Breast cancer-related lymphedema and its treatment: how big is the financial impact?
Decongestive lymphatic treatment (DLT) is still the gold standard for treatment of breast cancer-related lymphedema (BCRL). With up to 17% of the patients treated for breast cancer developing BCRL, this morbidity imposes a tremendous financial burden for patients and society. Knowledge about this economic burden related to BCRL and its conservative treatment in a European setting is lacking. The aim of this prospective, longitudinal cohort study was to estimate the direct healthcare costs related to BCRL and its treatment in a European setting. Patients with BCRL were treated with DLT consisting of an intensive treatment phase of 3 weeks, followed by a maintenance treatment phase of 6 months. Additionally, the follow-up period comprised 6 months. During these 3 weeks and 12 months, all direct costs associated with the treatment of BCRL and its sequelae were documented through billing prices and a self-developed questionnaire which was administered after the intensive treatment phase, and subsequently 3-monthly during the entire period. A total of 194 patients were enrolled in this study. Of these, 17% (n = 32) showed lymphedema stage I, 56% (n = 109) had lymphedema stage IIa, and 27% (n = 53) had lymphedema stage IIb. Total direct healthcare costs per patient were €2248.93 on average during the entire period of 3 weeks of intensive treatments and 12 months of maintenance decongestive therapy. Within these mean direct costs, €1803.35 (80%) was accounted for statutory health insurances, and €445.58 (20%) was out-of-pocket expenses for patients. This study is one of the first standardized high-quality health economic analyses of BRCL treatment in Europe. The present study indicates that the price tag of BCRL treatment in Belgium is high not only for the health insurance but also for the patients Clinical trial registration number The study makes part of a double-blind, multi-center, randomized controlled trial (EFforT-BCRL trial), which is registered in clinicaltrials.gov (NCT02609724). CME reference S58689, EudraCT Number 2015-004822-33.


Pneumocystis jirovecii pneumonia in liver transplant recipients in an era of routine prophylaxis.
Pneumocystis jirovecii pneumonia (PCP) is an opportunistic infection in organ transplant recipients that may be prevented by antibiotic prophylaxis. We aimed to investigate the incidence rate (IR) of PCP and the related hospitalization and mortality rates in liver transplant recipients in an era of routine prophylaxis. We included all adult liver transplant recipients transplanted at Rigshospitalet between January 1, 2011 and October 1, 2019. Microbiology data were obtained from the Danish Microbiology Database (MiBa), a national database containing all data from all Departments of Clinical Microbiology in Denmark receiving samples from both hospitals and general practices. According to local guidelines, PCP prophylaxis was initiated 1 week posttransplantation and discontinued after 6 months or sooner in patients experiencing side effects. We included 343 liver transplant recipients with 1153 person-years of follow-up (PYFU), of which 269 (78%) received PCP prophylaxis during the first 6 months posttransplantation. Seven (2%) recipients were diagnosed with PCP during follow-up. In the first 6 months posttransplantation and in 269 transplant recipients who received prophylaxis there were zero PCP events while the IR was 32 (95% confidence interval [CI] 2.9-148) per 1000 PYFU in 74 recipient who did not receive prophylaxis. During 7th to 12th month posttransplantation the IR was 20 (95% CI: 5.5-53) per 1000 PYFU. All seven (100%) recipients diagnosed with PCP were hospitalized, however none died. PCP was not detected in liver transplant recipients while on prophylaxis. Though, it worth mentioning that two out of the seven PCP patients received high-dose prednisolone before the PCP event. All liver transplant recipients with PCP were hospitalized, but none died. Randomized clinical trials to determine the optimal duration of prophylaxis are warranted.


Atypical furunculosis vaccines for Atlantic cod (Gadus morhua); vaccine efficacy and antibody responses.
Atypical furunculosis caused by atypical Aeromonas salmonicida, is an emerging problem in farming of Atlantic cod (Gadus morhua) in Norway, and vaccines are needed. Atypical A. salmonicida comprises a heterogeneous group of bacteria differing in surface antigens such as the A-layer protein and lipopolysaccharides (LPS). Except for one of the experimental oil-adjuvanted whole cell vaccines based on various isolates they all resulted in moderate protection. No clear correlation between vaccine efficacies and the A-protein group or LPS type of the vaccine isolates was revealed, while a correlation between efficacy and the presence of cross-reacting LPS-specific antibodies is indicated.


Stentless endoscopic transnasal repair of bilateral choanal atresia starting with resection of vomer.
To assess the results of a transnasal endoscopic repair of congenital choanal atresia beginning by resection of the posterior portion of the vomer and ending by no stent. Seven patients with bilateral congenital choanal atresia aged ranging from 3 to 15 days were operated upon between June 2009 and September 2011. This transnasal endoscopic approach allowed resection of the posterior portion of the vomer first then the atretic plates and part of the medial pterygoid plate if needed leaving no stent. Postoperative control included office fiberoptic nasal endoscopy. Adequate functional nasal breathing was maintained in all patients during follow up of 11 to 23 months. Apart from one case that complicated by palatal defect, no any other complications were detected. The described technique was proved to be very effective, allowing fast recovery, and one step surgery with early discharge from hospital using neither stents nor nasal packing. Good patency with no reduction in functional quality was also observed.


HLA antigens among Chinese in Taiwan: association of Cw1 and Cw3 on the same haplotype.
HLA-A, B and C phenotypes and gene frequencies of Chinese living in Taiwan are presented. Cw1 and Cw3 were frequently found to segregate together on the same haplotype.


Development of an assay of seven biochemical items, HbA1c, and hematocrit using a small amount of blood collected from the fingertip.
Lifestyle-related diseases in Japan account for 30% of the entire medical expenditure of the country and cause 60% of all deaths. For the prevention of lifestyle-related diseases, medical examination by laboratory tests on metabolic syndrome is important. To undertake examination by collection of blood from a fingertip, we developed the "Well Kit". About 65 μl of blood collected from a fingertip was diluted with buffer solution, which contained two internal standard materials. The kit also separated corpuscles and diluted plasma with a special filter. It measured the obtained diluted plasma using the JCA-BM2250. This measurement system was evaluated for the quantitative analysis of 8 items. The uncertainties of tested items of this measurement system were 1.7% to 6.4%. The coefficients of correlation of all tested items between this measurement value and the venous plasma sample value were 0.876-0.991, and hematocrit was 0.958. This system for testing blood collected from a fingertip is simple to use and can be applied in testing for metabolic syndrome. In addition, this testing system is useful in the medical examination of the personal healthcare and inhabitants.


New species of Plectropsyche Ross 1947 (Trichoptera: Hydropsychidae: Hydropsychinae).
Two new species from Mexico and Central America of the genus Plectropsyche Ross are described and the male and female genitalia are figured. The only extant previous described species, Plectropsyche hoogstraali Ross and its synonym Plectropsyche pitella (Denning) from Mexico are studied. A map with the distribution of all known Plectropsyche species is presented and an illustrated key for the males of the extant species are included.


Mycobacterium thermoresistibile as a source of thermostable orthologs of Mycobacterium tuberculosis proteins.
The genus Mycobacterium comprises major human pathogens such as the causative agent of tuberculosis, Mycobacterium tuberculosis (Mtb), and many environmental species. Tuberculosis claims ~1.5 million lives every year, and drug resistant strains of Mtb are rapidly emerging. To aid the development of new tuberculosis drugs, major efforts are currently under way to determine crystal structures of Mtb drug targets and proteins involved in pathogenicity. However, a major obstacle to obtaining crystal structures is the generation of well-diffracting crystals. Proteins from thermophiles can have better crystallization and diffraction properties than proteins from mesophiles, but their sequences and structures are often divergent. Here, we establish a thermophilic mycobacterial model organism, Mycobacterium thermoresistibile (Mth), for the study of Mtb proteins. Mth tolerates higher temperatures than Mtb or other environmental mycobacteria such as M. smegmatis. Mth proteins are on average more soluble than Mtb proteins, and comparison of the crystal structures of two pairs of orthologous proteins reveals nearly identical folds, indicating that Mth structures provide good surrogates for Mtb structures. This study introduces a thermophile as a source of protein for the study of a closely related human pathogen and marks a new approach to solving challenging mycobacterial protein structures.


Epitope mapping of gibberellin to the anti-gibberellin A(4) monoclonal antibody by saturation transfer difference NMR spectroscopy.
Saturation transfer difference (STD) NMR spectroscopy is a promising tool for rapid screening, identifying ligands that interact with a target protein, and characterizing the epitopes of the ligands. Gibberellins (GAs) are a class of plant hormones and form a large family consisting of more than 120 members. A few of them, called "active" GAs, are considered to be perceptible to a receptor that remains unknown. We applied STD NMR spectroscopy to detect the binding activity and identify the binding epitope of gibberellin A(3) (GA(3)) that is recognized by monoclonal antibody 4-B8(8)/E9. This is one of the antibodies that can mimic a GA receptor in the manner of recognition of active GAs. The information on the binding epitope, obtained by STD NMR, was in good agreement with that shown by analyzing the crystal structure of the antibody-GA(4) complex. This suggests that STD NMR spectroscopy would be very useful to characterize the interaction between GAs and such binding proteins as GA-catabolic enzymes and receptors.


Developing the ontological foundations of a terminological system for end-stage diseases, organ failure, dialysis and transplantation.
The Etablissement français des Greffes (EfG) is a state agency dealing with Public Health issues related to organ, tissue and cell transplantation in France. The evaluation of organ retrieval and transplantation activities, one of its missions, is supported by a national information system (EfG-IS). The EfG-IS is moving towards a new n-tier architecture comprising a terminology server for end-stage diseases, organ failure, dialysis and transplantation (EfG-TS). Following a preliminary audit of the existing coding system and in order to facilitate data recording, to improve the quality of information, to assume compatibility with terminological existing standards and to allow semantic interoperability with other local, national or international registries, a specific work has been conducted on the thesauri to integrate within the EfG-TS. In this paper focusing on the server's content rather than the container, we report first the functional and cognitive requirements that resulted from the preliminary audit. We then describe the methodological approach used to build the terminological server on "sound ontological foundations". We performed the semantic analysis of existing medical terms to set up disease description frame-like structures. These diseases description frames consist of a limited set of nosological discriminating slots such as etiology, semiology, pathology, evolution and associated diseases. Each relevant medical term is thus associated to a concept defined and inserted within a hierarchy according to disease description frame resulting from the semantic analysis. Last, because this terminological server is shared by various transplant and dialysis centers to record patient data at different time point, contextualization of terms appeared as one of the functional requirements. We will also point out various contexts for medical terms and how they have been taken into account.


