Cross-cultural nursing research.
International cross-cultural comparative nursing research is considered important for the advancement of nursing knowledge offering a global perspective for nursing. Although this is recognised in policy statements and quality standards, international comparative studies are rare in database citations. To highlight the need for cross-cultural comparative research in nursing and to share some of the insights gained after conducting three international/cross-cultural comparative studies. These are: an examination of patients' autonomy, privacy and informed consent in nursing interventions BIOMED 1998-2001, the ICProject International Patient Study 2002-2006 and the Ethical Codes in Nursing (ECN) project 2003-2005. There are three critical issues raised here for discussion from the international cross-cultural studies. These are: the planning and formulating of an international study, the conduct of cross-cultural research including the implementation of rigorous data collection and analysis and the reporting and implementing the results. International and cross-cultural nursing research is powerful tool for the improvement of clinical nursing practise, education and management and advancement of knowledge. Such studies should be carried out in order to improve European evidence based health care development in which the patients' perspective plays an important part in the evaluation and benchmarking of services.


The failure of indomethacin to alter ACTH-induced adrenal hyperaemia or steroidogenesis in the anaesthetized dog.
1 The response of adrenal blood flow to adrenocorticotropic hormone (ACTH) was measured with radioactive microspheres in anaesthetized, dexamethasone-treated, mongrel dog. 2 Adrenocorticotropic hormone (2 u/h i.v.) increased adrenal blood flow within 15 min and this persisted for the duration of the infusion. 3 Cortisol concentrations also rose with ACTH infusion. 4 Indomethacin (6 mg/kg i.v. followed by 1 mg/min) did not effect the adrenal response to ACTH although plasma concentrations of indomethacin (21.9 +/- 2.5 micrograms/ml) adequate to suppress prostaglandin synthesis were achieved. 5 We conclude that prostaglandins are not required for steroidogenesis or the adrenal haemodynamic response to ACTH.


Ultrastructure of Klebsiella O3 lipopolysaccharide isolated from culture supernatant: comparison with other lipopolysaccharides.
Klebsiella O3 lipopolysaccharide (KO3 LPS) isolated from the culture supernatant, which was found to exhibit a very strong adjuvant activity in augmenting antibody response and delayed-type hypersensitivity to protein antigens in mice, was examined by electron microscopy. When negatively stained with uranyl acetate or ammonium molybdate, the KO3 LPS was found to consist principally of flat ribbon-like structures branching freely (average width 16 nm and average thickness 7 nm) and to contain a small proportion of spheres (diameter 20-50 nm), both structures covered with fine hairy structures (average length approximately 10 nm). When the polysaccharide of KO3 LPS was stained by the periodic acid-thiosemicarbazide-silver proteinate procedure, silver granules were deposited on the ribbon-like structures and around the spheres, suggesting that the polysaccharide moiety is located on their surface and that the fine hairy structures consist of the polysaccharide moiety. Comparison by means of preparations stained with uranyl acetate or ammonium molybdate showed that KO3 LPS isolated from the culture supernatant has structural features in common with KO3 LPS isolated from bacterial cells, Escherichia coli O9 LPS isolated from the culture supernatant, and E. coli O127 LPS isolated from bacterial cells. On the basis of the present results, schematic representations of the common physical structure of LPS were drawn; the fine hairy structures attach to the wide surface of the flat ribbon-like structures along their lateral margin.


Mouse monoclonal antibodies against rat estramustine binding protein.
Hybridomas producing antibodies against rat prostatic estramustine binding protein (rEMBP) have been obtained by fusion of spleen lymphocytes from Balb/c mice, immunized with rEMBP, and SP2/0 Ag 14 mouse myeloma cells. Anti-rEMBP IgG producing cultures were identified in a solid phase ELISA using alkaline phosphatase conjugated sheep antimouse IgG. Cultures producing specific antibodies were subcloned and expanded. The produced immunoglobulins were characterized according to interaction with subunits of rEMBP. No interaction was found with [3H]estramustine-human estramustine binding protein. Following development of a radioimmunoassay, tissue distribution of rEMBP in the rat was studied. Despite high specificity, shown by selective interaction with rEMBP (F and S subunits), macromolecules interacting with anti-rEMBP were found in high concentrations in the prostrate and also in low concentrations, in other tissues of the male genital tract, and further in the adrenals, pancreas and submaxillary gland. The high specificity also makes it possible to study the F and S subunit selectively. These results show that macromolecules very similar to rEMBP are present in hormone-sensitive tissues in the rat.


[4-(4-Meth-oxy-phen-yl)-8-oxo-3-(phenyl-selan-yl)spiro-[4.5]deca-3,6,9-trien-2-yl]methyl-cyanamide.
The title compound, C25H22N2O2Se, crystallizes in the space group P21/c with one mol-ecule in the asymmetric unit. The compound was synthesized by the addition of phenyl-selenyl bromide to a cyanamide. The phenyl-selenyl portion and the cyano group, as well as the ketone functional group in the cyclo-hexa-2,5-dien-1-one portion of the structure, are disordered, with occupancy factors of 0.555 (14) and 0.445 (14).


Using Machine Learning to Identify Predictors of Sexually Transmitted Infections Over Time Among Young People Living With or at Risk for HIV Who Participated in ATN Protocols 147, 148, and 149.
Sexually transmitted infections (STIs) among youth aged 12 to 24 years have doubled in the last 13 years, accounting for 50% of STIs nationally. We need to identify predictors of STI among youth in urban HIV epicenters. Sexual and gender minority (gay, bisexual, transgender, gender-diverse) and other youth with multiple life stressors (homelessness, incarceration, substance use, mental health disorders) were recruited from 13 sites in Los Angeles and New Orleans (N = 1482). Self-reports and rapid diagnostic tests for STI, HIV, and drug use were conducted at 4-month intervals for up to 24 months. Machine learning was used to identify predictors of time until new STI (including a new HIV diagnosis). At recruitment, 23.9% of youth had a current or past STI. Over 24 months, 19.3% tested positive for a new STI. Heterosexual males had the lowest STI rate (12%); African American youth were 23% more likely to acquire an STI compared with peers of other ethnicities. Time to STI was best predicted by attending group sex venues or parties, moderate but not high dating app use, and past STI and HIV seropositive status. Sexually transmitted infections are concentrated among a subset of young people at highest risk. The best predictors of youth's risk are their sexual environments and networks. Machine learning will allow the next generation of research on predictive patterns of risk to be more robust.


Impact of computed tomography metal artifact reduction protocol on periprosthetic tissue characterization after total hip arthroplasty: A cadaveric study.
Metal artifact reduction (MAR) has improved computed tomography (CT) imaging of total hip arthroplasty (THA) but the assessment of osteolysis and implant to bone contact relies on the accurate depiction of bone defects, cancellous bone, and cement. This study evaluates the impact of available single and dual-energy protocols on periprosthetic tissue characterization in a cadaveric phantom. Bilateral THA was performed on a fresh frozen cadaveric pelvis with simulated osteolytic cavities. CT acquisitions with projection-based MAR and noise equivalence were performed using single energy 140 kVp, single energy 150 kVp with 0.6 mm tin filtration, and dual-energy at 100/150 kVp with 0.6 mm tin filtration, from which simulated energies were extracted. Image subtraction, segmentation, region of interest histograms, and line profiles were used to characterize tissue density and separation. Tissue densities were heavily dependent on the energy profile of the protocol. Cancellous bone ranged from 182 to 45 HU and cement from 1012 to 131 HU using 140 kVp compared to dual-energy with weighted high energy tube, respectively. Spectral separation between cancellous bone, osteolytic defect, and cement was reduced for all protocols compared with 140 kVp. Spectral overlap was most severe using dual-energy with heavily weighted high-energy tubes. Dual-energy algorithms reduced trabecular contrast within the cancellous bone and cortical edge response. Although the dual-energy acquisition has been proposed as an additive to projection-based MAR techniques in THA, reduced density and contrast in clinically relevant periprosthetic tissue compared to 140 kVp single energy may limit its use in characterizing periprosthetic tissues.


Dairy cows welfare quality in tie-stall housing system with or without access to exercise.
Tie-stall housing of dairy cows is used extensively worldwide, despite of the welfare concerns regarding the restriction of voluntary movement and limitation of expression of the cows' natural behaviour. The aim of this study was to compare the welfare quality of dairy cows kept in two types of tie-stall housing systems: with regular outdoor exercise and without access to exercise. In addition, the study investigated the relationship between different welfare measures of dairy cows kept in tie-stalls. 3,192 lactating cows were assessed using the Welfare Quality® assessment protocol for cattle in 80 commercial dairy farms, half of the farms providing outdoor access for the animals to exercise. The descriptive statistical indicators were determined for the assessed measures and for the welfare criteria and principle scores. The data obtained in the two housing types were compared and the correlation coefficients were calculated between the different welfare measures. The significant differences found between the two housing systems for the majority of the animal based measures indicate the positive effect of exercise on the welfare of tethered cows. Many of the animal welfare parameters correlated with each other. For the farms allowing the cows' turnout in a paddock, pasture or both, the mean scores for the welfare criteria and principles were higher than for the farms with permanent tethering of the cows, except the criteria absence of prolonged hunger and expression of social behaviours. The lowest scores were obtained for the criterion positive emotional state, in both housing systems. With regard to the overall classification, none of the farms were considered excellent. In the not classified category were only farms with all-year-round tethering of the animals and in the enhanced category only farms where the cows had outdoor access. The welfare quality of the investigated dairy cows was significantly better in the tie-stall farms which allow exercise for cows (paddocks, pasture or both) than in those which do not. In the light of our results we consider that dairy cattle welfare is not necessarily poor in tie-stall housing systems, its quality depending on the management practices.


KLF2 is downregulated in pancreatic ductal adenocarcinoma and inhibits the growth and migration of cancer cells.
Members of the Kruppel-like factor (KLF) family have been considered as the tumor suppressors for their inhibitory effects on cell proliferation. Dysregulation of KLF2, a member of KLF family, has been observed in various cancer types. However, its expression pattern and functions in the pancreatic ductal adenocarcinoma (PDAC) are unknown. In this study, we examined the expression of KLF2 in PDAC clinical samples and evaluated the functions of KLF2 in the progression of PDAC. KLF2 is shown to be downregulated in PDAC clinical samples and overexpression of KLF2 inhibits the growth, migration, and metastasis of PDAC cancer cells. KLF2 interacts with beta-catenin and negatively regulates the beta-catenin/TCF signaling. Taken together, this study suggests the suppressive functions of KLF2 in PDAC.


