Environmental management by the learning curve.
This is a futuristic appreciation of waste management challenges and their solution by means of good management models. A literature review, administrative initiatives, research results, and experiences from practice are combined in this study to render an evolutionary picture of the change in paradigm relative to municipal solid waste possible to occur between 2000 and 2025. The principal stages of progress in the 25 years studied were: the correct characterization of municipal solid waste as a function of geographical location and recycling potential, the divided collection model and its corresponding learning curve, correct opportunity cost accounting tools, and the generally admitted and accepted changeover of municipal solid waste treatment from a technical to a management problem. It is reported that as a result of this progress, the municipal landfill is a species in extinction. Regional landfills with long life spans are the rule in 2025.


Periprocedural management of anticoagulation in patients taking novel oral anticoagulants: Review of the literature and recommendations for specific populations and procedures.
An increasing number of individuals are on novel oral anticoagulants (NOAC) for anticoagulation instead of vitamin K antagonists (VKA) and roughly 10% of these individuals will require interruption of these agents for procedures annually. Recent evidence surrounding bridging as well as the FDA approval of a new NOAC call for a comprehensive review and update regarding periprocedural NOAC management. The periprocedural management of NOACs involves striking a balance between the risks of bleeding and thromboembolism associated with interruption, bridging, and reinitiation of anticoagulation. NOACs have a distinct pharmacokinetic advantage in this setting with their quick onset and elimination from the body. Procedures at low risk for bleeding do not require interruption and can be scheduled at the start of the next dosing interval. Procedures at moderate-high risk of bleeding require interruption of NOAC for 5 half lives prior to the procedure to allow for adequate elimination of the drug. In light of new evidence highlighting the risks of bleeding, and given shorter "unprotected" times with NOAC interruption versus VKA, patients at low-moderate risk for thromboembolism should not be bridged when "unprotected" time is less than 96 h. For patients at high risk for thromboembolism, individual patient and surgical factors need to be considered before the decision to bridge is made. The benefit of bridging these patients who have a considerable risk of bleeding may not outweigh the benefits. Focused randomized studies on periprocedural management of NOACs are urgently needed.


Myofunctional device use in oral care and swallowing: a protocol for a feasibility study in an aged care population.
Poor oral health is a known predictor of aspiration pneumonia in vulnerable populations such as the elderly and chronically ill and has been linked to systemic disease, morbidity, and mortality. Reduced oral health not only places individuals at a greater risk of aspiration pneumonia but may result in pain or poorer dentition which can impact on mastication and swallowing. Consequences of this may include reduced oral intake, malnutrition, poorer health outcomes, and reduced quality of life. Few evidence-based protocols exist to manage oral care in aged care populations, and maintenance of good oral hygiene is difficult for nursing and care staff to facilitate. However, a recent literature review found that improvements in oral hygiene, oral behaviors, and swallowing, along with breathing and speech have been found to be associated with the use of myofunctional devices due to positive changes in orofacial functions such as lip seal, mastication, swallowing, and nasal breathing patterns. The primary aim of this study is to assess the feasibility of using a myofunctional device to improve oral care and swallowing function in an aged care population. This project is a feasibility study that involves a 5-week intervention for oral hygiene and dysphagia for residents >65 years old in an aged care setting. Feasibility will be determined by the acceptability of the intervention, study recruitment and retention, and adherence to the intervention. Feasibility testing will also include an evaluation of clinical outcome measures, and sensitivity to detect changes in oral health and swallowing in an aged care population. The results of this trial will provide important information regarding the feasibility of utilizing a myofunctional device to improve oral care and dysphagia in elderly patients in an aged care facility. This knowledge will further guide and inform design of a larger trial or future research. This trial was registered August 10, 2021, with the Australian New Zealand Clinical Trials Registry and allocated the ACTRN: ACTRN12621001359820.


Experience with the duodenal switch operation in the presence of intestinal malrotation.
The presence of intestinal malrotation (IM) may pose unexpected problems during bariatric operations. We reviewed the records of patients with IM undergoing bariatric operations at our institution over the last 5 years. Three patients underwent four procedures. These included an open duodenal switch, an attempted laparoscopic gastric bypass with open duodenal switch as a second-stage procedure, and lastly a laparoscopic robot-assisted duodenal switch. All patients have had good outcomes. The key anatomic principles of a tension-free duodeno-enterostomy and maintaining appropriate orientation at the distal enteroenterostomy are emphasized.


Isolation of poly(A)+ RNA by paper affinity chromatography.
Poly(A)+ RNA was isolated from in vitro short-term-labeled total cytoplasmic RNA of Ehrlich ascites tumor cells by oligo(dT) cellulose chromatography. This poly(A)+ RNA fraction was compared with a poly(A)+ RNA fraction isolated by a new procedure which involves specific binding of poly(A)+ RNA to messenger affinity paper (mAP) and its release in hot (70 degrees C) water. In typical experiments 10-11 micrograms (2.3%) of poly(A)+ RNA can be retained from 500 micrograms of total cytoplasmic RNA per cm2 of mAP in a quick one-step procedure. The poly(A)+ RNA preparations isolated by the two methods proved to be almost identical with respect to their fraction in total cytoplasmic RNA, specific radioactivities, sucrose gradient profiles, and translation assays. Since the isolation of poly(A)+ RNA by mAP is much less time consuming than that by oligo(dT) column chromatography and since the poly(A)+ RNA can be recovered from mAP in small volumes, which avoids further loss during precipitations, it can be advantageously used for preparative isolation of poly(A)+ RNA.


Rapid and effective diagnosis of tuberculosis and rifampicin resistance with Xpert MTB/RIF assay: a meta-analysis.
Xpert MTB/RIF (Cepheid) assay has been introduced for the diagnosis of tuberculosis (TB) and RIF-resistance. The meta-analysis was used to establish the overall accuracy of Xpert MTB/RIF assay for diagnosing TB and RIF-resistance. Based on comprehensive searches of the Pubmed and Embase, we identified outcome data from all articles estimating diagnostic accuracy with Xpert MTB/RIF assay. A summary estimation for sensitivity, specificity, diagnostic odds ratios (DOR) and the area under the summary ROC curve (AUC) was calculated by using the bivariate random-effects approach. The meta-analysis included 18 studies (10,224 suspected specimens). The summary estimate was 90.4% (95%CI 89.2%-91.4%) for sensitivity, 98.4% (95%CI 98.0%-98.7%) for specificity and 328.3/0.9822 for DOR/AUC in pulmonary tuberculosis (PTB). The sensitivity, specificity and DOR/AUC of detecting RIF-resistance were 94.1%, 97.0% and 177.8/0.9832, respectively. For extrapulmonary tuberculosis, the overall pooled sensitivity was 80.4% and specificity was 86.1%. The findings in subgroup analysis were as follows: the accuracy of Xpert MTB/RIF assay is higher in smear-positive specimens and the sensitivity of diagnosing PTB in adults was higher than that in children (90.8% versus 74.3%). TB and RIF-resistance can be rapidly and effectively diagnosed with Xpert MTB/RIF assay.


Immune responses against oxidative stress-derived antigens are associated with increased circulating tumor necrosis factor-alpha in heavy drinkers.
Growing evidence indicates that pro-inflammatory cytokines play a key role in alcoholic liver disease (ALD). This study investigates whether immune response toward oxidative stress-derived antigens could be involved in promoting cytokine production in alcohol abusers. Cytokine profile and circulating IgG against human serum albumin modified by malondialdehyde (MDA-HSA) and against oxidized cardiolipin (Ox-CL) were evaluated in 59 heavy drinkers (HD) with (n=30) or without (n=29) ALD and 34 healthy controls. IgG against MDA-HSA and Ox-CL were significantly higher in HD with ALD than in HD without liver injury or healthy controls. The elevation of these antibodies was associated with higher circulating levels of IL-2 (p=0.005) and TNF-alpha (p=0.001), but not of IL-6 or IL-8. The prevalence of abnormal TNF-alpha was 5-fold higher in HD with oxidative stress-induced IgG than in those without. HD with the combined elevation of both TNF-alpha and oxidative stress-induced IgG had 11-fold (OR 10.7; 95%CI 1.2-97.2; p=0.023) greater risk of advanced ALD than those with high TNF-alpha, but no immune responses. Moreover, the combined elevation of TNF-alpha and lipid peroxidation-derived IgG was an independent predictor of ALD in HD. We propose that immune responses towards oxidative stress-derived antigen promote TNF-alpha production and contribute to liver damage in alcohol abusers.


Analysis of 5' UTR composition and gene expression: canonical versus non-canonical start codons.
The overall composition upstream of start codons in Escherichia coli was evaluated and viewed in connection with global transcriptome data. Genes starting with AUG as initiation codon tended to be expressed at higher levels than the non-AUG genes, and the upstream region of the non-AUG genes showed negligible signs of Shine-Dalgarno sequences. The latter is in sharp contrast to the AUG genes. Viewing these findings in connection with the current literature, it is proposed that a distinct mechanism for initiation of translation might exist for non-AUG genes that are not preceded by a Shine-Dalgarno sequence. A survey covering a range of other eubacteria (Firmicutes, Proteoacteria, and Actinobacteria) reveals that it is mainly among the Proteobacteria that non-AUG genes do not display clear signs of Shine-Dalgarno regions.


Searching for a therapy of creatine transporter deficiency: some effects of creatine ethyl ester in brain slices in vitro.
Creatine, an ergogenic compound essential for brain function, is very hydrophilic and needs a transporter to cross lipid-rich cells' plasma membranes. Hereditary creatine transporter deficiency is a severe incurable neurological disease where creatine is missing from the brain. Creatine esters are more lipophylic than creatine and may not need the transporter to cross plasma membranes. Thus, they may represent a useful therapy for hereditary creatine transporter deficiency. Creatine ethyl ester (CEE) is commercially available and widely used as a nutritional supplement. It was reported that it enters the cells of patients lacking the transporter but was not useful when administered in vivo, by oral route, to affected patients. In this paper we investigated the effects of CEE in in vitro brain slices before and after biochemical block of the creatine transporter. We found that CEE is rapidly degraded in the aqueous incubation medium to creatinine, however it remains in solution long enough to cause an increase in tissue content of creatine and, more prominently, phosphocreatine. Both CEE and creatine delayed the anoxia-induced failure of synaptic transmission, and there was no difference between the two compounds. Contrary to what we expected, CEE did not increase tissue creatine content after the creatine transporter was blocked. We confirm that CEE is probably not an effective treatment for hereditary creatine transporter deficiency. Two factors seem to affect the possibility for creatine esters to be exploited in the therapy of creatine transporter deficiency. First, the size of their alcohol moiety should be increased since this would increase the lipophilicity of the compound and improve its ability to diffuse through biological membranes. Second, creatine esters should be further modified to slow their degradation to creatinine and increase their half-life in aqueous solutions. Moreover, we should not forget the possibility that they are degraded in vivo by plasma esterases.


