The development and implementation of a theory-informed, integrated mother-child intervention in rural Uganda.
A randomised cluster effectiveness trial of a parenting intervention in rural Uganda found benefits to child development among children 12-36 months, relevant parenting practices related to stimulation, hygiene and diet, and prevented the worsening of mothers' depressive symptoms. An examination of underlying implementation processes allows researchers and program developers to determine whether the program was implemented as intended and highlight barriers and facilitators that may influence replication and scale-up. The objectives of this study were to describe and critically examine (a) perceived barriers and facilitators related to implementation processes of intervention content, training and supervision and delivery from the perspectives of delivery agents and supervisors; (b) perceived barriers and facilitators related to enactment of practices from the perspective of intervention mothers participating in the parenting program; and c) whether the program was implemented as intended. Semi-structured interviews were conducted at midline with peer delivery agents (n = 12) and intervention mothers (n = 31) and at endline with supervisors (n = 4). Content analysis was used to analyze qualitative data in terms of barriers and facilitators of intervention content, training and supervision, delivery and enactment. Additionally, mothers' recall and enactment of practices were coded and analyzed statistically. Monitoring of group sessions and home visits were examined to reveal whether the program was implemented as intended. Among the program's five key messages, 'love and respect' targeting maternal psychological well-being was the most practiced by mothers, easiest to implement by delivery agents, and mothers reported the most internal facilitators for this message. A detailed manual and structured monitoring forms were perceived to facilitate training, intervention delivery, and supervision. Interactive and active strategies based on social-cognitive learning theory were reported as facilitators to intervention delivery. Only program attendance, but not barriers, facilitators or message recall, was significantly positively related to message enactment. Monitoring of group sessions and home visits showed that the program was largely implemented as intended. This implementation assessment revealed a number of important barriers and facilitators from the perspectives of delivery agents, supervisors and program participants. The methods and results are useful to examining and informing the content, delivery, and scaling up of the current program as well as future mother-child interventions in LMIC settings.


Thiol-ene oligomers as dental restorative materials.
The aim of this work was to prereact thiol-ene monomers to create reactive thiol or vinyl (ene)-functionalized oligomers, and to investigate the use of these materials as novel dental restorative material. Investigation has focused on the application of oligomeric thiol-ene materials as dental restorative resins with lower polymerization shrinkage and polymerization stress as compared to monomeric thiol-ene systems and particularly with respect to current dimethacrylate-based systems. Reactive thiol-functionalized oligomers were created via photopolymerization using triallyl-1,3,5-triazine-2,4,6-trione (TATATO), trimethylolpropane tris(3-mercaptopropionate) (trithiol) and pentaerythritol tetramercaptopropionate (tetrathiol). Kinetic and mechanical investigation of Bis-GMA/TEGDMA, and oligomeric and monomeric thiol-ene systems were conducted. More specifically, polymerization shrinkage and stress, polymerization kinetics, glass transition temperature, flexural strength and flexural modulus were evaluated. Upon evaluation, the polymerization stress of oligomeric thiol-ene systems was dramatically reduced by as much as 33% when compared with the stress exhibited by monomeric thiol-ene systems and as much as a 92% reduction in stress relative to the current dimethacrylate-based dental restorative materials. Furthermore, the flexural strength and modulus of the monomeric and oligomeric thiol-ene resins were not significantly different. Oligomeric thiol-ene systems offer potential as alternative dental restorative resins due to the significant reduction in polymerization shrinkage and stress while retaining the mechanical properties of monomer-based thiol-ene resins.


Histone H3 lysine 9 methylation and HP1gamma are associated with transcription elongation through mammalian chromatin.
Methylation of histones modulates chromatin structure and function. Whereas methylation of histone H3 on lysines 4, 36, and 79 has been linked with gene activation, methylation of H3 on lysines 9 and 27 and histone H4 on lysine 20 is associated with heterochromatin and some repressed genes within euchromatin. Here, we show that H3K9 di- and trimethylation occur in the transcribed region of active genes in mammalian chromatin. This modification is dynamic, as it increases during activation of transcription and is rapidly removed upon gene repression. Heterochromatin Protein 1gamma (HP1gamma), a protein containing a chromo-domain that recognizes H3K9 methylation, is also present in the transcribed region of all active genes examined. Both the presence of HP1gamma and H3K9 methylation are dependent upon elongation by RNA polymerase II. These findings demonstrate novel roles for H3K9 methylation and HP1gamma in transcription activation.


Role of protein and calcium in stratum corneum cell cohesion.
The work reported here indicates that protein and calcium have roles in stratum corneum cell cohesion. A zwitterionic surfactant, 6-octadecyldimethyl ammoniohexanoate (C18AH), was found to completely disaggregate pig and human stratum corneum into intact, individual cells. This method of disaggregation provided a tool to determine the role of tissue components in cell cohesion. The C18AH disaggregation of pig and human stratum corneum was accelerated by proteolytic enzyme and ethylenediaminetetraacetate (EDTA). The C18AH disaggregation could be blocked by pretreatment of the stratum corneum with the serine-type proteolytic enzyme inhibitor phenylmethylsulfonyl fluoride (PMSF). The blockage could be overcome by addition of proteolytic enzyme or divalent metal ion chelator. These and other data indicate the importance of protein and calcium in stratum corneum cell cohesion.


Significance of the fluid-blood interface in intracranial hematomas in anticoagulated patients.
Six patients receiving anticoagulant medication who had laboratory evidence of impaired hemostasis as manifested by laboratory parameters exceeding the therapeutic range developed intracranial hemorrhages. None of these patients had a history of preceding trauma. None of the 6 anticoagulated had CNS symptoms prior to initiation of anticoagulant medication. Within the intracranial hemorrhage there was a fluid-blood interface in these 6 patients; this finding was seen only in hemorrhages in anticoagulated patients. In 3 cases the fluid-blood interface changed to a homogeneous hyperdense lesion when adequate hemostasis was achieved. In one case there were multiple hemorrhages and in the other there was a solitary intracerebral hemorrhage.


Action of cholera toxin on dispersed acini from rat pancreas. Post-receptor modulation involving cyclic AMP and calcium.
In dispersed acini from rat pancreas, cholera toxin caused a significant increase in cellular cyclic AMP but little or no change in amylase secretion. The presence of a secretagogue that causes mobilization of cellular calcium (e.g., cholecystokinin, carbamylcholine, bombesin or ionophore A23187) caused a substantial increase in the effect of cholera toxin on enzyme secretion. Cholera toxin did not alter calcium transport or the changes in calcium transport caused by other secretagogues, and secretagogues that mobilize cellular calcium did not alter cellular cyclic AMP or the increase in cyclic AMP caused by cholera toxin. These results indicate that in dispersed acini from rat pancreas there is post-receptor modulation of the action of cholera toxin by secretagogues that mobilize cellular calcium and that this modulation is a major determinant of the effect of the toxin on enzyme secretion.


Examination of ancestry and ethnic affiliation using highly informative diallelic DNA markers: application to diverse and admixed populations and implications for clinical epidemiology and forensic medicine.
We and others have identified several hundred ancestry informative markers (AIMs) with large allele frequency differences between different major ancestral groups. For this study, a panel of 199 widely distributed AIMs was used to examine a diverse set of 796 DNA samples including self-identified European Americans, West Africans, East Asians, Amerindians, African Americans, Mexicans, Mexican Americans, Puerto Ricans and South Asians. Analysis using a Bayesian clustering algorithm (STRUCTURE) showed grouping of individuals with similar ethnic identity without any identifier other than the AIMs genotyping and showed admixture proportions that clearly distinguished different individuals of mixed ancestry. Additional analyses showed that, for the majority of samples, the predicted ethnic identity corresponded with the self-identified ethnicity at high probability (P > 0.99). Overall, the study demonstrates that AIMs can provide a useful adjunct to forensic medicine, pharmacogenomics and disease studies in which major ancestry or ethnic affiliation might be linked to specific outcomes.


Respiration and acid-base balance of blood after diffuse experimental brain injury.
Diffuse brain injury in rabbits was caused by injecting olive oil and saline into one internal carotid artery. In this report, the fourth of a series, the effects of this experimental brain injury on respiration and acid-base balance of blood are analyzed. The animals that withstood the injury best were those that had a lower pre-traumatic pCO2; the animals that suffered a rise in intracranial pressure and succumbed to the injury quickly did so in spite of pronounced hyperventilation after the injury. Arterial pCO2 immediately before the injury was the only significant prognostic factor in this analysis. Respiratory rate only dropped immediately before respiratory arrest and death. The findings concerning pCO2 tally with results after experimental ligation of a cerebral artery, but less so with results after other types of experimental brain injury. This emphasizes again that conclusions drawn from one type of brain injury must not be extrapolated to other types.


Mesenchymal and stem-like prostate cancer linked to therapy-induced lineage plasticity and metastasis.
Bioinformatic analysis of 94 patient-derived xenografts (PDXs), cell lines, and organoids (PCOs) identifies three intrinsic transcriptional subtypes of metastatic castration-resistant prostate cancer: androgen receptor (AR) pathway + prostate cancer (PC) (ARPC), mesenchymal and stem-like PC (MSPC), and neuroendocrine PC (NEPC). A sizable proportion of castration-resistant and metastatic stage PC (M-CRPC) cases are admixtures of ARPC and MSPC. Analysis of clinical datasets and mechanistic studies indicates that MSPC arises from ARPC as a consequence of therapy-induced lineage plasticity. AR blockade with enzalutamide induces (1) transcriptional silencing of TP53 and hence dedifferentiation to a hybrid epithelial and mesenchymal and stem-like state and (2) inhibition of BMP signaling, which promotes resistance to AR inhibition. Enzalutamide-tolerant LNCaP cells re-enter the cell cycle in response to neuregulin and generate metastasis in mice. Combined inhibition of HER2/3 and AR or mTORC1 exhibits efficacy in models of ARPC and MSPC or MSPC, respectively. These results define MSPC, trace its origin to therapy-induced lineage plasticity, and reveal its sensitivity to HER2/3 inhibition.