18-Fluorine-labelled 2-deoxy-2-fluoro-D-glucose positron emission tomography/computed tomography standardised uptake values: a non-invasive biomarker for the risk of metastasis from choroidal melanoma.
To correlate the clinical, ultrasound and pathological features of the eyes first evaluated by 18-fluorine-labelled 2-deoxy-2-fluoro-d-glucose (FDG) positron emission tomography (PET)/computed tomography and then enucleated for choroidal melanoma. 14 consecutive patients enucleated for choroidal melanoma were examined. At presentation, clinical, ultrasound and PET/computed tomography imaging were carried out. Ultrasound was used to measure the tumour size and evaluate the tumour shape and intrinsic vascularity (blood flow). Histopathological and immunohistochemical evaluations included tumour cell type, necrosis, glycogen content, vascularity and extrascleral extension. 13 tumours were T3 and one T2 (American Joint Committee on Cancer - International Union against Cancer). The mean tumour height was 10.6 (range 3.5-17.7) mm with a largest basal dimension of 19.3 (range 14.5-30) mm. Patients having melanoma with the highest six standardised uptake values ((SUV) > or =4.0) were (on average) >10 years older, their melanomas had larger basal dimensions and were epithelioid-cell type; three melanomas were centred anterior to the equator; three contained enlarged blood vessels (>150 mum in diameter); and three formed extrascleral extension. Patients with the two highest SUV tumours died due to metastatic melanoma. PET/computed tomography imaging offers a physiological assessment of glucose metabolism in primary choroidal melanomas. Increased FDG PET/computed tomography SUV was positively correlated with known clinical, pathological and ultrasound features linked to metastatic potential of choroidal melanoma.


Measuring anomalies in cigarette sales using official data from Spanish provinces: Are the anomalies detected by the Empty Pack Surveys (EPSs) used by Transnational Tobacco Companies (TTCs) the only anomalies?
There is a literature that questions the veracity of the studies commissioned by transnational tobacco companies (TTCs) to measure the illicit tobacco trade. Furthermore, there are studies that have indicated that the empty pack surveys (EPSs) ordered by TTCs overestimate the size of this trade. This study simultaneously analyzed whether the EPSs established in each of the 47 Spanish provinces were accurate and measured anomalies observed in provinces where sales exceed expected values. To achieve the objectives of this study, provincial data on cigarette sales, prices and GDP per capita were used. These data were modeled with machine learning techniques that are widely used to detect anomalies in other areas. The magnitude of the average anomaly in provinces where sales are higher than their expected values exceeds 40%, while the average anomaly in provinces where sales are lower than their expected values (as detected by the EPSs) is <15%. Furthermore, the results reveal that there is a clear geographical pattern to the provinces in which sales below reasonable values are observed. In addition, the values provided by the EPSs in Spain, as indicated in the previous literature, are slightly overestimated. Finally, some regions bordering other countries or that are highly influenced by tourism have observed sales that are higher than their expected values. Cooperation between countries in their tobacco control policies can have better effects than policies developed based on information from a single country. The lack of control over the transactions of tourists and the inhabitants of bordering countries can cause important anomalies that distort the understanding of tobacco consumption that governments have based on official data.


Assessment of the cerebral venous system from the transcondylar ultrasound window using virtual navigator technology and MRI.
The Chronic Cerebro-Spinal Venous Insufficiency, recently described as a possible role in Multiple Sclerosis pathogenesis, is diagnosed and classified with Echo Color Doppler (ECD) examination of the extra- and intra-cranial veins. As to the intracranial examination, the presence of reflux in the deep cerebral veins (DCVs) or in the dural sinuses is inspected, with a new insonation approach, i.e. the transcondylar window. This work describes a procedure for the co-registration of anatomical Proton Density-weighted Magnetic Resonance Images (MRI) with the intracranial ECD obtained through the transcondylar window. The procedure, preliminarily tested on 10 volunteers, allowed to assess what are the DCVs visible from this new insonation approach and their position relative to the surrounding brain tissues.


The colchicine derivative CT20126 shows a novel microtubule-modulating activity with apoptosis.
New colchicine analogs have been synthesized with the aim of developing stronger potential anticancer activities. Among the analogs, CT20126 has been previously reported to show immunosuppressive activities. Here, we report that CT20126 also shows potential anticancer effects via an unusual mechanism: the modulation of microtubule integrity and cell cycle arrest at the G2/M phase before apoptosis. When we treated COS-7 cells with CT20126 (5 μM), the normal thread-like microtubules were disrupted into tubulin dimers within 10 min and thereafter repolymerized into short, thick filaments. In contrast, cells treated with the same concentration of colchicine exhibited microtubule depolymerization after 20 min and never underwent repolymerization. Furthermore, optical density (OD) analysis (350 nm) with purified tubulin showed that CT20126 had a higher repolymerizing activity than that of Taxol, a potent microtubule-polymerizing agent. These results suggest that the effects of CT20126 on microtubule integrity differ from those of colchicine: the analog first destabilizes microtubules and then stabilizes the disrupted tubulins into short, thick polymers. Furthermore, CT20126 induced a greater level of apoptotic activity in Jurkat T cells than colchicine (assessed by G2/M arrest, caspase-3 activation and cell sorting). At 20 nM, CT20126 induced 47% apoptosis among Jurkat T cells, whereas colchicine induced only 33% apoptosis. Our results suggest that the colchicine analog CT20126 can potently induce apoptosis by disrupting microtubule integrity in a manner that differs from that of colchicine or Taxol.


[ADIPOSE-DERIVED STEM CELLS DIFFERENTIATION INTO NEURON-LIKE CELLS INDUCED BY CO-CULTURE WITH SCHWANN CELLS].
To investigate the differentiation of rat adipose-derived stem cells (ADSCs) into neuron- like cells by indirect co-culture with Schwann cells (SCs) in vitro so as to look for the ideal seed cells for tissue engineering. SCs were isolated from sciatic nerves of 1-2 days old Sprague-Dawley rats with enzymatic digestion method. Immunofluorescence staining was used to identify SCs with the marker S-100. ADSCs were isolated from the epididymal fat pads of adult male Sprague-Dawley rats by means of differential attachment. And the cell phenotypes (CD29, CD34, CD45, CD73, CD90, and CD105) of ADSCs at passage 3 were determined by flow cytometry analysis. Primary SCs and ADSCs at passage 3 were co-cultured at a ratio of 2:1 in Transwell culture dishes (experimental group), and ADSCs cultured alone served as control group. Immunofluorescence and flow cytometry were adopted to investigate the neural differentiation of ADSCs at 14 days. The expression differences for neuron-specific enolase (NSE), microtubule-associated protein 2 (MAP2), neuronal nuclei protein (NeuN), and glial fibrillary acidic protein (GFAP) were detected, and the percentage of positive cells was calculated. ADSCs were successfully extracted and can passage in a considerable large amount. Flow cytometry analysis showed that ADSCs at passage 3 were positive for CD29, CD90, CD73, and CD 105 expression, but negative for CD34 and CD45 expression. The ADSCs of the experimental group showed contraction of nucleus, increasing of soma refraction , and several long and thick protrusions of cell body. The cell shape had no obvious change in the control group. Both immunofluorescence and flow cytometry analysis results showed the expressions of MAP2, NSE, NeuN, and GFAP at 14 days after co-cultured with SCs, and the positive cell ratios were significantly higher than those in the control group (P < 0.01). Co-culture with SCs not only can promote the survival regeneration of ADSCs, but also can induce the differentiation of ADSCs into neuron-like cells.


Latent class analysis stratifies mortality risk in patients developing acute kidney injury after high-risk intraabdominal general surgery: a historical cohort study.
Risk stratification for postoperative acute kidney injury (AKI) evaluates a patient's risk for developing this complication using preoperative characteristics. Nevertheless, it is unclear if these characteristics are also associated with mortality in patients who actually develop this complication, so we aimed to determine these associations. The 2011-15 American College of Surgeons National Surgical Quality Improvement Program was used to obtain a historical, observational cohort of high-risk intraabdominal general surgery patients with AKI, which was defined as an increase in serum creatinine > 177 µmol·L-1 (2 mg·dL-1) above the preoperative value and/or the need for dialysis. Latent class analysis, a model-based clustering technique, classified patients based on preoperative comorbidities and risk factors. The associations between the latent classes and the time course of AKI development and mortality after AKI were assessed with the Kruskall-Wallis test and Cox models. A seven-class model was fit on 3,939 observations (derivation cohort). Two patterns for the time course of AKI diagnosis emerged: an "early" group (median [interquartile range] day of diagnosis 3 [1-10]) and a "late" group (day 9 [3-16]). Three patterns of survival after AKI diagnosis were identified (groups A-C). Compared with the group with the lowest mortality risk (group A), the hazard ratios (95% confidence intervals) for 30-day mortality were 1.79 [1.55 to 2.08] for group B and 3.55 [3.06 to 4.13] for group C. These differences in relative hazard were similar after adjusting for the postoperative day of AKI diagnosis and surgical procedure category. Among patients with AKI after high-risk general surgery, the preoperative comorbid state is associated with the time course of and survival after AKI. This knowledge can stratify mortality risk in patients who develop postoperative AKI.


HLA-B*27 subtype specificity determines targeting and viral evolution of a hepatitis C virus-specific CD8+ T cell epitope.
HLA-B*27 is associated with spontaneous HCV genotype 1 clearance. HLA-B*27-restricted CD8+ T cells target three NS5B epitopes. Two of these epitopes are dominantly targeted in the majority of HLA-B*27+ patients. In chronic infection, viral escape occurs consistently in these two epitopes. The third epitope (NS5B2820) was dominantly targeted in an acutely infected patient. This was in contrast, however, to the lack of recognition and viral escape in the large majority of HLA-B*27+ patients. Here, we set out to determine the host factors contributing to selective targeting of this epitope. Four-digit HLA class I typing and viral sequence analyses were performed in 78 HLA-B*27+ patients with chronic HCV genotype 1 infection. CD8+ T cell analyses were performed in a subset of patients. In addition, HLA/peptide affinity was compared for HLA-B*27:02 and 05. The NS5B2820 epitope is only restricted by the HLA-B*27 subtype HLA-B*27:02 (that is frequent in Mediterranean populations), but not by the prototype HLA-B*27 subtype B*27:05. Indeed, the epitope is very dominant in HLA-B*27:02+ patients and is associated with viral escape mutations at the anchor position for HLA-binding in 12 out of 13 HLA-B*27:02+ chronically infected patients. The NS5B2820 epitope is immunodominant in the context of HLA-B*27:02, but is not restricted by other HLA-B*27 subtypes. This finding suggests an important role of HLA subtypes in the restriction of HCV-specific CD8+ responses. With minor HLA subtypes covering up to 39% of specific populations, these findings may have important implications for the selection of epitopes for global vaccines.


