Managing household income and antiretroviral therapy adherence among people living with HIV in a low-income setting: a qualitative data from the HPTN 071 (PopART) trial in South Africa.
South Africa is reported to have the highest burden of HIV with an estimated 8.2 million people living with HIV (PLHIV) in 2021- despite adopting the World Health Organisation (WHO) universal HIV test and treat (UTT) recommendations in 2016. As of 2021, only an estimated 67% (5.5 million) of all PLHIV were accessing antiretroviral therapy (ART), as per recorded clinic appointments attendance. Studies in sub-Saharan Africa show that people living in low-income households experience multiple livelihood-related barriers to either accessing or adhering to HIV treatment including lack of resources to attend to facilities and food insecurity. We describe the interactions between managing household income and ART adherence for PLHIV in low-income urban and semi-urban settings in the Western Cape, South Africa. We draw on qualitative data collected as part of the HPTN 071 (PopART) HIV prevention trial (2016 - 2018) to provide a detailed description of the interactions between household income and self-reported ART adherence (including accessing ART and the ability to consistently take ART as prescribed) for PLHIV in the Western Cape, South Africa. We included data from 21 PLHIV (10 men and 11 women aged between 18 and 70 years old) from 13 households. As part of the qualitative component, we submitted an amendment to the ethics to recruit and interview community members across age ranges. We purposefully sampled for diversity in terms of age, gender, and household composition. We found that the management of household income interacted with people's experiences of accessing and adhering to ART in diverse ways. Participants reported that ART adherence was not a linear process as it was influenced by income stability, changing household composition, and other financial considerations. Participants reported that they did not have a fixed way of managing income and that subsequently caused inconsistency in their ART adherence. Participants reported that they experienced disruptions in ART access and adherence due to competing household priorities. These included difficulties balancing between accessing care and/or going to work, as well as struggling to cover HIV care-related costs above other basic needs. Our analysis explored links between managing household income and ART adherence practices. We showed that these are complex and change over the course of treatment duration. We argued that mitigating negative impacts of income fluctuation and managing complex trade-offs in households be included in ART adherence support programmes.


Deviated lysis: transfer of complement lytic activity to unsensitized cells. IV. Parital isolation of the activity.
Deviated lysis (d.l.) was previously characterized as the lysis of non-sensitized erythrocytes by activated complement (C) in the presence of EDTA (1, 2, 3). The lytic activity was present in serum fractions of a m.w. in the proximity of 220,000. All the C factors C5 through C9 were found in these fractions and they were all needed for lysis. It is proposed that in d.l. small aggregates of the C components C5 through C9 coexist in the reaction mixture without further interaction. Only when appropriate receptors such as present on target cells surfaces are available, the factors react in a sequential order eventually to result in lysis of the target cell.


Medroxyprogesterone acetate-resistant endometrial cancer cells are susceptible to ferroptosis inducers.
Medroxyprogesterone acetate (MPA) is the most common fertility-sparing treatment in patients with early-stage endometrial cancer. If MPA treatment fails, hysterectomy is recommended. Thus, there is an urgent need for novel treatment approaches for MPA-resistant endometrial cancer patients who wish to preserve their fertility. Ferroptosis is a recently discovered type of regulated cell death caused by the excessive accumulation of reactive oxygen species (ROS), followed by aberrant lipid peroxidation. Recent studies have shown that inducing ferroptosis is a potential therapeutic strategy for cancer. However, the role of ferroptosis in endometrial cancer treatment remains to be discussed. We therefore investigated the effects of ferroptosis inducers on MPA-resistant endometrial cancer cells. The levels of solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4), the main mediators of ferroptosis, were examined. Cell viability was evaluated after treatment with the ferroptosis inducers sulfasalazine, erastin, or RSL3. The degree of intracellular oxidative stress after treatment with these drugs was evaluated by the glutathione level, ROS level, ferrous iron level, lipid peroxidation and changes in mitochondrial morphology. The effect of ferroptosis inducers in vivo was also examined. The expression of SLC7A11 and GPX4 in MPA-resistant ECC-1 cells decreased in comparison to parental ECC-1 cells. Sulfasalazine, erastin, and RSL3 significantly reduced cell viability and increased intracellular oxidative stress in MPA-resistant ECC-1 cells. Ferroptosis inducers also suppressed in vivo tumor growth more effectively in MPA-resistant ECC-1. Treatment with ferroptosis inducers could be a novel therapeutic approach for MPA-resistant endometrial cancer.


A cell array biosensor for environmental toxicity analysis.
In this study, a cell-based array technology that uses recombinant bioluminescent bacteria to detect and classify environmental toxicity has been implemented to develop two biosensor arrays, i.e., a chip and a plate array. Twenty recombinant bioluminescent bacteria, having different promoters fused with the bacterial lux genes, were immobilized within LB-agar. About 2 microl of the cell-agar mixture was deposited into the wells of either a cell chip or a 384-well plate. The bioluminescence (BL) from the cell arrays was measured with the use of highly sensitive cooled CCD camera that measured the bioluminescent signal from the immobilized cells and then quantified the pixel density using image analysis software. The responses from the cell arrays were characterized using three chemicals that cause either superoxide damage (paraquat), DNA damage (mitomycin C) or protein/membrane damage (salicylic acid). The responses were found to be dependent upon the promoter fused upstream of the lux operon within each strain. Therefore, a sample's toxicity can be analyzed and classified through the changes in the BL expression from each well. Moreover, a time of only 2 h was needed for analysis, making either of these arrays a fast, portable and economical high-throughput biosensor system for detecting environmental toxicities.


Transrectal thin-needle aspiration biopsy of prostate: four years' experience.
Fine-needle aspiration biopsy of the prostate is of great advantage in the diagnosis of prostatic disease. The procedure is quick, safe, and reliable. Several aspirations can be done even in outpatients with minimum trauma. Complications are rare. In this study cytologic diagnosis was obtained in 511 consecutive patients. To evaluate the cytologic accuracy, 195 cytologic diagnoses were compared with histologic findings obtained from transperineal biopsy on the same patients. Correlation was achieved in 96.42 per cent of these cases. The findings in 127 histologically graded prostatic cancers were compared with the cytologic differentiation observed in aspiration smears of the same patients. Cytologic grading of prostatic carcinoma corresponded to the histologic grading in 85.8 per cent of the cases.


Pregnane-x-receptor controls hepatic glucuronidation during pregnancy and neonatal development in humanized UGT1 mice.
In humanized UDP glucuronosyltransferase-1 (hUGT1) mice that express the entire UGT1 locus, the maternal hepatic UGT1A genes are dramatically induced 12-14 days after conception. Steroid induction of the UGT1A1 gene indicates that xenobiotic sensors, such as the pregnane X receptor (PXR) and constitutive androstane receptor (CAR), may underlie the induction process. In contrast, neonatal hUGT1 mice display severe hyperbilirubinemia, with limited expression of the UGT1A genes. This study identifies PXR as both a positive and negative regulator of the UGT1A1 gene. Pregnancy hormones, in particular the glucocorticoids, target PXR as a positive regulator of human glucuronidation. Employing reverse genetics, where PXR has been genetically deleted, hUGT1/Pxr(-/-) mice show limited induction of the liver UGT1A genes during pregnancy, whereas the exact opposite occurs in newborn mice. Neonatal hUGT1 mice show delayed expression of hepatic UGT1A1 and are severely hyperbilirubinemic. However, in hUGT1/Pxr(-/-) mice, hyperbilirubinemia is greatly reduced due to induction of hepatic UGT1A1. Thus, PXR serves to repress UGT1A1 gene expression during development. Transcriptional silencing of the UGT1A1 gene was relieved in neonatal hUGT1 hepatocytes through interruption of PXR by small interfering RNA. PXR is a key regulator of pregnancy induced glucuronidation capacity in addition to modulating the severity of neonatal jaundice.


Dual effect of aucubin on promoting VEGFR2 mediated angiogenesis and reducing RANKL-induced bone resorption.
Angiogenesis is regarded as a critical role in bone repair and regeneration, involving in pathological bone disorders such as osteoporosis. Aucubin, an iridoid glycoside primarily derived from Eucommia ulmoides, is reported to inhibit osteoclast activity, enhance bone formation and promote angiogenesis in osteoporosis models. Our study is to further investigate the anti-osteoporosis effect of aucubin in transgenic medaka, and the pro-angiogenic effect of aucubin and its mechanism of action both in vivo and in vitro. The anti-osteoporosis effect of aucubin was confirmed by using RANKL-stimulated bone resorption transgenic medaka. The pro-angiogenic effect of aucubin in vivo was investigated using vascular endothelial growth factor (VEGF) tyrosine kinase inhibitor II (VRI)-induced vascular insufficient transgenic zebrafish model. Furthermore, endothelial cell proliferation, migration, tube formation and the mechanisms were evaluated to identify the pro-angiogenic effect of aucubin in normal and su5416-injured human umbilical vein endothelial cells (HUVECs). Aucubin decreased the resorption of the mineralized bone matrix and centra degradation in heat-shocked transgenic col10α1:nlGFP/rankl:HSE:CFP medaka. Moreover, aucubin reversed VRI-induced vascular insufficiency in zebrafish through regulating flt1, kdr, kdrl, vegfaa, ang-1, ang-2, tie1 and tie2 mRNA expressions in Tg(fli1a:EGFP)y1 or AB wild type zebrafish. Aucubin promoted cell proliferation by upregulating p-mTOR, p-Src, p-MEK, p-Erk1/2, p-Akt and p-FAK in HUVECs. Furthermore, aucubin exhibited a pro-angiogenic effect on su5416-injured HUVECs by promoting their proliferation, migration, and tube formation through regulating the phosphorylation of VEGFR2, MEK, ERK and the ratio of Bcl2-Bax. Aucubin could reduce bone resorption in RANKL-induced osteoporosis medaka by live imaging. Meanwhile, aucubin exhibited a protective effect in VRI-induced vascular insufficient zebrafish by regulating VEGF-VEGFR and Ang-Tie signaling pathways. Additionally, aucubin promoted the proliferation, migration and tube formation of HUVECs probably by mediating VEGFR2/MEK/ERK, Akt/mTOR and Src/FAK signalling pathways. This study further indicated the dual effect of aucubin on angiogenesis and osteogenesis which may be beneficial to its treatment of osteoporosis.


