Corrections and clarifications.
In the report "Reversal of Raf-1 activation by purified and membrane-associated protein phosphatases" by P. Dent, T. Jelinek, D. K. Morrison, M. J. Weber, and T. W. Sturgill, (30 June, p. 1902), reference 25 on page 1906 should have included, after the first sentence, "Buffers (4) and buffer E contained 0.2% (v/v) 2-mercaptoethanol."


Methylmercury Production and Degradation under Light and Dark Conditions in the Water Column of the Hells Canyon Reservoirs, USA.
Methylmercury (MeHg) is a highly toxic form of mercury that can bioaccumulate in fish tissue. Methylmercury is produced by anaerobic bacteria, many of which are also capable of MeHg degradation. In addition, demethylation in surface waters can occur via abiotic sunlight-mediated processes. The goal of the present study was to understand the relative importance of microbial Hg methylation/demethylation and abiotic photodemethylation that govern the mass of MeHg within an aquatic system. The study location was the Hells Canyon complex of 3 reservoirs on the Idaho-Oregon border, USA, that has fish consumption advisories as a result of elevated MeHg concentrations. Our study utilized stable isotope addition experiments to trace MeHg formation and degradation within the water column of the reservoirs to understand the relative importance of these processes on the mass of MeHg using the Water Quality Analysis Simulation Program. The results showed that rates of MeHg production and degradation within the water column were relatively low (<0.07 d-1 ) but sufficient to account for most of the MeHg observed with the system. Most MeHg production within the water column appeared to occur in the spring when much of the water column was in the processes of becoming anoxic. In the surface waters, rates of photodemethylation were relatively large (up to -0.25 d-1 ) but quickly decreased at depths >0.5 m below the surface. These results can be used to identify the relative importance of MeHg processes that can help guide reservoir management decisions. Environ Toxicol Chem 2021;40:1829-1839. © 2021 SETAC. This article has been contributed to by US Government employees and their work is in the public domain in the USA.


Screening of Small Molecule Microarrays for Ligands Targeted to the Extracellular Epitopes of Living Cells.
The screening of living cells using high-throughput microarrays is technically challenging. Great care must be taken in the chemical presentation of potential ligands and the number of collisions that cells make with them. To overcome these issues, we have developed a glass slide-based microarray system to discover small molecule ligands that preferentially bind to one cell type over another, including when the cells differ by only a single receptor. Chemical spots of 300 ± 10 μm in diameter are conjugated covalently to glass slides using an arraying robot, and novel near-infrared fluorophores with peak emission at 700 nm and 800 nm are used to label two different cell types. By carefully optimizing incubation conditions, including cell density, motion, kinetics, detection, etc. we demonstrate that cell-ligand binding occurs, and that the number of cells bound per chemical spot correlates with ligand affinity and specificity. This screening system lays the foundation for high-throughput discovery of novel ligands to the cell surface.


Oxidation Responsive Polymers with a Triggered Degradation via Arylboronate Self-Immolative Motifs on a Polyphosphazene Backbone.
Oxidation responsive polymers with triggered degradation pathways have been prepared via attachment of self-immolative moieties onto a hydrolytically unstable polyphosphazene backbone. After controlled main-chain growth, postpolymerization functionalization allows the preparation of hydrolytically stable poly(organo)phosphazenes decorated with a phenylboronic ester caging group. In oxidative environments, triggered cleavage of the caging group is followed by self-immolation, exposing the unstable glycine-substituted polyphosphazene which subsequently undergoes to backbone degradation to low-molecular weight molecules. As well as giving mechanistic insights, detailed GPC and 1H and 31P NMR analysis reveal the polymers to be stable in aqueous solutions, but show a selective, fast degradation upon exposure to hydrogen peroxide containing solutions. Since the post-polymerization functionalization route allows simple access to polymer backbones with a broad range of molecular weights, the approach of using the inorganic backbone as a platform significantly expands the toolbox of polymers capable of stimuli-responsive degradation.


Identification of an HLA-A2-restricted CD147 epitope that can induce specific CTL cytotoxicity against drug resistant MCF-7/Adr cells.
Cluster of differentiation (CD)147 is highly expressed in drug-resistant tumor cell lines and is involved in the formation of tumor drug resistance. Therefore, immunotherapy utilizing CD147 epitope peptides is a promising approach for the elimination of drug-resistant tumor cells. However, like most tumor-associated antigens (TAAs), CD147 belongs to the autoantigen category, and T cells that recognize high affinity, immunodominant epitopes from autoantigens are deleted though thymic negative selection. Furthermore, wild-type autoantigen peptides cannot effectively activate and expand T lymphocytes with lower affinity T cell receptors in vivo. However, mutations of TAA peptides have been demonstrated to increase the affinity of major histocompatibility complex molecules and their binding to T cell receptor molecules, leading to activation of T lymphocytes in vitro. In the present study, a high-affinity point mutation peptide, CD147126-134L2, was predicted by the human leukocyte antigen (HLA) binding prediction algorithm and its affinity was testified using a T2 binding assay. In addition, when peptide-specific cytotoxic T lymphocytes (CTLs) were stimulated with dendritic cells loaded with the CD147126-134L2 peptide under HLA-A*02:01 restriction, interferon-γ release and cytotoxicity assays showed that peptide-specific CTLs effectively cross-recognized and lysed T2 target cells loaded either with the wild-type (CD147126-134) or mutated peptide (CD147126-134L2). Moreover, the CD147126-134L2 peptide-specific CTLs exerted strong cytotoxic activity against drug-resistant MCF-7/Adr cells, which express a high level of CD147 and are HLA-A*02:01-positive, but not against normal MCF-7 cells. Thus, this suggests that the wild-type peptide (CD147126-134) is naturally presented on HLA-A*02:01 of CD147-expressing MCF-7/Adr cells and is cross-recognized by CTLs. In conclusion, an HLA-A*02:01-restricted CD147-point mutant epitope peptide was identified that induces CTLs to efficiently lyse drug-resistant MCF-7 cells that highly express CD147. Therefore, this immunotherapeutic approach should be explored as a potential treatment for drug-resistant tumors.


Nonconstant Thermal Regimes Enhance Overwintering Success and Accelerate Diapause Development for Smicronyx fulvus (Coleoptera: Curculionidae).
Recent populations of the red sunflower seed weevil, Smicronyx fulvus LeConte (Coleoptera: Curculionidae), have been inconsistent or declining, particularly in North Dakota. Consequently, research on weevil biology, including development of resistant germplasm, has been limited. To determine whether cold storage of diapausing larvae could be improved, nonconstant temperature treatments (fluctuating thermal regime [FTR] and thermoperiod [TP]) were tested versus a constant 6°C for storage up to 365 d. Both alternate temperature treatments produced more adult weevils than constant 6°C for short (42, 91 d) storage, while all temperature treatments were good (≥60% adult emergence) at moderate term (182 d) cold storage, and FTR was best for long (365 d) periods. Excluding the 14-d storage period, which produced too few weevils for comparison, each doubling of cold storage time (e.g., from 42 to 91 d, 91 to 182 d), usually decreased the number of days to 50% relative emergence by ∼10 d. After 365 d of larval storage, emerged S. fulvus adults successfully infested sunflowers in a plant growth chamber, with damage per female similar to that observed in field trials. Compared with previous efforts to store weevil larvae, the method of collection and FTR storage is either more effective (greater adult emergence and reduced parasitism) or more time-efficient, and should permit year-round research using S. fulvus adults. Because successful emergence under FTR was >75% after 365 d, additional research would be required to determine the maximum effective duration of cold storage for S. fulvus.


Palladium-catalyzed dehydrogenative direct arylations of 1,2,3-triazoles.
Palladium-catalyzed intramolecular dehydrogenative direct arylations of 1,2,3-triazoles were accomplished under ambient pressure of air, which set the stage for a modular synthesis of annulated phenanthrenes through a reaction sequence comprising two distinct catalytic C-H bond functionalization reactions.


Oral, genital and anal human papillomavirus infections among female sex workers in Ibadan, Nigeria.
There are limited data on the epidemiology of HPV in different anatomical sites of female sex workers (FSW). We investigated the prevalence and concordance of cervical, vulval, oral and anal HPV among FSW in Ibadan, Nigeria. FSWs aged 18-45 years were enrolled in a cross-sectional survey. After interview and clinical examination, samples were collected from mouth, cervix, vulva and anus. HPV genotyping was done with Anyplex II 28HPV assay. Multivariable analyses were performed to explore associated risk factors and concordance of HPV infections across sites. In total, 315 FSWs participated in the study with a mean age of 30-6.5 years. The prevalence of any HPV infection was 88% in the vulva, 84% in the cervix, 75% in the anus and 24% in the oral cavity. HPV 35 was the most prevalent and concordant high-risk type in the four sites. The risk factors for HPV infection by anatomic site varied. This large study showed a high prevalence and concordance of HPV infections of cervical, vulval, oral and anal HPV among FSWs in Nigeria. The potential to acquire and transmit HPV is high in this population, and we highlighted the urgency to protect young women through HPV vaccination.


Visualizing millisecond chaotic mixing dynamics in microdroplets: A direct comparison of experiment and simulation.
In order to fully explore and utilize the advantages of droplet-based microfluidics, fast, sensitive, and quantitative measurements are indispensable for the diagnosis of biochemical reactions in microdroplets. Here, we report an optical detection technique using two-photon fluorescence lifetime imaging microscopy, with an aligning-summing and non-fitting division method, to depict two-dimensional (2D) maps of mixing dynamics by chaotic advection in microdroplets with high temporal and spatial resolution. The mixing patterns of two dye solutions inside droplets were quantitatively and accurately measured. The mixing efficiency in a serpentine droplet mixer was also quantified and compared with the simulation data. The mapped chaotic mixing dynamics agree well with the numerical simulation and theoretical prediction. This quantitative characterization is potentially applicable to the real-time kinetic study of biological and chemical reactions in droplet-based microfluidic systems.


Online CME options: an update.
Online options for continuing medical education (CME) are multiplying, thanks to technologies such as really simple syndication (RSS) feeds, podcasts, and blogs. As with traditional CME modalities, there are issues of accreditation, quality, cost, and relevance. Physician-directed syndication technologies are especially significant in the area of relevance, because they provide subscriber-side filtering of the growing amount of information available online. As the medical education community embraces the technologies enabling targeted dissemination of information, physicians can expect more and better focused medical education experiences.