Effects of increased solar ultraviolet radiation on materials.
Synthetic polymers such as plastics, as well as naturally occurring polymer materials such as wood, are extensively used in building construction and other outdoor applications where they are routinely exposed to sunlight. The UV-B content in sunlight is well known to affect adversely the mechanical properties of these materials, limiting their useful life. Presently their outdoor lifetimes depend on the use of photostabilizers in the case of plastics and on protective surface coatings in the case of wood. Any increase in the solar UV-B content due to a partial ozone depletion would therefore tend to decrease the outdoor service life of these materials. It is the synergistic effect of increased UV radiation with other factors such as the temperature that would determine the extent of such reduction in service life. The increased cost associated with such a change would be felt unevenly across the globe. Those developing countries that depend on plastics as a prime material of construction and experience high ambient temperatures are likely to be particularly affected in spite of the relatively small fractional decrease in ozone at those locations. Assessment of the damage to materials, associated with ozone depletion, requires a knowledge of the wavelength dependence as well as the dose-response characteristics of the polymer degradation processes of interest. While the recent literature includes some reliable spectral sensitivity data, little dose-response information has been reported, so it is difficult to make such assessments reliably at the present time. This is particularly true for the naturally occurring materials popularly used in construction applications. To maintain polymers at the same useful lifetime in spite of increased solar UV-B content, the amount of photostabilizers used in the formulations might be increased. This strategy assumes that conventional stabilizers will continue to be effective with the spectrally altered UV-B-enhanced solar radiation. While the present understanding of the degradation chemistry suggests the strategy to have merit, its effectiveness, in an altered solar radiation environment, has not been demonstrated for common polymers. The availability of these data is crucial for reliably estimating the cost of mitigating the increased damage to materials as a result of a possible partial depletion of the ozone layer using this approach.


Difficult-To-Treat Juvenile Idiopathic Arthritis: Current and Future Options.
Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease in childhood and is usually treated with non-steroidal anti-inflammatory drugs or disease-modifying anti-rheumatic drugs (DMARDs) such as methotrexate or sulfasalazine. However, not all patients respond to these treatments, and toxicities may limit long-term use or diminish compliance. With advances in pharmacotherapy and the development of new therapeutic agents, there have been improvements in treatment of both systemic and non-systemic JIA, particularly with biologic agents such as anti-tumor necrosis factor (TNF)-α, anti-interleukin (IL)-1, and anti-IL6. Anti-cell therapies, such as co-stimulator blockers or anti-CD20, small molecules, and biosimilars represent new areas of interest, and, while many are not yet currently commercially available for use in children, preliminary studies appear to be promising. In the present article, the authors review therapeutic strategies for the different JIA subtypes, mainly according to guidelines and recommendations. Newer and possible future treatments for arthritis, already approved in adults but currently under study in children, are also discussed. Drugs currently in development plans for rheumatoid arthritis, which hopefully will also be useful for JIA patients in the future, are also mentioned in this paper.


Preoperative Inflammatory Markers in Liver Resection for Colorectal Liver Metastases: A National Registry-Based Study.
Preoperative inflammatory markers were shown to be associated with prognosis following surgery for hepato-pancreato-biliary cancer. Yet little evidence exists about their role in patients with colorectal liver metastases (CRLM). This study aimed to examine the association between selected preoperative inflammatory markers and outcomes of liver resection for CRLM. Data from the Norwegian National Registry for Gastrointestinal Surgery (NORGAST) was used to capture all liver resections performed in Norway within the study period (November 2015-April 2021). Preoperative inflammatory markers were Glasgow prognostic score (GPS), modified Glasgow prognostic score (mGPS) and C-reactive protein to albumin ratio (CAR). The impact of these on postoperative outcomes, as well as on survival were studied. Liver resections for CRLM were performed in 1442 patients. Preoperative GPS ≥ 1 and mGPS ≥ 1 were present in 170 (11.8%) and 147 (10.2%) patients, respectively. Both were associated with severe complications but became non-significant in the multivariable model. GPS, mGPS, CAR were significant predictors for overall survival in the univariable analysis, but only CAR remained such in the multivariable model. When stratified by the type of surgical approach, CAR was a significant predictor for survival after open but not laparoscopic liver resections. GPS, mGPS and CAR have no impact on severe complications after liver resection for CRLM. CAR outperforms GPS and mGPS in predicting overall survival in these patients, especially following open resections. The prognostic significance of CAR in CRLM should be tested against other clinical and pathology parameters relevant for prognosis.


Improved quorum sensing capacity by culturing Vibrio harveyi in microcapsules.
Microcapsule entrapped low density cells with culture (ELDCwc), different from free cell culture, conferred stronger stress resistance and improved cell viability of microorganisms. In this paper, the quorum sensing (QS) system of Vibrio harveyi was used to investigate changes when cells were cultured in microcapsules. Cells in ELDCwc group grew into cell aggregates, which facilitated cell-cell communication and led to increased bioluminescence intensity. Moreover, the luxS-AI-2 system, a well-studied QS signal pathway, was detected as both luxS gene and the AI-2 signaling molecule, and the results were analyzed with respect to QS capacity of unit cell. The V. harveyi of ELDCwc also showed higher relative gene expression and stronger quorum sensing capacity when compared with free cells. In conclusion, the confined microcapsule space can promote the cell aggregates formation, reduce cell-cell communication distance and increase local concentration of signal molecule, which are beneficial to bacterial QS.


Priority Research Topics and Patient and Family Needs in a National Sample of Hospice Agencies.
Various contextual factors surrounding hospice care have reinforced the need for scholars to pursue practice-relevant research questions. Although priority-setting is a primary approach to streamline such efforts, research appears yet to have conducted priority-setting with hospice professionals. To describe the areas of needed research and clinical focus voiced by a national probability sample of US hospice agency representatives. A national probability sample of 600 hospice agencies proportionately stratified by state and profit status was surveyed. At the end of the survey, participants indicated whether or not they were willing to answer two additional open-ended questions. These two questions requested participants' input on areas of needed attention related to (1) research topics and (2) unmet needs for patients and families. Responses were content analyzed. A total of 317 surveys were completed (response rate = 61.8%). Viable responses were recorded by 129 participants responding to at least one item. Content analysis generated the following five categories (and various subcategories): earlier access to hospice, education (outside physicians, patients and families, public), policy barriers to hospice enrollment (hospice eligibility and reimbursement, gaps in insurance coverage), effects of policy restrictions on hospice care (reimbursement for care, pain management, clinician issues), and improving the provision of in-home hospice care (community resources, supports for caregivers, supports for when caregiver assistance is inadequate, needs already are being met). These findings presented by hospice agency representatives reflect directions for research and clinical development. Efforts are needed to cohere professional- and patient-reported areas of needed attention.


Patterns of sexual commerce among women at US Syringe Exchange Programs.
In the USA, the majority of research on sex work has examined the experiences of women recruited from social locations commonly referred to as the 'sex industry', such as street strolls or escort services. This paper presents data from female syringe exchange participants who had sold sex in the last 30 days. The women interviewed for this study report a much broader array of commercial transactions than found in previous US studies, including selling sex to women, paying men for sex, and considerable role fluidity between buying and selling. In addition, approximately one-third of the women report only selling sex 1 day per week or less, and appear to be more socio-economically stable than women who sell sex more often. We argue that this data suggests the existence of an array of commercial sexual transactions outside of the socially recognized sex industry, and that social location may affect condom use.


Nevus Lipomatosus Cutaneous Superficialis Associated with Trichofolliculoma: An Uncommon Duet of Rare Pathologies.
Nevus lipomatosus cutaneous superficialis (NLCS) and trichofolliculoma (TF) are both rare cutaneous hamartomatous lesions. However, the coexistence of NLCS and TF as a single lesion has been reported only in two other cases, that too in middle-aged individuals. We report the first case of NLCS associated with TF in pediatric age group and also, to the best of our knowledge, the first case reported from India.


Design of Japanese multicenter prospective cohort study of endoscopic resection for early gastric cancer using Web registry (J-WEB/EGC).
A Japanese multicenter prospective cohort study is currently being conducted on endoscopic resection (ER) for early gastric cancer (EGC) using a Web registry system developed to determine short-term and long-term outcomes based on the absolute and expanded indications. All consecutive patients with EGC or suspected EGC undergoing ER at the 41 participating institutions from July 2010 to June 2012 are being enrolled in the study cohort using the Web registry system, and each patient will be followed up for a minimum of 5 years. The study investigation includes baseline patient and lesion characteristics as well as short-term and long-term outcomes. A survey program to collect information on long-term outcomes is also being introduced for patients subsequently followed up in institutions other than their original participating institutions, as well as patients for whom the original participating institutions have been losing track of their follow-up. The primary endpoint is 5-year overall survival, with en bloc resection, curative resection, complication, local recurrence, distant metastasis, metachronous EGC, and recurrence-free survival being secondary endpoints in addition to the successful collection of long-term outcome data on enrolled patients utilizing the survey program.


Effect of the inhibition of serotonin biosynthesis on the antinociception induced by nonsteroidal anti-inflammatory drugs.
The antinociceptive activity of nonsteroidal anti-inflammatory drugs (NSAIDs) has been explained mainly on the basis of their inhibition of the enzyme cyclooxygenase (COX); however, this inhibition is not enough to completely explain the analgesic efficacy of these drugs. The modulation exerted by serotonergic systems on antinociception is well known. The purpose of the present work was to further explore the role of serotonin in the antinociceptive activity of NSAIDs using the writhing test and the tail-flick test of the mice after the inhibition of serotonin biosynthesis with intraperitoneal p-chlorophenylalanine (p-CPA). Pretreatment with p-CPA produced a significant decrease in the antinociceptive activity of NSAIDs administered either by the intraperitoneal or intrathecal routes, in both algesiometric tests. These results suggest a complementary mechanism of antinociception for NSAIDs, independent of their ability to inhibit the activity of COX, involving the activation of descending serotonergic pathways. By the pharmacological nature of the study, one limitation was the absence of biochemical measurement of the synthesis of 5-HT, since the reduction of the brain 5-HT synthesis by pretreatment with p-CPA will be expressed as a diminished antinociceptive activity of NSAIDs, which would be a new argument to consider NSAIDs acting as central analgesic agents.


