Lack of compensation for COVID-19-related overtime work and its association with burnout among EMS providers in Korea.
This study examined the association between lack of compensation for COVID-19-related overtime work (LCCOW) and burnout among emergency medical service (EMS) providers in Seoul, Korea. We conducted a cross-sectional survey of 693 EMS providers in Seoul, Korea. Participants were classified into 3 groups according to their experience of coronavirus disease 2019 (COVID-19)-related overtime work and LCCOW: (1) "did not experience," (2) "experienced and was compensated," and (3) "experienced and was not compensated." Burnout was measured using the Korean version of the Copenhagen Burnout Inventory, which has 3 subdomains: personal burnout (PB), work-related burnout (WRB), and citizen-related burnout (CRB). Multiple linear regression was applied to examine whether LCCOW was associated with burnout after adjusting for potential confounders. In total, 74.2% of participants experienced COVID-19-related overtime work, and 14.6% of those who worked overtime experienced LCCOW. COVID-19-related overtime work showed a statistically non-significant association with burnout. However, the association differed by LCCOW. Compared to the "did not experience" group, the "experienced and was not compensated" group was associated with PB (β=10.519; 95% confidence interval [CI], 3.455 to 17.584), WRB (β=10.339; 95% CI, 3.398 to 17.280), and CRB (β=12.290; 95% CI, 6.900 to 17.680), whereas no association was observed for the "experienced and was compensated" group. Furthermore, an analysis restricted to EMS providers who worked overtime due to COVID-19 showed that LCCOW was associated with PB (β=7.970; 95% CI, 1.064 to 14.876), WRB (β=7.276; 95% CI, 0.270 to 14.283), and CRB (β=10.000; 95% CI, 3.435 to 16.565). This study suggests that LCCOW could be critical in worsening burnout among EMS providers who worked overtime due to COVID-19.


Effect of subcellular distribution on nC₆₀ uptake and transfer efficiency from Scenedesmus obliquus to Daphnia magna.
The potential uptake and trophic transfer ability of nanoparticles (NPs) in aquatic organisms have not been well understood yet. There has been an increasing awareness of the subcellular fate of NPs in organisms, but how the subcellular distribution of NPs subsequently affects the trophic transfer to predator remains to be answered. In the present study, the food chain from Scenedesmus obliquus to Daphnia magna was established to simulate the trophic transfer of fullerene aqueous suspension (nC60). The nC60 contaminated algae were separated into three fractions: cell wall (CW), cell organelle (CO), and cell membrane (CM) fractions, and we investigated the nC60 uptake amounts and trophic transfer efficiency to the predator through dietary exposure to algae or algal subcellular fractions. The nC60 distribution in CW fraction of S. obliquus was the highest, following by CO and CM fractions. nC60 uptake amounts in D. magna were found to be mainly relative to the NPs' distribution in CW fraction and daphnia uptake ability from CW fraction, whereas the nC60 trophic transfer efficiency (TE) were mainly in accordance with the transfer ability of NPs from the CO fraction. CW fed group possessed the highest uptake amount, followed by CO and CM fed groups, but the presence of humic acid (HA) significantly decreased the nC60 uptake from CW fed group. The CO fed groups acquired high TE values for nC60, while CM fed groups had low TE values. Moreover, even though CW fed group had a high TE value; it decreased significantly with the presence of HA. This study contributes to the understanding of fullerene NPs' dietary exposure to aquatic organisms, suggesting that NPs in different food forms are not necessarily equally trophically available to the predator.


On Schistosoma margrebowiei Le Roux, 1933: the morphology of the egg, miracidium and cercaria, the compatibility with species of Bulinus, and development in Mesocricetus auratus.
The morphology of the egg, miracidium, and cercaria of Schistosoma margrebowiei are described. The compatibility of S. margrebowiei with species of Bulinus has been examined. The parasite develops well in the diploid, tetraploid and octoploid snails of the truncatus/tropicus complex with overall infection rates of 38.1%, 30.1% and 29.1% respectively, and in reticulatus group snails (Bulinus wrighti) with an infection rate of 45.8% of those snails surviving the prepatent period. Only two species of the forskali complex (Bulinus bavayi, Aldabra; Bulinus beccarii, South Arabia) are slightly compatible, and snails of the africanus group are incompatible. The overall worm return from 24 hamsters exposed individually to 100 cercariae was 39.8%; 82.1% of the worms were paired, the remainder unpaired. The growth of the paired worms was recorded from 28-60 days. The prepatent period in hamsters in 33 days, in sheep 38 days. The mean egg production was 837 eggs/day in infections ranging from 33 to 60 days. Most eggs (80.9%) were deposited in the intestine, and only 18.2% were deposited in the liver. The parasite is pathogenic in hamsters, and peak death rate occurred in the 50-60 day group infections which coincided with the period of peak egg production.


Differences in lipid distribution and expression of peroxisome proliferator-activated receptor gamma and lipoprotein lipase genes in torafugu and red seabream.
Lipid content is one of the major determinants of the meat quality in fish. However, the mechanisms underlying the species-specific distribution of lipid are still poorly understood. The present study was undertaken to investigate the mechanisms associated with lipid accumulation in two species of fish: torafugu (a puffer fish) and red seabream. The lipid content of liver and carcass were 67.0% and 0.8% for torafugu, respectively, and 8.8% and 7.3% for red seabream, respectively. Visceral adipose tissue was only apparent in the red seabream and accounted for 73.3% of its total lipid content. Oil red O staining confirmed this species-specific lipid distribution, and further demonstrated that the lipid in the skeletal muscle of the red seabream was mainly localized in the myosepta. We subsequently cloned cDNAs from torafugu encoding lipoprotein lipase 1 (LPL1) and LPL2, important enzymes for the uptake of lipids from blood circulation system into various tissues. The relative mRNA levels of peroxisome proliferator-activated receptor gamma (PPARγ) and the LPLs of torafugu were determined by quantitative real-time PCR together with their counterparts in red seabream previously reported. The relative mRNA levels of PPARγ and LPL1 correlated closely to the lipid distribution of both fish, being significantly higher in liver than skeletal muscle in torafugu, whereas the highest in the adipose tissue, followed by liver and skeletal muscle in red seabream. However, the relative mRNA levels of LPL2 were tenfold lower than LPL1 in both species and only correlated to lipid distribution in torafugu, suggesting that LPL2 has only a minor role in lipid accumulation. In situ hybridization revealed that the transcripts of LPL1 co-localized with lipids in the adipocytes located along the myosepta of the skeletal muscle of red seabream. These results suggest that the transcriptional regulation of PPARγ and LPL1 is responsible for the species-specific lipid distribution of torafugu and red seabream.


Endpoints in clinical trials: What do patients consider important? A survey of the Ovarian Cancer National Alliance.
In order to understand the patient's perspective in regards to meaningful surrogate clinical trial endpoints and the impact of treatment-related toxicity, and quality of life, we surveyed women with gynecological cancers to ascertain their preferences. A 28-question anonymous online survey was posted on the OCNA website (www.ovariancancer.org). Survey questions included demographic factors, tumor data, and patients' preference regarding side effects and therapy endpoints. Data was analyzed for frequency and percentage of each response. Student t-test, Fisher's exact test and Wilcoxon rank sums were preformed. There were 1413 survey responses. Participants reported that for a new agent to be meaningful, the minimum extension of progression-free survival (PFS) and overall survival (OS) should be five or more months, 77% and 85% of the time, respectively. Most subjects (55%, n=612) were interested in an agent that would keep tumor growth relatively static without change in OS. Addressing the impact of adverse aspects from a hypothetical new agent as a function of response, there was significant migration (p<0.0001) to acceptance of greater toxicity and cost under the scenario of a 5-6months OS gain, despite three-fold higher neurotoxicity, as compared to a PFS gain of 3-4months/no OS gain without toxicity. Response patterns weren't altered by recurrence status. Herein, we show that magnitude of outcome is a desired effect, even given the prospect of significant toxicity and cost. However, these preferences appear to differ between those with primary and recurrent disease.


Modification by diltiazem, a calcium antagonist, of the pulmonary vagal and cardiac sympathetic chemoreflexes in the dog.
1. Experiments were performed on anaesthetized, open-chest dogs to determine the effects of diltiazem on: the pulmonary vagal chemoreflex evoked by intravenous (i.v.) injection of capsaicin; cardiac sympathetic chemoreflexes activated by epicardial application of bradykinin or capsaicin; and baroreflex-mediated changes in heart rate resulting from both pressor and depressor effects produced by i.v. injections of noradrenaline and bradykinin, respectively. 2. Diltiazem infused i.v. at a rate of 10-30 micrograms/kg per min (mean cumulative dose 0.53 +/- 0.05 mg/kg, n = 9), did not affect basal heart rate, despite significant (P less than 0.001) reduction of resting blood pressure. 3. Diltiazem treatment did not affect the pressor responses to i.v. noradrenaline (0.3 micrograms/kg) or the hypotensive effects of i.v. bradykinin (0.3 micrograms/kg), but reduced significantly both the baroreflex-mediated bradycardia (P less than 0.01) and tachycardia (P less than 0.05) occurring with noradrenaline and bradykinin, respectively. 4. In contrast, diltiazem greatly enhanced reflex bradycardia (P less than 0.001) and systemic hypotension (P less than 0.01) resulting from activation of the afferent vagal pulmonary receptors by i.v. capsaicin (3-5 micrograms/kg). 5. Reflex pressor responses evoked by activation of the afferent cardiac sympathetic neurons by epicardial application of bradykinin (1 microgram) or capsaicin (10-20 micrograms) were not affected by diltiazem, but the corresponding reflex increases in heart rate evoked by both substances were significantly (P less than 0.01) reduced. 6. The results indicate that diltiazem, while reducing the influence of sinoaortic baroreceptors on heart rate, facilitates the reflex vagal control of the cardiac pacemaker by the afferent cardiopulmonary vagal receptors. These nervous reflex mechanisms, which include attenuation of positive chronotrophic effects that may result from ischaemia-induced activation of the afferent cardiac sympathetic neurons, may play an important role in the protective action of diltiazem in ischaemic heart disease.


Coxsackievirus B cardiopathy and angiopathy in the hypercholesterolemic host.
Studies on the pathogenic potential of the human cardiotropic enterovirus, coxsackievirus B5, show that this agent localizes and replicates in the aorta of mice. Nutritionally-induced hypercholesterolemia leads to an increased replication and persistence of virus in tissues, specifically the aorta. Coxsackievirus B cardiopathy is markedly augmented in the hypercholesterolemic host, resulting in a persistent cardiomyolysis which is not evident in virus-infected animals with normal cholesterol levels. Pathological changes in the aorta become evident only months after the acute infection, and only in hypercholesterolemic animals previously infected with coxsackievirus B5. Our findings of coxsackievirus B-induced angiopathy and cardiopathy in the hypercholesterolemic host extend the known pathogenic range of these human viruses, and further emphasizes their potential as etiological agents of cardiovascular disease.


