Transplantation of human skeletal muscle-derived progenitor cells ameliorates knee osteoarthritis in streptozotocin-induced diabetic mice.
The epidemiological and experimental evidence suggests that diabetes can be an independent risk factor for osteoarthritis. The osteoarthritis-like cartilage damage has been shown in streptozotocin-induced diabetic mice. The therapeutic effects of human skeletal muscle-derived progenitor cells (HSMPCs) on diabetic osteoarthritis still remain unclear. Here, we investigated the therapeutic potential of HSMPCs on diabetic knee osteoarthritis. The in vitro chondrogenic ability of HSMPCs was determined by pellet culture assay. Male mice were used to develop the model of streptozotocin-induced type 1 diabetes and its related osteoarthritis. HSMPCs were injected intra-articularly to rescue osteoarthritis. Protein expressions of advanced glycation end-products, cyclooxygenase-2, and type-2 collagen in tissues were determined by immunohistochemistry. The pellet culture assay showed that HSMPCs cultured in differentiation medium for chondrogenesis significantly produced larger pellets with an overproduction of extracellular matrix than in growth medium. In in vivo experiments, intra-articular injection of HSMPCs for 4 weeks significantly prevented the progression of degenerative changes in the cartilage of streptozotocin-induced diabetic mice, including an obvious increase of total articular cartilage thickness and a decrease of fibrous cartilage thickness. HSMPCs transplantation also exerted the decline in advanced glycation end-products and cyclooxygenase-2 protein expression, but increased the type-2 collagen protein expression in streptozotocin-induced osteoarthritic cartilages. Moreover, HSMPCs transplantation also inhibited the increased serum interleukin-6 and matrix metalloproteinase-3 levels in diabetic mice. These results demonstrated for the first time that HSMPCs transplantation ameliorates cartilage degeneration in diabetes-related osteoarthritis mice. These findings suggest that HSMPCs transplantation may apply as a potential therapeutic use of diabetes-related osteoarthritis. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1886-1893, 2017.


Iron-assisted biological wastewater treatment: Synergistic effect between iron and microbes.
Iron-assisted biological wastewater treatment processes have shown a promising potential in removing various types of contaminants. Synergistic effects between iron and microbes on the contaminant degradation make the role of iron beyond that of a nutritional necessity. Exploration of the synergistic mechanisms and the interactions between iron species and microbes and their metabolic products in bio‑iron systems is therefore of significant importance. Iron, including zero-valent iron, ferrous/ferric ions and iron minerals are all reported to be capable of enhancing specific contaminant removals. Although the main role of different iron species in stimulating biological process may differ between each other, their similar transformation pathways may bring us useful information about bio‑iron systems. In this paper, an overview of iron-assisted biological wastewater treatments, including anaerobic digestion, S and Cl reduction, N and P removal, heavy metal immobilization, aromatic and halogenated hydrocarbon compounds degradation, and sludge granulation is provided. Also, the potential synergistic effects between iron and microbes involved in these processes are explored. Furthermore, the main advantages, limitations, and challenges for the development of iron-assisted treatment processes are envisaged.


Use of a modified chitosan-dextran gel to prevent peritoneal adhesions in a porcine hemicolectomy model.
The prevention of peritoneal adhesions following abdominal surgery remains an ongoing challenge, with the ideal product for adhesion reduction still elusive. This study examines the outcome of application of a modified chitosan-dextran (CD) gel within the intraperitoneal cavity of a porcine model to assess its effect on adhesion formation. This is a unique synthetic gel, its active ingredients being succinyl chitosan and dextran aldehyde. Twenty female domestic pigs were randomized to undergo surgery alone or to receive CD gel at the time of surgery. The surgical procedures comprised of laparotomy and ileocaecal resection with ileo-colic anastomosis. At postoperative d 21, a laparoscopy was performed, and adhesions graded using a predetermined adhesion measurement score. Adhesiolysis was then performed and CD gel applied to all animals. After a further 21 d animals were euthanized and adhesions graded using the same scoring regimen. Adhesions involving the wound were significantly reduced following application of the gel at the time of open surgery (P = 0.01). Following adhesiolysis and further application of the gel, a decrease in adhesion scores involving the bowel was noted (P = 0.03). No significant adverse outcomes were observed with application of the gel, specifically no anastomotic leak occurred. Chitosan-dextran gel is a well tolerated hydrogel with beneficial properties, which has been designed in an effort to reduce postoperative peritoneal adhesion formation. The observed reduction of adhesion scores following the application of the gel is encouraging and should stimulate further development of this product. The lack of adverse outcomes following application of CD gel is reassuring when used around a bowel anastomosis.


Spot size and quality of scanning laser correction of higher-order wavefront aberrations.
To investigate the effect of laser spot size on the outcome of aberration correction with scanning laser corneal ablation. Cleveland Clinic Foundation, Cleveland, Ohio, USA. Corrections of wavefront aberrations of Zernike modes from the second to eighth order were simulated. Gaussian and top-hat beams of 0.6 to 2.0 mm full-width-half-maximum diameters were modeled. The fractional correction and secondary aberration (distortion) were evaluated. Using a distortion/correction ratio of less than 0.5 as a cutoff for adequate performance, a 2.0 mm or smaller beam was adequate for spherocylindrical correction (Zernike second order), a 1.0 mm or smaller beam was adequate for correction of up to fourth-order Zernike modes, and a 0.6 mm or smaller beam was adequate for correction of up to sixth-order Zernike modes. Since ocular aberrations above the Zernike fourth order are relatively insignificant in normal eyes, current scanning lasers with a beam diameter of 1.0 mm or less are theoretically capable of eliminating most higher-order aberrations.


Synthesis of novel substituted 2-phenylpyrazolopyridines with potent activity against herpesviruses.
Herpesviruses are a significant source of human disease; amongst these herpes simplex virus 1 (HSV-1) and HSV-2 are very prevalent and cause recurrent infections. We recently identified a pyrazolo[1,5-a]pyridine scaffold that showed promising activity against HSV-1 and HSV-2 in Vero cell antiviral assays. Here, we describe the synthesis and anti-herpetic activity of several 3-pyrimidinyl-2-phenylpyrazolo[1,5-a]pyridines with differing 2-phenyl substitution patterns. Approaches to rapidly access a number of analogs with different 2-phenyl substitution patterns are outlined. Several of the compounds described have comparable activity to acyclovir against HSV-1 and HSV-2.


Hydrophilic polydopamine-coated magnetic graphene nanocomposites for highly efficient tryptic immobilization.
In this work, polydopamine-coated magnetic graphene (MG@PDA) nanocomposites were synthesized by a facile method. Trypsin was then directly immobilized on the surface of the nanocomposites through simple PDA chemistry with no need for introducing any other coupling groups. The as-made MG@PDA nanocomposites inherit not only the large surface area of graphene which makes them capable of immobilizing high amount of trypsin (up to 0.175 mg/mg), but also the good hydrophilicity of PDA which greatly improves their biocompatibility. Moreover, the strong magnetic responsibility makes them easy to be separated from the digested peptide solution when applying a magnetic field. The feasibility of the trypsin-immobilized MG@PDA (MG@PDA-trypsin) nanocomposites for protein digestion was investigated and the results indicated their high digestion efficiency in a short digestion time (10 min). In addition, the reusability and stability of the MG@PDA-trypsin nanocomposites were also tested in our work. To further confirm the efficiency of MG@PDA-trypsin nanocomposites for proteome analysis, they were applied to digest proteins extracted from skimmed milk, followed by nano RPLC-ESI-MS/MS analysis, and a total of 321 proteins were identified, much more than those obtained by 16-h in-solution digestion (264 proteins), indicating the great potential of MG@PDA-trypsin nanocomposites as the supports for high-throughput proteome study.


Carcinoma of the ureter with extensive squamous differentiation and positive immunoperoxidase staining for carcinoembryonic antigen: a case report.
A case of ureteral carcinoma with extensive squamous differentiation and positive staining for carcinoembryonic antigen by the immunoperoxidase method is presented. Ureteral carcinoma should be added to the list of tumors that may produce carcinoembryonic antigen or antigen-like material.


Children's oppositional defiant disorder symptoms make parents difficult to be nice: Longitudinal association among parent emotion regulation, child emotion regulation and children's oppositional defiant disorder symptoms in Chinese children with oppositional defiant disorder.
The current study aims to clarify the longitudinal relations among parent emotion regulation (ER), child ER, and children's oppositional defiant disorder (ODD) symptoms. In the current study, parents of 275 children (195 boys, 70.1%) with ODD symptoms (Mage = 9.32 years, SD = 1.64) reported their ER using the Difficulties in Emotion Regulation Scale, child ERs using the Emotion Regulation Checklist, and children's ODD symptoms using the eight symptoms indicated in the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR) at three time points (T1, T2, and T3) within 2 years. Results indicated the longitudinal relationships between parent ER and children's ODD symptoms were directly influenced by each other. Children's ODD symptoms had important effects on both child ER and parent ER. Findings suggested that to reduce children's ODD symptoms, it is necessary not only to improve child ER but also to improve parent ER.


The sense of agency during skill learning in individuals and dyads.
The sense of agency has received much attention in the context of individual action but not in the context of joint action. We investigated how the sense of agency developed during individual and dyadic performance while people learned a haptic coordination task. The sense of agency increased with better performance in all groups. Individuals and dyads showed a differential sense of agency after initial task learning, with dyads showing a minimal increase. The sense of agency depended on the context in which the task was first learnt, as transfer from joint to individual performance resulted in an illusory boost in the sense of agency. Whereas the quality of performance related to the sense of agency, the generated forces to achieve the task did not. Our findings are consistent with a predictive model account at the perceptual level, such that the sense of agency relies most strongly on sharable perceptual information.


A dose-response meta-analysis between serum concentration of 25-hydroxy vitamin D and risk of type 1 diabetes mellitus.
It remains debatable whether vitamin D plays any role as a risk factor for type 1 diabetes mellitus (T1DM). We have summarized the effect of circulating 25-hydroxy vitamin D [25(OH)D] concentration on the risk of developing T1DM via a dose-response meta-analysis. We undertook a database search on PubMed, Embase, and Cochrane Library from inception to January 2020. A meta-analysis based on random-effects model was applied. Subgroup analysis and meta-regression were performed to inspect the source of heterogeneity. Dose-response data were examined using the generalized least squares trend estimation method. This study was registered with the PROSPERO (ID: CRD42020166174). In total, 16 studies including 10,605 participants (3913 case patients) were included. The pooled odds ratios (OR) and 95% confidence intervals (95% CI) for the highest versus the lowest 25(OH)D concentration was 0.39 (0.27, 0.57), with a high heterogeneity (I2 = 76.7%, P < 0.001). Meta-regression analysis identified latitude (P = 0.02), adjustment for gender (P = 0.001), and 25(OH)D stratification (P < 0.001) as sources of heterogeneity. Furthermore, the nonlinear dose-response analysis determined the OR (95% CI) of T1DM to be 0.91 (0.90, 0.93) per 10 nmol/L increase in the 25(OH)D concentration. A 'U'-shaped association was found between serum 25(OH)D concentration and risk of T1DM. The present study highlights the significant inverse association between the circulating 25(OH)D concentration and the risk of T1DM.


