Absorbing random walks interpolating between centrality measures on complex networks.
Centrality, which quantifies the importance of individual nodes, is among the most essential concepts in modern network theory. As there are many ways in which a node can be important, many different centrality measures are in use. Here, we concentrate on versions of the common betweenness and closeness centralities. The former measures the fraction of paths between pairs of nodes that go through a given node, while the latter measures an average inverse distance between a particular node and all other nodes. Both centralities only consider shortest paths (i.e., geodesics) between pairs of nodes. Here we develop a method, based on absorbing Markov chains, that enables us to continuously interpolate both of these centrality measures away from the geodesic limit and toward a limit where no restriction is placed on the length of the paths the walkers can explore. At this second limit, the interpolated betweenness and closeness centralities reduce, respectively, to the well-known current-betweenness and resistance-closeness (information) centralities. The method is tested numerically on four real networks, revealing complex changes in node centrality rankings with respect to the value of the interpolation parameter. Nonmonotonic betweenness behaviors are found to characterize nodes that lie close to intercommunity boundaries in the studied networks.


Charge order and three-site distortions in the Verwey structure of magnetite.
The mineral magnetite (Fe(3)O(4)) undergoes a complex structural distortion and becomes electrically insulating at temperatures less than 125 kelvin. Verwey proposed in 1939 that this transition is driven by a charge ordering of Fe(2+) and Fe(3+) ions, but the ground state of the low-temperature phase has remained contentious because twinning of crystal domains hampers diffraction studies of the structure. Recent powder diffraction refinements and resonant X-ray studies have led to proposals of a variety of charge-ordered and bond-dimerized ground-state models. Here we report the full low-temperature superstructure of magnetite, determined by high-energy X-ray diffraction from an almost single-domain, 40-micrometre grain, and identify the emergent order. The acentric structure is described by a superposition of 168 atomic displacement waves (frozen phonon modes), all with amplitudes of less than 0.24 ångströms. Distortions of the FeO(6) octahedra show that Verwey's hypothesis is correct to a first approximation and that the charge and Fe(2+) orbital order are consistent with a recent prediction. However, anomalous shortening of some Fe-Fe distances suggests that the localized electrons are distributed over linear three-Fe-site units, which we call 'trimerons'. The charge order and three-site distortions induce substantial off-centre atomic displacements and couple the resulting large electrical polarization to the magnetization. Trimerons may be important quasiparticles in magnetite above the Verwey transition and in other transition metal oxides.


Fosfomycin.
The treatment of bacterial infections suffers from two major problems: spread of multidrug-resistant (MDR) or extensively drug-resistant (XDR) pathogens and lack of development of new antibiotics active against such MDR and XDR bacteria. As a result, physicians have turned to older antibiotics, such as polymyxins, tetracyclines, and aminoglycosides. Lately, due to development of resistance to these agents, fosfomycin has gained attention, as it has remained active against both Gram-positive and Gram-negative MDR and XDR bacteria. New data of higher quality have become available, and several issues were clarified further. In this review, we summarize the available fosfomycin data regarding pharmacokinetic and pharmacodynamic properties, the in vitro activity against susceptible and antibiotic-resistant bacteria, mechanisms of resistance and development of resistance during treatment, synergy and antagonism with other antibiotics, clinical effectiveness, and adverse events. Issues that need to be studied further are also discussed.


[Clinical characteristics of digestive system cancers metastatic to the heart].
Objective: To investigate the clinical features of patients with cardiac metastases from digestive system tumors. Methods: This retrospective study collected and analyzed the medical records of patients with cardiac metastases from digestive system tumors who received treatments in the Cancer Hospital, Chinese Academy of Medical Sciences between January 1999 and January 2021. Kaplan-Meier method was used for survival analysis. Results: A total of 19 patients were identified. The primary tumors were esophageal squamous cell carcinoma (n=7), gastric or gastroesophageal junction adenocarcinoma (n=6), hepatobiliary cancers (n=3) and colorectal cancers (n=3). 16 patients had pericardial metastases, 2 patients had right atrium metastases, and 1 patient had left ventricle metastasis. The most common symptom was dyspnea, which was present in 8 cases. 7 patients received locoregional treatment, while 11 patients underwent systemic therapies. The median overall survival from diagnosis of primary cancer was 31.4 months, and the median overall survival time from diagnosis of cardiac metastasis was 4.7 months. Conclusion: Cardiac metastasis from digestive system tumors is associated with low incidence and a poor prognosis. Systemic treatment remains the cornerstone of management, while novel anti-tumor drugs may improve therapeutic efficacy.


Identification of a neurovirulence factor from Marek's disease virus.
In addition to tumors, Marek's disease (MD) virus (MDV) can induce a variety of syndromes linked to the central nervous system. In fact, early descriptions of MD suggested that it was a condition affecting mainly the nervous system. Cytokines and other immune-related genes have been suggested to play a crucial role in MDV-mediated neuropathology, but the mechanisms behind the viral-induced neurologic dysfunction are still poorly understood. In the present study we have used reverse genetic strategies to show that pp14 is not involved in the oncogenic phenotype of MDV1 and is not required for viral replication; however, we provide evidence indicating that the absence of pp14 expression is correlated with increased survival of MDV1-infected chickens, and that its expression is associated with enhanced viral neurovirulence. Our data identify for the first time pp14 as a neurovirulence factor from MDV1 and open the possibility to investigate the molecular mechanisms by which pp14 mediates the damage to the avian nervous system.


Sucrose monolaurate improves the efficacy of sodium hypochlorite against Escherichia coli O157:H7 on spinach.
It is well-recognized that chlorine has limited efficacy when applied to inactivate pathogens on fresh produce. One of the many factors limiting efficacy is the high interfacial tension of chlorine-based sanitizers that limits the access of chlorine to the microorganisms. In this work, we investigated the efficacy of sodium hypochlorite (200 ppm, pH 6.0) at 4 and 20 °C against Escherichia coli O157:H7 inoculated on baby spinach leaves as affected by the surfactant sucrose monolaurate (SML) at below (100 ppm), above (250 ppm), and well above (10,000 ppm) the critical micelle concentration (CMC) of ~200 ppm at 20 °C. The surfactant-containing chlorine treatments were compared to those with buffer only, surfactant only, and chlorine only. Significantly improved inactivation, as evidenced by survival of E. coli O157:H7 was achieved when 250 or 10,000 ppm SML was added with chlorine. This is attributed to the reduction of interfacial tension between the sanitizing solutions and spinach surface. Treatments at 20 °C resulted in greater mean inactivation than those at 4 °C but the difference was not significant. Comparisons of SML concentrations in treatment solutions before and after sanitization showed that SML decreased more at a lower temperature and when chlorine was present, resulting from adsorption of SML onto spinach matrix. Our work illustrates the importance of using surfactants at concentrations above the CMC to enhance the efficacy of chlorine sanitization.


An assessment of the interaction between human neutrophils, hydroxyapatite and dichloromethylene bisphosphonate in vitro: an electron microscopic and chemiluminescence study.
The potentially destructive effects of neutrophils, following particulate stimulus such as by hydroxyapatite (HA) crystals, may be pertinent to the progression of some inflammatory diseases, including rheumatoid arthritis. This study was designed to examine the interaction between pure hydroxyapatite particles and human neutrophil granulocytes by transmission electron microscopy and chemiluminescence (CL). The influence of dichloromethylene bisphosphonate (clodronate) in this model was investigated. Neutrophils convincingly phagocytosed HA particles within 15 min and a high CL response was elicited by the zymosan stimulated CL reaction. Clodronate alone appeared to have little effect on the cell morphology or CL. When HA was combined with clodronate, phagocytosis was more rapid, and the zymosan-stimulated CL was 50% of that of the HA group. The results demonstrate neutrophil phagocytosis of HA particles and subsequent cellular activation, which may play a role in the pathogenesis of tissue damage and suggest that the anti-inflammatory role of clodronate should be further investigated.


The social life of data points: Antecedents of digital technologies.
Recent technological advances such as microprocessors and random-access memory have had a significant role in gathering, storing and processing digital data, but the basic principles underpinning such data management were established in the century preceding the digital revolution. This paper maps the emergence of those older technologies to show that the logic and imperative for the surveillance potential of more recent digital technologies was laid down in a pre-digital age. The paper focuses on the development of the data point from its use in punch cards in the late 19th century through its manipulation in ideas about correlation to its collection via self-completion questionnaires. Some ways in which medicine and psychology have taken up and deployed the technology of data points are used as illustrative exemplars. The paper concludes with a discussion of the role of data points in defining human identity.


Reducing Cardiovascular Disease Risk in Women Beyond Statin Therapy: New Insights 2020.
Management of residual and persistent cardiovascular disease (CVD) risk among statin-treated individuals has emerged as an important preventive strategy. The purpose of this article is to review the unique landscape of CVD in women and relevant prior prevention trials, and to discuss how the recent results of the Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial (REDUCE-IT) might apply to the contemporary management of CVD risk among statin-treated women. Women have unique risk factors that may impact CVD and its prevention. Historically, women have been underrepresented in CVD trials, posing a challenge to development of clinical recommendations for women. Low-density lipoprotein cholesterol-targeting treatments have demonstrated CVD risk reduction, with comparable effects in both sexes. In contrast, triglyceride-lowering treatments (niacin, fenofibrate, and omega-3 fatty acids) have reported mixed findings for CVD risk reduction. Recent clinical trials of combination omega-3 fatty acids (docosahexaenoic acid/eicosapentaenoic acid [EPA]) have not found significant CVD risk reduction. The recently published REDUCE-IT study found that icosapent ethyl, an EPA-only omega-3 fatty acid, in combination with statins, significantly reduced CVD events in high-risk patients. The icosapent ethyl group had a significantly lower occurrence of the primary composite CVD endpoint (17.2%) than the placebo group (22.0%; hazard ratio 0.75; 95% confidence interval 0.68-0.83; p < 0.001). CVD risk reduction with icosapent ethyl treatment was comparable between women and men (p for interaction, 0.33). Data from REDUCE-IT suggest women benefit similarly to men with respect to icosapent ethyl, a novel therapy for prevention of CVD.