Evaluation of the respective contribution of anode and cathode for triclosan degradation in a bioelectrochemical system.
In this work, the bioelectrochemical system (BES) is a feasible alternative for successfully degrading typical refractory emerging contaminant triclosan (TCS). A single-chamber BES reactor with an initial TCS concentration of 1 mg/L, an applied voltage of 0.8 V, and a solution buffered with 50 mM PBS degraded 81.4 ± 0.2% of TCS, exhibiting TCS degradation efficiency improvement to 90.6 ± 0.2% with a biocathode formed from a reversed bioanode. Both bioanode and biocathode were able to degrade TCS with comparable efficiencies of 80.8 ± 4.9% and 87.3 ± 0.4%, respectively. Dechlorination and hydrolysis were proposed as the TCS degradation pathway in the cathode chamber, and another hydroxylation pathway was exclusive in the anode chamber. Microbial community structure analysis indicated Propionibacteriaceae was the predominant member in all electrode biofilms, and the exoelectrogen Geobacter was enriched in anode biofilms. This study comprehensively revealed the feasibility of operating BES technology for TCS degradation.


Accuracy of high resolution computed tomography in direct diagnosis of cerebral aneurysms.
With high resolution computed tomography (CT) of the skull, performing rapid series of 1.5 mm slices during an intravenous bolus injection of contrast medium, an angiography-like image (angio-CT) of the basal cerebral arteries can be obtained. From 76 consecutive angiographically or autopsy-verified cerebral aneurysms of various size down to 3 mm in diameter, 74 (97.4%) were shown up by the angio-CT. One ruptured and one incidental aneurysm escaped CT visualization. Besides the correct localization of the aneurysms, angio-CT provides information concerning the size and main direction of the aneurysms and yields, in addition, a coronal view of the aneurysms and their surrounding structures. Pitfalls for mis-diagnosis can be the following: Aneurysms of below 5 mm in diameter, located at the supraclinoid part of the carotid artery, multiple or non-ruptured aneurysms, bony or movement artefacts, poorly contrasted vessels due to wrong injection technique of contrast medium or vasospasm, and incorrect interpretation.


Tau and neurodegenerative disease: the story so far.
In 1975, tau protein was isolated as a microtubule-associated factor from the porcine brain. In the previous year, a paired helical filament (PHF) protein had been identified in neurofibrillary tangles in the brains of individuals with Alzheimer disease (AD), but it was not until 1986 that the PHF protein and tau were discovered to be one and the same. In the AD brain, tau was found to be abnormally hyperphosphorylated, and it inhibited rather than promoted in vitro microtubule assembly. Almost 80 disease-causing exonic missense and intronic silent mutations in the tau gene have been found in familial cases of frontotemporal dementia but, to date, no such mutation has been found in AD. The first phase I clinical trial of an active tau immunization vaccine in patients with AD was recently completed. Assays for tau levels in cerebrospinal fluid and plasma are now available, and tau radiotracers for PET are under development. In this article, we provide an overview of the pivotal discoveries in the tau research field over the past 40 years. We also review the current status of the field, including disease mechanisms and therapeutic approaches.


Ponalrestat: a potent and specific inhibitor of aldose reductase.
Many of the complications of diabetes appear to be closely linked to increased conversion of tissue glucose to sorbitol which is catalysed by aldose reductase (aldehyde reductase 2, ALR2). Inhibition of ALR2 could, therefore, lead to a reduction in the development of diabetic complications. Ponalrestat ["Statil" (a trademark, the property of Imperical Chemical Industries PLC), "Prodiax" (a trademark, the property of Merck, Sharp and Dohme), ICI 128436, MK538] inhibits ALR2 from a number of sources. Until now, the mechanism of this inhibition has not been fully elucidated. In this paper, we present a detailed mechanism for inhibition of bovine lens ALR2 by ponalrestat. Treatment of humans with some ALR2 inhibitors leads to side-effects, some of which may result from interactions with other enzymes. Aldehyde reductase (ALR1) is probably the most closely related enzyme to ALR2. Inhibition of ALR1 from bovine kidney was, therefore, investigated in order to assess the specificity of ponalrestat. The values of Ki and Kies (apparent dissociation constants for inhibitor from enzyme-inhibitor and enzyme-inhibitor-substrate complexes, respectively) for the interactions of ponalrestat with ALR1 and ALR2 has been calculated by non-linear fitting of kinetic data. These values indicate that ponalrestat does not compete with binding of glucose of NADPH to ALR2, nor with binding of glucuronate or NADPH to ALR1. Lack of competition and the structural dissimilarity of substrates and inhibitor make it unlikely that ponalrestat will utilize substrate binding sites on other enzymes, and so produce undesirable side-effects via such a mechanism. Ponalrestat is a potent inhibitor (Ki = Kies = 7.7 nM) of ALR2 and follows a pure noncompetitive mechanism with respect to glucose. Efficacy, therefore, will not be decreased by development of hyperglycaemia. The compound is a mixed noncompetitive inhibitor of ALR1 when glucuronate is varied. The values of Ki and Kies are 60 microM and 3 microM, respectively, so that inhibition tends towards uncompetitive. The selectivity of ponalrestat in favour of ALR2, therefore, lies in the range 390 to 7,800-fold, being higher at lower concentrations of glucuronate. The high selectivity of ponalrestat in favour of ALR2 rather than ALR1 suggests that the compound is unlikely to inhibit other enzymes which have less homology with ALR2.


[Recurrent epistaxis in a patient with aortic valve stenosis: a variant of Heyde syndrome?].
The Heyde syndrome describes the coincidence of aortic valve stenosis and intestinal bleeding. The pathophysiologic link between both entities has remained unclear so far. In several studies the intestinal bleedings have been attributed to angiodysplasia. Cessations of the intestinal bleedings following replacement of the aortic valve have been described by numerous reports. We describe the history of a 70-year-old man with a calcified aortic valve stenosis. In addition, he suffered from recurrent severe epistaxis over several years. Replacement of the aortic valve by bioprosthesis resulted in complete cessation of the nasal bleedings over a follow-up period of 6 years. This case report suggests that aortic valve stenoses may be associated with extraintestinal bleedings as well.


Mitral valve function after cryoablation of the posterior papillary muscle in the dog.
Extensive cryoablation of an arrhythmogenic left ventricular posterior papillary muscle associated with ventricular arrhythmias may affect mitral valve function. We studied the long-term effects of extensive cryoablation of the posterior papillary muscle and its ventricular attachment in 10 dogs. The dogs had hemodynamic, electrophysiological, and angiographic testing 1 month after operation. Seven dogs were then killed, and the hearts were examined at that time. Three dogs had repeat assessments 2 and 3 months after operation before they were killed. At 1 month, left ventricular angiography showed normal mitral valve function in all dogs. Pathological examination revealed that the posterior papillary muscle and its left ventricular attachment were replaced by a discrete dense, fibrous scar. The fibrous process involved the mitral valve in 2 dogs. At 3 months, pathological examination showed a marked fibrous scar with chondroid metaplasia and fibrous involvement of the mitral valve chordae and posterior leaflet in all 3 dogs. We conclude that extensive cryoablation of the posterior papillary muscle is not associated with long-term mitral valve dysfunction, and may be the best surgical technique to ablate an arrhythmogenic papillary muscle.


[Modern magnetic resonance imaging of the liver].
Magnetic resonance imaging (MRI) of the liver has become an essential tool in the radiological diagnostics of both focal and diffuse diseases of the liver and is subject to constant change due to technological progress. Recently, important improvements could be achieved by innovations regarding MR hardware, sequences and postprocessing methods. The diagnostic spectrum of MRI could be broadened particularly due to new examination sequences, while at the same time scanning time could be shortened and image quality has been improved. The aim of this article is to explain both the technological background and the clinical application of recent MR sequence developments and to present the scope of a modern MRI protocol for the liver.


Associations between sleep bruxism and (peri-)implant complications: lessons learned from a clinical study.
To report and discuss the lessons learned from the conduct of a clinical study on the associations between sleep bruxism and (peri-)implant complications, the protocol of which has been pre-published. A single-center, double-blind, prospective cohort study with a 2 year follow-up was performed in the Academic Centre for Dentistry Amsterdam (ACTA), The Netherlands. Eleven adult participants were included, where an inclusion of 98 was planned. Sleep bruxism was assessed by multiple single-channel electromyographic (EMG) recordings. Main outcomes were biological and technical complications. Results of the study are presented alongside with comments on encountered difficulties. Insufficient participant recruitment and failed EMG recordings were encountered. The small sample size did not allow answering the study's main aim, and was mainly attributed to the study's protocol complexity. EMG recording failures were attributed to insufficient quality of the EMG signal and detachments of the electrode. The lessons learned from the conduct of this study can be used to design successful future clinical studies. Adequate participant recruitment, effective EMG recordings, and a careful selection of predictor variables are important ingredients for the successful conduct of a longitudinal clinical study on the association between sleep bruxism and (peri-)implant complications.


Expression of mitochondria-related genes is elevated in overfeeding-induced goose fatty liver.
Mitochondrion, the power house of the cell, is an important organelle involving in energy homeostasis. Change in mitochondrial mass and function may lead to metabolic disorders. Previous studies indicate that mitochondrial mass loss and dysfunction are associated with non-alcoholic fatty liver disease (NAFLD) in human and mouse. However, it is unclear whether mitochondrial genes are involved in the development of goose fatty liver. To address this, we determined the response of goose mitochondrial genes to overfeeding and other fatty liver-related factors (e.g., hyperinsulinemia, hyperglycemia, and hyperlipidemia). We first employed RNA-seq technology to determine the differentially expressed genes in the livers from normally-fed vs. overfed geese, followed by bioinformatics analysis and quantitative PCR validation. Data indicated that a majority of mitochondrial genes in the liver were induced by overfeeding. To understand how these genes are regulated in the context of fatty liver, we treated goose primary hepatocytes with high levels of glucose, fatty acids and insulin. The results indicated that these factors had an influence on the expression of some mitochondria related genes. Together, these findings suggest that the induction of mitochondrial gene expression by overfeeding is required for the development of goose fatty liver, and this induction is partially attributable to hyperglycemia, hyperlipidemia and hyperinsulinemia.


