Metallic radial head arthroplasty improves valgus stability of the elbow.
The stabilizing influence of radial head arthroplasty was studied in eight medial collateral ligament deficient anatomic specimen elbows. An elbow testing apparatus, which used computer controlled pneumatic actuators to apply tendon loading, was used to simulate active elbow flexion. The motion pathways of the elbow were measured using an electromagnetic tracking device, with the forearm in supination and pronation. As a measure of stability, the maximum varus to valgus laxity over the range of elbow flexion was determined from the difference between varus and valgus gravity loaded motion pathways. After transection of the medial collateral ligament, the radial head was excised and replaced with either a silicone or one of three metallic radial head prostheses. Medial collateral ligament transection caused a significant increase in the maximum varus to valgus laxity to 18.0 degrees +/- 3.2 degrees. After radial head excision, this laxity increased to 35.6 degrees +/- 10.3 degrees. The silicone implant conferred no increase in elbow stability, with a maximum varus to valgus laxity of 32.5 degrees +/- 15.5 degrees. All three metallic implants improved the valgus stability of the medial collateral ligament deficient elbow, providing stability similar to the intact radial head. The use of silicone arthroplasty to replace the radial head in the medial collateral ligament deficient elbow must be questioned. Metallic radial head arthroplasty provides improved valgus stability, approaching that of an intact radial head.


Genetic labelling of specific axonal pathways in the mouse central nervous system.
We report on transgenic mouse lines in which several sensory systems in the brain are specifically visualized genetically. We employed GAP-lacZ as an axon-targeted reporter protein that was constructed by fusing the membrane-anchoring domain of the GAP-43 protein to lacZ. The reporter gene was introduced into the genome under the control of a promoter element of Brn3b transcription factor to establish transgenic mouse lines. The individual lines thus generated afforded clear images of specific axonal pathways of the visual, vomeronasal, pontocerebellar, and auditory systems. The reporter protein labelled the entire axonal process as well as the cell body of developing and mature neurons on staining with X-gal. We show that these lines facilitate the developmental and anatomical study of these neural systems. This strategy should be applicable to a variety of neural systems by using various specific promoter elements.


Vestibular disorders in primary thrombocytosis.
Balance disturbances are some of the most common symptoms among the clinical manifestations of chronic myeloproliferative disorders (MPDs) with a high platelet count, such as essential thrombocythaemia (ET) and polycythaemia vera (PV). In this study, we evaluated the vestibulo-oculomotor and vestibulospinal reflexes in a group of patients suffering from these diseases. Evaluation of balance disturbances. Department of Neurosciences, ENT Unit, University of Pisa, Italy. In this study, we evaluated 43 patients suffering from ET and PV who underwent otoneurologic examination, based on a study of the vestibulo-oculomotor and vestibulospinal reflexes. There was exclusive central vestibular involvement in 26 cases (60.4%), peripheral and central signs were associated in 8 cases (18.6%), and the involvement was purely peripheral in 1 patient. In six patients (14%), the otoneurologic examination revealed no alterations. The high percentage of balance disorders in cases of ET and PV probably depends upon disorders of the microcirculation due to platelet dysfunction. We also postulate a full explanation of the involvement of the central vestibular system on the basis of a greater availability of central activated serotonin acting as neuromediator.


Mouse mammary tumor virus (MMTV) - like exogenous sequences are associated with sporadic but not hereditary human breast carcinoma.
The inheritance of mutated suppressor genes, such as BRCA1 and BRCA2, is acknowledged as an etiological factor in hereditary breast carcinoma (HBC). Two different molecular mechanisms are possible; the Knudson's "two hits" or the gene haploinsufficiency. Etiology of sporadic breast carcinoma (SBC) is not known, although data support the possible role of the betaretrovirus Mouse Mammary Tumor Virus (MMTV). This study analyzes the presence of MMTV exogenous sequences in two representative groups of HBC and SBC, excluding any contamination by murine and retroviral material and endogenous betaretroviruses. The 30.3% of 56 SBC contained MMTV sequences, against the 4.2% of 47 HBC (p < 0.001). Cases positive for viral sequences showed the presence of p14, signal peptide of the MMTV envelope precursor. This result was expected based on the fact that HBCs, having a specific genetic etiology, do not need the action of a carcinogenetic viral agent. Moreover, the striking results obtained by comparing two groups of vastly different tumors represent an additional element of quality control: the distinction between HBC and SBC is so well-defined that results cannot be ascribed to mere coincidence. This paper strengthens the hypothesis for a viral etiology for human sporadic breast carcinoma.


[Follicular and mantle cell lymphoma diagnosed in biopsies of gastroenterocolic region].
The authors present a retrospective analysis of follicular lymphomas (FL) and mantle cell lymphomas (MCL) diagnosed according to the WHO classification (2008) in consecutive biopsies of GI organs in a period of 11 years. The series includes 18 patients with FL verified in 22 biopsies and 44 patients with MCL diagnosed in 54 biopsies. FL represented always a solitary tumor, most often - up to ¾ of all the cases - of a small intestine, more often in its jejunoileal than duodenal parts. The biopsies were obtained almost equally by endoscopical approach, they were usually mucosal and rarely polypectomic, as well as by surgical resections (54,5 % and 45,5 % of the cases respectively). FL of grade 3 was identified in approximately 11 % of the cases, while majority of the patients showed FL of grade 1 or 2. Only 2 patients with duodenal FL relapsed and bioptically verified recidives did not show signs of a high grade transformation. Although it was difficult to identify a nodular growth pattern in more common small biopsies, a typical histomorphology and phenotype mostly allowed the FL diagnosis in the majority of the cases. The FL diagnosis had to be supported by detection of BCL2 translocation only in one case. MCL appeared most often in the stomach and large intestine, the small intestinal cases represented less than 23 %. In ¼ of the patients the lymphoma was multifocal and manifested as lymphomatoid polyposis affecting most often both large and small intestine. In a majority of the MCL patients, the diagnosis was done in mucosal and polypectomic endoscopic biopsies, surgical intervention and resection was recorded in less than 10 % of the cases. Most of the patients showed conventional "centrocytic" MCL morphology and approximately ¼ of the cases showed blastoid MCL. The rebiopsies of 9 patients revealed a relaps of the disease which was locoidentical in 5 of them; in other 4 patients the biopsies documented a dissemination to other GI organs. The blastic transformation was recognized only in one of the relapsing patients. In contrast to FL, in 18 % of the biopsies the MCL diagnosis required a CCND1 gene rearrangement detection by FISH. In summary both of the studied GI lymphomas showed different and heterogenous incidence, clinical manifestation and necessity to support the biopsy diagnosis also by FISH examination. The correct FL and MCL diagnosis represents a conditio sine qua non for an indication of different therapeutical modalities as well as for the prognostic stratification of the patients.


Shallow Sparsely-Connected Autoencoders for Gene Set Projection.
When analyzing biological data, it can be helpful to consider gene sets, or predefined groups of biologically related genes. Methods exist for identifying gene sets that are differential between conditions, but large public datasets from consortium projects and single-cell RNA-Sequencing have opened the door for gene set analysis using more sophisticated machine learning techniques, such as autoencoders and variational autoencoders. We present shallow sparsely-connected autoencoders (SSCAs) and variational autoencoders (SSCVAs) as tools for projecting gene-level data onto gene sets. We tested these approaches on single-cell RNA-Sequencing data from blood cells and on RNA-Sequencing data from breast cancer patients. Both SSCA and SSCVA can recover known biological features from these datasets and the SSCVA method often outperforms SSCA (and six existing gene set scoring algorithms) on classification and prediction tasks.


Vertebral Trabecular Bone Mechanical Properties Vary Among Functional Groups of Cetaceans.
Since their appearance in the fossil record 34 million years ago, modern cetaceans (dolphins, whales, and porpoises) have radiated into diverse habitats circumglobally, developing vast phenotypic variations among species. Traits such as skeletal morphology and ecologically linked behaviors denote swimming activity; trade-offs in flexibility and rigidity along the vertebral column determine patterns of caudal oscillation. Here, we categorized 10 species of cetaceans (families Delphinidae and Kogiidae; N = 21 animals) into functional groups based on vertebral centra morphology, swimming speeds, diving behavior, and inferred swimming patterns. We quantified trabecular bone mechanical properties (yield strength, apparent stiffness, and resilience) among functional groups and regions of the vertebral column (thoracic, lumbar, and caudal). We extracted 6 mm3 samples from vertebral bodies and tested them in compression in 3 orientations (rostrocaudal, dorsoventral, and mediolateral) at 2 mm min-1. Overall, bone from the pre-fluke/fluke boundary had the greatest yield strength and resilience, indicating that the greatest forces are translated to the tail during caudal oscillatory swimming. Group 1, composed of 5 shallow-diving delphinid species, had the greatest vertebral trabecular bone yield strength, apparent stiffness, and resilience of all functional groups. Conversely, Group 3, composed of 2 deep-diving kogiid species, had the least strong, stiff, and resilient bone, while Group 2 (3 deep-diving delphinid species) exhibited intermediate values. These data suggest that species that incorporate prolonged glides during deep descents in the water column actively swim less, and place relatively smaller loads on their vertebral columns, compared with species that execute shallower dives. We found that cetacean vertebral trabecular bone properties differed from the properties of terrestrial mammals; for every given bone strength, cetacean bone was less stiff by comparison. This relative lack of material rigidity within vertebral bone may be attributed to the non-weight-bearing locomotor modes of fully aquatic mammals.


The Unique Properties of Placental Mesenchymal Stromal Cells: A Novel Source of Therapy for Congenital and Acquired Spinal Cord Injury.
Spinal cord injury (SCI) is a devasting condition with no reliable treatment. Spina bifida is the most common cause of congenital SCI. Cell-based therapies using mesenchymal stem/stromal cells (MSCS) have been largely utilized in SCI. Several clinical trials for acquired SCI use adult tissue-derived MSC sources, including bone-marrow, adipose, and umbilical cord tissues. The first stem/stromal cell clinical trial for spina bifida is currently underway (NCT04652908). The trial uses early gestational placental-derived mesenchymal stem/stromal cells (PMSCs) during the fetal repair of myelomeningocele. PMSCs have been shown to exhibit unique neuroprotective, angiogenic, and antioxidant properties, all which are promising applications for SCI. This review will summarize the unique properties and current applications of PMSCs and discuss their therapeutic role for acquired SCI.