Frequency and antibiotic susceptibility pattern of mycobacterial isolates from extra-pulmonary tuberculosis cases.
To determine the frequency and antimicrobial susceptibility pattern of extra-pulmonary tuberculosis in Rawalpindi. Department of Microbiology, Armed Forces Institute of Pathology, Rawalpindi. Between September 2000 and August 2002, 899 pulmonary and 460 extra-pulmonary specimens from suspected cases of tuberculosis were examined. The radiometric BACTEC 460 TB system was used for culture and antimicrobial susceptibility testing. Mycobacteria were isolated from 291 pulmonary specimens and 98 extra-pulmonary specimens. The frequency of extra-pulmonary tuberculosis was 25.2%. The commonest source of isolation was pus (44.9%, frequency 11.3%), followed by lymph nodes (13.3%, frequency 3.3%) and pleural fluid (13.3%, frequency 3.3%). We tested the anti-microbial susceptibility of the isolates to the four first line anti-tuberculous drugs, rifampicin, isoniazid, streptomycin and ethambutol. Of the extra-pulmonary isolates 13.3% were resistant to a single drug, 21.4% were multi-drug resistant and 9.2% were resistant to all the four drugs. Increased awareness of the magnitude of the problem posed by extra-pulmonary tuberculosis is required so that appropriate control measures can be adopted.


Serum enzyme activities after cardioversion.
Serum aspartate aminotransferase (SGOT), alanine aminotransferase (SGPT), creatinine phosphokinase (CPK), and butyric acid dehydrogenase (BDH) were determined in 94 patients before, 1(1/2) hours, and 24 hours after cardioversion. An increase in SGOT and CPK activity was observed 24 hours after cardioversion in the group of patients treated with two or more DC shocks. The importance of this enzyme activity increase is discussed. It originates in the skeletal muscles and probably has no clinical significance, as no other signs of myocardial damage were observed simultaneously in a large group of patients.


Differential effects of estradiol and raloxifene on collagen biosynthesis in cultured human skin fibroblasts.
The dose-dependent effect of a 24 h treatment with estradiol (E(2)) (1, 2, 5, 10 nM) and raloxifene (Rx) (1, 5, 10, 20 microM) on ER alpha and ER beta mRNA expression, collagen bio-synthesis, prolidase activity, MMP-2, MMP-9, insulin-like growth factor I receptor expression (IGF-1R) and beta1-integrin expressions in cultured fibroblasts obtained from postmenopausal women were examined. Both ligands increased mRNA expression of ER compared to control. Rx at 5 and 10 microM concentrations had greater stimulative effect on collagen biosynthesis, prolidase activity and IGF-1R expression compared to E(2) at 2 and 5 nM concentration. Both studied ER ligands had no effect on beta1-integrin receptor expressions. MMP-2 expression was not detected in human skin fibroblast culture. In contrast to estradiol raloxifene inhibited the expression of MMP-9. Raloxifene had stronger positive stimulative effects on collagen biosynthesis, through different biochemical mechanisms, than estradiol in human skin fibroblasts and might reverse some of the postmenopausal changes in skin or connective tissue. Increase of collagen synthesis induced by raloxifene may be activated by both estrogen receptor dependent and independent pathways such as up-regulation of estrogen receptors, up-regulation of IGF receptor, transcriptional regulation of collagen genes by estrogen receptor-raloxifene complex, increasing of prolidase activity or finally by inhibition of MMP-9 expression.


Distinct brain perfusion pattern associated with CSF biomarkers profile in primary progressive aphasia.
A new classification of primary progressive aphasia (PPA) was recently proposed to differentiate between non-fluent aphasia (NF-PPA), semantic variant of PPA (S-PPA) and logopenic aphasia (LPA) by their phenotypic presentations. CSF biomarkers (BM) may differentiate PPA with atypical Alzheimer's disease (AD) that presents with LPA from PPA with frontotemporal lobe degeneration that presents with either NF-PPA or S-PPA. Single photon emission computed tomography (SPECT) was used to investigate brain hypoperfusion differences among PPA subtypes according to their CSF AD profiles. 34 PPA patients underwent lumbar puncture and brain perfusion SPECT. PPA patients were classified into two subgroups according to the Aβ(42):tau ratio: PPA BM positive (with an AD CSF profile) and PPA BM negative (not having an AD CSF profile). The biological classification was made while blind to the phenotypical presentation. The brain perfusion profiles of the PPA subgroups were compared with those of 24 healthy subjects. PPA BM positive patients had left-side predominant hypoperfusion in the temporoparietal cortex that extended to the dorsolateral prefrontal cortex and perisylvian region while PPA BM negative patients had hypoperfusion that was predominant in the temporal poles (p<10(-4) corrected). Distinct hypoperfusion patterns in PPA BM positive and PPA BM negative patients were observed, similar to those that have been described for S-PPA and LPA. These results support using CSF biomarkers to classify PPA.


B cells and T cells are critical for the preservation of bone homeostasis and attainment of peak bone mass in vivo.
Bone homeostasis is regulated by a delicate balance between osteoblastic bone formation and osteoclastic bone resorption. Osteoclastogenesis is controlled by the ratio of receptor activator of NF-kappaB ligand (RANKL) relative to its decoy receptor, osteoprotegerin (OPG). The source of OPG has historically been attributed to osteoblasts (OBs). While activated lymphocytes play established roles in pathological bone destruction, no role for lymphocytes in basal bone homeostasis in vivo has been described. Using immunomagnetic isolation of bone marrow (BM) B cells and B-cell precursor populations and quantitation of their OPG production by enzyme-linked immunosorbent assay (ELISA) and real-time reverse transcriptase-polymerase chain reaction (RT-PCR), cells of the B lineage were found to be responsible for 64% of total BM OPG production, with 45% derived from mature B cells. Consistently B-cell knockout (KO) mice were found to be osteoporotic and deficient in BM OPG, phenomena rescued by B-cell reconstitution. Furthermore, T cells, through CD40 ligand (CD40L) to CD40 costimulation, promote OPG production by B cells in vivo. Consequently, T-cell-deficient nude mice, CD40 KO mice, and CD40L KO mice display osteoporosis and diminished BM OPG production. Our data suggest that lymphocytes are essential stabilizers of basal bone turnover and critical regulators of peak bone mass in vivo.


Patient's behavior of selection physician in online health communities: Based on an Elaboration likelihood model.
With the rapid development of "Internet + medicine" and the impact of the COVID-19 epidemic, online health communities have become an important way for patients to seek medical treatment. However, the mistrust between physicians and patients in online health communities has long existed and continues to impact the decision-making behavior of patients. The purpose of this article is to explore the influencing factors of patient decision-making in online health communities by identifying the relationship between physicians' online information and patients' selection behavior. In this study, we selected China's Good Doctor (www.haodf.com) as the source of data, scrapped 10,446 physician data from December 2020 to June 2021 to construct a logit model of online patients' selection behavior, and used regression analysis to test the hypotheses. The number of types of services, number of scientific articles, and avatar in physicians' personal information all has a positive effect on patients' selection behavior, while the title and personal introduction hurt patients' selection behavior. Online word-of-mouth positively affected patients' selection behavior and disease risk had a moderating effect. Focusing on physician-presented information, this article organically combines the Elaboration likelihood model with trust source theory and online word-of-mouth from the perspective of the trusted party-physician, providing new ideas for the study of factors influencing patients' selection behavior in online health communities. The findings provide useful insights for patients, physicians, and community managers about the relationship between physician information and patients' selection behavior.


Metatarsus proximus and digital divergence. Association with intermetatarsal neuromas.
A retrospective radiologic study was performed to determine whether there is an increased finding of metatarsus proximus and digital divergence in patients with a confirmed diagnosis of intermetatarsal neuroma when compared with an asymptomatic group. The study included 48 patients with pathologic confirmation of neuroma and 100 asymptomatic patients. Results of the study revealed no statistical relationship between the radiologic findings of metatarsus proximus and digital divergence and the physical occurrence of neuromas. An unexpected finding was an increased intermetatarsal angle of the affected interspace in the neuroma group.


Interventions for Hidradenitis Suppurativa: Updated Summary of an Original Cochrane Review.
Which treatments have been shown to be effective in randomized clinical trials (RCTs) for hidradenitis suppurativa (HS) in adults? There is high-quality evidence of benefit from adalimumab given weekly, while every other week dosing is ineffective, with reductions in Dermatology Life Quality Index (DLQI) scores compared with placebo of 2.8 points (95% CI, -3.7 to -2.0 points) and 1.6 points (95% CI, -3.9 to 0.6 points), respectively. Moderate-quality evidence suggests that infliximab is beneficial; RCT evidence for other interventions was lower in quality or absent, limiting further conclusions.


[SUBCLINICAL HYPOTHYROIDISM].
Subclinical hypothyroidism is a rather common disorder of the thyroid gland. Despite the fact that subclinical hypothyroidism has no clear-cut clinical picture, this condition is associated with changes in various organs and systems, moreover, it is a risk factor of cardiovascular diseases. The article summarizes the available data on subclinical hypothyroidism, principles of its diagnostics and treatment.


Change of tourism organizations: Implications from a review of cultural tourism research.
Change has been universally acknowledged as the perpetual theme for routine organizational life. As cultural tourism, a major element of global tourism consumption accounting for 40% of tourism employment, is becoming increasingly flourishing and promising, tourism organizations are also obliged to implement a series of organizational changes to adapt to the trending culturalization in the tourism domain. In light of this, this research, by outlining important sub-themes and trends of cultural tourism research, tracks the evolution of cultural tourism as a research field over the previous decades so as to analyze existing interconnections between the systematic review and tourism organizational change. Based on these interconnections, the research also manages to propose several potential implications for tourism organizations to optimize their future implement of daily organizational changes for the sake of adaptative survival and development.


Frontal Fibrosing Alopecia: An Update on Pathogenesis, Diagnosis, and Treatment.
Frontal fibrosing alopecia (FFA), first described by Kossard in the early 1990s, is a form of primary lymphocytic cicatricial alopecia characterized by selective involvement of the frontotemporal hairline and eyebrows. Since the original description, an increasing number of cases have been reported worldwide and the clinical aspects of the disease have been better characterized. However, the pathogenesis is still unknown and several hypotheses have been made about possible triggering factors, including hormones, neurogenic inflammation, smoking, UV filters, and ingredients in leave-on facial products. A genetic basis has also been hypothesized as the disease can occur in siblings and members of the same family. Besides its pathogenesis, research is also focused on treatment; FFA is a chronic condition and at present there is no validated or approved treatment for this disorder. Commonly prescribed topical treatments include corticosteroids, minoxidil, and calcineurin inhibitors. Systemic treatments include 5α-reductase inhibitors, hydroxychloroquine, and retinoids. Intralesional triamcinolone acetonide is also utilized, especially for the eyebrows. Other possible treatments include pioglitazone, naltrexone, tofacitinib, and lasers.


miR-142-3p inhibits aerobic glycolysis and cell proliferation in hepatocellular carcinoma via targeting LDHA.
Cancer cells are addictively dependent on glycolysis even in an oxygen-rich condition. However, the mechanism underlying micro (mi)RNA regulation of aerobic glycolysis in cancer cells has not been fully understood. Here, we demonstrated that the expression of miR-142-3p was lower in hepatocellular carcinoma (HCC) as compared to adjacent non-tumor samples, which was confirmed in The Cancer Genome Atlas (TCGA) HCC cohorts and Gene Expression Omnibus (GEO) datasets. Function and pathway analysis showed that miR-142-3p was most relevent with metabolism. As predicted, the overexpression of miR-142-3p inhibited aerobic glycolysis and thus proliferation of HCC cells. Mechanistically, we identified lactate dehydrogenase A (LDHA), one of the important catalyticase for aerobic glycolysis, as the target of miR-142-3p. Exogenous expression of miR-142-3p reduced the protein levels of LDHA in both SK-Hep-1 and Huh7 cells. Dual luciferase report assays showed the expression of LDHA was directly modulated by miR-142-3p. miR-142-3p-induced deduction of aerobic glycolysis and proliferation were reversed by LDHA overexpression. Taken together, these results indicate that miR-142-3p could act as a tumor suppressor in HCC by targeting LDHA, suggesting new therapeutic targets for HCC treatment.