Positron emission tomography imaging of dopamine D2 receptors using a highly selective radiolabeled D2 receptor partial agonist.
A series of microPET imaging studies were conducted in anesthetized rhesus monkeys using the dopamine D2-selective partial agonist, [(11)C]SV-III-130. There was a high uptake in regions of brain known to express a high density of D2 receptors under baseline conditions. Rapid displacement in the caudate and putamen, but not in the cerebellum, was observed after injection of the dopamine D2/3 receptor nonselective ligand S(-)-eticlopride at a low dosage (0.025mg/kg/i.v.); no obvious displacement in the caudate, putamen and cerebellum was observed after the treatment with a dopamine D3 receptor selective ligand WC-34 (0.1mg/kg/i.v.). Pretreatment with lorazepam (1mg/kg, i.v. 30min) to reduce endogenous dopamine prior to tracer injection resulted in unchanged binding potential (BP) values, a measure of D2 receptor binding in vivo, in the caudate and putamen. d-Amphetamine challenge studies indicate that there is a significant displacement of [(11)C]SV-III-130 by d-Amphetamine-induced increases in synaptic dopamine levels.


The significance of hematuria in patients infected with the human immunodeficiency virus.
We determined the importance of hematuria in patients infected with the human immunodeficiency virus (HIV). The records of 1,326 HIV infected patients with yearly evaluations were reviewed for hematuria and evaluation results. Mean followup was 2.1 years. A total of 331 patients (25.0%) had 1 episode of hematuria and 67 were evaluated with 5 significant diagnoses made. Management was affected in only 3 of these patients. No occult genitourinary tumors were found. In young, asymptomatic, HIV infected patients with microscopic hematuria a urological evaluation can be safely omitted in the presence of normal renal function and a benign urological history.


Relation between high-density lipoprotein cholesterol and peripheral vasomotor function.
Low levels of high-density lipoprotein (HDL) cholesterol are one of the most common lipid abnormalities in patients with coronary artery disease. Endothelial dysfunction is also highly prevalent in patients with coronary artery disease. We sought to determine whether HDL cholesterol levels are correlated with endothelium-dependent vasomotion in patients being evaluated for atherosclerosis. Peripheral vascular endothelial function was assessed by high-resolution brachial artery ultrasound. Flow-mediated dilation (FMD) during reactive hyperemia was defined as the percent change in arterial diameter following 5-minute arterial occlusion. All patients underwent stress testing with nuclear single-photon emission computed tomographic imaging to determine percent left ventricular ejection fraction and define the presence or absence of coronary artery disease. One hundred fifty-one subjects (87 men, 64 women) were enrolled (average age 58 +/- 11 years). Total cholesterol, HDL cholesterol, low-density lipoprotein cholesterol, and triglyceride levels were 188 +/- 48, 47 +/- 13, 108 +/- 37 and 154 +/- 88 mg/dl, respectively. The mean FMD for the entire group was 9.9 +/- 5.2%. Subjects with an HDL cholesterol of <40 mg/dl (n = 39) had lower FMD (7.4 +/- 3.6%) compared with those with an HDL cholesterol >/=40 mg/dl (11.0 +/- 5.5%, p <0.001). There was a significant correlation between FMD and HDL cholesterol level (linear regression, p <0.001), and in multivariate analysis, HDL cholesterol was an independent predictor of FMD. Peripheral endothelial function was abnormal in subjects with low HDL cholesterol and well-preserved in those with high HDL cholesterol. These data suggest that impaired endothelial function associated with low HDL cholesterol may be an additional, previously unrecognized mechanism contributing to the increased risk of atherosclerosis in these patients.


Iron metabolism: State of the art in hypoxic cancer cell biology.
The tumor microenvironment (TME) promotes the malignant transformation of cancer cells, mainly through metabolic reprogramming. As one of the most prominent features of the TME, hypoxia contributes to cancer cell death resistance, invasion, metastasis, and therapy-resistant phenotypes. As an important cofactor for various enzymes, iron is essential for ATP generation, antioxidant protein function, and DNA-damage repair in hypoxic cancer cells. Iron metabolism, as a promoter of aggressive hypoxic cancer cell biology, has attracted an increasing amount of attention. Iron utilization, storage, and efflux are enhanced in hypoxic cancer cells, which further contributes to cancer cell proliferation, metastasis, ferroptosis resistance, and immune escape. This review describes the relationship between iron metabolism and proliferation, metastasis, and ferroptosis of hypoxic cancer cells, as well as several iron-targeted cancer therapy strategies. Understanding the hypoxia-specific regulatory mechanism of iron metabolism could aid the development of targeted therapy against refractory hypoxic cancer cells.


Higher prostate-specific antigen levels predict improved survival in patients with hormone-refractory prostate cancer who have skeletal metastases and normal serum alkaline phosphatase.
Higher prostate-specific antigen (PSA) and alkaline phosphatase (ALK-P) levels predicted worse survival in men with metastatic hormone-refractory prostate cancer (HRPC). In the current study, the authors evaluated the combined effects of PSA and ALK-P on survival. Two hundred twenty-four men who had HRPC with bone metastases and who were receiving chemotherapy were identified, and 143 of those men had data available on both ALK-P and PSA levels at chemotherapy initiation. The primary endpoint of the study was overall survival (OS) after chemotherapy. The men were dichotomized into normal and abnormal ALK-P groups according to levels based on institutional normal ranges. The effect of PSA was evaluated as both a categorical value and a continuous value using Cox regression. Eighty-nine of 143 patients (62%) had elevated ALK-P levels. The median PSA was 147 ng/mL (93 ng/mL in patients with normal ALK-P, 171 ng/mL in patients with elevated ALK-P). At a median follow-up of 30 months after chemotherapy initiation, 93 patients had died. The median OS after chemotherapy was 15.8 months (95% confidence interval, 12.8-18.4 months) and was significantly longer if ALK-P was in the normal range (21.3 months vs 14 months; P = .005). For the group with normal ALK-P levels, the median OS was 12.5 months, 24.5 months, and 36.9 months for patients with low, medium, and high PSA levels, respectively. In contrast, the effect of PSA on survival was not as evident in the group with elevated ALK-P levels (16.5 months vs 11.9 months vs 12.1 months, respectively; P = .14 for interaction). Age-adjusted multivariate analysis demonstrated statistically significant interactions of PSA and ALK-P with OS (P = .02). ALK-P significantly predicted OS in men with HRPC who had bone metastases. In patients with normal ALK-P levels, higher PSA levels were associated with improved survival.


5-Benzoyl triazole as new structural dimension in glycoconjugates.
In recent years, 1,4-triazole rings are being widely used for the synthesis of carbohydrate derived biomimetics, due to their easy synthesis and wide range of functional group compatibility. These triazole rings lead to synthetic molecules with improved enzymatic stability, bioavailability, and structural diversity. In this present work, a benzoyl group has been introduced at the C-5 position of the triazole ring present in the synthetic glycoconjugates providing further structural diversity to the molecule. 5-Benzoyl 1,4-triazole ring containing glycoconjugates were synthesized using Cu(I) catalyzed [3 + 2] cycloaddition reaction of per-O-acetylated glycopyranosyl azide and phenyl acetylene followed by in situ electrophilic addition of benzoyl group to the Cu(I) coordinated triazole intermediate. The X-ray crystal structure of one of the 5-benzoyl 1,4-triazole linked glycoconjugate derived from d-xylose {1-N-(2,3,4-tri-O-acetyl-β-d-xylopyranosyl)-4-phenyl-5-benzoyl-1,2,3-triazole} showed unique pattern of intermolecular CH…O interactions arranging the molecules in an anti-parallel orientation. The structure and morphology of the compounds were further explored using computational calculation and scanning electron microscopic (SEM) study which firmly established the uniqueness of 5-benzoyl 1,4-triazole linked glycoconjugates compared to that of 5-H 1,4-triazole linked derivative.


The limits of narrative: medical student resistance to confronting inequality and oppression in literature and beyond.
Upon designing and implementing a literature course on family values for Year 4 medical students, we found that while the supposed benefits of literary inquiry were to lead students to a deeper understanding of difficult issues such as illness and violence in the family, many of our students were unable to engage critically with the course material. This, we believe, was a result of their resistance to confronting issues such as inequality and oppression. This paper is an attempt to theorise student resistance to difficult, unruly subjects they encounter in a literature class, particularly those surrounding race, gender, social class and sexual identity. We modify some of the expansive claims made by narrative medicine and put forth a new pedagogical and curricular approach to the uses of literature in medical education. We found that many students resisted course material and corresponding discussions, especially those related to sexual identity and non-traditional family values, male-female relationships and white racism. To reduce student resistance, we pose a more critical approach to narrative inquiry in medical settings that may deepen students' willingness to imagine what it is like to be someone who is suffering, and to work against oppressive social structures that sustain such suffering. Thus, we recommend moving narrative inquiry beyond a focus on the self and the patient in that individualised, circumscribed relationship and into a collective process involving the social, political, cultural and economic conditions that affect health and well-being.


Exercise Motivation and Self-Efficacy Vary Among Patients with Heart Failure - An Explorative Analysis Using Data from the HF-Wii Study.
To examine profiles in patients with heart failure (HF) regarding their exercise motivation and self-efficacy. The baseline data of patients with HF participating in the HF-Wii study were analysed. In total, 517 patients were divided into four groups based on their exercise motivation (exercise motivation index) and self-efficacy (exercise self-efficacy scale). To describe the differences in demographic and clinical variables between the groups, chi-square cross-tabulations and ANOVAs were conducted. The four groups were labelled as insecure avoiders (25%), laid-back strugglers (10%), conscientious self-doubters (42%) and determined achievers (22%). Patients' profiles differ according to their motivations and self-efficacy towards exercise. Most patients were conscientious self-doubters (high motivation and low self-efficacy), and these patients had more comorbidities and lower exercise capacity compared to the other groups, which could decrease their confidence in exercising. However, only half of the patients who were determined achievers (high motivation and high self-efficacy) reached the recommended amount of physical activity per week. This indicates that motivation and self-efficacy are crucial determinants, but more factors are important for becoming more physically active. Understanding patients' motivations and self-efficacy are necessary in order to provide meaningful physical activity counselling and promotion.