Association between hemodynamics in the common carotid artery and severity of carotid atherosclerosis in patients with essential hypertension.
Carotid intima-media thickness (IMT) and plaque burden evaluated by B-mode ultrasound have been used as relevant indicators for carotid atherosclerosis. This study was aimed to investigate the relationship between hemodynamic parameters in the common carotid artery (CCA) and the severity of carotid atherosclerosis in untreated hypertensive patients. Carotid IMT and plaque burden were evaluated in bilateral CCA, bifurcations, external and internal carotid arteries using duplex ultrasound in 80 untreated hypertensive patients. The patients were divided into four groups according to plaque burden. Hemodynamic parameters of CCA, including peak and mean circumferential wall tension (CWT), tensile stress (TS), wall shear stress (WSS), and Young's elastic modulus (YEM), were calculated after measurements of internal diameter (ID), IMT, and peak and mean flow velocities of CCA. Arterial stiffness was also assessed using the brachial-ankle pulse wave velocity (baPWV). Age, pulse pressure, creatinine, carotid IMT, and mean TS were shown to have significant differences among the four plaque groups (P < 0.05). Peak CWT and peak TS were also shown to have marginal differences. In univariate analysis, the peak and mean CWT and TS were significantly correlated with plaque score. Stepwise multiple regression analysis showed that carotid IMT, age, and peak CWT were independently associated with plaque score. These results suggest that the CWT and TS of the CCA are associated with the severity of carotid atherosclerosis in untreated hypertensive patients. Hence, the hemodynamics of vessels may contribute to the plaque burden of low-resistance arteries.


Higher-order structure in pericentric heterochromatin involves a distinct pattern of histone modification and an RNA component.
Post-translational modification of histone tails is thought to modulate higher-order chromatin structure. Combinations of modifications including acetylation, phosphorylation and methylation have been proposed to provide marks recognized by specific proteins. This is exemplified, in both mammalian cells and fission yeast, by transcriptionally silent constitutive pericentric heterochromatin. Such heterochromatin contains histones that are generally hypoacetylated and methylated by Suv39h methyltransferases at lysine 9 of histone H3 (H3-K9). Each of these modification states has been implicated in the maintenance of HP1 protein-binding at pericentric heterochromatin, in transcriptional silencing and in centromere function. In particular, H3-K9 methylation is thought to provide a marking system for the establishment and maintenance of stably repressed regions and heterochromatin subdomains. To address the question of how these two types of modifications, as well as other unidentified parameters, function to maintain pericentric heterochromatin, we used a combination of histone deacetylase inhibitors, RNAse treatments and an antibody raised against methylated branched H3-K9 peptides. Our results show that both H3-K9 acetylation and methylation can occur on independent sets of H3 molecules in pericentric heterochromatin. In addition, we identify an RNA- and histone modification-dependent structure that brings methylated H3-K9 tails together in a specific configuration required for the accumulation of HP1 proteins in these domains.


Impact of high frequency stimulation to confirm a complete box isolation in catheter ablation of non-paroxysmal atrial fibrillation.
Pulmonary vein (PV) isolation (PVI) including the left atrial posterior wall (LAPW) (Box-PVI) is proposed as an additional strategy for non-paroxysmal atrial fibrillation (NPAF), however, the efficacy remains controversial. The more reliable and durable the Box-PVI we can create, the better the rhythm outcomes might be than with a conventional PVI alone. This study focused on the potential exit conduction of the box lesion and investigated whether the conventional Box-PVI would be sufficient. We enrolled 350 consecutive patients with NPAF that underwent a conventional encircling Box-PVI and examined whether latent exit conduction and dormant "exit" conduction independently remained on the LAPW and in the PVs using high frequency stimulation (HFS) and an adenosine triphosphate (ATP) injection. All electrograms inside the box lesion were eliminated in all cases, however, HFS inside the box propagated outward in 23 cases (6.6%) without any exit conduction by conventional burst stimulation, and 24 cases (6.9%) exhibited only dormant "exit" conduction of the LAPW. Additional ablation where positive HFSs were observed created a complete bidirectional Box-PVI in 43 (41.3%) of the cases without a first pass Box-PVI. The recurrence rates depended on the groups classified according to the HFS response. HFS delivered with an ATP injection on the LAPW and in the PVs following a Box-PVI could not only elucidate true exit block but also identified possible incomplete lesions or connections outside the ablation line, whose elimination could achieve a complete Box-PVI leading to a better rhythm outcome.


Acquisition of NOTCH dependence is a hallmark of human intestinal stem cell maturation.
NOTCH signaling is a key regulator involved in maintaining intestinal stem cell (ISC) homeostasis and for balancing differentiation. Using single-cell transcriptomics, we observed that OLFM4, a NOTCH target gene present in ISCs, is first expressed at 13 weeks post-conception in the developing human intestine and increases over time. This led us to hypothesize that the requirement for NOTCH signaling is acquired across human development. To test this, we established a series of epithelium-only organoids (enteroids) from different developmental stages and used γ-secretase inhibitors (dibenzazepine [DBZ] or DAPT) to functionally block NOTCH signaling. Using quantitative enteroid-forming assays, we observed a decrease in enteroid forming efficiency in response to γ-secretase inhibition as development progress. When DBZ was added to cultures and maintained during routine passaging, enteroids isolated from tissue before 20 weeks had higher recovery rates following single-cell serial passaging. Finally, bulk RNA sequencing (RNA-seq) analysis 1 day and 3 days after DBZ treatment showed major differences in the transcriptional changes between developing or adult enteroids. Collectively, these data suggest that ISC dependence on NOTCH signaling increases as the human intestine matures.


Adherence to tyrosine kinase inhibitor and clinical outcomes in patients with chronic myeloid leukemia.
To ensure optimal care for patients with chronic myeloid leukemia (CML), adherence to tyrosine kinase inhibitors (TKIs) has emerged as a critical component. The objective of this study was to assess the impact of TKIs adherence on clinical outcomes in a cohort of Chinese CML patients who received treatment with TKIs. This retrospective study employed a cross-sectional design utilizing questionnaires to assess adherence to TKIs in a sample of 398 patients diagnosed with CML. Adherence was measured using the Morisky Medication Adherence Scale (MMAS-8), which dichotomizes patients into low, medium, and high adherence groups. Of the patients included in this study, 34.2% were classified as highly adherent, with 43.2% and 22.6% of patients categorized as having medium and low adherence, respectively. Compared to the low-adherence group, patients in the medium- and high-adherence groups exhibited significantly higher rates of achieving major molecular response (MMR) and lower rates of switching TKIs. Moreover, patients who failed to adhere to TKIs treatment demonstrated significantly lower event-free survival and failure-free survival compared to those in the high-adherence group. Notably, regular molecular monitoring and utilization of the "CML Academy" mobile application were positively associated with increased TKI adherence. On the other hand, patients receiving third-generation or above first-line TKIs treatment displayed reduced adherence. The findings suggest that high adherence to TKIs treatment confers clinical benefits to patients with CML. Accordingly, the implementation of effective guidance and intervention measures aimed at promoting adherence to TKIs therapy in real-world settings is imperative.


[Species-specific detection of Listeria monocytogenes by directed DNA amplification].
A highly sensitive species-specific test system which allows detection Listeria monocytogenes in animal tissues is elaborated using the principle of a polymerase chain reaction. The potentialities of its application were studied in the conditions of experimental infection of animals. It is shown that while the procedure of detection is relatively simple and fast, the test system is as sensitive and specific as traditional microbiological methods.


Associations between smoking and clinical outcomes after total hip and knee arthroplasty: A systematic review and meta-analysis.
Smoking increases risk of several complications after total hip or knee arthroplasty (THA/TKA), so we systematically reviewed and meta-analyzed the literature to take into account all relevant evidence, particularly studies published since 2010. The PubMed, Ovid Embase, Web of Science, and EBSCOHost databases were searched and studies were selected and analyzed according to MOOSE recommendations. Methodological quality of included studies was assessed using the Newcastle-Ottawa Scale. Data were qualitatively synthesized or meta-analyzed using a random-effects model. A total of 40 studies involving 3,037,683 cases were included. Qualitative analysis suggested that smoking is associated with worse patient-reported outcomes within one year after surgery, and meta-analysis showed that smoking significantly increased risk of the following outcomes: total complications (OR 1.41, 95% CI 1.01-1.98), wound complications (OR 1.77, 95% CI 1.50-2.10), prosthetic joint infection (OR 1.84, 95% CI 1.52-2.24), aseptic loosening (OR 1.62, 95% CI 1.12-2.34), revision (OR 2.12, 95% CI 1.46-3.08), cardiac arrest (OR 4.90, 95% CI 2.26-10.60), cerebrovascular accident (OR 2.22, 95% CI 1.01-4.85), pneumonia (OR 2.35, 95% CI 1.17-4.74), acute renal insufficiency (OR 2.01, 95% CI 1.48-2.73), sepsis (OR 4.35, 95% CI 1.35-14.00), inpatient mortality (OR 12.37, 95% CI 4.46-34.28), and persistent opioid consumption (OR 1.64, 95% CI 1.39-1.92). Smoking patients undergoing THA and TKA are at increased risk of numerous complications, inpatient mortality, persistent opioid consumption, and worse 1-year patient-reported outcomes. Pre-surgical protocols for these outcomes should give special consideration to smoking patients.


Bioinformatics: databasing and gene annotation.
"Omics" experiments amass large amounts of data requiring integration of several data sources for data interpretation. For instance, microarray, metabolomic, and proteomic experiments may at most yield a list of active genes, metabolites, or proteins, respectively. More generally, the experiments yield active features that represent subsequences of the gene, a chemical shift within a complex mixture, or peptides, respectively. Thus, in the best-case scenario, the investigator is left to identify the functional significance, but more likely the investigator must first identify the larger context of the feature (e.g., which gene, metabolite, or protein is being represented by the feature). To completely annotate function, several different databases are required, including sequence, genome, gene function, protein, and protein interaction databases. Because of the limited coverage of some microarrays or experiments, biological data repositories may be consulted, in the case of microarrays, to complement results. Many of the data sources and databases available for gene function characterization, including tools from the National Center for Biotechnology Information, Gene Ontology, and UniProt, are discussed.