Targeted deletion of SAP1 abolishes the expression of infectivity factors necessary for successful malaria parasite liver infection.
Malaria parasite sporozoites prepare for transmission to a mammalian host by upregulation of UIS (Upregulated in Infectious Sporozoites) genes. A number of UIS gene products are essential for the establishment of the intrahepatocytic niche. However, the factors that regulate the expression of genes involved in gain of infectivity for the liver are unknown. Herein, we show that a conserved Plasmodium sporozoite low-complexity asparagine-rich protein, SAP1 (Sporozoite Asparagine-rich Protein 1), has an essential role in malaria parasite liver infection. Targeted deletion of SAP1 in the rodent malaria parasite Plasmodium yoelii generated mutant parasites that traverse and invade hepatocytes normally but cannot initiate liver-stage development in vitro and in vivo. Moreover, immunizations with Pysap1(-) sporozoites confer long-lasting sterile protection against wild-type sporozoite infection. Strikingly, lack of SAP1 abolished expression of essential UIS genes including UIS3, UIS4 and P52 but not the constitutively expressed genes encoding, among others, sporozoite proteins CSP and TRAP. SAP1 localization to the cell interior but not the nucleus of sporozoites suggests its involvement in a post-transcriptional mechanism of gene expression control. These findings demonstrate that SAP1 is essential for liver infection possibly by functioning as a selective regulator controlling the expression of infectivity-associated parasite effector genes.


Site-specific endonuclease AbaI from Azospirillum brasilense UQ 1796 is an isoschizomer of endonuclease BclI.
The site-specific endonuclease AbaI was isolated and purified to functional purity from the soil nitrogen-fixing bacterium Azospirillum brasilense UQ 1796. Purification included successive chromatography on columns with phosphocellulose, heparin-Sepharose, and hydroxyapatite. The purified enzyme recognizes the palindromic DNA sequence 5'-T decreases ATCA-3' and cleaves it as shown by the arrow. The isolated enzyme belongs to class II restriction endonuclease and is an isoschizomer of endonuclease BclI. The enzyme of AbaI is active at 26-56 degrees C. The optimal temperature is 48 degrees C and the optimal buffer is LRB.


Next-generation sequencing identifies rare variants associated with Noonan syndrome.
Noonan syndrome (NS) is a relatively common genetic disorder, characterized by typical facies, short stature, developmental delay, and cardiac abnormalities. Known causative genes account for 70-80% of clinically diagnosed NS patients, but the genetic basis for the remaining 20-30% of cases is unknown. We performed next-generation sequencing on germ-line DNA from 27 NS patients lacking a mutation in the known NS genes. We identified gain-of-function alleles in Ras-like without CAAX 1 (RIT1) and mitogen-activated protein kinase kinase 1 (MAP2K1) and previously unseen loss-of-function variants in RAS p21 protein activator 2 (RASA2) that are likely to cause NS in these patients. Expression of the mutant RASA2, MAP2K1, or RIT1 alleles in heterologous cells increased RAS-ERK pathway activation, supporting a causative role in NS pathogenesis. Two patients had more than one disease-associated variant. Moreover, the diagnosis of an individual initially thought to have NS was revised to neurofibromatosis type 1 based on an NF1 nonsense mutation detected in this patient. Another patient harbored a missense mutation in NF1 that resulted in decreased protein stability and impaired ability to suppress RAS-ERK activation; however, this patient continues to exhibit a NS-like phenotype. In addition, a nonsense mutation in RPS6KA3 was found in one patient initially diagnosed with NS whose diagnosis was later revised to Coffin-Lowry syndrome. Finally, we identified other potential candidates for new NS genes, as well as potential carrier alleles for unrelated syndromes. Taken together, our data suggest that next-generation sequencing can provide a useful adjunct to RASopathy diagnosis and emphasize that the standard clinical categories for RASopathies might not be adequate to describe all patients.


Secondary metabolites and bioactivities from higher fungi in China.
Higher fungi (i.e. macrofungi) do not form a natural taxonomic or ecological group. They are defined as those fungi that produce large, easily observed and collected sporocarps. Most of the higher fungi species are from the phyla Basidiomycota and Ascomycota. These fungi are of particular interest because of their importance as food resource and culture component in many places of the world. Therefore, study of their diverse natural products has become a hot topic. China has the most diverse fungi in the world. We investigated the chemical constituents of Basidiomycetes and Ascomycetes from China, and our ongoing search bioactive metabolites from higher fungi could potentially be developed into new 'lead' compounds. We review the isolation, structural elucidation and biologically activity of the rich natural products newly derived from higher fungi collected in China after July 2007.


Anxiolytic effect of estradiol in the median raphe nucleus mediated by 5-HT1A receptors.
Estrogen deficiency has been associated with stress, anxiety and depression. Estrogen receptors have been identified in the median raphe nucleus (MRN). This structure is the main source of serotonergic projections to the hippocampus, a forebrain area implicated in the regulation of defensive responses and in the resistance to chronic stress. There is evidence showing that estrogen modulates 5-HT1A receptor functions. In the MRN, somatodendritic 5-HT1A receptors control the activity of serotonergic neurones by negative feedback. The present study evaluated the effect of intra-MRN injection of estradiol benzoate (EB) (600 or 1200ng/0.2microl) on the performance of ovariectomised rats submitted to the elevated plus-maze test of anxiety and to the open-field test. Additionally, the same effect was evaluated with a previous intra-MRN injection of WAY 100635(100ng/0.2microl), an antagonist of 5-HT1A receptors. The results showed that both doses of EB increased the percentage of entries and the percentage of time spent into the open arms, suggestive of an anxiolytic effect. The highest dose of the drug also increased the number of entries into the enclosed arm and locomotion in the open field, indicating a stimulatory motor effect. WAY 100635 antagonised the effect of estradiol in the elevated plus-maze and in the open-field. The results show that estrogen receptors of the MRN are implicated in the regulation of anxiety-related behaviour. The results also support claims that the effect of estrogen involves a change in 5-HT1A receptor function.


Simultaneous unilateral moyamoya disease and ipsilateral dural arteriovenous fistula: case report.
Previous reports have described an association between moyamoya disease and arteriovenous malformations, but this unusual case is the first report of a unilateral moyamoya pattern simultaneously associated with an ipsilateral dural arteriovenous fistula (dAVF). A 44-year-old man presented with headache, tinnitus, and an intraventricular hemorrhage, as seen on computed tomographic scans. Cerebral angiography showed a right moyamoya pattern and an ipsilateral dAVF fed by branches of the external carotid artery and draining into the transverse sinus. After the intraventricular hemorrhage resolved, the patient underwent transarterial embolization of the dAVF with Onyx (EV3, Inc. Irvine, CA), followed by a direct superficial temporal artery-to-middle cerebral artery bypass. Subsequent reconstitution of the dAVF required transvenous embolization, which obliterated the dAVF. At his 2-month follow-up examination, the patient was asymptomatic and neurologically intact. Recent investigations have established that both moyamoya disease and dAVFs are associated with dural angiogenesis. These factors may represent a mechanism for vaso-occlusive ischemia contributing to the formation of dAVF. This extremely rare coincidental presentation may have deeper pathogenic implications.


Molecular basis of auxin-regulated extension growth and role of dextranase.
The first step in the extension growth of the plant cell is a process in which the cell wall becomes ductile or plastic, after which the actual enlargement takes place passively under the influence of turgor. The nature of this process has not been explained, although much research has been carried out concerning it. In the present report, it is shown that a specific enzyme, which is identical or nearly so with dextranase (alpha-1,6-D-glucan 6-glucanohydrolase, EC 18.104.22.168) and is associated with the cell walls of growing coleoptiles, plays a prominent role in this process. The action of this enzyme is dependent on the level of growth hormone, auxin, in the tissue. Under its action, certain cell wall components are broken down to yield arabinose and glucose. These sugars are also released during autolysis of cell wall material. The molecular linkages broken in the process are probably the arabinogalactan crosslinks of the hemicellulose matrix, which are the main constituents of the wall containing arabinose. This is substantiated by the finding that dextranase can break down arabinan and compounds containing arabinose chains with the release of arabinose, just as in the action of the enzyme on the wall. The breaking of these crosslinks will impart the necessary plasticity to the wall for cell extension to occur.


Relapsing and remitting multiple sclerosis: pathology of the newly forming lesion.
The study describes the clinical and pathological findings in 12 patients with relapsing and remitting multiple sclerosis, who died during or shortly after the onset of a relapse. Pathological changes not previously associated with the formation of new symptomatic lesions were observed in seven cases, namely, extensive oligodendrocyte apoptosis and microglial activation in myelinated tissue containing few or no lymphocytes or myelin phagocytes. No current laboratory model of multiple sclerosis, in particular, experimental allergic encephalomyelitis, is known with these features, which raises the possibility of some novel process underlying new lesion formation in multiple sclerosis.


Physical exercise for the prevention and treatment of type 2 diabetes.
The prevalence of type 2 diabetes is rapidly increasing worldwide, yet its primary prevention and treatment are still a challenge. The objectives of this review are to assess the effects of exercise on the prevention of type 2 diabetes in high-risk individuals and on glycaemic control in type 2 diabetic patients. Considering the available reports, there is unequivocal and strong evidence that physical exercise can prevent or delay progression to type 2 diabetes in subjects with impaired glucose tolerance. Also, lifestyle interventions, including diet and physical exercise, can result in a reduction of around 50% in diabetes incidence that persists even after the individual lifestyle counselling has stopped. In addition, short-term randomized studies have confirmed that physical training based on endurance and/or resistance exercises can also improve blood glucose control in type 2 diabetics with a mean glycated haemoglobin decrease of 0.6%. Thus, physical exercise should be part of any therapeutic strategy to slow the development of type 2 diabetes in high-risk individuals and to improve glucose control in type 2 diabetes.


Preferential flow estimates to an agricultural tile drain with implications for glyphosate transport.
Agricultural subsurface drains, commonly referred to as tile drains, are potentially significant pathways for the movement of fertilizers and pesticides to streams and ditches in much of the Midwest. Preferential flow in the unsaturated zone provides a route for water and solutes to bypass the soil matrix and reach tile drains faster than predicted by traditional displacement theory. This paper uses chloride concentrations to estimate preferential flow contributions to a tile drain during two storms in May 2004. Chloride, a conservative anion, was selected as the tracer because of differences in chloride concentrations between the two sources of water to the tile drain, preferential and matrix flow. A strong correlation between specific conductance and chloride concentration provided a mechanism to estimate chloride concentrations in the tile drain throughout the storm hydrographs. A simple mixing analysis was used to identify the preferential flow component of the storm hydrograph. During two storms, preferential flow contributed 11 and 51% of total storm tile drain flow; the peak contributions, 40 and 81%, coincided with the peak tile drain flow. Positive relations between glyphosate [N-(phosphonomethyl)glycine] concentrations and preferential flow for the two storms suggest that preferential flow is an important transport pathway to the tile drain.


