Urinary phthalate metabolites are associated with biomarkers of DNA damage and lipid peroxidation in pregnant women - Tainan Birth Cohort Study (TBCS).
Phthalate exposure and oxidative stress have been linked to adverse reproductive outcomes in experimental studies, whereas no clear line has been drawn for human, especially in pregnant women. This study explored relationships between urinary phthalate metabolites and biomarkers of lipid peroxidation and oxidative and nitrosative DNA damage. Measurements from 97 Taiwanese pregnant women were taken at three different times during second and third trimesters. Five oxidative/nitrosative stress biomarkers - 8-hydroxy-2'-deoxyguanosine (8-OHdG), 8-nitroguanine (8-NO2Gua), 4-hydroxy-2-nonenal-mercapturic acid (HNE-MA), 8-isoprostaglandin F2α (8-isoPF2α), and malondialdehyde (MDA), and 11 phthalate metabolites were measured in urine samples. Linear regressions in each visit and linear mixed-model regressions were fitted to estimate percent changes in oxidative/nitrosative stress biomarkers resulting from inter-tertile increase of phthalate metabolite level and the cumulative concentrations of di (2-ethylhexyl) phthalate (DEHP) and dibutyl phthalate. The highest urine concentrations of phthalate metabolites and the greatest number of significant positive associations between phthalate metabolites and oxidative/nitrosative stress biomarkers were observed in the third visit and in repeated measurements analysis, respectively. Of the biomarkers related to DNA damage, 8-OHdG (25.4% inter-tertile increase for mono-iso-butyl phthalate) was more sensitive to phthalate exposure than 8-NO2Gua. Among the biomarkers of lipid peroxidation, HNE-MA (61.2% inter-tertile increase for sum of DEHP metabolites) was more sensitive than 8-isoPF2α and MDA. Our findings support the hypothesis that pregnant phthalate exposure increases the oxidative stress biomarkers of DNA damage and lipid peroxidation. Future research may elucidate the mediating roles of oxidative/nitrosative stress biomarkers in the link between phthalate exposure and adverse reproductive outcomes.


Another reason for impeccable oral hygiene: oral hygiene-sperm count link.
1. To investigate the relationship between periodontitis and infertility. 2. To evaluate the importance of oral hygiene to general health. Eighty-six men requiring seminal fluid analysis as part of an on-going investigation for infertility in their spouses were serially recruited into the study. Basic dental and periodontal examination were performed. Each participant was also screened for periodontitis using a lateral flow immunoassay kit which detected levels of active membrane metalloproteinase-8. RESULTS were read-off as a color change. Due to some incomplete entries, only 76 participants were involved in the final data analysis. There were 55 subjects with subnormal counts (of which ten were found to be azoospermic, 41 oligospermic) and 25 normospermic controls. A positive association was found between periodontitis and subnormal sperm count in only one age group but statistically significant association was found between poor oral hygiene and subnormal sperm count across all age groups. For the first time, there appears to be a significant association between poor oral and subnormal sperm count. There also appears to an association between chronic periodontitis and subnormal sperm count. These relationships warrant further investigation. There appears to be a link between poor oral hygiene and low sperm count.


[Dynamic changes of endothelin in sera of rats at early burn stage and its effects on endothelial cell permeability in vitro].
The dynamic changes of endothelin in sera of early burnt rats and the effects of endothelin-1 on the permeability of vascular endothelial cells were investigated. In the early phase of 30% (II degree) total body surface area (TBSA) burn rat model, we measured the concentration of endothelins in plasma, the water contents in main organs and the permeability of endothelial monolayer cultured on micropore membrane to Hank's solution or 5 g/L albumin Hank's solution. Endothelin concentration in burnt rat sera was firstly increased dramatically, showing a peak at 6 hours postburn, and then remained significantly higher than the basic level (P < 0.01). The changes of endothelin were correlated with the alteration in water contents in main organs after burn. Moreover, if the cultured endothelial cells were exposed to 0, 1, 10, 100 nmol/L endothelin 1 for 60 min, it was found that the filtration volume (Jv) and the filtration coefficient (Kf) of endothelial monolayer were significantly enhanced as determined by either Hank's or albumin (5 g/L) perfusion, while the osmotic reflection coefficient (sigma) (to protein) decreased in a dose-dependent pattern. The present results suggest that the postburn elevated endothelin may not only mediate the blood flow distribution via potent vasoconstriction, but also directly increase the vascular permeability. The mechanism(s) of the latter event needs to be further clarified.


Recent work with microcomputers for census processing in developing countries.
The use of microcomputers to process census data in developing countries is discussed. Specifically, the authors describe the Integrated Microcomputer Processing System (IMPS) developed by the U.S. Bureau of the Census and focus "on the recent experience of Burkina Faso and Senegal in using microcomputers. A summary is given of the use of IMPS by an increasing number of countries. Additionally, this paper describes the latest enhancements and future plans for IMPS. It concludes with some thoughts on the use of microcomputers in the areas of data collection and processing, as well as in the use and dissemination of census data."


The effect of RAAS blockade on markers of renal tubular damage in diabetic nephropathy: u-NGAL, u-KIM1 and u-LFABP.
Blockade of the renin-angiotensin-aldosterone system (RAAS) affects both the glomerulus and tubules. We aimed to investigate the effect of irbesartan on the tubular markers: urinary (u) neutrophil gelatinase associated protein (NGAL), Kidney injury molecule 1 (KIM1) and liver-fatty acid-binding protein (LFABP). A substudy of a double-masked, randomized, cross-over study including 52 patients with type 2 diabetes, hypertension and microalbuminuria. After 2 months washout of all antihypertensive medication except bendroflumethiazid, patients were treated in random order with irbesartan 300, 600 and 900 mg for 2 months. Urinary tubular markers at baseline and after each treatment period (ELISA), 24-h blood pressure, glomerular filtration rate (GFR, (51)CrEDTA) and 24-h urine albumin excretion (UAER). Fifty-two patients completed the study (41 male). Age (mean (SD)): 58(10) years and diabetes duration 13(8) years. Baseline GFR was 101(24) and UAER (geometric mean [95%CI]) 133 (103-172) mg/24 h. With increasing doses of irbesartan (300, 600, 900 mg) u-KIM1 was reduced with 15%, 10% and 15% (p = 0.07 between 300 mg vs. baseline and no difference between doses). Patients with high u-KIM1 at baseline (above median) had a 32% reduction in u-KIM1 during treatment (p = 0.01). No significant decline in U-NGAL compared to baseline. U-LFABP increased during treatment (p < 0.01). Irbesartan treatment reduced levels of the tubular marker u-KIM1 in patients with type 2 diabetes and microalbuminuria. u-NGAL changed insignificantly and u-LFABP increased. More studies with longer follow up are needed to determine the role of tubular markers in monitoring treatment effect and prediction of prognosis in diabetic nephropathy.


The coordinated development of manufacturing industry and logistics industry in the Yangtze River Economic Belt: Empirical study by stages based on Haken Model.
It has great significance for improving the logistics service ability of the Yangtze River economic belt, optimizing the industrial structure of manufacturing industry, and realizing the integrated development of the Yangtze River economic belt to explore the collaborative evolution of logistics industry and manufacturing industry in the Yangtze River economic belt, and identify the leading position of the collaborative development of the two industries, so as to. Based on the Haken Model, this paper summarizes the coevolution law of logistics industry and manufacturing industry in the Yangtze River economic belt through two-stage empirical analysis, and identifies the order parameters of the co-development of logistics industry and manufacturing industry. The results show that the overall degree of coordination between the logistics industry and the manufacturing industry in the Yangtze River economic belt is high. And the order parameter has been changed from manufacturing industry in 2003-2009 to logistics industry in 2010-2017. The gap between regions has been reduced, and the western region has the advantage of post development.


Simulation as a Tool to Illustrate Clinical Pharmacology Concepts to Healthcare Program Learners.
This article provides an overview of simulation as an effective and evolving tool for teaching clinical pharmacology within the health professions. Further, opportunities for positioning this methodology to meet current educational challenges are presented. Clinical pharmacology is an essential core competency for all health professionals, correlating with ability to appropriately and safely prescribe, administer, or optimize medication regimens. Computer-assisted learning became the earliest form of simulation applied to pharmacology teaching, arising from increasing pressure to deviate from animal and tissue experiments in undergraduate education in the 1990s. In the last decade, high fidelity patient simulation, using manikin technology, has demonstrated benefit in building connectivity between knowledge and clinical application within patient care. Serious games, or computer-based educational games, provide an alternative method for creating context, with potential realized for newer technologies like augmented reality. These tools, while beneficial, are not applied in a uniform manner across programs. We advocate for routine incorporation of these tools as they offer significant opportunities to address the challenges faced in today's healthcare education, particularly with the need for continued social distancing and limitations on in-person educational engagement during coronavirus. Partnership with faculty utilizing simulation in other areas of the curriculum will assist in overcoming potential barriers to implementation. Simulation provides various methods that have significant potential to address the challenges in today's provision of clinical pharmacology education, especially with new directives for social distancing and limitations for in-person educational engagement.


New approximate analytical expressions for transient concentration profiles and current pertaining to a homogeneous chemical reaction at hemispherical microelectrodes.
A mathematical model corresponding to homogeneous chemical reactions under transient chronoamperometry conditions at hemispherical microelectrodes has been developed. The analytical solutions for the concentration of species and current were obtained using Duhamel's theorem. This closed-form theoretical expression pertains to the transient concentration profiles and fluxes of chemical species involved in chemical and electrochemical reactions at hemispherical microelectrodes. As t → ∞, the analytical expressions corresponding to the concentration and current approach steady-state values. The solutions obtained are explicit only under limiting current conditions. The approximate expressions for concentrations and current as functions of time corresponding to the EC' and CE mechanisms at hemispherical microelectrodes are also reported.


