Telmisartan.
Telmisartan is a nonpeptide angiotensin II receptor antagonist which selectively and insurmountably inhibits the angiotensin II AT1 receptor subtype without affecting other receptor systems involved in cardiovascular regulation. Oral telmisartan dose-dependently reduced blood pressure (BP) in various animal models of hypertension. In transgenic rats, telmisartan reduced cardiac hypertrophy and glomerulosclerosis. When administered at dosages of 40 to 160 mg once daily to patients with mild to moderate hypertension, telmisartan significantly reduced systolic and diastolic BP compared with placebo and was at least as effective as atenolol 50 or 100 mg and lisinopril 10 to 40 mg. One study showed telmisartan 80 mg/day to be more effective than enalapril 20 mg/day. In 2 studies that used ambulatory BP monitoring, once daily telmisartan provided better control of diastolic BP for the full dosing interval than losartan potassium 50 mg or amlodipine 5 or 10 mg. In a single study in patients with severe hypertension, a telmisartan-based regimen had antihypertensive efficacy similar to that of an enalapril-based regimen. Telmisartan had a tolerability profile similar to that of placebo in clinical studies.


Immunohistochemical analysis of ras oncogene product p21 in human endometrial carcinoma.
Monoclonal antibody rp-28 directed against the ras gene product p21 has been used to evaluate ras p21 expression in endometrial lesions. Endometrial cancer showed a variable reactivity according to histological type: in well differentiated adenocarcinoma 63% were positive (12/19); in moderately differentiated adenocarcinoma 53% were positive (8/15); in poorly differentiated adenocarcinoma 40% were positive (2/5). The staining intensity of ras p21 seemed to be stronger in the more differentiated types of endometrial carcinoma. In endometrial carcinoma with premenopausal women, 27% were positive (3/11), and with postmenopausal women 71% were positive (20/28). The difference between premenopausal and postmenopausal groups was statistically significant (Mantel-Haenszel procedure, M-H chi 2 = 6.765, P < 0.01). The results suggest the existence of different carcinogenetic mechanisms in these two groups of endometrial cancer.


Risk factors for emergence agitation during the awakening period in elderly patients after total joint arthroplasty: a retrospective cohort study.
This study aimed to explore the incidence and risk factors for emergence agitation (EA) in elderly patients who underwent total joint arthroplasty (TJA) under general anaesthesia, and to assess their predictive values. Single-centre retrospective cohort study. A 1600-bed general tertiary hospital in China. This study enrolled 421 elderly patients scheduled for elective primary TJA under general anaesthesia. EA was assessed using the Richmond Agitation Sedation Scale during the awakening period after surgery in the post-anaesthesia care unit. Risk factors for EA were identified using univariate and multivariable logistic analyses. The receiver operating characteristic (ROC) curve was used to assess the predictive values of the risk factors for EA. The incidence of EA in elderly patients who underwent TJA was 37.6%. According to the multivariable logistic analysis, postoperative pain (95% CI: 1.951 to 3.196), male sex (95% CI: 1.781 to 6.435), catheter-related bladder discomfort (CRBD) (95% CI: 4.001 to 15.392) and longer fasting times for solids (95% CI: 1.260 to 2.301) and fluids (95% CI: 1.263 to 2.365) were independent risk factors for EA. As shown by the ROC analysis, postoperative pain and fasting times for solids and fluids had good predictive values, with areas under the ROC curve equalling 0.769, 0.753 and 0.768, respectively. EA is a common complication after TJA in elderly patients. Some risk factors, including postoperative pain, male sex, CRBD and longer fasting times, can increase the incidence of EA. These risk factors may contribute to identifying high-risk patients, which facilitates the development of effective strategies to prevent and treat EA. ChiCTR1800020193.


Long-term clinical outcomes of successful revascularization with drug-eluting stents for chronic total occlusions: A systematic review and meta-analysis.
To determine whether successful percutaneous coronary intervention (PCI) using drug-eluting stents (DESs) have beneficial effects on long-term outcomes in patients with chronic total occlusions (CTOs) compared with failed PCIs for CTOs. Several observational studies have evaluated the long-term clinical outcomes of successful PCIs using DESs for CTOs. However, the results of these studies were inconsistent and inconclusive. We searched five online electronic databases to identify all the publications assessing the long-term outcomes of successful and failed PCIs using DESs for CTOs. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated by STATA software. A total of nine studies involving 5958 CTO patients who underwent successful PCI and 1511 CTO patients who underwent failed PCI were included in this meta-analysis. The results of the analysis indicated that successful CTO PCIs using DESs were associated with lower long-term all-cause mortality(OR = 0.55, 95% CI = 0.45-0.67, P < 0.001), lower risk of myocardial infarction (OR = 0.45, 95% CI = 0.23-0.74, P = 0.002), lower risk of major adverse cardiac events (MACEs, OR = 0.44, 95% CI = 0.27-0.72, P = 0.001), and less incidence of subsequent coronary artery bypass grafting (OR = 0.10, 95% CI = 0.05-0.21, P < 0.001) than failed CTO PCIs. However, there was no difference in the incidence of target vessel revascularization (OR = 1.06, 95% CI = 0.17-6.60, P > 0.05) between the two groups. Successful CTO PCI using DESs can reduce long-term all-cause mortality and the risks of MI, MACEs, and CABG in patients with CTOs. © 2017 Wiley Periodicals, Inc.


The role of exercise and types of exercise in the rehabilitation of chronic pain: specific or nonspecific benefits.
Chronic pain is one of the most common complaints seen in general practitioners' offices, and it contributes to social, emotional, physical, and economical losses. The management of this problem poses challenges for health care providers when the current treatment of choice for chronic pain is pharmacological management, which may not be a sufficient and/or holistic approach to the management of chronic pain. Our goal is to increase awareness of the significance of physical activity, as well as examine additional cost-effective, integrated approaches to help manage the complex and debilitating effects of this condition. This article summarizes the types of exercise in the rehabilitation of chronic pain patients and provides practical recommendations for the clinician based on empirical and clinical experience. This safe, cost-free, nonpharmacologic way of managing pain has been found to reduce anxiety and depression, improve physical capacity, increase functioning and independence, and reduce morbidity and mortality.


Effects of estrogen and progestin on hypothalamic blood flow autoregulation.
The consequences of female sex hormone deficiency and the effects of hormone replacement therapy are controversial because individual hormones and their derivates can result in partially antagonistic activities. This intricate system involving cerebral autoregulatory mechanisms caused by ovariectomy and female sex hormone replacement was studied in rats. The lower limit of cerebral blood flow autoregulation was determined by stepwise reduction of systemic arterial pressure while simultaneously measuring the changes of the hypothalamic blood flow (HBF) using the hydrogen gas-clearance method. In ovariectomized rats resting HBF decreased substantially and the threshold of cerebrovascular autoregulation decreased to 40 mm Hg. Estrogen replacement prevents the former change and shifts the latter upwards. Similarly, progestin replacement restores autoregulation to the physiological levels found in control animals, whereas it has no influence on the ovariectomy-induced reduction of resting blood flow. Steady-state HBF and compensatory changes of regional cerebral vascular autoregulation are altered significantly following ovariectomy. Estrogen or progestin replacement has an opposite effect on these cerebral circulatory parameters. Our observations highlight the essential role of female sex hormones in hypothalamic autoregulation during hypotensive stress.


The future ocean we want.
Backcasting involves the design of a desirable future that is not simply predicted with forecasts being, instead, proactively aimed at with effective action. So far, all initiatives towards sustainability failed, probably due to lack of investments in the acquisition of knowledge on the structure and the function of natural systems (i.e. biodiversity and ecosystem functioning), and to the reliance on models and estimates based on incomplete data.


[Epidemiological aspects relating to the determination of fosfomycin sensitivity: results of a study on 300 strains isolated in a hospital milieu in Turin].
The AA. evaluated the sensitivity to Fosfomycin and to other commonly used antibiotics of 105 bacterial strains isolated from hospital environment and 195 from pathological materials. They also studied the problem of bacterial resistence to Fosfomycin considering the frequency of "inner colonies" and of bacterial cross-resistance to other antibiotics.


Editorial for the Special Issue "COVID-19 Vaccines: A Public Health Perspective".
Public health is aimed at protecting and promoting citizens' and communities' health through different interventions, including vaccinations [...].


Development of Biomimetic NiTi Alloy: Influence of Thermo-Chemical Treatment on the Physical, Mechanical and Biological Behavior.
A bioactive layer, free of nickel, has been performed for its greater acceptability and reliability in clinical applications for NiTi shape memory alloys. In the first step, a safe barrier against Ni release has been produced on the surface by means of a thicker rutile/anastase protective layer free of nickel. In the second step, a sodium alkaline titanate hydrogel, which has the ability to induce apatite formation, has been performed from oxidized surface. An improvement of host tissue-implant integration has been achieved in terms of Ni ions release and the bioactivity of the treated NiTi alloys has been corroborated with both in vitro and in vivo studies. The transformation temperatures (As, Af, Ms, and Mf), as well as the critical stresses (σβ⇔M), have been slightly changed due to this surface modification. Consequently, this fact must be taken into account in order to design new surface modification on NiTi implants.


The effects of human and rhesus macaque blood meal sources on mosquito reproduction and adult survival under laboratory conditions.
Mass rearing of mosquitoes as required to fulfil research studies is a technically challenging endeavor. Blood meal source has been recognized as a key consideration in mass rearing of mosquitoes that affects colony health and fecundity. Four species of laboratory-colonized mosquitoes from the Department of Entomology, US Army Medical Directorate - Armed Forces Research Institute of Medical Sciences (USAMD-AFRIMS); Anopheles cracens, An. dirus, An. minimus and An. sawadwongporni were fed blood meals from human and rhesus macaque sources using an artificial membrane feeder. The effects of different blood meal sources were evaluated concerning blood-feeding, survival and reproduction (fecundity and hatching rates). Adult survival was monitored at days 7, 14 and 21 post blood-feeding. Although the mosquitoes fed on human blood exhibited higher rates of engorgement, there were no significant differences in blood-feeding rates in An. cracens (P = 0.08) and An. dirus (P = 0.91) between rhesus macaque and human blood sources. Twenty-one days post-feeding, no significant differences were observed in the survival rates of mosquitoes fed on human versus rhesus macaque blood. Except for An. dirus, which had better survival rates with human blood (97.5%) than after feeding on rhesus macaque blood (95.4%). All mosquito species fed on human blood produced significantly more eggs when compared to those fed on rhesus macaque blood. However, there was no statistical difference in hatching rates between blood sources, except for An. dirus, which had better hatching rates with human blood. These results indicate that human and rhesus macaque blood may be a viable alternative for maintaining Anopheles mosquitoes in colony.


