Weekly SARS-CoV-2 screening of asymptomatic kindergarten to grade 12 students and staff helps inform strategies for safer in-person learning.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission in K-12 schools was rare during in 2020-2021; few studies included Centers for Disease Control and Prevention (CDC)-recommended screening of asymptomatic individuals. We conduct a prospective observational study of SARS-CoV-2 screening in a mid-sized suburban public school district to evaluate the incidence of asymptomatic coronavirus disease 2019 (COVID-19), document frequency of in-school transmission, and characterize barriers and facilitators to asymptomatic screening in schools. Staff and students undergo weekly pooled testing using home-collected saliva samples. Identification of >1 case in a school prompts investigation for in-school transmission and enhancement of safety strategies. With layered mitigation measures, in-school transmission even before student or staff vaccination is rare. Screening identifies a single cluster with in-school staff-to-staff transmission, informing decisions about in-person learning. The proportion of survey respondents self-reporting comfort with in-person learning before versus after implementation of screening increases. Costs exceed $260,000 for assays alone; staff and volunteers spend 135-145 h per week implementing screening.


Characterization of culturable anaerobic bacteria from the forestomach of an eastern grey kangaroo, Macropus giganteus.
To determine the culturable biodiversity of anaerobic bacteria isolated from the forestomach contents of an eastern grey kangaroo, Macropus giganteus, using phenotypic characterization and 16S rDNA sequence analysis. Bacteria from forestomach contents of an eastern grey kangaroo were isolated using anaerobic media containing milled curly Mitchell grass (Astrebla lappacea). DNA was extracted and the 16S rDNA sequenced for phylogenetic analysis. Forty bacterial isolates were obtained and placed in 17 groups based on phenotypic characteristics and restriction enzyme digestion of 16S rDNA PCR products. DNA sequencing revealed that the 17 groups comprised five known species (Clostridium butyricum, Streptococcus bovis, Clostridium sporogenes, Clostridium paraputrificum and Enterococcus avium) and 12 groups apparently representing new species, all within the phylum Firmicutes. Foregut contents from Australian macropod marsupials contain a microbial ecosystem with a novel bacterial biodiversity comprising a high percentage of previously unrecognized species. This study adds to knowledge of Australia's unique biodiversity, which may provide a future bioresource of genetic information and bacterial species of benefit to agriculture.


Pathological conditions re-shape physiological Tregs into pathological Tregs.
CD4+FOXP3+ regulatory T cells (Tregs) are a subset of CD4 T cells that play an essential role in maintaining peripheral immune tolerance, controlling acute and chronic inflammation, allergy, autoimmune diseases, and anti-cancer immune responses. Over the past 20 years, significant progress has been made since Tregs were first characterized in 1995. Many concepts and principles regarding Tregs generation, phenotypic features, subsets (tTregs, pTregs, iTregs, and iTreg35), tissue specificity (central Tregs, effector Tregs, and tissue resident Tregs), homeostasis (highly dynamic and apoptotic), regulation of Tregs by receptors for PAMPs and DAMPs, Treg plasticity (re-differentiation to other CD4 T helper cell subsets, Th1, Th2, Tfh and Th17), and epigenetic regulation of Tregs phenotypes and functions have been innovated. In this concise review, we want to briefly analyze these eight new progresses in the study of Tregs. We have also proposed for the first time a novel concept that "physiological Tregs" have been re-shaped into "pathological Tregs" in various pathological environments. Continuing of the improvement in our understanding on this important cellular component about the immune tolerance and immune suppression, would lead to the future development of novel therapeutics approaches for acute and chronic inflammatory diseases, allergy, allogeneic transplantation-related immunity, sepsis, autoimmune diseases, and cancers.


Histological changes associated with an artificial anterior cruciate ligament.
To investigate the histopathological features of the synovial lining of the knee following implantation of an artificial cruciate ligament. Eighty two patients underwent anterior cruciate ligament reconstruction for chronic, symptomatic instability of the knee. The cruciate ligament was reconstructed with a scaffold type prosthetic ligament. All patients underwent arthroscopy at the time of cruciate reconstruction and also as a "second look" procedure at a mean 26.5 months later, at which time synovial biopsy specimens were obtained in all cases. The most frequent histological finding was granulomatous synovitis in 48% (39/82) of patients. Particulate polyester debris produced a greater response than carbon fibres. In 24% (20/82), nonspecific inflammation was present and in 28% (23/82) the synovium was considered normal. When the prosthetic ligament was fully covered by soft tissue in-growth, a granulomatous reaction was present in 42% (24/57), irrespective of whether the ligament was partially or totally uncovered. Stabilisation of the joint did not prevent subsequent deterioration in the articular cartilage; other factors such as increasing patient age, interval between injury and reconstruction and altered knee kinematics after reconstruction are probably important. Granulomatous synovitis was not associated with progressive chondral changes. Although present in 48% of cases, granulomatous synovitis was not shown to have adverse effects on either chondral surface or the prosthetic material of the ligament. Rupture of the implant is caused by mechanical factors and granulomatous synovitis is not responsible for implant failure.


X-Chromosome Inactivation and Escape from X Inactivation in Mouse.
X chromosome inactivation silences one X chromosome in female mammals. However, this silencing is incomplete, and some genes escape X inactivation. We describe methods to determine the chromosome-wide X inactivation status of genes in tissues or cell lines derived from mice using a combination of skewing of X inactivation and allele-specific analyses of gene expression based on RNA-seq.


Short Communication: Manα1-2Man-Binding Anti-HIV Lectins Enhance the Exposure of V2i and V3 Crown Neutralization Epitopes on the V1/V2 and V3 Hypervariable Loops of HIV-1 Envelope.
This study aimed to explore the contribution of high-mannose glycans in the masking of conserved V3 crown (GPG) and V2i epitopes on the hypervariable loops of most exposed distal surface of HIV-1 Env. Using lectins specific to Manα1-2Man residue containing Man6-9GlcNAc2 glycans extensively decorating HIV-1 Env, we found that Manα1-2Man-binding lectins enhance the exposure of these partially and transiently exposed epitopes and consequentially increase the neutralization strength of antibodies against these epitopes.


Dorsal arachnoid web: A rare cause of syringomyelia and myelopathy.
Dorsal arachnoidal webs are condensations of arachnoidal tissue densely adherent to the pial surface of the posterior aspect of the dorsal spinal cord. Infrequently described in literature they disrupt the flow of CSF in the spinal subarachnoid space leading to syringomyelia and myelopathy. While there are several theories on their origin, the "scalpel sign" on magnetic resonance imaging is considered to be pathognomonic of this condition. An illustrative case of a 58 year old man with syringomyelia and dorsal cord indentation who presented with spastic paraparesis, gait instability, parasthesias and bilateral non radicular upper limb pain that resolved following excision of the web is described to highlight the importance of considering this diagnosis when cases of so called "idiopathic" syringomyelia are encountered.


Human fetal sympathoadrenal responsiveness.
A reference range of fetal noradrenaline levels related to gestational age was calculated from 27 normal pregnancies between 16 and 36 weeks of gestation. Growth retarded, hypoxic fetuses had significantly elevated noradrenaline levels (P less than 0.01).


The transfer of 6-mercaptopurine in the dually perfused human placenta.
The immunosuppressant azathioprine is increasingly being used in pregnancy. The human placenta is considered a relative barrier to the major metabolite, 6-mercaptopurine (6-MP), and likely explains the lack of proven teratogenicity in humans. The aim of this study was to determine how the human placenta restricts 6-MP transfer using the human placental perfusion model. After addition of 50 ng/ml (n=4) and 500 ng/ml (n=3) 6-MP into the maternal circulation, there was a biphasic decline in its concentration and a delay in fetal circulation appearance. Under equilibrative conditions, the fetal-to-maternal concentration ratio was >1.0 as a result of ion trapping. Binding to placental tissue and maternal pharmacokinetic parameters are the main factors that restrict placental transfer of 6-MP. Active transport is unlikely to play a significant role and drug interactions involving, or polymorphisms in, placental drug efflux transporters are not likely to put the fetus at risk of higher 6-MP exposure.


Paediatric emergency care at an academic referral hospital in Mozambique.
Improved emergency care of children with acute illness or injuries is needed for countries in Africa to continue to reduce childhood mortality rates. Quality improvement efforts will depend on robust baseline data, but little has been published on the breadth and severity of paediatric illness seen in Mozambique. This was a retrospective review of routinely collected provider shift summary data from the Paediatric Emergency Department (PED) at Hospital Central de Maputo (HCM), the principal academic and referral hospital in the country. All children 0-14 years of age seen in the 12-month period from August 2018-July 2019 were included. Descriptive statistical analyses were performed. Data from 346 days and 64,966 patient encounters were analyzed. The large majority of patients (96.4%) presented directly to the PED without referral from a lower level facility. An average of 188 patients was seen per day, with significant seasonal variation peaking in March (292 patients/day). The most common diagnoses were upper respiratory infections (URI), gastroenteritis, asthma, and dermatologic problems. The highest acuity diagnoses were neurologic problems (59%), asthma (57%), and neonatal diagnoses (50%). Diagnoses with the largest proportion of admissions included neurologic problems, malaria, and neonatal diagnoses. Rapid malaria antigen tests were the most commonly ordered laboratory test across all diagnostic categories; full blood count (FBC) and chemistries were also commonly ordered. Urinalysis and HIV testing were rarely done in the PED. This epidemiologic profile of illness seen in the HCM PED will allow for improved resource utilisation. We identified opportunities for evidence-based care algorithms for common diagnoses such as respiratory illness to improve patient care and flow. The PED may also be able to optimize laboratory and radiology evaluation for patients and develop standardized admission criteria by diagnosis.


The curious case of IL-33 in homeostasis and infection.
The importance of interleukin (IL)-33 in promoting effective antiviral immune responses is evident, yet the critical cellular sources of IL-33 in homeostasis and infection are largely unknown. In this issue of the European Journal of Immunology, Aparicio-Domingo et al. [Eur. J. Immunol. 2021. 51: 76-90] explore the main source of IL-33 expression in lymph nodes (LNs) and dissect its role in LN homeostasis and antiviral adaptive immune response. The authors reveal that fibroblastic reticular cells and lymphatic endothelial cells are both producing IL-33 in steady-state LNs. Remarkably, however, by using cell-type specific deletion approaches, the authors demonstrate that exclusively fibroblastic reticular cells, and not lymphatic endothelial cells, are the critical cellular source for promoting antiviral CD8+ T-cell responses upon infection. These findings provide an important insight into the role of specific LN stromal cell subsets as potent modulators of antiviral immunity.