A scoping review on disparities in exposure to advertising for e-cigarettes and heated tobacco products and implications for advancing a health equity research agenda.
Disparities in exposure to and density of tobacco advertising are well established; however, it is still unclear how e-cigarette and heated tobacco product (HTP) advertising vary by age, education, sex, gender identity, race/ethnicity, sexual orientation, socioeconomic status (SES), and/or urban/rural area. Through a scoping review, we sought to identify potential disparities in exposure to e-cigarette and HTP advertising and promotion across populations. In January 2020, a systematic literature search was conducted in five databases: PubMed, Scopus, Embase, Web of Science, and the Cochrane Library. The search was updated in October 2020. Articles reporting on exposure to e-cigarette and/or HTP advertising and promotion across age, education, sex, gender identity, race/ethnicity, sexual orientation, SES, and/or urban/rural areas were included for full-text review (n = 25). Of those, 15 were deemed relevant for data extraction. The majority of the studies were from the U.S. (n = 12) and cross-sectional (n = 14). Studies were published between 2014 and 2020 and focused on determining causal relationships that underlie disparities; only one study assessed HTP advertising and promotion. Exposure to e-cigarette and HTP advertising was assessed at the individual-level (e.g., recall seeing ads on television) and at the neighborhood-level (e.g., ad density at the point-of-sale). Studies addressed differences across age (n = 6), education (n = 2), sex (n = 6), gender identity and sexual orientation (n = 3), race/ethnicity (n = 11), SES (n = 5), and urban/rural (n = 2). The following populations were more likely to be exposed to e-cigarette advertising: youth, those with more than a high school diploma, males, sexual and gender minorities, Whites, and urban residents. At the neighborhood-level, e-cigarette advertisements were more prevalent in non-White neighborhoods. Exposure to e-cigarette/HTP advertising varies based on sociodemographic characteristics, although the literature is limited especially regarding HTPs. Higher exposure among youth might increase tobacco-related disparities since it can lead to nicotine/tobacco use. Research should incorporate and apply a health equity lens from its inception to obtain data to inform the elimination of those disparities.


Endothelial progenitor cells enter the aging arena.
Age is a significant risk factor for the development of vascular diseases, such as atherosclerosis. Although pharmacological treatments, including statins and anti-hypertensive drugs, have improved the prognosis for patients with cardiovascular disease, it remains a leading cause of mortality in those aged 65 years and over. Furthermore, given the increased life expectancy of the population in developed countries, there is a clear need for alternative treatment strategies. Consequently, the relationship between aging and progenitor cell-mediated repair is of great interest. Endothelial progenitor cells (EPCs) play an integral role in the cellular repair mechanisms for endothelial regeneration and maintenance. However, EPCs are subject to age-associated changes that diminish their number in circulation and function, thereby enhancing vascular disease risk. A great deal of research is aimed at developing strategies to harness the regenerative capacity of these cells. In this review, we discuss the current understanding of the cells termed "EPCs," examine the impact of age on EPC-mediated repair and identify therapeutic targets with potential for attenuating the age-related decline in vascular health via beneficial actions on EPCs.


Oxalate oxidase from Abortiporus biennis - protein localisation and gene sequence analysis.
We have described for the first time the localisation of oxalate oxidase (OXO, EC 188.8.131.52) in Abortiporus biennis cells, using histochemical and immunochemical methods coupled with transmission electron microscopy. Rabbit anti-oxalate oxidase immunoglobulins with anti-rabbit secondary antibody conjugated with 10-nm gold particles were used. Moreover, the formation of electron dense precipitation of reaction of diaminobenzidine (DAB) with horseradish peroxidase (HRP) for histochemical localisation of the enzyme was found. OXO was localised close to the membranous structures of the cell membranes, in membranous vesicles located close to the outer cell membrane, and vacuolar membranes surrounding vacuoles. The positive immunoreaction to OXO was also intense in cell wall areas. Moreover, we proved that gene coding for OXO was expressed in the same cultures. Corresponding mRNA was isolated, full length cDNA was synthesized, cloned and sequenced. Two copies of cupin domains were found in the sequence of amino-acids conserved domain coding for the cupin enzyme. Comparison of the genomic DNA and cDNA sequences has revealed the presence of seventeen introns in the gene. The isoelectric point of the protein was estimated at pH 4.5 and several possible N-glycosylation sites were predicted.


[Characteristics of mouse hematopoietic stem cells in the phase of enhanced radioresistance after sublethal irradiation].
Haemopoietic stem cells of mice which displayed an increased radioresistance 12 days following sublethal irradiation, exhibited higher proliferative, granulocyte-repopulating and migration activities as compared with those of intact animals.


Reconfigurable honeycomb metamaterial absorber having incident angular stability.
Ultrawide-angle electromagnetic wave absorbers with excellent mechanical properties are required in many diverse applications such as sensing, and stealth technologies. Here, a novel 3D reconfigurable metamaterial absorber (MMA) consisting of honeycomb and VO2 films is proposed. The proposed MMA exhibits a strong absorptivity above 90% in the widest incident angle up to [Formula: see text] for TM- and TE polarized oblique incidences for THz wave propagating in yoz-plane. Under normal incidence, when VO2 films are in the insulating state, the proposed absorber exhibits high absorptivity in the frequency band of 1-4 THz. By increasing the temperature of the whole structure, the structural transformation of VO2 occurs and turns into the metallic phase. We have shown that under oblique incidence, the ohmic losses of VO2 films especially those parallel to the direction of the incident electric field are the most important absorption principles of the proposed MMA. Due to the ultra wide-angle absorption (angular stability) and mechanical performance, it is expected that the presented MMA may find potential applications, such as camouflage technologies, electromagnetic interference, imaging, and sensing. To the best knowledge of authors, the proposed MMA configuration exhibits the absorptivity in the widest incident angle ever reported.


Lactulose production from cheese whey using recyclable catalyst ammonium carbonate.
Ammonium carbonate ((NH4)2CO3) was used as an alkaline catalyst of lactulose production from cheese whey. Maximum yield of 29.6% was obtained at reaction time of 28.44 min, (NH4)2CO3 of 0.76% at 97°C. During reaction, (NH4)2CO3 was fully decomposed to NH3 and CO2, and these gases were recovered. To boost up NH3 recovery, various methods such as heating, aeration, and pH adjustment were applied. The optimal condition for the purpose of NH3 retrieval was temperature of up to 60°C alongside aeration. Easy separation and recovery make (NH4)2CO3 a catalyst alternative to common alkaline chemicals especially for the weak alkaline reaction.


Semen parameters in patients with unilateral testicular cancer compared to patients with other malignancies.
The aim of our study was to evaluate pretreatment semen quality in patients with unilateral testicular cancer in comparison to semen parameters of patients suffering from other malignancies. Semen analysis according to WHO recommendations were performed in 16 patients suffering from unilateral testicular cancer (group 1) and in 21 patients who were diagnosed to have other malignant tumors (group 2: non-Hodgkin's lymphoma: n=7, Hodgkin's disease: n=6, leukemia: n=3, osteosarcoma: n=2, rectal cancer: n=2, thyroid carcinoma: n=1) prior to anti-cancer treatment. Normozoospermia was observed in none of the testicular cancer patients but in five of the other patients ( p=0.047). Sperm concentration was significantly decreased in the patients of group 1 compared to those of group 2 (18.7+/-22.3x10(6)/ml versus 35.6+/-31.3x10(6)/ml, p=0.03). The percentage of rapid progressive motile spermatozoa was significantly less in testicular cancer patients than in patients suffering from other malignancies (WHO group a: 1.1+/-2.0% versus 4.7+/-5.6%, p=0.02). Normal morphological findings of spermatozoa were found in a smaller percentage in group 1 (16.2+/-6.0% versus 26.1+/-18.0%, p=0.03). Our investigations revealed that especially testicular cancer has an adverse influence on sperm quality. Hence, we advise careful and sufficient cryopreservation of semen in those patients taking the negative impact of cytotoxic treatments on semen parameters into account.


A single-ensemble-based hybrid approach to clutter rejection combining bilinear Hankel with regression.
Clutter regarded as ultrasound Doppler echoes of soft tissue interferes with the primary objective of color flow imaging (CFI): measurement and display of blood flow. Multi-ensemble samples based clutter filters degrade resolution or frame rate of CFI. The prevalent single-ensemble clutter rejection filter is based on a single rejection criterion and fails to achieve a high accuracy for estimating both the low- and high-velocity blood flow components. The Bilinear Hankel-SVD achieved more exact signal decomposition than the conventional Hankel-SVD. Furthermore, the correlation between two arbitrary eigen-components obtained by the B-Hankel-SVD was demonstrated. In the hybrid approach, the input ultrasound Doppler signal first passes through a low-order regression filter, and then the output is properly decomposed into a collection of eigen-components under the framework of B-Hankel-SVD. The blood flow components are finally extracted based on a frequency threshold. In a series of simulations, the proposed B-Hankel-SVD filter reduced the estimation bias of the blood flow over the conventional Hankel-SVD filter. The hybrid algorithm was shown to be more effective than regression or Hankel-SVD filters alone in rejecting the undesirable clutter components with single-ensemble (S-E) samples. It achieved a significant improvement in blood flow frequency estimation and estimation variance over the other competing filters.


Understanding uncoupling in the multiredox centre P450 3A4-BMR model system.
Understanding the uncoupling at the haem active site and/or at the level of multidomain electron transfer is an important element in cytochrome P450 chemistry. Here a chimeric model system consisting of human cytochrome P450 3A4 and the soluble reductase domain of CYP102A1 from Bacillus megaterium (BMR) is used to study the relationship between electron transfer and the coupling efficiency in substrate monoxygenation. Several regulatory features were considered. FAD and FMN added to apoenzyme in oversaturating concentrations influence neither formaldehyde production nor coupling efficiency. The optimal conditions of coupling efficiency depended only on the NADPH concentration. The pH (8.0) and ionic strength (50 mM potassium phosphate) were found to modulate the level of coupling, indicating an influence over the formation of a productive interaction between the BMR and the haem domain. Overall, uncoupling is found to be an intrinsic property of the haem domain, and the covalent linkage of the reductase in a single polypeptide chain has little influence over the activity coupled to product formation.


Morganella morganii-associated arthritis in a diabetic patient.
This case report involves a 60-year-old diabetic man who developed septic arthritis as a result of the pathogen Morganella morganii. The patient had complaints of elevated body temperature, malaise, rigors and pain in the left knee, despite no history of trauma. On examination of the knee, erythema, warmth, tenderness and swelling was observed. Arthrocentesis performed on his left knee indicated the presence of straw-coloured, cloudy fluid without crystals. Bacterial identification based on biochemical and automated methods indicated the growth of M morganii. M morganii was also isolated sedimentafrom the exudate of a diabetic ulcer in the left foot, with antibiotic susceptibilities identical to those from the knee effusion. This case indicates that M morganii may be considered as a possible cause of septic arthritis in diabetic patients, especially those with diabetic foot infections.