Deleterious Germline BLM Mutations and the Risk for Early-onset Colorectal Cancer.
Bloom syndrome is an autosomal recessive disorder characterized by chromosomal instability and increased cancer risk, caused by biallelic mutations in the RECQL-helicase gene BLM. Previous studies have led to conflicting conclusions as to whether carriers of heterozygous BLM mutations have an increased risk to develop colorectal cancer (CRC). We recently identified two carriers of a pathogenic BLM mutation in a cohort of 55 early-onset CRC patients (≤45 years of age), suggesting an overrepresentation compared to the normal population. Here, we performed targeted sequencing using molecular inversion probes to screen an additional cohort of 185 CRC patients (≤50 years of age) and 532 population-matched controls for deleterious BLM mutations. In total, we identified three additional CRC patients (1.6%) and one control individual (0.2%) that carried a known pathogenic BLM mutation, suggesting that these mutations are enriched in early-onset CRC patients (P = 0.05516). A comparison with local and publically available databases from individuals without suspicion for hereditary cancer confirmed this enrichment (P = 0.003534). Analysis of family members of the five BLM mutation carriers with CRC suggests an incomplete penetrance for CRC development. Therefore, these data indicate that carriers of deleterious BLM mutations are at increased risk to develop CRC, albeit with a moderate-to-low penetrance.


Nonrandom karyotypic changes in immortal and tumorigenic Syrian hamster cells induced by diethylstilbestrol.
Treatment of Syrian hamster embryo cells with diethylstilbestrol (DES) resulted in the induction of immortal cell lines that progressed and formed tumors in nude mice. Four independently treated cell lines were analyzed cytogenetically at several passages during neoplastic progression. The immortal cell lines at the early passages had no structural abnormalities but did have numerical changes. For example, gain of chromosome 11 was found in all immortal cell lines, and gain of chromosome 19 was found in two of four cell lines. Tumorigenic cells showed not only a variety of numerical abnormalities but also structural abnormalities. Loss of a sex chromosome and gain of chromosome 19 were found in six of seven tumors. Gain of chromosome 11, which was found in all immortal cell lines, disappeared in five of seven tumors. Structural abnormalities involving chromosomes 2 and 3 were found in three of seven tumors. Many marker chromosomes were also found in the tumors. These results support our hypothesis that DES-induced nondisjunction is important in its ability to induce cell transformation and suggests that gain of chromosome 11 and/or 19 may play a role in DES-induced neoplastic progression. Furthermore, these results indicate that for the acquisition of tumorigenicity, additional numerical or structural changes are needed, suggesting that multiple genetic events are required in the multistep process of carcinogenesis.


Solid-phase assembly and in situ screening of protein tyrosine phosphatase inhibitors.
A highly efficient solid-phase strategy for assembly of small molecule inhibitors against protein tyrosine phosphatase 1B (PTP1B) is described. The method is highlighted by its simplicity and product purity. A 70-member combinatorial library of analogues of a known PTP1B inhibitor has been synthesized, which upon direct in situ screening revealed a potent inhibitor ( Ki = 7.0 microM) against PTP1B.


Potential Therapeutic Roles for Direct Factor Xa Inhibitors in Coronavirus Infections.
Human factor Xa (FXa) is a serine protease of the common coagulation pathway. FXa is known to activate prothrombin to thrombin, which eventually leads to the formation of cross-linked blood clots. While this process is important in maintaining hemostasis, excessive thrombin generation results in a host of thrombotic conditions. FXa has also been linked to inflammation via protease-activated receptors. Together, coagulopathy and inflammation have been implicated in the pathogenesis of viral infections, including the current coronavirus pandemic. Direct FXa inhibitors have been shown to possess anti-inflammatory and antiviral effects, in addition to their established anticoagulant activity. This review summarizes the pharmacological activities of direct FXa inhibitors, their pharmacokinetics, potential drug-drug interactions and adverse effects, and the details of clinical trials involving direct FXa inhibitors in coronavirus disease 2019 (COVID-19) patients.


The impact of an enhanced interpreter service intervention on hospital costs and patient satisfaction.
Many health care providers do not provide adequate language access services for their patients who are limited English-speaking because they view the costs of these services as prohibitive. However, little is known about the costs they might bear because of unaddressed language barriers or the costs of providing language access services. To investigate how language barriers and the provision of enhanced interpreter services impact the costs of a hospital stay. Prospective intervention study. Public hospital inpatient medicine service. Three hundred twenty-three adult inpatients: 124 Spanish-speakers whose physicians had access to the enhanced interpreter intervention, 99 Spanish-speakers whose physicians only had access to usual interpreter services, and 100 English-speakers matched to Spanish-speaking participants on age, gender, and admission firm. Patient satisfaction, hospital length of stay, number of inpatient consultations and radiology tests conducted in the hospital, adherence with follow-up appointments, use of emergency department (ED) services and hospitalizations in the 3 months after discharge, and the costs associated with provision of the intervention and any resulting change in health care utilization. The enhanced interpreter service intervention did not significantly impact any of the measured outcomes or their associated costs. The cost of the enhanced interpreter service was $234 per Spanish-speaking intervention patient and represented 1.5% of the average hospital cost. Having a Spanish-speaking attending physician significantly increased Spanish-speaking patient satisfaction with physician, overall hospital experience, and reduced ED visits, thereby reducing costs by $92 per Spanish-speaking patient over the study period. The enhanced interpreter service intervention did not significantly increase or decrease hospital costs. Physician-patient language concordance reduced return ED visit and costs. Health care providers need to examine all the cost implications of different language access services before they deem them too costly.


A novel peptidoglycan cross-linking enzyme for a beta-lactam-resistant transpeptidation pathway.
The beta-lactam antibiotics remain the most commonly used to treat severe infections. Because of structural similarity between the beta-lactam ring and the d-alanyl(4)-d-alanine(5) extremity of bacterial cell wall precursors, the drugs act as suicide substrates of the dd-transpeptidases that catalyze the last cross-linking step of cell wall assembly. Here, we show that this mechanism of action can be defeated by a novel type of transpeptidase identified for the first time by reverse genetics in abeta-lactam-resistant mutant of Enterococcus faecium. The enzyme, Ldt(fm), catalyzes in vitro the cross-linking of peptidoglycan subunits in a beta-lactam-insensitive ld-transpeptidation reaction. The specificity of Ldt(fm) for the l-lysyl(3)-d-alanine(4) peptide bond of tetrapeptide donors accounts for resistance because the substrate does not mimic beta-lactams in contrast to d-alanyl(4)-d-alanine(5) in the pentapeptide donors required for dd-transpeptidation. Ldt(fm) homologues are encountered sporadically among taxonomically distant bacteria, indicating that ld-transpeptidase-mediated resistance may emerge in various pathogens.


Antihyperalgesic activity of a novel synthesized analogue of lidocaine in diabetic rats.
The purpose of this study was to assess the antinociceptive and antihyperalgesic effects of a lidocaine analogue N-(2,6-dichlorophenyl)-2-(4-methyl-1-piperidinyl)acetamide (LIA). The structure of LIA was established by elemental analysis and compatible IR, (1) H NMR, (13) C NMR, and spectral data. Nociceptive and hyperalgesic activity were evaluated in normoglycaemic and streptozocin-induced diabetic rats using the formalin test. Formalin-evoked flinching, an indication of nociception and hyperalgesia, was increased in diabetic rats (using 0.5% formalin) compared with nondiabetic rats (using 1% formalin). Local administration of LIA into the dorsal surface of the right hind paw (0.18-5.6 mg per paw) significantly reduced the formalin-induced nociceptive and hyperalgesic behaviour of nondiabetic and diabetic rat. The antinociceptive effect of LIA was higher than that of lidocaine injection, furthermore this effect was higher than that of gabapentin. LIA may have potential as a treatment for diabetic hyperalgesia. Further investigations of the antinociceptive mechanisms and the safety of this new compound are necessary.


Hemopoietic recovery and infectious complications in breast cancer and multiple myeloma after autologous CD34+ cell-selected peripheral blood progenitor cell transplantation.
Autografting with CD34+ cell-selected peripheral blood progenitor cells (PBPC) is often associated with a prolonged recovery time and a higher incidence of infections. The aim of our study was to evaluate whether underlying disease influences hemopoietic recovery and the infectious complications occurring after transplantation. We studied 19 breast cancer (BC) patients and 17 multiple myeloma (MM) patients entered in a high-dose chemotherapy (HDC) program of tandem autografting with CD34+ cell-selected PBPC. PBPC were collected after mobilizing chemotherapy plus granulocyte colony-stimulating factor and were processed for selection of CD34+ cells. After selection, a median of 53% CD34+ cells was recovered with a median final purity of 92% with no significant differences between the MM (52% and 92%, respectively) and BC (53% and 89%, respectively) patients. Medians of 4.5 x 10(6)/kg CD34+ cells (BC, 4.4 x 10(6)/kg; MM, 5.4 x 10(6)/kg) and 18 x 10(4)/kg colony-forming units-granulocyte-macrophage (BC, 21 x 10(4)/kg: MM, 16 x 10(4)/kg) were reinfused after each HDC. Twenty-six patients (10 MM and 16 BC) underwent tandem autografting, and 10 patients received only 1 autograft because of inadequate collection (5 patients), clinical condition (3 patients), and refusal (2 patients). In the BC patients, the HDC regimen included a high-dose melphalan course followed by an ICE (ifosfamide, carboplatin, and etoposide) course. In the MM patients, the regimen consisted of a course of high-dose melphalan therapy and a course of ICBV (idarubicin, cyclophosphamide [Cytoxan], BCNU, and etoposide) or total body irradiation, etoposide, and Cytoxan. We found a significantly prolonged time for neutrophil recovery to > 500/microL in the MM patients (13 days versus 10 days; P < .002), whereas the times for platelet recovery to > 20,000/microL in the two groups were not different (13 days versus 12 days; not significant). No late engraftment failures and no toxic deaths were observed. The incidences of extrahematologic toxicity were similar for the two patient groups. All patients received similar anti-infection prophylaxis for 3 months after transplantation. After 12 months of observation, we found a statistically significant higher incidence of bacterial infections in MM patients in both the early (77.8% versus 48.6%; P < .034) and the late (41.1% versus 0%; P < .014) posttransplantation periods, whereas the incidences of fungal infections were similar in the two groups. Viral infections consisted of herpes zoster virus infection in 2 patients of each group, and cytomegalovirus infection was observed in 3 MM patients and no BC patients. Our experience demonstrates a prolonged neutrophil recovery time and higher incidences of bacterial and viral infections in MM patients compared with BC patients. These observations, although limited by the small sample size, suggest that the underlying disease may influence the incidence of infections after CD34- cell-selected transplantation and should be considered in the planning of appropriate antimicrobial prophylaxis in the autologous transplantation setting.