Postoperative outcome of 37 patients with lobar intracerebral hemorrhage related to cerebral amyloid angiopathy.
Several recent studies have suggested that neurosurgical procedures are not contraindicated in patients with cerebral amyloid angiopathy (CAA). The purpose of this study was to elucidate the clinical factors influencing the outcome of patients with CAA-related intracerebral hemorrhage (ICH) treated surgically. A total of 50 neurosurgical procedures (42 intracerebral hematoma evacuations, 4 ventriculoperitoneal shunts, 3 ventricular drainages, and 1 brain biopsy) were performed in 37 patients with CAA-related ICH. To ascertain the clinical factors that may influence their postoperative outcome, their clinical data (demographics, medical history, recurrent lobar hemorrhage, radiographic characteristics, multiple lobar hemorrhage, surgical details, and postoperative hemorrhage) were examined retrospectively and subjected to multivariate analysis. Twenty patients (54%) had a good outcome, and only 4 (11%) died. Parietal hematomas, advanced age (>/=75 years), and intraventricular hemorrhages had significant adverse influence on the postoperative outcome. Clinically significant postoperative hemorrhage requiring evacuation occurred after 2 (5%) of 42 intracerebral hematoma evacuations. Postoperative hemorrhage did not have significant adverse influence on the outcome. Neurosurgery can be performed relatively safely in patients with CAA-related ICH, and their postoperative outcome is better than that reported previously. Surgical treatment should be considered for such patients aged <75 years without a parietal hematoma and intraventricular hemorrhage.


Poliomyelitis cases in northern Greece during 1976-1990.
During the period 1976-1990 fourteen cases of paralytic poliomyelitis were recorded in Northern Greece, which has a total population of 2.5 million. Twelve wild strains of poliovirus type-1 were isolated from an equal number of children with paralytic disease from 1976 to 1982. Also, three Sabin-like poliovirus vaccine strains were isolated from two infants with paralytic disease. Since 1985 no paralytic cases have been reported in Northern Greece.


Statistical approach for the estimation of daily physical activity levels using the probability density function of heart rate.
An investigation was undertaken into the statistical properties of heart rate during daily physical activity. The probability density function of the heart rate was estimated using the Gram-Charlier series. In addition, the probability density was separated into two Gaussian distributions: relatively low and relatively high heart rates. The former appeared to correspond to the metabolic rate associated with basic daily living and the latter appeared to be associated with more active physical activity of the type necessary to sustain or elevate the level of physical fitness. The higher heart rate distribution of five subjects occupied 8.72 +/- 2.15% of a period of waking. The validity of the statistical approach was confirmed with fractional estimation error of 1.22 +/- 0.62%.


High Luteinizing Hormone and Lower Levels of Sex Hormones in Younger Men With Distal Radius Fracture.
This study investigates the sex steroid hormone profile in younger men with distal radius fracture (DRF) to elucidate if this could explain the low bone density and osteoporosis previously observed. In a case-control study, 73 men with DRF (mean age 38 ± 9 years; range, 20-51) was compared with 194 age-matched, population controls. Performed assays: total testosterone (TT), calculated free testosterone (cFT), luteinizing hormone (LH), follicle-stimulating hormone (FSH), sex hormone-binding globulin (SHBG), and total estradiol (E2). BMD hip and spine were measured. Fracture cases had lower cFT (298 versus 329 pmol/L; p = 0.008), but not TT, compared with controls. FSH and SHBG were not statistically different. LH was almost 30% higher (5.7 versus 4.5 IU/L; p < 0.001) and a lower E2 was observed (80.0 versus 87.1; p = 0.098). Men with DRF had a lower E2/SHBG ratio compared with controls (2.3 versus 2.9; p = 0.013). A higher proportion of the fracture group had low TT (<10.5 nmol/L; 21% versus 11%; p = 0.052), low cFT (<220 pmol/L; 18% versus 8%; p = 0.017), and low E2 (<73 pmol/L; 48% versus 35%; p = 0.044). Odds ratio (OR) for fracture when having low cFT was 2.3 (95% CI, 1.02-5.49; p = 0.044); with low E2, the OR was 1.7 (95% CI, 0.96-2.96). In this study in young men with DRF exploring sex hormone levels, we find that sex hormone profiles may be disturbed with a lower E2/SHBG ratio, lower cFT, and higher LH. Estrogen is also a strong determinant of bone mass in men; hence, low levels of E2 may be contributing to the observed lower BMD and these differences may be relevant to fracture risk. © 2020 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.


Investigation of parasitic contamination of salad vegetables sold by street vendors in city markets in Damascus, Syria.
Monitoring parasitic contamination in raw vegetables used in salads is an important measure in controlling the occurrence of gastroenterological diseases, which may be life-threatening. This study aimed to inspect the parasitological contamination of some raw vegetables used in salads. Eight commonly consumed vegetable types were purchased from street vendors in the city markets. Vegetables were washed and the sediments were obtained for microscopic examination. Genomic DNA was isolated from contaminated samples. Our result showed that 34.4% of the studied samples were contaminated with one or more species of parasites. Lettuce was the most commonly contaminated vegetable type (29.5%), while tarragon leaves showed the lowest level of contamination (2.3%). The risk of contamination was significantly higher in lettuce samples in comparison with the other samples studied. Giardia duodenalis was the most prevalent parasite detected (38.6%) and was abundantly found in lettuce isolates (23.5%). Molecular typing revealed that all Giardia samples found in the contaminated specimens belonged to Assemblage B. Blastocystis spp. were the second most prevalent parasite in samples (29.5%), they were frequently detected in lettuce leaves (30.8%). Other parasites were found in low frequencies. The high level of parasitic contamination found in our study indicates an urgent need to identify the sources of contamination and to monitor irrigation water and ensure its cleanliness.


Behenoyl cytosine arabinoside, aclacinomycin A, 6-mercaptopurine, and prednisolone combination therapy for acute non-lymphocytic leukaemia in adults.
38 consecutive, previously untreated adult patients with acute non-lymphocytic leukaemia (ANLL) were treated with BHAC-AMP (N4-behenoyl-1-beta-D-arabinofuranosyl-cytosine, aclacinomycin A, 6-mercaptopurine, and prednisolone) therapy between March 1980 and February 1985. 25 patients (65.8%) achieved complete remission (CR). Median CR duration and median survival of patients who achieved CR were 14, and 24 months, respectively. The Kaplan-Meier analysis revealed a probability for remaining in CR of 18.0% at 5 years. Analysis of failure cases revealed that most of them were due to resistant disease. Major toxicities were infection, diarrhoea, liver dysfunction, nausea and vomiting but these were acceptable. The results indicate that BHAC-AMP therapy is comparable to the regimen with daunorubicin and cytosine arabinoside and a further clinical trial is necessary for previously untreated adult patients with ANNL.


Alterations in growth performance and stress responses in juvenile rockfish, Sebastes schlegelii, exposed to dietary chromium with varying levels of dietary ascorbic acid supplementation.
Juvenile rockfish Sebastes schlegelii (mean length 10.8 ± 1.4 cm, and mean weight 31.7 ± 3.6 g) were exposed for 4 weeks to different levels of dietary chromium (Cr6+) at 0, 120, and 240 mg/L and ascorbic acid (AsA) at 100, 200, and 400 mg/L. Growth performance of S. schlegelii was significantly decreased due to dietary Cr exposure, whereas lysozyme activity was notably increased. Exposure to dietary Cr resulted in substantial accumulation of Cr in the blood. Levels of two stress indicators, plasma cortisol and heat shock protein 70, of S. schlegelii were increased due to dietary Cr exposure. The results indicated that dietary Cr exposure affected growth performance, lysozyme activity, and stress responses of S. schlegelii, and high levels of AsA supplementation significantly attenuated dietary Cr-induced toxicity.


Metabolic healthy obesity is associated with higher incidence of mild decrease estimate glomerular rate in rural northeast Chinese.
Metabolic healthy obesity (MHO), a phenotype of obesity, seems to be associated with a lower risk of cardiovascular disease. However, MHO has a close relationship with a higher incidence of metabolic syndrome and diabetes. This study aimed to investigate the prevalence of MHO at baseline, the changes in the obese metabolic phenotype at follow-up and the relationship of this phenotype with the incidence of mildly reduced estimated glomerular filtration rate (eGFR) in rural Northeast Chinese. The Chronic Kidney Disease Epidemiology (CKD-EPI) equation was used to calculate eGFR. A total of 4903 participants aged ≥35 years with eGFR > 90 ml/min/1.73 m2 at baseline were enrolled and successfully followed. All participants completed the questionnaires, anthropometric measurements, and blood tests during baseline and follow-up. Mild renal dysfunction was defined as mildly reduced eGFR between 60 and 90 ml/min/1.73 m2. The prevalence of MHO was 20.0% at baseline (19.0% for women and 21.1% for men), which was secondary to metabolic abnormal obesity (MAO) (24.4, 27.2% for women and 21.5% for men). A total of 38.4% of women and 38.9% of men experienced phenotypic changes during follow-up. The cumulative incidence of mildly reduced eGFR in the MHO group was 20.1% (17.7% for women and 22.3% for men), which was also secondary to the incidence in the MAO group (20.8, 18.6% for women and 23.5% for men). After adjusting for age, current smoking, current drinking, chronic diseases, LDL-C, ALT, and AST, MHO was associated with a higher incidence of mildly reduced eGFR among women [OR (95% CI) =1.6 (1.2, 2.3)] and men [OR (95% CI) =1.6(1.2, 2.1)], whereas MAO was related to a higher incidence of mildly reduced eGFR among men only [OR (95% CI) =1.7 (1.3, 2.3)]. MHO was associated with a higher incidence of mildly reduced eGFR in both sexes; however, there was a specific relationship between MAO and mildly reduced eGFR in men only. Therefore, it is necessary to monitor kidney function among participants with both MHO and MAO.


Myristoylated Alanine-Rich Protein Kinase Substrate (MARCKS) Regulates Small GTPase Rac1 and Cdc42 Activity and Is a Critical Mediator of Vascular Smooth Muscle Cell Migration in Intimal Hyperplasia Formation.
Transcription of the myristoylated alanine-rich C kinase substrate (MARCKS) is upregulated in animal models of intimal hyperplasia. MARCKS knockdown inhibits vascular smooth muscle cell (VSMC) migration in vitro; however, the mechanism is as yet unknown. We sought to elucidate the mechanism of MARCKS-mediated motility and determine whether MARCKS knockdown reduces intimal hyperplasia formation in vivo. MARCKS knockdown blocked platelet-derived growth factor (PDGF)-induced translocation of cortactin to the cell cortex, impaired both lamellipodia and filopodia formation, and attenuated motility of human coronary artery smooth muscle cells (CASMCs). Activation of the small GTPases, Rac1 and Cdc42, was prevented by MARCKS knockdown. Phosphorylation of MARCKS resulted in a transient shift of MARCKS from the plasma membrane to the cytosol. MARCKS knockdown significantly decreased membrane-associated phosphatidylinositol 4,5-bisphosphate (PIP2) levels. Cotransfection with an intact, unphosphorylated MARCKS, which has a high binding affinity for PIP2, restored membrane-associated PIP2 levels and was indispensable for activation of Rac1 and Cdc42 and, ultimately, VSMC migration. Overexpression of MARCKS in differentiated VSMCs increased membrane PIP2 abundance, Rac1 and Cdc42 activity, and cell motility. MARCKS protein was upregulated early in the development of intimal hyperplasia in the murine carotid ligation model. Decreased MARKCS expression, but not total knockdown, attenuated intimal hyperplasia formation. MARCKS upregulation increases VSMC motility by activation of Rac1 and Cdc42. These effects are mediated by MARCKS sequestering PIP2 at the plasma membrane. This study delineates a novel mechanism for MARCKS-mediated VSMC migration and supports the rational for MARCKS knockdown to prevent intimal hyperplasia.