In vivo anti-hepatitis B activity of Artemisia argyi essential oil-loaded nanostructured lipid carriers. Study of its mechanism of action by network pharmacology and molecular docking.
Hepatitis B virus (HBV) infection remains a major global health burden, due to the increasing risk of complications, such as cirrhosis and hepatocellular carcinoma. Novel anti-HBV agents are critical required. Our previous study suggested that Artemisia argyi essential oil (AAEO) significantly inhibited the replication of HBV DNA and especially the secretion of hepatitis B antigen in vitro. The aim of this study was to prepare AAEO loaded nanostructured lipid carriers (AAEO-NLCs) for the delivery of AAEO to the liver, investigated the therapeutic benefits of AAEO-NLCs against HBV in a duck HBV (DHBV) model and explored its potential mechanism. AAEO-NLCs were prepared by hot homogenization and ultrasonication method. The DHBV-infected ducks were treated with AAEO (4 mg/kg), AAEO-NLCs (0.8, 4, and 20 mg/kg of AAEO), and lamivudine (20 mg/kg) for 15 days. The DHBV DNA levels in the serum and liver were measured by quantitative Real-Time PCR. Pharmacokinetics and liver distribution were performed in rats after oral administration of AAEO-NLCs and AAEO suspension. The potential antiviral mechanism and active compounds of AAEO were investigated by network pharmacology and molecular docking. AAEO-NLCs markedly inhibited the replication of DHBV DNA in a dose-dependent manner and displayed a low virologic rebound following withdrawal the treatment in DHBV-infected ducks. Moreover, AAEO-NLCs led to a more pronounced reduction in viral DNA levels than AAEO suspension. Further investigations of pharmacokinetics and liver distribution in rats confirmed that NLCs improved the oral bioavailability and increased the liver exposure of AAEO. The potential mechanisms of AAEO against HBV explored by network pharmacology were associated with signaling pathways related to immune response, such as tumor necrosis factor, nuclear factor kappa B, and sphingolipid signaling pathways. Furthermore, a total of 16 potential targets were obtained, including prostaglandin-endoperoxide synthase-2 (PTGS2), caspase-3, progesterone receptor, etc. Compound-target docking results confirmed that four active compounds of AAEO had strong binding interactions with the active sites of PTGS2. AAEO-NLCs displayed potent anti-HBV activity with improved oral bioavailability and liver exposure of AAEO. Thus, it may be a potential therapeutic strategy for the treatment of HBV infection.


Comparative study of the adverse event profile of hydroxychloroquine before and during the Sars-CoV2 pandemic.
At the beginning of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, there were no clinically-tested medications for the effective treatment of coronavirus disease. In this context, on 5 March 2020, the French Public Health Council issued several recommendations for the therapeutic management of this new disease, including the use of hydroxychloroquine (HCQ). An unexpected cardiovascular safety signal was quickly identified as being more frequent than expected thanks to the reports of adverse drug reactions (ADRs) submitted to French regional pharmacovigilance centres (RPVC). The objective of this study was to compare all ADRs reported with HCQ used in its usual indication, collected before the pandemic period (1985 to 31 December, 2019) with those reported with the coronavirus disease 2019 (COVID-19) indication (1 January to 21 July, 2020). For this purpose, reports were extracted from the French pharmacovigilance database and analysed for these two periods. Our study showed a different safety profile in COVID-19 patients with more cardiac disorders (57% of ADRs versus 5% before the pandemic period), especially QT interval prolongation, resulting from an interaction with azithromycin in more than 20% of cases. Hepatobiliary disorders were also significantly more frequent. These observations could be associated with the effect of the virus itself on the various organs, the profile of the patients treated, and concomitant drug treatments.


Possible involvement of terminal complement complex in active Heymann nephritis.
We investigated whether the appearance of various complement components in renal deposits of immune complexes correlated with the development of proteinuria in rats with active Heymann nephritis. Sequential kidney biopsy specimens and serum samples were obtained from Lewis rats immunized with Fx1A in complete Freund's adjuvant. Circulating antibodies against purified auto-antigen renal tubular epithelial glycoprotein, as measured by ELISA, were found in the circulation together with a diffuse granular deposition of IgG1, IgG2a, and IgG2b in the glomeruli within 2 weeks after immunization. Biopsy specimens taken 4 weeks after immunization showed diffuse deposition of C4 and C3, which indicated that activation of complement by the classical pathway had occurred. The detection of the C5b-9 complex of complement in glomerular deposits coincided with the development of abnormal proteinuria indicating that the glomerular damage in this autoimmune disease may be caused by complement-mediated lesions in the glomerular capillary walls.


Inhibition of platelet activation by the nitrate Sin-1: studies with human aequorin-loaded platelets.
The effects of the nitrovasodilator Sin-1, which is thought to work through cyclic-GMP, were studied using human, aequorin-loaded, washed platelets. Changes in light transmission (shape change, aggregation), and in intracellular calcium were simultaneously recorded. Evidence was obtained for an inhibitory effect distal to calcium changes, in a similar way than a prostacyclin analogue, Iloprost. By contrast the response to an activator of protein kinase C was unaffected. There was a partial, parallel decrease in calcium changes and aggregation induced with thrombin, and a total inhibition of the responses to ADP (linked to a calcium influx).


Analysis of chromosome aberrations and sister-chromatid exchanges in human lymphocytes exposed in vitro to Hydergine.
Hydergine (dihydroergotoxine mesylate, Sandoz) was examined for its capability to induce chromosome damage and sister-chromatid exchanges (SCEs) in human lymphocyte in vitro. For the chromosome-aberration study, cultures set up from 6 individuals were divided into 5 groups: negative control, positive control (caffeine, 0.5 mg/ml), and Hydergine (0.1, 0.25 and 0.5 micrograms/ml). For the SCE examination, which used 8 individuals, 4 cultures were made per person in the following way: negative control, positive control (mitomycin C, 0.1 microgram/ml), and Hydergine (0.1 and 0.5 micrograms/ml). Lymphocytes were cultivated for 72 h, being exposed to the respective treatments during the final 24 h. The results showed that Hydergine induced no chromosome damage in human lymphocytes in vitro.


The sorting effect in healthcare access: Those left behind.
Many governments have sought to enhance patient choice in hospital by intensifying competitive pressure on hospital administrations that is expected to improve efficiency, quality, and innovation. However, there is mixed evidence on whether patients travel past their local hospitals to seek better quality care and whether higher-income patients are those most sensitive to respond to competitive pressures. Using detailed data from 17 million inpatient stays admitted in France during 2019, this paper explores patients' choice of provider where for-profit, non-profit, research hospital and local hospitals are allowed to compete with each other. We estimate the extent to which deprivation gradient plays on patient's choice of provider. We found that, in general, patients travel for their care, with just one-quarter of them going to the nearest hospital. In fact, the most vulnerable patients (i.e., those socio-economically deprived, and very aged) are mostly treated in local public hospitals with the lowest quality service level, and with large variability in quality as well, while those with less socio-economic deprivation seek care at higher-quality for-profit hospitals. Our counterfactual simulations show that admission to university hospitals attenuates existing inequalities. However, whether it delays the healthcare access sought by this population remains an open question.


[Valvular aortic stenosis, left anterior cusp hypoplasia and obstruction of left main coronary artery ostium by a congenital membrane].
Aortic stenosis and obstruction of the left main coronary artery ostium is very rare. This report describes the case of one patient with valvular aortic stenosis, left anterior cusp hypoplasia and obstruction of the left main coronary artery by a congenital membrane. Surgical treatment with aortic valve removal and excision of the congenital membrane was successful.


Study of Clinical Characteristics and Cytokine Profiles of Asthmatic Children with Rhinovirus Infection during Acute Asthma Exacerbation at National Hospital of Pediatrics.
In children with asthma, the viral infection of airways is usually a main cause of acute asthma exacerbation and hospitalization. However, few studies on clinical and biomolecular characteristics of asthmatic children in this field have been done, especially in emergent countries. This study described the clinical and biological characteristics of asthmatic children who had acute asthma exacerbation and rhinovirus (RV) infection. Children under 15 years of age hospitalized for acute asthma exacerbation were included. They underwent clinical examination and peripheral blood analyses for the cytokine profile. The severity of acute asthma exacerbation was evaluated by Pediatric Asthma Score (PAS). Healthy children under 15 years of age were also invited in this study. One hundred fifteen asthmatic children were included in this study. There were 18.2% of mild PAS, 37.4% of moderate PAS, and 44.4% of severe PSA. Among them, 63/115 (54.8%) asthmatic children had positive RV infection (RV+). The percentages of asthmatic children with RV+ had increased polymorphonuclear leucocytes were significantly higher than asthmatic children with RV-. There were no significant differences of the concentrations of non-Th2-related cytokines in asthmatic children with RV- and RV+. The concentration of Th2-related cytokines (IL-5 and IL-13) in asthmatic children with RV+ was significantly higher than those with RV-. However, there was no significant difference for the cytokine profile between mild, moderate, and severe asthma. RV infection is a main cause of acute asthma exacerbation in children with asthma. The increase of Th2-related cytokines, especially IL-5 and IL-13, is a relevant biomarker for RV infection in asthmatic children with severe exacerbation.


Comparison of CD34+ cell collection efficiency on the COBE Spectra and Fenwal CS-3000 Plus.
Optimal collections of mobilized CD34+ cells are important in terms of both patient toxicity and cost. The factors that determine CD34+ collection efficiency (CD34eff) of cell separators have not been well studied. In addition, because several cell separators are available, the type of collection device may also be a significant variable. Previous studies comparing the Baxter-Fenwal CS3000 and the COBE Spectra have not yielded consistent conclusions. Therefore, we retrospectively analyzed the collection outcomes of 163 consecutive donors with a peripheral CD34+ cell concentration (pCD34) of > or =5 cells/microl on the first collection that had been harvested on one or the other device. The CS3000 was found to yield a significantly higher CD34eff (50% vs. 39%, P = 0.006). However, donors were not balanced for several prognostic factors, which may contribute to CD34eff including mobilization with G-CSF vs. chemotherapy+G-CSF, average flow rate, and total volume of peripheral blood processed. When appropriate variables were included in a stepwise multiple variable analysis, cell separator type emerged as a significant independent predictive factor for CD34eff (P = 0.018). Our data indicates that the CS3000 will, on average, show a higher absolute CDeff of 8%. Furthermore, since the two devices differ in mechanism, prognostic factors may also differ. Comparisons suggest that peripheral blood WBC and hematocrit may be more important predictors for the CS3000.


Multiple genes for Xenopus activin receptor expressed during early embryogenesis.
Four distinct cDNAs for activin receptor designated as XSTK2, 3, 8 and 9 have been cloned from a Xenopus laevis cDNA library. The protein structures deduced from the cDNAs have shown that they all have a putative extracellular ligand-binding domain, a single transmembrane domain and cytoplasmic Ser/Thr kinase domain, except that XSTK2 is extremely similar to the XSTK3 gene but lacks a carboxyl-terminal part of the kinase motif. Northern blot analysis showed that all transcripts are maternally inherited. The levels of transcript for XSTK2, 3 and 8 appeared to fluctuate during early development while those for XSTK9 maintain constant.


