Sexual violence and associated factors among women of reproductive age in Rwanda: a 2020 nationwide cross-sectional survey.
Sexual violence against women is a global public health issue with both short- and long-term effects on the physical and mental health of women. This study aimed to determine the prevalence of sexual violence and its associated factors among women of reproductive age in Rwanda. We used secondary data from the 2020 Rwanda Demographic and Health Survey of 1,700 participants, who were selected using multistage stratified sampling. Multivariable logistic regression was conducted to explore factors associated with sexual violence using SPSS (version 25). Of the 1,700 women of reproductive age, 12.4% (95%CI: 11.0-14.1) had experienced sexual violence. Justified beating (AOR = 1.34, 95%CI: 1.16-1.65), not having health insurance (AOR = 1.46, 95%CI: 1.26-2.40), not being involved in healthcare decision-making (AOR = 1.64, 95%CI: 1.99-2.70), having a husband/partner with primary (AOR = 1.70, 95%CI: 5.47-6.21) or no education (AOR = 1.84, 95%CI: 1.21-3.37), as well as having a husband/partner who sometimes (AOR = 3.37, 95%CI: 1.56-7.30) or often (AOR = 12.87, 95%CI: 5.64-29.38) gets drunk were positively associated with sexual violence. However, women from male-headed households (AOR = 0.52, 95%CI: 0.29-0.92) were less likely to experience sexual violence. There is a need to demystify negative culturally-rooted beliefs favouring sexual violence, such as justified beating, as well as increase efforts to promote women's empowerment and healthcare access. Moreover, engaging men in anti-sexual violence strategies is paramount to addressing male-related issues that expose women to sexual violence.


Relationship of PCDD/F and Co-PCB concentrations in breast milk with infant birthweights in Tokyo, Japan.
To observe how PCDD/F and Co-PCB concentrations in breast milk relate to infant birthweights in Tokyo, Japan. Breast milk samples were collected from 240 mothers (aged 25-34years old) residing in Tokyo to measure the concentrations of polychlorinated dibenzo-p-dioxins (PCDDs; 14 congeners), polychlorinated dibenzofurans (PCDFs; 15 congeners), and coplanar polychlorinated biphenyls (Co-PCBs; 12 congeners) in the breast milk fat. Individual milk samples (about 50ml) were obtained 30days after delivery, between the months of June and September in 1999 and 2000. The relationship of the infant birthweights with the PCDD/F and Co-PCB concentrations was observed. The birthweights were negatively correlated the concentrations of many of the PCDD/F and Co-PCB congeners, with the mean toxic equivalent quantities (TEQs) of the Co-PCBs, and with the sum of the PCDD, PCDF and Co-PCBs, although their correlation coefficients were less than 0.200. Multiple regression analysis showed octachlorodioxin was statistically significant explanatory variate. There were slight relationship between the dioxins levels of breast milk and the birthweights of the infants.


Prediction of the response to beta-blocker therapy in patients with dilated cardiomyopathy: comparison of 123I-MIBG scintigraphy and low-dose dobutamine stress echocardiography.
In this study, we aimed to compare low-dose dobutamine stress echocardiography (DSE) and iodine 123-metaiodobenzylguanidine (MIBG) scintigraphy for predicting the response to beta-blocker therapy in patients with dilated cardiomyopathy (DCM). MIBG imaging was performed in 10 patients with DCM (mean EF 28 ± 8%), who were subsequently treated with beta-blocker therapy. The heart-to-mediastinum (H/M) MIBG uptake ratio was evaluated in initial and delayed images, and the percent washout ratio of myocardial MIBG was determined. DSE was also performed in all patients to measure left ventricular ejection fraction (LVEF) at rest and during dobutamine infusion (10 μg/kg/min). LVEF at rest was also assessed by echocardiography before and after 6 months of beta-blocker therapy. LVEF was significantly improved after beta-blocker therapy (28 ± 8 to 41 ± 11%, p < 0.001). The relative change in LVEF after beta-blocker therapy was significantly correlated with the relative change in LVEF during DSE (r = 0.68, p < 0.03). The H/M MIBG uptake ratio in both early and delayed imaging was not significantly correlated with the relative change in LVEF in response to beta-blockade therapy. The relative change in LVEF during DSE, but not MIBG imaging predicted the relative change in LVEF in response to beta-blockade therapy in a limited number of DCM patients.


Effect of growth hormone-releasing hormone (GHRH) and GHRH antagonist (MZ-4-71) on interferon-gamma secretion from human peripheral blood mononuclear cells in vitro.
Numerous reports indicate close interactions between the neuroendocrine and the immune systems. Hypothalamic neuropeptide, growth hormone-releasing hormone (GHRH) stimulates growth hormone (GH) secretion from the anterior pituitary gland, but recently some immunomodulatory properties of this peptide have also been demonstrated. In the present studies we evaluated the effect of human synthetic GHRH(1-44)NH(2) and GHRH antagonist (MZ-4-71) on interferon (IFN)-gamma secretion from human peripheral blood mononuclear cells (PBMC). GHRH(1-44)NH(2) at 10(-10), 10(-8) and 10(-6) M concentrations significantly (p < 0.05) increased the IFN-gamma level in supernatants of cultured cells, as compared with the controls. GHRH antagonist (MZ-4-71) at 10(-10), 10(-8) and 10(-6) M concentrations diminished the IFN-gamma level in supernatants in a dose-dependent manner, but statistically significant differences were observed only at 10(-8) M and 10(-6) M (p < 0.05 vs controls). Our results demonstrate that GHRH and GHRH antagonist MZ-4-71 can modulate IFN-gamma secretion in vitro by human peripheral blood mononuclear cells.


Public health guidance and the role of new NICE.
This paper describes the operating and methods for the newly established centre for Public Health Excellence in the National Institute of Health and Clinical Excellence (NICE). The origins of the establishment of this organisation are described and the types of public health guidance which will be produced are outlined. The Advisory Committee Structure for the new organisation is also presented. The importance of the application of evidence based guidance in public health is considered.


A cytotoxic monoclonal antibody specific for the private alloantigenic determinant of the HLA-B 13 molecule.
A murine monoclonal antibody (TU 110) prepared against blast cells of a patient with acute "undifferentiated" leukemia was tested in the microcytotoxicity assay on peripheral blood lymphocytes of 122 normal Caucasian donors. The TU 110 reactivity was found to show a correlation coefficient of 1.0 in population analysis for the presence of the HLA-B locus specificity B 13 as defined by alloantisera. Family segregation studies confirmed MHC linked inheritance of the TU 110 antigenic determinant strictly on HLA-B 13 positive haplotypes. As the first monoclonal reagent against the private specificity of this HLA-B locus antigen, TU 110 provides the possibility to study the structural relationships of sub- and supertypic determinants on this allotype and may help to correlate antigenic domains of HLA-B 13 with definable functional properties.


Attenuation of the progression of articular cartilage degeneration by inhibition of TGF-β1 signaling in a mouse model of osteoarthritis.
Transforming growth factor beta 1 (TGF-β1) is implicated in osteoarthritis. We therefore studied the role of TGF-β1 signaling in the development of osteoarthritis in a developmental stage-dependent manner. Three different mouse models were investigated. First, the Tgf-β receptor II (Tgfbr2) was specifically removed from the mature cartilage of joints. Tgfbr2-deficient mice were grown to 12 months of age and were then euthanized for collection of knee and temporomandibular joints. Second, Tgfbr2-deficient mice were subjected to destabilization of the medial meniscus (DMM) surgery. Knee joints were then collected from the mice at 8 and 16 weeks after the surgery. Third, wild-type mice were subjected to DMM at the age of 8 weeks. Immediately after the surgery, these mice were treated with the Tgfbr2 inhibitor losartan for 8 weeks and then euthanized for collection of knee joints. All joints were characterized for evidences of articular cartilage degeneration. Initiation or acceleration of articular cartilage degeneration was not observed by the genetic inactivation of Tgfbr2 in the joints at the age of 12 months. In fact, the removal of Tgfbr2 and treatment with losartan both delayed the progression of articular cartilage degeneration induced by DMM compared with control littermates. Therefore, we conclude that inhibition of Tgf-β1 signaling protects adult knee joints in mice against the development of osteoarthritis.


Valproic acid triggers differentiation and apoptosis in AML1/ETO-positive leukemic cells specifically.
Valproic acid (VPA) has extensive effects on leukemic blasts through its inhibition of histone deacetylases. The main goal of this study was to identify the subgroup of patients who may benefit most from VPA treatment. We examined the significance of t(8;21) chromosomal aberration for VPA treatment response among acute myeloid leukemia (AML) patients by direct comparison of AML1/ETO-negative vs. positive leukemic cell-lines as well as bone marrow blasts from AML patients. In t(8;21) AML, leukemogenesis is supposed to be induced via aberrant recruitment of histone deacetylases. AML cell lines of different genotypes (Kasumi-1, Kasumi-6, MV4;11, K562) and diagnostic bone marrow samples from patients were treated with VPA. VPA induced apoptosis in AML1/ETO-positive and MLL-AF4-positive cells in a dose-dependent manner. Differentiation, as indicated by changes in immunophenotype, was observed only in AML1/ETO-positive cells. VPA increased the expression of AML1 target genes - PU.1, C/EBPa, BPI and IGFBP7 only in AML1/ETO-positive cells. This AML1/ETO-specific effect was confirmed also using patient blasts isolated at the time of diagnosis. AML1/ETO-positive leukemia shows specific mechanism of VPA residing from differentiation followed by apoptosis that is accompanied by an increase in the expression of repressed AML1 target genes. Our data suggest that AML1/ETO-positive patients might derive the greatest benefit from VPA treatment.


Hyperdense pericardial effusion in dermatomyositis and contrast induced nephropathy.
Pericardial involvement in dermatomyositis is rare and usually asymptomatic. In many instances, a diagnosis of pericardial involvement is not found until autopsy. Renal failure associated with connective tissue disorders can result in or potentially exaggerate pericardial inflammation. We report an unusual case of high-density pericardial effusion in a patient with dermatomyositis consequent upon contrast nephropathy as demonstrated by computed tomography. High-density pericardial effusion can be a result of an insidious cause such as pericardial inflammation rather than the more usual causes such as coronary or cardiac perforation.


Suck-Back Impact on Fluid Behavior at Filling Needle Tip.
Needle clogging induces several issues during the filling step of injectable drugs, which makes essential to avoiding it to ensure a favorable outcome for the process. The suck-back function, present in peristaltic pumps, is often used empirically to that end. This study aims at describing and understanding the fluid behavior after suck-back application, which provides some quantitative specifications to prevent needle clogging.