Combined HSV-TK/GCV and secondary lymphoid tissue chemokine gene therapy inhibits tumor growth and elicits potent antitumor CTL response in tumor-bearing mice.
Suicide gene therapy in combination with pro-drugs represents an attractive approach to the treatment of cancer. Unfortunately this approach is limited by difficulty in targeting all tumor cells, especially those at the distant metastases associated with the most complex tumors. For this reason, attempts to stimulate global anti-tumor immune responses at the sites of effective suicide gene/pro-drug-mediated tumor cell destruction are appealing. Here we show that, by including a gene coding for secreted secondary lymphoid tissue chemokine (SLC) along with the herpes simplex virus thymide kinase (HSV-TK) gene in a bicistronic vector for anti-tumor gene therapy in conjunction with the pro-drug ganciclovir (GCV), we are able to mediate a greatly enhanced anti-tumor effect in the murine B16 melanoma tumor model. The data presented suggests that this enhanced antitumor effect is the result of a strong induced CTL immune response resulting from the recruitment of immune cells to the site of HSV-TK/GCV-induced tumor destruction by the potent chemokine SLC.


SOCS1 regulates CCR7 expression and migration of CD4+ T cells into peripheral tissues.
Suppressors of cytokine signaling (SOCS) proteins control many aspects of lymphocyte function through regulation of STAT pathways. SOCS1-deficient mice develop severe skin and eye diseases that result from massive infiltration of inflammatory cells into these tissues. In this study, we have used SOCS1-, STAT1-, or STAT6-deficient mice, as well as, T cells with stable overexpression or deletion of SOCS1, to examine whether SOCS1 is involved in regulating lymphocyte trafficking to peripheral tissues. We show that SOCS1-deficient mice have increased numbers of T cells with characteristics of effector memory cells and expression of CCR7, a protein that promotes retention of T cells in lymphoid tissues, is markedly reduced in these cells. The decrease in CCR7 expression correlates with hyperactivation of STAT6, suggesting that aberrant recruitment of T cells into SOCS1-deficient mouse skin or eye results from abrogation of negative feedback regulation of STAT6 activation and CCR7 expression. Consistent with in vivo regulation of CCR7 expression and lymphocyte migration by SOCS1, forced overexpression of SOCS1 in T cells up-regulates CCR7 expression and enhances chemotaxis toward CCL19 or CCL21. CCR6 and CXCR3 are also up-regulated on SOCS1-deficient T cells and in situ analysis of the cornea or retina further reveal that these cells may mediate the chronic skin and eye inflammation through recruitment of Th1 and Th17 cells into these tissues. Collectively, these results suggest that SOCS1 regulates steady-state levels of chemokine receptors through its inhibitory effects on STAT pathways and this may underscore its role in regulating recruitment and retention of effector cells into nonlymphoid tissues.


Anticonvulsants for neuropathic pain and detoxification.
It is now well demonstrated that several anticonvulsants have a role in the treatment of neuropathic pain and also in withdrawal from benzodiazepines, sedatives, and perhaps alcohol. Valproic acid, carbamazepine, gabapentin, clonazepam, and lamotrigine are appropriate treatments for neuropathic pain, effective to a degree dependent on the underlying pathophysiology. While less effective than newer agents, there are situations in which phenytoin remains useful. Currently, a limited understanding of both the processes responsible for pain and the specific effects of each agent prevents prediction of individual response to these drugs, often necessitating trials of several drugs before the best one is found. It is interesting that the anticonvulsant drugs most useful for neuropathic pain are the same ones effective in sedative withdrawal, bipolar disorder, and several anxiety disorders. Issues of neural hypersensitivity and kindling, therefore, may prove to be unifying concepts for these conditions.


A functional toll-like receptor 8 variant is associated with HIV disease restriction.
Toll-like receptors (TLRs) play an important role in the innate immune response to pathogens. TLR8 has been found to recognize RNA derived from various viruses, including human immunodeficiency virus (HIV). Presently, very little is known about the influence of TLR8 genetic variation on susceptibility to and progression of HIV disease. We genotyped a population of 782 HIV-positive adults and 550 healthy control subjects for 3 nonsynonymous TLR8 single-nucleotide polymorphisms. We found that the presence of the most frequent TLR8 polymorphism, TLR8 A1G (rs3764880), confers a significantly protective effect regarding progression of the disease. In overexpression assays, we demonstrated that this receptor variant displays impaired NF-kappaB activation in vitro. Furthermore, we analyzed different cell types obtained from individuals differing in their TLR8 genotype and assessed their response to TLR8 ligands in vitro. The presence of the mutated receptor variant was associated with modulation of cytokine secretion profiles and lipid mediator synthesis patterns in monocytes and neutrophils. This first report of a functional TLR8 variant associated with a different clinical course of an RNA viral disease may have implications for the individual risk assessment of patients infected with HIV and other RNA viruses as well as for future HIV vaccine development.


Bupropion sustained release: side effect profile.
Bupropion IR (immediate release) has been on the market since 1988 and is an effective and usually well-tolerated antidepressant. In late 1996, a new sustained-release formulation, bupropion SR, was approved and is now available. Compared with the IR formulation, the SR formulation demonstrates similar efficacy and has been found to have similar, but to some degree fewer, side effects. Its efficacy is similar to that of other newer antidepressants. Side effects of bupropion SR are limited and are not dissimilar to those of the serotonergic antidepressants; however, bupropion SR produces neither substantial sexual side effects nor drug interactions. Study data demonstrate that seizure incidence, which is a concern with high-dose IR, is substantially lower with the new SR formulation.


The Empirical Study of College Students' E-Learning Effectiveness and Its Antecedents Toward the COVID-19 Epidemic Environment.
Due to the impact of COVID-19, universities are forced to suspend their classes, which begin to depend on the usage of online teaching. To investigate the relationship among e-learning self-efficacy, monitoring, willpower, attitude, motivation, strategy, and the e-learning effectiveness of college students in the context of online education during the outbreak of COVID-19. A 519 first- to fifth-year undergraduate students from a medical university were selected for the research in this study. Structural equation model (SEM) was used for a data analysis, which led to the results showing that: (1) e-learning self-efficacy and monitoring have significant positive influence on e-learning strategy, and indirectly influence e-learning effectiveness through e-learning strategy; (2) e-learning willpower and attitude have a significant positive influence on e-learning motivations, and indirectly influence e-learning effectiveness through e-learning motivation and strategy; (3) e-learning motivation is having significant influence on e-learning effectiveness, while e-learning strategy is playing a mediating role; (4) There is a significant positive correlation between e-learning strategy and e-learning effectiveness; and (5) The presence of e-learning experience has a moderating influence on e-learning effectiveness as well as its influential factors. Results from this study provide the necessary information as to how higher education institutions and students can enhance students' effectiveness of the e-learning system in order to support the usage of online technologies in the learning and teaching process. These results offer important implications for online learning effectiveness.


Research progress of aldehyde oxidases in plants.
Plant aldehyde oxidases (AOs) are multi-functional enzymes, and they could oxidize abscisic aldehyde into ABA (abscisic acid) or indole acetaldehyde into IAA (indoleacetic acid) as the last step, respectively. AOs can be divided into four groups based on their biochemical and physiological functions. In this review, we summarized the recent studies about AOs in plants including the motif information, biochemical, and physiological functions. Besides their role in phytohormones biosynthesis and stress response, AOs could also involve in reactive oxygen species homeostasis, aldehyde detoxification and stress tolerance.


Could be a link between non atopic asthma and HP infection?
A potential role of Helicobater Pylori (HP) infection in several extra-intestinal pathologies has been recently suggested. The aim of our study was to assess the role of serology positive for HP in atopic and non atopic infants and children affected by atopic dermatitis, urticaria, rhinitis and asthma. We included 615 children affected by atopic diseases. According to prick test positivity and age, we divided the patients into two groups: atopic or non-atopic patients and infants (0-2 years) or children (2-12 years). The serum levels of antibodies for H. pylori immunoglobulin G were measured by using an ELISA test. We found a not significant difference between group 1 and group 2 about atopy. There was a significant higher frequency of HP positive serology in older children. As for infants, a higher significant prevalence of HP positive serology was found in non-atopic patients. HP positive serology was significantly higher only in non-atopic infants affected by atopic dermatitis and urticaria than in atopic. In group 2, non atopic children shown a significant increase in the prevalence of HP serum positivity than atopic children. As for asthma, there was an higher prevalence of HP serology positive in non atopic asthmatic children group than in atopic asthmatics. On the contrary, the prevalence of positive HP serology was not significantly different between atopic and non atopic children affected by dermatitis, urticaria, and rhinitis. The present data confirm an inverse association between HP positive serology and atopy in both groups. However, the higher prevalence of positive HP serology was observed in non atopic asthmatics children than in atopic asthmatics. We could speculate that HP infection can favour non-atopic asthma onset.


Fatal Embolic ST-Elevation Myocardial Infarction Secondary to Healed-Phase Mitral Valve Infective Endocarditis.
Embolic myocardial infarction (MI) caused by infective endocarditis (IE) is rare, but it is increasingly recognized as an important complication. This complication typically occurs in patients with aortic valve endocarditis during the acute phase of the infection. It is also known to have a high mortality rate; however, the best practice for its management is unclear owing to scarce available data. In addition, most cases of embolic acute MI (AMI) caused by IE are indirectly diagnosed with a combination of angiographic examination such as coronary angiography or cardiac computed tomography. Herein, we report a case of fatal embolic ST-elevation MI (STEMI) caused by mitral valve IE during the healed phase, which was clearly proven by the pathology findings.