Infective endocarditis mimicking left atrial myxoma.
Infective endocarditis (IE) is an inflammatory disease of the endocardium and can be seen with various clinical presentations such as large intracardiac vegetations. The differential diagnosis of intracardiac mass is important to guide the management. Echocardiography is of critical use in the diagnosis of intracardiac mass. Herein we present a rare case with left atrial IE and a giant vegetation mimicking left atrial myxoma.


Identification and structure activity relationships of quinoline tertiary alcohol modulators of RORγt.
A high-throughput screen of the ligand binding domain of the nuclear receptor retinoic acid-related orphan receptor gamma t (RORγt) employing a thermal shift assay yielded a quinoline tertiary alcohol hit. Optimization of the 2-, 3- and 4-positions of the quinoline core using structure-activity relationships and structure-based drug design methods led to the discovery of a series of modulators with improved RORγt inhibitory potency and inverse agonism properties.


Evaluation of mosquito densoviruses for controlling Aedes aegypti (Diptera: Culicidae): variation in efficiency due to virus strain and geographic origin of mosquitoes.
Four mosquito densovirus strains were assayed for mortality and infectivity against Aedes aegypti larvae from different geographic regions. The viral titers were quantified by real-time PCR using TaqMan technology. Firstinstar larvae were exposed to the same titer of each densovirus strain for 48 hours. All strains of densoviruses exhibited larvicidal activity and caused more than 80% mortality and infectivity in the three mosquito strains. AalDNV-exposed larvae had the highest mortality rate. The mean time to death of AalDNV-exposed larvae was shorter than other DNVs-exposed larvae. We can conclude that different densovirus strains exhibit some variations in their pathogenicity to different populations of Ae. aegypti mosquitoes. A few mosquitoes from Chachoengsao and Bangkok exposed to AeDNV and AThDNV survived to the adult stage to lay eggs and showed 22% to 50% vertical transmission in the F1 generation. Phylogenetic analysis of four densovirus strains indicated that mosquito densoviruses are separated into two distinct clades.


Grandmaternal exercise improves metabolic health of second-generation offspring.
A major factor in the growing world-wide epidemic of obesity and type 2 diabetes is the increased risk of transmission of metabolic disease from obese mothers to both first (F1) and second (F2) generation offspring. Fortunately, recent pre-clinical studies demonstrate that exercise before and during pregnancy improves F1 metabolic health, providing a potential means to disrupt this cycle of disease. Whether the beneficial effects of maternal exercise can also be transmitted to the F2 generation has not been investigated. C57BL/6 female mice were fed a chow or high-fat diet (HFD) and housed in individual cages with or without running wheels for 2 wks before breeding and during gestation. Male F1 offspring were sedentary and chow-fed, and at 8-weeks of age were bred with age-matched females from untreated parents. This resulted in 4 F2 groups based on grandmaternal treatment: chow sedentary; chow trained; HFD sedentary; HFD trained. F2 were sedentary and chow-fed and studied up to 52-weeks of age. We find that grandmaternal exercise improves glucose tolerance and decreases fat mass in adult F2 males and females, in the absence of any treatment intervention of the F1 after birth. Grandmaternal exercise also improves F2 liver metabolic function, including favorable effects on gene and miRNA expression, triglyceride concentrations and hepatocyte glucose production. Grandmaternal exercise has beneficial effects on the metabolic health of grandoffspring, demonstrating an important means by which exercise during pregnancy could help reduce the worldwide incidence of obesity and type 2 diabetes.


A study of the concentrations of substance P and neurotensin in the gastrointestinal tract of various mammals.
Immunoreactive substance P and neurotensin in extracts of the digestive tract of man, cat, guinea-pig, pig, rabbit, and rat were measured by radioimmunoassay using antisera directed against the C-terminal portions of the two peptides. In all species except the cat, the concentrations of substance P were highest in the small intestine, intermediate in the large intestine and lowest in the stomach and oesophagus: the digestive tract of the cat displayed a rather even distribution of substance P. As observed in the ileum of guinea-pig, rabbit, and rat, the external muscle layer including the myenteric plexus contained 2-5 times higher concentrations of substance P than the whole ileal wall, whereas the substance P concentrations in the mucosa were only about one sixth of those in the whole wall. High performance liquid chromatography of extracts of human, feline and rabbit ileum showed that all the immunoreactive substance P eluted at the positions of substance P and substance P sulfoxide. The distribution of immunoreactive neurotensin along the digestive system of all six species was very similar. The highest concentrations of neurotensin were measured in the distal part of the small intestine, whereas the large intestine, stomach and oesophagus contained only low concentrations of neurotensin relative to the concentrations in the ileum. As examined in the ileum of guinea-pig, rabbit, and rat, the mucosa exhibited 2.5-4 times higher concentrations of neurotensin than the whole ileal wall, while the concentrations of neutrotensin in the external muscle layer including the myenteric plexus were only 4-20% of those in the whole wall. High performance liquid chromatography of the immunoreactive neurotensin extracted from the cat ileum yielded a single peak corresponding to neurotensin while the immunoreactive neurotensin extracted from the ileum of man and rabbit was eluted in two peaks, 55 and 72% of the recovered immunoreactivity, respectively, corresponding to neurotensin. These findings are in line with the proposed roles of substance P in the neural, and neurotensin in the endocrine, control and maintenance of gastrointestinal motility.


Modulation of the host skeletal muscle niche for donor satellite cell grafting.
Skeletal muscle tissue has a remarkable capability of regenerating in pathological conditions or after injury. The principal muscle stem cells, satellite cells, are responsible for this prompt and efficient process. Normally quiescent in their niches underneath the basal lamina of each muscle fiber, satellite cells become activated to repair or form new fibers. Ideally, healthy donor stem cells could be transplanted to regenerate the skeletal muscle tissue to repair a genetic defect. However, to be efficient, cell grafting requires modulation of the host muscle environment to allow homing of, and regeneration by, donor satellite cells. Here, we provide methods to modulate the host mouse muscle environment in order to destroy or preserve the muscle niche before transplanting donor satellite cells. We also describe methods to investigate donor-derived muscle regeneration and self-renewal.


Contemporary outcomes of diffuse leptomeningeal glioneuronal tumor in pediatric patients: A case series and literature review.
Diffuse leptomeningeal glioneuronal tumor (DLGNT), also known as oligodendrogliomatosis, is a rare neuro-oncologic condition along the neuraxis that remains poorly understood in children. We sought to describe our institutional experience and quantitively summarize the clinical survival and prognostic features of DLGNT in the pediatric population across the contemporary literature. We report four institutional cases of pediatric DLGNT diagnosed between 2000 and 2020 based on retrospective review of our records, and performed a comprehensive literature search for published cases from 2000 onwards to create an integrated cohort for analysis. Kaplan-Meier estimations, Fisher's exact test, and logistic regression were utilized to interrogate the data. Of our four cases, three females aged 2-, 3- and 13-years old at diagnosis survived 6-years, 3-years and 14-months respectively, and one male aged 5-years old at diagnosis was still alive 5 years later. Our overall integrated cohort consisted of 54 pediatric DLGNT patients, with 19 (35%) female and 35 (65%) male patients diagnosed at an average age of 6.4 years (range, 1.3-17 years) by means of surgical biopsy. Chemotherapy was used in 45 cases (83%), and mean follow-up time of 54 months (range, 3-204). Across the entire cohort, overall survival 1 month after diagnosis was 96% (95% CI 86-99%), and by 10 years was 69% (95% CI 49-82%). On multivariate analysis of complete data, chemotherapy treatment (HR=0.23, P = 0.04) was statistically predictive of longer overall survival. More than 2-out-of-3 pediatric DLGNT patients survive beyond one decade. Chemotherapy is statistically associated with longer survival in DLGNT pediatric patients and should form the core of any treatment regimen in this setting. Early detection by means of judicious imaging and surgical biopsy for tissue diagnosis can lead to earlier treatment and likely superior outcomes.


Assessment of Citations of the Retracted Article by Wakefield et al With Fraudulent Claims of an Association Between Vaccination and Autism.
The number of citations can be used to show the influence of an article or to measure the validity of a research study. The article by Wakefield et al that fraudulently reported an association between vaccination and autism continues to accumulate citations even after it was retracted. To examine the characteristics of citations from scholarly literature that reference the 1998 article by Wakefield et al and to investigate whether authors are accurately citing retracted references. In this cross-sectional bibliographic analysis of the scholarly publications that cited a 1998 article by Wakefield et al, cited references were collected from a Web of Science Core Collection search performed on March 11, 2019. A total of 1211 articles were identified, with 58 citing works excluded because they were non-English-language publications or the citation to the study by Wakefield et al could not be located by reviewers. Citing works consisted of books, research articles, letters, editorials, news items, and other scholarly literature. Citations to the article by Wakefield et al were identified and analyzed by 2 reviewers in a blinded screening. Reviewers assigned a characteristic to each citation and indicated whether the retraction was documented. The characteristics of citations to the article by Wakefield et al, were categorized as negative, affirmative, or contrastive; if not, persuasive; and if not, assumptive, perfunctory, methodologic, or conceptual. Whether the partial retraction or notice of retraction was included in the citing work was also documented. Among the 1153 citing works included in this analysis, the most common citation characteristics were negative (838 [72.7%]) followed by perfunctory (106 [9.2%]) and affirmative (94 [8.2%]). A total of 123 of 322 citing works (38.2%) published between 2005 and 2010 documented the partial retraction. After the notice of retraction was published in 2010, the percentage of citing works that documented the partial retraction and/or notice of retraction between 2011 and 2018 increased to 360 of 502 (71.7%). Since the article by Wakefield et al was initially published, authors have mostly negated the findings of the study. A significant number of authors did not document retractions of the article by Wakefield et al. The findings suggest that improvements are needed from publishers, bibliographic databases, and citation management software to ensure that retracted articles are accurately documented.


Anomalous electrophoretic behavior of the membrane (M) protein of influenza virus in polyacrylamide gels.
The relative position of M and NS 1 on polyacrylamide gels depends on the concentration of cross-linker in the gel. Inversion in position of M and NS 1 occurs at a cross-linker concentration of 1.2 percent.