Traditional medicinal uses, pharmacology, phytochemistry, and distribution of the Genus Fagaropsis (Rutaceae).
Genus Fagaropsis belonging to the Rutaceae family, is widely distributed in Africa. The various parts of the species in this genus are used in traditional herbal medicine in different parts of the continent for the treatment of malaria, intestinal disorders, cancer, respiratory diseases, and other ailments. This study provides a comprehensive and updated review on the ethnobotanical uses, phytochemistry, and pharmacology of Fagaropsis species and highlights possible research gaps for further research opportunities, which will be important in the development of new therapeutic drugs. The data was retrieved using ethnobotanical books, published articles, electronic sources, and scientific databases such as Google Scholar, Plants of the World, The Plant List, Scopus, Wiley, Web of Science, PubMed, Science direct, and Sci-Finder. Various key search words Fagaropsis, pharmacological activities, phytochemistry, and ethnobotanical uses were used in the detailed study survey. Fagaropsis species are used traditionally to treat a wide range of infections such as respiratory diseases, cancer, malaria, intestinal diseases, and ethnoveterinary. Phytochemical investigations indicated 18 phytoconstituents that have been isolated as the main compounds in this genus; triterpenoids (limonoids, norhopane, and norneohopane derivatives), alkaloids, and essential oils. Few in vitro and in vivo pharmacological activities have been analyzed in this genus. They indicated that the extracts and pure compounds contained anti-inflammatory, antiplasmodial, anti-cancer, anti-bacterial, anti-fungal, and insecticidal activities. The phytochemical compounds that may be responsible for these activities are flavonoids, terpenoids, and alkaloids. The ethnobotanical values, phytochemistry, and pharmacology discussed in this review paper showed that Fagaropsis species contain different compounds possessing a wide range of biological activities, and they have high medicinal value that is significant in treating different types of diseases. Phytochemical analyses have been performed on two species (F. angolensis and F. glabra) in the literature. More scientific research analyses are still required to explore this genus. In addition, the majority of the currently available bioactivity-related analyses were applied to crude extracts. Thus, further research studies are important to reveal the links between ethnobotanical uses and bioactivity in the future.


Clinically relevant effects of solriamfetol on excessive daytime sleepiness: a posthoc analysis of the magnitude of change in clinical trials in adults with narcolepsy or obstructive sleep apnea.
To evaluate the clinical relevance of solriamfetol in treating excessive daytime sleepiness in participants with narcolepsy or obstructive sleep apnea (OSA). This posthoc analysis includes data from two 12-week, randomized phase 3 studies in participants with narcolepsy or OSA treated with once-daily placebo or solriamfetol 37.5 mg (OSA only), 75 mg, 150 mg, or 300 mg. Excessive daytime sleepiness was assessed with the Epworth Sleepiness Scale (ESS) at baseline and at week 12. Cumulative distribution function plots were generated using a last-observation-carried-forward approach to determine the percentage of participants who achieved ESS scores ≤ 10, within the normal range, and the percentage who achieved a reduction (improvement) in ESS ≥ 25% relative to baseline. Safety was also assessed. In narcolepsy (n = 231), 30.5%-49.2% of participants treated with solriamfetol (across doses) reported ESS scores ≤ 10 and 44.1%-62.7% achieved a ≥ 25% decrease from baseline in ESS scores at week 12, compared with 15.5% and 27.6%, respectively, of placebo recipients. In OSA (n = 459), 51.8%-73.0% of participants treated with solriamfetol (across doses) reported ESS scores ≤ 10 and 50.0%-81.9% achieved a ≥ 25% decrease from baseline in ESS scores at week 12, compared with 37.7% and 36.8%, respectively, of placebo recipients. Results were generally dose-dependent, with more responders at higher solriamfetol doses. Common treatment-emergent adverse events (≥ 5% of solriamfetol recipients in either study) were headache, nausea, decreased appetite, nasopharyngitis, dry mouth, and anxiety. A greater percentage of participants treated with solriamfetol achieved normal ESS scores (≤ 10) or clinically meaningful improvements on the ESS compared with those receiving placebo. The safety profile was similar between participants with narcolepsy and those with OSA. Registry: ClinicalTrials.gov. Names: TONES 2 and TONES 3. URLs: https://www.clinicaltrials.gov/ct2/show/NCT02348593 and https://www.clinicaltrials.gov/ct2/show/NCT02348606. Identifiers: NCT02348593, NCT02348606. Registry: European Union Drug Regulating Authorities Clinical Trials. Names: TONES 2 and TONES 3. URL: https://www.eudract.ema.europa.eu. Identifiers: EudraCT 2014-005487-15, EudraCT 2014-005514-31.


Interatrial shunting after major thoracic surgery: a rare but clinically significant event.
Interatrial shunting after thoracic surgery through a patent foramen ovale or previously asymptomatic atrial septal defect has been reported as a rare, clinically significant and potentially treatable condition. The incidence, presentation, management, and outcome after thoracic surgery have yet to be defined. We performed a retrospective cohort study of all patients undergoing major thoracic surgery (pneumonectomy, extrapleural pneumonectomy, pleurectomy) at our institution between January 2005 and December 2009. Perioperative records were reviewed up to 1 year postoperatively. The presenting clinical symptoms, and complications were identified, and data from the cardiac investigations (right-side heart catheterization, echocardiogram) were extracted into our database. In all, 581 patients underwent major thoracic surgery during the period of study. We identified 8 cases of postoperative interatrial shunting, of which 7 occurred after right-sided surgery. The most common presentations were dyspnea, increase in oxygen requirements, and platypnea-orthodeoxia. Two patients presented with neurologic complications secondary to paradoxic embolism. The median time to presentation was 14 days after the operation. Five patients had increased pulmonary pressures postoperatively. Two patients required intervention, and the symptoms of the rest resolved with conservative management. Interatrial shunting is a rare but clinically significant complication after thoracic surgery. The presentation is myriad, and can occur immediately postoperatively or more than a month later. Some cases may require interventions, although most resolve with conservative management.


Blood storage XXIV: red blood cell 2,3-DPG and ATP maintenance for six weeks in CPD-adenine with higher phosphate, pyruvate, and dihydroxyacetone.
The individual and collective effects of various phosphate, pyruvate and dihydroxyacetone concentrations on 2,3-DPG and ATP maintenance during blood storage with CPD-adenine (0.25 mM), were studied. Phosphate concentrations ranged from 2 to 100 mM. Low concentations were best for 2,3-DPG maintenance during the first three weeks, after which there was no difference. ATP concentrations were better maintained by the highest phosphate concentrations in the first week. After the second week the lower concentrations of phosphate were better. With pyruvate 40 and 60 mM were the best for 2,3-DPG levels through six weeks of storage. ATP concentrations were poorest with high pyruvate. Maintenance of 2,3-DPG was above half normal for six weeks of storage in the 60, 80 and 100 mM DHA preservatives. ATP concentrations were best maintained in the preservative lacking DHA. Combinations of phosphate, pyruvate and DHA in concentrations which had been found to be effective when used individually were studied. Best maintenance of 2,3-DPG (above half normal levels) for six weeks was afforded by pyruvate, phosphate and DHA, and by pyruvate and DHA. ATP maintenance was best afforded by CPD-adenine alone and CPD-adenine with pyruvate and phosphate. Pyruvate alone maintained ATP less well and the pyruvate-DHA was worst. Intermediate in maintenance of ATP was the preservative containing pyruvate, phosphate and DHA.


Service integration and teen friendliness in practice: a program assessment of sexual and reproductive health services for adolescents.
To aid front-line program administrators and providers in adopting national reproductive health recommendations, this exploratory case study examines the implementation of service integration and teen friendliness as strategies to improve adolescent sexual and reproductive health. The project team conducted semi-structured interviews with administrators, providers, and adolescent clients from 10 clinical adolescent sexual and reproductive health service agencies in Alameda County, California. Programs were placed into a topology of integrated service delivery models. The teen friendliness of each program was assessed. Spearman rank correlations were calculated to evaluate the relationship between integration and teen friendliness. Clinical programs exhibited a great range of service delivery models within the integration topology. Human immunodeficiency virus (HIV) counseling and testing services were poorly integrated into clinic services. Teen friendliness and integration showed a negative, but not statistically significant, correlation (R = -.45, p = .19). Programs have made different levels of commitment to service integration or teen friendliness policies. Lessons learned through the integration of sexually transmitted disease (STD) and family planning services may assist efforts to better integrate HIV services for adolescents. Further work to elucidate the relationship between integration and teen friendliness is needed. Periodic reviews can ensure that recommended clinical guidelines, specifically annual risk assessment, are being met, as well as identifying achievable next steps to improve adolescent sexual and reproductive health service delivery.


A combined proteomics and metabolomics analysis reveals the invisible regulation of plant root responses to oxybenzone (benzophenone-3) stress.
Oxybenzone, an environmental pollutant affecting both agriculture and aquatic ecological integrity, has been demonstrated to act as a physiological and metabolic inhibitor on plants, animals, and microorganisms. Research on oxybenzone in higher plants has focused on the above-ground anatomy (leaves), while research on the under-ground parts (roots) has been neglected. In this study, the changes in plant root protein expression and metabolic pathways under oxybenzone treatment were explored through a combined proteomics and metabolomics analysis. A total of 506 differential proteins and 96 differential metabolites were identified, which were mainly distributed in critical pathways such as those for carbon (C) and nitrogen (N) metabolism, lipid metabolism, and antioxidation. Bioinformatics analysis shows that oxybenzone toxicity is predominantly reflected in alterations to root respiratory homeostasis and the manifestation of damaging reactive oxygen species (ROS) and membrane lipid peroxidation, changes to disease resistance-associated proteins, changes to normal C-flow distribution, and the inhibition of cell absorption and utilization of N sources. Plants respond to oxybenzone stress mainly by reconfiguring the mitochondrial electron-transport-chain to bypass oxidative-damage components; improving the efficiency of the antioxidant system to remove excessively accumulated ROS; promoting the detoxification of harmful membrane lipid peroxides; increasing osmotic adjustment substance (such as proline and raffinose) accumulation; adjusting C flow distribution to produce more nicotinamide adenine dinucleotide phosphate (NADPH) for the glutathione cycle; and accumulating free amino acids to increase plant stress tolerant. Our results are the first to map the changes in the physiological and metabolic regulatory network of higher plant roots under oxybenzone stress.


