Extracorporeal membrane oxygenation as a bridge to durable mechanical circulatory support or heart transplantation.
Patients with cardiogenic shock may require extracorporeal membrane oxygenation (ECMO) prior to durable mechanical circulatory support (dMCS) or heart transplantation (HTx). We investigated the clinical characteristics and outcomes of adult patients with ECMO support as bridge to dMCS or HTx between 1/1/13 and 12/31/20. Of 57 patients who underwent bridging ECMO, 41 (72%) received dMCS (approximately half with biventricular support) and 16 (28%) underwent HTx, 13 (81%) after the 2018 UNOS allocation system change. ECMO → HTx patients had shorter ventilatory time (3.5 vs 7.5 days; p = 0.018), ICU stay (6 vs 18 days; p = 0.001), and less need for inpatient rehabilitation (18.8% vs 57.5%; p = 0.016). The 1-year survival post HTx was 81.3% in the ECMO → HTx group and 86.4% in the ECMO → dMCS group (p = 0.11). For those patients in the ECMO → dMCS group who did not undergo HTx, 1-year survival was significantly lower, 31.6% (p = 0.001). Patients on ECMO who undergo HTx, with or without dMCS bridge, have acceptable post-HTx survival. These findings suggest that HTx from ECMO is a viable option for carefully selected patients deemed acceptable to proceed with definitive advanced therapies, especially in the era of the new UNOS allocation system.


Current therapy in childhood brain tumors.
This article reviews the current approach to the treatment of childhood brain tumors. Common childhood brain tumors are profiled in separate sections, and the conclusion includes a discussion of the long-term clinical effects of radiation and chemotherapy.


Expression of the group I metabotropic glutamate receptor in the hippocampus of patients with mesial temporal lobe epilepsy.
Immunocytochemical studies at light and electron microscopic levels in hippocampi of patients with mesial temporal lobe epilepsy showed mGluR1 and mGluR5 immunoreactivity in the molecular layer of the dentate gyrus and CA1 area, especially at the border between stratum oriens and alveus. By electron microscopy, degenerating neuronal elements were found in all areas studied. There were glial filamentous tangles which appeared similar to intranuclear inclusions in astrocytes in all areas studied. Reactive product for mGluR1 was localised only in post-synaptic elements. However, mGluR5 immunoreactivity was demonstrated in both post- and pre-synaptic elements in the molecular layer of the dentate gyrus and CA1 area. Reactive product for mGluR5 was also demonstrated in astrocytes and in the periphery of fibrillary tangles. We postulate that in patients with mesial temporal lobe epilepsy, mGluR1 may increase hippocampal excitability through postsynaptic activation, and mGluR5 may do so through both pre- and post-synaptic mechanisms.


The Effect of Mn, Al Doping on the CO2 Hydrogenation Performance of CaCO3 -Supported Fe-Based Catalysts.
With increasingly serious environmental problems caused by the greenhouse effect, it has also become essential to reduce the concentration of CO2 in the atmosphere. In this paper, CaCO3 -supported Fe-based catalysts doped with Mn, Al, and K are prepared by a straightforward method and used for CO2 hydrogenation. The fresh and spent catalysts were characterized by SEM-EDS, BET, TG, CO2 -TPD, XRD, and XPS. The experimental results show that the highest CO2 conversion rate of Fe10Mn2Al10Ca is 35.99 %, the maximum FTY value is 293.98 μmolCO2 ⋅ g Fe - 1 ${{\rm{g}}_{{\rm{Fe}}}^{ - 1} }$ ⋅ s-1 , the maximum O/P value is 6.61, and the lowest CO selectivity is 32.21 %. At the same time, according to the characterization results, the doping of Mn and Al increased the Fe3 O4 /FeCx ratio. As the Fe3 O4 /FeCx ratio increases, the proportion of short-chain hydrocarbons (CH4 , C2-4 ) in the products increases, and the proportion of long-chain hydrocarbons (C5+ ) decrease. Therefore, the co-doping of Mn and Al promotes the conversion of CO and reduces its selectivity, and promotes the formation of light olefins. Finally, it is hoped that this study can provide a reference for further research on CaCO3 -supported Fe catalysts.


The alkaline phosphatase of beef, horse, pig and sheep brain have been purified. In each case, the alkaline phosphatase activity can be separated into two or three components by DEAE-cellulose chromatography and by electrophoresis. Although the properties of these enzyme fractions are very similar, there are sufficient differences to identify each species.Furthermore two of the three components separated in sheep brain differ in their Michaelis constants using beta-glycerophosphate as substrate, whereas the two pig brain components are not different in this respect. This supports the view of two alkaline phosphatase isoenzymes in sheep brain.


Melanin from the Lichens Cetraria islandica and Pseudevernia furfuracea: Structural Features and Physicochemical Properties.
Lichens are symbiotic photosynthesizing organisms with thalli formed by fungi and algae/cyanobacteria that possess high stress tolerance. One of the factors that contributes to the ability of a lichen to tolerate harsh environmental conditions is the presence of unique metabolites, including high-molecular-weight dark pigments termed melanins. The chemical composition and structure of lichen melanins remain poorly studied. We analyzed the elemental composition, the main functional groups, and the physicochemical properties of melanin extracted from Cetraria islandica and Pseudevernia furfuracea lichens. Based on the C/N ratio, this pigment is allomelanin. We also identified functional groups that provide photoprotective and antioxidant properties of melanin. Melanin synthesis might be an essential defense mechanism contributing to the survival of lichens under exposure to UV radiation.


Characterization and active component identification of Premna herbacea roxb. root extract reveals anti-inflammatory effect and amelioration of imiquimod induced psoriasis via modulation of macrophage inflammatory response.
1-2.88% of human populations are affected by psoriasis, one type of chronic inflammatory skin disease. Skin thickenings, erythema, scaling in skin are the most important symptoms of psoriasis. There are renewed interests amongst scientists in studying anti-inflammatory property of the plant extracts due to lower side effects and cost effectiveness. There are few reports suggesting anti-inflammatory activity of Premna herbacea roxb. but lacks systematic evaluation of these properties. We, initially tested the anti-inflammatory activity of crude root methanolic extract in vitro, where it significantly reduced LPS generated ROS in splenic macrophages. We further tested the TLC and HPLC fraction in order to find active ingredient in Premna herbacea roxb. root extract that ameliorated the chronic inflammation of skin and performed GC-MS and LC-MS studies to identify active component. Upon finding significant anti-inflammatory effect of the crude root extract in vitro, We studied the efficacy of the Premna herbacea roxb. root extract in Imiquimod induced psoriasis like skin inflammation in male BALB/C mice that closely resembles human psoriasis. Immunophenotyping, Cytokine productions were observed by flow cytometry, status of gene expression was done by Real time PCR and nuclear co-localization was studied by confocal microscopy. We observed progressive increase in signs and symptoms of the disease in imiquimod treated diseased animals but the Premna herbacea roxb. Root Methanolic Extract (PHRME) reduced the thickening of the skin, redness and scaling in these animals. In our study, along with progression of the disease, the production of macrophages increases and with the application of PHRME, the percentage of macrophages have reduced. As per the previous Indigenous traditional knowledge regarding use of Premna herbacea roxb. against inflammatory disorder and lack of detail mechanistic study of the crude root extract prompted us to elucidate the efficacy of the root extract in vitro and in vivo psoriatic mice model. For the first time we have identified three putative bioactive active components (5‑hydroxy-7-methoxyflavanone, 3-Hydroxy-7,8,2',3'-tetramethoxyflavone, 2,4',6'-trimethoxy chalcone) from Premna herbacea root methanolic extract (PHRME) and we suggest PHRME and purified active fractions influence NFκB and COX2 signaling pathway to suppress inflammatory conditions. All of the purified components show strong binding efficiency in our molecular docking analysis. Our study also suggests that Premna herbacea roxb. root extract may be explored as cost effective alternative for established treatment regimen as our study also indicates low side effect of the extract against pre-clinical psoriatic model.


COVID-19: Reducing the risk via diet and lifestyle.
This review shows that relatively simple changes to diet and lifestyle can significantly, and rapidly, reduce the risks associated with coronavirus disease 2019 (COVID-19) in terms of infection risk, severity of disease, and even disease-related mortality. A wide range of interventions including regular exercise, adequate sleep, plant-based diets, maintenance of healthy weight, dietary supplementation, and time in nature have each been shown to have beneficial effects for supporting more positive health outcomes with COVID-19, in addition to promoting better overall health. This paper brings together literature from these areas and presents the argument that non-pharmaceutical approaches should not be overlooked in our response to COVID-19. It is noted that, in several cases, interventions discussed result in risk reductions equivalent to, or even greater than, those associated with currently available vaccines. Where the balance of evidence suggests benefits, and the risk is minimal to none, it is suggested that communicating the power of individual actions to the public becomes morally imperative. Further, many lives could be saved, and many harms from the vaccine mandates avoided, if we were willing to embrace this lifestyle-centred approach in our efforts to deal with COVID-19.


Tolerance to alprazolam after intravenous bolus and continuous infusion: psychomotor and EEG effects.
A study was undertaken to compare the time course of changes in psychomotor performance and spectral edge (SE) of the EEG and to relate these changes to alprazolam concentrations in a pharmacokinetic/pharmacodynamic tolerance model. Digit symbol substitution (DSS) tests were administered and EEG data were obtained for SE calculation in a four-way crossover study in four normal men. Each treatment consisted of a 2-minute bolus injection followed by an 8-hour infusion. Treatment A, placebo, consisted of a 50% propylene glycol injection followed by a saline infusion. Active drug treatments were: B, 0.5 mg alprazolam plus saline infusion; C, 2.0 mg alprazolam plus saline; and D, 1.0 mg plus 72 micrograms alprazolam/hr for a total dose of 1.576 mg in 8 hours. For both DSS and SE data, three distinct effect-concentration curves result from the three alprazolam treatments, with successive shifts to the right as dose increases. A tolerance rate constant (kt) of 0.15 hr-1 was calculated from the DSS vs. time data during the 8 hour alprazolam infusion. The Hill equation was altered by using kt in an exponential modification of EC50. The resulting tolerance model describes both DSS and SE vs. concentration data from the rapid-injection and continuous-infusion treatments.


