Sutured coronary artery grafting utilizing the Heartflo anastomosis device--first clinical experiences.
The Heartflo device was developed to facilitate consistency in distal coronary anastomosis quality. The device automates the suturing process during the anastomosis procedure via simultaneous delivery of ten standard 7-0 polypropylene sutures through the graft and the coronary vessel wall. In 30 elective coronary artery bypass patients, one distal anastomosis was intentionally performed with the anastomosis device. Device success was stated if a patent anastomosis with a minimal flow of 50 ml/min resulted, additional stitches were counted if bleeding occurred. 4 cases of device failure occurred in the first 5 patients. The subsequent patients were operated without any mechanical problems. In 16 patients (53 %), a patent anastomosis with a mean flow of 75 +/- 6 ml/min using 1.7 +/- 0.3 additional stitches was achieved. Anastomoses were completed in 19.0 +/- 0.7 min; postoperative course was uneventful in all patients. We have shown that coronary anastomoses are feasible using the Heartflo device, representing a promising step on the way to automated coronary anastomoses. Its application is still limited by the size and tissue quality of the target vessel and difficult suture management during the anastomosis procedure.


Conflicting functional assessment of stenoses in patients with previous myocardial infarction.
The utility of fractional flow reserve, absolute and relative flow reserve, and intravascular ultrasound may have an impact on decision-making for percutaneous coronary intervention in patients with previous myocardial infarction and microvascular dysfunction. The role for fractional flow reserve, absolute and relative flow reserve, and intravascular ultrasound is discussed.


Alkaline phosphatase-fast red, a new fluorescent label. Application in double labelling for cell cycle analysis.
We have observed that the red reaction product of alkaline phosphatase immuno-conjugates and certain substrate preparations produces a brilliant red fluorescence that is visible by fluorescence microscopy using both fluorescein and rhodamine filter combinations. This provides a level of sensitivity greater than that obtained with other commonly used red fluorochromes or by inspection of the reaction product under bright field illumination. Of particular value, the reaction product is unaffected by the denaturing conditions required for the detection of incorporated nuclear BrdU with FITC conjugated anti-BrdU antibody and provides a simple and robust method for the simultaneous detection of cell proliferation and cell surface markers.


Differential modulation of claudin 4 expression and myosin light chain phosphorylation by thyroid function in lung injury.
Trauma and ventilator-induced lung injury is often associated with endothelial-epithelial barriers breakdown, which may lead to multiple system organ failure (MSOF) and death in critically ill patients. Although molecular mechanism involved in MSOF is not known, junctional opening is believed to happen. In vitro, thyroid hormones inhibit myosin light chain (MLC) phosphorylation and may, thus, inhibit cellular contraction and junctional opening. Trauma is also associated with tissue hypo-thyroid state. Therefore, we examined the effects of thyroid function on expression of phospho-MLC (pp-MLC) and claudin 4 (Clud4), key proteins involved in regulation of junctional tightness, in lung injury. Rats were rendered hypo-thyroid (Hypo) or hyperthyroid (Hyper) by adding methimazole or levo-thyroxine, respectively, to their drinking water. Untreated euthyroid (Eue) animals were used as control. Lung pp-MLC and Clud4 proteins were assessed by western blotting and in situ immunodetection, respectively. Lung injury was induced by high tidal volume mechanical ventilation. Lung injury was significantly enhanced in Hypo animals and attenuated in Hyper animals. Parallel changes in expression of lung pp-MLC were detected. Alterations in lung histomorphology correlated with the level of pp-MLC. Expression of alveolar and bronchiolar Clud4 protein was differentially affected by the state of thyroid gland. Our data suggest that thyroid function plays significant role in lung injury perhaps by modulating expression of the proteins involved in junctional tightness. Besides, they strongly support the idea that the tissue hypo-thyroid state may contribute to endothelial-epithelial barriers breakdown associated with trauma.


Transgenic zebrafish model for quantification and visualization of tissue toxicity caused by alloying elements in newly developed biodegradable metal.
The cytotoxicity of alloying elements in newly developed biodegradable metals can be assessed through relatively low-cost and rapid in vitro studies using different cell types. However, such approaches have limitations; as such, additional investigations in small mammalian models are required that recapitulate the physiological environment. In this study, we established a zebrafish (Danio rerio) model for cytotoxicity evaluations that combines the physiological aspects of an animal model with the speed and simplicity of a cell-based assay. The model was used to assess the cytotoxicity of five common alloying elements in biodegradable implant materials. Conventional in vitro testing using heart, liver, and endothelial cell lines performed in parallel with zebrafish studies revealed statistically significant differences in toxicity (up to 100-fold), along with distinct changes in the morphology of the heart, liver, and blood vessels that were undetectable in cell cultures. These results indicate that our zebrafish model is a useful alternative to mammalian systems for accurately and rapidly evaluating the in vivo toxicity of newly developed metallic materials.


Vortex Filament Equation for a Regular Polygon in the Hyperbolic Plane.
The aim of this paper is twofold. First, we show the evolution of the vortex filament equation (VFE) for a regular planar polygon in the hyperbolic space. Unlike in the Euclidean space, the planar polygon is open and both of its ends grow up exponentially, which makes the problem more challenging from a numerical point of view. However, using a finite difference scheme in space combined with a fourth-order Runge-Kutta method in time and fixed boundary conditions, we show that the numerical solution is in complete agreement with the one obtained by means of algebraic techniques. Second, as in the Euclidean case, we claim that, at infinitesimal times, the evolution of VFE for a planar polygon as the initial datum can be described as a superposition of several one-corner initial data. As a consequence, not only can we compute the speed of the center of mass of the planar polygon, but the relationship also allows us to compare the time evolution of any of its corners with the evolution in the Euclidean case.


Medical therapy of pediatric glaucoma and glaucoma in pregnancy.
Although surgery remains the definitive treatment for congenital and other childhood glaucomas, medical therapy can be effective in lowering intraocular pressure as a temporizing measure before surgery or as long-term adjunctive treatment in disease refractory to surgical measures. Carbonic anhydrase inhibitors, beta-blockers, cholinergic drugs, and the prostaglandin-related drugs all play an effective role in pediatric glaucoma management. The usefulness and safety profile of the adrenergic agonists and the osmotic agents are less well established. In medically treating the pediatric patient or the pregnant woman for glaucoma, the clinician must be mindful of the possibility of adverse effects and be prepared to alter or terminate treatment if needed.


Biomedical engineering of polysaccharide-based tissue adhesives: Recent advances and future direction.
Tissue adhesives have been widely used for preventing wound leaks, sever bleeding, as well as for enhancing drug delivery and biosensing. However, only a few among suggested platforms cover the circumstances required for high-adhesion strength and biocompatibility, without toxicity. Antibacterial properties, controllable degradation, encapsulation capacity, detectability by image-guided procedures and affordable price are also centered to on-demand tissue adhesives. Herein we overview the history of tissue adhesives, different types of polysaccharide-based tissue adhesives, their mechanism of gluing, and different applications of polysaccharide-based tissue adhesives. We also highlight the latest progresses in engineering of tissue adhesives followed by existing challenges in fabrication processes. We argue that future studies have to place focus on a holistic understanding of biomaterials and tissue surface properties, proper fabrication procedures, and development of magnetic and conductive responsive adhesives in order to bridge the huge gap between the present studies for clinical implementation.


Comparison of blood toluene levels after inhalation and oral administration.
The purpose of this investigation was to compare blood toluene levels in Sprague-Dawley rats after oral and inhalation administration. Groups of 30 rats were dosed by gavage with 86.7, 217, 433, or 867 mg toluene/kg body wt or exposed for up to 6 hr, 5 rats per exposure, to an atmosphere of either 200 or 1000 ppm toluene. Blood was sampled by cardiac puncture from 5 rats in each of the six dose groups at 0.5, 1.0, 2.0, 4.0, 6.0, and 24.0 hr after gavage dosing or the beginning of the inhalation exposure. Blood toluene levels were analyzed. A four-parameter model was fitted to the blood toluene levels of the orally dosed rats. The area under the curve generated by this model, representing total blood toluene concentration over 6 hr, was calculated and compared to the area under the blood toluene curve for the 6-hr inhalation exposure. Integrated areas from the two routes of exposure were used for direct comparison of oral and inhalation exposures. The data demonstrate that gavage dosing can be used to approximate inhalation exposure to toluene.


Factors affecting the separation and loading capacity of proteins in preparative gradient elution high-performance liquid chromatography.
The optimum conditions for the purification of proteins by gradient elution in reversed-phase liquid chromatography were studied, with emphasis on the column length. Because of the strong dependence of the retention of proteins on the mobile phase composition, very short columns can be used successfully to perform analytical separations. A similar conclusion is extended to preparative separations. Columns with different lengths and diameters were used. The dependence of the loading capacity for touching band separation on the column length, diameter and volume was studied, in addition to the regeneration time between successive runs, the starting mobile phase composition and the necessary column efficiency.


Catheter-related bloodstream Mycobacterium wolinskyi infection in an umbilical cord blood transplant recipient: a case report.
Catheter-related bloodstream infection (CRBSI), caused by rapidly growing mycobacteria (RGM), is a rare infectious complication in hematopoietic stem cell transplant (HSCT) recipients and can often be misdiagnosed as Gram-positive rod (GPR) bacteremia. We present a case of CRBSI caused by Mycobacterium wolinskyi, a rare RGM, in a 44-year-old female patient who received an umbilical cord blood transplant. Rapidly growing mycobacteria can stain as GPRs and may grow in routine blood culture media after 3-4 days of incubation. These features are not widely known to clinicians, and acid-fast staining is therefore recommended when unidentifiable GPRs are detected in blood cultures, especially in immunocompromised patients, such as those with hematologic malignancies or intravascular devices.


Stakeholders' Perceptions Regarding the Use of Patient Photographs Integrated with Medical Imaging Studies.
Integrating digital facial photographs of pediatric patients as identifiers (ID) with medical imaging (integrated photographic IDs) may increase the detection of mislabeled studies. The purpose of this study was to determine how different stakeholders would receive this novel technology. Parents or guardians of patients in a children's hospital outpatient radiology department, radiology faculty and residents, and radiology technologists and nurses were asked to complete a survey. The perception about the anticipated use of integrated photographic ID in different clinical scenarios was investigated, and its predictors were determined using logistic regression analysis. Four hundred ninety-eight parents responded (response rate 83 %); 96 and 97 % supported the use of integrated photographic ID, if it improves the radiologist's imaging interpretation or decreases the rate of mislabeled errors, respectively. Thirty-eight percent were worried that photographic IDs would impact patients' privacy. Ninety-four percent believed that they should be asked for their consent prior to obtaining their child's photograph. Seventy-eight radiologists responded (response rate 39 %); 63 and 59 % believed that the use of integrated photographic ID would result in improvement in accurate interpretation of images and identification of mislabeled patient errors, respectively. Forty-nine percent of radiologists had concern that integrated photographic ID would increase interpretation time. Fifty technologists and nurses responded (response rate 59 %); 71 and 73 % supported the technology if it resulted in more acute interpretation of images and identification of mislabeled patients, respectively. A majority of stakeholders support integrated photographic ID in order to improve safety. A majority of parents believe that consent should be obtained.