In vitro pharmacokinetic phantom for two-compartment modeling in DCE-MRI.
Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is an established minimally-invasive method for assessment of extravascular leakage, hemodynamics, and tissue viability. However, differences in acquisition protocols, variety of pharmacokinetic models, and uncertainty on physical sources of MR signal hamper the reliability and widespread use of DCE-MRI in clinical practice. Measurements performed in a controlled in vitro setup could be used as a basis for standardization of the acquisition procedure, as well as objective evaluation and comparison of pharmacokinetic models. In this paper, we present a novel flow phantom that mimics a two-compartmental (blood plasma and extravascular extracellular space/EES) vascular bed, enabling systemic validation of acquisition protocols. The phantom consisted of a hemodialysis filter with two compartments, separated by hollow fiber membranes. The aim of this phantom was to vary the extravasation rate by adjusting the flow in the two compartments. Contrast agent transport kinetics within the phantom was interpreted using two-compartmental pharmacokinetic models. Boluses of gadolinium-based contrast-agent were injected in a tube network connected to the hollow fiber phantom; time-intensity curves (TICs) were obtained from image series, acquired using a T1-weighted DCE-MRI sequence. Under the assumption of a linear dilution system, the TICs obtained from the input and output of the system were then analyzed by a system identification approach to estimate the trans-membrane extravasation rates in different flow conditions. To this end, model-based deconvolution was employed to determine (identify) the impulse response of the investigated dilution system. The flow rates in the EES compartment significantly and consistently influenced the estimated extravasation rates, in line with the expected trends based on simulation results. The proposed phantom can therefore be used to model a two-compartmental vascular bed and can be employed to test and optimize DCE-MRI acquisition sequences in order to determine a standardized acquisition procedure leading to consistent quantification results.


Arginine metabolism in insects. Role of arginase in proline formation during silkmoth development.
1. Ornithine delta-transaminase (l-ornithine-2-oxo acid aminotransferase, EC 188.8.131.52) and Delta(1)-pyrroline-5-carboxylate reductase [l-proline-NAD(P) 5-oxidoreductase, EC 220.127.116.11] were demonstrated in fat-body and flight-muscle tissues of the silkmoth Hyalophora gloveri. Arginase (l-arginine ureohydrolase, EC 22.214.171.124) is also present in these tissues. 2. Arginase, ornithine transaminase and pyrroline-carboxylate reductase are generally considered to make up the catabolic pathway for the conversion of arginine into proline. The conversion of l-[U-(14)C]arginine into [(14)C]proline by intact fat-body tissue was used to show that the enzymes in insect fat body also function in this capacity. 3. Of the three enzymes of the catabolic pathway, only arginase increased during adult development and the increase coincided with the emergence of the winged adult moth. Since proline appears to be a major substrate utilized in insect flight metabolism, the increase in arginase activity at this stage suggests a major role for arginase in proline formation.


Genome sequencing and analysis reveals possible determinants of Staphylococcus aureus nasal carriage.
Nasal carriage of Staphylococcus aureus is a major risk factor in clinical and community settings due to the range of etiologies caused by the organism. We have identified unique immunological and ultrastructural properties associated with nasal carriage isolates denoting a role for bacterial factors in nasal carriage. However, despite extensive molecular level characterizations by several groups suggesting factors necessary for colonization on nasal epithelium, genetic determinants of nasal carriage are unknown. Herein, we have set a genomic foundation for unraveling the bacterial determinants of nasal carriage in S. aureus. MLST analysis revealed no lineage specific differences between carrier and non-carrier strains suggesting a role for mobile genetic elements. We completely sequenced a model carrier isolate (D30) and a model non-carrier strain (930918-3) to identify differential gene content. Comparison revealed the presence of 84 genes unique to the carrier strain and strongly suggests a role for Type VII secretion systems in nasal carriage. These genes, along with a putative pathogenicity island (SaPIBov) present uniquely in the carrier strains are likely important in affecting carriage. Further, PCR-based genotyping of other clinical isolates for a specific subset of these 84 genes raise the possibility of nasal carriage being caused by multiple gene sets. Our data suggest that carriage is likely a heterogeneic phenotypic trait and implies a role for nucleotide level polymorphism in carriage. Complete genome level analyses of multiple carriage strains of S. aureus will be important in clarifying molecular determinants of S. aureus nasal carriage.


Headache and Bilateral Optic Disc Edema as the Initial Manifestation of Vogt-Koyanagi-Harada Disease.
A 31-year-old healthy Asian man presented with new headaches and blurred vision. He was found to have bilateral optic disc edema (ODE) and peripapillary subretinal fluid and was initially investigated for causes of raised intracranial pressure. After referral to neuro-ophthalmology, he received a diagnosis of Vogt-Koyanagi-Harada (VKH) disease and his symptoms, ODE, and vision improved promptly with prednisone treatment. HLA typing was performed and returned positive for the HLA-DRB1*04 subtype. Although VKH disease usually presents with granulomatous uveitis or serous retinal detachments, ODE may manifest early in the disease course. Those with ODE in VKH disease are believed to be older and female, but this case demonstrates that these findings were also seen in a young man.


Repair of diaphragmatic hernias: Retrospective analysis of 70 cases.
Congenital and traumatic diaphragmatic hernias (DH) can lead to respiratory and gastrointestinal complications that can be the cause of serious morbidity and mortality. In this study, we aimed to share our experience with the surgical repair of complicated or non-complicated DH. Patients who were operated on under emergency or elective conditions with the diagnosis of DH between 2009 and 2023 were analyzed retrospectively. Demographic characteristics, histories, symptoms, etiology of DH, computed tomography find-ings, surgical techniques, and postoperative outcomes of the patients were recorded. The mean age of the cases was 51.5±18.5, and 29 were female and 41 were male. Hernia etiology was found to be con-genital (40%), traumatic (32.8%), spontaneous (14.3%), and iatrogenic (12.8%), respectively. The mean diameter of the defects was 7.3±2.76 cm (range: 3-15 cm), and 84% of the defects were on the left side. Sixty percent of the cases were treated by laparoscopic surgery and 11.4% by laparotomy. The conversion rate from laparoscopic to open was 24.3%. Dual mesh was used in 48% of the pa-tients, and primary suturing was applied in 34%. The postoperative mortality rate was 7.1%. DH is an important cause of morbidity and mortality due to abdominal organ strangulation and pulmonary and cardiac complications. When a DH is diagnosed, laparoscopic or open surgery is the treatment that should be preferred.


Quantitative analysis of redox-sensitive proteome with DIGE and ICAT.
Oxidative modifications of protein thiols are important mechanisms for regulating protein functions. The present study aimed to compare the relative effectiveness of two thiol-specific quantitative proteomic techniques, difference gel electrophoresis (DIGE) and isotope coded affinity tag (ICAT), for the discovery of redox-sensitive proteins in heart tissues. We found that these two methods were largely complementary; each could be used to reveal a set of unique redox-sensitive proteins. Some of these proteins are low-abundant signaling proteins and membrane proteins. From DIGE analysis, we found that both NF-kappaB-repressing protein and epoxide hydrolase were sensitive to H 2O 2 oxidation. In ICAT analysis, we found that specific cysteines within sacroplasmic endoplamic reticulum calcium ATPase 2 and voltage-dependent anion-selective channel protein 1 were sensitive to H 2O 2 oxidation. From these analyses, we conclude that both methods should be employed for proteome-wide studies, to maximize the possibility of identifying proteins containing redox-sensitive cysteinyl thiols in complex biological systems.


Specific 13C functional pathways as diagnostic targets in gastroenterology breath-tests: tricks for a correct interpretation.
Breath tests are non-invasive, non-radioactive, safe, simple and effective tests able to determine significant metabolic alterations due to specific diseases or lack of specific enzymes. Carbon isotope (13)C, the stable-non radioactive isotope of carbon, is the most used substrate in breath testing, in which (13)C/(12)C ratio is measured and expressed as a delta value, a differences between readings and a fixed standard. (13)C/(12)C ratio is measured with isotope ratio mass spectrometry or non-dispersive isotope-selective infrared spectrometer and generally there is a good agreement between these techniques in the isotope ratio estimation. (13)C/(12)C ratio can be expressed as static measurement (like delta over baseline in urea breath test) or as dynamic measurement as percent dose recovery, but more dosages are necessary. (13)C Breath-tests are involved in many fields of interest within gastroenterology, such as detection of Helicobacter pylori infection, study of gastric emptying, assessment of liver and exocrine pancreatic functions, determination of oro-caecal transit time, evaluation of absorption and to a lesser extend detection of bacterial overgrowth. The use of every single test in a clinical setting is vary depending on accuracy and substrate costs. This review is meant to present (13)C the meaning of (13)C/(12)C ratio and static and dynamic measure and, finally, the instruments dedicated to its use in gastroenterology. A brief presentation of (13)C breath tests in gastroenterology is also provided.


Transverse sinus septum: a new aetiology of idiopathic intracranial hypertension?
A venographic cryptic stenosis at the junction of middle and lateral third of the transverse sinus has been observed in patients suffering from idiopathic intracranial hypertension. After reviewing the anatomical and embryological literature of the transverse sinus, 20 transverse sinuses were explored (in a pilot study of 10 human cadavers) in order to determine the anatomical basis of this stenosis. The presence of septa of varying sizes was observed. We conclude that the presence of a large septum is one of the causes of venographic cryptic stenosis observed in these patients and might be one of the aetiological factors involved in idiopathic intracranial hypertension.


Exploring the responsiveness of public and private hospitals in lagos, Nigeria.
According to the World Health Report 2000, health system responsiveness is proposed as one of the three key objectives of any health system. This multi-domain concept describes how well a health system responds to the expectations of their users concerning the non-health enhancing aspects of care. In this study we aim to compare the levels of responsiveness experienced by users of private and publicly managed hospitals in Nigeria, and through these insights, to propose recommendations on how to improve performance on this measure. This quantitative, cross-sectional study uses a questionnaire that is adapted from two responsiveness surveys designed by the World Health Organization (WHO). Researchers collected responses from 520 respondents from four hospitals in Lagos, Nigeria. Analysis of the data using statistical techniques found that significant differences exist between the performance of public and private hospitals on certain domains of responsiveness, with privately operated hospitals performing better where differences exist. Users of private hospitals also reported a higher level of overall satisfaction. Private hospitals were found to perform particularly better on the domains of dignity, waiting times, and travel times. These findings have implications for the management of public hospitals in focusing their efforts on improving their performance in low scoring domains. Performance in these hospitals can be improved by emphasis on staff training and demand management.