A mechanical checkpoint controls multicellular growth through YAP/TAZ regulation by actin-processing factors.
Key cellular decisions, such as proliferation or growth arrest, typically occur at spatially defined locations within tissues. Loss of this spatial control is a hallmark of many diseases, including cancer. Yet, how these patterns are established is incompletely understood. Here, we report that physical and architectural features of a multicellular sheet inform cells about their proliferative capacity through mechanical regulation of YAP and TAZ, known mediators of Hippo signaling and organ growth. YAP/TAZ activity is confined to cells exposed to mechanical stresses, such as stretching, location at edges/curvatures contouring an epithelial sheet, or stiffness of the surrounding extracellular matrix. We identify the F-actin-capping/severing proteins Cofilin, CapZ, and Gelsolin as essential gatekeepers that limit YAP/TAZ activity in cells experiencing low mechanical stresses, including contact inhibition of proliferation. We propose that mechanical forces are overarching regulators of YAP/TAZ in multicellular contexts, setting responsiveness to Hippo, WNT, and GPCR signaling.


Calcium-dependent ATPase unlike ecto-ATPase is located primarily on the luminal surface of brain endothelial cells.
Numerous cytochemical studies have reported that calcium-activated adenosine triphosphatase (Ca2+-ATPase) is localized on the abluminal plasma membrane of mature brain endothelial cells. Since the effects of fixation and co-localization of ecto-ATPase have never been properly addressed, we investigated the influence of these parameters on Ca2+-ATPase localization in rat cerebral microvessel endothelium. Formaldehyde at 2% resulted in only abluminal staining while both luminal and abluminal surfaces were equally stained following 4% formaldehyde. Fixation with 2% formaldehyde plus 0.25% glutaraldehyde revealed more abluminal staining than luminal while 2% formaldehyde plus 0.5% glutaraldehyde produced vessels with staining similar to 4% and 2% formaldehyde plus 0.25% glutaraldehyde. The abluminal reaction appeared unaltered when ATP was replaced by GTP, CTP, UTP, ADP or when Ca2+ was replaced by Mg2+ or Mn2+ or p-chloromercuribenzoate included as inhibitor. But the luminal reaction was diminished. Contrary to previous reports, our results showed that Ca2+-specific ATPase is located more on the luminal surface while the abluminal reaction is primarily due to ecto-ATPase. The strong Ca2+-specific-ATPase luminal localization explains the stable Ca2+ gradient between blood and brain, and is not necessarily indicative of immature or pathological vessels as interpreted in the past.


Applications, opportunities, and challenges in using Telehealth for burn injury management: A systematic review.
Burns are global public health devastating and life-threatening injuries. Telehealth can be an appropriate answer for the effective utilization of health care resources, prevention referrals and reduce socio-economic burden of burns injuries. Thus, this study aimed to systematically evaluate the applications, opportunities, and challenges of using telehealth in burn injuries management. A structured search was conducted according to PRISMA statement guidelines in the Web of Science, PubMed, Scopus, and Science Direct as well as the Google Scholar for studies published until June 28, 2022. Of the total 2301 yielded studies, 36 articles were included in the final review. Quality appraisal was done according to the Mixed Methods Appraisal Tool (MMAT) version 2018. Thematic analysis was applied for data analysis. Patient triage, transfer, and referral (38.9%) follow-up (22%), care (22%), consultation (9%), education (3%), and rehabilitation (3%) were the most prevalent application of telehealth, respectively. Our findings identified 72 unique concepts, eight initial themes, and two clinical and administrative final themes for opportunities of using telehealth in burn injury management. Furthermore, we identified 27 unique concepts, three initial themes, and two clinical and administrative final themes for remaining challenges. Despite providing pivotal opportunities such as improving burn injury diagnosis and quality of care, increasing patient and provider satisfaction, and cost containment using telehealth in burn injuries management, the concept faces challenges such as the impossibility of the physical examination of patients and technological difficulties. Our findings provide valuable information for policymakers and decision-makers infield of burn injuries and effective planning for using telehealth technology.


Investigation of a 6-MSA Synthase Gene Cluster in Aspergillus aculeatus Reveals 6-MSA-derived Aculinic Acid, Aculins A-B and Epi-Aculin A.
Aspergillus aculeatus, a filamentous fungus belonging to the Aspergillus clade Nigri, is an industrial workhorse in enzyme production. Recently we reported a number of secondary metabolites from this fungus; however, its genetic potential for the production of secondary metabolites is vast. In this study we identified a 6-methylsalicylic acid (6-MSA) synthase from A. aculeatus, and verified its functionality by episomal expression in A. aculeatus and heterologous expression in A. nidulans. Feeding studies with fully (13) C-labeled 6-MSA revealed that 6-MSA is incorporated into aculinic acid, which further incorporates into three compounds that we name aculins A and B, and epi-aculin A, described here for the first time. Based on NMR data and bioinformatic studies we propose the structures of the compounds as well as a biosynthetic pathway leading to formation of aculins from 6-MSA.


The severity of dextran sodium sulfate-induced colitis can differ between dextran sodium sulfate preparations of the same molecular weight range.
We hypothesized that the severity of dextran sodium sulfate (DSS)-induced colitis could differ between DSS preparations of the same molecular weight, and that this difference may be affected by the sulfur content. To test this, we used three DSS preparations of similar molecular weights but with different sulfur contents. Three DSS preparations with molecular weights of 40,000 to 50,000 were tested: MP Biomedicals (MP Bio), USB (USB), and The Lab Depot (The Lab). Epithelial cell lines were used to assess the levels of poly (ADP-ribose) polymerase (PARP) in the presence of 2.0% DSS in vitro. Eight-week-old female C57/B6 mice were fed 2.0% DSS in water for 1 week, and then sacrificed to investigate the effects of the DSS preparations in vivo. In vitro experiments using CaCo-2 and CMT-93 cells revealed decreased PARP levels from all DSS preparations. Notably, the PARP level was significantly decreased in CaCo-2 cells treated with DSS from USB as compared to The Lab Mice treated with The Lab DSS had significantly decreased body weight losses on day 7 as compared to mice receiving DSS from MP Bio and USB. This result was supported by their DAI score, colon weight/length ratio, and histological scores. The severity of colitis can differ between similar DSS preparations of the same molecular weight range. This difference in colitogenic properties may be affected by the total sulfur content of each DSS preparation.


Emergence and predominance of norovirus GII.17 in Huzhou, China, 2014-2015.
Norovirus (NoV) has been recognized as the leading cause of both outbreaks and sporadic cases of acute gastroenteritis in children and adults worldwide. Stool samples collected from outpatients with clinical symptoms of acute gastroenteritis in all age groups at the First People's Hospital in Huzhou, Huzhou, China between March 2014 and February 2015 were analyzed to gain insight into the epidemiology and genetic variation in NoV strains circulating in China. Real-time RT-PCR (qPCR) was performed for Norovirus detection. RT-PCR were used for genomic amplification and sequencing. Genogroup and genotype were assigned using the NoV Noronet typing tool and the strains were named according to the time of isolation. The phylogenetic analysis was conducted using MEGA 5. Of the 809 specimens, 193 (23.9 %) were positive for NoV, with GII.4 and GII.17 the most commonly identified strains. Phylogenetic analysis confirmed the presence of five recombinant strains in Huzhou. Recombinants GII.P13/GII.17 and GII.P12/GII.4 were newly detected in China. The GII.P13/GII.17 recombinant was first identified in October 2014 and steadily replaced GII.Pe/GII.4 (GII.4 Sydney 2012) as the predominant circulating NoV genotype. This is the first report of the detection of GII.17 in the Huzhou area and of a NoV genotype being detected in greater numbers than GII.4. Furthermore, our results indicated that following the emergence of GII.17 in October 2014, it steadily replaced the previous circulating GII.4 Sydney2012 strain, which was the dominant circulating genotype for the past 2 years. As norovirus are the important cause of nonbacterial gastroenteritis, continuous and comprehensive study of the norovirus strains involved in large and cost-effective acute gastroenteritis would help understanding the molecular epidemiology of norovirus infections and development of improved prevention and control measures.


CRISPR-Cas9-guided oncogenic chromosomal translocations with conditional fusion protein expression in human mesenchymal cells.
Gene editing techniques have been extensively used to attempt to model recurrent genomic rearrangements found in tumor cells. These methods involve the induction of double-strand breaks at endogenous loci followed by the identification of breakpoint junctions within a population, which typically arise by nonhomologous end joining. The low frequency of these events, however, has hindered the cloning of cells with the desired rearrangement before oncogenic transformation. Here we present a strategy combining CRISPR-Cas9 technology and homology-directed repair to allow for the selection of human mesenchymal stem cells harboring the oncogenic translocation EWSR1-WT1 found in the aggressive desmoplastic small round cell tumor. The expression of the fusion transcript is under the control of the endogenous EWSR1 promoter and, importantly, can be conditionally expressed using Cre recombinase. This method is easily adapted to generate any cancer-relevant rearrangement.


Changes in speeding on Virginia roads during the beginning of the COVID-19 pandemic.
We investigated changes in the prevalence of speeding during March-June 2020, the beginning of the COVID-19 pandemic, in Virginia. Vehicle speed data from 506 permanent speed counter stations around the state collected during March-June 2019 and March-June 2020 were analyzed. Increases in the proportion of vehicles traveling at least 5 mph and 10 mph above the speed limit were greatest on urban interstates and other freeways, during early morning (6:00-8:59 a.m.) and afternoon commuting hours (3:00-5:59 p.m.) on weekdays, and during afternoons (12:00-5:59 p.m.) on weekends. Logistic regression revealed that the risk of speeding by at least 5 mph increased in 2020 by 22% and by at least 10 mph increased 51% after accounting for road type, time of day, day of week, and traffic volume, relative to 2019. Future research should continue to identify where and when speeding problems are most severe, and countermeasures should be directed to the roads and time periods with the largest speeding problems.


Sleep and future cardiovascular risk: prospective analysis from the English Longitudinal Study of Ageing.
Hypertension and inflammation may contribute to the increased risk of cardiovascular disease in individuals with suboptimal sleep, but large prospective studies are lacking. This study tested whether sleep duration and disturbance were predictive of incident hypertension and inflammation four years later. Participants were men and women aged 50 years and older from the English Longitudinal Study of Ageing. Sleep was assessed by self-report, incident hypertension (N = 3068) was defined by clinical examination and C-reactive protein and fibrinogen (N = 3768) were measures of inflammation. Both men (odds ratio, OR:1.73, confidence interval, C.I. 1.08-2.76) and women (OR: 1.44, C.I. 1.00-2.07) reporting short sleep at baseline had increased odds of incident hypertension 4 years later, after adjustment for covariates. Age-stratified analyses revealed that short sleep was predictive of incident hypertension in men (OR: 2.27, C.I. 1.01-5.11) and women (OR: 2.10, C.I. 1.08-4.09) younger than 60 years but not in older people. Disturbed sleep also predicted incident hypertension in men (OR: 1.20, C.I. 1.02-1.41). In women, disturbed sleep was associated with elevated C-reactive protein (B = 0.030, C.I. 0.00-0.06) and fibrinogen (B = 0.030, C.I. 0.01-0.05) at follow-up controlling for baseline inflammation and other covariates. Sleep duration was unrelated to inflammatory markers in either sex. This study of older men and women adds to growing evidence that aberrant sleep patterns may increase the risk of cardiovascular outcomes through its adverse impact on blood pressure and inflammation.