Distribution of congenital heart malformations in an autopsied child population.
All stillborn and all deceased children were autopsied during a 27-year period in a given territory with some 1,220,000 inhabitants. Of the 3969 stillborn children, 81 (2.1%) had a congenital heart malformation. Out of the 470,188 liveborn children, 13,629 died before the age of 15 years. Autopsy demonstrated a heart malformation in 1008 (0.21%) of these liveborn children. Thus, with 1089 cases found in the combined stillborn and liveborn and later deceased children, congenital heart malformation was found in 6.2% of all autopsied children. This represented 7.4% of the total mortality of liveborn children and 41.4% of all congenital malformation discovered in the deceased children. In total, 2257 congenital heart lesions were identified with a mean of 2.1 lesions per child. The lesions were classified in 37 categories of heart malformation. The most common malformation was ventricular septal defect, followed by hypoplastic left ventricle and complete transposition. The most frequent heart lesion was also ventricular septal defect followed by patency of the arterial duct. The frequency of the different heart malformations in stillborns differed from that in the liveborn children. The ratio of boys and girls in the overall series was 1.28:1, with pronounced differences in sex distribution being observed in some malformations.


Single-Step GBLUP and GWAS Analyses Suggests Implementation of Unweighted Two Trait Approach for Heat Stress in Swine.
The purpose of this study was to perform a genome-wide association study to determine the genomic regions associated with heat stress tolerance in swine. Phenotypic information on carcass weight was available for 227,043 individuals from commercial farms in North Carolina and Missouri, U.S. Individuals were from a commercial cross of a Duroc sire and a dam resulting from a Landrace and Large White cross. Genotypic information was available for 8232 animals with 33,581 SNPs. The pedigree file contained a total of 553,448 animals. A threshold of 78 on the Temperature Humidity Index (THI) was used to signify heat stress. A two-trait analysis was used with the phenotypes heat stress (Trait One) and non-heat stress (Trait Two). Variance components were calculated via AIREML and breeding values were calculated using single step GBLUP (ssGBLUP). The heritability for Traits One and Two were calculated at 0.25 and 0.20, respectively, and the genetic correlation was calculated as 0.63. Validation was calculated for 163 genotyped sires with progeny in the last generation. The benchmark was the GEBV with complete data, and the accuracy was determined as the correlation between the GEBV of the reduced and complete data for the validation sires. Weighted ssGBLUP did not increase the accuracies. Both methods showed a maximum accuracy of 0.32 for Trait One and 0.54 for Trait Two. Manhattan Plots for Trait One, Trait Two, and the difference between the two were created from the results of the two-trait analysis. Windows explaining more than 0.8% of the genetic variance were isolated. Chromosomes 1 and 14 showed peaks in the difference between the two traits. The genetic correlation suggests a different mechanism for Hot Carcass Weight under heat stress. The GWAS results show that both traits are highly polygenic, with only a few genomic regions explaining more than 1% of variance.


Mannose inhibition of Escherichia coli adherence to urinary bladder epithelium: comparison with yeast agglutination.
The adherence of piliated strains of Escherichia coli (E. coli) to mammalian epithelial cells has been reported by several investigators to be specifically inhibited by D(+)-mannose or its derivatives. Much of this work utilized mannose type compounds to inhibit agglutination of mannan containing yeast cells by E. coli to demonstrate mannose sensitivity. This report investigates the ability of the neotype strain of E. coli (which is sensitive to mannose inhibition of yeast cell agglutination) to bind and metabolize radiolabeled D(+)-mannose. In addition the relative efficacy of D(+)-mannose and heparin to inhibit the adherence of E. coli to rabbit bladder mucosa was compared. Results showed that although D(+)-mannose did block E. coli--yeast cell agglutination in a reversible manner, radiolabeled D(+)-mannose binding by E. coli could not be displaced by 1,000 fold excess unlabeled D(+)-mannose. This suggests uptake of the sugar as opposed to a surface binding phenomenon which was confirmed by the demonstration of significant metabolism of mannose by E. coli. The same concentration of D(+)-mannose which prevented E. coli--yeast cell agglutination was not particularly effective in preventing E. coli adherence to the acid denuded rabbit bladder. Heparin treatment of the acid denuded bladder was very effective in preventing E. coli adherence but was ineffective in preventing E. coli--yeast cell agglutination. This indicates that E. coli--yeast cell agglutination should not be correlated with E. coli adherence to mammalian epithelial tissue.


A three-component multi-b-value diffusion-weighted imaging might be a useful biomarker for detecting microstructural features in gliomas with differences in malignancy and IDH-1 mutation status.
The purpose of the study was to explore the performance of a three-component diffusion model in evaluating the degree of malignancy and isocitrate dehydrogenase 1 (IDH-1) gene type of gliomas. Overall, 60 patients with gliomas were enrolled. The intermediate and perfusion-related diffusion coefficients (Dint and Dp) and fractions of strictly limited, intermediate, and perfusion-related diffusion (Fvery-slow, Fint, and Fp) were obtained with a three-component diffusion model. Parameters were also obtained from a diffusion kurtosis model and mono- and biexponential models. All parameters were compared between different tumor grades and IDH-1 gene types. Diagnostic performance and logistic regression analyses were performed. High-grade gliomas (HGGs) had significantly higher Fint, Fvery-slow, and Dp values but significantly lower Fp and Dint values than low-grade gliomas (LGGs), and Fint and Fp differed significantly among grade II, III, and IV gliomas (p < 0.05 for all). Fint achieved the highest AUC of 0.872 in differentiating between LGGs and HGGs. Logistic regression analysis revealed that in each model, Fint, diffusion coefficient (D), apparent diffusion coefficient (ADC), mean diffusivity (MD), and mean kurtosis (MK) were associated with glioma grading. After multiple regression analysis, Fint remained the only differentiator. Additionally, Fint and Fp showed significant differences between IDH-1 mutated and IDH-1 wild-type gliomas (p = 0.007 and 0.01, respectively). The three-component DWI model served as a useful biomarker for detecting microstructural features in gliomas with different grades and IDH-1 mutation statuses. • The three-component model enables the estimation of an intermediate diffusion component. • The three-component model performed better than the other models in glioma grading and genotyping. • Fint was useful in evaluating the grade and genotype of gliomas.


Pre-stimulus alpha and post-stimulus N2 foreshadow imminent errors in a single task.
Performance errors have been attributed to distinct neural mechanisms in different tasks. Two temporally and physiologically dissociable neural patterns prior to errors, i.e., pre-stimulus alpha (8-13 Hz) power indicative of sustained attention and post-stimulus N2 amplitude indicative of cognitive control, have been widely (but independently) reported in many studies. However, it is still largely unknown whether these two neural mechanisms for error commission exist in a single task at the same time and, if so, whether they can be probed simultaneously and how they lead to response accuracy (collectively or separately). To this end, we measured high-density electroencephalography (EEG) signals in a color-word matching Stroop task. We quantified both patterns on EEG data from individual stimulus condition (congruent or incongruent), as well as on pooled data from both conditions. Enhanced pre-stimulus alpha power for errors was identified over the parieto-occipital area in the congruent condition and the pooled data. Reduced post-stimulus N2 amplitude was only revealed in the incongruent condition. More importantly, for the first time, a balanced interaction between these two EEG patterns was revealed in correct trials, but not in error trials. These findings suggest that errors in one task could occur due to distinct neural mechanisms, e.g., poor sustained attention, poor cognitive control, or missed balance between these two. The present results further suggest that the detection of neural patterns related to different neural mechanisms could be complicated by other modulation factors, such as stimulus condition. Therefore, more than one neural marker should be simultaneously monitored to effectively predict imminent errors.


Nanoparticle-Based Combination Therapy Enhances Fulvestrant Efficacy and Overcomes Tumor Resistance in ER-Positive Breast Cancer.
Nanoparticles (NP) spanning diverse materials and properties have the potential to encapsulate and to protect a wide range of therapeutic cargos to increase bioavailability, to prevent undesired degradation, and to mitigate toxicity. Fulvestrant, a selective estrogen receptor degrader, is commonly used for treating patients with estrogen receptor (ER)-positive breast cancer, but its broad and continual application is limited by poor solubility, invasive muscle administration, and drug resistance. Here, we developed an active targeting motif-modified, intravenously injectable, hydrophilic NP that encapsulates fulvestrant to facilitate its delivery via the bloodstream to tumors, improving bioavailability and systemic tolerability. In addition, the NP was coloaded with abemaciclib, an inhibitor of cyclin-dependent kinases 4 and 6 (CDK4/6), to prevent the development of drug resistance associated with long-term fulvestrant treatment. Targeting peptide modifications on the NP surface assisted in the site-specific release of the drugs to ensure specific toxicity in the tumor tissues and to spare normal tissue. The NP formulation (PPFA-cRGD) exhibited efficient tumor cell killing in both in vitro organoid models and in vivo orthotopic ER-positive breast cancer models without apparent adverse effects, as verified in mouse and Bama miniature pig models. This NP-based therapeutic provides an opportunity for continual and extensive clinical application of fulvestrant, thus indicating its promise as a treatment option for patients with ER-positive breast cancer. A smart nanomedicine encapsulating fulvestrant to improve its half-life, bioavailability, and tumor-targeting and coloaded with CDK4/6 inhibitor abemaciclib to block resistance is a safe and effective therapy for ER-positive breast cancer.


Towards an understanding of the information dynamics of the handover process in aged care settings--a prerequisite for the safe and effective use of ICT.
Poor clinical handover has been associated with inaccurate clinical assessment and diagnosis, delays in diagnosis and test ordering, medication errors and decreased patient satisfaction in the acute care setting. Research on the handover process in the residential aged care sector is very limited. The aims of this study were to: (i) Develop an in-depth understanding of the handover process in aged care by mapping all the key activities and their information dynamics, (ii) Identify gaps in information exchange in the handover process and analyze implications for resident safety, (iii) Develop practical recommendations on how information communication technology (ICT) can improve the process and resident safety. The study was undertaken at a large metropolitan facility in NSW with more than 300 residents and a staff including 55 registered nurses (RNs) and 146 assistants in nursing (AINs). A total of 3 focus groups, 12 interviews and 3 observation sessions were conducted over a period from July to October 2010. Process mapping was undertaken by translating the qualitative data via a five-category code book that was developed prior to the analysis. Three major sub-processes were identified and mapped. The three major stages are Handover process (HOP) I "Information gathering by RN", HOP II "Preparation of preliminary handover sheet" and HOP III "Execution of handover meeting". Inefficient processes were identified in relation to the handover including duplication of information, utilization of multiple communication modes and information sources, and lack of standardization. By providing a robust process model of handover this study has made two critical contributions to research in aged care: (i) a means to identify important, possibly suboptimal practices; and (ii) valuable evidence to plan and improve ICT implementation in residential aged care. The mapping of this process enabled analysis of gaps in information flow and potential impacts on resident safety. In addition it offers the basis for further studies into a process that, despite its importance for securing resident safety and continuity of care, lacks research.