Experiences, views and needs of first-time fathers in pregnancy-related care: a qualitative study in south-East Nigeria.
Given the relevance of paternal involvement in maternal care, there is a need to prepare first-time fathers to participate in pregnancy and childbirth actively. This study explores the experiences and needs of first-time fathers; and how these influences their involvement during pregnancy and childbirth in Nigeria. A descriptive qualitative study was conducted. Semi-structured interviews with 50 men recruited from rural and urban workplaces, hospitals, and markets, generated data used to explore the experiences, views and needs of first-time fathers' in pregnancy-related care in south-east Nigeria. All data were transcribed and analysed using thematic analysis. Six major themes were identified: gender roles, antenatal involvement, care costs and delivery choices, need to be informed, dealing with emotions, and dealing with the delivery day. The key finding reveals that inexperience and perceptions of gender roles greatly influenced the support provided by first-time fathers to their spouses and the support they received from their social support networks. Two primary needs were identified: need to be informed and the need to know about the cost of care in health settings. First-time fathers acknowledged the role of information on their decision making and final choices. Findings reveal the influence of gender norms, beliefs, and social support on first-time fathers' involvement in pregnancy and childbirth. This study also highlights the urgent need to provide informational support for first-time fathers and presents insights into what hospitals can do to achieve this need.


Bloodstream yeast infections in a university hospital in Northeast Turkey: a 4-year survey.
This study presents data on species distribution and antifungal susceptibility profiles of Candida bloodstream isolates obtained from a Turkish Tertiary Care Hospital during a 4-year period. All hospitalized patients who had ≥ 1 blood culture positive for yeast during their hospital stay from January 2005 through 2009 were included in this study. All isolates were identified to species level using CHROMagar and ID 32 C. Fluconazole and voriconazole antifungal susceptibility testing was performed using the disk diffusion method according to CLSI M44-A. In vitro activity of amphotericin B was determined by the Etest. Of all 166 yeast isolates, C. albicans was the dominant species (34.3%), followed by Candida parapsilosis (28.9%) and C. tropicalis (8.4%). All of the 48 C. parapsilosis strains were identified as C. parapsilosis sensu stricto. Resistance to fluconazole was more common among C. krusei isolates. Voriconazole resistance was absent. One C. lusitaniae strain showed a high amphotericin MIC (4 μg/ml). Our survey indicated an increase of some non-C. albicans Candida species in our hospital while antifungal resistance was uncommon.


An integral blood-brain barrier in adulthood relies on microglia-derived PDGFB.
Pericyte is an indispensable cellular constituent of blood-brain barrier (BBB) and its homeostasis heavily rely on PDGFB-PDGFRβ signaling. However, the primary cellular sources of PDGFB in the central nervous system (CNS) are unclear. Microglia is not considered a component of BBB and its role in maintaining BBB integrity in steady state is controversial. In this study, by analyzing transcriptomic data and performing in situ hybridization, we revealed a transition of the primary central PDGFB producers from endothelial cells in newborns to microglia in adults. Acute loss of microglial PDGFB profoundly impaired BBB integrity in adult but not newborn mice, and thus, adult mice deficient of microglial PDGFB could not survive from a sublethal endotoxin challenge due to rampant microhemorrhages in the CNS. In contrast, acute abrogation of endothelial PDGFB had minimal effects on the BBB of adult mice but led to a severe impairment of CNS vasculature in the neonates. Moreover, we found that microglia would respond to a variety of BBB insults by upregulating PDGFB expression. These findings underscore the physiological importance of the microglia-derived PDGFB to the BBB integrity of adult mice both in steady state and under injury.


Using HMOs to serve the Medicaid population: what are the effects on utilization and does the type of HMO matter?
States have increasingly used Health Maintenance Organizations (HMOs) to provide medical services to the Medicaid population. However, the effects of these initiatives on total health-care expenses, the mix of utilization, and access to care remain unclear. We examine the effect of changes in Medicaid HMO penetration between 1996 and 2002 on these outcomes using data for the nonelderly Medicaid population in the Community Tracking Study's Household Survey. We develop market-level measures of Medicaid HMO penetration from CMS and InterStudy data, distinguish whether the HMOs specialize in serving the Medicaid population, and use a market fixed-effects model to focus on changes in HMO penetration rates over time. Although limited by imprecise estimates, we find some evidence that utilization and access are related to the market penetration rates of commercial and Medicaid-dominant HMOs, but the pattern of results we observe does not appear to be consistent with welfare improvements.


Relationship Between Biotype and Bone Morphology in the Lower Anterior Mandible: An Observational Study.
Different clinical parameters have been advocated as potential predictors of alveolar and basal jawbone morphology. The aim of this study is to describe, by tomographic means, alveolar and basal osseous dimensions of the anterior mandible in healthy individuals and evaluate potential correlations with biotype, along with other clinical parameters. One hundred consecutive healthy patients needing surgery in the posterior mandible were enrolled in this observational study (group 1 = 50 patients with thin biotype; group 2 = 50 patients with thick biotype). Data were collected for: 1) Little irregularity index for anterior crowding; 2) molar and canine class relationship; 3) previous orthodontic treatment; 4) gingival recession; and 5) band of keratinized gingiva for each of the six anterior mandibular teeth (#22 through #27). At the most mid-buccal computerized tomography slice of each tooth, other parameters were measured, including: 1) distance from the cemento-enamel junction to the bone crest; 2) tooth torque (TT); 3) labial cortical bone thickness (BT) for alveolar and basal bone; and 4) BT 5 and 10 mm apical to the tooth apex. Data were statistically analyzed, and significance was set at P ≤0.05. Mean thickness of alveolar bone ranged from 6.66 to 4.51 mm (standard deviation [SD] = 1.46 for tooth #27; SD = 1.01 for tooth #25) whereas mean thickness of basal bone ranged from 8.9 to 8.2 mm (SD = 2.06 for tooth #22; SD = 2.06 for tooth #26). Mean thickness of bone at 5 mm from apex ranged from 11.94 to 10.47 mm (SD = 2.96 for tooth #25; SD = 2.22 for tooth #22), whereas mean thickness of bone at 10 mm from apex ranged from 13.75 to 11.08 mm (SD = 2.79 for tooth #25; SD = 2.53 for tooth #27). No statistically significant differences were detected among biotypes, whereas: 1) TT, 2) age, and 3) smoking habit were often predictors of reduction in BT in a multiple linear regression model. Male sex was often a predictor of positive changes in BT, and previous orthodontic therapy was a protective factor against developing bone loss >5 mm. Although some differences were detected among biotypes, data indicate that biotype does not play a fundamental role in influencing alveolar BT, whereas other variables (i.e., TT, sex, age, and smoking habit) do influence alveolar BT. Further studies are needed to better understand the extent of influence of each clinical variable.


Disorganization of F-actin cytoskeleton precedes vacuolar disruption in pollen tubes during the in vivo self-incompatibility response in Nicotiana alata.
The integrity of actin filaments (F-actin) is essential for pollen-tube growth. In S-RNase-based self-incompatibility (SI), incompatible pollen tubes are inhibited in the style. Consequently, research efforts have focused on the alterations of pollen F-actin cytoskeleton during the SI response. However, so far, these studies were carried out in in vitro-grown pollen tubes. This study aimed to assess the timing of in vivo changes of pollen F-actin cytoskeleton taking place after compatible and incompatible pollinations in Nicotiana alata. To our knowledge, this is the first report of the in vivo F-actin alterations occurring during pollen rejection in the S-RNase-based SI system. The F-actin cytoskeleton and the vacuolar endomembrane system were fluorescently labelled in compatibly and incompatibly pollinated pistils at different times after pollination. The alterations induced by the SI reaction in pollen tubes were visualized by confocal laser scanning microscopy. Early after pollination, about 70 % of both compatible and incompatible pollen tubes showed an organized pattern of F-actin cables along the main axis of the cell. While in compatible pollinations this percentage was unchanged until pollen tubes reached the ovary, pollen tubes of incompatible pollinations underwent gradual and progressive F-actin disorganization. Colocalization of the F-actin cytoskeleton and the vacuolar endomembrane system, where S-RNases are compartmentalized, revealed that by day 6 after incompatible pollination, when the pollen-tube growth was already arrested, about 80 % of pollen tubes showed disrupted F-actin but a similar percentage had intact vacuolar compartments. The results indicate that during the SI response in Nicotiana, disruption of the F-actin cytoskeleton precedes vacuolar membrane breakdown. Thus, incompatible pollen tubes undergo a sequential disorganization process of major subcellular structures. Results also suggest that the large pool of S-RNases released from vacuoles acts late in pollen rejection, after significant subcellular changes in incompatible pollen tubes.


A Four-Channel Broadband MRI Receive Array Coil.
Low-impedance preamplifier decoupling is commonly used in RF coil array construction to minimize coupling between elements through mutual impedance. The trap circuit is an essential component in preamp decoupling techniques, but becomes a limiting factor in constructing multi-tuned, multi-nuclear coil arrays. In principle, it is possible to double-tune or multi-tune the trap circuits, but will add complexity and loss. We present a broadband decoupling approach using high impedance preamplifiers. A dual-tuned prototype four-channel array using this approach which targets 2H and 23 Na at 4.7T, has been previously constructed, evaluated and reported. Without any retuning of the array, the same setup is tested at the 23Na and 31P frequencies for 3T. Initial bench measurements and Chemical Shift Imaging (CSI) results are acquired and presented in this study.Clinical Relevance- This study could reduce the complexity of multi-nuclear array coil design.


Single-cell transcriptome profiling of primary tumors and paired organoids of pancreatobiliary cancer.
Single-cell RNA-seq (scRNA-seq) and cancer organoid model have shown promise in investigating tumor microenvironment heterogeneity and facilitating chemotherapeutic drug testing to inform treatment selection. It is still unknown whether the scRNA-seq results based on organoid can faithfully reflect the heterogeneity of primary pancreatobiliary cancer. To reveal the similarities and differences between primary tumors and their matched organoids at transcriptome level, we conducted scRNA-seq for paired primary tumors and organoids from one cholangiocarcinoma (CCA) and two pancreatic ductal adenocarcinoma (PDAC) patients. We identified inter-patient and intra-tumor heterogeneity and found that the organoids retained copy number variation (CNV) patterns of primary tumors. There was no significant difference in cancer stem cell (CSC) properties between the primary tumors and the organoids, whereas organoid from one PDAC case had increased mesenchymal-score and decreased epithelial-score compared with the primary tumors. All organoids showed a transition tendency from the classical subtype to the basal-like subtype in the transcriptional level. Organoids and primary tumors differed in metabolic and unfolded protein response (UPR) signatures. In addition, we revealed the heterogeneity of cancer associated fibroblasts (CAFs) and T cells, and explored the developmental trajectory of T cells. Our findings facilitate further understanding of organoid model and confirm its application prospects in pancreatobiliary cancer.