Atypical and anaplastic meningiomas treated with bevacizumab.
Atypical and anaplastic (WHO Grades II and III) meningiomas are aggressive tumors, and patients often progress despite surgery and radiation. There is no known effective chemotherapeutic option for these patients. Meningiomas have a high expression of vascular endothelial growth factor receptor (VEGFR). We sought to retrospectively study the activity of bevacizumab, which is an anti-angiogenic agent targeting the VEGF pathway in these tumors. This is a retrospective review of WHO Grade II and III meningiomas treated at four institutions, selecting only those patients who received bevacizumab. We analyzed radiographic response according to standard RANO criteria, progression-free survival (PFS) and overall survival from the initiation of bevacizumab therapy using Kaplan-Meier statistics. We identified 15 patients across four institutions who carried a diagnosis of atypical or anaplastic meningioma and were treated with bevacizumab. Best radiographic response was stable disease. MR perfusion studies showed decreased tumor blood volume in one patient. Three patients developed non-fatal intratumoral hemorrhage. Median PFS was 26 weeks (95 % CI, 10-29 weeks). Six month PFS rate was 43.8 % (95 % CI, 15.7-69.1 %). Bevacizumab was well-tolerated in our patients, and may be considered in patients who have exhausted radiation and surgical options. Prospective studies are required to define the safety and efficacy of bevacizumab in atypical and anaplastic meningiomas.


Polyhydroxyalkanoate production from rice straw hydrolysate: Insights into feast-famine dynamics and microbial community shifts.
Activated sludge contains a versatile microbiome capable of converting wastes into valuable chemicals like polyhydroxyalkanoates (PHA). This study investigated the influence of repeated feast and famine phases on PHA production as well as the corresponding microbial population dynamics using waste activated sludge (WAS) as inoculum. Hydrolysate derived from rice straw was employed as a substrate for PHA production. The 16sRNA analysis results revealed that Corynebacteriaceae (40%), Bacillaceae (23%), and Pseudomonas (5%) were the primary contributors to PHA synthesis. Notably, Bacillaceae and Pseudomonas thrived in all the feast and famine phases. The achieved PHA concentration was 3.5 ± 0.2 g/L, and its structure and composition were assessed using Fourier Transform Infrared Spectroscopy (FTIR) and Nuclear Magnetic Resonance (NMR). The analysis revealed that the PHA consists of a copolymer of hydroxybutyrate (HB) and hydroxyvalerate (HV), specifically identified as Poly(hydroxybutyrate-co-hydroxyvalerate) (PHBV).


Optical sectioning microscopy with planar or structured illumination.
A key requirement for performing three-dimensional (3D) imaging using optical microscopes is that they be capable of optical sectioning by distinguishing in-focus signal from out-of-focus background. Common techniques for fluorescence optical sectioning are confocal laser scanning microscopy and two-photon microscopy. But there is increasing interest in alternative optical sectioning techniques, particularly for applications involving high speeds, large fields of view or long-term imaging. In this Review, I examine two such techniques, based on planar illumination or structured illumination. The goal is to describe the advantages and disadvantages of these techniques.


The effect of using adjuvant aromatase inhibitors on cognitive functions in postmenopausal women with hormone receptor-positive breast cancer.
Breast cancer is the most frequently diagnosed cancer in women worldwide. Aromatase inhibitors (AIs) are effective treatment options for both early-stage and advanced hormone receptor-positive breast cancer. Because of AIs are used long term in adjuvant therapy, side effects are also very important. It is considered that AIs may affect cognitive functions by decreasing the level of estrogen in the brain. The purpose of our study is that evaluate the relationship between duration of treatment and cognitive functions in patients with breast cancer who use AIs in adjuvant therapy. Two-hundred patients diagnosed with breast cancer who were treated with AIs as adjuvant treatment were included. The patients were surveyed for demographic characteristics. Montreal Cognitive Assessment (MoCA) and Standardized Mini-Mental State Examination (SMMT) tests were performed to evaluate patients' cognitive functions. The total scores of the tests and the orientation, short-time memory, visuospatial functions, attention, language, executive functions which are the MoCA subscales were evaluated separately. Patients were grouped as 0-6, 6-12, 12-24, 24-36, 36, and more months according to the duration of AIs using time. The total MoCA and SMMT scores were affected by factors such as age, education level, and employment status. There was no relationship between duration of treatment and cognitive functions in patients with breast cancer who use AIs in adjuvant therapy (P > 0.05). In addition, no statistically relationship was found in the evaluation of MoCA subscales (P > 0.05). Prolonged adjuvant treatment with AIs does not affect cognitive functions in hormone receptor-positive breast cancer patients.


Effects of dietary exposure of 4-nonylphenol on growth and smoltification of juvenile coho salmon (Oncorhynchus kisutch).
There is considerable concern that endocrine disrupting substances such as 4-nonylphenol (4-NP) in the freshwater environment may have adverse effects on the growth, survival, and osmoregulatory ability of salmonids during and after their transfer to sea water. This study was conducted to examine the effects of dietary exposure of coho salmon (Oncorhynchus kisutch) to 4-NP during the parr-smolt transformation phase of their life cycle. Under laboratory conditions, juvenile fish were fed by hand twice daily to satiation diets dosed with one of several concentrations of 4-NP (doses varied between 0 (control) and 2000 mg/kg) for 4 weeks, then immediately transferred to sea water. Growth was observed for two successive 6-week periods following sea water transfer when all groups were fed the control diet (no supplemental 4-NP) only. In addition to 4-NP measurement in fish tissues, thyroid hormone concentrations in blood plasma were followed and related to diet treatment and sampling time. Dietary treatment of 4-NP did not influence the growth and smoltification of coho salmon, a result that conflicts to some extent with other reports in which deleterious effects of water-borne 4-NP on the smoltification process of salmonids were linked to disruption of the endocrine system. Appreciable concentrations of 4-NP were present in the livers, gall bladders and tissues after the 4-week exposure of coho salmon to the highest dietary dose of 4-NP, but 4-NP appeared to be effectively eliminated from the fish by the biliary-fecal pathway after sea water transfer.


Impairment of proteostasis network in Down syndrome prior to the development of Alzheimer's disease neuropathology: redox proteomics analysis of human brain.
DS is the most frequent genetic cause of intellectual disability characterized by the anomalous presence of three copies of chromosome 21. One of the peculiar features of DS is the onset of Alzheimer's disease neuropathology after the age of 40years characterized by deposition of senile plaques and neurofibrillary tangles. Growing studies demonstrated that increased oxidative damage, accumulation of unfolded/damaged protein aggregates and dysfunction of intracellular degradative system are key players in neurodegenerative processes. In this study, redox proteomics approach was used to analyze the frontal cortex from DS subjects under the age of 40 compared with age-matched controls, and proteins found to be increasingly carbonylated were identified. Interestingly, our results showed that oxidative damage targets specifically different components of the intracellular quality control system such as GRP78, UCH-L1, V0-ATPase, cathepsin D and GFAP that couples with decreased activity of the proteasome and autophagosome formation observed. We also reported a slight but consistent increase of Aβ 1-42 SDS- and PBS-soluble form and tau phosphorylation in DS versus CTR. We suggest that disturbance in the proteostasis network could contribute to the accumulation of protein aggregates, such as amyloid deposits and NFTs, which occur very early in DS. It is likely that a sub-optimal functioning of degradative systems occur in DS neurons, which in turn provide the basis for further accumulation of toxic protein aggregates. The results of this study suggest that oxidation of protein members of the proteostatis network is an early event in DS and might contribute to neurodegenerative phenomena.


Membrane-associated crystallization of calcium oxalate in vitro.
Incubation of proximal tubular brush border membrane in a metastable calcium oxalate solution of low supersaturation resulted in the equimolar depletion of calcium and oxalate and the formation of monoclinic calcium oxalate crystals. We propose that membrane fragments from sloughed epithelial cells of the nephron can similarly induce crystallization in urine that is metastable for calcium oxalate.


Ultrasonography evaluation during the weaning process: the heart, the diaphragm, the pleura and the lung.
On a regular basis, the intensivist encounters the patient who is difficult to wean from mechanical ventilatory support. The causes for failure to wean from mechanical ventilatory support are often multifactorial and involve a complex interplay between cardiac and pulmonary dysfunction. A potential application of point of care ultrasonography relates to its utility in the process of weaning the patient from mechanical ventilatory support. This article reviews some applications of ultrasonography that may be relevant to the process of weaning from mechanical ventilatory support. The authors have divided these applications of ultrasonography into four separate categories: the assessment of cardiac, diaphragmatic, and lung function; and the identification of pleural effusion; which can all be evaluated with ultrasonography during a dynamic process in which the intensivist is uniquely positioned to use ultrasonography at the point of care. Ultrasonography may have useful application during the weaning process from mechanical ventilatory support.


Extracorporeal liver support techniques: a comparison.
ExtraCorporeal Liver Support (ECLS) systems were developed with the aim of supporting the liver in its detoxification function by clearing the blood from hepatic toxic molecules. We conducted a retrospective comparative analysis on patients presenting with liver failure who were treated with different extracorporeal techniques in our intensive care unit to evaluate and compare their detoxification abilities. To verify the effectiveness of the techniques, mass balance (MB) and adsorption per hour were calculated for total bilirubin (TB), direct bilirubin (DB), and bile acids (BA) from the concentrations measured. MB represents the total amount (mg or mcMol) of a molecule removed from a solution and is the only representative parameter to verify the purification effectiveness of one system as it is not affected by the continuous production of the molecules, released in the circulation from the tissues, as it is the case for the reduction rate (RR). The total adsorption per hour is calculated by the ratio between MB and the time duration and shows the adsorption ability in an hour. Our comparative study shows the superior adsorption capability of CytoSorb system regarding TB, DB, and BA, evaluated through the MB and adsorption per hour, in comparison with CPFA, MARS, Prometheus, and PAP. In conclusion, as extracorporeal purification in liver failure could be considered useful for therapeutic purposes, Cytosorb, being more performing than other systems considered, could represent the device of first choice.


Study of the allogeneic response induced by endothelial cells expressing HLA class II after lentiviral transduction.
Rejection is still the major cause of allograft loss following organ transplantation and a more complete comprehension of the alloimmune response is required in order to develop new therapeutic approaches. Allogenicity is primarily generated by the expression of major histocompatibility complex (MHC) molecules in the donor organ. Graft microvascular endothelial cells express both HLA class I and class II molecules. They are the first target of the allogeneic response because of their vascular localization and are also able to present antigen to recipient T cells. The endothelium can therefore be considered as both a stimulator of and a target for alloimmune responses and both aspects require further study. We have established a model of constitutive expression of HLA-DR by human microvascular endothelial cells following transduction with a lentiviral vector. This model was employed in a study demonstrating that endothelial cells can induce allogeneic expansion of regulatory and pro-inflammatory CD4(+) T lymphocyte subsets. Because microvascular endothelial cells rapidly lose their expression of HLA-DR ex vivo, this experimental system of lentiviral-mediated expression of HLA-DR allows the study of alloantigen presentation without requiring addition of inflammatory cytokines and thus provides a model for the study of the intra-graft allogeneic CD4(+) T cell response at the single-cell level.


