Autogenic training reduces anxiety after coronary angioplasty: a randomized clinical trial.
Autogenic training (AT) is a method of autosuggestion with some potential for reducing anxiety. This study tests whether AT lowers anxiety levels experienced by patients undergoing coronary angioplasty. Fifty-nine patients were randomly assigned to receive regular AT or no such therapy as an adjunct to standard care for 5 months. The primary outcome measure was State Anxiety at 2 months. Qualitative information was generated by face-to-face interviews. State Anxiety showed a significant intergroup difference both at 2 and 5 months. This finding was corroborated by secondary outcome measures, for example, quality of life, and by qualitative information about patients' experiences. The results do not allow us to determine whether the observed effects are specific to AT or of a nonspecific nature. Our results suggest that AT may have a role in reducing anxiety of patients undergoing coronary angioplasty.


In vitro anti-uveal melanoma activity of phenolic compounds from the Egyptian medicinal plant Acacia nilotica.
Anti-uveal melanoma activity-guided fractionation of the MeOH extract of Acacia nilotica pods resulted in the isolation of the new compound gallocatechin 5-O-gallate in addition to methyl gallate, gallic acid, catechin, catechin 5-O-gallate, 1-O-galloyl-β-D-glucose, 1,6-di-O-galloyl-β-D-glucose and digallic acid. The structures of the isolated compounds were elucidated on the basis of HRESIMS, NMR spectroscopy and CD data. In addition to uveal melanoma, the antiproliferative activities of the isolated compounds and the related compound epigallocatechin 3-O-gallate (EGCG) were evaluated against cutaneous melanoma, ovarian cancer, glioblastoma and normal retinal pigmented cells.


Health-related quality of life in breast cancer patients treated with CDK4/6 inhibitors: a systematic review.
Evaluation of health-related quality of life (HR-QoL) among cancer patients has gained an increasing importance and is now a key determinant of anticancer treatments' value. HR-QoL has been assessed in trials testing cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) in breast cancer (BC), using various questionnaires at different timepoints. HR-QoL reports from BC patients treated with CDK4/6i in the real-world setting are also available. We systematically reviewed the literature, searching for full-length articles, and selected conference abstracts reporting data on HR-QoL in BC patients at any stage and of any molecular subtype treated with abemaciclib, palbociclib or ribociclib. A total of 533 full-length articles and 143 abstracts were retrieved. After screening for eligibility, 38 records were included (31 clinical trials; 7 real-world reports). Assessment methods were heterogeneous across studies in terms of questionnaires, evaluation timepoints and endpoints. Overall, adding CDK4/6i to endocrine therapy did not worsen patients' HR-QoL, with a positive trend towards pain improvement. Gastrointestinal scores (diarrhea, nausea and appetite loss) statistically favored the control arm among metastatic BC patients receiving abemaciclib, whereas they were superimposable in the early setting. The combination of palbociclib and endocrine therapy showed similar HR-QoL outcomes compared with endocrine therapy alone, but determined better scores compared with chemotherapy. HR-QoL was specifically assessed in premenopausal patients treated with ribociclib, showing similar scores compared with postmenopausal patients. Despite methodological heterogeneity does not allow a proper comparison, HR-QoL was generally maintained with CDK4/6i. However, differences between abemaciclib, palbociclib and ribociclib exist and mainly rely on the distinct safety profiles of the compounds. These differences should be acknowledged and taken into account in the clinical practice.


Limiting factors for seed production in Cynoglossum officinale.
Over three years of study, small plants of Cynoglossum officinale consistently produced more flowers per unit of dry weight than large plants. In contrast to earlier results, weight of all seeds tended to increase more than proportional to size. As a result a positive correlation existed between seed set per flower and plant size. The correlation between the mean number of pollinator visits per flower and size was positive but not significant. In a field experiment we found that resources rather than pollen were limiting seed set. Thus, it is unlikely that enhanced pollination of the largest plants causes the size-dependency of seed set per flower. Alternative hypotheses are discussed briefly.


Investigation of physicochemical properties of Bulgarian strain 258 of enterovirus type 71. Brief report.
In the present report some general physicochemical properties and RNA characteristics of strain 258 of enterovirus (EV) 71, isolated in 1975 from cases of poliomyelitis-like disease in Bulgaria (1), are described. It is concluded, that the features of the virus are consistent with the previous identification, based on biological studies, of this virus strain as a member of enterovirus subgroup of picornaviridae family.


In vitro susceptibility of Gabonese wild isolates of Plasmodium falciparum to artemether, and comparison with chloroquine, quinine, halofantrine and amodiaquine.
The in vitro activity of artemether against 63 African isolates of Plasmodium falciparum from Libreville, Gabon was evaluated using an isotopic drug susceptibility semi-microtest. The 50% inhibitory concentration (IC50) values for artemether were in a narrow range from 0.8 to 34.8 nM (mean IC50 5.0 nM) and the 95% confidence interval (CI95%) was 3.6-6.3 nM. In vitro decreased susceptibility or resistance were observed with artemether (14%), to chloroquine (90%), to quinine (32%). Isolate susceptibility to amodiaquine and halofantrine was high i.e. 100% and 98%, respectively. There was a significant positive correlation between responses to artemether and amodiaquine (r2 = 0.45, P < 0.001), artemether and chloroquine (r2 = 0.36, P < 0.001), artemether and quinine (r2 = 0.31, P < 0.001), and artemether and halofantrine (r2 = 0.19, P < 0.01). Positive correlation between these drugs suggests in vitro cross-resistance or at least common features in drug uptake and/or mode of action or resistance.


In vitro effects of new artemisinin derivatives in Neospora caninum-infected human fibroblasts.
From a panel of 34 artemisinin derivatives tested in vitro, artemisone, GC007 and GC012 were most efficacious at inhibiting Neospora caninum replication (IC50 values of 3-54nM), did not notably impair the invasiveness of tachyzoites and were non-toxic for human foreskin fibroblasts (HFFs). Transmission electron microscopy of drug-treated N. caninum-infected HFFs demonstrated severe alterations in the parasite cytoplasm, changes in the composition of the matrix of the parasitophorous vacuole (PV) and diminished integrity of the PV membrane. To exert parasiticidal activity, parasites had to be cultured continuously in the presence of 5μM artemisone or GC007 for 3 weeks. N. caninum tachyzoites readily adapted to a stepwise increase in concentrations (0.5-10μM) of GC012, but not to artemisone or GC007. Drugs induced the expression of elevated levels of NcBAG1 and NcSAG4 mRNA, but only NcBAG1 could be detected by immunofluorescence. Thus, artemisinin derivatives represent interesting leads that should be investigated further.


Serotonin is the main tryptophan metabolite associated with psychiatric comorbidity in abstinent cocaine-addicted patients.
The lack of effective treatments and a high rate of relapse in cocaine addiction constitute a major health problem. The present study was conducted to examine the expression of tryptophan-derived metabolites in the context of cocaine addiction and psychiatric comorbidity, which is common in addicted subjects. Abstinent patients with cocaine use disorder (CUD) and control subjects were recruited for a cross-sectional study. Participants were assessed with a semi-structured diagnostic interview (PRISM) based on DSM-IV-TR for substance and mental disorders. Plasma concentrations of tryptophan metabolites and their association with relevant CUD-related variables and psychiatric comorbidity were explored. We observed decreased plasma kynurenic acid concentrations in the cocaine group, however no associations between CUD-related variables and tryptophan-derived metabolites were found. In contrast, 5-HT concentrations were increased in CUD-patients and the diagnosis of different psychiatric disorders in the cocaine group was related to higher plasma 5-HT concentrations compared with non-comorbid patients. Therefore, while changes in plasma kynurenic acid concentrations appear to be directly associated with lifetime CUD, changes in 5-HT concentrations are associated with psychiatric comorbidity. These results emphasize the need to find potential biomarkers for a better stratification of cocaine-addicted patients in order to develop therapeutic approaches to prevent cocaine relapse.


Band Structure Engineering and Thermoelectric Properties of Charge-Compensated Filled Skutterudites.
Thermoelectric properties of semiconductors are intimately related to their electronic band structure, which can be engineered via chemical doping. Dopant Ga in the cage-structured skutterudite Co4Sb12 substitutes Sb sites while occupying the void sites. Combining quantitative scanning transmission electron microscopy and first-principles calculations, we show that Ga dual-site occupancy breaks the symmetry of the Sb-Sb network, splits the deep triply-degenerate conduction bands, and drives them downward to the band edge. The charge-compensating nature of the dual occupancy Ga increases overall filling fraction limit. By imparting this unique band structure feature, and judiciously doping the materials by increasing the Yb content, we promote the Fermi level to a point where carriers are in energetic proximity to these features. Increased participation of these heavier bands in electronic transport leads to increased thermopower and effective mass. Further, the localized distortion from Ga/Sb substitution enhances the phonon scattering to reduce the thermal conductivity effectively.


Integrative metabolomics science in Alzheimer's disease: Relevance and future perspectives.
Alzheimer's disease (AD) is determined by various pathophysiological mechanisms starting 10-25 years before the onset of clinical symptoms. As multiple functionally interconnected molecular/cellular pathways appear disrupted in AD, the exploitation of high-throughput unbiased omics sciences is critical to elucidating the precise pathogenesis of AD. Among different omics, metabolomics is a fast-growing discipline allowing for the simultaneous detection and quantification of hundreds/thousands of perturbed metabolites in tissues or biofluids, reproducing the fluctuations of multiple networks affected by a disease. Here, we seek to critically depict the main metabolomics methodologies with the aim of identifying new potential AD biomarkers and further elucidating AD pathophysiological mechanisms. From a systems biology perspective, as metabolic alterations can occur before the development of clinical signs, metabolomics - coupled with existing accessible biomarkers used for AD screening and diagnosis - can support early disease diagnosis and help develop individualized treatment plans. Presently, the majority of metabolomic analyses emphasized that lipid metabolism is the most consistently altered pathway in AD pathogenesis. The possibility that metabolomics may reveal crucial steps in AD pathogenesis is undermined by the difficulty in discriminating between the causal or epiphenomenal or compensatory nature of metabolic findings.


