Vi antigen. S. Typhi regulates expression of genes involved in the biosynthesis of Vi antigen in response to osmolarity. Beside Vi-positive isolates, Vi-negative (acapsulated) isolates are also pathogenic. However, Vi-positive isolates are more prevalent. The present study was planned to investigate comparative growth of Vi-positive and Vi-negative S. Typhi isolates in an ex vivo human whole blood model. Four isolates of each type were tested for growth in human whole blood and in an enrichment medium (Tryptic soy broth-TSB) as a control. It was found that capsulated (Vi-positive) strains formed smooth circular colonies and grew with shorter lag and generation time than Vi-negative isolates. Overall growth pattern of S. Typhi isolates both in vitro and ex vivo conditions showed that Vi-positive isolates grew at a faster rate. Especially in human blood, the lag time of acapsulated isolates was almost doubled as compared to capsulated S. Typhi isolates. It was also observed that Vi-negative isolates reduced in number up to 81 % during the first 12 hours of incubation in human whole blood. Interestingly, both types of isolates had similar growth curve in TSB indicating that Vi capsule is dispensable for bacterial growth in vitro. This study shows for the first time that absence of capsular antigen retards the growth of Vi-negative isolates on initial contact with human blood, but with passage of time they adjust themselves according to the new environment.


Interleukin-2 release from lymphocytes of patients with head and neck cancer.
Interleukin-2 (IL-2) plays a central role in cellular immune regulation. In vitro this cytokine is secreted after mitogenic stimulation with phorbolester (PMA), phytohemagglutinin A (PHA), or the monoclonal T cell antibody OKT3. In our experiments the IL-2 concentration was measured in a biologic system using an IL-2-dependent murine cytotoxic T cell line. Control subjects who were age-matched to patients with head and neck cancers did not show an altered IL-2 production in vitro, irrespective of whether they were accustomed to high alcohol consumption or cigarette smoking. Patients with cancer of the larynx did not differ significantly from control subjects. Most prominent was the significant reduction in IL-2 release of patients with cancer of the oropharynx and in patients with positive lymph nodes in the neck. Impaired IL-2 secretion in head and neck cancer patients may therefore be an additional prognostic indicator worthy of further investigation.


Resolution- versus sensitivity-effective diameter in pinhole collimation: experimental verification.
To account for photon penetration, the formulae used to calculate the geometric resolution of a pinhole collimator use an effective diameter d(e) rather than the physical diameter of the aperture. The expressions commonly used for d(e), however, were originally derived to include penetration in sensitivity calculations. To predict the full width at half maximum (FWHM) resolution of the point-spread function (PSF) of a knife-edge pinhole collimator, we have previously proposed simple expressions for a resolution-effective diameter d(re). Unlike those for d(e), expressions for d(re) predict both a dependence on the polar angle of the source (theta) and a non-isotropic PSF. In this paper, the new theory was tested by measuring experimentally the FWHM of the PSF. Results confirm the theoretical predictions that (a) d(re) provides the best estimates of the experimental FWHM as a function of theta and of the direction in the plane of the pinhole, (b) Paix's expression for d(e) tends to overestimate the FWHM, (c) Anger's is a better approximation, but still cannot predict the dependence on theta, and (d) the FWHM decreases with decreasing theta, i.e. resolution improves for sources at the edge of the field-of-view.