Amphetamine-induced activity after fetal alcohol exposure and undernutrition in rats.
Behavioral responses to amphetamine were examined in 28- and 42-day-old rats whose mothers consumed a liquid diet consisting of 35% ethanol-derived calories (EDC) during pregnancy. Offspring of pair-fed (0% EDC) and ad lib chow (LC) dams were included as controls. Animals received 0.0, 0.5, 1.0, or 2.0 mg/kg/ml d-amphetamine prior to single 2-hr tests in automated activity monitors. At 28 days of age, when there were no differences in activity after saline injection, 35% EDC males were more active (measured by distance traveled) than LC and 0% EDC males following treatment with 2.0 mg/kg amphetamine. Thirty-five percent EDC females exhibited brief reductions in activity relative to LC females but were not different from 0% EDC females at 28 days of age following 2.0 mg/kg amphetamine. When treated with 1.0 mg/kg amphetamine, 28-day-old 0% EDC males were less active than LC and 35% EDC males, who did not differ from each other at this dose. At 42 days of age, animals from both liquid diet groups were less active than LC controls following 2 mg/kg amphetamine. These results suggest that both prenatal alcohol exposure and undernutrition may influence the postnatal functional status of catecholamine systems but that the nature of those functional changes varies with type of prenatal insult, sex and age of the animal at testing.


[Transition in home care service in our hospital].
Progress of medical team ability, including analgesic treatment and nursing care, and a building closer connections with welfare services including visiting nurse station, is necessary for home medical care for the terminal cancer patient.


Growing the next generation of trauma surgeon-scientists: Reflections on 20 years of research investment.
The Eastern Association for the Surgery of Trauma mission includes fostering research and providing career development opportunities. Eastern Association for the Surgery of Trauma has awarded for 20 years a research scholarship to a promising young investigator. The research mentorship efforts were expanded 5 years ago with the INVEST-C Hack-a-thon. INVEST-C provides an intensive, short-term engagement to propel junior faculty toward establishing research independence. This study investigates the impact of these programs on academic productivity. Pubmed records, National Institutes of Health (NIH) Reporter data, and SCOPUS h-index were acquired for all scholarship (SCH) awardees from 2002 to 2021 (n = 20) and all INVEST-C (INV) participants (2017-2020, n = 19). Current type of practice, total number of funding awards, and timing of first award were ascertained. INVEST-C participants were also surveyed on an annual basis to track their progress. Medians (interquartile range [IQR]) are reported and compared (analysis of variance). Median publications (PUBs) of SCH awardees were 56 (IQR, 33-88), h-index was 16 (IQR, 12-21), and 25% of awardees have ≥1 NIH grant since their SCH. Among the last 10 awardees with a minimum of 2 years from SCH, 40% have received an NIH award compared with a mean NIH funding rate of 18.5% over the same period. For those remaining in academics (90% SCH), PUBs were higher for those >5 years (66 [IQR, 51-115]) versus <5 years from their SCH (33 [22-59]; p = 0.05), but there was no difference in h-index (16 [IQR, 14-25] vs. 15 [9-19], p = NS). Comparing the most recent 5 years of SCH to INV group, there was no difference in academic productivity as measured by total PUBs (SCH, 33 [IQR, 22-59] vs. INV, 34 [IQR, 18-44]; p = 0.7) or h-index (INV, 9 [IQR, 5-14]; p = 0.1). However, no attendee held research funding before INV, but 31.6% (6 of 19 attendees) have subsequently acquired ≥1 funding award (11 non-NIH, 1 NIH) in the short interval since participation. Investments in research activities have translated to significant extramural funding. Those in the last 5 years have been particularly fruitful with INV participants already achieving equal median academic productivity to SCH recipients. Prognostic and Epidemiologic; Level III.


Catheter-directed thrombolysis compared with systemic thrombolysis and anticoagulation in patients with intermediate- or high-risk pulmonary embolism: systematic review and network meta-analysis.
Therapeutic options for intermediate- or high-risk pulmonary embolism (PE) include anticoagulation, systemic thrombolysis and catheter-directed thrombolysis (CDT); however, the role of CDT remains controversial. We sought to compare the efficacy and safety of CDT with other therapeutic options using network meta-analysis. We searched PubMed (MEDLINE), Embase, ClinicalTrials.gov and Cochrane Library from inception to Oct. 18, 2022. We included randomized controlled trials and observational studies that compared therapeutic options for PE, including anticoagulation, systemic thrombolysis and CDT among patients with intermediate- or high-risk PE. The efficacy outcome was in-hospital death. Safety outcomes included major bleeding, intracerebral hemorrhage and minor bleeding. We included data from 44 studies, representing 20 006 patients. Compared with systemic thrombolysis, CDT was associated with a decreased risk of death (odd ratio [OR] 0.43, 95% confidence interval [CI] 0.32-0.57), intracerebral hemorrhage (OR 0.44, 95% CI 0.29-0.64), major bleeding (OR 0.61, 95% CI 0.53-0.70) and blood transfusion (OR 0.46, 95% CI 0.28-0.77). However, no difference in minor bleeding was observed between the 2 therapeutic options (OR 1.11, 95% CI 0.66-1.87). Compared with anticoagulation, CDT was also associated with decreased risk of death (OR 0.36, 95% CI 0.25-0.52), with no increased risk of intracerebral hemorrhage (OR 1.33, 95% CI 0.63-2.79) or major bleeding (OR 1.24, 95% CI 0.88-1.75). With moderate certainty of evidence, the risk of death and major bleeding complications was lower with CDT than with systemic thrombolysis. Compared with anticoagulation, CDT was associated with a probable lower risk of death and a similar risk of intracerebral hemorrhage, with moderate certainty of evidence. Although these findings are largely based on observational data, CDT may be considered as a first-line therapy in patients with intermediate- or high-risk PE. PROSPERO - CRD42020182163.


Pyridine nucleotide-dependent generation of hydrogen peroxide by a particulate fraction from human neutrophils.
The catalytic oxidation of [14C]-formate to 14CO2 was adapted to measure H2O2 formation in cellfree system. Standard curves employing glucose-glucose oxidase and xanthine-xanthine oxidase demonstrated linearity between 14CO2 evolution and enzyme concentration. A particulate fraction from human neutrophils was capable of oxidizing [14C]-formate; this reaction was dependent upon the presence of catalase, reduced pyridine nucleotide, and cellular material. Reaction increased with time of incubation and protein concentration, although not in a strictly linear fashion. The pH optimum was approximately 5.5 NADPH was a significantly better substrate than NADH, although both were capable of generating H2O2. The particulate fraction derived from phagocytizing cells was more active than a corresponding fraction from resting cells with either substrate. H2O2 production was abnormal in particulate fractions derived from 2 patients with chronic granulomatous disease. H2O2 production was markedly inhibited by superoxide dismutase or cytochrome c (scavengers of superoxide anion) but not by scavengers of singlet oxygen or hydroxyl radical. Reaction was greatly stimulated by the addition of manganous ion. These results are consistent with the hypothesis that the respiratory burst in human neutrophils is initiated by an oxidase that can utilize either NADPH or NADH but exhibits a marked preference for the former. Further, the inhibitor studies strongly support a mechanism involving an initial enzymatic reaction followed by a self-sustaining free radical reaction involving superoxide anion.


Immune Checkpoint Inhibitors in Hepatocellular Carcinoma: Opportunities and Challenges.
Hepatocellular carcinoma (HCC) is the most common malignancy worldwide, and is especially common in China. A total of 70%-80% of patients are diagnosed at an advanced stage and can receive only palliative care. Sorafenib has been the standard of care for a decade, and promising results for regorafenib as a second-line and lenvatinib as a first-line treatment were reported only 1 or 2 years ago. FOLFOX4 was recently recommended as a clinical practice guideline by the China Food and Drug Administration. All approved systemic therapies remain unsatisfactory, with limited objective response rates and poor overall survival. Immune checkpoint inhibitors (CPIs) offer great promise in the treatment of a rapidly expanding spectrum of solid tumors. Immune checkpoint molecules are involved in almost the whole process of viral-related hepatitis with cirrhosis and HCC and in the most important resistance mechanism of sorafenib. The approval of nivolumab by the U.S. Food and Drug Administration on September 23, 2017, for the treatment of patients with HCC, based only on a phase I/II clinical trial, is a strong hint that immunotherapy will introduce a new era of HCC therapy. CPI-based strategies will soon be a main approach in anticancer treatment for HCC, and we will observe the rapid advances in the therapeutic use of CPIs, even in an adjuvant setting, with great interest. How shall we face the opportunities and challenges? Can we dramatically improve the prognosis of patients with HCC? This review may provide some informed guidance. IMPLICATIONS FOR PRACTICE: Immune checkpoint molecules are involved in almost the whole process of viral-related hepatitis with cirrhosis and hepatocellular carcinoma (HCC) and in the most important resistance mechanism of sorafenib. As all approved systemic therapies in HCC remain unsatisfactory, checkpoint inhibitor (CPI)-based strategies will soon be a main approach in anticancer treatment for advanced stage of HCC, even in an adjuvant setting. In virus-related HCC, especially hepatitis B virus-related HCC, whether CPIs can control virus relapse should be further investigated. Combination strategies involving conventional therapies and immunotherapies are needed to increase clinical benefit and minimize adverse toxicities with regard to the underlying liver disease.


Exploring the drivers of COVID-19 protective behaviors among Singaporean tourists to Indonesia using travel bubbles.
This study investigats the relationships among positive emotions, perceived threats, protection motivation, coronavirus disease 2019 (COVID-19) vaccination intentions, quarantine-free travel intentions and COVID-19 protective behaviors in the context of quarantine-free travel. Data were collected from Singaporean tourists in Batam and Bintan of Indonesia using travel bubbles. A total of 387 respondents completed the questionnaires. The findings can help tourism managers create and implement market-driven service initiatives to increase positive emotions, protection motivation, and intentions to take quarantine-free travel and decrease perceived threats in order to enable tourists to have accurate COVID-19 protective behaviors.


The dihydrolipoyl acyltransferase (BCE2) subunit of the plant branched-chain alpha-ketoacid dehydrogenase complex forms a 24-mer core with octagonal symmetry.
Little is known of the plant branched-chain alpha-ketoacid dehydrogenase complex. We have undertaken a detailed study of the structure of the dihydrolipoyl acyltransferase (BCE2) subunit that forms the core of the complex, to which two other enzymes attach. Mature Arabidopsis thaliana BCE2 was expressed in Escherichia coli. The soluble recombinant protein was purified using a Superose 6 size-exclusion column to >90% homogeneity and was catalytically active. The recombinant protein formed a stable complex with a native molecular mass of 0.95 MDa and an S coefficient of 19.4, consistent with formation of a 24-mer. Negative-staining transmission electron microscopy of the recombinant protein confirmed that BCE2 forms a core with octagonal symmetry. Despite divergence of mammalian and plant BCE2s, there is clearly conservation of structure that is independent of primary sequence.