Study on the reaction of CH2 with H2 at high temperature.
Thermal decomposition of CH(2)I(2) [sequential C-I bond fission processes, CH(2)I(2) + Ar → CH(2)I + I + Ar (1a) and CH(2)I + Ar → (3)CH(2) + I + Ar (1b)], and the reactions of (3)CH(2) + H(2) → CH(3) + H (2) and (1)CH(2) + H(2) → CH(3) + H (3) have been studied by using atomic resonance absorption spectrometry (ARAS) of I and H atoms behind reflected shock waves. Highly diluted CH(2)I(2) (0.1-0.4 ppm) with/without excess H(2) (300 ppm) in Ar has been used so that the effect of the secondary reactions can be minimized. From the quantitative measurement of I atoms in the 0.1 ppm CH(2)I(2) + Ar mixture over 1550-2010 K, it is confirmed that two-step sequential C-I bond fission processes of CH(2)I(2), (1a) and (1b), dominate over other product channels. The decomposition step (1b) is confirmed to be the rate determining process to produce (3)CH(2) and the least-squares analysis of the measured rate gives, ln(k(1b)/cm(3) molecule(-1) s(-1)) = -(17.28 ± 0.79) - (30.17 ± 1.40) × 10(3)/T. By utilizing this result, we examine reactions 2 and 3 by monitoring evolution of H atoms in the 0.2-0.4 ppm CH(2)I(2) + 300 ppm H(2) mixtures over 1850-2040 K. By using a theoretical result on k(2) (Lu, K. W.; Matsui, H.; Huang, C.-L.; Raghunath, P.; Wang, N.-S.; Lin, M. C. J. Phys. Chem. A 2010, 114, 5493), we determine the rate for (3) as k(3)/cm(3) molecule(-1) s(-1) = (1.27 ± 0.36) × 10(-10). The upper limit of k(3) (k(3max)) is also evaluated by assuming k(2) = 0, i.e., k(3max)/cm(3) molecule(-1) s(-1) = (2.26 ± 0.59) × 10(-10). The present experimental results on k(3) and k(3max) is found to agree very well with the previous frequency modulation spectroscopy study (Friedrichs, G.; Wagner, H. G. Z. Phys. Chem. 2001, 215, 1601); i.e., the importance of the contribution of (1)CH(2) in the reaction of CH(2) with H(2) at elevated temperature range is reconfirmed.


Variation in Accessory Genes Within the Klebsiella oxytoca Species Complex Delineates Monophyletic Members and Simplifies Coherent Genotyping.
Members of the Klebsiella oxytoca species complex (KoSC) are emerging human pathogens causing infections of increasing significance especially in healthcare settings. KoSC strains are affiliated with distinct phylogroups based on genetic variation at the beta-lactamase gene (bla OXY) and it has been proposed that each major phylogroup represents a unique species. However, since the typing methods applied in clinical settings cannot differentiate every species within the complex, existing clinical, epidemiological and DNA sequence data is frequently misclassified. Here we systematically examined the phylogenetic relationship of KoSC strains to evaluate robustness of existing typing methods and to provide a simple typing strategy for KoSC members that cannot be differentiated biochemically. Initial analysis of a collection of K. oxytoca, K. michiganensis, K. pasteurii, and K. grimontii strains of environmental origin showed robust correlation of core phylogeny and blaOXY grouping. Moreover, we identified species-specific accessory gene loci for these strains. Extension of species correlation using database entries initially failed. However, assessment of average nucleotide identities (ANI) and phylogenetic validations showed that nearly one third of isolates in public databases have been misidentified. Reclassification resulted in a robust reference strain set for reliable species identification of new isolates or for retyping of strains previously analyzed by multi-locus sequence typing (MLST). Finally, we show convergence of ANI, core gene phylogeny, and accessory gene content for available KoSC genomes. We conclude that also the monophyletic members K. oxytoca, K. michiganensis, K. pasteurii and K. grimontii can be simply differentiated by a PCR strategy targeting bla OXY and accessory genes defined here.


Interleukin-22 and CD160 play additive roles in the host mucosal response to Clostridium difficile infection in mice.
Our previous work has shown the significant up-regulation of Il22 and increased phosphorylation of signal transducer and activator of transcription 3 (STAT3) as part of the mucosal inflammatory response to Clostridium difficile infection in mice. Others have shown that phosphorylation of STAT3 at mucosal surfaces includes interleukin-22 (IL-22) and CD160-mediated components. The current study sought to determine the potential role(s) of IL-22 and/or CD160 in the mucosal response to C. difficile infection. Clostridium difficile-infected mice treated with anti-IL-22, anti-CD160 or a combination of the two showed significantly reduced STAT3 phosphorylation in comparison to C. difficile-infected mice that had not received either antibody. In addition, C. difficile-infected mice treated with anti-IL-22/CD160 induced a smaller set of genes, and at significantly lower levels than the untreated C. difficile-infected mice. The affected genes included pro-inflammatory chemokines and cytokines, and anti-microbial peptides. Furthermore, histopathological and flow cytometric assessments both showed a significantly reduced influx of neutrophils in C. difficile-infected mice treated with anti-IL-22/CD160. These data demonstrate that IL-22 and CD160 are together responsible for a significant fraction of the colonic STAT3 phosphorylation in C. difficile infection. They also underscore the additive effects of IL-22 and CD160 in mediating both the pro-inflammatory and pro-survival aspects of the host mucosal response in this infection.


Substrate recognition by recombinant serine collagenase 1 from Uca pugilator.
Uca pugilator serine collagenase 1 was cloned and sequenced from a fiddler crab hepatopancreas cDNA library. A full-length sequence encodes a 270-amino acid pre-pro-enzyme highly identical in structure to the chymotrypsin family of serine proteases. The zymogen form of the enzyme was expressed in Saccharomyces cerevisiae as a fusion with the alpha-factor signal sequence under control of the alcohol dehydrogenase/glyceraldehyde-3-phosphate dehydrogenase promoter. Upon activation with trypsin, the recombinant collagenase possesses collagenolytic properties identical to those of the enzyme isolated from the crab hepatopancreas. The collagenase substrate binding pocket recognizes a wide range of basic, hydrophobic, and neutral polar residues. beta-Branched and acidic amino acids are poor substrates. Acylation is rate-limiting for collagenase versus peptidyl amides, rather than deacylation, as for trypsin and chymotrypsin. Correlations relating substrate volume and hydrophobicity to catalysis were found for collagenase and compared to those for chymotrypsin and elastase. Relative enzyme efficiencies on single amino acid versus tetrapeptide amide substrates show that collagenase derives less catalytic efficiency from binding of the primary substrate residue than trypsin or chymotrypsin, but compensates in binding of the extended peptidyl residues. Serine collagenase 1 is a novel member of the chymotrypsin protease family, by virtue of its amino acid sequence and multifunctional active site.


Hardware implementation of photoelectrically modulated dendritic arithmetic and spike-timing-dependent plasticity enabled by an ion-coupling gate-tunable vertical 0D-perovskite/2D-MoS2 hybrid-dimensional van der Waals heterostructure.
Brain-inspired nanodevices have been demonstrated to possess outstanding characteristics for implementing neuromorphic computing. Among these devices, photoelectrically modulated neuromorphic transistors are regarded as the basic building blocks for applications in emerging brain-like devices. However, to date, efficient optoelectronic-hybrid neuromorphic devices are still lacking. Because conventional transistors based on mono-semiconductor materials cannot absorb adequate light to ensure efficient light-matter interactions, they pose significant challenges to the synchronous processing of photoelectric information. Here, a novel photoelectrically modulated neuromorphic device based on an ion-coupling gate-tunable vertical 0D-CsPbBr3-quantum-dots/2D-MoS2 hybrid-dimensional van der Waals heterojunction is demonstrated by using a polymer ion gel electrolyte as the gate dielectric. A super-efficient heterojunction interface for photo-carrier transport is developed by integrating CsPbBr3 quantum dots with 2D-layered MoS2 semiconductors. We experimentally demonstrate that the drain-source current can be modulated by applying spikes to the drain and gate terminals, and the conductance can also be tuned by external light stimulus. Most importantly, photoelectrically modulated spiking Boolean logics, dendritic integrations in both temporal and spatial modes, and Hebbian learning rules can be successfully mimicked in our proposed hybrid-dimensional device using this intriguing optical and electrical synergy approach. These results suggest that the proposed device has great potential in intelligent cognitive systems and neuromorphic computing applications.


Population competition.
A Population Oratorical Competition between upper secondary pupils aimed at getting students interested in population problems will be held in Johore from May to June. The competition will be launched on 20th May 1981 in Segamat by En. Nordin bin Nazir the Deputy Director of Education, Johore. 81 secondary schools will be sending 184 students to participate at this oratorical competition. The Districts of Kluang, Segamat, Batu Pahat, Muar and Johore Bahru will send students who will face an elimination round during the 1st stage of the competition. The competition is jointly organized by the State Education Department and the National Family Planning Board with a funding support of $3500 from the National Family Planning Board. The Director-General, National Family Planning Board Malaysia, Datin Dr. Hajjah Nor Laily Aziz is scheduled to officiate at the opening ceremony and to give away the prizes on 27th June 1981.


Quantitative videographic analysis of blinking in normal subjects and patients with dry eye.
To study patterns of eye blinking in normal subjects and patients with dry eye. We developed an automated, noninvasive blink monitor that permits quantitative analysis of 6 parameters of blinking. We used this method under normal conditions and then examined the effects on the patterns of blinking in patients with dry eye; several steps in this method were designed to exacerbate or ameliorate ocular surface desiccation. The mean (+/-SD), maximum, and coefficient of variation of the interblinking time in normal subjects and patients with dry eye were 4.0 +/- 2.0 and 1.5 +/- 0.9 seconds, 8.9 +/- 4.0 and 4.2 +/- 2.4 seconds, and 55% +/- 21% and 65% +/- 24%, respectively. Those values for the blinking time were 0.20 +/- 0.04 and 0.27 +/- 0.16 seconds, 0.35 +/- 0.12 and 0.99 +/- 1.30 seconds, and 23% +/- 9% and 46% +/- 34%, respectively. The use of artificial tears or spectacles with moist panels and moist inserts tended to normalize the patterns of blinking in the patients with dry eye, whereas exposure to wind made them more abnormal. Our technique permitted a rigorous analysis of blinking that was previously unavailable. We have shown that local ocular surface conditions alone can significantly affect patterns of blinking. This method should be applicable to studying psychologic and any other factors that may influence blinking.


Effectiveness and Safety Analysis of Plasma Beam in the Treatment of Facial Depressed Scars.
The study aimed to analyze the effectiveness and safety of microplasma beam in the treatment of facial depression scars. 106 patients with facial depression scars treated in the hospital between January 2017 and September 2021 were selected as the observation subjects. According to different treatment methods, the patients were divided into the control group (receiving ultrapulsed carbon dioxide lattice laser treatment, n = 51) and the observation group (undergoing plasma beam treatment, n = 55). The two groups were treated for 6 months, and the treatment effects were compared between the two groups. The Visual Analogue Scale (VAS) was used to compare the pain between the two groups, and the duration of pain and the time of scab shedding were recorded. The improvement of scars was compared between the two groups according to the Evaluation Clinique des Cicatrices d' Acne (ECCA), and the adverse reactions during treatment were compared between the two groups. A clinical effective rate of 94.55% in the observation group was higher than a clinical effective rate of 82.35% in the control group (P < 0.05). The VAS score in the observation group was lower than that in the control group, and the pain duration and the scab shedding time were shorter than those in the control group (P < 0.05). ECCA scores in the observation group after twice and 3 times of treatments were lower than those in the control group (P < 0.05). The total incidence rate of adverse reactions of 10.91% in the observation group was lower, whereas it was 25.49% in the control group (P > 0.05). Plasma beam has a significant efficacy in the treatment of facial depressed scars, and it has mild pain, quick recovery, and high safety. Clinical Trial Registration Number. The clinical trial registration number is T2017081.