How parents assist children's emotion regulation in Turkey: The Turkish adaptation of the parental assistance with child emotion regulation (PACER) questionnaire.
Parents play a critical role in emotional socialization and the development of emotion regulation during childhood. The tools to measure how parents assist children's emotion regulation are very limited. The Parental Assistance with Child Emotion Regulation (PACER) Questionnaire is a novel scale developed for this purpose with excellent psychometric properties. The aim of this study is to adapt the PACER to Turkish and investigate its psychometric properties in the Turkish cultural setting. The data were collected from 700 parents who have children aged birth to 17 years. In addition to the PACER, participants filled out some scales about their own beliefs and behaviors, also their children's psychological symptoms. We confirmed the original ten-factor structures of the PACER in a Turkish sample and the measurement invariance supported the PACER's structure across subgroups. The high internal consistencies of factors were achieved; however, the test-retest reliability was lower than expected. The factors of maladaptive emotion regulation strategies (e.g., rumination, expressive suppression, avoidance) were positively associated with parents' own emotion regulation deficit, symptoms, and child's symptoms, while others (e.g., reappraisal, problem-solving) were negatively associated with them. Overall, our results suggest that the Turkish version of the PACER is a psychometrically valid and reliable measurement to assess how parents support their children to regulate their emotions. We believe that this adaptation allows the scale to be used in developmental and clinical psychology studies and will pave the way for cross-cultural studies.


A complete sequence of mitochondrial genome of Neolamarckia cadamba and its use for systematic analysis.
Neolamarckia cadamba is an important tropical and subtropical tree for timber industry in southern China and is also a medicinal plant because of the secondary product cadambine. N. cadamba belongs to Rubiaceae family and its taxonomic relationships with other species are not fully evaluated based on genome sequences. Here, we report the complete sequences of mitochondrial genome of N. cadamba, which is 414,980 bp in length and successfully assembled in two genome circles (109,836 bp and 305,144 bp). The mtDNA harbors 83 genes in total, including 40 protein-coding genes (PCGs), 31 transfer RNA genes, 6 ribosomal RNA genes, and 6 other genes. The base composition of the whole genome is estimated as 27.26% for base A, 22.63% for C, 22.53% for G, and 27.56% for T, with the A + T content of 54.82% (54.45% in the small circle and 54.79% in the large circle). Repetitive sequences account for ~ 0.14% of the whole genome. A maximum likelihood (ML) tree based on DNA sequences of 24 PCGs supports that N. cadamba belongs to order Gentianales. A ML tree based on rps3 gene of 60 species in family Rubiaceae shows that N. cadamba is more related to Cephalanthus accidentalis and Hymenodictyon parvifolium and belongs to the Cinchonoideae subfamily. The result indicates that N. cadamba is genetically distant from the species and genera of Rubiaceae in systematic position. As the first sequence of mitochondrial genome of N. cadamba, it will provide a useful resource to investigate genetic variation and develop molecular markers for genetic breeding in the future.


[Construction of porous hydroxyapatite (HA) block loaded with cultured chondrocytes].
To construct a kind of bone healing enhancing implant with cultured chondrocytes bound to hydroxyapatite (HA). Chondrocytes were obtained from the costicartilage of rat and were cultured on the porous HA blocks, 3 mm x 3 mm x 4 mm size, for three and seven days. Scanning electron micrograph was taken to show whether the cells grew outside and inside the pore of HA block. The cells cultured on tiny glass sheet for 2 days were used to prove where the cells come from by in situ hybridization technique with alpha1 (II) cDNA probe. Scanning electron micrographs showed that the pores of the HA surface and inside of the blocks are filled with cultured cells, especially the longer cultured block. The cells were chondrocytes confirmed by in situ hybridization. The porous HA can be used as cell cultured substrate and chondrocyte can adhere and proliferate inside the porous HA block.


The enzyme glutamine synthetase I of Drosophila melanogaster is associated with a modified RNA.
Glutamine synthetase I (L-glutamate:ammonia ligase, ADP forming; EC 220.127.116.11) was purified from Drosophila melanogaster larvae. The complete enzyme has an apparent molecular weight of 380,000. The subunit of the active enzyme has an apparent molecular weight of 43,000 after sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis. Routine preparations yield enzymes which have at least another polypeptide component of apparent molecular weight of 64,000. Several factors suggest that the 64,000-dalton polypeptide might be a transformation product of the 43,000-dalton subunit which occurs in association with enzyme inactivation. Distinct from its protein subunit, from pure glutamine synthetase I a material can be extracted which can be labeled with 32P-labeled gamma-ATP using polynucleotide kinase. After alkaline hydrolysis the majority of the radioactivity is recovered as 5'2' and 5'3' ribonucleotide diphosphates, and after venom phosphodiesterase digestion as 5' ribonucleotide. We therefore conclude that the native glutamine synthetase I enzyme contains, or at least is reproducibly associated with, an RNA component. Several characteristics of the labeled material indicate that the RNA is small in size and is bound to polymer molecules different from RNA.


Eliminating the Imbalanced Mobility Bottlenecks via Reshaping Internal Potential Distribution in Organic Photovoltaics.
The imbalanced carrier mobility remains a bottleneck for performance breakthrough in even those organic solar cells (OSCs) with recorded power conversion efficiencies (PCEs). Herein, a counter electrode doping strategy is proposed to reshape the internal potential distribution, which targets to extract the low mobility carriers at far end. Device simulations reveal that the key of this strategy is to partially dope the active layer with a certain depth, therefore it strengthens the electric field for low mobility carriers near counter electrode region while avoids zeroing the electric field near collection electrode region. Taking advantage of these, PCE enhancements are obtained from 15.4% to 16.2% and from 16.9% to 18.0%, respectively, via cathode p-doping and anode n-doping. Extending its application from opaque to semitransparent devices, the PCE of dilute cell rises from 10.5% to 12.1%, with a high light utilization efficiency (LUE) of 3.5%. The findings provide practical solutions to the core device physical problem in OSCs.


Conversational Interfaces for Health: Bibliometric Analysis of Grants, Publications, and Patents.
Conversational interfaces (CIs) in different modalities have been developed for health purposes, such as health behavioral intervention, patient self-management, and clinical decision support. Despite growing research evidence supporting CIs' potential, CI-related research is still in its infancy. There is a lack of systematic investigation that goes beyond publication review and presents the state of the art from perspectives of funding agencies, academia, and industry by incorporating CI-related public funding and patent activities. This study aimed to use data systematically extracted from multiple sources (ie, grant, publication, and patent databases) to investigate the development, research, and fund application of health-related CIs and associated stakeholders (ie, countries, organizations, and collaborators). A multifaceted search query was executed to retrieve records from 9 databases. Bibliometric analysis, social network analysis, and term co-occurrence analysis were conducted on the screened records. This review included 42 funded projects, 428 research publications, and 162 patents. The total dollar amount of grants awarded was US $30,297,932, of which US $13,513,473 was awarded by US funding agencies and US $16,784,459 was funded by the Europe Commission. The top 3 funding agencies in the United States were the National Science Foundation, National Institutes of Health, and Agency for Healthcare Research and Quality. Boston Medical Center was awarded the largest combined grant size (US $2,246,437) for 4 projects. The authors of the publications were from 58 countries and 566 organizations; the top 3 most productive organizations were Northeastern University (United States), Universiti Teknologi MARA (Malaysia), and the French National Center for Scientific Research (CNRS; France). US researchers produced 114 publications. Although 82.0% (464/566) of the organizations engaged in interorganizational collaboration, 2 organizational research-collaboration clusters were observed with Northeastern University and CNRS as the central nodes. About 112 organizations from the United States and China filed 87.7% patents. IBM filed most patents (N=17). Only 5 patents were co-owned by different organizations, and there was no across-country collaboration on patenting activity. The terms patient, child, elderly, and robot were frequently discussed in the 3 record types. The terms related to mental and chronic issues were discussed mainly in grants and publications. The terms regarding multimodal interactions were widely mentioned as users' communication modes with CIs in the identified records. Our findings provided an overview of the countries, organizations, and topic terms in funded projects, as well as the authorship, collaboration, content, and related information of research publications and patents. There is a lack of broad cross-sector partnerships among grant agencies, academia, and industry, particularly in the United States. Our results suggest a need to improve collaboration among public and private sectors and health care organizations in research and patent activities.


Budesonide mitigates pathological changes in animal model Of COPD through reducing neutrophil elastase expression.
This study was conducted to investigate a molecular mechanism by which budesonide inhalation may mitigate pathological responses of cigarette smoke-induced COPD. Rats were exposed to air (control) and cigarette smoke (smoking) in the presence and absence of budesonide. Cell count in bronchoalveolar lavage fluid (BALF), lung function test, mean liner intercept in lung tissue, mean alveolar number, right ventricular hypertrophy index (RVHI) and morphological changes in lungs were assessed, respectively. Alpha-1 antitrypsin (A1AT) and neutrophil elastase (NE) mRNA expression in lung tissues and their protein productions in BALF were examined as well. Smoking rats showed significant changes in the above assessments as compared to those of the control rats (all P < 0.01 or 0.05). Budesonide applied for the smoking rat significantly decreased differential cell counts in BALF and ameliorated lung function and RVHI (P < 0.01 or 0.05) with mitigated peribronchiolar inflammation and pulmonary bullae formation in the smoke-exposed lungs. Treatment with budesonide resulted in obvious decreases in NE mRNA and protein expression levels (both P < 0.05). Budesonide inhalation serves to improve lung function and right ventricular dysfunction through attenuating pulmonary inflammatory response and NE expression level in the diseased lungs.