Effects of gremlin-2 on the transition of primordial follicles during early folliculogenesis in the human ovary.
To investigate the localization and function of gremlin-2 during human ovarian folliculogenesis. Ovarian tissue from a gynecologic cancer patient was cultured in the presence or absence of gremlin-2 and then analyzed histologically. Growing follicles were counted by the microscopic observations of ovarian histological sections. Immunocytochemical staining was carried out to detect the expression of bone morphogenetic protein (BMP) 4 and phosphorylated Smad 1/5/8 (p-Smad 1/5/8). Gremlin-2 was detected in human primordial, primary, and early growing follicles before culture. By day 4 of culture, the follicle growth rate in the presence of gremlin-2 (13.7%; 24/175) was significantly lower than that of the control (54.8%; 92/175; p<0.01). BMP4 expression was similar in the presence and absence of gremlin-2, whereas the p-Smad 1/5/8 signal was noticeably stronger in the absence of gremlin-2 in primordial and early-stage growing follicles. Gremlin-2 maintains the follicle store as primordial follicles by suppressing Smad 1/5/8 signaling in the human ovary. The data presented here provide potential insight into reproductive medicine for cases of intractable infertility, such as premature ovarian insufficiency and cancer survivors.


Accuracy of 16-row multislice computerized tomography angiography for assessment of intracranial aneurysms.
Sixteen-row multislice CT has great potential for use in vascular studies. The aim of the study was to assess the diagnostic accuracy of 16-row multislice CTA in detecting intracranial aneurysms compared with 2D-DSA and surgical findings. One hundred fifty-two consecutive patients were included in the study and successively underwent 16-slice CTA, 2D-DSA, and surgery in some patients. This was performed with a 16-row multislice CT machine, detector slice of 0.75 mm, reconstruction interval of 0.40 mm, and timing determined by bolus trigger. The 16-slice CTA and 2D-DSA results were evaluated independently by 3 different neuroradiologists who performed aneurysm detection using MIP, SSD, and VRT. With the combination of 16-slice CTA, 2D-DSA, and intraoperative findings, 92 aneurysms were detected in 86 of the 152 patients. Two aneurysms were missed when 16-slice CTA was used. Three aneurysms were not clearly depicted at 2D-DSA, but proven at surgery. There was no statistically significant difference in sensitivity between 16-slice CTA and 2D-DSA (P = 1.0). The sensitivity of 16-slice CTA for detecting aneurysms <4 mm, between 4 and 10 mm, and >10 mm was 96% (95% CI: 79.6%-99.9%), 98.1% (95% CI: 89.7%-100%), and 100% (95% CI: 78.2%-100%), respectively, on a per-aneurysm basis. The sensitivity, specificity, and accuracy of 16-slice CTA for detecting aneurysms were 97.8% (95% CI: 92.4%-99.7%), 100% (95% CI: 94.6%-100%), and 98.7% (95% CI: 95.5%-99.8%), respectively, on a per-aneurysm basis. Sixteen-slice CTA shows promising diagnostic accuracy that appears to be comparable with 2D-DSA for the detection of suspected intracranial aneurysms, and 16-slice CTA is sensitive enough to replace 2D-DSA in detecting aneurysms.


[Resection of metastases from prostate cancer].
Surgical resection of a solitary or a limited number of metastases is a controversy in patients with prostate cancer that is increasingly being discussed. The improved accuracy of the detection of local or distant recurrences after primary treatment using modern imaging techniques including choline PET/CT led to an increased demand for salvage surgical procedures. Apart from the resection of synchronous metastases at the time of radical prostatectomy the oncological efficacy of a salvage lymphadenectomy or a salvage resection of visceral or osseous metastases remains to be proven. Here, the available data covering the different clinical scenarios for the resection of metastases in prostate cancer and recommendations of recently published guidelines are reviewed.


Inequalities in early initiation of breastfeeding in Bangladesh: an estimation of relative and absolute measures of inequality.
Evidence suggested that inequalities based on education, wealth status, place of residence, and geographical regions significantly influence the key breastfeeding indicators including early initiation of breastfeeding. This study aimed to estimate the trends and magnitude of inequalities in early initiation of breastfeeding practice in Bangladesh from 2004 to 2017 applying both absolute and relative measures of inequality. We used data from the last five Bangladesh Demographic Health Survey (BDHS) from 2004 to 2017 to measure the inequalities in early initiation of breastfeeding practice using the WHO's Health Equity Assessment Toolkit (HEAT) software. Following summary measures were estimated to measure the inequalities: Population Attributable Risk (PAR), Population Attributable Fraction (PAF), Difference (D), and Ratio (R) where the equity dimensions were wealth status, education level, sex of child, place of residence, and subnational regions (divisions). For each measure, point estimates along with a 95% confidence interval (CI) were reported. An uprising pattern in the prevalence of early initiation of breastfeeding was found, where early initiation of breastfeeding increased from 24.9% to 2004 to 59.0% in 2017. We found significant wealth-driven inequalities in early initiation of breastfeeding practice in every wave of survey favoring the poorest wealth quintile (in 2017, D -10.5; 95% CI -16.6 to -4.3). We also identified geographical disparities in early initiation of breastfeeding practice (in 2017, PAF 11.1; 95% CI 2.2 to 19.9) favoring the Rangpur (65.5%), and Sylhet (65.3%) divisions. Education-related disparities were observed in 2004 only, but not in later survey years, which was due to a much lower level of adherence among those with secondary or higher education. There were no significant disparities in early initiation of breastfeeding based on the urban vs. rural residence and sex of the child. The highest attention should be placed in Bangladesh to attain the WHO's 100% recommendation of timely initiation of breastfeeding. This study emphasizes on addressing the existing socioeconomic and geographic inequalities. Awareness-raising outreach programs focusing the mothers from wealthier sub-groups and divisions with lower prevalence should be planned and implemented by the joint effort of the government and non-government organizations.


Metabolic adaptation of tissues to stress releases metabolites influencing innate immunity.
Recent developments have demonstrated that metabolic rewiring imposed by adaptation of tissues to stress leads to the release of various metabolites which directly or indirectly impact innate immune responses and inflammation. Some metabolites can behave as second messengers and leave local cues in tissues. Immune cells which infiltrate stressed tissues reorient their metabolism to cope with these microenvironmental cues while preserving their effector functions in tissues.


A Brief Mindfulness-Based Intervention (bMBI) to Reduce Teacher Stress and Burnout.
Teacher stress and burnout contribute to attrition and stress-related health concerns. Despite some positive effects, previous mindfulness-based interventions (MBI) have failed to incorporate key elements of methodological rigor and have included large dosages despite research suggesting that such dosages are iatrogenic. The current study demonstrates the efficacy of a brief MBI (bMBI; four sessions, six total hours) to reduce self-reported stress, burnout, and depression, and suggests the bMBI can protect against deleterious impacts to physiological functioning. The study informs the design and implementation of future MBIs, including strategies for reducing intervention dosages, in order to improve effectiveness and maximize cost-effectiveness.


The identification and characterization of a testis-specific cDNA during spermatogenesis.
Using bioinformatics and experimental validation, we obtained a cDNA (named srsf) which was exclusively expressed in the mouse testes. RT-PCR analysis showed that srsf mRNA was not expressed in the gonad during the sex determination period or during embryogenesis. In developing mouse testis, srsf expression was first detected on post-natal day 10, reached its highest level on day 23, and then reduced to and remained at a moderate level throughout adulthood. In situ hybridization analysis demonstrated that srsf mRNA was expressed in pachytene spermatocytes and round spermatids in the testes. The predicted protein contains one RNA-binding domain (RBD) and a serine-arginine rich domain (RS), which are characterized by some splicing factors of SR family members. These findings indicate that srsf may play a role during spermatogenesis.


Geochemistry of soil around a fluoride contaminated area in Nayagarh District, Orissa, India: factor analytical appraisal.
Fluoride contamination in soil was studied in the vicinity of a hot spring in Nayagarh district of Orissa. Both bulk soil from 0 to 30 cm depth and profile soils from 0 to 90 cm depth were analyzed for total fluoride (F(t)) and 0.01 M CaCl(2) extractable fluoride (F(ca)), major elements, pH, EC and Organic Carbon (OC). High concentrations of both F(t) and F(ca) were observed in the area surrounding the hot spring and the village of Singhpur. Principal factor analysis (PFA) on the parameters of the bulk soils suggests that two major chemical processes due to three factors, control the soil geochemistry of the area. Factor-1 contributes 37.11% of the total variance and is strongly loaded with Al, Si, Fe, F(t)and F(ca), and explains the fluoride enrichment of the soil, whereas the second and the third factors contribute 16.6 and 12.2%, respectively and explain the controlling process of carbonate precipitation and soil alkalinity. Multiple regression analysis of the scores of the factors was performed to derive a fluoride contamination index in soil. The magnitude of the factor effect on the contamination index follows the order of Factor-1 > Factor-2 > Factor-3. The spatial distribution of the contamination index is used to classify the area into highly contaminated, moderately contaminated and uncontaminated zones.


Production of Cardiomyocyte-Like Cells by Fibroblast Reprogramming with Defined Factors.
Over the last decade, great achievements have been made in the field of direct epigenetic reprogramming, which converts one type of adult somatic cells into another type of differentiated cells, such as direct reprogramming of fibroblasts into cardiomyocytes, without passage through an undifferentiated pluripotent stage. Discovery of direct cardiac reprogramming offers a promising therapeutic strategy to prevent/attenuate cardiac fibrotic remodeling in a diseased heart. Furthermore, in vitro reprogramming of fibroblasts into cardiomyocyte-like cells provides new avenues to conduct basic mechanistic studies, to test drugs, and to model cardiac diseases in a dish. Here, we describe a detailed step-by-step protocol for in vitro production of induced cardiomyocyte-like cells (iCMs) from fibroblasts. The related procedures include high-quality fibroblast isolation of different origins (neonatal cardiac, tail-tip, and adult cardiac fibroblasts), retroviral preparation of reprogramming factors, and iCM generation by fibroblast reprogramming via retroviral transduction of Gata4, Mef2c, and Tbx5. A detailed written protocol will help many other laboratories, inexperienced in this area, to use and further improve this technology in their studies of cardiac regenerative medicine.


Proposed competencies for the performance of cardiovascular computed tomography in pediatric and adult congenital heart disease.
Cardiovascular computed tomography (CCT) is rated appropriate by published guidelines for the initial evaluation and follow up of congenital heart disease (CHD) and is an essential modality in cardiac imaging programs for patients of all ages. However, no recommended core competencies exist to guide CCT in CHD imaging training pathways, curricula development, or establishment of a more formal educational platform. To fill this gap, a group of experienced congenital cardiac imagers, intentionally inclusive of adult and pediatric cardiologists and radiologists, was formed to propose core competencies fundamental to the expert-level performance of CCT in pediatric acquired and congenital heart disease and adult CHD. The 2020 SCCT Guideline for Training Cardiology and Radiology Trainees as Independent Practitioners (Level II) and Advanced Practitioners (Level III) in Cardiovascular Computed Tomography (1) for adult imaging were used as a framework to define pediatric and CHD-specific competencies. Established competencies will be immediately relevant for advanced cardiac imaging fellowships in both cardiology and radiology training pathways. Proposed future steps include radiology and cardiology society collaboration to establish provider certification levels, training case-volume recommendations, and continuing medical education (CME) requirements for expert-level performance of CCT in pediatric and adult CHD.