Ligature-associated bacterial profiles are linked to type 2 diabetes mellitus in a rat model and influenced by antibody treatment against TNF-α or RAGE.
There is a bidirectional relationship between periodontal disease (PD) and type 2 diabetes mellitus (T2D). T2D may lead to ecological perturbations in the oral environment, which may facilitate an altered microbiota. However, previous studies have been inconclusive in determining the effect of T2D on oral bacterial profiles. Therefore, we aimed to evaluate the influence of T2D on the ligature-associated bacterial profile in a diabetic rat model with PD and investigated the impact of blocking inflammatory pathways with antibodies targeting either Tumor Necrosis Factor α (TNF-α) or the receptor of advanced glycation end-products (RAGE). A total of 62 Zucker obese rats (45 T2D) and 17 lean (non-T2D) were divided into 4 treatment groups; lean with PD, obese with PD, obese with PD and anti-TNF-α treatment, and obese with PD with anti-RAGE treatment. Periodontal disease was ligature induced. Ligature-associated bacterial profiles were analyzed using Human Oral Microbe Identification Microarray (HOMIM). Ligature-associated bacterial profiles differed between lean and obese rats. Furthermore, treatment with antibodies against TNF-α or RAGE had an impact on subgingival bacterial profiles. T2D phenotypes are associated with different ligature-associated bacterial profiles and influenced by treatment with antibodies against TNF-α or RAGE.


Differentiating children with familial Mediterranean fever from other recurrent fever syndromes: The utility of new Eurofever/PRINTO classification criteria.
In this study, we aimed to investigate the performance of Eurofever Registry and the Paediatric Rheumatology International Trials Organisation (PRINTO) classification criteria in pediatric patients with familial Mediterranean fever (FMF). This retrospective, cross-sectional study included a total of 130 pediatric FMF patients (67 males, 63 females; mean age: 12.4±3.6 years; range, 2.5 to 17.7 years) with at least one M694V mutation in MEFV gene between July 2010 and July 2019. Demographic features and disease characteristics were recorded. The control group was consisted of 41 patients (19 males, 22 females; mean age: 7.8±4.0 years; range, 2.1 to 17.8 years) with other hereditary autoinflammatory diseases (AIDs), including periodic fevers with aphthous stomatitis, pharyngitis, and adenitis syndrome (n=30), mevalonate kinase deficiency (n=9), and tumor necrosis factor receptor-associated periodic syndrome (n=2). Sensitivity and specificity of the Eurofever/PRINTO classification criteria were calculated. The sensitivity and specificity were 97.7% and 56.1% for Yalcinkaya-Ozen criteria, respectively and 93.1% and 90.2% for Tel Hashomer criteria, respectively. The Eurofever/PRINTO classification criteria reached a sensitivity and specificity of 94.6% and 82.9% and 93.1% and 80.5%, respectively, when genetic plus clinical criteria and clinical-only criteria were applied. The Eurofever/PRINTO classification criteria have a comparable sensitivity for avoidance of FMF underdiagnosis in childhood. The Yalcinkaya-Ozen criteria have the highest sensitivity without a significant specificity. The Tel Hashomer criteria and Eurofever/PRINTO classification criteria were superior to Yalcinkaya-Ozen criteria to differentiate FMF from other AIDs, thus leading to less complications relevant to underdiagnosis of other AIDs.


Post-exposure active immunoprophylaxis of spouses of acute viral hepatitis B patients.
Post-exposure efficacy of hepatitis B vaccine was evaluated in susceptible sexual partners of acute hepatitis B patients in a randomized double-blind, placebo-controlled trial in Greece. Vaccine (20 micrograms dose) or placebo was repeated one and six months after initial administration. Nine months' follow-up was completed by 146/160 entrants. Vaccinated (16.0%) and control spouses (18.3%) showed similar attack rates for all infections. The vaccine group had fewer clinical infections (2.7% against 7.0%) and fewer infections occurring more than one month after first vaccination (8.7% against 14.7%). These differences are not statistically significant, but suggest modification of infection. Overall, the attack rate was lower (p less than 0.01) for male spouses (6.4%) than for females (22.4%). It may be necessary to complement hepatitis B vaccination with hepatitis B immunoglobulin to protect this high-risk group.


Prostate Cancer Ambassadors: Enhancing a Theory-Informed Training Program for Informed Decision-Making.
Despite the high burden of prostate cancer in African American communities, there is a paucity of knowledge about prostate health. This paper describes the enhancement of a curriculum for training lay health advisors, called prostate cancer ambassadors, on informed decision-making for prostate cancer screening. Adult learning theory informed the structuring of the training sessions to be interactive, self-directed, and engaging. Trainings were developed in a manner that made the material relevant to the learners and encouraged co-learning. The research team developed strategies, such as using discussions and interactive activities, to help community members weigh the pros and cons of prostate-specific antigen (PSA) screening and to make an informed decision about screening. Furthermore, activities were developed to bolster four social cognitive theory constructs: observational learning, self-efficacy for presenting information to the community and for making an informed decision themselves, collective efficacy for presenting information to the community, and outcome expectations from those presentations. Games, discussions, and debates were included to make learning fun and encourage discovery. Practice sessions and team-building activities were designed to build self-efficacy for sharing information about informed decision-making. Topics added to the original curriculum included updates on prostate cancer screening, informed decision-making for screening, skills for being a lay health advisor, and ethics. This dynamic model and approach to lay health advisor (ambassador) training is flexible: while it was tailored for use with prostate cancer education, it can be adjusted for use with other types of cancer and even other diseases.


Simultaneous nitrate and phosphate removal based on thiosulfate-driven autotrophic denitrification biofilter filled with volcanic rock and sponge iron.
This study constructed two thiosulfate-driven autotrophic denitrification biofilters filled with volcanic rock (VR-BF), sponge iron and volcanic rock (SIVR-BF), respectively. The nitrate removal load (3200 g/m3/d) and efficiency (98 %) of SIVR-BF were higher than those of VR-BF. The removal of phosphate in SIVR-BF was mainly through forming FePO4 and Fe3(PO4)2(OH)2. Sulfur and iron cycles in SIVR-BF contributed to Fe (II)/Fe (III) electron shuttle, as well as S2-, S0, Sn2- electron buffer and energy storage, which improved nitrate removal and electron utilization. The formation of multi-path collaborative denitrification dominated by sulfur autotrophic denitrification (64.2 ∼ 89.6 %) in SIVR-BF. The other denitrification pathways, such as iron autotrophic denitrification, which buffered pH and reduced sulfate production. Thiobacillus (38.6 %) and Ferritrophicum (25.3 %) were the dominant genus of VR-BF and SIVR-BF, respectively, which played crucial roles in autotrophic denitrification of iron and sulfur. SIVR-BF was a promising process to realize iron-sulfur coupling autotrophic denitrification and phosphate removal.


A review of research on the impact of E171/TiO2 NPs on the digestive tract.
Nanotechnology utilises particles of between 1 and 100 nm in size. In recent years, it has enjoyed widespread application in a variety of areas. However, this has also raised increasing concerns regarding the effects that the use of nanoparticles may have on human health. The nanoparticles of titanium dioxide (TiO2 NPs) are among the most promising nanomaterials and have already found wide use in cosmetics, medicine and, the food industry. A nano-sized (diameter < 100 nm) fraction of TiO2 is present, at a certain percentage, in the E171 ( in the EU) pigment commonly used as an additive in food, whose presence raises particular concerns in terms of its potential negative health impact. The consumption of E171 food additive is increasingly associated with disorders of the intestinal barrier, including intestinal dysbiosis. It may disrupt the normal functions of the gastrointestinal tract (GIT) including: enzymatic digestion of primary nutrients (lipids, proteins, or carbohydrates). The aim of this review is to provide a comprehensive and reliable overview of studies conducted in recent years in terms of the substance's potentially negative impact on human and animal alimentary systems.


Acetabular revision with the Burch-Schnieder antiprotrusio cage and cancellous allograft bone.
A retrospective review of 25 patients who underwent 28 acetabular revisions with the Burch-Schnieder antiprotrusio cage (Protek, Berne, Switzerland) and cancellous allograft bone was performed. Follow-up periods averaged 33 months. Patients had averaged 2.1 prior operations per hip. Twenty-two hips had American Academy of Orthopaedic Surgeons type III (combined segmental and cavitary bone loss) acetabular deficiency. Five hips had type II (cavitary bone loss) and one hip had type I (segmental bone loss) acetabular deficiency. After surgery, 80% of the patients had mild or no pain and 80% functioned as at least a community ambulator. Radiographic analysis included a detailed study of implant migration and the degree to which the hip center and bone stock were restored. Significant component migration was documented in 14% of the acetabular reconstructions. The hip center was improved from a preoperative side-to-side difference of 12.5 mm to 4.9 mm at final evaluation (P = .01). Average medial wall bone stock was improved from 1.9 mm before surgery to 10.1 mm postrevision (P < .01). No patients required revision of the antiprotrusio cage for problems related to the acetabular reconstruction. For failed acetabular components associated with moderate to massive bone loss, the antiprotrusio cage reliably reconstituted the hip joint center and acetabular bone stock. The short-term incidence of mechanical loosening parallels that of previously reported acetabular reconstruction techniques.


Transdermal Iontophoretic Delivery of Lysine-Proline-Valine (KPV) Peptide Across Microporated Human Skin.
Lysine-proline-valine (KPV) is a C-terminal peptide fragment of α-melanocyte stimulating hormone with potent anti-inflammatory properties. Present study investigates various transdermal enhancement strategies such as iontophoresis (ITP), microneedles (MN), and their combination (ITP + MN) on KPV delivery across dermatomed human skin. KPV attains a positive charge at pH less than 7.0, thus anodal ITP was used. The influence of current strength, KPV concentration, and duration of current application on the KPV delivery was investigated. At defined ITP parameters, the influence of MN on KPV delivery (ITP + MN) across skin was also determined. KPV permeation was less than detectable levels (limit of detection, 0.01 μg/mL) by simple passive diffusion. However, KPV permeation was increased to 4.4 μg/cm2/h by MN treatment. Furthermore, ITP and ITP + MN increased the permeation rate by 8 and 35 fold, respectively, as compared to MN alone. The skin retention levels of KPV by MN, ITP, and ITP + MN were increased by 5, 10, and 10 fold, respectively, as compared to passive diffusion. Confocal studies indicate that fluorescein isothiocyanate-labeled KPV migrated through the stratum corneum, along the microchannels and into the lower epidermal tissue because the fluorescence was observed beyond the depth of 100 μm.