Effect of thiol antioxidant on body fat and insulin reactivity.
Insulin signaling is enhanced by moderate concentrations of reactive oxygen species (ROS) and suppressed by persistent exposure to ROS. Diabetic patients show abnormally high ROS levels and a decrease in insulin reactivity which is ameliorated by antioxidants, such as N-acetylcysteine (NAC). A similar effect of NAC has not been reported for non-diabetic subjects. We now show that the insulin receptor (IR) kinase is inhibited in cell culture by physiologic concentrations of cysteine. In two double-blind trials involving a total of 140 non-diabetic subjects we found furthermore that NAC increased the HOMA-R index (derived from the fasting insulin and glucose concentrations) in smokers and obese patients, but not in nonobese non-smokers. In obese patients NAC also caused a decrease in glucose tolerance and body fat mass. Simultaneous treatment with creatine, a metabolite utilized by skeletal muscle and brain for the interconversion of ADP and ATP, reversed the NAC-mediated increase in HOMA-R index and the decrease in glucose tolerance without preventing the decrease in body fat. As the obese and hyperlipidemic patients had lower plasma thiol concentrations than the normolipidemic subjects, our results suggest that low thiol levels facilitate the development of obesity. Supplementation of thiols plus creatine may reduce body fat without compromising glucose tolerance.


Being good to look good: Self-reported moral character predicts moral double standards among reputation-seeking individuals.
Moral character is widely expected to lead to moral judgements and practices. However, such expectations are often breached, especially when moral character is measured by self-report. We propose that because self-reported moral character partly reflects a desire to appear good, people who self-report a strong moral character will show moral harshness towards others and downplay their own transgressions-that is, they will show greater moral hypocrisy. This self-other discrepancy in moral judgements should be pronounced among individuals who are particularly motivated by reputation. Employing diverse methods including large-scale multination panel data (N = 34,323), and vignette and behavioural experiments (N = 700), four studies supported our proposition, showing that various indicators of moral character (Benevolence and Universalism values, justice sensitivity, and moral identity) predicted harsher judgements of others' more than own transgressions. Moreover, these double standards emerged particularly among individuals possessing strong reputation management motives. The findings highlight how reputational concerns moderate the link between moral character and moral judgement.


The presence and distribution of glycogen particles in chondrogenic cells of the tibiotarsal anlage of developing chick embryos.
The distribution and localization of glycogen particles in mesenchymal cells, chondroblasts and in young, hypertrophic and degenerating chondrocytes of the tibiotarsal anlage of developing chick embryos were examined ultrastructurally using the periodic acid--thiocarbohydrazide--silver proteinate. The distribution of glycogen particles increased with the degree of differentiation and maturation of the chondrogenic cells. Mesenchymal cells showed minimal content of glycogen particles which gradually increased in the chondroblasts. The young chondrocytes further showed increased glycogen particle content compared to chondroblasts. This content reached a maximum level in hypertrophic chondrocytes. This level subsided in degenerating chondrocytes which showed a much reduced distribution of glycogen particles compared to hypertrophic chondrocytes. The morphological nature of glycogen particles depended on the degree of cellular differentiation. Both mesenchymal cells and chondroblasts contained single particles, while the glycogen particles of chondrocytes aggregated and formed a series of interconnected particles.


Merging of a Perylene Moiety Enables a RuII Photosensitizer with Long-Lived Excited States and the Efficient Production of Singlet Oxygen.
Invited for the front cover of this issue are Stefanie Tschierlei, Sven Rau and co-workers. The image shows the fusion of an organic chromophore with a RuII polypyridine moiety resulting in a unique bichromophoric photosensitizer. Read the full text of the article at 10.1002/chem.202103609.


Colonic malacoplakia and abdominal tuberculosis in a child. Report of a case with review of the literature.
A 4 1/2-year-old girl had colonic malacoplakia of two years' duration, the presenting symptom being rectal bleeding. Abdominal tuberculosis and Escherichia coli lumbar abscess were diagnosed at the age of 3 1/2 years. Despite antituberculous treatment, there was no improvement and she died from protein-losing enteropathy. The patient is discussed and the literature reviewed, with special emphasis on the incidence of malacoplakia in children, the aggressive nature of colonic malacoplakia, and the lack of response to treatment. A brief review of the pathogenesis of malacoplakia is considered.


Reconsidering priorities for forest conservation when considering the threats of mining and armed conflict.
Many threats to biodiversity can be predicted and are well mapped but others are uncertain in their extent, impact on biodiversity, and ability for conservation efforts to address, making them more difficult to account for in spatial conservation planning efforts, and as a result, they are often ignored. Here, we use a spatial prioritisation analysis to evaluate the consequences of considering only relatively well-mapped threats to biodiversity and compare this with planning scenarios that also account for more uncertain threats (in this case mining and armed conflict) under different management strategies. We evaluate three management strategies to address these more uncertain threats: 1. to ignore them; 2. avoid them; or 3. specifically target actions towards them, first individually and then simultaneously to assess the impact of their inclusion in spatial prioritisations. We apply our approach to the eastern Democratic Republic of the Congo (DRC) and identify priority areas for conserving biodiversity and carbon sequestration services. We found that a strategy that avoids addressing threats of mining and armed conflict more often misses important opportunities for biodiversity conservation, compared to a strategy that targets action towards areas under threat (assuming a biodiversity benefit is possible). We found that considering mining and armed conflict threats to biodiversity independently rather than simultaneously results in 13 800-14 800 km2 and 15 700-25 100 km2 of potential missed conservation opportunities when undertaking threat-avoiding and threat-targeting management strategies, respectively. Our analysis emphasises the importance of considering all threats that can be mapped in spatial conservation prioritisation.


The Impact of Navya-Nyāya on Mādhva Vedānta: Vyāsatīrtha and the Problem of Empty Terms.
In this article, I explore the encounter of the Mādhva philosopher Vyāsatīrtha with the works of the Navya-Naiyāyika Gaṅgeśa Upādhyāya. The article is based on original translations of passages from Vyāsatīrtha's Nyāyāmr̥ta and Tarkatāṇḍava. Philosophically, the article focuses on the issue of empty-terms/nonexistent entities, particularly in the context of the theory of inference. I begin by outlining the origin of the Mādhva and Nyāya positions about these issues in their respective analyses of perceptual illusion. I then contrast the role of Gaṅgeśa's thought in the Nyāyāmr̥ta and Tarkatāṇḍava and show how Vyāsatīrtha responds to Gaṅgeśa's ideas in different ways in those texts. I conclude with a discussion of how Vyāsatīrtha defends the Mādhva theory of "substrate-free" qualities against Gaṅgeśa in order to show that we can think and make valid inferences about nonexistent things.


Examination of the Development and Asymmetry of the Cerebellum and Its Lobules in Individuals Aged 1-18 Years: A Retrospective MRI Study.
Developmental studies of cerebellar lobules were limited. To our knowledge, structural asymmetry has not been studied in immature cerebellar lobules in the 1-18 age group. This study investigated the effect of age and gender on the volumetric development and asymmetry of the global cerebellum and cerebellar lobules in children and adolescents. In this retrospective study, we included 670 individuals [376 (56.1%) males] aged 1-18 years with normal brain MRIs between 2012 and 2021. volBrain CERES automatically segmented the right and left sides of the cerebellar lobules on three-dimensional T1-weighted MRIs. Volume and asymmetry data from individuals in 16 different age ranges were compared with SPSS (ver.28). The absolute volumetric development of the total cerebellum was consistent with the "S" development model in both sexes. The developmental trajectories of the cerebellar lobules were different from each other and showed sexual dimorphism. In the 1-18 age group, the absolute volumes of the total cerebellum and cerebellar lobules were significantly greater in males (p < 0.05). Absolute volumes of lobules IV, VIIB, VIIIA and VIIIB in the age groups had more gender differences. However, sexual dimorphism was insignificant in the cerebellum's total and lobular relative volume. Lobules IV, V, VI, VIIIA and VIIIB had left > right asymmetry and other lobules and total cerebellum had right > left asymmetry. This study confirmed the developmental heterogeneity and sexual dimorphism in the cerebellar lobules. It also provided volumetric data of the immature cerebellum to enable comparison in various neurological and neuropsychiatric diseases.


Intestinal tumour chemoprevention with the antioxidant lipoic acid stimulates the growth of breast cancer.
Breast and intestinal cancers chemoprevention would significantly impact on cancer care. Hence, we assessed the chemopreventive efficacy of the antioxidant lipoic acid (LA) in mice overexpressing a wild-type Her2/neu, as an animal model of breast cancer, and in APCmin mice for intestinal cancer. Mice were randomised at weaning, and were treated with LA for lifetime. Tumour incidence, growth rate and histopathology were analysed on an individual tumour basis. LA efficiently chemoprevented tumour appearance in APCmin mice. Strikingly, though, LA doses, that were chemopreventive in APCmin mice (> or = 300 microg/day), increased breast cancer growth in Her2/neu mice. Even in experimental groups, where LA overall reduced tumour risk (80 microg/day), LA consistently stimulated the growth rate of established breast tumours. Breast and colon tumours incidence was unaffected by LA, indicating no significant impact of LA on tumour initiation and no protection from mutations driving tumour progression. Stimulation of breast cancer growth and inhibition of intestinal tumours by LA indicate that diverse growth control mechanisms are modulated by LA in different organs. Concern is raised about the use of LA for cancer chemoprevention.


Co-prescribing of medications used to treat obstructive lung disease, congestive heart failure and depression among users of topical beta blockers: estimates from three US Veterans Affairs Medical Centers.
To estimate the frequency of co-prescribing of medications used to treat obstructive lung disease, congestive heart failure, and depression among US armed service veterans for whom topical beta blockers (TBB) have been prescribed. Prescription data from the computerized medical record systems of three US Veterans Affairs Medical Centers were obtained during Fall 1999 to identify patients for whom active prescriptions existed for TBB and/or drugs commonly used to treat obstructive lung disease, congestive heart failure, and depression. Among TBB users, the estimated co-prescribing rate of medications used to treat obstructive lung disease is in the range of 7.8-9.7%, of medications used to treat congestive heart failure is in the range of 4.3-25.1%, and of medications used to treat depression is in the range of 8.8-11.7%. The total number of TBB users with a concurrent prescription for one or more of the conditions studied was in the range of 30.2-45.7%. Since TBB may cause systemic side-effects and thus potentially cause exacerbations of selected chronic conditions, it is important for researchers and prescribers to be aware of the frequency with which their patients with glaucoma may have other concomitant conditions.