Effects of smoking history on selective attention in schizophrenia.
Smoking prevalence is highly elevated in schizophrenia compared to the general population and to other psychiatric populations. Evidence suggests that smoking may lead to improvements of schizophrenia-associated attention deficits; however, large-scale studies on this important issue are scarce. We examined whether sustained, selective, and executive attention processes are differentially modulated by long-term nicotine consumption in 104 schizophrenia patients and 104 carefully matched healthy controls. A significant interaction of 'smoking status' × 'diagnostic group' was obtained for the domain of selective attention. Smoking was significantly associated with a detrimental conflict effect in controls, while the opposite effect was revealed for schizophrenia patients. Likewise, a positive correlation between a cumulative measure of nicotine consumption and conflict effect in controls and a negative correlation in patients were found. These results provide evidence for specific directional effects of smoking on conflict processing that critically dissociate with diagnosis. The data supports the self-medication hypothesis of smoking in schizophrenia and suggests selective attention as a specific cognitive domain targeted by nicotine consumption. A potential mechanistic model explaining these findings is discussed.


Acute reversal of flunitrazepam effects by Ro 15-1788 and Ro 15-3505: inverse agonism, tolerance, and rebound.
A phase 1 double blind crossover comparison of a new benzodiazepine antagonist (Ro 15-3505) with Ro 15-1788 and placebo, in the reversal of sedative and psychophysiological effects of single IV doses of flunitrazepam (2 mg), was carried out in 12 normal volunteers. The antagonists were equally effective, leading to full reversal of all effects with a potency ratio of approximately 2.5 mg Ro 15-1788 for 1 mg Ro 15-3505. Inverse agonism, in the form of unpleasant feelings and symptoms, was reported by all subjects following Ro 15-3505 but none after Ro 15-1788. Adaptational phenomena such as acute tolerance and rebound of sedative effects of flunitrazepam were also detected and their potential implications are discussed.


[Aspects of interest on vitamin D for the traumatologist and orthopaedic surgeon].
Vitamin D deficiency or insufficiency is a clinical problem particularly prevalent in elderly patients with low-energy fractures, particularly hip fractures, but has also been associated with stress fractures and high energy fractures. There is much evidence that supports the need to maintain adequate levels of vitamin D in the blood in order to; reduce the number of fragility fractures, furthering the consolidation of these, improve neuromuscular function of patients, prevent falls, prevent surgical infections, or improve the length of arthroplasties. However, it is rare for the orthopaedic surgeon to request the values of vitamin D in these patients and give the appropriate treatment It is recommended to maintain levels higher than 30-40ng/ml (75-100nmol/l) and increase vitamin D intake, in almost all cases, from 800 to 1,000IU/day to achieve these levels.


Distribution map of natural gamma-ray dose rates for studies of the additional exposure dose after the Fukushima Dai-ichi Nuclear Power Station accident.
The information on the absorbed dose rate which is derived from natural radionuclides is needed to evaluate additional exposure dose. However, there is inadequate positional resolution and precision for such data around Fukushima Dai-ichi Nuclear Power Station (FDNPS). In this study, we created a map of the absorbed dose rate that is derived from natural radionuclides based on several airborne radiation monitoring data. The reliability and accuracy of the created map was verified by comparison with the many in-situ measurements on the ground. To evaluate the effectiveness of this study, the effective half-lives of the ambient dose rate at residential areas of Fukushima Prefecture were assessed by discriminating these absorbed dose rate of the natural background from the results of a periodic dose rate survey by local government. The results of the distribution of natural background absorbed dose rates are expected to contribute to the evaluation of the additional exposure dose after the FDNPS accident.


Rare case of double aortic arch with hypoplastic right dorsal segment and associated tetralogy of Fallot: MR findings.
We report a rare case of double aortic arch with a hypoplastic right dorsal arch segment, which was also associated with tetralogy of Fallot. Accurate characterization of the hypoplastic right arch segment by MRI preoperatively determined the optimal surgical approach to releasing the symptomatic vascular ring. MRI was also useful in assessing and monitoring associated tracheomalacia.


When digestive physiology doesn't match "diet": Lumpenus sagitta (Stichaeidae) is an "omnivore" with a carnivorous gut.
What an animal ingests and what it digests can be different. Thus, we examined the nutritional physiology of Lumpenus sagitta, a member of the family Stichaeidae, to better understand whether it could digest algal components like its better studied algivorous relatives. Although L. sagitta ingests considerable algal content, we found little evidence of algal digestion. This fish species has a short gut that doesn't show positive allometry with body size, low amylolytic activity that actually decreases as the fish grow, no ontogenetic changes in digestive enzyme gene expression, elevated N-acetyl-glucosaminidase activity (indicative of chitin breakdown), and an enteric microbial community that is consistent with carnivory and differs from members of its family that consume and digest algae. Hence, we are left concluding that L. sagitta is not capable of digesting the algae it consumes, and instead, are likely targeting epibionts on the algae itself, and other invertebrates consumed with the algae. Our study expands the coverage of dietary and digestive information for the family Stichaeidae, which is becoming a model for fish digestive physiology and genomics, and shows the power of moving beyond gut content analyses to better understand what an animal can actually digest and use metabolically.


Is systemic heparin a risk factor for catheter-related sepsis in dialysis patients? An evaluation of various biofilm and traditional risk factors.
Biofilms are dense aggregates of surface adherent microorganisms embedded in a polysaccharide matrix. Intravenous iron and heparin are thought to promote the formation of biofilm. Both are commonly employed during hemodialysis treatments which might affect the incidence of catheter-related sepsis. 559 patients who underwent hemodialysis treatment with a catheter were reviewed. Episodes of sepsis were analyzed for the use of systemic heparin and intravenous iron as well as all other risk factors for sepsis. Sepsis developed in 141 of the 796 catheters. Analysis of variance revealed that the number of days that the catheter remained in place was the most significant variable (p < 0.0001) associated with catheter-related sepsis along with multiple other variables, but a Cox proportional hazards analysis revealed that only the two biofilm risk factors (intravenous iron [p < 0.001], and mid-treatment bolus of heparin [p = 0.046]) along with previously reported factor of a depressed serum albumin (p = 0.001) are of significance. In addition to duration of catheter use, we found three significant risk factors for sepsis and two of those three have been associated with the development of biofilm.


Clostridium difficile in broiler chickens sold at market places in Zimbabwe and their antimicrobial susceptibility.
Clostridium difficile has been shown to be a nosocomial pathogen associated with diarrhoea and pseudomembranous colitis in hospitalised patients and the infection is believed to be acquired nosocomially. Community-acquired C. difficile-associated diarrhoea has also been reported. Recent studies have shown the occurrence of C. difficile in food animals which may act as a source of infection to humans. The aim of this study was to determine the occurrence of C. difficile in broiler chickens sold at market places in an urban area in Zimbabwe. Faeces of broiler chickens were collected from the cages at the market places and soils were collected from areas around the market places. The chicken faeces and soil samples were cultured for C. difficile. The C. difficile isolates were tested for toxins A or B production as well as for their susceptibility to antimicrobial drugs. C. difficile was isolated from 29.0% of 100 chicken faeces samples and 22.0% of 100 soil samples. Some of the C. difficile isolates from chickens (89.7%) and soils (95.5%) were toxigenic. All the isolates were susceptible to metronidazole, vancomycin, doxycycline, chloramphenicol and tetracycline. Over 70% of the isolates were susceptible to erythromycin, co-trimoxazole and ampicillin. They were all resistant to cefotaxime, gentamicin, ciprofloxacin, norfloxacin and nalidixic acid. The results of the present study suggest that broiler chickens sold at market places in the urban area are an important source of C. difficile, which may infect humans through consumption of chicken meat.


Position-dependent obstructive sleep apnea and its influence on treatment success of mandibular advancement devices.
Depending on the severity of pre-treatment obstructive sleep apnea (OSA) and the criteria used to define treatment success, the efficacy of mandibular advancement devices (MADs) ranges from 30 to 69%. Identifying suitable candidates is the key to increasing the efficacy of a MAD. Positive predictors include a low body mass index, a low apnea-hypopnea index (AHI), and low age. Another consideration is whether or not a patient's OSA is position dependent. To evaluate the effect of such dependency on MAD treatment success, we studied the following: treatment success across the patient's total AHI and in the supine and non-supine sleeping positions; the influence of pre-treatment position dependency on MAD treatment success; and the effect of MAD treatment on post-treatment shifts in position dependency. This is a single-center retrospective study of patients with OSA. Patients were diagnosed through an overnight polysomnography and treated with a MAD between February 2015 and January 2018. They were defined as being positional if the AHI in supine sleeping position was at least twice as high as in the non-supine position. Complete treatment success was achieved in 32% of study population (n = 96) and partial success in 54%. Complete treatment success was significantly higher (p = 0.004) when a patient was sleeping in the non-supine position. Treatment success did not differ significantly between patients who were position dependent and those who were not. When treated with a MAD, patients did not spend significantly more time in supine position. Neither did we find any post-treatment shifts in position dependency. A MAD is an effective treatment modality that may significantly reduce the total AHI, supine, and non-supine AHI. Since position dependency has no impact on MAD treatment success, it does not determine whether or not a patient is a suitable candidate for MAD treatment.


New graduate midwives' transition to practice: A scoping review.
To map and synthesise the literature underpinning the transition to practice for new graduate midwives internationally, with a focus on continuity of care and traditional transition to practice models. Scoping review of the literature METHODS: Relevant databases were searched to identify primary research studies. Key words, Boolean terms, and an inclusion/exclusion criterion were used to extrapolate key pieces of research. All study types and methods published in English between 2008 - May 2021 that met the inclusion criteria were considered. 20 studies met inclusion criteria. These were conducted in Australia, the United Kingdom, and New Zealand. New graduate midwives' value structured rotations and feel very supported in continuity models, where strong mentorship and support are offered. Within this context confidence was promoted as a new practitioner. Upholding woman-centred care in busy hospital environments was a key challenge. Emerging literature indicates new graduate midwives' transition optimally within a continuity model, however more research is needed. Transitioning midwives into practice within continuity of care midwifery models may address workforce attrition and enhance early career midwife confidence.