Biological embedding of maternal postpartum depressive symptoms: The potential role of cortisol and telomere length.
Although maternal postpartum depressive symptoms (PDS) are associated with child behavior problems, the underlying biological mechanisms are poorly understood. Thus, the current study focused on 193 healthy mother-child dyads and investigated child cortisol and telomere length as potential mediating factors. At 3 and 6 months postpartum, mothers reported on PDS. At age 6, children provided saliva and buccal swab samples. At age 10, mothers and children reported on child behavior problems. Structural equation modelling revealed (a) no association between PDS and child behavior problems and thus no possibility of mediation, but that (b) lower cortisol forecast more child-reported internalizing problems, and (c) shorter telomere length predicted more child-reported internalizing and externalizing problems. These findings raise mediational questions about the determinants of these biomarkers.


An algorithm to identify medical practices common to both the General Practice Research Database and The Health Improvement Network database.
PURPOSE: To identify practices common to both the General Practice Research Database and The Health Improvement Network database for purposes of combining the databases for analysis without duplicate records. METHODS: We developed two independent algorithms to identify practices common to the two databases. The first used the total number of patients in the therapy and clinical data sets and the total number of etoricoxib and celecoxib users each year during the study period. The second used the total number of patients stratified by gender and four different categories of birth year. Further checking of potential matched practice pairs identified by the two algorithms was performed by comparing the patient-level medical records by birth year, dates of clinical visits, and diagnosis codes. RESULTS: Three hundred twelve potential matched pairs of practices were found by both algorithms. Fifteen additional potential pairs were matched by only one algorithm: 13 by algorithm 1 (A1) only and 2 by algorithm 2 (A2) only. The examination of the patient-level visit dates and diagnosis codes for the matches revealed that all of the 327 potential pairs of duplicate practices were in fact the same practice in the two databases. CONCLUSIONS: The two algorithms successfully found the practices common to the two different databases without de-identifying the practices. The identification of the common practices allows for combining the two databases without duplicate records to create a larger data set for analysis, with 168 more practices than when using the General Practice Research Database alone, or with 268 more practices than when using The Health Improvement Network alone. Copyright © 2012 John Wiley & Sons, Ltd.


Metabolic imaging with deuterium labeled substrates.
Deuterium metabolic imaging (DMI) is an emerging clinically-applicable technique for the non-invasive investigation of tissue metabolism. The generally short T1 values of 2H-labeled metabolites in vivo can compensate for the relatively low sensitivity of detection by allowing rapid signal acquisition in the absence of significant signal saturation. Studies with deuterated substrates, including [6,6'-2H2]glucose, [2H3]acetate, [2H9]choline and [2,3-2H2]fumarate have demonstrated the considerable potential of DMI for imaging tissue metabolism and cell death in vivo. The technique is evaluated here in comparison with established metabolic imaging techniques, including PET measurements of 2-deoxy-2-[18F]fluoro-d-glucose (FDG) uptake and 13C MR imaging of the metabolism of hyperpolarized 13C-labeled substrates.


Ca2+/Mg(2+)-dependent ATPase activity in Hymenolepis diminuta mitochondria.
Ca2+ and Mg2+ caused a concentration-dependent activation of ATP hydrolysis by mitochondrial membranes of Hymenolepis diminuta, a rat intestinal cestode. Ca2+ was the more potent, but Mg2+ the more effective. The Lineweaver-Burk plot yielded Km and Vmax values of 1.15 nM and 217.4 nmol Pi min-1 mg-1 protein for Ca(2+)-dependent activity, and 1.86 mM and 333.3 nmol Pi min-1 mg-1 protein for Mg(2+)-dependent activity, respectively. Neither Na+ nor K+, nor a combination of the two cations, induced the hydrolysis of ATP. Ouabain, a specific inhibitor of Na+/K+ ATPase, did not affect the rate of ATP hydrolysis induced by Mg2+ alone or in combination with Na+ or K+. The membrane-bound enzyme was not affected by neuraminidase and concanavalin A. Ca2+ and Mg2+ also induced appreciable hydrolysis of other nucleoside triphosphates by the membranes. Some known anthelmintics, e.g. niclosamide, praziquantel and mebendazole, had no effect on ATPase activities. In addition to other compounds including respiratory inhibitors and uncouplers of phosphorylation, ruthenium red, which blocks Ca2+ influx into the cestode mitochondria, had no influence on the rate of ATP hydrolysis induced by the cations. Triton X-100 was found most suitable for solubilization of both activities. The differences between cestode ATPase and its mammalian counterpart have been discussed.


An optimized method of venous anastomosis for right donor kidney transplantation in rat.
Insufficient length of right renal vein (RV) increases the difficulty of venous anastomosis and blocks the promotion of transplantation of both kidneys, which could significantly reduce operative time and donor numbers. This study sought to discover a quick, safe method of venous anastomosis for right kidney donation. Three venous anastomotic methods (n = 20 in each group) were used for right donor kidney heterotopic transplantation: End-to-side, vena cava bypass, and modified end-to-end, namely, harvesting the right donor kidney with a part of the vena cava and then anastomosing the proximal end to the recipient RV followed by a ligation of the distal end. The conventional end-to-end venous anastomosis was used for left donor kidney orthotopic transplantation as a control (n = 60). We compared operative times and complications. The operative time of the modified end-to-end group (18.45 ± 0.69 minutes) and end-to-side group (17.95 ± 1.54 minutes) were both less than the vena caval bypass group (32.60 ± 2.84 minutes); (P < .05), but equal to the control group (17.60 ± 1.89; P > .05). The overall complication rate among the modified end-to-end group (2/20) was less than those for the end-to-side (8/20) and vena caval bypass groups (9/20; P < .05), but similar to the control group (7/60; P > .05). A modified end-to-end technique is the preferred venous anastomotic method for right donor kidney transplantation.


Approaches to Observe Anthropogenic Aerosol-Cloud Interactions.
Anthropogenic aerosol particles exert an-quantitatively very uncertain-effective radiative forcing due to aerosol-cloud interactions via an immediate altering of cloud albedo on the one hand and via rapid adjustments by alteration of cloud processes and by changes in thermodynamic profiles on the other hand. Large variability in cloud cover and properties and the therefore low signal-to-noise ratio for aerosol-induced perturbations hamper the identification of effects in observations. Six approaches are discussed as a means to isolate the impact of anthropogenic aerosol on clouds from natural cloud variability to estimate or constrain the effective forcing. These are (i) intentional cloud modification, (ii) ship tracks, (iii) differences between the hemispheres, (iv) trace gases, (v) weekly cycles and (vi) trends. Ship track analysis is recommendable for detailed process understanding, and the analysis of weekly cycles and long-term trends is most promising to derive estimates or constraints on the effective radiative forcing.


The Queensland Cancer Risk Study: general population norms for the Functional Assessment of Cancer Therapy-General (FACT-G).
To derive Australian normative scores for the Functional Assessment of Cancer Therapy-General Population (FACT-GP) and to confirm its factor structure. Quality of life (QoL) data (as measured by the FACT-GP) were collected within the Queensland Cancer Risk Study (QCRS) in 2004. The QCRS explored cancer screening and cancer risk behaviours among 9419 English-speaking residents of Queensland aged 20-75 years. Information was collected through computer-assisted telephone interviews and augmented by mailed, Self-Administered Questionnaires (SAQ). A total of 2727 participants largely comparable to the general population of Queensland self-completed the FACT-GP; however, participants were somewhat higher educated, more likely to have had cancer and less likely to be of indigenous heritage. The Queensland population reported a FACT-GP summary score of 85.9 (SD=15.1), with subscale scores (range: 19.2 for social well-being to 25.1 for physical well-being (PWB)). In this study, men and women within different age groups reported similar QoL. QoL was clinically and significantly lower among participants not married, with a body mass index (BMI) deviating from normal weight and with one or more self-reported morbidities. A four-factor solution was confirmed with good goodness-of-fit indices (RSMEA<0.05 for all three age groups). The reference values from the general population reported here can be used for comparison with the QoL measured in populations of cancer patients, providing a benchmark against which clinicians can evaluate the impact of the disease and/or the treatments on QoL.


The Role of Anti-PLA2R and Anti-THSD7A Antibodies in the Pathogenesis and Diagnostics of Primary Membranous Nephropathy: A Review of Current Knowledge for Clinical Practice.
Primary membranous nephropathy (PMN) is considered a major cause of nephrotic syndrome. The discovery of circulating autoantibodies directed against glomerular podocytes helped to classify them as autoimmune diseases. Over the past years, there has been an increasing significance of anti-Phospholipase A2 Receptor (anti-PLA2R), which has been detected in 70-80% of PMN cases, and relevance of anti-Thrombospondin type I domain-containing 7A (anti-THSD7A) even though they are present in 2-5% of patients. The results of clinical and experimental studies indicate that these antibodies are pathogenic. It radically changed the diagnostic and therapeutic approach. Measurement of antibody titers in the serum seems to be a valuable tool for identifying PMN and for the assessment of disease activity. By monitoring pathogenic antibodies levels rather than proteinuria or reduced glomerular filtration rate (GFR) as an indicator of glomerular disease, physicians would easier divide patients into those with active and inactive PMN disease and decide about their therapy. The aim of this review is to evaluate scientific evidence about the role of autoantibodies, namely anti-PLA2R and anti-THSD7A, as PMN biomarkers. The present manuscript focuses on PMN pathogenesis and key data of diagnosis, monitoring of the disease, and treatment strategies that are currently being used in clinical practice.


A synthesis of the factors that contribute to pressure sore formation.
Information about the etiology of pressure sores has been contradictory and is inconsistent with the idea that pressure sore formation is due extensively to depriving a tissue region of blood. Based on these observations and on studies done in the cooperating laboratories, an hypothesis has been formulated that integrates the published data and is consistent with clinical observations. The hypothesis states that a major contributing factor to pressure sores is tissue necrosis that is caused by cell to cell contact or accumulation of anaerobic metabolic waste products and that emotional stress is an independent variable that mediates how long a person can tolerate a set load on a soft tissue region without irreversible tissue damage.


Identification and expression of amphioxus beta-microseminoprotein (MSP)-like gene encoding an ancient and rapidly evolving protein in chordates.
The cDNA encoding beta-microseminoprotein-like (beta-MSPL) was identified from the gut cDNA library of amphioxus. It contains a 336 bp open reading frame corresponding to a deduced protein of 111 amino acids and has eight cysteines conserved and located at the same positions as those in the vertebrate beta-MSPs. At amino acid level, it shares 12-20% similarity to the vertebrate beta-MSPs, and seems lacking the signal peptide at the N-terminus. This not only confirms that beta-MSP is a rapidly evolving protein during phylogeny, but also provides further data on the degree of diversity between species of this protein. RT-PCR and Northern blotting show that amphioxus beta-MSPL is expressed in all tissues examined, suggesting that beta-MSPL plays a fundamental role. However, in situ hybridization reveals that positive hybridization signals were present in all blastomeres of the embryos from 4-cell to gastrula stages, while its expression is restricted exclusively to notochord, somites and primitive gut in neurulae and larvae, and disappears in the ectoderm including the neural tube differentiated from the ectoderm. This suggests that beta-MSPL is possibly involved in the differentiation of ectoderm during embryonic development of cephalochordate amphioxus though it is ubiquitously expressed in embryos prior to gastrula stage and in the adult animal.