Automatic epileptic seizure detection in EEGs using MF-DFA, SVM based on cloud computing.
Epilepsy is a chronic disease with transient brain dysfunction that results from the sudden abnormal discharge of neurons in the brain. Since electroencephalogram (EEG) is a harmless and noninvasive detection method, it plays an important role in the detection of neurological diseases. However, the process of analyzing EEG to detect neurological diseases is often difficult because the brain electrical signals are random, non-stationary and nonlinear. In order to overcome such difficulty, this study aims to develop a new computer-aided scheme for automatic epileptic seizure detection in EEGs based on multi-fractal detrended fluctuation analysis (MF-DFA) and support vector machine (SVM). New scheme first extracts features from EEG by MF-DFA during the first stage. Then, the scheme applies a genetic algorithm (GA) to calculate parameters used in SVM and classify the training data according to the selected features using SVM. Finally, the trained SVM classifier is exploited to detect neurological diseases. The algorithm utilizes MLlib from library of SPARK and runs on cloud platform. Applying to a public dataset for experiment, the study results show that the new feature extraction method and scheme can detect signals with less features and the accuracy of the classification reached up to 99%. MF-DFA is a promising approach to extract features for analyzing EEG, because of its simple algorithm procedure and less parameters. The features obtained by MF-DFA can represent samples as well as traditional wavelet transform and Lyapunov exponents. GA can always find useful parameters for SVM with enough execution time. The results illustrate that the classification model can achieve comparable accuracy, which means that it is effective in epileptic seizure detection.


Cavalier King Charles Spaniels with Chiari-like malformation and Syringomyelia have increased variability of spatio-temporal gait characteristics.
Chiari-like malformation in the Cavalier King Charles Spaniel is a herniation of the cerebellum and brainstem into or through the foramen magnum. This condition predisposes to Syringomyelia; fluid filled syrinxes within the spinal cord. The resulting pathology in spinal cord and cerebellum create neuropathic pain and changes in gait. This study aims to quantify the changes in gait for Cavalier King Charles Spaniel with Chiari-like malformation and Syringomyelia. We compared Cavalier King Charles Spaniel with Chiari-like malformation with (n = 9) and without (n = 8) Syringomyelia to Border Terriers (n = 8). Two video cameras and manual tracking was used to quantify gait parameters. We found a significant increase in coefficient of variation for the spatio-temporal characteristics and ipsilateral distance between paws and a wider base of support in the thoracic limbs but not in the pelvic limbs for Cavalier King Charles Spaniels compared with the border terrier.


Doubly robust estimation of generalized partial linear models for longitudinal data with dropouts.
We develop a doubly robust estimation of generalized partial linear models for longitudinal data with dropouts. Our method extends the highly efficient aggregate unbiased estimating function approach proposed in Qu et al. (2010) to a doubly robust one in the sense that under missing at random (MAR), our estimator is consistent when either the linear conditional mean condition is satisfied or a model for the dropout process is correctly specified. We begin with a generalized linear model for the marginal mean, and then move forward to a generalized partial linear model, allowing for nonparametric covariate effect by using the regression spline smoothing approximation. We establish the asymptotic theory for the proposed method and use simulation studies to compare its finite sample performance with that of Qu's method, the complete-case generalized estimating equation (GEE) and the inverse-probability weighted GEE. The proposed method is finally illustrated using data from a longitudinal cohort study.


Anomalous origin of the fetal pulmonary artery.
This study aims to investigate the efficacy of prenatal ultrasonography in diagnosing the anomalous origin of the fetal pulmonary artery (AOFPA). A total of 26 AOFPA cases were retrospectively analyzed from January 2014 to January 2023. The features of the AOFPA were characterized by comparing the prenatal ultrasonic data with the results of anatomical casting after pregnancy termination or postnatal imaging and surgical intervention. Missed diagnoses and misdiagnoses were expounded. Of the 26 AOFPA cases, there were 13 cases of pulmonary artery sling, 8 cases of anomalous origin of the unilateral pulmonary artery, and five cases of unilateral absence of the pulmonary artery; 17 cases received pathological anatomy and casting after pregnancy termination, and nine cases were confirmed by postnatal imaging and surgery. Nineteen cases were accurately prenatally diagnosed (19/26, 73.1%), and seven cases were missed or misdiagnosed (7/26, 26.9%). Prenatal ultrasonography has a favorable diagnostic efficacy for anomalous origin of the fetal pulmonary artery. The absence of either the left or right pulmonary artery from the image of pulmonary artery bifurcation may indicate origin abnormalities of the pulmonary artery in fetuses, which signifies the necessity to detect the abnormal origin of the pulmonary artery on the affected side and other potential intracardiac malformation complications.