Protein kinase A regulatory subunits in colon cancer.
The protein kinase A (PKA) is classified as type I or II depending on the association of the catalytic subunit with either the R(I) or R(II) regulatory subunits. Alterations in the levels of these regulatory subunits and PKA activity itself appear to affect cellular proliferation and tumorigenesis. We examined colorectal tumor specimens from 45 patients to investigate the potential role of cAMP-related signaling molecules in regulating tumorigenesis. Western blot analysis (PKA subunit protein levels) and in vitro kemptide phosphorylation assays (PKA catalytic subunit activity) were performed on human colorectal tumor tissue homogenates. R(I)beta protein levels were decreased 200% in ascending and 50% in descending colonic tumors compared to adjacent mucosa. R(II) protein levels were decreased 77% in descending colonic tumors but no change was observed in ascending colonic tumors compared to adjacent mucosa. PKA activity and the absolute amount of catalytic subunit protein in ascending and descending tumors were unchanged compared to adjacent mucosa. Differences in cAMP-related signaling molecules exist between neoplastic and normal colorectal tissues. These differences may not only serve as potential therapeutic targets for chemotherapeutic agents, but also lead to the identification of novel regulatory mechanisms involved in cellular proliferation and tumorigenesis.


Estimating malaria transmission risk through surveillance of human-vector interactions in northern Ghana.
Vector bionomics are important aspects of vector-borne disease control programs. Mosquito-biting risks are affected by environmental, mosquito behavior and human factors, which are important for assessing exposure risk and intervention impacts. This study estimated malaria transmission risk based on vector-human interactions in northern Ghana, where indoor residual spraying (IRS) and insecticide-treated nets (ITNs) have been deployed. Indoor and outdoor human biting rates (HBRs) were measured using monthly human landing catches (HLCs) from June 2017 to April 2019. Mosquitoes collected were identified to species level, and Anopheles gambiae sensu lato (An. gambiae s.l.) samples were examined for parity and infectivity. The HBRs were adjusted using mosquito parity and human behavioral observations. Anopheles gambiae was the main vector species in the IRS (81%) and control (83%) communities. Indoor and outdoor HBRs were similar in both the IRS intervention (10.6 vs. 11.3 bites per person per night [b/p/n]; z = -0.33, P = 0.745) and control communities (18.8 vs. 16.4 b/p/n; z = 1.57, P = 0.115). The mean proportion of parous An. gambiae s.l. was lower in IRS communities (44.6%) than in control communities (71.7%). After adjusting for human behavior observations and parity, the combined effect of IRS and ITN utilization (IRS: 37.8%; control: 57.3%) on reducing malaria transmission risk was 58% in IRS + ITN communities and 27% in control communities with ITNs alone (z = -4.07, P < 0.001). However, this also revealed that about 41% and 31% of outdoor adjusted bites in IRS and control communities respectively, occurred before bed time (10:00 pm). The mean directly measured annual entomologic inoculation rates (EIRs) during the study were 6.1 infective bites per person per year (ib/p/yr) for IRS communities and 16.3 ib/p/yr for control communities. After considering vector survival and observed human behavior, the estimated EIR for IRS communities was 1.8 ib/p/yr, which represents about a 70% overestimation of risk compared to the directly measured EIR; for control communities, it was 13.6 ib/p/yr (16% overestimation). Indoor residual spraying significantly impacted entomological indicators of malaria transmission. The results of this study indicate that vector bionomics alone do not provide an accurate assessment of malaria transmission exposure risk. By accounting for human behavior parameters, we found that high coverage of ITNs alone had less impact on malaria transmission indices than combining ITNs with IRS, likely due to observed low net use. Reinforcing effective communication for behavioral change in net use and IRS could further reduce malaria transmission.


Use of Selective Serotonin Reuptake Inhibitors and Outcomes in Stroke Rehabilitation: A Prospective Observational Pilot Cohort Study.
The aim of this study was to examine the association between selective serotonin reuptake inhibitor (SSRI) therapy and rehabilitation outcomes, specifically disability and quality of life (QOL), in a real-world setting of multi-ethnic Asian patients with first-ever stroke. In this prospective observational pilot cohort study, we included patients with first-ever stroke admitted to two inpatient rehabilitation centres in Singapore between January and July 2018. Outcomes were measured using Functional Independence Measure (FIM)-motor scale, modified Barthel Index (MBI) and the Stroke and Aphasia Quality of Life Scale-39 generic (SAQOL-39g) questionnaire. Linear regression was used to assess the association between SSRI therapy and outcomes. Regression coefficients and 95% confidence intervals (CIs) were reported. Among 57 patients included for analyses, 38.6% received SSRIs. Although SSRI therapy was significantly associated with gains in MBI (coefficient 11.35; 95% CI 0.21-22.50) and SAQOL-39g overall score (coefficient 0.45; 95% CI 0.05-0.85) based on simple linear regression, no significant association between SSRI therapy and any of the investigated outcomes was found after adjustment for confounders. However, an increase in the mean number of physiotherapy and occupational therapy (PT/OT) sessions per day significantly improved FIM-motor (coefficient 16.86; 95% CI 2.64-31.07) and MBI (coefficient 22.79; 95% CI 2.35-43.23) scores. SSRI therapy did not improve disability and QOL in multi-ethnic Asian patients with first-ever stroke undergoing rehabilitation.


Fetal death as an outcome of acute respiratory distress in pregnancy, during the COVID-19 pandemic: a population-based cohort study in Bahia, Brazil.
Fetal loss is one of the most serious adverse outcomes of pregnancy. Since the onset of the COVID-19 pandemic, Brazil has recorded an unprecedented number of hospitalizations of pregnant women due to acute respiratory distress (ARD), thereby, we aimed to assess the risk of fetal deaths associated to ARD during pregnancy in Bahia state, Brazil, in the context of the COVID-19 pandemic. This is an observational population-based retrospective cohort study, developed with women at or after 20 weeks of pregnancy, residents in Bahia, Brazil. Women who had acute respiratory distress (ARD) in pregnancy during the COVID-19 pandemic (Jan 2020 to Jun 2021) were considered 'exposed'. Women who did not have ARD in pregnancy, and whose pregnancy occurred before the onset of the COVID-19 pandemic (Jan 2019 to Dec 2019) were considered 'non-exposed'. The main outcome was fetal death. We linked administrative data (under mandatory registration) on live births, fetal deaths, and acute respiratory syndrome, using a probabilistic linkage method, and analyzed them with multivariable logistic regression models. 200,979 pregnant women participated in this study, 765 exposed and 200,214 unexposed. We found four times higher chance of fetal death in women with ARD during pregnancy, of all etiologies (adjusted odds ratio [aOR] 4.06 confidence interval [CI] 95% 2.66; 6.21), and due to SARS-CoV-2 (aOR 4.45 CI 95% 2.41; 8.20). The risk of fetal death increased more when ARD in pregnancy was accompanied by vaginal delivery (aOR 7.06 CI 95% 4.21; 11.83), or admission to Intensive Care Unit (aOR 8.79 CI 95% 4.96; 15.58), or use of invasive mechanical ventilation (aOR 21.22 CI 95% 9.93; 45.36). Our findings can contribute to expanding the understanding of health professionals and managers about the harmful effects of SARS-CoV-2 on maternal-fetal health and alerts the need to prioritize pregnant women in preventive actions against SARS-CoV-2 and other respiratory viruses. It also suggests that pregnant women, infected with SARS-CoV-2, need to be monitored to prevent complications of ARD, including a careful assessment of the risks and benefits of early delivery to prevent fetal death.


Successful integration of fixed and removable prosthodontics.
The management of complex prosthodontics requires special consideration during treatment as well as maintenance visits after treatment is complete. The anticipated design of the removable partial denture framework must be recorded prior to restorative procedures. Preparation of the abutment teeth should provide space for the critical portions of the removable partial denture that will require subsequent restorations. Portions of a removable partial denture essential to the construction of a restoration are guide planes, rests, retentive clasps, and reciprocal components. The wax patterns of the restorations should be contoured on a surveyor in harmony with the path of insertion and design of removable partial dentures. Successful integration of fixed and removable prosthodontics is dependent on adequate diagnostic information and perceptive execution of restorative procedures.


Anaesthesia for Angelman syndrome.
We describe the administration of anaesthesia to a patient with Angelman syndrome, which is characterised by an abnormality of chromosome 15, where a subunit of the GABA receptor is coded. This has far-reaching anaesthetic implications as many drugs used in anaesthesia are thought to act via GABA receptors. Our patient had an uneventful peri-operative period and was discharged home on the second postoperative day.


Differential expression of phosphacan/RPTPbeta isoforms in the developing mouse visual system.
The chondroitin sulfate proteoglycan DSD-1-PG/phosphacan represents one of four splice variants of receptor-protein-tyrosine-phosphatase-beta/zeta (RPTPbeta/zeta). This receptor is expressed by glial cells and occurs in two isoforms, RPTPbeta(long) and RPTPbeta(short). The secreted forms phosphacan and phosphacan short isoform (PSI) bind to extracellular matrix and adhesion molecules and might mediate astroglial effects on neuronal differentiation. Phosphacan and RPTPbeta(long) both carry the DSD-1 epitope, a glycosaminoglycan modification that is involved in stimulating neurite outgrowth of embryonic rat mesencephalic and hippocampal neurons in a polycationic environment. Additionally, phosphacan inhibits neurite outgrowth of embryonic DRG neurons in the presence of laminin. In the light of these functional properties we examined the expression patterns of the DSD-1 epitope and phosphacan isoforms in the developing mouse visual system. During retinal development the DSD-1 epitope appears around embryonic day (E)13, peaks around postnatal day (P)6, and is downregulated from P9 to adolescence. By comparison, the phosphacan core protein is first detectable at E12, reaches maximal levels around P14, and persists, although at lower levels, to adulthood. The DSD-1 epitope is restricted to the nerve fiber and the inner plexiform layers. In contrast, the phosphacan core protein immunoreactivity extends from the nerve fiber layer to the outer plexiform layer. The level of expression of the phosphacan/RPTPbeta gene was investigated by reverse-transcriptase polymerase chain reaction. These experiments suggest that there is a shift in the expression patterns of the different phosphacan/RPTPbeta isoforms during late embryonic and postnatal development. In situ hybridization experiments support the conclusion that at least one of the phosphacan/RPTPbeta isoforms in the retina is expressed by neurons.


Bilateral colobomas in a horse.
Bilateral true colobomas with retrobulbar cysts located over the optic nerves are described in an 8-year-old Quarterhorse mare with a history of progressive blindness. Colobomas result from the failure of an embryonic fissure to close and retrobulbar cysts result from eversion of the neuroectoderm through the colobomas. It could not be determined whether the small optic nerves and the scars, rosettes and disorganization of the cell layers in the retina were the result of concurrent dysplasia or were secondary to degeneration.