Mitochondrial translation factors reflect coordination between organelles and cytoplasmic translation via mTOR signaling: Implication in disease.
Mitochondria are semi-autonomous organelle possessing their own translation machinery to biosynthesize mitochondrial DNA (mtDNA)-encoded polypeptides, which are the core subunits of oxidative phosphorylation (OXPHOS) complexes. Mitochondrial translation elongation factor 4 (mtEF4) is a key quality control factor in mitochondrial translation (mt-translation) that regulates mitochondrial tRNA translocation and modulates cellular responses by influencing cytoplasmic translation (ct-translation). In addition to mtEF4, mt-translational activators, mitochondrial microRNAs (mitomiRs), and MITRAC have been reported recently as crucial mt-translation regulators. Here, we focus on the novel ways how these factors regulate mt-translation, discuss the main cellular response of mammalian target of rapamycin (mTOR) signalling upon mt-translation defects, and summarize the related human diseases.


Endobronchial granulocytic sarcoma causing acute respiratory failure in acute myelogenous leukemia.
Infiltration by leukemic cells may occur in many organs. When localized masses caused by myeloid leukemic infiltration occur, they are called granulocytic sarcomas. Such tumors may be mistaken for primary carcinomas. In this report, we describe a 63-yr-old man with acute myelogenous leukemia who developed progressive atelectasis of the left lower lobe of the lung. Bronchoscopy revealed a fungating endobronchial tumor completely obstructing the left lower lobe bronchus and partially occluding the left upper lobe bronchus. Biopsies from this lesion showed an endobronchial granulocytic sarcoma. Despite chemotherapy, the patient developed progressive hypoxemia and died.


Emerging Approaches for Solid Tumor Treatment Using CAR-T Cell Therapy.
Cancer immunotherapy is becoming more important in the clinical setting, especially for cancers resistant to conventional chemotherapy, including targeted therapy. Chimeric antigen receptor (CAR)-T cell therapy, which uses patient's autologous T cells, combined with engineered T cell receptors, has shown remarkable results, with five US Food and Drug Administration (FDA) approvals to date. CAR-T cells have been very effective in hematologic malignancies, such as diffuse large B cell lymphoma (DLBCL), B cell acute lymphoblastic leukemia (B-ALL), and multiple myeloma (MM); however, its effectiveness in treating solid tumors has not been evaluated clearly. Therefore, many studies and clinical investigations are emerging to improve the CAR-T cell efficacy in solid tumors. The novel therapeutic approaches include modifying CARs in multiple ways or developing a combination therapy with immune checkpoint inhibitors and chemotherapies. In this review, we focus on the challenges and recent advancements in CAR-T cell therapy for solid tumors.


A method for radiographic evaluation of pedicle screw violation of the vertebral endplate. Technique.
This study evaluated the utility of intraoperative radiographs for minimizing the risk of pedicle screw tip violation of the superior vertebral endplate. An intraoperative radiographic technique is demonstrated that ensures that a screw has not penetrated the intervertebral disk. Although methods to avoid penetration of the medial pedicle cortex and the anterior body cortex have been described, no study has discussed screw penetration of the superior endplate and disc. Pedicle screws were inserted into 11 cadaveric lumbar spines, randomly, with the tip interior to the endplate, at the endplate, and through the endplate. Radiographs were evaluated to measure the penetration, if any, of the screws. Spine segments were dissected and evaluated anatomically. The anatomic and radiographic results were then compared. The overall error rate for radiographs was 22/312 (7%). Oblique radiographs gave a much higher error rate. A true lateral or anteroposterior radiographic view of the vertebra provides a high degree of certainty that the screw has not crossed the endplate when a "safe zone" of 3 mm remains superior to the screw tip. Intraoperative radiography can reduce concern about violation of the superior vertebral endplate.


The relationship between low maternal serum vitamin D levels and glycemic control in gestational diabetes assessed by HbA1c levels: an observational cross-sectional study.
A great association between vitamin D deficiency and type 2 diabetes mellitus has been suggested in literature. During pregnancy, this deficiency is even more critical. It appears that vitamin D insufficiency during pregnancy may be associated with maternal hazards. The aim of this study was to assess the relation between the levels of 25-hydroxy-cholecalciferol (vitamin D), and the glycemic control in pregnant women. An observational cross-section study including 160 pregnant women between 20-40 years in age, in their third trimester, divided into two equal groups. First group consisted of 80 women with established diagnosis of gestational diabetes and the second group with proved normal blood glucose levels. We assessed vitamin D in serum, fasting blood glucose, serum insulin and glycosylated hemoglobin (HbA1c) levels and we depicted the insulin sensitivity using the Quantitative insulin sensitivity check index (Quicki). The results were collected and statistically correlated. The mean vitamin D levels were 46.61 ± 6.087 and 47.25 ± 10.181in controls and women with gestational diabetes mellitus (GDM) respectively. The fasting insulin levels were significantly higher in the group with GDM with a mean of 18.51 ± 6.44 compared to 8.95 ± 2.52 in the control group.The correlation coefficient (r) between HbA1c levels and Vitamin D level was -0.492 with a P value <0.05. Similar associations were also found with the fasting blood sugar levels (r = -0.386) and with Quicki values (r = -0.250). Vitamin D levels correlated significantly with the fasting blood glucose, the fasting serum insulin and the HbA1c levels, the P value in all these correlations were <0.05. The P value with Quicki results was 0.064. There is a statistically significant negative correlation between the glycemic control and vitamin D levels in serum in the whole study population. The effect of adequate vitamin D replacement on glycemic control was not studied in our work correlation. We suggest larger scale studies addressing this issue.


Cord-Based Microfluidic Chips as A Platform for ELISA and Glucose Assays.
This paper describes the development and application of microfluidic cord-based analytical devices (µCADs) in two enzyme-linked immunosorbent assays (ELISAs) and glucose assay. In this study, biotinylated goat anti-mouse immunoglobulin (IgG) antibody, rabbit IgG antibody, and glucose are quantitatively detected. In the ELISA systems, the antibody is spotted on the cord at the detection site and a series of washes, followed by streptavidin-alkaline phosphatase (Strep-ALP) or alkaline phosphatase (ALP)-conjugated secondary antibody and colorimetric substrate, completing the experiment. The devices are subsequently scanned and analyzed yielding a correlation between inverse yellow or inverse blue intensity and antibody concentration. For the first ELISA, a linear range of detection was observed at lower concentrations (2.50 × 10-4-1.75 × 10-3 mg/mL) of Strep-ALP with saturation of the enzyme achieved at higher concentrations (>2.50 × 10-4). For the second ELISA, the L50 was demonstrated to be 167.6 fmol/zone. The glucose assay consisted of spotting increasing concentrations of glucose on the analysis sites and transporting, via capillary action, a solution containing glucose oxidase (GOx), horseradish peroxidase (HRP), and potassium iodide (KI) to the detection sites realizing a yellow-brown color indicating oxidation of iodide to iodine. The device was then dried, scanned, and analyzed to show the correlation between yellow inverse intensity and glucose. Glucose in artificial urine showed good correlation using the devices.


Phenylketonuria: practical dietary management.
Phenylketonuria (PKU) is an autosomal recessively inherited disorder which prevents the normal metabolism of protein foods. Phenylalanine builds up in the blood and if untreated will cause mental retardation. PKU is treatable by a low-phenylalanine diet for life. The prognosis is good provided the condition is diagnosed within the first two weeks of life and dietary treatment started promptly. Special low-phenylalanine formulae and foods are available on prescription in the UK. Supervision by a dietitian and regular monitoring of phenylalanine levels in the blood are essential. The health visitor and school nurse have an important part to play during the school years in supporting the family. Midwives also play an important part in ensuring that women with PKU adhere to a strict low-phenylalanine diet around the time of conception and during pregnancy. They also take blood samples from all newborn babies to be tested for PKU.


Therapeutic Potential of Platelet-Rich Plasma in Canine Medicine.
Platelets are the reservoir of growth factors and play a major role in several physiological processes, such as coagulation, angiogenesis, immune response, and tissue repair. Platelet concentrates are broadly classified into two groups depending on their fibrin content, namely platelet-rich plasma (PRP) and platelet-rich fibrin (PRF). They are further divided based on their leucocyte contents. The PRP is plasma containing supra-physiological concentrations of the platelets. The growth factors present in the PRP play a crucial role in the promotion of local angiogenesis, regulation of cellular activity, stem cell homing, proliferation and differentiation of different stem cells, and deposition of matrix proteins contributing to tissue regeneration. This review aimed to establish the therapeutic potential of PRP in canine medicine with a particular focus on the applications in ophthalmology, dermatology, and musculoskeletal disorders. A systematic literature review was performed to identify the literature published during the past 20 years (2001-2021) using authentic academic databases, such as PubMed, Science Direct, Google Scholar, and Scopus. In the initial search, 556 articles were identified and based on the specific inclusion and exclusion criteria, 59 articles were selected for further analysis. The clinical efficacy of PRP depends on the number of platelets and the growth factor concentration. The PRP-based biological therapy has broad clinical applications in musculoskeletal pathologies. It is a simple, safe, and cost-effective method that can be used to treat various diseases and disorders in canine practice. For example, PRP is used for managing corneal ulcers, corneal erosion, alkali burn, keratoconjunctivitis sicca, burn wounds, chronic wounds, cutaneous ulcers, acute traumatic bone fractures, tendinopathies, cartilage pathologies, osteoarthritis, and abdominal wall defects either as monotherapy or as an adjunctive therapeutic agent. In addition, PRP is widely used as a carrier of mesenchymal stem cells for transplanting into bone defects. Therefore, allogeneic PRP therapy can be considered a simple, safe, and cost-effective method for the treatment of various diseases and disorders in canine practice. The therapeutic application of PRP in canine medicine is limited in the present study due to the lack of consensus for collection, characterization, and clinical use. Hence, further studies are required to establish the actual worth of PRP-based regenerative strategies in canine medicine.


Peptic ulceration in Crohn's disease (reional enteritis).
The incidence of peptic ulceration in a personal series of 300 patients with Crohn's disease was 8%. Resection of 60 or more centimetres of the small intestine was associated with significantly increased acid output, both basally and following pentagastrin stimulation. Only five (4%) of the 124 patients who received steroid steroid therapy developed peptic ulceration. It is suggested that resection of the distal small bowel may be a factor in the probable increase of peptic ulceration in Crohn's disease.


BioSin UFMG Club: Engaging a multilevel and multidisciplinary community in synthetic biology.
Learning synthetic biology is often seen as a far distant possibility, restricted to those who have the privilege of an academic career. We propose a student-centered discussion group around synthetic biology, aimed at people from high school onwards with different backgrounds to interact and learn about synthetic biology. We developed a 14-week long program with three modules: "Leveling," "Introducing," and "Discussion." By completing the first two modules, the members should be more comfortable with biological names, structures, concepts, and techniques. The modules developed are available in Portuguese, Spanish, and English via the Open Lab Idea Real website (https://ideareal.org/clube-de-biologia-sintetica/) and can be used to implement the Club either in place or virtually around the world. We put it to practice at Universidade Federal de Minas Gerais (UFMG) creating the Club named BioSin. There are programs such as the International Genetically Engineered Machine (iGEM) competition focused on disseminating synthetic biology. Although iGEM is one fantastic way of learning about synthetic biology, there is a high cost. Because of that, a study and discussion Club is a tool to spread knowledge and engage with the study area.