Microvascular involvement in migraine: an optical coherence tomography angiography study.
The aim of this study was to evaluate the microvasculature of the macula and the optic nerve in patients affected by migraine with aura (MA) and without aura (MO) by optical coherence tomography angiography (OCTA), comparing the findings with healthy controls (HC). We collected data from ocular and orthotic examinations, including eye motility, intraocular pressure measurement, best-corrected visual acuity (BCVA) measurement, objective refraction measurement, fundus examination, macular and optic disk OCTA examination. All subjects were imaged with solix fullrange OCT. The following OCTA parameters were recorded: macular vessel density (VD), inside disc VD, peripapillary VD, disc whole image VD, fovea choriocapillaris VD, fovea VD, parafovea VD, peripapillary thickness, fovea thickness, parafovea thickness, macular full retinal thickness, and foveal avascular zone (FAZ) parameters. Clinical and demographical data about migraine patients were collected by a neurologist. We included 56 eyes from 28 patients with a diagnosis of MO, 32 eyes from 16 patients with a diagnosis of MA, and 32 eyes from 16 HC subjects. The FAZ area was 0.230 ± 0.099 mm2 in the MO group, 0.248 ± 0.091 mm2 in the MA group and 0.184 ± 0.061 mm2 in the control group. The FAZ area was significantly larger in the MA group than in the HC group (p = 0.007). The foveal choriocapillaris VD was significantly lower in MA patients (63.6 ± 2.49%) when compared with MO patients (65.27 ± 3.29%) (p = 0.02). An impairment of retinal microcirculation can be detected in patients with MA, as demonstrated by the enlargement of FAZ. Moreover, the study of choroid circulation may reveal microvascular damage in patients with migraine with aura. OCTA is a useful non-invasive screening tool for the detection of microcirculatory disturbance in patients with migraine.


Influence of isaxonine on reinnervation of the rat gastrocnemius muscle.
Isaxonine is reported to have a favourable effect on nerve regeneration. The histological and histochemical changes were compared in the gastrocnemius muscles of 20 rats, in which the left sciatic nerve was frozen-crushed for 10 s at the level of the buttock. The animals received a daily dose of intraperitoneal isaxonine and ten others the solvent only. After 8 weeks small type grouping was seen in rats receiving solvent only and large type grouping in rats treated with isaxonine. After 10 weeks a checkerboard pattern of the fibre types was observed in the muscles of animals receiving solvent only but fibre type grouping was present in those treated with isaxonine. This experiment indicates that isaxonine prevents synaptic remodelling by suppression of the redundant nerve endings from additional axons, which have regenerated more slowly, in making contact with motor endplates.


Laparoscopic vs open hemicolectomy for colon cancer.
The role of laparoscopic resection in the management of colon cancer is still a subject of debate. In this clinical study, we compared the perioperative results and long-term outcome for two unselected groups of patients undergoing either laparoscopic or open hemicolectomy for colon cancer. This prospective nonrandomized study was based on a series of 248 consecutive patients operated on by the same surgical team using the same type of surgical technique for right (RHC) and left (LHC) hemicolectomy, excluding segmental resections; the only difference was the type of access, which was either laparoscopic or open. The choice of type of access was left up to the patient after he or she had read the informed consent form. Operative time, length of stay, complications, and long-term outcome for the two groups were compared. Follow-up time ranged between 12 and 92 months (mean, 42). Between March 1992 and January 2000, 140 patients underwent a laparoscopic hemicolectomy (55 RHC and 86 LHC); at the same time, 107 patients (44 RHC and 63 LHC) were treated via an open approach. There were no conversions to open surgery in the laparoscopic RHC group, but six patients (7%) in the laparoscopic LHC group were converted. The mean operative time for laparoscopic surgery was significantly longer than the time for open surgery (190 vs 140 min for RHC, 240 vs 190 min for LHC,); however, with increasing experience, this time decreased significantly. The mean hospital stay for the patients who underwent laparoscopic procedures was significantly shorter in both the RHC and the LHC groups (9.2 vs 13.2 days for RHC, 10.0 vs 13.2 days for LHC). No statistically significant difference between the two laparoscopic and open groups was observed for the major complication rate (1.9% vs 2.3% for RHC, 7.5% vs 6.3% for LHC). The patient in the laparoscopic RHC group were lost to follow-up. The local recurrence rate was lower after laparoscopic surgery in both arms (5.4% vs 9% for RHC, 1.5% vs 7.5% for LHC), but the differences were not statistically significant. Two port site recurrences were observed in the laparoscopic groups, one after RHC (2.7%) and one after LHC (1.5%). Metachronous metastases rates were similar for the two groups (16.2% vs 15.1% for RHC, 4.4% vs 5.7% for LHC). Cumulative survival probability at 48 months after laparoscopic RHC was 0.865, as compared to 0.818 after open surgery, and 0.971 after laparoscopic LHC, as compared to 0.887 after open surgery. These results suggest that laparoscopic hemicolectomy for colonic cancer can be performed safely, with morbidity, mortality, and long-term results comparable to those of open surgery.


Partial nephrectomy for renal cell carcinoma with a normal opposite kidney.
The role of nephron-sparing surgery in patients with unilateral renal carcinoma and a normal opposite kidney is controversial. The number and selection criteria of patients undergoing a partial nephrectomy versus radical nephrectomy from 1979 to 1991 were compared. Of 230 patients having curative surgery for unilateral renal cell carcinoma, 41 had a partial nephrectomy. The percentage of partial compared with total nephrectomies performed increased from 8% in 1979-84, to 20% in 1984-88, and 30% in 1989-91. The increased number of partial versus radical nephrectomies performed reflected an increased detection of small (3.5 cm) incidental renal tumors by radiologic imaging. The local recurrence rate was 2.4% (one patient), and the survival rate was 95% (average, 3 years). Complete local excision of the small serendipitous renal tumor is feasible and reasonable in the patient with an otherwise normal opposite kidney.


Physical activity promotion in primary health care: results from a German physician survey.
Primary care physicians are positioned to play an important role in changing physical activity and other health behaviour of their patients. However, little is known about the practice of physical activity promotion in German primary care settings and the factors associated with physical activity promotion. 260 randomly selected physicians from the State Medical Association of Baden-Wuerttemberg, Germany, took part in this survey (response rate: 13.3%) and provided data on physical activity promotion (physical activity assessment and advice), attitudes towards health promotion and cooperation activities. Factors associated with physical activity promotion were identified using logistic regression. The physicians who replied had positive attitudes towards health promotion. However, 26.9% reported they had inadequate knowledge to provide counselling and 36.7% felt they were unsuccessful in motivating their patients to increase physical activity. Physical activity assessment and advice occurred in 54.9% of the physicians. Compared to their counterparts, physicians in large cities (odds ratio (OR) 3.93; and 95% confidence interval (95%CI): 1.55-9.99), those convinced to offer their patients a great deal in the way of lifestyle counselling (OR 1.92; 95%CI: 1.09-3.40) and those cooperating with sports clubs (OR 1.75; 95%CI: 1.03-2.96) were more likely to provide physical activity promotion. There is a need for interventions to increase the frequency of physical activity promotion by primary care physicians. In particular physicians in rural regions should be assisted and cooperation activities with sports clubs or other health care providers should be encouraged.


Environmental Factors in Nursing Workplaces that Promote Resilience during Pandemics: Scoping Review.
This scoping review explored the main environmental factors in the workplace that contribute to nursing resilience in respiratory infectious pandemic events. There is strong evidence in the literature about the influence of individual factors on nurses' resilience and a growing interest on the impact of the workplace environment on these factors. Therefore, a review that synthesizes environmental factors that support nurses' resilience in pandemic events is timely. A scoping review of publications written in English, Spanish, and Portuguese of registered publications until December 2020 in MEDLINE, Embase, PubMed, Scopus, SciELO, CINAHL, WoS, BVS, and APA identified 10,767 potential papers. Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR) guidelines were used during the literature review process. The Health Services Workplace Environmental Resilience Model (HSWERM) was used to guide exploration and synthesis. Thirty-two (32) publications met inclusion criteria. Most of the HSWERM workplace factors were mentioned in the literature. The main workplace environmental factors that were identified included communication, inter-professional collaboration, access to equipment, targeted training, and supporting well-being. Recognition of these key environmental factors in the workplace will help to implement more effective actions to promote resiliency prior to and during emergency situations. It will also enable managers to include, in any preparation planning, contingencies to protect these factors with the view of sustainable resilience of nursing staff throughout the emergency event.


Photochromism and electrical transport characteristics of a dyad and a polymer with diarylethene and quinoline units.
The synthesis of a series of photochromic compounds incorporating a phenylquinoline unit and the photophysical and electric transport properties are described. The dyad and polymer with a quinoline unit show a high quantum yield due to the enforced antiparallel conformation of the dithienylethene moieties. High carrier conductivity was observed in the closed form of the diarylethene with a phenylquinoline unit.


Usefulness of 18F-Choline Positron Emission Tomography - Computed Tomography in the therapeutic management of patients with biochemical recurrence of prostate adenocarcinoma treated with brachytherapy.
The objective of the study was to evaluate the usefulness of 18F-choline PET/CT in biochemically recurrent prostate cancer patients treated with brachytherapy, as well as to assess the changes in therapeutic management derived from its outcome. Retrospective study of 20 patients between 51 and 78 years old, with a history of prostate adenocarcinoma that had been treated with brachytherapy and presented biochemical recurrence (PSA 3.1-12 ng/ml) and staging tests (CT and bone scan) without alterations, were included. The findings visualized in the PET/CT scan with 18F-choline were correlated with the histopathology and/or the evolution of the PSA after therapy. 18F-choline PET/CT scan only detected local recurrence in 15 patients. Local and regional recurrences were seen in 4 patients, and 1 patient presented local and bone recurrence. Local recurrence detected in PET was confirmed by anatomopathological studies in 85% of the cases. In one patient, these findings (PET scan) turned out to be prostatitis, and it could not be confirmed in another patient. Of the cases with local and regional recurrence, local recurrence was histologically confirmed in 3 out of 4 patients. 18F-choline PET/CT changed the therapeutic management in 25% of the patients, discarding the initially planned salvage surgery in 3 cases, 1 radiotherapy and 1 brachytherapy. 18F-choline PET/CT could be a useful technique in the group of patients with biochemical recurrence after brachytherapy, providing locoregional and distant involvement findings which had not been detected with conventional imaging tests, thus determining a more adequate therapeutic management.