Long-term deficits in health-related quality of life after recovery from thrombotic thrombocytopenic purpura.
After recovery from thrombotic thrombocytopenic purpura (TTP), patients commonly describe persistent problems with memory, concentration, and endurance. The Oklahoma TTP-HUS Registry, an inception cohort of 364 patients, January 1, 1989, through June 30, 2007, has annually evaluated health-related quality-of-life since 1998 with the Short Form (SF)-36, a widely used questionnaire that assesses eight domains of physical and mental health. A total of 128 patients were eligible for this study (age >or= 18 years, alive in January 1998 without prior relapse, survival and no relapse >or=1 year after recovery, no overt disability or additional disorders); 118 (92%) completed the SF-36. At their initial assessment, these patients had significantly worse functioning and well-being than the US population for all domains (p < 0.05). Forty-nine patients who had their initial assessment more than 2 years after recovery had better scores for three domains than 69 patients who had their initial assessment 2 years or less after recovery (p < 0.05). Among these 69 patients, there was no difference between subgroups: 1) idiopathic versus other categories of TTP, 2) the presence or absence of severe ADAMTS13 deficiency, 3) the presence or absence of severe neurologic abnormalities during the episode of TTP, and 4) less than 10 or 10 or more plasma exchange treatments required to achieve remission (p > 0.05). Analysis of serial assessments in 72 (61%) of the 118 patients who had two or more assessments within 5 years of recovery and no intervening relapses demonstrated no significant improvement in any of the domains. After recovery from TTP, patients may have persistent cognitive and physical difficulties.


Editorial Highlights from the Comorbidities and Complications of Cerebral Palsy Special Issue.
Cerebral palsy is a life-long condition and the most common cause of physical disability in childhood [...].


The interaction in vitro of the intermediate filament protein vimentin with naturally occurring RNAs and DNAs.
The binding of the intermediate filament protein vimentin to a variety of naturally occurring RNAs and DNAs was studied. The relative capacities of the various nucleic acids to associate with pure [3H]vimentin were determined in competition experiments with 28 S rRNA from Ehrlich ascites tumor cells. The reaction products were analyzed by sucrose gradient centrifugation at low ionic strength and in the presence of EDTA. Under these ionic conditions, vimentin reacted preferentially with single-stranded nucleic acids, particularly with those of high (G + C) content. The vimentin binding potentials of single-stranded RNAs and DNAs were largely comparable. However, when the concentrations of mono- and divalent cations were raised to physiological and higher values, only single-stranded DNA retained its vimentin binding capacity. With increasing KCl concentrations at 0 to 1 mM Mg2+, increasing amounts of vimentin were detected in complexes which sedimented considerably faster than the bulk of the DNA, suggesting cooperative binding of vimentin. The salt optimum of this cooperativity was at 200 mM KCl. Thus, the capability of vimentin to discriminate between single-stranded RNA and DNA under physiological ionic conditions points to specificity of the interaction of vimentin with nucleic acids.


Antioxidant and anti-inflammatory activities of Thai medicinal plants in Sahasthara remedy for muscle pain treatment.
Twenty one plants as ingredients of Thai traditional preparation called Sahasthara for relieve muscles pain and distal numbness were studied for their antioxidant and anti-inflammatory activities. The extracts were obtained by maceration with 95% ethanol. They were tested for their antioxidant activity by DPPH scavenging assay and anti-inflammatory activity by determination of inhibitory activity on lipopolysaccharide (LPS) induced nitric oxide (NO) production in RAW 264.7 cell lines using Griess reagent. The ethanolic extract of Terminalia chebula Retz. (Gall) showed the highest antioxidant activity (EC50 = 3.34 microg/ml). Its fruit extract also exhibited the most potent inhibitory activity on lipopolysaccharide (LPS) induced nitric oxide (NO) production in RAW 264.7 cells, followed by Atractylodes lancea and Baliospermum montanum (IC50 = 3.3, 9.7 and 12.6 microg/ ml, respectively). The results obtained for anti-inflammatory and antioxidant activities of these plants correspond with their traditional use for muscle pain and inflammatory-related diseases.


A novel approach to operating room readiness for airborne precautions using simulation-based clinical systems testing.
The emergence of the COVID-19 disease as a global pandemic caused major challenges and strained busy operating room environments. This required institutions to rethink current system functioning and urgently develop safe medical practices and protocols. To use a novel approach combining simulation-based clinical system testing with rapid cycle deliberate practice concepts for identifying latent safety threats presented by newly developed operating room COVID-19 protocols and collecting frontline staff recommendations for mitigation. This study design combined a training/education approach with probing the systems function. The primary outcomes were the number of latent safety threats and staff evaluations of this approach for feasibility and utility on immediate and four-month post surveys. Participants started the simulation which took place in the operating room, in the assistant role before graduating to the primary airway manager. Simulation staff members observed the simulations and noted whether elements in the protocols/checklists were followed and whether latent safety threats were present using an observation form. Solutions to latent safety threats were sought during the debriefing period. This approach identified 17 latent safety threats not foreseen during the planning stages and allowed for corrections to the protocols prior to impacting patient outcomes. Post-simulation surveys indicated that the program was well received and all who responded agreed that it was worth the time it took. Fifty-seven percent of respondents to four-month follow-up survey reported using the work products to care for an actual COVID-19 patient. This study demonstrated a flexible methodology that effectively integrated simulation-based training and systems tests to train staff and detect latent safety threats in the new workflows and provide recommendations for mitigation. While COVID was the specific prompt, this approach can be applicable in diverse clinical settings for training medical staff, testing system function, and mitigating potential latent safety threats.


Imaging features of hepatocellular carcinoma in nonalcoholic fatty liver disease and nonalcoholic steatohepatitis: a systematic review and meta-analysis.
To investigate the imaging features of hepatocellular carcinoma (HCC) in patients with non-alcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) through a systematic review and meta-analysis. MEDLINE, EMBASE, and the Cochrane Library database were searched for studies providing data on imaging features of HCC in NAFLD and NASH between January 1, 2011 and July 19, 2021. Random effects models were used to calculate the pooled percentages of the three major features of arterial-phase hyperenhancement (APHE), washout, and enhancing capsule. Sensitivity analysis and subgroup analysis were performed according to underlying liver disease (NASH vs. NAFLD) and imaging modality (CT vs. MRI). Five studies (170 patients with 193 HCCs) were included in the analysis. The pooled percentages of APHE, washout, and enhancing capsule were 94.0% (95% confidence interval [CI] 89.1-96.7%), 72.7% (95% CI 63.3-80.4%), and 57.5% (95% CI 45.1-69.1%), respectively. The percentages of these three major features did not significantly differ between NAFLD and NASH (p ≥ 0.21). MRI showed similar pooled percentages of APHE (94.3% vs. 93.4%, p = 0.82) and washout (70.4% vs. 77.2%, p = 0.38) to CT, but a higher pooled percentage of enhancing capsule (67.1% vs. 44.7%, p = 0.02). HCC in patients with NAFLD and NASH had a similar frequency of APHE to HCC with other etiology. However, it showed a relatively low frequency of washout and enhancing capsule.


Cell separator operation within temperature ranges to minimize effects on Chinese hamster ovary cell perfusion culture.
A cell retention device that provides reliable high-separation efficiency with minimal negative effects on the cell culture is essential for robust perfusion culture processes. External separation devices generally expose cells to periodic variations in temperature, most commonly temperatures below 37 degrees C, while the cells are outside the bioreactor. To examine this phenomenon, aliquots of approximately 5% of a CHO cell culture were exposed to 60 s cyclic variations of temperature simulating an acoustic separator environment. It was found that, for average exposure temperatures between 31.5 and 38.5 degrees C, there were no significant impacts on the rates of growth, glucose consumption, or t-PA production, defining an acceptable range of operating temperatures. These results were subsequently confirmed in perfusion culture experiments for average exposure temperatures between 31.6 and 38.1 degrees C. A 2(5-1) central composite factorial design experiment was then performed to systematically evaluate the effects of different operating variables on the inlet and outlet temperatures of a 10L acoustic separator. The power input, ambient temperature, as well as the perfusion and recycle flow rates significantly influenced the temperature, while the cell concentration did not. An empirical model was developed that predicted the temperature changes between the inlet and the outlet of the acoustic separator within +/-0.5 degrees C. A series of perfusion experiments determined the ranges of the significant operational settings that maintained the acoustic separator inlet and outlet temperatures within the acceptable range. For example, these objectives were always met by using the manufacturer-recommended operational settings as long as the recirculation flow rate was maintained above 15 L day(-1) and the ambient temperature was near 22 degrees C.


The effect of larval competition on development time and adult size in the seaweed fly, Coelopa frigida.
The effect of larval competition on adult size and egg to adult development time has been investigated in laboratory populations of the seaweed fly, Coelopa frigida. Increased larval density results in longer development times and smaller adults, suggesting a strong interference element to the competition. This may be due to a limiting rate of food supply rather than interactions between larvae. The relationship between development time and size suggests that both these characters are involved in control of the onset of pupation. C. frigida is polymorphic for an inversion on chromosome I. Differences in relative viability between the karyotypes are not related to the development time or size differences.


Hydrogen gas generation from refuse-derived fuel (RDF) under wet conditions.
An explosion has recently occurred at a silo containing refuse-derived fuels (RDF) in Japan. There is a possibility that microorganisms are involved in generation of combustible gas from RDF and this study was aimed at showing the presence of bacteria that can ferment RDF pellets. All RDF samples tested contained a relatively high number of viable bacterial cells, 1.4x10(5) to 3.2x10(6) viable cells/g. These bacteria in the RDF samples fermented them to generate heat and hydrogen gas.


Design of enkephalin modifications protected from brain extracellular peptidases providing long-term analgesia.
The main obstacle to the use of many therapeutic peptides in practice is their rapid destruction by extracellular peptidases. Earlier we have found that active in the extracellular medium of mammalian brain exopeptidases are unable to break the bonds formed by β-alanine. We have designed several modified forms of opioid peptide enkephalin (Tyr-Gly-Gly-Phe-Met; Enk) with end βAla: ModEnk1 (βAla-Tyr-Gly-Gly-Phe-Met-βAla), ModEnk2 (βAla-Tyr-Gly-Gly-Phe-NH2), ModEnk3 (βAla-Tyr-Gly-Phe-NH2). These modifications are much more stable than Enk in the suspension of isolated axonal endings (synaptosomes) that mimics the brain extracellular medium. ModEnk1-3 have been tested in standard "pain" experiment "tail flick" on rats using intranasal peptide administration. ModEnk1 and ModEnk2 (but not ModEnk3) have fully preserved pain-relieving properties of Enk, but their efficiency was maintained for much longer. Compared to ModEnk1, ModEnk2 is more stable and provides longer analgesia because it is less accessible for endopeptidases. They are potent non-toxic analgesics.