Aβ and tau prions feature in the neuropathogenesis of Down syndrome.
Down syndrome (DS) is caused by the triplication of chromosome 21 and is the most common chromosomal disorder in humans. Those individuals with DS who live beyond age 40 y develop a progressive dementia that is similar to Alzheimer's disease (AD). Both DS and AD brains exhibit numerous extracellular amyloid plaques composed of Aβ and intracellular neurofibrillary tangles composed of tau. Since AD is a double-prion disorder, we asked if both Aβ and tau prions feature in DS. Frozen brains from people with DS, familial AD (fAD), sporadic AD (sAD), and age-matched controls were procured from brain biorepositories. We selectively precipitated Aβ and tau prions from DS brain homogenates and measured the number of prions using cellular bioassays. In brain extracts from 28 deceased donors with DS, ranging in age from 19 to 65 y, we found nearly all DS brains had readily measurable levels of Aβ and tau prions. In a cross-sectional analysis of DS donor age at death, we found that the levels of Aβ and tau prions increased with age. In contrast to DS brains, the levels of Aβ and tau prions in the brains of 37 fAD and sAD donors decreased as a function of age at death. Whether DS is an ideal model for assessing the efficacy of putative AD therapeutics remains to be determined.


Radioimmunoassay of 2-hydroxyesterone and 2-methoxyestrone in human urine.
An assay for the quantitative determination of 2-hydroxyestrone and 2-methoxyestrone in human urine is described. The analytical procedure involves several purification steps: XAD-2 column chromatography of urine (1 ml), hot acid hydrolysis under reducing conditions, extraction with benzene/ethyl acetate, separation of monophenolic steroids from catecholestrogens by the formation of borate complexes, and partition between different solvents. Quantitation is achieved by radioimmunoassay using highly specific antibodies. For correction of procedural losses [6, 7-3H2] 2-hydroxyestrone and [6, 7-3H2] 2-methoxyestrone are used as internal standards. The method is highly specific as checked by comparison to a double-isotope-derivative method and a newly developed gas chromatography-mass spectrometry procedure. Using this method the urinary excretion of 2-hydroxyestrone and 2-methoxyestrone was studied in children, men, cycling, pregnant and postmenopausal women. Special interest was focussed on the molar ratios of 2-hydroxyestrone to 2-methoxyestrone and the so called "total estrogens" which vary markedly within the different groups investigated. The excretion of 2-hydroxyestrone is especially favoured in women during the menstrual cycle and pregnancy.


Replicating premeiotic germ cells of the mouse contain a novel DNA primase stimulatory factor.
A protein factor that stimulates DNA primase activity associated with DNA polymerase alpha has been identified in mouse germ cell populations enriched in spermatogonia and preleptotene spermatocytes. The partially purified factor enhances DNA primase activity from homologous cell types as well as DNA primase activity from Xenopus laevis oocytes in a poly dT or M 13 directed reaction. The factor does not stimulate DNA polymerase alpha activity in a gapped salmon sperm or poly dT-rA directed reaction. The DNA primase stimulating factor is identified in a male mouse germ cell population enriched in premeiotic cells; it is not detectable in middle-late pachytene spermatocytes, spermatids, Sertoli cells or fibroblasts.


Elevated carboxyhemoglobin associated with sodium nitroprusside treatment.
To report four cases of carboxyhemoglobinemia associated with high doses of sodium nitroprusside after cardiac transplant in children. Four children in the pediatric care unit of a university hospital aged 6 months-4 years. Carboxyhemoglonemia developed at levels of 5.5-7.7% in patients receiving high doses of sodium nitroprusside (7-16 microg/kg per minute and no other medication that could caused elevated carboxyhemoglobin). One patient died, and three recovered with no sequelae after discontinuation of sodium nitroprusside. High doses of sodium nitroprusside can induce carboxyhemoglobinemia in children after heart transplant, probably by inducing hemeoxygenase, with no other secondary effects.


Synthesis and evaluation of new arylsulfonamidomethylcyclohexyl derivatives as human neuropeptide Y Y5 receptor antagonists for the treatment of obesity.
NPY is the most potent orexigenic peptide identified up to now. Stimulation of food intake is measured by the Y(1) and Y(5) receptor subtypes. In this study, the synthesis and evaluation of new arylsulfonamidomethylcyclohexyl derivatives are described as potential selective antagonists of the human NPY Y(5) receptor. The SAR of these series was examined and the amide derivatives were the compounds that showed the best activities. trans-N-(4-[(Quinolin-3-yl)aminocarbonyl]cyclohexylmethyl)-2,4-dichlorobenzenesulfonamide (42) bound to the human neuropeptide Y Y(5) receptor with a 2 nM IC(50).


Femoral neck stress fracture return to activity and the effect of metabolic dysfunction on recovery: A systematic review.
Femoral neck stress fractures are rare fractures traditionally found in athletes and military personnel. There is limited literature on return to activity. To report return to activity rates and times, and long-term outcomes for femoral neck stress fractures reported in the literature. To examine the effects of bone metabolic dysfunction and surgical management on return to activity following FNSF. A systematic literature review of case reports and case series on adults with femoral neck stress fracture that were diagnosed by gross fracture line on X-ray or gold-standard diagnosis with MRI was conducted. Initial search was limited to articles published from January 1997 to Jan 2023 listed in Medline, Embase, and Scopus. Additional articles were manually added via search of retained paper sources. Patient demographics, fracture type, return to activity time, and surgical vs non-surgical treatment modality were collected. In addition, long-term outcomes and metabolic effects, if reported, were abstracted. A total of 40 case reports or case series were retained. 123 stress fractures of the femoral neck from 103 patients were compiled. Of the 103 patients, data on return to activity at least one year following treatment was available for 53 patients. 71% (37/53) of those with long-term follow-up information returned to full pre-injury activity. 24% (13/53) at long-term follow-up had functional recovery but did not return to pre-injury activity due to residual pain. 4% (3/53) had disabling pain. Metabolic workup information was available for 36 patients. Long-term follow-up and return to activity information following FNSF treatment are not commonly reported. Based on the available data, outcomes appear benign with most returning to full activity. There is a clear need for standardization of follow-up periods and hip function measure after FNSF treatment. Additionally, a sizable proportion of FNSF occurred in a new population of low-activity individuals with abnormal bone metabolism, which warrants further exploration.


Comparison of the response to ovarian stimulation between women with one ovary and those with two ovaries, in a program of ICSI/ET.
Women with a single ovary form a group of special interest in assisted reproduction. The aim of this study was to compare the outcome of intracytoplasmic sperm injection cycles between women with one and two ovaries. To our knowledge, this is the first study reporting the outcome of intracytoplasmic sperm injection cycles with women with a single ovary. Sixty-three intracytoplasmic sperm injection cycles in 24 women with a single ovary were compared with 191 intracytoplasmic sperm injection cycles in 109 women with both ovaries. All cycles were stimulated with triptorelin-long protocol. Statistically significant differences were found in the following parameters between women with a single ovary and women with two ovaries: total number of administrated gonadotropins (63.22 +/- 45.03 vs. 44.72 +/- 21.92), number of follicles (8.29 +/- 5.02 vs. 14.45 +/- 7.94), estradiol peak levels (1695.05 +/- 1177.34 vs. 2728.51 +/- 1852.67), number of retrieved metaphase II oocytes (6.95 +/- 3.78 vs. 11.72 +/- 6.11) and number of 2 PN oocytes (4.07 +/- 2.85 vs. 6.53 +/- 4.14). There were no differences in duration of stimulation, number of transferred embryos, and cumulative embryo score. In the group of women with a single ovary 14 pregnancies were achieved (22.2%), whereas 33 pregnancies were achieved in the group of women with two ovaries (17.28%). Women with a single ovary have a decreased response to external ovarian stimulation than women with both ovaries, but they present a higher, although not statistically significant, pregnancy rate.


Postnatal hearing loss: a study of children who passed neonatal TEOAE hearing screening bilaterally.
Universal newborn hearing screening (UNHS) contributes to the early diagnosis of hearing loss. However, not all permanent pediatric hearing impairments can be identified by UNHS. To investigate children who have successfully passed the UNHS, but have later-onset hearing loss at an early stage. UNHS of children, was reviewed retrospectively from databases at Karolinska University Hospital, Sweden. Gender, age, the reason for contact, the first contact and the most recent audiogram, the hearing diagnosis, the degree of hearing loss when they were enrolled in hearing rehabilitation, and the hearing aids they used were analysed. 63 children who had passed the UNHS at birth and were diagnosed with a hearing impairment at a later stage were included in the study. The average age was 3.3 and 3.9 years old when the children were diagnosed and were finally enrolled in the hearing habilitation, respectively. The reasons for diagnostic evaluation of a suspected hearing loss at present study are preschool hearing tests at the Child Health Care Centres, parents suspect, and/or delayed speech and language development. Our findings suggest that a passed UNHS does not exclude a future delayed onset of hearing loss, particularly in children with risk factors.


Salt Bridge in Aqueous Solution: Strong Structural Motifs but Weak Enthalpic Effect.
Salt bridges are elementary motifs of protein secondary and tertiary structure and are commonly associated with structural driving force that increases stability. Often found on the interface to the solvent, they are highly susceptible to solvent-solute interactions, primarily with water but also with other cosolvents (especially ions). We have investigated the interplay of an Arginine-Aspartic acid salt bridge with simple salt ions in aqueous solution by means of molecular dynamics simulations. Besides structural and dynamical features at equilibrium, we have computed the mean force along the dissociation pathway of the salt bridge. We demonstrate that solvated ions influence the behavior of the salt bridge in a very specific and local way, namely the formation of tight ionic pairs Li+/Na+-Asp-. Moreover, our findings show that the enthalpic relevance of the salt bridge is minor, regardless of the presence of solvated ions.


A tale of two components: a novel kinase and a regulatory switch.
Histidine protein kinases and response regulators form the basis of phosphotransfer signal transduction pathways. Commonly referred to as two-component systems, these modular and adaptable signaling schemes are prevalent in prokaryotes. Structures of the core domains of histidine kinases reveal a protein kinase fold different from that of the Ser/Thr/Tyr protein kinase family, but similar to that of other ATP binding domains. Recent structure determinations of phosphorylated response regulator domains indicate a conserved mechanism for the propagated conformational change that accompanies phosphorylation of an active site Asp residue. The altered molecular surface promotes specific protein-protein interactions that mediate the downstream response.


Medication errors: the problem and its scope.
Nurses can take an important lead role in protecting their patients, their peers, and themselves from the unfortunate consequences of medication errors. Medication errors occurs for a variety of reasons, including inaccurate communications and deficits in knowledge and performance by and among all health care professionals. These problems and deficits need to be addressed. USP stresses the importance of focusing on the process or system in which the error occurred, rather than focusing blame on an individual. By acknowledging all actual and potential errors, and by consistently assessing and reassessing systems, nurses can help reduce medication errors and contribute significantly to improve patient safety.