Identification and functional study of detoxification-related genes in response to tolfenpyrad stress in Glyphodes pyloalis Walker (Lepidoptera: Pyralidae).
Glyphodes pyloalis Walker (G. pyloalis) is a common destructive mulberry pest. Due to the long-term and frequent use of insecticides, it has developed tolerance to commonly used insecticides. Tolfenpyrad (TFP) is a novel pyrazole heterocyclic insecticide. In order to understand the TFP detoxification mechanism of G. pyloalis larvae, we first estimated the LC30 dose of TFP for 3rd instar G. pyloalis larvae. Next, we identified genes that were differentially expressed in 3rd instar G. pyloalis larvae treated with TFP compared to the control group by transcriptome sequencing. In total, 86,949,569 and 67,442,028 clean reads were obtained from TFP-treated and control G. pyloalis larvae, respectively. A total of 5588 differentially expressed genes (DEGs) were identified in TFP-treated and control G. pyloalis larvae, of which 3084 genes were upregulated and 2504 genes were downregulated. We analyzed the expression of 43 candidate detoxification enzyme genes associated with insecticide tolerance using qPCR. According to the spatiotemporal expression pattern of DEGs, we found that CYP6ABE1, CYP333A36 and GST-epsilon8 were highly expressed in the midgut, while CarEs14 was strongly expressed in haemolymph. Furthermore, we successfully knocked down these genes by RNA interference. After silencing CYP6ABE1 and CYP333A36, bioassay showed that the mortality rate of TFP-treated G. pyloalis larvae was significantly higher compared to the control group. This study provides a theoretical foundation for understanding the sensitivity of G. pyloalis to TFP and establish the basis for the effective and green management of this pest.


Evaluating causal associations of chronotype with pregnancy and perinatal outcomes and its interactions with insomnia and sleep duration: a Mendelian randomization study.
Observational studies suggest that chronotype is associated with pregnancy and perinatal outcomes. Whether these associations are causal is unclear. To explore associations of a lifetime genetic predisposition to an evening preference chronotype with pregnancy and perinatal outcomes, and explore differences in associations of insomnia and sleep duration with those outcomes between chronotype. We conducted two-sample Mendelian randomization (MR) using 105 genetic variants reported in a genome-wide association study (N=248 100) to instrument for lifelong predisposition to evening-versus morning-preference chronotypes. We generated variant-outcome associations in European ancestry women from UK Biobank (UKB, N=176 897), Avon Longitudinal Study of Parents and Children (ALSPAC, N=6826), Born in Bradford (BiB, N=2940) and Norwegian Mother, Father and Child Cohort Study (MoBa, with linked data from the Medical Birth Registry of Norway (MBRN), N=57 430), and extracted equivalent associations from FinnGen (N=190 879). We used inverse variance weighted (IVW) as main analysis, with weighted median and MR-Egger as sensitivity analyses. We also conducted IVW analyses of insomnia and sleep duration on the outcomes stratified by genetically predicted chronotype. Self-reported and genetically predicted chronotype, insomnia and sleep duration. Stillbirth, miscarriage, preterm birth, gestational diabetes, hypertensive disorders of pregnancy, perinatal depression, low birthweight and macrosomia. In IVW and sensitivity analyses we did not find robust evidence of effects of chronotype on the outcomes. Insomnia was associated with a higher risk of preterm birth among evening preference women (odds ratio 1.61, 95% confidence interval: 1.17, 2.21), but not among morning preference women (odds ratio 0.87, 95% confidence interval: 0.64, 1.18), with an interaction P-value=0.01. There was no evidence of interactions between insomnia and chronotype on other outcomes, or between sleep duration and chronotype on any outcomes. This study raises the possibility of a higher risk of preterm birth among women with insomnia who also have an evening preference chronotype. Our findings warrant replications due to imprecision of the estimates. Question: Does an evening preference chronotype adversely affect pregnancy and perinatal outcomes? Is there an interaction between chronotype and either insomnia or sleep duration in relation to those outcomes?Findings: There was no evidence that evening preference was associated with pregnancy or perinatal outcomes. Women with a genetically predicted insomnia had a higher risk of preterm birth, if they also had a genetically predicted preference for evening chronotype.Meaning: The suggestive interaction between insomnia and evening preference on preterm birth, if replicated, supports targeting insomnia prevention in women of reproductive age with an evening chronotype.


Effects of interleukin-23 on the activation of mucosal-associated invariant T cells from oral lichen planus.
Oral lichen planus (OLP) is a T cell-mediated inflammatory condition in the oral cavity. Mucosal-associated invariant T (MAIT) cells are gaining more relevance in immune diseases because they can be activated by cytokines without T cell receptor stimulation. Herein, we tested the effect of interleukin-23 (IL-23) on the activation status of OLP MAIT cells. Peripheral blood mononuclear cells (PBMCs) isolated from OLP patients were stimulated by IL-23 in the absence or presence of phorbol myristate acetate (PMA) and ionomycin. The activation status of MAIT cells was analyzed by flow cytometry after staining for CD3, CD4, CD8, CD161, TCR Vα7.2, and CD69. The fraction of MAIT cells in OLP peripheral blood was approximately 0.38% to 3.97%, and CD8+ subpopulations overwhelmed CD4+ cells. The mean percentages of OLP MAIT cells in PBMCs and CD8+MAIT cells in MAIT cells were approximately 40%. PMA and ionomycin significantly increased CD69 expression on OLP T cells, MAIT cells, and CD8+MAIT cells. Cells with enhanced activation had different responsiveness to exogenous IL-23, showing increased CD69 expression on OLP T cells, decreased CD69 on OLP CD8+MAIT cells, and no significant change on OLP MAIT cells. IL-23 showed different effects on the activation status of OLP MAIT cells and CD8+MAIT cells.


Purification and characterization of the fructose-inducible HPr-like protein, FPr, and the fructose-specific enzyme III of the phosphoenolpyruvate: sugar phosphotransferase system of Salmonella typhimurium.
The proteins comprising the fructose-specific phosphoenolpyruvate:sugar phosphotransferase system were investigated using a strain of Salmonella typhimurium which lacks the general phosphotransferase system proteins, HPr and Enzyme I, synthesizes the fructose phosphotransferase system proteins, FPr, Enzyme IIfru, Enzyme IIIfru, and fructose-1-phosphate kinase, constitutively, and expresses the Enzyme I-like protein Enzyme I. Enzyme I activity was found in the cytoplasmic fraction, Enzyme IIfru in the membrane fraction, and FPr and Enzyme IIIfru activities were distributed between the two fractions. Extraction of membranes with butanol and urea led to quantitative release of the membrane-associated Enzyme IIIfru and FPr activities, while Enzyme IIfru remained with the membranes. FPr was purified to homogeneity using ion exchange chromatography, gel filtration, and reversed phase high pressure liquid chromatography (HPLC), and its amino acid composition and N-terminal sequence were determined. A complex of FPr and Enzyme IIIfru (Mr 50,000) was also purified to near homogeneity using ion exchange chromatography, gel filtration, and chromatography on hydroxylapatite. When the purified complex was analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, it was visualized as two protein bands with mobilities corresponding to molecular weights of about 40,000 (Enzyme IIIfru) and 9,000 (FPr). Neither the FPr and Enzyme IIIfru activities nor the proteins represented by these two bands separated during the above chromatography steps or using any of several other techniques, including reversed phase HPLC, indicating a very tight association. Active Enzyme IIIfru free of FPr was never isolated or observed. The proteins could be separated in denatured form by gel filtration in the presence of guanidine HCl or urea. Free FPr and the FPr-Enzyme IIIfru complex were characterized, and the properties of free and complexed FPr were compared to those of HPr.


Association between maternal single-nucleotide polymorphisms in HLA-G gene and risk of preeclampsia.
To determine the relationship between the maternal single-nucleotide polymorphisms (SNPs) in human leukocyte antigen G (HLA-G) gene and preeclampsia (PE), so as to provide guidance for the early risk prediction of PE. From October 2017 to October 2019, a total of 99 pregnant women were enrolled in this cross-sectional study. The PE group included 51 pregnant women with severe PE, and the control group included 48 pregnant women with normal delivery during the same period. DNA was extracted and the SNPs in HLA-G gene of the two groups were sequenced. Maternal SNPs in HLA-G gene affecting the occurrence of the PE were determined. In this study, patients with PE had increased gravidity (p = .002), increased BMI before delivery (p = .004), reduced neonatal weight (p < .001), reduced gestational weeks (p < .001), reduced placental weight (p < .001), and increased proportion of cesarean section (p < .001). There were significant differences in SNPs at locus 29794467, 29796376, and 29799440 between the two groups (p < .05). In locus 29799440, patients with genotype CC had a lower risk of PE than patients with genotype TT (p = .047), with an odds ratio (OR) of 0.347(95%CI: 0.031, 3.881). And there was no significant difference in the risk of PE between patients with genotype CT, and those with genotype TT (p = .090) (OR = 2.344 95%CI: 0.187, 29.344). There is an association between a SNP in locus 29799440 of the HLA-G gene and susceptibility of PE in Han Chinese pregnant women, and the risk of PE increases with genotype CT/TT in pregnant women.


The historical foundations of the research-practice distinction in bioethics.
The distinction between clinical research and clinical practice directs how we partition medicine and biomedical science. Reasons for a sharp distinction date historically to the work of the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research, especially to its analysis of the "boundaries" between research and practice in the Belmont Report (1978). Belmont presents a segregation model of the research-practice distinction, according to which research and practice form conceptually exclusive sets of activities and interventions. This model is still the standard in federal regulations today. However, the Commission's deliberations and conclusions about the boundaries are more complicated, nuanced, and instructive than has generally been appreciated. The National Commission did not conclude that practice needs no oversight comparable to the regulation of research. It debated the matter and inclined to the view that the oversight of practice needed to be upgraded, though the Commission stopped short of proposing new regulations for its oversight, largely for prudential political reasons.


Complete rectal prolapse: the anatomical and functional results of treatment by an extended abdominal rectopexy.
Between 1970 and 1985 (inclusive), 66 patients presented with complete rectal prolapse; 59 (89 per cent) were treated by extended abdominal rectopexy. Forty-four patients (75 per cent) have been followed for more than 2 years: all cases were cured of their complete prolapse, no patients died, and major complications were few. Constipation (47 per cent) and incontinence (19 per cent) caused serious problems for many patients postoperatively.