Leukocyte accumulation in sparganosis: further characterization of an eosinophil chemotactic factor of the plerocercoid of Spirometra erinacei.
An eosinophil chemotactic (ECF) was partially purified from plerocercoids of Spirometra erinacei by a combination of anion-exchange chromatography on DE52 and gel filtration on Sephacryl S-200. The molecular weight of ECF was estimated to be 25,000-45,000 by high-pressure liquid chromatography. The ECF was bound with concanavalin A-Sepharose. The ECF was sensitive to periodate oxidation and to heating (56 degrees C, 30 min). On isoelectric focusing, eosinophil chemotactic activity was clearly revealed at pI 4.1. These results suggest that ECF of S. erinacei plerocercoid is an acidic glycoprotein. An intradermal injection of ECF eosinophil attractions in the normal guinea pig skin.


DNA sequences coding for the H2B histone of Psammechinus miliaris.
Starting from restriction enzyme cleavage sites of known topologies the DNA sequences coding for two thirds of the H2B histone protein, together with some 3 inch extracistronic sequences, have been determined for the sea urchin Psammechinus miliaris. This unambiguously identifies this gene and further reveals its 5 inch-3inch polarity and accurate map position in a cloned histone DNA repeat unit.


Thyroid testing in pregnant women with thyroid dysfunction in Tayside, Scotland: the thyroid epidemiology, audit and research study (TEARS).
To investigate the rate of thyroid testing during pregnancy. Population-based, retrospective record-linkage study. Health care data on pregnant women in Tayside, Scotland. All pregnant women who were 18 years and above and who delivered between 1 January 1993 and 31 March 2011 in Tayside were identified. Patients were included in the study if they have had at least three thyroxine prescriptions prior to pregnancy of which at least one prescription was within 6 months prior to pregnancy. Number of thyroid-stimulating hormone (TSH) assays performed during pregnancy and the changes in dosage of thyroxine prescribed during pregnancy. We identified 950 pregnancies that had thyroxine prescribed prior to pregnancy. Overall, 96.9% (95% CI: 96-98) of these pregnancies had at least one TSH assay performed during or just prior to pregnancy, with 81.2% (95% CI: 79-84) in the first trimester. The prescription of thyroxine was increased in 60.0% (95% CI: 57-63) at any time during pregnancy and in 34.0% (95% CI: 31-37) of pregnancies during the first trimester. Overall, 60% (95% CI: 57-63) of pregnancies had at least one elevated serum TSH during pregnancy with 55% (95% CI: 51-58) in the first trimester. The TSH concentration is raised in many pregnancies in women taking long-term thyroxine.


[Cause of late death in liver transplant recipients].
The objective is to present the causes of late death in patients subjected to liver transplantation. A total of 209 patients were subjected to 223 liver transplantations (14 retransplantations). The computerized study protocol sheets were evaluated to determine the causes of late death (> 6 months after transplantation). Of the 209 patients, 30 had late death. Ductopenic rejection (chronic rejection) was the most common cause and it was observed in 10 patients. Time after transplantation at the moment of death of this group of patients varied from 11 to 57 months, with an average of 29 months. Seven patients died at the hospital admission of hepatic retransplantation. Other causes of late death were sepsis, lymphoproliferative disease, chronic renal insufficiency, and hepatic insufficiency. The most common cause of late death after liver transplantation is ductopenic rejection, followed by complications of retransplantation and sepsis. Death owing to ductopenic rejection may occur even many years after transplantation.


Endoscopic and Imaging Predictors of Complete Pathologic Response After Chemoradiation for Esophageal Cancer.
Locally advanced esophageal cancer is frequently treated preoperatively with chemotherapy and radiation. The degree of response to this preoperative therapy varies in different patients, and a complete pathological response (pCR) has important implications in the management and prognosis of these patients. This is a review of the different modalities currently available to detect pCR and the clinical context of their use. While research is still ongoing, no single technique has emerged as the modality of choice to reliably predict pCR in all patients. Studies investigating the sensitivity, specificity, and accuracy of these modalities have had promising results, but no single modality has been firmly validated as the modality if choice. The emergence of functional imaging techniques and the use of biomarkers are newer developments which need further evaluation before adoption in routine clinical practice. While no single technique reliably predicts pCR, a combination of imaging and diagnostic modalities (endoscopic appearance, biopsy, EUS, and PET/CT) may provide a better diagnostic yield rather than any of these modalities taken alone.


Src-mediated tyrosine phosphorylation of dynamin is required for beta2-adrenergic receptor internalization and mitogen-activated protein kinase signaling.
Some forms of G protein-coupled receptor signaling, such as activation of mitogen-activated protein kinase cascade as well as resensitization of receptors after hormone-induced desensitization, require receptor internalization via dynamin-dependent clathrin-coated pit mechanisms. Here we demonstrate that activation of beta2-adrenergic receptors (beta2-ARs) leads to c-Src-mediated tyrosine phosphorylation of dynamin, which is required for receptor internalization. Two tyrosine residues, Tyr231 and Tyr597, are identified as the major phosphorylation sites. Mutation of these residues to phenylalanine dramatically decreases the c-Src-mediated phosphorylation of dynamin following beta2-AR stimulation. Moreover, expression of Y231F/Y597F dynamin inhibits beta2-AR internalization and the isoproterenol-stimulated mitogen-activated protein kinase activation. Thus, agonist-induced, c-Src-mediated tyrosine phosphorylation of dynamin is essential for its function in clathrin mediated G protein-coupled receptor endocytosis.


A Study of Population Size and Activity Patterns and Their Relationship to the Prey Species of the Eurasian Lynx Using a Camera Trapping Approach.
Revealing the behavioral relationships between predators and their prey is fundamental in understanding the community structure and ecosystem functions of such animals. This study aimed at detecting the population size and activity patterns of Eurasian lynx (Lynx lynx) (along with its prey) by camera trapping monitoring from 2014 to 2017 at the Saihanwula nature reserve in central Inner Mongolia. The total effective trapping days were 29,892 and 20 lynx were identified from 343 trapping photos based on the inner side patterns of their forelimbs. The daily activity rhythms of the lynx overlapped with those of different prey in different seasons. The yearly activity pattern of the lynx was influenced by its main prey's biology. In conclusion, this study reveals that the activity patterns of the top predator matched those of its prey in different time periods. Habitat management strategies promoting the restoration of prey communities would benefit the lynx in maintaining a stable community structure.


Macrofungal species distributions depend on habitat partitioning of topography, light, and vegetation in a temperate mountain forest.
The habitat partitioning hypothesis provides a conceptual framework for explaining the maintenance of plant and animal diversity. Its central tenet assumes environmental conditions are spatially structured, and that this structure is reflected in species distributions through associations with different habitats. Studies confirming habitat partitioning effects have focused primarily on spatial distributions of plants and animals, with habitat partitioning hypothesis under explored for macrofungi. Here, we examined the sporocarps of macrofungi in a 5-ha forest dynamics plot in China. We used four different methods to define microhabitats for habitat partitioning analyses based on topography, understory light availability, plant community, or a combination of these factors, and analyzed the effect of microhabitat partitioning on epigeous macrofungal community. Our results showed that the characteristics of the macrofungal assemblages varied among the habitats. A total of 85 species examined were associated with one or more of the habitat types (85/125, 68%). The factors related to the sporocarp composition differed among the various microhabitats. Our findings suggest that different microhabitats favor occurrence of different macrofungal species, and sporocarps -environment relation varied among the different microhabitats at this temperate mountain forest locality. These findings shed new light to the biodiversity conservation in macrofungi in temperate deciduous broad-leaved forest and point to the potential importance of microhabitat partitioning for sporocarp formation.


Bone metastases in soft tissue sarcoma: a survey of natural history, prognostic value and treatment options.
We surveyed the natural history of bone metastases in patients affected by soft tissue sarcoma (STS). This multicenter retrospective observational study included 135 patients. Histological subtype, characteristics of bone metastases, treatment, skeletal related events (SREs) and disease outcome were recorded. The most represented histological subtypes were leiomyosarcoma (27%) angiosarcoma (13%) and undifferentiated sarcoma (8%). Axial skeleton was the most common site for bone involvement (70%). In 27% of cases, bone metastases were present at the time of diagnosis. Fifty-four (40%) patients developed SREs and the median time to first SRE was 4 months (range 1-9). The most common SRE was the need for radiotherapy (28%) followed by pathological fracture (22%). Median survival after bone progression was 6 months (range 1-14). SREs were associated with decreased overall survival (OS) (P = 0.04). A subgroup analysis revealed that bisphosphonates significantly prolonged median time to first SRE (5 versus 2 months; P = 0.002) while they did not determine an improvement in OS, although a favourable trend was identified (median: 7 versus 5 months; P = 0.105). This study illustrates the burden of bone disease from STS and supports the use of bisphosphonates in this setting.


Regulatory groundwater monitoring: Realistic residues of pinoxaden and metabolites at vulnerable locations.
A bespoke groundwater monitoring programme was designed to generate a database of pinoxaden and metabolite concentrations in shallow groundwater at agricultural locations across Europe. The data generated from this programme represent a higher tier refinement of modelled exposure estimates and provide realistic information on groundwater quality at vulnerable locations which will aid plant protection product (PPP) assessment in Europe in relation to Regulation (EC) No. 1107/2009. The Regulatory GeoPEARL_3.3.3 model developed by RIVM was used to estimate the vulnerability of cereal growing regions to leaching of two pinoxaden metabolites across the entire EU at a 1 km2 level using 20 years of daily weather data (MARS, EU JRC). Seventy sites located within the upper 50th percentile of leaching vulnerability from this modelling exercise, crop density and shallow groundwater were selected for monitoring groundwater. Retrospective and prospective pinoxaden product applications at candidate sites were recorded and these data used to place sites in the distribution for Europe. The 70 sites all fulfil the site assessment criteria and have no confining layers which may prevent or delay leaching. All sites equipped with groundwater wells had a minimum of two pinoxaden applications in the preceding four years to cereal crops. A total of 1326 samples were analysed from up to 90 down hydraulic gradient wells at 70 locations between June 2015 and July 2018. Results indicate that pinoxaden and pinoxaden metabolites are very unlikely to reach shallow groundwater at concentrations greater than 0.1 μg/L for relevant metabolites, or 10 μg/L for non-relevant metabolites, respectively (Sanco/221/2000-rev.10). Over 38 months of groundwater monitoring the annual average and 90th percentile for pinoxaden or its metabolites never exceeded 0.1 μg/L and it is proposed that these data infer that exposure to these metabolites is minimal.