Genetic control of the immune response to myoglobin. IX. Overcoming genetic control of antibody response to antigenic sites by increasing the dose of antigen used in immunization.
Previously, it was reported that the immune response to myoglobin (Mg) was under genetic control, with the response to each site being under separate Ir-gene control. Here we have investigated the effect of antigen dose on the control of the antibody response to the five antigenic sites of sperm-whale Mb to determine whether or not the overcoming of genetic control by antigen dose has a uniform effect on all five antigenic sites. The antibody response to sperm whale myoglobin (Mb) and its five antigenic was measured in the following inbred strains of mice, C57BL/6J, AKR and SWR/J. These strains of mice are low responders to Mb following immunization with 50 micrograms, responding only to site 4. After immunization with 200 micrograms Mb: C57BL/6J mice are high responders to Mb and respond to antigenic sites 1, 3, 4 and 5; AKR mice are high responders to Mb and respond to antigenic sites 1 and 4; SWR/J mice are high responders to Mb and respond to all five antigenic sites. It was concluded that the genetic control of the immune response to Mb and its synthetic antigenic sites is dependent on antigen dose. Also, these studies have enabled us for the first time to separate the response to site 1 from the response to site 2 and thus have conclusively established that sites 1 and 2 are controlled by separate Ir-genes.


Siberian and temperate ecosystems shape Northern Hemisphere atmospheric CO2 seasonal amplification.
The amplitude of the atmospheric CO2 seasonal cycle has increased by 30 to 50% in the Northern Hemisphere (NH) since the 1960s, suggesting widespread ecological changes in the northern extratropics. However, substantial uncertainty remains in the continental and regional drivers of this prominent amplitude increase. Here we present a quantitative regional attribution of CO2 seasonal amplification over the past 4 decades, using a tagged atmospheric transport model prescribed with observationally constrained fluxes. We find that seasonal flux changes in Siberian and temperate ecosystems together shape the observed amplitude increases in the NH. At the surface of northern high latitudes, enhanced seasonal carbon exchange in Siberia is the dominant contributor (followed by temperate ecosystems). Arctic-boreal North America shows much smaller changes in flux seasonality and has only localized impacts. These continental contrasts, based on an atmospheric approach, corroborate heterogeneous vegetation greening and browning trends from field and remote-sensing observations, providing independent evidence for regionally divergent ecological responses and carbon dynamics to global change drivers. Over surface midlatitudes and throughout the midtroposphere, increased seasonal carbon exchange in temperate ecosystems is the dominant contributor to CO2 amplification, albeit with considerable contributions from Siberia. Representing the mechanisms that control the high-latitude asymmetry in flux amplification found in this study should be an important goal for mechanistic land surface models moving forward.


[Psychiatric epidemiology].
This paper presents a critical synthesis of models and methods in psychiatric epidemiology, with special reference to the developing world. Basic epidemiological concepts and their application to psychiatric epidemiology are reviewed. Lastly, the relevance of these developments for the Third World is described, underlining their role in General Health and Mental Health planning and policy.


Intracellular pH topography of Penicillium cyclopium protoplasts. Maintenance of delta pH by both passive and active mechanisms.
The intracellular pH distribution in protoplasts of Penicillium cyclopium has been studied using the recently developed fluorescent probe microscopic technique. The technique gives detailed pH maps of the interior of the protoplasts with the exception of vacuoles (no fluorescence signal from vacuoles was observed). In the cytoplasm two separate layers were distinguished: a thinner outer layer with acidic pH (around 5) and the larger core region with near neutral pH. The pH of the core region is decreased by the addition of uncouplers, inhibitors of respiration and during the uptake of L-phenylalanine. These compounds do not change the pH of the surface layer, which is, however, acidified by addition of vanadate, an inhibitor of the proton pump of the plasmalemma. We suggest that the pH of the surface layer is maintained by the combined effects of a Donnan distribution of protons (bound to postulated anion binding proteins) and the proton extrusion via the plasmalemma proton pump. This mechanism explains the protection of the cytoplasmic core of acidophilic eukaryotes from the influence of the usually acidic environment.


Breast disease: the radiologist's expanding role.
The role of the diagnostic radiologist in breast cancer has expanded during the eight-decade history of breast imaging. The radiologist's role now encompasses both breast cancer diagnosis and treatment. This article traces the expansion of the radiologist's role through the history of mammography. The current roles of the radiologist in breast cancer diagnosis are discussed, including screening mammography in the asymptomatic patient, problem-solving breast imaging, breast ultrasound, and galactography. The radiologist's roles in breast cancer treatment that are discussed include preoperative needle localization, percutaneous breast biopsy, and evaluation of the postoperative breast.


Histomorphological Evaluation of Non-Neoplastic Lesions of Uterine Cervix and a Correlation of the Lesion with the Clinical Factors.
This study investigates the prevalence of non-malignant lesions of the cervix among various biopsy samples. This case study consists of 50 cases of cervical biopsy over almost two years. The case history and clinical details of the patients were obtained. 60% of the cases that participated in this study reported white discharge per vaginum as a common clinical symptom. 4 cases (8%) showed koilocytic changes specific to the human papillomavirus during the study. Only 2% of the non-specific cervicitis showed lymphoid aggregates. Endocervical changes projected papillary endocervicitis with 9 cases (18%), squamous metaplasia with 7 cases (14%), and nabothian follicle cyst with 3 cases (6%). It has been concluded that 50 cases were studied histologically, which had adequate representation of both ecto and endocervical tissue. Moreover, 31-40 years of age of patients showed the highest percentage of non-neoplastic lesions of the cervix when compared to other age groups.


Plasma levels of apoprotein B in patients with diabetes mellitus: the effect of glycemic control.
Patients with diabetes mellitus often exhibit abnormalities in plasma lipoprotein concentrations. We have examined the effect of glycemic control (as assessed by hemoglobin A1 levels) on the concentrations of plasma lipoproteins and apoproteins in 109 patients with type I diabetes mellitus. HbA1 levels showed positive correlations with plasma LDL-cholesterol levels (r = 0.31; P less than 0.002) and triglyceride levels (r = 0.41; P less than 0.002), but not with HDL-cholesterol levels. The strongest correlation was between HbA1 and plasma levels of apoprotein B (r = 0.57; P less than 0.001). We have also examined the effect of long-term improvement in glycemic control (achieved with insulin infusion pump therapy) on plasma lipoproteins in six patients with type I diabetes. Patients were followed for 5 to 12 months, with mean (+/- SD) HbA1c levels decreasing from 11.4 +/- 2.5 to 9.1 +/- 1.8. Most, but not all, patients showed reduction in plasma LDL-cholesterol levels and increase in plasma HDL-cholesterol levels, but these did not reach statistical significance. Only the decrease in plasma apo B levels was statistically significant (from 112 +/- 38 mg/dL before pump therapy to 91 +/- 33 mg/dL at the end of the follow-up, P less than 0.05). We conclude that glycemic control plays an important role in regulating the levels of plasma LDL-cholesterol and triglycerides in patients with type I diabetes. Apoprotein B is a particularly sensitive indicator to alterations in glycemic control. It is possible that tight glycemic control may have "antiatherogenic" effects through reduction of apo B levels.


Effect of storage media on chondrocyte viability during cold storage of osteochondral dowels.
Osteochondral allograft transplantation is a successfully proven method to repair articular cartilage defects and prevent the degenerative effects of osteoarthritis. The number of osteochondral transplantations that can be performed each year is limited by availability of donor cartilage tissue and storage time constraints. Osteochondral transplantation success has been linked to high chondrocyte viability of the donor cartilage tissue at the time of implantation. Determining optimal storage conditions for donor cartilage is essential for tissue banks to safely provide quality cartilage tissue. In this study, we compared three tissue/cell media (DMEM/F12, RPMI-1640 and X-VIVO 10) for their ability to maintain chondrocyte viability during hypothermic storage for 28 days. Porcine osteochondral dowels were stored in each media for 28 days and cell viability was assessed every 7 days. Over the 28 day storage period, the chondrocyte viability of dowels stored in DMEM/F12, RPMI-1640, and X-VIVO 10 media all declined in a similar fashion. Our results show that all three media were equivalent in their ability to maintain cell viability of the cartilage tissue and provides rationale for the use of lower cost cell media (DMEM/F12 and RPMI-1640) for hypothermic storage of articular cartilage tissue.


Gene structure and transcriptional regulation specific to the groESL operon from the psychrophilic bacterium Colwellia maris.
The groESL operon of a psychrophilic bacterium, Colwellia maris, was cloned and sequenced. The operon contains two ORFs of 291 bp and 1,650 bp separated by 210 bp. Northern blot analysis suggested that the groESL operon was transcribed as a bicistronic mRNA, and that the amount of mRNA markedly increased after the temperature was raised from 10 degrees C to 20 degrees C. Although the optimum temperatures for GroESL function are different in psychrophilic, mesophilic, and thermophilic bacteria, the deduced amino acid sequences of C. maris GroES and GroEL showed remarkably high similarity with those of GroES and GroEL from mesophilic and thermophilic bacteria. A putative promoter similar to the Escherichia coli sigma(32) consensus sequence was identified. One specific feature of C. maris groESL was that in the putative untranslated region the G+C content was about 24 mol%, which is much lower than that of mesophilic bacteria such as E. coli. The low G+C content may be important for maintaining transcription at low temperatures.


Development of a synbiotic that protects against ovariectomy-induced trabecular bone loss.
The gut microbiome has the capacity to regulate bone mass. The aim of this study was to develop a nutritional synbiotic dietary assemblage at an optimal dose to maintain bone mass in ovariectomized (Ovx) mice. We performed genomic analyses and in vitro experiments in a large collection of bacterial and fungal strains (>4,000) derived from fresh fruit and vegetables to identify candidates with the synergistic capacity to produce bone-protective short-chain fatty acids (SCFA) and vitamin K2. The candidate SBD111-A, composed of Lactiplantibacillus plantarum, Levilactobacillus brevis, Leuconostoc mesenteroides, Pseudomonas fluorescens, and Pichia kudriavzevii together with prebiotic dietary fibers, produced high levels of SCFA in vitro and protected against Ovx-induced trabecular bone loss in a dose-dependent manner in mice. Metagenomic sequencing revealed that SBD111-A changed the taxonomic composition and enriched specific pathways for synthesis of bone-protective SCFA, vitamin K2, and branched-chain amino acids in the gut microbiome.NEW & NOTEWORTHY We performed genomic analyses and in vitro experiments in a collection of bacterial and fungal strains. We identified a combination (SBD111-A) that produced high levels of SCFA in vitro and protected against ovariectomy-induced bone loss in a dose-dependent manner in mice. Metagenomic sequencing revealed that SBD111-A changed the taxonomic composition and function of the gut microbiome and enriched pathways for synthesis of bone-protective SCFA, vitamin K2, and branched-chain amino acids.