Structural heterogeneity in p30 molecules of type C viruses.
Tryptic digests of p30 proteins from mouse type C viruses were subjected to cation-exchange chromatography. Structural heterogeneity of p30 molecules was seen in two specific areas of the peptide elution profiles. These hypervariable regions of p30 proteins were used to discriminate representative ecotropic (N- and B-tropic), xenotropic (alpha and beta) and amphotropic viruses.


Microbiology of urinary tract infections in Gaborone, Botswana.
The microbiology and epidemiology of UTI pathogens are largely unknown in Botswana, a high prevalence HIV setting. Using laboratory data from the largest referral hospital and a private hospital, we describe the major pathogens causing UTI and their antimicrobial resistance patterns. This retrospective study examined antimicrobial susceptibility data for urine samples collected at Princess Marina Hospital (PMH), Bokamoso Private Hospital (BPH), or one of their affiliated outpatient clinics. A urine sample was included in our dataset if it demonstrated pure growth of a single organism and accompanying antimicrobial susceptibility and subject demographic data were available. A total of 744 samples were included. Greater than 10% resistance was observed for amoxicillin, co-trimoxazole, amoxicillin-clavulanate, and ciprofloxacin. Resistance of E. coli isolates to ampicillin and co-trimoxazole was greater than 60% in all settings. HIV status did not significantly impact the microbiology of UTIs, but did impact antimicrobial resistance to co-trimoxazole. Data suggests that antimicrobial resistance has already emerged to most oral antibiotics, making empiric management of outpatient UTIs challenging. Ampicillin, co-trimoxazole, and ciprofloxacin should not be used as empiric treatment for UTI in this context. Nitrofurantoin could be used for simple cystitis; aminoglycosides for uncomplicated UTI in inpatients.


Stereotyping. Physical and occupational therapists characterize themselves and each other.
Physical therapists (n = 53) and occupational therapists (n = 53) appraised themselves and each other by selecting personal and job-based adjectives (54 pairs) on the Health Team Stereotype Scale. The PTs' self-appraisal differed statistically from the OTs' perception of PTs on 31 adjective pairs (57%). The OTs judged PTs as having fewer of the qualities PTs professed on 16 pairs. On 15 pairs, the OTs chose negative adjectives, whereas the PTs chose the positive. The OTs' self-assessment differed statistically from the PTs' perception of OTs on 24 pairs. The PTs perceived OTs as having fewer of the positive adjectives than did the OTs. The PTs' and OTs' self-assessments differed statistically on pairs such as Strong-Weak, Intelligent-Unintelligent, and Aggressive-Passive, with the PTs' mean scores being higher than the OTs'. Overall, the PTs' self-appraisal mean scores were higher than the OTs'. The extent of differences perceived by another profession may explain team conflict or team effectiveness.


Children and sports medicine in the 1990s.
Sports participation is an opportunity for children of all ages to improve their fitness, level of maturation, and physical and psychologic condition. A primary physician can play a significant role in promoting enhanced physical fitness in the office or as a team doctor.


Taking Charge: A Proposed Psychological Intervention to Improve Pulmonary Rehabilitation Outcomes for People with COPD.
Pulmonary rehabilitation (PR) is an important, evidence-based treatment that improves outcomes for people with COPD. Individualized exercise programmes aim to improve exercise capacity; self-management education and psychological support are also provided. Translating increased exercise capacity into sustained behavioural change of increased physical activity is difficult. Other unresolved problems with PR programmes include improving uptake, completion, response and sustaining long-term benefit. We offer a different perspective drawn from clinical experience of PR, quantitative and qualitative studies of singing groups for people with COPD, and stroke rehabilitation research that gives psychological factors a more central role in determining outcomes after PR. We discuss Take Charge; a simple but effective psychological intervention promoting self-management--that could be used as part of a PR programme or in situations where PR was declined or unavailable. This may be particularly relevant now when traditional face-to-face group programmes have been disrupted by COVID-19 precautions.


Rural-urban difference in the prevalence of hypertension in West Africa: a systematic review and meta-analysis.
Urbanisation is considered a major contributor to the rising prevalence of hypertension in West Africa, yet the evidence regarding rural-urban differences in the prevalence of hypertension in the region has been mixed. A systematic literature search of four electronic databases: PubMed, Embase, African Journals Online, and WHO's African Index Medicus; and reference lists of eligible studies was carried out. Original quantitative studies describing the rural-urban difference in the prevalence of hypertension in one or more countries in West Africa, and published in English language from the year 2000 to 2021 were included. A random effects meta-analysis model was used to estimate the odds ratio of hypertension in rural compared to urban locations. A limited sex-based random effects meta-analysis was conducted with 16 studies that provided sex-disaggregated data. Of the 377 studies screened, 22 met the inclusion criteria (n = 62,907). The prevalence of hypertension was high in both rural, and urban areas, ranging from 9.7% to 60% in the rural areas with a pooled prevalence of 27.4%; and 15.5% to 59.2% in the urban areas with a pooled prevalence of 33.9%. The odd of hypertension were lower in rural compared to urban dwellers [OR 0.74, 95% CI: 0.66-0.83; p < 0.001]. The pooled prevalence of hypertension was 32.6% in males, and 30.0% in females, with no significant difference in the odds of hypertension between the sexes [OR 0.91, 95% CI: 0.8-1.05, p = 0.196]. Comprehensive hypertension control policies are needed for both rural, and urban areas in West Africa, and for both sexes.


False-positive results in immunoglobulin M (IgM) toxoplasma antibody tests and importance of confirmatory testing: the Platelia Toxo IgM test.
Although tests for detection of immunoglobulin M (IgM) toxoplasma antibodies have been reported to have a high degree of accuracy, it is well recognized by investigators in the United States and Europe that false-positive results may occur with many of these tests, at times to an alarming degree. Unfortunately, this information is not well documented in the literature. Studies on various toxoplasma IgM test kits are frequently flawed. The investigators often use reference tests which have not previously been carefully evaluated as well as sera that were not appropriate to answer the question of how often false-positive results might occur. We recently had the unique opportunity to evaluate the accuracy of the Platelia Toxo IgM test in 575 serum samples obtained during an outbreak of toxoplasmosis which occurred in 1995 in the Capital Regional District of British Columbia, Canada. When compared with results obtained in a reference IgM enzyme-linked immunosorbent assay (ELISA), the Platelia Toxo IgM test had a sensitivity of 99.4%, specificity of 49.2%, positive predictive value of 51.9%, negative predictive value of 99.3%, and an overall agreement of 67.0%. In an attempt to resolve discrepancies between these two tests, a serological profile (Sabin-Feldman dye test, IgA and IgE antibody tests, differential agglutination [AC/HS] test, and IgG avidity method) was performed. Of 153 serum samples that were positive in the Platelia Toxo IgM test and negative in the IgM ELISA, 71 (46.4%) were negative in the Sabin-Feldman dye test. Of the serum samples that were positive in the dye test, 77 (93.9%) had a serological profile most compatible with an infection acquired in the distant past. These results reveal high numbers of false-positive results in the Platelia Toxo IgM test and highlight the importance of appropriate evaluation of commercial tests that are currently being marked. Our results also emphasize the importance of confirmatory testing to determine whether the results of an IgM antibody test reflect the likelihood of a recently acquired infection.


Bone Density, Geometry, and Mass by Peripheral Quantitative Computed Tomography and Bone Turnover Markers in Children with Diabetes Mellitus Type 1.
The type 1 diabetes mellitus (T1DM) is a chronic systemic autoimmune-mediated disease characterised by the insulin deficiency and hyperglycaemia. Its deleterious effect on bones concerns not only bone mass, density, and fracture risk but also may involve the linear growth of long bones. Studies on the lower leg in children with T1DM by pQCT have generated conflicting results, and most of the studies published so far focused only on a selected features of the bone. An additional information about growth, modelling, and remodelling processes can be gathered by the bone turnover marker measurement. The objective of the study was to evaluate bone mineral density, mass, and geometry using peripheral quantitative computed tomography as well as bone turnover markers in the patients with type 1 diabetes mellitus. Material and Methods. Bone mineral density, mass, and geometry on the lower leg using peripheral quantitative computed tomography and serum osteocalcin (OC) and carboxyterminal cross-linked telopeptide of type 1 collagen (CTx) were measured in 35 adolescents with T1DM (15 girls) aged 12.3-17.9 yrs. The results were compared to age- and sex-adjusted reference values for healthy controls. Both sexes reveal lower than zero Z-scores for lower leg 66% total cortical bone cross-sectional area to muscle cross-sectional area ratio (-0.97 ± 1.02, p = 0.002517 and -0.98 ± 1.40, p = 0.007050, respectively) while tibia 4% trabecular bone density Z-score was lowered in boys (-0.67 ± 1.20, p = 0.02259). In boys in Tanner stage 5 bone mass and dimensions were diminished in comparison to Tanner stages 3 and 4, while in girls, such a phenomenon was not observed. Similarly, bone formation and resorption were decreased in boys but not in girls. Consistently, bone turnover markers correlated positively with bone size, dimensions, and strength in boys only. T1DM patients revealed a decreased ratio of cortical bone area/muscle area, reflecting disturbed adaptation of the cortical shaft to the muscle force. When analyzing bone mass and dimensions, boys in Tanner stage 5 diverged from "less-mature" individuals, which may suggest that bone development in these individuals was impaired, affecting all three: mass, size, and strength. Noted in boys, suppressed bone metabolism may result in impairment of bone strength because of inadequate repair of microdamage and accumulation of microfractures.


