A cost-effectiveness analysis of vaginal carbon dioxide laser therapy compared with standard medical therapies for genitourinary syndrome of menopause-associated dyspareunia.
Topical vaginal estrogen therapy is considered the gold standard treatment for genitourinary syndrome of menopause-associated dyspareunia, but early investigations of energy-based devices show promise for patients with contraindications or those who are refractory to vaginal estrogen cream therapy. Although evaluating safety, efficacy, and long-term outcomes for novel technologies is critically important when new technologies become available to treat unmet healthcare needs, evaluation of the costs of these new technologies compared with existing therapies is also critically important but often understudied. We sought to perform a cost-effectiveness analysis of 3 therapies for genitourinary syndrome of menopause, including vaginal estrogen therapy, oral ospemifene therapy, and vaginal CO2 laser therapy and determine if vaginal laser therapy is a cost-effective treatment strategy for dyspareunia associated with genitourinary syndrome of menopause. An institutional review board-exempt cost-effectiveness analysis was performed by constructing a decision tree using decision analysis software (TreeAge Pro; TreeAge Software, Inc, Williamstown, MA) using integrated empirical data from the published literature. Tornado plots and 1-way and 2-way sensitivity analyses were performed to assess how changes in the model's input parameters altered the overall outcome of the cost-effectiveness analysis model. All 3 treatment methods were found to be cost-effective below the willingness-to-pay threshold of $50,000.00 per quality-adjusted life year for moderate dyspareunia. The incremental cost-effectiveness ratio for vaginal CO2 laser therapy was $16,372.01 and the incremental cost-effectiveness ratio for ospemifene therapy was $5711.14. Although all 3 treatment strategies were on the efficient frontier, vaginal CO2 laser therapy was the optimal treatment strategy with the highest effectiveness. In a 1-way sensitivity analysis of treatment adherence, vaginal CO2 laser therapy was no longer cost-effective when the adherence fell below 38.8%. Vaginal estrogen cream and ospemifene therapies remained cost-effective treatment strategies at all ranges of adherence. When varying the adherence to 100% for all strategies, oral ospemifene therapy was "dominated" by both vaginal CO2 laser therapy and vaginal estrogen cream therapy. In a 2-way sensitivity analysis of vaginal CO2 laser therapy adherence and vaginal CO2 laser therapy cost, vaginal CO2 laser therapy still remained the optimal treatment strategy at 200% of its current cost ($5554.00) when the adherence was >55%. When the cost fell to 20% of its current cost ($555.40), it was the optimal treatment strategy at all adherence values above 29%. This study showed that vaginal fractional CO2 laser therapy is a cost-effective treatment strategy for dyspareunia associated with GSM, as are both vaginal estrogen and oral ospemifene therapies. In our model, vaginal CO2 laser therapy is the optimal cost-effective treatment strategy, and insurance coverage should be considered for this treatment option if it is proven to be safe and effective in FDA trials.


Legionnaires' disease. A cause of severe abscess-forming pneumonia.
In two previously well nonsmokers fatal pneumonia developed with extensive abscess formation. Legionnaires' bacillus was the only pathogen isolated. These cases indicate that Legionnaires' bacillus is capable of causing extensive necrosis of the lung.


Long non-coding RNA EPIC1 promotes cholangiocarcinoma cell growth.
Cholangiocarcinoma (CCA) is the as the most frequently observed biliary tract malignancy, which has low survival rate in addition to constrained treatment options. However, the fundamental molecular mechanism underlying malignant progression of CCA is quite ambiguous. Recent studies reported that long non-coding RNA (lncRNA) might play critical roles in regulating chemo-resistant of multiple types of cancer. In this study, our results indicate that the LncRNA-EPIC1 expression were significantly increased in cholangiocarcinoma tissues, compared to adjacent normal tissues. And also, its expression also increased in several CCA cancer cell lines than that in human normal immortalized cholangiocyte cell. Loss-and-gain of Lnc-EPIC1 contributes to the CCA cell growth, colony formation, cell apoptosis and also cell cycle. Myc has been reported to directly interact with Lnc-EPIC1 in several cancer cells. Myc targets, including Cyclin A/D and CDK9 were downregulated by Lnc-EPIC1 siRNA. Myc knockout also suppresses the CCA cell growth, colony formation and cell apoptosis. However, Lnc-EPIC1 knockdown failed to enhance the Myc-KO-induced suppression of CCA tumor progression. RNA immunoprecipitation (RIP) results showed the direct interaction between Lnc-EPIC1 and Myc. Taken together, our results show that Lnc-EPIC1 promotes CCA cancer progression by targeting Myc.


Drive-thru anticoagulation clinic: Can we supersize your care today?
Warfarin therapy requires maintenance of a therapeutic international normalized ratio (INR) and thus requires routine monitoring to ensure benefits of anticoagulation, while avoiding complications. As the pharmacist's role evolves from traditional medication dispensing towards direct patient care, many anticoagulation management services are pharmacist-managed. Due to the coronavirus disease 2019 (COVID-19) pandemic, healthcare providers were faced with re-evaluating anticoagulation management practices to minimize person-to-person exposure risk. Although being anticoagulated is not considered high risk for illness from the coronavirus, these patients are often of advanced age and frequently have multiple comorbidities, putting them at increased risk. Consequently, two hospital-based, pharmacist-managed outpatient anticoagulation management services developed drive-thru curbside clinics to continue providing care to warfarin patients. The services utilized universal COVID-19 precautions to conduct curbside appointments where pharmacists determined patient's warfarin therapy plan, scheduled timely follow-up, and provided dosing instructions. With the unexpected coronavirus outbreak, this immediate change to traditional anticoagulation management was essential for safe and effective anticoagulation therapy. Implementing a curbside clinic allowed for safe distancing while managing warfarin appropriately.


A new species of Xiphinema americanum group (Nematoda: Longidoridae) from Iran, with additional data on three known species.
One new and three known species of the genus Xiphinema from the rhizosphere of fruit trees and rose shrubs in East Azarbaijan province, Iran, are presented based on the morphological, morphometric and molecular characters. The new species is distinguished by its 2.0-2.1 mm long body, relatively flattened lip region with 8.7-10.0 µm width, set off from body contour by a deep constriction, odontostyle 82.5-88.0 µm long, V = 52-54, reproductive system didelphic-amphidelphic with symbiotic bacteria in the reflexed ovaries, tail conoid, dorsally convex with rounded to slightly subdigitate tip (42.0-43.5 µm long, c = 61-65, c' = 1.6-1.8), and males unknown. The new species, X. babaii sp. n., looks very close to X. californicum, and is regarded as its cryptic species, being separated from it using some morphological differences. Their separation was further corroborated using molecular data. Three known species belonging to the Xiphinema americanum group namely X. primum, X. pachtaicum and X. simile were also collected during present study, and new data were provided for them. Xiphinema simile is a new record for the Iran's nematode fauna. Molecular phylogenetic studies using partial sequences of 28S rRNA gene D2-D3 fragments were performed, and the phylogenetic relationships of the new species were discussed.


WTP and WWTP sludge management: a case study in the metropolitan area of Campinas, southeastern Brazil.
Disposal of sludges generated at water treatment plants (WTPs) and wastewater treatment plants (WWTPs) located in highly urbanized regions challenges water industry. Legal restrictions based on public health and sustainability push managers forward in order to find beneficial use markets rather than deficit and high-cost landfilling. A GIS-based linear optimization method for sludge management was firstly proposed. The metropolitan area of Campinas belongs to the watershed of the rivers Piracicaba, Capivari, and Jundiaí (PCJ), which comprises 76 municipalities, representing over 5 million urban consumers, supplied by 100 WTPs and 116 WWTPs. An assessment of soils feasibility for WWTP sludge reception was carried out. The beneficial uses assumed to be the best for WTP and WWTP sludges were, respectively, addition in the industrial process of ceramic bricks manufacture, and application on sugarcane crop areas for ethanol production. Three scenarios were set for sludges from WTPs and also for WWTPs. Those scenarios represented maximum, intermediate, and minimum reception capability for each reception location or area. Ceramic industries located within PCJ watershed showed to be capable of receptioning the total amount of WTP sludges, if a minimum 2% mass/mass replacement of raw materials (mainly clay) is provided. There are plenty of feasible areas for WWTP sludge application; thus, sludge agronomic quality and farmers' acceptance constitute the only steps to climb. This paper brings an innovative tool regarding sludge management which may be useful to decision-makers, especially wherever several sources and reception areas are playing on game board. The proposed method can be applied at different locations and for other sludge uses.


Nonsurgical management of primary ovarian pregnancy with transvaginal ultrasound-guided local administration of methotrexate.
Primary ovarian pregnancy is a rare form of ectopic gestation and one that is often diagnosed only at the time of surgery. We report the first case to our knowledge of a live primary ovarian pregnancy diagnosed by transvaginal ultrasonography and successfully treated with transvaginal-guided aspiration and injection of methotrexate. Primary ovarian pregnancy can be diagnosed early in gestation with transvaginal sonography, affording the opportunity to successfully be managed with local administration of methotrexate.


Boosting photocatalytic hydrogen peroxide production by regulating electronic configuration of single Sb atoms via carbon vacancies in carbon nitrides.
Single-atom catalysts supported on semiconductors can serve as active sites for efficient oxygen reduction to hydrogen peroxide (H2O2). However, researchers have long been puzzled by the lack of guidance on optimizing the performance of single-atom photocatalysts. In this study, we propose a versatile strategy that utilizes carbon vacancies to regulate the electronic configuration of antimony (Sb) atoms on carbon nitrides (C3N4). This strategy has been found to significantly enhance the photocatalytic production of H2O2. The H2O2 evolution rate of Sb single-atom on carbon vacancy-rich C3N4 (designated as Sb1/Cv-C3N4) is 5.369 mmol g-1h-1, which is 10.9 times higher than C3N4 alone. By combining experimental characterizations and density functional theory simulations, we reveal the strong electronic interaction between Sb atoms and carbon vacancy-rich C3N4. This interaction is capable for maintaining the electron-rich state of Sb atoms, facilitating efficient electron transfer to pauling-type absorbed oxygen, and ultimately enhancing the formation of *OOH intermediates. This innovative defect-engineering approach can manipulate the electronic configuration of single-atom catalysts, providing a new avenue to boost the photocatalytic oxygen reduction reaction towards H2O2 production.