Metaoptronic Multiplexed Interface for Probing Bioentity Behaviors.
Biointerface sensors have brought about remarkable advances in modern biomedicine. To accurately monitor bioentity's behaviors, biointerface sensors need to capture three main types of information, which are the electric, spectroscopic, and morphologic signals. Simultaneously obtaining these three types of information is of critical importance in the development of future biosensor, which is still not possible in the existing biosensors. Herein, by synergizing metamaterials, optical, and electronic sensing designs, we proposed the metaoptronic multiplexed interface (MMI) and built a MMI biosensor which can collectively record electric, spectroscopic, and morphologic information on bioentities. The MMI biosensor enables the real-time triple-monitoring of cellular dynamics and opens up the possibility for powerlessly monitoring ocular dryness. Our findings not only demonstrate an advanced multiplexed biointerface sensor with integrated capacities but also help to identify a uniquely significant arena for the nanomaterials, meta-optics, and nanotechnologies to play their roles in a complementary manner.


Infants' sensitivity to shape changes in 2D visual forms.
Research in developmental cognitive science reveals that human infants perceive shape changes in 2D visual forms that are repeatedly presented over long durations. Nevertheless, infants' sensitivity to shape under the brief conditions of natural viewing has been little studied. Three experiments tested for this sensitivity by presenting 128 seven-month-old infants with shapes for the briefer durations under which they might see them in dynamic scenes. The experiments probed infants' sensitivity to two fundamental geometric properties of scale- and orientation-invariant shape: relative length and angle. Infants detected shape changes in closed figures, which presented changes in both geometric properties. Infants also detected shape changes in open figures differing in angle when figures were presented at limited orientations. In contrast, when open figures were presented at unlimited orientations, infants detected changes in relative length but not in angle. The present research therefore suggests that, as infants look around at the cluttered and changing visual world, relative length is the primary geometric property by which they perceive scale- and orientation-invariant shape.


Occurrence of succinyl derivatives in the catabolism of arginine in Pseudomonas cepacia.
Pseudomonas cepacia NCTC 10743 utilizes arginine as the sole source of carbon and nitrogen for growth. Arginine is degraded to glutamate via succinyl derivatives. The catabolic sequence in this pathway is L-arginine----N2-succinylarginine----N2-succinylornithine--- -N2-succinylglutamate semialdehyde----N2-succinylglutamate----glutamate + succinate. The formation of the enzymes responsible for arginine degradation is regulated not only by induction but also by both carbon and nitrogen catabolite repression.


Doppler sonographic confirmation of thalamic and basal ganglia vasculopathy in three infants with trisomy 13.
A prospective review of 1746 head sonographic examinations performed from July 1993 to December 1995 revealed three scans that demonstrated a linear, branching echogenic pattern within the thalamus or basal ganglia. All three of these patients had trisomy 13. This finding has been described previously and is presumed to be of vascular causation. Doppler evaluation of the thalamus and basal ganglia in our three cases confirmed the vascular nature of the echogenic, branching pattern.


Function and Regulation of microRNA171 in Plant Stem Cell Homeostasis and Developmental Programing.
MicroRNA171 (miR171), a group of 21-nucleotide single-strand small RNAs, is one ancient and conserved microRNA family in land plants. This review focuses on the recent progress in understanding the role of miR171 in plant stem cell homeostasis and developmental patterning, and the regulation of miR171 by developmental cues and environmental signals. Specifically, miR171 regulates shoot meristem activity and phase transition through repressing the HAIRYMERISTEM (HAM) family genes. In the model species Arabidopsis, miR171 serves as a short-range mobile signal, which initiates in the epidermal layer of shoot meristems and moves downwards within a limited distance, to pattern the apical-basal polarity of gene expression and drive stem cell dynamics. miR171 levels are regulated by light and various abiotic stresses, suggesting miR171 may serve as a linkage between environmental factors and cell fate decisions. Furthermore, miR171 family members also demonstrate both conserved and lineage-specific functions in land plants, which are summarized and discussed here.


The efficacy and safety of fire needle therapy for COVID-19: Protocol for a systematic review and meta-analysis.
Coronavirus disease 2019 (COVID-19), a new type of coronavirus, first reported in Wuhan, China at the end of December 2019. As a result of the worldwide outbreak, the number of patients continues to increase. With multiple therapeutic interventions, more and more patients are recovering. Fire needle is used as an alternative therapy. At present, there are no relevant articles for systematic review and meta-analysis, so this study will evaluate the efficacy and safety of fire needle in the treatment of COVID-19 pneumonia. The following electronic bibliographic databases will be searched to identify relevant studies from December 2019 to December 2020: MEDLINE, PubMed, Embase, Cochrane library, Web of Science, China National Knowledge Infrastructure (CNKI), Chinese Technical Periodicals (VIP), Wan-fang data, Chinese Biological Medicine Database (CBM), and other databases. All included articles were randomized controlled trial without any language restrictions. Two reviewers will independently conduct cations retrieval, de-duplication, filtering, quality assessment, and data analysis by the Review Manager (V.5.3). Meta-analysis, subgroup analysis and/or descriptive analysis were performed on the included data. This study will investigate the application of fire needle in the treatment or prevention of COVID-19, and provide a high-quality synthesis to evaluate whether fire needle is an effective and safe intervention for COVID-19. PROSPERO registration number: CRD 42020193703.


The neo-adjuvant treatment in gastrointestinal stromal tumor.
Gastrointestinal Stromal Tumor (GIST) is a rare intra-abdominal tumor, characterized by a specific histological and immunohistochemical pattern. These tumors affect with higher frequency stomach and small bowel and occur at a median age of 60 years with a slight male predominance. An early stage of GIST often don't cause any symptoms, so most GISTs are diagnosed in later stages of the disease. We report a case of GIST diagnosed only with clinical data and positron emission tomography (PET). We demonstrate the usefulness of neoadjuvant treatment with Imatinib mesylate, a newly developed tyrosine kinase receptor inhibitor. The neoadjuvant treatment with Imatinib reduced the mass size and vascularization, making possible a surgical approach.


Solidarity: an innovative perspective in the management and organization of Sanitary Surveillance actions.
This is a theoretical essay about the development of the concept of solidarity, a word used in the regulatory framework and in political proposals to reorient the Brazilian Unified Health System (SUS). The methodology consisted of mapping authors addressing human action aspects related to this theme from Durkheim's tradition, linking them to his followers, like Marcel Mauss and authors from the "anti-utilitarianism" movement in social sciences. Solidarity is one way to express a "gift" and appears as a multidimensional action, where duty and freedom, instrumental interest and disinterest interpose and interlace. The planning and execution of sanitary surveillance (VISA) actions requires comprehension of organizational forms and solidary relationship management among agents involved in health risk control, transcending the strongly normative aspect of the prevailing supervision actions. The development of associative actions involving sanitary surveillance professionals, economic agents and consumers, aiming to share the responsibilities in the health risk control of products, services and environments subjected to Sanitary Surveillance action is suggested.


Double-helical character of ribonucleic acid from virus-like particles found in Penicillium chrysogenum.
1. RNA was isolated from virus-like particles found in Penicillium chrysogenum and resolved into two fractions by gel filtration through agarose columns. 2. Fraction 1 was excluded and had the following properties: 50.9% G+C [AMP 0.246, UMP 0.246, CMP 0.252, GMP 0.255 (mole fraction)]; mol.wt. about 1.2x10(6) daltons; s(20,w) 12.3S and ;melting' temperature about 100 degrees C (solvent 0.15m-sodium chloride-0.015m-sodium citrate pH7.2); optical rotation [alpha](max.) 6000 degrees at 278nm; circular dichroism (epsilon(L)-epsilon(R))(max.)=8.181mol(-1) cm(-1) at 260nm. 3. Properties of fraction 2 include 37.8% G+C [AMP 0.313, UMP 0.312, CMP 0.186, GMP 0.189 (mole fraction)]; mol.wt. about 140000 daltons; s(20,w) 7.3S, T(m) about 85 degrees C (solvent 0.15m-sodium chloride-0.015m-sodium citrate, pH7.2); optical rotation [alpha](max.) 6000 degrees at 278nm; circular dichroism (epsilon(L)-epsilon(R))(max.)=8.241mol(-1) cm(-1) at 260nm. 4. The properties of both fractions were consistent with a double-helical conformation.


miR-143 inhibits cell proliferation by targeting autophagy-related 2B in non-small cell lung cancer H1299 cells.
microRNAs (miRNAs) are small, non‑coding RNAs involved in multiple biological pathways by regulating post-transcriptional gene expression. Previously, autophagy has been reported to suppress the progression of non-small cell lung cancer (NSCLC). However, how miRNAs regulate autophagy in NSCLC remains to be elucidated. In the present study, the autophagy gene, autophagy-related 2B (ATG2B), was identified as a novel target of miR-143. The overexpression of miR-143 was able to downregulate the expression of atg2b at the transcriptional and translational levels by direct binding to its 3' untranslated region. Cell proliferation was significantly inhibited by the ectopic expression of miR-143 in H1299 cells. Knockdown of ATG2B resulted in a similar phenotype, with the overexpression of miR-143 in NSCLC cells. Furthermore, knockdown of ATG2B and hexokinase 2, a key enzyme in glycolysis and another target of miR-143, co-ordinated to inhibit the proliferation of H1299 cells. The results of the present study demonstrated that miR-143 was a novel and important regulator of autophagy by targeting ATG2B and repression of gene expression in autophagy and high glycolysis had a coordinate effect in H1299 cells. These results suggested that ATG2B may be a new potential therapeutic target for NSCLC. Furthermore, it was implied that interrupting autophagy and glycolysis improves NSCLC therapy.