Ethnic disparities in traumatic occupational injury.
Workers of different ethnicities differ in patterns of employment and occupational risks. We use the Illinois Trauma Registry to evaluate ethnic disparities among the occupational traumatic injuries occurring in the State of Illinois between 1997 and 2003. We analyze incidence, severity, cause and place of injury, disability and in-hospital mortality. The incidence rates of traumatic injuries among Hispanics were more than two times higher than whites, however, the risk of severe injury (Injury Severity Score >or=16) was more than 50% lower. Among African-American workers, the incidence and severity of traumatic injuries were lower than whites. Machinery was the primary external cause of injury among Hispanics. blacks were disproportionately injured in road accidents and homicides/assaults. There are substantial racial/ethnic differences in incidence, severity and outcome of work-related traumatic injuries treated in level I and II trauma centers in Illinois.


Detection of tumour necrosis factor from lipopolysaccharide-stimulated human mononuclear cells by enzyme-linked immunosorbent assay and cytotoxicity bioassay.
Tumour necrosis factor (TNF) or cachectin is an important mediator of endotoxic activity. To investigate the production of TNF from human mononuclear cells (MNC) in response to lipopolysaccharide (LPS), we developed a sensitive and specific enzyme immunoassay (ELISA) and a cytotoxicity bioassay for TNF. The ELISA utilizes the biotin/avidin system and includes four incubation steps. The detection limit was 25 pg recombinant TNF (rTNF)/100 microliter. There was no interference of medium, serum, plasma, spinal fluid, or urine and no cross-reaction with natural or recombinant IL-1-alpha, IL-1-beta, IL-2, IFN-gamma, or lymphotoxin (TNF-beta). Recovery of TNF added to the media was 85-123% (n = 22). The relative standard deviations within and between assays were 7% and 8%, respectively. TNF-induced cytotoxicity was measured on actinomycin-D-treated L-M mouse fibroblasts. The detection limit in this bioassay was 0.5 U/30 microliter or 12.5 pg/30 microliter of rTNF. IL-1-alpha and IL-1-beta slightly inhibited the cytotoxic activity of rTNF. In this bioassay, cytotoxic activity (50-300 U/ml) was detected only when MNC were stimulated with high concentrations of LPS (100-1000 ng/ml). In contrast, using 0.01-100 ng/ml of LPS, the ELISA detected TNF in a dose-dependent manner (0.25 ng/ml to 40 ng/ml). It is concluded that TNF is liberated from human blood MNC if stimulated with minute amounts of LPS. It is suggested that human TNF may be secreted in a relatively inactive form or that inhibitors of TNF are generated along with the monokine. Because of this, and because commonly used bioassays for TNF fail to distinguish between TNF and lymphotoxin, specific ELISA are recommended to supplement TNF bioassays.


Comparison of serum and lung extracts for surveys of wild animals for antibodies to Francisella tularensis biovar palaearctica.
A comparative study of the antibody titer against Francisella tularensis biovar palaearctica in serum and lung extract was made using different immunoassays. Samples were taken from experimentally-infected goshawks (Accipiter gentilis) and European beavers (Castor fiber), and in a field survey of wild beavers. Good accordance between the antibody titer in serum and in lung extract was found in the experimental studies. However, the antibody titer was generally one- to three-fold lower in lung extract than was the titer of serum. Results in the field survey were less reliable. Estimating antibody titer in lung extract is a practical method for surveys for antibody levels, and an alternative to serological surveys, despite lower sensitivity as compared to serum.


Production of(14)C-ochratoxin A byPenicillium verrucosum sp. 1761 in liquid culture.
The synthesis of(14)C-labelled ochratoxin A was carried out by biosynthesis withPénicillium verrucosum sp. 1761 in liquid culture using 2-(14)C-Na-acetate and 2-(14)C-malonic acid as precursor. The largest amount of ochratoxin A produced byPénicillium verrucosum was detected in a minimal medium after an incubation period of 28 days. By addition of citric acid and 2,4-dichlorophenoxy acetic acid larger ochratoxin A contents could be measured. For transformation studies of ochratoxin A, a molecule which is exclusively labelled in the isocoumarin moiety is best suitable. This labelling could be obtained by using labelled malonic acid as precursor, whereas with 2-(14)C-Na-acetate as precursor the whole molecule was labelled. Incorporation rates of radioactivity into the molecule were from 0.04% to 0.11%, specific radioactivities from 0.02 μCi/mg to 0.07 μCi/mg.


Epidemiology of bovine ephemeral fever virus infection in Taiwan.
Sick animals with excessive nasal discharges and protruding tongue as a result of dyspnea were observed in the August of 1996. Eight strains of BEF virus were isolated from heparinized blood samples of the affected cattle. Most of the affected cattle were difficult to be treated and had a poor prognosis. A total of 516 farms in the 9 districts of Taiwan were affected in 1996. Among a population of 110,247 dairy cattle, 14,993 (13.6%) cattle were found to be clinically ill. During the epidemic, 1,685 (11.3%) affected cattle were culled or dead after the onset of the disease. Furthermore, a strain of Ibaraki virus was isolated from the blood sample of a sick cattle that showed pyrexia, labored respiration and solitary behavior in the affected farm. The cattle with Ibaraki virus infection had typical symptoms of BEF at the early stage of the disease, but neither stomatitis nor pharyngoesophageal paralysis was observed at the onset of the disease. The outbreak was presumably brought about by the low level or non-immune status of a large cattle population due to the negligence of BEF vaccination. Therefore, the disease easily recurred in Taiwan after a typhoon episode in the August of 1996, which resulted in the proliferation of biting midges in the field. No difference in the antigenicty was found between the new and the previous isolates of BEF virus. As analyzed by cross neutralization test, the isolated BEF viruses showed no relationship to the Kimberley and Berrimah viruses that were isolated from the blood of cattle and related to BEF virus in Australia. We have tried to advise farmers that they must vaccinate their cattle annually to prevent BEF outbreak in the future.


Key lessons and strategies for implementing single IRB review in the Trial Innovation Network.
The Trial Innovation Network has established an infrastructure for single IRB review in response to federal policies. The Network's single IRB (sIRBs) have successfully supported over 70 multisite studies via more than 800 reliance arrangements. This has generated several lessons learned that can benefit the national clinical research enterprise, as we work to improve the conduct of clinical trials. These lessons include distinguishing the roles of the single IRB from institutional Human Research Protections programs, establishing a consistent sIRB review model, standardizing collection of local context and supplemental, study-specific information, and educating and empowering lead study teams to support their sites.


Calcitonin gene-related peptide increases acetylcholine quantal size in neuromuscular junctions of mice.
We used an intracellular microelectrode technique to study the mechanisms of action of two isoforms (human and rat) of calcitonin gene-related peptide (CGRP) on the evoked and spontaneous quantal secretion of acetylcholine (ACh) in mouse diaphragm motor synapses. Recordings of miniature endplate potentials (MEPPs) and evoked multiquantal endplate potentials (EPPs) in a cut neuromuscular preparation showed that CGRP increased the amplitude of EPPs without influencing their quantal content. Both isoforms of CGRP in a wide range of concentrations (1nM-1μM) provoked a similar considerable increase in MEPPs amplitude in a dose-dependent manner (up to 150-160% compared to control) without changing their frequency, rise-time, and decay. Inhibition of CGRP-receptors by truncated CGRP (CGRP8-37) completely prevented the potentiating effect of CGRP on the MEPPs amplitude. The effect of CGRP was not accompanied by changes in input resistance of muscle fiber membrane but was fully prevented by inhibition of vesicular ACh transport by vesamicol. Inhibition of protein kinase A (PKA) by H-89 also prevented CGRP action on the MEPPs amplitude. It is concluded that, in mammalian neuromuscular junctions, different isoforms of exogenously applied CGRP uniformly potentiate amplitudes of evoked and spontaneous postsynaptic potentials acting presynaptically via an increase in ACh quantal size.


Victimization and PTSD in a Danish national youth probability sample.
To investigate the prevalence of traumatic events and life events in relation to posttraumatic stress disorder (PTSD). In a Danish national representative sample of 390 eighth-grade students with a mean age of 14.5 years, 20 prevalent potential traumatizing and distressing events were described, along with the psychological impact of these events. Eighty-seven percent of the females and 78% of the males were exposed to at least one event. The most common events were the death of a family member, threat of violence, or serious accidents. The most distressing subjective events were rape, suicide attempts, death in the family, serious illness, and childhood abuse. Gender, parents' education, and living with a single parent were associated with specific events. The estimated lifetime prevalence of PSTD was 9.0%, whereas another 14.1% reached a subclinical level of PTSD. After exposure, females suffered from PTSD twice as often as males. Being exposed to multiple traumatic events was associated with an increase in PTSD. The findings in this study suggest substantial mental health problems in adolescents who are associated with various types of victimization.


Treatment options for chronic cholestasis in infancy and childhood.
Altered bile flow physiology leads to many complications commonly seen in patients with cholestatic liver disease, regardless of the etiology. For each individual patient, a coordinated and effective treatment strategy must address the presence and the severity spectrum of malabsorption, malnutrition, vitamin and micronutrient deficiencies, pruritus, xanthomata, ascites, and liver failure, which are attributed directly or indirectly to diminished bile flow. An aggressive approach to maximizing the nutritional status of the child is vital to ensure optimal growth and development. Protein-calorie and/or fat supplementation is best discussed early. Decreasing the percentage of dietary long-chain triglycerides, providing medium-chain triglycerides, and ensuring adequate essential fatty acid and adequate protein intake may be helpful. Fat-soluble vitamin (A, D, E, and K) levels and micronutrient levels must be carefully and serially monitored and supplemented as necessary. Because the mechanisms that mediate pruritus of cholestasis remain to be determined, the use of empirical therapies continues to be standard practice. Ursodeoxycholic acid may ameliorate pruritus. Antihistamines and rifampicin may also provide temporary relief for some children. Based on the evidence that increased central opioidergic tone is present in chronic cholestasis, the use of opiate antagonists is promising but has not been evaluated in children. Selected patients with refractory pruritus that have failed maximal medical therapy have benefited from partial external biliary diversion. Ongoing dialogue with the family regarding the indications for liver transplantation is reasonable. Optimization and adherence with the pretransplant medical management enhance the chances for a successful outcome from liver transplantation. Specific to the pediatric patient, optimizing growth, development and nutrition, minimizing discomfort and disability, and aiding the child and family in coping with the stress, social, and emotional effects of chronic liver disease remain paramount.