Artificial urinary sphincter for recurrent female urinary incontinence: indications and results.
A retrospective review of our experience with the artificial urinary sphincter in 32 women is presented. All patients had a history of recurrent urinary incontinence after failed bladder suspension procedures. Of 32 devices 31 were functioning, with an average followup of 2.5 years, and 91 per cent of the patients were dry without pads. Mechanical complications requiring surgical repair occurred in 21 per cent of the patients. Indications for artificial urinary sphincter implantation in the female patient and technical aspects of the procedure are discussed. The artificial urinary sphincter appears to be an acceptable treatment modality for urethral sphincter deficiency resulting in recurrent urinary stress incontinence in female patients.


Newly qualified practice nurses get training cash.
General practices can soon apply for funding awards of £8,000 to support the training and development of each newly qualified nurse they take on.


Antineoplastic efficacy of melphalan and N-(2-chloroethyl)-N-nitrosocarbamoyl-omega-lysine, in combination with diazoxide or insulin in autochthonous mammary carcinoma of the Sprague-Dawley rat.
The anticancer activity of melphalan and N-(2-chloroethyl)-N-nitrosocarbamoyl-omega-lysine (CNC-omega-Lys), was compared in the autochthonous, methylnitrosourea-induced mammary carcinoma of the Sprague-Dawley rat. In addition, the influence on the therapeutic efficacy of the combination with diazoxide, causing a mild, reversible diabetes, and with insulin was investigated. The comparison of melphalan and CNC-omega-Lys clearly showed the superiority of melphalan. Both compounds displayed a significant tumour inhibition in their medium and the highest dosages in comparison to the untreated control. The combination with diazoxide resulted for almost all groups in an increased tumour inhibition. Only the lowest dose of CNC-omega-Lys + diazoxide did not reduce the tumour volume significantly versus the control group. The combination with insulin, however, resulted in a loss of tumour inhibition compared to the effect of the cytotoxic drug alone, although in these groups, too, a significant decrease of tumour volumes versus controls could be observed. Mortality was within tolerable limits (less than 20%) through the treatment period for all experimental groups. Median lifespans were increased in all therapy groups, but no additional benefit could be observed in the combination treatment groups.


A colony procedure for transformation of Saccharomyces cerevisiae.
A rapid and simple yeast transformation procedure has been developed using colonies on agar plates. Saccharomyces cerevisiae SHY3 cells were picked up from colonies on YPD plates grown freshly or stored at 4 degrees C and incubated with M13RK9-T DNA at 30 degrees C for 1-2 h in a solution of Li+, Ca2+, Mg2+, triacetin and polyethylene glycol. About 3,500 transformants were obtained per microgram of double stranded M13RK9-T DNA. Unlike the existing spheroplast techniques, single stranded M13RK9-T DNA transformed intact cells below one-hundredth frequency of the duplex form.


mTORC2 promotes cell survival through c-Myc-dependent up-regulation of E2F1.
Previous studies have reported that mTORC2 promotes cell survival through phosphorylating AKT and enhancing its activity. We reveal another mechanism by which mTORC2 controls apoptosis. Inactivation of mTORC2 promotes binding of CIP2A to PP2A, leading to reduced PP2A activity toward c-Myc serine 62 and, consequently, enhancement of c-Myc phosphorylation and expression. Increased c-Myc activity induces transcription of pri-miR-9-2/miR-9-3p, in turn inhibiting expression of E2F1, a transcriptional factor critical for cancer cell survival and tumor progression, resulting in enhanced apoptosis. In vivo experiments using B cell-specific mTORC2 (rapamycin-insensitive companion of mTOR) deletion mice and a xenograft tumor model confirmed that inactivation of mTORC2 causes up-regulation of c-Myc and miR-9-3p, down-regulation of E2F1, and consequent reduction in cell survival. Conversely, Antagomir-9-3p reversed mTORC1/2 inhibitor-potentiated E2F1 suppression and resultant apoptosis in xenograft tumors. Our in vitro and in vivo findings collectively demonstrate that mTORC2 promotes cell survival by stimulating E2F1 expression through a c-Myc- and miR-9-3p-dependent mechanism.


Responses to Mycobacterium leprae by lymphocytes from new and old leprosy patients: role of exogenous lymphokines.
Lepromatous leprosy patients generally have reduced response to Mycobacterium leprae antigens in an in vitro lymphocyte transformation test, which could be due to insufficient generation of reactions or to active suppression of any reaction generated. We could detect 3 types of lack of reactivity: one which could be restored by the addition of supernatants from healthy, PHA-stimulated lymphocyte cultures, one which could not thus be restored and one in which the culture supernatant contained factors able to suppress mitogen responses of healthy cells. We compared responses of cells from untreated patients, patients treated for 12-20 months with multiple drug therapy and patients with up to 20 years of dapsone treatment; all types of the disease were represented. Untreated patients of all types had low responses which were not always reconstituted by lymphokine-rich supernatants, but they did not produce the non-specific soluble suppressive factors. In most cases, including BL/LL types, after the initial months of treatment, antigen response improved and was further increased by the addition of supernatants containing lymphokines. Most of the long-term-treated, stable patients had a lymphokine-reconstitutable antigen response, and in most cases also produced non-specific suppressive factor(s). The question as to why leprosy patients do not respond to M. leprae antigen is a complex one; our results suggest that it is related to the activity of the infection in each group of patients.


Should rheumatologists retain ownership of fibromyalgia? A survey of Ontario rheumatologists.
Fibromyalgia is a controversial widespread chronic pain disorder that includes a wide constellation of somatic and emotional symptoms. This study surveyed the opinion of Ontario rheumatologists with respect to their beliefs about the nature and management of fibromyalgia. A key objective was to ascertain if rheumatologists should continue to be the main care providers for these patients. A survey comprising 13 questions was sent electronically to all 150 Ontario rheumatologists. The questionnaire was designed to obtain demographic data as well as opinions regarding different aspects of fibromyalgia. Data were analysed descriptively, and comparisons were made using chi-square tests. A total of 80 respondents completed our survey for a completion rate of 53 %. The majority had completed their training in Canada (85 %) and had been practising for more than 15 years (50 %). Key findings were: (1) 71 % believe that rheumatologists should not retain ownership of fibromyalgia, (2) 55 % believe that fibromyalgia is primarily a psychosomatic illness as opposed to a physical illness, (3) 89 % believe that the family physician should be the main care provider for these patients, and (4) rheumatologists who consider fibromyalgia to be a physical illness were also significantly more likely to believe that rheumatologists should retain ownership of this disease (p = 0.023) and were more likely to continue managing these patients in their practice (p = 0.011). The majority of Ontario rheumatologists do not wish to retain ownership of fibromyalgia. However, most of them continue to manage these patients, even though they believe that the family physician should be the main care provider for patients with fibromyalgia. Rheumatologists may be providing care to these patients primarily because this care is not available to them from their primary care physicians.


Hepatoprotective role of myricitrin isolated from Mimusops elengi Linn. leaves extract on γ-radiation-induced liver damage in rats: Phyto-biochemical investigations.
The hepatoprotective effects of methanol extract of Mimusops elengi Linn. (M. elengi L.) leaves and isolated pure myricitrin (3-, 4-, 5-, 5, 7-five hydroxyflavone-3-O-α-l-rhamnoside) (Myr) were evaluated in male rats exposed to γ-irradiation. The extraction of M. elengi L. leaves was performed using ethyl acetate (EtOAC). Seven groups of rats were used: control group, irradiated (IRR) group (6 Gy of γ-rays in a single dose), vehicle group (oral administration of 0.5% carboxymethyl cellulose for 10 days), EtOAC extract group (100 mg/kg body weight of extract, orally for 10 days), EtOAC + IRR group (administration of extract and exposure to γ-rays on Day 7), Myr group (50 mg/kg body weight Myr, orally for 10 days), and Myr + IRR group (administration of Myr and exposure to γ-rays on Day 7). High-performance liquid chromatography and 1H-nuclear magnetic resonance were used to isolate and characterize the compounds from M. elengi L. leaves. Enzyme-linked immunosorbent assay was used for biochemical analyses. Identified compounds were Myr, myricetin 3-O-galactoside, myricetin 3-O-rahmnopyranoside (1 → 6) glucopyranoside, quercetin, quercitol, gallic acid, α-,β-amyrin, ursolic acid, and lupeol. Serum aspartate transaminase and alanine transaminase activities were significantly increased, while serum protein and albumin levels were significantly decreased after irradiation. Hepatic levels of tumor necrosis factor-α, prostaglandin 2, inducible nitric oxide synthase, interleukin-6 (IL-6), and IL-12 were increased following irradiation. Improvements were observed in most serological parameters after treatment with extract or pure Myr, with histological analyses confirming decreased liver injury in treated rats. Our study demonstrates that pure Myr has a greater hepatoprotective effect than M. elengi leaf extracts against irradiation-induced hepatic inflammation.


Determinants of transitions in water and sanitation services in two urban slums of Nairobi: A multi-state modeling approach.
Access to improved water, sanitation, and hygiene (WASH) services at the household level remains a good strategy to improve the health and well-being of individuals. Informal settlements, such as urban slums, are at risk of the spread of diseases due to the relative lack of access to safe, clean drinking water and basic sanitation, as well as poor hygiene. Global initiatives, such as the Sustainable Development Goals (SDGs) adopted by the United Nations, are aimed at transitioning households and communities from unimproved to sustained improved states of WASH services. To deepen understanding of the time dynamics between states of WASH services in the Nairobi Urban and Demographic Surveillance System (NUHDSS), this study employs the multi-state transition model to assess the influence of potential risk factors on these transitions. Results indicated that study sites, wealth tertile, age of household head, poverty status, the ethnicity of household head, household ownership, and food security were associated with household transitions of WASH services. There was a lower probability for households to transition from unimproved to improved toilet services than the reverse transition, but a higher chance for households to transition from unimproved to improved water and garbage services. The estimated average time that households spent in the unimproved and improved states before transitioning were, respectively, 35 months and 9 months for toilet services, 7 months and 66 months for water services, and 16 months and 19 months for garbage services. Thus, households tend to remain longer in the unimproved state of toilet and garbage services, and when in the improved states, they transition back relatively faster compared to water services. In conclusion, sanitation services in Nairobi informal settings remain largely unsatisfactory as transitions to improved services are not sustained. It is therefore important for governments, policy-makers, and stakeholders to put in place policies and interventions targeting vulnerable households for improved and sustained WASH services.