Lack of thromboxane A2 involvement in the arrhythmias occurring during acute myocardial ischemia in dogs.
Coronary artery occlusion (CAO) followed by reperfusion of the ischemic myocardium has been associated with the onset of ventricular arrhythmias. It has been suggested that platelet aggregates in the ischemic area may release thromboxane A2 (TxA2) which may then be responsible for the arrhythmias that occur during reperfusion. To study this possibility, the effect of TxA2 synthetase inhibition on arrhythmias was examined in anesthetized dogs during occlusion and for 60 minutes following release. Imidazole (30 mg/kg) was infused intravenously for 10 minutes, followed by continuous infusion of 100 mg/kg/hr for 125 minutes. The left anterior descending coronary artery was occluded, 5 minutes after the initial dose, for 60 minutes. Three minutes after release of CAO, TxB2 concentrations were significantly higher in the arterial blood of vehicle-treated animals (2.06 +/- 0.53 pmoles/ml) than in either CAO + imidazole (0.66 +/- 0.16 pmoles/ml) or sham-CAO animals receiving imidazole (0.66 +/- 0.09 pmoles/l). However, CAO dogs whether receiving imidazole or 0.9% NaCl generated a significantly greater number of ectopic beats during and after occlusion than sham-CAO animals. Therefore, release of TxA2 does not appear to be a major causative factor in the generation of reperfusion arrhythmias in dogs following coronary artery occlusion.


Unplanned Extubation in the Pediatric Intensive Care Unit.
Unplanned extubations (UEs) are common, potentially avoidable complications of endotracheal intubation among pediatric patients. UE can be associated with adverse patient outcomes including increased length of stay, hospitalization cost, and cardiorespiratory decompensation. Inconsistency in the definition of UE has led to underreporting. Staff must be able to recognize and intervene appropriately when an UE occurs. Risk factors have been identified and quality improvement initiatives aimed at reducing UE have shown to be effective in reducing the incidence. The lack of consistent definition may lead to underreporting and may not lead to effective quality improvement initiatives.


Firing up mitochondrial activities with PTPMT1.
Pagliarini et al (2005) recently identified a new mitochondrial specific protein tyrosine phosphatase, PTPMT1. This report comments on its consequences for mitochondrial function and on its potential to act as a therapeutic target in diabetes and cancer.


Frontal midline theta activity and platelet MAO in human subjects.
The distinctive theta rhythm that appears at the frontal midline during the performance of mental tasks has been designated as frontal midline theta (Fm theta). Fm theta shows individual differences and seems to be related to certain personality traits. In several studies, it has been indicated that low platelet monoamine oxidase (MAO) activity is also associated with certain personality traits. In the present study, we found a negative correlation between the appearance of Fm theta and platelet MAO activity. Subjects with marked extroversion show a high amount of Fm theta and low MAO activity. It is therefore suggested that Fm theta, an electrophysiological marker, may be useful in the investigation of monoamine functions in the central nervous system (CNS) by way of platelet MAO activity, a biochemical marker.


Comparative Study of Bacterial Communities in Nepenthes Pitchers and Their Correlation to Species and Fluid Acidity.
Pitchers are specialized digestive organs of carnivorous plants which evolved for trapping prey and represent a unique environment harboring hidden diversity of unexplored microbes forming transient hydrolytic microcosms. In this study, the diversity of bacterial communities in the pitcher fluids of seven local Nepenthes found in Thailand was assessed by tagged 16S ribosomal RNA (rRNA) gene amplicon sequencing on an Ion PGM™ platform. A total of 1,101,000 filtered sequences were obtained which were taxonomically classified into 20 phyla, 48 classes, 72 orders, 153 families, and 442 genera while the remainder (1.43 %) could not be assigned to any existing taxa. Proteobacteria represented the predominant members in closed pitchers and more diversified bacterial taxa particularly Bacteriodetes and Actinobacteria, showed increasing abundance in open pitchers containing insect bodies. Principal coordinate analysis revealed that distribution of bacterial taxa was not significantly related to the Nepenthes species but strongly correlated to the pH of the pitcher fluids (pH 1.7-6.7). Acidicella was a highly dominant bacterial genus in acidic pitcher fluids while Dyella and Mycobacterium were also common genera in most pitchers. A unique microbial community structure was found in Nepenthes ampullaria which could reflect their adaptation to digest leaf litter, in addition to insect prey. The work revealed the highly unexplored nature of bacterial microcosms in Nepenthes pitcher fluids and provides insights into their community structure in this unique ecological system.


Molecular cloning and differential expression of somatic and testis-specific H2B histone genes during rat spermatogenesis.
We have cloned cDNA of a testis-specific histone, TH2B (a variant of H2B), and rat somatic H2B gene to investigate regulation of testis-specific histone genes during rat spermatogenesis. The amino acid sequences deduced from DNA sequences show extensive sequence divergence in the N-terminal third of the two histones. The rest is highly conserved. One cysteine residue was found in TH2B. No cysteine is present in somatic histones except in H3 histone. We investigated the expression of TH2B and H2B genes using the regions of sequence divergence as hybridization probes. The TH2B gene is expressed only in the testis, and the expression of this gene is detected 14 days after birth, reaching a maximum at Day 20. The level of H2B mRNA shows a reciprocal pattern. This contrasting pattern can be explained by the gradually changing proportion of spermatogonia and spermatocytes with testicular maturation. In situ cytohybridization studies show that H2B gene is expressed primarily in proliferating spermatogonia and preleptotene spermatocytes, whereas TH2B gene is expressed exclusively in pachytene spermatocytes which first appear in testis about 14 days after birth. H2B and TH2B genes appear to be ideal markers for the study of proliferation and differentiation events in spermatogenesis and their regulatory mechanisms.


Oral thromboprophylaxis in pelvic trauma: a standardized protocol.
Thromboprophylaxis for deep vein thrombosis (DVT) after lower-extremity trauma could include rivaroxaban, an oral medication that does not need laboratory monitoring. To assess rivaroxaban's efficacy in preventing DVTs after pelvic trauma compared to its historical incidence. All patients admitted with pelvic fractures in a 12-month period followed a standardized thromboprophylaxis protocol: 1) rivaroxaban 10 mg/day within 24 h of injury or upon hemodynamic stability; 2) pre-operative, post-operative, and 30-day extremity ultrasound; 3) ventilation-perfusion scintigraphy for clinical signs of pulmonary embolus; and 4) a 45-, 90-, and 120-day re-evaluation. Rivaroxaban administration ceased the day of surgery and restarted 12 h post-operatively or upon hemodynamic stability, continuing for 30 days. Excluded patients had severe neurological or hepatosplenic injuries, heparin hypersensitivity, or hemodynamic instability. Of 113 patients assessed, 84 patients (66 males), average age 46.6 years (range 19-69 years), were included. They had isolated pelvic trauma (n = 37), associated lower limb injuries (n = 47), average Injury Severity Score 21.4 (range 16-50), and average Glasgow Coma Scale score 13.6 (range 9-15). Patients receiving thromboprophylaxis soon after their fracture (n = 64) had a lower incidence of DVT than those receiving delayed thromboprophylaxis (n = 20) (p = 0.02). One patient (1.2%) died from a pulmonary embolus; 13 had asymptomatic below-the-knee DVTs. Rivaroxaban did not increase intra- or post-operative bleeding in surgical wounds. DVT incidence after pelvic fractures is reduced by administering antithrombotics within 24 h of injury or, if the patient is hemodynamically unstable, 24 h after stabilization. Rivaroxaban is a safe and effective method of providing this thromboprophylaxis.


Pediatrician Guidance in Supporting Families of Children Who Are Adopted, Fostered, or in Kinship Care.
The child welfare system strives to provide children and adolescents in foster care with a safe, nurturing environment through kinship and nonkinship foster care placement with the goal of either reunification with birth parents or adoption. Pediatricians can support families who care for children and adolescents who are fostered and adopted while attending to children's medical needs and helping each child attain their developmental potential. Although this report primarily focuses on children in the US child welfare system, private and internationally adopted children often have similar needs.


Production of cytotoxic factor(s) in human T cell lines transformed by a human retrovirus.
Human T cell lines, MT-2, TCL-Ter, TCL-Haz, and TCL-Kan which were transformed by a human retrovirus, constitutively produced cytotoxic factor(s) (CF) in the culture supernatants. In these cell lines, MT-2 produced the largest amount of CF. The amount of CF produced by MT-2 was 9-10 or 3-4 times larger than that produced by a human B cell line, RPMI 1788, or normal peripheral blood leukocytes stimulated with mitogens and phorbol ester. The kinetics of the production by MT-2 was similar in media with and without serum. The activity was stable at 56 degrees C for 30 min but was lost at 80 degrees C for 30 min and at pH 2 for 20 hr. On gel filtration, the molecular weight of the factor produced by MT-2 was approximately 90,000. On isoelectric focusing, the activity was recovered in the fraction at pH 6.5-7.0.


Transcriptional Spatial Profiling of Cancer Tissues in the Era of Immunotherapy: The Potential and Promise.
Intratumoral heterogeneity poses a major challenge to making an accurate diagnosis and establishing personalized treatment strategies for cancer patients. Moreover, this heterogeneity might underlie treatment resistance, disease progression, and cancer relapse. For example, while immunotherapies can confer a high success rate, selective pressures coupled with dynamic evolution within a tumour can drive the emergence of drug-resistant clones that allow tumours to persist in certain patients. To improve immunotherapy efficacy, researchers have used transcriptional spatial profiling techniques to identify and subsequently block the source of tumour heterogeneity. In this review, we describe and assess the different technologies available for such profiling within a cancer tissue. We first outline two well-known approaches, in situ hybridization and digital spatial profiling. Then, we highlight the features of an emerging technology known as Visium Spatial Gene Expression Solution. Visium generates quantitative gene expression data and maps them to the tissue architecture. By retaining spatial information, we are well positioned to identify novel biomarkers and perform computational analyses that might inform on novel combinatorial immunotherapies.


Prevalence of the coagulation factor XIII polymorphism Val34Leu in women with recurrent miscarriage.
Recurrent miscarriage (RM) syndrome is not an uncommon obstetrical problem of multifactorial etiology. We investigated the role of the coagulation factor XIII (FXIII) Val34Leu polymorphism in RM. We recruited 80 subjects (40 normal and 40 with history of RM; of each group 20 pregnant and 20 non-pregnant) and analyzed the prevalence of this polymorphism. The women recruited for the present study had similar age and did not have history of any hemostatic disorders. FXIII levels and activity and the rate of fibrin cross-linking by FXIII genotype Val34Val and Val34Leu were studied. Genotype analyses of patients and normal revealed that the frequencies distribution of Val/Val and Val/leu were statistically similar (P<0.05): 62.5% and 60%, and 37.5% and 40%, respectively; no Leu/leu genotype was found. The FXIII-A subunit levels and activity were also found similar between Val/Val and Val/leu genotypes in the different groups, pregnant and non-pregnant, normal or with RM. The rate of FXIII alpha and gamma-chains fibrin cross-linking was not different between the 2 genotypes. From our results we conclude that FXIII Val34Leu polymorphism does not appear to be associated to RM.