Radiographic, clinical, and histopathologic evaluation with surgical treatment of Forestier's disease.
Diffuse idiopathic skeletal hyperostosis (Forestier's disease) is a common disorder found in the spinal region, but the notable finding in this case presentation is the associated dysphagia and dysphonia that occurred with it. Asymptomatic hypertrophic spurs of the anterior surface of the cervical vertebrae may occur in 20% to 30% of the population. Rarely, dysphagia and/or dysphonia may be caused by these cervical osteophytes pressing against the esophagus, trachea, or pharyngeal tissues. A recent case of spondylitic dysphagia exhibited striking radiographic and computerized tomographic (CT) findings. In this case, the anterior cervical exostosis was resected through the anterior cervical approach with excellent relief of dysphagia.


Ependymomas in two sisters and a maternal male cousin with mosaicism with monosomy 22 in tumour.
A family with two sisters and their mother's male cousin had ependymomas. Of note is the fact that chromosome analysis on the tumour of the younger sister showed two cell lines, one a normal female line, the other with monosomy of chromosome 22.


Precision prevention of Alzheimer's and other dementias: Anticipating future needs in the control of risk factors and implementation of disease-modifying therapies.
Empirical evidence suggests that a fair proportion of dementia cases are preventable, that some preventive actions can be taken immediately, and others may soon be implemented. Primary prevention may target cognitively normal persons with modifiable risk factors through lifestyle and multiple domain interventions (including general cardiovascular health). While the effect on individuals may be modest, it might have a large societal impact by decreasing overall dementia incidence by up to 35%. Secondary prevention will target cognitively normal persons at high risk of dementia due to Alzheimer's disease pathology with future anti-amyloid, anti-tau, or other drugs. This approach is likely to have major benefits to both individuals and society. Memory clinics will need structural and functional changes to adapt to novel technologies and increased patients' demands, and brand-new services may need to be developed with specific skills on risk profiling, risk communication, and personalized risk reduction plans.


Epipericardial fat necrosis in chest CT and MRI: a case report of an unusual cause of chest pain associated with the initial diagnosis of undifferentiated connective tissue disease.
Epipericardial fat necrosis (EFN) is a benign and self-limited condition of unknown cause with a good prognosis, usually affecting otherwise healthy patients. Clinically, it presents with severe acute left pleuritic chest pain, often leading the patient to the Emergency Room (ER). A 23-year-old male, smoker (5 pack-years), was evaluated in the ER due to left pleuritic chest pain, worsening with deep breathing and Valsalva maneuver. It was not associated with trauma and did not present other symptoms. The physical examination was unremarkable. The arterial blood gases while breathing room air and the laboratory tests, including D-dimers and high-sensitivity cardiac Troponin T, were normal. The chest radiograph, electrocardiogram, and transthoracic echocardiogram showed no abnormalities. A computed tomography (CT) pulmonary angiogram showed no signs of pulmonary embolism but depicted at the left cardiophrenic angle a focal 3 cm ovoid-shaped fat lesion with stranding and thin soft tissue margins, consistent with necrosis of the epicardial fat, which was confirmed by magnetic resonance (MRI) of the chest. The patient was medicated with ibuprofen and pantoprazole, with clinical improvement in four weeks. At a two-month follow-up, he was asymptomatic and presented radiologic resolution of the inflammatory changes of the epicardial fat of the left cardiophrenic angle on chest CT. Laboratory tests revealed positive antinuclear antibodies, positive anti-RNP antibody, and positive lupus anticoagulant. The patient complained of biphasic Raynaud's phenomenon initiated five years ago, and a diagnosis of undifferentiated connective tissue disease (UCTD) was made. This case report highlights the diagnosis of EFN as a rare and frequently unknown clinical condition, which should be considered in the differential diagnosis of acute chest pain. It can mimic emergent conditions such as pulmonary embolism, acute coronary syndrome, or acute pericarditis. The diagnosis is confirmed by CT of the thorax or MRI. The treatment is supportive and usually includes non-steroidal anti-inflammatory drugs. The association of EFN with UCTD has not been previously described in the medical literature.


Effect of water turbidity on the visual acuity of harbor seals (Phoca vitulina).
The underwater visual acuity (the angle subtended by the minimal resolvable line width of high contrast square wave gratings at a viewing distance of 2m) of two male harbor seals was determined at different levels of water turbidity. Starting with visual acuity angles of 5.5' and 12.7' in clear water we found visual acuity to decrease rapidly with increasing turbidity at rates of 7.4' and 6.0' per formazin nephelometric unit (FNU). Besides the individual differences in visual performance of the harbor seals tested, our results reveal a dramatic loss of visual acuity even at moderate levels of turbidity. At sites in the German Wadden Sea, where harbor seals are known to roam and forage, we measured turbidity levels exceeding 40FNU. These data suggest that turbidity has to be considered as an important factor in the sensory ecology of pinnipeds.


Gastric ghrelin cells in obese patients are hyperactive.
Distribution and activity of ghrelin cells in the stomach of obese subjects are controversial. We examined samples from stomachs removed by sleeve gastrectomy in 49 obese subjects (normoglycemic, hyperglycemic and diabetic) and quantified the density of ghrelin/chromogranin endocrine cells by immunohistochemistry. Data were compared with those from 13 lean subjects evaluated by gastroscopy. In 44 cases (11 controls and 33 obese patients) a gene expression analysis of ghrelin and its activating enzyme ghrelin O-acyl transferase (GOAT) was performed. In 21 cases (4 controls and 17 obese patients) the protein levels of unacylated and acylated-ghrelin were measured by ELISA tests. In 18 cases (4 controls and 14 obese patients) the morphology of ghrelin-producing cells was evaluated by electron microscopy. The obese group, either considered as total population or divided into subgroups, did not show any significant difference in ghrelin cell density when compared with control subjects. Inter-glandular smooth muscle fibres were increased in obese patients. In line with a positive trend of the desacylated form found by ELISA, Ghrelin and GOAT mRNA expression in obese patients was significantly increased. The unique ghrelin cell ultrastructure was maintained in all obese groups. In the hyperglycemic obese patients, the higher ghrelin expression matched with ultrastructural signs of endocrine hyperactivity, including expanded rough endoplasmic reticulum and reduced density, size and electron-density of endocrine granules. A positive correlation between ghrelin gene expression and glycemic values, body mass index and GOAT was also found. All obese patients with type 2 diabetes recovered from diabetes at follow-up after 5 months with a 16.5% of weight loss. Given the known inhibitory role on insulin secretion of ghrelin, these results suggest a possible role for gastric ghrelin overproduction in the complex architecture that takes part in the pathogenesis of type 2 diabetes.


Equine Cardiovascular Therapeutics.
Heart disease can be defined as any abnormality of the heart whether it is a cardiac dysrhythmia or structural heart disease, either congenital or acquired. Heart failure occurs when a cardiac abnormality results in the inability of the heart to pump enough blood to meet the body's needs. Heart disease can be present without leading to heart failure. Heart failure, however, is a consequence of heart disease. There are 4 main areas where the clinician can intervene to improve cardiac output with heart failure: preload, afterload, myocardial contractility, and heart rate.


Arteriovenous fistula reconstruction in patients with kidney allograft failure.
Kidney recipients with failing allograft function face the vascular access problem again before returning to hemodialysis. An autologous arteriovenous fistula (AVF), according to the recent Kidney Disease Outcomes Quality Initiative (KDOQI) guidelines, is the optimal vascular access and the use of prosthetic grafts and catheters should be limited. The objective of this study was to assess the feasibility of AVF reconstruction in patients reentering hemodialysis after kidney allograft failure. Two hundred and forty-one transplant recipients reentered hemodialysis between 1990 and 2005. Before kidney transplantation, 221 patients had a functioning AVF on the forearm. Fistula reconstruction was attempted in 112 (51%) patients because of AVF thrombosis. Three strategies were applied according to forearm vein patency: a new radial-cephalic fistula, a radial-perforating vein fistula, or a radial-basilic forearm transposition was created. Forearm AVFs were successfully reconstructed in 85 of the 112 patients (73%). The primary patency of the reconstructed AVFs was 57.6% and 44% at 12 and 24 months. Secondary patency was 64.9% and 54.9% at 12 and 24 months, respectively. The reconstruction of an old, thrombosed AVF is possible in kidney recipients returning to dialysis, even if the time from thrombosis to fistula repair is a few years.


Patient Insurance Status Is Associated With Care Received After Transfer Among Pediatric Patients in the Emergency Department.
To determine whether frequency of interfacility transfer varied by insurance status among pediatric emergency department (ED) patients. Secondarily, we tested for an association between insurance status and odds of transfer with discharge from the second ED without observation or admission. We used the 2016 New York State ED and Inpatient Databases to identify all patients <18 years. ED and hospital characteristics were from American Hospital Association and National ED Inventory-USA. Among all ED patients, we calculated the proportion transferred stratified by insurance status (private, public, none). Among ED-to-ED transfers, we identified transfers without subsequent observation or admission, and used hierarchical logistic regression modeling (adjusting for patient and transferring ED/hospital characteristics) to determine whether insurance status was associated with odds of discharge from the second ED without observation or admission. Of 1,303,575 pediatric ED visits, 6086 (0.5%) were transferred. Transfers were less frequent among patients with public or no insurance. Of 3801 ED-to-ED transfers, 1451 (38%) were without subsequent observation or admission. In bivariate and multivariable analysis, transferred patients with public and with no insurance were less likely to be discharged without observation or admission relative to privately insured patients. Among ED-to-ED transfers, pediatric patients with public or without insurance were more often kept for observation or admission at the second hospital after transfer. Differences in disease acuity or in providers' perception of follow-up availability may play a role in explaining these patterns. This disparity merits further investigation.