Design, synthesis and biological evaluation of mogrol derivatives as a novel class of AMPKα2β1γ1 activators.
Adenosine monophosphate-activated protein kinase (AMPK) has been considered as a promising drug target for its regulation in both glucose and lipid metabolism. Mogrol was originally identified from high throughput screening as a small molecule activator of AMPK subtype α2β1γ1. In order to enhance its potency on AMPK and summarize the structure-activity relationships, a series of mogrol derivatives were designed, synthesized and evaluated in pharmacological AMPK activation assays. The results showed that the amine derivatives at the 24-position can improve the potency. Among them, compounds 3 and 4 exhibited the best potency (EC50: 0.15 and 0.14 μM) which was 20 times more potent than mogrol (EC50: 3.0 μM).


[Tropical spastic paraparesis - anesthetic approach].
HTLV-1 infection is endemic in Japan, Caribbean, Africa, and South America. It is transmitted from mother to child, sexual contact, blood transfusions, or sharing needles. Tropical Spastic paraparesis (TSP) is a chronic degenerative neurological disease associated with this infection. It results from a spinal cord symmetrical degeneration at the thoracic level and is characterized by progressive motor weakness in the lower limbs, hyperreflexia, sensitivity changes, urinary incontinence, and bladder dysfunction. Female, 53 years old, HTLV-1 infection and TSP. She had decreased strength in the lower limbs and hyperreflexia, paretic gait, spasticity, and neurogenic bladder symptoms, with recurrent urinary infections. She was scheduled for cystectomy. The patient was monitored according to standard ASA. Due to severe coagulopathy and the possibility of neurological worsening, epidural catheter was not placed. The induction of general anesthesia was performed with midazolam and fentanyl, followed by etomidate and cisatracurium. She was intubated with a tube size seven and maintained with desflurane and oxygen. Anesthesia was uneventful; the surgery lasted 1 hour and 50minutes. There were no complications in the immediate postoperative period, during hospitalization, nor deterioration of the neurological examination. The patient was discharged 20 days later. There are reports of decreased electromyographic response and neurological deterioration associated with propofol in these patients, etomidate was used. The hepatic metabolism of rocuronium posed a risk, we chose to use cistracurium. It was concluded that the anesthesia chosen did not affect the course of the disease.


Molecular events in follicular thyroid tumors.
Knowledge of the molecular events that govern human thyroid tumorigenesis has grown considerably in the past ten years. Key genetic alterations and new oncogenic pathways have been identified. Molecular genetic aberrations in thyroid carcinomas bear noteworthy resemblance to those in acute myelogenous leukemias. Thyroid carcinomas and myeloid leukemias both possess transcription factor gene rearrangements-PPARgamma-related translocations in thyroid carcinoma and RARalpha-related and CBF-related translocations (amongst others) in myeloid leukemia. PPARgamma and RARalpha are closely related members ofthe same nuclear receptor subfamily, and the PML-RARalpha and PAX8-PPARgamma fusion proteins both function as dominant negative inhibitors of their wild-type parent proteins. Thyroid carcinomas and myeloid leukemias also both harbor NRAS mutations (15-25% of both cancers) and receptor tyrosine kinase mutations--RET mutations in thyroid carcinomas and FLT3 mutations in myeloid leukemias. The NRAS and tyrosine receptor kinase mutations are not observed in the same thyroid carcinoma or leukemia patients, suggesting that multiple initiating pathways exist in both. Lastly, thyroid carcinomas and myeloid leukemias possess p53 mutations at relatively low frequency (10-15%) in patients who tend to be older and have more aggressive, therapy resistant disease. Such parallels are unlikely to occur by chance alone and argue that common mechanisms underlie these diverse epithelial and hematologic cancers. The comparison of thyroid carcinomas and myeloid leukemias may highlight areas of thyroid cancer investigation worthy of further focus. For example, few collaborating mutations have been defined in thyroid carcinomas even though they play a clear role in myeloid leukemias, as exemplified by RARalpha rearrangements and FLT3 mutations that together dictate the promyleocytic leukemia phenotype. Functional interactions between collaborating mutations are possible at multiple levels, and it is tempting to speculate that some thyroid carcinomas might develop through an unique combination or co-activation of RET and RAS and/or RET and PPARgamma (and/or other) signaling systems. In fact, the ELE1-RET (PTC3) fusion protein contains the ELE1 nuclear receptor co-activator domain and it appears to physically associate with and inhibit wild-type PPARgamma in some papillary carcinomas. The similarities of the fusion proteins in thyroid carcinoma and myeloid leukemia suggest that a more directed search for fusion genes in non-thyroid carcinomas is warranted. In fact, novel fusion genes have been identified recently in aggressive midline, secretory breast, and renal cell carcinomas, although the epithelial nature of the latter is not well-documented. Interestingly, these cancers all tend to present more frequently in adolescence and young adulthood in a manner similar to thyroid and myeloid malignancies that have fusion genes. The analyses of cancers that present earlier in life may enhance fusion gene recognition in other carcinoma types. Definition and biologic characterization of the precursor cells that give rise to thyroid carcinoma will also be important. Myeloid leukemias are thought to arise from stem/progenitor cells that acquire disturbed self-renewal and differentiation capacities but retain characteristics of the myeloid lineages. Although the presence of comparable stem/progenitor cells in the thyroid are not defined, distinct thyroid cancer lineages and patterns of differentiation exist and candidate stem/progenitor cells such as the p63-immunoreactive solid cell nests are apparent. A last important area is development of molecular-based therapies for thyroid carcinoma patients resistant to standard radio-iodine treatment. Treatments for such cancers are limited and pathways defined by thyroid cancer mutations are prime targets for pharmacologic interventions with molecular inhibitors. Tyrosine kinase inhibitors and nuclear receptor ligands have proven dramatically effective in some myeloid leukemia patients. Various molecular inhibitors are being investigated now in thyroid cancer models. Such developments predict that the thyroid cancer model will continue to provide biologic insights into human carcinoma biology and that improved pathologic diagnosis and treatment for thyroid cancer patients sit on the not too distant horizon.


Comparison of ultrasonography-guided central venous catheterization between adult and pediatric populations.
The purpose of this study was to compare the technical success and complication rates of ultrasonography-guided central venous catheterization between adult and pediatric patients which have not been reported previously. In a 4-year period, 859 ultrasonography-guided central vein catheterizations in 688 adult patients and 247 catheterizations in 156 pediatric patients were retrospectively evaluated. Mean age was 56.3 years (range, 18 to 95 years) for adults and 3.3 years (range, 0.1 to 16.3 years) for children. The preferred catheterization site was internal jugular vein in 97% of adults and 85% of children. The technical success rate, mean number of punctures, and rate of single wall puncture were 99.4%, 1.04 (range, 1-3), and 83% for adults and 90.3%, 1.25 (range, 1-5), and 49% for children, respectively. All the differences were statistically significant (p < 0.05). Complication rates were 2.3% and 2.4% for adults and children, respectively (p > 0.05). Major complications such as pneumothorax and hemothorax were not seen in any group. In conclusion, ultrasonography-guided central venous catheterization has a high technical success rate, lower puncture attempt rate, and higher single wall puncture rate in adults compared to children. Complication rates are comparable in the two groups.


Toxocara seroprevalence in schizophrenic patients in Turkey.
To investigate the seroprevalence of toxocariasis in patients diagnosed as schizophrenia. Ninety-eight schizophrenic patients hospitalized at The Elazig Psychiatric Hospital were included in the study. Anti-Toxocara IgG and/or IgM antibodies were determined by using commercial Toxocara canis IgG and/or IgM ELISA kit. Seropositivity for T. canis was detected in 45 (45.9%) of 98 patients and 2 (2.0%) of 100 control subjects the difference was statistically significant (p<0.001). The seroprevalence was 40.4% (19 cases) and 51.0% (26 cases) for female and male subjects, respectively (p=0.3). When the seropositive and seronegative schizophrenic patients were compared with respect to the age group environment they were living in, occupation period of follow up and number of hospitalizations, there were no differences between the two groups (all, p>0.05). In conclusion, the schizophrenic state seems to present a high risk for Toxocara infection in Turkey.


Use of the cytomegalovirus promoter for transient and stable transgene expression in mouse embryonic stem cells.
Embryonic stem (ES) cells are pluripotent cells derived from the epiblast of preimplantation embryos. These cells are emerging as a key model system for elucidating mechanisms involved in development and disease as well as having a unique potential as a source of unlimited somatic cells for transplantation therapies. ES cells can be easily manipulated at the DNA level, allowing both transient and stable expression of complementary DNA encoding transgenes of interest. The human cytomegalovirus (CMV) immediate-early enhancer and promoter is commonly used for transient expression of transgenes in ES cells. However, its use in the formation of stable cell lines is less common. We demonstrate an electroporator transformation technique that results in up to 90% transfection efficiency of CMV-encoding vectors in ES cells. Furthermore, we describe the design of vectors and cloning techniques that allow stable expression of transgenes under control of the CMV promoter and a fluorescent microscopy method for detecting protein expression in ES cells in situ.


Crossed cerebellar diaschisis during migraine with prolonged aura: a possible mechanism for cerebellar infarctions.
Migraineurs with frequent aura (>or=1 per month) are at a 12-fold increased risk of posterior circulation infarctions. Although the mechanism is unclear, these lesions are located in the arterial borderzone of the cerebellum. This case illustrates, for the first time, crossed cerebellar diaschisis in a patient with migraine with prolonged aura, and raises the possibility that hypoperfusion may be responsible in part for the development of these lesions.


Configuration of the magnetic field and reconstruction of Pangaea in the Permian period.
The virtual geomagnetic poles of Laurasia and Gondwanaland in the Carboniferous and Permian periods diverge significantly when these continents are reassembled according to the fit calculated by Bullard et al. Two interpretations have been offered: Briden et al. explain these divergences by a magnetic field configuration very different from that of a geocentric axial dipole; Irving (and private communication), Van der Voo and French(4) suggest a different reconstruction and it is shown here that these two interpretations are not incompatible and that the first may help the second.


Angiographic features of upper cervical extradural neurinoma. Case Report.
A case of upper cervical extradural neurinoma in a teenage girl is reported. The value of investigating the spinal arteries in such lesions is stressed.