Disease knowledge, medical experience, health-related quality of life and health-care costs among patients with advanced colorectal cancer in China: protocol for a nationwide multicentre survey.
Colorectal cancer (CRC) is one of the most common cancers in China. Most patients have developed advanced stage at diagnosis, leading to a low 5-year survival rate. To optimise prevention strategies, we planned a survey to evaluate the disease knowledge, medical experience and health-related quality of life (HRQOL) before and after the treatment of CRC, and healthcare costs among patients with advanced CRC in China. This is a nationwide, hospital-based, multicentre survey. Nineteen hospitals in seven cities were selected by multistage stratified sampling. Mainland China is divided into seven regions according to the traditional administrative district definition; two cities of each region were selected through simple random sampling, and then one tertiary cancer hospital and one general hospital were selected for each city. More than 4445 patients with CRC in the selected hospitals with stage III or IV will be enrolled in this study. The trained interviewers will collect information through patients' self-report and/or medical records, including demographics and medical history; knowledge about CRC high-risk factors, screening procedure and treatment methods; medical experience on CRC screening, diagnosis and treatment; HRQOL before and after CRC treatment; and costs of CRC. All data will be input by two independent staff and verified using Epidata V.3.1 software. Data validation plan will be made to guide data checking. All statistical analyses will be conducted using SAS V.9.4 and SPSS V.24.0 software. The study was approved by the ethics committees of Henan Cancer Hospital, the leading participant hospital. Findings of this study will be disseminated through peer-reviewed open-access journals and presented as posters and/or oral sections in national and international conferences. Results will also be popularised to the public via media or the internet.


Isolation of Candida tropicalis auxotrophic mutants.
An enrichment scheme using nystatin was designed for the isolation of auxotrophic mutants from the diploid-alkane-utilizing yeast Candida tropicalis. A collection of 194 auxotrophs representing 7 phenotypes was isolated. One class of mutants was identified as having a defect in histidinol dehydrogenase activity and a second class of mutants was identified as having a defect in orotidine monophosphate decarboxylase activity. These strains are good candidates to be carrying mutations corresponding to the HIS4 and URA3 genes of Saccharomyces cerevisiae.


Prediction of the moments in advection-diffusion lattice Boltzmann method. II. Attenuation of the boundary layers via double-Λ bounce-back flux scheme.
Impact of the unphysical tangential advective-diffusion constraint of the bounce-back (BB) reflection on the impermeable solid surface is examined for the first four moments of concentration. Despite the number of recent improvements for the Neumann condition in the lattice Boltzmann method-advection-diffusion equation, the BB rule remains the only known local mass-conserving no-flux condition suitable for staircase porous geometry. We examine the closure relation of the BB rule in straight channel and cylindrical capillary analytically, and show that it excites the Knudsen-type boundary layers in the nonequilibrium solution for full-weight equilibrium stencil. Although the d2Q5 and d3Q7 coordinate schemes are sufficient for the modeling of isotropic diffusion, the full-weight stencils are appealing for their advanced stability, isotropy, anisotropy and anti-numerical-diffusion ability. The boundary layers are not covered by the Chapman-Enskog expansion around the expected equilibrium, but they accommodate the Chapman-Enskog expansion in the bulk with the closure relation of the bounce-back rule. We show that the induced boundary layers introduce first-order errors in two primary transport properties, namely, mean velocity (first moment) and molecular diffusion coefficient (second moment). As a side effect, the Taylor-dispersion coefficient (second moment), skewness (third moment), and kurtosis (fourth moment) deviate from their physical values and predictions of the fourth-order Chapman-Enskog analysis, even though the kurtosis error in pure diffusion does not depend on grid resolution. In two- and three-dimensional grid-aligned channels and open-tubular conduits, the errors of velocity and diffusion are proportional to the diagonal weight values of the corresponding equilibrium terms. The d2Q5 and d3Q7 schemes do not suffer from this deficiency in grid-aligned geometries but they cannot avoid it if the boundaries are not parallel to the coordinate lines. In order to vanish or attenuate the disparity of the modeled transport coefficients with the equilibrium weights without any modification of the BB rule, we propose to use the two-relaxation-times collision operator with free-tunable product of two eigenfunctions Λ. Two different values Λ_{v} and Λ_{b} are assigned for bulk and boundary nodes, respectively. The rationale behind this is that Λ_{v} is adjustable for stability, accuracy, or other purposes, while the corresponding Λ_{b}(Λ_{v}) controls the primary accommodation effects. Two distinguished but similar functional relations Λ_{b}(Λ_{v}) are constructed analytically: they preserve advection velocity in parabolic profile, exactly in the two-dimensional channel and very accurately in a three-dimensional cylindrical capillary. For any velocity-weight stencil, the (local) double-Λ BB scheme produces quasi-identical solutions with the (nonlocal) specular-forward reflection for first four moments in a channel. In a capillary, this strategy allows for the accurate modeling of the Taylor-dispersion and non-Gaussian effects. As illustrative example, it is shown that in the flow around a circular obstacle, the double-Λ scheme may also vanish the dependency of mean velocity on the velocity weight; the required value for Λ_{b}(Λ_{v}) can be identified in a few bisection iterations in given geometry. A positive solution for Λ_{b}(Λ_{v}) may not exist in pure diffusion, but a sufficiently small value of Λ_{b} significantly reduces the disparity in diffusion coefficient with the mass weight in ducts and in the presence of rectangular obstacles. Although Λ_{b} also controls the effective position of straight or curved boundaries, the double-Λ scheme deals with the lower-order effects. Its idea and construction may help understanding and amelioration of the anomalous, zero- and first-order behavior of the macroscopic solution in the presence of the bulk and boundary or interface discontinuities, commonly found in multiphase flow and heterogeneous transport.


Dynamic Kinetic Resolution of α-Trifluoromethyl Hemiaminals without α-Hydrogen via NHC-Catalyzed O-Acylation.
Following the well-recognized dynamic kinetic resolution (DKR) of hemiaminals with α-hydrogen under lipase and chiral DMAP catalysis, the unprecedented DKR of hemiaminals without α-hydrogen was developed via N-heterocyclic carbene catalyzed O-acylation of 3-hydroxy-3-trifluoromethylbenzosultams. The racemic hemiaminals without α-hydrogen were effectively racemized and differentiated by chiral NHCs under basic conditions. The resulting esters were obtained in high yields with good to high enantioselectivities.


[Disorders with elevated immunoglobulin E levels].
Immunoglobulin E (IgE) was first described in 1967. It has the lowest serum concentration of all circulating immunoglobulin isotypes. Serum IgE concentration at birth is low and rises until the age of 10-15 years. The increment of serum IgE in children with predisposition to atopic reactions is usually more abrupt. Total serum IgE levels decline from the second to the eight decade of life. Usually, elevated IgE concentration is related to atopic diseases but there are many other disorders combined with elevated serum IgE (for example: infections, neoplasms, immunodeficiency syndromes, skin disorders, inflammatory diseases). The spectrum of diseases combined with serum IgE elevation was presented in the present article.


Privileged but pressured? A study of affluent youth.
The purpose of this study was to build on preliminary findings of unusually high internalizing symptoms and substance use among suburban high school students. The sample consisted of 302 sixth- and seventh-grade students in an affluent, suburban community. Findings corroborated expectations regarding several domains of vulnerability, showing (1) high rates of clinically significant depressive symptoms among older girls, (2) significant links between various internalizing symptoms and substance use among both boys and girls, and (3) peers' approval of substance use among older boys. In exploring potential causes of distress in this suburban sample, associations were found for achievement pressures (particularly excessive perfectionistic strivings), and isolation from parents (particularly low perceived closeness to mothers). Findings of this study are discussed in terms of widespread stereotypes about affluent families, as well as implications for future research and preventive interventions for a subgroup of youth typically viewed as being at "low risk."


Photo-responsive MOFs: light-induced switching of porous single crystals containing a photochromic diarylethene.
Herein we report the synthesis and characterization of light responsive metal organic framework (MOF) single crystals containing the photochromic diarylethene 1,2-bis(2,5-dimethyl-thien-3-yl)perfluorocyclopentene. Polarized light microscopy on single crystals indicates that the photochrome is preferentially aligned along the c-axis of the host.


[Isolated dislocation of the os triquetrum--a rare wrist injury].
The isolated traumatic dislocation of the triquetrum is an extremely rare injury. The clinical signs are unspecific. Roentgenograms of the wrist in posteroanterior and lateral views, possibly complemented by oblique views, will help to provide the diagnosis. The best therapy appears to be the open reduction and fixation with Kirschner wires. With the presented case report, the difficulties in using the classification carpal injuries are discussed. Finally, corresponding to the carpus ring theory, the plausibility of additional injuries to carpal ligaments in such trauma is pointed out.


Source of endoproteolytic activity associated with purified ribulose bisphosphate carboxylase.
The association of endoproteolytic activity with purified ribulose bisphosphate carboxylase (RuBPCase) from barley (Hordeum vulgare var Numar) leaves was investigated. RuBPCase purified by chromatography on agarose gel and diethylaminoethyl-cellulose was free of associated endoproteolytic activity. The addition of leupeptin and casein to the extraction buffer completely eliminated proteolysis during initial extraction of RuBPCase. Endoproteolytic activity previously found associated with RuBPCase was identified as being due to contamination of endoproteinases from broken vacuoles.


The Clinical Outcome Study for dysferlinopathy: An international multicenter study.
To describe the baseline clinical and functional characteristics of an international cohort of 193 patients with dysferlinopathy. The Clinical Outcome Study for dysferlinopathy (COS) is an international multicenter study of this disease, evaluating patients with genetically confirmed dysferlinopathy over 3 years. We present a cross-sectional analysis of 193 patients derived from their baseline clinical and functional assessments. There is a high degree of variability in disease onset, pattern of weakness, and rate of progression. No factor, such as mutation class, protein expression, or age at onset, accounted for this variability. Among patients with clinical diagnoses of Miyoshi myopathy or limb-girdle muscular dystrophy, clinical presentation and examination was not strikingly different. Respiratory impairment and cardiac dysfunction were observed in a minority of patients. A substantial delay in diagnosis was previously common but has been steadily reducing, suggesting increasing awareness of dysferlinopathies. These findings highlight crucial issues to be addressed for both optimizing clinical care and planning therapeutic trials in dysferlinopathy. This ongoing longitudinal study will provide an opportunity to further understand patterns and variability in disease progression and form the basis for trial design.


Short-Chain Chitin Oligomers: Promoters of Plant Growth.
Chitin is the second most abundant biopolymer in nature after cellulose, and it forms an integral part of insect exoskeletons, crustacean shells, krill and the cell walls of fungal spores, where it is present as a high-molecular-weight molecule. In this study, we showed that a chitin oligosaccharide of lower molecular weight (tetramer) induced genes in Arabidopsis that are principally related to vegetative growth, development and carbon and nitrogen metabolism. Based on plant responses to this chitin tetramer, a low-molecular-weight chitin mix (CHL) enriched to 92% with dimers (2mer), trimers (3mer) and tetramers (4mer) was produced for potential use in biotechnological processes. Compared with untreated plants, CHL-treated plants had increased in vitro fresh weight (10%), radicle length (25%) and total carbon and nitrogen content (6% and 8%, respectively). Our data show that low-molecular-weight forms of chitin might play a role in nature as bio-stimulators of plant growth, and they are also a known direct source of carbon and nitrogen for soil biomass. The biochemical properties of the CHL mix might make it useful as a non-contaminating bio-stimulant of plant growth and a soil restorer for greenhouses and fields.