NR4A3 Immunohistochemistry Reliably Discriminates Acinic Cell Carcinoma from Mimics.
Acinic cell carcinoma (AciCC) harbors a recurrent t(4;9)(q13;q31) translocation, which leads to upregulation of Nuclear Receptor Subfamily 4 Group A Member 3 (NR4A3). Previous work on tissue microarrays suggests that NR4A3 immunohistochemistry (IHC) may be useful in the diagnosis of AciCC. Thus far, only a single study has evaluated the utility of NR4A3 immunohistochemistry (IHC) in the diagnosis of AciCC, using a tissue microarray to assess most non-AciCC tumor types. Herein we evaluate the diagnostic performance of NR4A3 IHC for AciCC in a large cohort of 157 salivary gland tumors, using whole tissue sections. The cohort consisted of 37 AciCC (6 of them (16%) with high grade transformation), 30 secretory carcinomas (SC), and 90 additional salivary gland tumors, including mucoepidermoid carcinomas (MEC), polymorphous adenocarcinomas (PAC), pleomorphic adenomas (PA), salivary duct carcinomas (SDC), and adenoid cystic carcinomas (AdCC). NR4A3 nuclear staining by IHC was considered positive if present in more than 5% of tumor cells. Overall, 92% of AciCC (34/37) expressed NR4A3 by IHC, with strong (89%) or moderate (3%) nuclear staining, yielding a sensitivity of 92%. IHC detected NR4A3 expression in all cases of recurrent/metastatic AciCC and tumors with high grade transformation. Importantly, all SC were negative for NR4A3 IHC, with no staining in 28/30 cases and weak focal staining, in < 5% of cells, in 2/30 (7%). Similarly, all MEC (20/20), SDC (20/20) and AdCC (10/10) were negative for NR4A3 by IHC, as were most PA (18/20; 15%) and PAC (18/20; 5%). Two PA and two PAC showed multifocal expression of NR4A3 in more than 5% of cells, of weak intensity in 3 cases and moderate in 1 PAC, yielding an overall specificity of 97% for NR4A3 IHC for the diagnosis of AciCC. In conclusion, NR4A3 is a highly sensitive and specific immunohistochemical marker for AciCC; moderate to strong and/or diffuse NR4A3 expression is a consistent and diagnostic feature of AciCC.


Effectiveness and cerebral responses of multi-points acupuncture for primary insomnia: a preliminary randomized clinical trial and fMRI study.
Primary insomnia (PI) is characterized by difficulties in initiating sleep or maintaining sleep, which lead to many serious diseases. Acupuncture for PI has drawn attention with its effectiveness and safety. However, the operation of choosing acupoints lacks scientific suggestion. Our trial aims to provide reference and scientific basis for the selection of acupoints and to explore its possible mechanism. A patient-assessor-blinded, randomized and sham controlled trial was designed to compare the efficacy of 5-weeks acupuncture at a single acupoint, the combination of multi-acupoints, and a sham point. The Pittsburgh sleep quality index and Athens Insomnia Scale questionnaire were used for the primary clinical outcomes, while polysomnography was performed for the secondary clinical outcomes. The resting state functional MRI was employed to detect the cerebral responses to acupuncture. The brain activity in resting state was measured by calculating the fractional amplitude of low-frequency fluctuations (fALFF), which reflected the idiopathic activity level of neurons in the resting state. These results were analyzed by two factorial ANOVA test and post-hoc t-tests. The clinical outcomes suggest that acupuncture could improve clinical symptoms, and the combination of multi-acupoints might lead to a better clinical efficacy. The rs-fMRI results suggested that the brain activity of certain regions was related to the sleep experience, and acupuncture could regulate the activity of these regions. Furthermore, the combination of multi-acupoints could impact more regions which were influenced by the sleep experience. Acupuncture has been proven to be beneficial for PI patients, and the combination of multi-acupoints might improve its efficacy. This trial has been registered on the U.S. National Library of Medicine (https://clinicaltrials.gov) ClinicalTrials.gov Identifier: NCT02448602 . Registered date: 14/04/2015.


Reduction in preterm birth among COVID-19-vaccinated pregnant individuals in the United States.
Most studies investigating preterm birth and COVID-19 vaccination have suggested no difference in preterm birth rates between vaccinated and unvaccinated pregnant individuals; however, 1 recent study suggested a protective effect of COVID-19 vaccination on preterm birth rates in Australia. This study aimed to determine whether a similar association and protective effect of COVID-19 vaccination on preterm birth would be found in our multistate, US cohort. A cohort study was conducted using the Vizient Clinical Database, which included data from 192 hospitals in 38 states. Pregnant individuals who delivered between January 2021 and April 2022 were included. Propensity score matching was used to match a "treated" group of pregnant individuals with any COVID-19 vaccination (incomplete or complete vaccination) to a group that had not received any COVID-19 vaccination (the "untreated" group). A complete vaccination series of ≥2 doses of the Moderna or Pfizer vaccines or at least 1 dose of the Johnson & Johnson vaccine was considered. An incomplete series was receipt of 1 dose of the Pfizer or Moderna vaccine. We examined the association between COVID-19 vaccination status and preterm birth at <28, <34, and <37 weeks of gestation. Multivariable logistic regression models were used to adjust for potential confounders, with adjusted odds ratios as the measure of treatment effect. Matching with replacement was performed for 5749 treated participants. After propensity score matching, there was no difference in maternal demographics of age, race, insurance status, parity, or comorbid conditions. Vaccinated individuals were 26% less likely to deliver at <37 weeks of gestation (adjusted odds ratio, 0.74; 95% confidence interval, 0.73-0.75; P<.001), 37% less likely to deliver at <34 weeks of gestation (adjusted odds ratio, 0.63; 95% confidence interval, 0.61-0.64; P<.001), and 43% less likely to deliver at <28 weeks of gestation (adjusted odds ratio, 0.57; 95% confidence interval, 0.55-0.60; P<0.001) than unvaccinated individuals. Vaccination against COVID-19 may be protective against preterm birth.


The effect of intracerebroventricular administration of somatostatin on prolactin and TSH release in rats.
We investigated the effect of intracerebroventricular (icv) administration of somatostatin (SRIF) on prolactin (PRL) and thyroid-stimulating hormone (TSH) release in freely moving rats chronically cannulated with an atrial catheter. The plasma PRL levels were significantly elevated following the icv administration of 0.5 microgram SRIF. No further increase in PRL following the icv administration of SRIF were found in the rats in the course of repeated intravenous of injection of 5.0 mg/kg sulpiride, a specific D2 receptor antagonist. On the other hand, the injection of 5.0 micrograms SRIF resulted in no significant change in the plasma TSH levels. These results suggest that the effect of SRIF on PRL release was exerted through brain D2 receptors.


Undaria pinnatifida soluble fiber regulates Angptl3-LPL pathway to lessen hyperlipidemia in mice.
Angiopoietin-like protein 3 (Angptl3)-lipoprotein lipase (LPL) pathway may be a useful pharmacologic target for hyperlipidemia. The present study was conducted to test the effect of soluble fiber extracted from Undaria pinnatifida (UP), on hyperlipidemia in apolipoprotein E-deficient (ApoE(-/-)) mice. Forty mice were divided into four groups (n = 10): control group (C57BL/6J mice), ApoE(-/-) mice group, and two groups of ApoE(-/-) mice treated with UP fiber (5 or 10 % per day). UP soluble fiber treatment significantly decreased plasma and hepatic total cholesterol, triglycerides levels, plasma low-density lipoprotein cholesterol, and malondialdehyde concentrations and increased plasma high-density lipoprotein cholesterol level and downregulated protein expression of Angptl3 concomitantly with upregulated protein expression of LPL. In addition, T0901317 caused elevated expression of hepatic Angptl3 protein, and the effect of T0901317 was also abrogated by UP soluble fiber in C57BL/6J mice. The present results suggest that the UP soluble fiber regulates Angptl3-LPL pathway to lessen hyperlipidemia in mice.


Syringomyelia: a retrospective study. Part I: Clinical features.
We performed a retrospective study of 62 patients with syringomyelia. Most noteworthy among the clinical features in our patient population are the following: segmental sensory disturbances are usually less restrictive than the classical thermoanalgesia, pain is a presenting symptom in almost 50% of cases, and skeletal abnormalities of the "status dysraphicus" are very common. The different hypotheses about the pathogenesis are also discussed.


When m-selection?
Caswell and Hastings (1980) introduced an explicit model for the relative merits, in terms of the growth rate λ, of developmental shifts vs. fecundity increases. Some aspects of their model are clarified by concentrating on the (fitness>1) half-plane rather than on the (accelerated reproduction) half-plane. There is no strict equivalence between Caswell and Hastings' key parameter [Formula: see text] and the dynamic behaviour of the population which is governed by λ. Thus in some stationary/declining populations time shifts of reproduction (forward or backward, according to the value of [Formula: see text]) are just as effective in promoting a high λ as they are in growing populations; therefore selection for higher m x may, but need not, prevail in stationary/declining populations.


[Effect of elastic pivot stable bite plate on treating irreducible temporal bone displacement of the temporomandibular joint].
To investigate the effect of elastic pivot stable bite plate on treating irreducible temporal bone displacement of the temporomandibular joint. Twenty-eight cases of irreducible temporal bone displacement of the temporomandibular joint treated with the elastic pivot stable bite plate from 2000 to 2004 were summarized. The ages of the patients ranged from 15 to 58 years including 11 men and 17 women. All the patients were treated for 1 month and followed up for 3 to 6 months. The effective rate was 87.51%. The patients who had shorter course of diseases obtained better effect than the patients who had longer courses of diseases. Elastic pivot stable bite plate is an effective alternative for treating irreducible temporal bone displacement of the temporomandibular joint and it exerts better effect on the patients that have short courses of diseases.


Does your child's weight influence how you judge yourself as a parent? A cross-sectional study to define and examine parental overvaluation of weight/shape.
Parents are integral stakeholders in children's health and development, and yet there is a dearth of research on parental attitudes and parents' personal weight and eating psychopathology, which have the potential to influence pediatric obesity and eating disorder treatments meaningfully. Overvaluation of weight/shape is a core concept in eating-disorder assessment and treatment defined as self-evaluation excessively based on weight/shape, which research has demonstrated to be clinically important psychopathology. A novel and related concept, parental overvaluation of weight/shape, could be defined as parents' self-evaluation unduly based on their child's weight/shape, yet this concept has not been studied and its clinical importance is unknown. The aim of this study was to examine the distinctiveness of parental overvaluation of weight/shape from personal overvaluation of weight/shape, and to examine associations of parental overvaluation with parents' psychopathology and children's weight and eating behaviors. The current study examined differences among parents with (n=134) and without (n=872) parental overvaluation using a cross-sectional design. Parental overvaluation was more common among parents with binge-eating disorder and bulimia than obesity and healthy-weight. Parental overvaluation was modestly associated with personal overvaluation. Parents with and without parental overvaluation differed on personal eating-disorder psychopathology and children's weight and eating behaviors. Importantly, differences remained after adjusting for personal overvaluation and child BMI. This study highlights a novel construct-parental overvaluation-associated with, but distinct from, parental eating disorders and personal overvaluation. Parental overvaluation may warrant clinical attention among parents seeking pediatric obesity or eating-disorder treatment, or treatment for personal eating disorders.