The Swedish Environmental Specimen Bank with reference to the National Contaminant Monitoring Programme in Sweden.
The environmental Specimen Bank (ESB) at the Swedish Museum of Natural History constitutes the base for the National Contaminant Monitoring Programme in Sweden. This is a part of the Swedish Environmental Monitoring Programme (PMK). Since the beginning of the 1960s more than 120,000 organisms have been collected and stored in the Swedish ESB. The present PMK-programme started in 1978 under the authority of the Swedish Environmental Protection Agency. The present paper gives a brief presentation of main types of material and species annually collected for storage in the Swedish ESB, with special reference to the Contaminant Monitoring Programme.


A review of the cardiometabolic risk experience among Canadian Métis populations.
Cardiometabolic risk is a growing concern in Western society in which rates of cardiovascular disease, diabetes, and obesity are on the rise. Aboriginal populations currently experience unequal burdens of these chronic conditions. However, limited information regarding the experience of cardiometabolic risk among Métis populations is available. This review sought to evaluate the cardiometabolic risk experience among Métis populations in Canada. Canada's Métis population currently experiences greater burdens of chronic conditions including metabolic syndrome, diabetes, obesity, and cardiovascular disease than that of the non-Aboriginal population. Métis populations also experience poorer life expectancy, education, and employment attainments, and reduced access to health care services compared with non-Aboriginal populations. Interventions addressing the deficiencies in sociodemographic, lifestyle, and social determinants among the Métis population might help combat rising experiences of chronic diseases faced by these people. Though the burden of chronic conditions, sociodemographic, lifestyle challenges, and social determinants of health among Métis populations are generally less than that of First Nations populations, Métis people experience these health challenges and influencing factors are generally more similar to that of First Nations than non-Aboriginal peoples. Subsequently, Métis populations need to be included in plans and strategies to reduce chronic conditions among Aboriginal populations. In conclusion, Métis populations experience greater burden of cardiometabolic risk and its components than the general Canadian population.


Nitrosamine levels in human blood, urine and gastric aspirate following ingestion of foods containing potential nitrosamine precursors or preformed nitrosamines.
In studies of the effect of diet on nitrosamine levels in selected human physiological fluids, volunteers were fed meals containing fish or beef (sources of precursor amines) or bacon (a source of preformed nitrosamines), in combination with spinach and vegetable juice to supply nitrite via possible reduction of nitrate. Blood, urine and gastric contents were sampled periodically for up to 4 hr after feeding. The results of the study indicated that traces of nitrosamines, usually N-nitrosodimethylamine, were present in many samples of blood, urine and gastric contents, even after an 8-hr fast. Eating the test meals led to a slight increase in nitrosamine levels in the blood and stomach contents in a few subjects. The data obtained from this study suggest that gastric formation of nitrosamine does not appear to be an important health factor in normal people, since the levels of nitrosamines found in physiological fluids are not markedly increased after eating.


A surface metric and software toolbox for EEG electrode grids in the macaque.
The past years have seen increased appreciation of electroencephalographic (EEG) recordings in non-human primates (NHP) as a tool for translational research. In humans, even large EEG electrode grids can easily and quickly be placed on standardized positions using commercially available EEG caps. In the NHP, the identification of standardized EEG electrode positions is more complicated and time-consuming. Here we introduce a surface metric and software package (NHP1020) that automates the planning of large, approximately evenly spaced electrode grids for EEG recordings in the NHP. Based on one CT and one MRI image as well as two intracranial markers, the NHP1020 software defines electrode positions on the brain surface using a surface-based spherical metric similar to the one used by the international 10-20 system. Standardized electrode grids can be shared, imported or defined with few high-level commands. NHP EEG electrodes can be placed relative to extracranial markers and measurements or relative to underlying neural structures of interest. Both approaches are time-consuming and require manual intervention. Furthermore, the use of extracranial markers in this species may be more problematic than in humans, because cranial muscles and ridges are larger and keep maturing long into adulthood. The presented surface metric and the NHP1020 toolbox provide fast and automated identification of entire electrode grids in the non-human primate based on a two-dimensional metric on the brain surface.


Herpes zoster in an immunocompetent boy following intrauterine exposure to varicella-zoster virus.
Herpes zoster (HZ) is caused by the varicella-zoster virus (VZV) and is considered to be a reactivation of latent infection. The first clinical manifestation of VZV infection during infancy typically presents as chickenpox; however, HZ can be observed in infants and children without a history of symptomatic varicella. We report the case of a 4-year-old immunocompetent boy who developed HZ after intrauterine exposure to VZV.


Closed-loop control of blood pressure, ventilation, and anesthesia delivery.
Closed-loop control systems have been in use for over 4,000 years, yet applications in medicine have developed only recently. When compared with manual control, closed-loop controllers for blood pressure, ventilation, and anesthesia delivery provide more rapid and more precise control of mean pressure, end-tidal CO2, and end-tidal anesthetic concentrations. Closed-loop control systems perform better in almost all situations. It must be remembered however, that the best anesthesiologist may perform better than the controller, particularly in his ability to anticipate clinical events which effect control. Although the convenience, precision of control, and immunity to distractions are reason enough to further pursue their development, their final application to clinical care will depend on the inclusion of appropriate safeguards and supervisory software algorithms to protect the systems from failure.


Binding of choleragen and anti-ganglioside antibodies to gangliosides incorporated into preformed liposomes.
Exogenously added gangliosides were taken up and incorporated into liposomes just as they are incorporated into cells. Ganglioside GM1 was rapidly taken up by liposomes containing dimyristoyl- or dipalmitoylphosphatidylcholine, cholesterol and dicetyl phosphate. When incubated with a wide range of GM1 concentrations for 18 h, the liposomes incorporated about 10% of the added ganglioside. The rate of GM1 uptake by preformed liposomes was both time- and temperature-dependent. The liposomes also incorporated other gangliosides to a similar extent. The GM1 taken up by preformed liposomes was predominantly located on the outer surface of the liposomes and did not appear to be internalized into the inner half of the lipid bilayer. Liposomes containing GM1 added after liposome formation bound as many anti-GM1 antibodies and as much choleragen as liposomes having GM1 added during the formation of the lipid bilayers. Thus, preformed liposomes sensitized by incubation with GM1 are a good model system for studying the interactions of antibodies and toxins with membrane-associated gangliosides.


Novel techniques for automated seizure registration: Patients' wants and needs.
Patient-reported seizure frequency is essential for therapy management and clinical research but lacks validity mainly due to seizure-induced seizure unawareness. Automated seizure detection by mobile monitoring devices promises to settle this serious methodological issue. Here, we explored attitudes and preferences towards future devices for seizure detection in adult patients with therapy-refractory epilepsies. A total of 102 inpatients enrolled and underwent a newly constructed semistructured 30-minute interview on automated seizure registration. Most patients would generally apply and permanently use seizure registration devices. Removable devices were preferred (e.g., wristband sensors), but also patch electrodes at invisible body sites appeared acceptable. Only a minority of patients would accept implantations for seizure registration (especially of depth electrodes). Also, permanent optical or acoustical surveillance were accepted by a few patients only. Most patients were ready to care for the device (e.g., charging battery), to have doctor's appointments for device control, and even to pay for the device. Seizure prediction was evaluated as an essential additional function. Only half of the patients wanted emergency calls in case of a seizure. Patients would accept automated seizure registration if the device had as little as possible negative effect on daily living. High acceptance might, therefore, be expected for hardware equipment as it is nowadays used by many healthy subjects for physiological self-monitoring and life-logging. The proper medical engineering task of the future, therefore, is to optimize sensors in those highly feasible devices and to establish reliable biomarkers and outcome measures for a diversity of diseases (including epilepsy) from data obtained by this generic hardware.


SMRT has tissue-specific isoform profiles that include a form containing one CoRNR box.
SMRT acts as a corepressor for a range of transcription factors. The amino-terminal part of the protein includes domains that mainly mediate transcriptional repression whilst the carboxy-terminal part includes domains that interact with nuclear receptors using up to three motifs called CoRNR boxes. The region of the SMRT primary transcript encoding the interaction domains is subject to alternative splicing that varies the inclusion of the third CoRNR box. The profile in mice includes an abundant, novel SMRT isoform that possesses just one CoRNR box. Mouse tissues therefore express SMRT isoforms containing one, two or three CoRNR boxes. In frogs, the SMRT isoform profile is tissue-specific. The mouse also shows distinct profiles generated by differential expression levels of the SMRT transcript isoforms. The formation of multiple SMRT isoforms and their tissue-specific regulation indicates a mechanism, whereby cells can define the repertoire of transcription factors regulated by SMRT.


Direct detection of two different tumor-derived extracellular vesicles by SAM-AuNIs LSPR biosensor.
Extracellular vesicles (EVs) are abundant in various biological fluids including blood, saliva, urine, as well as extracellular milieu. Accumulating evidence has indicated that EVs, which contain functional proteins and small RNAs, facilitate intercellular communication between neighbouring cells, and are critical to maintain various physiological processes. In contrast, EV-derived toxic signals can spread out over the tissues adjacent to the injured area in certain diseases, including brain tumors and neurodegenerative disorders. This demands better characterization of EVs which can be employed for liquid biopsy clinically as well as for the study of intercellular signalling. Exosomes and microvesicles share a number of similar characteristics, but it is important to distinguish between these two types of EVs. Here, we report for the first time that our in-house developed Localized Surface Plasmon Resonance biosensor with self-assembly gold nanoislands (SAM-AuNIs) can be used to detect and distinguish exosomes from MVs isolated from A-549 cells, SH-SY5Y cells, blood serum, and urine from a lung cancer mouse model. Exosomes, compared with MVs, produced a distinguishable response to the bare LSPR biosensor without functionalization, suggesting a different biophysical interaction between exosomes and MVs with SAM AuNIs. This sensor attains the limit of detection to 0.194µg/ml, and the linear dynamic range covers 0.194-100µg/ml. This discovery not only reveals great insight into the distinctive membrane property of tumor-derived exosomes and MVs, but also facilitate the development of novel LSPR biosensors for direct detection and isolation of heterogeneous EVs.


Correction to: Transcriptional Regulators as Targets for Alcohol Pharmacotherapies.
Figure 1 was published incorrectly in this chapter. The original chapter was corrected.