Skeletal findings in the first 12 months following initiation of glucocorticoid therapy for pediatric nephrotic syndrome.
Incident vertebral fractures and lumbar spine bone mineral density (BMD) were assessed in the 12 months following glucocorticoid initiation in 65 children with nephrotic syndrome. The incidence of vertebral fractures was low at 12 months (6 %) and most patients demonstrated recovery in BMD Z-scores by this time point. Vertebral fracture (VF) incidence following glucocorticoid (GC) initiation has not been previously reported in pediatric nephrotic syndrome. VF was assessed on radiographs (Genant method); lumbar spine bone mineral density (LS BMD) was evaluated by dual-energy X-ray absorptiometry. Sixty-five children were followed to 12 months post-GC initiation (median age, 5.4 years; range, 2.3-17.9). Three of 54 children with radiographs (6 %; 95 % confidence interval (CI), 2-15 %) had incident VF at 1 year. The mean LS BMD Z-score was below the healthy average at baseline (mean ± standard deviation (SD), -0.5 ± 1.1; p = 0.001) and at 3 months (-0.6 ± 1.1; p < 0.001), but not at 6 months (-0.3 ± 1.3; p = 0.066) or 12 months (-0.3 ± 1.2; p = 0.066). Mixed effect modeling showed a significant increase in LS BMD Z-scores between 3 and 12 months (0.22 SD; 95 % CI, 0.08 to 0.36; p = 0.003). A subgroup (N = 16; 25 %) had LS BMD Z-scores that were ≤-1.0 at 12 months. In these children, each additional 1,000 mg/m(2) of GC received in the first 3 months was associated with a decrease in LS BMD Z-score by 0.39 at 12 months (95 % CI, -0.71 to -0.07; p = 0.017). The incidence of VF at 1 year was low and LS BMD Z-scores improved by 12 months in the majority. Twenty-five percent of children had LS BMD Z-scores ≤-1.0 at 12 months. In these children, LS BMD Z-scores were inversely associated with early GC exposure, despite similar GC exposure compared to the rest of the cohort.


Factors Influencing The Participation Of Nurses In Knowledge-Sharing Within Mobile Instant Messaging Based Virtual Communities Of Practice: A Qualitative Content Analysis.
The emergence of mobile instant messaging (MIM) based virtual communities of practice (VCoPs) has provided new opportunities for nurses to share their knowledge and promote collaborative learning. This study was conducted with the aim of exploring the factors influencing nurses' participation in knowledge-sharing within MIM-based VCoPs. This is a qualitative study conducted in Tehran, Iran, between April 2017 and July 2018. The participants were 18 nurses that selected through purposeful sampling technique; then, in-depth and semi-structured interviews were conducted with them. Data was analyzed using conventional content analysis based on Graneheim and Lundman (2004). Accordingly, all interviews were transcribed and read several times; then, meaning units were identified from the transcribed text based on the aim of the study and codes were extracted from them. Finally, the codes were classified into categories and themes. A total of 26 sub-categories, seven categories, and two themes were extracted. Motivations for nurses' participating in knowledge-sharing activities within MIM-based VCoPs included the theme "Stimuli for professional interactions" with three categories: "The individual drives", "Attractive interactive environment", and "User-friendly media". On the other hand, participation barriers included the theme "Impediments for professional interactions" with four categories of "Individual hindrances", "Social harm", "Unprofessional interactive environment" and "Undesirable media". The findings of this exploratory study indicated that individual, social and technological factors as well as factors associated with the virtual-community interactive environment could influence nurses' participation in knowledge-sharing within MIM-based VcoPs as motivations and barriers. The insights obtained from this study can be a guide for administrators and educators in the nursing profession to facilitate and enhance nurses' participation in knowledge-sharing within MIM-based VCoPs by strengthening motivations and minimizing barriers.


CRISPR-Cas9 Targeting of PCSK9 in Human Hepatocytes In Vivo-Brief Report.
Although early proof-of-concept studies of somatic in vivo genome editing of the mouse ortholog of proprotein convertase subtilisin/kexin type 9 (Pcsk9) in mice have established its therapeutic potential for the prevention of cardiovascular disease, the unique nature of genome-editing technology-permanent alteration of genomic DNA sequences-mandates that it be tested in vivo against human genes in normal human cells with human genomes to give reliable preclinical insights into the efficacy (on-target mutagenesis) and safety (lack of off-target mutagenesis) of genome-editing therapy before it can be used in patients. We used a clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated (Cas) 9 genome-editing system to target the human PCSK9 gene in chimeric liver-humanized mice bearing human hepatocytes. We demonstrated high on-target mutagenesis (approaching 50%), greatly reduced blood levels of human PCSK9 protein, and minimal off-target mutagenesis. This work yields important information on the efficacy and safety of CRISPR-Cas9 therapy targeting the human PCSK9 gene in human hepatocytes in vivo, and it establishes humanized mice as a useful platform for the preclinical assessment of applications of somatic in vivo genome editing.


Clinical and genetic factors associated with sacroiliitis in Crohn's disease.
Radiographic sacroiliitis (SI), often asymptomatic, is considered the most frequent extra-intestinal manifestation (EIM) of Crohn's disease (CD). Data on the association of SI with other clinical features of CD are limited. Association of SI with CARD15 polymorphisms has recently been suggested. In a multicenter study, we investigated the association of SI in CD patients with clinical phenotypes, other EIM and CARD15 polymorphisms. Radiographs of the sacroiliac joints were taken in 251 CD patients from three Belgian university hospitals and scored by two blinded rheumatologists. Clinical features were obtained from medical records. Forty-three percent of patients carried at least one CARD15 polymorphism. Sacroiliitis, defined as the presence of at least grade 2 unilateral changes, was diagnosed in 65 of the 244 scorable radiographs (27%). Only 16 of these patients were previously diagnosed with ankylosing spondylitis (AS). HLA-B27 positivity was observed in 53% of patients with AS and 7% of patients with radiographic SI. In univariate and multivariate analysis, associations between the presence of SI and peripheral arthritis (P = 0.005) and between AS and uveitis (P = 0.005) were found. No associations with other recorded clinical features or with CARD15 polymorphisms were observed. We confirm the high prevalence of radiographic sacroiliitis in a multicenter CD cohort. Uveitis is only associated with AS whereas all patients with SI are more prone to develop peripheral arthritis during their disease course, suggesting similar pathogenetic mechanisms in the development of these EIM. The previously reported association between SI and CARD15 polymorphisms was not confirmed.


Expression of melanocortin receptors and pro-opiomelanocortin in the rat spinal cord in relation to neurotrophic effects of melanocortins.
Although neurotrophic effects of alpha-melanocyte-stimulating hormone (alpha-MSH) are well established, the mechanism underlying these effects is unknown. To identify candidate components of the signaling system that may mediate these effects, in the present study rat spinal cord, dorsal root ganglia, sciatic nerve and soleus muscle were analysed for the expression of the neural MC3, MC4 and MC5 receptors and for the expression of the melanocortin precursor pro-opiomelanocortin (POMC). In rat lumbar spinal cord, the MC4 receptor was the only MC receptor subtype for which mRNA was detectable using RNAse protection assays. In situ binding studies using 125I-NDP-MSH, a synthetic alpha-MSH analogue, demonstrated MC receptor protein in the rat spinal cord, predominantly localised in substantia gelatinosa and area X, surrounding the central canal. Furthermore, POMC mRNA was demonstrated in rat spinal cord and dorsal root ganglia. These findings suggest a functional melanocortin system in the rat spinal cord, that might be involved in peripheral nerve repair. Regulation of POMC or MC receptor transcripts does not appear to be involved in the response to peripheral nerve crush in rats, since no change in mRNA expression patterns was detected after sciatic nerve crush, using quantitative RNAse protection assays. Nevertheless, subtle changes in melanocortin receptor binding did occur postsurgically in several regions of the spinal cord in both sham-operated and sciatic nerve-lesioned rats. The robust expression of MC receptor protein in spinal cord regions that are generally associated with nociception suggests a potentially broader involvement of endogenous melanocortins in spinal pathways which mediate the responses to peripheral injury, in addition to any direct melanocortin effects on sprouting and neurite outgrowth.


Joint infection, with consideration of underlying disease and sources of bacteremia in hematogenous infection.
Joint infection commonly results from hematogenous spread of infection from a distant site. Pre-existing joint disease increases the risk of joint infection during bacteremia. Most patients present with pain, swelling, heat, and limitation of motion of the affected joint, often with fever, but presentation may be atypical, especially in patients with rheumatoid arthritis, systemic corticosteroid therapy, or infected prosthetic joints. Diagnosis is best made by analysis and culture of synovial fluid. The infecting microorganism often provides a clue to remote infection or underlying disease, which may require special attention. Therapy consists of high-dose parenteral antibiotics and adequate drainage. Outcome depends on early diagnosis and appropriate therapy.


Voltammetric determination of boron by using Alizarin Red S.
A novel voltammetric method for boron determination in ppb level is described. Boron complexes with Alizarin Red S (ARS) and the complex, as well as the free ligand, both adsorbs on a hanging mercury drop electrode. The method is based on the monitoring the anodic peak of the complex at -0.47 V in ammonium acetate-phosphate buffer (pH 7). The maximum peak current was obtained by scanning the potential from -700 mV versus Ag/AgCl to more positive potentials without accumulation in the presence of 1 x 10(-6) mol L(-1) of ARS. The instrumental parameters were mainly differential pulse mode with a pulse duration of 0.02 s and a scan rate of 5 mV s(-1). The limit of detection based on signal to ratio of 3 was calculated as 15 microgL(-1). The calibration plot for boron was linear in the range of 0-500 microg L(-1). The interference of various ions was examined and serious interference was observed from antimony(III). The relative standard deviation was found to be 5.1% for the 100 microg L(-1) boron level (n=10). The method was applied to the determination of boron in water and seawater samples with high boron content. The results obtained from the developed method were compared with Azomethine-H-method and no statistically significant difference was found.


Laryngeal effects on respiratory pressures and timing in rabbits: role of the vagi.
Tidal breathing through a tracheostomy and through the larynx were compared in two groups of rabbits. Ten control and fourteen rabbits with chronically vagally denervated lungs were anaesthetized and spontaneously breathing. Inspiratory and expiratory tracheal pressure and timing components of respiratory pattern were measured in both groups of animals before and after carotid sinus/body denervation and cervical vagotomy. Breathing through the larynx significantly increased the inspiratory pressure and, to a lesser degree, affected expiratory pressure in both groups of animals and changed the respiratory timing by prolongation of TI and shortening of TE. Our results indicate that the larynx prominently influences pressures within the lower respiratory tract but its effect on the pattern of breathing is confined only to animals with an intact lung innervation.