Generation of double knockout cattle via CRISPR-Cas9 ribonucleoprotein (RNP) electroporation.
Genome editing has been considered as powerful tool in agricultural fields. However, genome editing progress in cattle has not been fast as in other mammal species, for some disadvantages including long gestational periods, single pregnancy, and high raising cost. Furthermore, technically demanding methods such as microinjection and somatic cell nuclear transfer (SCNT) are needed for gene editing in cattle. In this point of view, electroporation in embryos has been risen as an alternative. First, editing efficiency of our electroporation methods were tested for embryos. Presence of mutation on embryo was confirmed by T7E1 assay. With first combination, mutation rates for MSTN and PRNP were 57.6% ± 13.7% and 54.6% ± 13.5%, respectively. In case of MSTN/BLG, mutation rates were 83.9% ± 23.6% for MSTN, 84.5% ± 18.0% for BLG. Afterwards, the double-KO embryos were transferred to surrogates and mutation rate was identified in resultant calves by targeted deep sequencing. Thirteen recipients were transferred for MSTN/PRNP, 4 calves were delivered, and one calf underwent an induction for double KO. Ten surrogates were given double-KO embryos for MSTN/BLG, and four of the six calves that were born had mutations in both genes. These data demonstrated that production of genome edited cattle via electroporation of RNP could be effectively applied. Finally, MSTN and PRNP from beef cattle and MSTN and BLG from dairy cattle have been born and they will be valuable resources for future precision breeding.


Characterisation and seasonal variations of particles in the atmosphere of rural, urban and industrial areas: Organic compounds.
Atmospheric aerosol samples (PM2.5-0.3, i.e., atmospheric particles ranging from 0.3 to 2.5μm) were collected during two periods: spring-summer 2008 and autumn-winter 2008-2009, using high volume samplers equipped with cascade impactors. Two sites located in the Northern France were compared in this study: a highly industrialised city (Dunkirk) and a rural site (Rubrouck). Physicochemical analysis of particulate matter (PM) was undertaken to propose parameters that could be used to distinguish the various sources and to exhibit seasonal variations but also to provide knowledge of chemical element composition for the interpretation of future toxicological studies. The study showed that PM2.5-0.3 concentration in the atmosphere of the rural area remains stable along the year and was significantly lower than in the urban or industrial ones, for which concentrations increase during winter. High concentrations of polycyclic aromatic hydrocarbons (PAHs), dioxins, furans and dioxin like polychlorinated biphenyls (DL-PCBs), generated by industrial activities, traffic and municipal wastes incineration were detected in the samples. Specific criteria like Carbon Preference Index (CPI) and Combustion PAHs/Total PAHs ratio (CPAHs/TPAHs) were used to identify the possible sources of atmospheric pollution. They revealed that paraffins are mainly emitted by biogenic sources in spring-summer whereas as in the case of PAHs, they have numerous anthropogenic emission sources in autumn-winter (mainly from traffic and domestic heating).


Survivorship Fellowship: Evaluation and Evolution of a Program for Advanced Practice Providers.
A comprehensive cancer center in the midwestern United States implemented a stakeholder-engaged quality improvement process to extend its existing one-year advanced practice provider (APP) fellowship program consisting of general oncology education and clinical experience to include an additional survivorship clinical rotation. APP fellowship alumni and program stakeholders reported noticeable benefits and greater importance attributed to program participation, validating inclusion of a survivorship clinic rotation as part of the fellowship program.


The CCND1 c.870G>A polymorphism is a risk factor for t(11;14)(q13;q32) multiple myeloma.
A number of specific chromosomal abnormalities define the subgroups of multiple myeloma. In a meta-analysis of two genome-wide association studies of multiple myeloma including a total of 1,661 affected individuals, we investigated risk for developing a specific tumor karyotype. The t(11;14)(q13;q32) translocation in which CCND1 is placed under the control of the immunoglobulin heavy chain enhancer was strongly associated with the CCND1 c.870G>A polymorphism (P = 7.96 × 10(-11)). These results provide a model in which a constitutive genetic factor is associated with risk of a specific chromosomal translocation.


Ultrasonographic findings in cattle and buffaloes with chronic hepatic fascioliosis.
The purpose of this study was to characterize the ultrasonographic findings in cattle and buffaloes with chronic hepatic fascioliosis. To the best of the author's knowledge, this report is the first to document ultrasonographic findings in buffaloes with chronic hepatic fascioliosis. Ultrasonographic findings included distended gallbladders with either homogenous or heterogeneous contents, edema of the gallbladder walls, which ranged from mild or moderate to severe and bile duct mineralization. In 78% of the buffaloes, there was an ultrasonographic picture of hepatic fibrosis in which heterogeneous and hyperechogenic hepatic parenchymas with multiple echogenic foci were imaged. Other ultrasonographic findings included peritoneal, pleural and pericardial effusions. Two cows and one buffalo were slaughtered and examined postmortem. Hence, it was possible to verify distended gallbladders, edema of the gallbladder wall, calcified bile ducts, cholestasis and hepatic fibrosis by using ultrasonography in the cows and buffaloes with chronic hepatic fascioliosis. The procedure offers a useful supplement to clinical, hematological and biochemical examinations on the diagnosis of this condition.


Correlation between chlamydia infection and clinical evaluation, vaginal wet smear, and cervical swab test in female adolescents.
Vaginal wet smear, endocervical swab test, gynecologic examination, and history were investigated in 148 healthy female adolescents. Cultures for Chlamydia trachomatis were obtained from all patients. The overall prevalence was 19/148 (13%). No significant correlation was found between chlamydia infection and any of the parameters investigated in the wet smear. Results of swab test or history showed no discrimination between young women with cultures positive for C. trachomatis and those with cultures negative for C. trachomatis. Chlamydia was found in 32% of patients when the gynecologic examination showed signs of infection and in 10% when no signs of infection were seen (p less than 0.025). Thirteen of the 19 (70%) adolescents with chlamydia infections had no signs of infection. We conclude that neither swab test, vaginal wet smear, nor the history of the patient can give conclusive evidence of a chlamydial infection. Detection of C. trachomatis in this population can be done only by culture or other specific methods.


A novel experimental in vivo model of cerebral immunomodulation induced by inactivated Staphylococcus epidermidis.
The genesis and appropriate treatment of neuroinflammation in various infectious and non-infectious disorders of the central nervous system is still a matter of debate. We introduce an alternative and simple experimental model for the investigation of the cellular inflammatory response to bacterial antigens by stereotactic intracerebral injection of heat-inactivated Staphylococcus epidermidis (HISE). HISE-injection resulted in well-circumscribed intraparenchymal deposits encompassed by an early micro- and astroglial response and a selective but sustained opening of the blood-brain barrier (BBB). After 24h, the HISE collections were densely infiltrated by granulocytes and few circumjacent macrophages that became the predominating immunocompetent cell type from day 4 on. CD8a+ lymphocytes peaked at day 4, whereas CD4+ and CD20+ lymphocytes increased gradually in number, developing a scattered infiltrate until day 17, indicating the initiation of an adaptive immune response. MHC class II presenting cells were abundantly recruited from day 1 and eventually shaped an increasingly dense accumulation within the lesion. Intracerebral HISE administration provides a controlled, highly reproducible and well defined influx of immunocompetent cells across the BBB leading to a distinct and condensed inflammatory reaction. The technique is straightforward, easily feasible and may significantly enable further investigations of the initiation, maintenance and therapeutic modulation of acute neuroinflammation.


Comparison of the optical quality vision between real post-LASIK myopic laser surgery and the simulated implantation of a phakic IOL in low myopia.
A phakic intraocular lens (PIOL) of - 4.5 D was characterized from its wavefront aberration profile. A preclinical study was conducted using pre- and post-surgery data from four patients that had undergone myopic laser refractive surgery. All these patients would have needed a PIOL of - 4.5 D. Pre-surgery data were used to simulate the effect of a PIOL implantation. Post myopic refractive surgery data were used to calculate the post-LASIK eye model. Modulation transfer function (MTF), point spread function (PSF) and simulation of optotypes vision were obtained and compared. The PIOL did not worsen the optical quality of the eyes evaluated. High order Aberrations were always higher in the post-LASIK eye model. Optics quality trended to be better in PIOL implantation than post-LASIK surgery as pupil size increased.


Effects of short-term selenium exposure on respiratory activity and proximate body composition of early-life stages of Catla catla, Labeo rohita and Cirrhinus mrigala.
Metal exposure impairs respiration, increases metabolic demand, and reduces energy storage/fitness in aquatic species. Respiratory impairment and energy storage was examined in acute selenium-exposed Indian major carps, Catla catla, Labeo rohita and Cirrhinus mrigala fry and were correlated with exposure concentrations. Toxicity effects were determined in a renewal bioassay using 96 h lethal selenium concentrations. Species sensitivity distribution (SSD) was also used to derive predicted no-effect concentrations, toxicity exposure ratios, for selenium exposures to early-life fish stages. Mortality was proportional with increasing concentrations. Oxygen consumption and lipid content compared to moisture and ash and of all protein content in tissues of C. catla and C. mrigala indicates that lowered oxygen consumption is directly predictive of lowered lipid content and selenium-induced hypoxia impacts the energy/nutritional status of the early-life stage of carp. This cross-taxa comparison will have major implications for advancing impact assessment and allow better targeting of species for conservation measures.


Rhodium-Catalyzed Formylation of Unactivated Alkyl Chlorides to Aldehydes.
The first rhodium-catalyzed formylation of non-activated alkyl chlorides with syn gas (H2 /CO) allows to produce aldehydes in high yields (25 examples). A catalyst optimization study revealed Rh(acac)(CO)2 in the presence of 1,3-bisdiphenylphosphinopropane (DPPP) as the most active catalyst system for this transformation. Key for the success of the reaction is the addition of sodium iodide (NaI) to the reaction system, which leads to the formation of activated alkyl iodides as intermediates. Depending on the reaction conditions, either the linear or branched aldehydes can be preferentially obtained, which is explained by a different mechanism.