Ultrasound and clinicopathological characteristics-based model for prediction of pathologic response to neoadjuvant chemotherapy in HER2-positive breast cancer: a case-control study.
The objective of this study was to develop a model combining ultrasound (US) and clinicopathological characteristics to predict the pathologic response to neoadjuvant chemotherapy (NACT) in human epidermal growth factor receptor 2 (HER2)-positive breast cancer. This is a retrospective study that included 248 patients with HER2-positive breast cancer who underwent NACT from March 2018 to March 2022. US and clinicopathological characteristics were collected from all patients in this study, and characteristics obtained using univariate analysis at p < 0.1 were subjected to multivariate analysis and then the conventional US and clinicopathological characteristics independently associated with pathologic complete response (pCR) from the analysis were used to develop US models, clinicopathological models, and their combined models by the area under the receiver operating characteristic (ROC) curve (AUC), accuracy, sensitivity, and specificity to assess their predictive efficacy. The combined model had an AUC of 0.808, a sensitivity of 88.72%, a specificity of 60.87%, and an accuracy of 75.81% in predicting pCR of HER2-positive breast cancer after NACT, which was significantly better than the clinicopathological model (AUC = 0.656) and the US model (AUC = 0.769). In addition, six characteristics were screened as independent predictors, namely the Clinical T stage, Clinical N stage, PR status, posterior acoustic, margin, and calcification. The conventional US combined with clinicopathological characteristics to construct a combined model has a good diagnostic effect in predicting pCR in HER2-positive breast cancer and is expected to be a useful tool to assist clinicians in effectively determining the efficacy of NACT in HER2-positive breast cancer patients.


Hydrocortisone selectively inhibits IgE-dependent arachidonic acid release from rat peritoneal mast cells.
Purified rat mst cells were used to study the effects of antiinflammatory steroids on the release of [1-14C]-arachidonic acid ([1-14C]AA) and metabolites. Mast cell were incubated overnight with glucocorticoids, [1-14C]AA incorporated into cellular phospholipids and the release of [1-14C]AA, and metabolites determined using a variety of secretagogues. Release of [1-14C]AA and metabolites by concanavalin A, the antigen ovalbumin and anti-immunoglobulin E antibody was markedly reduced by glucocorticoid treatment. Neither the total incorporation of [1-14C]AA nor the distribution into phospholipids was altered by hydrocortisone pretreatment. Glucocorticoid pretreatment did not alter [1-14C]AA release stimulated by somatostatin, compound 48/80, or the calcium ionophore, A23187. These data indicate that antiinflammatory steroids selectively inhibit immunoglobulin dependent release of arachidonic acid from rat mast cells. These findings question the role of lipomodulin and macrocortin as general phospholipase inhibitors and suggest that they may be restricted to immunoglobulin stimuli.


Treatment of metastatic bone pain with strontium-89.
We have utilized 89Sr as palliative treatment for bone pain secondary to metastatic cancer in the skeleton of over 200 patients. The best results have been in patients with carcinoma of the prostate (80% response rate) and breast (89%). Results in a small number of patients with a variety of other cell types were not nearly as encouraging. Strontium-89 provides excellent palliation in the management of bone pain secondary to prostate and breast carcinoma.


Incidence and treatment costs attributable to medication errors in hospitalized patients.
A significant financial burden arises from medication errors that cause direct injury and those without patient harm that represent waste and inefficiency. To estimate the incidence, types, and causes of medication errors as well as their attributable costs in a hospital setting. For a retrospective case-control study, data were collected for 57,554 patients admitted to two New Jersey (U.S. State) hospitals during 2005-2006 as well as hospital-specific voluntary error reports from these two hospitals for the same period. Medication errors were classified into categories of stage, error type, and proximal cause, and the incidence was estimated. The costs attributable to medication errors were calculated using both the recycled prediction method, and the Blinder-Oaxaca decomposition method after propensity score matching. Medication errors occurred at a rate of 0.8 per 100 admissions, or 1.6 per 1000 patient days. Most errors occurred at the administration stage of the medication use process. The most frequent types of errors were wrong time, wrong medication, wrong dose, and omission errors. Treatment costs attributable to medication errors were in the range of $8,439 using the Blinder-Oaxaca decomposition method and $8,898 using the recycled prediction method. Medication errors are associated with significant additional costs, even without patient harm. Considering the substantial costs associated with adverse drug events, the elimination of medication errors should be further emphasized and promoted, and guidelines should be developed to facilitate this goal.


Implementation of an anaemia walk-in clinic: Feasibility and preliminary data from the Orthopedic University Hospital.
Approximately one in three patients suffers from preoperative anaemia. Even though haemoglobin is measured before surgery, anaemia management is not implemented in every hospital. Here, we demonstrate the implementation of an anaemia walk-in clinic at an Orthopedic University Hospital. To improve the diagnosis of iron deficiency (ID), we examined whether reticulocyte haemoglobin (Ret-He) could be a useful additional parameter. In August 2019, an anaemia walk-in clinic was established. Between September and December 2019, major orthopaedic surgical patients were screened for preoperative anaemia. The primary endpoint was the incidence of preoperative anaemia. Secondary endpoints included Ret-He level, red blood cell (RBC) transfusion rate, in-hospital length of stay and anaemia at hospital discharge. A total of 104 patients were screened for anaemia. Preoperative anaemia rate was 20.6%. Intravenous iron was supplemented in 23 patients. Transfusion of RBC units per patient (1.7 ± 1.2 vs. 0.2 ± 0.9; p = 0.004) and hospital length of stay (13.1 ± 4.8 days vs. 10.6 ± 5.1 days; p = 0.068) was increased in anaemic patients compared to non-anaemic patients. Ret-He values were significantly lower in patients with ID anaemia (33.3 pg [28.6-40.2 pg]) compared to patients with ID (35.3 pg [28.9-38.6 pg]; p = 0.015) or patients without anaemia (35.4 pg [30.2-39.4 pg]; p = 0.001). Preoperative anaemia is common in orthopaedic patients. Our results proved the feasibility of an anaemia walk-in clinic to manage preoperative anaemia. Furthermore, our analysis supports the use of Ret-He as an additional parameter for the diagnosis of ID in surgical patients.


Tissue plasminogen activator thrombolytic therapy for acute ischemic stroke in 4 hospital groups in Japan.
In October 2005 in Japan, the recombinant tissue plasminogen activator (tPA) alteplase was approved for patients with acute ischemic stroke within 3 hours of onset at a dose of 0.6 mg/kg. The present study was undertaken to assess the safety and efficacy of alteplase in Japan. Between October 2005 and December 2009, a total of 114 consecutive patients admitted to 4 hospitals received intravenous tPA within 3 hours of stroke onset. Clinical backgrounds and outcomes were investigated. The patients were divided into 2 chronological groups: an early group, comprising 45 patients treated between October 2005 and December 2007, and a later group, comprising 69 patients treated between January 2008 and December 2009. The mean time from arrival at the hospital to the initiation of treatment was significantly reduced in the later group, from 82.6 minutes to 70.9 minutes. Intracerebral hemorrhage (ICH) occurred in 26 patients (22.8%); compared with patients without ICH, these patients had a significantly higher prevalence of cardiogenic embolism (88.5% vs 58.0%); greater warfarin use (26.8% vs 6.8%); higher mean National Institutes of Health Stroke Scale (NIHSS) scores on admission (16 vs 10), at 3 days after admission (14 vs 5), and at 7 days after admission (13.5 vs 3); and a lower Diffusion-Weighted Imaging-Alberta Stroke Program Early CT Score (7.8 vs 9.1). Patients who received edaravone had a higher prevalence of cardiogenic embolism (70.9% vs 36.4%), a higher recanalization rate (77.7% vs 36.4%), and lower NIHSS scores on admission and at 3 and 7 days after admission compared with those who did not receive edaravone. Our data suggest that administration of intravenous alteplase 0.6 mg/kg within 3 hours of stroke onset is safe and effective, that the NIHSS and Diffusion-Weighted Imaging-Alberta Stroke Program Early CT Score are useful predictors of ICH after tPA administration, and that warfarin-treated patients are more likely to develop symptomatic ICH despite an International Normalized Ratio <1.7.


Bleomycin cytotoxicity is prevented by superoxide dismutase in vitro.
The cytotoxicity of the antitumor antibiotic bleomycin (BLM) on Chinese hamster ovary cells in vitro was studied. Approximately 50% of the cells were killed by exposure to 9.6 micrograms/ml BLM for 1 h. The cytotoxicity could be partially reversed by the prior addition of superoxide dismutase (SOD) or catalase, but not with the addition of mannitol or histidine. These results indicate that superoxide anion and hydrogen peroxide but not hydroxyl radical are involved in the cytotoxic action of BLM.


Structural Factors and Quality of Diabetes Health Services in Hail, Saudi Arabia: A Cross-Sectional Study.
The chronic disease burden in Saudi Arabia has created adverse health, social and economic consequences that require urgent attention from health and political authorities. Diabetes has become an epidemic in Saudi Arabia. Data on personal and structural factors associated with diabetes in the Hail region are scarce. Such data are imperative to develop effective strategies to control the epidemic in the region. A cross-sectional study of diabetes patients attending diabetes health care facilities in Hail was conducted using a sample of 392 patients. An interviewer-administered questionnaire was used. A slightly higher proportion of female participants (54.1%) were included in the sample. Most of the participants were from rural areas (73.9%), and 70.9% of the participants were from the middle-age (30-50 years) category. A close proximity to the diabetes clinic (OR = 1.98; 95% CI: 1.08-3.44), good transport facilities (OR = 1.67; 95% CI: 1.11-2.78) and feeling contented with supportive services (OR = 2.03; 95% CI: 1.12-4.04) were associated with patients' satisfaction with the overall quality of the diabetes clinic services. The presence of good-quality health care professionals working in these treatment centers also seemed to contribute to patients' satisfaction with the services they received. These structural factors associated with patients' satisfaction with the services they received from diabetes clinics must be considered in diabetes control programs in the region. The minimization of structural barriers will eventually assist the national strategic plan, Vision 2030, which aims to improve the quality of life of the Saudi people by 2030.