Weight Change Is Associated with Osteoporosis: A Cross Sectional Study Using the Korean Community Health Survey.
The purpose of the present study was to analyze the associations between weight change and osteoporosis in Korean adults. Data from the 2016 Korean Community Health Survey were analyzed. A total of 159,741 participants who were ≥40 years of age were included. The histories of osteoporosis were surveyed in two ways: 'osteoporosis for entire life' and 'current osteoporosis'. The participants were grouped into three categories for simplification as follows: 'Weight L&M' (Tried to lose weight or Tried to maintain weight), 'Weight gain' (Tried to gain weight), and 'Never tried'. Additionally, we analyzed their relationship with obesity using the BMI. The adjusted ORs for 'osteoporosis for entire life' were 1.20 (95% confidence interval [CI] 1.13-1.27) in the Weight L&M group and 1.83 (95% CI 1.64-2.05) in the Weight gain group. The adjusted ORs for 'current osteoporosis' were 1.16 (95% CI 1.08-1.25) in the Weight L&M group and 1.77 (95% CI 1.54-2.02) in the Weight gain group. Compared to the Never tried group, being in either the Weight L&M or Weight gain groups showed a significant impact on the possibility of osteoporosis.


Incidence of complications associated with cervical spine surgery and post-operative physical therapy and implications for timing of initiation of post-operative physical therapy: a retrospective database study.
To describe the incidence of complications associated with cervical spine surgery and post-operative physical therapy (PT), and to identify if the timing of initiation of post-operative PT impacts the incidence rates. MOrtho PearlDiver database was queried using billing codes to identify patients who had undergone Anterior Cervical Discectomy and Fusion (ACDF), Posterior Cervical Fusion (PCF), or Cervical Foraminotomy and post-operative PT from 2010-2019. For each surgical procedure, patients were divided into three 12-week increments for post-operative PT (starting at post-operative weeks 2, 8, 12) and then matched based upon age, gender, and Charlson Comorbidity Index score. Each group was queried to determine complication rates and chi-square analysis with adjusted odds ratios, 95% confidence intervals, and p-values were used. Following matching, 3,609 patients who underwent cervical spine surgery at one or more levels and had post-operative PT (ACDF:1784, PCF:1593, and cervical foraminotomy:232). The most frequent complications were new onset cervicalgia (2-14 weeks, 8-20 weeks, 12-24 weeks): ACDF (15.0%, 14.0%, 13.0%), PCF (18.8%, 18.0%, 19.9%), cervical foraminotomy (16.8%, 16.4%, 19.4%); revision: ADCF (7.9%, 8.2%, 7.4%), PCF (9.3%, 10.6%, 10.2%), cervical foraminotomy (11.6%, 10.8% and 13.4%); wound infection: ACDF (3.3%, 3.4%, 3.1%), PCF (8.3%, 8.0%,7.7%), cervical foraminotomy (5.2%, 6.5%, < 4.7%). None of the comparisons were statistically significant. The most common post-operative complications included new onset cervicalgia, revision and wound infection. Complications rates were not impacted by the timing of initiation of PT whether at 2, 8, or 12 weeks post-operatively.


[Clinical significance of sentinel lymph nodes detection in patients with early stage cervical cancer].
To study the value of sentinel lymph nodes (SLN) in prediction of the pelvic lymph nodes status and to determine the significance of SLN detection in pelvic lymph nodes dissection in patients with early stage cervical carcinoma. From November 2002 to August 2003, 23 patients with early stage cervical carcinoma planned to undergo radical hysterectomy and extensive pelvic lymph nodes dissection received an intracervical injection of technetium-labeled sulfur colloid as well as blue dye to identify and perform resection of SLNs. The SLNs were pathologically compared with non-SLNs with frozen section, paraffin section, and anti-cytokeratin immunohistochemical staining. Out of 23 patients, SLNs were detected in 19 patients. A total of 59 SLNs were identified and the mean was 3 per patient. The detection rate of SLN was 83%. Sensitivity, specificity and accuracy of the SLN biopsy were 83%, 100% and 95%, respectively. SLNs detection can predict the pelvic lymph nodes status in early stage cervical carcinoma, but the feasibility and safety of this technique to substitute conventional surgical modality should be evaluated by large series of prospective studies.


Hidradenitis suppurativa: pathogenesis and management.
Hidradenitis suppurativa (HS) is a chronic disease manifested by recurrent abscesses, sinus tracts and scarring. It arises most commonly, however, not exclusive from apocrine gland bearing skin. This review article sets out to clarify the importance of early diagnosis, the pathogenesis and aetiology of HS, and evidence for medical and surgical therapies for this debilitating disease.HS is caused primarily by follicular occlusion with secondary involvement of the apocrine glands. The aetiology is still poorly understood. There is a genetic component with probable hormonal influence on gene expression. Shearing forces from obesity and tight clothing contribute to its development. Management should be appropriately tailored for the severity and distribution of HS as well as quality of life of the patient. Medical management with appropriate antibiotics, if initiated early, can be successful in mild to moderate severity HS as well as improving disease control prior to attempted curative surgery in severe HS. Other helpful measures include advice on lifestyle changes, intralesional steroids, systemic retinoids, hormonal manipulation, and a revival of interest in the use of radiotherapy for HS. While there is a place for 'conservative' surgical procedures (including CO(2) laser) in selected cases of mild to moderate HS, radical excision of all apocrine-bearing tissue is the definitive treatment. We advocate close interdisciplinary collaboration as well as a cautionary approach to timing and planning of surgery to minimise recurrence rates.


Prevalence of diabetic retinopathy in India stratified by known and undiagnosed diabetes, urban-rural locations, and socioeconomic indices: results from the SMART India population-based cross-sectional screening study.
National and subnational estimates of the prevalence of diabetic retinopathy and vision-threatening diabetic retinopathy (VTDR) are needed to inform the stepwise implementation of systematic retinal screening for people with diabetes in India to decrease the rate of blindness. We aimed to assess these national and subnational estimates and to stratify the prevalence of diabetic retinopathy and VTDR on the basis of people with known versus undiagnosed diabetes, urban versus rural residence, and epidemiological transition level (ETL) and Socio-demographic Index (SDI) categories of states. We did a multicentre cross-sectional screening study for diabetic retinopathy using a complex cluster sampling design in people aged 40 years or older in ten Indian states and one union territory between Dec 20, 2018, and March 20, 2020. We did non-mydriatic retinal screening and assessed risk factor burden for people with diabetes. We estimated nationally weighted prevalence of diabetic retinopathy and VTDR for individuals with known and undiagnosed diabetes by urban versus rural residence, and by state categorisation by ETL and SDI. We also assessed adjusted risk factors. From 42 146 participants screened, 7910 (18·8%) were identified to have diabetes. Of these, 6133 (77·5%; 4350 with known diabetes and 1783 with undiagnosed diabetes) had gradable retinal images. 3411 (56%) participants were women and 2722 (44%) were men, and the median age was 56 years (IQR 49-65). The estimated national prevalence was 12·5% (95% CI 11·0-14·2) for diabetic retinopathy and 4·0% (3·4-4·8) for VTDR, with no significant differences between urban and rural residence for diabetic retinopathy. Compared with individuals with undiagnosed diabetes, we observed a higher prevalence of diabetic retinopathy (15·5% [13·4-17·8] vs 8·0% [6·3-10·1]) and VTDR (5·3% [4·5-6·3] vs 2·4% [1·6-3·6]) in individuals with known diabetes. The prevalence was significantly lower in low ETL-SDI states compared with high and middle ETL-SDI states for diabetic retinopathy (by 7·0%, 1·9-12·2, p=0·024) and VTDR (by 4·8%, 3·0-6·6, p<0·0001). Hyperglycaemia was the strongest modifiable risk factor. We estimate that, in absolute numbers, approximately 3 million people aged 40 years or older have VTDR in India, with a higher prevalence in those with known diabetes residing in high and middle ETI-SDI states. UKRI Global Challenge Research Fund.


Meeting the educational and social needs of children with language impairment or autism spectrum disorder: the parents' perspectives.
There is increasing interest in examining the perspectives of parents of children with special educational needs (SEN). Exploring the view of parents of a child with language impairment (LI) or autism spectrum disorder (ASD) is particularly important because of their high prevalence, at over 30% of children with SEN in England, and the increasing evidence of overlapping profiles of their needs. To examine the similarities and differences between the perspectives of parents of children with LI or ASD on three issues: (1) their child's educational progress, and their behavioural, emotional and social development; (2) the provision made to support their child's education and meet their SEN; and (3) their own involvement in decision-making about provision for their child. The parents of 129 children with LI (n = 76) or ASD (n = 53) were interviewed using a semi-structured protocol that gathered both quantitative data (parent ratings) and qualitative, in-depth explorations of their perspectives. There were no significant differences between the perspectives of parents of children with LI and parents of children with ASD with respect to their child's educational progress; the provision made to meet their child's educational needs; or their involvement in decision-making during the statutory assessment procedure, including the determination of a statement of SEN, and the current provision made by their child's school. Both parent groups were generally positive about these but parents of children with ASD were more concerned about their child's peer relationships. Parents whose child attended a mainstream school with a specialist resource tended to be more positive about the provision made than parents whose child was included individually into a mainstream school. Although previous research indicates that parents of children with ASD are overrepresented among those who express dissatisfaction with the provision made to meet their child's needs, this study indicates high levels of satisfaction and overlap between the perspectives of parents of children with LI or ASD regarding their child's educational progress and their own involvement in decision-making about the child's provision. The findings indicate the importance for policy and practice of focusing on identified needs rather than diagnostic category; and the importance of practitioners and administrators engaging meaningfully with parents in collaborative decision-making.


Gender Bias in the Treatment of Menopausal Women: I am Hot as Hell and Not Going to Take It Anymore, Part 1.
Gender bias within hormone replacement therapy has been prevalent for decades, and the circumstances surrounding this bias continue to worsen. A billion-dollar industry has been built on dozens of testosterone replacement therapies and medications to treat andropause and erectile dysfunction for men; women have been less fortunate. This article discusses this bias and the well-orchestrated attempt by the pharmaceutical industry to eliminate bioidentical hormones, as well as to downplay the important role of compounding pharmacies in fulfilling the needs of women in this longstanding gender gap.


CT and MR imaging findings of systemic complications occurring during pregnancy and puerperal period, adversely affected by natural changes.
Dynamic physiological and anatomical changes for delivery may adversely induce various specific non-obstetric complications during pregnancy and puerperal period. These complications can be fatal to both the mother and the fetus, thus a precise and early diagnosis ensued by an early treatment is essential. Along with ultrasonography, computed tomography (CT) and magnetic resonance imaging (MRI) have assumed an increasing role in the diagnosis. This article aims to discuss the pathophysiology of these complications, the indications for CT and MRI, and the imaging findings.