Hepatocellular cancer: the impact of obesity, type 2 diabetes and a multidisciplinary team.
Hepatocellular cancer (HCC) commonly complicates chronic liver disease and increases in incidence have been reported despite falling prevalences of viral hepatitis. Following the introduction of centralised specialist teams to manage patients with cancer in England, we characterised the demographics of patients with HCC referred to the Newcastle-upon-Tyne Hospitals NHS Foundation Trust between 2000 and 2010. Regional HCC mortality data was from Public Health England. HCC related mortality in the region rose 1.8 fold in 10 years, from 2.0 to 3.7 per 100,000. 632 cases were reviewed centrally, with 2-3 fold increases in referrals of patients with associated hepatitis C, alcoholic liver disease or no chronic liver disease and a >10 fold increase in HCC associated with non-alcoholic fatty liver disease (NAFLD). By 2010 NAFLD accounted for 41/118 (34.8%) cases. Irrespective of associated etiologies, metabolic risk factors were present in 78/118 (66.1%) cases in 2010, associated with regional increases in obesity and diabetes. Median overall survival was just 10.7 months. Although patients with NAFLD associated HCC were older (71.3 yr vs. 67.1 yr; p<0.001) and their cancers less often detected by surveillance, their survival was similar to other etiologies. This was attributed to significantly higher incidental presentation (38.2%) and lower prevalence of cirrhosis (77.2%). HCC related mortality is increasing, with typical patients being elderly with metabolic risk factors. The prognosis for most of the cases is poor, but older patients with co-morbidities can do well, managed, within a specialist multidisciplinary team if their cancer is detected pre-symptomatically.


SGLT-2 inhibitors may be targeting higher risk patients with diabetes possibly justifying higher cost: Single center repeated cross-sectional analysis.
We studied the use of all hypoglycemic agents in periods before and after introduction of SGLT-2 inhibitors in the USA by repeated cross sectional analysis to initially assess improvement in HbA1c control among patients with type 2 diabetes and hypertension. We sought to identify changes in glucose management related to the availability of the SGLT-2 inhibiting agents. We hypothesized that patients transitioned to SGLT-2 inhibitor-based therapy represented a higher risk group that derived benefits in terms of Hba1c control. Deidentified records of patients seen at least twice during the relevant time periods at Joslin Clinic between January 1, 2010 and December 31, 2012 and/or between January 1, 2014 and December 31, 2016 were examined. Records required all of the following: demographic information of gender, age, height, weight, BMI, HbA1c, eGFR, blood pressure, smoking status and completed medication lists. 10,191 patients met criteria for analysis, 7769 seen in period 1 and 6576 in period 2. 4625 patients were seen in both periods. The group of patients defined by SGLT-2 use had significantly higher BMI and HbA1c. Notable shifts in medication use were observed as SGLT-2 use increased from none to 14%. Increased use (all p < 0.001) of GLP-1 agents (16.0 to 23.8%), insulin (56.1 to 60.5%) and statins (78.4 to 81.5%) and statistically significant decreases (all p < 0.001) in use of biguanides (69.5 to 66.3%) and sulfonylurea compounds (44.7 to 39.4%), thiazolidinediones (13.6 to 3.4%) and diuretics (32.4 to 28.9%) were observed. Statistically significant decreases (all p < 0.001) of HbA1c (7.9 to 7.8%), BMI (32.5 to 32.1), eGFR (80.6 to 77.5 ml/min) and increased systolic blood pressure (130 to 132 mm Hg) were documented. In the absence of glycemia treatment resistance or clinical heart failure SGLT-2 inhibitor use may not be cost effective. Enthusiasm for use of SGLT-2 inhibition should be based upon long-term cardiorenal protection rather than short-term glycemia control given limited impact upon HbA1c levels in our tertiary care type 2 diabetes population.


Calpain-2 promotes MKP-1 expression protecting cardiomyocytes in both in vitro and in vivo mouse models of doxorubicin-induced cardiotoxicity.
We recently reported that doxorubicin decreased the expression of calpain-1/2, while inhibition of calpain activity promoted doxorubicin-induced cardiac injury in mice. In this study, we investigated whether and how elevation of calpain-2 could affect doxorubicin-triggered cardiac injury. Transgenic mice with inducible cardiomyocyte-specific expression of calpain-2 were generated. An acute cardiotoxicity was induced in both transgenic mice and their relevant wild-type littermates by injection of a single dose of doxorubicin (20 mg/kg) and cardiac injury was analyzed 5 days after doxorubicin injection. Cardiomyocyte-specific up-regulation of calpain-2 did not induce any adverse cardiac phenotypes under physiological conditions by age 3 months, but significantly reduced myocardial injury and improved myocardial function in doxorubicin-treated mice. Cardiac protection of calpain-2 up-regulation was also observed in a mouse model of chronic doxorubicin cardiotoxicity. Up-regulation of calpain-2 increased the protein levels of mitogen activated protein kinase phosphatase-1 (MKP-1) in cultured mouse cardiomyocytes and heart tissues. Over-expression of MKP-1 prevented, whereas knockdown of MKP-1 augmented doxorubicin-induced apoptosis in cultured cardiomyocytes. Moreover, knockdown of MKP-1 offset calpain-2-elicited protective effects against doxorubicin-induced injury in cultured cardiomyocytes. Mechanistically, up-regulation of calpain-2 reduced the protein levels of phosphatase and tensin homolog and consequently promoted Akt activation, leading to increased MKP-1 protein steady-state levels by inhibiting its degradation. Collectively, this study reveals a new role of calpain-2 in promoting MKP-1 expression via phosphatase and tensin homolog/Akt signaling. This study also suggests that calpain-2/MKP-1 signaling may represent new therapeutic targets for doxorubicin-induced cardiac injury.


Fibrillation of human insulin B-chain by pulsed hydrogen-deuterium exchange mass spectrometry.
Insulin forms amyloid fibrils under slightly destabilizing conditions, and B-chain residues are thought to play an important role in insulin fibrillation. Here, pulsed hydrogen-deuterium exchange mass spectrometry (HDX-MS), far-UV circular dichroism spectroscopy, thioflavin T (ThioT) fluorescence, turbidity, and soluble fraction measurements were used to monitor the kinetics and mechanisms of fibrillation of human insulin B-chain (INSB) in acidic solution (1 mg/mL, pH 4.5) under stressed conditions (40°C, continuous shaking). Initially, INSB rapidly formed β-sheet-rich oligomers that were protected from HD exchange and showed weak ThioT binding. Subsequent fibril growth and maturation was accompanied by even greater protection from HD exchange and stronger ThioT binding. With peptic digestion of deuterated INSB, HDX-MS suggested early involvement of the N-terminal (1-11, 1-15) and central (12-15, 16-25) fragments in fibril-forming interactions, whereas the C-terminal fragment (25-30) showed limited involvement. The results provide mechanistic understanding of the intermolecular interactions and structural changes during INSB fibrillation under stressed conditions and demonstrate the application of pulsed HDX-MS to probe peptide fibrillation.


Developing Normative Integration among Professionals in an Intersectoral Collaboration: A Multi-Method Investigation of an Integrated Intervention for People on Sick Leave Due to Common Mental Disorders.
Intersectoral integration is recommended in vocational rehabilitation, though difficult to implement. We describe barriers to and strategies for the development of normative integration in an intersectoral, team-based vocational rehabilitation intervention. Attitudes and behaviours regarding the development of shared culture, norms, and goals in the collaboration between health care professionals and employment consultants were investigated through 30 semi-structured interviews, participant observation of 12 intersectoral meetings, and document analysis of 12 joint plans. Organisational factors and unsettled power balance between professionals constituted barriers to the development of a shared culture. These issues were resolved by establishing smaller work teams, and through health care professionals' gradual acceptance of employment consultants' control in their capacity as administrators of legislation. Some barriers to shared norms were resolved explicitly, whereas implicit diverging norms were continuously negotiated. The development of shared goals was supported by clarifying the fit between individual, professional, and organisational goals, though the alignment of goals required a paradigmatic change of mindset among the health care professionals. This study shows how normative integration among health care professionals and employment consultants is feasible in co-located intersectoral teams, with positive implications for the delivery of coherent support.


Comparison of binaural release from forward masking in animals and humans. Electrophysiological studies.
Evoked potentials in the inferior colliculus and auditory areas of the cortex were studied in anesthetized guinea pigs and long-latency auditory evoked potentials (LAEP) were studied in waking humans using sequential binaural presentation of pairs of clicks--the masker and the masked signal--with a variable interval between them, to provide the conditions needed for the psychophysical phenomenon of direct forward masking. Introduction of phase differences between the masker and the masked signal led to decreases in suppression of responses to the masked signal and to faster recovery of the reaction types recorded. The greatest relative differences between response magnitudes to antiphase and synphase masked signals were seen at the beginning of the recovery process, and were 1.6, 1.5, and 1.4 respectively for responses from the inferior colliculus, auditory area of the cortex, and LAEP at stimulus intensities of 50-65 dB sound pressure level, differences subsequently decreasing to zero. There was a positive correlation between this measure and the stimulus intensity. The greatest differences between the time at which the recovery process ended for responses to antiphase and synphase masked signals were 4, 250, and about 2000 msec respectively for the inferior colliculus, auditory area of the cortex, and LAEP.


Soft-Chemical Method for Synthesizing Intermetallic Antimonide Nanocrystals from Ternary Chalcogenide.
The synthesis of intermetallic antimonides usually depends on either the high-temperature alloying technique from high-purity metals or the flux method in highly poisonous Pb-melt. In this paper, we introduced a soft-chemical method to synthesize intermetallic antimonides from ternary chalcogenide precursors under an argon atmosphere below 200 °C. Powder X-ray diffraction and compositional analysis clearly indicate that a new phase of the Ag3Sb nanocrystal was synthesized from the Ag3SbS3 precursors. Three types of trialkylphosphines (TAPs) were applied as desulfurization agents, and the transformation mechanism was elucidated. The capability of the desulfurization agent follows the sequence of triphenylphosphine (TPP) > tributylphosphine (TBP) > trioctylphosphine (TOP). Besides, this TAP-driven desulfurization route to synthesize the intermetallic phase could also be possible for AgSbSe2 and Sb2S3. Therefore, this paper provides an efficient and mild technique for the fabrication of intermetallic nanocrystals.