The Early Influence and Effects of the Coronavirus Disease 2019 (COVID-19) Pandemic on Resident Education and Adaptations.
The novel coronavirus disease 2019 (COVID-19) has had a major impact on the education of trainees in the radiology environment. The precipitous drop in patient volumes and sequestering of faculty and trainees to maintain social distancing affects experiential learning. The shift of nearly all teaching settings to a virtual environment has been challenging but may also allow more interaction during teaching sessions than traditional readout sessions or didactic lectures. Faculty development is key in ensuring competence and confidence in this new environment. Recruitment of trainees using a virtual platform will require communication of opportunities as well as the culture of the department and institution as well as the community. Delay of the board examinations has caused angst as well as disruption of the timing of clinical rotations but may ultimately result in a shift of how the examinations are administered. The exceptional disruption of the COVID-19 pandemic allows us to reconsider how the educational aspects of imaging can emerge as improved in the years to come.


Substance P-like immunoreactive neurons in the tuberoinfundibular area of rat hypothalamus. Light and electron microscopy.
Immunoreactive substance P (ir SP) neurons were examined with special reference to their links with other neurons and blood vessels in the tuberoinfundibular hypothalamic area of normal and colchicine-treated male rats. On intraventricular administration of colchicine, ir SP neuronal cell bodies appeared in both the arcuate nucleus and the ventral portion of the ventromedial nucleus. These ir fibers were seen in the nuclei of untreated animals closely surrounding ir methionine-enkephalin and ACTH cell bodies, suggesting the presence of synaptic junctions. Electron microscopic examination of the arcuate nucleus stained with anti-SP serum showed synapses of ir SP fiber terminals on unlabeled neuronal cell bodies and fibers, some of which might be methionine-enkephalin and ACTH neurons. The ir fiber terminals contained numerous small clear and/or cored vesicles and a few large cored vesicles. Fiber terminals with the same ultrastructural characteristics were seen protruding into the pericapillary space in the external and subependymal layers of the median eminence. The possible role of the SP neurons in the tuberoinfundibular area is discussed.


Integration of data from remote monitoring systems and programmers into the hospital electronic health record system based on international standards.
Remote follow-up of implanted ICDs may offer a solution to the problem of overcrowded outpatient clinics. All major device companies have developed a remote follow-up solution. Data obtained from the remote follow-up systems are stored in a central database system, operated and owned by the device company and accessible for the physician or technician. However, the problem now arises that part of the patient's clinical information is stored in the local electronic health record (EHR) system in the hospital, while another part is only available in the remote monitoring database. This may potentially result in patient safety issues. Ideally all information should become available in the EHR system. IHE (Integrating the Healthcare Enterprise) is an initiative to improve the way computer systems in healthcare share information. To address the requirement of integrating remote monitoring data in the local EHR, the IHE Implantable Device Cardiac Observation (IDCO) profile has been developed. In our hospital, we have implemented the IHE IDCO profile to import data from the remote databases from two device vendors into the departmental Cardiology Information System. Data are exchanged via an HL7/XML communication protocol, as defined in the IHE IDCO profile.


Low dose lisuride in advanced Parkinson disease.
Lisuride was investigated for therapeutic effects in 19 patients with advanced Parkinson disease, no longer satisfactorily responding to routine L-Dopa therapy. The patients were treated with oral Lisuride (0.6-2.5 mg/die) and L-Dopa. The follow-up was at least 6 months. We noted a significant improvement on the Webster Rating Scale at 1st, 3rd and 6th months. Disability and on-off phenomen were reduced. Side effects were few. Lisuride is a valuable tool in this type of patient.


Simple and Easy Synthesis of γ-Amido-dNTPs in Water and Their Polymerase Reaction Properties.
γ-Amido-modified 2'-deoxynucleoside triphosphates (dNTPs) and nucleoside triphosphates (NTPs) are becoming increasingly important as biological tools. We herein describe the simple and easy synthesis of γ-amido-dNTPs and -NTPs from commercially available corresponding dNTPs and NTPs in a one-pot reaction using water-soluble carbodiimide and ammonia solution. We examined the effects of synthesized γ-amido-dNTPs on the DNA polymerase reaction. The results obtained showed the incorporation of these derivatives into the DNA primer while maintaining nucleobase selectivity; however, their incorporation efficiency by DNA polymerase was lower than that of dNTP. This is the first study to demonstrate the successful synthesis of four sets of γ-amido-dNTPs and clarify their properties.


Comparison of soluble microbial product (SMP) production in full-scale anaerobic/aerobic industrial wastewater treatment and a laboratory based synthetic feed anaerobic membrane system.
This study focused on the characterisation of soluble microbial products (SMPs) produced from a full-scale multi-stage (anaerobic/aerobic) industrial wastewater treatment plant, and contrasted them to the SMPs detected in the effluent of a lab-scale AnMBR treating synthetic wastewater to determine if there were any common solutes detected irrespective of the feed organics. Recently developed analytical methods using gas chromatography coupled mass spectrometry (GC-MS) and liquid chromatography coupled quadrupole-time-of-flight (LC-Q-ToF) for SMP characterisation in a wide molecular weight (MW) range of 30-2000 Da (Da) were applied. Samples collected from the Industrial Wastewater plant were the upflow anaerobic sludge blanket (UASB) influent and effluent, and aerobic membrane bioreactor (MBR) effluent before discharge. The GC-MS detected a spike in cyclooctasulphur in the UASB effluent, an indicator of shock-loading, which disappeared after the MBR process. Alkanes, acids and nitrogenous compounds were found to be the end-products from the GC-MS results, while LC-Q-ToF analysis revealed that eicosanoids, a group of cell-signalling molecules, were produced in the aerobic MBR, and made up 71% of its effluent. A comparison of the submerged anaerobic membrane bioreactor (SAMBR) and aerobic MBR effluents using GC-MS showed that there was only a small degree of similarity between the SMPs, comprising mainly long chain alkanes and phthalate. On the other hand, LC-Q-ToF showed a large contrast in compound composition, mostly having cell-signalling functions, which deepened our understanding of the different metabolic processes occurring in aerobic and anaerobic systems. These data could be useful for future work in various areas such as controlling quorum-sensing and biofilm formation, process optimisation and control, and microbial ecology.


Construct validity of the EORTC quality of life questionnaire information module.
Providing sufficient information about diagnosis and treatment is an important feature of high-quality patient care in oncology. To measure patient satisfaction with information received, the European Organisation for Research and Treatment of Cancer Quality of Life Group has recently developed a new tool, the information module (INFO25). The aim of this study was to evaluate the scale structure of the INFO25. A total of n = 423 patients completed the INFO25 after finishing cancer therapy. The internal consistency of multi-item subscales was calculated using Cronbach's Alpha. The scale structure was evaluated using multi-trait methods and confirmatory factor analysis. Cronbach's Alpha of the multi-item scales ranged from 0.79 to 0.88. Only two items correlated somewhat higher with another scale than with their own, indicating a good scale structure. Construct validity with latent variable models, including a general information factor and four multi-item scales, resulted in the following fit indices CFI = 0.96, RMSEA = 0.08, TLI = 0.99 and WRMR = 1.03. The suggested construct of the INFO25 with a total score (general factor) in addition to the subscales is valid.


Degradable injectable bone cement in maxillofacial surgery: indications and clinical experience in 27 patients.
A carbonated apatite cement (NORIAN SRS) was used as a bone mineral substitute for the calvaria or viscerocranium in 27 patients. It has the consistency of a paste and hardens at physiologic pH and body temperature due to dahllite crystallization, which has the stoichiometric formula Ca(8.8)(HPO(4))(0.7)(PO(4))(4.5)(CO(3))(0.7)(OH)(1.3). The cement was used for posttraumatic bone defects in the orbital, periorbital or malar regions (nine patients), posttraumatic deformities of the frontal bone (six patients), tumour-dependent bony defects of the calvaria (two patients) and posttraumatic or cystic defects of the mandible (five patients). In another five patients, the material was used to augment the atrophic anterior mandible in combination with the insertion of dental implants. Follow-up varied between 6 and 40 months (mean: 29 months). There was no inflammatory reaction surrounding the implanted material. There was no sign of infection in any of the patients and only one case of partial wound dehiscence with superficially exposed material. The defect fillings and augmentations were successful in all patients. None of the 19 dental implants which were inserted in combination with the material showed any sign of infection or loosening. Also, there was no loosening of the implants after loading (mean follow-up: 15 months). From the check-up radiographs, the material could be seen as a dense, radio-opaque structure. There were no material fractures or dislocations. Radiologically, the material seemed to be completely replaced by bony tissue after 30 months. Our 5-year clinical experience suggests that the material is a suitable bone mineral substitute for cranio-maxillofacial surgery especially for moderate-sized defects of the calvaria and forehead bone. It has advantages over preformed, solid bone substitute materials, and, due to its initial plasticity and eventual great compressive strength, it can also stabilize dental endosseous implants in the atrophic mandible.


Relationship between Helicobacter pylori infection and vomiting induced by gastrointestinal cancer chemotherapy.
Nausea and vomiting are the most common adverse reactions to chemotherapy. To discuss the relationship between Helicobacter pylori and chemotherapy-induced nausea and vomiting (CINV). A total of 112 patients with malignant tumours of the gastrointestinal tract was selected. Based on the 14C-urea breath test results, the patients were divided into H. pylori-positive (n = 59) and H. pylori-negative (n = 53) groups. Both groups received prophylactic antiemetic treatment during chemotherapy. The incidence of nausea and vomiting and their effects on the patients' life functions was recorded using the Multinational Association of Supportive Care in Cancer (MASCC) Antiemetic Tool (MAT) and the Functional Living Index Emesis (FLIE) from 0-120 h after chemotherapy. Records of the H. pylori-positive and H. pylori-negative groups were compared. The rates of nausea and vomiting remission were higher in the H. pylori -negative group than in the H. pylori -positive group. The proportions of no effect in daily life (NIDL) patients in the nausea and vomiting section were 73.4 and 75.5% in the H. pylori -negative group respectively. There was a higher proportion of NIDL patients in the H. pylori -negative group than in the H. pylori -positive group (P < 0.001, P = 0.046). A multivariate unconditional logistic regression analysis was performed, and the results showed that H. pylori infection was a factor affecting the nausea scores on the FLIE (odds ratio = 0.757, 95% confidence interval 0.597-0.960, P = 0.021). H. pylori infection in patients with cancer may be a factor that increases CINV.