Anaesthesia of a Sumatran tiger on eight occasions with ketamine, medetomidine and isoflurane.
An 18-month-old male Sumatran tiger was referred for endoscopy and dilatation of an oesophageal stricture. Anaesthesia and bouginage was undertaken on eight occasions 2-3 weeks apart to dilate the oesophageal stricture. On the first occasion, sedation was induced with a combination of medetomidine (30 microg/kg) and ketamine (2.35 mg/kg) given intramuscularly. Cardiopulmonary depression (characterised by bradycardia, ventricular arrhythmias, hypoventilation and cyanosis) was severe and in subsequent anaesthesias the medetomidine dose was decreased to about 18 microg/kg and the ketamine dose increased to about 3 microg/kg given intramuscularly. Immobilisation was adequate and the severity of the cardiopulmonary depression was reduced at the revised drug dosages. Atipamezole was effective in reversing both the cardiopulmonary and central nervous system depression. The dosage of medetomidine and ketamine recommended in the literature for immobilising tigers produced severe cardiopulmonary depression in this animal. A reduced dosage of medetomidine and higher dosage of ketamine provided adequate restraint with decreased cardiopulmonary depression.


Microarray analysis of localization of maternal transcripts in eggs and early embryos of the ascidian, Ciona intestinalis.
The establishment of body axes and specification of early embryonic cells depend on maternally supplied transcripts and/or proteins, several of which are localized at specific regions of fertilized eggs and early embryos. The ascidian is known to exhibit a mosaic mode of development, and this mode is largely dependent on localized maternal factors. Using blastomere isolation, microarray and whole-mount in situ hybridization, the present study of Ciona intestinalis demonstrates that maternal transcripts of a total of 17 genes are localized at the posterior-most region of fertilized eggs and early embryos. Ten of them are newly identified in the present study, while the remaining seven genes have already been characterized in previous studies. In addition, maternal transcripts of two genes, in addition to 14 genes encoded by the mitochondrial genome, showed a mitochondria-like distribution. Despite the present comprehensive approach, we could not identify maternal transcripts that are clearly localized to the animal-pole side, the vegetal-pole side, the anterior-side or other specific regions of the early embryo. Therefore, we concluded that the posterior-most localization and mitochondria-like distribution appear to be major specialized patterns of maternal transcripts in early Ciona embryos.


The efficiency of the synaptic vesicle cycle at central nervous system synapses.
Presynaptic nerve terminals rely heavily on membrane traffic to maintain efficient neurotransmission between cells. It is often assumed that, as neurons can fire action potentials at high frequency, the cell biological machinery for vesicle cycling must be highly specialized. Here, we examine the demands that are placed on the recycling machinery in three model systems used to characterize vertebrate vesicle recycling--small hippocampal synapses, calyx-type brainstem synapses, and ribbon-type sensory synapses--and the molecular pathways thought to underlie certain aspects of the vesicle cycle.


Intravenous granisetron--establishing the optimal dose. The Granisetron Study Group.
Three double-blind, dose-ranging studies, involving 996 chemotherapy-naive patients, were conducted to determine the optimal prophylactic dose of intravenous (i.v.) granisetron for prevention of cytotoxic-induced emesis. The antiemetic efficacy of prophylactic i.v. granisetron doses ranging from 2-40 micrograms/kg (study 1) and 40-160 micrograms/kg (study 2) were examined in patients receiving high-dose cisplatin regimens. In study 3, i.v. doses of 40 and 160 micrograms/kg were compared in patients receiving other emetogenic cytotoxic therapies. In study 1, 67.9% (36/53) of patients were complete responders at 24 h following the 40 micrograms/kg dose compared with 61.5% (32/52) and 30.8% (16/52) in the 10 and 2 micrograms/kg groups, respectively (40 vs. 2 micrograms/kg; P less than 0.001). There were no significant differences between doses of 40 and 160 micrograms/kg in any efficacy parameter in Studies 2 and 3. Granisetron was well tolerated across the dose range examined and no dose-related toxicity was observed. In conclusion, a single 40 micrograms/kg prophylactic dose provides optimal control of cytotoxic-induced nausea and vomiting. A simple 3 mg single-dose i.v. regimen (equivalent to 40 micrograms/kg in a 75 kg person) is recommended for prevention of acute emesis associated with all cytotoxic regimens.


Synergistic cytotoxic effects in myeloid leukemia cells upon cotreatment with farnesyltransferase and geranylgeranyl transferase-I inhibitors.
As deregulation of RAS signaling is important in the pathogenesis of myeloid leukemias, molecular targeting of RAS signaling may be a promising therapeutic strategy. Farnesyl transferase inhibitors (FTIs) are the most promising class of these new cancer therapeutics. Several FTIs have entered phase II clinical trials in acute myeloid leukemia (AML). Since geranylgeranylation of K-RAS and N-RAS in the presence of FTIs may represent an important mechanism of FTI resistance, 6 geranylgeranyl transferase-I inhibitors (GGTIs) were screened alone and in combination with FTI for growth inhibition of myeloid leukemia cells. Significant growth inhibition (>70%) in myeloid cell lines was observed for GGTI-286 (9/19), GGTI-298 (14/19), GGTI-2147 (16/19) and FTI L-744,832 (17/17). GGTI treatment of NB-4 cells resulted in an accumulation of cells in G(0)/G(1), whereas FTI L-744,832 primarily caused an increase in G(2)/M. FTI and GGTIs both induced apoptosis. In all cases, FTI/GGTI cotreatment led to synergistic cytotoxic effects in both myeloid cell lines (5/5) and primary AML cells (6/6). This synergy coincided with increased apoptosis. FTI/GGTI cotreatment caused an accumulation of unprocessed N-RAS and inactive N-RAS-RAF complexes. Our results suggest that alternative geranylgeranylation of N-RAS may represent an important mechanism of resistance to FTI monotherapy in myeloid leukemia cells.


The effect of background illumination on pattern onset visual evoked potentials.
The early part (first 200 msec) of pattern onset VEPs elicited by a dartboard pattern was studied in conditions of varying level of background illumination. The effect of pattern adaptation and pattern blurr was also studied. The observed complex behaviour of the main negativity within this part of the VEP can be best described in terms of a composite of two independent negative peaks labelled N100 and N130. In high luminance conditions peak N100 was dominant and the presence of N130 was indicated only by a 'notch' on the rising slope of the negativity. As luminance decreased the situation was reversed and N130 became a dominant feature of the negative wave. This finding did not depend on the particular choice of reference site. For checkerboard stimulation the same features were present, but variability of the VEP wave form was greater than in the case of dartboard stimulation. Present results relate the well-known pattern specific properties of the negativity in onset VEPs to N100 only, whereas N130 is not pattern specific. Lower and upper half-field stimulation produced peaks of opposite polarity at 100 msec but no change was observed in polarity of N130. These findings support the suggestion that these two parts of the negativity in pattern onset VEPs may have different cortical sources.


The role of radiotherapy in the overall treatment of melanoma.
Radiotherapy has become an effective treatment in the management of melanoma patients. It has its place beneath surgical treatment options in a tumor entity that has only limited response to systemic medical therapies. New therapies, such as ipilimumab and vemurafenib, may prolong survival for several months but will cure only a few patients. Radiotherapy will still be required in adjuvant settings to reduce the local recurrence rate and in palliative situations, particularly in brain and bone metastasis. We review several indications for radiotherapy in the management of malignant melanoma with an effect on the guidelines in our clinical practice.


Bimanual coordination in dyslexic adults.
Various types of dyslexia have been associated with tactile-motor coordination deficits and inefficient transfer of information between the two cerebral hemispheres. Twenty-one dyslexic adults were compared to 21 controls on the Bimanual Coordination Task, a test of tactile-motor coordination and interhemispheric collaboration. When compared to control subjects, dyslexics showed a consistent pattern of deficits in bimanual motor coordination, both with and without visual feedback. In particular, dyslexics had greater difficulty relative to normals when the left hand had to move faster than the right, and when the hands had to make opposite (mirror-image) movements, suggesting problems with interhemispheric modulation of visuomotor control. In addition, accuracy on this bimanual coordination task was significantly correlated with the Block Design subtest of the WAIS--R, but not with a rhyme fluency task, suggesting some contribution of right hemisphere controlled visuospatial skill to performance.


Predicting lysine lipoylation sites using bi-profile bayes feature extraction and fuzzy support vector machine algorithm.
Lipoylation is a highly conserved post-translational modification which has been found to be involved in many biological processes and closely associated with various metabolic diseases. The accurate identification of lipoylation sites is necessary to elucidate the underlying molecular mechanisms of lipoylation. As the traditional experimental methods are time consuming and expensive, it is desired to develop computational methods to predict lipoylation sites. In this study, a novel predictor named LipoPred is proposed to predict lysine lipoylation sites. On the one hand, an effective feature extraction method, bi-profile bayes encoding, is employed to encode lipoylation sites. On the other hand, a fuzzy support vector machine algorithm is proposed to solve the class imbalance and noise problem in the prediction of lipoylation sites. As illustrated by 10-fold cross-validation, LipoPred achieves an excellent performance with a Matthew's correlation coefficient of 0.9930. Therefore, LipoPred can be a useful bioinformatics tool for the prediction of lipoylation sites. Feature analysis shows that some residues around lipoylation sites may play an important role in the prediction. The results of analysis and prediction could offer useful information for elucidating the molecular mechanisms of lipoylation. A user-friendly web-server for LipoPred is established at 184.108.40.206/LipoPred/.