Metabolic Profiling of Buddleia indica Leaves using LC/MS and Evidence of their Antioxidant and Hepatoprotective Activity Using Different In Vitro and In Vivo Experimental Models.
LC-ESI-MS (Liquid Chromatography coupled with Electrospray Ionization Mass Spectrometry profiling of a methanol extract from Buddleia indica (BIM) leaves revealed 12 main peaks in which verbascoside and buddlenoid B represent the major compounds. The antioxidant and hepatoprotective activities of BIM were investigated using different in vitro and in vivo experimental models. BIM exhibited substantial in vitro antioxidant properties in DPPH· and HepG2 assays. Regarding CCl4 (carbon tetrachloride) induced hepatotoxicity in a rat model, oxidative stress markers became significantly ameliorated after oral administration of BIM. Lipid peroxide levels showed a 51.85% decline relative to CCl4-treated rats. Super oxide dismutase (SOD), total antioxidant status (TAS), and catalase (CAT) revealed a marked increase by 132.48%, 187.18%, and 114.94% relative to the CCl4 group. In a tamoxifen-induced hepatotoxicity model, BIM showed a considerable alleviation in liver stress markers manifested by a 46.06% and 40% decline in ALT (Alanine Transaminase) and AST (Aspartate Transaminase) respectively. Thiobarbituric acid reactive substances (TBARS) were reduced by 28.57% and the tumor necrosis factor alpha (TNF-α) level by 50%. A virtual screening of major secondary metabolites of BIM to TNF-alpha employing the C-docker protocol showed that gmelinoside H caused the most potent TNF- α inhibition as indicated from their high fitting scores. Thus, BIM exhibited a potent hepatoprotective activity owing to its richness in antioxidant metabolites.


A neutral metallo endoprotease involved in the processing of an F1-ATPase subunit precursor in mitochondria.
A post-translational processing assay of the precursor to the yeast F1-ATPase subunit has been utilized to examine a mitochondrial endoprotease which cleaves this subunit precursor to the size of a mature subunit. The endoprotease is extracted from purified mitochondria as a soluble complex of Mr = 115,000 which is composed of subunits of lower molecular weight when examined on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. It exhibits a pH optimum of between pH 7 and 8 and is inactive at pH 6.5 and below. The mitochondrial endoprotease is insensitive to serine esterase inhibitors, but is inhibited by EDTA and o-phenanthroline. Restoration of precursor subunit processing activity in the presence of metal chelators is strictly dependent on excess Co2+ and Mn2+ over other heavy metals examined. These and additional data indicate that this soluble metallo endoprotease is involved in the processing of other cytoplasmically synthesized precursor subunits of the ATPase complex in addition to the subunit 2 precursor. The role of this processing enzyme in the assembly of mitochondrial inner membrane complexes is discussed in light of the current model of mitochondrial biogenesis.


Differential sensitivity of naive and memory CD8+ T cells to apoptosis in vivo.
Apoptosis is a critical regulator of homeostasis in the immune system. In this study we demonstrate that memory CD8(+) T cells are more resistant to apoptosis than naive cells. After whole body irradiation of mice, both naive and memory CD8(+) T cells decreased in number, but the reduction in the number of naive cells was 8-fold greater than that in memory CD8(+) T cells. In addition to examining radiation-induced apoptosis, we analyzed the expansion and contraction of naive and memory CD8(+) T cells in vivo following exposure to Ag. We found that memory CD8(+) T cells not only responded more quickly than naive cells after viral infection, but that secondary effector cells generated from memory cells underwent much less contraction compared with primary effectors generated from naive cells (3- to 5-fold vs 10- to 20-fold decrease). Increased numbers of secondary memory cells were observed in both lymphoid and non-lymphoid tissues. When naive and memory cells were transferred into the same animal, secondary effectors underwent less contraction than primary effector cells. These experiments analyzing apoptosis of primary and secondary effectors in the same animal show unequivocally that decreased downsizing of the secondary response reflects an intrinsic property of the memory T cells and is not simply due to environmental effects. These findings have implications for designing prime/boost vaccine strategies and also for optimizing immunotherapeutic regimens for treatment of chronic infections.


Zoonotic Infection with Oz Virus, a Novel Thogotovirus.
Oz virus is a novel thogotovirus isolated from ticks that causes lethal infection in mice. We conducted serosurveillance of Oz virus infection among humans and wild mammals in Japan using virus-neutralization tests and ELISAs. Results showed that Oz virus may be naturally infecting humans and other mammalian hosts.


Increased serum levels of granulocyte colony-stimulating factor in patients with severe congenital neutropenia.
Severe congenital neutropenia (SCN), also known as Kostmann Syndrome, is characterized by a maturation arrest of myelopoiesis at the level of promyelocytes with absence of neutrophils in bone marrow (BM) and blood. Hypotheses of the pathophysiology of SCN include (1) defective production of granulocyte colony-stimulating factor (G-CSF), and/or (2) defective response to G-CSF. To exclude defective G-CSF production we tested sera from patients with SCN for the presence of G-CSF using Western blot analysis and NFS-60 proliferation assay. Using these assays we were able to detect increased G-CSF serum levels in SCN patients (150 to 910 pg/mL) as compared with normal controls (between undetectable and 100 pg/mL). These results suggest that patients with SCN have no defect in G-CSF production but a defective response of neutrophil precursors to endogenous G-CSF.


Cholinesterase inhibitors: A new class of psychotropic compounds.
This article reviews evidence indicating that acetylcholinesterase inhibitors have psychotropic properties. The author reviewed the English-language literature pertinent to the response of neuropsychiatric symptoms in Alzheimer's disease and related conditions to cholinergic agents. The cholinergic system originates in the basal forebrain and projects diffusely to the cerebral cortex; the limbic and paralimbic regions receive the most abundant cholinergic projections. The basal forebrain nuclei are positioned at the interface of the limbic system and cerebral cortex, where they play a role in mediating emotional responses. The basal forebrain nuclei are atrophic in Alzheimer's disease, leading to a widespread cholinergic deficit. The cholinergic disturbance may contribute to neuropsychiatric manifestations of the disease. The treatment of patients with Alzheimer's disease with acetylcholinesterase inhibitors reduces neuropsychiatric symptoms, particularly apathy and visual hallucinations. In some studies, a variety of other neuropsychiatric symptoms have been reported to respond to treatment with acetylcholinesterase inhibitors. Response profiles vary among acetylcholinesterase inhibitors. Acetylcholinesterase inhibitors have psychotropic effects and may play an important role in controlling neuropsychiatric and behavioral disturbances in patients with Alzheimer's disease. These agents also may contribute to the management of other disorders with cholinergic system abnormalities and neuropsychiatric symptoms. The beneficial response is most likely mediated through limbic cholinergic structures.


Effects of Combined Estradiol-Sulpiride Treatment and Follicle Ablation on Vernal Transition in Mares: Evaluation of Plasma and Follicular Fluid Hormones and Luteinizing Hormone Receptor Gene Expression.
This experiment assessed the hormonal production, secretory aspects, and changes in luteinizing hormone (LH) receptor gene expression of early induced ovulatory-sized follicles relative to the first ovulatory-sized follicles occurring naturally in the spring. Anovulatory mares were treated on January 21 with (1) 50 mg of estradiol cypionate (ECP, n = 8) alone or (2) with ECP followed by two 3-g sulpiride injections (n = 8), 5 and 12 days later. Half of each group also received complete follicle ablation via transvaginal aspiration before ECP treatment. Ovaries were scanned regularly until detection of a 32-35 mm follicle; follicular fluid was recovered via aspiration for analysis of hormonal concentrations. Blood was collected regularly to characterize plasma prolactin, LH, follicle stimulating hormone, progesterone, and estradiol concentrations. Mean date to first 35-mm follicle was earlier (P < .05) in sulpiride-treated mares: five of eight (63%) responded within 28 days of the first sulpiride injection. Ablation did not affect ovarian response. Plasma prolactin was stimulated (P < .0001) in ECP-sulpiride-treated mares for 16 days but did not dictate ovarian response. Estradiol stimulated plasma LH (P < .05), which was higher (P < .05) in treated mares that responded. There was no effect of treatment or ablation on follicular fluid concentrations of estradiol, progesterone, leptin, or insulin-like growth factor 1 or on LH receptor gene expression. These latter similarities indicate that ECP-sulpiride early induced follicles have apparently reached a degree of maturity equivalent to naturally occurring ovulatory-sized follicles later in the spring.


Stimulation of distinct T cell subsets in MLR using human macrophage hybridomas differentially expressing class II antigens.
Recognition of class II antigens by alloreactive T cells is thought to be the major mechanism by which tissues undergo rejection. However, the specific role of the various class II antigens in the stimulation of these alloreactive cells remains to be elucidated. We have recently generated a series of human monocyte hybridomas that express distinct patterns of class II antigen expression. HLA-DR+ as well as HLA-DR-DP+DQ+ hybrids were capable of promoting T cell proliferation in a unidirectional mixed lymphocyte reaction. T cells stimulated by the HLA-DR+ clone 16.1 were predominantly of the CD4 (helper/inducer) phenotype. In contrast, T cells stimulated by the HLA-DR-DP+DQ+ clone 13 appear to reside in the CD8+ T cell subpopulation. Functional assessment of the T cell blasts generated in these cultures demonstrated a predominant helper T cell effect by those T cells stimulated by the HLA-DR+ clone 16.1, while suppressor cell activity was exhibited by T cells stimulated with the HLA-DR-DP+DQ+ clone 13. These data suggest that there may be a differential role for distinct class II molecules in the stimulation of T cell subpopulations.