Identification and Quality Evaluation of Raw and Processed Asarum Species Using Microscopy, DNA Barcoding, and Gas Chromatography-Mass Spectrometry.
Asarum (Aristolochiaceae) is one of the common herbs used to relieve exterior syndromes. Some volatile components of Asarum which have toxic effect may cause adverse reactions such as headache, general tension, unconsciousness, and respiratory paralysis. Therefore, Asarum is normally processed to reduce such toxicity and adverse effects. The bioactive ingredients contained in different Asarum herbs vary significantly; this variation may be attributed to their differences in species, origins, or processing methods. In this study, 16 batches of Asarum herbs were collected, and their species were identified using DNA barcoding, which is a method for distinguishing plant species, coupled with microscopy. A gas chromatography-mass spectrometry (GC-MS) method for simultaneous determination of 10 compounds was established to evaluate the contents of raw and processed Asarum herbs. Multivariate analysis was then applied to compare different batches of herbs based on the GC-MS data. DNA barcoding identified the herbs as being derived from four sources, and herbs from different origins showed different microscopic features. The results demonstrated that most of the samples were clearly clustered into distinct groups that corresponded to species types. All raw and processed samples were classified by partial least squares discriminant analysis (PLS-DA) based on the 10 analyzed compounds. The findings suggested that safrole and methyleugenol with a variable importance in the project (VIP) > 1 are unique compounds that can be used to differentiate between Asarum species. Safrole, methyleugenol, and 2,6,6-trimethylcyclohepta-2,4-dien-1-one were identified as significant constituents, the presence of which can be used to differentiate between raw and processed Asarum samples. These results indicate that species and processing methods show important effects on the composition of Asarum herbs.


Inhibition of experimental oral carcinogenesis by topical beta carotene.
beta-Carotene was found to significantly inhibit the formation of 7,12-dimethylbenz[a]anthracene (DMBA)-induced squamous cell carcinoma of hamster buccal pouch when applied topically on days alternate to the application of 0.25% DMBA in heavy mineral oil thrice weekly for 22 weeks. An initial experiment utilized 40 male young adult Syrian hamsters divided into four equal groups. Group 1 had DMBA applied to left buccal pouches thrice weekly. Group 2 had DMBA applied as in group 1 but also beta-carotene thrice weekly on days alternate to the DMBA application. Group 3 animals were painted with only beta-carotene and group 4 animals were untreated controls. In a second experiment with 80 animals, beta-carotene was found to inhibit oral carcinogenesis in an initiation--promotion hamster buccal pouch system using 0.1% DMBA as initiator and 40% benzoyl peroxide as promoter. beta-Carotene inhibited both initiation and promotion.


Spontaneous mutation at the hypervariable mouse minisatellite locus Ms6-hm: flanking DNA sequence and analysis of germline and early somatic mutation events.
Hypervariability at minisatellite loci is maintained by spontaneous mutation to new-length alleles. At the most variable loci, mutation rate is directly measurable by pedigree analysis. The mouse minisatellite locus Ms6-hm has a germline mutation rate of 2.5% per gamete and is therefore one of the most unstable loci yet identified in the mouse genome. Mutation events at this locus also occur during early mouse development, resulting in mice mosaic for cells carrying a common non-parental allele in different somatic tissues and the germline. The DNA sequence flanking Ms6-hm is rich in dispersed repetitive elements; the minisatellite array has expanded from within a member of the Mouse Transcript family which is flanked by two additional Mouse Transcript elements, and a B2 element lies further 3' to the minisatellite. To define the characteristics of mutation events at Ms6-hm we have analysed 19 germline and 13 somatic length-change events. Germline mutation events at Ms6-hm are not accompanied by the exchange of flanking markers in three informative mutant alleles analysed.


Endoscopic full‑thickness resection with clip‑ and snare‑assisted traction for gastric submucosal tumours in the fundus: A single‑centre case series.
Exposed endoscopic full-thickness resection (Eo-EFTR) has been recognized as a feasible therapy for gastrointestinal submucosal tumours (SMTs) originating deep in the muscularis propria layer; however, Eo-EFTR is difficult to perform in a retroflexed fashion in the gastric fundus. As a supportive technique, clip- and snare-assisted traction may help expose the surgical field and shorten the operation time in endoscopic resection of difficult regions. However, the application of clip- and snare-assisted traction in Eo-EFTR of SMTs in the gastric fundus is limited. Between April 2018 and December 2021, Eo-EFTR with clip- and snare-assisted traction was performed in 20 patients with SMTs in the gastric fundus at The First Affiliated Hospital of Soochow University. The relevant clinical data were collected retrospectively for all of the patients and analysed. All 20 patients underwent Eo-EFTR successfully without conversion to open surgery or severe adverse events. The en bloc resection rate and R0 resection rate were both 100%. Two patients had abdominal pain and fever after the operation, and five patients had fever, which recovered with medical therapy. No complications, such as delayed bleeding or delayed perforation, were observed. The postoperative pathology indicated that 19 cases were gastrointestinal stromal tumours and one case was leiomyoma. During the follow-up, no residual tumour, local recurrence or distant metastasis was detected by endoscopy or abdominal computed tomography. In conclusion, Eo-EFTR with clip- and snare-assisted traction appears to be a relatively safe and effective treatment for gastric SMTs in the fundus. However, prospective studies on a larger sample size are required to verify the effect of the clip- and snare-assisted traction in Eo-EFTR.


Characterization of chromosomes and localization of the rDNA locus in the aye-aye (Daubentonia madagascariensis).
The karyotype of a prosimian primate, the aye-aye (Daubentonia madagascariensis), is described. Results from a variety of staining methods (Q-, R-, G-, and C-banding, distamycin A/DAPI and methyl-green/DAPI) are reported. Sites of methylation were visualized using antibodies against 5-methylcytosine. Digestion of aye-aye fixed metaphase chromosomes with the restriction endonuclease HaeIII produced G-banding. No other restriction enzymes tested produced clear G- or C-banding patterns. Ag-staining of the nucleolar organizer regions (NORs) revealed the location of rDNA sites on the short arms of the smallest pairs of acrocentric chromosomes, 13p and 14p.


Prospective multicenter study of second-trimester nuchal skinfold thickness in unaffected and Down syndrome pregnancies.
To determine the distribution of nuchal skinfold thickness in normal and Down syndrome pregnancies and to evaluate the use of this sonographic measurement as a screening test for fetal Down syndrome. A prospective, multicenter, population-based study was performed by experienced obstetric sonographers on 1382 women with sonographically normal fetuses undergoing second-trimester amniocentesis for the indication of advanced maternal age. A standard, well-defined sonographic image was obtained at all collaborating centers. The distributions of nuchal skinfold thickness were compared between euploid and Down syndrome fetuses. There were 1346 chromosomally normal pregnancies, 13 fetuses with Down syndrome (1:106), and 23 other chromosome abnormalities. Seventeen fetuses had measurements of 6 mm or greater, and one of these had Down syndrome. The median nuchal skinfold thickness in Down syndrome was 3.2 mm and in euploid fetuses was 3.1 mm. By the Mann-Whitney rank-sum test, there was no statistically significant difference in nuchal skinfold between the euploid and Down syndrome fetuses (P = .5). Overall, using a nuchal skinfold thickness of 6 mm or greater as a screening test, the detection rate for Down syndrome was one of 13 (8%), the false-positive rate was 16 of 1382 (1.2%), the positive predictive value was one of 17 (6%), and the probability of detecting Down syndrome was 6.5%. In this investigation, excess nuchal skinfold thickness was a poor and unreliable screening test for Down syndrome.


Cellular plasmid content and cloned-gene expression: some useful equations.
Cellular plasmid content determines the yield of closed-gene product, affects plasmid replication, and influences the behavior of the culture by dictating the extent of metabolic burden on the host cell and plasmid segregation at cell division. Hence, it is a variable of primary importance in the study of recombinant cell cultures. In this article, equations are developed to enable the conversion of experimental determinations of cellular plasmid content into theoretically important units. The importance of different units in characterizing plasmid effect on cell response is highlighted. Also, equations that relate cellular plasmid content to cloned-gene expression are developed and successfully tested on several sets of data from literature.


Left ventricular structural characteristics in Cushing's syndrome.
The aim of the present study was to assess structural characteristics of the left ventricle by echocardiography in a group of patients with Cushing's syndrome compared with a control population. Eighteen patients with Cushing's syndrome and 18 controls, matched for sex, age, body weight, body surface area, blood pressure (BP) and duration of hypertension were investigated by M-mode (2-D derived) echocardiography. In each of the two groups, 11 of 18 subjects were hypertensive. Relative wall thickness (RWT) was above normal (> 0.45) in 11 (five normotensive and six hypertensive) of 18 patients with Cushing's syndrome and in two (hypertensive) of 18 controls. Left ventricular mass index was abnormal in three (one normotensive and two hypertensive) patients with Cushing's syndrome and in four hypertensive controls. All other systolic function indices were within normal and similar in both groups. No correlation was found between RWT and BP as well as between RWT and urinary cortisol levels in patients with Cushing's syndrome. A significant correlation was found between RWT and duration of disease. Echocardiography after successful surgery showed normalisation of RWT in five of six patients in whom it was previously abnormal. Our data suggest that time factor, i.e. long-lasting exposure to increased cortisol, rather than hormone or BP levels is the most relevant determinant of left ventricular concentric remodeling in patients with Cushing's syndrome.


The Role of Laparoscopy in Abdominal Trauma: A 10-Year Review.
Laparoscopy is accepted in penetrating abdominal trauma (PAT), but its role in blunt trauma (BAT) remains a controversial one. Our study assessed the utility of diagnostic laparoscopy (DL) and therapeutic laparoscopy (TL) in abdominal trauma between December 2006 and January 2016. We analysed the indication for laparoscopy, type of lesions, TL, conversion rate, complications and length of hospital stay. 49 patients had a DL: 42 males and 7 females, with a mean age of 36.1+-13.3. We had 20 PAT and 30BAT. The indications for laparoscopy were: diagnosis of penetration in PAT, suspicion of hollow organ injury or diaphragm injury, active bleeding in organ injuries in BAT. 11/48 of preoperative ultrasounds and 4/48 of CT's were false negative. In 3 of 20 PAT, DL was negative and in 4 nontherapeutic. There were 4 TL's and 7 conversions. The main injuries in BAT were: 9 hollow organ perforations, 6 mesenteric lacerations, 2 diaphragmatic and 2 splenic injuries. There were 10 TL's, 9 conversions and 14 TL. The operative time and length of hospital stay was higher in the conversion group. There were 6 complications and 3 mortalities. There were no missed injuries. An unnecessary laparotomy was avoided in 18/49 cases (36.73%). In selected cases of PAT and BAT with equivocal clinical and imaging diagnosis, laparoscopy is a useful tool with therapeutic role, that reduces unnecessary laparotomies, complication rate and hospital stay.