Is there a general autoantibody signature for cancer?
There is longstanding evidence for the diagnostic potential of single autoantibodies for cancer and other diseases and more recently for the potential of complex autoantibody signatures. Here we address the question whether cancer specific signatures exist. We analysed our autoantibody screening data both newly and previously generated using a single array platform with 1827 identified immunogenic clones. These clones were tested for their reactivity against a total of 428 human sera including 191 sera of patients with different cancer entities, 60 sera of healthy individuals and 177 sera of patients with non-cancer diseases by using bioinformatics approaches. Principal Component Analysis and hierarchical clustering revealed significant differences between the three cohorts. Evaluating the autoantibody reactivities in the three groups using Support Vector Machines, we were able to separate cancer sera from normal sera with an accuracy of 94.08%. A pathway analysis that was based on antigens with an increased reactivity in patients' sera as compared to controls indicated glycolysis as central pathway. The separation between cancer and non-cancer disease sera was possible with an accuracy of only 69.58%, which is still significantly higher than by random classification. As for single autoantigens, we show that proteins that are frequently reactive with cancer sera are also frequently reactive with non-cancer sera. While these results underline the potential of autoantibody signatures for cancer diagnosis, they also caution to premature claim specificity of a signature.


Does chronic nociceptive stimulation alter the development of morphine tolerance?
Conflicting results exist concerning the issues of whether chronic nociceptive stimulation (a) increases or decreases the effectiveness of morphine analgesia, and (b) facilitates or inhibits the development of narcotic tolerance. We carried out a series of experiments with appropriate controls in order to examine these two issues and their possible relationship. In experiment 1, rats received complete Freund's adjuvant (CFA), a chronic nociceptor, injected into a single hind paw or anesthesia without injection, together with morphine or placebo pellets in a 2 x 2 study design. The data indicate that the presence of the chronic nociceptive stimulus significantly facilitated the development of tolerance to morphine analgesia as measured using tail-flick latency (TFL) testing. Experiment 2 was designed to compare the analgetic effectiveness of an acute injection of morphine in rats experiencing chronic nociceptive stimulation and in controls. CFA was injected in the right hindpaw, and nine days later TFLs were tested after morphine doses of 1 and 2 mg/kg s.c. The data obtained showed that chronic nociceptive stimulation significantly reduced the effectiveness of morphine at the 1 mg/kg dose. However, baseline TFLs appeared to be shorter in rats treated with CFA, suggesting that the decrease in morphine effectiveness could be due to a general increase in pain sensitivity. Therefore, a third experiment was performed, using a less intense thermal stimulus to prolong baseline TFLs and accentuate any potential differences. Sixteen rats either received CFA or served as controls. TFLs were then measured at baseline and one hour after a 0.5 mg/kg dose of morphine.(ABSTRACT TRUNCATED AT 250 WORDS)


Donor substrate specificity of bovine kidney gamma-glutamyltransferase.
The enzyme γ-glutamyltransferase (GGT) catalyzes the hydrolysis of the γ-glutamyl isopeptide bond of glutathione conjugates (donor substrates), releasing glutamic acid, or the transfer of the donor's γ-glutamyl group to an acceptor substrate, such as a dipeptide. The specificity of GGT for xenobiotic donor substrates has not been fully characterized. The transpeptidation activity of bovine kidney GGT was measured with glycylglycine as the acceptor substrate and several glutathione conjugate donor substrates, representative of detoxication products of polycyclic aromatic xenobiotics. HPLC separation with UV detection was used for quantitation. The commonly-used chromogenic substrate γ-glutamyl-p-nitroanilide was also tested. Michaelis constants (K(m)) were obtained for 4-nitrobenzylglutathione (0.075 mM), 2,4-dinitrophenylglutathione (0.30 mM), 4-methylbiphenylylglutathione (0.12 mM), 1-menaphthylglutathione (0.23 mM), and 9-methylanthracenylglutathione (0.22 mM), indicating a trend towards higher values for bulkier substrates. These results provide insight into the capacity of GGT to act in the biotransformation of aromatic compounds, many of which are of toxicological importance.


Design and facile solid-phase synthesis of conformationally constrained bicyclic peptoids.
Triazine-bridged bicyclic peptoids as conformationally constrained peptidomimetics are described. Bicyclic peptoids composed of 6-12 peptoid residues (m, n = 3-6) were synthesized in excellent yields using a highly efficient solid-phase synthetic route.


Prevalence and risk factors of sleep disturbance in continuous ambulatory peritoneal dialysis patients in Guangzhou, southern China.
Sleep disturbance is significantly associated with overall morbidity, mortality, and quality of life in end-stage renal disease patients. Although it was reported that the prevalence of poor sleep quality was 41-83% in hemodialysis patients, sleep disturbance was not well understood in peritoneal dialysis (PD) patients, especially in Asian PD patients. The present study attempted to assess the prevalence and related risk factors of sleep disturbance among continuous ambulatory peritoneal dialysis (CAPD) patients in Guangzhou, southern China. Pittsburgh Sleep Quality Index (PSQI) was used to assess the sleep quality in eligible 212 CAPD patients (53.3% men), average age 49.9 ± 16.7 years. The average global PSQI score of the CAPD patients was 9.5 ± 5.2, with 171 (80.4%) poor sleepers (PSQI scores > or = 5). The PSQI score was negatively correlated with serum albumin (r = -0.21, P = 0.003) subjective global assessment (SGA) score (r = -0.27, P = 0.001) and positively correlated with age (r = 0.34, P < 0.001), high-sensitivity C-reactive protein (r = 0.20, P = 0.008), level of calcium × phosphate product (r = 0.19, P = 0.009), cardiovascular disease (r = 0.17, P = 0.019), Charlson comorbidity index score (r = 0.21, P = 0.004), malnutrition-inflammation score (MIS) (r = 0.31, P < 0.001), and duration on CAPD (r = 0.20, P = 0.005). In multiple analysis, old age, high calcium × phosphate product, low SGA score (β = -0.23, P = 0.042), and high MIS (β = 0.30, P = 0.007) were independent predictors of sleep disturbance in CAPD patients. We clearly demonstrated the novel relationship of malnutrition and calcium × phosphate product with poor sleep quality in CAPD patients, which may be a part of the explanation for the strong links between sleep quality and overall morbidity and mortality.


Evolution of natural populations in the Drosophila melanogaster sigma system II. Northern and central France.
A survey of French natural populations of Drosophila melanogaster has been systematically performed, concerning their status of infection by the sigma virus and the characteristics of viral clones. These investigations, which were not as extensive as those performed in the Languedoc region (Fleuriet et al., 1990) nevertheless give a good representation of the evolution of this system because of the long period involved (almost 20 years). Some trends were observed in all French populations such as (1) a decrease in the high efficiency of transmission by males (which is an important parameter for the viral invading ability); (2) high frequency of a best adapted viral Type. These high frequencies might be due to a recent invasion which is expected to spread to other European populations. However, the frequency of infected flies remained low in northern and central France, unlike in Languedoc. The complexity of this, apparently simple, system of two well-known coevolving organisms should once again be stressed. It is impossible with the known parameters to arrive at a general interpretation of observations made in Languedoc and the rest of France. These data may also throw some light on the structure of French wild populations of D. melanogaster which appear to be subdivided into local populations between which gene flow might be low.


Acceptability of HPV vaccination among young adults aged 18-30 years--a population based survey in Sweden.
Acceptability of human papillomavirus (HPV) vaccination seems to be high in the Western world but fewer data are available for men than for women. There are also concerns that HPV vaccination might lead young people to change their healthcare-related behaviours. We investigated these issues in a population-based survey performed in Sweden during January-May, 2007, just after HPV vaccination had been licensed. A total of 10567 men and women aged 18 to 30 years participated. The intention to accept HPV vaccination among these young adults was relatively high but could likely be improved with higher awareness of HPV-related diseases as well as of the safety and efficacy of vaccines in general. Also, the cost of the vaccine needs to be affordable. Even though few young adults stated their healthcare-related behaviours would change after HPV vaccination, a significant number were uncertain, suggesting a need for continued educational efforts when HPV-vaccinating this group.


Parental practices in late adolescence, a comparison of three countries: Canada, France and Italy.
The objective of this study was to examine parental practices, such as affection, control and conflict, in three countries: Canada, France and Italy. The sample was composed of more than 900 late adolescents with an average age of 17 years, from three large cities: Montreal, Paris and Rome. Participants answered a self-report questionnaire that assessed five measures: emotional bonds with the father and mother, parental supervision, tolerance towards friends, punitiveness for violation of rules, and conflict frequency. Analyses of the results indicated that the country of origin discriminated for most of the parental practice dimensions. Canadian adolescents considered their parents to be more tolerant and rated them as using less punitive measures when rules were broken. Canadian parents also seemed to adopt comparable norms for boys and girls, which could be interpreted as a form of sexual egalitarianism, whereas Italian and French parents appeared less tolerant towards girls. Italian adolescents reported strong emotional bonds with each parent, and also identified more conflicts in their relationships with parents. French adolescents reported weaker emotional bonds with each parent and less parental supervision. Results were interpreted in the light of studies that have reported an influence of cultural background on both parental practices and parental decisions in each of these countries.


A unique case of intracorneal aberrant lenticular rest.
Phakomatous chorsitomas are rare congenital tumors of lenticular anlage believed to be caused by invagination of surface ectoderm into the mesoderm. They may present as a mass lesion in the eyelid or in the orbit. We report a rare case of lenticular anlage occurring within the corneal stroma in a 6-month-old boy.


Use of rabbit red cells for adsorption of cold autoagglutinins.
This study investigated the use of formaldehyde-fixed rabbit red cells and rabbit red cell stroma for the adsorption of cold autoagglutinins. Both methods were equally effective and removed all antibody activity at room temperature in 92 percent of the samples. However, some alloantibodies such as anti-D, -E, and -Leb were also reduced in titer or completely absorbed.


Changes in the pulmonary DNA, RNA and protein levels by semicarbazide in the perinatal and adult life of the rat.
Semicarbazide, injected intraperitoneally in a single dose of 100 mg/kg, reduced the nucleic acid and protein content in the lung of the adult and pregnant rats. The descendant of treated mothers on day 10 of gestation showed a significant decrease of DNA, RNA and protein levels in the lung when these foetuses were 21 days old, as well as during the first week of life in the protein levels.