Occurrence and influencing factors of antibiotics and antibiotic resistance genes in sediments of the largest multi-habitat lakes in Northern China.
Baiyangdian Lake is a typical and largest multi-habitat lake in the North plain of China. To understand the generation and transmission of antibiotics resistance genes (ARGs) in multi-habitat lakes, the contents of nutrients (TC, TOC, TN, TP and TS), heavy metals (Zn, Cr, Ni, Cu, Pb, As, Cd and Hg), 22 antibiotics, 16S-rRNA(16S), Class I integron (intI1) and 20 ARGs were determined. Samples were taken from the Fuhe river, river estuaries, reed marshes, living area, fish ponds and open water of Baiyangdian Lake. The results showed that quinolones were the main pollutants in six habitats, and the content range was ND-104.94 ng/g. Thereinto, aac (6') -IB, blaTEM-1, ermF, qnrA, qnrD, tetG, sul1, sul2 and tetM were detected in all the analyzed samples. The absolute abundance of sul1 was the highest (5.25 × 105 copies/g-6.21 × 107 copies/g) in most of the samples. In these different habitats, the abundance of antibiotics and ARGs in river estuary was the highest, and that in reed marshes was the lowest. There was a significant positive correlation between the abundance of heavy metals (Cu, Pb, Zn, Ni, Cd, Hg) and the absolute abundance of 11 ARGs (P < 0.01). Redundancy analysis showed that Cu, Zn, intI1, TP and macrolides were the important factors affecting the distribution of ARGs. Our finding provides a more likely driving and influencing factor for the transmission of ARGs in lakes with complex and diverse habitats.


Palbociclib negatively regulates fatty acid synthesis due to upregulation of AMPKα and miR-33a levels to increase apoptosis in Panc-1 and MiaPaCa-2 cells.
Fatty acids (FAs) synthesis mechanism has various regulators such as fatty acid synthase (FASN), AMP-regulated protein kinase (AMPK), or mammalian target of rapamycin (mTOR), which are aberrantly dysregulated in various pancreatic cancer cells. In this study, we aim to understand the regulatory role of palbociclib, a CDK4/6 inhibitor, on the cellular energy metabolism through regulation of AMPK/mTOR signaling by modulation of intracellular miR-33a levels in Panc-1 and MiaPaCa-2 cells. Palbociclib downregulated FAs metabolism more effectively in MiaPaCa-2 cells than Panc-1 cells. Moreover, palbociclib treatment increased the levels of miR-33a in each cell line albeit a higher increase was evident in MiaPaCa-2 cells. Stress-mediated activation of mTOR signaling axis was found associated with palbociclib-mediated AMPKα activation and miR33a upregulation. These findings provided that a deeper understanding about possible interactions of cell cycle activity and reduction of FAs synthesis may facilitate the enhancement of cell death mechanisms in pancreatic cancer cells.


Antibiotic modification of native grafts: improving upon nature's scaffolds.
Infection associated with inert implants is complicated by bacterial biofilm formation that renders the infection antibiotic insensitive. The goal of this investigation was to synthesize and characterize a vancomycin (VAN)-modified bone allograft that could render the tissue inhospitable to bacterial colonization and the establishment of infection. We found that the numbers of primary amines, which could serve as anchors for chemical synthesis, increased with limited demineralization. Using these amines, we coupled two linkers and VAN to bone using Fmoc chemistry. By immunohistochemistry, VAN was abundant on the surface of the allograft; based on elution and measurement of bound antibody, this coupling yielded at least approximately 26 ng VAN/mg bone. The coupled VAN appeared to be permanently bound to the allograft, as it showed no elution in a disk diffusion assay, and, importantly, resisted colonization by Staphylococcus aureus challenges. We suggest that this chimeric construct represents a new generation of antibiotic-modified allografts that provide antibacterial properties.


Selective sensitivity of Caenorhabditis elegans neurons to RNA interference.
RNA interference is a new approach to knockdown gene expression, but effectiveness varies depending on the organism, cell type or target sequence. Studies with Caenorhabditis elegans have shown that subsets of cells including neurons are often resistant to RNA interference. We measured RNA interference using green fluorescent protein reporter strains and feeding, soaking and injection delivery methods in a number of Caenorhabditis elegans neuron subtypes (dopaminergic, GABAergic, cholinergic, glutamatergic, touch). The sensitivity to RNA interference varied: GABAergic and dopaminergic neurons showed greater resistance while cholinergic, glutamatergic and touch neurons were more sensitive. Dysfunctional RRF-3, a putative RNA-directed RNA polymerase, had a significant effect on increasing neuron sensitivity in most subtypes. These results demonstrate that Caenorhabditis elegans neurons vary in their sensitivity to RNA interference.


Glutamate Ionotropic Receptor Kainate Type Subunit 3 (GRIK3) promotes epithelial-mesenchymal transition in breast cancer cells by regulating SPDEF/CDH1 signaling.
Glutamate Ionotropic Receptor Kainate Type Subunit 3 (GRIK3) is an important excitatory neurotransmitter receptor that plays a significant role in various neurodegenerative diseases. However, the biological functions of GRIK3 in malignancies are largely unknown because of limited related studies. Here, we primarily reported that the expression of GRIK3 was higher in breast cancer tissues than in adjacent noncancerous tissues. GRIK3 expression was also positively correlated with the prognosis of patients with breast cancer. GRIK3 promoted the proliferation and migration abilities of breast cancer cells and enhanced the growth of orthotopically implanted tumors. Mechanically, GRIK3 influenced a range of signaling pathways and key signal transducers, including two epithelial-mesenchymal transition regulators, SPDEF and CDH1. Heterogenous expression of SPDEF and CDH1 counteracted the migration and invasion abilities, respectively, of breast cancer cells induced by GRIK3. Moreover, overexpression of GRIK3 increased the expression of mesenchymal markers and decreased the expression of epithelial markers, resulting in the translocation of β-catenin into the nucleus and the increased β-catenin transcriptional activity. In conclusion, the present study reported a novel oncogenic role of GRIK3. Meanwhile, GRIK3, as a membrane receptor, may also serve as a potential therapeutic target for the treatment of breast cancer.


[Use of beta-blockers in the treatment of chronic heart failure].
Recently in the world literature with increasing frequency reports are found on clinical studies investigating the use of beta-blockers in the treatment of chronic heart failure. The authors present a review of the problem comprising pathophysiological mechanisms at a receptor level up to investigations of the effect of beta-blockers on haemodynamics, the functional state of the left ventricle and survival. Although this promising and frequently controversial treatment is not accepted universally so far, partial data in the mentioned investigations indicate that when a more accurate dosage pattern is established and indications are specified in more detail, the use of beta-blockers is one way how to approach - in addition to the use of diuretics, cardiotonics and angiotensin converting enzyme inhibitors - a comprehensive therapeutic control of chronic heart failure.


Nocturia and circadian blood pressure profile in healthy elderly male volunteers.
Nocturia is attributed to nocturnal polyuria and/or decreased functional bladder capacity. In this study we elucidated the mechanisms behind circadian fluid regulation and the occurrence of nocturia in healthy elderly males, specifically to determine the role of urine output and regulating hormones, blood pressure, and average voided volumes. A total of 18 males 55 to 73 years old (mean age 61.1) were included in the study. Voiding habits were assessed by completion of a 7-day frequency volume chart recording all fluid intake and voiding. The subjects subsequently underwent inpatient circadian studies measuring the diurnal rhythm of blood pressure, vasopressin, atrial natriuretic peptide, angiotensin II, aldosterone and urine volume. Of the nightly home recordings 25% showed nocturia, characterized by a higher 24-hour and nighttime urine volume. During the inpatient studies 12 of the 18 participants experienced a nocturnal void. Nocturia nights were characterized by significantly decreased day-to-night ratios in urine output and a higher nighttime mean arterial blood pressure. A circadian variation in plasma arginine vasopressin was seen only in the group without nocturia. The other hormones revealed a circadian rhythm similar in the 2 groups. In healthy males with occasional nocturia, the occurrence of nocturia seems to be associated with a blunting of the circadian rhythm of diuresis and increased arterial blood pressures during the night. These findings may implicate a role for a baroregulatory related mechanism in nocturia.


Iowa Health System takes QI statewide.
Tailoring QI efforts to meet local conditions plays second fiddle at the Iowa Health System. Instead, the focus is on consistent, predictable QI methods that can be replicated statewide. The strategy is paying off.


An Updated Review of Porcine Deltacoronavirus in Terms of Prevalence, Pathogenicity, Pathogenesis and Antiviral Strategy.
The recent experience with SARS-COV-2 has raised our alarm about the cross-species transmissibility of coronaviruses and the emergence of new coronaviruses. Knowledge of this family of viruses needs to be constantly updated. Porcine deltacoronavirus (PDCoV), a newly emerging member of the genus Deltacoronavirus in the family Coronaviridae, is a swine enteropathogen that causes diarrhea in pigs and may lead to death in severe cases. Since PDCoV diarrhea first broke out in the United States in early 2014, PDCoV has been detected in many countries, such as South Korea, Japan and China. More importantly, PDCoV can also infect species other than pigs, and infections have even been reported in children, highlighting its potential for cross-species transmission. A thorough and systematic knowledge of the epidemiology and pathogenesis of PDCoV will not only help us control PDCoV infection, but also enable us to discover the common cellular pathways and key factors of coronaviruses. In this review, we summarize the current knowledge on the prevalence, pathogenicity and infection dynamics, pathogenesis and immune evasion strategies of PDCoV. The existing anti-PDCoV strategies and corresponding mechanisms of PDCoV infection are also introduced, aiming to provide suggestions for the prevention and treatment of PDCoV and zoonotic diseases.


The worldwide market for skilled migrants: can Australia compete?
"The purpose of this article is to...[analyze] the relative importance of internal and external factors on the demand for skilled immigration visas to Australia. Our objectives are to determine how the size of the pool of potential migrants is influenced by factors such as relative economic conditions and U.S. and Canadian immigration policies and to determine what implications these factors have on the relative quality (skill level) of potential migrants to Australia. Our results indicate that the demand for skilled immigration visas to Australia is related to the number of immigrants accepted by the United States and Canada as well as employment possibilities in Australia. We do not find a relationship between U.S. and Canadian policy and the relative quality of the applicant pool."


[Bilateral rupture of the quadriceps tendon].
Simultaneous, bilateral, and spontaneous rupture of the quadriceps tendon is a very rare injury. Individuals with this injury are usually predisposed by chronic renal disease with secondary hyperparathyroidism, gout, diabetes, and lupus erythematosus. Often, primary diagnostic confusion can lead to a delay in treatment. Two cases of a bilateral lesion of the quadriceps tendon, that were treated surgically using the technique of Scuderi, followed by an intense rehabilitation programme, are presented. Surgical treatment yields satisfactory results.