A high precision method for mapping phase to amplitude in direct digital synthesis and its hardware implementation.
There exist a number of algorithms to map the phase to amplitude in direct digital synthesis (DDS). For DDS with more than 14 output bits, the Coordinate Rotation Digital Computer (CORDIC) algorithm is well known for its high precision. Also, it is effective in solutions where there is the need of in-phase and quadrature components simultaneously because the algorithm calculates both. In this paper, a Taylor expansion based method was proposed to calculate both in-phase and quadrature at the same time. Numerical simulations for different data format, e.g., double and finite bits, were carried out in Matlab and Quartus, which were followed by the hardware implementation in Field Programmable Gate Array. The results demonstrated that the proposed method possessed higher precision and exhausted less logic elements than the CORDIC algorithm.


Rhodium(III)-Catalyzed C(sp3)-H Bond Aminocarbonylation with Isocyanates.
Rh(III)-catalyzed C(sp3)-H bond aminocarbonylation of 8-methylquinolines and isocyanates has been realized under mild conditions. This approach is applicable to different aryl and alkyl isocyanates, leading to the synthesis of various α-quinolinyl amide compounds in moderate to excellent yields. A plausible mechanism for this transformation is proposed according to the experimental results obtained.


Bumper issue of COVID-19 pandemic studies of relevance to Aotearoa New Zealand.
In response to the COVID-19 pandemic, Aotearoa New Zealand adopted a clear 'elimination strategy', which has (up to June 2021) been very successful in both health and economic terms compared to other OECD countries. Nevertheless, the pandemic response has still been a very major shock to the New Zealand health system. This issue of the New Zealand Medical Journal has 14 new pandemic-related articles. Some of this work can help inform vaccination prioritisation decisions and inform preparations of primary and secondary care services and social services for any future raising of levels in the pandemic Alert Level system. Particularly strong themes are around the value (and challenges) of telehealth services, and also the need for responses throughout the health system to ensure health equity and support for the most vulnerable citizens.


Brista: a gene involved in the specification and differentiation of distal cephalic and thoracic structures in Drosophila melanogaster.
A gene Brista has been identified in chromosome 2R, in the region 60D11-E4, in which mutations cause homoeotic transformation of distal antennal structures to distal leg derivatives, and in which certain alleles also lead to upsets in the formation of distal elements of the legs. This gene is haploinsufficient for the homoeotic phenotype. Several putative null and two hypomorphic alleles have been recovered. The effects of exposure to the non-permissive temperature of a temperature-sensitive allele are cummulative and depend upon the length of the exposure during the period of antennal cell proliferation. It is suggested that this gene contributes to the stability of the state of determination in distal domain of the antennal and leg discs, and its relationship to other genes with similar mutant phenotype is discussed.


Cyclic ADP-ribose (cADPR) and nicotinic acid adenine dinucleotide phosphate (NAADP): novel regulators of Ca2+-signaling and cell function.
Ca2+ ions are involved in the regulation of many diverse functions in animal and plant cells, e.g. muscle contraction, secretion of neurotransmitters, hormones and enzymes, fertilization of oocytes, and lymphocyte activation and proliferation. The intracellular Ca2+ concentration can be increased by different molecular mechanisms, such as Ca2+ influx from the extracellular space or Ca2+ release from intracellular Ca2+ stores. Release from intracellular Ca2+ stores is accomplished by the small molecular compounds D-myo-inositol 1,4,5-trisphosphate (InsP3), cyclic ADP-ribose (cADPR) and nicotinic acid adenine dinucleotide phosphate (NAADP). This review concentrates on (i) receptor-mediated formation of cADPR by ADP-ribosyl cyclases, (ii) intracellular and extracellular effects of cADPR in a variety of cell types, and (iii) cADPR in the nucleus. Though our understanding of the role of NAADP is still unclear in many aspects, important recent findings are reviewed, e.g. Ca2+ release activity and binding studies in mammalian cell types.