The role of three-dimensional ultrasonography fetal lung volume measurement in the prediction of neonatal respiratory function outcome.
Respiratory distress is commonly encountered among premature babies immediately after birth resulting in significant neonatal morbidity or mortality. To evaluate the possible correlation between three dimensional fetal lung volumes (FLVs) and neonatal respiratory outcomes. A cohort study included 100 pregnant women who participated in the study and were divided into two groups; group A (n: 50 - women pregnant ±34-37 weeks) and group B (n: 50 - women pregnant ±37+1 to 40 weeks). A three dimensional measurement of the right fetal lung was made using virtual organ computer-aided analysis (VOCAL) software then correlated to neonatal respiratory functions namely Apgar score at birth and the occurrence of respiratory distress syndrome (RDS). In group A, FLV was negatively correlated with Apgar score and the occurrence of RDS. In group B, FLV showed no statistical correlation with Apgar score and the occurrence of RDS. Three dimensional fetal lung volumes might be an accurate noninvasive predictor for the development of RDS among preterm fetuses.


The study of wear behaviors on abducted hip joint prostheses by an alternate finite element approach.
An acetabular cup with larger abduction angles is able to affect the normal function of the cup seriously that may cause early failure of the total hip replacement (THR). Complexity of the finite element (FE) simulation in the wear analysis of the THR is usually concerned with the contact status, the computational effort, and the possible divergence of results, which become more difficult on THRs with larger cup abduction angles. In the study, we propose a FE approach with contact transformation that offers less computational effort. Related procedures, such as Lagrangian Multiplier, partitioned matrix inversion, detection of contact forces, continuity of contact surface, nodal area estimation, etc. are explained in this report. Through the transformed methodology, the computer round-off error is tremendously reduced and the embedded repetitive procedure can be processed precisely and quickly. Here, wear behaviors of THR with various abduction angles are investigated. The most commonly used combination, i.e., metal-on-polyethylene, is adopted in the current study where a cobalt-chromium femoral head is paired with an Ultra High Molecular Weight Polyethylene (UHMWPE) cup. In all illustrations, wear coefficients are estimated by self-averaging strategy with available experimental datum reported elsewhere. The results reveal that the THR with larger abduction angles may produce deeper depth of wear but the volume of wear presents an opposite tendency; these results are comparable with clinical and experimental reports. The current approach can be widely applied easily to fields such as the study of the wear behaviors on ante-version, impingement, and time-dependent behaviors of prostheses etc.


Timing and setting of billed advance care planning among Medicare decedents in 2017-2019.
The Centers for Medicare & Medicaid Services (CMS) began to reimburse clinicians for advance care planning (ACP) discussions, effective January 1, 2016. We sought to characterize the timing and setting of first-billed ACP discussions among Medicare decedents to inform future research on ACP billing codes. Using a random 20% sample of Medicare fee-for-service beneficiaries aged 66 years and older who died in 2017-2019, we described the timing (relative to death) and setting (inpatient, nursing home, office, or outpatient with or without Medicare Annual Wellness Visit [AWV], home or community, or elsewhere) of the first-billed ACP discussion for each beneficiary. Our study included 695,985 decedents (mean [SD] years of age, 83.2 [8.8]; 54.2% female); the proportion of decedents who had at least one billed ACP discussion increased from 9.7% in 2017 to 21.9% in 2019. We found that the proportion of first-billed ACP discussions held during the last month of life decreased from 37.0% in 2017 to 26.2% in 2019, while the proportion of first-billed ACP discussions held more than 12 months before death increased from 11.1% in 2017 to 35.2% in 2019. We also found that the proportion of first-billed ACP discussions held in the office or outpatient setting along with AWV increased over time (from 10.7% in 2017 to 14.1% in 2019), while the proportion held in the inpatient setting decreased (from 41.7% in 2017 to 38.0% in 2019). We found that with increasing exposure to the CMS policy change, uptake of the ACP billing code has increased; first-billed ACP discussions are occurring sooner before the end-of-life stage and are more likely to occur with AWV. Future studies should evaluate changes in ACP practice patterns, rather than only an increasing uptake in ACP billing codes, following the policy implementation.


Working memory load differentially affects tip-of-the-tongue states and feeling-of-knowing judgments.
Tip-of-the-tongue states (TOTs) are judgments of the likelihood of imminent retrieval for items currently not recalled, whereas feeling-of-knowing judgments (FOKs) are predictions of successful recognition for items not recalled. The assumption has been that similar metacognitive processes dictate these similar judgments. In Experiment 1, TOTs and FOKs were compared for general information questions. Participants remembered four digits (working memory load) during target retrieval for half of the questions, and there was no memory load for the other questions. Working memory did not affect recall but decreased the number of TOTs and increased FOKs. In Experiment 2, participants maintained six digits during retrieval. TOTs decreased in the working memory condition, but FOKs remained constant. Experiment 3 replicated the results of Experiment 2 while asking for FOKs for recall. In each of the first three experiments, positive metacognitive judgments also affected working memory performance, supporting the idea that working memory and metamemory use similar monitoring processes. In Experiment 4, visual working memory did not affect TOTs or FOKs. The data support a view that TOTs and FOKs are separable metacognitive entities.


Differential expression and localisation of WWP1, a Nedd4-like protein, in epithelia.
Ubiquitination of proteins such as ion transporters appears to be an important process in the regulation of their membrane expression. Recently, using two-hybrid screening, we have selected a potential partner for the alpha-subunit of the amiloride-sensitive epithelial sodium channel (ENaC): the WWP1 protein, a ubiquitin ligase belonging to the Nedd4 family. To establish whether WWP1 is co-expressed with ENaC, we employed in situ hybridisation, immunohistochemistry and Western blotting to determine the expression of WWP1 in various tissues and cell lines, including those known to express ENaC. As expected, WWP1 was expressed, like ENaC, in the bronchiolar epithelium. However it was also present in the proximal colon and the proximal part of the nephron (where ENaC is not expressed) and absent in the distal parts of the nephron (where ENaC is expressed abundantly). These results suggest that other channels or transport proteins, containing specific domains, such as PY motifs, could be the targets for regulation by WWP1.


Systemic nano-delivery of low-dose STING agonist targeted to CD103+ dendritic cells for cancer immunotherapy.
Current methods of STING activation based on intra-tumoral injections of cyclic dinucleotides (CDNs) are not suitable for addressing tumor heterogeneity or for inaccessible, metastatic and abscopal tumors. In this study, we developed systemically administered CD103+ dendritic cell (DCs) targeted liposomal formulations and evaluated the anti-tumor efficacy with low dose. Liposomal CDN formulations were prepared using Clec9a targeting peptide and evaluated therapeutic efficacy in vitro and in vivo in subcutaneous MC38 and B16F10 tumor models. Targeted delivery of CDNs is expected to enhance anti-tumor immune response as well as reduce off-target toxicities. With intravenous 0.1 mg/kg systemic CDN dose of the targeted liposomal formulation, our results showed robust immune response with significant antitumor efficacy both as a monotherapy and in combination with anti-PD-L1 antibody. These results show that a CD103+ DC targeted CDN formulation can lead to potent immune stimulation upon systemic administration even in relatively "cold" tumors such as B16F10.


The talking eyes: Pupillometry to index verbal fluency in normal aging.
Verbal fluency tasks are widely used to assess cognitive and linguistic abilities in older adults. In this study, we investigated whether pupillometry can be used to measure verbal fluency in healthy older adults. We invited 45 older adults (Mean age = 66.55 years, SD = 4.32) to perform a verbal fluency task, which involves generating as many words as possible beginning with the letter "P" for a duration of one minute. We also invited participants to perform a control task, which involves counting aloud for one minute. In both tasks, we recorded pupil activity with eye-tracking glasses. Analysis demonstrated a larger pupil size during the verbal fluency condition than in the counting condition. Significant positive correlations were observed between pupil size and correct responses on the verbal fluency task. The larger pupil size during the verbal fluency condition can be attributed to the cognitive load inherent in the verbal fluency task and/or to the ability of older adults to produce correct answers on this task. Our study demonstrates how pupillometry can be used as an ecological physiological assessment of not only verbal fluency, but also linguistic ability in general, in normal aging.


Triterpenoids and steroids isolated from Anatolian Capparis ovata and their activity on the expression of inflammatory cytokines.
Capparis L. (Capparaceae) is grown worldwide. Caper has been used in traditional medicine to treat various diseases including rheumatism, kidney, liver, stomach, as well as headache and toothache. To isolate and elucidate of the secondary metabolites of the C. ovata extracts which are responsible for their anti-inflammatory activities. Buds, fruits, flowers, leaves and stems of C. ovata Desf. was dried, cut to pieces, then ground separately. From their dichloromethane/hexane (1:1) extracts, eight compounds were isolated and their structures were elucidated by NMR, mass spectroscopic techniques. The effects of compounds on the expression of inflammatory cytokines in SH-SY5Y cell lines were examined by qRT-PCR ranging from 4 to 96 µM. Cell viability was expressed as a percentage of the control, untreated cells. This is a first report on isolation of triterpenoids and steroids from C. ovata with anti-inflammatory activity. One new triterpenoid ester olean-12-en-3β,28-diol, 3β-pentacosanoate (1) and two new natural steroids 5α,6α-epoxycholestan-3β-ol (5) and 5β,6β-epoxycholestan-3β-ol (6) were elucidated besides known compounds; oleanolic acid (2), ursolic acid (3), β-sitosterol (4), stigmast-5,22-dien-3β-myristate (7) and bismethyl-octylphthalate (8). mRNA expression levels as EC10 of all the tested seven genes were decreased, particularly CXCL9 (19.36-fold), CXCL10 (8.14-fold), and TNF (18.69) by the treatment of 26 µM of compound 1 on SH-SY5Y cells. Triterpenoids and steroids isolated from C. ovata were found to be moderate-strong anti-inflammatory compounds. Particularly, compounds 1 and 3 were found to be promising therapeutic agents in the treatment of inflammatory and autoimmune diseases.