Topography-Guided vs Wavefront-Optimized Surface Ablation for Myopia Using the WaveLight Platform: A Contralateral Eye Study.
to compare treatments with wavefront-optimized and topography-guided ablations. this prospective, randomized, contralateral study comprised 40 eyes (20 patients) with low to moderate myopia with or without astigmatism that underwent topography-guided photorefractive keratectomy (PRK) (ALLEGRO Topolyzer, Alcon Laboratories Inc) in one eye and wavefront-optimized PRK (ALLEGRETTO WAVE software version 2.020 default treatment, Alcon Laboratories Inc) in the fellow eye. Visual acuity, refractive error, contrast sensitivity, and Orbscan (Bausch & Lomb) 3- and 5-mm corneal irregularities were measured preoperatively and 3 and 6 months postoperatively. The results were compared between the two eyes. in both groups, preoperative corrected distance visual acuity (CDVA) (0.03±0.09 logMAR for topography-guided and 0.01 ± 0.06 logMAR for wavefront-optimized [P=.1]), 3-month postoperative uncorrected distance visual acuity (UDVA) (-0.0 1± 0.03 logMAR for topography-guided and -0.01 ± 0.03 logMAR for wavefront-optimized [P=.4]), and 6-month postoperative UDVA (0.01 ± 0.03 logMAR for topography-guided and 0.0 ± 0.01 logMAR for wavefront-optimized [P=.3]) were the same. All wavefront-optimized and 18 (90%) topography-guided eyes had UDVA of 20/20 or better. No significant differences were noted between groups in pre- and postoperative spherical and cylindrical refractive errors or corneal irregularity and contrast sensitivity measurements. Six months postoperatively, contrast sensitivity values at 3, 6, 12, and 18 cycles/degree were 5.7 ± 0.7, 6.0 ± 1.5, 6.1 ± 1.3, and 5.5 ± 1.5, respectively, in the topography-guided group, and 6.2 ± 0.6, 6.4 ±1.2, 6.4 ± 1.1, and 5.8 ± 1.3, respectively, in the wavefront-optimized group (P=.3, P=.5, P=.4, and P=.6, respectively). using the WaveLight excimer laser platform for PRK, CDVA and contrast sensitivity outcomes were statistically similar between the wavefront-optimized and topography-guided ablations in eyes with low to moderate myopia with and without astigmatism.


On the accuracy and precision of PLANET for multiparametric MRI using phase-cycled bSSFP imaging.
In this work we demonstrate how sequence parameter settings influence the accuracy and precision in T1 , T2 , and off-resonance maps obtained with the PLANET method for a single-component signal model. In addition, the performance of the method for the particular case of a two-component relaxation model for white matter tissue was assessed. Numerical simulations were performed to investigate the influence of sequence parameter settings on the accuracy and precision in the estimated parameters for a single-component model, as well as for a two-component white matter model. Phantom and in vivo experiments were performed for validation. In addition, the effects of Gibbs ringing were investigated. By making a proper choice for sequence parameter settings, accurate and precise parameter estimation can be achieved for a single-component signal model over a wide range of relaxation times at realistic SNR levels. Due to the presence of a second myelin-related signal component in white matter, an underestimation of approximately 30% in T1 and T2 was observed, predicted by simulations and confirmed by measurements. Gibbs ringing artifacts correction improved the precision and accuracy of the parameter estimates. For a single-component signal model there is a broad "sweet spot" of sequence parameter combinations for which a high accuracy and precision in the parameter estimates is achieved over a wide range of relaxation times. For a multicomponent signal model, the single-component PLANET reconstruction results in systematic errors in the parameter estimates as expected.


Manno(rhamno)biose-containing capsular polysaccharides of Klebsiella pneumoniae enhance opsono-stimulation of human polymorphonuclear leukocytes.
We tested the relationship between the capsular and the O-antigen structures and the ability of bacteria to trigger respiratory burst in human polymorphonuclear leukocytes (PMNL). Capsulated and non-capsulated variants as well as capsule-switched derivatives of Klebsiella serotypes bearing or lacking manno(rhamno)biose repeats in their capsular polysaccharides and expressing either mannose-rich or mannose-poor O antigens were tested for their ability to induce respiratory burst and survive in human PMNL. Luminol-enhanced chemiluminescence (CL) was measured to quantify respiratory burst. Intracellular survival was quantified by determining the viable counts of intracellular bacteria. K serotypes and the capsule-switched derivative lacking manno(rhamno)biose induced significantly lower CL than those expressing manno(rhamno)biose. Manno(rhamno)biose-lacking serotypes survived in the cells significantly better than serotypes expressing these repeats. C1q depletion did not affect CL induced by the manno(rhamno)biose-containing serotype, whereas factor B depletion revealed a significantly reduced CL. Likewise, EGTA in the presence of Mg(2+) significantly decreased CL, but the values were higher than those induced by the bacterium opsonized with factor B-depleted serum. In the presence of EGTA, Mg(2+)-treated factor B-depleted serum revealed a significant reduction in the CL response compared with the responses induced by opsonization with factor B-depleted serum alone. These results indicate, in addition to the alternative pathway, a manno(rhamno)biose pattern recognition of Klebsiella by PMNL probably by the complement lectin pathway.


Enhanced transformation of CO2 over microporous Ce-doped Zr metal-organic frameworks.
Metal-organic frameworks (MOF) have been studied extensively for the adsorption and catalytic conversion of CO2. However, previous studies mainly focused on the adsorption capabilities of partially or totally Ce substituted UiO-66, there are few studies focusing on transformation of the structure and catalytic activity of these materials. In this work, a series of Zr/Ce-based MOFs with UiO-66 architecture catalysts were prepared for the conversion of CO2 into value-added dimethyl carbonate (DMC). Owing to the different addition order of the two metals, significantly varied shapes and sizes were observed. Accordingly, the catalytic activity is greatly varied by adding a second metal. The different catalytic activities may arise from the different acid-base properties after Ce doping as well as the morphology and shape changes. Besides, the formation of terminal methoxy (t-OCH3) was found to be the rate limiting step. Finally, the reaction mechanism of CO2 transformation in the presence of a dehydrating agent was proposed.


Determination of ambroxol hydrochloride, guaifenesin, and theophylline in ternary mixtures and in the presence of excipients in different pharmaceutical dosage forms.
Determination of ternary mixtures of ambroxol hydrochloride, guaifenesin, and theophylline with minimum sample pretreatment and without analyte separation has been successfully achieved by using chemometric and RP-HPLC methods. The developed chemometric models are partial least squares (PLS) and genetic algorithm coupled with PLS. Data of the analyses were obtained from UV-Vis spectra of the studied drugs in different concentration ranges. These models have been successfully updated to be applied for determination of the proposed drugs in Farcosolvin syrup and in the presence of a syrup excipient (methyl paraben). In the developed RP-HPLC method, chromatographic runs were performed on an RP-C18 analytical column with the isocratic mobile phase 0.05 M phosphate buffer-methanol-acetonitrile-triethylamine (63.5 + 27.5 + 9 + 0.25, v/v/v/v, pH 5.5 adjusted with orthophosphoric acid) at a flow rate of 1.2 mL/min. The analytes were detected and quantified at 220 nm. The method was optimized in order to obtain good resolution between the studied components and to prevent interference from methyl paraben. Method validation was performed with respect to International Conference on Harmonization guidelines and the validation acceptance criteria were met in all cases. The proposed methods can be considered acceptable for QC of the studied drugs in pharmaceutical capsules and syrup. The results obtained by the suggested chemometric methods for determination of the studied mixture in different pharmaceutical preparations were statistically compared to those obtained by applying the developed RP-HPLC method, and no significant difference was found.


Factors for success of awake prone positioning in patients with COVID-19-induced acute hypoxemic respiratory failure: analysis of a randomized controlled trial.
Awake prone positioning (APP) improves oxygenation in coronavirus disease (COVID-19) patients and, when successful, may decrease the risk of intubation. However, factors associated with APP success remain unknown. In this secondary analysis, we aimed to assess whether APP can reduce intubation rate in patients with COVID-19 and to focus on the factors associated with success. In this multicenter randomized controlled trial, conducted in three high-acuity units, we randomly assigned patients with COVID-19-induced acute hypoxemic respiratory failure (AHRF) requiring high-flow nasal cannula (HFNC) oxygen to APP or standard care. Primary outcome was intubation rate at 28 days. Multivariate analyses were performed to identify the predictors associated to treatment success (survival without intubation). Among 430 patients randomized, 216 were assigned to APP and 214 to standard care. The APP group had a lower intubation rate (30% vs 43%, relative risk [RR] 0.70; CI95 0.54-0.90, P = 0.006) and shorter hospital length of stay (11 interquartile range [IQR, 9-14] vs 13 [IQR, 10-17] days, P = 0.001). A respiratory rate ≤ 25 bpm at enrollment, an increase in ROX index > 1.25 after first APP session, APP duration > 8 h/day, and a decrease in lung ultrasound score ≥ 2 within the first 3 days were significantly associated with treatment success for APP. In patients with COVID-19-induced AHRF treated by HFNC, APP reduced intubation rate and improved treatment success. A longer APP duration is associated with APP success, while the increase in ROX index and decrease in lung ultrasound score after APP can also help identify patients most likely to benefit. This study was retrospectively registered in ClinicalTrials.gov at July 20, 2021. Identification number NCT04477655. https://clinicaltrials.gov/ct2/show/NCT04477655?term=PRO-CARF&draw=2&rank=1.


Excess mortality during the COVID-19 pandemic (2020-2021) in an urban community of Bangladesh.
Measuring COVID-19-related mortality is vital for making public health policy decisions. The magnitude of COVID-19-related mortality is largely unknown in low- and middle-income countries (LMICs), including Bangladesh, due to inadequate COVID-19 testing capacity and a lack of robust civil registration and vital statistics systems. Even with the lack of data, cemetery-based death records in LMICs may provide insightful information on potential COVID-19-related mortality rates; nevertheless, there is a dearth of research employing cemetery-based death records. This study aimed to assess the excess mortality during the COVID-19 pandemic in an urban setting in Bangladesh using a cemetery-based death registration dataset. A total of 6,271 deaths recorded between January 2015 and December 2021 were analysed using a Bayesian structural time series model. Exploratory analysis found that the average monthly number of deaths was 69 during the pre-COVID-19 period (January 2015-February 2020), but significantly increased to 92 during the COVID-19 period (March 2020-December 2021). The increase in male deaths was twice as large as the increase in female deaths. Model-based results were not statistically significant (relative effect 17%, 95% credible interval: -18%, 57%), but there was an overall increasing trend during the COVID-19 period, and specific months or shorter periods had a substantial increase. This first-of-its-kind study in Bangladesh has assessed the excess mortality in an urban community during the COVID-19 pandemic. Cemetery-based death registration appears to aid in tracking population mortality, especially in resource-limited countries where collecting data on the ground is challenging during crisis periods; however, additional large-scale research is required.