Shp2 is required for protein kinase C-dependent phosphorylation of serine 307 in insulin receptor substrate-1.
The function of insulin receptor substrate-1 (IRS-1), a key molecule of insulin signaling, is modulated by phosphorylation at multiple serine/threonine residues. Phorbol ester stimulation of cells induces phosphorylation of two inhibitory serine residues in IRS-1, i.e. Ser-307 and Ser-318, suggesting that both sites may be targets of protein kinase C (PKC) isoforms. However, in an in vitro system using a broad spectrum of PKC isoforms (alpha, beta1, beta2, delta, epsilon, eta, mu), we detected only Ser-318, but not Ser-307 phosphorylation, suggesting that phorbol ester-induced phosphorylation of this site in intact cells requires additional signaling elements and serine kinases that link PKC activation to Ser-307 phosphorylation. As we have observed recently that the tyrosine phosphatase Shp2, a negative regulator of insulin signaling, is a substrate of PKC, we studied the role of Shp2 in this context. We found that phorbol ester-induced Ser-307 phosphorylation is reduced markedly in Shp2-deficient mouse embryonic fibroblasts (Shp2-/-) whereas Ser-318 phosphorylation is unaltered. The Ser-307 phosphorylation was rescued by transfection of mouse embryonic fibroblasts with wild-type Shp2 or with a phosphatase-inactive Shp2 mutant, respectively. In this cell model, tumor necrosis factor-alpha-induced Ser-307 phosphorylation as well depended on the presence of Shp2. Furthermore, Shp2-dependent phorbol ester effects on Ser-307 were blocked by wortmannin, rapamycin, and the c-Jun NH2-terminal kinase (JNK) inhibitor SP600125. This suggests an involvement of the phosphatidylinositol 3-kinase/mammalian target of rapamycin cascade and of JNK in this signaling pathway resulting in IRS-1 Ser-307 phosphorylation. Because the activation of these kinases does not depend on Shp2, it is concluded that the function of Shp2 is to direct these activated kinases to IRS-1.


Correction to: Treatment of severely ill COVID-19 patients with anti-interleukin drugs (COV-AID): A structured summary of a study protocol for a randomised controlled trial.
An amendment to this paper has been published and can be accessed via the original article.


Rapid Response Team-Quality Champion Registered Nurse: Observations and Perceptions.
Operationalization of the rapid response team (RRT) and its quality champion (QC) nurses at a community hospital is unique and provides benefits not entirely captured by analysis of mortality data. The purpose was to determine the perceived benefits of the RRT at the facility and behaviors and activities observed during actual RRT responses. Also examined was the timeliness of the RRT calls. This was a mixed-method study including qualitative (interviews, focus groups, and surveys) and quantitative (retrospective chart reviews) data collection. Themes included teaching/education, foster development of critical thinking skills, expertise/resource, communication/facilitation/go-between, safety net/security, validation, and advocate/foster collaboration. RRT calls were made quickly after clinical deterioration. Benefits of the RRT-QC registered nurse were extensive. Observations showed support, education, and teamwork in an effort to improve outcomes and support clinicians.


Contribution of the IGCR1 regulatory element and the 3 'Igh CBEs to Regulation of Igh V(D)J Recombination.
Immunoglobulin heavy chain variable region exons are assembled in progenitor-B cells, from V H , D, and J H gene segments located in separate clusters across the Igh locus. RAG endonuclease initiates V(D)J recombination from a J H -based recombination center (RC). Cohesin-mediated extrusion of upstream chromatin past RC-bound RAG presents Ds for joining to J H s to form a DJ H -RC. Igh has a provocative number and organization of CTCF-binding-elements (CBEs) that can impede loop extrusion. Thus, Igh has two divergently oriented CBEs (CBE1 and CBE2) in the IGCR1 element between the V H and D/J H domains, over 100 CBEs across the V H domain convergent to CBE1, and 10 clustered 3' Igh -CBEs convergent to CBE2 and V H CBEs. IGCR1 CBEs segregate D/J H and V H domains by impeding loop extrusion-mediated RAG-scanning. Down-regulation of WAPL, a cohesin unloader, in progenitor-B cells neutralizes CBEs, allowing DJ H -RC-bound RAG to scan the VH domain and perform VH-to-DJH rearrangements. To elucidate potential roles of IGCR1-based CBEs and 3' Igh -CBEs in regulating RAG-scanning and elucidate the mechanism of the "ordered" transition from D-to-J H to V H -to-DJ H recombination, we tested effects of deleting or inverting IGCR1 or 3' Igh -CBEs in mice and/or progenitor-B cell lines. These studies revealed that normal IGCR1 CBE orientation augments RAG-scanning impediment activity and suggest that 3' Igh -CBEs reinforce ability of the RC to function as a dynamic loop extrusion impediment to promote optimal RAG scanning activity. Finally, our findings indicate that ordered V(D)J recombination can be explained by a gradual WAPL down-regulation mechanism in progenitor B cells as opposed to a strict developmental switch. To counteract diverse pathogens, vertebrates evolved adaptive immunity to generate diverse antibody repertoires through a B lymphocyte-specific somatic gene rearrangement process termed V(D)J recombination. Tight regulation of the V(D)J recombination process is vital to generating antibody diversity and preventing off-target activities that can predispose the oncogenic translocations. Recent studies have demonstrated V(D)J rearrangement is driven by cohesin-mediated chromatin loop extrusion, a process that establishes genomic loop domains by extruding chromatin, predominantly, between convergently-oriented CTCF looping factor-binding elements (CBEs). By deleting and inverting CBEs within a critical antibody heavy chain gene locus developmental control region and a loop extrusion chromatin-anchor at the downstream end of this locus, we reveal how these elements developmentally contribute to generation of diverse antibody repertoires.


Y chromosome loss detected by FISH in bladder cancer.
To examine the significance of Y chromosome losses in bladder cancer, fluorescence in situ hybridization (FISH) was used to determine its prevalence and associations with known parameters of malignancy. Cells were dissociated from formalin-fixed paraffin-embedded bladder tumors from 68 male patients and from 11 post-mortem bladder washes of male patients with a negative bladder cancer history, and were examined by FISH using centromeric probes for chromosomes X, Y, 7, 9, and 17. Nullisomy for chromosome Y was seen in 23 of 68 tumors (34%), monosomy in 28 of 68 tumors (41%), and polysomy in 17 of 68 tumors (25%). There was no association between chromosome Y loss and tumor grade, stage, tumor growth fraction (Ki67 LI), p53 immunostaining, and presence of p53 deletions. Patient age was higher for tumors with a Y loss (73.5 +/- 12.0 years) than for tumors without Y loss (66.6 +/- 10.8 years; p = 0.0207). In one normal bladder wash, a distinct subpopulation (38% of cells) with Y nullisomy was seen. These data suggest that Y loss is a frequent event that can occur early in bladder cancer, although there is no evidence for a role of Y loss in tumor progression.


Measuring fatigue following acquired brain injury: A validation study of the Psychomotor Vigilance Test.
To evaluate the construct validity of Psychomotor Vigilance Test performance for measuring fatigue in people with acquired brain injury. Observational cross-sectional study. Fifty-four people with acquired brain injury and 61 healthy controls. Participants performed the Psychomotor Vigilance Test and reported momentary fatigue before and after this test and general fatigue. Associations between performance and fatigue in patients were tested by correlational and hierarchical multiple linear regression analyses, controlling for sleep quality, daytime sleepiness, and mood. Patients performed worse on the test compared with controls. Within the patient group, worse test performance was associated with increases in momentary post-test fatigue and general fatigue, indicating convergent validity, but also with daytime sleepiness, and mood complaints, indicating a lack of divergent validity. When controlling for sleepiness and mood, the association between performance and general fatigue was no longer significant, whereas the association between performance and post-test fatigue remained. Performance on the Psychomotor Vigilance Test cannot be used as a specific measure for fatigue, but it appears to be a more general measure of severity of symptoms including fatigue, mood, and sleepiness. Therefore, the Psychomotor Vigilance Test may be a useful measure to examine the effects of interventions aimed at reducing these symptoms.


CD45-mediated signaling pathway is involved in Rhizoctonia bataticola lectin (RBL)-induced proliferation and Th1/Th2 cytokine secretion in human PBMC.
We earlier reported the mitogenic and immunostimulatory activities of Rhizoctonia bataticola lectin (RBL), purified from phytopathogenic fungus R. bataticola in human PBMC. The lectin demonstrates specificity towards glycoproteins containing complex N-glycans. Since CD45-protein tyrosine phosphatase that abundantly expresses N-glycans is important in T-cell signaling, the study aimed to investigate the involvement of CD45 in the immunomodulatory activities of RBL. Flowcytometry and confocal microscopy studies revealed that RBL exhibited binding to PBMC and colocalized with CD45. The binding was comparable in cells expressing different CD45 isoforms-RA, -RB and -RO. CD45 blocking antibody reduced the binding and proliferation of PBMC induced by RBL. CD45-PTPase inhibitor dephostatin inhibited RBL-induced proliferation, expression of CD25 and pZAP-70. RBL-induced secretion of Th1/Th2 cytokines were significantly inhibited in presence of dephostatin. Also, dephostatin blocked phosphorylation of p38MAPK and STAT-5 that was crucial for the biological functions of RBL. The study demonstrates the involvement of CD45-mediated signaling in RBL-induced PBMC proliferation and Th1/Th2 cytokine secretion through activation of p38MAPK and STAT-5.


Effects of Laetiporus sulphureus-Fermented Wheat Bran on Growth Performance, Intestinal Microbiota and Digesta Characteristics in Broiler Chickens.
This study investigated the effects of a Laetiporus sulphureus-fermented wheat bran (LS) supplementation on the microbiota and digesta characteristics of broiler chickens. Two hundred and forty male broilers (Ross 308) were randomly allocated into three groups fed with a corn-soybean-based diet (control), and the control diet being replaced with 5% wheat bran (WB) and 5% LS, respectively. Each group had four replicates and 20 birds per pen. Metagenomics analysis results of the ileum microbiota showed that, at the family level, the 5% LS groups had over 40% higher Lactobacillaceae compared to the control group in a mean difference comparison. Heat maps showed that, at the phylum level, the population of Firmicutes was higher and Proteobacteria was lower in the ileum of 5% LS compared to the control group. Results of the stack column plots of the top ten OTUs at the family level showed that a 5% LS and 5% WB supplementation altered the broiler microbiota distribution by increasing the relative abundance of Lactobacillaceae. Cecal microbiota analysis showed that the 5% LS-supplemented group had approximately 5% and 3% higher Veillonellaceae and Lactobacillaceae, respectively. Stack column plots of the top ten OTUs indicated that the distribution of cecal bacteria in each group was not markedly different. Both the ileum and cecum digesta in the 5% LS supplementation group had a slight and not significant elevation on the total VFA, while the pH values and ammonia nitrogen were significantly lowered compared to the control and 5% WB groups (p < 0.05). In addition, the 5% LS supplementation group had a significantly higher lactic acid concentration in both the ileum and cecum compared to the control and 5% WB groups (p < 0.05). In conclusion, a 5% LS supplementation could potentially enhance the feed conversion ratio and European Broiler Index (EBI) of broilers by elevating the family Lactobacillaceae and suppressing the phylum Proteobacteria's population, thus creating changed intestinal environments that may potentially favor the growth and health of the broilers.