Prospective Study of Skipping Meals to Lose Weight as a Predictor of Incident Type 2 Diabetes With Potential Modification by Cardiometabolic Risk Factors: The Canadian 1995 Nova Scotia Health Survey.
Skipping meals is an increasingly common practice to lose weight among North American adults. However, the long-term effect of this practice on incident type 2 diabetes mellitus (T2DM) remains unknown. We assessed whether skipping meals to lose weight is associated with T2DM risk and whether this association is modified by cardiometabolic risk factors. Skipping meals to lose weight was assessed by questionnaire in 2,288 adults from the 1995 Nova Scotia Health Survey and was linked to administrative health databases to determine T2DM incidence in the following 23 years. Multivariable-adjusted Cox proportional hazards models estimated hazard ratios (aHRs) and 95% confidence intervals (CIs) for T2DM. During follow up, 378 T2DM cases were diagnosed. Compared with participants who did not skip meals to lose weight, those who did (2.2%) had a 125% higher risk of T2DM (aHR, 2.25; 95% CI, 1.31 to 3.86). This association was no longer present after further adjustment for baseline body mass index (BMI) (aHR, 1.66; 95% CI, 0.96 to 2.85). Skipping meals to lose weight was associated with T2DM among participants who were men (n=1,135; aHR, 2.09; 95% CI, 1.09 to 4.02) or had a BMI <30 kg/m2 (n=1,676; aHR, 2.64, 95% CI, 1.15 to 6.06), elevated cholesterol (n=1,146; aHR, 2.11; 95% CI, 1.06 to 4.22), high blood pressure (n=1,133; aHR, 2.10; 95% CI, 1.10 to 4.01) and restless sleep (n=1,186; aHR, 2.19; 95% CI, 1.13 to 4.25), but not among women, those with a BMI of ≥30 kg/m2 and those without elevated cholesterol, high blood pressure or restless sleep. Skipping meals to lose weight may be a predictive modifiable risk factor for developing T2DM over time, potentially working in connection with other T2DM risk factors.


Mechanisms of changing speciation and bioavailability of selenium in agricultural mollisols of northern cold regions.
The distribution, speciation, and bioavailability of selenium (Se) - an essential micronutrient for human beings - in agricultural soils influence the resource recovery of agricultural benefits and the sustainable use of Se in agroecosystems. Quantitative understanding in this regard however remains limited in the world's mollisol agroecosystems, despite their critical importance in securing global food supply. Herein, a systematic investigation of Se in the river sediment-irrigation water-mollisols-rhizosphere-rice seeds continuum, at the core zone of the northern mollisol regions, was conducted to elucidate the hydrological-hydrogeochemical processes and mechanisms responsible for the distribution and bioavailability of Se. The content of total Se in the mollisols ranged between 0.12 and 0.54 mg/kg with an average of 0.31 mg/kg. At the riverside flood plains, humic-acid bound Se accounted on average for 39 % of total Se. This pool of Se can be transformed to water-soluble and ion-exchangeable Se(VI), supporting a higher potential of Se bioavailability at riparian agricultural mollisols. For mollisol lands far from the river channels, the topography affects the speciation and partitioning of Se presumably through regulating water retention and organic matter transport. Moreover, altering pH and redox conditions in response to irrigation with the river water may boost Se bioavailability in weakly acidic and high Eh mollisols. It can be in part ascribed to the transformation of organic-bound Se along with infiltrated oxygenated water that leads to the increase of water-soluble and ion-exchangeable Se. These findings reinforce that hydrological-hydrogeochemical perturbations due to irrigation with surface water need to be assessed carefully in the management of Se resources in the mollisol agroecosystems.


Heterogeneity in potential impact and cost-effectiveness of ETEC and Shigella vaccination in four sub-Saharan African countries.
Diarrheal disease burden has become more heterogenous in low- and lower middle-income countries as access to clean water, sanitation and health care has increased in wealthier urban populations. Enterotoxigenic Escherichia coli (ETEC) and Shigella are among the top five causes of diarrheal mortality in children living in sub-Saharan Africa. Here, we explored how accounting for subnational and economic heterogeneity in ETEC and Shigella disease burden affects projected vaccine impact and cost-effectiveness of standalone ETEC and Shigella vaccines during the first decade after introduction in four sub-Saharan African countries. We developed dynamic models for provincial areas and socioeconomic subpopulations of children in the Democratic Republic of Congo (DRC), Kenya, Zambia, and Zimbabwe. We estimated deaths and morbidity due to ETEC and Shigella diarrhea plus additional deaths from other infectious diseases attributable to ETEC- and Shigella-induced stunting. We analyzed cost-effectiveness using Incremental Cost-Effectiveness Ratios (ICERs) with Disability-Adjusted Life Years (DALYs) and Moderate-and-Severe Diarrheal episodes (MSD) averted as denominators. Other infectious disease deaths due to induced stunting accounted for 9-28% and 9-32% of the total provincial level ETEC and Shigella disease burden, respectively, across these four countries from years 2025 to 2034. Our results indicated that the lowest and most cost-effective provincial DALYs averted ICERs were below $600 and $500/DALY averted for ETEC and Shigella vaccination, respectively in Zimbabwe. ICERs were the highest in Zambia and Kenya, where all provincial ICERs where above $2000/DALY. The highest national and provincial MSD averted ICERs were in DRC, while the lowest were in Kenya and Zimbabwe. Vaccinations were most cost-effective in averting DALYs in lower wealth subpopulations living in the highest burden provincial areas. Our approach focused on subnational heterogeneity in ETEC and Shigella burden and vaccination access found that impact and cost-effectiveness were more favorable if vaccinations reach the most vulnerable children in underserved provinces.


Investigation of internal damage evolution in gneiss considering water softening.
In soft rock tunnels, there are often large deformations during construction, especially when the groundwater seepage and softens the surrounding rock. For achieving the purpose of studying the softening effect of water immersion on strength and stability of surrounding rock, 15 rock samples were selected for physical and mechanical tests under 5 conditions: natural state and free immersion for 1, 3, 6, and 9 months, and nuclear magnetic resonance technology(NMR) was also adopted to test the internal pore structure of specimens with different immersion durations, thus the micro structure features of the gneiss, such as the NMR relaxation time T2 spectrum distribution, porosity, and pore volume ratio of different pore sizes under water softening were then obtained. The NMR results shows that the longer the free immersion duration of the rock sample, the greater the porosity; at the same time, the number of micropores in the rock gradually decreases under the interaction of water and rock, and the mesopores increase slightly first and then decrease all the time. The number of macropores is gradually increasing. When the immersion duration is 6 months, the number of macropores begins to increase significantly, and the mechanical properties of the specimens begin to drop significantly. By 9 months, the proportion of macropores in the rock has reached 57.6%. The results showed that the number growth of macropores is the root cause of the macroscopic failure of rock sample. The study results have significance for on-site construction in water-rich areas.


Clinical characteristics of tuberculous infection following renal transplantation.
This study investigated the clinical characteristics of patients with tuberculosis (TB) following renal transplantation (RT) in order to identify markers or signs that can facilitate early diagnosis. A retrospective analysis was performed on 12 cases of Mycobacterium tuberculosis infection treated at our hospital between 2005 and 2020. The incidence of TB after RT at our hospital was 0.9%, and the median postoperative onset time was 22 months. The average age of patients included in our analysis was 44.2 ± 9.4 years; 11 of the 12 patients were male, and most patients had (low) fever as the first or only manifestation. Five patients had respiratory symptoms; 5 had typical computed tomography (CT) presentation; and 2 had a confirmed history of TB. Two sputum smears from 12 patients were positive by acid fast staining, and M. tuberculosis was detected in peripheral blood samples by metagenomic next-generation sequencing (NGS). One patient had a positive result in the purified protein derivative (PPD) test, 7 were positive with the interferon gamma release assay (IGRA), 8/12 patients were confirmed to have TB infection by NGS and 1 was confirmed positive by lung biopsy. Because of the use of immunosuppressive agents, most patients with TB following RT have atypical clinical symptoms and CT findings, and may have a high probability of a false negative result with the traditional PPD test and a low probability of M. tuberculosis detection, making early diagnosis difficult. Therefore, in RT recipients with prolonged fever of unknown origin and unusual clinical manifestations, especially those who are unresponsive to antibiotic treatment, a diagnosis of TB should be considered. The interferon gamma release assay and NGS are relatively new detection methods with high sensitivity and specificity; these along with regular, repeated testing by various approaches can aid the early diagnosis of TB.


Effects of inhibition of prostaglandin-synthesis on renal electrolyte excretion and concentrating ability in healthy man.
In five healthy subjects inhibition of prostaglandin (PG)-synthesis with indomethacin did not significantly alter glomerular filtration, urinary flow rate or sodium and potassium excretion during control urine collection periods or i.v. hypertonic saline infusion. Saline administration was accompanied by a fall in urinary PGEI-excretion from 0.58 +/- 0.14 to 0.26 +/- 0.09 ng/min (p less than 0.05). While indomethacin had no effect on basal urinary osmolality (Uosm), renal concentrating ability following hypertonic saline or i.v. administration of 100 mU lysine-vasopressin significantly increased in the presence of indomethacin with Uosm rising from 805 +/- 25 to 970 +/- 53 mosm/L (p less than 0.01) and from 839 +/- 47 to 996 +/- 62 mosm/L (p less than 0.01), resp. Since this was not accompanied by respective changes in urinary excretion of cyclic adenosine monophosphate (cAMP) mechanisms other than PG-antagonism of vasopressin, such as decreased medullary washout of solute, may contribute to enhanced renal concentrating ability following inhibition of PG-synthesis with indomethacin.


Fine specificity of antibody recognition of carcinoma-associated epithelial mucins: antibody binding to synthetic peptide epitopes.
The protein core of polymorphic epithelial mucins consists predominantly of a repeating 20 amino acid peptide motif. Many monoclonal antibodies reactive with breast carcinomas recognise determinants located within the mucin protein core, and epitope mapping techniques have demonstrated that these antibodies bind to epitopes of three, four or five amino acids within the hydrophilic sequence, P D T R P A P. Each of these mucin core-reactive antibodies map to epitopes containing the central arginine residue. The fine specificity of a panel of anti-mucin antibodies binding to the tetrameric peptides P D T R or R P A P (synthesised on the heads of polyethylene pins) was examined by systematically replacing each amino acid in turn with all other 19 natural amino acids, and then testing these analogues for antibody binding. We have (i) identified those amino acids in epitopes which are essential for antibody binding, (ii) shown that for each epitope there is a hierarchy of residues required for immune recognition--certain amino acids may be replaced with little or no loss of antibody binding, while the presence of others is essential, and (iii) concluded that antibody specificity is further regulated by the residue(s) flanking an epitope motif which may impose conformational constraints upon the presentation of the epitope to an antibody.