Herpes simplex virus and human papillomavirus sites correlate with chromosomal breakpoints in human cervical carcinoma.
The distribution of 1,912 breakpoints observed in a series of 148 cervical cancers was analyzed. Fifty bands were shown to be nonrandomly involved in chromosome structural rearrangements. One hundred thirty-three breaks were noted in bands known to contain a human papillomavirus integration site, and 454 breaks were noted in bands containing a herpes simplex virus breakage site. We suggest that herpes simplex viruses and, possibly, papillomaviruses play an important role in the carcinogenesis and/or development of cytogenetic abnormalities in cervical cancers.


When Will the Pandemic End? Suggestions for US Communities to Manage Well-Being in the Face of COVID-19.
With COVID-19 largely spread through communities, and the lack of a national strategy to manage the spread and impact of COVID-19 into communities in the United States (US), community well-being is at risk. Without a vaccine, the COVID-19 pandemic is likely to continue for years and cause millions of deaths, primarily among the elderly and the chronically ill. A vaccine for the COVID-19 could safeguard community well-being, but cannot be counted upon at this point. We believe it is imperative for communities to form and implement strategies to manage the spread and impacts of COVID-19 and that understanding the overall death rate and for young people (ages 15-35) as well at the length of the pandemic in important to planning. We calculate an overall death rate at 1/116, a death rate of 1/3944 for young adults, and that at the current rate of infection the pandemic will last for just under 10 years or possibly indefinitely as there is no guarantee that immunity will last. Measures such as social distancing and self-quarantining are effective but have detrimental economic, educational, social and psychological impacts. Community leaders and organizers need to understand that a growing number of young people will likely not adhere to social distancing and self-quarantining indefinitely. We recommend that communities form and implement plans to managing the spread and impact of COVID-19 within a specific time frame and urge young people to adhere to measures to stop the spread for the specific time frame. Community plans should be based on a community development (CD) approach and should entail inclusive and participatory decision-making process that engaged young people. Communities should use this time to transitioning to a well-being-based local economy and implement interventions that allow for human interaction such as negative pressure ventilation and filtration of air in indoor spaces, availability of universal testing, contract tracing and the widespread use of personal powered air purifying respirators (PAPRs).


The methylation status of FBXW7 beta-form correlates with histological subtype in human thymoma.
FBXW7 is reported to be a tumor suppressor gene, and the functional inactivation of FBXW7 has been reported in various human tumors. In this study, we investigated the FBXW7 gene in human thymoma; although no mutations were evident, a significantly high frequency of methylation in the FBXW7 beta-form promoter was observed in types B1 or higher (P=0.014). We propose a novel mechanism for the pathogenesis of thymoma by FBXW7 beta-form and hypothesize that expressional suppression plays an important role in the malignant potential of thymoma.


In vitro activities of Acacia nilotica (L.) Delile bark fractions against Oral Bacteria, Glucosyltransferase and as antioxidant.
Dental caries and periodontal disease are the most common chronic infectious oral diseases in the world. Acacia nilotica was commonly known in Sudan as Garad or Sunt has a wide range of medicinal uses. In the present study, antibacterial activity of oral bacteria (Streptococcus sobrinus and Porphyromonas gingivalis), inhibitory activity against glucosyltransferase (GTF) enzyme and antioxidant activity were assayed for methanolic crude extract of A. nilotica bark and its fractions. Methanoilc crude extract of A. nilotica bark was applied to a Sephadex LH-20 column and eluted with methanol, aqueous methanol, and finally aqueous acetone to obtain four fractions (Fr1- Fr4). Furthermore, the crude extract and fractions were subjected to analytical high performance liquid chromatography (HPLC). The crude extract and its fractions were assayed for antibacterial activity against S. sobrinus and P. gingivalis using a microplate dilution assay method to determine the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC), as well as GTF inhibition and antioxidant activity using ABTS radical scavenging method. Fractions (Fr1 and Fr2) exhibited MIC values of 0.3 mg/ml against the P. gingivalis. Additionally, Fr2 displayed MBC value of 1 mg/ml against two types of bacteria. Fr4 showed an especially potent GTF inhibitory activity with IC50 value of 3.9 μg/ml. Fr1 displayed the best antioxidant activity with IC50 value of 1.8 μg/ml. The main compound in Fr1 was identified as gallic acid, and Fr2 was mostly a mixture of gallic acid and methyl gallate. The results obtained in this study provide some scientific rationale and justify the use of this plant for the treatment of dental diseases in traditional medicine. A. nilotica bark, besides their antibacterial potentiality and GTF inhibitory activity, it may be used as adjuvant antioxidants in mouthwashes. Further studies in the future are required to identify the rest of the active compounds.


Retroperitoneal ancient schwannoma: case report and analysis of clinico-radiological findings.
Ancient schwannoma is a rare subtype of typical schwannoma, with histological predominance of degenerative findings. We report the second case of retroperitoneal ancient schwannoma (occurred in a 45-year-old female referred to our institution for an unremitting right lumbar pain) and pinpoint clinical, radiological, prognosis and therapeutic aspects of this tumor.


Draft Genome Sequences of Six Strains of Lactococcus lactis (Phylum Firmicutes), Spanning the Seeds of Cucumis sativus L. (Cucumber), Cucumis melo L. (Cantaloupe), and Cucurbita pepo var. turbinate (Acorn Squash).
We announce the draft genome sequences of six strains of Lactococcus lactis (EKM101L, EKM102L, EKM201L, EKM203L, EKM501L, and EKM502L). These candidate plant probiotics were isolated from surface-sterilized seeds of Cucumis sativus L. (cucumber), Cucumis melo L. (cantaloupe), and Cucurbita pepo var. turbinate (acorn squash). They display beneficial activities, including biocontrol.


Meso-portal bypass in children with portal vein thrombosis: rapid increase of the intrahepatic portal venous flow after direct portal hepatic reperfusion.
In children with portal vein (PV) thrombosis, hepatopetal portal flow can be restored by an innovative surgical procedure, the meso-portal-bypass (MPB), if the umbilical portion of the intrahepatic left PV and the superior mesenteric vein are patent. This is associated with resolution of symptoms related to extrahepatic portal hypertension (EHPH). However, no data are available yet on intrahepatic hemodynamic changes after MPB. The aim of this study was to evaluate morphologic adaptation and flow characteristics of the intrahepatic PV branches (ihPVb) after MPB. Prospective follow-up Doppler scans of the ihPVb were performed at 0.5 to 1, 3 to 6 and 12 months after MPB in 13 consecutive patients (2000-2002) and compared with preoperative findings. Only small ihPVb were detected preoperatively on Doppler in 8 of 13 cases. Postoperatively (median follow up 12; range, 6 to 24 months), all 13 patients had patent MPB with hepatopetal flow, and ihPVb were easy to detect with satisfactory vessel diameters and flow velocities. The preoperatively small ihPVb increase rapidly in diameter and hepatopetal flow velocity in patients benefiting from MPB. This correlates well with progressive resolution of their symptoms related to EHPH and reflects rapid adaptation of ihPVb.


Cross-immunity between strains explains the dynamical pattern of paramyxoviruses.
Viral respiratory tract diseases pose serious public health problems. Our ability to predict and thus, be able to prepare for outbreaks is strained by the complex factors driving the prevalence and severity of these diseases. The abundance of diseases and transmission dynamics of strains are not only affected by external factors, such as weather, but also driven by interactions among viruses mediated by human behavior and immunity. To untangle the complex out-of-phase annual and biennial pattern of three common paramyxoviruses, Respiratory Syncytial Virus (RSV), Human Parainfluenza Virus (HPIV), and Human Metapneumovirus (hMPV), we adopt a theoretical approach that integrates ecological and immunological mechanisms of disease interactions. By estimating parameters from multiyear time series of laboratory-confirmed cases from the intermountain west region of the United States and using statistical inference, we show that models of immune-mediated interactions better explain the data than those based on ecological competition by convalescence. The strength of cross-protective immunity among viruses is correlated with their genetic distance in the phylogenetic tree of the paramyxovirus family.


Multigenerational familial medullary thyroid cancer (FMTC): evidence for FMTC phenocopies and association with papillary thyroid cancer.
Occurrence in a familial setting is well established for medullary thyroid carcinoma (MTC) and has been more recently reported for papillary thyroid cancer (PTC). Germline mutations or rearrangements of the RET proto-oncogene are the genetic background of the majority of hereditary MTCs and of about 25-40% of PTCs. A large multigenerational familial medullary thyroid cancer (FMTC) family, comprised of four generations and a total of 60 subjects, has been fully evaluated. Studies on germline RET mutations and polymorphisms, on somatic RET activation and on haplotyping with RET-linked markers, were performed. RET mutational analysis revealed a rare missense point mutation in exon 15 of RET (A891S), associated with FMTC. Haplotype analysis showed a co-segregation between the allelic variant 5 of D10S578 marker (which is tightly linked to the RET locus) and the RET mutation. Two patients, from different branches of the family, did not harbour the point mutation A891S despite histological confirmation of MTC. In these cases, haplotype analysis excluded the involvement of the RET gene itself in the pathogenesis of the MTC. In three patients, the coexistence, in different foci, of medullary and papillary thyroid cancer was documented. The genetic studies did not show ret/PTC rearrangements. The microsatellite analysis excluded co-segregation of RET locus with the MTC/PTC phenotype. We report a full clinical and molecular analysis of a large FMTC kindred with an uncommon RET mutation. In two family members, phenotype and genotype were not concordant, representing the first evidence of FMTC phenocopies. Furthermore, the association of familial forms of medullary and papillary thyroid cancers has been found in 30% of patients undergoing thyroidectomy for MTC. In these situations, genetic analyses excluded the possible germline involvement of RET. Though FMTC phenocopies are likely to represent an exceptional finding, such a possibility should be taken into account in the genetic counselling for MEN 2 syndromes.


Hypercholesterolemia blunts forearm vasorelaxation and enhances the pressor response during acute systemic hypoxia.
During hypoxia, active substances released by the endothelium play a key role in the cardiovascular and respiratory responses elicited to optimize oxygen delivery. As hypercholesterolemia is a major cause of endothelial dysfunction, it may interfere with these responses. We studied cardiovascular and ventilatory responses to acute systemic hypoxia in 14 patients with hypercholesterolemia (HC) and 13 control (CO) subjects. Oxygen saturation decreased similarly in both groups. Diastolic blood pressure increased only in the HC group (P=0.0002) and, despite systolic blood pressure increases both in the HC group, 140+/-4 (95% confidence interval [CI],131 to 149 mm Hg) to 154+/-4 mm Hg (95% CI,145 to 164 mm Hg), and in the CO group, 133+/-3 (95% CI,126 to 140 mm Hg) to 140+/-4 mm Hg (95% CI,132 to 148 mm Hg), the HC group showed an enhanced pressor response (P=0.03, group comparison). Both groups had increased forearm blood flow, but the decrease in forearm vascular resistance in the CO group, 40+/-5 (95% CI, 30 to 51 UR) to 31+/-4 UR (95% CI,23 to 39 UR) (P=0.0001) was not seen in the HC group, 29+/-3 (95% CI, 22 to 37 UR) to 26+/-3 UR (95% CI, 20 to 33 UR), (P=0.03, group comparison). Hypercholesterolemic patients demonstrate a hyperreactive pressor response and absence of forearm vasodilation during acute systemic hypoxia.