Audio-visual aid in teaching "fatty liver".
Use of audio visual tools to aid in medical education is ever on a rise. Our study intends to find the efficacy of a video prepared on "fatty liver," a topic that is often a challenge for pre-clinical teachers, in enhancing cognitive processing and ultimately learning. We prepared a video presentation of 11:36 min, incorporating various concepts of the topic, while keeping in view Mayer's and Ellaway guidelines for multimedia presentation. A pre-post test study on subject knowledge was conducted for 100 students with the video shown as intervention. A retrospective pre study was conducted as a survey which inquired about students understanding of the key concepts of the topic and a feedback on our video was taken. Students performed significantly better in the post test (mean score 8.52 vs. 5.45 in pre-test), positively responded in the retrospective pre-test and gave a positive feedback for our video presentation. Well-designed multimedia tools can aid in cognitive processing and enhance working memory capacity as shown in our study. In times when "smart" device penetration is high, information and communication tools in medical education, which can act as essential aid and not as replacement for traditional curriculums, can be beneficial to the students. © 2015 by The International Union of Biochemistry and Molecular Biology, 44:241-245, 2016.


Managing simple food allergy in community settings: A pilot study investigating a new model of care.
The prevalence of food allergy in Australia has increased, paralleled by an increase in waiting time to access tertiary paediatric allergy care. We aimed to test whether a new model of care, based on serum specific IgE testing, was feasible and acceptable to Australian families. A prospective pilot intervention study was conducted in community paediatric practices within 20-40 km of The Royal Children's Hospital, Melbourne. Children ≤7 years with likely food allergy referred to the Department of Allergy and Immunology at RCH were included; children with anaphylaxis, drug allergy or complex food allergy (>three food groups) were excluded. Community general paediatricians, recruited through the Australian Paediatric Research Network, were trained via webinars on the management of four common food allergy-related scenarios. Paediatrician and child and family parameters were assessed at baseline and 3 months, including safety. 34/45 (76%) eligible families and 10/12 (83%) paediatricians participated. Paediatricians managed 27/34 (80%) of children independently, with 7/34 (20%) requiring referral to an allergist for more complex food allergy. Paediatricians reported improved knowledge and competency in managing food allergy: (mean (standard deviation) scores pre = 35 (5.3) and post = 43.3 (3.9) training). The majority of children received appropriate management; there were no anaphylaxis episodes. There was no significant change in child quality of life or parent mental health. Management of simple food allergy by community paediatricians appears feasible and acceptable to paediatricians and families alike. Future research will evaluate this approach in an adequately powered and controlled trial.


Family Planning and Reproductive Health in Cystic Fibrosis.
Family planning in cystic fibrosis (CF) is an increasingly important aspect of care, as improvements in care and outcomes lead to a rise in the number of pregnancies and parenthood in people with CF. This article highlights: (1) Health considerations for people with CF related to pregnancy, contraception, and parenthood. (2) Facets of reproductive planning, fertility, and preconception counseling. (3) Relationship-centered reproductive health discussions.


Fostering environmental champions: a process to build their capacity to drive change.
This paper describes a six-step process to build the leadership capacity of environmental champions. This process was developed during research involving champions in Australian water agencies. The process, like leadership, is sensitive to context. It includes gathering local information on the factors that assist particular types of champion to exert influence, and using this information to build customized capacity building tools, such as leadership development programs. The paper explains each step in the process and provides illustrative examples from research on water agency champions. Practical and theoretical implications are discussed, including the hypothesis that the process should be transferable to other work environments under certain circumstances.


Combination anchorage technique: an update of current mechanics.
Experience and advances in design and technique have greatly enhanced combination orthodontic techniques during the past 5 years. Improvements have made the delivery of treatment more effective and reduced the problems with appliance adjustment and esthetics. Some of these improvements are in the bracket itself, which has been modified for efficiency and esthetics. A modification of treatment technique by the addition of tandem wires, stabilizing arch wires, Dual Flex arch wires, and sectional wires have increased the movement capabilities and anchorage control. A technique of orthodontic mechanics has evolved that is called combination anchorage technique (CAT). The technique is designed to broaden the treatment effectiveness of the orthodontist by providing a combination of orthodontic technical capabilities. Use of the two different bracket slots provides a simple and efficient means to vary (1) anchorage (dynamic or static), (2) movement (tipping or bodily), (3) technique (light wire or straight wire), (4) resistance (one tooth or multiple teeth), and (5) treatment compensation (skeletal or dental).


Bioelectrochemical immunoassay of polychlorinated biphenyl.
A simple, rapid, and highly sensitive bioelectrochemical immunoassay method based on magnetic beads (MBs) and disposable screen-printed electrodes (SPE) has been developed to detect polychlorinated biphenyls (PCBs). The principle of this bioassay is based on a direct competitive enzyme-linked immunosorbent assay using PCB-antibody-coated MBs and horseradish peroxidase (HRP)-labeled PCB (HRP-PCB). A magnetic process platform was used to mix and shake the samples during the immunoreactions and to separate free and unbound reagents after the liquid-phase competitive immunoreactions among PCB-antibody-coated MBs, PCB analyte, and HRP-PCB. After a complete immunoassay, the HRP tracers attached to MBs were transferred to a substrate solution containing o-aminophenol and hydrogen peroxide for electrochemical detection. The different parameters, including the amount of HRP-PCB conjugates, immunoreaction time, and the concentration of substrate that governs the analytical performance of the immunoassay have been studied in detail and optimized. The detection limit of 10 gmL(-1) was obtained under optimum experimental conditions. The performance of this bioelectrochemical immunoassay was successfully evaluated with untreated river water spiked with PCBs, and the results were validated by commercial PCB enzyme-linked immunosorbent assay kit, indicating that this convenient and sensitive technique offers great promise for decentralized environmental application and trace PCBs monitoring.


Prenatal Evaluation of Intracranial Hemorrhage on Fetal MRI: A Retrospective Review.
The evaluation and characterization of germinal matrix hemorrhages have been predominantly described on postnatal head sonography in premature neonates. However, germinal matrix hemorrhages that are seen in premature neonates can be also seen in fetuses of the same postconceptual age and are now more frequently encountered in the era of fetal MR imaging. Our aim was to examine and describe the MR imaging findings of fetuses with intracranial hemorrhage. A retrospective review of diagnostic-quality fetal MRIs showing intracranial hemorrhage from January 2004 to May 2020 was performed. Images were reviewed by 2 radiologists, and imaging characteristics of fetal intracranial hemorrhages were documented. Corresponding postnatal imaging and clinical parameters were reviewed. One hundred seventy-seven fetuses with a mean gestational age of 25.73 (SD, 5.01) weeks were included. Germinal matrix hemorrhage was identified in 60.5% (107/177) and nongerminal matrix hemorrhage in 39.5% (70/177) of patients. Significantly increased ventricular size correlated with higher germinal matrix hemorrhage grade (P < .001). Fetal growth restriction was present in 21.3% (20/94) of our population, and there was no significant correlation with germinal matrix grade or type of intracranial hemorrhage. An increased incidence of neonatal death with grade III germinal matrix hemorrhages (P = .069) compared with other grades was identified; 23.2% (16/69) of the neonates required ventriculoperitoneal shunts, with an increased incidence in the nongerminal matrix hemorrhage group (P = .026). MR imaging has become a key tool in the diagnosis and characterization of intracranial hemorrhage in the fetus. Appropriate characterization is important for optimizing work-up, therapeutic approach, and prenatal counseling.


Toward a versatile allylation reagent: practical, enantioselective allylation of acylhydrazones using strained silacycles.
A highly practical method for the enantioselective allylation of acylhydrazones has been developed. The previously reported strained silacycle reagent 1 reacts with a wide variety of acylhydrazones to give the hydrazide products with good enantioselectivity (83-89% ee, typically). It has been demonstrated that the products may be isolated without chromatography by recrystallization in >/=98% ee.


Adding pegylated interferon to a current nucleos(t)ide therapy leads to HBsAg seroconversion in a subgroup of patients with chronic hepatitis B.
Nucleos(t)ides effectively halt disease progression in hepatitis B but require long-term medication. To determine whether add-on of peg-IFN to an ongoing nucleos(t)ide therapy accelerates decline of HBsAg and induces seroconversion. We observed HBsAg kinetics in 12 patients on a stable oral therapy with undetectable HBV-DNA who additionally received peg-IFN-alfa 2a as an individualized therapy. 3 patients were HBeAg positive. Mean baseline HBsAg was 4695 (range 16-15,120)IU/ml. A continuous decline of HBsAg was observed in 2 patients. The slope, respectively, became detectable at week 8 or 16. HBsAg had dropped by 2.90log(10) or 4.25log(10) fold at week 48, and anti-HBs appeared at week 40 or 32. Patient A - HBe-positive, genotype A, F3 fibrosis - had been HBV-DNA negative for 10 months receiving entecavir plus tenofovir. Previous therapy with peg-IFN had been unsuccessful, but now the patient experienced HBeAg seroconversion at week 24. Patient B - HBeAg negative, genotype D, cirrhosis - had a low initial HBsAg level of 16U/l. Receiving entecavir, his HBV-DNA had previously been non-detectable for 27 months. In the remaining 10 patients HBsAg declined only by a mean of 0.09log(10) (range 0.01-0.25log(10)) after 8-24 (mean 16.4) weeks, and therefore, peg-IFN was stopped. No unexpected side effects were observed. We observed that the add-on of peg-IFN induced HBsAg seroconversion in 2 out of 12 patients. Response rates may have been higher with prolongation of therapy. The add-on concept merits to be evaluated in a clinical trial.