Impaired somatodendritic responses to pituitary adenylate cyclase-activating polypeptide (PACAP) of supraoptic neurones in PACAP type I -receptor deficient mice.
The role of pituitary adenylate cyclase-activating polypeptide (PACAP) type I receptor (PAC1 receptor) in regulating hypothalamic supraoptic neurones was investigated using PAC1 receptor-deficient male mice (PAC1-/-). The effects of PACAP on [Ca2+]i were investigated in freshly dissociated supraoptic neurones and on the somatodendritic release of vasopressin and oxytocin, examined on intact supraoptic nuclei. In supraoptic neurones from wild-type mice (PAC1+/+), 100 nm PACAP induced an increase in [Ca2+]i and release of vasopressin and oxytocin, whereas in heterozygous (PAC1+/-) and null-mutant mice (PAC1-/-), PACAP was much less effective. PACAP had no effect on these two parameters when applied to isolated neurohypophysial nerve terminals of PAC1+/+ and PAC1-/- mice, and rats. In conclusion, the PAC1 receptor is solely responsible for the PACAP-induced [Ca2+]i signalling and secretion of vasopressin and oxytocin in the somatodendritic region of supraoptic neurones.


Multiple phases of cross-sensory interactions associated with the audiovisual bounce-inducing effect.
Using event-related potential (ERP) recordings, the present study investigated the cross-modal neural activities underlying the audiovisual bounce-inducing effect (ABE) via a novel experimental design wherein the audiovisual bouncing trials were induced solely by the ABE. The within-subject (percept-based) analysis showed that early cross-modal interactions within 100-200 ms after sound onset over fronto-central and occipital regions were associated with the occurrence of the ABE, but the cross-modal interaction at a later latency (ND250, 220-280 ms) over fronto-central region did not differ between ABE trials and non-ABE trials. The between-subject analysis indicated that the cross-modal interaction revealed by ND250 was larger for subjects who perceived the ABE more frequently. These findings suggest that the ABE is generated as a consequence of the rapid interplay between the variations of early cross-modal interactions and the general multisensory binding predisposition at an individual level.


3D reconstruction of the lumbar vertebrae from anteroposterior and lateral dual-energy X-ray absorptiometry.
Current vertebral fracture prevention measures use Dual-energy X-ray Absorptiometry (DXA) to quantify the density of the vertebrae and subsequently determine the risk of fracture. This modality however only provides information about the projected Bone Mineral Density (BMD) while the shape and spatial distribution of the bone determines the strength of the vertebrae. Quantitative Computed Tomography (QCT) allows for the measurement of the vertebral dimensions and volumetric densities, which have been shown to be able to determine the fracture risk more reliably than DXA. However, for the high cost and high radiation dose, QCT is not used in clinical routine for fracture risk assessment. In this work, we therefore propose a method to reconstruct the 3D shape and density volume of lumbar vertebrae from an anteroposterior (AP) and lateral DXA image used in clinical routine. The method is evaluated for the L2, L3 and L4 vertebra. Of these vertebrae a statistical model of the vertebral shape and density distribution is first constructed from a large dataset of QCT scans. All three models are then simultaneously registered onto both AP and lateral DXA image. The shape and volumetric BMD at several regions of the reconstructed vertebrae is then evaluated with respect to the ground truth QCT volumes. For the L2, L3 and L4 vertebrae respectively the shape was reconstructed with a mean (2RMS) point-to-surface distance of 1.00 (2.64) mm, 0.93(2.52) mm and 1.34(3.72) mm and a strong correlation (r > 0.82) was found between the trabecular volumetric BMD extracted from the reconstructions and from the same subject QCT scans. These results indicate that the proposed method is able to accurately reconstruct the 3D shape and density volume of the lumbar vertebrae from AP and lateral DXA, which can potentially improve the fracture risk estimation accuracy with respect to the currently used DXA derived areal BMD measurements.


Nonreciprocal exchange between alleles of the yeast mitochondrial 21S rRNA gene: kinetics and the involvement of a double-strand break.
A 1.1 kb intron containing an open reading frame (ORF) in one allele (omega+) of the yeast mitochondrial 21S rRNA gene is nearly quantitatively inserted in crosses into a 21S rRNA allele lacking that intron (omega-). We have determined that this nonreciprocal exchange initiates soon after cells fuse to form zygotes and is complete by 10-16 hr after mating. We have discovered a unique in vivo double-strand cut in omega- mitochondrial DNA (mtDNA) at or near the site of intron insertion that is implicated in the process. Markers flanking the intron insertion site are coconverted with frequencies inversely proportional to their distance from that site. There is no net conversion of omega- to omega+ in crosses between petites retaining these alleles, nor do we observe the unique double-strand cut in the mtDNA from zygotes of such crosses. The data suggest that a translation product of the intron ORF is required for the double-strand cut and nonreciprocal recombination at omega.


Engaging Adolescents and Young Adults in Decisions About Return of Genomic Research Results: a mixed-methods longitudinal clinical trial protocol.
To protect minors' future autonomy, professional organizations have historically discouraged returning predictive adult-onset genetic test results and carrier status to children. Recent clinical guidance diverges from this norm, suggesting that when minors have genomic sequencing performed for clinical purposes, parents and children should have the opportunity to learn secondary findings, including for some adult-onset conditions. While parents can currently opt in or out of receiving their child's secondary findings, the American Society of Human Genetics Workgroup on Pediatric Genetic and Genomic Testing suggests including adolescents in the decision-making process. However, it is not clear what factors young people consider when given the opportunity to learn genetic findings for themselves. We are examining adolescents', young adults', and parents' (if applicable) decisions about learning genomic information for the adolescent. We are enrolling assenting (ages 13-17) adolescents and consenting (ages 18-21) young adults in a prospective genomic screening study to assess the choices they make about receiving individual genomic results. Participants use an online tool to indicate whether they want to learn their personal genetic risk for specific preventable, treatable, and adult-onset conditions, as well as carrier status for autosomal recessive conditions. We are examining 1) how choices differ between adolescent and young adult cohorts (as well as between adolescents/young adults and parents) and 2) decisional conflict and stability across study timepoints. Results are returned based on participants' choices. Qualitative interviews with a subset of participants explore decisional stability, adolescent/young adult engagement with parents in decision-making, and the impact of learning pathogenic/likely pathogenic and carrier results. This study explores decision making and decision stability between adolescents and parents (where applicable), as well as the ethical implications and impact of return of clinical-grade genetic research results to adolescents and young adults. The results of this study will contribute empirical evidence to support best practices and guidance on engaging young people in genetic research studies and clinical care that offer return of results.


Role of green financing in developing sustainable business of e-commerce and green entrepreneurship: implications for green recovery.
The present study examines the impact of green financing on the development of sustainable businesses operating in the e-commerce and green entrepreneurship sectors. The findings of this research have potential implications for promoting green recovery. The research primarily examines the issue of financing constraints that impede the growth and long-term viability of green businesses, with a specific focus on low-income countries and emerging economies. This study employs panel data from 2010 to 2020, encompassing multiple countries, and utilizes an econometric model to examine the association between green financing and the advancement of sustainable enterprises. The study's findings illustrate the favorable effects of green financing on the expansion and long-term viability of e-commerce and green entrepreneurship. The analysis demonstrates that the availability of green financing plays a substantial role in facilitating the advancement of business models that prioritize environmental sustainability. This, in turn, supports promoting a green recovery and facilitates sustainable economic development. The study emphasizes the significance of customized financial assistance mechanisms that cater to the distinct requirements and attributes of the e-commerce and green entrepreneurship industries. The findings emphasize the capacity of green financing to facilitate the shift toward a more sustainable and ecologically aware economy. The findings of this study hold considerable implications for policymakers, financial institutions, and entrepreneurs operating in low-income countries and emerging economies. It offers valuable insights into the crucial role that green financing plays in fostering the development of sustainable businesses and facilitating initiatives aimed at achieving environmental recovery.


Cefoxitin in the treatment of aerobic and anaerobic infections. Prospective correlation of in vitro susceptibility methods with clinical outcome.
Anaerobic isolates from patients with intra-abdominal infection were tested in vitro by eight methods for susceptibility to cefoxitin. Broth disk elution correlated poorly with clinical outcome. The clinical breakpoint for anaerobic susceptibility to cefoxitin was less than or equal to 32 micrograms/ml.


Factors influencing the fascial closure rate after open abdomen treatment: Results from the European Hernia Society (EuraHS) Registry : Surgical technique matters.
Definitive fascial closure is an essential treatment objective after open abdomen treatment and mitigates morbidity and mortality. There is a paucity of evidence on factors that promote or prevent definitive fascial closure. A multi-center multivariable analysis of data from the Open Abdomen Route of the European Hernia Society included all cases between 1 May 2015 and 31 December 2019. Different treatment elements, i.e. the use of a visceral protective layer, negative-pressure wound therapy and dynamic closure techniques, as well as patient characteristics were included in the multivariable analysis. The study was registered in the International Clinical Trials Registry Platform via the German Registry for Clinical Trials (DRK00021719). Data were included from 630 patients from eleven surgical departments in six European countries. Indications for OAT were peritonitis (46%), abdominal compartment syndrome (20.5%), burst abdomen (11.3%), abdominal trauma (9%), and other conditions (13.2%). The overall definitive fascial closure rate was 57.5% in the intention-to-treat analysis and 71% in the per-protocol analysis. The multivariable analysis showed a positive correlation of negative-pressure wound therapy (odds ratio: 2.496, p < 0.001) and dynamic closure techniques (odds ratio: 2.687, p < 0.001) with fascial closure and a negative correlation of intra-abdominal contamination (odds ratio: 0.630, p = 0.029) and the number of surgical procedures before OAT (odds ratio: 0.740, p = 0.005) with DFC. The clinical course and prognosis of open abdomen treatment can significantly be improved by the use of treatment elements such as negative-pressure wound therapy and dynamic closure techniques, which are associated with definitive fascial closure.