Sex-specific associations between cardiovascular risk factors and physical function: the Gambian Bone and Muscle Ageing Study.
In Sub-Saharan Africa, the prevalence of obesity, cardiovascular disease (CVD) and impaired physical function are increasing due to rapid urbanization. We investigated sex differences in associations between cardiac workload, arterial stiffness, peripheral vascular calcification (PVC) and physical function in Gambian adults. A total of 488 Gambians aged 40-75+ years were recruited (men: 239; and women: 249). Supine blood pressure and heart rate were measured to calculate rate pressure product and pulse pressure. Presence of PVC was determined from tibia peripheral quantitative computed tomography scans. Physical function was assessed by chair rise test (CRT), single two-legged jump (s2LJ) and hand grip strength (HGS). Body composition was measured by dual-energy x-ray absorptiometry; body size corrections were used to calculate fat mass index (FMI) and appendicular lean mass index (ALMI). Estimated glomerular filtration rate (eGFR) was measured from fasting blood samples. The relationship between rate pressure product, pulse pressure or presence of PVC (independent variable) with physical function parameters (dependent variable) was tested using linear regression. Sex-interactions were tested (p-int) adjusting for age, eGFR and ALMI/FMI. Results were expressed as mean differences between men and women with 95% confidence intervals. Mediation analyses used ALMI/FMI as mediator. Women weighed less (54.7 kg ± 10.3 vs. 59.9 kg ± 10.3) and were shorter (157.8 cm ± 6.0 vs. 169.2 cm ± 7.0) compared with men (both P < 0.0001). Women had higher FMI (6.8 kg/m2 ± 2.9 vs. 2.9 kg/m2 ± 2.0, P < 0.0001) and eGFR (263.7 mL/min/1.73 m2 ± 133.1 vs. 237.6 mL/min/1.73 m2 ± 134.6), but lower ALMI (6.2 kg/m2 ± 0.7 vs. 8.02 kg/m2 ± 1.0, P < 0.0001) compared with men. There were significant mean differences between men and women in rate pressure product and s2LJ power (-1.08 [-1.21, -0.95]) and force (-0.57 [-0.63, -0.51]), only after adjusting for age, eGFR and FMI. There were significant mean differences in the associations between pulse pressure and CRT power (-0.28 [-0.31, -0.25]), s2LJ power (-1.07 [-1.20, -0.93]) and HGS (-11.94 [-13.35, -10.54]); these differences were greater after adjusting for age, eGFR and FMI, than ALMI. There were similar differences in the associations between PVC and physical function parameters. In men, FMI mediated the association between rate pressuree product and CRT power (P = 0.002), s2LJ force (P < 0.001) and s2LJ power (P = 0.001). ALMI did not mediate associations for either men or women. Multiple risk factors for CVD were associated with poorer physical function in men and were mediated by FMI. There is a need to identify strategies to slow/prevent the rising CVD burden and poor physical function in Sub-Saharan Africa.


Utilization rates and predictors of sodium glucose cotransporter 2 inhibitor use in patients with heart failure with or without type 2 diabetes.
Sodium glucose cotransporter 2 (SGLT2) inhibitors have been demonstrated to reduce cardiovascular deaths and heart failure (HF) hospitalizations in patients with HF. Despite this, utilization remains low. The purpose of this study was to characterize SGLT2 inhibitor utilization rates and predictors of use in a population of patients with or without type 2 diabetes (T2D). This was a retrospective, single-center, descriptive chart review study. Individuals 18 years of age or older with HF were eligible for inclusion. Charts were reviewed between August 2021 and February 2022. The primary objective was to identify rates of SGLT2 inhibitor prescribing for patients with HF within a large academic medical center. Logistic regression analyses were conducted to identify potential SGLT2 inhibitor utilization predictors (demographic characteristics, medical history, laboratory results, specialty provider visits, medication use, and medication coverage). A total of 800 patients with HF were included: 377 with HF with reduced ejection fraction (HFrEF), 88 with mildly reduced EF, and 335 with preserved EF. Key baseline characteristics were as follows: 43% female; 47% Hispanic; 42% with T2D; 49% with established atherosclerotic cardiovascular disease; and mean age, 65 years. SGLT2 inhibitor utilization was 6.5% overall. Key predictors of utilization were as follows: T2D (odds ratio [OR], 33.4; 95% CI, 8.01-139.55), HFrEF (OR, 2.8; 95% CI, 1.45-5.51), HF clinic visit (OR, 2.5; 95% CI, 1.40-4.60), visit with pharmacist with prescriptive authority (OR, 5.8; 95% CI, 3.14-10.88), and enrollment in the hospital patient assistance program (OR, 2.3; 95% CI, 1.08-4.97). Despite guideline recommendations, SGLT2 inhibitors are underutilized in patients with HF with or without T2D.


Weight loss and weight gains in patients starting peritoneal dialysis; the effect of peritonitis.
Earlier studies reported that peritoneal dialysis (PD) patients gained fat mass after initiating dialysis. Clinical practice and demographics have changed over time with earlier initiation of dialysis and increasing numbers of elderly, co-morbid patients. As such, we wished to review changes in body composition with dialysis. Changes in body composition were compared by dual x-ray absorptiometry (DXA) in 151 adult PD patients, 81 males (54.6%), 50 diabetic (30.1%), mean age 60.5 ± 16.7 years, shortly after starting PD and then a median of 24 months later, to allow for the initial impact of dialysis. Overall, weight appeared stable (71.7 ± 15.4 vs. 71.9 ± 15.3 kg). On follow-up, total weekly urea clearance fell from 2.29 (1.85-3.0) to 1.93 (1.63-2.4) whereas peritoneal glucose absorption increased from 119 (46-217) to 321 (187-805) mmol/day, p < .001, and estimated dietary protein (nPNA) fell from 0.92 ± 0.23 to 0.86 ± 0.23 g/kg/day, p = .006. However, 69 (45.7%) patients gained weight, with greater change in both lean and fat mass index versus those with weight loss (0.8 [-0.5 to 2.0] vs. -0.7 [-2.1 to 0.2] and 0.9 [-0.1 to 2.3] vs. 0 [-2.6 to 0.8] kg/m2 , p < .001), respectively. Although there were no differences in hospital admissions, patients who gained weight experienced fewer episodes of PD peritonitis (0 [0-1] vs. 1[0-2], p = .019). Dietary protein intake declined over time, and more PD patients lost weight. The major difference between those who gained and lost weight was episodes of peritonitis. Greater attention to nutritional support may potentially reduce loss of lean body mass.


[Assessment of Body-Related Avoidance Behaviour: Validation of the German Version of the Body Image Avoidance Questionnaire (BIAQ) in Adolescents with Anorexia and Bulimia Nervosa and Healthy Controls].
Body image avoidance is conceptualised as a behavioural manifestation of body image disturbance, and describes efforts to avoid confrontation with one's own body. While studies have provided hints that body image avoidance in adulthood contributes to the development and maintenance of eating disorders, so far, there are no corresponding findings for adolescence. The Body Image Avoidance Questionnaire (BIAQ) is the most widely used international questionnaire for measuring body-related avoidance behaviour. As its German version has only been validated in an adult sample, the aim of the present study is to statistically test the questionnaire in adolescents with eating disorders. In total, N=127 female adolescents, including n=57 with Anorexia Nervosa, n=24 with Bulimia Nervosa, and n=46 healthy controls, answered the BIAQ as well as various other instruments for assessing body image disturbance and eating disorder symptoms. The factor structure assumed for the original English version, comprising the higher-order factor "body-related avoidance behaviour" and the 4 subfactors "clothing", "social activities", "eating restraint" and "grooming and weighing", was confirmed by a confirmatory factor analysis. With the exception of the scale "grooming and weighing", all scales showed mostly acceptable internal consistencies, test-retest reliability, differential validity and construct validity. Due to their satisfying psychometric properties, the use of the BIAQ scales "clothing", "social activities" and "eating restraint" can be recommended in research and practice for adolescence.


Condylar erosion and disc displacement: detection with high-resolution ultrasonography.
Our goal was to determine the feasibility of high-resolution sonography for the detection of condylar erosion and associated disc displacement at the temporomandibular joint (TMJ) condyle. Forty-eight consecutive patients (96 joints) with TMJ disorders were investigated prospectively using a 12.5-MHz array transducer. Images were assessed for condylar erosion and disc displacements. Sonographic findings were correlated with those of magnetic resonance imaging (MRI). At MRI, 18 osseous changes were diagnosed with condylar erosion. Sonographically, 15 of the 18 condylar erosions were diagnosed correctly. Sensitivity, specificity, and accuracy of sonography in the depiction of condylar erosion were 83%, 63%, and 67%, respectively. The positive predictive value was 34%, and the negative predictive value was 94%. Disc displacement without reduction (43 of 96) and disc displacement without reduction concomitant with condylar erosion (16 of 96) were detected with an accuracy of 93% and 80%. Sonography is an insufficient imaging technique for the detection of condylar erosion. Assessment of disc displacement without reduction may be reliably made with sonography.


Compensatory effect by sigma1 (sigma1) receptor stimulation during alcohol withdrawal in mice performing an object recognition task.
Chronic alcohol consumption (CAC) provokes intense neurobiological alterations, which lead, notably, to an important abstinence syndrome upon withdrawal with deleterious cognitive consequences. We here examined the effect of activation or inactivation of the sigma(1) receptor during CAC withdrawal on the cognitive abilities of Swiss mice. Animals consumed an alcohol 10%/sucrose 30 g/l solution during 4 months. Control groups consumed only the sucrose vehicle solution. Then, animals experienced a progressive, 16 days long, CAC withdrawal, during which they were administered once daily with saline, igmesine (10 mg/kg i.p.), a sigma(1) receptor agonist, or BD1047 (10 mg/kg i.p.), a sigma(1) antagonist. Mice were then tested using an object exploration task, to evaluate their locomotor and exploratory activities and reactions to object habituation, spatial change or novel object presentation. CAC-treated animals showed augmentation of locomotion, anxiety and object exploration, which impeded correct reaction to object habituation, spatial change or novelty. Treatment with the sigma(1) ligands, ineffective in control groups, resulted in decrease of the hyper-responsiveness and restored habituation. However, correct reactions to spatial change and novelty were only produced by the sigma(1) agonist treatment. Moreover, the sigma(1) receptor hippocampal expression was increased in CAC-treated mice. Treatments with both sigma(1) ligands regulated its expression, but subcellular fractionation experiments revealed that the agonist treatment increased [(3)H](+)-pentazocine binding to sigma(1) sites in the plasma membrane fraction, while the antagonist maintained it only in the microsomal, putatively endoplasmic reticulum, fraction. In conclusion, CAC increased the sigma(1) receptor expression in the hippocampus of mice. Regulation of its expression during withdrawal, notably using a selective agonist, allowed not only to attenuate the CAC-induced hyper-responsiveness, but also to restore correct cognitive abilities.