Synthesis of C2 alkynylated purines, a new family of potent inhibitors of cyclin-dependent kinases.
The synthesis of a new family of inhibitors of the cell cycle regulating cyclin-dependent kinases (CDK's) is reported. These compounds, related to the purines olomoucine and roscovitine, are characterised by the presence of alkynylated side chains at C2. They inhibit CDK's with IC50's in the 200 nM range.


Emerging point-of-care technologies for sickle cell disease diagnostics.
Sickle cell disease (SCD) is a serious and life-threatening disorder. SCD is considered a public health issue affecting 25% of the population in Central and West Africa. Some countries in this region lack the necessary resources to treat and diagnose many diseases including SCD. Current methods for screening SCD are time-consuming and require expensive laboratory equipment and facilities. This leads to an inability to diagnose the disease early. Lack of early diagnosis and treatment can lead to childhood death. The number of childhood deaths is significantly higher in developing countries. There is unmet need to develop novel methods for diagnosing and monitoring SCD that are both cost effective and portable. The point-of-care (POC) platforms provide the cost effectiveness and portability that allows for the potential diagnosis of millions of people in countries with few resources. In this review, we summarized the important features, benefits, limitations and potential of POC devices. We conducted a comprehensive literature analysis to compare the sensitivity and specificity of several POC diagnostics developed for SCD with a focus on their usages in resource limited settings.


Therapeutic Effects of Salvianolic Acid B on Angiotensin II-Induced Atrial Fibrosis by Regulating Atrium Metabolism via Targeting AMPK/FoxO1/miR-148a-3p Axis.
The present study highlights the effects of salvianolic acid B (Sal B) on angiotensin II (Ang II)-activated atrial fibroblasts as well as the associated potential mechanism from the metabonomics perspective. Metabolic profile analysis performed an optimal separation of the Ang II and control group, indicating a recovery impact of Sal B on Ang II-activated fibroblasts (FBs). We found that metabolite levels in the Ang II + Sal B group were reversed to normal. Moreover, 23 significant metabolites were identified. Metabolic network analysis indicated that these metabolites participated in purine metabolism and FoxO signaling pathway. We found that Sal B activated AMP-activated protein kinase (AMPK) phosphorylation, which further promoted FoxO1 activation and increased miR-148a-3p level. We further verified that Sal B modulate the abnormal AMP, phosphocreatine, glutathione (GSH), and reactive oxygen species (ROS) production in Ang II-stimulated FBs. Collectively, Sal B can protect the Ang II-activated FBs from fibrosis and oxidative stress via AMPK/FoxO1/miRNA-148a-3p axis.


A monoclonal antibody against human colonic adenoma recognizes difucosylated Type-2-blood-group chains.
A monoclonal antibody C14/1/46/10 showing preferential binding to membranes of human colorectal carcinomas over normal colon mucosae was obtained by immunization of mice with extra-nuclear membranes of a human colonic adenoma. Binding and inhibition of binding assays using blood cells or glycoproteins with known blood-group activities indicated that the antibody recognizes a carbohydrate antigen co-existing with the blood-group-H determinant: Fuc alpha 1 leads to 2 Gal. Inhibition assays with structurally defined oligosaccharides showed that the antigenic determinant involves difucosylated Type-2-blood-group chains with the structure: (formula; see text)


Strain differences in a high response-cost daily time-place learning task.
Previous research has shown that rats, unlike birds, do not readily demonstrate daily time-place learning (TPL). It has been suggested, however, that rats are more successful at these tasks if the response cost (RC) is increased. Widman et al. (2000) found that female Sprague Dawley (SD) rats learned a daily TPL task in which they were required to climb different towers depending on the time of day to find a food reward. Using a similar apparatus, we found that male SD rats learned the task, while male Long Evans rats did not. While all rats quickly learned to restrict the majority of their searching to the two towers that provided food, only the SD rats learned to go to the correct location at the correct time of day. Thus, there appears to be a strain difference in the effectiveness of a high RC task to promote learning. Tests of the timing strategies used revealed individual differences with one rat using a circadian strategy and another using an ordinal strategy. Post criterion decrements in performance did not allow sufficient testing to determine the timing strategies of the remaining rats. Possible interactions between strain, response cost, species typical behaviors and dependent measures are discussed.


Choroidal and adnexal extranodal marginal zone B-cell lymphoma: presentation, imaging findings, and therapeutic management in a series of nine cases.
To describe the clinical and imaging presentation, pitfalls in the diagnosis of choroidal extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT), as well as the therapeutic management and prognosis. A retrospective case review of nine choroidal MALT lymphomas was performed. Initial clinical presentation and imaging findings of these histologically confirmed cases of lymphoma were analyzed. Treatment methods, time to diagnosis, systemic work-up, and treatment prognosis were assessed. Initial presentation was essentially blurred vision. The features described on examination were: anterior and posterior scleritis, iridocyclitis, choroidal infiltration, and exudative retinal detachment. Fluorescein and indocyanine green angiography as well as ultrasonography and optic coherence tomography provided arguments in favor of the diagnosis. Biopsy sites included conjunctiva, Tenon's capsule, deep scleral tissue, episclera, lacrimal gland, and choroid. Treatment mostly consisted of a combination of chemotherapy and radiotherapy. The mean time to diagnosis was 12 months. Owing to the insidious onset of these tumors and their ability to simulate other conditions, the diagnosis is commonly delayed. The prognosis is generally good and treatment is effective in the case of localized lymphoma.


Below-knee femoropopliteal bypass using externally supported polytetrafluoroethylene (PTFE) grafts.
Twenty-seven externally supported polytetrafluoroethylene (PTFE) grafts were implanted in the femoropopliteal position crossing the knee joint. All patients underwent surgery because of limb threatening ischemia (rest pain or gangrene). There was one early graft failure (successful thrombectomy). No patient died postoperatively. The mean follow-up period was 17.32 months (range 3-44 months). Cumulative patency rate for this follow-up period was 73%. Absence of kinking when bending the knee joint was determined by ankle Doppler pressure measurements and arteriography. If an adequate saphenous vein is not available for knee-crossing femoropopliteal bypass, externally supported PTFE can be used, yielding short-term patency rates comparable to those obtained with autologous venous bypasses.


rac-(2aS,2a1 R,3aR,3a1 S,5aS,6aR)-2a-Allyl-2,4-di-chloro-2a,2a1,3a1,5a,6,6a-hexa-hydro-3aH-3-oxadi-cyclo-penta-[cd,gh]penta-len-3a-ol.
The title racemic triquinane, C14H14Cl2O2, is composed of four five-membered rings, one of which is a tetra-hydro-furan ring to which an allyl group on one side and a hydroxyl group on the other side are attached. The core of the triquinane unit has a cis-syn-cis configuration. In the crystal, the mol-ecules are linked by pairwise O-H⋯O hydrogen bonds, generating inversion dimers featuring R 2 2(8) loops.


Simulation of antibiotic pharmacodynamic exposure for the empiric treatment of nosocomial bloodstream infections: a report from the OPTAMA program.
We developed a model to predict the pharmacodynamic exposure of antibiotics against bacteria commonly implicated in nosocomial bloodstream infections to determine which dosage regimens would provide the greatest likelihood of obtaining a bactericidal effect. Pharmacodynamic exposures were simulated for 5000 subjects receiving standard doses of ceftazidime, cefepime, piperacillin/tazobactam, meropenem, imipenem, or ciprofloxacin. Exposures were indexed to the MICs of bacteria weighted by their prevalence in causing nosocomial bloodstream infections, derived from 2002 SENTRY data. Enterococci were excluded. MIC data were derived from the 2003 Meropenem Yearly Surveillance Test Information Collection resistance study. The probabilities of achieving bactericidal exposures (ie, target attainment) for each antibiotic regimen were compared. The effect of increasing prevalence of methicillin-resistant Staphylococcus aureus (MRSA) on attainment of bactericidal targets was tested. All dosage regimens except ciprofloxacin and ceftazidime 1 g q8h achieved >90% likelihood of bactericidal exposure. The rank order of target attainment was as follows: imipenem 500 mg q6h, 100.0%; imipenem 1 g q8h, 99.9%; cefepime 2 g q12h, 99.4%; meropenem 1 g q8h, 98.4%; cefepime 1 g q12h, 98.2%; piperacillin/tazobactam 3.375 g q6h, 97.9%; piperacillin/tazobactam 4.5 gq8h, 95.0%; ceftazidime 2 g q8h, 94.2%; ceftazidime 1 g q8h, 71.7%; ciprofloxacin 400 mg q8h, 63.3%; and ciprofloxacin 400 mg q12h,63.0%. Target attainments dropped to <90% for all agents when MRSA was modeled at > or =10% prevalence. The results of this model analysis suggest that standard doses of the carbapenems, piperacillin/tazobactam, and cefepime, and higher doses of ceftazidime, may provide optimal likelihood of achieving bactericidal exposure against pathogens implicated in nosocomial bloodstream infections, excluding MRSA and enterococci. When MRSA rates are > or =10%, therapy with an antibiotic that has activity against this phenotype should be empirically initiated.


Bias-Free Solar-Driven Syngas Production: A Fe2 O3 Photoanode Featuring Single-Atom Cobalt Integrated with a Silver-Palladium Cathode.
Photoelectrochemical syngas production from aqueous CO2 is a promising technique for carbon capture and utilization. Herein, we demonstrate the efficient and tunable syngas production by integrating a single-atom cobalt-catalyst-decorated α-Fe2 O3 photoanode with a bimetallic Ag/Pd alloy cathode. A record syngas production activity of 81.9 μmol cm-2 h-1 (CO/H2 ratio: ≈1 : 1) was achieved under artificial sunlight (AM 1.5 G) with an excellent durability. Systematic studies reveal that the Co single atoms effectively extract the holes from Fe2 O3 photoanodes and serve as active sites for promoting oxygen evolution. Simultaneously, the Pd and Ag atoms in bimetallic cathodes selectively adsorb CO2 and protons for facilitating CO production. Further incorporation with a photovoltaic, to allow solar light (>600 nm) to be utilized, yields a bias-free CO2 reduction device with solar-to-CO and solar-to-H2 conversion efficiencies up to 1.33 and 1.36 %, respectively.