Antioxidant defense response induced by Trichoderma viride against Aspergillus niger Van Tieghem causing collar rot in groundnut (Arachis hypogaea L.).
The study was conducted to examine the antioxidant enzymes induced by Trichoderma viride JAU60 as initial defense response during invasion of rot pathogen Aspergillus niger Van Tieghem in five groundnut varieties under pot culture. Seed treatment of T. viride JAU60 reduced 51-58% collar rot disease incidence in different groundnut varieties under pathogen infected soil culture. The activities of the antioxidant enzymes, viz., superoxide dismutase (SOD, EC 22.214.171.124), guaiacol peroxidase (GPX, EC 188.8.131.52) and ascorbate peroxidase (APX, EC 188.8.131.52), elevated in response to pathogen infection, in higher rate by tolerant varieties (J-11 and GG-2) compared with susceptible (GAUG-10, GG-13, GG-20) and further induced by T. viride treatment. Trichoderma treatment remarkably increased the 2.3 fold SOD, 5 fold GPX and 2.5 fold APX activities during disease development in tolerant varieties and the same was found about 1.2, 1.5 and 2.0 folds, respectively, in susceptible varieties. Overall, T. viride JAU60 treated seedlings (T3) witnessed higher activities of SOD (1.5 fold), GPX (3.25 fold) and APX (1.25 fold) than pathogen treatment (T2) possibly suggest the induction of antioxidant defense response by Trichoderma bio-controller to combat oxidative burst produced by invading pathogen.


Wernicke's syndrome during parenteral feeding: not an unusual complication.
Wernicke's encephalopathy (WE) is an acute disorder due to thiamine deficiency, characterized by ophthalmoplegia, ataxia, and mental confusion, similar to that classically observed in alcoholism. Some cases of WE were reported to coincide with other conditions such as hyperemesis gravidarum, bariatric surgery, and total parenteral nutrition. In this study the objective was to retrospectively evaluate the prevalence of WE among intravenously fed patients in our hospital during the previous 2 y. Among all cases of WE diagnosed by cranial magnetic resonance scan during a 2-y period in the Azienda Ospedaliera of Padua, we identified patients who exhibited WE during parenteral feeding. Albumin plasma levels, measured at the onset of WE symptoms, were used to estimate nutritional status. We found seven cases of WE that coincided with intravenous feeding. WE occurred, on average, 13 d after the start of glucose infusion. The five subjects with albumin plasma levels lower than 35 g/L at the onset of WE received glucose infusion for fewer days. In six cases the clinical signs disappeared the day after thiamine infusion. In one case mental function did not normalize and the patient developed Korsakoff's syndrome despite prolonged thiamine treatment. During a 2-y period we observed a high prevalence of WE in intravenously fed patients due to lack of thiamine supplementation. A prophylactic treatment must be performed in at-risk patients and multivitamin infusion containing thiamine must be administered daily during the course of intravenous feeding.


Different biological behaviors in left-sided pancreatic cancer according to Yonsei criteria: Proposal of a modified Yonsei criteria score.
Our institutional experience has demonstrated that bloodless and margin-negative resection is the most potent prognostic factor in treating left-sided pancreatic cancer and we developed selection guideline. The Yonsei criteria (YC) is selection criteria for oncologically safe and effective resection of left-sided pancreatic cancer by a minimally invasive approach. In this study, we investigated whether left-sided pancreatic cancer with YC can be more individualized to predict long-term survival by using clinically and pathologically detectable parameters. From January 2000 to December 2015, 105 patients underwent distal pancreatectomy for left-sided pancreatic cancer. The medical records of the patients were retrospectively reviewed. Among clinically and pathologically detectable parameters to predict tumor conditions, radiologically determined tumor size (p = 0.080) and SUVmax (p = 0.086) were identified as predictors of early tumor recurrence with marginal significance. Among them, 20% of the patients with YC were identified as having the most favoring tumor condition, with an modified YC score of 3. The patient group with the lowest mYC score was found to have a very long disease-free survival time, with a mean of 108 months, which was statistically different from those with other mYC scores (mYC score = 4, mean 47.1 months [95% CI: 27.8-69.5] vs. mYC score = 5, mean 36.7 months [95% CI: 12.7-60.7], vs. mYC score = 6, mean 10.7 months [95% CI: 3.9-17.4]). Modified Yonsei criteria score can predict long-term survival in resected left-sided pancreatic cancer. And patients within YC with a mYC score = 3 could have a favorable survival outcome.


The moderation effects of task attributes and mental fatigue on post-interruption task performance in a concurrent multitasking environment.
In a concurrent multitasking environment, performing many types of tasks increases task complexity, and working long hours makes a person susceptible to mental fatigue. Emerging technologies may lead to more task interruptions. This study examines the effects of task attributes and mental fatigue on interrupted task performance in a concurrent multitasking environment. Thirty-four participants performed the MATB-Ⅱ under eight conditions (two-level task interruption, two-level task complexity, two-level fatigue). The results revealed the significant interaction effects of interruption × task complexity and of interruption × fatigue state. The findings show that more time is required to return to a complex primary task, and there are differences among subtask types. Mental fatigue negatively affects primary task performance, workload, and the resumption lag after an interruption. The findings are explained by the increasing information cues needed to resume complex tasks and the negative effect of fatigue on memory activation.


Tight glycaemic control in the intensive care unit: pitfalls in the testing of the concept.
Tight glycaemic control emerged on the scene of critical care in 2001. Surprisingly, not many confirmation trials have been published so far. The randomised controlled trial by De La Rosa and colleagues is a timely and valuable attempt to repeat the landmark Leuven studies. The failure to replicate the beneficial effects of tight glycaemic control may boil down to some less obvious defaults in the set-up of the trial despite a seemingly adequate study design. The incorporation of ample power calculations and strict adherence to glucose targets are essential to fairly compare studies on tight blood glucose control. Only if these basic conditions of study design are fulfilled can the effectiveness of the therapy be assessed.


Cloning of the PABA peptide hydrolase alpha subunit (PPH alpha) from human small intestine and its expression in COS-1 cells.
PABA peptide hydrolase (PPH) from human enterocytes is comprised of two subunits, alpha and beta. PPH alpha is over 70% identical to meprin, a protease isolated from mouse and rat kidney. The enzyme shows a modular organization in that it contains an astacin protease domain, an adhesive domain, an EGF-like domain, an a putative C-terminal membrane spanning domain. Expression of a chimeric meprin-PPH alpha cDNA in COS-1 cells led to the synthesis of immature, transport-incompetent homodimers. In addition, complex glycosylated forms were detected in the culture medium, suggesting that the enzyme is secreted after proteolytic removal of the membrane anchor.


A Bis-heteroleptic Imidazolium-bipyridine Functionalized Iridium(III) Complex for Fluorescence Lifetime-based Recognition and Sensing of Phosphates.
A new IrIII based 3,3'-([2,2'-bipyridine]-5,5'-diylbis(methylene))bis(1-ethyl-1H-imidazol-3-ium) functionalized receptor Ir-1 has been synthesized for selective recognition, sensing and as a lifetime based sensor for H2 PO4 - and HP2 O7 3- in acetonitrile. An increase in the lifetime (τ) from 0.03543 μs to 0.2736 μs and 0.1323 μs in the presence of H2 PO4 - and HP2 O7 3- , respectively, among all other competitive anions establishes Ir-1 as a simple lifetime-based sensor. Furthermore, 13.7- and 8.5-fold enhancement in PL intensities of Ir-1 along with blue-shifting is seen with H2 PO4 - and HP2 O7 3- , respectively. High selectivity of Ir-1 for these two ions even in the presence of a large excess of other anions also displayed sensitive detection (LOD=0.035 μM for HP2 O7 3- and 0.040 μM for H2 PO4 - ). NMR data further suggest that the recognition of phosphates by Ir-1 is occurring through C-H⋅⋅⋅phosphate hydrogen bond (HB) interaction.


Sustained CD28 costimulation is required for self-renewal and differentiation of TCF-1+ PD-1+ CD8 T cells.
During persistent antigen stimulation, such as in chronic infections and cancer, CD8 T cells differentiate into a hypofunctional programmed death protein 1-positive (PD-1+) exhausted state. Exhausted CD8 T cell responses are maintained by precursors (Tpex) that express the transcription factor T cell factor 1 (TCF-1) and high levels of the costimulatory molecule CD28. Here, we demonstrate that sustained CD28 costimulation is required for maintenance of antiviral T cells during chronic infection. Low-level CD28 engagement preserved mitochondrial fitness and self-renewal of Tpex, whereas stronger CD28 signaling enhanced glycolysis and promoted Tpex differentiation into TCF-1neg exhausted CD8 T cells (Tex). Furthermore, enhanced differentiation by CD28 engagement did not reduce the Tpex pool. Together, these findings demonstrate that continuous CD28 engagement is needed to sustain PD-1+ CD8 T cells and suggest that increasing CD28 signaling promotes Tpex differentiation into more functional effector-like Tex, possibly without compromising long-term responses.


The dynamics and trophic ecology of grasshoppers (Acridoidea) in a South African savanna : Trophic ecology of grasshoppers in South African savanna.
1. A grasshopper population was monitored for three seasons in broad leaved savanna in South Africa. The biomass at corresponding times in successive seasons varied by up to a factor of four. Climatic factors may have been responsible. 2. The energetics of the grasshopper population are described for one year of intensive study. In this year a mean grasshopper biomass of 0.73 kg ha-1 ingested 94 kg ha-1 of plant material. In addition, 36 kg ha-1 was wasted in the course of feeding. Grasshoppers removed 16% of grass production, but this dropped to about 7% in the following year. 3. Production efficiency and ecological efficiency were lower than those measured for grasshoppers in other systems. Reasons are suggested. 4. Grasshopper diets were examined by epidermal analysis of crop fragments. All grasshopper species examined fed from a wide range of plant species, but diets could be grouped according to the physical characteristics of the food items. There was limited dietary overlap between the whole grasshopper population and large grazing mammals. 5. Vegetation structure is more significant than species composition as a determinant of habitat selection within the savanna type.


Prognosis in critically ill children requiring continuous renal replacement therapy.
We performed an observational prospective study in 53 critically ill children to analyze the prognostic factors of children requiring continuous renal replacement therapy. Pediatric index of mortality (PIM), pediatric risk of mortality score (PRISM), multi-organ failure score, serum lactate levels, blood pressure, vasoactive drugs, renal function and characteristics of renal replacement therapy were analyzed. The mortality was 32.1%, with multi-organ failure being the most frequent cause of death (59%). The children who died presented a significantly lower blood pressure and required more doses of vasoactive drugs, dopamine and epinephrine than did the survivors. The PRISM and PIM scores and the serum lactate levels and the number of organs suffering failure were significantly higher in the patients who died than in the survivors. However, the PRISM and PIM scores underestimated the risk of mortality. The age, sex, urea and creatinine levels, type of pump and volume of ultrafiltrate did not affect the prognosis. The association of a mean BP<55 mmHg and epinephrine dose >0.6 mug/kg/min was predictive of mortality in 76% of the patients. We conclude that the prognosis in children requiring renal replacement therapy depends on the severity of the clinical state at the time of starting therapy, principally on the hemodynamic situation.