Human milk proresolving mediators stimulate resolution of acute inflammation.
Human milk contains nutrients and bioactive products relevant to infant development and immunological protection. Here, we investigated the proresolving properties of milk using human milk lipid mediator isolates (HLMIs) and determined their impact on resolution programs in vivo and with human macrophages. HLMIs reduced the maximum neutrophil numbers (14.6±1.2 × 10(6)-11.0±1.0 × 10(6) cells per exudate) and shortened the resolution interval (Ri; 50% neutrophil reduction) by 54% compared with peritonitis. Using rigorous liquid-chromatography tandem-mass spectrometry (LC-MS-MS)-based lipid mediator (LM) metabololipidomics, we demonstrated that human milk possesses a proresolving LM-specialized proresolving mediator (LM-SPM) signature profile, containing SPMs (e.g. resolvins (Rv), protectins (PDs), maresins (MaRs), and lipoxins (LXs)) at bioactive levels (pico-nanomolar concentrations) that enhanced human macrophage efferocytosis and bacterial containment. SPMs identified in human milk included D-series Rvs (e.g., RvD1, RvD2, RvD3, AT-RvD3, and RvD4), PD1, MaR1, E-series Rvs (e.g. RvE1, RvE2, and RvE3), and LXs (LXA4 and LXB4). Of the SPMs identified in human milk, RvD2 and MaR1 (50 ng per mouse) individually shortened Ri by ∼75%. Milk from mastitis gave higher leukotriene B4 and prostanoids and lower SPM levels. Taken together, these findings provide evidence that human milk has proresolving actions via comprehensive LM-SPM profiling, describing a potentially novel mechanism in maternal-infant biochemical imprinting.


Rituximab maintenance improves survival in male patients with diffuse large B-cell lymphoma. Results of the HD2002 prospective multicentre randomized phase III trial.
In the multicentre prospective randomized HD2002 trial, rituximab maintenance therapy (375 mg/m(2) every 3 months for 2 years) versus observation was evaluated for CD20(+) B-cell lymphoma. Out of 321 patients [161 randomized to the treatment group (TG), 160 to the observation group (OG)], 295 data sets were evaluable for statistical analysis. Estimated 5-year relapse-free survival (RFS) was 81% in the TG and 70% in the OG (logrank test, P = 0·047). In the diffuse large B-cell lymphoma (DLBCL) subgroup (n = 152), 5-year RFS was excellent, at 87% in the TG and 84% in the OG (logrank test, P = 0·35). Of note, only in male patients of the DLBCL subgroup was RFS significantly superior in the TG in comparison to the OG (5-year RFS: 88% vs. 74%; logrank test, P = 0·05). Cox regression analysis showed a significant interaction between treatment and gender regarding overall survival (OS) (P = 0·006) and RFS (P = 0·02), with a lower hazard in females than males in the OG [OS: hazard ratio (HR) (female:male) = 0·11; 95% confidence interval (CI) = 0·00-1·03; RFS: HR (female:male) = 0·27; 95% CI = 0·05-0·97], and no significant differences between males and females in the TG. We conclude that Rituximab maintenance therapy improves survival in male patients with DLBCL.


Orthotopic liver transplantation in patients with biliary atresia and situs inversus.
Situs inversus (SI) and the polysplenia syndrome (PS) occur relatively frequently in patients with biliary atresia, the largest subgroup of pediatric liver transplantation patients. We present two cases of orthotopic liver transplantation (OLT) in pediatric patients with SI. One had SI totalis, where a normal liver was placed in the left upper quadrant (LUQ) with the right lobe overlying the vertebral column. The second had PS and isolated SI of the liver, and a living-related left-lateral-segment graft was placed in the LUQ. Although multiple, often unpredictable vascular and intestinal anomalies occur frequently in association with SI, particularly in the setting of the PS, these cases, as well as several others recently reported, reveal that these anomalies can be managed successfully by a variety of technical modifications of the standard OLT technique. Likewise, concerns about the placement of a situs solitus liver in the midline or LUQ position of a SI abdomen have proved to be unfounded.


Facile calcium ion-regulated grafting of dense and highly stretched hyaluronan for selective mediation of cancer cells rolling under high-speed flow.
The development of materials that selectively mediate the rolling of cancer cells is important for the high-throughput enrichment of high-speed cancer cells. Here we constructed a dense and stretched low molecular weight hyaluronic acid (HA9.6k)-modified surface to selectively promote the rolling of CD44-high cancer cells. The HA surface (calcium ion-regulated HA9.6k surface, Ca-rHA) was fabricated via a calcium ion-regulated method, where calcium ion incorporation induced the shrink of HA9.6k chains to achieve the highest reported grafting density of about 2.73 ± 0.20 × 104 HA chains μm-2. Upon the removal of calcium ions, the dense HA9.6k chains switched to a highly stretched conformation. The high density and flexibility of Ca-rHA bearing abundant binding sites enhanced the rolling of CD44-high cancer cells and reduced the velocity of cells from 1389 µm s-1 to 99 µm s-1 (7%), comparable to that of the physiological rolling event and outperforming traditional grafting-to HA and E-selectin, without causing phenotypic changes. When processing complex samples under high-speed flow, Ca-rHA selectively mediated the rolling of cancer cells and enriched their ratio to peripheral blood mononuclear cells from 1:1 to 15:1. As the only reported artificial biomaterial capable of selectively mediating the rolling of cancer cells under a physiological high-speed flow, Ca-rHA holds promise in enriching intact cells for downstream analysis in the clinics by encouraging the surface-cell contacts. STATEMENT OF SIGNIFICANCE: The development of materials that selectively mediate the rolling of cancer cells is important for the high-throughput enrichment of cancer cells rolling under high-speed flow, yet is less reported. To selectively promote the rolling of cancer stem cell marker CD44-high cancer cells, a surface with dense and stretched low molecular weight hyaluronic acid (HA9.6k) was constructed. With Ca2+ regulation, HA9.6k chains shrank to achieve the highest reported grafting density of 2.73 ± 0.20 × 104 chains μm-2 and further switched to a highly stretched conformation after the removal of Ca2+ ions. As the only reported artificial biomaterial capable of selectively mediating the rolling of cancer cells under a physiological high-speed flow, this Ca2+-regulated HA9.6k surface holds promise in enriching intact cells for downstream analysis in the clinics.


Magnetic resonance imaging and computer tomography of brain lesions in water buffaloes and cattle stunned with handguns or captive bolts.
Owing to the demand for genuine mozzarella, some 330 water buffaloes are being slaughtered every year in Switzerland albeit a stunning procedure meeting animal welfare and occupational safety requirements remains to be established. To provide a basis for improvements, we sized anatomical specifics in water buffaloes and cattle and we assessed brain lesions after stunning with captive bolts or handguns by diagnostic imaging. In water buffaloes and cattle, the median distance from the frontal skin surface to the inner bone table was 74.0mm (56.0-100.0mm) vs 36.6mm (29.3-44.3mm) and from skin to the thalamus 144.8mm (117.1-172.0mm) vs 102.0 (101.0-121.0mm), respectively. Consequently, customary captive bolt stunners may be inadequate. Free bullets are potentially suitable for stunning buffaloes but involve occupational safety hazards. The results of the present study shall be used to develop a device allowing effective and safe stunning of water buffaloes.


Polyaniline/poly (2-acrylamido-2-methyl-1-propanesulfonic acid) modified cellulose as promising material for sensors design.
A material based on cellulose coated with polyaniline/poly (2-acrylamido-2-methyl-1-propanesulfonic acid) (Cell/PANI-PAMPSA) was synthesized in a simple way starting from cellulose fibres, aniline and using PAMPSA as dopant. The morphology, mechanical properties, thermal stability, and electrical conductivity were investigated by means of several complementary techniques. The obtained results highlight the excellent features of the Cell/PANI-PAMPSA composite with respect to the Cell/PANI one. Based on the promising performance of this material, novel device functions and wearable applications have been tested. We focused on its possible single use as: i) humidity sensors and ii) disposable biomedical sensors to provide immediate diagnostic services as close to the patient as possible for heart rate or respiration activity monitoring. To our knowledge, this is the first time that Cell/PANI-PAMPSA system has been used for such applications.


Optimizing the number of cleavage stage embryos to transfer on day 3 in women 38 years of age and older: a Society for Assisted Reproductive Technology database study.
To determine the optimal number of day 3 embryos to transfer in women >or=38 years by conducting an evidence-based evaluation. Retrospective analysis of 2000-2004 national SART data. National writing group. A total of 36,103 day 3 embryo transfers in women >or=38 years undergoing their first assisted reproductive technology cycle. None. Logistic regression was used to model the probability of pregnancy, delivery, and multiple births (twin or high order) based on age- and cycle-specific parameters. Pregnancy rates, delivery rates, and multiple rates increased up to transfer of three embryos in 38-year-olds and four in 39-year-olds; beyond this number, only multiple rates increased. In women >or=40 years, delivery rates and multiple rates climbed steadily with increasing numbers transferred. Multivariate analysis confirmed the statistically significant effect of age, number of oocytes retrieved, and embryo cryopreservation on delivery and multiple rates. Maximum FSH level was not an independent predictor by multivariate analysis. Use of intracytoplasmic sperm injection was associated with lowered delivery rate. No more than three or four embryos should be transferred in 38- and 39-year-olds, respectively, whereas up to five embryos could be transferred in >or=40-year-olds. Numbers of embryos to transfer should be adjusted according to number of oocytes retrieved and availability of excess embryos for cryopreservation.


Effect of the IMPase inhibitor L690,330 on sea urchin development.
A variety of concentrations of the IMPase inhibitor L690,330 were added to sea urchin embryos. Immediate arrest of development was obtained for concentrations from 7.5 mm on. Concentrations lower than 3.5 mm permitted gastrulation but inhibited skeletogenesis and disturbed elongation along the animal-vegetal axis. The latter results are similar to those obtained by counteracting lithium effect with myoinositol, which are suggested to be due to partial relief of IMPase inhibition.


Potentiation of odor by taste and odor aversions in rats are regulated by cholinergic activity of dorsal hippocampus.
Limbic cholinergic activity is critically involved in the retention of learned aversions tasks. The purpose of these experiments was to assess the role of cholinergic mechanisms of the dorsal hippocampus in the acquisition of both odor and potentiated odor aversions through taste aversion. Cholinergic activity was increased by physostigmine (Phys). When Phys was applied before the presentation of an odor-taste compound during acquisition, the potentiation of odor-aversion was disrupted, while taste aversion was left intact. When hippocampal cholinergic activity was reduced with the muscarinic antagonist scopolamine (Scop), enhancement of potentiated odor aversion was observed, again with no effect on taste aversion. Moreover, when Phys was applied before an odor alone it also disrupted odor avoidance in two different odor tests conditioning situations, i.e., odor was followed immediately by lithium chloride or foot shock. Neither Scop nor Phys had any effect on taste or potential odor aversions when applied to fronto-parietal cortex. These results suggest that cholinergic activity of the hippocampus is involved in the acquisition of odor aversion conditioning.


Echocardiographic guidance for transcatheter patent ductus arteriosus closure in extremely low birth weight infants.
Echocardiographic imaging provides real-time guidance during transcatheter patent ductus arteriosus (PDA) closure in extremely low birth weight (ELBW) infants. Transthoracic echocardiogram provides detailed assessment of the PDA and surrounding structures prior to, during, and after transcatheter closure. This article aims to review the different echocardiographic techniques and concepts utilized during transcatheter PDA closure in ELBW infants.