Cellular monitoring of the nuclear factor kappaB pathway for assessment of space environmental radiation.
A screening assay for the detection of NF-kappaB-dependent gene induction using the destabilized variant of the reporter protein enhanced green fluorescent protein (d2EGFP) is used for assessing the biological effects of accelerated heavy ions as a model of space environmental radiation conditions. The time course of d2EGFP expression and therefore of activation of NF-kappaB-dependent gene expression was measured after treatment with TNFA or after heavy-ion exposure using flow cytometry. The reported experiments clearly show that accelerated argon ions (95 MeV/nucleon, LET 230 keV/microm) induce the NF-kappaB pathway at low particle densities (1-2 particle hits per nucleus), which result in as few as 5-50 induced DSBs per cell.


Localized therapy using anti-PD-L1 anchored and NIR-responsive hollow gold nanoshell (HGNS) loaded with doxorubicin (DOX) for the treatment of locally advanced melanoma.
Drug resistance and inefficient localization of chemotherapeutic agent limit the current treatment strategy in locally advanced melanoma (MEL), accounting to the 10-year survival rate from 24% to 68%. In this study we constructed anti-PD-L1 conjugated and doxorubicin loaded hollow gold nanoshell (T-HGNS-DOX) for targeted and localized chemo-photothermal therapy of MEL by the conjugation of LA-PEG-anti-PD-L1 antibody and short PEG chain on the surface of HGNS-DOX. Near infrared (NIR) as well as pH dependent drug release profile was observed. Significant uptake of DOX following NIR due to high PD-L1 receptors resulted in pronounced anticancer effect of T-HGNS-DOX. Following intratumoral administration, maximum nanoparticles retention with the significant reduction in tumor growth was observed as a result of elevated apoptosis marker (cleaved caspase-3, cleaved PARP) as well as downregulation of proliferative (Ki-67) and angiogenesis marker (CD31). Cumulatively, our system avoids the systemic toxicities of the nanosystem thereby providing maximum chemotherapeutic retention in tumor.


Enumeration of lymphocyte subsets during follow-up in the pulmonary tuberculosis patients with co morbid diabetes mellitus.
The present study was designed to evaluate percentage of lymphocyte subsets in peripheral blood mononuclear cells of pulmonary tuberculosis patients with diabetes mellitus (TBDM) and household contacts (HHC) at the time of diagnosis and at different intervals of follow-up. T-lymphocyte subsets, monocytes and natural killer cells were evaluated using fluorescence associated cell sorting (FACS) in a total of 125 subjects including TBDM, pulmonary tuberculosis (PTB) patients, HHC, diabetes mellitus (DM) patients and healthy controls (HC), 25 in each category. CD4 proportion was significantly low in TBDM (p = 0.003), PTB (p = 0.0008) and HHC (p = 0.005) when compared to HCs and increased with treatment in PTB at 6 M and 12 M (p = 0.008). CD8 percentage was significantly low in DM (p = 0.01); Significantly high mean percentage was observed with respect to CD14 in TBDM (p = 0.008), PTB (p = 0.018), HHC (p = 0.008) and DM (p = 0.014); with CD16 in TBDM (p = 0.0001), PTB (p = 0.0001), HHC (p = 0.045); with CD56 in TBDM (p = 0.0003), PTB (p = 0.002) and HHC (p = 0.015) respectively when compared to HCs. These results indicate that TBDM patients have altered lymphocyte homeostasis and FACS analysis might have the potential of a non-invasive clinical indicator for the early detection and monitoring of TB in HHC.


Removal of bisphenol A by waste zero-valent iron regulating microbial community in sequencing batch biofilm reactor.
The removal of bisphenol A (BPA) by waste zero-valent iron (ZVI) regulating microbial community in sequencing batch biofilm reactor (SBBR) was investigated. Compared with SBBR-BPA, the acclimation time of microorganisms in the presence of waste ZVI and BPA (SBBR-ZVI+BPA) decreased from 56 d to 49 d. During stable operation period, BPA was removed completely at 150th min and 100th min in the SBBR-BPA and SBBR-ZVI+BPA, respectively. The optimal initial pH and BPA concentration in the SBBRs were respectively 8.0 and 10 mg/L. The composition and content analysis of extracellular polymeric substances (EPS) using fluorescence spectrometer showed that the yield of EPS was enhanced by the addition of ZVI. The analysis of microbial community structure in the SBBRs using Illumina Miseq sequencing method indicated that the indexes of ACE, Chao1 and Shannon were higher and Simpson index was lower in the SBBR-ZVI+BPA. Moreover, the abundance of BPA biodegradation strains was increased in the presence of ZVI. This study provided a promising method with low cost of effectively removing BPA from wastewater.


The family medicine clerkship over the past 10 years at Ben Gurion University of the Negev.
Most medical teaching takes place in the academic hospital setting and students continue to have little exposure to community-based medicine. The Goldman School of Medicine of the Ben-Gurion University of the Negev is a 6-year program. The 6-week family medicine clerkship takes place in the 5th year. It includes experience with home care, patient and family centered care, ongoing comprehensive responsibility, common office clinical skills, and specific organization of practicing in the community. At the end of the clerkship, students are asked to complete anonymous feedback forms to evaluate the clerkship, its formal curriculum, and the teachers. Over the last 3 years, 157 general course evaluation forms were returned (84.4% compliance). The mean general evaluation and satisfaction score was 3.4 out of 4, ranking it very high compared to other clerkships in our medical school. In the same time period, 176 specific teachers evaluation forms were returned, with a mean score of 4.6 (2=weak; 5=excellent), compared with a mean score of 4.5 in 1,485 teachers evaluation forms from other clinical clerkships. As the focus of patient care shifts to the community, the focus of medical teaching should follow the same route. We hope that our experience will help in promoting this change and in developing new ideas for teaching family medicine and primary care.


Long-distance dispersal by a parasitoid (Anagrus delicatus, Mymaridae) and its host.
We demonstrate that an egg parasitoid, Anagrus delicatus (Mymaridae, Hymenoptera) and its host, Prokelesia marginata (Delphacidae, Homoptera) regularly disperse 1 km or more in a north Florida saltmarsh. Anagrus delicatus were caught on yellow sticky traps on offshore islets and oyster bars throughout the spring, summer, and fall, whereas P. marginata were caught during one pulse in the spring. Parasitism rates were higher on offshore islets than at mainland sites, even though egg densities were higher at the mainland sites. The majority of parasitoids caught offshore were females. Long-distance dispersal by A. delicatus may be a cause of inverse density-dependent or density-independent spatial patterns of parasitism and may represent a risk-spreading strategy.


Multiple mRNAs from the Punch locus of Drosophila melanogaster encode isoforms of GTP cyclohydrolase I with distinct N-terminal domains.
The GTP cyclohydrolase I gene of Drosophila melanogaster, the Punch locus, encodes alternative transcripts of 1.7 and 1.75 kilobases (kb). These transcripts are differentially expressed throughout Drosophila development. cDNA clones representing these transcripts, corresponding genomic regions and polymerase chain reaction-amplified primer extensions of the 5' ends of the RNAs were sequenced. Both RNAs contain five exons and derive from primary transcripts that extend over approximately 8 and 4 kb for the 1.7- and 1.75-kb RNAs, respectively. Their 5'-most exons are unique and spliced onto common 3' exons. The cDNAs each contain a single long open reading frame, which can be translated into a polypeptide of 273 amino acids for the 1.7-kb mRNA and 308 amino acids for the 1.75-kb mRNA. The unique exons confer distinct N-terminal domains to each predicted protein. Sequence comparisons reveal that the Drosophila GTP cyclohydrolase isoforms encoded by the multiple transcripts are highly similar to GTP cyclohydrolases from humans, rodents, and bacteria, with one significant exception. The N-terminal domains encoded by the transcript-specific 5' exons cannot be aligned with the N termini of any other GTP cyclohydrolases. These domains are predicted to confer distinct physical characteristics to the alternate isoforms, and it is hypothesized that they aid in regulating the expression of the enzyme in diverse cellular environments.


Long-term regulation of hexose transport by insulin in cultured mouse (3T3) adipocytes.
Observations in vivo suggest that insulin acts as a long-term regulator of hexose uptake in fat cells. In the present study, we examined the long-term effect of insulin on hexose uptake in vitro. Exposure of fully differentiated mouse 3T3-L1 adipocytes to insulin induced a time-, concentration-, and protein synthesis-dependent increase in basal 2-deoxyglucose uptake (up to 40%) and a decrease in the 'acute' insulin response. The decrease in insulin effect was due to post-receptor alterations, since insulin binding was not substantially altered. The increase in basal 2-deoxyglucose uptake was due to an increase in the apparent Vmax of the transport system rather than to the observed increase (30%) in hexokinase activity, since the concentration of non-phosphorylated 2-deoxyglucose inside the cell was far below the extracellular concentration. The increase in apparent Vmax was most likely due to a protein synthesis-dependent increase in de novo synthesis of hexose transporters. Glucose was not essential for the effect. The mechanism responsible for the loss in insulin response remains to be solved. It can be concluded that insulin has the ability to act as a long-term regulator of hexose uptake in fat cells in vitro.


Tornado-like appearance of spontaneous echo contrast assessed by real-time 3D transesophageal echocardiography.
We report a case showing that real-time 3D transesophageal echocardiography provides unique information about the dynamic nature of spontaneous echo contrast (SEC) in 3D space and has the potential to provide better understanding of SEC.


Enhanced selective removal of arsenic(V) using a hybrid nanoscale zirconium molybdate embedded anion exchange resin.
Selective removal of trace arsenic is crucial for obtaining safe drinking water. Here, the selective adsorptive performance of arsenate (As(V)) on a hybrid ZMAE (nanoscale zirconium molybdate embedded a macroporous anion exchange resin) was examined. It was found that the As(V) adsorption efficiency of ZMAE was almost retained in the presence of competing ions (NO3- or SO42-) up an [SO42-]/[As] or [NO3-]/[As] ratio of 150/1, whereas that of bare AE (anion exchange resin) was negligible for [SO4]/[As] over 15/1. In addition, the As(V) maximum adsorption capacity of ZMAE was found to be 41.2 mg/g, which is in contrast with the negligible adsorption of bare AE under sulfate-rich condition. The enhanced arsenate selectivity of ZMAE can be attributed to the excellent selectivity of ZM NPs (zirconium molybdate nanoparticles), which contributed up to 45% of the adsorption capacity of ZMAE. The behavior of ZMAE towards arsenate was compared with that towards phosphate showing similar adsorption performances between them, which indicates the similar affinity of ZMAE towards arsenate and phosphate. Finally, ZMAE examined for fixed-bed column adsorption for As(V) removal from synthetic As(V) water was effective for up to 5100 BVs, treating As(V) from 0.1 mg/L to below 0.01 mg/L (meeting the WHO guidelines).