CuO quantum-dot-sensitized mesoporous ZnO for visible-light photocatalysis.
How to extend ultraviolet photocatalysts to the visible-light region is a key challenge for solar-driven photocatalysis. Herein, we show that ultraviolet ZnO photocatalysts can present high visible-light photocatalytic activity when combined with CuO quantum dots (QDs; <3 nm). Theoretical analysis demonstrates that the quantum size effect plays a key role in the photoactivity of the CuO/ZnO composite. For CuO QDs smaller than 3 nm, the separated charges could transfer from CuO QDs to the conduction bands of ZnO due to quantum splitting of the CuO energy level and phonon compensation for the difference in the conduction band minimum of CuO and ZnO; however, this process would not occur with the disappearance of the quantum size effect. Further structural analysis demonstrates that interfacial charge separation and transfer between ZnO and CuO dominate the photocatalytic processes instead of a single CuO or ZnO surface. Compared with ZnO-noble metal structures (e.g., ZnO-Ag or ZnO-Au), these ZnO-CuO QD composites present wider absorption bands, higher visible photocatalytic efficiencies, and lower costs.


Antigen Receptor-Intrinsic Non-Self: The Key to Understanding Regulatory Lymphocyte-Mediated Idiotypic Control of Adaptive Immune Responses.
The clone-specific or idiotypic characters of B as well as T cell antigen receptors (BCRs/TCRs) are associated with (1) the third-complementarity-determining regions (CDR3s) that are created during V(D)J recombination (they scarcely occur in antibody light chains) and (2) BCR idiotopes created by somatic hypermutations (SHMs) during immune responses. Therefore, BCR/TCR idiotypic sites are antigen receptor-intrinsic Non-Self (AgR-iNS) portions that fulfill two tasks: serving as a crucial component of the epitope-binding paratope and serving as target sites for anti-idiotypic BCR/TCR paratopes of other anti-Non-Self clones that are contained in both normal repertoires. The antigen-induced immune response is thus directed not only toward the environmental stimulus but also against the AgR-iNS portions of the directly and further activated clones that form a subsiding idiotypic cascade. These idiotypic chain reactions form a completely integrated idiotypic control circuit among B and T cells which contains all regulatory T and B cells. However, this circuit cannot be viewed as a network of fixed interacting nodes but rather uses the genetic Self as reference. Hence, AgR-iNS offers a mechanistic understanding of regulatory lymphocyte-mediated idiotypic control of adaptive immune responses and reconciles clonal selection and idiotypic network theories hitherto believed to be incompatible.


Hepatitis B "immune" globulin: effectiveness in prevention of dialysis-associated hepatitis.
A randomized, double-blind, multicenter study of hepatitis prevention by immune serum globulin with high anti-HBs titer ("hepatitis B immune globulin") was carried out among 318 new patients and 296 staff members of renal dialysis units. Three milliliters of high titer globulin, repeated at four months, was compared with equal doses of intermediate or normal titer globulin. Among staff members, the cumulative percentages developing hepatitis or HBs Ag, or both, within eight months were 6.9, 11.7, and 11.1 in the high, intermediate, and normal titer groups respectively. The lower incidence associated with high titer globulin was not significant (P greater than 0.05). However, among the patients the respective percentages were 7.9, 21.3, and 23.1 and the lower incidence in the high titer globulin group was significant.


The G-protein-coupled receptors GPR3 and GPR12 are involved in cAMP signaling and maintenance of meiotic arrest in rodent oocytes.
In mammalian and amphibian oocytes, the meiotic arrest at the G2/M transition is dependent on cAMP regulation. Because genetic inactivation of a phosphodiesterase expressed in oocytes prevents reentry into the cell cycle, suggesting autonomous cAMP synthesis, we investigated the presence and properties of the G-protein-coupled receptors (GPCRs) in rodent oocytes. The pattern of expression was defined using three independent strategies, including microarray analysis of GV oocyte mRNAs, EST database scanning, and RT-PCR amplification with degenerated primers against transmembrane regions conserved in the GPCR superfamily. Clustering of the GPCR mRNAs from rat and mouse oocytes indicated the expression of the closely related Gpr3, Gpr12, and Edg3, which recognize sphingosine and its metabolites as ligands. Expression of these mRNAs was confirmed by RT-PCR with specific primers as well as by in situ hybridization. That these receptors are involved in the control of cAMP levels in oocytes was indicated by the finding that expression of the mRNA for Gpr3 and Gpr12 is downregulated in Pde3a-deficient oocytes, which have a chronic elevation of cAMP levels. Expression of GPR3 or GPR12 in Xenopus laevis oocytes prevented progesterone-induced meiotic maturation, whereas expression of FSHR had no effect. A block in spontaneous oocyte maturation was also induced when Gpr3 or Gpr12 mRNA was injected into mouse oocytes. Downregulation of GPR3 and GPR12 caused meiotic resumption in mouse and rat oocytes, respectively. However, ablation of the Gpr12 gene in the mouse did not cause a leaky meiotic arrest, suggesting compensation by Gpr3. Incubation of mouse oocytes with the GPR3/12 ligands SPC and S1P delayed spontaneous oocyte maturation. We propose that the cAMP levels required for maintaining meiotic arrest in mouse and rat oocytes are dependent on the expression of Gpr3 and/or Gpr12.


Mild idiopathic lateral cerebral ventricular dilatation in utero: sonographic evaluation.
The authors prospectively studied 20 fetuses with mild dilatation of the lateral cerebral ventricles but no other detectable central nervous system abnormality. One case (5%) occurred in a diabetic pregnancy, and three (15%) involved twin pregnancies. Fifteen (75%) fetuses were male, and one (5%) had trisomy 21. Postnatal follow-up at 15-31 months showed a normal outcome in eight cases (40%), an uncertain prognosis in four cases (20%), and death in eight cases (40%). Serial antenatal sonograms were obtained in 17 cases. Among the eight cases with a normal outcome, seven demonstrated no additional sonographic abnormalities and six showed resolution of the ventricular dilatation antenatally. Conversely, all 12 fetuses with demise or an uncertain prognosis demonstrated additional sonographic abnormalities, and six showed stable or progressive ventricular dilatation on follow-up sonograms. Since mild idiopathic lateral ventricular dilatation has a widely variable prognosis, antenatal detection of this finding warrants search for additional findings and follow-up sonography.


Characterization of the mechanism of cellular and cell free protein synthesis inhibition by an anti-tumor ribonuclease.
Onconase, a protein with anti-tumor activity, causes potent inhibition of protein synthesis in the rabbit reticulocyte lysate (IC50 10(-11) M) and when microinjected into Xenopus oocytes (IC50 10(-10) M). Onconase is a member of the RNase A superfamily; however, unlike RNase A, the mechanism of protein synthesis inhibition does not involve apparent degradation of lysate or cellular ribosomal RNAs. Rather, reticulocyte and oocyte tRNA is hydrolyzed after Onconase treatment. Furthermore, re-addition of tRNA to Onconase pretreated lysates or oocytes restores the translational capacity of the system. Taken together these results suggest that Onconase causes potent protein synthesis inhibition by a mechanism involving inactivation of cellular tRNA.


Treatment of murine Th1- and Th2-mediated inflammatory bowel disease with NF-kappa B decoy oligonucleotides.
The Th1 and Th2 T cell responses that underlie inflammatory bowel diseases (IBDs) are likely to depend on NF-kappaB transcriptional activity. We explored this possibility in studies in which we determined the capacity of NF-kappaB decoy oligodeoxynucleotides (decoy ODNs) to treat various murine models of IBD. In initial studies, we showed that i.r. (intrarectal) or i.p. administration of decoy ODNs encapsulated in a viral envelope prevented and treated a model of acute trinitrobenzene sulfonic acid-induced (TNBS-induced) colitis, as assessed by clinical course and effect on Th1 cytokine production. In further studies, we showed that NF-kappaB decoy ODNs were also an effective treatment of a model of chronic TNBS-colitis, inhibiting both the production of IL-23/IL-17 and the development of fibrosis that characterizes this model. Treatment of TNBS-induced inflammation by i.r. administration of NF-kappaB decoy ODNs did not inhibit NF-kappaB in extraintestinal organs and resulted in CD4+ T cell apoptosis, suggesting that such treatment is highly focused and durable. Finally, we showed that NF-kappaB decoy ODNs also prevented and treated oxazolone-colitis and thus affect a Th2-mediated inflammatory process. In each case, decoy administration led to inflammation-clearing effects, suggesting a therapeutic potency applicable to human IBD.


Conformations of Protonated AlaDap and DapAla Characterized by IRMPD Spectroscopy and Molecular Modeling.
Oligopeptides containing 2,3-diaminopropionic acid (Dap) serve as a unique model to study conformational effects on the ionizability of a side-chain group. In this study, conformations of acetylated isomeric dipeptide ions containing alanine (Ala) and Dap, AlaDapH+ and DapAlaH+, are studied by infrared multiple photon dissociation (IRMPD) spectroscopy and computation. The IRMPD spectra are characterized in detail by comparing them with theoretical IR spectra of a set of low-energy conformations calculated at the ωB97X-D/6-311+G(d) level of theory. The averaged IR spectra according to the Boltzmann distribution of the set of conformations have a good match to the IRMPD spectra. The characteristic amide I band of AlaDapH+ appears to be downshifted compared to that of DapAlaH+. The relative positions of the amide band suggest a stronger hydrogen-bonding interaction between the charged side-chain amino group and the amide carbonyl groups in AlaDapH+ than in DapAlaH+. The stronger hydrogen bonding in the former is likely due to a better alignment of the N-H and O═C bonds, which enables an effective sequestering of the positive charge at the amino group. The effect results in a higher proton affinity of acetylated dipeptides with the Dap residue at the C-terminus.


Tolerance of Micronized Mineral Pigments for Intrastromal Keratopigmentation: A Histopathology and Immunopathology Experimental Study.
To study the tolerance and biocompatibility of mineral pigments for corneal pigmentation histopathologically and immunologically in an experimental animal model. Manual intralamellar keratopigmentation was performed in 28 New Zealand white rabbits using micronized mineral pigments. Histopathological examination was performed 3 months after the surgery to determine the level of pigment diffusion, the level of inflammation, and the presence/absence of neovascularization. An immunological analysis was also performed. No pigment diffusion or changes in color, inflammation, or neovascularization were detected in the treated eyes. Histopathological examination corroborated clinical results regarding inflammation. Pigmented corneas showed a good cosmetic appearance without signs of ocular toxicity. From the immunological perspective, the pigments do not generate an inflammatory response in the rabbit cornea or in vitro. Micronized mineral pigments could be a valid alternative treatment for corneal pigmentation. Manual intralamellar keratopigmentation technique presented good cosmetic appearance without adverse effects in the treated eyes.