The strategy for establishment of the multiple reaction monitoring based characteristic chemical profile of triterpenes in Alismatis rhizoma using two combined tandem mass spectrometers.
It was reported that triterpenes compounds in Alismatis rhizoma (AR) contributed to the lipid lowering effect on high fat diet (HFD)-induced hyperlipidemia. To date only 24 triterpenes (including the isomers) were characterized by LC-QTOF-MS/MS due to the lack of strategies for systematic discovery, classification and identification of triterpenes in AR. In this study, an integrated strategy combining various QTOF-MS/MS and QTRAP-MS/MS scan functions was developed for systematic identification and specific characterization of triterpenes in AR and processed AR. First, MS/MS fragmentation behaviors of different types of triterpenes were investigated and their diagnostic product ions were systematically summarized for discovery and classification of triterpenes. Second, diagnostic product ions were used to filter the data acquired by UHPLC-QTOF MS/MS for efficient identification of targeted triterpenes. Third, MRM-based characteristic chemical profile (CCP) of triterpenes was established using 30 MRM transitions by UHPLC-QTRAP-MS/MS. Fourth, MRM-based CCP was applied for comparative analyses of triterpenes in AR from different regions and from two other processed AR (salt processed AR and bran processed AR). Consequently, a total of 80 triterpenes including 14 novel compounds were identified in the AR, and 7 more triterpenes compounds were discovered using MRM-based CCP in the processed AR. This work is the most comprehensive characterization of triterpenes compounds in AR to date. The established MRM-based CCP of triterpenes compounds can be instructive for qualitative analyses and relative quantitative analyses of triterpenes in AR and its related medicinal products for potential applications including quality control and classification of different AR materials.


Simultaneous symptomatic biliary and renal calculi in a child.
We report on the unusual finding of both symptomatic biliary and renal calculi in a child. A review of the literature failed to provide any definite common etiologic factors, although the possible role of systemic infection cannot be ruled out.


Development and validation of a risk prediction model and scoring system for post-endoscopic retrograde cholangiopancreatography pancreatitis.
A few models have been proposed for the prediction of the risk of post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP), but many include factors that are not assessed routinely. Herein, we intend to develop and validate a predictive model for the occurrence of PEP. Data of patients who underwent endoscopic retrograde cholangiopancreatography (ERCP) from January 01, 2016 to May 16, 2019 (training set and internal test set) and from May 17, 2019 to December 25, 2019 (external test set) were retrospectively collected. The performance of the model was validated in the two validation cohorts. A total of 342 patients were included for the external test set, and 47 (13.7%) developed PEP. The variables included in the scoring system were gastrectomy history, high direct bilirubin (DBIL), high albumin (ALB), villous type of papillary orifice, nodular type of papillary orifice, pancreatic guidewire passages, precut sphincterotomy, and high operator experience. A total score >5 indicated high risk. In the external test set, the area under the curve (AUC) was 0.718, the sensitivity was 0.723, and the specificity was 0.676. In the external test set, the probability of PEP was 6.1%, 17.0%, and 37.5% in patients with low (<0), moderate (0-5), and high (>5) risk scores, respectively. This study established a scoring system for predicting the risk of PEP using routinely measured clinical variables. Its application in routine work warrants further investigation.


Liberalizing the killing of endangered wolves was associated with more disappearances of collared individuals in Wisconsin, USA.
Although poaching (illegal killing) is an important cause of death for large carnivores globally, the effect of lethal management policies on poaching is unknown for many populations. Two opposing hypotheses have been proposed: liberalizing killing may decrease poaching incidence ('tolerance hunting') or increase it ('facilitated poaching'). For gray wolves in Wisconsin, USA, we evaluated how five causes of death and disappearances of monitored, adult wolves were influenced by policy changes. We found slight decreases in reported wolf poaching hazard and incidence during six liberalized killing periods, but that was outweighed by larger increases in hazard and incidence of disappearance. Although the observed increase in the hazard of disappearance cannot be definitively shown to have been caused by an increase in cryptic poaching, we discuss two additional independent lines of evidence making this the most likely explanation for changing incidence among n = 513 wolves' deaths or disappearances during 12 replicated changes in policy. Support for the facilitated poaching hypothesis suggests the increase (11-34%) in disappearances reflects that poachers killed more wolves and concealed more evidence when the government relaxed protections for endangered wolves. We propose a refinement of the hypothesis of 'facilitated poaching' that narrows the cognitive and behavioral mechanisms underlying wolf-killing.


Detection of virus-like particles in liver biopsies from HCV-infected patients.
In order to directly ascertain the presence of HCV virus infection in livers of patients with HCV chronic hepatitis, we investigated, by transmission electron microscopy (TEM), liver biopsies from 2 adults and 4 children for the presence of virus-like particles (VLPs). The plasmas of these HCV-positive patients were HCV-RNA-positive, with high ALT values. In liver tissue samples examined, we were able to detect plus and minus strands of HCV RNA by strand-specific RT-PCR. Aggregates or single VLPs of about 45 nm in diameter were detectable in variable amounts in endoplasmic cisternae and in hepatocyte cytoplasms of infected patients. These results emphasize the relevance of performing TEM assays to confirm the diagnosis of HCV infection.


Neutral red (NR) assay for cell viability and xenobiotic-induced cytotoxicity in primary cultures of human and rat hepatocytes.
Neutral red (NR) in medium was absorbed and concentrated in lysosomes of cultured rat and human hepatocytes. NR uptake increased with the time of incubation and reached a plateau in 2 hr. Uptake was proportional to the concentration of the NR solution and the numbers of viable liver cells. Prolonged culture of hepatocytes increased the numbers of lysosomes, and thus, the dye accumulation. The NR can be extracted from lysosomes for quantitative measurement of hepatocyte viability and cytotoxicity of xenobiotics. With this assay, several serum-free media (e.g., Waymouth's, MEM, LHC-8, etc.) were compared for the maintenance of viable hepatocytes in vitro. Interestingly, LHC-8 medium, which is used to grow human bronchial epithelial cells, best preserved viable rat hepatocytes. The cytotoxic effects of dimethylnitrosamine (DMN) and aflatoxin B1 (AFB1) were examined by NR assay on rat and human hepatocyte cultures and were found to be dependent on dose and time of the exposures. NR50 was 20 mM for DMN and 0.072 microM for AFB1 in rat hepatocytes with 24 hr of exposures and reduced to 12.5 mM for DMN and 0.053 mu microM for AFB1 with 48 hr exposures. Human hepatocytes were more resistant to the toxicity of both chemicals; NR50 values were 100 mM DMN and 1.8 microM AFB1 respectively, for 24 hr treatments. Compared with lactate dehydrogenase (LDH) leakage test, the NR assay was simpler and more sensitive in determining the viability and cytotoxicity of xenobiotics in primary cultures of hepatocytes.


Multidimensional scaling analysis identifies pathological and prognostically relevant profiles of circulating T-cells in chronic lymphocytic leukemia.
Antitumor immunity in chronic lymphocytic leukemia (CLL) is hampered by highly dysfunctional T-cells. Although certain T-cell subsets have been reported to be of prognostic significance in this disease, their interplay is complex and it remains incompletely understood which of these subsets significantly drive CLL progression. Here, we determined immunological profiles of 24 circulating T-cell subsets from 79 untreated individuals by multiparametric flow cytometry. This screening cohort included healthy donors, patients with monoclonal B-cell lymphocytosis (MBL), Rai 0 CLL and advanced CLL. We applied multidimensional scaling analysis as rigorous and unbiased statistical tool to globally assess the composition of the circulating T-cell environment and to generate T-cell scores reflecting its integrity. These scores allowed clear distinction between advanced CLL and healthy controls, whereas both MBL and Rai 0 CLL showed intermediate scores mirroring the biological continuum of CLL and its precursor stages. T-cell stimulation and suppression assays as well as longitudinal T-cell profiling showed an increasingly suppressive regulatory function initiating at the MBL stage. Effector function was impaired only after transition to CLL and partially recovered after chemoimmunotherapy. In an independent validation cohort of 52 untreated CLL cases, aberrant T-cell profiles were significantly associated with shorter time to treatment independently of other prognostic parameters. Random forest modeling predicted regulatory T-cell, gamma/delta and NKT-cells, as well as exhaustion of the CD8+ subset as potential drivers of progression. Our data illustrate a pathological T-cell environment in MBL that evolves toward a more and more suppressive and prognostically relevant profile across the disease stages.


The effects of platelet-activating factor on flow rate and eicosanoid release in the isolated perfused rat gastric vascular bed.
In the isolated rat stomach perfused via the vasculature in situ under constant pressure bolus injections of platelet-activating factor (PAF, 3, 16, or 50 ng) induced dose-dependent, long-lasting reductions of flow rates and simultaneously significant increases in the release of cysteinyl-leukotrienes (cys-LT), thromboxane (TX) B2 and 6-keto-prostaglandin (PG) F1 alpha. Reversed phase high pressure liquid chromatography demonstrated the release of a mixture of comparable amounts of LTC4, LTD4 and LTE4 by PAF. Inhibition of cys-LT synthesis by the lipoxygenase inhibitors nordihydroguaiaretic acid (NDGA) and L-651,896 did not significantly affect PAF-induced flow reduction indicating that endogenous cys-LT are of minor importance for the PAF effect on gastric vascular flow. This conclusion is supported by the fact that the cys-LT receptor antagonist FPL 55712 in a concentration (1 x 10(-6) M) that completely antagonized gastric flow reduction by exogenous LTC4 (1 x 10(-7) M) had no effect on the PAF-induced reduction of flow. The cyclooxygenase inhibitor indomethacin aggravated the PAF-induced flow reduction suggesting that the endogenous vasodilator PGI2 might act as a functional PAF antagonist in the rat gastric vascular bed. In contrast to FPL 55712 the PAF antagonist BN 52021 significantly and concentration-dependently antagonized the PAF effect on gastric vascular flow. The results demonstrate that PAF and LTC4 induce flow reductions in the rat gastric vascular bed by activating different receptors and that endogenous eicosanoids released by PAF do not contribute significantly to the PAF effect on gastric vascular flow.


Role of drivers' personal characteristics in understanding traffic sign symbols.
This study investigated the role of age, marital status, gender, nationality, educational background and monthly income in drivers' comprehension of traffic signs. The populations sampled here were from five Arabian Gulf Countries. A total of 28 symbolic warning and regulatory signs were investigated. A questionnaire specially prepared to collect the necessary data was distributed to over 9000 drivers in the five countries; 4774 responded (53%). The results indicated substantial problems with the level of comprehension among the drivers about the traffic signs. The percentages of drivers who correctly identified the regulatory signs and warning signs were around 55 and 56%, respectively. Age, gender, education and income played major roles in determining drivers' comprehension of signs, whereas marital status showed no significant effect. Drivers who are young, female, those with lower levels of education or lower incomes understand the signs significantly worse than drivers who are older, male, with higher levels of education or higher incomes. Drivers from Europe and USA are significantly better than Asian and Arab drivers. These findings are believed to be important for the designers of road signs for international applications.