The reading and semantic link tests: a comparison between probable Alzheimer patients and reading-matched controls.
The performance in those diagnosed as probably suffering from Alzheimer's disease was compared with age-matched controls on a test of semantic and contextual processing relative to a test of silent reading. The former test, the Semantic Link Test, was hypothesized to deteriorate to a greater degree in those suffering from Alzheimer's disease. The controls were matched on reading performance as well as on age. Consequently, a deterioration in performance on the Semantic Link Test for Alzheimer's patients relative to controls was hypothesized. This hypothesis was confirmed, lending further support to the notion that Alzheimer's disease can specifically affect semantic processes.


Psychosocial profile of patients on the liver transplant list.
Researchers have shown that psychosocial factors influence adherence to treatment and, consequently, prognosis. Psychosocial assessment during the preoperative outpatient phase has allowed physicians to make better treatment decisions. We sought to describe the psychosocial profile of patients on the liver transplant list referred for psychological assessment. We reviewed all files of patients referred for pretransplant psychological assessment over a 14-month period. The sample included 73 patients: mean age 49.46 +/- 11.18 years and; mean formal schooling 7.35 +/- 4.65 years. Of those, 56.1% reported a cognitive complaint; 33%, symptoms of anxiety, and 17%, depression. Of the sample, 45.8% were referred for alcohol use, and 37.5% for mood changes. During the assessment, 15.9%, 34.4%, and 1.6%, of patients reported using alcohol, tobacco, or some other type of drug, respectively. Of patients, 53.6% reported having used alcohol at some point in their life-26% tobacco and 10.9% some other type of drug. After the assessment, the main referrals were 35.6% to family counseling, 32.1% to cognitive assessment, and 28.5% to psychological counseling. This study highlighted the prevalence of cognitive complaints and current/previous use of chemical substances. These findings were identified through psychological inquiry, which was able to direct the individual treatments. Although these conditions prevailed among this population, their early detection allowed for early intervention to improve adherence and minimize possible intervening problems.


Dynamical nonequilibrium molecular dynamics reveals the structural basis for allostery and signal propagation in biomolecular systems.
A dynamical approach to nonequilibrium molecular dynamics (D-NEMD), proposed in the 1970s by Ciccotti et al., is undergoing a renaissance and is having increasing impact in the study of biological macromolecules. This D-NEMD approach, combining MD simulations in stationary (in particular, equilibrium) and nonequilibrium conditions, allows for the determination of the time-dependent structural response of a system using the Kubo-Onsager relation. Besides providing a detailed picture of the system's dynamic structural response to an external perturbation, this approach also has the advantage that the statistical significance of the response can be assessed. The D-NEMD approach has been used recently to identify a general mechanism of inter-domain signal propagation in nicotinic acetylcholine receptors, and allosteric effects in β -lactamase enzymes, for example. It complements equilibrium MD and is a very promising approach to identifying and analysing allosteric effects. Here, we review the D-NEMD approach and its application to biomolecular systems, including transporters, receptors, and enzymes.


Aging-related mitochondrial alterations in bovine oocytes.
Advanced maternal age is an emerging health problem which involves many functional and structural alterations in oocytes, and its study is relevant to design better approaches to improve the reproductive function in women of advanced age. A constraint to this type of studies is the limited amount of samples and the ethical problems of working with human gametes. This study aims to characterize the in vitro-induced age-related modifications in a bovine model, as well as to determine if this model is a reliable approach to study human aging. For this purpose, we have focused on aging-related alterations related to oocyte mitochondrial dysfunction, a key hallmark in aging. Morphological and bioenergetic in vitro-induced alterations in bovine oocytes were compared to an in vivo aged group and to the already reported information regarding humans and other animal models. Parameters monitored included ooplasmic volume; mitochondrial mass, distribution and aggregation, assessed by MitoTracker Green; mitochondrial activity, monitored by JC-1; and the mitochondrial levels of hydrogen peroxide (H2O2), quantified using MitoPY. Results show a significant decrease in oocyte cytoplasmic volume after both in vitro and in vivo aging (p < 0.001). Additionally, the levels of H2O2 increased significantly after in vitro and in vivo aging (p < 0.001) and mitochondrial aggregation patterns were significantly different after 30 h of in vitro maturation, with MII oocytes presenting small aggregates inside the cytoplasm, whereas aged oocytes had a lack of granularity (p < 0.001). In contrast, there were no differences between the different aging groups in terms of mitochondrial mass, distribution and activity. In conclusion, this in vitro approach of inducing aging-related alterations may be considered as a reliable approach to study the aging process in human female gametes, since it causes the same types of alterations in both species.


The hybrid political role of feminism on Twitter during COVID-19: SISMA Mujer in Colombia.
Twitter proved to be strategic for the dissemination of information, and for the activation of feminist social movements. This article identifies the patterns of representation around feminist movements on Twitter during the COVID-19 pandemic. We analyzed the discourse around a Colombian NGO known as Sisma Mujer, in a corpus of 4415 tweets posted during the first year of COVID-19. The results showed five significant topic categories: gender-based violence, women in peacebuilding, women's human rights, gender equality, and social protest. This activity re-contextualized the online activism of this movement into a new, hybrid role with important political implications for the social movement. Our analysis highlights this role by pointing out how feminist activists framed gender-based violence to generate a discourse on Twitter.


Tyrosinase-mediated melanogenesis in melanoma cells: Array comparative genome hybridization integrating proteomics and bioinformatics studies.
We investigated the tyrosinase-associated melanogenesis in melanoma cells by using OMICS techniques. We characterized the chromosome copy numbers, including Chr 11q21 where the tyrosinase gene is located, from several melanoma cell lines (TXM13, G361, and SK-MEL-28) by using array CGH. We revealed that 11q21 is stable in TXM13 cells, which is directly related to a spontaneous high melanin pigment production. Meanwhile, significant loss of copy number of 11q21 was found in G361 and SK-MEL-28. We further profiled the proteome of TXM13 cells by LC-ESI-MSMS and detected more than 900 proteins, then predicted 11 hub proteins (YWHAZ; HSP90AA1; HSPA5; HSPA1L; HSPA9; HSP90B1; HSPA1A; HSPA8; FKSG30; ACTB; DKFZp686DQ972) by using an interactomic algorithm. YWHAZ (25% interaction in the network) is thought to be a most important protein as a linking factor between tyrosinase-triggered melanogenesis and melanoma growth. Bioinformatic tools were further applied for revealing various physiologic mechanisms and functional classification. The results revealed clues for the spontaneous pigmentation capability of TXM13 cells, contrary to G361 and SK-MEL-28 cells, which commonly have depigmentation properties during subculture. Our study comparatively conducted the genome-wide screening and proteomic profiling integrated interactomics prediction for TXM13 cells and suggests new insights for studying both melanogenesis and melanoma.


1.5-5 years of uninterrupted cis-diamminedichloroplatinum II chemotherapy for metastatic cervical cancer.
In an attempt to prolong remission duration in patients with metastatic cervical cancer to cis-platinum based chemotherapy, patients were treated on an every other month basis after a minimum of 1 year of cis-platinum based chemotherapy. To date, five patients have received 5, 4.5, 2.3, 2.3, and 1.5 years, respectively, of uninterrupted cis-platinum based chemotherapy. All remain in complete remission after receiving a total dose of cis-platinum of 2523 mg (1530 mg/m2), 2.408 mg (1655 mg/m2), 1496 mg (880 mg/m2), 1325 mg (970 mg/m2), and 1640 mg (950 mg/m2), respectively. The only apparent toxicity has been asymptomatic hypomagnesemia. In contrast, three other patients in complete remission on cis-platinum based chemotherapy voluntarily discontinued such therapy and have subsequently developed uncontrolled recurrent cervical cancer. It is concluded that patients in complete remission from cis-platinum chemotherapy for metastatic cervical cancer can receive long-term cis-platinum based chemotherapy and that such therapy appears to be without significant toxicity.


Transport pathways of beta-VLDL by aortic endothelium of normal and hypercholesterolemic rabbits.
The uptake and transport of beta-VLDL by the aortic endothelium was investigated in normal and hyperlipidemic rabbits fed a cholesterol-enriched diet for 1 week to 5 months. Weekly (in the first month) or every other week afterwards, animals were given one of the following probes: (a) [125I]-beta-VLDL injected in vivo and after 24 h the whole aorta or its intima and media were separately collected and examined by spectrometry and autoradiography; (b) [125I]-beta-VLDL coupled to the fluorescent probe 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate perfused in situ for 1-2 h and aorta examined by radioassay and fluorescence microscopy; (c) beta-VLDL-gold complex perfused in situ for 10-15 min and aortic fragments examined by electron microscopy. In addition, cryosections of aortic wall were processed for the immunocytochemical detection of apolipoprotein B and apolipoprotein E. The results showed that both in normal and hyperlipidemic rabbits, the aortic endothelium transports plasma beta-VLDL by a dual pathway: (i) endocytosis involving coated pits and vesicles, endosomes, multivesicular bodies and lysosomes, and (ii) transcytosis, the predominant process, carried out by plasmalemmal vesicles. Both processes, and especially transcytosis, are markedly increased in hyperlipidemia leading to progressive accumulation of beta-VLDL or/and its components in the subendothelial extracellular matrix. In prelesional stages of atherogenesis, beta-VLDL-gold complexes or deposits of apo B and apo E were detected in close association with extracellular liposomes. With the appearance of intimal macrophage-derived foam cells, the immunoperoxidase reaction product, revealing the presence of the two apolipoproteins, could also be seen in intracellular lipid inclusions.


Maize dispersal patterns associated with different types of endosperm and migration of indigenous groups in lowland South America.
The lowlands of South America appear to be remarkably important in the evolutionary history of maize, due to new evidence that suggests that maize dispersed from Mexico and arrived in this region in a state of partial domestication. This study aimed to identify dispersal patterns of maize genetic diversity in this part of the continent. A total of 170 maize accessions were characterized with 4398 single nucleotide polymorphisms (SNPs) and analysed to determine if maize dispersal was associated with types of endosperm and indigenous language families. Four genetic groups were identified in the discriminant analysis of principal components and five groups in the cluster analysis (neighbour-joining method). The groups were structured according to the predominance of endosperm types (popcorn, floury, flint/semi-flint). Spatial principal component analysis of genetic variation suggests different dispersal patterns for each endosperm type and can be associated with hypotheses of expansions of different indigenous groups. From a possible origin in Southwestern Amazonia, different maize dispersal routes emerged: (1) towards Northern Amazonia, which continued towards the Caatinga and south-eastern Atlantic Forest (Floury); (2) towards Southern Brazil, passing through the Cerrado and Southern Atlantic Forest reaching the Pampa region (Floury); and (3) along the Atlantic Coast, following Tupi movements originating from two separate expansions: one (Tupinamba) from north to south, and the other (Guarani) in the opposite direction, from south to north (flint, floury and popcorn).