Auxin 2012: a rich mea ho'oulu.
In December 2012, scientists from around the world gathered in Waikoloa, Hawaii for 'Auxin 2012', a meeting organized by Paula McSteen (University of Missouri, USA), Ben Scheres (Utrecht University, The Netherlands) and Yunde Zhao (University of California, San Diego, USA). At the meeting, participants discussed the latest advances in auxin biosynthesis, transport and signaling research, in addition to providing context for how these pathways intersect with other aspects of plant physiology and development. Fittingly, the meeting began with a traditional Hawaiian ceremony that recognized the centrality of the harvest of plant life ('mea ho'oulu' in Hawaiian) for continued human survival.


Effects of gingerols-rich extract of ginger on growth performance, serum metabolites, meat quality and antioxidant activity of heat-stressed broilers.
In order to investigate the effects of dietary ginger extract (GE) enriched in gingerols on broilers under heat stress (HS) from 21 to 42 days of age, a total of 144 Ross 308 male broilers were randomly allocated to three groups with six replicates of eight broilers per replicate. Broilers in the control group were raised at 22 °C and fed a basal diet, and broilers in the other two groups were raised under cyclic HS (34 °C from 9:00 to 17:00 and at 22 °C for the rest of the time) and fed the basal diet with or without 1000 mg/kg GE. Supplementation of GE improved (P < 0.05) final body weight, average daily gain and feed conversion ratio of broilers under HS, and tended (P < 0.1) to increase breast muscle yield. The alterations of serum total protein, albumin, total cholesterol levels and aspartate aminotransferase activity under HS were reversed (P < 0.05) by GE, which also decreased (P < 0.05) serum triglyceride level and alanine aminotransferase activity. The decreased redness (a* value) and increased drip loss of breast muscle induced by HS were restored (P < 0.05) by GE. Moreover, GE supplementation increased (P < 0.05) total antioxidant capacity and decreased (P < 0.05) malondialdehyde content in liver and breast muscle, and increased (P < 0.05) glutathione peroxidase activity in serum and breast muscle. In conclusion, dietary GE supplementation restored growth performance, serum metabolites and meat quality of broilers under HS possibly by improving antioxidant activity.


Pulmonary haemangiosarcoma with main pulmonary artery thrombosis imitating subacute pulmonary embolism with infarction.
We report a patient with subacute pulmonary hypertension caused by unilateral massive pulmonary artery thrombosis due to a pulmonary haemangiosarcoma of the lower lobe with pulmonary arterial and bronchial invasion. The patient was misdiagnosed as having subacute pulmonary embolism and underwent thrombolytic therapy complicated by severe pulmonary haemorrhage. The imaging features of pulmonary artery thrombosis with underlying malignancy and their differential diagnosis are discussed.


Accurate identification of RNA D modification using multiple features.
As one of the common post-transcriptional modifications in tRNAs, dihydrouridine (D) has prominent effects on regulating the flexibility of tRNA as well as cancerous diseases. Facing with the expensive and time-consuming sequencing techniques to detect D modification, precise computational tools can largely promote the progress of molecular mechanisms and medical developments. We proposed a novel predictor, called iRNAD_XGBoost, to identify potential D sites using multiple RNA sequence representations. In this method, by considering the imbalance problem using hybrid sampling method SMOTEEEN, the XGBoost-selected top 30 features are applied to construct model. The optimized model showed high Sn and Sp values of 97.13% and 97.38% over jackknife test, respectively. For the independent experiment, these two metrics separately achieved 91.67% and 94.74%. Compared with iRNAD method, this model illustrated high generalizability and consistent prediction efficiencies for positive and negative samples, which yielded satisfactory MCC scores of 0.94 and 0.86, respectively. It is inferred that the chemical property and nucleotide density features (CPND), electron-ion interaction pseudopotential (EIIP and PseEIIP) as well as dinucleotide composition (DNC) are crucial to the recognition of D modification. The proposed predictor is a promising tool to help experimental biologists investigate molecular functions.


Flexible blue-emitting encapsulated organic semiconductor DFB laser.
Mechanically flexible distributed feedback (DFB) lasers are fabricated by a low-cost approach using soft-lithography from a holographic master grating. The gain material is a star-shaped oligofluorene providing laser emission from 425 to 442 nm with a soft pump threshold at 14.4 μJ/cm (2.7 kW/cm). Encapsulation of the devices enables stable operation in ambient atmosphere at a 1/e degradation energy dosage of 53 J/cm.


Hypertensive disorders during pregnancy are associated with reduced severe intraventricular hemorrhage in very-low-birth-weight infants.
To determine differences in severe intraventricular hemorrhage (IVH) between very-low-birth-weight (≤1500 g, VLBW) infants born to mothers with and without hypertensive disorders (HD). Retrospective analysis from the Optum Neonatal Database. The primary outcome of interest was severe IVH (grade 3 or 4). Secondary outcomes included other neonatal morbidities, mortality, and length of hospitalization. Outcomes were compared between VLBW infants born to mothers with and without HD. A total of 5456 infants met inclusion criteria. After multivariable regression analysis, risks of severe IVH and bronchopulmonary dysplasia (BPD) were lower ([OR 0.42, 95% CI 0.33-0.89, p = 0.01] and [OR 0.75, 95% CI 0.58-0.97, p = 0.03], respectively) and median length of hospitalization was decreased in the HD group (49 versus 61 days, p < 0.001). VLBW infants born to mothers with HD have a decreased risk of severe IVH, BPD, and a shorter duration of hospitalization.


Enhancement of therapeutic effectiveness by combining liposomal honokiol with cisplatin in ovarian carcinoma.
Honokiol, a well-tolerated natural product, can inhibit the proliferation of cancer cells. But its water insolubility hampers its systemic administration for therapy of cancer. As a drug delivery system, the pegylated liposome (PEGL) can increase the water solubility and targeting of the drug. Honokiol has been successfully encapsulated by PEGL in our laboratory. We wondered whether the combination treatment with pegylated liposomal honokiol (H-PEGL) and cisplatin (DDP) could improve the antitumor efficacy in ovarian carcinoma. H-PEGL could introduce apoptosis of SKOV3 cells in vitro, which was quantified by flow cytometric analysis, and the cellular morphologic changes were determined by propidium iodide staining. In a human ovarian carcinoma mouse model, combination treatment with H-PEGL (0.4 mg/day for 30 days; intraperitoneal) and DDP (5 mg/kg on days 7, 11, 15, 19; intraperitoneal) acted synergistically to inhibit tumor growth by 91.48% without notable toxicity, but H-PEGL and DDP alone only inhibit tumor growth by 66.83% and 52.5% as compared to the NaCl solution control, respectively. Assessment of microvessel density and apoptosis index by CD31 and terminal deoxynucleotidyl transferase-mediated nick end labeling immunohistochemistry respectively suggested that the antitumor activity of H-PEGL is mediated by angiogenesis inhibition and introduction of apoptosis. Our results showed us a splendid prospect of the clinical application of combination treatment on patients suffering from ovarian cancer with H-PEGL and DDP.


Functional bowel symptoms in quiescent inflammatory bowel diseases: role of epithelial barrier disruption and low-grade inflammation.
To determine the role of colonic barrier defects and low-grade inflammation in irritable bowel syndrome (IBS)-like symptoms in quiescent inflammatory bowel disease (IBD). Caecal biopsies were collected from 51 IBS, 49 quiescent IBD (31 Crohn's disease (CD) and 18 ulcerative colitis (UC)) patients and 27 controls. IBS was assessed using the Rome III criteria and the IBS severity score. Epithelial barrier integrity was evaluated by determining the paracellular permeability of biopsies mounted in Ussing chambers and the mRNA expression of tight junction proteins (ZO-1, α-catenin and occludin). Low-grade inflammation was evaluated by counting cells, including intraepithelial lymphocytes (IELs), eosinophils and mast cells, and by determining the mRNA and protein expression of tumour necrosis factor (TNF)-α in biopsies and culture supernatants. IBS-like symptoms were present in 35.4 and 38% of CD and UC patients, respectively. Paracellular permeability was significantly increased in both quiescent IBD with IBS-like symptoms and IBS compared with quiescent IBD without IBS-like symptoms (p<0.01, respectively) or controls (p<0.01, respectively). Significantly lower expression of ZO-1 and α-catenin was detected in IBS and quiescent IBD with IBS-like symptoms. IELs and TNF-α were significantly increased in quiescent IBD with IBS-like symptoms, but not in IBS. In quiescent IBD, IBS-like symptoms related to persistent subclinical inflammation associated with increased colonic paracellular permeability. A persistent increase in TNF-α in colonic mucosa may contribute to the epithelial barrier defects associated with abdominal pain in quiescent IBD, but not in IBS. Optimisation of anti-inflammatory therapy may be considered in quiescent IBD with IBS-like symptoms.


Diagnosis of upper aerodigestive tract tumours using autofluorescence endoscopy in south east asian patients.
Diagnosis of upper aerodigestive tract tumours using autofluorescence endoscopy in south east asian patients. Autofluorescence is a highly sensitive, and specific, complementary diagnostic tool for the photodiagnosis of head and neck squamous cell carcinomas. Together with ease of use, these properties suggest that autofluorescence, used alongside white light endoscopy, could be a promising tool for the screening of high-risk populations. The aim of this study was to evaluate its effectiveness in detecting tumours involving the upper aerodigestive tract, in comparison with histopathologic examination. A cross-sectional prospective study was carried out from June 2011 till March 2012. Forty-five patients with clinical evidence of suspicious lesions involving the upper aerodigestive tract were enrolled and examined using conventional white light, and autofluorescence endoscopy. A biopsy of each lesion was subsequently submitted for histopathologic examination. Using histology as our gold standard, we compared the sensitivity, specificity, and predictive values of autofluorescence endoscopy in detecting upper aerodigestive tract tumours. In comparison to histopathologic examination, the sensitivity of autofluorescence endoscopy was 95%, with a specificity of 74% (P value<0.001). The positive and negative predictive values were 78%, and 94% respectively. These data confirm a statistically significant correlation between autofluorescence and histopathologic diagnoses. Autofluorescence endoscopy was effective in detecting upper aerodigestive tract tumours, with excellent discrimination between benign and malignant phenotypes; this methodology is an ideal adjunct to white light endoscopy.