Identification of a receptor for an extinct virus.
The resurrection of endogenous retroviruses from inactive molecular fossils has allowed the investigation of interactions between extinct pathogens and their hosts that occurred millions of years ago. Two such paleoviruses, chimpanzee endogenous retrovirus-1 and -2 (CERV1 and CERV2), are relatives of modern MLVs and are found in the genomes of a variety of Old World primates, but are absent from the human genome. No extant CERV1 and -2 proviruses are known to encode functional proteins. To investigate the host range restriction of these viruses, we attempted to reconstruct functional envelopes by generating consensus genes and proteins. CERV1 and -2 enveloped MLV particles infected cell lines from a range of mammalian species. Using CERV2 Env-pseudotyped MLV reporters, we identified copper transport protein 1 (CTR1) as a receptor that was presumably used by CERV2 during its ancient exogenous replication in primates. Expression of human CTR1 was sufficient to confer CERV2 permissiveness on otherwise resistant hamster cells, and CTR1 knockdown or CuCl(2) treatment specifically inhibited CERV2 infection of human cells. Mutations in highly conserved CTR1 residues that have rendered hamster cells resistant to CERV2 include a unique deletion in a copper-binding motif. These CERV2 receptor-inactivating mutations in hamster CTR1 are accompanied by apparently compensating changes, including an increased number of extracellular copper-coordinating residues, and this may represent an evolutionary barrier to the acquisition of CERV2 resistance in primates.


Staging of liver fibrosis in chronic hepatitis B patients with a composite predictive model: a comparative study.
To evaluate the efficacy of 6 noninvasive liver fibrosis models and to identify the most valuable model for the prediction of liver fibrosis stage in chronic hepatitis B (CHB) patients. Seventy-eight CHB patients were consecutively enrolled in this study. Liver biopsy was performed and blood serum was obtained at admission. Histological diagnosis was made according to the METAVIR system. Significant fibrosis was defined as stage score > or = 2, severe fibrosis as stage score > or = 3. The diagnostic accuracy of 6 noninvasive liver fibrosis models, including serum aspartate aminotransferase (AST) to platelet ratio index (APRI), FIB-4, Forn's index, Fibrometer, Hepascore, and Shanghai Liver Fibrosis Group's index (SLFG), was investigated. The APRI, FIB-4 and Forn's index under receiver operating characteristic curve (AUROC) for significant fibrosis were 0.71, 0.75 and 0.79, respectively, with a diagnosis accuracy of 67%, 77% and 80%, respectively, and 0.80, 0.87 and 0.86, respectively, under the AUROC for severe fibrosis. The Hepascore, SLFG, and Fibrometer were 0.80, 0.83 and 0.85, respectively under the AUROC for significant fibrosis (P < 0.01). The diagnosis accuracy of Hepascore and SLFG was 86% and 88%, respectively. The Hepascore, SLFG, and Fibrometer were 0.95, 0.93, and 0.94, respectively, under the AUROC for severe fibrosis (P < 0.01). The models containing direct serum markers have a better diagnostic value than those not containing direct serum markers.


A simple method for estimating the skeletal uptake of diphosphonates.
It is possible to obtain an estimate of the bone uptake of diphosphonates after 3 h (BU) on the basis of the difference between the dose administered and the sum of the component eliminated in the urine plus the component present in the extra-osseous volume of distribution. The results of this simple method have been compared in 15 patients using whole body retention at 24 h (determined by means of a complete urine collection) and the ratio of plasma concentrations of 51Cr-EDTA/99Tcm-HMDP after 3 h (DPS). Both DPS and BU can be used on a practical basis, and therefore be used routinely with scintigraphy. The added advantage is that, for BU, the use of a second radiopharmaceutical is avoided.


[Effect of gemcitabine in enhancing the radiosensitivity of HepG2 hepatoma cells and the possible mechanism].
To evaluate the effect of gemcitabine in enhancing the radiosensitivity of hepatoma cell line HepG2 and explore its mechanisms. Clonogenic survival assay is employed to calculate the ratios of L-Q model radiation biology parameters and radiosensitization after different doses of irradiation. Flow cytometry was used to detect the changes in HepG2 cell cycle and apoptosis rate after gemcitabine treatment and radiation exposure. The survival fraction at 2 Gy of HepG2 cells treated with gemcitabine was significantly lower, and the value of alpha was significantly higher than those of untreated cells. GEM treatment increased the percentage of radiation-induced G0/G1 phase cells and cell apoptosis. Gemcitabine can significantly enhance the radiosensitivity of HepG2 cells by enhancing radiation-induced cell cycle arrest in G0/G1 phase and cell apoptosis.


A prospective study of the impact of automated dipstick urinalysis on the diagnosis of preeclampsia.
To determine prospectively in hypertensive pregnant women 1) the accuracy of dipstick testing for proteinuria using automated urinalysis, 2) factors that might affect such accuracy, and 3) the potential impact of automated dipstick testing on the accuracy of diagnosis of preeclampsia according to acceptance of proteinuria at either 1 + or 2 + level. Prospective study. Antenatal day assessment unit and antenatal ward of St George Hospital, a teaching hospital in Sydney, Australia. 170 hypertensive pregnant women attending as outpatients or inpatients. 503 midstream urine samples were collected prospectively on separate occasions from 170 women. Full urinalysis was recorded using the Bayer Clinitek 50 automated urinalysis device and Multistix 10SG urinalysis strips (Bayer Diagnostics, Victoria, Australia). Each MSU was analysed for spot protein/creatinine ratio and also for culture and sensitivity if symptoms of a urinary tract infection were present or dipstick included positive nitrites. Urinalysis protein results were compared with spot urinary protein/creatinine ratio (previously shown to correlate with 24-hr urine protein excretion) to determine the accuracy of urinalysis. True proteinuria was defined as a ratio >/= 30 mg protein/mmol creatinine. False positive dipstick tests ranged from 7% at 3 + level to 71% at 1 + proteinuria level while false negative rates were 7% for "nil" and 14% for "trace" proteinuria, 9% overall. Accepting the dipstick proteinuria result at face value led to an incorrect diagnosis of preeclampsia or gestational hypertension in 85 (50%) women. Dipstick proteinuria was significantly more likely to be correct (true positive/true negative) if diastolic blood pressure was elevated > 90 mmHg (p = 0.032) and in the absence of ketonuria (p = 0.001). Accepting a diagnosis of preeclampsia on the basis of de novo hypertension and dipstick testing alone was accurate less often (70%) when > 1 + was used as a discriminant value than at the 82% of presentations when > 2 + was used (p = 0.001). Accepting "nil" or "trace" proteinuria as a true negative dipstick results fails to identify approximately 1 in 11 hypertensive pregnant women with true proteinuria, a false negative rate that may be acceptable provided these women are subject to ongoing vigilant clinical review. Even with automated urinalysis the false positive rate for dipstick levels >/= 1 + is very high, particularly in the presence of ketonuria and relying on this alone to diagnose preeclampsia leads to significant errors in diagnosis. Accepting >/= 2 + dipstick proteinuria improves overall diagnostic accuracy for preeclampsia at the expense of a higher false negative rate. This study emphasizes the need to confirm dipstick proteinuria with a further test such as a spot urine protein/creatinine ratio in all hypertensive pregnant women, particularly in research studies.


Ex vivo culture of cord blood CD34+ cells expands progenitor cell numbers, preserves engraftment capacity in nonobese diabetic/severe combined immunodeficient mice, and enhances retroviral transduction efficiency.
Ex vivo culture of hematopoietic stem/progenitor cells could potentially improve the efficacy of human placental/umbilical cord blood (CB) in clinical hematopoietic stem cell (HSC) transplantation and allow gene transduction using conventional retroviral vectors. Therefore, we first examined the effects of a 7-day period of ex vivo culture on the hematopoietic capacity of CB CD34+ cells. Medium for the ex vivo cultures contained either serum and six recombinant human hematopoietic growth factors (GFs), including Flt-3 ligand (FL), Kit ligand (KL = stem cell factor), thrombopoietin (Tpo), interleukin 3 (IL-3), granulocyte colony-stimulating factor (G-CSF), and interleukin 6 (IL-6), or a serum-free medium containing only FL, KL, and Tpo. After culture under both ex vivo conditions, the total numbers of viable cells, CD34+ cells, colony-forming cells (CFCs), and long-term culture initiating cells (LTC-ICs) were increased. In contrast, the severe combined immunodeficiency (SCID) mouse engrafting potential (SEP) of cultured cells was slightly decreased, as compared with fresh cells. Nevertheless, cultured human CB CD34+ cells were able to generate engraftment, shown to persist for up to 20 weeks after transplantation. We next tested the efficacy of retroviral transduction of cultured cells. Transduced cultured human cells were able to engraft in NOD/SCID mice, as tested 4 weeks after transplantation, and EGFP+CD34+ cells and EGFP+ CFCs were isolated from the chimeras. Thus, although additional improvements in ex vivo culture are still needed to expand the numbers and function of human HSCs, the current conditions appear to allow gene transduction into hematopoietic SCID engrafting cells, while at least qualitatively preserving their in vivo engraftment potential.


Three-dimensional meshwork structure of glomerular basement membrane revealed by chemical treatment.
In order to study the three-dimensional ultrastructure of the glomerular basement membrane (GBM), isolated GBM was treated with elastase, sodium dodecyl sulfate, and 2-mercaptoethanol and examined by transmission electron microscopy using ultrathin sectioning method and stereoscopic view. This treatment revealed clearly three-dimensional meshwork structure of GBM mainly composed of type IV collagen. Numerous regular polygonal small pores were present in the meshwork structure. The average short dimension of the small pores was 4.1 +/- 1.8 nm and the average long dimension was 4.8 +/- 2.2 nm. Our present results further support the molecular sieve theory of the basement membrane.


In Vitro Anti-Epstein Barr Virus Activity of Olea europaea L. Leaf Extracts.
Olea europaea L. var. sativa (OESA) preparations are widely used in traditional medicine in the Mediterranean region to prevent and treat different diseases. In this research, olive extracts derived from the leaves of the OESA tree have been screened for antioxidant activity by two methods: the DPPH free radical scavenging assay (DPPH) and the Ferric reducing antioxidant power (FRAP) assay. The DPPH assay showed that OESA possesses a stronger antioxidant activity (84%) at 1 mg/mL while the FRAP method showed a strong metal ion chelating activity (90%) at 1 mg/mL. The low IC50 values, obtained by two different methods, implies that OESA has a noticeable effect on scavenging free radicals comparable to standards. During EBV infection, the free radicals increased triggering lipid oxidation. Therefore, the monitoring of the secondary lipid peroxidation products was done by measuring malonaldehyde (MDA) and conjugated dienes (DC). The simultaneous treatment of Raji cells with OESA and TPA, as an inductorof the lytic cycle, generated a significant decrease in MDA levels and DC (p < 0.05). Besides, Raji cells simultaneously exposed to TPA and OESA exhibited a percentage of EBV-positive fluorescence cells lower than TPA treated cells (**** p < 0.0001). This suggests that OESA treatment has a protective effect against EBV lytic cycle induction.