Metabolic inhibitors and intermediate filament organization in human fibroblasts.
A number of metabolic inhibitors including the mRNA transcription inhibitor actinomycin D; the protein synthesis inhibitors emetine, cycloheximide, and puromycin; the energy metabolism inhibitors sodium azide and oligomycin; the amino acid analog L-azetidine-2-carboxylic acid; sodium fluoride; and acrylamide each cause the collapse of vimentin filament organization while leaving microtubule organization apparently unaffected in the human fibroblastic cell line MCH23. The protein kinase inhibitor N-[2-(methylamino)ethyl]-5-isoquinolinesulfonamide dihydrochloride (H8) caused a partial collapse of vimentin organization but its effect was more difficult to discern, since it also induced a dramatic change in cellular morphology. Each of these drugs produced a significant inhibition of protein synthesis at concentrations that affected vimentin organization. The mechanisms by which these drugs affect intermediate filament organization are unclear, but our results demonstrate that intermediate filament organization in MCH23 cells is affected by a wide range of drugs and that such drugs cannot be used without great caution as reagents for the study of intermediate filament organization and function.


Recommendations were made for diagnosis and management of allergic reactions to COVID-19 vaccines.
Greenhawt M, Abrams EM, Shaker M, et al. The risk of allergic reaction to SARS-CoV-2 vaccines and recommended evaluation and management: a systematic review, meta-analysis, GRADE assessment, and international consensus approach. J Allergy Clin Immunol Pract. 2021;9:3546-67. 34153517.


Emotion processing in children who do and do not stutter: An ERP study of electrocortical reactivity and regulation to peer facial expressions.
Event-related brain potentials (ERPs) were used to investigate the neural correlates of emotion processing in 5- to 8-year-old children who do and do not stutter. Participants were presented with an audio contextual cue followed by images of threatening (angry/fearful) and neutral facial expressions from similarly aged peers. Three conditions differed in audio-image pairing: neutral context-neutral expression (neutral condition), negative context-threatening expression (threat condition), and reappraisal context-threatening expression (reappraisal condition). These conditions reflected social stimuli that are ecologically valid to the everyday life of children. P100, N170, and late positive potential (LPP) ERP components were elicited over parietal and occipital electrodes. The threat condition elicited an increased LPP mean amplitude compared to the neutral condition across our participants, suggesting increased emotional reactivity to threatening facial expressions. In addition, LPP amplitude decreased during the reappraisal condition- evidence of emotion regulation. No group differences were observed in the mean amplitude of ERP components between children who do and do not stutter. Furthermore, dimensions of childhood temperament and stuttering severity were not strongly correlated with LPP elicitation. These findings are suggestive that, at this young age, children who stutter exhibit typical brain activation underlying emotional reactivity and regulation to social threat from peer facial expressions.


Increased pretreatment levels of serum LDH and ALP as poor prognostic factors for nasopharyngeal carcinoma.
Serum enzymes that play potential roles in tumor growth have recently been reported to have prognostic relevance in a diverse array of tumors. However, prognosis-related serum enzymes are rarely reported for nasopharyngeal carcinoma(NPC). To clarify whether the level of serum enzymes is linked to the prognosis of NPC, we reviewed the pretreatment data of lactate dehydrogenase(LDH), alkaline phosphatase (ALP), and glutamyl transferase (GGT) in 533 newly diagnosed NPC patients who underwent radical radiotherapy between May 2002 and October 2003 at Sun Yat-sen University Cancer Center. Patients were grouped according to the upper limit of normal values of LDH, ALP, and GGT. The Kaplan-Meier method and log-rank test were used for selecting prognostic factors from clinical characteristics and serum enzymes, and the chi-square test was applied to analyze the relationships of clinical characteristics and serum enzymes. Finally, a Cox proportional hazards model was used to identify the independent prognostic factors. We found that increased levels of LDH had poor effects on both overall survival and distant metastasis-free survival (P = 0.009 and 0.035, respectively), and increased pretreatment level of serum ALP had poor effects on both overall survival and local recurrence-free survival (P = 0.037 and 0.039, respectively). In multivariate analysis, increased LDH level was identified as an independent prognostic factor for overall survival. Therefore, we conclude that increased pretreatment serum LDH and ALP levels are poor prognostic factors for NPC.


Bioavailability and toxicity of soil particle-associated copper as determined by two bioluminescent Pseudomonas fluorescens biosensor strains.
We report the development and application of a novel, solid phase-contact bioassay based on two whole-cell bacterial biosensor strains. Our data indicate that a significant fraction of particle-associated Cu may be available to bacteria in dilute soil suspensions but also support the conventional view that mainly the soluble fraction of Cu is directly available to bacteria under more realistic soil conditions.


The anxiolytic effects of preoperative administration of pregabalin in comparison to diazepam and placebo.
We aimed to evaluate the potential anxiolytic effects of premedication with pregabalin, compared with diazepam and placebo. We conducted this non-inferiority, double-blind, randomized controlled trial in ASA classification I-II patients aged 18-70 years, scheduled for elective surgery under general anesthesia. They were allocated to receive pregabalin (75 mg the night before surgery and 150 mg 2 h before surgery), diazepam (5 and 10 mg in the same manner) or placebo. Preoperative anxiety was evaluated using verbal numerical rating scale (VNRS) and Amsterdam Preoperative Anxiety and Information Scale (APAIS) before and after premedication. Sleep quality, sedation level, and adverse effects were assessed as secondary outcomes. A total of 231 patients were screened and 224 completed the trial. The mean change (95%CI) in anxiety scores from before to after medication in pregabalin, diazepam, and placebo groups for VNRS were - 0.87 (- 1.43, - 0.30), - 1.17 (- 1.74, - 0.60), and - 0.99 (- 1.56, - 0.41), and for APAIS were - 0.38 (- 1.04, 0.28), - 0.83 (- 1.49, - 0.16), and - 0.27 (- 0.95, 0.40). The difference in change for pregabalin versus diazepam was 0.30 (- 0.50, 1.11) for VNRS and 0.45 (- 0.49, 1.38) for APAIS, exceeding the limit of inferiority for APAIS of 1.3. Sleep quality was statistically different between pregabalin and placebo groups (p = 0.048). Sedation in pregabalin and diazepam groups were significantly higher than placebo group (p = 0.008). No significant differences of other side effects, except dry mouth was higher in placebo group compared with diazepam (p = 0.006). The study filed to provide evidence at non-inferiority of pregabalin compared to diazepam. Furthermore, premedication with either pregabalin or diazepam did not significantly reduce the preoperative anxiety in comparison to placebo, despite the fact that both resulted in higher levels of sedation. Clinicians should weigh the benefits and risks of premedication with these 2 drugs.Thai Clinical Trials Registry: TCTR20190424001 (24/04/2019) Registry URL: https://www.thaiclinicaltrials.org/ .


Long-lasting response to vinorelbine in unresectable non-small cell lung carcinoma: a case with concomitant good quality of life.
The authors observed a long-lasting response to uninterrupted vinorelbine treatment in a 72-year-old patient with a stage IIIB unresectable non-small cell carcinoma. The progressive tumor mass reduction was assessed by computed tomographic scans over a 2-year period. In the literature, data of randomized trials confirm that the appeal of single-agent vinorelbine therapy in elderly patients is also good for the patient's quality of life during treatment.


Enrichment of anammox bacteria from marine environment for the construction of a bioremediation reactor.
In the global ocean nitrogen cycle, the anaerobic ammonium-oxidizing (anammox) process is recognized as important. In this study, we established an enrichment culture of marine anammox bacteria (MAB) in a column-type reactor. The reactor, which included a porous polyester non-woven fabric that had been placed at the sea floor in advance for enrichment, was continuously fed with NH(4)Cl and NaNO(2) for more than 1 year. Anammox activity in the MAB reactor was confirmed by (15)N tracer analysis using (15)NH(4)Cl and Na(14)NO(2). We identified two 16S rRNA genes in the amplified DNA fragments derived from MAB, which were highly homologous with those from Candidatus "Scalindua wagneri" and an uncultured planctomycete clone. Fluorescence in situ hybridization analysis using an anammox-specific probe also confirmed that MAB predominated in the reactor. To our knowledge, this is the first report on the establishment of an enrichment culture of anammox bacteria from the marine environment using a continuous culture system.


Condom use among antiretroviral therapy naive people living with HIV at a tertiary health care hospital in Lagos, Nigeria: implication for prevention of new infections.
The consistent use of male latex condom significantly reduces the risk of HIV infection among men and women. This study was designed to assess the prevalence and pattern of male and female condom use among antiretroviral therapy naïve people living with HIV (PLHIV) in Lagos, Nigeria. This was a cross-sectional descriptive study. Interviewer administered questionnaires were used to collect demographic data of age, gender, marital status, rate, pattern of and reasons for not using condoms among PLHIV. Four hundred and forty three respondents were interviewed with age rangefrom 14 to 75 years and a mean of 35 ± 9 years. There were 175 (39.5%) males and 268 (60.5%) females in the study. Overall, 71 (16.0%) of respondents used condom consistently. Only 55 (12.4%) of the respondents were aware of female condom while 9 (2%) used it. This study reveals that there is a low consistent use of male condoms and a very low awareness and use of female condoms among studied PLHIV.


Genetic disruption of NRF2 promotes the development of necroinflammation and liver fibrosis in a mouse model of HFE-hereditary hemochromatosis.
In hereditary hemochromatosis, iron deposition in the liver parenchyma may lead to fibrosis, cirrhosis and hepatocellular carcinoma. Most cases are ascribed to a common mutation in the HFE gene, but the extent of clinical expression is greatly influenced by the combined action of yet unidentified genetic and/or environmental modifying factors. In mice, transcription factor NRF2 is a critical determinant of hepatocyte viability during exposure to acute dietary iron overload. We evaluated if the genetic disruption of Nrf2 would prompt the development of liver damage in Hfe-/- mice (an established model of human HFE-hemochromatosis). Wild-type, Nrf2-/-, Hfe-/- and double knockout (Hfe/Nrf2-/-) female mice on C57BL/6 genetic background were sacrificed at the age of 6 (young), 12-18 (middle-aged) or 24 months (old) for evaluation of liver pathology. Despite the parenchymal iron accumulation, Hfe-/- mice presented no liver injury. The combination of iron overload (Hfe-/-) and defective antioxidant defences (Nrf2-/-) increased the number of iron-related necroinflammatory lesions (sideronecrosis), possibly due to the accumulation of toxic oxidation products such as 4-hydroxy-2-nonenal-protein adducts. The engulfment of dead hepatocytes led to a gradual accumulation of iron within macrophages, featuring large aggregates. Myofibroblasts recruited towards the injury areas produced substantial amounts of collagen fibers involving the liver parenchyma of double-knockout animals with increased hepatic fibrosis in an age-dependent manner. The genetic disruption of Nrf2 promotes the transition from iron accumulation (siderosis) to liver injury in Hfe-/- mice, representing the first demonstration of spontaneous hepatic fibrosis in the long term in a mouse model of hereditary hemochromatosis displaying mildly elevated liver iron.