HMDB: A curated database of genes involved in hydrocarbon monooxygenation reaction with homologous genes as background.
The investigation of hydrocarbon degradation potential of environmental microorganisms is an important research topic, whether for the global carbon cycle or oil pollution remediation. Under aerobic conditions, the microorganisms employ a range of monooxygenases to use hydrocarbons substrates as a source of carbon and energy. With the explosion of sequencing data, mining genes in genomes or metagenomes has become computationally expensive and time-consuming. We proposed the HMDB, which is a professional gene database of hydrocarbon monooxygenases. HMDB contains 38 genes, which encode 11 monooxygenases responsible for the hydroxylation of 8 hydrocarbons. To reduce false positives, the strategy of using homologous genes as background noise was applied for HMDB. We added 10,095 gene sequences of homologous enzymes which took non-hydrocarbons as substrates to HMDB. The classic BLAST method and best-hit strategy were recommended for HMDB usage, but not limited. The performance of HMDB was validated using 264,402 prokaryote genomes from RefSeq and 51 metagenomes from SRA. The results showed that HMDB database had high sensitivity and low false positive rate. We release the HMDB database here, hoping to speed up the process for investigation of hydrocarbon monooxygenases in massive metagenomic data. HMDB is freely available at http://www.orgene.net/HMDB/.


No discrimination against previous mates in a sexually cannibalistic spider.
In several animal species, females discriminate against previous mates in subsequent mating decisions, increasing the potential for multiple paternity. In spiders, female choice may take the form of selective sexual cannibalism, which has been shown to bias paternity in favor of particular males. If cannibalistic attacks function to restrict a male's paternity, females may have little interest to remate with males having survived such an attack. We therefore studied the possibility of female discrimination against previous mates in sexually cannibalistic Argiope bruennichi, where females almost always attack their mate at the onset of copulation. We compared mating latency and copulation duration of males having experienced a previous copulation either with the same or with a different female, but found no evidence for discrimination against previous mates. However, males copulated significantly shorter when inserting into a used, compared to a previously unused, genital pore of the female.


Genome-Wide Screen for Enhanced Noncanonical Amino Acid Incorporation in Yeast.
Numerous applications of noncanonical amino acids (ncAAs) in basic biology and therapeutic development require efficient protein biosynthesis using an expanded genetic code. However, achieving such incorporation at repurposed stop codons in cells is generally inefficient and limited by complex cellular processes that preserve the fidelity of protein synthesis. A more comprehensive understanding of the processes that contribute to ncAA incorporation would aid in the development of genomic engineering strategies for augmenting genetic code manipulation. In this work, we used a series of fluorescent reporters to screen a pooled Saccharomyces cerevisiae molecular barcoded yeast knockout (YKO) collection. Fluorescence-activated cell sorting enabled isolation of strains encoding single-gene deletions exhibiting improved ncAA incorporation efficiency in response to the amber (TAG) stop codon; 55 unique candidate deletions were identified. The deleted genes encoded for proteins that participate in diverse cellular processes, including many genes that have no known connection with protein translation. We then verified that two knockouts, yil014c-aΔ and alo1Δ, exhibited improved ncAA incorporation efficiency starting from independently acquired strains possessing the knockouts. Using additional orthogonal translation systems and ncAAs, we determined that yil014c-aΔ and alo1Δ enhance ncAA incorporation efficiency without loss of fidelity over a wide range of conditions. Our findings highlight opportunities for further modulating gene expression with genetic, genomic, and synthetic biology approaches to improve ncAA incorporation efficiency. In addition, these discoveries have the potential to enhance our fundamental understanding of protein translation. Ultimately, cells that efficiently biosynthesize ncAA-containing proteins will streamline the realization of applications utilizing expanded genetic codes ranging from basic biology to drug discovery.


Afferent vagal activity during hyperthermic polypnea in the pigeon.
Respiration-modulated activity in afferent vagal fibers was recorded in 10 pigeons during euthermic breathing and thermal panting. Of these fibers, 13 were identified as intra-pulmonary chemoreceptors (IPCs), that increased discharge with diminishing lung gas PCO2, and 13 as mechanoreceptors, that increased firing with lung inflation. Two types of IPC were observed that were distinct by their firing pattern during panting. Phasic IPCs displayed phasic discharge within the respiratory cycle, even at respiratory frequencies (fresp) as high as 400 min-1. Tonic IPC fired tonically and increased their discharge as fresp increased. Several IPCs were silent during euthermic breathing, but discharged tonically as fresp increased with thermal polypnea. Discharge of neither type of IPC was consistently related to PaCO2. Discharge from mechanoreceptors was phasic with respiration, up to values of fresp as high as 350 min-1. However, the average number of impulses per breath decreased as fresp increased. We conclude that discharge from phasic intrapulmonary chemoreceptors and mechanoreceptors may contribute to setting the respiratory pattern during hyperthermic polypnea.


Fluorophore labeling of core-crosslinked polymeric micelles for multimodal in vivo and ex vivo optical imaging.
To enable multimodal in vivo and ex vivo optical imaging of the biodistribution and tumor accumulation of core-crosslinked polymeric micelles (CCPMs). mPEG-b-p(HPMAm-Lac)-based polymeric micelles, core-crosslinked via cystamine and covalently labeled with two different fluorophores (Dy-676/488), were synthesized. The CCPMs were intravenously injected into CT26 tumor-bearing mice. Upon intravenous injection, the CCPMs accumulated in CT26 tumors reasonably efficiently, with values reaching approximately 4%ID at 24 h. Ex vivo two-photon laser scanning microscopy confirmed efficient extravasation of the image-guided CCPMs out of tumor blood vessels and relatively deep penetration into the tumor interstitium. CCPMs were labeled with multiple fluorophores, and the results obtained exemplify that combining several different in vivo and ex vivo optical imaging techniques is highly useful for analyzing the biodistribution and tumor accumulation of nanomedicines.


Study of hydrogen sulfide biosynthesis in synovial tissue from diabetes-associated osteoarthritis and its influence on macrophage phenotype and abundance.
Type 2 diabetes (DB) is an independent risk factor for osteoarthritis (OA). However, the mechanisms underlying the connection between both diseases remain unclear. Synovial macrophages from OA patients with DB present a marked pro-inflammatory phenotype. Since hydrogen sulphide (H2S) has been previously described to be involved in macrophage polarization, in this study we examined H2S biosynthesis in synovial tissue from OA patients with DB, observing a reduction of H2S-synthetizing enzymes in this subset of individuals. To elucidate these findings, we detected that differentiated TPH-1 cells to macrophages exposed to high levels of glucose presented a lower expression of H2S-synthetizing enzymes and an increased inflammatory response to LPS, showing upregulated expression of markers associated with M1 phenotype (i.e., CD11c, CD86, iNOS, and IL-6) and reduced levels of those related to M2 fate (CD206 and CD163). The co-treatment of the cells with a slow-releasing H2S donor, GYY-4137, attenuated the expression of M1 markers, but failed to modulate the levels of M2 indicators. GYY-4137 also reduced HIF-1α expression and upregulated the protein levels of HO-1, suggesting their involvement in the anti-inflammatory effects of H2S induction. In addition, we observed that intraarticular administration of H2S donor attenuated synovial abundance of CD68+ cells, mainly macrophages, in an in vivo model of OA. Taken together, the findings of this study seem to reinforce the key role of H2S in the M1-like polarization of synovial macrophages associated to OA and specifically its metabolic phenotype, opening new therapeutic perspectives in the management of this pathology.


Fetal lung disaturated phosphatidylcholine. Ostensible increase following exposure to dexamethasone.
Fetal rat lung removed at 15 days gestation and placed in organ culture incorporates choline into phosphatidylcholine. Addition of 10(-9) M dexamethasone resulted in increased rates of choline incorporation per micrograms protein after both 6 and 12 days culture. This concentration of dexamethasone did not increase tissue phosphatidylcholine or disaturated phosphatidylcholine. Thus, at a culture time when dexamethasone had a significant effect on choline incorporation, there was no change in either the total phospholipid or disaturated phosphatidylcholine content of the lung tissue. The transplacental administration of dexamethasone decreased fetal lung DNA and phospholipid content. At the mid-range dosage tested (400 micrograms), dexamethasone depressed DNA (51%) appreciably more than total phosphatidylcholine (28%) and disaturated phosphatidylcholine (33%). These results show that the hormone does not increase the total amount of surfactant per lung. The increased disaturated phosphatidylcholine per mg DNA results in an ostensible beneficial effect of dexamethasone on surfactant and may reflect an increased proportion of Type II cells in fetal lung both in vitro and in vivo following hormone exposure. Disaturated phosphatidylcholine per Type II alveolar cell is no doubt increased but the trade-off is fewer total cells in the lung.


Erythrocyte membrane proteins of premature and full-term newborn infants.
Erythrocyte membrane proteins of premature and full-term infants were analyzed by polyacrylamide gel electrophoresis. There were no qualitative or gross quantitative differences in the pattern of membrane proteins from premature infants, full-term infants, and adults.


Variability and validity of a simple visual rating scale in grading white matter changes on magnetic resonance imaging.
A new simple visual rating scale can be used in magnetic resonance imaging (MRI) to grade the severity of white matter changes (WMC). The authors sought to study the interobserver variability and the validity of this visual rating scale against a computer-aided quantitative method in measuring WMC. The authors examined 220 magnetic resonance images from stroke-free patients with traditional risk factors for atherosclerosis and middle cerebral artery stenosis who were participants in a clinical trial requiring MRI examination. The severity of WMC was graded from 0 (no WMC) to 3 (severe WMC). For the quantitative assessment of WMC, the volume of WMC were measured with a computer-aided, automated segmentation method. The interobserver variability was also determined. The mean volumes were significantly different among the different groups, which were scored 1, 2, and 3 (1324.59, 6475.48, and 25,440.05 mm3, respectively; 1-way analysis of variance, P < .001). Interobserver variability for grading WMC was good in different locations of the brain. Excellent results were found in the frontal lobe (kappa = 0.829) and the parietal-occipital lobe (kappa = 0.646), whereas poor results were found in the basal ganglia (kappa = 0.391). There was perfect agreement between the 2 observers in 89.1% for the frontal lobe and 77.0% for the parietal-occipital lobe. The results suggest that this simple visual rating scale is a valid and reliable method for grading WMC in the lobar region but not in the basal ganglion.