Serum periostin is a potential biomarker for non-alcoholic fatty liver disease: a case-control study.
Recent animal studies support close associations of Periostin with hepatosteatosis and steatohepatitis. This study is to evaluate the role of serum periostin in non-alcoholic fatty liver disease (NAFLD). A hospital-based age-/sex-matched case-control study was conducted. Binary logistic regression and receiver operating characteristic (ROC) curve were performed. Serum adipokines were measured by Adipokine Magnetic Bead Panel kits. The serum concentration of Periostin in NAFLD (1914.16 [1323.59-2654.88] ng/ml, P < 0.001) was higher than it in control (1244.94 [837.87-2028.55] ng/ml). The frequency of NAFLD grew (29.8, 52.6, and 67.2%, P < 0.001), as Periostin concentration increased among its tertiles. Compared with the 1st tertile, the 2nd and the 3rd tertiles of Periostin indicated significant associations with higher odds of NAFLD [adjusted odds ratio = 2.602 (95% confidence interval (CI) 1.030-6.575), P = 0.043 and 2.819 (95% CI 1.629-4.878), P < 0.001]. ROC curve of Periostin was developed to predict the presence of NAFLD (area under ROC = 0.693 [95% CI 0.614-0.771], P < 0.001). Lastly, Periostin correlated with several adipokines, including Resistin (r = 0.269, P = 0.018), Adiponectin (r = -0.352, P = 0.002), Interleukin (IL)-6 (r = 0.359, P = 0.001), IL-8 (r = 0.364, P = 0.001), Lipocalin-2 (r = 0.623, P < 0.001), Hepatocyte growth factor (r = 0.522, P < 0.001), and Nerve growth factor (r = 0.239, P = 0.036). It suggests Periostin as a potential biomarker in the management of NAFLD.


Polyaniline coating enables electronic structure engineering in Fe3O4to promote alkaline oxygen evolution reaction.
The electronic structure of active sites is of importance for catalysts to achieve an optimized interaction with the intermediates. In this study, a unique organic-inorganic hybrid oxygen evolution reaction electrocatalyst composed of electrochemically inactive conducting polyaniline (PANI) and non-precious Fe-based oxide Fe3O4is presented. PANI molecules werein situloaded on Fe3O4nanoparticles through an efficient and simple process under mild conditions. The electronic structure of Fe3O4was modulated by creating a strong interaction with PANI molecules, leading to enhanced activity and stability of the catalyst to achieve 10 mA cm-2geometrical current density at overpotential of 265 mV in 1 M aqueous KOH solution. This work demonstrates that a highly efficient electrocatalyst can be achieved by molecular modification and provides a novel strategy for the optimization of the inactive non-precious catalysts.


The management of elevated intracranial pressure and sinus vein thrombosis associated with mastoiditis: the experience of eighteen patients.
Cerebral sinus vein thrombosis (CSVT) associated with acute mastoiditis is a rare complication of acute otitis media. Elevated intracranial pressure (ICP) frequently occurs secondary to CSVT. The study aims to review the 5 years of experience of four medical centres to treat sigmoid sinus thrombosis and elevated intracranial pressure in children. Patients with CSVT that developed secondary mastoiditis from 2016 through 2021 were evaluated in four centres from Turkey. Patients diagnosed with a preceding or synchronous mastoiditis and intracranial sinus thrombosis were included in the study. Magnetic resonance imaging (MRI), magnetic resonance venography (MRV), ICP measurements, ophthalmological examinations, thrombophilia studies and treatments for increased ICP have also been recorded. The study group comprises 18 children. Twelve patients were diagnosed with right-sided, six patients with left-sided sinus vein thrombosis. All of the patients had ipsilateral mastoiditis. The most common presenting symptoms were fever, ear pain, headache, visual disorders and vomiting. The most encountered neurologic findings were papilledema, strabismus and sixth cranial nerve palsy. ICP was over 20 cm H2O in eleven patients. Anticoagulant treatment, antibiotics, pressure-lowering lumbar puncture and lumboperitoneal shunt were among the treatment modalities. Elevated ICP can damage the brain and optic nerve irreversibly, without treatment. For treating elevation of ICP associated with cerebral sinus thrombosis, pressure-lowering lumbar puncture (LP), acetazolamide therapy, optic nerve sheath fenestration (ONSF) and cerebrospinal fluid (CSF)-shunting procedures are suggested in case of deteriorated vision.


Tropomyosin isoforms define distinct microfilament populations with different drug susceptibility.
Two tropomyosin isoforms, human Tm5(NM1) and Tm3, were over-expressed in B35 rat neuro-epithelial cells to examine preferential associations between specific actin and tropomyosin isoforms and to determine the role tropomyosin isoforms play in regulating the drug susceptibility of actin filament populations. Immunofluorescence staining and Western blot analysis were used to study the organisation of specific filament populations and their response to treatment with two widely used actin-destabilising drugs, latrunculin A and cytochalasin D. In Tm5(NM1) cells, we observed large stress fibres which showed predominant co-localisation of beta-actin and low-molecular-weight gamma-tropomyosin isoforms. Tm3 cells had an abundance of cellular protrusions which contained both the beta- and gamma-actin isoforms, predominately populated by high-molecular-weight alpha- and beta-tropomyosin isoforms. The stress fibres observed in Tm5(NM1) cells were more resistant to both latrunculin A and cytochalasin D than filaments containing the high-molecular-weight tropomyosins observed in Tm3 cells. Knockdown of the over-expressed Tm5(NM1) isoform with a human-specific Tm5(NM1) siRNA reversed the phenotype and caused a reversal in the observed drug resistance. We conclude that there are preferential associations between specific actin and tropomyosin isoforms, which are cell type specific, but it is the tropomyosin composition of a filament population which determines the susceptibility to actin-targeting drugs.


Reasons for Non-Disclosure of Sexual Orientation Among Behaviorally Bisexual Men: Non-Disclosure as Stigma Management.
Although bisexual men are known to be less likely to disclose their sexual orientation to others than gay men, the reasons why bisexual men choose or feel unable to disclose have received minimal research attention. To examine the reasons behaviorally bisexual men offer for not disclosing to their friends, family, and female partners, in-depth interviews were conducted with an ethnically diverse sample of 203 men who had not disclosed their same-sex behavior to their female sexual partners in New York City. Men were recruited from multiple venues and online sources using a targeted sampling approach. Transcripts were thematically analyzed using Atlas.ti software. Contrary to the theory that non-disclosure is due to uncertainty about one's sexual identity, the reasons offered for non-disclosure revealed that it was largely a method to avoid stigmatizing reactions from others. Men reported a number of specific reasons for non-disclosure, including (1) anticipation of negative emotional reactions; (2) anticipation of negative changes in relationships; (3) belief that others held stigmatizing attitudes toward homosexuality; (4) prior experience with negative reactions to disclosure; (5) wanting to maintain others' perceptions of him; (6) fear that those told would disclose to additional people; and (7) fear of rejection due to culture or religion. These findings provide insights into the reasons why many behaviorally bisexual men choose not to disclose, potential reasons why bisexual and gay men differ in the extent to which they disclose, and potential reasons why some bisexual men report greater emotional distress than gay men. Further, they suggest that greater attention needs to be placed on addressing the stigmatizing contexts that confront bisexual men and providing them with strategies to manage stigma.


Antibacterial evaluation of novel organoarsenic compounds by the microcalorimetric method.
Antibacterial activities of novel organoarsenic compounds As(III)-containing Schiff bases on Escherichia coli (CCTCCAB91112) were investigated by microcalorimetry in this study. The experimental result showed that the arsenic(III)-containing Schiff bases at micromolar concentration exhibit strong inhibition on the E. coli. Specifically, the growth rate constant k decreased, and the generation time t G and the inhibitory ratio I (percentage) increased with the increased dose of the arsenicals as inhibitors. All of the arsenicals display the feature of considerable lag phase inhibition on the cell growth. The compound 4-(4-bromobenzaliminyl)phenylarsenoxide makes the lag phase of E. coli cell growth cycles to reach 650 min at 5 μmol/L. The compounds with donating electron groups at aromatic ring B have lower IC50 to present higher antibacterial activity. The compound 4-(4-hydroxyl-3-methoxylbenzaliminyl)phenylarsenoxide has the lowest IC50 (1.82 μmol/L) to show the strongest antibacterial activity among them.


Monitoring and modulation of Epstein-Barr virus loads in pediatric transplant patients.
A major risk faced by bone-marrow and solid organ transplant patients is the development of post-transplant lymphoproliferative disease or post-transplant lymphoma (PTLD). In pediatric transplantation, PTLD onset is often associated with a rapid rise in Epstein-Barr virus (EBV) load in peripheral blood mononuclear cells (PBMC). We have analyzed EBV viral loads in PBMC over time using real-time quantitative PCR in 56 patients, 19 of which have been followed for more than 1 year. In nine patients; eight bone marrow (BMT) and one kidney transplant, PTLD was associated with a rapid rise in viral load, exceeding 1 x 10(5) EBV genomes/microg of PBMC-derived DNA. Four of these patients exceeded 1 x 10(6) EBV genomes/microg PBMC DNA. All patients with viral loads exceeding 1 x 10(5) EBV genomes/microg PBMC DNA were clearly at high risk for transplant-associated mortality, with only six of nine surviving. Importantly, only one of these deaths was directly attributable to EBV. A second elevated state of EBV load, defined as exceeding 2 x 10(4) EBV genomes/microg PBMC, was seen in a total of 12 BMT, kidney, heart, and liver transplant patients. These patients did not appear to be at immediate lethal risk for PTLD and one EBV-attributable death was found in this group as well. Thirty-four transplant patients whose EBV viral load oscillated from undetectable to 10 000 EBV genomes/microg PBMC DNA are reported as well. The threshold for normal EBV viral load based on our combined experience with viral load analysis is defined as 1 x 10(4) EBV genomes/microg PBMC DNA. The ability to rapidly analyze EBV load allows rapid changes in viral load, such as those that occur with PTLD onset, and the impact of anti-CD20 antibody therapy to be rapidly detected.