Isolation and partial characterization of a monoclonal antibody to the Rous sarcoma virus transforming protein pp60src.
Transformation of cells by Rous sarcoma virus is mediated by the product of the viral src gene, pp60src. A hybridoma cell line producing an immunoglobulin G3 antibody to pp60src was isolated after lymph node cells from immune mice were fused with mouse myeloma cells (P3-NS1-1). Mice were immunized with p60src purified from Escherichia coli cells expressing the src gene product. The monoclonal antibody immunoprecipitated pp60src from Rous sarcoma virus-transformed cells and recognized an antigenic determinant located in the amino-terminal third of the pp60src protein.


Whole-exome analysis in Tunisian Imazighen and Arabs shows the impact of demography in functional variation.
Human populations are genetically affected by their demographic history, which shapes the distribution of their functional genomic variation. However, the genetic impact of recent demography is debated. This issue has been studied in different populations, but never in North Africans, despite their relevant cultural and demographic diversity. In this study we address the question by analyzing new whole-exome sequences from two culturally different Tunisian populations, an isolated Amazigh population and a close non-isolated Arab-speaking population, focusing on the distribution of functional variation. Both populations present clear differences in their variant frequency distribution, in general and for putatively damaging variation. This suggests a relevant effect in the Amazigh population of genetic isolation, drift, and inbreeding, pointing to relaxed purifying selection. We also discover the enrichment in Imazighen of variation associated to specific diseases or phenotypic traits, but the scarce genetic and biomedical data in the region limits further interpretation. Our results show the genomic impact of recent demography and reveal a clear genetic differentiation probably related to culture. These findings highlight the importance of considering cultural and demographic heterogeneity within North Africa when defining population groups, and the need for more data to improve knowledge on the region's health and disease landscape.


A flexible luminescence film with temperature and infrared response based on Eu2+/Dy3+ co-doped Sr2Si5N8 phosphors for optical information storage applications.
Deep-trap luminescent materials have attracted great attention for optical information storage applications. However, the flexible luminescence films based on red luminescence materials with temperature and infrared response are scarce. In this study, we have successfully developed various novel flexible red emitting films based on Eu2+/Dy3+ co-doped Sr2Si5N8 phosphors through screen-printing and spin-coating technologies, respectively. Interestingly, the fabricated flexible luminescence films exhibit unique temperature and infrared responsive properties for optical information storage by releasing photons in response to thermal or infrared stimulation. Notably, deep-trap red emitting Eu2+/Dy3+ co-doped Sr2Si5N8 phosphors are crucial for the optical information storage properties of the films. Two emission peaks of Sr2Si5N8:Dy3+ phosphors at 476 nm and 577 nm are observed under excitation at 345 nm, corresponding to the radiative transition occurs from the 4F9/2 level to the 6H13/2 and 6H15/2 levels of Dy3+. When Dy3+ and Eu2+ ions are co-doped in Sr2Si5N8, the energy transfer from Dy3+ to Eu2+ in Sr2Si5N8 matrix is found and the decay time confirms that Dy3+ ions can be acted as deep trap centers to storage photons. For Sr2Si5N8:Eu2+,Dy3+ phosphors and the corresponding flexible luminescence films, the specific patterns (for example apple and note patterns) are firstly recorded under NUV or blue light excitation and then reappear through thermal stimulation or near-infrared photo-stimulation (980 nm laser). This work not only validates the feasibility of Sr2Si5N8:Eu2+,Dy3+ phosphors as deep-trap red emitting luminescence materials, but also suggests the applications of flexible luminescence films for optical information storage.


Phytochemical Profiling, Antimicrobial and α-Glucosidase Inhibitory Potential of Phenolic-Enriched Extracts of the Aerial Parts from Echium humile Desf.: In Vitro Combined with In Silico Approach.
The current study aimed to evaluate the naturally occurring antimicrobial and antidiabetic potential of various Echium humile (E. humile) solvent extracts (hexane, dichloromethane, ethyl acetate, methanol and aqueous). The bioactive compounds were identified using HPLC-MS, revealing the presence of sixteen phytochemical compounds, with the most abundant being p-coumaric acid, followed by 4,5-di-O-caffeoylquinic acid, trans-ferulic acid and acacetin. Furthermore, E. humile extracts showed marked antimicrobial properties against human pathogen strains, with MIC values for the most relevant extracts (methanol and ethyl acetate) ranging from 0.19 to 6.25 mg/mL and 0.39 to 12.50 mg/mL, respectively. Likewise, methanol was found to be bactericidal towards S. aureus, B. cereus and M. luteus, fungicidal against P. catenulatum and F. oxysporum and have a bacteriostatic/fungicidal effect for the other strains. In addition, the E. humile methanolic extract had the greatest α-glucosidase inhibitory effect (IC50 = 0.06 ± 0.29 mg/mL), which is higher than the standard drug, acarbose (IC50 = 0.80 ± 1.81 mg/mL) and the aqueous extract (IC50 = 0.70 ± 0.67 mg/mL). A correlation study between the major phytochemicals and the evaluated activities was investigated. Docking studies evidenced that most of the identified phenolic compounds showed strong interactions into the binding sites of S. aureus tyrosyl-tRNA synthetase and human lysosomal acid-α-glucosidase, confirming their suitable inhibitory effect. In summary, these results may provide rational support to explore the clinical efficacy of E. humile and its secondary metabolites in the treatment of dual diabetes and infections.


An electromechanically reconfigurable plasmonic metamaterial operating in the near-infrared.
Current efforts in metamaterials research focus on attaining dynamic functionalities such as tunability, switching and modulation of electromagnetic waves. To this end, various approaches have emerged, including embedded varactors, phase-change media, the use of liquid crystals, electrical modulation with graphene and superconductors, and carrier injection or depletion in semiconductor substrates. However, tuning, switching and modulating metamaterial properties in the visible and near-infrared range remain major technological challenges: indeed, the existing microelectromechanical solutions used for the sub-terahertz and terahertz regimes cannot be shrunk by two to three orders of magnitude to enter the optical spectral range. Here, we develop a new type of metamaterial operating in the optical part of the spectrum that is three orders of magnitude faster than previously reported electrically reconfigurable metamaterials. The metamaterial is actuated by electrostatic forces arising from the application of only a few volts to its nanoscale building blocks-the plasmonic metamolecules-that are supported by pairs of parallel strings cut from a flexible silicon nitride membrane of nanoscale thickness. These strings, of picogram mass, can be driven synchronously to megahertz frequencies to electromechanically reconfigure the metamolecules and dramatically change the transmission and reflection spectra of the metamaterial. The metamaterial's colossal electro-optical response (on the order of 10(-5)-10(-6) m V(-1)) allows for either fast continuous tuning of its optical properties (up to 8% optical signal modulation at up to megahertz rates) or high-contrast irreversible switching in a device only 100 nm thick, without the need for external polarizers and analysers.


Carbonyl-scavenging drugs & protection against carbonyl stress-associated cell injury.
This mini-review highlights the chemical and cytoprotective properties of various hydralazine analogues that block the induction of cell death by acrolein, a highly toxic contributor to "carbonyl stress" during a diverse range of human diseases. Recent work on the action of hydralazine against various carbonyl-mediated pathologies is also reviewed.


Concise Review: Endothelial Progenitor Cells in Regenerative Medicine: Applications and Challenges.
Endothelial progenitor cells (EPCs) are currently being studied as candidate cell sources for revascularization strategies. Significant advances have been made in understanding the biology of EPCs, and preclinical studies have demonstrated the vasculogenic, angiogenic, and beneficial paracrine effects of transplanted EPCs in the treatment of ischemic diseases. Despite these promising results, widespread clinical acceptance of EPCs for clinical therapies remains hampered by several challenges. The present study provides a concise summary of the different EPC populations being studied for ischemic therapies and their known roles in the healing of ischemic tissues. The challenges and issues surrounding the use of EPCs and the current strategies being developed to improve the harvest efficiency and functionality of EPCs for application in regenerative medicine are discussed. Endothelial progenitor cells (EPCs) have immense clinical value for cardiovascular therapies. The present study provides a concise description of the EPC subpopulations being evaluated for clinical applications. The current major lines of investigation involving preclinical and clinical evaluations of EPCs are discussed, and significant gaps limiting the translation of EPCs are highlighted. The present report could be useful for clinicians and clinical researchers with interests in ischemic therapy and for basic scientists working in the related fields of tissue engineering and regenerative medicine.


Burrow builders as ecosystem engineers for pit-building antlions (Neuroptera: Myrmeleontidae).
Burrow builders are often classified as ecosystem engineers because their digging activities regulate the availability of resources for other organisms. As antlion larvae prefer to construct their traps in bare sandy or loose soil, they could benefit from burrowing activities. We investigated the role of burrow builders as ecosystem engineers for antlions (Myrmeleontidae) in a tropical semideciduous forest in Mexico. The number of traps of antlion larvae was recorded on 30 sampling quadrats (45 cm) at the entrance of burrows (of unidentified builders) and on 30 paired off-burrow quadrats. Additionally, the percentage of bare soil was estimated for the 60 quadrats sampled. Of the 30 quadrats at the entrance of burrows, a total of 336 traps were recorded, with 21 (70%) of them having at least one trap, while for the 30 off-burrows quadrats, only two (6.6%) of them had traps, just three in total. The percentage of bare soil and the abundance of traps were significantly greater in quadrats at the entrance of burrows compared to quadrats without burrows. The abundance of traps at the entrance of burrows was positively affected by the percentage of bare soil. The few traps in the off-burrows quadrats suggested that, in addition to the limited bare soil, ground compactness probably limits the establishment of antlion larvae. Otherwise, when digging, burrow builders create small patches of bare sandy soils that are used by these insects. We concluded that the ecosystem engineering effect of burrow builders is an important structuring element for antlion populations in the tropical semideciduous forest studied.


The results of posterior chamber lens implantation.
We studied 1,216 consecutive cases where the surgeon's intent was to implant a posterior chamber lens. In 37 cases, the surgeon elected to put in an anterior chamber lens because of events occurring at the time of surgery. In no instance was the intraocular lens procedure aborted and a lens not implanted. In the 37 cases implanted with anterior chamber lenses, 76% had a final visual acuity of 20/40 or better. In the 1,179 cases that had posterior chamber lenses implanted, 90% had visual acuity of 20/40 or better, and only 1% had worse than 20/400 vision. Senile macular degeneration accounted for over one-half of the 104 patients with a visual acuity of 20/40 or worse. Visual results appeared to be age related; 96% of patients who were less than 75-years-old achieved an acuity of 20/40 or better, whereas only 80% of those over 75 years achieved this level. Our results suggest that extracapsular extraction with posterior chamber lens implantation is safe and provides good visual results.