Growth hormone treatment increases cytochrome P450-mediated antipyrine clearance in man.
We used the antipyrine clearance test (APC) to examine the effect of growth hormone (GH) therapy on hepatic cytochrome P450 (CYP) enzyme activity. Eleven GH deficient adults were randomized to receive GH or placebo for 6 months, all subjects subsequently received GH. Before treatment, APC was below the normal range in six subjects. We found an increase in APC in the subjects randomized to receive GH compared to those on placebo (median change +0.14 ml/min/kg [range + 0.04 to + 0.20]vs -0.04 ml/min/kg [range -0.07 to + 0.04], p = 0.011). The stimulatory effect of GH on drug metabolism was confirmed by the data for 3 months GH treatment in all 11 subjects, with APC increasing from 0.33 ml/min/kg (range 0.22 to 0.69) to 0.50 ml/min/kg (range 0.27 to 0.83), p = 0.018). These data indicate that GH modulates hepatic CYP activity. This has important clinical implications, as the hepatic metabolism of drugs and hormones may be altered in patients undergoing GH therapy.


GnRH-agonist induced depressive and anxiety symptoms during in vitro fertilization-embryo transfer cycles.
To determine whether the use of a GnRH agonist inducing a hypogonadic state during IVF-ET cycles induces negative mood symptoms, we conducted a prospective randomized study in 108 women comparing two different controlled ovarian stimulation protocols. A significant phase effect was observed for depression and anxiety symptoms during IVF-ET cycles reflecting an increase in symptoms between the hypogonadal phase and the peak in gonadotropin stimulation; however, the hypogonadal phase induced by the GnRH agonist was not associated with a significant increase in any of the studied mood parameters.


Influence of receptor axons on the formation of olfactory glomeruli in a hemimetabolous insect, the cockroach Periplaneta americana.
The embryonic development of the hemimetabolous insect Periplaneta americana requires approximately 31 days. Deafferentation experiments were used to investigate the role of ingrowing receptor axons during embryogenesis, specifically their influence 1) on the subdivision of the antennal lobe neuropil into glomeruli, 2) on the morphology and number of glial cells, and 3) on the arborization pattern of central neurons. The flagellum of one antenna was removed from embryos at different developmental stages starting with day 10. Subsequently, they were raised in culture until a total age of 26 days. At day 10, the deutocerebrum has received only a very small number (ca. 0.4%) of antennal receptor axons; deafferentation at this stage allowed us to deprive the deutocerebrum of approximately 99% of its normal antennal input. Deafferentation has marked effects on the organization of the antennal lobe neuropil. The deafferented lobe is reduced in volume compared to the control side; the characteristic glomeruli are missing. During normal development glomeruli are formed between day 19 and 22, first in dorsal and then in ventral antennal lobe regions. By removing the antenna before day 20, their formation is disturbed in all parts of the antennal lobe. If deafferentation is performed after stage 20, glomeruli persist in dorsal regions, but are missing in ventral regions. On day 24 or later, glomeruli in both dorsal and ventral regions are unaffected by deafferentation. Glial cells continue to extend fine processes into the neuropil in the absence of ingrowing receptor axons. The number of glial cells is reduced compared to control lobes. Multiglomerular local interneurons and other gamma-amino butyric acid-immunoreactive neurons, as well as projection neurons, fail to develop glomerular arborization patterns in antennal lobes deprived of sensory axons.


Apatite-mediated actin dynamics in resorbing osteoclasts.
The actin cytoskeleton is essential for osteoclasts main function, bone resorption. Two different organizations of actin have been described in osteoclasts, the podosomes belt corresponding to numerous F-actin columns arranged at the cell periphery, and the sealing zone defined as a unique large band of actin. To compare the role of these two different actin organizations, we imaged osteoclasts on various substrata: glass, dentin, and apatite. Using primary osteoclasts expressing GFP-actin, we found that podosome belts and sealing zones, both very dynamic actin structures, were present in mature osteoclasts; podosome belts were observed only in spread osteoclasts adhering onto glass, whereas sealing zone were seen in apico-basal polarized osteoclasts adherent on mineralized matrix. Dynamic observations of several resorption cycles of osteoclasts seeded on apatite revealed that 1) podosomes do not fuse together to form the sealing zone; 2) osteoclasts alternate successive stationary polarized resorption phases with a sealing zone and migration, nonresorption phases without any specific actin structure; and 3) apatite itself promotes sealing zone formation though c-src and Rho signaling. Finally, our work suggests that apatite-mediated sealing zone formation is dependent on both c-src and Rho whereas apico-basal polarization requires only Rho.


Wavelength switching in an actively mode-locked Fabry-Perot laser diode with a highly dispersive external cavity.
We demonstrate a simple and reliable scheme for wavelength switching in an actively harmonic mode-locked Fabry-Perot laser diode (FPLD) that is coupled to a highly dispersive external fiber cavity. Wavelength switching between FPLD modes is achieved by detuning of the modulation frequency applied to the FPLD. A side-mode suppression ratio of as much as 40 dB is maintained, and the supermode noise suppression ratio is more than 50 dB for the whole wavelength switching operation range of 4.7 nm when the pulse repetition rate is ~2 GHz. The wavelength-switching mechanism of our laser is based on the wavelength-dependent cavity resonance frequency shift that is due to chromatic dispersion, and we verify that our experimental results closely coincide with analytical results.


The epidemiology of drug-induced akathisia: Part I. Acute akathisia.
This article reviews the epidemiological data on drug-induced acute akathisia, examining studies in which akathisia was the primary focus as well as those in which it was one of a number of drug side effects studied. The studies are diverse in methodology and suffer from many limitations. Incidence rates for acute akathisia with conventional neuroleptics vary from 8 to 76 percent, with 20 to 30 percent being a conservative estimate; preliminary evidence suggests that the newer atypical antipsychotic drugs are less likely to produce acute akathisia. A number of nonneuroleptic drugs--in particular the serotonin-specific reuptake inhibitors--have been implicated in the development of akathisia, but the epidemiological data are limited. Risk factors for neuroleptic-induced akathisia are not completely understood. Drug dose, rate of increment of dose, and drug potency seem to be important, but the role of sociodemographic factors and other treatment-related variables is modest. Drug-induced parkinsonism is significantly correlated with akathisia. Evidence for iron deficiency as a risk factor is conflicting, and its contribution is likely to be minor.


After-meal blood glucose level prediction using an absorption model for neural network training.
Diabetes Mellitus outpatients would benefit from a lifestyle support tool that delivers reliable short term Blood Glucose Level (BGL) predictions. To develop a method for BGL prediction based on the baseline BGL, the insulin dosing and a dietary log. A new training method is proposed for a neural network in which an absorption model is applied that uses the nutrient contents of meals. The numerical characteristics of the computed absorption curve are fed to the neural network as training inputs along with the applied insulin doses and BGL evolution measured by a Continuous Glucose Monitoring System. For comparison, another version of the training in which raw carbohydrate values are used as dietary inputs has also been implemented. The method was validated in a clinical trial with 5 patients using a total of 167 meals. It was found that the proposed method performed significantly better on the 60- and 120-min prediction horizons, with a Root Mean Square Error of 1.12 mmol/l and 1.75 mmol/l, respectively, and more than 96% of the predicted values falling in the 'clinically acceptable' class according to clinical practice. These results surpass those published results to which our method is directly comparable, and also those of the carbohydrate-only version (1.81 mmol/l and 2.53 mmol/l). The integration of the absorption model in the training process has successfully contributed to the success of the model. Future research will focus on a new trial with more patients to verify these promising results.


IL-13 and its genetic variants: effect on current asthma treatments.
Airway hyperresponsiveness is an essential part of the definition of asthma associated temporally with exposure to allergens, certain respiratory viruses, pollutants such as ozone, and certain organic chemicals. Interleukin-13 (IL-13) is implicated as a central regulator in immunoglobulin E (IgE) synthesis, mucus hypersecretion, airway hyperresponsiveness, and fibrosis. The importance of IL-13 in allergic disorders in humans is supported by consistent associations between tissue IL-13 levels and genetic variants in the IL-13 gene and asthma and related traits. Single-nucleotide polymorphisms in IL-13 are associated with allergic phenotypes in several ethnically diverse populations. Glucocorticoids are anti-inflammatory medications often used as maintenance therapy in acute and chronic asthma; however, some patients with severe asthma are steroid resistant. IL-13 remains elevated in glucocorticoid insensitive asthma but not in glucocorticoid sensitive asthma. Thus targeting IL-13 and its associated receptors may be a therapeutic approach to the treatment of asthma and/or allergy. This review focuses on the role of IL-13 on airway hyperresponsiveness and corticosteroids resistant asthma both preclinically and clinically.


Frequency of coeliac disease in Hungarian children with type 1 diabetes mellitus.
Coeliac disease and type 1 diabetes mellitus can frequently coexist, presumably due to a common genetic predisposition. The present study was designed to evaluate the frequency of coeliac disease among Hungarian diabetic children and to study the effect of gluten-free diet on glycaemic control. A total of 205 diabetic children (age range 2.0-17.0 years, median 11.6 years) were screened for coeliac disease by determination of IgA-endomysium (EMA) antibodies. In the positive cases, a jejunal biopsy was performed and, in addition to routine histology, the number of intraepithelial gamma/delta T-cells was also determined. Insulin requirement, glycosylated haemoglobin level and body mass index of diabetic children with coeliac disease were determined before and 3 months after the introduction of gluten-free diet. IgA-EMA was positive in 24 cases, 17 of them (8.3% of all diabetic children) had a subtotal villous atrophy and thus coeliac disease was diagnosed. In all but two of these children, the mean number of gamma/delta T-cells was elevated (above 7 cells/mm). Of the remaining seven patients with positive EMA but normal villous structure, five (2.4%) had elevated number of epithelial gamma/delta T-cells, indicating probable latent coeliac disease. The insulin requirement of the children had significantly increased 3 months after the introduction of gluten-free diet (median values 0.64 versus 0.48 U/kg per day, P<0.05). Median body mass indices also showed significant elevation after this period (16.8 versus 14.2 kg/m(2), P<0.05) CONCLUSION: the frequency of coeliac disease was high in the studied group. Introduction of a gluten-free diet improved the somatic development of these children. A latent form of coeliac disease is also frequent in children with type 1 diabetes mellitus.