Glucose-Triggered Gelation of Supramolecular Peptide Nanocoils with Glucose-Binding Motifs.
Peptide self-assembly is a powerful tool to prepare functional materials at the nanoscale. Often, the resulting materials have high aspect-ratio, with intermolecular β-sheet formation underlying one-dimensional fibrillar structures. Inspired by dynamic structures in nature, peptide self-assembly is increasingly moving toward stimuli-responsive designs wherein assembled structures are formed, altered, or dissipated in response to a specific cue. Herein, a peptide bearing a prosthetic glucose-binding phenylboronic acid (PBA) is demonstrated to self-assemble into an uncommon nanocoil morphology. These nanocoils arise from antiparallel β-sheets, with molecules aligned parallel to the long axis of the coil. The binding of glucose to the PBA motif stabilizes and elongates the nanocoil, driving entanglement and gelation at physiological glucose levels. The glucose-dependent gelation of these materials is then explored for the encapsulation and release of a therapeutic agent, glucagon, that corrects low blood glucose levels. Accordingly, the release of glucagon from the nanocoil hydrogels is inversely related to glucose level. When evaluated in a mouse model of severe acute hypoglycemia, glucagon delivered from glucose-stabilized nanocoil hydrogels demonstrate increased protection compared to delivery of the agent alone or within a control nanocoil hydrogel that is not stabilized by glucose. This article is protected by copyright. All rights reserved.


Reduction of Mo(VI) by the bacterium Serratia sp. strain DRY5.
The need to isolate efficient heavy metal reducers for cost effective bioremediation strategy have resulted in the isolation of a potent molybdenum-reducing bacterium. The isolate was tentatively identified as Serratia sp. strain DRY5 based on the Biolog GN carbon utilization profiles and partial 16S rDNA molecular phylogeny. Strain DRY5 produced 2.3 times the amount of Mo-blue than S. marcescens strain Dr.Y6, 23 times more than E. coli K12 and 7 times more than E. cloacae strain 48. Strain DRY5 required 37 degrees C and pH 7.0 for optimum molybdenum reduction. Carbon sources such as sucrose, maltose, glucose and glycerol, supported cellular growth and molybdate reduction after 24 hr of static incubation. The most optimum carbon source that supported reduction was sucrose at 1.0% (w/v). Ammonium sulphate, ammonium chloride, glutamic acid, cysteine, and valine supported growth and molybdate reduction with ammonium sulphate as the optimum nitrogen source at 0. 2% (w/v). Molybdate reduction was optimally supported by 30 mM molybdate. The optimum concentration of phosphate for molybdate reduction was 5 mM when molybdate concentration was fixed at 30 mM and molybdate reduction was totally inhibited at 100 mM phosphate. Mo-blue produced by this strain shows a unique characteristic absorption profile with a maximum peak at 865 nm and a shoulder at 700 nm, Dialysis tubing experiment showed that 95.42% of Mo-blue was found in the dialysis tubing suggesting that the molybdate reduction seen in this bacterium was catalyzed by enzyme(s). The characteristics of isolate DRY5 suggest that it would be useful in the bioremediation ofmolybdenum-containing waste.


Meta-analysis of B type natriuretic peptide and N-terminal pro B natriuretic peptide in the diagnosis of clinical heart failure and population screening for left ventricular systolic dysfunction.
We set out to review the validity of tests for B type natriuretic peptide (BNP) and N-terminal pro BNP (NTproBNP) in the diagnosis of clinical heart failure (HF) in primary care and hospital settings and to examine the effect of age. We also examined the accuracy of the test in population screening for left ventricular systolic dysfunction. Medline and Embase were searched systematically till June 2005. Forty-seven studies were identified for systematic review and 27 were included in meta-analyses. Test performance was summarized as the diagnostic odds ratio (DOR). As a secondary data analysis, this paper does not require ethical approval. In groups of symptomatic patients with average age less than 80 years, the summary DOR of 27 for BNP equates to a sensitivity of 85% and specificity of 84% in the detection of clinical HF. Summary of head-to-head studies shows BNP is a better indicator than NTproBNP. The performance of both tests decreased with the age of patients, the DOR declining by a factor of 2.0 for BNP and 2.5 for NTproBNP for each decade of increasing age. BNP correlated better to clinical status than to echocardiographic parameters, and test performance was similar in acute inpatient and general practice settings. Tests for BNP are helpful in the diagnosis of clinical HF or in screening for left ventricular systolic dysfunction and are superior to NTproBNP. In the clinical setting, test performance declined with increasing patient age.


Dystocia in Formosan sambar deer (Cervus unicolor swinhoei) in semi-domesticated herds.
Over a nine-year period (2000 to 2008), 22 instances of dystocia and 50 normal fawnings in Formosan sambar deer (Cervus unicolor swinhoei) hinds from semi-domesticated herds were investigated. The majority of the hinds (17, 77.3 per cent) that suffered dystocia were categorised as having a body condition score (BCS) in the medium range (between 2.5 and 3.5 inclusive), indicating that there was no significant relationship between obesity (BCS >3.5) in hinds and the occurrence of dystocia. In addition, maternal body condition had no effect on the birthweight of the offspring. Among the 22 instances of dystocia, 16 of the fawns (72.7 per cent) did not survive; one of these deaths was anteparturient and the other 15 were parturient. Eighteen (81.8 per cent) of the cases of dystocia involved male fawns, and 15 (93.8 per cent) of the deaths were of male fawns (P=0.044). Nine (40.9 per cent) of the instances of dystocia resulted from maternal excitement, mainly attributable to disturbances caused by human beings. In 12 of the cases that resulted in the death of the fawn, the request for veterinary assistance had been delayed at least one day. There were six cases in which the fawns survived; these were the ones that had received assistance within six hours after the onset of parturition.


Risperidone-induced retrograde ejaculation: case report and review of the literature.
Medication adherence with antipsychotics is adversely impacted by the burden of untoward adverse effects. In particular, sexual side-effects may interfere with compliance, but are often underreported by patients. Sexual dysfunction related to hyperprolactinemia is commonly described, but ejaculatory disturbance due to potent alpha1 adrenergic antagonism may also occur, and has been reported frequently with certain typical antipsychotics such as thioridazine, but rarely with atypical antipsychotics. Presented here is the case of a 51 year old male with schizophrenia who developed retrograde ejaculation on high dose risperidone therapy (8 mg/day) with prompt resolution of symptoms upon dose reduction. The absence of decreased libido or erectile dysfunction indicates that alpha1 adrenergic antagonism and not low serum testosterone due to hyperprolactinemia is the etiology for this side-effect. This case illustrates another mechanism for sexual adverse effects, and the need for routine inquiry into sexual dysfunction during atypical antipsychotic therapy.


Comparison of nitrogen utilization and urea kinetics between yaks (Bos grunniens) and indigenous cattle (Bos taurus).
Under traditional management on the Qinghai-Tibetan Plateau, yaks () graze only on natural pasture without supplements and are forced to cope with sparse forage of low N content, especially in winter. In contrast, indigenous Tibetan yellow cattle () require supplements during the cold season. We hypothesized that, in response to harsh conditions, yaks cope with low N intakes better than cattle. To test this hypothesis, a study of whole-body N retention and urea kinetics was conducted in 2 concurrent 4 × 4 Latin squares, with 1 square using yaks and 1 square using cattle. Four isocaloric forage-concentrate diets differing in N concentrations (10.3, 19.5, 28.5, and 37.6 g N/kg DM) were formulated, and by design, DMI were similar between species and across diets. Urea kinetics were determined with continuous intravenous infusion of NN urea for 104 h, and total urine and feces were concomitantly collected. Urea production, urea recycling to the gut, and ruminal microbial protein synthesis all linearly increased ( < 0.001) with increasing dietary N in both yaks and cattle. Urinary N excretion was less ( = 0.04) and N retention was greater ( = 0.01) in yaks than in cattle. Urea production was greater in yaks than in cattle at the 3 lowest N diets but greater in cattle than in yaks at the highest N diet (species × diet, < 0.02). Urea N recycled to the gut ( < 0.001), recycled urea N captured by ruminal bacteria ( < 0.001), and ruminal microbial protein production ( = 0.05) were greater in yaks than in cattle. No more than 12% of urea recycling was through saliva, with no difference between species ( = 0.61). Glomerular filtration rate was lower ( = 0.05) in yaks than in cattle. The higher urea recycling and greater capture of recycled urea by ruminal microbes in yaks than in cattle suggest that yaks use mechanisms to utilize dietary N more efficiently than cattle, which may partially explain the better survival of yaks than cattle when fed low-N diets.


Surveillance of cirrhosis for hepatocellular carcinoma: systematic review and economic analysis.
To evaluate the effectiveness, cost-effectiveness and cost-utility of surveillance of patients with cirrhosis [alcoholic liver disease (ALD)-, hepatitis B (HBV)- and C virus (HCV)-related], using periodic serum alpha-fetoprotein (AFP) testing and/or liver ultrasound examination, to detect hepatocellular carcinoma (HCC), followed by treatment with liver transplantation or resection, where appropriate. Electronic databases were searched up to March 2006. A systematic review was carried out using standard methodological guidelines. A computerised decision-analytic model was then developed to compare various surveillance strategies. No studies were identified that met the criteria of the systematic review. Based on the assumptions used in the model, the most effective surveillance strategy uses a combination of AFP testing and ultrasound at 6-monthly intervals. Compared with no surveillance, this strategy is estimated to more than triple the number of people with operable HCC tumours at time of diagnosis, and almost halves the number of deaths from HCC. On all effectiveness measures and at both testing frequencies, AFP- and ultrasound-led surveillance strategies are very similar. This may be because test sensitivity was varied according to tumour size, which means that AFP testing is capable of identifying many more small tumours than ultrasound. The best available evidence suggests that AFP tests will detect approximately six times as many small tumours as ultrasound. Increasing the frequency of either test to 6-monthly intervals is more effective than performing combined testing on an annual basis. The undiscounted lifetime cost of the surveillance strategies, including all care and treatment costs, ranges from 40,300 pounds (annual AFP triage) to 42,900 pounds (6-monthly AFP and ultrasound). The equivalent discounted costs are 28,400 pounds and 30,400 pounds. Only a small proportion of these total costs results from the cost of the screening tests. However, screening test costs, and the cost of liver transplants and caring for people post-transplant, accounted for most of the incremental cost differences between alternative surveillance strategies. The results suggest that different surveillance strategies may provide the best value for money in patient groups of different cirrhosis aetiologies. The surveillance of people with HBV-related cirrhosis for HCC provides the best value for money, while surveillance in people with ALD-related cirrhosis provides the poorest value for money. In people with HBV-related cirrhosis, at an assumed maximum willingness to pay (WTP) for a quality-adjusted life-year (QALY) of 30,000 pounds, both the deterministic and probabilistic cost-utility analyses suggest the optimal surveillance strategy would be 6-monthly surveillance with the combination of AFP testing and ultrasound. In contrast, for those with ALD-related cirrhosis, annual screening with AFP as a triage test is the only surveillance strategy that is likely to be considered cost-effective at this WTP. The probabilistic analysis implies that the estimated benefits of a 6-monthly AFP triage strategy will only be worth the cost in those with ALD when society's WTP for a QALY exceeds around 40,000 pounds. For people with HCV-related cirrhosis, the model suggests that the most cost-effective surveillance strategy at a WTP threshold of 30,000 pounds/QALY would be surveillance with a 6-monthly AFP triage strategy. In a mixed-aetiology cohort, the most effective surveillance strategy is to screen each patient with AFP assay and ultrasound imaging on a 6-monthly basis. However, when costs are taken into account it is doubtful whether ultrasound should be routinely offered to those with blood AFP of less than 20 ng/ml, unless policy-makers are prepared to pay over 60,000 pounds per QALY for the benefits achieved. Furthermore, the cost-effectiveness of surveillance for HCC varies considerably depending on the aetiology of cirrhosis; it is much more likely to be cost-effective in those with HBV-related cirrhosis, and much less likely to be cost-effective in those with ALD-related cirrhosis. Further development of the model would help to enable refinement of an optimal screening strategy. Research into the use of contrast-enhanced ultrasound technology for HCC detection would also be valuable, as would research into the epidemiology and natural history of ALD-related cirrhosis. Studies are also needed to investigate the influence of cirrhosis aetiology on tumour AFP expression.