Effect of interferon on phospholipid methylation by peripheral blood mononuclear cells.
The effect of human interferon (IFN) preparations on the metabolic pathway leading to the synthesis of phosphatidylcholine (PC) by a stepwise addition of methyl groups to phosphatidylethanolamine (PE) was investigated in human peripheral blood mononuclear (PBMN) cells. An inhibition of the synthesis of PC via this pathway was regularly observed with both alpha- (recombinant or natural) and beta-IFN. This inhibition was apparent within the first 5 min of treatment, reached its maximum between 15 min and 1 hr, and persisted at the same level until 6 hr, the last time point examined. Each of the transmethylated products of PE underwent a similar inhibition, as measured by the turnover rate of individual products. The intracellular pool of the methyl donors, methionine and S-adenosyl-methionine (SAM), was shown to be unaffected. The methyltransferase activity of IFN-pretreated cell extracts was unchanged. These findings support the hypothesis that IFN induces a functional change in phospholipid methylation at the level of organized membrane-bound phospholipid methyltransferase enzymes in intact cells.


The enediolate analogue 5-phosphoarabinonate as a mechanistic probe for phosphoglucose isomerase.
A stable analogue has been prepared of the enediolate anion believed to occur transiently in the reaction of phosphoglucose isomerase. This compound, 5-phosphoarabinonate, is the strongest known competitive inhibitor of the enzyme (Ki = 3 times 10(-7) M below pH 7). A distinctive pH dependence of binding, also found for two other aldonic acid omega-phosphates, 6-phosphogluconate and 4-phosphoerythronate, involves pertubation of a pKa from 7.0 in the free enzyme to 9.0 in the enzyme-inhibitor complex. This perturbation may reflect a catalytically advantageous increase in basicity which occurs around the transition state of the normal enzymatic reaction.


Thermodynamic parameters of the interaction of Urtica dioica agglutinin with N-acetylglucosamine and its oligomers.
The interaction between Urtica dioica agglutinin (UDA) and N-acetylglucosamine (GlcNAc) and its beta(1-4)-linked oligomers was studied by fluorescence titration and isothermal titration microcalorimetry. UDA possesses one significant binding site that can be measured calorimetrically. This site is composed of three subsites, each subsite accommodating one GlcNAc residue. The interaction is enthalpically driven, and the binding area of UDA is characterized by a deltaH of interaction for a given oligosaccharide considerably smaller than that of wheat germ agglutinin (WGA), despite the fact that they both belong to a family of proteins composed entirely of hevein domains. Relatively high deltaCp values of the UDA-carbohydrate interactions and more favorable entropy term compared to WGA suggest that binding of the carbohydrate ligands by UDA has a higher hydrophobic component than that of WGA.


Genetic trends production and somatic cell count for Jersey cattle in Zimbabwe born from 1994 to 2005.
Genetic trends for Jersey dairy cattle in Zimbabwe were estimated. A total of 10,986 lactation records were obtained from Zimbabwe Livestock Identification Trust, with cows calving in the period 1996 to 2008. An ASReml program fitting an animal model was used for the analyses. The animal model that was used included overall mean, herd-year-season, previous calving interval, and days dry as fixed effects while linear and quadratic regression coefficients of age at calving as covariates. Random effects were cow, permanent environmental effects, and residual error. The pedigree file included 1,228 animals born from 1994 to 2005. The traits studied were milk yield, fat yield, protein yield, fat percent, protein percent, and Log(10)SCC. Results indicated that milk yield, fat yield, and protein yield increased genetically (P < 0.0001) on average by 1.420, 0.160, and 0.164 kg per year, respectively. Fat percent, protein percent, and Log(10)SCC declined over the past 12 years (P < 0.0001) at the rate of -0.021, -0.015, and -0.0002 per year, respectively. This was due to the negative correlation between milk composition and milk yield. The results implies that the selection applied in the last decade has achieved genetic progress and that there is genetic variance for continued improvement and for setting up an effective dairy breeding program in Zimbabwean Jersey herds for milk, fat, and protein production.


Anthracosilicosis mimicking extensive nodal metastasis from early gastric cancer: A case report.
Lymph node metastasis is one of the most important prognostic factors in gastric cancer and precise assessment of nodal status facilitates optimal therapeutic decisions. Many diagnostic modalities including endoscopic ultrasound (EUS), computed tomography (CT), and sometimes, positron emission tomography (PET) have been utilized to improve diagnostic accuracy in detecting metastatic lymph nodes; however, their accuracy remains unsatisfactory. We report a case of a 73-year old male patient who was erroneously diagnosed with stage IV gastric cancer due to the distant nodal metastasis from early gastric cancer lesion during the initial staging process. However, surgical exploration revealed an anthracosilicosis-associated lymphadenopathy that mimicked extensive distant nodal metastasis in the preoperative CT and PET-CT scans. The patient was finally diagnosed with stage I gastric cancer confined to the mucosa without nodal metastasis. We report a rare case of gastric cancer concurrent extensive nodal involvement of anthracosilicosis mimicking metastatic nodal disease in the imaging studies. This case implies that PET-CT scan for clinical staging is not specific enough to clearly delineate malignant lesions, causing a diagnostic dilemma. When the characteristics of the primary tumor is poorly correlated to the findings of imaging studies, surgical exploration can be a viable option for a definitive diagnosis before making a hasty decision based only upon the diagnostic imaging results.


Effects of bisphosphonates on isolated rat osteoclasts as examined by reflected light microscopy.
The bisphosphonates 4-amino-1-hydroxybutylidene-1,1-bisphosphonic acid (ABP), 3-amino-1,1-hydroxypropane-1,1-diphosphonic acid (APD), and 1-hydroxyethane-1,1-diphosphonic acid (EHDP) were compared for their ability to inhibit the osteoclastic resorption of bone in culture. This was achieved by measuring the effect of bisphosphonate concentration on the number of resorption pits formed and the total area of resorption. During this analysis, a new application of reflected polarized light microscopy was developed that has advantages over other microscopy techniques, including scanning electron microscopy (SEM), as applied to the analysis of resorbed bone surfaces. Based on area analysis, the bisphosphonates were effective for the range 10(-7)-10(-8) M, with ABP about two to five times more effective than EHDP or APD. Similar data were obtained by counting the number of resorption pits but with EC50 10 times higher. At lower concentrations (10(-9) M), bisphosphonates may enhance the formation of resorption pits. APD was found to be more toxic (10 times) than ABP or EHDP to osteoclasts and mononuclear cells, but toxic concentrations were at least 10(2) times higher than the resorption EC50. These data plus immunofluorescence, SEM, and transient incubation experiments show that it is the bisphosphonate-bone complex that directly inhibits the excavation of resorption pits by mature osteoclasts. The mechanism of action does not appear to require inhibition of osteoclast differentiation or toxic elimination of osteoclasts. Bisphosphonates, however, subtly affect the cytoskeleton of osteoclasts.


Adaptation of timing behavior to a regular change in criterion.
This study examined how operant behavior adapted to an abrupt but regular change in the timing of reinforcement. Pigeons were trained on a fixed interval (FI) 15-s schedule of reinforcement during half of each experimental session, and on an FI 45-s (Experiment 1), FI 60-s (Experiment 2), or extinction schedule (Experiment 3) during the other half. FI performance was well characterized by a mixture of two gamma-shaped distributions of responses. When a longer FI schedule was in effect in the first half of the session (Experiment 1), a constant interference by the shorter FI was observed. When a shorter FI schedule was in effect in the first half of the session (Experiments 1, 2, and 3), the transition between schedules involved a decline in responding and a progressive rightward shift in the mode of the response distribution initially centered around the short FI. These findings are discussed in terms of the constraints they impose to quantitative models of timing, and in relation to the implications for information-based models of associative learning. This article is part of a Special Issue entitled: Associative and Temporal Learning.


Adherence of Streptococcus gordonii HG 222 in the presence of saliva.
The influence of the presence of saliva from different salivary glands on the adherence of Streptococcus gordonii strain HG 222 to saliva-coated polystyrene surfaces was tested. In the presence of undiluted parotid saliva or diluted whole, submandibular and sublingual saliva the adherence of HG 222 was enhanced by the formation of small aggregates on the attachment surface. In the presence of undiluted whole, submandibular and sublingual saliva large aggregates were formed and the adherence to saliva-coated polystyrene surfaces was inhibited. Adherence in the presence of whole saliva compared to adherence in buffer was decreased when lower densities of bacterial suspension were used, although in this case in the presence of whole saliva smaller bacterial aggregates were formed. In conclusion, these results suggest that the presence of saliva in solution may both enhance and decrease the adherence of S. gordonii HG 222 to saliva-coated polystyrene surfaces, partly depending on the size of bacterial aggregates that are formed in the presence of saliva.


Gynaecological and obstetrical bleeding in women with factor XI deficiency - a systematic review.
Menstrual bleeding, pregnancy and delivery present an intrinsic haemostatic challenge to women with bleeding disorders such as factor XI (FXI) deficiency. To provide a systematic overview of studies on gynaecological and obstetrical bleeding problems in women with FXI deficiency. We searched MEDLINE, EMBASE and the Cochrane library for studies that present original data on the incidence of and treatment options for gynaecological and obstetrical bleeding in FXI-deficient women. We identified 27 studies, including a total of 372 women with FXI deficiency. All studies were observational, no interventional treatment studies were found. Most patients had a mild deficiency (FXI ≥ 20 IU dL-1 ). Heavy menstrual bleeding (HMB) was reported in 7-67%. In 7/19 (37%) women who underwent gynaecological procedures, a bleeding complication occurred, including in 2/7 hysterectomies (29%). About 3-20% of reported pregnancies ended in a miscarriage; of these miscarriages 0-25% (4/23 miscarriages) were complicated by bleeding. Terminations of pregnancies (TOP) were complicated by bleeding in 4 out of 11 cases (36%). In 90 out of 498 (18%) deliveries a postpartum haemorrhage (PPH) was reported, ranging from 0 to 50% in individual studies. In 21% (66/321) of deliveries, prophylaxis was given. This was associated with 9% (6/66) PPH, compared to 19% in deliveries without prophylaxis (84/432). Epidural analgesia was performed without complications in 44 patients. Women with FXI deficiency have a clearly increased risk of HMB, and of bleeding complications after miscarriage, TOP and delivery. No high quality data are available regarding prophylactic treatment.