Stereotactic radiotherapy of irregular targets: a comparison between static conformal beams and non-coplanar arcs.
Stereotactic radiotherapy using a linear accelerator is usually equated with the technique of delivery using multiple non-coplanar arcs, which achieves a spherical dose distribution. As the majority of intracranial lesions are not spherical, a range of schematized tumour shapes were planned to assess the role of static conformal beams in the treatment of irregular lesions. A sphere and 2 ellipsoids, ranging from 20 to 50 mm maximum diameter located intracranially were planned using 3, 4, and 6 non-coplanar static beams with conformal blocks and were compared with four 120 degree non-coplanar arcs. Comparison of the plans was made by the relative sparing of normal tissue outside the target volume using three-dimensional dose-volume distributions. Non-coplanar arcs spared more normal tissue at low isodoses and achieved the best high dose sparing for spherical targets. For the majority of irregular targets, 3 and 4 static beams spared more tissue at doses > or = 50% and > or = 80% than the arc technique. For all irregular volumes, maximum sparing of normal tissue to isodoses > or = 50% and > or = 80% of the treatment isodose was obtained with 6 static conformal beams. We conclude that irregularly shaped tumours suitable for stereotactic radiotherapy with a linear accelerator are better treated with conformal static non-coplanar beams rather than with the multiple arc technique.


T2 Relaxation Times at Cardiac MRI in Healthy Adults: A Systematic Review and Meta-Analysis.
Background T2 mapping is an important cardiac MRI technique with applications in various conditions. However, a comprehensive evaluation of the T2 literature for normal values is lacking. Purpose To characterize the ranges of normal values and variability of myocardial T2 relaxation times using a systematic review and meta-analysis of the T2 literature. Materials and Methods PubMed and Cochrane Central were searched from June 2019 to January 2020 for myocardial T2 measurements in healthy adults. Studies quantifying T2 relaxation times conducted at 1.5 T or 3.0 T using gradient and spin-echo (GRASE) or T2-prepared balanced steady-state free precession sequences were included. Summary means were generated using a random-effects model. Subgroup analysis and meta-regression were performed to assess factors causing heterogeneity. Results Of the 2481 articles retrieved, 42 studies were included with 954 healthy adults (mean age, 42.4 years ± 10.5 [standard deviation]; 538 men). The pooled mean of T2 across studies was 52 msec at 1.5 T (95% confidence interval [CI]: 51 msec, 53 msec) and 46 msec at 3.0 T (95% CI: 44 msec, 48 msec) (P ≤ .001). I2 was 98% at 1.5 T and 3.0 T. Meta-regression at 1.5 T and 3.0 T identified vendor (β at 1.5 T = -4 msec [with Philips as reference], P < .001; β at 3.0 T = -5 msec, P = .02) and pulse sequence (β at 1.5 T = -5 msec [with GRASE as reference], P < .001; β at 3.0 T = -6 msec, P = .002) as significant covariates, but it did not identify any association with covariates of age (β at 1.5 T = 0 msec per year, P = .70; β at 3.0 T = 0 msec per year, P = .83) or sex (β at 1.5 T = -1 msec, P = .88; β at 3.0 T = 6 msec, P = .42). Conclusion The pooled mean of T2 relaxation times in healthy adults had marked heterogeneity across studies with field strength, vendor, and pulse sequence identified as covariates associated with T2. T2-prepared measurements were similar between vendors at each field strength. © RSNA, 2020 Online supplemental material is available for this article.


What controls glycolysis in bloodstream form Trypanosoma brucei?
On the basis of the experimentally determined kinetic properties of the trypanosomal enzymes, the question is addressed of which step limits the glycolytic flux in bloodstream form Trypanosoma brucei. There appeared to be no single answer; in the physiological range, control shifted between the glucose transporter on the one hand and aldolase (ALD), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), phosphoglycerate kinase (PGK), and glycerol-3-phosphate dehydrogenase (GDH) on the other hand. The other kinases, which are often thought to control glycolysis, exerted little control; so did the utilization of ATP. We identified potential targets for anti-trypanosomal drugs by calculating which steps need the least inhibition to achieve a certain inhibition of the glycolytic flux in these parasites. The glucose transporter appeared to be the most promising target, followed by ALD, GDH, GAPDH, and PGK. By contrast, in erythrocytes more than 95% deficiencies of PGK, GAPDH, or ALD did not cause any clinical symptoms (Schuster, R. and Holzhütter, H.-G. (1995) Eur. J. Biochem. 229, 403-418). Therefore, the selectivity of drugs inhibiting these enzymes may be much higher than expected from their molecular effects alone. Quite unexpectedly, trypanosomes seem to possess a substantial overcapacity of hexokinase, phosphofructokinase, and pyruvate kinase, making these "irreversible" enzymes mediocre drug targets.


Hydrolysis of thyroglobulin inside isolated rat thyroid and liver lysosomes.
In vitro, poorly iodinated thyroglobulin (Tg) is hydrolysed at the same rate whether it is enclosed in thyroid or in liver lysosomes, while fully iodinated Tg is degraded faster inside liver lysosomes. After in vivo TSH administration, thyroid lysosomes hydrolyse fully iodinated Tg as fast as do liver lysosomes.


Society for Acute Medicine Trainee Update, Autumn 2017.
Tehmeena Khan has replaced Sanjay Krishnamoorthy as a Trainee Representative for SAM. We would like to thank Sanjay for all his hard work and contribution during his tenure as Rep. Tehmeena is a final year trainee from North East & Central London. Tehmeena's specialist skills are Leadership, Management and Quality Improvement. She has previously been a Darzi Fellow and has undertaken a Winston Churchill Fellowship. She has recently joined the Health Foundation Q Community.


Radiotherapy for non-gastric intestinal versus gastric MALT lymphoma: a comparison of treatment outcomes.
Radiotherapy is often used for treating patients with gastric mucosa-associated lymphoid tissue (MALT) lymphomas who fail to respond to Helicobacter pylori eradication. However, non-gastric intestinal MALT lymphoma is rare, and no standard therapeutic strategies have been established. This study was designed to assess the long-term prognosis of non-gastric intestinal MALT lymphoma treated with radiotherapy and to compare the outcomes with that of post-radiotherapy gastric MALT lymphoma. The study included 34 patients with stage I EA gastrointestinal MALT lymphoma according to the Ann Arbor classification who underwent definitive radiotherapy. The primary site was the rectum in 3, the duodenum in 1, and the stomach in 30 patients. The radiotherapy dose was 1.5?2.0 Gy (median, 1.5 Gy) and the total dose was 30?40 Gy (median, 30 Gy). The clinical target volume (CTV) was defined as the volume of the entire organ with the lymphoma. Adjacent lymph node areas were not routinely included in the CTV. Complete response (CR) was achieved in all patients. There were no local recurrences, and two cases of recurrence were observed at other sites. The 5-year overall survival rates for non-gastric and gastric MALT lymphomas were 100% and 94.7%, respectively, and the 5-year disease-free survival rates were 100% and 95.7%, respectively. None of the patients died of the current illness. Radiotherapy for non-gastric intestinal MALT lymphoma is expected to result in good local control and long-term survival, similar to that for gastric MALT lymphoma.


A Monte Carlo Analysis of Actual Maximum Exposure From a 5G Millimeter-Wave Base Station Antenna for EMF Compliance Assessments.
International radio frequency (RF) electromagnetic field (EMF) exposure assessment standards and regulatory bodies have developed methods and specified requirements to assess the actual maximum RF EMF exposure from radio base stations enabling massive multiple-input multiple-output (MIMO) and beamforming. Such techniques are based on the applications of power reduction factors (PRFs), which lead to more realistic, albeit conservative, exposure assessments. In this study, the actual maximum EMF exposure and the corresponding PRFs are computed for a millimeter-wave radio base station array antenna. The computed incident power densities based on near-field and far-field approaches are derived using a Monte Carlo analysis. The results show that the actual maximum exposure is well below the theoretical maximum, and the PRFs similar to those applicable for massive MIMO radio base stations operating below 6 GHz are also applicable for millimeter-wave frequencies. Despite the very low power levels that currently characterize millimeter-wave radio base stations, using the far-field approach can also guarantee the conservativeness of the PRFs used to assess the actual maximum exposure close to the antenna.


Giant retroperitoneal hemangiopericytoma.
Hemangiopericytomas are rare vascular tumours that are derived from pericytes. Retroperitoneal hemangiopericytomas are usually bulky but clinically silent when diagnosed because of their slow rate of growth. A 49-year-old man, who presented with only vague symptoms of abdominal fullness for several months, was found on computed tomography to have a huge well-defined mass with areas of low attenuation and well-enhanced septa. The tumour was successfully resected and was confirmed to be a malignant retroperitoneal hemangiopericytoma. It measured 30 cm in the greatest dimension. We are prompted to present this case as it is believed to be the largest tumour reported to date.


A geneticist's approach to psychiatric disease.
The pattern of the genetics of psychiatric disease is various, in detail and in kind; one cannot always expect to find simple, trustworthy explanations of what are complex relationships. There will be some diseases, mostly of the disruptive type, that will prove to be Mendelian defects; but it would be idle to expect that of most. Many disorders will be elucidated only when the nub of the problem is better defined. Mindless application of standard genetic techniques devised for quite different purposes is no substitute for articulate speculation built on sound fact and cogent testing. In this respect genetic evidence is no different from that of physiology, pathology and pharmacology, which are perhaps less unfamiliar to readers than genetics. Finally, no answer has been found unless it deals in those terms in which the question first arose. If the topic of the genetic analysis is some psychosis, the final predicate must be a statement about the psychosis, not about some arbitrary abstraction from it.


Bioavailability and pharmacokinetics of ibuprofen in the broiler chicken.
The intravenous, intramuscular and oral pharmacokinetics of ibuprofen in broiler chickens were investigated. In a preliminary study, plasma ibuprofen concentration-time profiles, following i.v. (25 mg/kg) dosing were best described by a 2-compartment model. After intravenous administration, the volume of distribution at steady-state (Vd(ss)), the total systemic clearance (ClB), the elimination half-life (t1/2 beta) and the MRT were 0.303 L/kg, 482.3 ml/h.kg, 2.71 h and 1.02 h, respectively. After intramuscular administration of ibuprofen, the tmax and Cmax were 0.37 h, and 42.2 micrograms/mL, respectively, with an estimated bioavailability of 46.7%. After oral administration of ibuprofen, the tmax and Cmax were 0.31 h and 23.91 micrograms/mL, respectively, with an estimated bioavailability of 24.2%. This is a preliminary study, examining the use of ibuprofen in broiler chickens, and should be followed by tissue residue and efficacy studies in different disease states.