Investigation of heavy-ion-induced sucrose radicals by electron paramagnetic resonance.
The production of sucrose radicals with heavy-ion irradiation was investigated by an EPR (electron paramagnetic resonance) spectroscopic method. We examined the correlation between the production of sucrose radicals and the ion species, as well as LET (linear energy transfer). The spectral pattern obtained was the same for various ion species, including helium, carbon, neon, argon and iron ions. Quantitative EPR analyses showed that the production of sucrose radicals depended on both the ion species and the LET for the same dose of 50 Gy. The spin yield obtained showed a logarithmic correlation with the LET. In addition, the EPR response had a linear relationship with dose in the dose range of 5-60 Gy. Thus the present EPR results show that sucrose can be used to monitor the ionizing particle based on the radical yield.


Halistaurin, phialidin and modified forms of aequorin as Ca2+ indicator in biological systems.
Two kinds of aequorin-type photoproteins, i.e., halistaurin and phialidin, and four kinds of modified forms of aequorin, i.e., products of acetylation, ethoxycarbonylation, fluorescamine-modification and fluorescein labelling, were prepared. The modified forms of aequorin were more sensitive to Ca2+ than was aequorin in their Ca2+-triggered luminescence reactions, whereas halistaurin and phialidin were less sensitive. The emission maxima of luminescence were all within a wavelength range 450-464 nm, except for fluorescein-labelled aequorin, which emitted yellowish light (lambda max. 520 nm). A new technique of measuring Ca2+ concentration is suggested.


Fowl adenovirus-induced diseases and strategies for their control - a review on the current global situation.
The stand-alone pathogenicity of fowl adenoviruses (FAdVs) had long been disputed, given the ubiquity of the viruses versus sporadic outbreaks, and variation between experimental studies. However, a globally emerging trend of FAdV-associated diseases has marked the past two decades, with hepatitis-hydropericardium syndrome mainly in Asia besides Arabian and Latin American countries, and geographically more disseminated outbreaks of inclusion body hepatitis. Finally, the appearance of FAdV-induced gizzard erosion (AGE) in Asia and Europe completed the range of diseases. Epidemiological studies confirmed serotype FAdV-4 as agent of hepatitis-hydropericardium syndrome, whereas inclusion body hepatitis is related to FAdV-2, -8a, -8b and -11. Members of the biologically more distant serotype FAdV-1 induce AGE. Urged by increasing problems in the field, numerous pathogenicity studies with FAdVs from outbreaks substantiated the primary aetiologic role of particular strains for distinct clinical conditions. Developments in the poultry industry towards highly specialized genetic breeds and rigorous biosecurity additionally contribute to the growing incidence of FAdV-related diseases. Confirming field observations, recent studies connected a higher susceptibility of broilers with their distinct physiology, implying the choice of bird type as a factor to be considered in infection studies. Furthermore, elevated biosecurity standards have generated immunologically naïve breeding stocks, putting broilers at risk in face of vertical FAdV transmission. Therefore, future prevention strategies should include adequate antibodies in breeders prior to production and - if necessary - vaccination, in order to protect progenies. This review aims to deliver a detailed overview on the current global situation about FAdV-induced diseases, their reproduction in vivo and vaccination strategies.


Nitric oxide mediates the blood pressure response to mental stress in humans.
Nitric oxide (NO) regulates arterial pressure by modulating peripheral vascular tone and sympathetic vasoconstrictor outflow. NO synthesis is impaired in several major cardiovascular disease states. Loss of NO-induced vasodilator tone and restraint on sympathetic outflow could result in exaggerated pressor responses to mental stress. We, therefore, compared the sympathetic (muscle sympathetic nerve activity) and haemodynamic responses to mental stress performed during saline infusion and systemic inhibition of NO-synthase by NG-monomethyl-L-arginine (L-NMMA) infusion. The major finding was that mental stress which during saline infusion increased sympathetic nerve activity by ~50 percent and mean arterial pressure by ~15 percent had no detectable sympathoexcitatory and pressor effect during L-NMMA infusion. These findings were not related to a generalised impairment of the haemodynamic and/or sympathetic responsiveness by L-NMMA, since the pressor and sympathetic nerve responses to immersion of the hand in ice water were preserved during L-NMMA infusion. Mental stress causes pressor and sympathoexcitatory effects in humans that are mediated by NO. These findings are consistent with the new concept that, in contrast to what has been generally assumed, under some circumstances, NO has a blood pressure raising action in vivo.


[Effect of diagnostic X-rays on implantable cardiac pacemakers and implantable cardioverter defibrillators, and its management].
The effects of diagnostic X-rays on implantable cardiac pacemakers and implantable cardioverter defibrillators (ICDs) were investigated. A total of 33 pacemakers from six manufacturers and nine ICDs from four manufacturers were irradiated using several X-ray units (plain X-ray diagnostic unit, under-table system fluoroscopy unit, over-table system fluoroscopy unit, biplane cardiac digital angiography unit, DSA unit and cone-beam CT unit). No systematic reset phenomena were observed in any pacemakers and ICDs under the X-ray irradiation. Nevertheless, over-sensing associated with the lack of a few pulses was observed in three of 33 pacemakers under radiation exposure. It has been proven that diagnostic X-rays might affect pacemaker function. Since the duration of the over-sensing under the radiation was very short and included transient episodes, this sensing failure, therefore, induced by radiation exposure would not affect the health of pacemaker recipients. ICDs were not affected by radiation exposure at a clinical dose. It is recommended that caution be exercised in direct irradiation to the pacemaker. Using a copper sheet of 2.0 mm thickness or more prevented over-sensing of pacemakers in the present study, especially when serial X-ray exposures were used with an over-table fluoroscopy system or cone-beam CT unit.


The role of Her2 and other oncogenes of the PI3K/AKT pathway in mitochondria.
Altered metabolism and resistance to cell death are typical hallmarks of cancer phenotype. Mitochondria are organelles central to cellular metabolism as well as to cell death induction. Hyperactivation of pro-survival and pro-proliferative pathways such as PI3K/AKT leads to cancer initiation, which affects mitochondria. Growing body of evidence indicates that oncogenes such as HER2, EGFR and RAS, as well as the downstream members of the PI3K/AKT signaling pathway, directly regulate mitochondria by translocating to the organelle. Here we discuss evidence of this scenario and consider mechanisms for direct regulation of mitochondrial function. Being in close proximity to mitochondrial bioenergetics machinery as well as to the regulators/executors of programed cell death, oncogenes in mitochondria may be ideally placed to perform this task. This represents a thus far under-explored area, which may be relevant to better understanding of cancer initiation, progression and treatment.


Indonesian Mangrove Sonneratia caseolaris Leaves Ethanol Extract Is a Potential Super Antioxidant and Anti Methicillin-Resistant Staphylococcus aureus Drug.
Methicillin-resistant Staphylococcus aureus (MRSA) is an S. aureus strain that has developed resistance against ß-lactam antibiotics, resulting in a scarcity of a potent cure for treating Staphylococcus infections. In this study, the anti-MRSA and antioxidant activity of the Indonesian mangrove species Sonneratia caseolaris, Avicennia marina, Rhizophora mucronata, and Rhizophora apiculata were studied. Disk diffusion, DPPH, a brine shrimp lethality test, and total phenolic and flavonoid assays were conducted. Results showed that among the tested mangroves, ethanol solvent-based S. caseolaris leaves extract had the highest antioxidant and anti-MRSA activities. An antioxidant activity assay showed comparable activity when compared to ascorbic acid, with an IC50 value of 4.2499 ± 3.0506 ppm and 5.2456 ± 0.5937 ppm, respectively, classifying the extract as a super-antioxidant. Moreover, S. caseolaris leaves extract showed the highest content of strongly associated antioxidative and antibacterial polyphenols, with 12.4% consisting of nontoxic flavonoids with the minimum inhibitory concentration of the ethanol-based S. caseolaris leaves extract being approximately 5000 ppm. LC-MS/MS results showed that phenolic compounds such as azelaic acid and aspirin were found, as well as flavonoid glucosides such as isovitexin and quercitrin. This strongly suggested that these compounds greatly contributed to antibacterial and antioxidant activity. Further research is needed to elucidate the interaction of the main compounds in S. caseolaris leaves extract in order to confirm their potential either as single or two or more compounds that synergistically function as a nontoxic antioxidant and antibacterial against MRSA.


Pupillometry in Chagas disease.
We investigated parasympathetic innervation abnormalities of the iris sphincter and ciliary muscles in chronic Chagas disease by measuring pupillary diameter and intraocular pressure. A group of 80 patients with Chagas disease was compared with 76 healthy individuals without chagasic infection. The following procedures were performed: pupillometry, hypersensitivity test to pilocarpine 0.125%, intraocular pressure measurement (IOP), basal pupil diameter (BPD), absolute pupillary constriction amplitude (ACA), relative pupillary constriction amplitude (RCA) and the presence of anisocoria. The prevalence of anisocoria was higher in chagasic patients (p<0.01). These patients had mean basal pupillary diameter, mean photopic pupillary diameter and mean value of absolute pupillary constriction amplitude significantly lower than non-chagasic ones (p<0.01, mean difference -0.50mm), (p=0.02, mean difference -0.20mm), (p<0.01, mean difference -0.29mm), respectively. The relative pupillary constriction amplitude did not differ between the two groups (p=0.39, mean difference -1.15%). There was hypersensitivity to dilute pilocarpine in 8 (10%) of the chagasic patients in the right eye and in 2 (2.5%) in the left eye and in 1 (1.25%) in both eyes. The mean value of intraocular pressure had a marginal statistical significance between the two groups (p=0.06, mean difference -0.91mmHg). Patients with chagasic infection may exhibit ocular parasympathetic dysfunction, demonstrable by pupillometry and the dilute pilocarpine hypersensitivity test.