Sometimes even apoptosis fails: implications for cancer.
Apoptosis is vital for the correct morphogenesis of multi-cellular organisms. However, like most physiological programs, the cell's ability to commit suicide is hijacked by cancer in its own proliferative and invasive interest. We recently showed that inefficient execution of apoptosis (or failed apoptosis) is used by cancer to boost invasiveness.


Environmental hormesis in living systems: The role of hormetic trade-offs.
Hormesis (low-dose stimulation and high-dose inhibition) can be accompanied by hormetic trade-offs, that is, stimulation of some traits and inhibition (trade-off 1) or invariability (trade-off 2) of others. Currently, trade-off options and their biological significance are insufficiently studied. Therefore, the review analyses trade-off types, their relationship with asynchronous stress responses of indicators, the importance of trade-offs for preconditioning, hormesis transgenerational effects, fitness, and evolution. The analysis has shown that hormetic trade-offs 1 and 2 can be observed in evolutionarily distant groups of organisms and at different biological levels (cells, individuals, populations, and communities) with abiotic and biotic stressors, as well as various pollutants. Trade-offs 1 and 2 are found both between different functional traits (e.g., self-maintenance and reproduction in animals, growth and defense in plants), and between the endpoints of the same functional trait (e.g., seed weight and seed number in plants). Asynchronous responses of indicators to a low-dose stressor can lead to hormetic trade-offs in two cases: 1) these indicators have different responses (hormesis, inhibition or zero reaction) in the same dose range; 2) these indicators have hormetic responses with different hormetic zones. Trade-offs can have a positive, negative or zero effect on preconditioning, offspring, and fitness of the population. Trade-offs can potentially affect evolution in two ways: 1) the creation of trends in genotype selection; 2) participation in the assimilation of phenotypic adaptations in the genotype through the Baldwin effect (selection of mutations copying adaptive phenotypes).


Draft Genome Sequences of the Avirulent Coxiella burnetii Dugway 7D77-80 and Dugway 7E65-68 Strains Isolated from Rodents in Dugway, Utah.
Here, we present the draft genome sequences of the Coxiella burnetii Dugway 7D77-80 and Dugway 7E65-68 strains, which were isolated from rodents in Dugway, UT, in the 1950s. The strains reside in a distinct genomic group of C. burnetii and are considered avirulent despite having the largest genomes of the Coxiella genus.


Sida cordifolia L. attenuates behavioral hypersensitivity by interfering with KIF17-NR2B signaling in rat model of neuropathic pain.
Sida cordifolia L., a perennial subshrub belonging to the Malvaceae family, holds noteworthy significance in the Indian Ayurvedic System and global texts. Roots of this plant are reported to be useful in neurodegenerative disorders, facial paralysis, and treating several neuropathic pain conditions such as neuralgia, and sciatica. However, despite these claims, there remains a dearth of experimental evidence showcasing the effectiveness of Sida cordifolia L. roots in mitigating neuropathic pain. The primary objective of this study was to assess the analgesic properties of the whole extract (SCE) obtained from the roots of Sida cordifolia L., as well as its aqueous fraction (SAF) in rat model of chronic constriction injury (CCI)-induced neuropathic pain. Furthermore, in-depth phytochemical and molecular biology studies were conducted to identify the potential phytoconstituents and unveil the underlying mechanisms of action. DCM: Methanol (1:1) was used to extract the roots of Sida cordifolia L. to get whole extract (SCE) and was subjected to phytochemical investigations including LC-MS analysis. Analgesic potential of SCE was evaluated in chronic constriction injury (CCI) model of neuropathic pain in rats followed by its bioactivity guided fractionation using in-vitro anti-inflammatory assay and assessment of most potent fraction (SAF) in in-vivo pain model. We have also performed the detailed phytochemical and molecular biology investigations to delineate the mechanism of action of Sida cordifolia root extract. Chronic constriction injury leads to significant decrease in paw withdrawal threshold and paw withdrawal latency indicating development of hypersensitivity in rodents. Treatment with SCE and its most potent aqueous fraction (SAF) leads to significant and dose-dependent reduction in pain-like behavior of nerve injured rats. Pro-inflammatory cytokines (TNF-α, IL-1β), glia cell markers (Iba1, ICAM1), neuropeptides (CGRP and Substance P), KIF-17 and NR2B expressions were found to be significantly upregulated in DRG and spinal cord of nerve injured rats. Treatment with SCE and SAF suppressed oxido-inflammatory cascade along with attenuation of KIF-17 mediated NR2B trafficking and neuroinflammation in DRG and spinal tissues of neuropathic rats. HPTLC and HR-MS analysis suggest betaine as major constituent in SAF which along with other phytoconstituents. Both the whole extract (SCE) and the aqueous fraction (SAF) demonstrate a significant reduction in mechanical and thermal hypersensitivity by inhibiting KIF-17 mediated NR2B signaling in nerve injured rats and may be used as a potential alternative for the treatment of chronic pain. Our findings support the use of roots of Sida cordifolia L. in neuropathic pain conditions as acclaimed by its traditional use.


Breast-feeding intention, initiation and duration among Hong Kong Chinese women: a prospective longitudinal study.
to (1) estimate the breast-feeding intention, initiation and duration rate; (2) identify the reasons to initiate and wean breast feeding and (3) explore predictors of breast-feeding duration. a prospective longitudinal study antenatal clinics of five regional hospitals from four clusters in Hong Kong a population-based sample of 2098 women in the second trimester of pregnancy was recruited with a systematic sampling method. three different sets of self-administered questionnaires were used to measure the breast-feeding intention, initiation and duration, demographic, socio-economic, obstetric, complications of pregnancy and intrapartum variables at three time points. Reasons for initiating and weaning breast feeding, the formal and informal supportive resources of participants during breast feeding were collated at the third time points. the rates of artificial feeding and breast feeding were 41.1% and 58.9%, whereas breast-feeding intention and initiation rates were 85.3% and 67.0%, respectively. The breast-feeding duration rates were 11.1%, 10.3%, 10.7% and 26.7%, for the 'within <1 week', '1-3 weeks', '>3-6 weeks' and '>6 weeks' groups. The common reasons for initiating breast feeding were that breast feeding is beneficial for both the baby (89.8%) and mother (39.7%). Reasons for weaning breast feeding were insufficient breast milk (32.7%), tiredness and fatigue (39.7%) and return to work (29.6%). Partner, relatives and nurse midwives were important supportive resource during breast feeding. Ordinal logistic regression analysis identified five predictive factors of breast-feeding duration. Participants who were working part-time or were housewives (p=0.037), had monthly family income of <HK$10,000 (p=0.034), more than one child (p=0.001), positive breast-feeding intention (p=0.001) and early breast feeding within the first hour (p<0.0001) were more likely to have longer breast feeding than their counterparts. mothers in Hong Kong do not meet the recommendation of the international standards for breast feeding. Understanding of reasons for initiation, weaning and predictors of breast-feeding duration can help nurse midwives to develop and customise effective strategies to promote and encourage breast feeding. the findings are important for a process-oriented breast-feeding training programme for nurse midwives. New strategies should be implemented for prolonging breast-feeding duration among perinatal women.


The role for ketogenic diets in epilepsy and status epilepticus in adults.
Ketogenic diet (KD) therapies are high fat, low carbohydrate diets designed to mimic a fasting state. Although studies demonstrate KD's success in reducing seizures stretching back nearly a century, the last 25 years have seen a resurgence in diet therapy for the management of drug-resistant epilepsy in children as well as adults. With ≥50% seizure reduction efficacy rates in adults of 22-55% for the classic KD and 12-67% for the modified Atkins diet, diet therapy may be in many instances comparable to a trial of an additional anti-epileptic medication and potentially with fewer side effects and other health benefits. Moreover, ketogenic diets offer promising new adjunctive strategies for the treatment of acute status epilepticus in the intensive care setting. Here, we review the efficacy and utility of ketogenic diets for the management of chronic epilepsy and refractory status epilepticus in adults and offer practical guidelines for diet implementation and maintenance.


Genome-wide association study reveals a locus for nasal carriage of Staphylococcus aureus in Danish crossbred pigs.
Staphylococcus aureus is an important human opportunistic pathogen residing on skin and mucosae of healthy people. Pigs have been identified as a source of human colonization and infection with methicillin-resistant Staphylococcus aureus (MRSA) and novel measures are needed to control zoonotic transmission. A recent longitudinal study indicated that a minority of pigs characterized by high nasal load and stable carriage may be responsible for the maintenance of S. aureus within farms. The primary objective of the present study was to detect genetic loci associated with nasal carriage of S. aureus in Danish crossbred pigs (Danish Landrace/Yorkshire/Duroc). Fifty-six persistent carriers and 65 non-carriers selected from 15 farms surveyed in the previous longitudinal study were genotyped using Illumina's Porcine SNP60 beadchip. In addition, spa typing was performed on 126 S. aureus isolates from 37 pigs to investigate possible relationships between host and S. aureus genotypes. A single SNP (MARC0099960) on chromosome 12 was found to be associated with nasal carriage of S. aureus at a genome-wide level after permutation testing (p = 0.0497) whereas the association of a neighboring SNP was found to be borderline (p = 0.114). Typing of S. aureus isolates led to detection of 11 spa types belonging to the three main S. aureus clonal complexes (CC) previously described in pigs (CC9, CC30 and CC398). Individual carriers often harbored multiple S. aureus genotypes and the host-pathogen interaction seems to be independent of S. aureus genotype. Our results suggest it may be possible to select pigs genetically resistant to S. aureus nasal colonization as a tool to control transmission of livestock-associated MRSA to humans.


Interactions between two C60 molecules measured by scanning probe microscopies.
C60-functionalized tips are used to probe C60 molecules on Cu(111) with scanning tunneling and atomic force microscopy. Distinct and complex intramolecular contrasts are found. Maximal attractive forces are observed when for both molecules a [6,6] bond faces a hexagon of the other molecule. Density functional theory calculations including parameterized van der Waals interactions corroborate the observations.