Modeling Agricultural Watersheds with the Soil and Water Assessment Tool (SWAT): Calibration and Validation with a Novel Procedure for Spatially Explicit HRUs.
Applications of the Soil and Water Assessment Tool (SWAT) model typically involve delineation of a watershed into subwatersheds/subbasins that are then further subdivided into hydrologic response units (HRUs) which are homogeneous areas of aggregated soil, landuse, and slope and are the smallest modeling units used within the model. In a given standard SWAT application, multiple potential HRUs (farm fields) in a subbasin are usually aggregated into a single HRU feature. In other words, the standard version of the model combines multiple potential HRUs (farm fields) with the same landuse/landcover, soil, and slope, but located at different places of a subbasin (spatially non-unique), and considers them as one HRU. In this study, ArcGIS pre-processing procedures were developed to spatially define a one-to-one match between farm fields and HRUs (spatially unique HRUs) within a subbasin prior to SWAT simulations to facilitate input processing, input/output mapping, and further analysis at the individual farm field level. Model input data such as landuse/landcover (LULC), soil, crop rotation, and other management data were processed through these HRUs. The SWAT model was then calibrated/validated for Raccoon River watershed in Iowa for 2002-2010 and Big Creek River watershed in Illinois for 2000-2003. SWAT was able to replicate annual, monthly, and daily streamflow, as well as sediment, nitrate and mineral phosphorous within recommended accuracy in most cases. The one-to-one match between farm fields and HRUs created and used in this study is a first step in performing LULC change, climate change impact, and other analyses in a more spatially explicit manner.


Blimp-1 is a prognostic indicator for progression of cervical intraepithelial neoplasia grade 2.
Progression of cervical intraepithelial neoplasia (CIN) to higher grade disease is associated with persistent human papillomavirus (HPV) infection and an absence of immune-mediated regression. However, the immune microenvironment that distinguishes progression from persistent or regressing lesions has not been well defined. A total of 69 patients under the age of 25 with high-risk HPV-positive cytology and biopsy-confirmed p16-positive CIN2 were included in the study. Biopsies were stained using 20 antibodies to a range of immune markers. Based on a 2-year follow-up, samples were analysed in "progressor" (CIN3 +) or "persister/regressor" (CIN1, 2 or normal) groups. Progression was most strongly associated with Blimp-1 positive cell staining in the lesion (P = 0.0019) and with low numbers of infiltrating CD4 cells in the dermal region beneath the lesion (P = 0.0022). The presence of CD4, CD8 and T bet-positive cells in the dermal region most strongly correlated with CD11c cells in the persister/regressor but not the progressor group. High numbers of Blimp-1 + cells in CIN2 lesions may predict progression to more severe disease. Measurement of Blimp-1 may have diagnostic utility for the determination of the need to treat women with cervical pre-cancer. CIN2 progression is associated with high numbers of Blimp-1 positive cells in the lesion. Detection of Blimp-1 in the lesion may have utility as a prognostic test to inform the need to treat CIN2.


Biliopancreatic Diversion with Duodenal Switch in the Elderly: Long-Term Results of a Matched-Control Study.
Biliopancreatic diversion with duodenal switch (BPD-DS) is one of the most effective surgical approaches for the treatment of severe obesity. The objective of this study is to compare perioperative complications and long-term results of open BPD-DS in elderly versus younger patients. All patients aged 60 years and above who underwent a primary open BPD-DS in our center were selected (n = 105). Patients were matched 1:1 for sex, BMI, the presence of type 2 diabetes (T2DM), and year of surgery with a group of younger patients (aged ≤55 years). The mean age of the patients was 62.3 ± 2.0 vs. 40.4 ± 7.0 years (p ≤ 0.0001). Initial BMI and prevalence of T2DM were similar in both groups, at 50.9 kg/m(2) and 57%, respectively. Mean operative time (178.6 ± 46.7 vs. 162.5 ± 39.9 min, p = 0.01), hospital stay (10.2 ± 8.3 vs. 6.3 ± 1.5 days, p = 0.0001), and blood loss (593 ± 484 vs. 474 ± 241 ml, p = 0.05) were significantly higher in elderly patients. No difference in 30-day mortality rate was observed (0.9% in each group). There was no significant difference in major complication rate (16.2 vs. 8.6%, p = 0.09). At a mean follow-up of 7.1 ± 4.1 years, excess weight loss (67.6 ± 19.2 vs. 72.7 ± 20.7%, p = 0.06) and BMI (32.2 ± 5.7 vs. 30.8 ± 6.6 kg/m(2), p = 0.15) were not significantly different. No significant difference was observed between the two groups for the resolution of T2DM (p = 0.53) and obstructive sleep apnea (p = 0.44). Open BPD-DS is associated with similar long-term benefits in elderly and younger patients, in terms of weight loss and resolution or improvement of obesity-related comorbidities. Perioperative complications might be more frequent in the elderly population, but this was not associated with increased mortality.


Separation of 9-Fluorenylmethyloxycarbonyl Amino Acid Derivatives in Micellar Systems of High-Performance Thin-Layer Chromatography and Pressurized Planar Electrochromatography.
The problems with separation of amino acid mixtures in reversed-phase mode are the result of their hydrophilic nature. The derivatisation of the amino group of mentioned above solutes leads to their solution. For this purpose, 9-fluorenylmethoxycarbonyl chloroformate (f-moc-Cl) as the derivatisation reagent is often used. In our study, the separation of some f-moc- amino acid derivatives (alanine, phenylalanine, leucine, methionine, proline and tryptophan) with the use of micellar systems of reversed-phase high-performance thin-layer chromatography (HPTLC) and pressurized planar electrochromatography (PPEC) is investigated. The effect of surfactant concentration, its type (anionic, cationic and non-ionic) and mobile phase buffer pH on the discussed above solute migration distances are presented. Our work reveals that the increase of sodium dodecylsulphate concentration in the mobile phase has a different effect on solute retention in HPTLC and PPEC. Moreover, it also affects the order of solutes in both techniques. In PPEC, in contrast to the HPTLC technique, the mobile phase pH affects solute retention. The type of surfactant in the mobile phase also impacts solute retention and migration distances. A mobile phase containing SDS improves system efficiency in both techniques. Herein, such an effect is presented for the first time.


Digital video recording of cardiac surgical procedures.
We attempted to find a method of reducing time and effort for recording videos of cardiac surgical procedures. A camera mounting arm designed by us provided a properly fixed digital camera location for undisturbed recording. The camera and its remote control unit provided an opportunity for the surgeon to record only the steps of the operation without need for editing. Digital videos produced by this method required no additional time from the surgeon except to record the commentary at leisure. The video recorded was of excellent quality and provided a well-focused recording of the steps of the operation. The technique described for video recording of cardiac surgical procedures provides a time-saving and easy method for good reproduction of surgical procedures.


Calmodulin resolution of multiple peaks of activity by preparative electrofocusing.
When the supernatant fractions from rat brain homogenates were subjected to preparative electrofocusing in a bed of Sephadex G75, several peaks of calmodulin were resolved. A minor peak representing free calmodulin migrated with a pI of 3.8 --4.4. Other peaks of calmodulin activity were observed with isoelectric points at pH 4.8, 5.2, 6.0 and 6.8. The peak of calmodulin activity at 5.2 co-migrated with phosphodiesterase activity which was stimulated 1.8-fold by calcium. A second peak of phosphodiesterase activity detected at pH 8.0 was stimulated 1.2-fold by calcium and occurred in an area where no calmodulin activity could be detected. If isoelectric focusing was done in the presence of 8 M urea only one peak of calmodulin activity was observed with a pI of 4.0--4.4. It is suggested that the multiple peaks of calmodulin resolved by electrofocusing represent calmodulin associated with various proteins which are subject to modulation by calmodulin and calcium.


Reality check: how do we know what's real?
How do we know what is real and what is merely a figment of our imagination? Dijkstra and Fleming tackle this question in a recent study. In contrast to the classic Perky effect, they found that once imagery crosses a 'reality threshold', it becomes difficult to distinguish from reality.


Insulin-producing cells from embryonic stem cells experimental considerations.
The main objective of cell bioengineering is to generate customized tissues that allow recovering the lost functions in the organism in the absence of immune rejection. Although the possibility of in vitro generation of entire organs is technically very complex, obtaining specific cell types for replacement therapies seems to be a more realistic goal at mean time. In this context, those pathologies affected by the dysfunction of a specific cell type, as it is the case of beta-cell in diabetes, would be in principle candidates to benefit from cell transplantation protocols. Embryonic stem cells offer interesting possibilities in this context because they fulfill two important criteria: (i) High proliferation rate by symmetric cell division, overcoming the problem of biomass scarcity and (ii) Plasticity of differentiating to all cell types present in the adult organism, including the germ line. Different approaches have been developed in vitro to obtain insulin-producing cells from embryonic stem cells. Nevertheless, a definitive protocol does not exist yet. However, the experience accumulated in this field by the different laboratories has provided considering key points that would help to design a preferred protocol in the future.


Standardized mortality ratios between street-connected young people and the general age-equivalent population in an urban setting in Kenya from 2010 to 2015.
There are currently no published estimates of mortality rates among street-connected young people in Kenya. In this short report, we estimate mortality rates among street-connected young people in an urban setting in Kenya and calculate standardized mortality ratios to assess excess mortality among street-connected young people compared to the general population of Kenyan adolescents. We collected data on deaths among street-connected young people aged 0-29 between 2010 and 2015. We calculated sex-stratified standardized mortality ratios for street-connected young people aged 0-19 and 20-29 from 2010 to 2015, using publicly available Kenya population data as reference. We found that between 2010 and 2015, there were 69 deaths among street-connected young people aged 0 to 29 years in 2013 was 1,248: 341 females (27%) and 907 males (73%). The standardized mortality ratios among street-connected females aged 0-19 and 20-29 years were 2.79 (95% CI 1.44-4.88) and 7.55 (95% CI 3.77-13.51), respectively; standardized mortality ratios among street-connected males aged 0-19 and 20-29 years were 0.71 (95% CI 0.32-1.35) and 5.48 (95% CI 3.86-7.55), respectively. In conclusion, we found that mortality among street-connected young people in an urban setting in Kenya is elevated compared to the general population of Kenyan young people. States should act urgently and take responsibility for protecting street-connected young people's human rights by scaling up programs to prevent morbidity and death associated with youth street involvement.


Autophosphorylation of degradation products of arginyl-tRNA synthetase protein, isolated from Bom:NMRI mouse liver.
Proteins of M(r) 140, 60, 57, 50, 22, and 14 kDa, all possessing arginyl-tRNA synthetase activity, were subjected to phosphorylation without addition of exogenous protein kinase activity. All proteins except the 14 kDa were shown to contain endogenous protein kinase activity. The product of autophosphorylation of the 60, 57, 50, and 22 kDa proteins was identified as a phosphorylated 14.9 kDa molecule. In some cases higher molecular weight phosphorylated proteins were also detected. Properties of the 60 kDa species are described.