Acute stroke care in a New York City comprehensive stroke center during the COVID-19 pandemic.
The coronavirus disease-2019 (COVID-19) pandemic caused unprecedented demand and burden on emergency health care services in New York City. We aim to describe our experience providing acute stroke care at a comprehensive stroke center (CSC) and the impact of the pandemic on the quality of care for patients presenting with acute ischemic stroke (AIS). We retrospectively analyzed data from a quality improvement registry of consecutive AIS patients at New York University Langone Health's CSC between 06/01/2019-05/15/2020. During the early stages of the pandemic, the acute stroke process was modified to incorporate COVID-19 screening, testing, and other precautionary measures. We compared stroke quality metrics including treatment times and discharge outcomes of AIS patients during the pandemic (03/012020-05/152020) compared with a historical pre-pandemic group (6/1/2019-2/29/2020). A total of 754 patients (pandemic-120; pre-pandemic-634) were admitted with a principal diagnosis of AIS; 198 (26.3%) received alteplase and/or mechanical thrombectomy. Despite longer median door to head CT times (16 vs 12 minutes; p = 0.05) and a trend towards longer door to groin puncture times (79.5 vs. 71 min, p = 0.06), the time to alteplase administration (36 vs 35 min; p = 0.83), door to reperfusion times (103 vs 97 min, p = 0.18) and defect-free care (95.2% vs 94.7%; p = 0.84) were similar in the pandemic and pre-pandemic groups. Successful recanalization rates (TICI≥2b) were also similar (82.6% vs. 86.7%, p = 0.48). After adjusting for stroke severity, age and a prior history of transient ischemic attack/stroke, pandemic patients had increased discharge mortality (adjusted OR 2.90 95% CI 1.77 - 7.17, p = 0.021) CONCLUSION: Despite unprecedented demands on emergency healthcare services, early multidisciplinary efforts to adapt the acute stroke treatment process resulted in keeping the stroke quality time metrics close to pre-pandemic levels. Future studies will be needed with a larger cohort comparing discharge and long-term outcomes between pre-pandemic and pandemic AIS patients.


An expanded role for the dorsal auditory pathway in sensorimotor control and integration.
The dual-pathway model of auditory cortical processing assumes that two largely segregated processing streams originating in the lateral belt subserve the two main functions of hearing: identification of auditory "objects", including speech; and localization of sounds in space (Rauschecker and Tian, 2000). Evidence has accumulated, chiefly from work in humans and nonhuman primates, that an antero-ventral pathway supports the former function, whereas a postero-dorsal stream supports the latter, i.e processing of space and motion-in-space. In addition, the postero-dorsal stream has also been postulated to subserve some functions of speech and language in humans. A recent review (Rauschecker and Scott, 2009) has proposed the possibility that both functions of the postero-dorsal pathway can be subsumed under the same structural forward model: an efference copy sent from prefrontal and premotor cortex provides the basis for "optimal state estimation" in the inferior parietal lobe and in sensory areas of the posterior auditory cortex. The current article corroborates this model by adding and discussing recent evidence.


[Causes and methods of re-operation in a patient with a jejuno-ileal bypass for obesity].
One case of re-operation in a patient who previously underwent a jejunoileal by-pass for obesity is described. The serious complications following first surgery are shown. Reasons for re-operation and special pre- and post-operative care are considered.


Oxytocin-secreting system: A major part of the neuroendocrine center regulating immunologic activity.
Interactions between the nervous system and immune system have been studied extensively. However, the mechanisms underlying the neural regulation of immune activity, particularly the neuroendocrine regulation of immunologic functions, remain elusive. In this review, we provide a comprehensive examination of current evidence on interactions between the immune system and hypothalamic oxytocin-secreting system. We highlight the fact that oxytocin may have significant effects in the body, beyond its classical functions in lactation and parturition. Similar to the hypothalamo-pituitary-adrenal axis, the oxytocin-secreting system closely interacts with classical immune system, integrating both neurochemical and immunologic signals in the central nervous system and in turn affects immunologic defense, homeostasis, and surveillance. Lastly, this review explores therapeutic potentials of oxytocin in treating immunologic disorders.


Different growth capacity between infant and adult mouse hepatocytes in vitro correlates to the cyclin D1 level without relation to oxidative DNA damage.
Proliferating capacity of hepatocytes is rapidly decreased during growth into maturity, but its exact reason(s) are not well known. Hepatocytes isolated from infant (10-14 days old) and adult (10-13 months old) B6C3F1 mice were cultivated in the medium containing epidermal growth factor and insulin. Proliferative capacity, apoptosis, morphological changes, cell cycle proteins and 8-hydroxy-2'-deoxyguanosine (8-OHdG) were compared between the two hepatocyte populations. Although adult hepatocytes rapidly underwent cellular crisis characterized by extended morphology and multiple nuclei without proliferation, infant hepatocytes could proliferate with less crisis. Cyclin D1 was much more abundant in the infant than adult cells, but there was no difference according to the expression of cdk4, cdk2, cyclin E and cdk inhibitors (p16(Ink4) (p16), p21(Cip1/Waf1) (p21) and p27(Kip1) (p27)). 8-OHdG became high soon after cultivation, while it rapidly went down after day 2 both in the infant and adult cells. The high growth capacity of infant hepatocytes in vitro was dependent on the cyclin D1 level, but there was no relation to 8-OHdG.


Genu recurvatum caused by partial growth arrest of the proximal tibial physis: simultaneous correction and lengthening with physeal distraction. A report of two cases.
Two cases of genu recurvatum deformity and leg length discrepancy after partial growth arrest of the proximal tibial physis are described. The patients are both boys thirteen and fifteen years old respectively. The etiology of the deformity is considered to be local pressure on the tibial tuberosity, in the first case after treatment with plaster cast after correction of an angular deformity in a tibial fracture and in the second case after prolonged treatment with patellar tendon bearing brace. The boys were treated with physeal distraction which corrected both the leg length discrepancy and the angular deformity. The technique is recommended because the correction is done at the site of the deformity and knee motion is possible during the entire treatment period.


Hydrogeological environments and radon activities of saline geothermal hot spring sites located along eastern and western coastlines of southern Thailand.
Hydrogeological settings and natural radionuclides of saline geothermal fields along the coastlines of the Gulf of Thailand and Andaman Sea in Southern Thailand are currently not fully understood. Six saline geothermal springs have been discovered in Surat Thani Province (Southern Thailand's east coast); SR2, SR3, and SR7 sites; Krabi Province (Southern Thailand's west coast); KB2, KB3, and KB4 sites. Based on total dissolved solid contents, we divided the saline geothermal springs into three categories: a) slightly saline geothermal spring had only SR7 (1828 mg/L), b) moderately saline geothermal spring consisted of SR2 (10,196 mg/L) and KB3 (3448 mg/L), and c) very saline geothermal spring comprised SR3 (11,856 mg/L), KB2 (17,014 mg/L) and KB4 (18,070 mg/L). The major ions in the saline geothermal groundwater represent decreasing trends with the distance from the coastline. Stable isotope signatures (δ18O and δ2H) relative to the VSMOW plotted in comparison with the global meteoric water line and local meteoric water line are presumably of meteoric origin and influenced by seawater/brackish water. However, the SR7 and KB3 sites indicated that the isotopic signatures were mainly recharged by rainwater. Significantly, the Na-K-Ca-Mg geothermometer can reasonably estimate the reservoir temperatures for the five saline geothermal springs to be in the range of 120 °C (KB3) to 169 °C (SR2). While the SR7, the silica-quartz geothermometer is proposed of approximately 115 °C. However, the silica-chalcedony and other cation geothermometers fail to estimate suitable reservoir temperatures. On the other hand, the radon concentrations in the saline geothermal groundwater along the Gulf of Thailand and Andaman Sea were assessed by RAD7-H2O, which varied from 18.64 ± 0.96 kBq/m3 (KB2; Andaman Sea side) to 8507.48 ± 1.06 kBq/m3 (SR7; Gulf of Thailand side). A comparison of radon activity with the saltwater intrusion showed that the saline geothermal groundwater on the Gulf of Thailand side had higher levels than that at the Andaman Sea side. The deposition of Quaternary sediments combined with significant saltwater inflow enriched with radon resulted from the decay of uranium from both non-marine and coastal deposits related to granitic mountain weathering along the Gulf of Thailand. Radon concentrations in the geothermal groundwater were highly influenced by the local geological environment and coastal sediments.


Flotsam, Jetsam, and Forward-Moving Vessels on the Sea of Well-Being: Commentary on "Emotional Well-Being: What Is it and Why it Matters".
I dispute the characterization of psychological aspects of well-being as fragmented and a landscape of confusion in need of an organizing conceptual framework. After 30+ years of research in this area, I see progress toward a multi-faceted, ever more differentiated understanding of what well-being is. This richness reflects decades of painstaking empirical inquiry. I also challenge the view that emotion is the overarching theme of well-being research. Missing from the target article was much-needed emphasis on empirical assessment tools. A growing problem in contemporary research is the proliferation of thin, poorly validated measures, which should concern all of the newly funded Emotion Networks. I conclude with a call for greater emphasis on major historical challenges that are undermining the well-being and health of many.


Trophic relationship between Salix flowers, Orthosia moths and the western barbastelle.
We present the results of a study which describes the relationship between the western barbastelle Barbastella barbastellus a highly specialised moth predator, and its prey-moths of the genus Orthosia, another selective animal known to converge around a dominant producer of pollen and nectar in early spring-willow trees Salix sp. In order to describe this trophic relationship, we conducted acoustic recordings at five paired sites (willow/control tree) in proximity to known barbastelle hibernation sites (Natura 2000: PLH080003 and PLH200014) beginning in mid-March 2022 after the first willow blossom sighting. Our study confirms a relationship between willow trees and barbastelles during early spring, as their activity around them was significantly higher than control sites. We also explore the activity of barbastelles over time, finding that activity levels around willows significantly decrease from the night of the first recorded bat, while the abundance of non-moth specialist bats remains consistent. Short-time importance (directly after hibernation) of willows for a moth specialist bat is probably due to other species blossom, attracting alternative prey, and in consequence-the bat. This newly described relationship should influence current conservation measures aimed at barbastelles.