The prostate cancer-up-regulated Myc-associated zinc-finger protein (MAZ) modulates proliferation and metastasis through reciprocal regulation of androgen receptor.
Prostate cancer (PCa) is one of the most commonly diagnosed malignancies in men and the second leading cause of male cancer mortality. MAZ (Myc-associated zinc-finger protein) is a transcription factor that regulates the transcription of oncogenes, and the deregulated MAZ expression is closely related to the development and progression of a variety of cancers. In the present study, the role of MAZ in PCa tumorigenesis and its interaction with androgen receptor (AR), which is essential to PCa development in humans, were investigated. MAZ expression was found to be higher in clinical PCa specimens than in benign prostatic hyperplasia (BPH) and adjacent normal tissues, and MAZ expression was positively correlated with AR expression, which was also observed in PCa cell lines. After knockdown of MAZ by siRNA, cell proliferation was notably inhibited, colony formation declined, the cell cycle was arrested at G0/G1 phase, and the number of cells in S phase decreased (p < 0.05). MAZ knockdown resulted in a significant decline in the migration and invasion capacity of the LNCaP-AD cell line. siRNA knockdown of AR significantly decreased MAZ expression, and knockdown of MAZ significantly increased the expression of AR and DHT-induced androgen response element (ARE). These results suggest that MAZ and AR are interrelated and that MAZ plays an important role in PCa pathogenesis, which could be a potential therapeutic target.


Relationship of imatinib-free plasma levels and target genotype with efficacy and tolerability.
Imatinib has revolutionised the treatment of chronic myeloid leukaemia (CML) and gastrointestinal stromal tumours (GIST). Using a nonlinear mixed effects population model, individual estimates of pharmacokinetic parameters were derived and used to estimate imatinib exposure (area under the curve, AUC) in 58 patients. Plasma-free concentration was deduced from a model incorporating plasma levels of alpha(1)-acid glycoprotein. Associations between AUC (or clearance) and response or incidence of side effects were explored by logistic regression analysis. Influence of KIT genotype was also assessed in GIST patients. Both total (in GIST) and free drug exposure (in CML and GIST) correlated with the occurrence and number of side effects (e.g. odds ratio 2.7+/-0.6 for a two-fold free AUC increase in GIST; P<0.001). Higher free AUC also predicted a higher probability of therapeutic response in GIST (odds ratio 2.6+/-1.1; P=0.026) when taking into account tumour KIT genotype (strongest association in patients harbouring exon 9 mutation or wild-type KIT, known to decrease tumour sensitivity towards imatinib). In CML, no straightforward concentration-response relationships were obtained. Our findings represent additional arguments to further evaluate the usefulness of individualizing imatinib prescription based on a therapeutic drug monitoring programme, possibly associated with target genotype profiling of patients.


PGD for inherited cardiac diseases.
Preimplantation genetic diagnosis (PGD) has been applied for more than 200 different inherited conditions, with expanding application to common disorders with genetic predisposition. One of the recent indications for PGD has been inherited cardiac disease, for which no preclinical diagnosis and preventive management may exist and which may lead to premature or sudden death. This paper presents the first, as far as is known, cumulative experience of PGD for inherited cardiac diseases, including familial hypertrophic and dilated cardiomyopathy, cardioencephalomyopathy and Emery-Dreifuss muscular dystrophy. A total of 18 PGD cycles were performed, resulting in transfer in 15 of them, which yielded nine unaffected pregnancies and the births of seven disease- or disease predisposition-free children. The data open the prospect of PGD for inherited cardiac diseases, allowing couples carrying cardiac disease predisposing genes to reproduce without much fear of having offspring with these genes, which are at risk for premature or sudden death. Preimplantation genetic diagnosis (PGD) is currently an established clinical procedure in assisted reproduction and genetic practices. Its application has been expanding beyond traditional indications of prenatal diagnosis and currently includes common disorders with genetic predisposition, such as inherited forms of cancer. This applies also to the diseases with no current prospect of treatment, which may manifest despite presymptomatic diagnosis and follow up, when PGD may provide the only relief for the at-risk couples to reproduce. One of the recent indications for PGD has been inherited cardiac disease, for which no preclinical diagnosis and preventive management may exist and which may lead to premature or sudden death. We present here our first cumulative experience of PGD for inherited cardiac diseases, including familial hypertrophic and dilated cardiomyopathy, cardioencephalomyopathy and Emery-Dreifuss muscular dystrophy. A total of 18 PGD cycles for these disorders was performed, resulting in transfer in 15 of them, which yielded nine unaffected pregnancies and birth of seven disease- or disease predisposition-free children. The data open the prospect of PGD for inherited cardiac diseases, allowing couples carrying cardiac disease predisposing genes to reproduce without much fear of having offspring with these genes at risk for premature or sudden death.


Hormone-mediated oviductal influence on mouse embryo development.
This study presents evidence that estradiol, mediated through oviduct fluid, may adversely affect the development of early embryos. Two-cell mouse embryos were cultured in Whitten-Biggers medium with or without 0.2 to 20 microgram/ml of estradiol or progesterone or in mouse oviduct fluid from donors treated with estradiol or estradiol and progesterone. Embryos cultured in fluid from estrogen-dominated donors were significantly less able to develop to morula (65%) or blastocyst (14%) than were those cultured in either Whitten-Biggers medium (91% and 41%) or progesterone-dominated fluid (87% and 36%). Transfer of cultured morulae and blastocysts to uteri of pseudopregnant recipients resulted in 2/3, 4/6, and 0/7 recipients' becoming pregnant for control, progesterone-dominated, and estrogen-dominated, respectively. When estradiol or progesterone was added directly to the control medium, no inhibitory effects were observed at levels higher than those found physiologically in plasma. Protein concentration and osmolalities for representative samples of oviduct fluid were 5.2 mg/ml and 329 mOsM for estrogen-dominated fluid and 1.6 mg/ml and 339 mOsM for progesterone-dominated fluid.


Lower general executive function is primarily associated with trait worry: A latent variable analysis of negative thought/affect measures.
This exploratory latent-variable study sought to identify common sources of variance between two multifaceted sets of constructs: executive functions (EFs) and negative thoughts/affect. One-hundred ninety-two college students completed nine tasks representing three types of EFs (inhibition, updating, and shifting) and a set of questionnaires assessing four facets of negative thought/affect (anxiety symptoms, depression symptoms, worry, and rumination). Results indicated that, although the four negative thought/affect constructs were substantially correlated with one another, trait worry was the construct uniquely associated with EFs. Specifically, worry was associated with general EF abilities underlying all three subtypes of EFs (common EF), but was not associated with specific EF abilities (i.e., shifting-specific and updating-specific). These findings highlight the importance of partitioning common and specific variances in both EFs and negative thought/affect when examining the associations between these two research domains. (PsycInfo Database Record (c) 2020 APA, all rights reserved).


Protocol of identical exercise programs with and without specific breathing techniques for the treatment of chronic non-specific low back pain: randomized feasibility trial with two-month follow-up.
Chronic low back pain (CLBP) is a leading cause of disability globally. Exercise therapies are one of the commonly prescribed treatment options for CLBP. The specific exercise therapies for CLBP most commonly target movement dysfunction, but seldom brain-based pain modulation. Exercise therapies with specific breathing techniques (SBTs) have been shown to influence and enhance brain-based structural and functional pain modulation. To assess the feasibility of the SBTs protocol, eligibility criteria, randomization, and dropout rates. To quantify the changes in patient outcome measures and choose the most relevant measure for larger-scale study. To quantify self-adherence levels to home exercise and monitor and record possible pain medication and other treatment modality usage, and adverse events during exercise. A parallel randomised analyst-blinded feasibility trial with two-month follow-up. Feasibility related to aims and objectives. Multiple pain- and health-related patient-reported outcome measures of pain intensity, disability, central sensitization, anxiety, kinesiophobia, catastrophising, self-efficacy, sleep quality, quality of life, and health and well-being status. Exercise adherence, pain medication and other treatment modality usage, and possible adverse events related to exercises will be monitored and recorded. Thirty participants will be randomized to movement control exercise with SBTs (15 subjects in experimental group) or movement control exercise without SBTs (15 subjects in control group) in private chiropractic practice setting with two-month follow-up. Trial registration number; NCT05268822. The clinical difference in effectiveness between practically identical exercise programs in uniform study settings with or without SBTs has not been studied before. This study aims to inform feasibility and help determine whether progression to a full-scale trial is worthwhile.


Direct copolymerization of ethylene with protic comonomers enabled by multinuclear Ni catalysts.
Ethylene/polar monomer coordination copolymerization offers an attractive way of making functionalized polyolefins. However, ethylene copolymerization with industrially relevant short chain length alkenoic acid remain a big challenge. Here we report the efficient direct copolymerization of ethylene with vinyl acetic acid by tetranuclear nickel complexes. The protic monomer can be extended to acrylic acid, allylacetic acid, ω-alkenoic acid, allyl alcohol, and homoallyl alcohol. Based on X-ray analysis of precatalysts, control experiments, solvent-assisted electrospray ionization-mass spectrometry detection of key catalytic intermediates, and density functional theory studies, we propose a possible mechanistic scenario that involves a distinctive vinyl acetic acid enchainment enabled by Ni···Ni synergistic effects. Inspired by the mechanistic insights, binuclear nickel catalysts are designed and proved much more efficient for the copolymerization of ethylene with vinyl acetic acid or acrylic acid, achieving the highest turnover frequencies so far for both ethylene and polar monomers simultaneously.


CHARGE association in neonates presenting with choanal atresia.
Ten infants presented with choanal atresia. Four showed 4 or more components of CHARGE association, 3 of whom died before the age of 2 months while infants with choanal atresia but not having other features of CHARGE association survived. The combination of choanal atresia and heart disease carries a very high risk.


Hamilton׳s Rule in finite populations with synergistic interactions.
Much debate has appeared in the literature over the generality of the inclusive fitness approach in the modeling of evolutionary behavior. Here I focus on the capacity of the inclusive fitness approach to effectively handle non-additive or synergistic interactions. I work with a binary interaction with the matrix game [abcd] and I restrict attention to transitive (homogeneous) populations with weak selective effects. First of all I observe that the construction of "higher-order" relatedness coefficients permits these synergistic interactions to be analyzed with an inclusive fitness analysis. These coefficients are an immediate generalization of Hamilton׳s original coefficient and can be calculated with exactly the same type of recursive equations. Secondly I observe that for models in which the population is not too large and local genetic renewal is rare (e,g, rare mutation), these higher order coefficients are not needed even with non-additive interactions; in fact the synergistic interaction is entirely equivalent to a closely-related additive one. The overall conclusion is that in the study of synergistic binary social interactions (2-player games) in a finite homogeneous population with weak selection and rare genetic renewal, a standard inclusive-fitness analysis is able to predict the direction of allele-frequency change. I apply this result to analyze a recent model of Allen and Nowak (2015).