The effect of expertise on postural control in elite sport ju-jitsu athletes.
Due to the high postural control demands of sport ju-jitsu, it is likely that long-term sport ju-jitsu training may induce sport-specific adaptations in postural control, especially in positions directly related to combat. The aim of the study was to assess the differences in postural control between elite sport ju-jitsu athletes and untrained controls in non-ecological and ecological conditions and to investigate the relative contribution of spinal and supraspinal mechanisms to postural control in expert athletes. The study was conducted on eleven male elite ju-jitsu athletes and ten non-athletes. The data was collected with the use of a force plate under two conditions: quiet standing and ju-jitsu combat stance. Apart from the standard analysis of the spatial-temporal parameters of center of foot pressure, non-linear measures were used, namely rambling-trembling and sample entropy. The non-parametric Mann-Whitney U test was used to compare both groups. The main findings of the study showed that in quiet standing, elite ju-jitsu athletes and non-athletes had comparable postural control in both the anterior-posterior and mediolateral planes. In contrast, in the combat stance, elite athletes had lower values of postural sway and rambling component (range and rms) and higher values of sample entropy in comparison to the non-athletes (p < 0.05). No differences were found in the trembling component of sway between groups in the combat stance (p < 0.05). Smaller postural sway and its rambling component in sport ju-jitsu athletes may indicate the more precise control of center of foot pressure and improved ability in estimating its position. The sample entropy results confirmed that the displacement of center of foot pressure for sport ju-jitsu athletes was more irregular, which demonstrates greater automatization in postural control. The results also confirm the importance of ecological validity in investigating postural adaptations associated with sports expertise.


Micro-structural characterization of precipitation-synthesized fluorapatite nano-material by transmission electron microscopy using different sample preparation techniques.
Fluorapatite is a naturally occurring mineral of the apatite group and it is well known for its high physical and chemical stability. There is a recent interest in this ceramic to be used as a radioactive waste form material due to its intriguing chemical and physical properties. In this study, the nano-sized fluorapatite particles were synthesized using a precipitation method and the material was characterized using X-ray diffraction (XRD) and transmission electron microscopy (TEM). Two well-known methods, called solution-drop and the microtome cutting, were used to prepare the sample for TEM analysis. It was found that the microtome cutting technique is advantageous for examining the particle shape and cross-sectional morphology as well as for obtaining ultra-thin samples. However, this method introduces artifacts and strong background contrast for high-resolution transmission electron microscopy (HRTEM) observation. On the other hand, phase image simulations showed that the solution-drop method is reliable and stable for HRTEM analysis. Therefore, in order to comprehensively analyze the microstructure and morphology of the nano-material, it is necessary to combine both solution-drop and microtome cutting techniques for TEM sample preparation.


Effects of heavy metal exposure on the condition and health of adult great tits (Parus major).
We examined the possible effects of heavy metal exposure on the quality and health of adult great tits (Parus major) at four study sites along a pollution gradient near a non-ferrous smelter in Belgium. Tarsus length, wing length, body mass and condition of great tits were compared with respect to study site, age (first-year and older great tits), sex and season (birds caught in winter and during breeding). Tarsus length did not differ significantly among study sites. The wing length of great tits was larger at the study site furthest from the smelter, especially for older great tits. The length of the outermost tail feathers, however, did not differ significantly among study sites. We found no signs of loss of body mass or condition towards the pollution source. The body mass and condition was lowest for female great tits at the site furthest from the smelter, especially during winter. Haematocrit values did not differ significantly among sites. Overall, we found no clear significant effects of heavy metal pollution on morphological measurements and health parameters of great tits.


Zn phytoextraction and recycling of alfalfa biomass as potential Zn-biofortified feed crop.
Zn is an essential micronutrient for living organisms and, in that capacity, it is added to animal feed in intensive livestock production to promote growth and eliminate diseases. Alfalfa (Medicago sativa L.) may have the potential to compensate and substitute the need for chemical Zn additives in feeds as a Zn-biofortified feed crop when grown on Zn-enriched soils. Thus, this possibility was investigated with a greenhouse experiment using three soils with Zn concentrations (mg kg-1) of 189 (soil A), 265 (soil B) and 1496 (soil C). Ethylenediamine-N,N'-disuccinate acid (EDDS) and Nitrilotriacetic acid (NTA) at different rates (0 as control, 0.5, 2 and 5 mmol kg-1) were applied as soil additives to enhance the phytoextraction efficiency of alfalfa. The results showed that Zn was highly transferable in alfalfa tissues in the three soils even without additives. EDDS was more effective than NTA in enhancing Zn phytoextraction by alfalfa. The maximum Zn accumulation in the third cutting shoots was obtained with the EDDS concentration of 5 mmol kg-1 in soil A and of 2 mmol kg-1 in soil B, with a 462% and 162% increase compared with controls, respectively. However, the higher EDDS concentration resulted in a significant reduction in biomass production. In soil C, all EDDS concentrations resulted in similar Zn accumulations in the third shoot. To improve the phytoextraction efficacy of Zn while minimizing its phytotoxicity on alfalfa, the rate of 2 mmol kg-1 EDDS proved to be optimal for soil B, and 0.5 mmol kg-1 EDDS for soils A and C. Findings suggest that phytoextraction of Zn-enriched soil can be combined with Zn biofortification, thus allowing to recycle Zn into biomass that can, to an extent, substitute Zn feed additives. This study provided a primary data set for the combination of Zn-biofortification and Zn-phytoextraction.


Adaptive changes in cardiac fibroblast morphology and collagen organization as a result of mechanical environment.
There is a growing body of work in the literature that demonstrates the significant differences between 2D versus 3D environments in cell morphologies, spatial organization, cell-ECM interactions, and cell signaling. The 3D environments are generally considered more realistic tissue models both because they offer cells a surrounding environment rather than just a planar surface with which to interact, and because they provide the potential for more diverse mechanical environments. Many studies have examined cellular-mediated contraction of 3D matrices; however, because the 3D environment is much more complex and the scale more difficult to study, little is known regarding how mechanical environment, cell and collagen architecture, and collagen remodeling are linked. In the current work, we examine the spatial arrangement of neonatal cardiac fibroblasts and the associated collagen organization in constrained and unconstrained collagen gels over a 24 h period. Collagen gels that are constrained by their physical attachment to a mold and similar gels, which have been detached (unconstrained) from the mold and subsequently contract, offer two simple mechanical models by which the mechanisms of tissue homeostasis and wound repair might be examined. Our observations suggest the presence of two mechanical regimes in the unconstrained gels: an outer ring where cells orient circumferentially and local collagen aligns with the elongated cells; and a central region where unaligned stellate/bipolar cells are radially surrounded by collagen, similar to that seen throughout constrained gels. The evolving organization of cell alignment and surrounding collagen organization suggests that cellular response may be due to the cellular perception of the apparent stiffness of local physical environment.


Predicting future weight status from measurements made in early childhood: a novel longitudinal approach applied to Millennium Cohort Study data.
There are reports that childhood obesity tracks into later life. Nevertheless, some tracking statistics such as correlations do not quantify individual agreement, whereas others such as diagnostic test statistics can be difficult to translate into practice. We aimed to employ a novel analytic approach, based on ordinal logistic regression, to predict weight status of 11-year-old children from measurements at age 5 years. The UK 1990 growth references were used to generate clinical weight status categories of 12 076 children enrolled in the Millennium Cohort Study. Using ordinal regression, we derived the predicted probability (percent chances) of 11-year-old children becoming underweight, normal weight, overweight, obese and severely obese from their weight status category at age 5 years. The chances of becoming obese (including severely obese) at age 11 years were 5.7% (95% confidence interval: 5.2 to 6.2%) for a normal-weight 5-year-old child and 32.3% (29.8 to 34.8%) for an overweight 5-year-old child. An obese 5-year-old child had a 68.1% (63.8 to 72.5%) chance of remaining obese at 11 years. Severely obese 5-year-old children had a 50.3% (43.1 to 57.4%) chance of remaining severely obese. There were no substantial differences between sexes. Nondeprived obese 5-year-old boys had a lower probability of remaining obese than deprived obese boys: -21.8% (-40.4 to -3.2%). This association was not observed in obese 5-year-old girls, in whom the nondeprived group had a probability of remaining obese 7% higher (-15.2 to 29.2%). The sex difference in this interaction of deprivation and baseline weight status was therefore -28.8% (-59.3 to 1.6%). We have demonstrated that ordinal logistic regression can be an informative approach to predict the chances of a child changing to, or from, an unhealthy weight status. This approach is easy to interpret and could be applied to any longitudinal data set with an ordinal outcome.


Survival benefit after neoadjuvant or adjuvant radiotherapy for stage II-III gastroesophageal junction adenocarcinoma: A large population-based cohort study.
The standard treatment for stage II-III gastroesophageal junction adenocarcinoma (GEJA) remains controversial, and the role of radiotherapy (RT) in stage II-III GEJA is unclear. Herein, we aimed to evaluate the prognosis of different RT sequences and identify potential candidates to undergo neoadjuvant RT (NART) or adjuvant RT (ART). In total, we enrolled 3,492 patients with resectable stage II-III GEJA from the Surveillance, Epidemiology, and End Results (SEER) database, subsequently assigned to three categories: T1-2N+, T3-4N-, and T3-4N+. Survival curves were evaluated using the Kaplan-Meier method along with the log-rank test. We compared survival curves for NART, ART, and non-RT in the three categories. To further determine histological types impacting RT-associated survival, we proposed new categories by combining the tumor, node, and metastasis (TNM) stage with Lauren's classification. ART afforded a significant survival benefit in patients with T1-2N+ and T3-4N+ tumors. In addition, NART conferred a survival advantage in patients with T3-4N+ and T3-4 exhibiting the intestinal type. Notably, ART and NART were both valuable in patients with T3-4N+, although no significant differences between treatment regimens were noted. Both NART and ART can prolong the survival of patients with stage II-III GEJA. Nevertheless, the selection of NART or ART requires a concrete analysis based on the patient's condition.


OPTN/SRTR 2017 Annual Data Report: Heart.
In 2017, 3273 heart transplants were performed in the United States. New listings continued to increase, and 3769 new adults were listed for heart transplant in 2017. Over the past decade, posttransplant mortality has declined. The number of new pediatric listings increased over the past decade, as did the number of pediatric heart transplants, although some fluctuation has occurred more recently. New listings for pediatric heart transplants increased from 481 in 2007 to 623 in 2017. The number of pediatric heart transplants performed each year increased from 330 in 2007 to 432 in 2017, slightly fewer than in 2016. Short-term and long-term mortality improved. Among pediatric patients who underwent transplant between 2015-2016, 4.8% had died by 6 months and 6.2% by 1 year.