Adjuvant chemotherapy for uroepithelial transitional cell carcinoma.
The effectiveness of adjuvant chemotherapy in transitional cell carcinoma of the bladder (T1/G3 and greater than or equal to T2) and the upper urinary tract were evaluated. Among a group of 136 patients (male 107, female 29) with such tumors, complete tumor resection was possible in 108, in whom duration of survival and disease-free interval with or without chemotherapy were compared. The combination of antineoplastic agents used was changed from 5-fluorouracil (5-FU) + vincristine (VCR) + bleomycin (BLM) or peplomycin (PEP) + mitomycin C (MMC) or 5-FU + VCR + PEP + cyclophosphamide (CPM) + adriamycin (ADM) to CPM + ADM + cis-platinum (DDP) or methotrexate (MTX) + vinblastine (VBL) + ADM + DDP. Of the 59 patients in the chemotherapy group, 23 (39%) had side effects due to the treatment; however, fever and gastrointestinal symptoms were the chief adverse effects and were well tolerated. The 5-year survival rate and mean disease-free interval in the chemotherapy group were 76.3% and 24.6+ months, respectively, in bladder cancer patients, and 78.2% and 25.8+ months in those with upper urinary tract tumors. However, in the non-chemotherapy group (n = 49) the corresponding values were 62.7% and 21.1+ months in patients with bladder cancer and 67.3% and 42.0+ months in those with upper urinary tract tumor. There was a statistically significant difference (P less than 0.05) in the disease-free intervals of the two treatment groups for bladder cancer patients. Recurrence, regardless of time, was observed in 25% of chemotherapy cases and in 65% of non-chemotherapy cases, and this difference was also statistically significant (P less than 0.001). These results suggest that adjuvant chemotherapy for uroepithelial transitional cell carcinoma may be effective in extending survival and significant by protracting the disease-free period, especially in cases of advanced bladder cancer.


The role of Stearoyl-CoA desaturase in hepatic de novo lipogenesis.
Obesity and the metabolic syndrome are global public health problems. Obesity is currently a worldwide epidemic and public health burden that increases the risk for developing insulin resistance and several chronic diseases such as diabetes, cardiovascular disease and non-alcoholic fatty liver disease. The multifactorial causes of obesity include several genetic, dietary and lifestyle variables that together result in an imbalance between energy intake and energy expenditure. Dietary approaches to limit fat intake are commonly prescribed to achieve the hypocaloric conditions necessary for weight loss. But dietary fat restriction is often accompanied by increased carbohydrate intake, which can dramatically increase endogenous fatty acid synthesis depending upon carbohydrate composition. Since both dietary and endogenously synthesized fatty acids contribute to the whole-body fatty acid pool, obesity can therefore result from excessive fat or carbohydrate consumption.


Effect of lornoxicam on postoperative analgesia after myomectomy.
In this prospective, randomized study, we evaluate the postoperative analgesic effect of lornoxicam after myomectomy operations. Forty ASA I-II patients scheduled for myomectomy operation were enrolled to this study. Patients were randomly divided into two groups and epidural block was performed with 0,75 % ropivacaine. After the operation, morphine Patient Controlled Epidural Analgesia (PCEA) combined with placebo (saline 2 ml iv) and morphine PCEA combined with lornoxicam 8 mg iv were administered to patients in Group I and Group II, respectively. Pain was assessed at the 0,1st, 2nd, 4th, 6th, 8th, 12th and 24th hours postoperatively. Chi-square and student's t tests were used for statistical analysis. VAS( Visual Analog Scale) scores were higher in Group I than Group II at 2nd, 4th, 6th and 24th hours. Total morphine consumption was 10.45+/- 4.03 in Group I and 4.25 +/- 1.74 in Group II. Single dose iv lornoxicam is a safe and an effective treatment option of post-myomectomy pain as it produces effective analgesia, reduces morphine consumption and does not increase the side effects.


Genetic polymorphism under cyclical selection in long-lived species: The complex effect of age structure and maternal selection.
Maternal selection and overlapping generations can facilitate the stable coexistence of alleles under temporally fluctuating environment. Using mathematical models, we considered the complex effect of both factors on the maintenance of genetic polymorphism in cyclically changing environments. We concentrated on asymmetric cyclic selection, which allows describing fluctuations of environments by analogy of food resources cycles with rare peaks and prolonged decline of prey abundance. The complex effect of maternal selection and overlapping generations turned out to work as follows: although overlapping generations always tend to dilate the polymorphism region, odd and even external cycles produce different types of polymorphism regions. Maternal selection under external odd cycles extends the coexistence region comparing with classic selection. Even cycles produce a part of parameter region, where the picture changes radically, and classic selection becomes more effective in maintaining polymorphism. Our models have clear biological interpretation, because we tried to model a situation demonstrated by natural populations of arctic foxes. The litter size being a major life history trait is a sex-limited female trait. It is influenced by maternal selection with cyclical fluctuations because of oscillations in food abundance. Arctic fox is a long-lived species having an age structure. The obtained results showed that compared with the simple Mendelian inheritance in the classic model, this trait inheritance allows polymorphism to be maintained in a wider range of the parameter that characterizes the advantage of survival in a small litter. Besides, adding overlapping generations to the model further broadens the parameter space for the protected polymorphism. Thus, this study shows that maternal selection and overlapping generations increases the chances of maintaining polymorphism in populations of arctic foxes.


Risk reduction in the intensive care unit.
Many potentially preventable complications occur in patients who receive intensive care. We have reviewed the epidemiology of three important complications (venous thromboembolism, stress-related upper gastrointestinal bleeding, and vascular catheter-related infection) and evaluated common preventive treatments to provide evidence-based recommendations for prevention. We used English language articles located by MEDLINE or cross-citation, giving preference to articles published in the last 10 years, meta-analyses, and clinical trials that were randomized, double-blinded, and used intention-to-treat analysis. We recommend prophylaxis against venous thromboembolism in most patients, whereas those without respiratory failure or coagulopathy may not require prophylaxis against stress-related upper gastrointestinal hemorrhage. Chlorhexidine gluconate is the preferred antiseptic for disinfecting the skin prior to and during intravascular catheterization. Central venous catheters impregnated with antibacterial or antiseptic agents should be considered in patients at high risk for vascular catheter-related infection. Finally, central venous, pulmonary arterial, and systemic arterial catheters should be changed only when clinically indicated.


Fetal gut-like differentiation in gallbladder cancer.
Adenocarcinomas showing fetal gut-like (enteroblastic) differentiation can arise in a variety of organs and are frequently accompanied by an elevated serum α-fetoprotein (AFP) level. However, no study has investigated fetal gut-like differentiation in gallbladder cancer in detail. Herein, we performed morphological and immunohistochemical analyses of fetal gut-like differentiation in 49 consecutive gallbladder cancer cases. The expression of Sal-like protein 4 (SALL4), an embryonic stem cell marker reported to represent fetal gut-like differentiation, as well as other oncofetal proteins, including glypican-3 (GPC3) and AFP, was assessed. We found 1 case of fetal gut-like adenocarcinoma that coexisted with conventional-type adenocarcinoma. The fetal gut-like adenocarcinoma component revealed diffuse immunoreactivity for SALL4 and partial positivity for AFP, whereas the conventional-type adenocarcinoma component was negative. We also found 2 poorly differentiated adenocarcinomas with hepatoid morphology and 1 clear cell carcinoma, none of which showed SALL4 positivity. In other conventional-type adenocarcinomas, focal immunoreactivity for SALL4 and GPC3 was occasionally observed. The overall positivity rates for SALL4 and GPC3 were 12.2% (6/49) and 16.3% (8/49), respectively. SALL4 and GPC3 expression was not associated with clinicopathological factors, including T category, lymphovascular invasion, and lymph node metastases. In conclusion, fetal gut-like adenocarcinoma was found in 2% of our gallbladder cancer series. We conclude that fetal gut-like adenocarcinoma is a distinct histological subtype of gallbladder cancer, characterized by SALL4 expression.


No single way to understand singlet oxygen signalling in plants.
When plant cells are under environmental stress, several chemically distinct reactive oxygen species (ROS) are generated simultaneously in various intracellular compartments and these can cause oxidative damage or act as signals. The conditional flu mutant of Arabidopsis, which generates singlet oxygen in plastids during a dark-to-light transition, has allowed the biological activity of singlet oxygen to be determined, and the criteria to distinguish between cytotoxicity and signalling of this particular ROS to be defined. The genetic basis of singlet-oxygen-mediated signalling has been revealed by the mutation of two nuclear genes encoding the plastid proteins EXECUTER (EX)1 and EX2, which are sufficient to abrogate singlet-oxygen-dependent stress responses. Conversely, responses due to higher cytotoxic levels of singlet oxygen are not suppressed in the ex1/ex2 background. Whether singlet oxygen levels lower than those that trigger genetically controlled cell death activate acclimation is now under investigation.


Paper jumpsuit: an adjunct for psoriasis therapy.
An inexpensive, disposable, durable paper jumpsuit is described as an adjunct to inpatient or outpatient psoriasis therapy.


Cardioembolic Stroke in a Patient with Coronavirus Disease of 2019 (COVID-19) Myocarditis: A Case Report.
There is a growing body of literature detailing coronavirus 2019 (COVID-19) cardiovascular complications and hypercoagulability, although little has been published on venous or arterial thrombosis risk. In this report, we present a single case of cardioembolic stroke in the setting of COVID-19 related myocarditis, diagnosed via cardiac magnetic resonance imaging and echocardiography. COVID-19 infection was confirmed via a ribonucleic acid polymerase chain reaction assay. Further research is needed to evaluate the hypercoagulable state of patients with COVID-19 to determine whether prophylactic anticoagulation may be warranted to prevent intracardiac thrombi and cardioembolic disease in patients with COVID-19 related myocarditis.


Childhood asthma treatment based on indirect hyperresponsiveness test: Randomized controlled trial.
The purpose of this study was to assess the usefulness of indirect airway hyperresponsiveness (AHR) test using hypertonic saline in determining the dose of inhaled corticosteroids (ICS) to maintain asthma control in children. A group of 104 patients (7-15 years) with mild-moderate atopic asthma were monitored for their asthma control and treatment for 1 year. Patients were randomly assigned to a symptom-only monitored group and a group with therapy changes based on the symptoms and severity of AHR. Spirometry, exhaled nitric oxide, and blood eosinophils (BEos) were assessed on enrollment and every 3 months thereafter. During the study period, the number of mild exacerbations was lower in the AHR group (44 vs. 85; the absolute rate per patient 0.83 vs. 1.67; relative rate 0.49, 95% confidence interval: 0.346-0.717 (p < 0.001)]. Mean changes from baseline in clinical (except asthma control test), inflammatory, and lung function parameters were similar between groups. Baseline BEos correlated with AHR and was a risk factor for recurrent exacerbation in all patients. There was no significant difference in the final ICS dose between AHR and symptoms group: 287 (SD 255) vs. 243 (158) p = 0.092. Adding an indirect AHR test to clinical monitoring of childhood asthma reduced the number of mild exacerbations, with similar current clinical control and final ICS dose as in the symptom-monitored group. The hypertonic saline test appears to be a simple, cheap, and safe tool for monitoring the treatment of mild-to-moderate asthma in children.