Ethnicity as a risk factor for consultations in primary health care and out-patient care.
To determine the influence of ethnicity, defined as foreign-born people, on consultation rates, admissions and prescriptions in out-patient care and primary health care. Prospective study of attenders at four different caregivers during seven consecutive weeks in 1988. Age-and sex-standardized relative risks and odds ratios with 95% confidence interval were calculated. A suburban area in Lund, a city located in the south of Sweden, with 28% foreign-born people. This population (N = 5085) made 1,348 consultations. Ethnic group and consultation rates of the local primary health care centre, the emergency department, hospital out-patient department, and private care, admissions to specialist care, prescriptions, and certified sick leave. Swedes made fewer age-and sex-standardized visits to the emergency department (RR = 0.69(0.48-0.99)) while the foreign-born people showed an opposite non-significant trend (RR = 1.37(0.95-1.99)). Latin Americans (RR = 1.60(1.02-2.51)) visited the local Primary Health Care centre in the residential area more than expected, while people born in Asia and Africa consulted the Primary Health Care centre less than expected (RR = 0.44(0.28-0.69)). There were no differences between Swedes and foreign-born people in being put on the sick-list, but foreign-born people were given significantly fewer prescriptions (RR = 0.07(0.03-0.19)) than Swedes. Foreign-born people, Latin Americans, and non-Swedish Scandinavians were referred significantly more often to hospital than other groups. There were important differences in consultations between Swedes and foreign-born people. It seems important to study these differences further to find out if they were due to morbidity or cultural differences in order to be able to meet the demands and needs of different ethnic groups.


Prostate Region-Wise Imaging Biomarker Profiles for Risk Stratification and Biochemical Recurrence Prediction.
Identifying prostate cancer (PCa) patients with a worse prognosis and a higher risk of biochemical recurrence (BCR) is essential to guide treatment choices. Here, we aimed to identify possible imaging biomarker (perfusion/diffusion + radiomic features) profiles extracted from MRIs that were able to discriminate patients according to their risk or the occurrence of BCR 10 years after diagnosis, as well as to evaluate their predictive value with or without clinical data. Patients with localized PCa receiving neoadjuvant androgen deprivation therapy and radiotherapy were retrospectively evaluated. Imaging features were extracted from MRIs for each prostate region or for the whole gland. Univariate and multivariate analyses were conducted. 128 patients (mean [range] age, 71 [50-83] years) were included. Prostate region-wise imaging biomarker profiles mainly composed of radiomic features allowed discriminating risk groups and patients experiencing BCR. Heterogeneity-related radiomic features were increased in patients with worse prognosis and with BCR. Overall, imaging biomarkers profiles retained good predictive ability (AUC values superior to 0.725 in most cases), which generally improved when clinical data were included (particularly evident for the prediction of the BCR, with AUC values ranging from 0.841 to 0.877 for combined models and sensitivity values above 0.960) and when models were built per prostate region vs. the whole gland. Prostate region-aware imaging profiles enable identification of patients with worse prognosis and with a higher risk of BCR, retaining higher predictive values when combined with clinical variables.


In vivo mapping of the fast and slow diffusion tensors in human brain.
Recent studies have shown that the diffusional signal decay in human brain is non-monoexponential and may be described in terms of compartmentalized water fractions. Diffusion tensor imaging (DTI), which provides information about tissue structure and orientation, typically uses b values up to 1000 s x mm(-2) so that the signal is dominated by the fast diffusing fraction. In this study b factors up to 3500 s x mm(-2) are utilized, allowing the diffusion tensor properties of the more slowly diffusing fraction to be mapped for the first time. The mean diffusivity (MD) of the slow diffusion tensor was found to exhibit strong white/gray matter (WM/GM) contrast. Maps depicting the principal direction of the slow tensor indicated alignment with the fast tensor and the known orientation of the WM pathways.


Preconditioning preserves energy metabolism in prolonged low-flow ischemia.
A reduction in coronary flow leads to a parallel decrease in contractile function. Thus, a flow/function balance is established in the myocardium under certain circumstances avoiding the development of a necrosis (referred to as "hibernating" myocardium). The impact of a preconditioning period on this critical balance was examined. In 116 isovolumetrically beating rat hearts, 3 h of hypoperfusion with 15% of control coronary flow were performed followed by 1 h reperfusion; 40 hearts served as controls. As a preconditioning period, in half of the rat hearts a 5 min no-flow ischemia followed by 10 min reperfusion was performed, preceding the prolonged hypoperfusion. Systolic function was identically reduced in both groups after 3 h hypoperfusion (LVP: 39 +/- 2 mmHg, 40 +/- 2 mmHg vs. controls 90 +/- 3 mmHg; p < 0.01). Without preconditioning hypoperfusion resulted in a marked initial decrease in function. This period was followed by an adaptation to a higher steady state level of function compared with non-preconditioned hypoperfused hearts (p < 0.05). After preconditioning hypoperfusion directly resulted in this level of contraction. Contractile reserve was reduced (p < 0.01) identically in both hypoperfusion groups. Adenine nucleotides were decreased (p < 0.01) after 3 h hypoperfusion to 2.1 +/- 0.2 mumol/gww vs. controls (4.7 +/- 0.2 mumol/gww). After initial preconditioning adenine nucleotides were better preserved (3.2 +/- 0.2 mumol/gww) going ahead with a creatine phosphate overshoot of 126% (p < 0.01). After reperfusion, systolic function and contractile reserve were identical in both groups. A period of preceding no-flow ischemia followed by reperfusion modifies functional adaptation to hypoperfusion and preserves high energy phosphates. Therefore, the metabolic balance during hypoperfusion is improved by preconditioning, although no impact on contractile reserve or the functional status of reperfused myocardium after low-flow ischemia can be seen.


What we do and do not know about managing respiratory disease in pregnancy.
Respiratory disorders are common in pregnant women, but their exclusion from clinical trials makes decisions around pharmacotherapy challenging. Developing programmes designed to improve evidence in pregnancy should be a priority for respiratory research. https://bit.ly/3n6aX42.


Oil loving hydrophobic gels made from glycerol propoxylate: Efficient and reusable sorbents for oil spill clean-up.
Glycerol propoxylate based oil loving sorbents were prepared through bulk polymerization, without using of an activator, initiator, or catalyst. Fourier transform infrared spectroscopy (FTIR), 13C and 29Si CPMAS nuclear magnetic resonance (NMR), as well as elemental analysis and thermal gravimetric analysis (TGA) were operated in order to identify the structural and thermal features of sorbents. The synthesized gels were employed as absorbents for various organic solvents and oils. The swelling capacity, absorption-desorption kinetics, reusability, and selective removal from an oil/water mixture were also examined. To explore the effects of a crosslinker's concentration on oil absorption capacity, star type propoxylate monomers were reacted at different concentration of tris[3-(trimethoxysilyl)propyl]isocyanurate (ICS) crosslinker; swelling capacity was calculated using dichloromethane as an organic solvent. Oil removal ability from the water surface is another important section contained within this article.


Join us on streets to demand our say in decisions on NHS reforms.
The government knows we have an NHS staffing shortage - that is something we can all agree on. It is also their selling point for the removal of NHS bursaries. If we introduce a loan system, they say, it will give us an additional 10,000 training places for nurses, midwives and allied health professionals.


A conserved regulatory role for antisense RNA in meiotic gene expression in yeast.
A significant fraction of the eukaryotic genome is transcribed into RNAs that do not encode proteins, termed non-coding RNA (ncRNA). One class of ncRNA that is of particular interest is antisense RNAs, which are complementary to protein coding transcripts (mRNAs). In this article, we summarize recent studies using different yeasts that reveal a conserved pattern in which meiotically expressed genes have antisense transcripts in vegetative cells. These antisense transcripts repress the basal transcription of the mRNA during vegetative growth and are diminished as cells enter meiosis. While the mechanism(s) by which these antisense RNAs interfere with production of sense transcripts is not yet understood, the effects appear to be independent of the canonical RNAi machinery.


Prenatal exposure to α-pinine improves reflexive motor behaviours in mice offspring.
α-pinene is a well-known compound representative of the monoterpenes group with a wide range of pharmacological activities. This article aims to determine effects of the prenatal exposure to α-pinene on reflexive motor behaviours in mice offspring. Forty pregnant female NMRI mice (8-10 weeks old) were allocated into four groups. Group 1 served as control and groups 2-4 were intraperitoneally (i.p.) injected α-pinene (0.1, 0.5 and 1 mg/kg) on 5, 8, 11, 14 and 17 days of gestation (GD). The control group was injected with saline at the same days. Following delivery, 20 pups from each litter were selected and reflexive motor behaviours determined using ambulation, hindlimb foot angle, surface righting, hindlimb strength, grip strength, front-limb suspension and negative geotaxis tests. Based on the findings of the present study, maternal exposure to α-pinene increased ambulation score, hind-limb suspension score, grip strength, front-limb suspension compared with the control group (P < 0.05). Also, prenatal exposure to α-pinene decreased surface righting, hind-limb foot angle and negative geotaxis in mice offspring compared with the control group (P < 0.05). α-pinene (0.1, 0.5 and 1 mg/kg) decreased blood MDA and increased SOD and GPx levels in mice offspring (P < 0.05). These results suggested α-pinene exposure during pregnancy has positive effect on reflexive motor behaviours in mice offspring possibly due to its antioxidant properties.


Reduction of nitrite to nitrous oxide by a cytoplasmic membrane fraction from the marine denitrifier Pseudomonas perfectomarinus.
A cytoplasmic membrane fraction from the marine denitrifier Pseudomonas perfectomarinus reduced nitrite to nitrous oxide in a stoichiometric reaction without nitric oxide as free intermediate. The membrane system had a specific requirement for FMN with NAD(P)H as electron donors. Other electron donors were ascorbate-reduced cytochrome c-551 or phenazine methosulfate. The membrane fraction contained tightly bound cytochrome cd which represented only a small portion of the total cytochrome cd of the cell. As further terminal oxidase cytochrome o was identified. The membrane fraction produced also nitrous oxide from nitric oxide, however, at a substantially lower rate than from nitrite when using ascorbate-reduced phenazine methosulfate as electron donor.