Regulation of Phosphoenolpyruvate Carboxylase from the Green Alga Selenastrum minutum: Properties Associated with Replenishment of Tricarboxylic Acid Cycle Intermediates during Ammonium Assimilation.
Two isoforms of phosphoenolpyruvate carboxylase (PEPC) with very different regulatory properties were partially purified from the green alga Selenastrum minutum. They were designated PEPC(1) and PEPC(2). PEPC(1) showed sigmoidal kinetics with respect to phosphoenolpyruvate (PEP) whereas PEPC(2) exhibited a typical Michaelis-Menten response. The S(0.5)(PEP) of PEPC(1) was 2.23 millimolar. This was fourfold greater than the S(0.5)(PEP) of PEPC(2), which was 0.57 millimolar. PEPC(1) was activated more than fourfold by 2.0 millimolar glutamine and sixfold by 2.0 millimolar dihydroxyacetone phosphate (DHAP) at a subsaturating PEP concentration of 0.625 millimolar. In contrast, PEPC(2) showed only 8% and 52% activation by glutamine and DHAP, respectively. The effects of glutamine and DHAP were additive. PEPC(1) was more sensitive to inhibition by glutamate, 2-oxoglutarate, and aspartate than PEPC(2). Both isoforms were equally inhibited by malate. All of these metabolites affected only the S(0.5)(PEP) not the V(max). The regulatory properties of S. minutum PEPC in vitro are discussed in terms of (a) increased rates of dark carbon fixation (shown to be catalyzed predominantly by PEPC) and (b) changes in metabolite levels in vivo during enhanced NH(4+) assimilation. Finally, a model is proposed for the regulation of PEPC in vivo in relation to its role in replenishing tricarboxylic acid cycle intermediates consumed in NH(4+) assimilation.


β-Ketoenamine-linked covalent organic frameworks capable of pseudocapacitive energy storage.
Two-dimensional covalent organic frameworks (2D COFs) are candidate materials for charge storage devices because of their micro- or mesoporosity, high surface area, and ability to predictably organize redox-active groups. The limited chemical and oxidative stability of established COF linkages, such as boroxines and boronate esters, precludes these applications, and no 2D COF has demonstrated reversible redox behavior. Here we describe a β-ketoenamine-linked 2D COF that exhibits reversible electrochemical processes of its anthraquinone subunits, excellent chemical stability to a strongly acidic electrolyte, and one of the highest surface areas of the imine- or enamine-linked 2D COFs. Electrodes modified with the redox-active COF show higher capacitance than those modified with a similar non-redox-active COF, even after 5000 charge-discharge cycles. These findings demonstrate the promise of using 2D COFs for capacitive storage.


Relationships between home care clients and their workers: implications for quality of care.
In-depth interviews were conducted with 54 home care clients and their home health aides and personal care attendants. The interview data reveal that home care relationships tend to be both formal and informal, in that job responsibilities tend to be diffusely defined and home care workers often become involved in the "backstage" world of their clients. The study also suggests, however, that personal bonds may be problematic for both workers and clients. For workers there is the risk of exploitation; for clients, there is the potential for loss of control over their own care. The quality of relationships also affects quality of care.


Hippocampal T cell infiltration promotes neuroinflammation and cognitive decline in a mouse model of tauopathy.
Alzheimer's disease is characterized by the combined presence of amyloid plaques and tau pathology, the latter being correlated with the progression of clinical symptoms. Neuroinflammatory changes are thought to be major contributors to Alzheimer's disease pathophysiology, even if their precise role still remains largely debated. Notably, to what extent immune responses contribute to cognitive impairments promoted by tau pathology remains poorly understood. To address this question, we took advantage of the THY-Tau22 mouse model that progressively develops hippocampal tau pathology paralleling cognitive deficits and reappraised the interrelationship between tau pathology and brain immune responses. In addition to conventional astroglial and microglial responses, we identified a CD8-positive T cell infiltration in the hippocampus of tau transgenic mice associated with an early chemokine response, notably involving CCL3. Interestingly, CD8-positive lymphocyte infiltration was also observed in the cortex of patients exhibiting frontemporal dementia with P301L tau mutation. To gain insights into the functional involvement of T cell infiltration in the pathophysiological development of tauopathy in THY-Tau22 mice, we chronically depleted T cells using anti-CD3 antibody. Such anti-CD3 treatment prevented hippocampal T cell infiltration in tau transgenic animals and reverted spatial memory deficits, in absence of tau pathology modulation. Altogether, these data support an instrumental role of hippocampal T cell infiltration in tau-driven pathophysiology and cognitive impairments in Alzheimer's disease and other tauopathies.


Primary gastrointestinal lymphoma.
Extranodal lymphoma may arise anywhere outside lymph nodes mostly in the gastrointestinal (GI) tract as non-Hodgkin's disease. We reviewed the clinicopathological features and treatment results of patients with primary GI lymphoma. A total number of 30 cases with primary GI lymphoma were included in this study. Patients referred to the Radiation Oncology Department of Omid Hospital (Mashhad, Iran) during a 5-year period (2006-11). Clinical, paraclinical, and radiological data was collected from medical records of the patients. Out of the 30 patients with primary GI lymphoma in the study, 12 were female (40%) and 18 were male (60%) (male to female ratio: 3/2). B symptoms were present in 27 patients (90%). Antidiuretic hormone (LDH) levels were elevated in 9 patients (32.1%). The most common primary site was stomach in 14 cases (46.7%). Other common sites included small intestine and colon each in 8 patients (26.7%). All patients had histopathologically proven non-Hodgkin's lymphoma. The most common histologic subtype was diffuse large B-cell lymphoma (DLBL) in 16 patients (53.3%). In addition, 28 patients (93.3%) received chemotherapy with cyclophosphamide, vincristine, doxorubicin, prednisolone (CHOP regimen). The median course of chemotherapy was 6 cources. Moreover, 8 patients (26.7%) received radiotherapy with cobalt 60. The median follow-up time was 26 months. The overall 5-year survival rate was 53% and the median survival time was 60 months. Primary GI lymphoma is commonly seen in stomach and small intestine and mostly is DLBCL or mucosa-associated lymphoid tissue (MALT) lymphoma.


CSF1R signaling is a regulator of pathogenesis in progressive MS.
Microglia serve as the innate immune cells of the central nervous system (CNS) by providing continuous surveillance of the CNS microenvironment and initiating defense mechanisms to protect CNS tissue. Upon injury, microglia transition into an activated state altering their transcriptional profile, transforming their morphology, and producing pro-inflammatory cytokines. These activated microglia initially serve a beneficial role, but their continued activation drives neuroinflammation and neurodegeneration. Multiple sclerosis (MS) is a chronic, inflammatory, demyelinating disease of the CNS, and activated microglia and macrophages play a significant role in mediating disease pathophysiology and progression. Colony-stimulating factor-1 receptor (CSF1R) and its ligand CSF1 are elevated in CNS tissue derived from MS patients. We performed a large-scale RNA-sequencing experiment and identified CSF1R as a key node of disease progression in a mouse model of progressive MS. We hypothesized that modulating microglia and infiltrating macrophages through the inhibition of CSF1R will attenuate deleterious CNS inflammation and reduce subsequent demyelination and neurodegeneration. To test this hypothesis, we generated a novel potent and selective small-molecule CSF1R inhibitor (sCSF1Rinh) for preclinical testing. sCSF1Rinh blocked receptor phosphorylation and downstream signaling in both microglia and macrophages and altered cellular functions including proliferation, survival, and cytokine production. In vivo, CSF1R inhibition with sCSF1Rinh attenuated neuroinflammation and reduced microglial proliferation in a murine acute LPS model. Furthermore, the sCSF1Rinh attenuated a disease-associated microglial phenotype and blocked both axonal damage and neurological impairments in an experimental autoimmune encephalomyelitis (EAE) model of MS. While previous studies have focused on microglial depletion following CSF1R inhibition, our data clearly show that signaling downstream of this receptor can be beneficially modulated in the context of CNS injury. Together, these data suggest that CSF1R inhibition can reduce deleterious microglial proliferation and modulate microglial phenotypes during neuroinflammatory pathogenesis, particularly in progressive MS.


Sterically Hindered Ketones via Palladium-Catalyzed Suzuki-Miyaura Cross-Coupling of Amides by N-C(O) Activation.
Herein, we report a new protocol for the synthesis of sterically hindered ketones that proceeds via palladium-catalyzed Suzuki-Miyaura cross-coupling of unconventional amide electrophiles by selective N-C(O) activation. Mechanistic studies demonstrate that steric bulk on the amide has a major impact, which is opposite to the traditional Suzuki-Miyaura cross-coupling of sterically hindered aryl halides. Structural and computational studies provide insight into ground-state distortion of sterically hindered amides and show that ortho-substitution alleviates the N-C(O) bond twist.


[Differences of clinical manifestations from cytomegalovirus infection in children of various age groups].
Newborns have been the focus group for most studies of cytomegalovirus infection. The objective of the study is to share some preliminary analysis on clinical manifestation differences resulting from cytomegalovirus infection in children of various age groups. The clinical data of 108 children with cytomegalovirus infection were retrospectively reviewed. The children were classified into three age groups: <6 months, 6-12 months and >12 months. The differences in clinical manifestations from cytomegalovirus infection among the three age groups were identified. Each age group carried distinctive differences in the occurrence of hepatic damage, jaundice, pneumonia, and hematological manifestations, as well as incidence rate of malformation (p<0.05 or 0.01). The primary clinical manifestations of group<6 months old were hepatic damage(83%), pneumonia(47%) and jaundice (43%). There was a similar proportion of anicteric-hepatitis and icteric-hepatitis; however a low incidence rate of hematological disease (6%) was found in group<6 months old. The primary clinical manifestations of group 6-12 months old were hepatic damage (86%), mostly with no presence of jaundice, pneumonia (33%), and hematological disease (20%). Hepatic damage (52%) and hematological disease (33%) were leading clinical symptoms in group>12 months old where jaundice and pneumonia were rare events. End-organ damage triggered by cytomegalovirus infection is related to the age of the affected children closely.


Protecting rare, old-growth, forest-associated species under the Survey and Manage Program guidelines of the Northwest Forest Plan.
The Survey and Manage Program of the Northwest Forest Plan (NWFP) represents an unparalleled attempt to protect rare, little-known species associated with late-successional and old-growth forests on more than 9.7 million ha of federal lands. Approximately 400 species of amphibians, bryophytes, fungi, lichens, mollusks, vascular plants, arthropod functional groups, and one mammal were listed under this program because viability evaluations indicated the plan's network of reserve land allocations might not sustain the species over time. The program's standards and guidelines used an adaptive approach, protecting known sites and collecting new information to address concerns for species persistence and to develop management strategies. Since implementation in 1994, approximately 68,000 known sites have been recorded at an expense of several tens of millions of dollars. New knowledge from surveys reduced concern for nearly 100 species, and they were removed from the protection list. Although successful in protecting hundreds of rare species not typically considered in most conservation programs, some of the enacted conservation measures created conflicts in meeting other management objectives of the plan, particularly timber harvest. The program accrued important gains in knowledge, reduced uncertainty about conservation of a number of species, and developed new methods of species inventory that will be useful in future management planning and implementation at many scales. The program, however was not completed because of changes in land-management philosophy. Ongoing litigation regarding its termination and potential changes to the plan cast further uncertainty on how the original goal of maintaining persistence of late-successional and old-growth species will be met and measured. The outcomes, controversies, and management frustrations of the program exemplify the inherent difficulties in balancing broad, regional conservation goals with social and economic goals of the NWFP Defining acceptable trade-offs to reach that balance and developing practical conservation solutions remain challenges for the science and management communities. Lessons learned from the program provide a valuable biological and managerial reference to benefit future discussion on meeting those challenges.