Associations of five food- and water-borne diseases with ecological zone, land use and aquifer type in a changing climate.
Food- and water-borne pathogens exhibit spatial heterogeneity, but attribution to specific environmental processes is lacking while anthropogenic climate change alters these processes. The goal of this study was to investigate ecology, land-use and health associations of these pathogens and to make future disease projections. The rates of five acute gastrointestinal illnesses (AGIs) (campylobacteriosis, Verotoxin- producing Escherichia coli, salmonellosis, giardiasis and cryptosporidiosis) from 2000 to 2013 in British Columbia, Canada, were calculated across three environmental variables: ecological zone, land use, and aquifer type. A correlation analysis investigated relationships between 19 climatic factors and AGI. Mean annual temperature at the ecological zone scale was used in a univariate regression model to calculate annual relative AGI risk per 1 °C increase. Future cases attributable to climate change were estimated into the 2080s. Each of the bacterial AGI rates was correlated with several annual temperature-related factors while the protozoan AGIs were not. In the regression model, combined relative risk for the three bacterial AGIs was 1.1 [95% CI: 1.02-1.21] for every 1 °C in mean annual temperature. Campylobacteriosis, salmonellosis and giardiasis rates were significantly higher (p < 0.05) in the urban land use class than in the rural one. In rural areas, bacteria and protozoan AGIs had significantly higher rates in the unconsolidated aquifers. Verotoxin-producing Escherichia coli rates were significantly higher in watersheds with more agricultural land, while rates of campylobacteriosis, salmonellosis and giardiasis were significantly lower in agricultural watersheds. Ecological zones with higher bacterial AGI rates were generally projected to expand in range by the 2080s. These findings suggest that risk of AGI can vary across ecosystem, land use and aquifer type, and that warming temperatures may be associated with an increased risk of food-borne AGI. In addition, spatial patterns of these diseases are projected to shift under climate change.


Oncologic safety of breast reconstruction with autologous fat grafting: A systematic review and meta-analysis.
Autologous fat grating has become increasingly popular as a breast reconstructive procedure. Nevertheless, preclinical studies show that fat transfer to a previous breast cancer site could activate latent cancer cells, creating a favourable environment for disease recurrence. A systematic review and meta-analysis was performed to investigate whether fat grafting increases the risk of locoregional recurrence in patients formerly treated for breast cancer. Based on PRISMA guidelines, a systematic review searching for randomised clinical trials and matched cohorts on the topic was performed in the electronic databases Pubmed, Embase, Web of Science, and Cochrane. The date of the last search was July 20, 2021. The meta-analysis assessed the comparison of locoregional recurrence between groups. From a total of 558 publications, data from nine matched cohorts (1.6%) reporting on 4247 subjects (1590 and 2657 subjects, respectively, in lipofilling and control groups) were suitable for inclusion in the meta-analysis. Neither of the outcomes had a statistically significant difference for disease recurrence. For the primary outcome, comparing locoregional recurrence rates between groups, the incidence rate ratio was 0.92 (95% CI: 0.68-1.26; P = 0.620). The present meta-analysis, which comprises the outcomes of the individual studies with the best current evidence on the topic so far, strengthens the evidence favouring the oncologic safety of lipofilling for breast reconstruction.


Exposure to smoking in movies and smoking initiation among black youth.
Black adolescents see more substance use in mainstream media but seem less responsive to it than other U.S. adolescents. Black-oriented media may be more personally relevant to them. To determine smoking exposure separately for black-oriented (BSME) and mainstream (MMSE) movies and assess their longitudinal relationships with smoking among black and other-race adolescents. Two-wave (2007-2009) national cohort survey of 2341 nonsmoking (at baseline) U.S. adolescents (aged 13-19 years), analyzed in 2012. The surveys determined BMSE and MMSE based on respondents' exposure to random subsets of 50 movies from a contemporary sample of 95 black-oriented and 288 mainstream movies previously content-coded for smoking. Outcome was smoking initiation. Black teens had significantly more BMSE and MMSE than other teens (p's <0.001). At follow-up, 23.5% of black and 29.0% of nonblack respondents had tried smoking. Among black respondents, BMSE was related to smoking initiation at follow-up but MMSE was not. For other adolescents, both BMSE and MMSE were related to smoking initiation. A prospective relationship was found between exposure to smoking in movies and smoking initiation. Among black adolescents in the U.S., this was only for black-oriented movies, suggesting the importance of personal relevance of the exposures. Parents, practitioners, and producers should be aware of these potential influences of media on black teen viewers.


Specificity of tumour associated transplantation antigens (TATA) of different clones from the same tumour.
The TATA of two clones from the same murine methylcholanthrene-induced fibrosarcoma have been investigated by immunizing syngeneic mice with irradiated cells of one or both clones and challenging them 14 days later with viable cells. The tumour had been induced in a female backcross CBA mouse heterozygous for the A and B alloenzymes of phosphoglycerate kinase-1 (PGK-1). One clone expressed A and the other B, and both A and B hosts were used in the experiments. Each clone was found to possess strong TATA but there was no demonstrable cross reactivity. The clonal composition of tumours produced by inoculating mice with a mixture of the two clones was profoundly altered by prior immunization with one of them. A second experiment was performed with 3 clones from another tumour; these expressed PGK-1 A, B and AB respectively. Again, there was no evidence of immunological cross reactivity between the A and B clones, but there was some cross reactivity between the A clone and AB clone. These results, coupled with previous observations of changes in the clonal composition of pleoclonal murine fibrosarcomas in culture and on transplantation, suggest that the antigenic specificity of these tumours is less stable than is commonly supposed.


Mechanism of rhodopsin phosphorylation.
A key reaction in the inactivation of rhodopsin is its phosphorylation by rhodopsin kinase. In recent years, extensive studies related to rhodopsin kinase function and enzymatic properties were carried out. Rhodopsin kinase is a Ser/Thr protein kinase and a member of the G protein-coupled receptor kinases sub-family (GRKs) which consists of six recently identified members. Photolyzed rhodopsin is phosphorylated by rhodopsin kinase sequentially, with the first phosphate transferred preferentially to Ser-338, and subsequent phosphates transferred to Ser-343 and Thr-336. The binding of arrestin to the receptor, and reduction of the photolyzed chromophore all-trans-retinal to all-trans-retinol limits physiologically significant phosphorylation at no more than three sites (H. Ohguro, R.S. Johnson, L.H. Ericsson, K.A. Walsh and K. Palczewski, Biochemistry, 33 (1994) 1023). A similar phosphorylation reaction is implicated in most, if not all, G protein-coupled receptors during their desensitization.


Exploring the regional pollution characteristics and meteorological formation mechanism of PM2.5 in North China during 2013-2017.
In the last decade, North China (NC) has been one of the most populated and polluted regions in the world. The regional air pollution has had a serious impact on people's health; thus, all levels of government have implemented various pollution prevention measures since 2013. Based on multi-city in situ environmental and meteorological data, as well as the meteorological reanalysis dataset from 2013 to 2017, regional pollution characteristics and meteorological formation mechanisms were analyzed to provide a more comprehensive understanding of the evolution of PM2.5 in NC. The domain-averaged PM2.5 was 79 ± 17 µg m-3 from 2013 to 2017, with a decreasing rate of 10 μg m-3 yr-1. Two automatic computer algorithms were established to identify 6 daily regional pollution types (DRPTs) and 48 persistent regional pollution events (PRPEs) over NC during 2014-2017. The average PM2.5 concentration for the Large-Region-Pollution type (including the Large-Moderate-Region-Pollution and Large-Severe-Region-Pollution types) was 113 ± 40 µg m-3, and more than half of Large-Region-Pollution days and PRPEs occurred in winter. The PRPEs in NC mainly developed from the area south of Hebei. The number of Large-Region-Pollution days decreased notably from 2014 to 2017, the annual number of days varying between 194 and 97 days, whereas a slight decline was observed in winter. In addition, the averaged PM2.5 concentrations and the numbers and durations of the PRPEs decreased. Lamb-Jenkinson weather typing was used to reveal the impact of synoptic circulations on PM2.5 across NC. Generally, the contributions of the variations in circulation to the reduction in PM2.5 levels over NC between 2013 and 2017 were 64% and 45% in summer and winter, respectively. The three most highly polluted weather types were types C, S and E, with an average PM2.5 concentration of 137 ± 40 µg m-3 in winter. Furthermore, three typical circulation dynamics were categorized in the peak stage of the PRPEs, namely, the southerly airflow pattern, the northerly airflow pattern and anticyclone pattern; the averaged relative humidity, recirculation index, wind speed and boundary layer height were 63%, 0.33, 2.0 m s-1 and 493 m, respectively. Our results imply that additional emission reduction measures should be implemented under unfavorable meteorological situations to attain ambient air quality standards in the future.


Novel Surgical Techniques to Control Flow With PreserFlo MicroShunt for Late Hypotony After Baerveldt Drainage Device Implantation.
We report a new surgical technique for controlling flow with a PreserFlo MicroShunt, in patients with late postoperative hypotony, following a Baerveldt glaucoma drainage device implantation. We present 2 cases with late postoperative hypotony after Baerveldt-shunt implantations. In both cases, the outflow resistance of the Baerveldt tube was modulated by the insertion of a PreserFlo MicroShunt into the lumen of the Baerveldt tube. In the first case, the Microshunt was inserted through the distal opening of the tube in the anterior chamber. In the second case, an end plate, sided approach was chosen after opening the conjunctiva. In both cases, the hypotony was successfully treated. The intraocular pressure rose immediately after the procedure, and it remained well controlled within the targeted range during the first postoperative months without additional pressure-lowering medication. This novel surgical technique provided predictable flow reductions, according to the Hagen-Poiseuille equation. This approach offers a valuable alternative to permanent tube ligation.


The Prevalence of Symptomatic Congenital Cytomegalovirus Disease in Korea; A 15-Year Multicenter Study and Analysis of Big Data From National Health Insurance System.
The birth prevalence of symptomatic congenital cytomegalovirus (cCMV) disease among live birth in Korea from a multicenter study was 0.06% during 2001-2015 with increasing frequency. The administrative prevalence of cCMV infection by big-data analysis from the national health insurance system was 0.01% and the average healthcare cost was US$2010 per person.