Renal anemia: current treatments and emerging molecules.
Anemia is a common complication of kidney disease and the prevalence increases as the disease progresses. It worsens the quality of life of patients and increases morbidity and mortality. The current rationale for treating renal anemia is based on the use of erythropoiesis-stimulating agents, iron supplementation and, to a lesser extent, the use of transfusions. Stimulation of endogenous erythropoietin synthesis and improvement of iron availability, through inhibition of prolil-hydroxilase-hypoxia-inducible factor (PH-HIF), represents a new oral alternative for renal anemia treatment. Clinical trials with PH-HIF inhibitors have demonstrated their efficacy in maintaining target hemoglobin levels. However, aspects concerning long-term safety are pending a clarification. In conclusion, advances in the pathogenesis of renal anemia make it possible to have current treatments to treat renal anemia. The development of new molecules, based on the inhibition of PH-HIF, represents a new effective alternative for anemia associated with kidney disease, especially in patients with resistance to erythropoiesis-stimulating agents.


Effects of growth hormone on the metabolism of lipids and water and their potential in causing adverse events during growth hormone treatment.
GH effects certain changes in the metabolism of lipids and body water in humans. The effects of GH, such as high blood pressure, an increase in cholesterol and triglycerides, and lipoatrophy, among others, must, however, be seen in the context of the diverse disorders being treated. The risks faced in acromegaly, for instance, are not necessarily shared by Turner's syndrome patients treated with GH. The various metabolic effects of GH could thus be said to lead to adverse events in certain risk groups, which makes the monitoring of relevant parameters essential during treatment with GH.


Synergistic effect of Mn-Si-COS on wound immune microenvironment by inhibiting excessive skin fibrosis mediated with ROS/TGF-β1/Smad7 signal.
Excessive oxidative stress and inflammation often impede wound healing and ultimately lead to excessive skin fibrosis formation. It was known that the structural properties of biomaterials can affect the healing and immune response of surrounding tissues. In this work, a composite structure of Mn-Si-chitooligosaccharides (COS) was designed (COS@Mn-MSN) and the ability of regulating wound microenvironment for inhibiting skin fibrosis was investigated. In order to reduce the negative effects of Mn, the nano-level Mn was doped into MSN to minimize its content. The results show that Mn in COS@Mn-MSN showed significant ability of scavenging excess intracellular ROS within 1 d. The Si released from COS@Mn-MSN can shift M2 macrophage polarization in the later stage (1-3 d), showing anti-inflammatory effect. Macrophage (RAW264.7) were activated alternatively by COS released from COS@Mn-MSN, with upregulated expression of anti-inflammatory factors (IL-10 and CD206) and downregulated expression of pro-inflammatory factors (TNF-α, CD80, and IL-1β) in the whole time. The expression of fibrosis associated factor TGF-β1 and CD26 in fibroblast cells (L929) were inhibited by COS and Si. Besides, the inflammatory microenvironment mediated by COS@Mn-MSN downregulated Smad-7 gene expression and upregulated Col-1α gene expression. With the function of reducing oxidative stress (0-1 d), the TGF-β1 inhibition (1-3 d) and anti-inflammatory effects (0-3 d), COS@Mn-MSN could inhibit excessive skin fibrosis formation mediated with ROS/TGF-β1/Smad7 signal. Therefore, the prepared COS@Mn-MSN shows great potential to active scarless wound therapy.


Expression of CD4 can confer major histocompatibility complex class II-associated superantigen reactivity upon a T cell receptor derived from a CD8-dependent cytotoxic T lymphocyte clone.
It has been shown that reactivity against major histocompatibility complex (MHC) class II-associated Mlsa determinants is mainly mediated by CD4+ V beta 6+ T cells. 3F9 is a CD8+ CTL clone which is specific for the alloantigen H-2Db. While 3F9 is V beta 6+, it is not Mlsa reactive, presumably because it does not express CD4. 3F9 utilizes the same T cell receptor (TcR) V alpha V beta combination as LB2, a CD4+ T helper clone specific for chicken red blood cells (cRBC)/I-Ab and yet differs from LB2 in the junctional sequences in both TcR chains. CD4+ CD8- and CD4-CD8- hybridomas expressing the 3F9 TcR were tested for reactivity against Mlsa and cRBC/I-Ab. Only the CD4+CD8- hybridomas were Mlsa reactive, and antibody inhibition studies revealed that this reactivity was both CD4 and MHC class II dependent. Therefore the expression of the CD4 molecule can make an MHC class I-restricted TcR Mlsa reactive. Neither type of hybridoma reacted against cRBC, thus the main difference in the antigen reactivity between 3F9 and LB2 lies in the TcR junctional regions.


Higher Prevalence of Bovine Aortic Arch Configuration in Patients Undergoing Blunt Isthmic Aortic Trauma Repair.
The prevalence of a bovine aortic arch configuration is higher in patients treated for thoracic aortic aneurysms and type B dissection; its prevalence in aortic isthmic trauma has not been described. A case control study was performed comparing consecutive patients treated at our institution for acute isthmic aortic transection after blunt trauma between 2002 and 2019 and a control group of consecutive sex-matched individuals undergoing imaging for nonaortic disease. Imaging and clinical findings were reviewed. Subjects were divided into bovine and nonbovine groups and prevalence was compared. The length of the aortic segment between the left subclavian artery (LSA) and the next proximal great vessel was measured in the control population and a comparison was performed between bovine and nonbovine aortic arch subjects. Thirty-three consecutive (30 male) patients were reviewed, 66 individuals (60 male) were included in the control group. A higher incidence of bovine arch in trauma patients was found: 57.6% vs. 34.8% (P = 0.007). The median (range, mm) and mean (SD) distance between the bovine trunk and the LSA were 13 mm (2-27) and 12.4 mm (5.9), respectively, compared with 5 mm (1-27) and 7.8 mm (6.1) between the left common carotid and LSA in nonbovine aortic arches (P < 0.005). A higher incidence of bovine arch in patients reaching out for surgical treatment for traumatic isthmic aortic transection was found in our population. Clinical interpretation of this finding can lead to several alternatives. Confirmation with larger series and data on prevalence of this anatomic variation in nonsurvivors is needed to provide a better understanding of this finding.


Ten years-experience of sunitinib in the treatment of advanced pan-NETs: an update on safety profile.
Sunitinib still represents a milestone in the treatment for progressive, well-differentiated, advanced panNETs. We performed an evidence reappraisal to critically discuss its safety profile. We included nine studies, five clinical trials and four real-world (RW) studies. Within non-real-world (NRW) studies, diarrhea was the most frequent clinical AE. With regard to G3-4 AEs, fatigue and hypertension were the two most frequent, while neutropenia was the most recurrent hematological one. Considering four real-world trials, hand-foot-syndrome (HFS) was the most frequent clinical any-grade AE of any grade and neutropenia was the most common G3-4. Alongside to the AEs rate, the discontinuation rate of sunitinib due to TRAEs was variable among all the nine selected studies, ranging from 10% to 35% in the NRW setting and from 7% to 31% in the RW setting. Conversely, temporary interruption is an accepted strategy to reduce toxicity, even though not specifically tested in pan-NET. Till now, sunitinib continues to be one of the main therapeutic options for patients with well differentiated advanced panNETs, potentially covering any line of treatment. Therefore, tolerability plays a crucial role to increase adherence to therapy and maximize QoL.


Gemfibrozil in Combination with Statins-Is It Really Contraindicated?
Gemfibrozil is a lipid-modifying agent that belongs to the fibric acid derivative class. Fibric acid derivatives activate peroxisome proliferator activated receptor α (PPAR-α). The primary role of these agents in clinical practice is for the management of hypertriglyceridemia. Triglycerides may be reduced by as much as 74 % in some patients. In addition to lowering triglycerides, these agents can also decrease very low-density lipoprotein cholesterol (VLDL-C) and low-density lipoprotein cholesterol (LDL-C) as well as raise high-density lipoprotein cholesterol (HDL-C). Based on the 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults and the National Lipid Association, pharmacologic therapy to reduce triglycerides should be considered when triglyceride levels are ≥500 mg/dL. While the use of gemfibrozil has decreased over the years for a variety of reasons, muscle-associated adverse effects is the predominant reason and the one that is most clinically relevant. However, despite these concerns, there are situations in which the use of gemfibrozil in combination with a statin may be necessary. Understanding the metabolism of gemfibrozil and the degree of interaction with the various statins will assist health-care providers to optimize safety when this combination is clinically indicated.


Polarized expression of Na+/H+ exchange activity in LLC-PK1/PKE20 cells: II. Hormonal regulation.
LLC-PK1/PKE20 cells (a continuous epithelial cell line) has two different Na/H exchange activities: Na/H-1 located in the basolateral membrane and Na/H-2 located in the apical membrane [Casavola et al. (1989) Biochem Biophys Res Commun 165:833-837; Haggerty et al. (1988) Proc Natl Acad Sci USA 86:6797-6801]. In the present report we have studied hormone regulation of these exchange activities by measuring Na-dependent recovery of pHi from an acid load (by using microspectrofluorometry and 2,7-bis(carboxyethyl)-5,6-carboxyfluorescein) in response to activation of regulatory cascades by either pharmacological agents or by vasopressin or calcitonin. Agents leading to activation of protein kinase A (cAMP-dependent), such as forskolin (10 microM), 8-Br-cAMP (0.25 mM), and isobutylmethylxanthine (0.5 mM), inhibited Na/H-2 and Na/H-1 by an average of 49%. Stimulation of protein kinase C by a phorbol ester (phorbol 12-myristate 13-acetate, TPA, 100 nM) inhibited Na/H-2 (by an average of 48%) and stimulated Na/H-1 (by an average of 38%); these effects of TPA were also observed in the presence of forskolin (100 microM). Addition of either vasopressin (2 microM) or calcitonin (0.3 microM) onto both sides of the monolayer decreased the activity of Na/H-2 by an average of 26.3% and 27.7% respectively, and stimulated the activity of Na/H-1 by an average of 17.4% and 38.7% respectively; exposure of cells to either hormone stimulated production of cAMP and inositol trisphosphate, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)


Synthesis and biological activity of phenoxyphenyl oxamic acid derivatives related to L-thyronine.
The synthesis of substituted phenoxyphenyl oxamic acid derivatives related to L-thyronine (L-T3) is described. The in vitro and in vivo cholesterol lowering and cardiovascular effects of these compounds are presented and discussed.


Mouse models of telencephalic development.
As the telencephalon first emerges from anterior neuroectoderm, signalling molecules and transcription factors combine to specify the identity and fate of cells in each of its regions. Studies of both naturally occurring and transgenic mutant mice have identified many genes that contribute to this process. The development of telencephalon and its regions is specified by signalling molecules produced at sites both surrounding and within the telencephalon. Different parts of the telencephalon express different combinations of transcription factors that control processes including proliferation, cell fate determination and migration in order to create the unique phenotype of each region.