Radiochemical pharmacokinetic profile of P10 peptide with antifungal properties.
Paracoccidioidomycosis (PCM) is a chronic granulomatous disease that is caused by the thermally dimorphic fungus Paracoccidioides brasiliensis. It is endemic in some countries of Latin America and can cause a high-burden fungal infection with significant morbidity and mortality. The peptide P10, which demonstrates immune protection against experimental PCM, was radiolabeled with a radioisotope and evaluated in vivo. The radiolabeling was conducted to trace the pharmacokinetics of the molecule in principal organs and tissues. This was achieved with high radiochemical purity. Biodistribution and scintigraphic imaging showed fast blood clearance that was mainly renal; however, hepatobiliar excretion was also, with marked uptake in cervical lymph nodes. This profile may be useful for the development of a prophylactic drug or vaccine for patients exposed to PCM.


The formation of sulphur-containing amino acids in germinating seeds of rape (Brassica napus L.).
Sodium [(35)S]sulphide was fed to batches of germinating rapeseed, in some instances with the addition of unlabelled cysteine. Both the total radioactivity and specific radioactivity of the free sulphur-containing amino acids were examined. Cysteine and homocysteine were rapidly labelled; label subsequently appeared in cystathionine and methionine. The results obtained indicated that both the sulphydration and trans-sulphuration pathways were operating. This conclusion was reinforced by the results of experiments in which batches of rapeseed were incubated with l-[(14)C]homoserine. These showed the formation of labelled homocysteine, cystathione and methionine. It was thought the trans-sulphuration pathway was making the greater contribution to the biosynthesis of methionine in germinating rapeseed.


Characteristics, origin, and potential for cancer diagnostics of ultrashort plasma cell-free DNA.
Current evidence suggests that plasma cell-free DNA (cfDNA) is fragmented around a mode of 166 bp. Data supporting this view has been mainly acquired through the analysis of double-stranded cfDNA. The characteristics and diagnostic potential of single-stranded and damaged double-stranded cfDNA in healthy individuals and cancer patients remain unclear. Here, through a combination of high-affinity magnetic bead-based DNA extraction and single-stranded DNA sequencing library preparation (MB-ssDNA), we report the discovery of a large proportion of cfDNA fragments centered at ∼50 bp. We show that these "ultrashort" cfDNA fragments have a greater relative abundance in plasma of healthy individuals (median = 19.1% of all sequenced cfDNA fragments, n = 28) than in plasma of patients with cancer (median = 14.2%, n = 21, P < 0.0001). The ultrashort cfDNA fragments map to accessible chromatin regions of blood cells, particularly in promoter regions with the potential to adopt G-quadruplex (G4) DNA secondary structures. G4-positive promoter chromatin accessibility is significantly enriched in ultrashort plasma cfDNA fragments from healthy individuals relative to patients with cancers (P < 0.0001), in whom G4-cfDNA enrichment is inversely associated with copy number aberration-inferred tumor fractions. Our findings redraw the landscape of cfDNA fragmentation by identifying and characterizing a novel population of ultrashort plasma cfDNA fragments. Sequencing of MB-ssDNA libraries could facilitate the characterization of gene regulatory regions and DNA secondary structures via liquid biopsy. Our data underline the diagnostic potential of ultrashort cfDNA through classification for cancer patients.


Work Efficiency and Economic Efficiency of Actual Driving Test of Proton Exchange Membrane Fuel Cell Forklift.
A 3.5 tonne forklift containing proton exchange membrane fuel cells (PEMFCs) and lithium-ion batteries was manufactured and tested in a real factory. The work efficiency and economic applicability of the PEMFC forklift were compared with that of a lithium-ion battery-powered forklift. The results showed that the back-pressure of air was closely related to the power density of the stack, whose stability could be improved by a reasonable control strategy and membrane electrode assemblies (MEAs) with high consistency. The PEMFC powered forklift displayed 40.6% higher work efficiency than the lithium-ion battery-powered forklift. Its lower use-cost compared to internal engine-powered forklifts, is beneficial to the commercialization of this product.


Effects of ammodytin L on miniature and endplate potentials in neuromuscular junction of frog m. cutaneus pectoris.
Neurotoxic effects of ammodytin L (AtnL), a potent phospholipase A2 homologue, was studied in frog neuromuscular preparation m. cutaneous pectoris by measuring the influence of the toxin on the amplitude and the frequency of miniature and endplate potentials (MEPPs, EPPs). AtnL, in 100 nM concentration, significantly increases spontaneous quantal acetylcholine release from the motor nerve endings, observed as the increase in MEPPs frequency. At 100 nM or higher concentration the toxin decreases EPPs amplitude and the membrane potential (MP) simultaneously. No significant effect of AtnL on EPPs was observed at any concentration bellow 100 nM. Our results indicate that in frog AtnL shows the typical myotoxic effects, but it also exerts presynaptic effects.


Atomic under-coordination fascinated catalytic and magnetic behavior of Pt and Rh nanoclusters.
Density functional theory (DFT) calculations with local spin density discrimination have been performed to examine the effect of atomic under-coordination on the catalytic and magnetic properties of cuboctahedral (CO) and marks decahedral (MD) structured Pt and Rh nanoclusters. Consistency between theoretical calculations and experimental observations confirmed the predictions based on the framework of bond-order-length-strength (BOLS) correlation and nonbonding electron polarization (NEP) notations. The BOLS-NEP notation suggests that the shorter-and-stronger bonds between under-coordinated atoms induce local densification and quantum entrapment of core electrons, which then polarize the otherwise conducting electrons and result in shifts of the binding energy. Such strong localization resolves the intriguing catalytic and magnetic attributes of Pt and Rh nanoclusters.


Environmental impact of water-use in buildings: Latest developments from a life-cycle assessment perspective.
Globally, buildings are recognized as one of the highest users of freshwater resources. Consuming enormous amounts of constructional and operational water deplete water resources and ultimately generates a high environmental impact. This is mainly due to the energy required for the water cycle of built environments, which involves raw water treatment and distribution, use within buildings, and wastewater treatment. Moreover, the impact of water use varies significantly among countries/regions, due to different water use cycles. For example, many countries use conventional water treatments, while others rely on advanced desalination. Unlike building energy use, the impact of water use in buildings has not been captured fully in research. Given the significant impact of water use in buildings and global environmental degradation, we aimed to review studies concentrating on constructional and operational water use and associated environmental impacts, as well as studies that employed life cycle assessment (LCA) on this topic. The review indicated that a limited number of studies have focused on this serious issue in recent years, and their aims differed greatly. Therefore, there is a notable research gap in comprehensive environmental impact assessment including the total human water use cycle. Complete environmental assessment through LCA enables building professionals to understand the wide-ranging impact of water use in a building's life cycle from the environmental perspective in a given region. Additionally, this approach can benefit policymakers setting guidelines for new sustainable water strategies aimed at reducing environmental impacts.


Prenatal stress produces learning deficits associated with an inhibition of neurogenesis in the hippocampus.
Early experiences such as prenatal stress significantly influence the development of the brain and the organization of behavior. In particular, prenatal stress impairs memory processes but the mechanism for this effect is not known. Hippocampal granule neurons are generated throughout life and are involved in hippocampal-dependent learning. Here, we report that prenatal stress in rats induced lifespan reduction of neurogenesis in the dentate gyrus and produced impairment in hippocampal-related spatial tasks. Prenatal stress blocked the increase of learning-induced neurogenesis. These data strengthen pathophysiological hypotheses that propose an early neurodevelopmental origin for psychopathological vulnerabilities in aging.


Trends in Relative Incidence and Prevalence of Dementia Across Non-Hispanic Black and White Individuals in the United States, 2000-2016.
In the US, dementia risk is higher in non-Hispanic Black individuals than in non-Hispanic White individuals. To evaluate progress toward reducing such disparities, tracking secular trends in racial disparities in dementia prevalence is essential. To examine whether relative racial disparities in dementia prevalence or incidence have changed in the US from 2000 to 2016. The Health and Retirement Study (HRS) is a nationally representative study of adults 50 years or older. New participants are recruited every 6 years, and study visits occur biennially. Approximately 17 000 to 22 000 respondents have been surveyed at each wave since 2000, achieving response rates of 81% to 89%. Data for this cohort study were obtained from non-Hispanic White and non-Hispanic Black participants aged 70 years and older from the 2000 to 2016 waves. For analyses of secular trends in racial disparities in dementia prevalence, each HRS wave was considered separately (range of participants meeting eligibility criteria in each wave, 6322-7579). For analyses of secular trends in racial disparities in dementia incidence, 7 subcohorts were created (range of participants meeting eligibility criteria in each subcohort, 5322-5961) following up people without dementia for 4 years from subcohort baseline visits in 2000, 2002, 2004, 2006, 2008, 2010, and 2012. Data were analyzed from October 2019 to August 2020. Race based on self-response to closed-ended survey questions. Dementia status was determined using 3 algorithms with similar sensitivity and specificity across non-Hispanic White and Black participants. Disparities were characterized using ratio measures. In this study, the mean age and percentage of male participants eligible for inclusion in analyses of racial disparities in dementia prevalence increased over time among non-Hispanic White participants (from 78.2 years and 40% in 2000 to 78.7 years and 44% in 2016) but remained steady in non-Hispanic Black participants during the same period (from 78.0 years and 37% in 2000 to 77.9 years and 38% in 2016). Prevalence ratios comparing Black and White participants ranged from approximately 1.5 to 1.9 across algorithms and years, whereas hazard ratios ranged from approximately 1.4 to 1.8. Although results suggest stable or declining dementia risk overall, there was no evidence suggesting change in relative racial disparities in dementia prevalence or incidence during follow-up. This study did not find evidence to suggest that the ratio of dementia risk across Black and White individuals changed in the US between 2000 and 2016. Additional efforts to identify and mitigate the source of these disparities is warranted.