Complement and renal disease.
The complement system is involved in several aspects of renal disease, including primary renal diseases, dialysis and renal transplant rejection. Initially, a role for complement in renal disease was inferred solely from the deposition of complement components in affected kidneys and changes in complement levels in the circulation during active disease. Recent studies have shown how complement modulates the onset, development and the resolution of renal disease. Current research provides clues on the role of individual complement components and activation pathways as well as possible modes of complement regulation in the management of renal disease.


Ocular findings in a Spanish cohort of myotonic dystrophy type 1.
Myotonic dystrophy type 1 is the most common muscular dystrophy in adulthood, caused by a triplet repeat in chromosome 19q13.3. The present study investigates the frequency of the different ocular alterations in Spanish patients with DM1 and its relationship with the severity of the genetic alteration. Cross-sectional and multicenter study was conducted on patients with genetically confirmed DM1. Ophthalmologic examinations included visual acuity assessment, manifest refraction, slit-lamp biomicroscopy, tonometry, ocular motility, corneal tomography, and macular and optic nerve optical coherence tomography. A total of 42 patients (84 eyes) were included. Mean age was 46.9 ± 13.4 (SD) years, and 57.1% were women. Fifteen patients had undergone cataract surgery in at least one eye (35.7%), and 13 (30.9%) had significant cataract. Mean intraocular pressure (IOP) was 10.5 ± 2.9 mmHg, and mean central corneal thickness (CCT) was 580.04 ± 48.61 μm. Half of the patients had significant ptosis, and 8 patients (9.75%) had undergone eyelid surgery. Macular abnormalities included retinal pigment epithelium alterations in 8 eyes of 6 patients, epiretinal membrane in 3 eyes, and lamellar hole in 2 eyes. A moderate correlation was found between IOP and ptosis with the number of triplet repeats. Early cataract onset, low IOP, thicker CCT, and ptosis were the most significant manifestations of DM in our sample. Correlation found between IOP and ptosis with CTG repeat could be interesting in order to improve diagnosis and medical care of these patients but should be confirmed in further studies.


Proliferation and migration mediated by Dkk-1/Wnt/beta-catenin cascade in a model of hepatocellular carcinoma cells.
Beta-catenin is a multifunctional protein acting as a key factor in the cadherin-mediated cell-cell adhesion system and in the Wnt signaling pathway. To demonstrate the molecular mechanisms of metastasis of hepatocellular carcinoma (HCC) cells, we established a metastatic subclone of human HCC H7402 cells, termed M-H7402, by isolating from transplantation of H7402 cells into severe combined immunodeficient (SCID) mice. Based on the 2 parallel cell lines, we investigated the roles of dickkopf-1 (Dkk-1) and Wnt/beta-catenin pathway in proliferation and migration of HCC cells. cDNA microarray showed that 24 genes were related to tumor metastasis differentially expressed between H7402 and M-H7402 cells. Western blot analysis revealed that the expression levels of beta-catenin, c-Myc, and cyclin D1 were upregulated, but Dkk-1 and nm23 were dramatically downregulated in M-H7402 cells, which suggests that the 2 cell lines were remarkably different in molecular events associated with metastasis. Furthermore, we found that overexpression of Dkk-1 by transfection was able to downregulate the expression of c-Myc and cyclin D1, and it also inhibited the growth and migration in M-H7402 cells. Although reduction of Dkk-1 expression by RNA interference was able to upregulate the expression of beta-catenin, c-Myc, and cyclin D1 in H7402 cells, it also promoted beta-catenin translocation from cytoplasm into nuclei and increased the migration of the cells. Therefore, we conclude that Dkk-1/Wnt/beta-catenin cascade may mediate the proliferation and migration of HCC cells during the metastasis process.


What Cigarillo Companies are Putting on Instagram: A Content Analysis of Swisher Sweets' Marketing from 2013 to 2020.
Tobacco marketing includes text and visual content, which conveys important meaning to consumers and influences use. Little is known about the marketing tactics used by a popular brand of cigarillos on social media to promote their products, including their visual design. A content analysis was conducted to analyze text and visuals for all posts on Swisher Sweets' official Instagram account from Jan 23, 2013 to Feb 28, 2020. We assessed product depictions (e.g. warnings, smoking cues), presence of FDA-prohibited or potentially misleading claims (e.g. lower risk, organic), marketing tactics (e.g. celebrities, selling propositions), flavors, and demographic representation. We coded 1402 posts. Smoking cues (e.g. images of people smoking, product imagery) were in 764 posts (54.5%), and a warning appeared in 690 (49.2%) posts, but obscured in 29.4% of those instances (n = 203). No posts included FDA-prohibited claims, but some potentially misleading language was identified, including the use of words or visual depictions of smooth (n = 254, 18.1%) and quality/well-made (n = 239, 17%). Marketing tactics such as scarcity (n = 159, 11.3%), event promotion (n = 586, 41.8%), and alcohol depictions (n = 171, 12.2%) were common, and flavor names appeared in 598 posts (42.7%). People depicted were often young adults (n = 709, 50.6%), Black/African American (n = 549, 39.2%), and in groups (n = 473, 33.7%). Both text and visuals are used to market Swisher Sweets on their Instagram account. Using social images of young adults, especially Black individuals, signals the intended use of the product. These images of visual-based social media may influence appeal, glamorization, and normalization of cigarillo smoking among vulnerable populations. Tobacco marketing, including from popular cigarillo brands like Swisher Sweets, is widely used to influence consumer perceptions and behavior. Social media marketing includes text and visual, both of which increase product appeal and encourage use. Visual-based social media from the industry itself have been understudied, particularly for cigarillos. This study characterizes the ways in which Swisher Sweets uses text and visuals to market their products through their Instagram account, including smoking cues, potentially misleading language, use of celebrity endorsers, and promotion and sponsorship of events.


Role of Na/K-ATPase in regulation of neurite growth in sensory neurons.
We studied the effects of acetylcholine and norepinephrine on the growth of neurites in organotypic culture of 10-12-day-old chick embryo sensory neurons. Acetylcholine (10(-8) M) and norepinephrine (10(-13) M) stimulated the growth on sensory neuron neurites. Experiments with combined application of acetylcholine and norepinephrine against the background of ouabain showed that the nonspecific action of the test neurotransmitters is related to modulation of Na/K-ATPase activity.


Sphere-in-fiber hybrid of N-doped carbon/cerium dioxide as an interlayer material with superior electrocatalytic performance for lithium sulfide precipitation and conversion.
The inferior conductivity and infamous "shuttle effect" of lithium-sulfur (Li-S) batteries lead to low sulfur utilization and undesired cycle stability, which both seriously affect their practical application. Here, a multifunctional nanofiber material based on cerium dioxide spheres embedded inside nitrogen-doped carbon fibers (denoted as NCF@CeO2) fabricated by electrospinning technology is used as an interlayer for high-performance Li-S batteries. The nitrogen-doped carbon fiber skeleton matrix provides a through-conducting grid to accelerate electron transfer at the interface of the nitrogen-doped carbon and the CeO2, and the large specific surface area guarantees a sufficient interfacial fast-redox reaction for sulfur species. CeO2 with a hollow structure provides strong physicochemical adsorption of lithium polysulfides (LiPSs) to weaken the migration behavior, and abundant oxygen defects as catalytic active sites are conducive to lithium sulfide conversion. The "sphere in fiber" construction minimizes the direct contact between the catalyst and electrolyte, effectively avoiding side reactions. Based on the multiple functions of nitrogen-doped carbon fibers and CeO2, Li-S batteries with NCF@CeO2 interlayers exhibit superior electrochemical performances, including a high discharge specific capacity of 1072.9 mAh g-1 at 0.2 C and a low capacity decay rate of only 0.063% per cycle after 1000 cycles. Moreover, the mechanisms of LiPSs adsorption-conversion and the quantification of the catalytic ability are elaborately clarified.


Mini-immersion in medical Spanish for family practice residents.
Residency programs vary widely in types of training to increase cultural competency and sensitivity. Moreover, few empirical studies exist regarding effectiveness of these experiences. The purpose of our study was to offer and evaluate a linguistic mini-immersion, !Español Rápido!, required of 8 new family practice interns during their orientation month at the University of North Carolina. The curriculum was based on accelerative learning, a pedagogy that considers all parts of the brain, the paraconscious, and the role of the emotions. Pretests and posttests and a postimmersion and 6-month follow-up evaluation indicated that the mini-immersion was successful. A simple t test for paired samples showed a significant improvement in interns' comprehension after the 6-day immersion, t(7)=11.399, p<.000. This brief experience should be viewed only as a first step in a long-term plan for a comprehensive curriculum to prepare family practice residents as culturally competent practitioners.


Lower fibroblast growth factor 23 levels in young adults with Crohn disease as a possible secondary compensatory effect on the disturbance of bone and mineral metabolism.
Fibroblast growth factor 23 (FGF-23) is a bone-derived circulating phosphaturic factor that decreases serum concentration of phosphate and vitamin D, suggested to actively participate in a complex renal-gastrointestinal-skeletal axis. Serum FGF-23 concentrations, as well as various other laboratory parameters involved in bone homeostasis, were measured and analyzed with regard to various diseases and patients' characteristics in 44 patients with Crohn disease (CD) and 20 healthy controls (HCs) included in this cross-sectional study. Serum FGF-23 levels were significantly lower in patients with CD (900.42 ± 815.85pg/mL) compared with HC (1410.94 ± 1000.53pg/mL), p = 0.037. Further analyses suggested FGF-23 as a factor independent from various parameters including age (r = -0.218), body mass index (r = -0.115), 25-hydroxy vitamin D (r = 0.126), parathyroid hormone (r = 0.084), and bone mineral density (BMD) of hip and lumbar (r = 0.205 and r = 0.149, respectively). This observation remained even after multivariate analyses, exhibiting that BMD was not affected by FGF-23, although parameters such as age (p = 0.026), cumulative prednisolone dose (p < 0.0001), and smoking status (p = 0.024) were strong determinants of BMD regarding hip. Lower FGF-23 levels in patients with bowel inflammation are accompanied but not directly correlated with lower vitamin D levels, showing no impact on BMD determination of young adults with CD. The downregulation of serum FGF-23 levels in CD appears as a secondary compensatory effect on the bone and mineral metabolism induced by chronic intestinal inflammation.