Scanning electron microscopy of normal, neoplastic and inflamed human bladder.
Scanning electron microscopy (SEM) was used to compare the topographic fine structure of urothelium from normal, neoplastic and inflamed human bladders. The three groups of patients show different patterns. The normal bladder lining is characterized by regularly arranged large superficial cells with ridged surfaces. By contrast, the surface cells of a transitional cell carcinoma are rounded up and covered with microvilli. In some patients with cystitis or post inflammatory hyperplasia SEM appearances intermediate between normal and neoplastic patterns are encountered. However, except in extremely severe cystitis it is possible on SEM to differentiate between inflamed and neoplastic urothelium. Surface microvilli provide a useful malignant marker for transitional cell carcinoma. However, severe inflammation of the bladder, when diagnosed on cystoscopic examination, can and must be excluded by light microscopy before this marker is considered diagnostic for neoplasia.


Protein folding in high-dimensional spaces: hypergutters and the role of nonnative interactions.
We explore the consequences of very high dimensionality in the dynamical landscape of protein folding. Consideration of both typical range of stabilizing interactions, and folding rates themselves, leads to a model of the energy hypersurface that is characterized by the structure of diffusive "hypergutters" as well as the familiar "funnels". Several general predictions result: 1), intermediate subspaces of configurations will always be visited; 2), specific but nonnative interactions may be important in stabilizing these low-dimensional diffusive searches on the folding pathway, as well as native interactions; 3), sequential barriers will commonly be found, even in "two-state" proteins; 4), very early times will show characteristic departures from single-exponential kinetics; and 5), contributions of nonnative interactions to Phi-values and "Chevron plots" are calculable, and may be significant. The example of a three-helix bundle is treated in more detail as an illustration. The model also shows that high-dimensional structures provide conceptual relations between different models of protein folding. It suggests that kinetic strategies for fast folding may be encoded rather generally in nonnative as well as in native interactions. The predictions are related to very recent findings in experiment and simulation.


Investigating Risk of Suboptimal Macro and Micronutrient Intake and Their Determinants in Older Danish Adults with Specific Focus on Protein Intake-A Cross-Sectional Study.
Suboptimal intake of nutrients is associated with adverse health outcomes. The current study investigated the risk of suboptimal macro and micronutrient intake and their potential determinants in a cross-sectional study of community-dwelling older Danish adults (65⁻81 years). Nutrient intake was obtained through a 3-day weighted dietary record and information on personal characteristics and attitudes towards specific foods and dietary habits and nutrition through questionnaires. Dietary Reference Values (DRV) from the Nordic Nutrition Recommendations were used for the assessment. Among 157 participants, 68% and 66% had risk of suboptimal intake of dietary fiber and saturated fatty acids (SFA). For mono-unsaturated fatty acids (MUFA) and poly-unsaturated fatty acids (PUFA), the numbers were 47% and 62%, respectively. Increased risk of suboptimal protein intake was estimated in 3 to 45% of the participants, depending on the criteria used for the DRV and of the mode of expressing protein intake. Fifty percent had intakes of alcohol above the maximum recommended intake. Risk of micronutrient inadequacy was particularly high for vitamin D and thiamine (80 and 45%, respectively). Total energy intake and attitude regarding healthy eating were associated with lower nutrient intake. The current study illustrates that there is room for improvements in the dietary quality of community dwelling older Danish adults.


Basic Fibroblast Growth Factor in Scarless Wound Healing.
The benefit and role of basic fibroblast growth factor (bFGF) in scarless wound healing in clinical application and basic mechanism are discussed. bFGF is a glycoprotein which is widely used in treating wounds and ulcers. bFGF is easily applicable to any type of wound and leads to a better outcome in color, texture, and firmness. The amniotic fluids from human mid-gestational trimester may play an important role in scarless wound healing. To investigate cell properties, we used amniotic fluid to augment both adult and fetal fibroblast mitogenic activities, including DNA synthesis and cell proliferation. Preincubation by both bFGF receptor blocker and anti-bFGF antibody significantly decreases proliferative activity in both adult and fetal skin fibroblasts. Adult wound healing, to some extent, demonstrates scar formation, leading to unfavorable clinical mismatch of tissue texture and color and causing stiffness. bFGF may improve the outcome of wound healing by normalizing the tissue texture and color to the adjacent intact skin and optimally enhancing wound healing. bFGF activates ERK and Akt phosphorylation in a dose-dependent manner in both adult and fetal skin fibroblasts, which suggests that bFGF in amniotic fluid plays the most major role in cell proliferation. Application of bFGF from an early wounding stage may lead to better fibroblast proliferation and DNA synthesis through the process of ERK/Akt phosphorylation.


Copper(I)-catalysed intramolecular hydroarylation-redox cross-dehydrogenative coupling of N-propargylanilines with phosphites.
Intramolecular hydroarylation-redox cross-dehydrogenative coupling of N-propargylanilines with phosphite diesters proceeded in the presence of Cu(I)-catalysts (20 mol%) to selectively give 2-phosphono-1,2,3,4-tetrahydroquinolines in good yields with 100% atomic utilization. P-H and two C-H bonds are activated at once and these hydrogen atoms are trapped by a propargylic triple bond in the molecule.


The effect of family history of hypertension and polymorphism of the ACE gene (rs1799752) on cardiac autonomic modulation in adolescents.
This study aims to analyze the behaviour of cardiac autonomic modulation in adolescents with a family history of hypertension along with polymorphism of the ACE gene (rs1799752). The study involved 141 adolescents, with a mean age of 14.89, divided into the following six groups: offspring of normotensive parents (ONP): DD, DI and II; and offspring of hypertensive parents (OHP): DD, DI and II. Blood pressure, body composition, family history of hypertension, sleep disorder, and sexual maturation were assessed for the groups' characterization. Afterwards, an electrocardiogram was performed, and oral mucosal cells were collected to analyze heart rate variability and genotypic research of angiotensin-converting enzyme. The main finding of this study was the decrease of vagal action in group OHP (genotype DD) relative to group ONP (genotype II): LF (%), 54.25 ± 3.14 vs 39.33 ± 3.80; HF (%), 45.74 ± 3.14 vs 60.66 ± 3.80; LF/HF, 1.48 ± 0.23 vs 0.68 ± 0.19. The results also showed changes in the variable diastolic blood pressure (DBP) in OHP (genotype DI) to ONP (genotype II) groups: 72.99 ± 2.33 vs 63.27 ± 1.72; and OHP (genotype DI) to ONP (genotype DD) groups. Adolescents with genotype DD and a family history of arterial hypertension present chances in cardiac autonomic modulation, the cardiac parasympathetic modulation is lower in these adolescents in comparison to participants of ONP + II group.


Outcome and treatment of bucillamine-induced nephropathy.
Bucillamine (BCL), a treatment for rheumatoid arthritis, occasionally causes proteinuria. Renal specimens are reported to show segmental granular deposition of immunoglobulin G, associated with membranous nephropathy. Long-term course and optimal treatment have remained unknown, and were investigated here. We examined clinical records of 400 patients treated with BCL for rheumatoid arthritis, at our hospital from 1998 to 2003, finding 17 with proteinuria and biopsy-proven BCL-induced nephropathy. In all 17 patients, proteinuria resolved without loss of renal function between 3 and 85 months after discontinuing BCL (14.1 +/- 3.4). The only factor influencing time to remission was pathologic stage of membranous nephropathy (stage I vs. stage II or III: 11.5 +/- 4.8 vs. 21.6 +/- 3.3 months; p = 0.02). Maximal proteinuria, total amount of BCL, BCL exposure time, and use of prednisolone or other immunosuppressant agents did not significantly influence time until remission. The most important therapeutic step in treating BCL-induced nephropathy is to discontinue BCL. Prednisolone or other immunosuppressant agents might not be effective.


[Preparation and in vitro evaluation of quercetin nanosuspension stabilized by gypenosides].
This study was designed to explore the potential of gypenosides as a novel natural stabilizer for the production of nanosuspensions. The gypenosides-stabilized quercetin nanosuspensions(QUE-NS) were prepared using the high-speed shearing and high-pressure homogenization method with quercetin as a model drug, followed by their in vitro evaluation.Based on the measured mean particle size and polydispersity index(PDI) of QUE-NS,the single factor experiment was conducted to optimize the preparation process parameters.The freeze-drying method was used to transform QUE-NS into freeze-dried powders, whose storage stability and saturation solubility were then studied.Moreover, the effects of pH and ionic strength on the physical stability of the nanosuspension system were examined.According to the results, the optimized process parameters were listed as follows: shear rate 13 000 r·min~(-1),shear time 2 min, homogenization pressure 100 MPa, and homogenization frequency 12 times.The mean particle size of QUE-NS prepared under the optimum process conditions was(461.9±2.4) nm, and the PDI was 0.059±0.016.During the two months of storage at room temperature, the freeze-dried QUE-NS powders remained stable.The saturation solubility of freeze-dried QUE-NS powders was proved higher than those of quercetin and the physical mixture.The results of stability testing demonstrated that QUE-NS stabilized with gypenosides exhibited good stability within the pH range of 6 to 8,while coalescence was prone to occur in the presence of salt.Overall, gypenosides is expected to become a new natural stabilizer for the preparation of nanosuspensions.


Central and peripheral self-conceptions are differentially influenced by mood: tests of the differential sensitivity hypothesis.
This article proposes a differential sensitivity hypothesis, according to which central (i.e., relatively high in personal descriptiveness and importance) and peripheral (i.e., relatively low in personal descriptiveness and importance) self-conceptions are differentially influenced by mood: Peripheral self-conceptions are subject to a mood-congruency bias, whereas central self-conceptions are unaffected by mood. In 4 experiments, participants were first placed into a sad, neutral, or happy mood state through a guided imagery task and later completed behavior self-descriptiveness ratings, trait self-descriptiveness ratings, and trait self-descriptiveness judgmental latencies. Strong support for the differential sensitivity hypothesis was obtained. Peripheral self-conceptions were influenced by mood because they were less elaborated and consolidated and were held with lower certainty, thus increasing the likelihood for the occurrence of constructive, affect-infusing processes (J.P. Forgas, 1995a).