Detection of glucose-6-phosphate dehydrogenase deficiency in erythrocytes: a spectrophotometric assay and a fluorescent spot test compared with a cytochemical method.
The results of a quantitative spectrophotometric enzyme assay, a fluorescent spot test and a cytochemical assay for glucose-6-phosphate dehydrogenase deficiency were compared systematically. The high sensitivity of the spectrophotometric assay and the fluorescent spot test in the detection of severely deficient individuals was confirmed. For the detection of heterozygote females, however both tests were unreliable; the sensitivities of the fluorescent spot test and the spectrophotometric assay being 32% and 11% respectively. Specificities for both tests were high (99%). Introduction of the ratio of glucose-6-phosphate dehydrogenase and pyruvate kinase (G-6-PD/PK ratio) activities increased the sensitivity of the spectrophotometric assay to nearly 100%. It is concluded that the fluorescent spot test should be used for the diagnosis of G-6-PD deficiency in developing countries; whereas if spectrophotometric enzyme assays are available, the G-6-PD/PK ratio should always be performed. In cases where the ratio is less than 0.70, cytochemical analysis is indicated.


Transient ischemia-induced paresis and complete paraplegia displayed distinct reactions of microglia and macrophages.
In this study, we perform a detailed analysis of the microglial and macrophage responses in a model of spinal cord ischemia and reperfusion (SCI/R) injury in Wistar rats. The rats underwent occlusion across the descending aorta for 13min, causing paraplegia or paresis of varying severity. They were divided into four groups based on neurological assessment: sham, mild paresis, moderate paresis, and severe (complete) paraplegia. To examine the origin of microglia and macrophages in the ischemic lesion, bone marrow from rats expressing green fluorescent protein (GFP) was transplanted into test subjects one month before performing SCI/R. Many GFP(+)/CD68(+) microglia and macrophages were present 7d after SCI/R. Resident (GFP(-)/Iba1(+)/CD68(-)) microglia and bone marrow-derived macrophages (BMDMs; GFP(+)/Iba1(+)/CD68(+)) colocalized in the mild group 7d after SCI/R. In the moderate group, BMDMs outnumbered resident microglia. A greater accumulation of BMDMs expressing insulin-like growth factor-1 (IGF-1) was observed in lesions in the severe group, relative to the moderate group. BMDMs in the severe group strongly expressed tumor necrosis factor α, interleukin-1β, and inducible nitric oxide synthase, in addition to IGF-1. A robust accumulation of BMDMs occupying the entire ischemic gray matter was observed only in the severe group. These results demonstrate that the magnitude of the microglial and BMDM responses varies considerably, and that it correlates with the severity of the neurological dysfunction. Remarkably, BMDMs appear to have a beneficial effect on the spinal cord in paresis. In contrast, BMDMs seem to exhibit both beneficial and harmful effects in severe paraplegia.


Can we predict patient outcome before extracorporeal membrane oxygenation for refractory cardiac arrest?
Refractory cardiac arrest resistant to conventional cardiopulmonary resuscitation (C-CPR) has a poor outcome. Although previous reports showed that extracorporeal cardiopulmonary resuscitation (E-CPR) can improve the clinical outcome, there are no clinically applicable predictors of patient outcome that can be used prior to the implementation of E-CPR. We aimed to evaluate the use of clinical factors in patients with refractory cardiac arrest undergoing E-CPR to predict patient outcome in our institution. This is a single-center retrospective study. We report 112 patients presenting with refractory cardiac arrest resistant to C-CPR between January 2012 and November 2017. All patients received E-CPR for continued life support when a cardiogenic etiology was presumed. Clinical factors associated with patient outcome were analyzed. Significant pre-ECMO clinical factors were extracted to build a patient outcome risk prediction model. The overall survival rate at discharge was 40.2, and 30.4% of patients were discharged with good neurologic function. The six-month survival rate after hospital discharge was 36.6, and 25.9% of patients had good neurologic function 6 months after discharge. We stratified the patients into low-risk (n = 38), medium-risk (n = 47), and high-risk groups (n = 27) according to the TLR score (low-flow Time, cardiac arrest Location, and initial cardiac arrest Rhythm) that we derived from pre-ECMO clinical parameters. Compared with the medium-risk and high-risk groups, the low-risk group had better survival at discharge (65.8% vs. 42.6% vs. 0%, p < 0.0001) and at 6 months (60.5% vs. 38.3% vs. 0%, p = 0.0001). The low-risk group also had a better neurologic outcome at discharge (50% vs. 31.9% vs. 0%, p = 0.0001) and 6 months after discharge (44.7% vs. 25.5% vs. 0%, p = 0.0003) than the medium-risk and high-risk groups. Patients with refractory cardiac arrest receiving E-CPR can be stratified by pre-ECMO clinical factors to predict the clinical outcome. Larger-scale studies are required to validate our observations.


Dietary sodium, potassium and calcium requirements of the house cricket, Acheta domesticus (L.).
1. The optimal level of sodium in an artificial diet for the house cricket was found to be 1126 ppm, of potassium 6487 ppm and of calcium 1366 ppm. 2. The revised salt mixture for the house cricket is 68.02 g NaCl, 120.00 g KCl, 310.00 g KH2PO4, 37.65 g CaHPO4, 53.34 g CaCO3, 90.50 g MgSO4.7H2O, 14.70 g FePO4.4H2O, 0.23 g MnSO4.H2O, 0.55 g ZnCO3 and 0.72 g CnSO4 in a total of 695.71 g salts.


Distribution of lidocaine and disopyramide in human blood and tissue, a case report of death caused by spinal anesthesia.
An 11-year-old girl was anesthetized with hyper-baric solution of lidocaine as spinal anesthesia for an appendectomy in a surgical clinic. Respiratory arrest which occurred soon after the injection, was not discovered for a period of time. Since spontaneous respiration recovered within 2 h of intensive resuscitation, the patient was transferred to a community hospital for intensive care. Ten hours after the spinal anesthesia, she died of cardiac failure. The concentration of lidocaine in the brain was 5-10 times more than that in other tissues. The relationship between the possibility of malpractice of spinal anesthesia and tissue distribution of the drug was discussed. In addition to lidocaine, a toxic amount of disopyramide, an antiarrhythmic drug, was detected in the body. The distribution of disopyramide was also estimated, and the pharmacokinetics of disopyramide in plasma and tissues were studied experimentally in rats.


High surgical volume is associated with a lower rate of secondary therapy after radical prostatectomy for localized prostate cancer.
To assess the relationship between surgical volume (SV), defined as the number of radical prostatectomies (RPs) within a calendar year, and the time to secondary therapy (ST) after RP, as this might represent an important determinant of cancer control. The study included 7937 men treated with RP by 130 urologists between 1989 and 2000. Radiotherapy or any form of hormonal manipulation represented ST. Univariable and multivariable Cox regression analyses was used to evaluate the time to ST after RP. SV was an independent (P = 0.02) predictor of ST-free survival after RP, and the multivariable rate of ST sharply decreased with increasing SV. The use of ST is inversely proportional to SV of up to 24 RPs per year. A higher annual SV might be indicative of less restrictive use of RP in high-risk patients who eventually require combined treatments.


Fluorescent intracellular imaging of reactive oxygen species and pH levels moderated by a hydrogenase mimic in living cells.
The catalytic generation of H2 in living cells provides a method for antioxidant therapy. In this study, an [FeFe]-hydrogenase mimic [Ru + Fe2S2@F127(80)] was synthesized by self-assembling polymeric pluronic F-127, catalytic [Fe2S2] sites, and photosensitizer Ru(bpy)3 2+. Under blue light irradiation, hydrated protons were photochemically reduced to H2, which increased the local pH in living cells (HeLa cells). The generated H2 was subsequently used as an antioxidant to decrease reactive oxygen species (ROS) levels in living cells (HEK 293T, HepG2, MCF-7, and HeLa cells). Our findings revealed that the proliferation of HEK 293T cells increased by a factor of about six times, relative to that of other cells (HepG2, MCF-7, and HeLa cells). Intracellular ROS and pH levels were then monitored using fluorescent cell imaging. Our study showed that cell imaging can be used to evaluate the ability of Ru + Fe2S2@F127 to eliminate oxidative stress and prevent ROS-related diseases.


Potential Role of Inflammation-Promoting Biliary Microbiome in Primary Sclerosing Cholangitis and Cholangiocarcinoma.
Primary sclerosing cholangitis (PSC) is a major risk factor for cholangiocarcinoma (CCA). We investigated biliary and fecal microbiota to determine whether specific microbes in the bile or stool are associated with PSC or CCA. Bile was obtained from 32 patients with PSC, 23 with CCA with PSC, 26 with CCA without PSC, and 17 controls. Over 90% of bile samples were from patients with perihilar CCA. Stool was obtained from 31 patients with PSC (11 were matched to bile), 16 with CCA with PSC (10 matched to bile), and 11 with CCA without PSC (6 matched to bile). Microbiota composition was assessed using 16SrRNA-marker-based sequencing and was compared between groups. Bile has a unique microbiota distinguished from negative DNA controls and stool. Increased species richness and abundance of Fusobacteria correlated with duration of PSC and characterized the biliary microbiota in CCA. Stool microbiota composition showed no significant differences between groups. We identified a unique microbial signature in the bile of patients with increased duration of PSC or with CCA, suggesting a role for microbiota-driven inflammation in the pathogenesis and or progression to perihilar CCA. Further studies are needed to test this hypothesis.


Interference strategy of Iridomyrmex pruinosum (Hymenoptera: Formicidae) during foraging.
The dolichoderine ant Iridomyrmex pruinosum and the formicines Myrmecocystus mimicus and M. depilis overlap widely in their niches. Although a worker of I. pruinosum is about four times smaller than a forager of Myrmecocystus, Iridomyrmex usually succeeds in displacing Myrmecocystus from the bait and often successfully blocks the nest entrance of its competitors, thus preventing Myrmecocystus foragers from leaving their nest. Iridomyrmex achieves this by quickly channeling large numbers of workers to food sources and nest entrances of Myrmecocystus, employing an effective chemical mass recruitment system, and chemicall repelling its competitors with secretions from the pygidial (anal) gland.


Quantitative vestibular assessment: The development and validation of a novel, remote video head impulse test against in-clinic measurements.
To develop a novel remote head impulse test (rHIT), and to provide preliminary data validating the rHIT vestibular-ocular reflex (VOR) gains against the in-clinic vHIT. A convenience sample of 10 patients referred for vestibular assessment at our institution was recruited. In-clinic vHIT was used to quantify lateral VOR gains. Patients subsequently underwent an rHIT protocol, whereby patients performed active, lateral head rotations while their eyes and heads were recorded using a laptop camera and video-conferencing software. The vHIT and rHIT VOR gains were compared using paired t-tests, and a Pearson correlation coefficient between the gains was calculated. Absolute accuracy, sensitivity, and specificity of the rHIT were additionally calculated. Of the 10 patients recruited, 4 were male, and the average ± standard deviation (SD) age was 61.4 ± 15.3 years. As determined by the vHIT, 2 patients had normal bilateral VOR gains, 6 with unilateral vestibular hypofunction, and 2 with bilateral vestibular hypofunction. The correlation between the rHIT and vHIT gains was 0.73 (p < .001). The rHIT exhibited an absolute accuracy of 75.0%, sensitivity of 70.0%, and specificity of 80.0%. When ears had a vHIT VOR gain less than 0.40, the rHIT exhibited 100.0% accuracy. Conversely, 60.0% of deficient ears with vHIT VOR gains greater than 0.40 were incorrectly categorized by the rHIT. The rHIT may be better suited for detecting more severe vestibular deficiencies. Future iterations of the rHIT should aim to increase the video frame-rate capabilities to detect subtler VOR impairments. 4.