Progress in quality control, detection techniques, speciation and risk assessment of heavy metals in marine traditional Chinese medicine.
Marine traditional Chinese medicines (MTCMs) hold a significant place in the rich cultural heritage in China. It plays an irreplaceable role in addressing human diseases and serves as a crucial pillar for the development of China's marine economy. However, the rapid pace of industrialization has raised concerns about the safety of MTCM, particularly in relation to heavy metal pollution. Heavy metal pollution poses a significant threat to the development of MTCM and human health, necessitating the need for detection analysis and risk assessment of heavy metals in MTCM. In this paper, the current research status, pollution situation, detection and analysis technology, removal technology and risk assessment of heavy metals in MTCM are discussed, and the establishment of a pollution detection database and a comprehensive quality and safety supervision system for MTCM is proposed. These measures aim to enhance understanding of heavy metals and harmful elements in MTCM. It is expected to provide a valuable reference for the control of heavy metals and harmful elements in MTCM, as well as the sustainable development and application of MTCM.


Comparison of reporting of Stevens-Johnson syndrome and toxic epidermal necrolysis in association with selective COX-2 inhibitors.
Stevens-Johnson syndrome and toxic epidermal necrolysis are closely related severe acute life-threatening, drug-induced skin disorders. The US FDA Adverse Events Reporting System (AERS) has received reports of Stevens-Johnson syndrome and toxic epidermal necrolysis associated with the use of the recently introduced selective cyclo-oxygenase (COX)-2 inhibitor NSAIDs, two of which are also sulfonamides. The objective of this study is to review cases of Stevens-Johnson syndrome and toxic epidermal necrolysis reported to the FDA associated with the use of the selective COX-2 inhibitor NSAIDs celecoxib, rofecoxib and valdecoxib, and to compare reporting rates of the two conditions associated with these drugs to each other, meloxicam (an oxicam NSAID that came on the US market at a similar time) and the background incidence rate. We reviewed all US cases of Stevens-Johnson syndrome and toxic epidermal necrolysis reported to the FDA AERS database associated with the use of celecoxib, rofecoxib, valdecoxib and meloxicam since these agents were first marketed. We utilised AERS and drug use data to calculate reporting rates for each drug after the first 2 years of marketing. We obtained the background rate from the medical literature. Up to the end of March 2004, there were 63 cases of Stevens-Johnson syndrome/toxic epidermal necrolysis reported with valdecoxib use, 43 with celecoxib, 17 with rofecoxib (the non-sulfonamide coxib) and none for meloxicam. In the first 2 years of marketing the reporting rate for Stevens-Johnson syndrome/toxic epidermal necrolysis with valdecoxib was 49 cases per million person-years of use, 6 cases per million person-years for celecoxib and 3 cases per million person-years for rofecoxib. The reporting rates for the sulfonamide coxibs were substantially higher than the background rate of 1.9 cases per million population per year, with the valdecoxib rate being 8-9 times that of celecoxib and approximately 25 times that of the background rate. There is a strong association between Stevens-Johnson syndrome/toxic epidermal necrolysis and the use of the sulfonamide COX-2 inhibitors, particularly valdecoxib. Physicians should be aware of the possibility of this serious life-threatening event when prescribing these drugs and advise patients to discontinue use at the earliest possible sign or symptom.


The uptake of 3H(G)L leucine into single muscle fibers in Charcot-Marine-Tooth disease.
In previous studies, the incorporation of 3H(G)L-leucine into muscles of patients with Charcot-Marie-Tooth (CMT) disease was shown to be increased in comparison with that observed in motor neuron disease (MND). To determine the cause of the increased uptake in CMT, studies of single fiber leucine incorporations have been undertaken. The results of this study indicate that the increased incorporation is into those muscle fibers which are undergoing regeneration following reinnervation. These results do not support the thesis that there is an associated myopathic process in CMT.


Conserved targeting information in mammalian and fungal peroxisomal tail-anchored proteins.
The targeting signals and mechanisms of soluble peroxisomal proteins are well understood, whereas less is known about the signals and targeting routes of peroxisomal membrane proteins (PMP). Pex15 and PEX26, tail-anchored proteins in yeast and mammals, respectively, exert a similar cellular function in the recruitment of AAA peroxins at the peroxisomal membrane. But despite their common role, Pex15 and PEX26 are neither homologs nor they are known to follow similar targeting principles. Here we show that Pex15 targets to peroxisomes in mammalian cells, and PEX26 reaches peroxisomes when expressed in yeast cells. In both proteins C-terminal targeting information is sufficient for correct sorting to the peroxisomal membrane. In yeast, PEX26 follows the pathway that also ensures correct targeting of Pex15: PEX26 enters the endoplasmic reticulum (ER) in a GET-dependent and Pex19-independent manner. Like in yeast, PEX26 enters the ER in mammalian cells, however, independently of GET/TRC40. These data show that conserved targeting information is employed in yeast and higher eukaryotes during the biogenesis of peroxisomal tail-anchored proteins.


Pierre Robin Sequence: A Familial, Clinical, and Pathoanatomical Record of an Affected Dachshund.
This study describes a spontaneous case of Pierre Robin sequence in a nonhuman animal species. A miniature dachshund with micrognathia developed glossoptosis, respiratory distress, dysphagia, temporomandibular ankylosis, and a misaligned upper jaw. The severity of this condition resulted in death by obstructive apnea at the age of 8 mo. Dogs with Pierre Robin sequence can provide further knowledge and a greater understanding of this abnormality, leading to better management of affected individuals and improvement of therapeutic methods.


Evaluation of Atherosclerotic Cardiovascular Risk Prediction Models in China: Results From the CHERRY Study.
Updated American or Chinese guidelines recommended calculating atherosclerotic cardiovascular disease (ASCVD) risk using the Pooled Cohort Equations (PCE) or Prediction for Atherosclerotic Cardiovascular Disease Risk in China (China-PAR) models; however, evidence on performance of both models in Asian populations is limited. The authors aimed to evaluate the accuracy of the PCE or China-PAR models in a Chinese contemporary cohort. Data were extracted from the CHERRY (CHinese Electronic health Records Research in Yinzhou) study. Participants aged 40 to 79 years without prior ASCVD at baseline from 2010 to 2016 were included. ASCVD was defined as nonfatal or fatal stroke, nonfatal myocardial infarction, and cardiovascular death. Models were assessed for discrimination and calibration. Among 226,406 participants, 5362 (2.37%) adults developed a first ASCVD event during a median of 4.60 years of follow-up. Both models had good discrimination: C-statistics in men were 0.763 (95% confidence interval [CI]: 0.754-0.773) for PCE and 0.758 (95% CI: 0.749-0.767) for China-PAR; C-statistics in women were 0.820 (95% CI: 0.812-0.829) for PCE and 0.811 (95% CI: 0.802-0.819) for China-PAR. The China-PAR model underpredicted risk by 20% in men and by 40% in women, especially in the highest-risk groups. However, PCE overestimated by 63% in men and inversely underestimated the risk by 34% in women with poor calibration (both P < 0.001). After recalibration, observed and predicted risks by recalibrated PCE were better aligned. In this large-scale population-based study, both PCE and China-PAR had good discrimination in 5-year ASCVD risk prediction. China-PAR outperformed PCE in calibration, whereas recalibration equalized the performance of PCE and China-PAR. Further specific models are needed to improve accuracy in the highest-risk groups.


Corrigendum: Psychophysiological Processing of Itch in Patients with Chronic Post-burn Itch: An Exploratory Study
This corrects the article DOI: 10.2340/00015555-2323.


Percutaneous transthoracic aspiration needle biopsy.
An experience based on 1,211 patients has shown aspiration needle biopsy to be a valuable technique for diagnosing bronchogenic carcinoma and other localized intrathoracic lesions that are beyond the reach of the fiberoptic bronchoscope. In 896 patients with malignant intrathoracic neoplasm, the aspirate demonstrated malignant cells in 96%. A false cytological diagnosis of carcinoma occured in 2 patients, for a true positive rate of 99%. However, the true negative rate was only 87%. In 77% of 31 immunosuppressed patients, the causative agent of a focal infectious process was diagnosed. Pneumothorax was the only notable complication, occuring in 24% of patients, with 14% requiring chest tube drainage. The procedure is relatively simple and rapid, generally causes little patient discomfort, and can be performed in virtually any hospital.


Subclavian artery stenting for coronary-subclavian steal syndrome.
To evaluate the safety and feasibility of subclavian artery stenting for coronary-subclavian steal syndrome (CSSS). CSSS is a rare cause of myocardial ischemia due to ipsilateral subclavian artery stenosis in patients who have undergone coronary artery bypass graft. However, current knowledge of the optimal therapy for CSSS is limited. The clinical data of 37 patients (33 male; mean age 65 ± 6 years) with CSSS who had undergone subclavian artery stenting between April 2007 and December 2015 were analyzed. The time elapsed between bypass surgery and the diagnosis of CSSS was 6.3 ± 4.3 years (median 5.2 years, range 1.3 months to 17.8 years). The technical success rate was 97.3% (100% for stenosis, 85.7% for occluded lesions). One patient experienced a transient ischemic attack; a second patient developed flow-limiting dissection involving the ostium of the internal mammary artery; and a third patient had a puncture site hematoma. The mean stenosis of target lesions decreased from 87.6 ± 10.6% to 5.9 ± 5.0% immediately after the procedure. A total of 35 (94.6%) patients were discharged with a complete remission of myocardial ischemia. During a follow-up of 44 ± 32 (range 6-112) months, no patient suffered from stroke or myocardial infarction. Stent-restenosis related unstable angina developing in one patient at 36 months and in another patient at 11 months, both of whom were relieved after balloon angioplasty and remained asymptomatic until the last follow-up. Subclavian artery stenting is feasible and safe in patients with CSSS, with a low incidence of perioperative complications and stent restenosis rate. © 2017 Wiley Periodicals, Inc.


Low-grade angiosarcoma of the skin of the breast: a complication of lumpectomy and radiation therapy for breast carcinoma.
A case of low-grade angiosarcoma arising in the skin of a breast previously irradiated for breast carcinoma is reported. Initially, an asymptomatic breast mass was detected. Excisional biopsy and axillary lymph node dissection revealed a 1.5-cm infiltrating ductal carcinoma with 21 negative lymph nodes. The neoplasm was staged as T1, N0, M0. The patient was entered in a research protocol and was treated with high-dose external beam (4,860 rad) and iridium implant (1,860 rad) irradiation. Seven years later the patient developed low-grade angiosarcoma of the breast skin. The lesion recurred following excision and eventually was treated by simple mastectomy. The patient never had evidence of lymphedema. Cutaneous angiosarcomas occurring as a complication of lumpectomy and radiation therapy for breast carcinoma are rare. In some reported cases the patients have had lymphedema, a known factor predisposing to angiosarcoma. Furthermore, almost all cases previously reported have been high grade. This case suggests that radiation therapy for breast carcinoma may also be complicated by low-grade angiosarcoma.