New amide derivatives of quinoxaline 1,4-di-N-oxide with leishmanicidal and antiplasmodial activities.
Malaria and leishmaniasis are two of the World's most important tropical parasitic diseases. Continuing with our efforts to identify new compounds active against malaria and leishmaniasis, twelve new 1,4-di-N-oxide quinoxaline derivatives were synthesized and evaluated for their in vitro antimalarial and antileishmanial activity against Plasmodium falciparum FCR-3 strain, Leishmania infantum and Leishmania amazonensis. Their toxicity against VERO cells (normal monkey kidney cells) was also assessed. The results obtained indicate that a cyclopentyl derivative had the best antiplasmodial activity (2.9 µM), while a cyclohexyl derivative (2.5 µM) showed the best activity against L. amazonensis, and a 3-chloropropyl derivative (0.7 µM) showed the best results against L. infantum. All these compounds also have a Cl substituent in the R⁷ position.


Outline of a prospective multicentric study on the clinical significance of the Kiel classification of non-Hodgkin's lymphomas.
Retrospective analysis of 405 patients suggested the clinical relevance of the Kiel classification of non-Hodgkin's lymphomas. In order to further clarify the clinical and prognostic features of the lymphoma entities diagnosed according to this histopathologic scheme, a prospective multicentric study was initiated by the Kiel Lymphoma Group. Initial staging evaluation is performed according to the Ann Arbor classification. On the basis of the hypothesis that like Hodgkin's disease non-Hodgkin's lymphomas originate, at least in part, as localized nodal or extranodal tumors, extended field irradiation is performed in localized disease (stages I and II) (with the exception of lymphoblastic lymphoma in children and young adults) whereas in more widespread disease (stages III and IV) (with the exception of stage III of centroblastic-centrocytic lymphoma) chemotherapy with additional radiotherapy is applied.


Entire Versus Medial Supraclavicular Nodal Irradiation for Patients With High-Risk Node-Positive Breast Cancer.
We aimed to examine whether elective inclusion of the posterolateral supraclavicular node (SCL) region to the standard medial SCL target volume improves SCL control and survival outcomes in patients with high-risk node-positive breast cancer undergoing regional nodal irradiation (RNI). We retrospectively reviewed 544 consecutive women with high-risk breast cancer treated with postoperative chest wall/breast and RNI in our center from January 2015 to December 2016. High-risk features were defined as clinical or pathologic stage N2-3b disease. Patients were classified into the medial SCL irradiation (M-SCLI) group and the entire SCL irradiation (E-SCLI) group, which included both the medial and the posterolateral SCL region. SCL recurrence (SCLR), disease-free survival (DFS), and overall survival (OS) were estimated and compared. Propensity-score matching (PSM) and multivariate cox regression were used for analysis. The median follow-up time was 64.2 months. Before PSM, there was no significant difference in the cumulative incidence of SCLR between the 2 groups, with 5-year rates of 2.0% in the M-SCLI group and 0.6% in the E-SCLI group (P = .1). After PSM, there was also no significant difference in the cumulative incidence of SCLR (2.1% vs 0.5%; P = .2). Only 2 patients had recurrence in the posterolateral SCL region, with 1 patient in each group. Similarly, there was no significant difference in DFS and OS between the M-SCLI and E-SCLI group both before PSM (5-year rates of 78.5% vs 78.8%, P = .8; 92.2% vs 90.0%, P = .2) and after PSM (76.7% vs 77.2%, P = .8; 91.5% vs 88.4%, P = .1). Multivariate analysis demonstrated that E-SCLI was not independently prognostic for DFS and OS. E-SCLI does not appear to be associated with improved SCL control and survival outcomes in high-risk node-positive breast cancer. These data do not support the routine use of E-SCLI in N2-3b disease. We initiated a multicenter randomized controlled phase 3 study comparing M-SCLI and E-SCLI to further validate these results.


Complete Genome Sequence of Psychrobacillus sp. Strain INOP01, a Phosphate-Solubilizing Bacterium Isolated from an Agricultural Soil in Germany.
We report the complete genome sequence of the phosphate-solubilizing bacterium Psychrobacillus sp. strain INOP01, isolated from an agricultural field in Rostock, Germany. In addition to its phosphate-solubilizing ability, the genome contains genes coding for proteins involved in phosphate (P) acquisition from various sources.


In silico and wet-bench identification of nuclear matrix attachment regions.
Chromatin loops are tethered at discrete regions that are approx 100-1000 bp in length. These regions of attachment serve as specific sequence landmarks, anchoring the DNA to the fibers of the chromosomal scaffold. It has been estimated that our genome contains 70,000 nuclear matrix attachment sites that serve as a dynamic nuclear organizer in both the interphase and metaphase cell. Approximately 30,000-40,000 matrix attachment regions (MARs) serve as origins of replication. MARs can also be associated with chromosomal segments densely populated with transcription factor-binding sites. This may facilitate transcription that is initiated within the region of the chromosome coincident with the surface of the nuclear matrix. Assuming an average somatic loop size of 100 kb, it is reasonable to propose that each cell utilizes 30,000 MARs to anchor each of the approx 20,000 active genic domains. This is sufficient to encompass the 30,000 functional genes in our genome that exist as members of single or multigenic families, each constituting a single chromatin domain. With the sequencing phase of various genome projects complete, in silico tools are being developed to identify the long-range control elements that modulate gene expression. This information is necessary to specifically target the time-intensive wet-bench verification and expression experiments that will provide a unified understanding of gene regulation. In this chapter we review some of the in silico strategies that are currently available and a new in vivo method based on the real-time polymerase chain reaction, to assess regions of matrix association.


Anti-inflammatory acetylenic meroterpenoids from the ascidian-derived fungus Amphichorda felina SYSU-MS7908.
A combination strategy of 13C NMR and bioinformatics was established to expedite the discovery of acetylenic meroterpenoids from the ascidian-derived fungus Amphichorda felina SYSU-MS7908. This approach led to the identification of 13 acetylenic meroterpenoids (1-13) and four biogenic analogs (14-17), including five new ones named felinoids A-E (1-4 and 15). Their structures and absolute configurations were elucidated using extensive spectroscopy, ECD quantum chemical calculations, and single-crystal X-ray diffraction analysis. Compound 1 possessed a rare cyclic carbonate in natural acetylenic meroterpenoids. The plausible shikimate-terpenoid biosynthetic pathways of 1-4 were also postulated. Five of these isolates exhibited anti-inflammatory activity by inhibiting NO production in LPS-induced RAW264.7 cells (IC50 = 11.6-19.5 μM). Moreover, oxirapentyn E diacetate showed a dose-dependent inhibition of pro-inflammatory cytokines IL-6 and TNF-α. Structural modification of oxirapentyn B yielded 29 new derivatives, among which seven showed improved activity (IC50 < 3 μM) and higher selectivity index (SI > 22). The structure-activity relationship study indicated that 7, 8-epoxy, and 6-acylation were crucial for the activity. These findings may provide a powerful tool to accelerate the discovery of new fungal acetylenic meroterpenoids for future anti-inflammatory drug development.


The modern enigma of radiation enteropathy: sequelae and solutions.
With the extended indications for abdominal and pelvic radiation therapy, administered at higher dosage levels, an increased incidence of radiation injury to the intestine can be anticipated. Increased efforts are urgently needed to develop innovative methods in the detection, prevention, and management of radiation-induced intestinal injury. Fifty cases of radiation enteropathy have been reviewed to highlight problems in management and to suggest preventive and therapeutic measures, both surgical and nonsurgical.


Growth factor starvation of bcl-2 overexpressing murine bone marrow cells induced refractoriness to IL-3 stimulation of proliferation.
Murine bone-marrow derived BAF3 cells, over-expressing the human Bcl-2 gene product, showed considerably delayed onset of apoptosis when deprived of IL-3. Such Bcl-2-BAF3 cells arrested rapidly in the G1 phase of the cell cycle upon IL-3 removal, then became refractory to IL-3 re-stimulation. The delay in IL-3 induced proliferation of Bcl-2 over-expressing cells was due to down-regulation of a specific signalling pathway. In the refractory cells, IL-3 was able to stimulate protein tyrosine phosphorylation and c-myc mRNA accumulation, but not rapid Erk2 activation or cdc2 mRNA accumulation.


Correlation between PCDD/F, PCB and PCBz in coal/waste combustion. Influence of various inhibitors.
In the flue gas of co-combustion of solid waste and coal in a laboratory scale furnace high concentrations of polychlorinated dibenzo-p-dioxin and furans (PCDD/F), polychlorinated biphenyls (PCB) and polychlorinated benzenes (PCBz) have been detected. These toxic emissions have been reduced by the help of various inhibitors added to fuel before incineration. Knowledge of the congener pattern and homologue profiles of PCDD/F, PCB and PCBz is important to elaborate the mechanism of formation and inhibition of the toxic compounds formed during co-combustion of solid waste and coal. Principle component analysis (PCA) is used in order to find the similarity between the samples and separate them according their toxicity. By the help of the component analysis (CA) the best correlated congeners are effectively detected. Using linear regression between the independent variables and the indicator parameters various good correlated pairs between PCDD/F, PCB and PCBz have been elaborated. Generally it was found that the samples with higher toxicity show a good correlation between tetra- and pentachlorinated benzenes and tetra- and pentachlorinated dibenzo-p-furans. The best indicator parameter for PCDD/F World Health Organization toxic equivalent (WHO-TEQ) among the PCBz congeners investigated is 1,2,4,5-TCBz. This isomer is also significantly correlated with PCDD/F WHO-TEQ and with the sum of PCDD/F WHO-TEQ and PCB WHO-TEQ. However for samples with higher percentage of inhibitors the above mentioned relationship between the surrogate and WHO-TEQ disappeared. The PCB homologues and congeners show no correlation with PCBz and PCDD/F homologues and congeners.


Radiologic evaluation of the mastoid segment of the facial nerve tract in the intact temporal bone.
To localize the facial nerve course in the mastoid segment and to measure its distances relative to the tympanic membrane. This is a cross-sectional descriptive study. During 2019 in a tertiary hospital, 129 non-contrast and non-pathologic temporal CT images were studied in a tertiary hospital. Facial nerve distances were measured from the planes passing through the annulus in the axial cross-sections at superior, umbo, and inferior levels of the tympanic membrane. It was done in two different dimensions which are anteroposterior (toward the plane of the ear canal wall) and mediolateral (toward the plane of the tympanic membrane). The least mean anteroposterior distance between the facial nerve and the posterior ear canal wall was at the level of umbo (3.66 ± 0.76 mm). The nearest point of the nerve toward the tympanic membrane was the inferior level (- 0.03 ± 0.81 mm). Overall external ear canal lengths were statistically significantly lower in women rather than men. There was a reverse correlation between the age and the ear canal length. Posterior canalplasty seems to be safe unless dissection does not cross the plane of annulus. In this study, the safe margin was 1.4 mm in posterior canal wall drilling. It also should be performed carefully if it extends to the inferior side of the canal. Measuring the mediolateral dimension of the nerve toward the annulus in the axial CT images seems to be practically beneficial, especially in the inferior where the ear canal wall turns and might not act as a good landmark. Paying attention to this plane may reduce the risks of nerve injury in any procedures with transcanal approaches, particularly in inferior canaloplasty.