Increasing brain glucose uptake by Gypenoside LXXV ameliorates cognitive deficits in a mouse model of diabetic Alzheimer's disease.
We have previously reported that Gypenoside LXXV (GP-75), a novel natural PPARγ agonist isolated from Gynostemma pentaphyllum, ameliorated cognitive deficits in db/db mice. In this study, we further investigated the beneficial effects on cognitive impairment in APP/PS1 mice and a mouse model of diabetic AD (APP/PS1xdb/db mice). Interestingly, intragastric administration of GP-75 (40 mg/kg/day) for 3 months significantly attenuated cognitive deficits in APP/PS1 and APP/PS1xdb/db mice. GP-75 treatment markedly reduced the levels of glucose, HbA1c and insulin in serum and improved glucose tolerance and insulin sensitivity in APP/PS1xdb/db mice. Notably, GP-75 treatment decreased the β-amyloid (Aβ) burden, as measured by 11 C-PIB PET imaging. Importantly, GP-75 treatment increased brain glucose uptake as measured by 18 F-FDG PET imaging. Moreover, GP-75 treatment upregulated PPARγ and increased phosphorylation of Akt (Ser473) and GLUT4 expression levels but decreased phosphorylation of IRS-1 (Ser616) in the hippocampi of both APP/PS1 and APP/PS1xdb/db mice. Furthermore, GP-75-induced increases in GLUT4 membrane translocation in primary hippocampal neurons from APP/PS1xdb/db mice was abolished by cotreatment with the selective PPARγ antagonist GW9662 or the PI3K inhibitor LY294002. In summary, GP-75 ameliorated cognitive deficits in APP/PS1 and APP/PS1xdb/db mice by enhancing glucose uptake via activation of the PPARγ/Akt/GLUT4 signaling pathways.


Review article: the antimicrobial effects of rifaximin on the gut microbiota.
Disruption of the gut microbiota through use of systemic antimicrobials or activation of the mucosal inflammatory response by pathogens can cause dysregulation of the intestinal mucosa. To explore the mechanisms of action of rifaximin that may underlie its clinical benefits in travellers' diarrhoea (TD). A literature search was performed using the terms 'rifaximin' and 'L/105' in combination with the terms 'in vitro activity', 'diarrhea', 'microbiota' and 'gut flora'. Rifaximin has been traditionally identified as a nonsystemic, broad-spectrum, bactericidal antibiotic. Evidence shows that the activity of rifaximin against enteropathogens in this setting is likely enhanced by its increased solubility in the presence of bile acids in the small intestine. Results of clinical studies show that although rifaximin is efficacious in TD, a clinical cure often occurs without apparent bacterial eradication and with minimal effect on the gut microbiota, suggesting an effect of rifaximin other than direct antibiotic activity. Although definitive studies on the effect of rifaximin on the gut microbiota in large cohorts of healthy volunteers or patients have not been published, pre-clinical studies provide some insight. These studies have shown that rifaximin may have effects on both the pathogen and host, including direct effects on pathogenic bacteria (such as reducing the expression of bacterial virulence factors) and indirect effects on the host (such as inhibiting bacterial attachment and internalisation at the intestinal mucosa and reducing mucosal inflammation).


The serum metabolite response to diet intervention with probiotic acidified milk in irritable bowel syndrome patients is indistinguishable from that of non-probiotic acidified milk by 1H NMR-based metabonomic analysis.
The effects of a probiotic acidified milk product on the blood serum metabolite profile of patients suffering from Irritable Bowel Syndrome (IBS) compared to a non-probiotic acidified milk product was investigated using (1)H NMR metabonomics. For eight weeks, IBS patients consumed 0.4 L per day of a probiotic fermented milk product or non-probiotic acidified milk. Both diets resulted in elevated levels of blood serum L-lactate and 3-hydroxybutyrate. Our results showed identical effects of acidified milk consumption independent of probiotic addition. A similar result was previously obtained in a questionnaire-based evaluation of symptom relief. A specific probiotic effect is thus absent both in the patient subjective symptom evaluations and at the blood serum metabolite level. However, there was no correspondence between symptom relief and metabolite response on the patient level.


Root Canal Preparation and Enlargement Using Thermally Treated Nickel-Titanium Rotary Systems in Curved Canals.
The purpose of this study was to evaluate root canal preparation and apical enlargement of curved canals using rotary heat-treated and heat/surface-treated systems by micro-computed tomographic imaging. Curved mesial root canals (n = 48) of mandibular molars (20°-40°) were prepared using ProDesign Logic (PDL; Easy Equipamentos Odontológicos, Belo Horizonte, MG, Brazil) 25/.01 and 25/.06 or HyFlex EDM (HFEDM) 10/.05, HyFlex CM 20/.04, and HFEDM 25/.08. Apical enlargement was performed using PDL 40/.05 or HFEDM 40/.04. Scanning (9 μm) was performed before and after preparation and after apical enlargement using micro-computed tomographic imaging. Volume, percentage of volume increase, debris, untouched root canal surface, and centering ability were analyzed. Statistical analysis was performed using Mann-Whitney, Wilcoxon, and unpaired t tests (α = .05). HFEDM promoted a higher volume increase of the root canals than PDL after preparation and after apical enlargement (P < .05). The apical enlargement promoted a significant decrease in debris and untouched surface in both groups (P < .05). The percentage of debris and untouched surface were similar between HFEDM and PDL after preparation and after apical enlargement (P > .05). Both systems promoted centered canals (P > .05). HFEDM instruments promoted greater volume of the root canal than PDL. However, the cleaning ability of the instruments was similar. The apical increase up to size 40 with both instruments provided less debris and untouched surfaces and allowed centralization of the curved root canals.


Survival in Patients with Degenerative Mitral Stenosis: Results from a Large Retrospective Cohort Study.
Severe mitral annular calcification causing degenerative mitral stenosis (DMS) is increasingly encountered in patients undergoing mitral and aortic valve interventions. However, its clinical profile and natural history and the factors affecting survival remain poorly characterized. The goal of this study was to characterize the factors affecting survival in patients with DMS. An institutional echocardiographic database was searched for patients with DMS, defined as severe mitral annular calcification without commissural fusion and a mean transmitral diastolic gradient of ≥2 mm Hg. This resulted in a cohort of 1,004 patients. Survival was analyzed as a function of clinical, pharmacologic, and echocardiographic variables. The patient characteristics were as follows: mean age, 73 ± 14 years; 73% women; coronary artery disease in 49%; and diabetes mellitus in 50%. The 1- and 5-year survival rates were 78% and 47%, respectively, and were slightly worse with higher DMS grades (P = .02). Risk factors for higher mortality included greater age (P < .0001), atrial fibrillation (P = .0009), renal insufficiency (P = .004), mitral regurgitation (P < .0001), tricuspid regurgitation (P < .0001), elevated right atrial pressure (P < .0001), concomitant aortic stenosis (P = .02), and low serum albumin level (P < .0001). Adjusted for propensity scores, use of renin-angiotensin system blockers (P = .02) or statins (P = .04) was associated with better survival, and use of digoxin was associated with higher mortality (P = .007). Prognosis in patients with DMS is poor, being worse in the aged and those with renal insufficiency, atrial fibrillation, and other concomitant valvular lesions. Renin-angiotensin system blockers and statins may confer a survival benefit, and digoxin use may be associated with higher mortality in these patients.


TNFSF15 facilitates human umbilical cord blood haematopoietic stem cell expansion by activating Notch signal pathway.
The lack of efficient ex vivo expansion methods restricts clinical use of haematopoietic stem cells (HSC) for the treatment of haematological malignancies and degenerative diseases. Umbilical cord blood (UCB) serves as an alternative haematopoietic stem cell source. However, currently what limits the use of UCB-derived HSC is the very low numbers of haematopoietic stem and progenitor cells available for transplantation in a single umbilical cord blood unit. Here, we report that TNFSF15, a member of the tumour necrosis factor superfamily, promotes the expansion of human umbilical cord blood (UCB)-derived HSC. TNFSF15-treated UCB-HSC is capable of bone marrow engraftment as demonstrated with NOD/SCID or NOD/Shi-SCID/IL2Rgnull (NOG) mice in both primary and secondary transplantation. The frequency of repopulating cells occurring in the injected tibiae is markedly higher than that in vehicle-treated group. Additionally, signal proteins of the Notch pathway are highly up-regulated in TNFSF15-treated UCB-HSC. These findings indicate that TNFSF15 is useful for in vitro expansion of UCB-HSC for clinical applications. Furthermore, TNFSF15 may be a hopeful selection for further UCB-HSC application or study.


MicroRNAs for Diagnosis and Treatment of Colorectal Cancer.
Colorectal cancer (CRC) is the third most common cancer worldwide, with high morbidity and mortality rates. The diagnosis and treatment of CRC have the most significant value for disease- free survival. Early diagnosis and early surgical resection are generally considered to be the most effective ways to reduce CRC mortality. In the past few years, many researchers have focused on the role of microRNAs in different tumors, making the functions of microRNAs gradually clear. The present study reviews the role of microRNAs in the diagnosis and treatment of colorectal cancer. Compared with the usual diagnosis methods and biomarker, circulating microRNAs can be promising new effective biomarkers for CRC diagnosis and treatment.


Chemical characteristics and source analysis on ionic composition of rainwater collected in the Carpathians "Cold Pole," Ciuc basin, Eastern Carpathians, Romania.
A study of precipitation chemistry was conducted for 11 years (01 January 2006-31 December 2016) in the Ciuc basin, Eastern Carpathians, Romania. The studied area is an enclosed basin, also called "the Carpathians cold pole." All collected samples were analyzed for major cations and anions. HCO3- concentrations were calculated based on the empirical relationship between pH and HCO3-. The multiannual arithmetic mean of pH values was found to be 6.57. The lowest and highest pH values were measured in 2009 and 2013, being 6.57% lower, respectively, 7.57% higher than the multiannual mean. Only 3.31% of the studied rainwater samples indicate acidic character. In descending order, the majority of the samples are as follows: NH4+ >Ca2+ >SO42- >Cl- >HCO3- >NO3- >Na+ >K+ >Mg2+ >NO2- >H+. Principal component analysis (PCA) showed the NH4+, Ca2+, and Mg2+ contribution to the neutralization process and their sources. The anthropogenic origin of SO42- was supported by the high non-sea-salt fraction (NSSF) (~ 91%). The results of this study suggest that rainwater chemistry is strongly influenced by local natural and anthropogenic sources (agricultural activities) rather than marine sources. The pollutants in rainwater samples were mainly derived from calcareous and dolomitic soil dust and specific local climatic conditions, long-range transport, local industry, and traffic sources.