Experimental study on the bioaccumulation of oxytetracycline and oxolinic acid by the blue mussel (Mytilus edulis). An evaluation of its ability to bio-monitor antibiotics in the marine environment.
The ability of blue mussel (Mytilus edulis) to act as a potential antibiotic bioindicator in marine waters was experimentally tested by the study of the kinetics of two veterinary antibiotics (oxolinic acid: OA and oxytetracycline: OTC). Antibiotic uptake was fast in the soft parts of the mussels. OA was quickly eliminated while OTC was released more slowly (half-life in viscera=3.9 days). OA and OTC were preferentially accumulated in gills and in viscera, respectively. Bio-accumulation factors were low (maximum: 2 for OTC in viscera) in accordance with the low K(ow)s. It was assumed that the higher OTC bioaccumulation pattern was related to its binding to mineral and organic compounds that led to its activity inhibition (62%). The antibiotics were persistent in shells (OTC half-life=8.3 days). Most veterinary and human antibiotics such as tetracyclines and sulphonamides have low log K(ow)(<2) and should weakly accumulate in mussel. This might limit the use of blue mussel to bio-monitor antibiotics in the marine environment.


Pertussis Pseudo-outbreak linked to specimens contaminated by Bordetella pertussis DNA From clinic surfaces.
We investigated a pertussis outbreak characterized by atypical cases, confirmed by polymerase chain reaction (PCR) alone at a single laboratory, which persisted despite high vaccine coverage and routine control measures. We aimed to determine whether Bordetella pertussis was the causative agent and advise on control interventions. We conducted case ascertainment, confirmatory testing for pertussis and other pathogens, and an assessment for possible sources of specimen contamination, including a survey of clinic practices, sampling clinics for B pertussis DNA, and review of laboratory quality indicators. Between November 28, 2008, and September 4, 2009, 125 cases were reported, of which 92 (74%) were PCR positive. Cases occurring after April 2009 (n = 79; 63%) had fewer classic pertussis symptoms (63% vs 98%; P < .01), smaller amounts of B pertussis DNA (mean PCR cycle threshold value: 40.9 vs 33.1; P < .01), and a greater proportion of PCR-positive results (34% vs 6%; P < .01). Cultures and serology for B pertussis were negative. Other common respiratory pathogens were detected. We identified factors that likely resulted in specimen contamination at the point of collection: environmentally present B pertussis DNA in clinics from vaccine, clinic standard specimen collection practices, use of liquid transport medium, and lack of clinically relevant PCR cutoffs. A summer pertussis pseudo-outbreak, multifactorial in cause, likely occurred. Recommendations beyond standard practice were made to providers on specimen collection and environmental cleaning, and to laboratories on standardizing PCR protocols and reporting results, to minimize false-positive results from contaminated clinical specimens.


Metabolic characterisation of a novel vanillylmandelate-degrading bacterium.
A newly isolated gram-negative bacterium, possibly Brevundimonas diminuta, utilised D,L-vanillylmandelate (D,L-VMA) as a sole carbon and energy source. The organism converted D,L-VMA to vanillylglyoxylate using a soluble NAD-dependent dehydrogenase specific for D-VMA and a dye-linked, membrane-associated L-VMA dehydrogenase. Vanillylglyoxylate was further metabolised by decarboxylation, dehydrogenation and demethylation to protocatechuate. A 4,5-dioxygenase cleaved protocatechuate to 2-hydroxy-4-carboxymuconic semialdehyde. Partially purified d-VMA dehydrogenase exhibited optimal activity at 30 degrees C and pH 9.5 and had an apparent Km for D-VMA of 470 microM. Although induced by several substituted mandelates, the enzyme had a narrow substrate specificity range with virtually no activity towards D-mandelate. Such properties render the enzyme of potential use in both diagnostic and biosynthetic applications.


Network motifs shape distinct functioning of Earth's moisture recycling hubs.
Earth's hydrological cycle critically depends on the atmospheric moisture flows connecting evaporation to precipitation. Here we convert a decade of reanalysis-based moisture simulations into a high-resolution global directed network of spatial moisture provisions. We reveal global and local network structures that offer a new view of the global hydrological cycle. We identify four terrestrial moisture recycling hubs: the Amazon Basin, the Congo Rainforest, South Asia and the Indonesian Archipelago. Network motifs reveal contrasting functioning of these regions, where the Amazon strongly relies on directed connections (feed-forward loops) for moisture redistribution and the other hubs on reciprocal moisture connections (zero loops and neighboring loops). We conclude that Earth's moisture recycling hubs are characterized by specific topologies shaping heterogeneous effects of land-use changes and climatic warming on precipitation patterns.


Evaluation of needling/microneedling as an adjunct to phototherapy in the treatment of stable acral vitiligo: a comparative clinical and immunohistochemical study.
To evaluate the efficacy and tolerability of needling/microneedling as an adjunct to NB-UVB phototherapy in the treatment of stable refractory patches of acral vitiligo, based upon clinical and immunohistochemical assessment of melanocyte count and distribution in response to needling/microneedling. Twenty patients with stable acral vitiligo (≥2 patches) were enrolled. One of the two index patches was randomized to receive needling or microneedling in conjunction with NB-UVB. Patients received phototherapy sessions 3 times weekly, while needling was carried out on biweekly basis for 6 months. Assessment was done clinically using point counting method, VESTA, and global patients' satisfaction, and immunohistochemically by quantitative assessment of melanocyte count by Melan-A. No statistically significant difference was observed between NB-UVB monotherapy and either of the combined therapy regimens as regards the mean percentage change in vitiligo surface area (p = .451), mean change in absolute melanocyte count from baseline (p = .589), and mean VESTA (p = .916). Patches subjected to adjuvant microneedling/needling were afflicted by koebnerization in 50% and 20% of cases, respectively. Neither microneedling nor needling appear to confer an added therapeutic value to NB-UVB phototherapy in the treatment of stable acral vitiligo. Moreover, both carry the risk of koebnerization.


Clinical predictors of diagnostic testing utility in the initial evaluation of chronic kidney disease.
No evidence-based approach to the evaluation of CKD has been established. We sought to identify clinical criteria to guide a rational diagnostic approach for the initial evaluation of CKD. We conducted a retrospective cohort study of 1487 patients presenting for initial evaluation of CKD over 3 years (1/2010-1/2013) to academic nephrology clinics. We utilized the electronic medical record to determine tests ordered, abnormal results and testing that affected diagnosis and/or management. Diagnostic and management yield of testing was defined as the percentage of tests that affected diagnosis and/or management. High yield for a given test was defined as an increased likelihood of the test affecting diagnosis and/or management. We identified clinical criteria predictive of high yield for paraprotein-related testing (one of the following: history of monoclonal disease, high risk of CKD progression, hypercalcemia or haemoglobin < 10.6), and clinical criteria predictive of high yield for glomerulonephritis testing (one of the following: abnormal urine sediment, 3+ or greater hematuria or proteinuria > 500 mg/gm). A prior history of hydronephrosis and renal artery stenosis was predictive of high yield of abnormal renal ultrasound. Higher yield of testing was associated with higher risk progression categories for ANA, SPEP, urine sediment, calcium, PTH, haemoglobin, iron and ferritin. We estimate that initial CKD evaluation costs range from $28 to $109 million/year in US-Medicare expenditure. Numerous tests without significant clinical utility are obtained in initial CKD evaluation. Identifying criteria that can guide diagnostic testing may lead to a more informed and cost-effective approach to evaluation.


Characterization of two full-length Araneus ventricosus major ampullate silk protein genes.
Major ampullate silk is noted for its great tensile strength and extensibility. The impressive material properties of major ampullate silk result from their component proteins that encoded by members of the spidroin (spider fibroin) gene family. Although the major ampullate spidroin type has evolved multiple variants within specific-species, most sequences are fragmented. Here, we present two complete major ampullate spidroin genes from the orb-weaving spider Araneus ventricosus. Due to the abundant GPG motifs in their repetitive region, the two MaSp genes were grouped in MaSp2 subclass and named MaSp2C and MaSp2D, respectively. Analysis of the full-length gene sequences reveals that both of them include a single enormous exon (10,851 bp for MaSp2C and 8640 bp for MaSp2D) that mainly translates into a central repetitive region containing multiple amino acid motifs that can be organized into five ensemble types. We use gene-specific PCR primers to search the cDNA from major ampullate glands and find evidence for alternative splicing of MaSp2D transcripts into a minor spliceoform lacking the entire repetitive domain as well as the partial terminal regions. Our results not only provide new templates for protein-based materials with tailored properties, but suggest gene and transcriptional diversity of major ampullate silk.


Factors associated with improvement in tibialis anterior weakness due to lumbar degenerative disease.
The weakness of the tibialis anterior remains to be a controversial topic. There has been no study that used electrophysiological assessment of the function of the lumbar and sacral peripheral motor nerves. The aim is to evaluate surgical outcomes in patients with weakness of the tibialis anterior using neurological and electrophysiological assessments. We enrolled 53 patients. Tibialis anterior weakness was quantified by muscle strength, as assessed using a manual muscle test on a scale of 1 through 5, with scores <5 indicating weakness. Postoperative improvement in muscle strength was classified as excellent (5 grades recovered), good (more than one grade recovered), or fair (less than one grade recovered). Surgical outcomes for tibialis anterior function were categorized as "excellent" in 31, "good" in 8, "fair" in 14 patients. Significant difference in outcomes were observed depending on diabetes mellitus status, type of surgery, and the compound muscle action potentials amplitudes of the abductor hallucis and extensor digitorum brevis (p < 0.05). Surgical outcomes were classified into two groups, patients with excellent and good outcomes (Group 1) and patients with fair outcome (Group 2). Using the forward selection stepwise method, sex and the compound muscle action potentials amplitudes of the extensor digitorum brevis were identified as significant factors for their positive association with Group 1 status. The diagnostic power of the predicted probability was as high as 0.87 in terms of area under curve of the receiver operating characteristic curve. There was a significant correlation between the prognosis of tibialis anterior weakness and sex and the compound muscle action potentials amplitude of extensor digitorum brevis, suggesting that recording the compound muscle action potentials amplitude of extensor digitorum brevis will aid the outcome assessment of future surgical interventions for tibialis anterior weakness.