Effects of indomethacin on steroid-induced changes in pressor responsiveness in man.
1. It has been shown previously that hydrocortisone (F) increases pressor responsiveness in normal subjects. The present study examined the role of vasodilator prostanoids in determining these changes. 2. Pressor responsiveness to angiotensin II (AII) (1-8 ng/kg per min) and phenylephrine (PE) (0.3-0.9 microgram/kg per min) was examined in six normal men receiving: no treatment (day 1); 100 mg indomethacin p.o. (INDO) in three divided doses over 20 h (day 2); 200 mg F for 5 days, 50 mg 6 hourly p.o. (day 6); F plus 100 mg INDO (day 7). 3. Blood pressure, body weight and plasma glucose rose with F and plasma potassium fell. F alone produced significant increases in response to AII at 2 ng/kg per min, for systolic pressure (SBP), diastolic pressure (DBP) and mean arterial pressure (MAP), and at 1 ng/kg per min for DBP. The threshold for SBP, DBP and MAP rises with AII was decreased by F. Responses to PE following F were greater at 0.6 microgram/kg per min for SBP, DBP and MAP and the threshold for all parameters fell. 4. INDO alone had no significant blood pressure or metabolic effects and no effect on the magnitude of the blood pressure rise with AII, but decreased the threshold dose for effects on MAP. INDO had no effect on the magnitude of the pressure rise with PE, but decreased the threshold dose for effects on SBP. 5. INDO did not modify responsiveness or threshold to AII following F. Responsiveness to PE was unchanged and threshold fell for SBP only during INDO.(ABSTRACT TRUNCATED AT 250 WORDS)


Monitoring Plasma Membrane Injury-Triggered Endocytosis at Single-Cell and Single-Vesicle Resolution.
Plasma membrane injury activates membrane trafficking and remodeling events that are required for the injured membrane to repair. With the rapidity of the membrane repair process, the repair response needs to be monitored at high temporal and spatial resolution. In this chapter, we describe the use of live cell optical imaging approaches to monitor injury-triggered bulk and individual vesicle endocytosis. Use of these approaches allows quantitatively assessment of the rate of retrieval of the injured plasma membrane by bulk endocytosis as well as by endocytosis of individual caveolae following plasma membrane injury.


Long-term persistence of polychlorinated dibenzo-p-dioxins and dibenzofurans in air, soil and sediment around an abandoned pentachlorophenol factory in China.
Air, soils and sediments surrounding an abandoned pentachlorophenol (PCP) factory were sampled to determine the levels of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs), unintentionally formed during PCP production. The mean concentration of PCDD/Fs in ambient air was one order of magnitude higher than that of the reference site. A trend of decreasing concentrations with increasing distance from the factory was observed, suggesting this site has a significant influence on the regional ambient air. As for soil samples collected within 3 km from the factory and sediment samples from the adjacent rivers, high levels of contamination were found with WHO-TEQ concentrations of 193 ± 211 pg/g and 667 ± 978 pg/g, respectively. The PCDD/F homologue profiles of all samples were consistent with those found in the technical product of PCP, with OCDD as the dominant congener. These results indicate PCDD/Fs in the historical contaminated site pose a long-term impact on surrounding environment.


Protein S100B release from rat brain slices during and after ischemia: comparison with lactate dehydrogenase leakage.
One hour of ischemia significantly increased protein S100B release from rat brain slices without altering lactate dehydrogenase leakage. Reoxygenation of the ischemic slices, however, increased the levels of these biochemical markers in the medium. Although removal of extracellular Ca(+2) ions from the medium did not alter the basal lactate dehydrogenase leakage from cortical slices, an excessive increase in basal protein S100B release was seen under this condition. Ischemia and/or reoxygenation induced enhancements in these markers were attenuated by removal of Ca(+2) ions from the medium. Ischemia significantly increased glutamate release, but neither ischemia nor reoxygenation induced rises in protein S100B and lactate dehydrogenase levels were altered by glutamate receptor antagonists. Rising the glutamate levels in the medium by each ouabain or exogenous glutamate, moreover, failed in exerting an ischemia like effect on protein S100B and LDH outputs. In contrast, exogenous glutamate added into the medium protected the slices against reoxygenation induced increments in protein S100B and lactate dehydrogenase levels. These results indicate that protein S100B has a greater sensitivity against ischemia than lactate dehydrogenase in in vitro brain slice preparations. Since neither exogenous glutamate nor enhancements of the extracellular glutamate levels by ouabain had an ischemia like effect, and since glutamate receptor antagonists were also unsuccessful, it seems unlikely that ischemia-induced increase in glutamate release is directly involved in protein S100B release or lactate dehydrogenase leakage determined in the present study.


The engineering of a more thermally stable lactate dehydrogenase by reduction of the area of a water-accessible hydrophobic surface.
A site-directed mutant of Bacillus stearothermophilus lactate dehydrogenase (lactate:NAD+ oxidoreductase, EC 22.214.171.124) has been engineered in which the conserved hydrophobic residue isoleucine-250 has been replaced by the more hydrophilic residue asparagine. This isoleucine forms a large part of a water-accessible, hydrophobic surface in the active site of the apo-enzyme which is covered by the B-face of the nicotinamide ring when coenzymes are bound. Reduction in the area of this hydrophobic surface results in the mutant tetramer being more thermally stable than the wild-type enzyme.


High Thermoelectric Performance in n-Type Perylene Bisimide Induced by the Soret Effect.
Low-cost, non-toxic, abundant organic thermoelectric materials are currently under investigation for use as potential alternatives for the production of electricity from waste heat. While organic conductors reach electrical conductivities as high as their inorganic counterparts, they suffer from an overall low thermoelectric figure of merit (ZT) due to their small Seebeck coefficient. Moreover, the lack of efficient n-type organic materials still represents a major challenge when trying to fabricate efficient organic thermoelectric modules. Here, a novel strategy is proposed both to increase the Seebeck coefficient and achieve the highest thermoelectric efficiency for n-type organic thermoelectrics to date. An organic mixed ion-electron n-type conductor based on highly crystalline and reduced perylene bisimide is developed. Quasi-frozen ionic carriers yield a large ionic Seebeck coefficient of -3021 μV K-1 , while the electronic carriers dominate the electrical conductivity which is as high as 0.18 S cm-1 at 60% relative humidity. The overall power factor is remarkably high (165 μW m-1 K-2 ), with a ZT = 0.23 at room temperature. The resulting single leg thermoelectric generators display a high quasi-constant power output. This work paves the way for the design and development of efficient organic thermoelectrics by the rational control of the mobility of the electronic and ionic carriers.


A radioimmunoassay for metoclopramide.
A radioimmunoassay for the anti-emetic drug, metoclopramide, in the pmol range was developed. The immunogen was prepared by photolytic coupling of metoclopramide to bovine serum albumin. A crosslinking reagent, N-hydroxy-succinimidyl-4-azidobenzoate, was first reacted with serum albumin through nucleophilic substitution. Ultraviolet irradiation (lambda greater than 300 nm) of the photoactive serum albumin conjugate in the presence of metoclopramide resulted in covalent attachment of the drug to the protein. An 125I-labelled metoclopramide derivative was prepared by diazotisation of the aromatic amine group and substitution of the resultant diazo group with 125I-. Binding data of the antibody with radioiodinated metoclopramide gave a linear Scatchard plot indicative of a homogeneous antibody population. A dissociation constant of 3 X 10(-11) mol/l was calculated for the antigen-antibody interaction. The antibodies showed negligible cross-reactivity with lignocaine which is structurally closely related to metoclopramide.


Association Between Measures of Trunk Recovery 5 to 10 Weeks Postpartum and Pelvic Floor Support and Symptoms 1 Year Postpartum in Primiparas Delivered Vaginally.
To determine whether 2 aspects of trunk recovery after childbirth, intraabdominal pressure (IAP) generation and trunk flexor endurance (TFE), predict measures of pelvic floor health 1 year postpartum. In this prospective cohort study, we enrolled nulliparas in their third trimester and followed up those delivered vaginally for 1 year. We measured IAP while lifting a weighted car seat (IAPLIFT), IAP during TFE testing (IAPTFE), and TFE duration 5 to 10 weeks postpartum and assessed pelvic floor support and symptoms 1 year postpartum. Mean age of the 624 participants was 28.7 years. At 5 to 10 weeks postpartum, mean (SD) maximal IAPLIFT and IAPTFE were 47.67 (11.13) and 51.57 (12.34) cm H2O, respectively. Median TFE duration was 126 seconds (Interquartile range, 74-211). At 1 year postpartum, 9.3% demonstrated worse support (maximal vaginal descent at or below hymen) and 54% met criteria for symptom burden (bothersome symptoms in ≥2 domains of Epidemiology of Prolapse and Incontinence Questionnaire). In multivariable models, neither IAPLIFT nor IAPTFE were associated with worse support or symptom burden (P = 0.54-1.00). Trunk flexor endurance duration increased prevalence of worse support (prevalence ratio, 1.05; 95% confidence interval, 1.01-1.08) per 60-second increase, P = 0.005) but not symptom burden (prevalence ratio, 1.00; 95% confidence interval, 0.98-1.03; P = 0.92). These results provide some reassurance to early postpartum women, who are unlikely to perform routine activities that generate IAP far outside the range tested. Further research is needed to understand why women with long TFE durations have increased prevalence of worse support.


Antilipogenic but not lipolytic effects of recombinant DNA-derived bovine somatotropin treatment on ovine adipose tissue; variation with genetic type.
1. Lambs from three breeds (East Friesland, Oxford and Texel) were treated with recombinant DNA-derived bovine somatotropin (BST) at 0.05, 0.10, 0.20 mg/kg per day and fat metabolism assessed in subcutaneous adipose tissue biopsy samples. 2. BST treatment decreased adipose cell volume, fatty acid synthesis and acylglycerol glycerol synthesis but did not alter lipolytic rates (basal or noradrenaline-stimulated). 3. Genetic type influenced metabolism in a number of ways, most notably East Friesland lambs had lower fatty acid esterification rates and responded poorly to BST in terms of reduced lipogenesis as compared to the Oxford and Texel lambs. 4. Blood urea concentration was decreased by BST treatment suggesting increased nitrogen retention. 5. These results emphasise the role of somatotropin as an inhibitor of adipose tissue lipogenesis but cast further doubt on a physiological role in regulating lipolysis.


The polycystic ovary syndrome: a position statement from the Polish Society of Endocrinology, the Polish Society of Gynaecologists and Obstetricians, and the Polish Society of Gynaecological Endocrinology.
Polycystic ovary syndrome (PCOS) diagnosis and therapy still arouse a lot of controversy. Each year brings new information, so, having collected the experience of three scientific societies, we present contemporary recommendations concerning PCOS diagnostics and treat-ment. In adult female diagnosis, we still use the Rotterdam criteria, which is two out of three of the follwing characteristics: a) ovulation abnormality, b) clinical or biochemical hyperandrogenism, and c) polycystic ovaries. In the case of teenagers, diagnostic criteria are as follows: menstruation disturbances two years after menarche and clinical or biochemical hyperandrogenism. The presence of polycysti-cally abnormal ovaries is not necessary. The consensus paper presents the threats resulting from imperfect diagnostic methods applied in PCOS (hyperandrogenism diagnostics, ultrasound examination of ovaries). Suggested therapy includes personalised schemes according to the dominant PCOS phenotype, i.e. metabolic, hyperandrogenic, or reproductive ones.