Molecular iodine-promoted oxidative cyclization for the synthesis of 1,3,4-thiadiazole-fused- [1,2,4]-thiadiazole incorporating 1,4-benzodioxine moiety as potent inhibitors of α-amylase and α-glucosidase: In vitro and in silico study.
Twenty-five analogs were synthesized based on 1,3,4-thiadiazole-fused-[1,2,4]-thiadiazole incorporating 1,4-benzodioxine moiety (1-25) and then tested for the antidiabetic profile. The entire afforded derivatives showed varied inhibition profiles ranging between 0.70 ± 0.01 and 30.80 ± 0.80 μM (against α-amylase) in comparison to standard acarbose (12.80 ± 0.10 μM). Similarly, synthetics analogs also displayed a varied range of α-glucosidase activity ranging from 0.80 ± 0.01 μM to IC50 = 29.70 ± 0.40 μM (against α-glucosidase) as compared to standard acarbose (IC50 = 12.90 ± 0.10 μM). Among synthesized analogs, compound 22 showed excellent potency due to the presence of di-hydroxy substitutions at the 2,3-position of the aryl ring. For all analogs, the structure-activity relationship was carried out based on the pattern of substitutions around the aryl ring, and further, the potent analogs were subjected to a molecular docking study to analyze how active residues of targeted enzymes interact with active parts of newly prepared analogs. The result obtained shows that these compounds furnish several key interactions with enzyme active sites and, hence, enhanced their enzymatic activities.


Elevated Glycated Haemoglobin (HbA1c) Is Associated with an Increased Risk of Pancreatic Ductal Adenocarcinoma: A UK Biobank Cohort Study.
The role of dysglycaemia as a risk marker for Pancreatic Ductal Adenocarcinoma (PDAC) is uncertain. We investigated the relationship between glycated haemoglobin (HbA1c) and incident PDAC using a retrospective cohort study within the UK Biobank. A study involving 499,804 participants from the UK Biobank study was undertaken. Participants were stratified by diabetes mellitus (DM) status, and then by HbA1c values < 42 mmol/mol, 42-47 mmol/mol, or ≥48 mmol/mol. Cox proportional hazard models were used to describe the association between HbA1c category (with time-varying interactions) and incident PDAC. PDAC occurred in 1157 participants during 11.6 (10.9-12.3) years follow up [(median (interquartile range)]. In subjects without known DM at baseline, 12 months after recruitment, the adjusted hazard ratios (aHR, 95% CI) for incident PDAC for HbA1c 42-47 mmol/mol compared to HbA1c < 42 mmol/mol (reference group) was 2.10 (1.31-3.37, p = 0.002); and was 8.55 (4.58-15.99, p < 0.001) for HbA1c ≥ 48 mmol/mol. The association between baseline HbA1c and incident PDAC attenuated with increasing duration of time of follow-up to PDAC diagnosis. Dysglycaemia detected by elevated HbA1c is associated with an increased risk of PDAC. The strength of the association between elevated HbA1c and incident PDAC is inversely proportional to the time from detecting dysglycaemia but remains significant for at least 60 months following HbA1c testing.


Biological effects triggered by chemical respiratory sensitizers on THP-1 monocytic cells.
Respiratory sensitization encompasses a group of diseases that manifest through airway hyperresponsiveness and airflow limitation. Although the concerns regarding human health, to date there are still no validated methods for preclinical assessment of this class of toxicants once the chemical respiratory allergy mechanistic framework is not fully understood. As Dendritic Cells (DCs) are the bridging elements between innate and adaptative immune responses, we preliminarily investigated the biological alterations triggered by seven different LMW respiratory allergens in the DC model THP-1. The results have shown that exposure to respiratory allergens promoted alterations in DCs maturation/activation status and triggered pro-inflammatory changes in these cells through increased expression for the CD86/HLA-DR/CD11c surface biomarkers and enhancement in IL-8 and IL-6 production by exposed THP-1 cells. Therefore, evidence was found to support the startpoint for chemical respiratory allergy pathogenesis elucidation, subsidizing the contribution of dendritic cells in such pathomechanisms.


IAP-targeted therapies for cancer.
DNA damage, chromosomal abnormalities, oncogene activation, viral infection, substrate detachment and hypoxia can all trigger apoptosis in normal cells. However, cancer cells acquire mutations that allow them to survive these threats that are part and parcel of the transformation process or that may affect the growth and dissemination of the tumor. Eventually, cancer cells accumulate further mutations that make them resistant to apoptosis mediated by standard cytotoxic chemotherapy or radiotherapy. The inhibitor of apoptosis (IAP) family members, defined by the presence of a baculovirus IAP repeat (BIR) protein domain, are key regulators of cytokinesis, apoptosis and signal transduction. Specific IAPs regulate either cell division, caspase activity or survival pathways mediated through binding to their BIR domains, and/or through their ubiquitin-ligase RING domain activity. These protein-protein interactions and post-translational modifications are the subject of intense investigations that shed light on how these proteins contribute to oncogenesis and resistance to therapy. In the past several years, we have seen multiple approaches of IAP antagonism enter the clinic, and the rewards of such strategies are about to reap benefit. Significantly, small molecule pan-IAP antagonists that mimic an endogenous inhibitor of the IAPs, called Smac, have demonstrated an unexpected ability to sensitize cancer cells to tumor necrosis factor-alpha and to promote autocrine or paracrine production of this cytokine by the tumor cell and possibly, other cells too. This review will focus on these and other developmental therapeutics that target the IAPs in cancer.


New improved Aggregator: predicting which clinical trial articles derive from the same registered clinical trial.
To identify separate publications that report outcomes from the same underlying clinical trial, in order to avoid over-counting these as independent pieces of evidence. We updated our previous model by creating larger, more recent, and more diverse positive and negative training sets consisting of article pairs that were (or not) linked to the same ClinicalTrials.gov trial registry number. Features were extracted from PubMed metadata; pairwise similarity scores were modeled using logistic regression and used to form clusters of articles that are likely to arise from the same registered clinical trial. Articles from the same trial were identified with high accuracy (F1 = 0.859), nominally better than the previous model (F1 = 0.843). Predicted clusters showed a low error rate of splitting of 8-11% (ie, when 2 articles belonged to the same trial but were assigned to different clusters). Performance was similar whether only randomized controlled trial articles or a more diverse set of clinical trial articles were processed. Metadata are surprisingly accurate in predicting when 2 articles derive from the same underlying clinical trial. We have continued confidence in the Aggregator tool which can be accessed publicly at http://arrowsmith.psych.uic.edu/cgi-bin/arrowsmith_uic/RCT_Tagger.cgi.


Immunoglobulins of the non-galliform birds: antibody expression and repertoire in the duck.
Galliform and non-galliform birds express three immunoglobulin isotypes, IgM, IgA and IgY. Beyond this we should not generalize because differences in gene organization may have functional consequences reflected in the immune response. At present, studies on non-galliform birds are largely restricted to ducks. Ducks express an alternatively spliced form of their IgY heavy chain (upsilon) gene, the IgY(DeltaFc), that lacks the Fc region and Fc-associated secondary effector functions. It is not known how common the expression of the IgY(DeltaFc) is among birds, nor the functional consequences. It is also not known whether the unusual organization of the duck IgH locus, also shared with the chicken, having the gene order of mu, alpha and upsilon, with alpha inverted in the locus, is unique to the galloanseriform lineage. Ducks, like chickens, have a single immunoglobulin light chain of the lambda (lambda) type. Evidence suggests that ducks, like chickens, generate their immunoglobulin repertoire through a single functional rearrangement of the variable (V) region, and generate diversity through gene conversion from a pool of pseudogenes. In Southern blots of germline and rearranged bursal DNA, both the heavy and light chain loci of ducks appear to each undergo one major rearrangement event. For both heavy and light chains, the functional V region element and the pseudogenes appear to consist of a single gene family. Further analysis of 26 heavy chain joining (JH) and 27 light chain JL segments shows there is use of a single J segment in ducks, which is diversified presumably through somatic mutations and gene conversion events. Despite this limitation on the rearrangement of immunoglobulin genes, analysis of 26 DH and 122 VL sequences suggests that extensive sequence diversity is generated.


Impact of socioeconomic status on new chronic opioid use after gastric bypass surgery.
Socioeconomic status may influence weight loss, postoperative complications, and health-related quality of life after bariatric surgery. Chronic use of opioid analgesics is a known risk after bariatric surgery, but whether socioeconomic factors are associated with new chronic use of opioid analgesics has not been investigated in depth. The aim of this study was to identify socioeconomic factors associated with the development of new chronic use of opioid analgesics after gastric bypass surgery. All hospitals performing bariatric surgery in Sweden. This was a retrospective cohort study with prospectively collected data including all primary gastric bypass procedures in Sweden between 2007 and 2015. Data were collected from the Scandinavian Obesity Surgery Registry, the Swedish Prescribed Drug Register, and Statistics Sweden. The primary outcome was new chronic opioid use. Of the 44,671 participants, 1438 patients became new chronic opioid users. Longer education (secondary education; odds ratio [OR] = .71; 95% CI, .62-.81) or higher education (OR = .45; 95% CI, .38-.53), higher disposable income (20th-50th percentile: OR = .75; 95% CI, .66-.85; 50th-80th percentile: OR = .50; 95% CI, .43-.58; and the highest 80th percentile: OR = .40; 95% CI, .32-.51) were significantly associated with lower risk for new chronic opioid use. Being a second-generation immigrant (OR = 1.54; 95% CI, 1.24-1.90), being on a disability pension or early retirement (OR = 3.04; 95% CI, 2.67-3.45), receiving social benefits (OR = 1.88; 95% CI, 1.59-2.22), being unemployed for <100 days (OR = 1.25; 95% CI, 1.08-1.45), being unemployed for >100 days (OR = 1.41; 95% CI, 1.16-1.71), and being divorced or a widow or widower (OR = 1.35; 95% CI, 1.17-1.55) were significantly associated with a higher risk for chronic opioid use. Given that long-term opioid use has detrimental effects after bariatric surgery, it is important that information and follow-up are optimized for patients with shorter education, lower income, and disability pension or early retirement because they are at an increased risk of new chronic opioid analgesics use.


An efficient route from trifluoroacetates to water soluble free amines using Diaion HP-20.
A series of polybasic lysine and ornithine derivatives were synthesised as trifluoroacetate salts. Attempts to prepare their free amines according to standard methodology were not successful due to the excellent water solubility of these compounds. Free amines were however efficiently obtained if the column with Diaion HP-20 adsorbent was loaded with the trifluoroacetate and 1% NaHCO(3) aq was passed, followed by elution of free amine with methanol.