A hexaphenylbenzene based AIEE active two photon probe for the detection of hydrogen sulfide with tunable self-assembly in aqueous media and application in live cell imaging.
Supramolecular aggregates of hexaphenylbenzene derivative exhibit aggregation induced emission enhancement and modulation of self-assembled architecture from spherical to flower-like assembly in the presence of H2S. Furthermore, probe displays higher photostability, low toxicity and bright green fluorescence in two-photon microscopy (TPM) imaging for the detection of H2S in live HeLa cells.


Phase II Trial of Combination Nab-paclitaxel and Gemcitabine in Non-squamous Non-small Cell Lung Cancer After Progression on Platinum and Pemetrexed.
Better therapies are needed to improve survival in metastatic non-small cell lung cancer (NSCLC). Given the synergy of combination nab-paclitaxel and gemcitabine in metastatic pancreatic cancer and their individual activity in advanced NSCLC, we sought to determine whether the same combination would confer a therapeutic benefit in the second-line therapy of recurrent or metastatic non-squamous (NSQ) NSCLC. This single-arm phase II trial of nab-paclitaxel and gemcitabine was performed from June 2015 to April 2020 at an academic referral cancer center. Patients with advanced NSQ-NSCLC whose disease progressed on first-line pemetrexed plus platinum +/- immunotherapy were enrolled. Patients received intravenous nab-paclitaxel 100 mg/m2 and gemcitabine 1000 mg/m2 on days 1 and 8 of each 21-day cycle. The primary endpoint was objective response rate (ORR). Secondary endpoints included disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). Safety and tolerability were evaluated by Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Thirty-seven patients (15 men [41%] and 22 women [59%]; median age, 66 years [range, 41-81 years]) were accrued. ORR was 13.5% (95% CI, 2.5-24.5%). DCR was 59.5% (95% CI, 43.5-75.5%). Median PFS was 2.6 months (95% CI, 1.4-3.8 months). Median OS was 6.2 months (95% CI, 4.2-8.2 months). 1-year OS was 24% (95% CI, 10-38%). Safety and tolerability were similar to other second-line chemotherapies, although there was an 11% incidence of grade 2-3 pneumonitis. Combination nab-paclitaxel and gemcitabine after platinum and pemetrexed for NSQ-NSCLC was not associated with greater efficacy than would be expected for single-agent chemotherapy in this setting. The higher-than-expected risk of pneumonitis was also concerning. ClinicalTrials.gov Identifier: NCT02303977 MICRO-ABSTRACT: In this phase II trial, 37 patients with metastatic non-squamous non-small cell lung cancer were treated with nab-paclitaxel/gemcitabine in second-line. ORR = 13.5% (95% CI, 2.5%-24.5%). Median PFS = 2.6 months (95% CI, 1.4-3.8 months). Median OS = 6.2 months (95% CI, 4.2-8.2 months). Nab-paclitaxel and gemcitabine was not associated with greater efficacy than would be expected for single-agent chemotherapy in this setting.


Genomewide copy number analysis of Müllerian adenosarcoma identified chromosomal instability in the aggressive subgroup.
Müllerian adenosarcomas are malignant gynecologic neoplasms. Advanced staging and sarcomatous overgrowth predict poor prognosis. Because the genomic landscape remains poorly understood, we conducted this study to characterize the genomewide copy number variations in adenosarcomas. Sixteen tumors, including eight with and eight without sarcomatous overgrowth, were subjected to a molecular inversion probe array analysis. Copy number variations, particularly losses, were significantly higher in cases with sarcomatous overgrowth. Frequent gains of chromosomal 12q were noted, often involving cancer-associated genes CDK4 (six cases), MDM2, CPM, YEATS4, DDIT3, GLI1 (five each), HMGA2 and STAT6 (four), without association with sarcomatous overgrowth status. The most frequent losses involved chromosomes 13q (five cases), 9p, 16q and 17q (four cases each) and were almost limited to cases with sarcomatous overgrowth. MDM2 and CDK4 amplification, as well as losses of RB1 (observed in two cases) and CDKN2A/B (one case), was verified by FISH. By immunohistochemistry, all MDM2/CDK4-coamplified cases were confirmed to overexpress both encoded proteins, whereas all four cases with (plus an additional four without) gain of HMGA2 overexpressed the HMGA2 protein. Both cases with RB1 loss were negative for the immunostaining of the encoded protein. Chromothripsis-like copy number profiles involving chromosome 12 or 14 were observed in three fatal cases, all of which harbored sarcomatous overgrowth. With whole chromosome painting and deconvolution fluorescent microscopy, dividing tumor cells in all three cases were shown to have scattered extrachromosomal materials derived from chromosomes involved by chromothripsis, suggesting that this phenomenon may serve as visual evidence for chromothripsis in paraffin tissue. In conclusion, we identified frequent chromosome 12q amplifications, including loci containing potential pharmacological targets. Global chromosomal instability and chromothripsis were more frequent in cases with sarcomatous overgrowth. To our knowledge, this is the first time that evidence of chromothripsis has been demonstrated in paraffin-embedded clinical tissues and in adenosarcomas.


Arrhythmias following cardiac surgery: relation to serum digoxin levels.
Arrhythmias were analyzed in 50 patients undergoing cardiac surgery: 27 with valve surgery, 15 with coronary artery bypass (CAB), 5 with CAB and valve surgery, and 3 with miscellaneous procedures. The role of electrolyte abnormalities, pericarditis, serum osmolarity, digoxin level, and the type of surgery performed was evaluated. Thirty-seven out of 50 patients (74 per cent) had a postoperative arrhythmia, and a total of 78 different arrhythmias were noted. Twenty-six out of 27 patients with valve surgery had an arrhythmia vs. six out of 15 patients with CAB (p less than 0.001). Atrial fibrillation was the most common arrhythmia in all groups. Although postoperative hypocalcemia, hypomagnesemia, pericarditis, and wide shifts in osmolarity were common, they did not correlate with arrhythmias. Seventeen patients developed postoperative arrhythmias compatible with digitalis toxicity, including junctional rhythm, atrioventricular dissociation, or atrial tachycardia with block. However, the range of serum digoxin levels in these patients was zero to 2.80 ng. per milliliter. This suggests increased sensitivity to digitalis glycosides or the effects of surgical trauma as the etiology of arrhythmia in many patients. The distinction between digitalis-induced arrhythmia and spontaneously occurring arrhythmia cannot be made with certainty in most postoperative patients. Therapy should reflect an awareness of the potential for postoperative digitoxicity.


Effects of oral physostigmine in Alzheimer's disease.
Previous studies of oral physostigmine in the treatment of Alzheimer's disease have: (1) assumed physostigmine is effective only in mildly affected patients; (2) relied on an initial "dose-finding" phase to determine the most effective dose and excluded nonresponders; and (3) primarily assessed memory. We examined the response of 22 patients to six different daily dosages of oral physostigmine, using selective reminding tests that were administered twice daily. Nine patients had a "best" dose/day (mode = 13 mg/day), which was used in a subsequent double-blind crossover study. The other 13 were given the highest tolerated dose. The selective reminding test and a full neuropsychological battery were given during the drug and placebo periods. As a group, the 22 patients improved significantly on the Wechsler Adult Intelligence Scale-Revised Digit Symbol subtest and a shape cancellation task (p less than 0.05). Nine patients showed improved performance on the selective reminding test during physostigmine treatment, and 9 showed no response; 4 patients performed better during placebo treatment. Dose finding did not help in predicting response in the crossover study; only 2 of the 9 who showed improvement had a best dose. Dementia severity did not predict crossover response. This suggests that: (1) physostigmine as administered had no pronounced effect on memory in Alzheimer's disease; (2) oral physostigmine produces no greater benefits on memory in mildly than in moderately demented patients; (3) response in a dose-finding phase does not predict response in double-blind crossover; and (4) Digit Symbol and cancellation tasks may be more sensitive than memory tests to the effects of oral physostigmine.


A novel method for dissolution and stabilization of non-mulberry silk gland protein fibroin using anionic surfactant sodium dodecyl sulfate.
The importance of silk protein has increased because of its potential use as a natural biopolymer for tissue engineering and biomedical applications. In this report we show a novel and ecofriendly method for dissolution of gland silk protein fibroin. Non-mulberry silk fibroin from mature fifth instar larvae of Antheraea mylitta was found to be optimally soluble in 1% (w/v) anionic surfactant sodium dodecyl sulfate (SDS). Regenerated fibroin showed distinct bands of approximately 395 and 197 kDa on electrophoresis in non-reducing and reducing conditions, respectively. Enhanced fibroin dissolution via internalization of hydrophobic amino groups inside a hydrophilic amino acid core in the form of micelles was observed. Prolonged storage stability without gelation of SDS-extracted fibroin was seen. Atomic force microscopy showed micellar aggregation with mean micellar aggregation size of 8 nm. Circular dichroism spectroscopy revealed predominantly helical conformation due to surfactant addition with internal protein conformational changes as revealed by fluorescence spectroscopic studies.


Application of biological and single-strand conformation polymorphism assays for characterizing potential mild isolates of Citrus tristeza virus for cross protection.
Citrus tristeza virus (CTV) by killing millions of citrus cultivars grown on sour orange rootstock worldwide has become one of the most dangerous viral pathogen. Characterization of 12 CTV isolates was analyzed by biological indexing. Infected samples of citrus were collected from citrus growing areas of Pakistan and CTV was detected by symptoms on indicator plants and confirmed by direct tissue blot immunoassay (DTBIA). CTV positive samples were graft inoculated on six biological indicator hosts in the study. A standardized protocol was deployed to study biological characteristics of these isolates. All biological indicators induced mild and from mild to moderate reactions against all of the CTV isolates tested. About two isolates produced stem-pitting symptoms from moderate to severe on Mexican lime. CTV strains were further characterized and confirmed by the analysis of p25 gene of CTV isolates using single-strand conformation polymorphism (SSCP) assay. SSCP analysis revealed that most isolates confined only one predominant sequence variant. SSCP profiles of PCR amplified products from CTV isolates showed bands patterns corresponding to mild and sever strain. Three isolates (4MF, 8KBS and 10GS) from different regions and cultivars were identified as potential source of mild strains for cross protection. These results are the best base for mild strain cross protection (MSCP) in the country.