Coronary artery calcium scoring with multislice computed tomography: in vitro assessment of a low tube voltage protocol.
We sought to compare an 80-kVp coronary calcium scoring protocol with the standard protocol of 120 kVp in terms of accuracy and reproducibility and to assess its dose reduction potential. An anthropomorphic heart phantom with calcium cylinders was scanned with different tube currents at 80 kVp and 120 kVp using a 16-slice multislice CT (MSCT) scanner. An adapted threshold for 80 kVp was calculated. Accuracy and reproducibility for calcium mass, volume, and Agatston score were analyzed using F-tests. The radiation doses needed to produce artifact-free images were determined. Accuracy (measurement errors: mass 120 kVp +4.6%, mass 80 kVp -6.9%, volume 120 kVp +78.8%, volume 80 kVp +58.2%) and reproducibility (F-tests: mass: P = 0.4998, volume: P = 0.9168, Agatston: P = 0.5422) were comparable at both tube voltages. Avoiding the appearance of artificial lesions, a CTDI(w,eff) of 10.7 mGy was needed at 120 kVp versus 4.6 mGy at 80 kVp (dose reduction of 57%). Using an 80-kVp protocol in coronary calcium scoring, a relevant dose reduction is possible without compromising reproducibility and accuracy.


Metabolic products of microorganisms. 258. Enzymatic bromination of nikkomycin Z.
Two brominated nikkomycins were produced by enzymatic halogenation of nikkomycin Z in the presence of a nonheme bromoperoxidase isolated from Streptomyces aureofaciens Tü 24. The monobrominated and dibrominated nikkomycin Z derivatives were substituted at the hydroxypyridyl moiety of the N-terminal amino acid of nikkomycin Z at position C-6"' (ZBr) or C-4"' and C-6"' (ZBr2). The brominated nikkomycin Z derivatives had a decreased affinity to chitin synthase of Coprinus cinereus as compared to nikkomycin Z and exhibited a low inhibitory activity towards various fungi and yeasts.


Protocol for a scoping review to understand what is known about how GPs make decisions with, for and on behalf of patients who lack capacity.
General Practitioners (GPs) and allied healthcare professionals working in primary care are regularly required to make decisions with, for and on behalf of patients who lack capacity. In England and Wales, these decisions are made for incapacitated adult patients under the Mental Capacity Act 2005, which primarily requires that decisions are made in the patient's 'best interests'. Regarding children, decisions are also made in their best interests but are done so under the Children Act 1989, which places paramount importance on the welfare of the child. Decisions for children are usually made by parents, but a GP may become involved if he or she feels a parent is not acting in the best interests of the child. Internationally, including elsewhere in the UK, different approaches are taken. We hypothesise that, despite the legislation and professional guidelines, there are many different approaches taken by GPs and allied healthcare professionals in England and Wales when making these complex decisions with, for and on behalf of patients who lack capacity. To better understand what is known about how these decisions are made, we plan to undertake a scoping review and directed content analysis of the literature. While the majority of decisions made in primary care are made by GPs, for completeness, this review will include all allied healthcare professionals working in primary care. To ensure a wide breadth of literature is captured, a scoping review will be undertaken as described by Arksey and O'Malley (2005). A five-stage approach will be taken when conducting this review: (1) identifying the research question; (2) identifying relevant papers; (3) study selection; (4) data extraction and (5) summarising and synthesis. The final stage will include a directed content analysis of the data to help establish the cross-cutting themes. The scoping review will be disseminated through conferences and peer-reviewed publications. This scoping review is the first (mapping) phase in a proposed larger study to explore how GPs make decisions with, for and on behalf of those who lack capacity. Qualitative research with GPs, patients and their families will follow, before all the results are synthesised using an 'empirical bioethics' methodology.


Analyzing Efficacy and Safety of Anti-Fungal Blue Light Therapy via Kernel-Based Modeling the Reactive Oxygen Species Induced by Light.
The goal of this study is to investigate the efficacy, safety, and mechanism of ABL for inactivating Candida albicans (C. albicans), and to determine the best wavelength for treating candida infected disease, by experimental measurements and dynamic modeling. The changes in reactive oxygen species (ROS) in C. albicans and human host cells under the irradiation of 385, 405, and 415 nm wavelengths light with irradiance of 50 mW/cm2 were measured. Moreover, a kernel-based nonlinear dynamic model, i.e., nonlinear autoregressive with exogenous inputs (NARX), was developed and applied to predict the concentration of light-induced ROS, whose kernels were selected by a newly developed algorithm based on particle swarm optimization (PSO). The ROS concentration was increased respectively about 10-12 times in C. albicans and about 3-6 times in human epithelial cells by the ABL treatment with the same fluence of 90 J/cm2. The NARX models were respectively fitted to the data from the experiments on both types of cells. Besides, four different kernel functions, including Gaussian, Laplace, linear and polynomial kernels, were compared in their fitting accuracies. The errors with the Laplace kernel turned out to be only 0.2704 and 0.0593, as respectively fitted to the experimental data of the C. albicans and human host cells. The results demonstrated the effectiveness of the NARX modeling approach, and revealed that the 415 nm light was more effective as an anti-fungal treatment with less damage to the host cells than the 405 or 385 nm light. The kernel-based NARX model identification algorithm offers opportunities for determining the effective and safe light dosages in treating various fungal infection diseases.


Telling it like it is.
Following a year of public engagement activities associated with the Royal Institution Christmas Lectures, Alison Woollard explains why scientists need to communicate with the public.


In Vivo and In Silico Assessment of Diabetes Ameliorating Potentiality and Safety Profile of Gynura procumbens Leaves.
Diabetes mellitus is one of the most notable health dilemmas. Analyzing plants for new antidiabetic remedies has become an impressive territory for life science researchers. Gynura procumbens has long been used to treat diabetes. Thus, we strived to ascertain the hypoglycemic potentiality of extract of leaves of G. procumbens by in vivo and in silico approaches. Fresh leaves of G. procumbens were collected and shade-dried to prepare ethanolic extracts to evaluate pharmacological parameters. Diabetes was induced in rats via injecting alloxan through the intraperitoneal route at a dose of 150 mg/kg body weight. Humalyzer 3000 was used to perform a biochemical assay of collected samples from rats. Anti-hyperglycemic activity study along with overdose toxicity test was performed. The pharmacological activity of this plant was also evaluated through a molecular docking study. This in silico study investigated the binding affinity of natural ligands from G. procumbens against glycoside hydrolase enzymes. We detected a peak plasma concentration of G. procumbens at 3 hours 45 minutes that is roughly similar to the peak plasma concentration of metformin. Again, in OGTT and anti-hyperglycemic tests, it has been ascertained that both plant extract and metformin can exert significant (P < 0.05) and highly significant (P < 0.01) hypoglycemic activity in a dose-dependent manner. Metformin exhibited better therapeutic efficacy than that of plant extract, but it possessed null statistical significance. Also, our safety profile expressed that, similar to metformin, the plant extract can restore the disturbed pathological state in a dose-oriented approach with a wide safety margin. In silico study also validated the potentialities of natural constituents of G. procumbens. Conclusion. This study suggested that G. procumbens can be considered as potential antidiabetic plant. Robust and meticulous investigation regarding plant chemistry and pharmacology in the future may bring about a new dimension that will aid in discovering antidiabetic drugs from this plant in the diabetes management system.


Barth syndrome: an X-linked cause of fetal cardiomyopathy and stillbirth.
Barth Syndrome (BTHS) is an X-linked multisystem disorder (OMIM 302060) usually diagnosed in infancy and characterized by cardiac problems [dilated cardiomyopathy (DCM) ± endocardial fibroelastosis (EFE) ± left ventricular non-compaction (LVNC)], proximal myopathy, feeding problems, growth retardation, neutropenia, organic aciduria and variable respiratory chain abnormalities. We wished to determine whether BTHS had a significant impact on fetal and perinatal health in a large cohort of family groups originating from a defined region. Case note review on 19 families originating from the UK and known to the Barth Syndrome Service of the Bristol Royal Hospital for Children. Details are presented on six kindreds (32%) with genetically and biochemically proven BTHS that demonstrate a wider phenotype including male fetal loss, stillbirth and severe neonatal illness or death. In these families, 9 males were stillborn and 14 died as neonates or infants but there were no losses of females. BTHS was definitively proven in five males with fetal onset of DCM ± hydrops/EFE/LVNC. These findings stress the importance of considering BTHS in the differential diagnosis of unexplained male hydrops, DCM, EFE, LVNC or pregnancy loss, as well as in neonates with hypoglycemia, lactic acidosis and idiopathic mitochondrial disease.


Solvent-resistant nanofiltration for product purification and catalyst recovery in click chemistry reactions.
The quickly developing field of "click" chemistry would undoubtedly benefit from the availability of an easy and efficient technology for product purification to reduce the potential health risks associated with the presence of copper in the final product. Therefore, solvent-resistant nanofiltration (SRNF) membranes have been developed to selectively separate "clicked" polymers from the copper catalyst and solvent. By using these solvent-stable cross-linked polyimide membranes in diafiltration, up to 98 % of the initially present copper could be removed through the membrane together with the DMF solvent, the polymer product being almost completely retained. This paper also presents the first SRNF application in which the catalyst permeates through the membrane and the reaction product is retained.


Surgical treatment of chronic osteomyelitis in children admitted from developing countries.
The surgical management of chronic osteomyelitis in children is still challenging in developing countries. This study analysed the extent of the disease and the therapeutic regime. This was a retrospective study in two primary health care hospitals from January 2009 to December 2013, 27 children (20 males and 7 females, mean age 7 years) admitted from developing countries who were treated for chronic osteomyelitis. Localization, duration of the disease, extent of the osseous involvement, spectrum of germs, number of previous and required surgical procedures and duration of hospital stay are reported. A total of 16 cases had haematogenous and 11 cases post-traumatic aetiology. The mean duration of the disease was 18 months. On average, three (range, 1-12) previous surgical procedures were performed. The affected bones were: Tibia in 11, femur in 8, forearm in 6 cases, spine and humerus each in 1 case. Staphylococcus aureus was the responsible germ in 75%. On average, four (range, 2-8) surgical procedures were required. Osseous stabilizations were necessary in 17, plastic soft tissue reconstructions in 8 cases. In three cases with metaphyseal/diaphyseal defect, bone transfers had to be performed (2 × fibula-pro-tibia, 1 × rib for radius). The mean hospital stay took 8 (range, 4-20) weeks. Three local recurrences occurred within 3 months, all could be cured surgically. The surgical treatment of chronic osteomyelitis in children requires a radical osseous debridement. The knowledge of different plastic-surgical procedures is necessary to reconstruct osseous and/or soft tissue defects.