Gefitinib enhances the efficacy of photodynamic therapy using 5-aminolevulinic acid in malignant brain tumor cells.
Since the ATP-binding cassette transporter ABCG2 plays a physiologically significant role of porphyrin efflux from living cells, the expression of ABCG2 may influences the efficacy of photodynamic therapy (PDT). In this study, we evaluated the effect of gefitinib, a potent ABCG2 inhibitor, on 5-aminolevulinic acid (5-ALA)-PDT in brain tumor cell lines in vitro. Four human glioma cell lines (U87MG, U118MG, A172, and T98G) and a malignant meningioma cell line (IOMM-Lee) were incubated with gefitinib (0.01-1.0μM) before incubation with 5-ALA (1mM). The effects gefitinib on intracellular protoporphyrin IX (PpIX), mRNA and protein expression of ABCG2, and PDT were evaluated, in vitro. At concentrations of 0.1μM or higher, gefitinib enhanced intracellular levels of PpIX in a dose-dependent manner in all those cell lines. Gefitinib decreased mRNA and plasma membrane protein expression of ABCG2, and efficiently enhanced the effect of 5-ALA-PDT in malignant brain tumor cells. Gefitinib can inhibit ABCG2-mediated PpIX efflux from malignant brain tumor cells to increase the intracellular PpIX and thereby enhance the PDT effect.


The antimicrobial effects of helium and helium-air plasma on Staphylococcus aureus and Clostridium difficile.
Healthcare-associated infections (HCAI) affect 5-10% of acute hospital admissions. Environmental decontamination is an important component of all strategies to prevent HCAI as many bacterial causes survive and persist in the environment, which serve as ongoing reservoirs of infection. Current approaches such as cleaning with detergents and the use of chemical disinfectant are suboptimal. We assessed the efficacy of helium and helium-air plasma in killing Staphylococcus aureus and Clostridium difficile on a glass surface and studied the impact on bacterial cells using atomic force microscopy (AFM). Both plasma types exhibited bactericidal effects on Staph. aureus (log3·6 - >log7), with increased activity against methicillin-resistant strains, but had a negligible effect on Cl. difficile spores (<1log). AFM demonstrated cell surface disruption. The addition of air increased the microbicidal activity of the plasma and decreased the exposure time required for an equivalent log reduction. Further evaluation of cold plasma systems is warranted with, for example, different bacteria and on surfaces more reminiscent of the health care environment as this approach has potential as an effective decontaminant. Many bacterial causes of healthcare infection can survive in the inanimate environment for lengthy periods and be transmitted to patients. Furthermore, current methods of environmental decontamination such as detergents, chemical disinfectants or gaseous fumigation are suboptimal for a variety of reasons. We assessed the efficacy of helium and helium-air plasma as a decontaminant and demonstrated a significant reduction in bacterial counts of Staphylococcus aureus on a glass surface. Atomic force microscopy morphologically confirmed the impact on bacterial cells. This approach warrants further study as an alternative to current options for hospital hygiene.


Effects of polymer-linked sulfonylurea derivatives on insulin release.
In order to elucidate whether polymerlinked sulfonylurea derivatives may serve as tools to locate the sulfonylurea receptor site, an easily detectable sulfonylurea was synthetized and coupled to cyanogen-bromide activated dextran. The conjugate proved to be unstable and to release sufficient amounts of free agent to explain its insulinotropic activity. Based on these findings previous results claiming that dextran-linked sulfonylureas retain biological activity may be questioned. A stable conjugate was obtained when the acrylyl derivative of the sulfonylurea was co-polymerized with acrylamide. Both a high (greater than 50000) and a low (1500) molecular weight fraction of this conjugate failed to stimulate insulin release from the perfused rat pancreas, questioning the ability of macromolecular conjugates to combine with the sulfonylurea receptor site.


Evaluation of transition services for young people with cystic fibrosis in Southeast London.
We report a project being launched to evaluate transition services for young people with Cystic Fibrosis (CF) living in Southeast London, UK, and attending either King's College Hospital (KCH) or University Hospital Lewisham (UHL).


(-)-Stepholidine antagonizes the inhibition by D2 receptor agonists on synaptosomal tyrosine hydroylase in rat corpus striatum.
To evaluate the action of (-)-stepholidine (SPD), a novel dopamine (DA) receptor antagonist, on inhibition by presynaptic D2 receptor agonists on the activity of synaptosomal tyrosine hydroxylase (TH) in the striatum. The TH activity was measured by HPLC-ECD. The mixed DA receptor agonist apomorphine (Apo 10.4 nmol L-1) and selective D2 receptor agonists N-0437 (0.4 pmol L-1) and quinpirole (0.8 mumol L-1) inhibited the activity of TH, while selective D1 receptor agonist SKF 38393 (0.001-10 mumol L-1) and SPD (1-100 mumol L-1) failed to inhibit the TH activity. The inhibition of N-0437 and quinpirole were antagonized by D2 receptor antagonist spiperone and SPD. The negative feedback regulation of presynaptic DA receptors is mediated via D2 receptors and SPD is an antagonist on presynaptic D2 DA receptors.


Dipeptidyl peptidase-4 inhibition by vildagliptin and the effect on insulin secretion and action in response to meal ingestion in type 2 diabetes.
The purpose of this study was to determine the mechanism by which dipeptidyl peptidase-4 inhibitors lower postprandial glucose concentrations. We measured insulin secretion and action as well as glucose effectiveness in 14 subjects with type 2 diabetes who received vildagliptin (50 mg b.i.d.) or placebo for 10 days in random order separated by a 3-week washout. On day 9 of each period, subjects ate a mixed meal. Insulin sensitivity (S(I)), glucose effectiveness, and beta-cell responsivity indexes were estimated using the oral glucose and C-peptide minimal models. At 300 min 0.02 unit/kg insulin was administered intravenously. Vildagliptin reduced postprandial glucose concentrations (905 +/- 94 vs. 1,008 +/- 104 mmol/6 h, P = 0.02). Vildagliptin did not alter net S(I) (7.71 +/- 1.28 vs. 6.41 +/- 0.84 10(-4) dl x kg(-1) x min(-1) x muU(-1) x ml(-1), P = 0.13) or glucose effectiveness (0.019 +/- 0.002 vs. 0.018 +/- 0.002 dl x kg(-1) x min(-1), P = 0.65). However, the net beta-cell responsivity index was increased (35.7 +/- 5.2 vs. 28.9 +/- 5.2 10(-9) min(-1), P = 0.03) as was total disposition index (381 +/- 48 vs. 261 +/- 35 10(-14) dl x kg(-1) x min(-2) x pmol(-1) x l(-1), P = 0.006). Vildagliptin lowered postprandial glucagon concentrations (27.0 +/- 1.1 vs. 29.7 +/- 1.5 microg x l(-1) x 6 h(-1), P = 0.03), especially after administration of exogenous insulin (81.5 +/- 6.4 vs. 99.3 +/- 5.6 ng/l, P = 0.02). Vildagliptin lowers postprandial glucose concentrations by stimulating insulin secretion and suppressing glucagon secretion but not by altered insulin action or glucose effectiveness. A novel observation is that vildagliptin alters alpha-cell responsiveness to insulin administration, but the significance of this action is as yet unclear.


Effect of thapsigargin on cardiac muscle cells.
The effect of thapsigargin on the activity of various enzymes involved in the Ca(2+)-homeostasis of cardiac muscle and on the contractile activity of isolated cardiomyocytes was investigated. Thapsigargin was found to be a potent and specific inhibitor of the Ca(2+)-pump of striated muscle SR (IC50 in the low nanomolar range). A strong reduction of the Vmax of the Ca(2+)-pump was observed while the Km (Ca2+) was only slightly affected. Reduction of the Vmax was caused by the inability of the ATPase to form the Ca(2+)-dependent acylphosphate intermediate. Thapsigargin did not change the passive permeability characteristics nor the function of the Ca(2+)-release channels of the cisternal compartments of the SR. In addition, no significant effects of thapsigargin on other ATPases, such as the Ca(2+)-ATPase and the Na+/K(+)-ATPase of the plasma membrane as well as the actomyosin ATPase could be detected. The contractile activity of paced adult rat cardiomyocytes was completely abolished by 300 nM thapsigargin. At lower concentrations the drug prolonged considerably the contraction-relaxation cycle, in particular the relaxation phase. The intracellular Ca(2+)-transients elicited by electrical stimulation (as measured by the changes in Fluo-3 fluorescence) decreased in parallel and the time needed to lower free Ca2+ down to the resting level increased. In conclusion, the results indicate that selective inhibition of the Ca(2+)-pump of the SR by thapsigargin accounts for the functional degeneration of myocytes treated with the drug.


A better way to measure disability in older people.
Health care experts, older people and carers were asked to weight 18 personal and social activities of daily living (ADLs) with regard to the importance of being able to perform them. All groups agreed on the order of importance but experts gave greater weight to personal ADLs. We have used these results to produce a ratio scale.


[Assessing knowledge, attitude, and practice on occupational blood exposure in caregiving facilities, in Morocco].
This study had for aim to evaluate practices and knowledge of infectious hazards, to determine the prevalence of viral infections related to occupational blood exposure among health care workers, and to propose a preventive policy. This descriptive multicentric and transversal epidemiological survey was carried out from 2003 to 2004 in 10 Moroccan cities. Two thousand eight hundred and forty four persons were contacted and 2086 accepted to answer the questionnaire (73.3 %). The mean age was 40.8+/-7.8 years and seniority 15.6+/-7.4 years. Blood was the most incriminated product (96.1%), followed by dirty linen and hospital waste. Instruments most often mentioned as dangerous were hollow needles (80.3%). The most feared infections were viral hepatitis (77.5%) and HIV (89.3%). Only 40.6% of the personnel were adequately vaccinated against hepatitis B. Post-vaccine serology was performed on only 1.8% of the vaccinated staff. During the last 12 months, 58.9% of the personnel underwent at least one occupational blood exposure 5.8% of which was reported. Universal precautions appeared poorly used as only 65.6% wore gloves for invasive acts and 61.5% correctly disinfected their hands. Re-sheathing used needles was frequent (51.2%). Infectious hazards in healthcare facilities are not sufficiently taken into account: the recent creation of occupational health services in hospital facilities should contribute to improve working conditions, make hepatitis B vaccination available and mandatory, and lead to more information and education on hazards related to occupational blood exposure for healthcare personnel.


A case of myasthenia gravis with thyrotoxicosis treated by combined subtotal thyroidectomy and total thymectomy.
Thyrotoxicosis occurring in conjunction with myasthenia gravis is rare. The usual treatment consists of medical control of the thyrotoxicosis, then thymectomy and later subtotal thyroidectomy. The case reported here concerns a 19-year-old girl who had surgical treatment for both lesions on the same occasion. With proper medical preparation, modern anaesthesia and respiratory care, the surgical treatment of both lesions can be accomplished in one stage.