Circadian rhythm regulation of the oxidation-antioxidant balance in Daphnia pulex.
Rhythmic changes in reactive oxygen species (ROS) levels with time have been previously reported, but circadian rhythmic changes in ROS levels in Daphnia pulex remain unexplored. Here, in light-dark (L/D 16:8, L/D 8:16), continuous light (LL), and continuous dark (DD) conditions were set up to analyze the accumulation of ROS and activity of antioxidant enzymes in D. pulex at different time points. We observed that ROS levels significantly varied from day to night. By fluorescence probe labeling, we noted that ROS majorly accumulated in the thoracic limbs, brood chamber, and rectum in D. pulex. In addition, in the L/D 16:8 and 8:16 groups, ROS level was negatively correlated to the gene expression level of catalase, glutathione S-transferase, and glutathione peroxidase. In the LL and DD groups, food supply emerged as a zeitgeber, driving D. pulex to maintain a specific biological rhythm. The ability to scavenge hydroxyl radicals and activity of antioxidant enzymes were also affected by L/D cycles. To summarize, we indicate that different L/D cycles can induce different oxidation-antioxidant system responses in D. pulex and that Daphnia can adapt to the living environment by circadian rhythm regulation of the oxidation-antioxidant balance.


Chlorine and heavy metals removal from municipal solid waste incineration fly ash by electric field enhanced oxalic acid washing.
Electric field enhanced oxalic acid (H2C2O4) washing was conducted to examine the simultaneously removal efficiency of heavy metals (HMs) and chlorine, especially insoluble chlorine from municipal solid waste incineration fly ash (MSW FA). Results show that chlorine and HMs can be effectively removed with a total chlorine, As, Ni and Zn removal rate of 99.10%, 79.08%, 75.42% and 71.43%, when the electrode exchange frequencies is 40 Hz, current density is 50 mA/cm2, H2C2O4 adding amount is 0.5 mol/L and the reaction time is 4 h. Insoluble chlorine removal efficiency is up to 95.32%, much higher than reported studies. And the chlorine content in the residue is lower than 0.14%. Meanwhile, HMs removal efficiency is remarkable, 41.62%-67.51% higher than that of water washing. The high-efficient removal effect is caused by the constantly changing direction of electrons hitting the fly ash surface, which provides more escape channels for internal chlorine and HMs. These results proved that electric field enhanced oxalic acid washing could be a promising method for removing contaminants from MSWI fly ash.


Release of methyl isocyanate from the antitumor agent caracemide (NSC-253272).
In recent phase 1 clinical trials, caracemide [N-acetyl-N-(methylcarbamoyloxy)-N-methylurea; NSC-253272] has demonstrated a marked potential to produce severe central nervous system (CNS) toxicity. Recent in vitro studies of this antitumor agent have presented indirect evidence indicating that methyl isocyanate is a likely metabolite which results from incubation of caracemide with either phosphate buffer or human plasma. This report presents evidence that methyl isocyanate is formed from caracemide in a concentration- and time-dependent manner. These data implicate the caracemide-mediated formation of methyl isocyanate as at least a plausible explanation for the CNS toxicity exhibited by this drug.


Abdominal cutaneous nerve entrapment syndrome: A cross sectional survey of treatment outcomes.
Abdominal Cutaneous Nerve Entrapment Syndrome (ACNES) is a common but under recognised cause of chronic abdominal wall Pain. This survey was carried out to understand the clinical course of the condition following interventions such as nerve blocks and surgical release of entrapped nerve. Retrospective, Cross-sectional survey. Pain Management clinic at University teaching hospital. Adult patients who had interventions either nerve block or surgical release over a 6 year period. After written informed consent, participants completed a questionnaire including Brief Pain Inventory (BPI), quality of health measure (EQ-5D-5L), and global impression of change scale as well as open-ended question about the outcomes. Baseline demographics, details of pain condition, interventions received were collected from the health records. The diagnosis of ACNES was established in 85.2% by ultrasound guided injections. The injection therapy with local anaesthetic and steroid was successful to 75.8% while the surgical release was successful in 90%. The cumulative duration of pain relief varied from 3 weeks to 5 years. A significant difference was noted in BPI (p = 0.001), EQ-5D-5L (p = 0.002) and health thermometer (p = 0.009) post interventions. Ultrasound guided injections aid the accurate diagnosis of ACNES. Appropriate treatment of ACNES improves both pain control and quality of life.


Biochemical and molecular investigation of thermal manipulation protocols during broiler embryogenesis and subsequent thermal challenge.
The aim of the current study was to evaluate the effect of different thermal manipulation (TM) protocols during embryogenesis on thermotolerance acquisition parameters during subsequent thermal challenge (TC) at posthatch day 28. A total of 1500 fertile chicken eggs were divided randomly into five treatments (300 eggs each): control was maintained at 37.8 °C and 56 % relative humidity (RH) whereas, TM1, TM2, TM3 and TM4 were subjected to 38.5, 39, 39.5 and 40 °C for 18 h and 65 % RH daily during embryonic days ED 12-18. Hatched chicks from each treatment group allocated randomly into two sub-treatment groups (thermo-neutral, naïve (TN) and thermal challenge (TC). At day 28 of age, chicks subjected to TC by adjusting room temperature to 42 °C for 6 h while naïve chicks kept under regular conditions (22 ± 1 °C and 50-60 % RH). Chick's response to TC evaluated by determination of plasma T3, T4, corticosterone, total proteins, albumin, selected enzymes and some electrolytes at the beginning (0 h) and after 1, 3 and 5 h of TC in TM and TN chicks. Furthermore, pectoral and thigh muscles mRNA expression of Atrogin-1, CK, avUCP, DIO3, DIO2 were evaluated in TC and TN sub-treatment groups. TM induced a significant reduction in free T3 and elevation in total proteins and albumin in plasma with significant down-regulation of Atrogin-1 and DIO2 and significant up-regulation of DIO3 mRNA expression in muscle of TM chicks compare to control. During TC at day 28, decrease in the concentrations of plasma free T3, total proteins and albumin with increase in T4 have been detected in control and TM chicks. TC induced up-regulation of Atrogin-1 and DIO3 with down-regulation of DIO2 gene expression in muscles of all TC chicks. The present study indicated that, TM improved thermotolerance acquisition by decreasing basal metabolic rate and muscle injury during thermal stress. Basal metabolic rate decreased via reduction of plasma T3 concentration with up and down regulation of expression of DIO3 and DIO2, respectively in muscles. Muscle injury protected by stimulation of protein biosynthesis and down-regulation of Atrogin-1 expression.


The preventive reduction of psychological risk in asymptomatic adolescents.
To explore the preventive efficacy of training in coping and social skills, 121 high school students were assigned to four risk classifications, assessed by measures of psychological vulnerability and environmental adversity; within each group, subjects were randomly assigned to a preventive intervention or assessment-only control condition. Findings suggest that group behavioral training can be a beneficial and economical preventive approach with symptom-free high school students, and that training in social skills may benefit those with behavior problems that presage maladjustment.


Brain pericytes serve as microglia-generating multipotent vascular stem cells following ischemic stroke.
Microglia are the resident macrophage population of the central nervous system (CNS) and play essential roles, particularly in inflammation-mediated pathological conditions such as ischemic stroke. Increasing evidence shows that the population of vascular cells located around the blood vessels, rather than circulating cells, harbor stem cells and that these resident vascular stem cells (VSCs) are the likely source of some microglia. However, the precise traits and origins of these cells under pathological CNS conditions remain unclear. In this study, we used a mouse model of cerebral infarction to investigate whether reactive pericytes (PCs) acquire microglia-producing VSC activity following ischemia. We demonstrated the localization of ionized calcium-binding adaptor molecule 1 (Iba1)-expressing microglia to perivascular regions within ischemic areas. These cells expressed platelet-derived growth factor receptor-β (PDGFRβ), a hallmark of vascular PCs. PDGFRβ(+) PCs isolated from ischemic, but not non-ischemic, areas expressed stem/undifferentiated cell markers and subsequently differentiated into various cell types, including microglia-like cells with phagocytic capacity. The study results suggest that vascular PCs acquire multipotent VSC activity under pathological conditions and may thus be a novel source of microglia.


Langerhans Cell Histiocytosis Presenting as Progressively Worsening Neck Pain: A Case Report With a Review of Literature.
A 29-year-old female with past medical history of chronic serous otitis media presented with worsening neck stiffness and pain over a period of 2 weeks. The patient described non-specific symptoms that were localized to the right side of her neck. She presented to the hospital only when the pain was so extreme that it limited her range of motion. The differential for acute neck pain without fever, chills or any inciting trauma is vast. They include medical emergencies such as meningitis, acute coronary syndromes and extend to rheumatologic diseases or simply musculoskeletal strain. On review of systems, she denied dizziness, headache, vision changes, dysphagia, or other facial pain. Based on the severity of her pain, she underwent a Computed Tomography scan of the neck, which was concerning for erosive calavarial lesions. Further imaging revealed multiple lytic foci and erosions from the right maxillary sinus to the right mandible to the C1 vertebra. Following requisite surgical intervention, she was found to have Langerhans cell histiocytosis, a rare disease of myeloid cells, usually affecting pediatric populations. Little is known about the adult manifestations of Langerhans Cell Histiocytosis. This review contributes to broadening the literature on this topic which can present with complaints as typical as neck pain.


Pharmacokinetics of isosorbide dinitrate, isosorbide-2-nitrate and isosorbide-5-nitrate in renal insufficiency after repeated oral dosage.
The pharmacokinetics of isosorbide dinitrate (ISDN) and its two active metabolites isosorbide-2-nitrate (IS-2-N) and isosorbide-5-nitrate (IS-5-N) were studied in 20 patients with normal and impaired renal function after repeated oral doses of standard 20 mg tablets ISDN t.i.d. Blood samples were taken in the steady-state on days 2 and 14, and the plasma concentrations were measured by electron capture capillary gas chromatography. We found a wide variation of pharmacokinetic parameters (AUCss0-8 and t1/2) of ISDN, IS-2-N, and IS-5-N in our patients. No correlation was detected between AUCss0-8 or t1/2 and the degree of renal insufficiency. No drug accumulation was observed after 14 days of administration.