Impact evaluation of a public bicycle share program on cycling: a case example of BIXI in Montreal, Quebec.
We examined associations between residential exposure to BIXI (BIcycle-taXI)-a public bicycle share program implemented in Montreal, Quebec, in 2009, which increases accessibility to cycling by making available 5050 bicycles at 405 bicycle docking stations-and likelihood of cycling (BIXI and non-BIXI) in Montreal over the first 2 years of implementation. Three population-based samples of adults participated in telephone surveys. Data collection occurred at the launch of the program (spring 2009), and at the end of the first (fall 2009) and second (fall 2010) seasons of implementation. Difference in differences models assessed whether greater cycling was observed for those exposed to BIXI compared with those not exposed at each time point. We observed a greater likelihood of cycling for those exposed to the public bicycle share program after the second season of implementation (odds ratio = 2.86; 95% confidence interval = 1.85, 4.42) after we controlled for weather, built environment, and individual variables. The implementation of a public bicycle share program can lead to greater likelihood of cycling among persons living in areas where bicycles are made available.


Congenital B-cell Acute Lymphoblastic Leukemia with Congenital Rubella Infection.
Congenital B-cell Acute lymphoblastic leukemia (ALL) is a rare malignancy. A newborn infant presented with purpuric spots and ecchymotic patches, blueberry muffin rash, depressed neonatal reflexes, respiratory distress and hepatosplenomegaly. Peripheral smear revealed atypical blast cells. Serum ELISA was positive for Rubella IgM and IgG antibodies. Flow cytometry suggested congenital B-cell ALL. The baby died after 3 days due to suspected intracranial hemorrhage. Congenital leukemia may be rarely associated with congenital rubella infection.


Disparities in Health, Health Care Access, and Life Experience Between American Indian and White Adults in South Dakota.
The objective of this study is to investigate the factors associated with depressive symptoms and chronic illnesses in American Indians compared with White adults born in the post-World War II period, 1946 to 1964, and living in South Dakota. A cross-sectional design of American Indian and White adults aged 50 and older in South Dakota (Brookings, Vermillion, Sioux Falls, and all others areas of South Dakota) between January 2013 and May 2013 was used. American Indian and White adults (born between 1946 and 1964; N = 349). Data included sociodemographic factors and measures of chronic physical health condition, health care access, adverse childhood experiences, body mass index (BMI), Alcohol Use Disorders Identification Test, Technology Acceptance Model, and Multidimensional Scale of Perceived Social Support and Depressive Symptoms. American Indian adults reported more chronic diseases and conditions, a lower self-perceived physical health, were more likely to be overweight or obese, had more adverse childhood experience (ACE), and reported a lower level of alcohol intake compared to White adults. BMI was significantly associated with an increased number of chronic conditions for both groups, and American Indians' better perception of their physical health was significantly associated with lower total number of chronic conditions. Self-perceived mental health, a better level of access to health care, and a higher degree of social support were significantly inversely associated with the number of depressive symptoms for American Indian adults, while a greater level of ACE was significantly associated with an increased number of depressive symptoms for this group. The current study not only support previous studies but also contributes to understanding the disparities in and risk factors potentially impacting American Indians' physical and mental health. Our findings highlight the need to investigate the American Indians' perceptions and knowledge about health care accessibility including availability as well as perceived barriers including social sensitivity and trust. Health professionals might need to pay attention to BMI, ACE, and social relationship among American Indian adults to improve physical and mental health.


Circular dichroism of quadruplex DNAs: applications to structure, cation effects and ligand binding.
Circular dichroism, CD, spectra can be used to gain information about quadruplex structures of DNAs as well as the effects of sequence, cations, chemical modification and ligand binding on quadruplex structure. There is not yet a validated approach to calculate a CD spectrum from a quadruplex structure nor is their one to go from a CD spectrum to a structure. However, it is possible to empirically correlate CD spectra features with quadruplex structural type in many cases. In this article four case studies are presented to indicate the strengths and limitations of CD in investigations of the properties of quadruplex structures formed by telomere repeat sequences. The case studies include determination of the quadruplex structural type present as a function of potassium concentration, the effect of sequence on the equilibrium between quadruplex structural types as a function of potassium concentration, the effect of ligand binding on quadruplex structure and the effect of 5' phosphorylation on quadruplex structural type.


Effects of d-amphetamine on behavioral and autonomic thermoregulation in mice.
d-Amphetamine has well-known behavioral and sympathomimetic effects in rodents, but its effects on thermoregulation are not well characterized. d-Amphetamine was administered IP to mice at doses of 0.1 to 10.0 mg/kg. Locomotor activity and preferred ambient temperature (Ta) were measured for 60 min after injection in a linear temperature gradient, and metabolic rate (MR) and evaporative water loss (EWL) were measured in a metabolic chamber at ambient temperatures of either 20 degrees C or 30 degrees C. Colonic temperatures (Tc) were obtained 60 min after injection in all cases. Doses of d-amphetamine at 0.3 mg/kg and above reduced preferred Ta from the control value of 30 degrees C to about 25 degrees C. Locomotor activity was reduced briefly by 0.3 mg/kg, and increased after 3.0 mg/kg d-amphetamine. Metabolic rate was suppressed by 0.3 mg/kg of the drug at both 20 and 30 degrees C. At 20 degrees C Ta, 10.0 mg/kg d-amphetamine increased MR but not EWL. At 30 degrees C, MR and EWL were both increased by doses of 3.0 and 10.0 mg/kg. Body temperatures varied both as a function of d-amphetamine dose and of apparatus, with pronounced hyperthermia (Tc greater than 38.5 degrees C) evident only after 10 mg/kg in the metabolic chamber. Thus, the behavioral and autonomic heat loss responses induced in mice by d-amphetamine suggest that its thermogenic action is detected by the animal at doses below those producing measurable thermogenesis and that appropriate effectors, from selection of a cool Ta to increasing EWL, are engaged in an orderly progression to maintain normothermia under all but the most challenging conditions.


Dormancy in solid tumors: implications for prostate cancer.
In cancer dormancy, residual tumor cells persist in a patient with no apparent clinical symptoms, only to potentially become clinically relevant at a later date. In prostate cancer (PCa), the primary tumor is often removed and many patients experience a prolonged period (>5 years) with no evidence of disease before recurrence. These characteristics make PCa an excellent candidate for the study of tumor cell dormancy. However, the mechanisms that constitute PCa dormancy have not been clearly defined. Additionally, the definition of tumor cell dormancy varies in the literature. Therefore, we have separated tumor cell dormancy in this review into three categories: (a) micrometastatic dormancy--a group of tumor cells that cannot increase in number due to a restrictive proliferation/apoptosis equilibrium. (b) Angiogenic dormancy--a group of tumor cells that cannot expand beyond the formation of a micrometastasis due to a lack of angiogenic potential. (c) Conditional dormancy--an individual cell or a very small number of cells that cannot proliferate without the appropriate cues from the microenvironment, but do not require angiogenesis to do so. This review aims to identify currently known markers, mechanisms, and models of tumor dormancy, in particular as they relate to PCa, and highlight current opportunities for advancement in our understanding of clinical cancer dormancy.


The effect of calcium on somatostatin inhibition of insulin release and cyclic AMP production in mouse pancreatic islets.
The effect of somatostatin on glucose-induced insulin secretion and cyclic AMP accumulation in isolated islets from obese, hyperglycemic ob/ob mice was studied in a microperifusion system. The normal biphasic pattern of insulin release as well as the inhibitory pattern of insulin release produced by somatostatin (0.5--1 microgram/ml) was matched by similar changes in the intracellular concentration of cyclic AMP. When islets were stimulated by glucose (3 mg/ml) plus 3-isobutyl-1-methylxanthine (0.1 mM), somatostatin (0.5 microgram/ml) failed to inhibit insulin secretion or cyclic AMP formation in the second phase whereas in the first phase both parameters were significantly reduced by somatostatin (0.5 microgram/ml). In batch-type incubations it was shown that addition of excess calcium (to 6 mM) reversed this inhibition. In the second phase calcium potentiated the (glucose + 3-isobutyl-1-methylxanthine)-stimulated insulin secretion without affecting the cyclic AMP production. This potentiation was inhibited by somatostatin (0.1 microgram/ml). Somatostatin (1 microgram/ml) inhibited adenylate cyclase activity in islet homogenates. No effect of somatostatin on islet glucose utilization could be demonstrated. The results indicate a dual action of somatostatin in the inhibition of insulin release, one involving the islet adenylate cyclase and one affecting the islet uptake of calcium.


Acute electrophysiological effect of pulsed gallium-arsenide low-energy laser irradiation on isolated frog sciatic nerve.
We evaluated the acute electrophysiological effects of low-energy pulsed laser irradiation on isolated frog sciatic nerve measured by extracellular recording technique. A pulsed gallium-arsenide (GaAs) laser (wavelength: 904 nm, pulse duration 220 ns, peak power per pulse: 27W, spot size: 0.28 cm(2), total applied energy density: 0.005-2.5J/cm(2)) was used for the experiment. Sixty isolated nerves were divided into six groups (n=10), each of which received a different laser dose. In each group, action potentials were recorded before laser irradiation which served as the control data. The extracellular action potentials were recorded for each combination of 1, 3, 5, 7, 10, 13 and 15 minutes of irradiation time and 4, 8, 16, 32, 64 and 128 repetition frequency by using a BIOPAC MP 100 Acquisition System Version 3.5.7 (Santa Barbara, USA). Action potential amplitude, area, duration and conduction velocity were measured. Statistical evaluation was performed using repeated measures variance analysis by SPSS 9.0. There were no statistically significant differences for action potential amplitude, area and conduction velocity among the laser groups and control data (p>0.05). The study showed that low-energy GaAs irradiation at 4-128 Hz repetition frequencies administered for irradiation times of 1-15 min generates no effect on action potential amplitude, area, duration and conduction velocity in isolated frog sciatic nerve.


Are pediatricians familiar with hereditary angioedema?
Hereditary angioedema (HAE) is an autosomal dominant disease characterized by recurrent episodes of subcutaneous or mucosal edema caused by excess bradykinin. The aim of the present study was to assess the knowledge of pediatricians about hereditary angioedema. An online survey with 12 HAE-related and 14 demographics-related questions was e-mailed to all pediatricians who were members of the Brazilian Society of Pediatrics (n = 17 145) once a week during the months of June and July 2021. The electronic questionnaire assessed clinical manifestations, diagnosis, and treatment of hereditary angioedema in children and adolescents. Four hundred and fifty-five pediatricians responded to the questionnaire (2.6%), of whom 55 (12.1%) were board certified in Allergy and Immunology (A/I), while 400 (87.9%) were not (N-A/I). Three hundred and sixty-eight (80.9%) were female, 289 (55.7%) were under 50 years of age, 286 (62.9%) graduated from Medical School more than 10 years previously, 83 (18.2%) held an MSc/PhD degree, and 253 (55.6%) were living in the Southeast Region of Brazil. The median number of correct answers to the questions related to HAE among A/I was 7 out of 12 (58.3%), with median ranging from 4.5 to 8 correct answers, while for N-A/I it was 3 (25%), with median ranging from 2.5 to 4 correct answers (p < 0.001). Knowledge about HAE among Brazilian pediatricians, whether board certified in Allergy and Immunology or not, was unsatisfactory. HAE is a rare disease, largely unknown among physicians; therefore, increasing awareness may lead to improvement in diagnosis and treatment.