Doppler velocimeter using diffraction grating and white light.
A Doppler velocimeter using a diffraction grating and white light is proposed. Using the theory of Fourier optics and fringe model, the principle of operation of this Doppler velocimeter, its performance, and advantages over other arrangements are discussed.


SARS-CoV-2 antibodies protect against reinfection for at least 6 months in a multicentre seroepidemiological workplace cohort.
Identifying the potential for SARS-CoV-2 reinfection is crucial for understanding possible long-term epidemic dynamics. We analysed longitudinal PCR and serological testing data from a prospective cohort of 4,411 United States employees in 4 states between April 2020 and February 2021. We conducted a multivariable logistic regression investigating the association between baseline serological status and subsequent PCR test result in order to calculate an odds ratio for reinfection. We estimated an odds ratio for reinfection ranging from 0.14 (95% CI: 0.019 to 0.63) to 0.28 (95% CI: 0.05 to 1.1), implying that the presence of SARS-CoV-2 antibodies at baseline is associated with around 72% to 86% reduced odds of a subsequent PCR positive test based on our point estimates. This suggests that primary infection with SARS-CoV-2 provides protection against reinfection in the majority of individuals, at least over a 6-month time period. We also highlight 2 major sources of bias and uncertainty to be considered when estimating the relative risk of reinfection, confounders and the choice of baseline time point, and show how to account for both in reinfection analysis.


Impact of sleep-disordered breathing on myocardial salvage and infarct size in patients with acute myocardial infarction.
Sleep-disordered breathing (SDB) may be a risk factor for expansion of infarct size early after acute myocardial infarction (MI) by exposing the heart to repetitive oxygen desaturations and increased cardiac afterload. The objective of this study was to assess the impact of SDB on myocardial salvage and infarct size within 3 months after acute MI. Patients with acute MI and percutaneous coronary intervention were enrolled in this prospective observational study. All patients underwent cardiovascular magnetic resonance (CMR) to define salvaged myocardium and infarct size within three to five days and at 3 months after acute MI. Patients were stratified according to apnoea-hypopnoea index (AHI) assessed by polysomnography at baseline into those with (AHI ≥ 15/h) and without (AHI < 15/h) SDB. Of the 56 patients included, 29 (52%) had SDB. The area at risk between both groups was similar (40 ± 12% vs. 40 ± 14%, P = 0.925). Patients with SDB had significantly less salvaged myocardium (myocardial salvage index 52% vs. 77%, P < 0.001), smaller reduction in infarct size (0.3% vs. 6.5%, P < 0.001) within 3 months after acute MI, a larger final infarct size (23% vs. 12%, P < 0.001), and a lower final left ventricular ejection fraction (48% vs. 54%, P = 0.023). In a multivariate analysis, including established risk factors for large MI, AHI was independently associated with less myocardial salvage and a larger infarct size 3 months after acute MI. Sleep-disordered breathing was associated with less myocardial salvage and a smaller reduction in infarct size. These findings suggest a contribution of SDB to impaired healing of MI.


Nurses in the workplace: expectations and needs.
It is important to understand nurses' attitudes toward their work environment. Prior studies in this area have been conducted. The interest was to identify a relative assessment of workplace challenges by studying nurses within developed and developing economies. A representative survey of 2203 nurses in 11 countries was conducted via a structured survey. Data from open-ended questions were content analysed and grouped thematically. The overall margin of error is +/-2.1% and +/-6.9% for country level results. Key findings included that 92% of nurses say they face time constraints and 96% say that spending more time with individual patients would have a significant impact on patient health. Forty-six per cent of nurses say their workload is worse today than it was 5 years ago. While only 53% of nurses say it is very likely they will be practising nursing in 5 years, national differences existed. Statistically significant parameters influencing the likelihood to stay in nursing included having greater independence and control over their practice area, sufficient staff, greater involvement in decisions impacting their work and patient care, and improved work-life balance. There is agreement across the surveyed countries regarding the existence of high workloads that are contributing to time constraints and the belief that patient outcomes are significantly impacted. These conditions contribute to nurses' lack of firm commitment to their profession. The systemic changes required to deliver quality health care to patients require these challenges to be addressed.


Kinematics of the prominentia laryngea at phonation onset.
The present paper deals with the problem of the temporal relations between the beginning of the glottal opening at phonation onset and the thyroid cartilage kinematics at the prominentia laryngea. Furthermore, some differences in comparison with a stationary phonation event are discussed here.


Evaluation of models for the low temperature combustion of alkanes through interpretation of pressure-temperature ignition diagrams.
The purpose of this paper is to show the application of global uncertainty analysis to comprehensive and reduced kinetic models as a tool to identify important thermochemical and reaction rate parameters as determinants of the conditions leading to autoignition. Propane oxidation is taken as the test case. The simulation of experimental investigations of the cool flames and two-stage ignitions, via the pressure-temperature ignition diagram, show that existing kinetic models for the low temperature combustion of propane at sub-atmospheric pressures reflect a greater reactivity than seems to be appropriate. That is, the models lead to a prediction of two-stage ignition at pressures somewhat lower and with ignition delays shorter than is found experimentally. The inconsistency between experiment and numerical simulation seems not to be an inherent problem of the qualitative structure of the models, but may derive from uncertainties in the parameters within the mechanism. By use of "brute force", Morris-one-at-a-time and Monte-Carlo simulations, we show that uncertainties in only a small number of parameters, and falling well within the errors that may reasonably be assigned, can shift the response appropriately. Moreover, it appears that in the low temperature combustion regime, thermochemistry is at least as, if not more, important than the reaction rates, yet usually receives less attention within sensitivity studies. In the present case, the main factors controlling the temperature reached in the first stage of two-stage ignition and the time to ignition appear to be connected with the thermochemistry of three specific hydroperoxyalkyl radicals and their derivatives. Other factors, such as heat and mass transport are also addressed, and their effects are mitigated to some extent by evaluation of initial and revised models against experimental data for ignition delay obtained under microgravity. The results highlight more general issues that pertain to the numerical simulation of the combustion of higher hydrocarbons and contribute to the development of the protocol necessary for testing kinetic models before they are ready for use in a predictive capacity.


Using mathematical modelling to help explain the differential increase in HIV incidence in New South Wales, Victoria and Queensland: importance of other sexually transmissible infections.
Since 1999 there has been an increase in the number of HIV diagnoses in Australia, predominantly among men who have sex with men (MSM), but the magnitude of increase differs between states: approximately 7% rise in New South Wales, approximately 96% rise in Victoria, and approximately 68% rise in Queensland. Epidemiological, clinical, behavioural and biological data were collated into a mechanistic mathematical model to explore possible reasons for this increase in HIV notifications in MSM. The model was then used to make projections to 2015 under various scenarios. The model suggests that trends in clinical and behavioural parameters, including increases in unprotected anal intercourse, cannot explain the magnitude of the observed rise in HIV notifications, without a substantial increase in a 'transmission-increasing' factor. We suggest that a highly plausible biological factor is an increase in the prevalence of other sexually transmissible infections (STI). It was found that New South Wales required an approximately 2-fold increase in other STI to match the data, Victoria needed an ~11-fold increase, and Queensland required an approximately 9-fold increase. This is consistent with observed trends in Australia for some STI in recent years. Future projections also indicate that the best way to control the current rise in HIV notifications is to reduce the prevalence of other STI and to promote condom use, testing for HIV, and initiation of early treatment in MSM diagnosed during primary infection. Our model can explain the recent rise in HIV notifications with an increase in the prevalence of other STI. This analysis highlights that further investigation into the causes and impact of other STI is warranted in Australia, particularly in Victoria.


High-resolution monitoring of the gastrointestinal transit of a magnetically marked capsule.
The purpose of this study was to demonstrate that it is possible to continuously monitor the gastrointestinal transit of magnetically marked, solid, oral dosage forms with multichannel biomagnetic measuring equipment and by magnetic source imaging (MSI) methods. For the investigations presented, a sucrose pellet was coated with powdered magnetite (Fe3O4) in poly(methyl methacrylate). Then, the pellet was enclosed in a capsule prepared from silicone rubber and magnetized to obtain a net magnetic dipole moment. After ingestion of the capsule, its magnetic field distribution over the abdomen was recorded for several time intervals with a 37-channel superconducting quantum interference device (SQUID) magnetometer. At each time point, the position of the capsule within the gastrointestinal tract was calculated from the measured field distribution, assuming a magnetic dipole model. The data presented here demonstrate that with this noninvasive method of magnetic marker monitoring it is possible to investigate the gastrointestinal transit of a solid oral dosage form with a temporal resolution in the order of milliseconds and a spatial resolution within a range of millimeters.


Apoptosis and diseases: regulation and clinical relevance.
It is increasingly clear that apoptosis plays a central role in the pathogenesis of several human diseases. For instance, an increase in apoptosis leads to cell loss accompanied by neurodegenerative diseases, whereas we know that genetically determined defects of apoptosis result in deregulated cell proliferation, typical of cancer. Hence, apoptosis may be relevant as therapeutic targets for many human diseases. This article reviews briefly the regulation and the clinical relevance of apoptotic mechanisms in several different human diseases.


Using gas lasers in road works.
Descriptions of two devices using unique properties of gas lasers are given: an automatic elevation guidance system and an apparatus for measuring plane defects, both applied to road making or road control.


Effect of an invasive and native ant on a field population of the black citrus aphid (Hemiptera: Aphididae).
Invasive ants often enter into facultative mutualisms that frequently lead to outbreaks of the hemipteran partner. Native ants may also enter into similar mutualisms but often these do not lead to outbreaks. However, field studies comparing the impact of an invasive and native ant on a honeydew-producing hemipteran are lacking. We monitored numerical changes of the black citrus aphid, Toxoptera aurantii, tended by adjacent colonies of the invasive Argentine ant, Linepithema humile, and the endemic odorous house ant, Tapinoma sessile, during 2005, 2006, and 2007. Ant-tended aphid numbers were higher than those of untended aphids, with L. humile-tended and T. sessile-tended T. aurantii populations being comparable in 2005 and 2007. However, in 2006, a severe storm, with heavy rainfall, reduced T. sessile and aphid populations in areas occupied by T. sessile, whereas L. humile and aphids tended by L. humile were not reduced. This suggested that T. sessile foraging activity and hemipteran-tending was negatively impacted by severe weather. A laboratory experiment simulating rainfall striking the surface of a leaf showed that T. sessile foraging activity declined sharply under severe simulated rainfall conditions, whereas foraging activity of L. humile did not. Maintaining populations of honeydew-producing Hemiptera across broad climatic conditions may be one mechanism by which L. humile gains a competitive advantage over native ants occupying overlapping niches.