Accelerating health equity: the key role of universal health coverage in the Sustainable Development Goals.
The Sustainable Development Goals (SDGs), to be committed to by Heads of State at the upcoming 2015 United Nations General Assembly, have set much higher and more ambitious health-related goals and targets than did the Millennium Development Goals (MDGs). The main challenge among MDG off-track countries is the failure to provide and sustain financial access to quality services by communities, especially the poor. Universal health coverage (UHC), one of the SDG health targets indispensable to achieving an improved level and distribution of health, requires a significant increase in government investment in strengthening primary healthcare - the close-to-client service which can result in equitable access. Given the trend of increased fiscal capacity in most developing countries, aiming at long-term progress toward UHC is feasible, if there is political commitment and if focused, effective policies are in place. Trends in high income countries, including an aging population which increases demand for health workers, continue to trigger international migration of health personnel from low and middle income countries. The inspirational SDGs must be matched with redoubled government efforts to strengthen health delivery systems, produce and retain more and relevant health workers, and progressively realize UHC.


N-benzyl-2-methoxy-5-propargyloxybenzoamides, a new type of bleaching herbicides targeting the biosynthesis pathway of plastoquinone.
Previously, the herbicidal activity of N-benzyl-2-methoxybenzamides was discovered during a random screening program in our laboratory. The chemicals resulted in bleaching effect of newly grown leaves by interfering with the biosynthesis of β-carotene in plant. A total of 28 benzamides were synthesized and subjected for the evaluation of herbicidal activity. Structure-activity relationship (SAR) showed that introducing propargyloxy group at 5-position of benzoyl-benzene ring and fluorine or methyl group at 3- or 4-position of benzyl-benzene ring is beneficial for the activity. Post-emergence herbicidal activities of compounds 406 and 412 were comparable to those of mesotrione and diflufenican. Studies on MOA showed that 406 decreased the level of both β-carotene and plastoquinone (PQ) in treated plants. The bleaching effect in green alga caused by 406 could be reversed by supplying exogenous homogentisic acid (HGA), the precursor of plastoquinone. N-benzyl-2-methoxy-5-propargyloxybenzoamides were discovered as new candidates for bleaching herbicides. Preliminary investigation on mechanism of action (MOA) showed that the title compounds might indirectly interfere with carotenoid biosynthesis by blocking the production of PQ. © 2023 Society of Chemical Industry.


Preoperative duloxetine on postoperative pain after laparoscopic gynecological surgeries: A systematic review and meta-analysis of randomized controlled trials.
To evaluate the efficacy and safety of preoperative duloxetine on postoperative pain management after gynecologic laparoscopic surgeries. A systematic search was done in Cochrane Library, PubMed, ISI web of science, and Scopus from inception to September 2021. We selected randomized clinical trials (RCTs) that compared preoperative duloxetine (intervention group) versus placebo (control group) among women undergoing gynecologic laparoscopic surgeries. Our primary outcomes were pain scores evaluated by the Visual Analog Scale (VAS) at 2, 6, 12, and 24 h postoperatively. Our secondary outcomes were the time required for the first analgesic request in minutes, postoperative analgesic consumption in milligrams, length of hospital stay in days, and side effects. Four RCTs with a total number of 244 patients were included in our systematic review and meta-analysis. We found duloxetine was linked to a significant reduction in VAS pain scores at different time intervals. The first analgesic request was significantly earlier in the placebo group than in the duloxetine group (p = 0.03). In addition, duloxetine significantly reduced the postoperative analgesic consumption compared to placebo (MD= -41.97, 95% CI [-53.23, -30.72], p<0.001). However, both groups did not differ in the length of hospital stay and side effects. Duloxetine administration prior to gynecological laparoscopic surgeries is safe and effective in improving postoperative pain and analgesia.


Early exposure to non-native language alters pre-attentive vowel discrimination.
The present study examined whether early exposure in language immersion would result in better pre-attentive discrimination of non-native speech sound contrasts. Mismatch negativity (MMN) responses were measured from two groups of Finnish children. The Monolingual group had no prior exposure to other languages than the native one, while the Immersion group consisted of children attending a French immersion program. The subjects were presented with two vowel contrasts in the oddball paradigm: the first pair was phonemic in the native language and the second was a within category pair in Finnish, but phonological in French. The results revealed that the Monolingual group showed a larger response to the native contrast in comparison with the non-native one, whereas both contrasts elicited a similar response in the Immersion group. These results suggest that early exposure to a new language enhances the pre-attentive discrimination ability reflected in increased MMN amplitude.


De novo assembly and characterization of the complete chloroplast genome of Elymus magellanicus (É.Desv.) Á.Löve, 1984 (Poaceae, Pooideae).
Elymus magellanicus (É.Desv.) Á.Löve is a foliage accent plant that originated in South America. In this study, the complete chloroplast genome of E. magellanicus is reported. It was found to have a total size of 133,249 bp. The chloroplast genome was found to consist of two inverted repeats (IRA and IRB) of 21,421 bp each, a small single-copy region of 12,709 bp, and a large single-copy region (77,698 bp). The annotation results show the GC content of the chloroplast genome to be 38.47%, including 40 tRNA genes, 82 protein-coding genes, and 8 rRNA genes. Phylogenetic analysis of 29 species revealed that E. magellanicus is closely related to E. arenarius.


Success of re-use of cardiac electrode catheters.
The feasibility of cardiac electrode catheter re-use was prospectively evaluated over a 5-year period (1981 to 1986), during which time 178 catheters were used 1,526 times for 847 electrophysiologic procedures. Detailed records of catheter testing and use were maintained. No complications were encountered during the study period. All re-used catheters functioned for cardiac pacing and electrographic recording. Surveillance cultures and biologic indicators revealed that adequate sterilization procedures were used. Thus, electrode catheters may be safely re-used provided a thorough cleaning, testing and record-keeping system is instituted. This may result in lower patient cost (approximately $30 per re-use vs [200 per single use) for electrophysiologic catheterization.


Anticancer drug-loaded nanospheres based on biodegradable amphiphilic ε-caprolactone and carbonate copolymers.
The aim was to investigate anticancer drug-loaded poly(carbonate-ester) nanospheres as potential drug delivery systems for cancer therapy. Functional poly(carbonate-ester) copolymers (HPCP-SD) were synthesized by the incorporation of sulfadiazine as the tumor-targeting groups to hydroxyl groups of poly(carbonate-ester) copolymers. Two types of anticancer drug-loaded poly(carbonate-ester) nanospheres I and II were further prepared by dialysis method and high-voltage electrostatic field-assisted atomization, respectively, using HPCP-SD as polymeric carriers. These carriers and anticancer drug-loaded nanospheres were characterized, and their properties in vitro and in vivo were evaluated. These anticancer drug-loaded poly(carbonate-ester) nanospheres had steady drug release rates and good controlled release properties. Moreover, anticancer drug-loaded poly(carbonate-ester) nanospheres II had faster drug release rates than those of anticancer drug-loaded nanospheres I. These anticancer drug-loaded nanospheres possessed lower cytotoxicity to HEK 293 cells and exhibited obviously higher anticancer efficiencies to the HeLa tumor cells than that of 5-fluorouracil. Anticancer drug-loaded nanospheres I possessed lower cytotoxicity to HEK 293 cells and higher anticancer activity to HeLa cells than those of anticancer drug-loaded nanospheres II. These anticancer drug-loaded poly(carbonate-ester) nanospheres showed the potential as drug delivery systems for cancer therapy.


The association between education and induced abortion for three cohorts of adults in Finland.
This paper explores whether the likelihood of abortion by education changed over time in Finland, where comprehensive family planning services and sexuality education have been available since the early 1970s. This subject has not previously been studied longitudinally with comprehensive and reliable data. A unique longitudinal set of register data of more than 250,000 women aged 20-49 born in 1955-59, 1965-69, and 1975-79 was analysed, using descriptive statistics, concentration curves, and discrete-time event-history models. Women with basic education had a higher likelihood of abortion than others and the association grew stronger for later cohorts. Selection into education may explain this phenomenon: although it was fairly common to have only basic education in the 1955-59 cohort, it became increasingly unusual over time. Thus, even though family planning services were easily available, socio-economic differences in the likelihood of abortion remained.


Comparison of CG, CKD-EPI[AS] and CKD-EPI[ASR] equations to estimate glomerular filtration rate and predict mortality in treatment naïve people living with HIV in Zimbabwe.
Renal impairment in people living with HIV (PWH) in Sub-Saharan Africa is common and associated with increased morbidity and mortality. The ideal equation to estimate glomerular filtration rate (eGFR) in this population remains unclear. That which best predicts clinical risk may be the most appropriate while validation studies are awaited. Here we compare the Cockcroft-Gault (CG), Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI[ASR]) and the CKD-EPI equation with the race coefficient removed (CKD-EPI[AS]), in a population of anti-retroviral therapy (ART) naïve PWH in Zimbabwe to assess which equation best predicts mortality. A retrospective cohort study of treatment naïve PWH at the Newlands Clinic in Harare, Zimbabwe was completed. The study included all patients commencing ART between 2007 and 2019. Predictors of mortality were assessed by multivariable logistic regression. A total of 2991 patients were followed-up for a median of 4.6 years. The cohort was 62.1% female, with 26.1% of patients having at least one comorbidity. The CG equation identified 21.6% of patients as having renal impairment compared with 17.6% with CKD-EPI[AS] and 9.3% with CKD-EPI[ASR]. There was a mortality rate of 9.1% across the study period. The highest mortality risk was seen in those with renal impairment as determined by the CKD-EPI[ASR] equation for both eGFR < 90 and eGFR < 60 with OR 2.97 (95%CI 1.86-4.76) and OR 10.6 (95%CI 3.15-18.04) respectively. In treatment naïve PWH in Zimbabwe, the CKD-EPI[ASR] equation identifies patients at highest risk of mortality when compared to the CKD-EPI[AS] and CG equations.