Detection of hepatitis C viral RNA in sporadic acute non-A, non-B hepatitis by polymerase chain reaction. Its usefulness for the early diagnosis of seronegative infection.
To determine the prevalence of hepatitis C viral infection in patients with sporadic non-A, non-B (NANB) acute hepatitis, hepatitis C viral RNA was studied in the plasma of 15 patients by reverse transcription-polymerase chain reaction assay. Plasma samples were sequentially obtained from 15 patients, and polymerase chain reaction was performed with two nested pairs of primers deduced from the 5'-non-coding region of hepatitis C viral sequences. Anti-C100 and anti-GOR antibodies were also measured with an enzyme-linked immunosorbent assay system. Plasma hepatitis C viral RNA was detected transiently in 7 of 15 patients (47%) at an early phase of the clinical course, while anti-C100 antibodies were detectable in only 2 (29%) of hepatitis C viral RNA-positive patients, and in 1 (13%) of the negative patients. Of 7 patients that were positive for plasma hepatitis C viral RNA, 4 (57%) had relapsing or protracted courses. In contrast, in all patients with undetectable hepatitis C viral RNA, hepatitis C viral RNA recovered and remained normal for at least 1 year. Thus, hepatitis C viral infection represents almost half the patients with acute sporadic NANB hepatitis, and detection of hepatitis C viral RNA in an early clinical phase is superior to anti-C100 measurement for diagnosing acute sporadic hepatitis C viral infection.


Lead and mercury mutagenesis: type of mutation dependent upon metal concentration.
Lead and mercury are toxic metals that are widely distributed in the atmosphere, soil, and groundwater. It is estimated that 2-4 x 10(4) tons of these metals are released annually into the environment by natural and industrial processes. Therefore, human exposure to low relatively nontoxic concentrations of these metals is unavoidable. However, the possible health effects of such exposure remain controversial. We have previously reported that low, subthreshold concentrations (0.1-1 microM) of these metals are mutagenic in the transgenic Chinese hamster ovary cell line AS52. The purpose of the present study is to determine the types of mutations induced in the gpt gene in AS52 cells. Using multiplex polymerase chain reaction and southern blot analyses, we characterized the 138 lead-induced, 192 mercury-induced, 29 reactive oxygen radical-induced, and 20 spontaneously arising mutants for point and deletion mutations in the gpt gene. Similar levels of point mutations were observed in the lead- and mercury-induced populations (47.8 and 53.6, respectively), which was significantly less than that occurring in the spontaneously arising and reactive oxygen intermediate-induced mutants. However, further examination of the data revealed that at concentrations of the metals of equal to or less than 0.4 microM, the majority of the mutations in the gpt gene were point mutations, while at higher concentrations, deletions (partial and complete) were the predominant type of mutation. These results are consistent with the hypothesis that lead and mercury induce mutations in eukaryotic cells by at least two distinct mechanisms.


Optimizing carbon emission forecast for modelling China's 2030 provincial carbon emission quota allocation.
Rational allocation of carbon quotas is the fundamental premise for the orderly operation of carbon markets. To achieve the set target of carbon peak by 2030, there is an urgent need to establish China's 2030 provincial carbon quota allocation scheme. Although some proposed schemes have been formulated, there are problems with the methods used for carbon emission forecasting and evaluating the rationality of a proposed allocation scheme. This study aimed to optimize carbon emission forecast by incorporating terrestrial carbon sinks into the mechanism for building China's 2030 provincial carbon emission quota allocation schemes. Aquila Optimizer's Double Support Vector Regression (AO-based TWSVR) that has the advantages in solving problems associated with small sample size, nonlinear and high-dimensional pattern recognition with fast training speed and insensitivity to noise was adopted to predict the net carbon emission. The results show that the application of AO-based TWSVR model allows satisfactory forecast of the net carbon emission in China for the period from 2021 to 2035. This allowed terrestrial carbon sequestration being incorporated into the mechanism to formulate China's 2030 provincial carbon quota allocation schemes. Comparison of the three provincial carbon quota allocation schemes using social network analysis suggests that the equity-based carbon quota allocation scheme is more suitable for China's national conditions compared to the efficiency-based scheme and the combined principle-based scheme. The findings obtained from this study have implications for optimizing the scheme of China's 2030 provincial carbon quota allocation.


The Effects of Aversive Mood State on the Affective Anticipation and Perception: An Event-Related Potential Study.
Deficits in the anticipation and experience of affective events represent a key risky factor for a variety of mental disorders, such as anxiety and depression. Here, we examined temporal dynamics underlying the modulations of the aversive mood state on neural responses of anticipating and perceiving affective pictures. Participants were asked to perform an affective cueing paradigm in both threat and safe contexts. In the task, a cue (S1) signaled the subsequent presentation of positive/negative event (e.g., happy or fearful faces) as an affective target stimulus (S2), and participants were instructed to indicate their subjective feelings in response to the target stimuli while electroencephalography (EEG) was recording. Our findings revealed that threat context compared with the safe context attenuated the contingent negative variation (CNV) responses to the cues of positive expressions, and decreased differential late positive potential (LPP) responses to the perception of negative and positive events. These findings suggest that aversive mood dampens the anticipation of positive events and inhibits the elaboration of negative events. The current findings do not only advance our understanding on the temporal characteristics of affective anticipation and experience but also have implications on the emotional deficits across various mental disorders characterized by chronic mood disturbances.


Aging influences cerebrovascular myogenic reactivity and BK channel function in a sex-specific manner.
The myogenic reactivity of the middle cerebral arteries (MCA) protects the brain by altering the diameter in response to changes in lumen pressure. Large conductance potassium (BK) channels are known to regulate the myogenic reactivity, yet, it is not clear how aging alters the myogenic reactivity via the BK channel in males and females. Thus, we hypothesize that age-associated changes in BK channel subunits modulate the myogenic reactivity in a sex-specific manner. We used vascular reactivity, patch-clamp, and biochemical methods to measure myogenic reactivity, BK channel function, and expression, respectively in cerebral vessels of adult and aged male and female Sprague Dawley rats. Our results suggest that aging and ovariectomy (OVX) exaggerated the myogenic reactivity of MCA in females but attenuated it in males. Aging induced outward eutrophic remodelling in females but inward hypertrophic remodelling in males. Aging decreased total, Kv, BK channel currents, and spontaneous transient outward currents (STOC) in vascular smooth muscle cells isolated from females, but not in males. Aging increased BKα subunit mRNA and protein both in males and females. However, aging decreased BKβ1 subunit protein and mRNA in females only. In males, BKβ1 mRNA is increased, but protein is decreased. Iberiotoxin-induced MCA constriction is lower in aged females but higher in aged males. Activation of BKα (10 µM NS1619) and BKβ1 (10 µM S-Equol) subunits failed to increase STOCs and were unable to decrease the myogenic reactivity of MCA in aged female but not in aged male rats. OVX decreased, but chronic supplementation of oestradiol restored BK channel expression and function. Overall our results suggest that aging or OVX-associated downregulation of the BKβ1 expression and function in females results in exaggerated myogenic reactivity of MCA. However, age-associated increase in BK channel function in males attenuated myogenic reactivity of MCA.


Direct immunofluorescence findings in peripheral nerve from patients with diabetic neuropathy.
Direct immunofluorescence examination was performed on peripheral nerve from 16 patients with diabetes mellitus and 53 additional patients with peripheral neuropathy of diverse cause. Six nerves from patients with diabetes mellitus yielded positive findings: 4 had granular and lamellar deposition of IgM within the perineurium (of which 2 also had fibrinogen, IgA, C3, and albumin and 1 also had IgG); 1 had IgM, C3, and C4, and perineurial fibrinogen; the sixth contained linear perineurial C3 and fibrinogen. These 6 nerves contained axonal degeneration (3), axonal degeneration with chronic demyelination (1), microvasculitis with wallerian degeneration (1), and no pathological change (1). Sixteen of 53 nerves from nondiabetics yielded positive findings with immunofluorescence, possibly as a result of vascular leakage or as a manifestation of impaired removal of plasma proteins. The deposition of immunoreactants, as well as other plasma proteins, in peripheral nerve from patients with diabetes mellitus probably represents a "trapping" phenomenon reflecting altered basement membrane permeability. Alternatively, the changes could reflect a defect in the blood-nerve barrier in diabetic microangiopathy.


Characterization of the novel HLA-DRB1*11:296 allele by two next-generation sequencing methods.
The novel HLA-DRB1*11:296 allele was characterized using two next generation sequencing technologies.


Retraction: Overexpression of SERCA2a alleviates cardiac microvascular ischemic injury by suppressing Mfn2-mediated ER/mitochondrial calcium tethering.
[This retracts the article DOI: 10.3389/fcell.2021.636553.].


3D power Doppler ultrasound in early diagnosis of preeclampsia.
Preeclampsia is a known cause of maternal, fetal and neonatal morbidity and mortality. Thus, evaluation of the predicting value of comparing 3D power Doppler indices (3DPD) of uteroplacental circulation (UPC) in the first and second trimester in patients who developed preeclampsia (PE) and those who did not and testing the hypothesis that the parameters of vascularization and placenta flow intensity, as determined by three-dimensional ultrasound (3D), are different in normal pregnancies compared with preeclampsia, could be a suitable screening method. A prospective observational study using 3D power Doppler were performed to evaluate the placental perfusion in 96 pregnant women who came to do the ultrasound routine between 11 and 14 weeks. The placental vascular index (VI), flow index (FI), blood vessels and blood flow index (VFI) by three-dimensional Doppler histogram were calculated. All patients repeated the exam between 16 and 20 weeks. The outcome was scored as normal or preeclamptic. Placental vascular indices including VI, FI and VFI were significantly lower in preeclamptic placentas compared with controls in the study performed in the second trimester (p<0.001). There was not any statistical difference in the patients examined in the first trimester. Our findings suggest that 3D-power Doppler assessment of placental vascular indices in the second trimester has the potential to detect women at risk for subsequent development of PE.


Centromere 3 specific tandem repeat from Chironomus pallidivittatus.
A 155-bp tandem repeat was previously reported to be present in all centromeric regions of the dipteran Chironomus pallidivittatus. We have now isolated a second centromere specific tandem repeat, 375 bp long. Two blocks were found of the new unit, differing in size, probably representing allelic forms. The repeat is present only in chromosome 3, bordering 155-bp repeat arrays. There are about 100 repeats per genome, compared to 1300 units for the 155-bp repeat. The two units contain an identical 9-bp sequence which can form target-site duplications flanking a short mobile element, Cp1. An inversion within the tandem array was isolated, the breakpoint of which is within the 9-bp target sequence. Another short shared motif, 10-bp long, is also present at the insertion site for a mobile element. The two repeat units are similar in having long regions with more than 80% AT and an overall high AT content.