[Medical oncological treatment of colorectal cancer in the elderly].
Medical treatment with chemotherapy is discussed in several situations in the treatment of colon cancer. In the adjuvant setting, chemotherapy with 5FU±oxaliplatin for six months should be considered in the case of lymph node involvement. In the metastatic setting, several protocols exist. The choice of treatments should be based on the expected objectives in terms of response and survival gain, but also of tolerance and quality of life for the patient. A thorough oncogeriatric assessment helps to better define the therapeutic programme. The continuation of geriatric follow-up throughout the treatment process shows a benefit for the patient in terms of quality of life and tolerance of treatments.


Perinatal circulatory physiology.
Fetal circulation is designed to utilize placenta for gas exchange whereas postnatal circulation uses lungs for gas exchange. Fetal circulatory pathways, namely, umbilical vessels, ductus venosus, foramen ovale and ductus arteriosus facilitate placental gas exchange and promote distribution of oxygenated blood to the vital organs of the fetus. Mechanical factors, prostaglandins and low PO2 in the lung keep the fetal circulatory pathways open. Postnatal circulatory changes include elimination of the placenta, development of pulmonary circulation, and closure of fetal circulatory pathways. Postnatal circulatory changes markedly influence the clinical presentation and clinical course of the neonate with congenital heart defects.


Disaggregating ethnoracial disparities in physician trust.
Past research yields mixed evidence regarding whether ethnoracial minorities trust physicians less than Whites. Using the 2002 and 2006 General Social Surveys, variegated ethnoracial differences in trust in physicians are identified by disaggregating a multidimensional physician trust scale. Compared to Whites, Blacks are less likely to trust the technical judgment and interpersonal competence of doctors. Latinos are less likely than Whites to trust the fiduciary ethic, technical judgment, and interpersonal competence of doctors. Black-Latino differences in physician trust are a function of ethnoracial differences in parental nativity. The ways ethnoracial hierarchies are inscribed into power-imbalanced clinical exchanges are discussed.


Random non-fasting C-peptide testing can identify patients with insulin-treated type 2 diabetes at high risk of hypoglycaemia.
The aim of this study was to determine whether random non-fasting C-peptide (rCP) measurement can be used to assess hypoglycaemia risk in insulin-treated type 2 diabetes. We compared continuous glucose monitoring-assessed SD of blood glucose and hypoglycaemia duration in 17 patients with insulin-treated type 2 diabetes and severe insulin deficiency (rCP < 200 pmol/l) and 17 matched insulin-treated control patients with type 2 diabetes but who had preserved endogenous insulin (rCP > 600 pmol/l). We then assessed the relationship between rCP and questionnaire-based measures of hypoglycaemia in 256 patients with insulin-treated type 2 diabetes and a comparison group of 209 individuals with type 1 diabetes. Continuous glucose monitoring (CGM)-assessed glucose variability and hypoglycaemia was greater in individuals with rCP < 200 pmol/l despite similar mean glucose. In those with low vs high C-peptide, SD of glucose was 4.2 (95% CI 3.7, 4.6) vs 3.0 (2.6, 3.4) mmol/l (p < 0.001). In the low-C-peptide vs high-C-peptide group, the proportion of individuals experiencing sustained hypoglycaemia ≤ 4 mmol/l was 94% vs 41% (p < 0.001), the mean rate of hypoglycaemia was 5.5 (4.4, 6.7) vs 2.1 (1.4, 2.9) episodes per person per week (p = 0.004) and the mean duration was 630 (619, 643) vs 223 (216, 230) min per person per week (p = 0.01). Hypoglycaemia ≤ 3 mmol/l was infrequent in individuals with preserved C-peptide (1.8 [1.2, 2.6] episodes per person per week vs 0.4 [0.1, 0.8] episodes per person per week for low vs high C-peptide, p = 0.04) and only occurred at night. In a population-based cohort with insulin-treated type 2 diabetes, self-reported hypoglycaemia was twice as frequent in those with rCP < 200 pmol/l (OR 2.0, p < 0.001) and the rate of episodes resulting in loss of consciousness or seizure was five times higher (OR 5.0, p = 0.001). The relationship between self-reported hypoglycaemia and C-peptide was similar in individuals with type 1 and type 2 diabetes. Low rCP is associated with increased glucose variability and hypoglycaemia in patients with insulin-treated type 2 diabetes and represents a practical, stable and inexpensive biomarker for assessment of hypoglycaemia risk.


Cutaneous carcinoma following psoralen and long-wave ultraviolet radiation (PUVA) therapy for psoriasis.
Multiple basal cell epitheliomas developed in two psoriatic patients during treatment with orally administered 8-methoxypsoralen and long-wave ultraviolet radiation (PUVA). Twenty-two basal cell epitheliomas (BCEs) were seen in the two patients, 80% occurring in non-sun-exposed areas. Since neither patient had any historical or clinical evidence of arsenic intake or the basal cell nevus syndrome, PUVA therapy may have been of pathogenetic responsibility for the development of these lesions.


Therapeutic approaches to the problem of biliary sludge and gallstone formation during total parenteral nutrition.
Prolonged total parenteral nutrition is associated with the development of biliary sludge, which consists of super-saturated bile containing cholesterol crystals, bilirubin granules and a very high concentration of mucin glycoprotein. Reduced gallbladder contractility in TPN patients appears to be essential for the pathogenesis of sludge, which represents an important stage in the formation of gallstones, a common and well recognised complication of TPN. Possible approaches to the prevention of these biliary complications of TPN include: 1) inhibition of prostaglandin mediated mucin hypersecretion with aspirin, NSAIDs or possibly by n-3 essential fatty acids; 2) stimulation of gallbladder contractility by early oral feeding or the use of CCK; and 3) reduction of cholesterol saturation and mucin secretion by ursodeoxycholic acid.


Behavioral correlates of renal damage and cardiac changes.
The locomotor activity (determined by open-field test) and analgesic response (measured by tail-flick latency) of rats were evaluated during exposure to novel stimuli and again after exposure to shock. The effects of shock stress on hearts and kidneys were evaluated. This study has found that the more active an animal is when exposed to a novel stimuli the more likely it is to develop renal damage or cardiac changes after shock. Shock stress was found to produce changes in locomotor activity and analgesic state, but shock did not correlate as well with cardiac changes as did the animal's response to novel stimuli. A novel system of evaluating renal damage, which correlated to behavioral changes and organ damage, is described.


Mechanical loading differentially regulates membrane-bound and soluble RANKL availability in MC3T3-E1 cells.
To understand the biochemical response of RANKL in response to mechanical loading, MC3T3-E1 cells were biequiaxially stretched. A murine RANKL cDNA with double epitopes, pEF6 HA-RANKL-V5His, was transfected into MC3T3-E1 cells, which were then stretched. Endogenous RANKL protein expression increased in response to mechanical loading. Membrane-bound RANKL (HA-RANKL-V5His) increased in cell lysates while soluble RANKL (RANKL-V5His) decreased in the conditioned media after mechanical loading. This may have resulted from the decreased activity of TACE after mechanical loading. Increased membrane-bound RANKL may be one of the mechanisms through which osteoblasts adapt to mechanical loading by regulating osteoclastogenic activity in a region-specific manner.


Adhesion molecule CD44 as a prognostic factor in tongue cancer.
Loss of expression of CD44 has been shown to be a factor of poor prognosis in some types of tumors. The purpose of this study was to analyze this in relation to the survival of patients with tongue cancer. The expression of adhesion molecule CD44 was studied in 56 patients with tongue cancer. Data were gathered on clinical (T, N, M and stage) and pathological (T, N, stage, extracapsular spread, differentiation, tumor thickness, surgical margin and CD44 expression) parameters. Immunohistochemistry studies were carried out using DF1485 anti-CD44 monoclonal antibody. In five tumors (8.9%) < 25%, in 11 (19.6%) 25%-49%, in 15 (26.8%) 50%-74% and in 25 (44.6%) > or = 75% of the neoplastic cells expressed CD44. A Cox proportional risks multivariate analysis identified CD44 expression as the parameter most associated with survival (p < 0.001). The reduced expression of CD44 behaves as a marker of poor tongue tumor prognosis.


Plasticity of claustroneocortical connections via the corpus callosum in the cat.
The cat's distribution of claustral cells that project to the contralateral visual cortex via the corpus callosum was examined. Horseradish peroxidase (HRP) was applied to severed callosal axons to label a heterogeneous population of callosal connections. Cats reared with optically induced strabismus, and Siamese cats, had HRP-filled cells extending more ventrally in the claustrum than in controls. In these groups the compaction of labeled cells was higher than in controls and the amount of increased labeled area was not dependent on the resulting eye alignment. This indicates possible plasticity of visual claustrocallosal connectivity in cats.


The effect of toothpaste with reduced concentration of fluoride-containing sodium trimetaphosphate and polyols on initial enamel erosion.
This in vitro study evaluated the efficacy of toothpaste containing fluoride (F), sodium trimetaphosphate (TMP), and xylitol and erythritol (XE) to inhibit or repair initial enamel erosion lesions. Bovine enamel blocks (n = 120) were selected according to surface hardness (SH) and randomly divided into 5 experimental groups (n = 24 blocks/group): Placebo (no F, TMP, XE); 1100 ppm F; 16% xylitol + 4% erythritol (XE); 200 ppm F + 0.2% TMP (200 ppm F/TMP); and 200 ppm F + 0.2% TMP + 16% xylitol + 4% erythritol (200 ppm F/TMP/XE). The sound and softened blocks were immersed in toothpaste slurry in human saliva for 2 min. The blocks were then submitted to 4 erosive challenges in citric acid (0.75%, pH 3.5), each challenge for 1 min, with stirring. The SH of the blocks was determined after treatment (t) and after the 4 erosive challenges. In addition, the precipitates were analyzed by scanning electron microscopy (SEM). Variables were submitted to a two-way repeated-measures analysis of variance followed by a Student-Newman-Keuls test (p < 0.05). Toothpaste containing 200 ppm F/TMP/XE led to the highest protective and repair effect compared to the other groups (p < 0.001). The protective and repair effect was XE > 200 ppm F/TMP > 1100 ppm F > placebo (p < 0.001). All groups produced precipitates with a thicker layer for XE and TMP groups. Toothpaste containing 200 ppm F, TMP, and polyols demonstrated a superior protective and repair effect in initial enamel erosive lesions in vitro. Toothpaste containing F and polyols could be an advantage in patients affected by dental erosion, due to its higher preventive potential, mainly in individuals who frequently drink acidic beverages. However, future studies are needed to confirm these results.