Role of the KEAP1-NRF2 Axis in Renal Cell Carcinoma.
NRF2 is a transcription factor that coordinates the antioxidant response in many different tissues, ensuring cytoprotection from endogenous and exogenous stress stimuli. In the kidney, its function is essential in appropriate cellular response to oxidative stress, however its aberrant activation supports progression, metastasis, and resistance to therapies in renal cell carcinoma, similarly to what happens in other nonrenal cancers. While at the moment direct inhibitors of NRF2 are not available, understanding the molecular mechanisms that regulate its hyperactivation in specific tumor types is crucial as it may open new therapeutic perspectives. Here, we focus our attention on renal cell carcinoma, describing how NRF2 hyperactivation can contribute to tumor progression and chemoresistance. Furthermore, we highlight the mechanism whereby the many pathways that are generally altered in these tumors converge to dysregulation of the KEAP1-NRF2 axis.


Joint toxicity of sediment-associated permethrin and cadmium to Chironomus dilutus: The role of bioavailability and enzymatic activities.
Pyrethroid insecticides and metals commonly co-occurred in sediment and caused toxicity to benthic organisms jointly. To improve accuracy in assessing risk of the sediments contaminated by insecticides and metals, it is of great importance to understand interaction between the contaminants and reasons for the interaction. In the current study, permethrin and cadmium were chosen as representative contaminants to study joint toxicity of pyrethroids and metals to a benthic invertebrate Chironomus dilutus. A median effect/combination index-isobologram was applied to evaluate the interaction between sediment-bound permethrin and cadmium at three dose ratios. Antagonistic interaction was observed in the midges for all treatments. Comparatively, cadmium-dominated group (the ratio of toxicity contribution from permethrin and cadmium was 1:3) showed stronger antagonism than equitoxicity (1:1) and permethrin-dominated groups (3:1). The reasons for the observed antagonism were elucidated from two aspects, including bioavailability and enzymatic activity. The bioavailability of permethrin, expressed as the freely dissolved concentrations in sediment porewater and measured by solid phase microextraction, was not altered by the addition of cadmium, suggesting the change in permethrin bioavailability was not the reason for the antagonism. On the other hand, the activities of metabolic enzymes, glutathione S-transferase and carboxylesterase in the midges which were exposed to mixtures of permethrin and cadmium were significantly higher than those in the midges exposed to permethrin solely. Cadmium considerably enhanced the detoxifying processes of permethrin in the midges, which largely explained the observed antagonistic interaction between permethrin and cadmium.


Tibialis anterior tendon transfer using suture anchor provides excellent alternative treatment for relapse clubfoot: A case report.
Relapsed clubfoot is defined as the recurrence of any component of deformity after a complete correction. While the Ponseti method has been known to have excellent outcomes, several relapse cases have been reported. Thus, further surgical intervention is needed to achieve a good and reliable long-term outcome. We report a presentation of a 5-year-old boy who came to the clinic with a relapsed bilateral clubfoot after serial Ponseti casting. Plantar fascia release, Achilles tendon lengthening, and tibialis anterior tendon transfer (TATT) were performed respectively followed by an above-knee cast. The patient gained acceptable walking balance and ability to perform high impact sports at one year follow-up. There are several factors contributing to the relapse clubfoot including adherence to post op foot abduction brace (FAB) protocol, muscle imbalance or inadequate correction of initial deformities. The current case report described a relapse clubfoot following serial Ponseti casting caused by non-compliance of the use of foot abduction brace. Further surgical interventions must be performed in the presence of relapse case of clubfoot. Relapse clubfoot is the presence of any recurring deformity following correction. Surgical intervention, especially TATT procedure provides a favorable outcome in treating patients with relapse clubfoot.


Surgical decompression timing for patients with foot drop from lumbar degenerative diseases: a meta-analysis.
To compare the outcomes of early (within 1 month after foot drop) decompression versus late (1 month or more after foot drop) decompression in order to determine the optimal surgical intervention timing for lumbar degenerative diseases. The MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Web of Science and SCOPUS electronic databases were searched for relevant articles published until May 2021 were conducted. Cochrane Collaboration guidelines were used for data extraction and quality assessment. Outcomes of interest were manual muscle testing (MMT) and recovery rate (MMT ≥ 4) for foot drop in lumbar degenerative diseases. Six clinical studies were retrieved, including 312 randomized participants. One hundred fifty-seven patients underwent early decompression surgery, and 155 underwent late decompression surgery. There were significant differences between the two groups in recovery rate (95% confidence interval [CI] 1.59, 2.57) and neurological improvement (95% confidence interval [CI] 0.21, 1.66). Early surgical decompression provided better recovery rate and neurological improvement for foot drop in lumbar degenerative diseases than late surgical decompression. Early surgical decompression within was beneficial in terms of recovery rate and neurological improvement compared with late surgery. Early surgical decompression (within 1 month) is recommended for patients with foot drop in lumbar degenerative diseases.


In vitro stimulation of Escherichia coli RNA polymerase sigma subunit synthesis by NusA protein.
A simplified DNA-directed in vitro system which measures synthesis of the NH2-terminal dipeptides of gene products has been used to study the expression of rpoD, the gene coding for the sigma subunit of Escherichia coli RNA polymerase. The rpoD gene is part of a complex operon which also includes the genes for ribosomal protein S21 (rpsU) and primase (dnaG). Primary promoters have been identified upstream of the structural genes, but there are secondary (internal) promoters within the dnaG gene that are involved in the expression of rpoD. Significant expression of the rpsU and rpoD genes was observed in the in vitro dipeptide system using plasmid pBS105, which contains both external and internal promoters. With plasmid pMRG-1, which contains only the internal promoters, only rpoD expression was observed. From either template, synthesis of the NH2-terminal dipeptide of sigma, fMet-Glu, is stimulated about threefold by the E. coli nusA gene product. In addition, NusA protein stimulates synthesis of the entire sigma protein in a defined in vitro system. NusA protein has no effect on the expression of the upstream gene rpsU, and the stimulation of rpoD expression by NusA protein is at the level of transcription. The results are consistent with the known role of NusA protein in modulating transcription at pause or attenuation sites.


Comparative evaluation of total PSA, free/total PSA, and complexed PSA in prostate cancer detection.
To compare the performance of prostate-specific antigen (PSA), the free/total PSA (F/T PSA) ratio, and complexed PSA (cPSA) in prostate cancer detection. Five hundred thirty-five patients evaluated at the UROMED prostate cancer detection clinic had total PSA, free PSA, and cPSA measured before undergoing transrectal ultrasonography and sextant prostate biopsies. A direct comparison was performed between the different PSA assays to evaluate their ability to detect prostate cancer. Of the 535 patients evaluated, 38.1% had prostate cancer detected. The mean age of the entire population was 63.6 years (range 35 to 86). Abnormal digital rectal examination findings were present in 33.4% of the patients. The mean and median values of PSA and cPSA were significantly higher and the F/T PSA ratio was lower in patients with prostate cancer. The F/T PSA ratio performed better than either cPSA or total PSA. A higher specificity was observed with the F/T PSA ratio than with cPSA using either the entire patient population or subsets of patients with PSA levels between 4.0 and 10 ng/mL or 4.0 to 6.0 ng/mL. The use of the F/T PSA ratio offers improved prostate cancer detection compared with either cPSA or total PSA.


Brain MRI in Progressive Supranuclear Palsy with Richardson's Syndrome and Variant Phenotypes.
Brain magnetic resonance imaging (MRI) is used to support the diagnosis of progressive supranuclear palsy (PSP). However, the value of visual descriptive, manual planimetric, automatic volumetric MRI markers and fully automatic categorization is unclear, particularly regarding PSP predominance types other than Richardson's syndrome (RS). To compare different visual reading strategies and automatic classification of T1-weighted MRI for detection of PSP in a typical clinical cohort including PSP-RS and (non-RS) variant PSP (vPSP) patients. Forty-one patients (21 RS, 20 vPSP) and 46 healthy controls were included. Three readers using three strategies performed MRI analysis: exclusively visual reading using descriptive signs (hummingbird, morning-glory, Mickey-Mouse), visual reading supported by manual planimetry measures, and visual reading supported by automatic volumetry. Fully automatic classification was performed using a pre-trained support vector machine (SVM) on the results of atlas-based volumetry. All tested methods achieved higher specificity than sensitivity. Limited sensitivity was driven to large extent by false negative vPSP cases. Support by automatic volumetry resulted in the highest accuracy (75.1% ± 3.5%) among the visual strategies, but performed not better than the midbrain area (75.9%), the best single planimetric measure. Automatic classification by SVM clearly outperformed all other methods (accuracy, 87.4%), representing the only method to provide clinically useful sensitivity also in vPSP (70.0%). Fully automatic classification of volumetric MRI measures using machine learning methods outperforms visual MRI analysis without and with planimetry or volumetry support, particularly regarding diagnosis of vPSP, suggesting the use in settings with a broad phenotypic PSP spectrum. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.


Evaluation of two commercial broiler male lines differing in efficiency of feed utilization.
Factors potentially influencing feed conversion were studied in two lines of broilers known to differ in efficiency of feed utilization. When fed diets differing in energy, line by diet interactions were seldom significant and line effects were greater than those between diets. Chicks from the more efficient line had less plumage cover, less fat, and spent more time sitting than those from the less efficient line. These data imply that improved feed conversion is a function of several traits.


Immune-Related Oral, Otologic, and Ocular Adverse Events.
Emerging immunotherapeutic agents, including immune checkpoint inhibitors targeting cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4), programmed cell death protein 1 (PD-1), and programmed cell death protein ligand 1 (PD-L1), have revolutionized cancer treatment. The first immune checkpoint inhibitor (ICI) ipilimumab, an anti-CTLA-4, was approved in 2011. Since then, the US Food and Drug Administration (FDA) has approved more than half a dozen immune checkpoint inhibitors to treat various malignancies. These agents are part of a broader class of chemotherapy agents termed immunotherapy, which selectively target different steps in the immune response cascade to upregulate the body's normal response to cancer. While the effects of traditional chemotherapy are well known, the toxicity profile of emerging immune therapies is not fully elucidated. They have been associated with atypical side effects labeled collectively as immune-related adverse events (irAEs).