Evaluation of Bar and Nightclub Intervention to Decrease Young Adult Smoking in New Mexico.
Over 20% of young adults in New Mexico currently smoke. We evaluated cigarette smoking prevalence of young adult bar patrons during an anti-tobacco Social Branding intervention. The Social Branding intervention used a smoke-free brand, "HAVOC," to compete with tobacco marketing within the "Partier" young adult peer crowd. A series of cross-sectional surveys were collected from adults aged 18-26 in bars and nightclubs in Albuquerque, New Mexico, from 2009 to 2013 using randomized time-location sampling. Multivariable multinomial regression using full information maximum likelihood estimation to account for missing data evaluated differences in daily and nondaily smoking during the intervention, controlling for demographics, other risk behaviors, and tobacco-related attitudes. Data were collected from 1,069 individuals at Time 1, and 720, 1,142, and 1,149 participants at Times 2, 3, and 4, respectively. Current smoking rates decreased from 47.5% at Time 1 to 37.5% at Time 4 (p < .001). Among Partiers, the odds of daily smoking decreased significantly, but nondaily smoking was unchanged. Partiers that recalled, liked, and understood the smoke-free message of HAVOC had lower odds of nondaily (odds ratio: .48, 95% CI: .31-.75) and daily (odds ratio: .31, 95% CI: .14-.68) smoking than those who did not recall HAVOC. HAVOC recall was associated with attitudes that were also associated with smoking behavior. The significant decrease in daily smoking among young adult Partiers in New Mexico was associated with HAVOC recall and understanding. Social Branding interventions efficiently target and may decrease tobacco use among young adult bar patrons.


In-utero idiopathic ductal constriction: a prenatal manifestation of Alagille and Williams syndrome arteriopathy.
Williams and Alagille syndromes are genetic disorders associated with pathologic arterial narrowing. We hypothesized that fetal idiopathic ductus arteriosus (DA) constriction may represent a prenatal manifestation of the arteriopathy associated with these syndromes. Multi-institutional case series review of the pre- and postnatal medical records, echocardiograms, and genetic test results of fetuses presenting with idiopathic DA constriction. We identified four cases of idiopathic fetal DA constriction at 21-36 weeks of gestation. All had right ventricular hypertension, dilation, hypertrophy, and dysfunction and either DA constriction or absence. All demonstrated progressive peripheral pulmonary artery stenosis after birth. Three met clinical diagnostic criteria for Alagille syndrome; two tested had confirmatory JAG1 mutations. One also developed supravalvar aortic stenosis after birth and was positive for 7q11.23 deletion (Williams syndrome). This is the first case series to suggest that idiopathic fetal DA constriction may be a prenatal manifestation of genetic arteriopathy.


Taxanes in paediatric oncology: and now?
Taxanes are a group of anticancer agents that target microtubules, promote their assembly, and stabilize them. The resulting effects are mitotic blockage and induction of apoptosis, whose mechanism of initiation remains to be fully determined. Among adults, taxanes are one of the most powerful and most commonly used anticancer drugs. They show a wide range of activity in malignancies such as breast, ovarian, and lung cancers. In paediatric oncology, pre-clinical and clinical data are quite limited. Six phase I studies, two phase II, and rare case reports have been published. This review will focus on the paediatric pre-clinical and clinical findings with taxanes. Based on data from the literature, we will try to explain the results and foresee the possible use of taxanes in paediatric oncology. Indeed, three main advances have been made regarding taxanes: (1) Increased efficacy when used in multidrug-based chemotherapy regimen. (2) New administration schedules based on anti-angiogenic properties when given at daily very low doses. (3) Development of new taxanes with decreased recognition by Pgp, the product of the MDR1 gene. Thus, although the initial experience with taxanes in paediatric oncology has been disappointing, it may be too early to leave out taxanes and we should further investigate their use among children with cancer.


Wilson disease.
Wilson disease is a recessively inherited disorder of copper transport. Clinical features are highly variable, with any combination of neurological, hepatic or psychiatric illness. The age of onset varies from 3 to 50 years of age. Diagnosis is challenging because no specific combination of clinical or biochemical features is necessarily definitive. The genetic defect is due to a variety of abnormalities in a copper-transporting membrane ATPase. Most of the more than 80 mutations are present at a low frequency, and mutations differ between ethnic groups. At least two mutations are sufficiently common to aid in rapid diagnosis, in European and Asian populations respectively. Molecular analysis can provide a definitive diagnosis for asymptomatic sibs. Treatment, using chelating agents or zinc, is most effective when started before permanent tissue damage occurs.


Genetic diagnosis of PLP gene duplications/deletions in patients with Pelizaeus-Merzbacher disease.
Genetic diagnosis of PLP gene duplications/deletions in patients with Pelizaeus-Merzbacher disease.PMD is an X-linked recessive disorder due to a proteolipid protein (PLP) deficiency. Duplications of PLP gene were shown to be the principle cause of the disorder, accounting for an estimated 50-70% of cases. To define a simple and reliable method for genetic diagnosis of PMD, a group of 42 patients with clinical manifestation of PMD was analyzed by means of real-time quantitative PCR. Parallel fluorescence in situ hybridization (FISH) analysis was performed on the same group of patients. Real-time PCR found seventeen samples had increased gene dosage, whereas FISH detected sixteen duplicated samples. Both methods identified a sample with PLP gene deletion. Our results indicate that real-time PCR is a sensitive and reliable method for the detection of gene duplications/deletions. We further discussed the advantages and limitations of each method in clinical diagnosis of PMD.


Significant Decrease in Pertactin-Deficient Bordetella pertussis Isolates, Japan.
Prevalence of pertactin-lacking Bordetella pertussis isolates has been observed worldwide. In Japan, however, we found that the frequency of pertactin-deficient isolates in 2014-2016 (8%) was significantly lower than the frequency in 2005-2007 (41%), 2008-2010 (35%), and 2011-2013 (25%). This reduction was closely associated with changes in genotypes.


Registry of left atrial appendage closure and initial experience with intracardiac echocardiography.
Percutaneous closure of the left atrial appendage (LAA) is a promising therapy in patients with atrial fibrillation with high risk for stroke and contraindication for oral anticoagulation (OAC). Intracardiac echocardiography (ICE) may make this percutaneous procedure feasible in patients in whom transesophageal echocardiography (TEE) is inadvisable. Our aim was to assess the efficacy and safety of LAA closure and the feasibility of ICE compared to TEE to guide the procedure. In this cohort study of patients who underwent LAA closure between May 2010 and January 2017, clinical and imaging assessment was performed before and after the procedure. In 82 patients (mean age 74±8 years, 64.4% male) the contraindications for OAC were severe bleeding or anemia (65%), high bleeding risk (14%), labile INR (16%), or recurrent embolic events (5%). The procedural success rate was 96.3%. The procedure was guided by TEE or ICE, and no statistically significant differences were observed between the two techniques. During follow-up, one patient had an ischemic stroke at 12 months, two had bleeding complications at six months, and there were four non-cardiovascular deaths. Embolic and bleeding events were less frequent than expected from the observed CHA2DS2VASc (0.6% vs. 6.3%; p<0.001) and HAS-BLED (1.2% vs. 4.1%; p<0.001) risk scores. In this population percutaneous LAA closure was shown to be safe and effective given the lower frequency of events than estimated by the CHA2DS2VASc and HAS-BLED scores. The clinical and imaging results of procedures guided by ICE in the left atrium were not inferior to those guided by TEE.


Intravitreal administration of recombinant human opticin protects against hyperoxia-induced pre-retinal neovascularization.
Opticin is an extracellular glycoprotein present in the vitreous. Its antiangiogenic properties offer the potential for therapeutic intervention in conditions such as proliferative diabetic retinopathy and retinopathy of prematurity. Here, we investigated the hypothesis that intravitreal administration of recombinant human opticin can safely protect against the development of pathological angiogenesis and promote its regression. We generated and purified recombinant human opticin and investigated its impact on the development and regression of pathological retinal neovascularization following intravitreal administration in murine oxygen-induced retinopathy. We also investigated its effect on normal retinal vascular development and function, following intravitreal injection in neonatal mice, by histological examination and electroretinography. In oxygen-induced retinopathy, intravitreal administration of human recombinant opticin protected against the development of retinal neovascularization to similar extent as aflibercept, which targets VEGF. Opticin also accelerated regression of established retinal neovascularization, though the effect at 18 h was less than that of aflibercept. Intravitreal administration of human recombinant opticin in neonatal mice caused no detectable perturbation of subsequent retinal vascular development or function. In summary we found that intraocular administration of recombinant human opticin protects against the development of pathological angiogenesis in mice and promotes its regression.


A magnetic urethral closure device: preliminary report of an experimental study.
The new magnetic urethral closure system consists of a retropubically implanted magnet and another removable intravaginal magnet, thus gently closing the urethra. The device has shown its proper function in 12 sheep during a period of observation of up to 33 weeks. There were no technical defects. The pressure on the tissue can be modulated by the size and strength of the removable magnet and the pressure action time can easily be limited to the actual needs of the patient. Necrosis of the vagina wall and urethra have not been observed, using smooth-edged magnets.


Retraction.
Retraction: "Upregulated expression of ROCK1 promotes cell proliferation by functioning as a target of miR-335-5p in non-small cell lung cancer," by Haicheng Tang, Wenwen Du, Yongqian Jiang, Hongmiao Li, Hongjian Bo, and Shu Song. The above article, published online in Journal of Cellular Physiology on 29 May 2019 in Wiley Online Library (https://onlinelibrary.wiley.com/doi/10.1002/jcp.28886) has been retracted by agreement between the authors, the journal's Editor in Chief, Prof. Dr. Gregg Fields, and Wiley Periodicals LLC. The authors asked for a retraction and stated that unintentional errors occurred during the research process, so that the experimental results cannot be verified. Thus, the conclusions are considered to be invalid. The authors were not available to approve the retraction text after the investigation was concluded.


Effects of preweaning doxazosin treatment on adult pressure in the spontaneously hypertensive rat.
1. The neonatal/preweaning period appears to represent a critical period of involvement of the sympathetic nervous system in the development of hypertension in spontaneously hypertensive rats (SHR). 2. We tested whether alpha1-adrenoceptor-mediated effects during the preweaning period are involved in the development of hypertension in the adult SHR. 3. Male SHR were treated with the alpha1-adrenoceptor antagonist doxazosin (10 mg/kg per day, s.c.) from postnatal day 1 to 21 inclusive. Direct conscious blood pressure and heart rate were measured via the caudal artery at 12 weeks of age. 4. Preweaning treatment with doxazosin had no significant effect on mean arterial blood pressure or heart rate in male SHR at 12 weeks of age. 5. These findings do not support the involvement of alpha1-adrenoceptor-mediated effects during the preweaning period in the development of hypertension in adult SHR.