Refolding of laccase in dilution additive mode with copper-based ionic liquid.
Ionic liquids (ILs) are molten salts which do not crystallize at room temperature. Tunable physicochemical properties of ILs including hydrophobicity and polarity facilitate their applications in many biological processes. In this study, a copper-based IL was employed in order to enhance the refolding efficiency of laccase from Trametes versicolor which requires copper as a cofactor. When 1-ethyl-3-methylimidazolium trichlorocuprate ([EMIM][CuCl₃]) was added to refolding buffer instead of urea, the laccase refolding yield was improved more than 2.7 times compared to the conventional refolding buffer which contains urea. When the refolding of laccase was carried out at different temperatures (4, 25, and 37 °C), the highest refolding yield was obtained at 25 °C. At low temperature, two conflicting effects, i.e., suppression of the aggregate formation and decrease of folding rate, influence the protein refolding. In contrast, a copper-based IL did not enhance the refolding of lysozyme, a non-copper-containing protein. From these results, we can conclude that this copper-based IL, [EMIM][CuCl₃], was exclusively effective on the refolding process of a copper-containing protein.


Deconstructing design thinking as a tool for the implementation of a population health initiative.
The translation of evidence-based practices and rapid uptake of innovations into global health practice is challenging. Design thinking is a consultative process involving multiple stakeholders and has been identified as a promising solution to create and apply implementation strategies in complex environments like health systems. We conducted a process evaluation of a real-world example, namely an initiative to innovate hypertension screening, diagnosis and care in São Paulo, Brazil. The parameters of the evaluation were informed by a specification rubric and categorization system, recommended for the investigation of implementation strategies, and the double-diamond conceptual framework to describe and examine the strategic architecture and nature of the design thinking approach, with particular emphasis on identifying potential areas of "value-add" particular to the approach. The retrospective evaluation was performed by an independent partner who had not been involved in the setting up and implementation of the design thinking process. The evaluation unveiled a dense catalogue of strategically driven, mostly theoretically based, activities involving all identified health system stakeholders including patients. Narrative reconstruction illuminated the systematic and coherent nature of this approach, with different resulting actions progressively accounting for all relevant layers of the health system to engineer a broad selection of specific implementation solutions. The relevance of the identified features and the mechanics used to promote more successful implementation practices was manifested in several distinct ways: design thinking offered a clear direction on which innovations really mattered and when, as well as several new dimensions for consideration in the development of an innovation mindset amongst stakeholders. It thereby promoted relationship quality in terms of familiarity and trust, and commitment to evidence-based enquiry and action. Design thinking was also able to navigate the territory between the need for intervention "fidelity" versus "adaptation" and provide the operational know-how to face familiar implementation hurdles. Lastly, it brought a new kind of skill set to the public health stakeholders that incorporated diplomacy, multidisciplinary approaches and management sciences-skills that are considered necessary but not yet widely taught as part of public health training. Design thinking is a sound and viable tool to use as part of an implementation strategy for engaging with health system stakeholders and successfully translating evidence-based practices and new innovations into routine practice, thereby addressing an important knowledge-practice gap and, more broadly, contributing to the strategic repertoire available to implementation science.


Skin permeation of different steroid hormones from polymeric coated liposomal formulations.
In this study, the effect of various polymers (polycarbophil, chitosan-EDTA, polymeric emulsifier and carrageenan) on the permeation, the chemical and microbial stability of 17-beta-estradiol, progesterone, cyproterone acetate (cpa) and finasteride incorporated in DPPC (1,2-dipalmitoyl-sn-glycero-3-phosphocholine) liposomes has been investigated. The liposomes contained 1% (w/w) of the steroid hormones. Standard diffusion experiments were performed. Drug stability was monitored by analysing the steroid hormone content in the different formulations over a time period of 8 weeks and visually inspecting for microbial contamination. In addition, viscosity measurements were performed. The permeation rate could be improved by addition of polymeric agents depending on their type and drug. In all tested formulations, finasteride exhibited the highest diffusion. Both the chemical and the microbial stability of the hormones were significantly improved by the polymers in comparison to the pure liposomes after an observation period of 8 weeks. After that time microbial stability was still evident for all semisolid formulations. In contrast to this in the pure liposomes already after 2 weeks the steroid drugs showed complete insufficient chemical stability and microbial contamination. Additional rheological measurements indicated an influence of the polymers and drugs on the viscosity in all formulations. The elasticity predominated in nearly all polymeric formulations.


Cholinergic mechanisms within the caudate nucleus mediate changes in blood pressure.
Microinjections of 10 micrograms of carbachol into the caudate nucleus induced changes in the blood pressure of cats anesthetized locally, paralyzed and artificially respired. These responses were dependent on the site of injection. Carbachol, microinjected at rostral levels of the caudate nucleus, elicited pressor responses while a decrease in blood pressure was observed following injections at caudal levels. Both of these effects were blocked by prior microinjection of atropine. Microinjections of carbachol outside the caudate did not affect the resting blood pressure. However, injections of carbachol into the lateral ventricle always produced pressor responses independent of the site of injection along the antero-posterior extension of the ventricle. On the other hand, microinjections of dopamine (20 micrograms) into the caudate nucleus failed to modify blood pressure. From this study, it is concluded that within the caudate nucleus there are two different muscarinic mechanisms, which when activated, mediate changes in blood pressure, possibly through the sympathetic nervous system.


Wet deposition of brominated flame retardants to the Great Lakes basin--status and trends.
This study examined the temporal and spatial trends in wet deposition of 19 legacy and emerging brominated flame retardants (14 polybrominated diphenyl ethers (PBDEs), 1,2-bis(2,4,6-tribromophenoxy)ethane (BTBPE), decabromodiphenylethane (DBDPE), hexabromocyclododecane (HBCD) and pentabromoethylbenzene (PBEB)) at 9 sites in the Canadian Great Lakes between 2004 and 2010. Concentrations of BDE-209 in wet deposition declined significantly. This indicates that the voluntary actions taken to phase out the use of BDE 209 in North America are having an immediate effect on its environment concentrations. The analysis also revealed the presence of 22 short-term high concentration events that dominated overall wet deposition loadings of current-use BFRs to the lakes. For instance, one sample in 2007 was responsible for 37% of the total loadings of HBCD to Lake Huron over the entire six-year sampling period. This questions the current paradigm of how we believe such pollutants enter the environment.


Stable, fragile and recreated - a qualitative study of agency in everyday life with breast and prostate cancer.
Purpose: This study aims to explore how agency is constructed in everyday life with cancer in relation to daily activities and habits. Agency is approached as a key element of daily life existence, and it is constructed in terms of "acting in the world", self-behaviour, changing routines, identity expectations and life course.Methods: The study is based on a social constructionist approach and the data of 32 participants were gathered through a public call for narratives on "everyday life with breast and prostate cancer" in Finland in 2009. The analysis was conducted by utilizing a discursive research approach and coding.Results: Three categories of agency were identified: stable-where agency continues fluently after cancer; fragile-where the ability to take care of daily activities has deteriorated; and recreated-where living with cancer adapts or creates a new basis for daily living.Conclusions: The findings of the study suggest that everyday life activities and habits define and (de)construct agency, and that these constructions are tightly linked to the ill person's overall life situation, physical abilities and cultural context. Having cancer can create new challenges to agency in daily life but does not suppress agency.


Disparities in Lung Cancer: miRNA Isoform Characterization in Lung Adenocarcinoma.
Despite the development of targeted therapeutics, immunotherapy, and strategies for early detection, lung cancer carries a high mortality. Further, significant racial disparities in outcomes exist for which the molecular drivers have yet to be fully elucidated. The growing field of Epitranscriptomics has introduced a new layer of complexity to the molecular pathogenesis of cancer. RNA modifications can occur in coding and non-coding RNAs, such as miRNAs, possibly altering their gene regulatory function. The potential role for such modifications as clinically informative biomarkers remains largely unknown. Here, we concurrently profiled canonical miRNAs, shifted isomiRs (templated and non-templated), and miRNAs with single-point modification events (RNA and DNA) in White American (W) and Black or African American (B/AA) lung adenocarcinoma (LUAD) patients. We found that while most deregulated miRNA isoforms were similar in W and B/AA LUAD tissues compared to normal adjacent tissues, there was a subgroup of isoforms with deregulation according to race. We specifically investigated an edited miRNA, miR-151a-3p with an A-to-I editing event at position 3, to determine how its altered expression may be associated with activation of divergent biological pathways between W and B/AA LUAD patients. Finally, we identified distinct race-specific miRNA isoforms that correlated with prognosis for both Ws and B/AAs. Our results suggested that concurrently profiling canonical and non-canonical miRNAs may have potential as a strategy for identifying additional distinct biological pathways and biomarkers in lung cancer.


Continued incorporation of circulating radiolabeled fibrinogen into preformed coronary artery thrombi.
This study measured the growth over time of experimental coronary artery (CA) thrombi by radiolabeled fibrinogen uptake. 125I-fibrinogen was injected into dogs and 24 hours later CA thrombi were induced by electrical current. Twenty-four hours after CA thrombus induction, 131I-albumin (group A) or 131I-fibrinogen (group B) was injected. At 48 hours after thrombi induction, the thrombi were removed, divided into segments, and their radioactivity measured. The 131I-fibrinogen in the group B thrombi was significantly greater than the 131I-albumin in group A thrombi (P less than 0.001). In further studies, the 131I-fibrinogen was given 48 and 72 hours post CA thrombus formation. Significant 131I was also found in these CA thrombi. 125I-fibrinogen and 131I-fibrinogen incorporation occurred in virtually all segments of the thrombi. The results suggest 1) CA thrombi growth continues for at least 72 hours after initial formation; 2) the presence of 131I in the thrombi was due to gradual fibrin deposition throughout the thrombus.