MicroRNA-7 inhibits cell proliferation of chronic myeloid leukemia and sensitizes it to imatinib in vitro.
MicroRNA is a large class of non-coding small RNA that exerts critical roles in many physiological processes including cell proliferation. MicroRNA-7 (miR-7) has been considered as a tumor suppressor in most malignant tumors versus a tumor promoter in some other ones. However, its role in chronic myeloid leukemia remains unknown. Herein, we found that K562 cell proliferation was largely suppressed when it was stably transfected with miR-7. In accordance with that, apoptosis was also significantly upregulated in miR-7 stably-transfected K562 cells. Moreover, we found that miR-7-overexpressed K562 cells were far more sensitive to imatinib than controls. Further investigations showed that the ABL1 was a direct target of miR-7. Expression level of BCR-ABL and the activity of its downstream PI3K/AKT pathway were significantly reduced in miR-7-transfected cells. Taken together, our results showed that miR-7 inhibited proliferation and promoted apoptosis in K562 cells, and miR-7 might help to sensitize them to imatinib through BCR-ABL/PI3K/AKT signaling in chronic myeloid leukemia.


Diversity of repetitive sequences within compact genomes of Phaseolus L. beans and allied genera Cajanus L. and Vigna Savi.
Repetitive sequences are ubiquitous and fast-evolving elements responsible for size variation and large-scale organization of plant genomes. Within tribe Phaseoleae (Fabaceae), some genera, such as Phaseolus, Vigna, and Cajanus, show small genome and mostly stable chromosome number. Here, we applied a combined computational and cytological approach to study the organization and diversification of repetitive elements in some species of these genera. Sequences were classified in terms of type and repetitiveness and the most abundant were mapped to chromosomes. We identified long terminal repeat (LTR) retrotransposons, especially Ogre and Chromovirus elements, making up most of genomes, other than P. acutifolius and Vigna species. Satellite DNAs (SatDNAs) were less representative, but highly diverse among species, showing a clear phylogenetic relationship. In situ localization revealed preferential location at pericentromeres and centromeres for both types of sequences, suggesting a heterogeneous composition, especially for centromeres. Few elements showed subterminal accumulation. Copy number variation among chromosomes within and among species was observed for all nine identified SatDNAs. Altogether, our data pointed two main elements (Ty3/Gypsy retrotransponsons and SatDNAs) to the diversification on the repetitive landscape in Phaseoleae, with a typical set of repeats in each species. The high turnover of these sequences, however, did not affect total genome size.


The importance of urethra visualization for preplanned permanent prostate implants.
To assess the potential consequences of using a surrogate urethra on urethral dose estimates in preplanned 125I prostate implants. For n=220 patients, the A-P and L-R extents of prostate and urethra contours were measured in transrectal ultrasound images. Treatment plans were then developed for 6 patients, of which 5 had atypical urethral positions. For each patient, three plan variations were made using the visualized and two different surrogate urethra contours. The urethra typically remains fixed in the L-R direction and extends slightly below midgland, but may veer off-center and can come within 0.5 cm of the posterior surface of the prostate. Use of a surrogate urethra can potentially result in up to 30% of the urethra receiving doses exceeding a planned limit of 1.5 x 145 Gy over a contiguous length of 2.0 cm. The urethra should be visualized for preplanning purposes, because unintended urethral doses arising from the use of a surrogate urethra can approach levels associated with late urinary morbidity. Visualization is also essential in the postimplant setting for accurate collection of dose-toxicity data.


Geant4 Monte Carlo investigation of the magnetic field effect on dose distributions in low-density regions in magnetic resonance image-guided radiation therapy.
It is necessary to evaluate the effect of the presence of a magnetic field when treating lung tumors with MRIgRT. In this study, the effect of transverse and longitudinal magnetic fields on dose distributions in low-density regions was quantitatively investigated. The dose distributions in a virtual lung phantom under the influence of magnetic fields were calculated using the Geant4 Monte Carlo code. The phantom size was 30 × 20 × 30 cm3, and it was composed of three layers: water (3 cm thickness), lung (12 cm thickness), and water (5 cm thickness). The density of the lung layer was set to 0.1, 0.3 and 0.6 g/cm3. The uniform magnetic flux densities of 0.35 T and 1.5 T were used for 2 × 2, 5 × 5, and 10 × 10 cm2 fields at a source-to-surface distance of 100 cm, using a 6 MV photon spectrum. The dose at the water-lung interface in a lung phantom increased by 58%, 51%, and 22% for the lung densities of 0.1, 0.3, and 0.6 g/cm3, respectively. In the 1.5 T longitudinal magnetic field, the penumbra at the lung center (at the depth of 9 cm) decreased by 5.14, 1.50 and 0.35 mm for a 5 × 5 cm2 field, respectively. The dose distributions in lowdensity regions are more affected by the magnetic field. In conclusion, the doses at the water-lung interface increased in the transverse magnetic field. The depth dose increased, and the penumbra decreased in the longitudinal magnetic field.


Draft Genome Sequences of Three Mycobacterium chimaera Respiratory Isolates.
Mycobacterium chimaera is an opportunistic human pathogen implicated in both pulmonary and cardiovascular infections. Here, we report the draft genome sequences of three strains isolated from human respiratory specimens.


Use of computational fluid dynamics to compare upper airway pressures and airflow resistance in brachycephalic, mesocephalic, and dolichocephalic dogs.
Brachycephalic dog breeds are prone to breathing difficulties because of their upper airway anatomy. Several surgical techniques exist to correct anatomical pathologies and common surgical approaches aim to correct functional abnormalities in the nares and/or the soft palate. However, further research is needed to improve clinical outcomes. This study evaluated air pressure and airflow resistance in the upper airways and trachea in nine sedated, sternally recumbent dogs of different skull types (dolichocephalic, n=3; mesocephalic, n=3; brachycephalic, n=3). CT images were acquired from the nostrils to the caudal border of the lungs and geometrical reconstruction of the upper airway and trachea was performed. Analysis of computational fluid dynamics was performed using inspiratory flow adapted to bodyweight for each dog. Flow (L/min) and pressure (cmH2O) were computed for the entire upper airway and trachea. Resistance (cmH2O/L/min) was calculated using pressure differences between the nose, larynx, and trachea. In this pilot study, statistical comparisons were not performed. Pressure maps, airflow, and resistance were similar in dolichocephalic and mesocephalic breeds. Median pressure difference (3.76cmH2O) and resistance (0.154cmH2O/L/min) between the nose and larynx were numerically higher in brachycephalic dogs than in other breeds (0.45cmH2O and 0.016cmH2O/L/min, respectively). Median pressure difference (0.205cmH2O) and resistance (0.009cmH2O/L/min) between the larynx and trachea was numerically similar in all dogs, except for the English bulldog. The methodology used in this preliminary study to quantify airflow characteristics such as pressure and resistance could improve the understanding of brachycephalic obstruction airway syndrome.


Clinical predictors of malaria in Gambian children with fever or a history of fever.
Diagnosis of malaria in children is difficult without laboratory support because the symptoms and signs of malaria overlap with those of other febrile illnesses such as pneumonia. Nevertheless, in many parts of Africa diagnosis of malaria must be made without laboratory investigation. Therefore, a scoring system has been developed to assist peripheral health care workers in making this diagnosis. Four hundred and seven Gambian children aged 6 months to 9 years who presented to a rural clinic with fever or a recent history of fever were investigated. A diagnosis of malaria was made in 159 children who had a fever of 38 degrees C or more and malaria parasitaemia of 5000 parasites/microL or more. Symptoms and signs in children with malaria were compared with those in children with other febrile illnesses to identify features which predicted malaria. Symptoms and signs were incorporated into various logistic regression models to test which were best independent predictors of malaria and these regression models were used to construct simple scoring systems which predicted malaria. A nine terms model predicted clinical malaria with a sensitivity of 89% and a specificity of 61%, values comparable to those obtained by an experienced paediatrician without laboratory support. The ability of peripheral health care workers to diagnose malaria using this approach is now being investigated in a prospective study.


An experimental study on the therapeutic effect of consecutive low-dose cisplatin with caffeine in sarcoma-bearing mice.
The aims of this study were to investigate the anti-tumor effects of consecutive low-dose cisplatin (LD-CDDP) in comparison with single high-dose CDDP (HD-CDDP) in combination with caffeine. Human fibrosarcoma cells (HT-1080) were transplanted in BALB/C-nu mice. According to the administration of CDDP and caffeine, 5 groups were defined: HD-CDDP, LD-CDDP, HD-CDDP +caffeine, LD-CDDP +caffeine and control group. The total dose of CDDP was 3.5 or 6 mg/kg. CDDP was injected i.p. bolus (HD-CDDP) or divided into 5 days (LD-CDDP). Caffeine was injected i.p. at a dose of 60 mg/kg twice a day for 4 days. Significant inhibition of tumor growth and prolongation of survival time were recognized in the HD- and LD-CDDP groups with and without caffeine compared to the control group. The caffeine-assisted groups had no advantage compared to the CDDP alone groups. The effects of LD-CDDP were similar to the effect of HD-CDDP.


Non-fasting changes of Hs-CRP level in Chinese patients with coronary heart disease after a daily meal.
High-sensitivity C-reactive protein (hs-CRP) is a key inflammatory factor in atherosclerotic cardiovascular diseases. In Chinese patients with coronary heart disease (CHD), the changes in hs-CRP levels after a daily meal and the effect of statins on those were never explored. A total of 300 inpatients with CHD were included in this study. Hs-CRP levels were measured in the fasting and non-fasting states at 2 h and 4 h after a daily breakfast. All inpatients were divided into two groups according to fasting hs-CRP ≤ 3 mg/L or not. Group with fasting hs-CRP ≤ 3 mg/L had a significantly higher percentage of patients with statins using ≥ 1 month (m) before admission than that with fasting hs-CRP > 3 mg/L (51.4% vs. 23.9%, P < 0.05). Hs-CRP levels increased significantly in the non-fasting state in two groups (P < 0.05). About 32% of patients with non-fasting hs-CRP > 3 mg/L came from those with fasting hs-CRP ≤ 3 mg/L. In conclusion, hs-CRP levels increased significantly in CHD patients after a daily meal. It suggested that the non-fasting hs-CRP level could be a better parameter to evaluate the inflammation state of CHD patients rather than fasting hs-CRP level.