COX-2 and prostaglandins in atherosclerosis.
Arachidonic acid metabolism is involved in acute ischemic syndromes affecting the coronary or cerebrovascular territory, as demonstrated by biochemical measurements of eicosanoid biosynthesis and the results of inhibitor trials in these settings. In particular, the efficacy of low-dose aspirin in reducing the complications of acute ischemic syndromes has focused attention on the cyclooxygenase (COX) pathway of arachidonic acid metabolism and its products, collectively termed prostanoids. Two cyclooxygenase (COX)-isozymes have been characterized, COX-1 and COX-2, that differ in terms of regulatory mechanisms of expression, tissue distribution, substrate specificity and preferential coupling to upstream and downstream enzymes. While the role of platelet COX-1 in acute ischemic diseases is firmly established, the role of COX-2 in atherothrombosis is still uncertain. Studies from our group suggest that variable expression of upstream and downstream enzymes in the prostanoid biosynthesis may represent important determinants of the functional consequences of COX-2 expression and inhibition in different clinical settings.


Single small enhancing CT Lesions, with special reference to neurocysticercosis: How I treat.
Single small enhancing CT lesions (SSECTL) have been very commonly encountered in clinical practice. These lesions typically are small (often < 20 mm), enhancing as a ring lesion or a disc and with varying amounts of surrounding edema. Most SSECTL present as focal seizures. Once the diagnosis of SSECTL and likely to be a solitary cysticercus lesion is made, the patient is given appropriate AED therapy. Depending on the resolution pattern on repeat imaging performed at intervals not less than six months if patient remains asymptomatic, cysticidal therapy is instituted along with AEDs. Any deviation from the classical clinical or radiological patterns needs further evaluation and other etiologies described for the SSECTL will need to be ruled out, including that of tuberculosis. Largely these lesions resolve and the clinical condition remains benign and in most patients AEDs can be withdrawn in two to three years period.


Mothers supporting children with autistic spectrum disorders: social support, mental health status and satisfaction with services.
Parents of children with autistic spectrum disorders (ASDs) are more likely to experience serious psychological distress than parents of children with other developmental disabilities. To examine the impact of a range of factors on psychological wellbeing, interviews were undertaken with 68 mothers of children with ASDs to explore aspects of social support, mental health status and satisfaction with services. Findings indicated that over half of mothers screened positive for significant psychological distress and that this was associated with low levels of family support and with bringing up a child with higher levels of challenging behaviour. Mothers were more likely to report lower levels of support if they were a lone parent, were living in poor housing, or were the mother of a boy with ASD. The study also investigated areas of useful support and areas of unmet need, the latter including care breaks and advice needs.


COVID-19 Susceptibility Mapping Using Multicriteria Evaluation.
Objective: The purpose of this research was to investigate coronavirus disease (COVID-19) susceptibility in districts of Bangladesh using multicriteria evaluation techniques.Methods: Secondary data were collected from different government organizations, 120 primary surveys were conducted for calculating weights, and results were validated through 12 key people's interviews. Pairwise comparison matrixes were calculated for 9 factors and subfactors. The analytic hierarchy process used for calculating the susceptibility index and map was prepared based on the results.Results: According to the results, multiple causal factors might be responsible for COVID-19 spreading in Bangladesh. Dhaka might be vulnerable to COVID-19 due to a higher population, population density, and international collaboration. According to the pairwise comparison matrix, the consistency ratio for subfactors and factors was in the permissible limit (ie, less than 0.10). The highest factor weight of 0.2907 was found for the factors type of port. The maximum value for the susceptibility index was 0.435219362 for Chittagong, and the minimum value was 0.076174 for Naogaon.Conclusions: The findings of this research might help the communities and government agencies with effective decision-making.


A metal-free aromative cascade for the synthesis of diverse heterocycles.
A metal-free aromative cascade has been developed for the synthesis of diverse heterocycles from readily accessible hydroxy/aminochalcones and acid/alkyl halides. The cascade being by a base-mediated intramolecular aldol cyclization/dehydration sequence to provide a triene, which sets the stage for a 6π-electrocyclization/oxidative aromatization to access diverse heterocyclic scaffolds.


Docosahexaenoic Acid and Bronchopulmonary Dysplasia in Preterm Infants.
Studies in animals and in humans have suggested that docosahexaenoic acid (DHA), an n-3 long-chain polyunsaturated fatty acid, might reduce the risk of bronchopulmonary dysplasia, but appropriately designed trials are lacking. We randomly assigned 1273 infants born before 29 weeks of gestation (stratified according to sex, gestational age [<27 weeks or 27 to <29 weeks], and center) within 3 days after their first enteral feeding to receive either an enteral emulsion providing DHA at a dose of 60 mg per kilogram of body weight per day or a control (soy) emulsion without DHA until 36 weeks of postmenstrual age. The primary outcome was bronchopulmonary dysplasia, defined on a physiological basis (with the use of oxygen-saturation monitoring in selected infants), at 36 weeks of postmenstrual age or discharge home, whichever occurred first. A total of 1205 infants survived to the primary outcome assessment. Of the 592 infants assigned to the DHA group, 291 (49.1% by multiple imputation) were classified as having physiological bronchopulmonary dysplasia, as compared with 269 (43.9%) of the 613 infants assigned to the control group (relative risk adjusted for randomization strata, 1.13; 95% confidence interval [CI], 1.02 to 1.25; P=0.02). The composite outcome of physiological bronchopulmonary dysplasia or death before 36 weeks of postmenstrual age occurred in 52.3% of the infants in the DHA group and in 46.4% of the infants in the control group (adjusted relative risk, 1.11; 95% CI, 1.00 to 1.23; P=0.045). There were no significant differences between the two groups in the rates of death or any other neonatal illnesses. Bronchopulmonary dysplasia based on a clinical definition occurred in 53.2% of the infants in the DHA group and in 49.7% of the infants in the control group (P=0.06). Enteral DHA supplementation at a dose of 60 mg per kilogram per day did not result in a lower risk of physiological bronchopulmonary dysplasia than a control emulsion among preterm infants born before 29 weeks of gestation and may have resulted in a greater risk. (Funded by the Australian National Health and Medical Research Council and others; Australian New Zealand Clinical Trials Registry number, ACTRN12612000503820 .).


Active smoking and breast cancer risk: original cohort data and meta-analysis.
The relationship between active cigarette smoking and breast cancer risk remains controversial because of unresolved issues of confounding and dose response. To investigate these issues further, we analyzed data from 73 388 women in the American Cancer Society's Cancer Prevention Study II (CPS-II) Nutrition Cohort. Analyses were based on 3721 invasive breast cancer case patients identified during a median follow-up of 13.8 years. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated from multivariable-adjusted Cox proportional hazard regression models. P values were two-sided. We also conducted meta-analyses of our results with those published from 14 other cohort studies. In CPS-II, incidence was higher in current (HR = 1.24, 95% CI = 1.07 to 1.42) and former smokers (HR =1.13, 95% CI = 1.06 to 1.21) than in never smokers. Women who initiated smoking before menarche (HR = 1.61, 95% CI = 1.10 to 2.34) or after menarche but 11 or more years before first birth (HR = 1.45, 95% CI = 1.21 to 1.74) had higher risk (P trend = .03). No relationships were observed with other smoking parameters. Alcohol consumption did not confound associations with smoking status, although neither current nor former smoking were associated with risk among never drinkers (P interaction = .11). In meta-analyses, current (HR = 1.12, 95% CI = 1.08 to 1.16) and former smoking (HR = 1.09, 95% CI = 1.04 to 1.15) were weakly associated with risk; a stronger association (HR = 1.21, 95% CI = 1.14 to 1.28) was observed in women who initiated smoking before first birth. These results support the hypothesis that active smoking is associated with increased breast cancer risk for women who initiate smoking before first birth and suggest that smoking might play a role in breast cancer initiation.


Hippocampal Endothelin-1 decreases excitability of pyramidal neurons and produces anxiolytic effects.
Anxiety disorders contribute to the pathophysiology of psychiatric diseases, including major depression, substance abuse, and schizophrenia. The hippocampus is important for anxiety modulation. However, the mechanisms that control the neuronal activity of the hippocampus in anxiety are still not clear. We found that Endothelin-1 (ET1) mRNA in the hippocampus was down-regulated in high-anxiety mice. Neutralizing endogenous ET1 in the hippocampal CA1 enhanced anxiety-like behaviors. We next revealed that most expression of ET1 and its receptors in the CA1 takes place in pyramidal neurons, and the ET1 signaling pathway directly regulated the excitability of CA1 pyramidal neurons and glutamatergic synaptic neurotransmission. Finally, we proved that neutralizing endogenous CA1 ET1 produces anxiogenic effects on low-anxiety mice, whereas infusing exogenous ET1 into the CA1 alleviates the anxiety susceptibility of high-anxiety mice. Together, these results indicate that ET1 signaling is critical in maintaining the excitability of glutamatergic neurons in the hippocampus and, thus, in modulating anxiety-like behaviors. Because ET1 is a risk factor for ischemic stroke, our findings might also help to explain the potential mechanism of emotional abnormality in stroke.


SP1-mediated transcriptional activation of PTTG1 regulates the migration and phenotypic switching of aortic vascular smooth muscle cells in aortic dissection through MAPK signaling.
Pituitary tumor-transforming gene 1 (PTTG1) has been found to be associated with the process of cell proliferation and invasion, and is highly expressed in aortic dissection (AD). However, its potential role and underlying mechanism in AD remain uncertain. This study aims at elucidating the roles of specificity protein 1 (SP1) and PTTG1 in the migration and phenotypic switching of aortic vascular smooth muscle cells (VSMCs) in AD. Aortic samples were collected from 35 patients with AD for examination of PTTG1 expression in the tissues by qPCR, western blot and immunofluorescence. Human aortic vascular smooth muscle cells (HAVSMCs) were stimulated with platelet-derived growth factor-BB (PDGF-BB) to establish the cellular model of AD. PTTG1 expression in VSMCs was also examined by qPCR and western blot. Cell viability was detected by CCK-8, cell proliferation by EdU staining and cell migration by wound healing and transwell. Western blot was then performed to assay migration-related proteins. After interference with PTTG1, the levels of smooth muscle pthenotypic switch markers smooth muscle protein 22 alpha (SM22-α) and osteopontin (OPN) were detected by qPCR, western blot and immunofluorescence. The binding of SP1 and PTTG1 was verified with dual-luciferase reporter assay and chromatin immunoprecipitation assay (ChIP). PTTG1 overexpression was found in AD patients. Interference with PTTG1 attenuated the proliferation and migration of PDGF-BB-stimulated HAVSMCs, in addition to their switching from contractile phenotype to synthetic phenotype. Transcription factor SP1 was up-regulated in PDGF-BB-stimulated HAVSMCs, combined with PTTG1 promoter sequence and regulated PTTG1 expression, whose overexpression reversed the effects of PTTG1 interference on cell proliferation, migration and phenotypic switching. SP1 transcriptional activation of PTTG1 activated MAPK/ERK signaling pathway. In conclusion, SP1 transcriptional activation of PTTG1 regulates the migration and phenotypic transformation of HAVSMCs in AD by MAPK Signaling.