Cu2+ removal and recovery by Spi SORB: batch stirred and up-flow packed bed columnar reactor systems.
The biosorption of Cu(2+) by free and poly acrylamide gel (PAG) immobilized Spirulina platensis (SpiSORB) was characterized under batch and continuous packed bed columnar reaction systems. The biosorption of Cu(2+) was shown to be highest at pH of 6.0 for both types of biomass. The PAG immobilization process did not interfere with the Cu(2+) binding sites present on biomass leading to cent percent (ca. 250 mg g(-1) of dry biomass) retention of biosorption as compared to free cells. Transmission electron microscopy on Cu(2+) localization revealed that majority of metal is being sequestered by the cell wall only. The infrared spectrum of metal treated S. platensis biomass indicated the possible involvement of amide, amino, and carboxyl groups in metal binding. Up-flow packed bed columnar reactor containing 2.0 g of PAG immobilized S. platensis shown a maximum of 143-fold volume reduction factor at the residence time of 4.6 min for Cu(2+) alone and found to decrease dramatically when Zn(2+ )is present in a bimetallic solution.


Cell proliferation and apoptosis in the anterior intestine of an amphibious, euryhaline mudskipper (Periophthalmus modestus).
In order to replace the diffusive loss of water to the surrounding environment, seawater (SW)-acclimated euryhaline fishes have gastrointestinal tracts with higher ion/water flux in concert with greater permeability, and contrast that to freshwater (FW)-acclimated fish. To understand the cellular basis for these differences, we examined cell proliferation and apoptosis in the anterior intestine of mudskipper transferred from one-third SW to FW or to SW for 1 and 7 days, and those kept out of water for 1 day. The intestinal apoptosis (indicated by DNA laddering) increased during seawater acclimation. TUNEL staining detected numerous apoptotic cells over the epithelium of SW-acclimated fish. Cell proliferation ([3H]thymidine incorporation) in the FW fish was greater than those in SW 7 days after transfer. Labeling with a Proliferating cell nuclear antigen (PCNA) antibody indicated that proliferating cells were greater in number and randomly distributed in the epithelium of FW fish, whereas in SW fish they were almost entirely in the troughs of the intestinal folds. There were no changes in cell turnover in fish kept out of water. During acclimation to different salinities, modification of the cell turnover and abundance may play an important role in regulating the permeability (and transport capacity) of the gastrointestinal tract of fish.


Assessment of prenatal depression among U.S. pregnant women without access to paid sick leave and regular place of care: National Health Interview Survey of U.S.-born and non-U.S.-born.
Prenatal depression is one of the most common risks during pregnancy. This study examined the prevalence and likelihood of prenatal depression association with sociodemographic factors, paid sick leave, and place of care among U.S. pregnant women. We conducted bivariate Chi-square tests to assess the statistical difference and multivariable logistic regression models to assess the association of prenatal depression using the National Health Interview Survey, cross-sectional data from 2010 to 2019 of pregnant women aged 18-44 years (N = 957). The prevalence of prenatal depression was 40.6%, 28.5%, and 27.2% among White, Black, and other racial pregnant women, respectively. Pregnant women with no regular/routine place of care had a prenatal depression prevalence rate of 58.1%, and those without access to paid sick leave had 46.9%. Also, pregnant women without access to paid sick leave were found to have an increased likelihood of reporting prenatal depression ([adjusted odds ratio] AOR = 2.50, 95% CI = 1.72-3.64), as well as those without a regular place of care (AOR = 2.43, 95% CI = 1.32-4.47). The findings identify factors that need to be addressed to minimize depression among U.S. pregnant women and establish the need for tailored interventions to address prenatal depression.


Tradeoffs between mating effort and parenting effort in a polygynandrous mammal.
Reproductive strategies are defined by expenditures of time and energy devoted to mating effort, which increases mating opportunities, and parenting effort, which enhances the survival of offspring. We examine tradeoffs between mating effort and parenting effort in male olive baboons, Papio anubis, a species in which males compete for mating opportunities, but also form ties to lactating females (primary associations) that represent a form of parenting effort. Males that are involved in more primary associations invest less in mating effort than males who are involved in fewer primary associations. Males that are involved in more primary associations play a smaller role in establishing proximity to their primary associates than other males, suggesting that males operate under temporal constraints. There is also some evidence that involvement in primary associations negatively affects paternity success. Taken together, the data suggest that males face tradeoffs between mating effort and parenting effort.


Environmental micro-niche filtering shapes bacterial pioneer communities during primary colonization of a Himalayas' glacier forefield.
The pedogenesis from the mineral substrate released upon glacier melting has been explained with the succession of consortia of pioneer microorganisms, whose structure and functionality are determined by the environmental conditions developing in the moraine. However, the microbiome variability that can be expected in the environmentally heterogeneous niches occurring in a moraine at a given successional stage is poorly investigated. In a 50 m2 area in the forefield of the Lobuche glacier (Himalayas, 5050 m above sea level), we studied six sites of primary colonization presenting different topographical features (orientation, elevation and slope) and harbouring greyish/dark biological soil crusts (BSCs). The spatial vicinity of the sites opposed to their topographical differences, allowed us to examine the effect of environmental conditions independently from the time of deglaciation. The bacterial microbiome diversity and their co-occurrence network, the bacterial metabolisms predicted from 16S rRNA gene high-throughput sequencing, and the microbiome intact polar lipids were investigated in the BSCs and the underlying sediment deep layers (DLs). Different bacterial microbiomes inhabited the BSCs and the DLs, and their composition varied among sites, indicating a niche-specific role of the micro-environmental conditions in the bacterial communities' assembly. In the heterogeneous sediments of glacier moraines, physico-chemical and micro-climatic variations at the site-spatial scale are crucial in shaping the microbiome microvariability and structuring the pioneer bacterial communities during pedogenesis.


Synovial lipoma arborescens of the hip.
Lipoma arborescens is a rare intra-articular tumor usually found in the knee joint. The reported lesion involved the inferomedial recess of the right hip synovium, in a 29-year-old male. The clinical findings were nonspecific. Both arthrography and computerized tomography (CT) of the hip disclosed the tumor which, on CT examination, showed an inhomogeneous low density, due to its fat content. The final diagnosis was given by histological examination of the resected mass. No recurrence was observed after one year. The long-term prognosis probably depends more on the underlying disorder of the joint than on the lipoma itself.


Loneliness in older adults is associated with diminished cortisol output.
Loneliness in older adults has been associated with increased mortality and health problems. One of the assumed underlying mechanisms is dysregulation of the hypothalamic-pituitary-adrenocortical axis (HPA-axis). The purpose of this study was to investigate whether loneliness in older adults is associated with HPA-axis dysregulation and whether this association differs between depressed and non-depressed persons. Cross-sectional data of 426 lonely and non-lonely older adults in the Netherlands Study of Depression in Older Persons (NESDO) were used. Linear regression analyses and multinominal logistic regression analyses were performed to examine the association between loneliness and morning cortisol, cortisol awakening response, diurnal slope and dexamethasone suppression ratio. In all analyses, confounders were introduced. In order to examine whether the association between loneliness and cortisol measures is different in depressed versus non-depressed persons, an interaction term for loneliness x depression diagnosis was tested. Cortisol output in the first hour after awakening and dexamethasone suppression ratio was lower in lonely participants. There were no significant interactions between loneliness and depression diagnosis in the association with the cortisol measures. This study is the first to investigate the association between the HPA-axis and loneliness in a large group of older adults aged 60-93years. We found lower cortisol output in the first hour after awakening and lower dexamethasone suppression ratio in lonely older depressed and non-depressed adults. Whether diminished cortisol output is the underlying mechanism that leads to health problems in lonely older adults is an interesting object for further study.


Tissue Doppler imaging for detecting onset of muscle activity.
Tissue Doppler imaging (TDI) is typically used to image and quantify tissue motion. We investigated whether this method would serve as a viable alternative to surface electromyography (EMG) in providing a reliable and valid measure of the onset of muscle activity. Ten healthy subjects performed maximal knee extension exercises at 0 degrees /s (isometric), 60 degrees /s, 120 degrees /s, 180 degrees /s, and 240 degrees /s (5 times each, on each side), using an isokinetic dynamometer. Simultaneous EMG and TDI velocity (superimposed on motion-mode ultrasound cine-loops) recordings were made from vastus lateralis. All tests were repeated 1 week later. There was a good correlation between the onset times determined with TDI velocity and EMG: r = 0.78 (day 1), and r = 0.80 (day 2) (each P < 0.001). The mean difference (and SD) in muscle onset time between the two methods (TDI minus EMG) was -20.3 +/- 31.0 ms (day 1) and -17.4 +/- 27.2 ms (day 2). TDI represents a reliable and valid measure of detecting onset of muscle activity. The mean difference between EMG and TDI onset times (approximately 20 ms) is likely explained by electromechanical delay. TDI represents a viable method for measuring the onset of muscle activity; it may offer a non-invasive alternative to fine-wire EMG for use with small or deep muscles.


Does amoxicillin improve outcomes in patients with purulent rhinorrhea? A pragmatic randomized double-blind controlled trial in family practice.
To compare the efficacy of amoxicillin vs placebo in patients with an acute upper respiratory tract infection and purulent rhinorrhea. Double-blind randomized placebo-controlled trial. The 416 patients included from 69 family practices were 12 years or older, presenting with acute upper respiratory complaints, and having a history of purulent rhinorrhea and no signs of complications of sinusitis. Therapy success (disappearance of symptoms that most greatly affected the patient's health) at day 10 and duration of general illness, pain, and purulent rhinorrhea. Therapy was successful in 35% of patients with amoxicillin and in 29% of patients with placebo (relative risk [RR] 1.14, 95% confidence interval [CI], 0.92-1.42). There was no effect on duration of general illness or pain. Duration of purulent rhinorrhea was shortened by amoxicillin (9 days vs 14 for clearing of purulent rhinorrhea in 75% of patients; P =.007). Diarrhea was more frequent with amoxicillin (29% vs 19%, RR 1.28, 95% CI, 1.05-1.57). No complications were reported. One patient (0.5%) receiving amoxicillin and 7 (3.4%) receiving placebo discontinued trial therapy because of exacerbation of symptoms (RR 0.25, 95% CI 0.04-1.56, P =.07). All 8 patients recovered with antibiotic therapy. Amoxicillin has a beneficial effect on purulent rhinorrhea caused by an acute infection of the nose or sinuses but not on general recovery. The practical implication is that all such patients, whatever the suspected diagnosis, can be safely treated with symptomatic therapy and instructed to return if symptoms worsen.