[Effect of imunofan on several indexes of immunity and pyoderma incidence among cadets of educational institutes].
It was discovered that during the first several months military service men have suppression of several indexes of immunity and a high level of morbidity by pyoderma. Was shown a high effectiveness of immunomodulatory agent Imunofan on correction of immunity status of servicemen and decrease of morbidity by pyoderma (more than on threefold): the effectiveness index is 3,25, the defense index is 69,2%. In addition, it was marked hepatitis- and stress-protect effect of the agent. It was made a conclusion about necessity of further examination of questions of correction of immunity status of military servicemen for the purpose of decrease of morbidity by infections, actual for studying units of the Armed Forces of RF.


Sabutoclax (BI97C1) and BI112D1, putative inhibitors of MCL-1, induce mitochondrial fragmentation either upstream of or independent of apoptosis.
Owing to the high levels of antiapoptotic B-cell lymphoma 2 (BCL-2) family members observed in several cancers, there has been a major effort to develop inhibitors of the BCL2-family as chemotherapeutic agents. Of the different members in the BCL-2 family, myeloid cell leukemia sequence 1 (MCL-1) is commonly amplified in human tumors and is associated with their relapse and chemoresistance. As a result, specific inhibitors of MCL-1 are being designed to treat resistant tumors. However, there is increasing evidence for other nonapoptotic roles of the BCL-2 family, ranging from ionic homeostasis and autophagy to the regulation of fission-fusion dynamics in subcellular organelles, including the endoplasmic reticulum and mitochondria. In this study, we characterize the specificity of two novel putative MCL-1 inhibitors, BI97C1 (Sabutoclax) and BI112D1, in inducing apoptosis in a BAX/BAK-dependent manner and in an MCL-1-dependent system. In addition to their being proapoptotic, these inhibitors also cause enhanced mitochondrial fragmentation that accompanies a time-dependent loss of optic atrophy 1 (OPA1), suggesting an impairment of mitochondrial fusion. This mitochondrial fragmentation occurs independently of dynamin-related protein 1 (DRP1)-mediated fission activity and, unlike most apoptotic stimuli, occurs upstream of and/or independent of BAX, BAK, and other BH3-only proteins. Furthermore, this mitochondrial fragmentation occurred rapidly and preceded other hallmarks of apoptosis, including the loss in mitochondrial membrane potential and the release of cytochrome c. Although such mitochondrial fragmentation did not deplete total cellular adenosine triphosphate (ATP) or alter other mitochondrial complexes, there was significant accumulation of reactive oxygen species.


Flux-Assisted Synthesis of Y2 Ti2 O5 S2 for Photocatalytic Hydrogen and Oxygen Evolution Reactions.
Photocatalytic water splitting is an ideal means of producing hydrogen in a sustainable manner, and developing highly efficient photocatalysts is a vital aspect of realizing this process. The photocatalyst Y2 Ti2 O5 S2 (YTOS) is capable of absorbing at wavelengths up to 650 nm and exhibits outstanding thermal and chemical durability compared with other oxysulfides. However, the photocatalytic performance of YTOS synthesized using the conventional solid-state reaction (SSR) process is limited owing to the large particle sizes and structural defects associated with this synthetic method. Herein, we report the synthesis of YTOS particles by a flux-assisted technique. The enhanced mass transfer efficiency in the flux significantly reduced the preparation time compared with the SSR method. In addition, the resulting YTOS showed improved photocatalytic H2 and O2 evolution activity when loaded with Rh and Co3 O4 co-catalysts, respectively. These improvements are attributed to the reduced particle size and enhanced crystallinity of the material as well as the slower decay of photogenerated carriers on a nanosecond to sub-microsecond time range. Further optimization of this flux-assisted method together with suitable surface modification is expected to produce high-quality YTOS crystals with superior photocatalytic activity.


Chronic Pain and Quality of Life in Maintenance Hemodialysis Patients in China: A Multicenter, Cross-Sectional Study.
Patients undergoing maintenance hemodialysis (MHD) frequently experience chronic pain, which can severely affect their quality of life (QOL). The objective of this study was to evaluate the prevalence of chronic pain in MHD patients and examine the factors associated with QOL. A cross-sectional questionnaire-based survey was conducted between October 2020 and April 2021, 1204 MHD patients from nine hemodialysis units were screened for chronic pain in Chengdu, China, and 296 MHD patients with chronic pain were enrolled in this study. We analyzed data on clinicodemographic characteristics, pain interference and severity (Brief Pain Inventory), QOL (Medical Outcomes Study 36-item Short Form Health Survey - mental component summary [MCS] and physical component summary [PCS]), pain self-efficacy (Pain Self-Efficacy Questionnaire), and social support (Social Support Rating Scale). The prevalence of chronic pain in MHD patients was 26.74% in this study. The most common areas of pain were lower back (63.5%), lower limbs (55.0%), and head (33.5%), 36.5% did not implement any measures to relieve it. Of the patients who did receive pain treatment or medication, 56.9% reported that the measures they took had less than half of the pain relief. MHD patients with chronic pain had poor QOL based on scores on the MCS (53 ± 16.76) and PCS (40.56 ± 13.81). Stepwise multiple regression identified age, financial strain, pain interference, social support, and pain self-efficacy as independent predictors of QOL. Pain self-efficacy was significantly associated with social support (r = 0.5, p < 0.01), MCS (r = 0.69, p < 0.01), and PCS (r = 0.8, p < 0.01). The mediating effects of pain self-efficacy were 70.31% on the relationship between social support and MCS, and 75.62% on the relationship between social support and PCS. Chronic pain is prevalent and undermanaged in Chinese MHD patients, resulting in worse QOL. Healthcare providers should focus on pain management and the impact of psychosocial factors on patient QOL. Further research should deepen our understanding of how pain self-efficacy mediates the relationship between social support and QOL.


Uranium microdistribution in renal cortex of rats after chronic exposure: a study by secondary ion mass spectrometry microscopy.
For a few years, the biological effects on ecosystems and the public of the bioaccumulation of radionuclides in situations of chronic exposures have been studied. This work, in keeping with the ENVIRHOM French research program, presents the uranium microdistribution by secondary ion mass spectrometry (SIMS) technique in the renal cortex of rats following chronic exposure to this low level element in the drinking water (40 mg/L) as a function to exposure duration (6, 9, 12, and 18 months). The SIMS mass spectra and 238U+ ion images produced with a SIMS CAMECA 4F-E7 show the kinetic of uranium accumulation in the different structures of the kidney. For the rats contaminated up to 12 months, the radioelement is mainly fixed in the proximal tubules; then after 18 exposure months, uranium is detected in all the segments of the nephron. This work has also shown that ion microscopy is an analytical method to detect trace elements and give elemental cartography at the micrometer scale.


Preservice teacher attitudes toward gay and lesbian parents.
Gay and lesbian parents are raising an increasing number of children, but little is known about how these parents are viewed by school personnel. In this study, preservice teacher attitudes toward gay and lesbian parents were assessed using implicit, explicit, behavioral, and behavioroid measures. Implicit measures indicate that participants rated same-gender targets more negatively than they rated heterosexual targets, and they rated targets of gay men more negatively than they rated lesbians; however, response patterns varied by participant sex. Furthermore, implicit measures of sexual prejudice generally correlated with explicit and behavioroid measures. The implications of these findings are discussed.


Hundred-watt-level high power random distributed feedback Raman fiber laser at 1150 nm and its application in mid-infrared laser generation.
Two kinds of hundred-watt-level random distributed feedback Raman fiber have been demonstrated. The optical efficiency can reach to as high as 84.8%. The reported power and efficiency of the random laser is the highest one as we know. We have also demonstrated that the developed random laser can be further used to pump a Ho-doped fiber laser for mid-infrared laser generation. Finally, 23 W 2050 nm laser is achieved. The presented laser can obtain high power output efficiently and conveniently and opens a new direction for high power laser sources at designed wavelength.


Dynamic Contrast-Enhanced MR Imaging for Soft Tissue Sarcomas.
Dynamic contrast-enhanced magnetic resonance imaging has recently emerged as an important method for evaluating soft tissue sarcomas for biopsy localization, chemotherapeutic response, and long-term follow-up because of its ability to detect viable tumor. This article presents the basic principles of contrast kinetics in soft tissue sarcomas after bolus injection of contrast agent and discusses the current postprocessing methods (subtraction, first-pass image and time-intensity curves with region of interest, and color-encoded techniques) used to display these dynamic studies. Because of its excellent temporal resolution, dynamic MR imaging can delineate the early uptake of contrast agent in sarcomas within seconds after injection, almost synchronous with arterial enhancement, and thereby differentiate the rapidly enhancing viable tumor from the nonenhancing necrotic tumor and the late enhancing changes after surgery, radiation therapy, and chemotherapy.


Machine learning approaches for the mortality risk assessment of patients undergoing hemodialysis.
Mortality is a major primary endpoint for long-term hemodialysis (HD) patients. The clinical status of HD patients generally relies on longitudinal clinical observations such as monthly laboratory examinations and physical examinations. A total of 829 HD patients who met the inclusion criteria were analyzed. All patients were tracked from January 2009 to December 2013. Taken together, this study performed full-adjusted-Cox proportional hazards (CoxPH), stepwise-CoxPH, random survival forest (RSF)-CoxPH, and whale optimization algorithm (WOA)-CoxPH model for the all-cause mortality risk assessment in HD patients. The model performance between proposed selections of CoxPH models were evaluated using concordance index. The WOA-CoxPH model obtained the highest concordance index compared with RSF-CoxPH and typical selection CoxPH model. The eight significant parameters obtained from the WOA-CoxPH model, including age, diabetes mellitus (DM), hemoglobin (Hb), albumin, creatinine (Cr), potassium (K), Kt/V, and cardiothoracic ratio, have also showed significant survival difference between low- and high-risk characteristics in single-factor analysis. By integrating the risk characteristics of each single factor, patients who obtained seven or more risk characteristics of eight selected parameters were dichotomized as high-risk subgroup, and remaining is considered as low-risk subgroup. The integrated low- and high-risk subgroup showed greater discrepancy compared with each single risk factor selected by WOA-CoxPH model. The study findings revealed WOA-CoxPH model could provide better risk assessment performance compared with RSF-CoxPH and typical selection CoxPH model in the HD patients. In summary, patients who had seven or more risk characteristics of eight selected parameters were at potentially increased risk of all-cause mortality in HD population.