Inhibition of Azotobacter vinelandii RNA polymerase by cibacron blue F3GA.
Cibacron blue F3GA is a potent inhibitor of the Azotobacter vinelandii DNA-directed RNA polymerase. Addition of 8 micrometer Cibacron blue F3GA prior to initiation results in a greater than 90% inhibition of the poly[d(A-T]-directed synthesis of poly[r(A-U)] while addition of the dye during the course of the reaction is without effect on chain elongation. Binding of RNA polymerase to [3H]poly[d(A-T)] is inhibited by only 15% in the presence of 8 micrometer Cibacron blue F3GA. Inhibition by Cibacron blue F3GA is noncompetitive with regard to ATP, UTP, or template. The poly[d(A-T)]-directed pyrophosphate exchange reaction is relatively resistant to inhibition by Cibacron blue F3GA. Rifampicin added to a similar reaction (in the presence of absence of Cibacron blue F3GA) results in 95% inhibition of the exchange reaction. The interaction of the RNA polymerase core enzyme with Cibacron blue F3GA is shown by the formation of a difference spectrum with a positive maximum at 675 nm which is not affected by the presence of a high concentration (4 micrometer) of rafampicin. The data indicate that Cibacron blue F3GA acts by binding to RNA polymerase and inhibits a step between the synthesis of the initial phosphodiester bond and formation of a stable ternary elongation complex.


Open Dialogue compared to treatment as usual for adults experiencing a mental health crisis: Protocol for the ODDESSI multi-site cluster randomised controlled trial.
Background 'Open Dialogue' is a social network model of crisis and continuing mental healthcare which involves elements of service delivery such as immediate response and a style of therapeutic meeting called network meetings. Although there are indications from non-randomised studies that it may help people in their recovery from severe mental health crises and improve long-term outcomes, this has yet to be tested in a randomised controlled trial. Methods This paper outlines the protocol for a multi-site cluster-randomised control trial assessing the clinical and cost-effectiveness of Open Dialogue compared to treatment as usual (TAU) for individuals presenting in crisis to six mental health services in England. The primary outcome is time to relapse, with secondary outcomes including measures of recovery and service use. Participants will be followed-up for two years, with data collected from electronic medical records and researcher-led interviews. The analysis will compare outcomes between treatment groups as well as investigating potential mediators of effect: shared decision-making and social network quality and size. Carers of a subsample of participants will be asked about their experiences of shared decision-making, carer burden, and satisfaction. Discussion This trial will provide evidence of whether Open Dialogue services implemented in the English mental health system is an effective alternative to current care and may have important implications for the organization of community mental health services. Trial registration: retrospectively registered (108 participants recruited of 570 target) on 20/12/2019, ISRCTN52653325.


Normal forms of dispersive scalar Poisson brackets with two independent variables.
We classify the dispersive Poisson brackets with one dependent variable and two independent variables, with leading order of hydrodynamic type, up to Miura transformations. We show that, in contrast to the case of a single independent variable for which a well-known triviality result exists, the Miura equivalence classes are parametrised by an infinite number of constants, which we call numerical invariants of the brackets. We obtain explicit formulas for the first few numerical invariants.


Repeat open intracardiac operation. Analysis of fifty operations.
Between December, 1972, and February, 1976, 50 open-heart operations were performed on 44 patients who had previously had open cardiotomies. Reasons for reoperation were failure of biological tissue valves (15 cases), failure of mechanical valves (12 cases), paraprosthetic reguritation (nine cases), recurrent or incompletely corrected congenital malformations (eight cases), prosthetic endocarditis (two cases), misdiagnoses (two cases), and miscellaneous causes (two cases). Operations performed included 20 aortic valve replacements, 10 mitral valve replacements, seven double valve replacements, five repairs of paraprosthetic leaks, one tricuspid valve replacement, and seven procedures for congenital defects. There were two deaths within 30 days of operation (operative mortality rate of 4 percent) and six deaths between 7 weeks and 3 years after operation. Postoperative complications were slightly more frequent than in patients undergoing similar operations for the first time. The late functional result was good in the majority (73%) of survivors.


Empowering human cardiac progenitor cells by P2Y14 nucleotide receptor overexpression.
Autologous cardiac progenitor cell (CPC) therapy is a promising approach for treatment of heart failure (HF). There is an unmet need to identify inherent deficits in aged/diseased human CPCs (hCPCs) derived from HF patients in the attempts to augment their regenerative capacity prior to use in the clinical setting. Here we report significant functional correlations between phenotypic properties of hCPCs isolated from cardiac biopsies of HF patients, clinical parameters of patients and expression of the P2Y14 purinergic receptor (P2Y14 R), a crucial detector for extracellular UDP-sugars released during injury/stress. P2Y14 R is downregulated in hCPCs derived from HF patients with lower ejection fraction or diagnosed with diabetes. Augmenting P2Y14 R expression levels in aged/diseased hCPCs antagonizes senescence and improves functional responses. This study introduces purinergic signalling modulation as a potential strategy to rejuvenate and improve phenotypic characteristics of aged/functionally compromised hCPCs prior to transplantation in HF patients. Autologous cardiac progenitor cell therapy is a promising alternative approach to current inefficient therapies for heart failure (HF). However, ex vivo expansion and pharmacological/genetic modification of human cardiac progenitor cells (hCPCs) are necessary interventions to rejuvenate aged/diseased cells and improve their regenerative capacities. This study was designed to assess the potential of improving hCPC functional capacity by targeting the P2Y14 purinergic receptor (P2Y14 R), which has been previously reported to induce regenerative and anti-senescence responses in a variety of experimental models. c-Kit+ hCPCs were isolated from cardiac biopsies of multiple HF patients undergoing left ventricular assist device implantation surgery. Significant correlations existed between the expression of P2Y14 R in hCPCs and clinical parameters of HF patients. P2Y14 R was downregulated in hCPCs derived from patients with a relatively lower ejection fraction and patients diagnosed with diabetes. hCPC lines with lower P2Y14 R expression did not respond to P2Y14 R agonist UDP-glucose (UDP-Glu) while hCPCs with higher P2Y14 R expression showed enhanced proliferation in response to UDP-Glu stimulation. Mechanistically, UDP-Glu stimulation enhanced the activation of canonical growth signalling pathways ERK1/2 and AKT. Restoring P2Y14 R expression levels in functionally compromised hCPCs via lentiviral-mediated overexpression improved proliferation, migration and survival under stress stimuli. Additionally, P2Y14 R overexpression reversed senescence-associated morphology and reduced levels of molecular markers of senescence p16INK4a , p53, p21 and mitochondrial reactive oxygen species. Findings from this study unveil novel biological roles of the UDP-sugar receptor P2Y14 in hCPCs and suggest purinergic signalling modulation as a promising strategy to improve phenotypic properties of functionally impaired hCPCs.


Vasodilation Mechanism of Cerebral Microvessels Induced by Neural Activation under High Baseline Cerebral Blood Flow Level Results from Hypercapnia in Awake Mice.
We investigated the effects of the baseline CBF level at resting state on neurovascular coupling. Diameters of arterioles, capillaries, and venulas in awake mouse brain were measured by a two-photon microscope. Vasodilation in each of the cerebral vessels was caused by three experimental conditions: (1) sensory stimulation, (2) 5% CO2 inhalation (hypercapnia), (3) simultaneous exposure to sensory stimulation and 5% CO2 inhalation. CBF and CBV were also measured by a microscope and a CCD camera. Increases in CBF and CBV were observed under all experimental conditions. After the increases in CBF and CBV due to hypercapnia, additional increases in CBF and CBV occurred during sensory stimulation. Diameter changes in arterioles were significantly larger than those in capillaries and venulas under both sensory stimulation and 5% CO2 inhalation. Additional vasodilation from sensory stimulation was observed under hypercapnia. The diameter change in each vessel type during sensory stimulation was maintained under simultaneous exposure to sensory stimulation and hypercapnia. The diameter change of cerebral vessels during neural activation is reproducible regardless of whether baseline CBF has increased or not. Our finding directly demonstrates the concept of uncoupling between energy consumption and energy supply during cortical activation.


Rat brain hypothalamic and hippocampal monoamine and hippocampal beta-adrenergic receptor changes during pregnancy.
The concentration of noradrenaline (NA), dopamine (DA), serotonin (5-HT), and their metabolites was measured in hypothalamic and hippocampal brain tissue obtained from non-pregnant, 15- or 20-day pregnant and 4-day postpartum rats. At 20 days of pregnancy, hypothalamic NA and DA concentrations were significantly decreased and their turnover increased relative to postpartum and estrous values, respectively. Hippocampal 3-methoxy-4-hydroxy-phenylglycol (MHPG) levels were significantly decreased at 15 days of pregnancy and 4 days postpartum compared to estrous and 20-day pregnant levels and the MHPG/NA ratio was significantly reduced at 4 days postpartum relative to the estrous value. Hippocampal 5-HT and 5-hydroxyindole-3-acetic acid (5-HIAA) levels were significantly decreased at 15 days of pregnancy while 5-HIAA levels and the 5-HIAA/5-HT ratio were significantly decreased at 20 days of pregnancy. Hippocampal beta-adrenergic receptor density was significantly lower at 4 days postpartum than at 15 days of pregnancy. A positive correlation was observed between plasma progesterone and hippocampal beta-adrenoceptor Kd values, suggesting a possible causal relationship between these two variables. The monoamine and beta-adrenoceptor changes which occur during pregnancy may be an important contributing factor in determining the mood changes which occur during pregnancy and postpartum.