Factors and Survival Implications associated with biopsy of hepatocellular carcinoma.
Hepatocellular carcinoma (HCC) is one of the few cancers that can be diagnosed based on imaging findings alone. The factors associated with the decision to perform a biopsy and the clinical impact have not been previously studied. We collected data of patients diagnosed with HCC between 2004 and 2015 from the National Cancer Database. We assessed associations between biopsy and survival with demographic and clinical factors. We included 160,507 patients. The median age was 62 (40-90), 74.1% were male and 74.9% were white. Over the 12-year period, 47.7% (76,524/160,517) underwent a biopsy. Factors associated with a biopsy were black race, older age, presence of metastatic disease, larger tumor size, and treatment at a community cancer center. Factors associated with increased mortality were older age, higher comorbidity index, larger tumor size, presence of metastatic disease, higher AFP and elevated bilirubin. There was a significant decreased use of biopsy over successive years (2007-2015). After adjusting for prognostic factors, biopsy had no significant impact on survival HR 1.01 (95%CI 1.00-1.03. p = 0.07). A significant number of patients underwent a biopsy. Performing a biopsy did not have a significant impact on survival.


Unexpected complication of successful nerve block. Morphine induced respiratory depression precipitated by removal of severe pain.
A case is reported of a 76-year-old man with a right-sided mesothelioma who required large doses of oral narcotics to control his severe chest pain. After a successful chlorocresol intrathecal nerve block, respiratory failure was induced by doses of oral morphine at the same level as those used before the block, and also by substantially smaller doses. A considerable reduction in analgesic requirements may be possible following non-drug intervention to relieve pain and may be essential in patients with compromised respiratory function. This observation emphasises the importance of pain as a potent stimulator of the respiratory centre in patients with reduced respiratory reserve who are receiving narcotic drugs.


Exposure to terrorism, stress-related mental health symptoms, and coping behaviors among a nationally representative sample in Israel.
The terrorist attacks on Israeli society have been ongoing since September 2000. However, few studies have examined the impact of terrorism on nationally representative population samples, and no study has examined the psychological impact of ongoing terrorism in Israel. To determine the level of exposure to terrorist attacks and the prevalence of traumatic stress-related (TSR) symptoms, symptoms of posttraumatic stress disorder (PTSD), and sense of safety after 19 months of terrorism in Israel, and to identify correlates of the psychological sequelae and the modes of coping with the terrorism. Telephone survey conducted April-May 2002, using a strata sampling method, of 902 eligible households and a representative sample of 742 Israeli residents older than 18 years (82% contact rate) and a final participation of 512 (57%). Number of TSR symptoms, rates of those with symptom criteria for PTSD and acute stress disorder assessed by the Stanford Acute Stress Reaction Questionnaire, self-reported feelings of depression, optimism, sense of safety, help-seeking, and modes of coping. Of 512 survey participants, 84 (16.4%) had been directly exposed to a terrorist attack and 191 (37.3%) had a family member or friend who had been exposed. Of 510 participants who responded to questions about TSR symptoms, 391 (76.7%) had at least 1 TSR symptom (mean, 4.0 [SD, 4.5]; range, 0-23; mean intensity, 0.8; range, 0-4). Symptom criteria for PTSD were met by 48 participants (9.4%) and criteria for acute stress disorder, by 1 participant; 299 (58.6%) reported feeling depressed. The majority of respondents expressed optimism about their personal future (421/512 [82.2%]) and the future of Israel (307/509 [66.8%]), and expressed self-efficacy with regard to their ability to function in a terrorist attack (322/431 [74.6%]). Most expressed a low sense of safety with respect to themselves (307/509 [60.4%]) and their relatives (345/507 [67.9%]). Few reported a need for professional help (27/506 [5.3%]). Female sex, sense of safety, and use of tranquilizers, alcohol, and cigarettes to cope were associated with TSR symptoms and symptom criteria for PTSD; level of exposure and objective risk were not. The most prevalent coping mechanisms were active information search about loved ones and social support. Considering the nature and length of the Israeli traumatic experience, the psychological impact may be considered moderate. Although the survey participants showed distress and lowered sense of safety, they did not develop high levels of psychiatric distress, which may be related to a habituation process and to coping mechanisms.


The ribosome as a missing link in prebiotic evolution II: Ribosomes encode ribosomal proteins that bind to common regions of their own mRNAs and rRNAs.
We have proposed that the ribosome may represent a missing link between prebiotic chemistries and the first cells. One of the predictions that follows from this hypothesis, which we test here, is that ribosomal RNA (rRNA) must have encoded the proteins necessary for ribosomal function. In other words, the rRNA also functioned pre-biotically as mRNA. Since these ribosome-binding proteins (rb-proteins) must bind to the rRNA, but the rRNA also functioned as mRNA, it follows that rb-proteins should bind to their own mRNA as well. This hypothesis can be contrasted to a "null" hypothesis in which rb-proteins evolved independently of the rRNA sequences and therefore there should be no necessary similarity between the rRNA to which rb-proteins bind and the mRNA that encodes the rb-protein. Five types of evidence reported here support the plausibility of the hypothesis that the mRNA encoding rb-proteins evolved from rRNA: (1) the ubiquity of rb-protein binding to their own mRNAs and autogenous control of their own translation; (2) the higher-than-expected incidence of Arginine-rich modules associated with RNA binding that occurs in rRNA-encoded proteins; (3) the fact that rRNA-binding regions of rb-proteins are homologous to their mRNA binding regions; (4) the higher than expected incidence of rb-protein sequences encoded in rRNA that are of a high degree of homology to their mRNA as compared with a random selection of other proteins; and (5) rRNA in modern prokaryotes and eukaryotes encodes functional proteins. None of these results can be explained by the null hypothesis that assumes independent evolution of rRNA and the mRNAs encoding ribosomal proteins. Also noteworthy is that very few proteins bind their own mRNAs that are not associated with ribosome function. Further tests of the hypothesis are suggested: (1) experimental testing of whether rRNA-encoded proteins bind to rRNA at their coding sites; (2) whether tRNA synthetases, which are also known to bind to their own mRNAs, are encoded by the tRNA sequences themselves; (3) and the prediction that archaeal and prokaryotic (DNA-based) genomes were built around rRNA "genes" so that rRNA-related sequences will be found to make up an unexpectedly high proportion of these genomes.


Salivary protein adsorption and Streptococccus gordonii adhesion to dental material surfaces.
The initial adhesion of microorganisms to clinically used dental biomaterials is influenced by physico-chemical parameters like hydrophobicity and pre-adsorption of salivary proteins. Here, polymethyl methacrylate (PMMA), polyethylene (PE), polytetrafluoroethylene (PTFE), silicone (Mucopren soft), silorane-based (Filtek Silorane) and methacrylate-based (Tetric EvoCeram) dental composites, a conventional glassionomer cement as well as cobalt-chromium-molybdenum (Co28Cr6Mo) and titanium (Ti6Al4V) were tested for adsorption of salivary proteins and adhesion of Streptococcus gordonii DL1. Wettability of material surfaces precoated with salivary proteins or left in phosphate-buffered saline was determined by the measurement of water contact angles. Amounts of adsorbed proteins were determined directly on material surfaces after biotinylation of amino groups and detection by horseradish peroxidase-conjugated avidin-D. The same technique was used to analyze for the binding of biotinylated bacteria to material surfaces. The highest amount of proteins (0.18μg/cm(2)) adsorbed to hydrophobic PTFE samples, and the lowest amount (0.025μg/cm(2)) was detected on silicone. The highest number of S. gordonii (3.2×10(4)CFU/mm(2)) adhered to the hydrophilic glassionomer cement surface coated with salivary proteins, and the lowest number (4×10(3)CFU/mm(2)) was found on the hydrophobic silorane-based composite. Hydrophobicity of pure material surfaces and the number of attached microorganisms were weakly negatively correlated. No such correlation between hydrophobicity and the number of bacteria was detected when surfaces were coated with salivary proteins. Functional groups added by the adsorption of specific salivary proteins to material surfaces are more relevant for initial bacterial adhesion than hydrophobicity as a physical property.


Mediastinal emphysema complicating a zygomatic fracture: a case report and review of the literature.
A case of a man with an otherwise simple facial fracture which was complicated by mediastinal emphysema is reported. A review of the literature indicating the pathogenesis, clinical and radiographic features and management of this condition is given.


Riding the emotional roller-coaster: a framework for improving nursing morale.
To examine the literature on employee morale and to construct a model of this area pertaining to nurses. This framework seeks to present morale in a holistic manner, illustrating the causal factors that influence nursing morale, the changes that occur in morale when these input variables are altered, and the consequences to patient care and individual and group nursing practices. A number of published works on morale, its causal factors and resulting consequences are critiqued. The findings from this literature review are used to develop a framework for nursing morale. The paper presents a definition of morale and, from the literature review, concludes that previous models on morale are fragmented; only tending to explore the variables that influence the employees' emotional state. Consequently, a framework of nursing morale is constructed in order to illustrate this topic from a holistic point-of-view. The paper concludes with a number of management and research implications. The management implications consist of a number of useful suggestions for senior nurses to enhance the morale within their units. This paper fulfils an identified gap in the literature, namely the lack of a holistic model of nursing morale, and offers practical help to senior nurses so that they can initiate processes within their wards that can improve their subordinates' morale.


Immunization safety priority project at the World Health Organization.
In 1999, the World Health Organization's (WHO) Department of Vaccines and Biologicals launched the Immunization Safety Priority Project with the aim of establishing a comprehensive system to ensure the safety of all immunizations given in national immunization programs. Countries are the primary focus of the project. WHO has a role, not only because of its technical and normative role, but also because of its privileged relationship with country authorities and other partners, and its global vision and mandate. The four major areas of focus in the project are to (1) promote and coordinate research and development of safer and simpler delivery systems; (2) ensure vaccine safety, from vaccine development all the way through clinical trials and vaccine distribution until use; (3) broaden access to safer and more efficient systems for vaccine delivery and management of sharps waste; and (4) establish efficient mechanisms to detect serious or potentially serious adverse events following immunization, and enable prompt and effective response. The project emphasizes the importance of advocating safety and building capacity at national levels.


Experimental evaluation of reexpansion pulmonary edema.
Reexpansion pulmonary edema following pneumothorax is clinically uncommon but occasionally life threatening. This study documents the functional and anatomical abnormalities that occur when a collapsed lung is reexpanded. Right pneumothorax was created through open tube thoracostomy in 30 goats. The animals were divided into six groups by duration of pneumothorax (24, 48, or 72 hours) and technique of reexpansion (waterseal vs 10 cm H2O suction). Arterial blood gases and alveolar-arterial oxygen tension difference (A-aDO2) were analyzed before pneumothorax and after reexpansion. Each lung was reexpanded for 2 hours, chest roentgenograms were obtained, and both lungs were removed. The left lung served as the control. Both lungs were checked for surfactant activity and pulmonary extravascular water volume (PEWY). Light and electron microscopy were also performed. Anatomical and functional changes were present in the reexpanded lung after relief of pneumothorax. Both increased time of collapse and suction reexpansion tended to correlate with increased PEWV, decreased surfactant and arterial PO2, and increased A-aDO2.