Disorders of the Reproductive Tract of Rabbits.
Disorders of the reproductive tract are common in rabbits. Conditions are different in rabbits that are farmed for their meat or fur and those that are kept as pets. Farmed rabbits suffer from infections and diseases associated with pregnancy. Congenital abnormalities are more likely to be recognized and treated in pet rabbits. Pet rabbits suffer from age-related changes to their genital tract (hyperplasia, neoplasia, or hernias). Neutering is an important part of prevention and treatment of reproductive disorders. Knowledge of normal male and female reproductive anatomy is essential to prevent complications. These are described and illustrated.


MR enterography: how to deliver added value.
MR enterography (MRE) is increasingly vital to the diagnosis and follow-up of children with Crohn disease. This diagnostic test, which can provide valuable information regarding the presence of intestinal inflammation, intestinal and intra-abdominal complications, and extra-intestinal disease-related manifestations, has the potential to directly impact both medical and surgical decision-making. Consequently, it is imperative that the interpretation and reporting of these examinations provide as much clinical information as possible. This article reviews specific ways radiologists can provide added value when interpreting MRE examinations in the setting of pediatric Crohn disease by (1) establishing the true extent of disease involvement, (2) subjectively and objectively assessing response to medical treatment and (3) accurately characterizing disease-related complications.


Body mass index, waist hip ratio, and waist circumference: which measure to classify obesity?
To determine the proportion of a representative population sample of adults in South Australia who have a body mass index (a measure of overall obesity) classified as normal or underweight, but who also have a waist circumference or waist hip ration (measures of central obesity) that indicates obesity. A representative population sample of adults aged 18 years and over living in the north west region of Adelaide (n = 2523) were recruited to the study. Clinical measures of height, weight, waist and hip circumference were obtained and used to determine body mass index, waist hip ratio and waist circumference. Among women with a normal body mass index, 19.0% had a high waist circumference (> or = 80 cm) and 8.5% had a high waist hip ratio (> 0.85). Among males with a normal body mass index, 3.4% had a high waist circumference (> or = 95 cm) and 0.1% had a high waist hip ratio (> 1.0). Body mass index, waist hip ratio and waist circumference all have a role in the identification of those who are obese or overweight.


Clinical results of endoscopic treatment without repair for partial thickness gluteal tears.
Various surgical treatments have been proposed for greater trochanteric pain syndrome (GTPS) related to gluteal tendinopathy with partial thickness tears. The clinical results of endoscopic debridement without repair of these gluteal tears are not well known. The objectives of this study were to determine if this procedure leads to: (1) reduction of pain, (2) functional improvement, (3) patient satisfaction (on scale of 0 to 10). Endoscopic treatment without tendon repair provides short-term pain relief in patients with GTPS due to partial thickness gluteal tears. Seventeen patients (16 women, 1 man) with GTPS due to partial thickness gluteal tears that was present for at least 6 months and was refractory to conservative treatment were included in the analysis. The average age at the time of the procedure was 53.5years (17-71). Pain was evaluated with a visual analogue scale (VAS). Functional outcomes were defined using the Harris Hip Score and the UCLA activity score. Satisfaction was evaluated using a VAS and Odom's criteria. The average follow-up was 37.6months (12-48). The average preoperative and follow-up values were respectively: (1) Pain: 7.2±1.1 (5-9) versus 3.3±1.9 (1-7) (P<0.001), (2) Harris score: 53.5±8.4 (36-68) versus 79.8±14.7 (45-96) (P<0.001). Seven patients (41.2%) were able to resume sports activities. The average satisfaction score for the surgery was 6.2±2.4 (0-9) at follow-up. Five patients had a poor outcome at the review: four still had pain and one had recurrence of the lateral snapping hip. Endoscopic treatment without repair of partial thickness gluteal tears is a treatment option with modest clinical results for GTPS patients refractory to conservative treatment. IV, retrospective study.


Inhibition of GR-mediated transcription by p23 requires interaction with Hsp90.
p23 is a regulatory co-chaperone of heat shock protein (Hsp) 90, but can also act as a general molecular chaperone by itself. Using novel point mutations of p23 that disrupt its interaction with Hsp90 we found its co-chaperone function to be required for its inhibitory effect on glucocorticoid receptor (GR). The C-terminal region of p23, which is required for its chaperone activity, is dispensable for inhibition of GR. Importantly, similar results were obtained with a constitutively active GR. Thus, the action of p23 on the nuclear stage of GR regulation requires its Hsp90 co-chaperone function, but not its chaperone activity.


Histopathology imagery dataset of Ph-negative myeloproliferative neoplasm.
Tumorous cancer has been a widely known and well-studied medical phenomenon; however, rare diseases like Myeloproliferative Neoplasm (MPN) have received less attention, leading to delayed diagnosis. Despite the availability of advanced technology in diagnostic tools that can boost the procedure, the morphological assessment of bone marrow trephine (BMT) images remains critical to confirm and differentiate MPN subtypes. This paper reports a histopathological imagery dataset that was created to focus on the most common MPN from the Philadelphia Chromosome (Ph)-negative type, namely Essential Thrombocythemia (ET), Polycythemia Vera (PV), and Primary Myelofibrosis (MF). The dataset consisted of 300 BMT images that can be used to enable computer vision applications, such as image segmentation, disease classification, and object recognition, in assisting the classification of the MPN disease. Ethical approval was obtained from the Ministry of Health, Malaysia and the bone marrow trephine images were captured using a digital microscope from the Olympus model (BX41 Dual head microscope) with x10, x20, and x40 lens types. The development of comprehensive tools deployed from this dataset can assist medical practitioners in diagnosing diseases, thus overcoming the current challenges.


How does Identity Theory contribute to the Continuance Use of E-learning: The mediating role of Inertia and moderating role of computer Self-efficacy.
Despite e-learning's rapid growth and significant benefits, especially during the COVID-19 pandemic, retaining students in this educational environment is a critical challenge in the post-corona era. Therefore, our research was conducted to explore how we can promote the continuance use of e-learning (CUEL) platforms. More specifically, this study examines how identity, inertia, and computer self-efficacy affect CUEL. Data were collected from 384 users and provided support for the model. The results indicated that social identity, relational identity, and inertia are critical determinants of CUEL. Furthermore, inertia mediates the relation between social identity and CUEL. In addition, we found that computer self-efficacy moderates the relation of inertia and relational identity with CUEL, but its moderating effect on the influence of social identity and CUEL is not supported. Finally, the theoretical and practical implications of this study are discussed.


Thioredoxin-Interacting Protein Inhibited Vascular Endothelial Cell-Induced HREC Angiogenesis Treatment of Diabetic Retinopathy.
Diabetic retinopathy is the most common reason for blindness among employed adults worldwide. Hyperglycemia and the overaccumulation of vascular endothelial growth factor (VEGF) lead to diabetic retinopathy, pathological angiogenesis in diabetic retinopathy, and consequent visual impairment. Expression levels of thioredoxin-interacting protein (TXNIP) substantially increase in retinal endothelial cells in diabetic circumstances. The part of TXNIP in retinal angiogenesis combined with diabetes remains unclear. This study examined the effect of reduced TXNIP expression levels and determined how it affects diabetic retinal angiogenesis. Display of human retinal vascular endothelial cells (HRECs) to moderately high glucose (MHG) encouraged tube formation and cell migration, not cell proliferation. In response to MHG conditions, in HRECs, TXNIP knockdown inhibited the production of reactive oxygen species (ROS), cell migration, tube formation, and the Akt/mTOR activation pathway. In addition, gene silencing of TXNIP decreased the VEGF-triggered angiogenic response in HRECs by preventing activation of both VEGF receptor 2 and the downstream components of the Akt/mTOR pathway signaling. Furthermore, TXNIP knockout mice reduced VEGF-induced or VEGF- and MHG-triggered ex vivo retinal angiogenesis compared to wild-type mice. Finally, our findings revealed that TXNIP knockdown suppressed VEGF- and MHG-triggered angiogenic responses in HRECs and mouse retinas, indicating that TXNIP is a promising therapeutic window against the proliferation of diabetic patients' retinopathy.


Exposure to BDE-47 and BDE-209 impaired antioxidative defense mechanisms in Brachionus plicatilis.
Polybrominated diphenyl ethers (PBDEs) are persistent organic pollutants (POPs) that pose serious challenges to aquatic animals and environments. Compared with BDE-47 which was one of the most toxic congeners known to date, BDE-209 is less toxic with higher abundance in biotic and abiotic samples. In this study, we have explored the effects of BDE-47 and BDE-209 at different concentrations on the radical oxygen species (ROS) levels and the antioxidant defense system of Brachionus plicatilis. Antioxidant indexes were measured, including total protein content (TSP), the activities of antioxidant enzymes, lipid peroxidation and DNA damage. The results indicated that while low concentrations of PBDEs could activate the antioxidant defense mechanisms, prolonged exposure to higher concentrations of PBDEs could impair the antioxidative capacity of B.plicatilis (P < 0.05). The overwhelming of the B.plicatilis antioxidant defense mechanism led to an accumulation of free radicals, resulting in the overactivation of lipid peroxidation and the increased frequency of DNA damage (P < 0.05). By studying the toxicity of PBDEs and the detoxification mechanism of B.plicatilis, our research has revealed useful indexes for detecting and monitoring the level of BDE-47 and BDE-209 in the future. Altogether, this study holds immense value in the field of ecotoxicology and environmental safety and will aid in the proper management of PBDEs pollution.


The prevalence of comorbid chronic pain conditions among patients with temporomandibular disorders: A systematic review.
This systematic review was designed to evaluate the presence of comorbid conditions among patients with temporomandibular disorders (TMDs). The authors reviewed studies that reported the prevalence or incidence of chronic pain conditions or psychiatric disorders (anxiety, mood, personality disorders) among patients with any type of TMD. The authors calculated sample size-weighted prevalence estimates when data were reported in 2 or more studies for the same comorbid condition. A total of 9 prevalence studies and no incidence studies were eligible for review; 8 of the studies examined chronic pain comorbidities. Weighted estimates showed high prevalence of pain comorbidities across studies, including current chronic back pain (66%), myofascial syndrome (50%), chronic stomach pain (50%), chronic migraine headache (40%), irritable bowel syndrome (19%), and fibromyalgia (14%). A single study examined psychiatric disorders and found that current depression was the most prevalent disorder identified (17.5%). There is a high prevalence of comorbid chronic pain conditions among patients with TMDs, with more than 50% of patients reporting chronic back pain, myofascial syndrome, and chronic stomach pain. Psychiatric disorders among patients with different types of TMDs were studied less commonly in this pain population. Knowledge of the distribution of these and other comorbid disease conditions among patients with different types of TMDs can help dentists and other health care providers to identify personalized treatment strategies, including the coordination of care across medical specialties.