Serratene triterpenoids from Lycopodium cernuum L. as α-glucosidase inhibitors: Identification, structure-activity relationship and molecular docking studies.
Phytochemical investigation of Lycopodium cernuum L. afforded seven undescribed serratene triterpenoids named 3β, 21β-dihydroxyserra-14-en-24-oic acid-3β-(5'-hydroxybenzoate) (1), 3β, 21β, 24-trihydroxyserrat-14-en-3β-(5'-hydroxyl benzoate) (2), 3β, 14α, 15α, 21β-tetrahydroxyserratane-24-methyl ester (3), 3β, 14α, 21β-trihydroxyserratane-15α-(4'-methoxy-5'-hydroxybenzoate)-24-methyl ester (4), 3β, 14α, 21β-trihydroxyserratane-15α-(4'-methoxy-5'-hydroxybenzoate) (5), 3β-hydroxy-21β-acetate-16-oxoserrat-14-en-24-oic acid (6), 3β, 21β-dihydroxy-16α, 29-epoxyserrat-14-en-24-methyl ester (7), together with eleven known compounds (8-18), whose chemical structures were elucidated through spectroscopic analysis of HRESIMS, 1D NMR, 2D NMR and comparison between the literature. All compounds were evaluated for their α-glucosidase inhibitory activity for the first time. The results showed that compounds 1, 2, 4, 5, 6, 10, 13, 15, and 16 were among the most potent α-glucosidase inhibitors, with IC50 values ranging from 23.22 ± 0.64 to 50.65 ± 0.82 μM. Structure-activity relationship (SAR) studies indicated that the combined properties of the 5-hydroxybenzoate moiety at C-3, β-OH at C-21, COOH- at C-24, and Δ14,15 groups enabled an increase in the α-glucosidase inhibitory effect. In addition, molecular docking studies showed that the potential inhibitors mainly interact with key amino acid residues in the active site of α-glucosidase through hydrogen bonds and hydrophobic forces.


Gradually closing the loop.
The Lariat device is an epicardial nonimplant suture delivery device capable of left atrial appendage closure. The current study offers promising results but is limited by small sample size and multiple foundational issues with study design. aMaze, a large multi-center prospective randomized trial is currently underway and will provide additional insight into the safety of this device and its efficacy in maintenance of sinus rhythm after atrial fibrillation ablation.


Light-sheets and smart microscopy, an exciting future is dawning.
Light-sheet fluorescence microscopy has transformed our ability to visualize and quantitatively measure biological processes rapidly and over long time periods. In this review, we discuss current and future developments in light-sheet fluorescence microscopy that we expect to further expand its capabilities. This includes smart and adaptive imaging schemes to overcome traditional imaging trade-offs, i.e., spatiotemporal resolution, field of view and sample health. In smart microscopy, a microscope will autonomously decide where, when, what and how to image. We further assess how image restoration techniques provide avenues to overcome these tradeoffs and how "open top" light-sheet microscopes may enable multi-modal imaging with high throughput. As such, we predict that light-sheet microscopy will fulfill an important role in biomedical and clinical imaging in the future.


Percutaneous diskectomy in the treatment of pediatric lumbar disk disease.
Intervertebral lumbar disk herniation in children and adolescents is rare. The incidence varies between 0.8% and 3.8% of all disks treated surgically. The uncertainty concerning operative or conservative treatment of this rare clinical entity has led to considering the use of atraumatic techniques, such as chemonucleolysis or percutaneous diskectomy. We report the unusual case of an 11-year-old girl with herniated disk at the L4-5 level treated by percutaneous diskectomy. This is, to our knowledge, the first case of a child treated by this technique. The technical simplicity, the minimal trauma it causes, and the excellent clinical result show that percutaneous diskectomy is a reasonable therapeutic alternative in the treatment of juvenile disks.


Validity of the Cancer and Aging Research Group Predictive Tool in Older Japanese Patients.
Background: This study aimed to evaluate the usefulness of the Cancer and Aging Research Group (CARG) predictive tool in older Japanese patients with cancer. Methods: Patients aged 65 years or older with solid tumors treated with new anticancer regimens in Kakogawa Central City Hospital between April 2016 and March 2019 were included. Grade 3 or higher risks of developing chemotherapy-related adverse events (CRAEs) were calculated using the tool (low-, intermediate-, or high-risk scores). The association between grade 3−5 CRAE incidence during the first course of each regimen and the calculated risk or the patient characteristics was evaluated. The difference in the incidences of CRAEs between the groups was evaluated by Fisher's exact test. Results: This study examined 76 patients (mean age: 71 (65−82) years). The incidence of grade 3−5 CRAE was 38%, 55%, and 76% in patients classified as low, medium, and high CARG risk scores (p = 0.035), and the incidence of severe non-hematological toxicities was 4%, 31%, and 52% (p < 0.01), respectively. Eastern Cooperative Oncology Group performance status and age were not associated with chemotherapy toxicity. Conclusions: The CARG predictive tool was valid, suggesting its usefulness in optimizing chemotherapy outcomes in older patients with cancer.


[Electroophthalmological investigations in amblyopia (author's transl)].
In the case of 8 amblyopic patients the ERG and the brightness VECP, as well as the TV-pattern reversal VECPs in whole field and upper and lower half field stimulation, were traced. In the ERG (a- and b-wave) and the brightness VECP significant differences were established neither in the amplitude nor in the latenz between amblyopic and healthy eyes. The amplitude of the pattern reversal VECPs in whole field and lower half field stimulation was significantly reduced in all 8 patients on the side of the amblyopic eye.


Increase of renal sympathetic nerve activity by metoprolol or propranolol in conscious spontaneously hypertensive rats.
1 Mean arterial pressure (MAP), heart rate (HR) and renal sympathetic nerve activity (RSNA) were recorded in conscious spontaneously hypertensive rats (SHR). 2 Infusion of metoprolol (4 mumol kg-1 h-1) or propranolol (1.5 mumol kg-1 h-1) reduced HR and significantly increased RSNA. 3 Administration of metoprolol caused a sustained decrease of MAP starting in the third hour of infusion. In contrast, administration of propranolol induced a biphasic response in MAP. It is suggested that the increase of RSNA after both beta-adrenoceptor blocking drugs is due to a decrease in arterial baroreceptor activity.


A new panfunduscopic lens: a +90D-Goldmann fundus lens combination.
A new panfunduscopic lens is made by combining a +90 D lens and Goldmann contact fundus lens. The optics involved is explained.


Myelin basic protein immunosensor for multiple sclerosis detection based upon label-free electrochemical impedance spectroscopy.
A novel highly sensitive impedimetric Myelin Basic Protein (MBP) immunosensor for the determination of a Multiple Sclerosis (MS) autoantibody, Anti-Myelin Basic Protein (Anti-MBP) was developed by immobilization of MBP on Gelatin and Gelatin-Titanium Dioxide (TiO₂) modified platinium electrode. Cyclic voltammetric (CV) and Electrochemical Impedance Spectroscopic (EIS) methods were employed in determination of the electrode responses and applicability. Gelatin-MBP and gelatin-TiO₂-MBP electrodes were prepared by chemical immobilization of the substrates onto the platinium electrodes. The formal potentials of MBP confined on gelatin-MBP and gelatin-TiO₂-MBP surfaces are estimated to be 195 and 205 mV, respectively. Thus, a little more reversible electron transfer reaction occurs on the gelatin-TiO₂-MBP immunosensor surface. The peak separations of MBP (150 mV and 110 mV s(-1) at 100 mV s(-1)) and the asymmetric anodic and cathodic peak currents indicate that the electron transfer between Anti-MBP and gelatin-MBP/gelatin-TiO₂-MBP immunosensor is quasireversible. Control samples containing a nonspecific human immunoglobulin G (hIgG) antibody were also studied, and calibration curves were obtained by subtraction of the responses for specific and nonspecific antibody-based sensors. Gelatin-MBP and gelatin-TiO₂-MBP immunosensors have detection limit of 0.1528 ng ml(-1) and 0.1495 ng ml(-1) respectively. This immunosensor exhibits high sensitivity and low response times (58 s for gelatin-MBP and 46 s for gelatin-TiO₂-MBP immunosensor). The developed label-free impedimetric immunosensors also provide a simple and sensitive detection method for the specific determination of Anti-MBP in human cerebrospinal fluid (CSF) and serum samples.


Study of folate-based carbon nanotube drug delivery systems targeted to folate receptor α by molecular dynamic simulations.
We designed targeted drug delivery systems containing folate (FOL), the functionalized carbon nanotube (f-CNT) and doxorubicin (DOX), and studied the targeting properties of folate, f-CNT-FOL and DOX/f-CNT-FOL to folate receptor α (FRα). Folate was actively targeted to FRα in molecular dynamics simulations, and the dynamic process, effect of folate receptor evolution, and characteristics were analyzed. On this basis, the f-CNT-FOL and DOX/f-CNT-FOL nano-drug-carrier systems were designed, and the drug delivery process targeted to FRα was studied by 4 times MD simulations. The system evolution and detailed interactions of f-CNT-FOL and DOX/f-CNT-FOL with FRα residues were examined. We found that though the connection of CNT with the FOL could decrease the insertion depth of the pterin of FOL into the pocket of FRα, the loading of drug molecules could reduce this effect. Representative snapshots from the MD simulations were analyzed, showing that the location of DOX on the surface of CNT was constantly changed during the MD simulation, but the surface of the four rings of DOX were almost always parallel to the surface of CNT. The RMSD and RMSF were used to further analyze. The results may provide new insights for the design of novel targeted nano-drug-delivery systems.


Fatal coxsackievirus B infection in early infancy characterized by fulminant hepatitis.
to clarify the major features of fatal coxsackievirus B infection characterized by fulminant hepatitis in early infancy. clinical manifestations and laboratory investigations concerning five consecutive young infants with overwhelming coxsackievirus B fulminant hepatitis between 1994 and 1997 were retrospectively reviewed. Aetiological diagnosis was made by viral cultures and confirmed by a neutralization test with a type-specific antiserum. all five had a deteriorating clinical course of severe hepatitis complicated by disseminated intravascular coagulopathy (DIC). Coxsackievirus B1 infection was established in four patients and coxsackievirus B3 in one. The pathological findings of the two cases illustrated extensive hepatocellular necrosis. Fulminant hepatitis can occur as a leading presentation of disseminated coxsackievirus B infections and dominant the clinical features in neonates and young infants. the liver was the target organ of fatal coxsackievirus B infection in our patients. Hepatic involvement progressed rapidly to jaundice and coagulopathy, and was considered to be indicative of poor prognosis. Coxsackievirus B hepatitis may be serious in early infancy.


The occurrence of Listeria monocytogenes in cheese from a manufacturer associated with a case of listeriosis.
A case of listeriosis was associated with the consumption of a soft cheese produced in England. Goats cheese and other products from the same food manufacturer were examined for the presence of Listeria over the following 11 months. Listeria monocytogenes was isolated from 16 of 25 cheese samples on retail sale, 12 of 24 cheese samples obtained directly from the factory, and from shelving within the plant. Phage-typing of 68 isolates of L. monocytogenes from cheese samples and the factory showed that 66 (97%) were indistinguishable from the strain isolated from the patient's cerebrospinal fluid and stool. L. monocytogenes was not isolated from seven goats milk or two yoghurt samples. Listeria innocua was isolated from 10 cheese samples, two of which contained no other species of Listeria. Levels of L. monocytogenes shortly after production were low (less than 10/g), but were higher (10(5)-10(7) cfu/g) in six of the 16 cheese samples obtained from retail outlets. Multiplication of L. monocytogenes was demonstrated in cheeses contaminated at the factory and held at 4 degrees C in the laboratory.