A Quadruped Robot Exhibiting Spontaneous Gait Transitions from Walking to Trotting to Galloping.
The manner in which quadrupeds change their locomotive patterns-walking, trotting, and galloping-with changing speed is poorly understood. In this paper, we provide evidence for interlimb coordination during gait transitions using a quadruped robot for which coordination between the legs can be self-organized through a simple "central pattern generator" (CPG) model. We demonstrate spontaneous gait transitions between energy-efficient patterns by changing only the parameter related to speed. Interlimb coordination was achieved with the use of local load sensing only without any preprogrammed patterns. Our model exploits physical communication through the body, suggesting that knowledge of physical communication is required to understand the leg coordination mechanism in legged animals and to establish design principles for legged robots that can reproduce flexible and efficient locomotion.


BCL11A expression in acute phase chronic myeloid leukemia.
Chronic myeloid leukemia (CML) has chronic and acute phases. In chronic phase myeloid differentiation is preserved whereas in acute phase myeloid differentiation is blocked. Acute phase CML resembles acute myeloid leukemia (AML). Chronic phase CML is caused by BCR-ABL1. What additional mutation(s) cause transition to acute phase is unknown and may differ in different persons with CML. BCL11A encodes a transcription factor and is aberrantly-expressed in several haematological and solid neoplasms. We analyzed BCL11A mRNA levels in subjects with chronic and acute phase CML. BCL11A transcript levels were increased in subjects with CML in acute phase compared with those in normals and in subjects in chronic phase including some subjects studied in both phases. BCL11A mRNA levels were correlated with percent bone marrow blasts and significantly higher in lymphoid versus myeloid blast crisis. Differentiation of K562 with butyric acid, a CML cell line, decreased BCL11A mRNA levels. Cytology and flow cytometry analyses showed that ectopic expression of BCL11A in K562 cells blocked differentiation. These data suggest BCL11A may operate in transformation of CML from chronic to acute phase in some persons.


Optical signatures of parity anomaly in a gapped graphene-like system.
Parity anomaly refers to the violation of coordinate reflection symmetry induced by the quantum fluctuations. It is proposed to exist in a graphene-like system with a finite bare mass for Dirac fermions, and manifests itself as a parity-violating quantum correction to the current of each species of fermions. Coulomb interaction greatly increases the fermion mass, and produces various types of excitons. Of particular interest is the ρ-exciton, which is directly connected to parity anomaly and can be generated by absorbing a specific photon. The exciton is a particle-hole bound state, and can be regarded as condensed-matter analogue of meson composed of quark-anti-quark pair. By virtue of this correspondence, we analyze the optical conductivity and calculate the mass of ρ-exciton by employing the Shifman-Vainshtein-Zakharov sum rule method that is widely used in the studies of hadron phenomenology. We show that ρ-exciton leads to a sharp peak in the optical conductivity, which is observable in optical experiments. Moreover, we study the impact of scalar-like excitons on two-photon processes by computing the decay amplitude, and also find peaks in the Raman spectra.


The prevalence of root resorption of maxillary incisors caused by impacted maxillary canines.
The aim of this study was to evaluate the prevalence of root resorption of maxillary incisors caused by impacted maxillary canines using low-dose dental computed tomography and to gain additional knowledge of the underlying aetiology and the progression of root resorption. A total of 440 patients (mean age, 24.7 years) with 557 impacted maxillary canines were examined regarding their location and the occurrence of root resorption of maxillary incisors. The frequency of root resorption was 2 % of central and 7.7 % of lateral maxillary incisors. The location of the 557 impacted canines within the dental arch was palatal in 67.5 %, buccal in 15.4 % and central in 17.1 %. No significant differences could be shown with respect to the width and the shape of the dental follicle of the impacted maxillary canines and the presence of root resorption of incisors. The presence of root resorption of central (p < 0.0001) and lateral (p < 0.023) maxillary incisors was significantly correlated with an existing contact relationship of the impacted maxillary canines. Our investigation confirms the theory of prior reports comprising a much larger patient population, hypothesising that the dental follicle of impacted maxillary canines does not cause resorption of adjacent maxillary incisors per se. Root resorption of maxillary incisors is correlated with effects of contact of the impacted maxillary canines, and these findings should be considered in treatment planning. Our findings are consistent with other reports and may develop new treatment approaches for the treatment of this sequela.


Case report: Levodopa-responsive parkinsonism with akinetic mutism after ventriculo-peritoneal shunt.
Parkinsonism and akinetic mutism (AM) following ventriculo-peritoneal shunt (VPS) without underdrainage used to be considered rare, but may be underdiagnosed in daily clinical practice. Although the pathophysiology is still unclear, in several case reports, the parkinsonism and AM after VPS shows responsiveness to dopaminergic treatment. We report a 19-year-old male that presented with severe parkinsonism and AM after VPS. Meanwhile, 18F-FDG-PET showed a cortical and subcortical hypometabolism. Fortunately, levodopa dramatically improved patient's symptoms and brain hypometabolism. This report provides support for the possibility that dopamine deficiency inhibits brain metabolism, and further elucidates the pathogenesis of parkinsonism and AM. This report highlights the presentation of a treatable parkinsonism and points out that Levodopa and/or dopamine agonist should be the first choice if the patients develop parkinson-like symptoms after VPS.


Sternal-Sparing Transapical, Beating Heart Mitral Valve Repair in an Adult With Repaired Tetralogy of Fallot.
We present the case of a 60-year-old male patient who underwent tetralogy of Fallot repair at 7 years of age and then developed severe degenerative mitral regurgitation during adulthood. Given the increased surgical risk (obesity, obstructive sleep apnea syndrome, and reoperation), the patient underwent a successful microinvasive mitral valve repair with neochordae implantation. (Level of Difficulty: Advanced.).


Acute pancreatitis in children.
Twenty-nine children with acute pancreatitis were managed during the period 1971 to 1983. Aetiology included trauma (5), mumps (5), drug therapy (4), biliary disease (1), and cystic fibrosis (1); 13 cases were classified as idiopathic. Diagnosis could be difficult, and unnecessary laparotomies were performed in 7 instances for suspected appendicitis. One patient, however, had a well-justified laparotomy revealing coexisting severe appendicitis and pancreatitis. Morbidity included relapses (7), pseudocysts (3), obstructive duodenal hematoma (1), and miscellaneous problems (4). Improvements in management included endoscopic retrograde cholangio-pancreatography (ERCP) to exclude anatomical anomalies in relapsing cases, ultrasonography for the diagnosis of pseudocysts and for follow-up measurements in two such cases successfully managed conservatively, and increasing use of total parenteral nutrition in cases with protracted disease or serious complications.


Key questions in the genetics and genomics of eco-evolutionary dynamics.
Increasing acceptance that evolution can be 'rapid' (or 'contemporary') has generated growing interest in the consequences for ecology. The genetics and genomics of these 'eco-evolutionary dynamics' will be--to a large extent--the genetics and genomics of organismal phenotypes. In the hope of stimulating research in this area, I review empirical data from natural populations and draw the following conclusions. (1) Considerable additive genetic variance is present for most traits in most populations. (2) Trait correlations do not consistently oppose selection. (3) Adaptive differences between populations often involve dominance and epistasis. (4) Most adaptation is the result of genes of small-to-modest effect, although (5) some genes certainly have larger effects than the others. (6) Adaptation by independent lineages to similar environments is mostly driven by different alleles/genes. (7) Adaptation to new environments is mostly driven by standing genetic variation, although new mutations can be important in some instances. (8) Adaptation is driven by both structural and regulatory genetic variation, with recent studies emphasizing the latter. (9) The ecological effects of organisms, considered as extended phenotypes, are often heritable. Overall, the study of eco-evolutionary dynamics will benefit from perspectives and approaches that emphasize standing genetic variation in many genes of small-to-modest effect acting across multiple traits and that analyze overall adaptation or 'fitness'. In addition, increasing attention should be paid to dominance, epistasis and regulatory variation.


Deferoxamine enhances alternative activation of microglia and inhibits amyloid beta deposits in APP/PS1 mice.
The neurotoxicity of amyloid-β peptide (Aβ), a predominant histopathological hallmark lesion of Alzheimer's disease (AD), is enhanced by iron, as found in amyloid plaques of Alzheimer's disease (AD) patients. We investigated whether deferoxamine (DFX) treatment promotes functional recovery and tissue repair in APP/PS1 double transgenic mice. Twelve-month-old APP/PS1 mice were randomly divided into two groups (APP/PS1 and DFX). Neurological deficits were monitored for 2weeks following DFX treatment. To characterize the activation of the microglia, expression of the M1 and M2 phenotypes was analyzed by immunohistochemistry and immunoblotting. Moreover, deposition of iron and Aβ, as well as apoptosis, were examined, and a behavioral test was performed. DFX significantly ameliorated cognitive function and deposition of Aβ as well as inhibited apoptosis in the brain. Consistent with these observations, DFX induced M2 activation of microglia and inhibited M1 activation of microglia in the hippocampus of APP/PS1 mice. In conclusion, DFX treatment improved functional recovery of AD mice, and the mechanism may involve DFX-induced M2 activation of microglia.


Prostacyclin release in the coronary circulation during sustained stimulation in in vitro and in in vivo experimental systems.
Prostacyclin release from rat isolated perfused hearts and from dog coronary circulation was studied by measuring immunoreactive 6-keto-PGF1 alpha (6-keto-PGF1a) in heart perfusate and in plasma obtained from the great cardiac vein respectively. Continuous infusion of arachidonic acid at constant concentration in isolated perfused hearts induced an increased prostacyclin release. This release showed a rapid peak within 10 min and a subsequent decrease. Low-flow ischemia induced an increased perfusate concentration of 6-keto-PGF1a but, considering the decreased flow, prostacyclin release was actually reduced. During the whole period of ischemia (60 min) prostacyclin release was constant. In open-chest anesthetized dogs 6-keto-PGF1a concentration in the great cardiac vein was increased after ligation of the left anterior descending coronary artery. A prolonged period of coronary occlusion (4.5 hours) resulted in a progressive rise of prostacyclin release. 6-keto-PGF1a determinations in the femoral vein and in the aorta did not show relevant variations during the observation period.


Membrane energization in relation with nitrogen fixation in Azotobacter vinelandii and Rhizobium leguminosarum bacteroids.
Nitrogen fixation in A. vinelandii and R. leguminosarum bacteroides shows identical characteristics with respect to the dependence on membrane energization, the sensitivity to uncouplers, the ATP/ADP-ratio, and the dependences on flavodoxinhydroquinone as electrondonor. Although we have been successful in preparing inside-out vesicles which can be energized, attempts to couple these membranes to N2-ase were still unsuccessful. One of the major problems could be the failure to energize these vesicles directly by ATP. Although subject to polymerisation after addition of MgCl2, it could be shown that the actual mol.wt. of the O2-stable N2-ase complex is about 300,000 in agreement with a 1:1:1 stoichiometry of the three constituent proteins, namely, component I, component II and the 2Fe-2S protein.