Ionic interactions play a role in the regulatory mechanism of scallop heavy meromyosin.
Heavy meromyosin from scallop (scHMM) striated muscle is regulated by calcium binding to the essential light chain. The regulation can be modeled with a calcium-dependent equilibrium between on and off scHMM conformations. The observed rate constant for mant-ADP dissociation from scHMM is calcium dependent, and we show here that it can be used to define the equilibrium constant (K(eq)) between on and off conformations. The data show that K(eq) is markedly ionic strength dependent, with high salt (>/=200 mM) abolishing the off state even in the absence of calcium and low salt (<50 mM) favoring the off state even in the presence of calcium. Debye-Huckel plots of the equilibrium constant (K(eq)) for the on and off forms gave parallel slopes (5.94 +/- 0.33 and 6.36 +/- 0.17 M(-0.5)) in the presence and absence of calcium. The presence of an equilibrium mixture of two conformations was confirmed by sedimentation data and the effects of ADP, calcium and ionic strength were in qualitative agreement. Thus scHMM exists in two conformations that can be distinguished in sedimentation profiles and by the rate of release of mant-ADP. Increasing salt concentrations biases the system toward the on state, suggesting a role for ionic interactions in stabilizing the off state.


Biochemical properties of cloned glutathione S-transferases from Schistosoma mansoni and Schistosoma japonicum.
cDNA clones encoding a 28-kDa subunit glutathione S-transferase (GST) from Schistosoma mansoni (Sm28GST) and a 26-kDa subunit GST from Schistosoma japonicum (Sj26GST) have been expressed in bacterial systems. The recombinant proteins were purified to homogeneity by batch-wash glutathione-agarose affinity chromatography and their biochemical properties investigated. Gel filtration chromatography indicated that both recombinant GSTs are homodimeric proteins. Resolution of Sm28GST and Sj26GST by chromatofocusing in the ranges pH 9-6 and pH 7-4 gave pI estimates of 7.4 and 5.0, respectively. Kinetic analyses suggested that both Sm28GST and Sj26GST operate via a sequential bisubstrate catalytic mechanism. Sm28GST and Sj26GST displayed a mosaic of mammalian Alpha-, Mu- and Pi-type substrate specificities and inhibitor sensitivities. However, multivariate analysis suggests that Sm28GST has an overall catalytic homology with mammalian Mu class GSTs, whilst the enzymatic properties of Sj26GST appear to constitute a hybridisation of Mu and Alpha class features. Both recombinant GSTs interact with a range of hydrophobic ligands including haematin and related compounds, bile acids and several anthelmintics. Sm28GST and Sj26GST possess relatively limited selenium-independent glutathione peroxidase activities, but are able to catalyse the glutathione conjugation of members of the trans,trans-alka-2,4-dienal, trans-alk-2-enal and 4-hydroxyalk-2-enal series of reactive carbonyls (known secondary products of lipid peroxidation).


Metamorphic changes in the cephalic neurosecretory cells and the retrocerebral neuroendocrine complex of Pericalia ricini Fabricius (Lepidoptera: Arctidae).
Aldehyde Fuchsin-positive (AF-positive) A-cells first appear in the pars intercerebralis of 4d old 1st instar larva. First sign of secretory activity is noted in 3d old 2nd instar. A gradual increase in the number of neurosecretory cells (NSC) is noted during successive larval instars. The secretion of neurosecretory material (NSM) is followed by the coalescence and finally release phases. This is a regular phenomenon, however, various NSC exhibit different phases of secretory activities at a particular time. In 4d old pupa, A4 and D-cells are absent in the tritocerebral region and in 7d, decrease in the number and size of AF-positive cells is noted. In 4-7d old pupae A4-cells are absent in the lateral region but are present in 8-10d old pupae. In unmated females 6A4-cells are present in the lateral region of the brain which are absent in unmated males. The optic region of unmated males and females have A4 and B2-cells whereas A2-cells are absent in the tritocerebrum of both the sexes. The total number of NSC in females is more than males. A1 and A3-cells of mated males and all the NSC of laid females lack NSM.


Monitoring of silica colloidal crystal-embedded chitosan hydrogel films swelling and its drug release application.
The hydrogels, because of their swelling properties in response to the environmental stimulus, are being widely considered for the design of controlled drug release systems. To meet the need for developing effective drug delivery methods, we developed special silica colloidal crystal (SCC)-embedded chitosan hydrogel films. The SCC films served as an interference substrate and drug storage layer, while the chitosan hydrogel served as a cover to regulate the drug release. The optical interferometry was performed to dynamically monitor the volume phase transition of chitosan hydrogel response to pH stimulation. Furthermore, the effects of crosslinking ratio and hydrogel thickness on the swelling properties of chitosan hydrogel were also evaluated. More importantly, the pH-responsive swelling of chitosan hydrogel was used to slowly release indomethacin. This system may provide support for drug delivery studies, therefore further expected to apply in the enhancement of the treatment efficiency of new drug therapies.


Comparison of widefield swept-source optical coherence tomography angiography with ultra-widefield fluorescein angiography for the evaluation of lesions in retinal vein occlusion.
To compare widefield swept-source optical coherence tomography angiography (SS-OCTA) with ultra-widefield fundus fluorescein angiography (UWF-FA) for detecting retinal vein occlusion (RVO) lesions. Thirty-four eyes of 32 patients with treatment-naïve RVO were enrolled at Peking University People's Hospital from September 2021 to March 2022. Patients were imaged with a UWF-FA (200°) and a widefield SS-OCTA using 24 × 20 mm scan single capture. Quantitative assessments of RVO lesions such as foveal avascular zone (FAZ) area and perimeter, non-perfusion areas (NPA), number of microaneurysms (MAs), capillary changes and collateral vessels were performed. The measurement of FAZ area and perimeter were comparable between SS-OCTA and UWF-FA (0.373 (range, 0.277-0.48) mm2 vs. 0.370 (range, 0.277-0.48) mm2, P = 0.818 and 2.480 (range, 2.011-2.998) vs. 2.330 (range, 2.027-2.807) mm, P = 0.536, respectively). Intraclass correlation coefficients (ICCs) of FAZ area and perimeter between SS-OCTA and UWF-FA was high (0.999, [0.997-0.999] and 0.996 [0.991-0.996], respectively), suggesting good agreement. The mean NPA area was larger on SS-OCTA than that on UWF-FA (89.977 ± 78.805 mm2vs. 87.944 ± 77.444 mm2, P = 0.037). The ICC of NPA area was also high (0.999, [0.999-1.000]). The median of total MA count was less on SS-OCTA than on UWF-FA (7 (range, 0-19) vs.12 (range, 0-23), P < 0.001). Agreement in detecting MAs between SS-OCTA and UWF-FA was found to be good (ICC = 0.920, [0.555-0.974]).The total capillary changes and collateral vessels count were less on UWF-FA than SS-OCTA (11 ± 9 vs 6 ± 7, P < 0.001 and 4 (range, 0-6) vs 0 (range, 0-0), P < 0.001, respectively). Agreement in detecting capillary changes and collateral vessels between OCTA and UWF-FA was found to be fair (ICC = 0.733, [0.081-0.905] and 0.564, [0.039-0.805], respectively). Compared with UWF-FA, widefield SS-OCTA was found comparable or even superior in detecting FAZ, NPA, capillary changes and collateral vessels except MAs in RVO. Widefield SS-OCTA may offer a more efficient alternative to FA for diagnosis and monitoring RVO.


Interaction among cadmium sulfide nanoparticles, acridine orange, and deoxyribonucleic acid in fluorescence spectra and a method for deoxyribonucleic acid determination.
Some studies on quantum dots (QD) as donors that enhance the fluorescence of a dye as an acceptor through fluorescence resonance energy transfer (FRET) have been reported. However, in the present work we discovered that CdS quantum dots sharply quenched the fluorescence of acridine orange (AO). Also, DNA enhanced the fluorescent signals of AO quenched by CdS. The extents of enhancement were in good proportion to the DNA concentrations. Based on this, a sensitive method was employed to determine DNA with both good selectivity and sensitivity. The calibration curve was linear over 60-4,000 ng mL(-1) and the determination limit (3sigma) was 4.39 ng mL(-1).


New Highly Oxygenated Germacranolides from Carpesium divaricatum and their Cytotoxic Activity.
Eight highly oxygenated germacranolides (1-8) including four new ones (2-5) were isolated from the whole plant of Carpesium divaricatum. The planar structures and relative configurations of the new compounds were determined by NMR experiment and HRESIMS data. The absolute configuration of 1 was established by circular dichroism (CD) method and X-ray diffraction, and the stereochemistry of the new compounds 2-5 were determined by similar CD spectra with 1. Compound 2 is the first hydroperoxyl germacrane from the genus Carpesium. The (13)C NMR data of 1, NMR data of 6-7, and their absolute configurations were reported for the first time. Two new compounds (2 and 4) and two known compounds (6 and 8) exhibited potent cytotoxicity against human cervical cancer (HeLa) cells, superior to that of the positive control doxorubicin.


Search for serum protein-binding disaccharides and disaccharide-binding serum proteins by affinity capillary electrophoresis.
The potential use of affinity capillary electrophoresis in a microscale search for mutually interacting substances in biological fluid is demonstrated. Some disaccharides, especially gentiobiose (Gen), derivatized with 1-phenyl-3-methyl-5-pyrazolone, caused peak retardation when electrophoresed in a neutral running buffer, containing human serum. Gen, the most significantly retarded disaccharide, was converted to its negatively charged bis-mercaptoethanesulfonate derivative (MerESGen), and a serum sample was analyzed in a neutral buffer containing the derivatized disaccharide. Two peaks, belonging to the beta-globulin fraction, were found to be remarkably retarded in the buffer containing MerES-Gen in a concentration-dependent way. These findings prove an interaction between disaccharides and serum proteins.


Downward penetrating endplate screw technique under O-arm navigation posterior fusion in patients with osteoporotic vertebral body fractures associated with diffuse idiopathic skeletal hyperostosis.
A downward penetrating endplate screw (PES) technique combined with caudal anchor screws inserted in the upward direction under O-arm navigation (i.e., crossing screw technique) avoided screw backout and proximal junctional kyphosis (PJK) in three patients with osteoporotic vertebral body fractures and diffuse idiopathic skeletal hyperostosis (DISH). The PES techniques were utilized for patients with T12 (one patient) and L1 (two patients) spontaneous fusion across the targeted vertebrae, with minimal damage to the involved endplates/intervertebral discs. The average number of instrumented vertebrae was 5.3. There were no perioperative complications over the mean follow-up period of 28.7 months; no screw loosening, and no PJK. The PES technique prevented screw backout, and PJK in three patients with lumbar osteoporotic vertebral fractures and DISH.