Optimal medical management in patients undergoing peripheral vascular interventions for chronic limb-threatening ischemia is associated with improved outcomes.
Optimizing medical management and risk factor modification are underused strategies in patients with chronic limb-threatening ischemia (CLTI), despite evidence of improved outcomes. The Vascular Quality Initiative (VQI) registry is a tool to improve quality of vascular care. In this study, we used the VQI to evaluate trends in medical management in patients with CLTI undergoing peripheral vascular interventions (PVI), and the impact of changes in management on overall survival (OS), amputation-free survival (AFS), and limb salvage (LS). Patients undergoing index PVI for CLTI between 2012 and 2016, with ≥24 months of follow-up were identified from the national VQI registry. Patient details including smoking status and medication use, OS, LS, and AFS were analyzed with linear-by-linear association, t test, and logistic regression. There were 12,370 PVI completed in 11,466 patients. There was a significant increase in infrapopliteal interventions (from 29.8% to 39.0%; P < .001) and PVI performed for tissue loss (from 59.1% to 66.5%; P < .001). The percentage of current smokers at time of PVI decreased (from 36.2% to 30.7%; P = .036). At discharge, statins were initiated in 25%, aspirin in 45%, and P2Y12 therapy in 58% of patients not receiving these medications before PVI. Over the course of follow-up, dual antiplatelet therapy (DAPT) (from 41.1% to 48.0%; P < .001), angiotensin-converting enzyme (ACE) inhibitor (from 46.2% to 51.3%; P < .001), and statin (from 70.4% to 77.5%; P < .001) use increased. Combined DAPT, ACE inhibitor and statin use increased from 33.6% to 39.6% (P ≤ .001). Significant improvement in 24-month OS and AFS was noted (OS, from 90.9% to 93.7% [P = .002]: AFS, from 81.2% to 83.1% [P = .046]), but not LS (from 89.6% to 89.0%; P = .83). Combined therapy with P2Y12 inhibitors, statins and ACE inhibitors was an independent predictor of improved OS (hazard ratio, 0.61; 95% confidence interval, 0.39-0.96; P = .034). DAPT was independent predictor of improved LS (hazard ratio, 0.83; 95% confidence interval, 0.79-0.87; P < .007). Antiplatelet, ACE inhibitor, and statin use increased over the study period and was associated with improved OS and AFS. LS trends did not change significantly over time, possibly owing to the inclusion of patients with a greater disease burden or inadequate medical management. Medical management, although improved, remained far from optimal and represents an area for continued development.


What is new in the Wolbachia/Dirofilaria interaction?
Presence of transovarially-transmitted endosymbiontic Wolbachia bacteria in Dirofilaria immitis, and in other filariae of man and animals, presents a new paradigm for our understanding of pathogenesis, treatment and diagnosis of filarial infections. Many of the basic biological characteristics of Wolbachia have yet to be elucidated, but the results obtained to date suggest that canine or the feline hosts can be exposed to D. immitis Wolbachia when larvae, or adult worms, are killed; when Wolbachia are expulsed, with the deposition of microfilariae, from the uterus of the females; and possibly through the excretory system of both male and female worms. The two organs that have the greatest potential of being affected by the Wolbachial metabolic products/antigens released from the adult worms are the lungs and the kidneys. Population of Wolbachia in D. immitis is polymorphic. The life cycle of Wolbachia is complex and may consist of two reproductive modes: multiplication of the bacillary forms by binary fission and by a more complex mode which resembles the Chlamydia-like cycle that consists of three morphological stages: a small, dense body, an intermediate stage with a dense inclusion, and a bacillary form which represents the final product of development and maturation of the small, dense body. The Chlamydia-like cycle offers a potential survival strategy for the Wolbachia by producing more progeny than multiplication by binary fission, and appears to be more active during growth and development of embryos and of the larvae. The small, dense bodies may be the infectious forms responsible for the spread of Wolbachia through the canalicular system, within the lateral chords of filariae. An amorphous membrane that lines the perienteric surface of the body wall may represent a physical barrier that limits the spread and movement of Wolbachia to the perienteric surface of the lateral chords. Wolbachia in D. immitis may also offer therapeutic and diagnostic possibilities. Elimination of Wolbachia by chemotherapy, and the suppressive effect of aposymbiosis on embryonic development of D. immitis, may have potential application for control (sterilization of female worms) and treatment of dirofilariasis. However, the three stages in the life cycle of Wolbachia may be antigenically different and each stage may have a different susceptibility to therapeutic agents. Persistence of dormant small, dense bodies after treatment would allow the Wolbachia to re-establish once the conditions for development would become favorable. Detection of Wolbachial antigens provides an attractive diagnostic possibility to identify D. immitis early in the infection. Further studies on Wolbachia of filariae, including those of D. immitis, will undoubtedly reveal additional information that can be applied towards treatment, diagnosis, and control of filarial infections.


Inflammation-related downregulation of zonula Occludens-1 in fetal membrane contributes to development of prelabor rupture of membranes.
The aim of this research was to study the alteration of three key tight junction proteins, to explore whether they were involved in the occurrence of prelabor rupture of the membrane (PROM) and to determine the correlation with intrauterine infection. A total of 208 women were enrolled between January 2015 to December 2018, including those with preterm and term PROM (PROM group) and normal pregnancies with intact fetal membrane (control group). We investigated the expressions of three key TJ molecules (Zonula occludens-1, Occludin and Claudin-5) in fetal membranes. The localization and expression of Zonula occludens-1 (ZO-1) in the amnion and chorion were studied by immunohistochemistry assay. The associations between ZO-1 expression levels and extent of inflammatory reactions as well as other obstetric characteristics were further studied using Spearman's rank correlation test and Mann-Whitney U test. ZO-1 was significantly downregulated in PROM group compared with control group (P < 0.001), whereas no significant changes were found for Occludin and Claudin-5. ZO-1 expression was reduced in the chorion and amnion layers in PROM group compared with that in control group, which showed a significant difference (P < 0.01), but no significant differences were observed between the preterm PROM and term PROM groups (P > 0.05). The expression levels of ZO-1 in the chorion were negatively correlated with the stage/grade of acute chorioamnionitis (P < 0.05). Our study suggests that inflammation-related downregulation of ZO-1 might be a pivotal event in the occurrence of PROM, which helps to clarify the mechanism of membrane rupture caused by infection.


Endovascular Therapy for Stroke Presenting Beyond 24 Hours: A Systematic Review and Meta-analysis.
Previous randomized clinical trials (RCTs) have supported the use of endovascular therapy (EVT) in late-window acute ischemic stroke (AIS; 6-24 hours). However, little is known about the use of EVT in very late-window AIS (>24 hours). To examine outcomes following EVT for very late-window AIS. A systematic review of the English language literature was conducted using Web of Science, Embase, Scopus, and PubMed to search for articles published from database inception until December 13, 2022. This systematic review and meta-analysis included published studies regarding very late-window AIS treated with EVT. Multiple reviewers screened studies, and an extensive manual search of the references of included articles was performed to identify any missed articles. Of the 1754 initially retrieved studies, 7 published between 2018 and 2023 were ultimately included. Data were extracted independently by multiple authors and evaluated for consensus. Data were pooled using a random-effects model. This study is reported per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guideline, and the protocol was prospectively registered with PROSPERO. The primary outcome of interest was functional independence, as assessed with 90-day modified Rankin Scale (mRS) scores (0-2). Secondary outcomes included thrombolysis in cerebral infarction (TICI) scores (2b-3 or 3), symptomatic intracranial hemorrhage (sICH), 90-day mortality, early neurological improvement (ENI), and early neurological deterioration (END). Frequencies and means were pooled with the corresponding 95% CIs. This review included 7 studies involving a total of 569 patients. The mean baseline National Institutes of Health Stroke Scale score was 13.6 (95% CI, 11.9-15.5), and the mean Alberta Stroke Program Early CT Score was 7.9 (95% CI, 7.2-8.7). The mean time from last known well and/or onset to puncture was 46.2 hours (95% CI, 32.4-65.9 hours). Frequencies for the primary and secondary outcomes were 32.0% (95% CI, 24.7%-40.2%) for functional independence (90-day mRS scores of 0-2) and 81.9% (95% CI, 78.5%-84.9%) for TICI scores of 2b to 3, 45.3% (95% CI, 36.6%-54.4%) for TICI scores of 3, 6.8% (95% CI, 4.3%-10.7%) for sICH, and 27.2% (95% CI, 22.9%-31.9%) for 90-day mortality. In addition, frequencies were 36.9% (95% CI, 26.4%-48.9%) for ENI and 14.3% (95% CI, 7.1%-26.7%) for END. In this review, EVT for very late-window AIS was associated with favorable frequencies of 90-day mRS scores of 0 to 2 and TICI scores of 2b to 3 and with low frequencies of 90-day mortality and sICH. These results suggest that EVT may be safe and associated with improved outcomes for very late-window AIS, although RCTs and prospective, comparative studies are needed to determine which patients may benefit from very late intervention.


The structure of bovine complement component 3 reveals the basis for thioester function.
The third component of complement (C3) is a 190 kDa glycoprotein essential for eliciting the complement response. The protein consists of two polypeptide chains (alpha and beta) held together with a single disulfide bridge. The beta-chain is composed of six MG domains, one of which is shared with the alpha-chain. The disulfide bridge connecting the chains is positioned in the shared MG domain. The alpha-chain consists of the anaphylatoxin domain, three MG domains, a CUB domain, an alpha(6)/alpha(6)-barrel domain and the C-terminal C345c domain. An internal thioester in the alpha-chain of C3 (present in C4 but not in C5) is cleaved during complement activation. This mediates covalent attachment of the activated C3b to immune complexes and invading microorganisms, thereby opsonizing the target. We present the structure of bovine C3 determined at 3 Angstroms resolution. The structure shows that the ester is buried deeply between the thioester domain and the properdin binding domain, in agreement with the human structure. This domain interface is broken upon activation, allowing nucleophile access. The structure of bovine C3 clearly demonstrates that the main chain around the thioester undergoes a helical transition upon activation. This rearrangement is proposed to be the basis for the high level of reactivity of the thioester group. A strictly conserved glutamate residue is suggested to function catalytically in thioester proteins. Structure-based design of inhibitors of C3 activation may target a conserved pocket between the alpha-chain and the beta-chain of C3, which appears essential for conformational changes in C3.


Segmental contribution to forces in vertical jump.
Performance of a vertical jump was analyzed with respect to the contribution of the different body segments to the forces acting on the whole body center of gravity. Both cinematograph and force-platform techniques were employed. The data disclosed that the take-off velocity in vertical jumps was caused by the different components as follows: knee extension 56%, plantar flexion 22%, trunk extension 10%, arm swing 10%, and head swing 2%. However, the average take-off velocity of the total performance (3.03 m/s) was only 76% from the theoretical maximum calculated from the segmental analyses. Optimal timing of the segmental performances was calculated to increase this "efficiency" to 84%. Great variance were observed among individuals in the total performance despite the similarities in utilization of the performance of individual segments.