Green tea catechins and their metabolites in human skin before and after exposure to ultraviolet radiation.
Dietary flavonoids may protect against sunburn inflammation in skin. Preliminary reports using less complete analysis suggest that certain catechins and their metabolites are found in skin biopsies and blister fluid after consumption of green tea; however, it is not known if they are affected by solar-simulated ultraviolet radiation (UVR) or whether conjugated forms, with consequently altered bioactivity, are present. The present study tested the hypothesis that UVR affects the catechin levels in the skin of healthy volunteers after consumption of green tea and how catechins in the plasma are related to their presence in skin tissue samples. In an open oral intervention study, 11 subjects consumed green tea and vitamin C supplements daily for 3months. Presupplementation and postsupplementation plasma samples, suction blister fluid and skin biopsies were collected; the latter two samples were collected both before and after UVR. A sensitive high-performance liquid chromatography/mass spectrometric assay was used to measure the intact catechin metabolites, conjugates and free forms. Seven green tea catechins and their corresponding metabolites were identified postsupplementation in skin biopsies, 20 in blister fluid and 26 in plasma, with 15 green tea catechin metabolites present in both blister fluid and plasma. The valerolactone, O-methyl-M4-O-sulfate, a gut microbiota metabolite of catechins, was significantly increased 1.6-fold by UVR in blister fluid samples. In conclusion, there were some common catechin metabolites in the plasma and blister fluid, and the concentration was always higher in plasma. The results suggest that green tea catechins and metabolites are bioavailable in skin and provide a novel link between catechin metabolites derived from the skin and gut microbiota.


Insight into the plant-associated bacterial interactions: Role for plant arsenic extraction and carbon fixation.
This study investigated the interactions between rhizosphere and endosphere bacteria during phytoextraction and how the interactions affect arsenic (As) extraction and carbon (C) fixation of plants. Pot experiments, high-throughput sequencing, metabonomics, and network analysis were integrated. Results showed that positive correlations dominated the interconnections within modules (>95 %), among modules (100 %), and among keystone taxa (>72 %) in the bacterial networks of plant rhizosphere, root endosphere, and shoot endosphere. This confirmed that cooperative interactions occurred between bacteria in the rhizosphere and endosphere during phytoextraction. Modules and keystone taxa positively correlating with plant As extraction and C fixation were identified, indicating that modules and keystone taxa promoted plant As extraction and C fixation simultaneously. This is mainly because modules and keystone taxa in plant rhizosphere, root endosphere, and shoot endosphere carried arsenate reduction and C fixation genes. Meanwhile, they up-regulated the significant metabolites related to plant As tolerance. Additionally, shoot C fixation increased peroxidase activity and biomass thereby facilitating plant As extraction was confirmed. This study revealed the mechanisms of plant-associated bacterial interactions contributing to plant As extraction and C fixation. More importantly, this study provided a new angle of view that phytoextraction can be applied to achieve multiple environmental goals, such as simultaneous soil remediation and C neutrality.


Midwives' and women's experiences with respectful maternity care around the globe: A meta-synthesis.
All women have the right to the highest attainable standards of health, including the right to respectful maternity care (RMC). A qualitative body of knowledge describing midwives' and women's experiences of the value and importance of RMC exists. However, no qualitative synthesis exists about midwives' and women's views of respectful care. This review aims to present a qualitative synthesis of global perceptions and experiences of midwives and women regarding RMC. A systematic search was conducted in October 2021 and updated in March 2023 on Science Direct, EBSCO host, PubMed, Nexus and ProQuest databases. The synthesis included qualitative studies published between 2010 and 2023. Qualified midwives and pregnant and postnatal women were the samples of the review. The studies' screening and selection for inclusion in the review are presented using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow chart, and the quality of the included studies was appraised using the Critical Appraisal Screening Programme (CASP) tool. Thematic analysis was conducted. Fifteen studies met the review inclusion criteria involving 266 women and 147 midwives. Five themes were identified from the data: commitment to women's rights; excellence in midwifery knowledge and skills; a facilitative built environment; optimising the interpersonal dimension; and the development of women's resourcefulness and resilience. Maternity care is collaborative, and midwives and women are partners in the process. Midwives play a significant role in promoting women's rights, fostering interpersonal working and client relationships, and addressing women's rights and needs.


Simple Synthesis of Molybdenum Disulfide/Reduced Graphene Oxide Composite Hollow Microspheres as Supercapacitor Electrode Material.
MoS₂/RGO composite hollow microspheres were hydrothermally synthesized by using SiO₂/GO microspheres as a template, which were obtained via the sonication-assisted interfacial self-assembly of tiny GO sheets on positively charged SiO₂ microspheres. The structure, morphology, phase, and chemical composition of MoS₂/RGO hollow microspheres were systematically investigated by a series of techniques such as FE-SEM, TEM, XRD, TGA, BET, and Raman characterizations, meanwhile, their electrochemical properties were carefully evaluated by CV, GCD, and EIS measurements. It was found that MoS₂/RGO hollow microspheres possessed unique porous hollow architecture with high-level hierarchy and large specific surface area up to 63.7 m²·g-1. When used as supercapacitor electrode material, MoS₂/RGO hollow microspheres delivered a maximum specific capacitance of 218.1 F·g-1 at the current density of 1 A·g-1, which was much higher than that of contrastive bare MoS₂ microspheres developed in the present work and most of other reported MoS₂-based materials. The enhancement of supercapacitive behaviors of MoS₂/RGO hollow microspheres was likely due to the improved conductivity together with their distinct structure and morphology, which not only promoted the charge transport but also facilitated the electrolyte diffusion. Moreover, MoS₂/RGO hollow microsphere electrode displayed satisfactory long-term stability with 91.8% retention of the initial capacitance after 1000 charge/discharge cycles at the current density of 3 A·g-1, showing excellent application potential.


Synthesis of trifluoromethyl ketones using polymer-supported reagents.
A two step synthesis of trifluoromethyl ketones from aldehydes is reported. A combination of polymer-supported reagents and sequestering agents were employed to effect the transformation without the need for chromatographic purification.


Ectopic UCP1 gene expression in HepG2 cells affects ATP production.
The UCP1 is an uncoupling protein located in the inner mitochondrial membrane of brown adipocytes, which has a well-documented role in diet-induced thermogenesis. The current study assessed whether UCP1 transfected liver cells demand more fuel substrates in the oxidative phosphorylation processes. Therefore, the purpose of this experiment was to achieve an ectopic expression of UCP1 in HepG2 cells to significantly decrease the production of ATP. The UCP1 gene was transferred into the hepatic cells by using a calcium phosphate precipitation protocol. The efficiency of the transfection was tested, 48 hours later, by bioluminescence of luciferase previously transfected, while the expression of mRNA of UCP1 was demonstrated by RT-PCR. In addition, measuring the production of ATP by using a bioluminescence procedure assessed the functionality of this protein. Transfected liver cells with UCP1 showed a decrease of 23% in ATP production in comparison with control cells without expression of UCP1 (2.23 vs. 2.90 RLU/pg protein, p=0.015). In conclusion, the ectopic expression of UCP1 decreased the production of ATP, possibly uncoupling the oxidative phosphorylation, which could be a novel approach for understanding thermogenic processes and eventually for energy metabolism and body weight management.


Effect of time to surgery on outcomes in stage I esophageal adenocarcinoma.
There are limited data on the safe interval from diagnosis to surgery in patients with stage I esophageal adenocarcinoma. We hypothesized that increased time to surgery would be associated with worse survival and increased nodal upstaging. The National Cancer Database was used to identify patients with cT1N0M0 esophageal adenocarcinoma (2004-2015) who underwent esophagectomy without induction therapy. The primary outcome was survival, and the secondary outcomes were the rate of margin-positive resection and pathologic nodal upstaging. Time to surgery was modeled as a categoric variable, dividing patients into quartiles (Q1-4), and as a continuous variable using piecewise linear splines centered on 50 and 100 days. A total of 2495 patients met study criteria. When examined in quartiles, there was no difference in survival between groups based on time to surgery in both unadjusted and multivariable analyses. As a continuous variable, increasing time to surgery less than 50 days was associated with improved survival (hazard ratio, 0.99; 95% confidence interval, 0.98-1.00), and time to surgery greater than 100 days was associated with worse survival (hazard ratio, 1.00; 95% confidence interval, 1.00-1.01) and increased margin-positive resection (odds ratio, 1.01; 95% confidence interval, 1.00-1.02). Treatment at a high-volume center, government insurance, and diagnosis and treatment at different centers were associated with surgery beyond 100 days. Increasing time to surgery greater than 100 days is associated with worse outcomes in patients with stage I esophageal adenocarcinoma. In this patient population, esophagectomy should be offered as soon as safely possible.


Nd-Fe-B alloy-densified agarose gel for expanded bed adsorption of proteins.
Novel dense composite adsorbents for expanded bed adsorption of protein have been fabricated by coating 4% agarose gel onto Nd-Fe-B alloy powder by a water-in-oil emulsification method. Two composite matrices, namely Nd-Fe-B alloy-densified agarose (NFBA) gels with different size distributions and densities, NFBA-S (50-165 microm, 1.88 g/ml) and NFBA-L (140-300 microm, 2.04 g/ml), were produced. Lysozyme was used as a model protein to test the adsorption capacity and kinetics for the NFBA gels modified by Cibacron blue 3GA (CB-NFBA gels). Liquid-phase dispersion behavior in the expanded beds was examined by measurements of residence time distributions, and compared with that of Streamline SP (Amersham-Pharmacia Biotech, Sweden). The dependence of axial mixing in the expanded beds on flow velocity, bed expansion degree. settled bed height, and viscosity of liquid phase was investigated. Breakthrough curves of lysozyme in the expanded beds of the CB-NFBA gels were also examined. The dynamic binding capacity at 5% breakthrough was 23.3 mg/ml matrix for the CB-NFBA-S gels, and 16.7 mg/ml matrix for the CB-NFBA-L, at a flow velocity of 220 cm/h. The results indicate that the NFBA gels are promising for expanded bed adsorption of proteins.


Saturated Boronic Acids, Boronates, and Trifluoroborates: An Update on Their Synthetic and Medicinal Chemistry.
Invited for the cover of this issue are Oleksandr Grygorenko and co-workers at Enamine Ltd., Institute of Organic Chemistry NAS Ukraine, and Taras Shevchenko National University of Kyiv. The image depicts a musical allegory for chemical synthesis: a guitar player in a flask, creating notes that become an orgoboron compound. Read the full text of the article at 10.1002/chem.202102108.