Comparison of auto-contouring and hand-contouring of ultrasound images of the tongue surface.
Contours traced by trained phoneticians have been considered to be the most accurate way to identify the midsagittal tongue surface from ultrasound video frames. In this study, inter-measurer reliability was evaluated using measures that quantified both how closely human-placed contours approximated each other as well as how consistent measurers were in defining the start and end points of contours. High reliability across three measurers was found for all measures, consistent with treating contours placed by trained phoneticians as the 'gold standard.' However, due to the labour-intensive nature of hand-placing contours, automatic algorithms that detect the tongue surface are increasingly being used to extract tongue-surface data from ultrasound videos. Contours placed by six automatic algorithms (SLURP, EdgeTrak, EPCS, and three different configurations of the algorithm provided in Articulate Assistant Advanced) were compared to human-placed contours, with the same measures used to evaluate the consistency of the trained phoneticians. We found that contours defined by SLURP, EdgeTrak, and two of the AAA configurations closely matched the hand-placed contours along sections of the image where the algorithms and humans agreed that there was a discernible contour. All of the algorithms were much less reliable than humans in determining the anterior (tongue-tip) edge of tongue contours. Overall, the contours produced by SLURP, EdgeTrak, and AAA should be useable in a variety of clinical applications, subject to spot-checking. Additional practical considerations of these algorithms are also discussed.


Roxadustat: First Global Approval.
Roxadustat (Ai Rui Zhuo® in China) is an orally administered, small molecule hypoxia-inducible factor (HIF) prolyl hydroxylase inhibitor that is being developed by FibroGen, in collaboration with Astellas and AstraZeneca, for the treatment of anaemia in patients with dialysis-dependent chronic kidney disease (CKD), non-dialysis-dependent CKD and in patients with myelodysplastic syndromes. The drug reversibly binds to and inhibits HIF-prolyl hydroxylase enzymes that are responsible for the degradation of transcription factors in the HIF family under normal oxygen conditions. Inhibition of these enzymes reduces HIF breakdown and promotes HIF activity, leading to an increase in endogenous erythropoietin production, thereby enhancing erythropoiesis. It also reduces the expression of the peptide hormone hepcidin, improves iron availability and increases haemoglobin levels. HIF regulates the expression of genes in response to reduced oxygen levels, including genes required for erythropoiesis and iron metabolism. Roxadustat is approved in China and is under regulatory review in Japan for the treatment of anaemia in patients with dialysis-dependent CKD. Studies are underway to investigate long-term cardiovascular outcomes with roxadustat versus placebo (for non-dialysis-dependent CKD) or standard of care (for dialysis-dependent CKD). This article summarizes the milestones in the development of roxadustat leading to this first approval.


New superselective intra-arterial infusion via superficial temporal artery for cancer of the tongue and tumour tissue platinum concentration after carboplatin (CBDCA) infusion.
We developed a new technique of superselective intra-arterial chemotherapy for tongue cancer using a modified (1.35 mm) angiographic catheter. The catheter was confirmed to be inserted into the lingual artery by the new technique. We measured the platinum concentrations in resected tumour tissues after infusion of carboplatin (CBDCA) at 20 mg/m2 over 30 min from 30 min before tumour resection in 12 patients with cancer of the tongue (6 patients: superselective intra-arterial infusion; 6 patients: conventional intra-arterial infusion). The mean platinum concentration in tumour tissue was 10.5 +/- 1.2 micrograms/g wet, which was more than twice higher than, and significantly different from, 4.3 +/- 3.8 micrograms/g wet by the conventional intra-arterial infusion method. This new superselective intra-arterial infusion method allows direct infusion of the anticancer agent into the artery supplying the tumour and is expected to become a new therapeutic modality for cancer of the tongue.


[Effects of electric stimulation of the dentate nucleus of the cerebellum on neuronal activity of the centrum medianum of the optic thalamus].
Electrical stimulation of the cerebellar dentate nucleus elicits in neurons of the center median responses with either constant or altering latencies. The constant latencies ranged from 2-3 to 8-12 msec. Responses with altering latencies were more numerous and had the latencies up to 20 msec. In both responses with early and late components were recorded as well. Dentate stimulations induced "periods of inhibition" in CM neurons with leading duration of 50-100 msec. Synchronization of the SM unit activity during low-frequency stimulation was also revealed, in many cases it was preceded by the "periods of inhibition". Activity of 49% of reactive neurons during 1, 7-12, and 70-100/sec stimulations was facilitated, 31% depressed, and 20% had a mixed type of responses: facilitation on one frequency and depression on another. Immediate cessation of the effects after termination of stimulations was observed in 34% of neurons, while tonic influences were manifest in 66%.


Effects of type I/type II interferons and transforming growth factor-beta on B-cell differentiation and proliferation. Definition of costimulation and cytokine requirements for immunoglobulin synthesis and expression.
In this report, we sought to determine the role of selected type I interferons [interferon-alpha (IFN-alpha) and interferon-tau (IFN-tau)], IFN-gamma and transforming growth factor-beta (TGF-beta) in the regulation of bovine antibody responses. B cells were stimulated via CD40 in the presence or absence of B-cell receptor (BCR) cross-linking. IFN-alpha enhanced IgM, IgG2 and IgA responses but did not enhance IgG1 responses. BCR signalling alone was more effective at inducing IgG2 responses with IFN-alpha than dual cross-linking with CD40. Recombinant ovine IFN-tau was less effective at inducing IgG2 responses when compared with IFN-alpha, though IgA responses were similar in magnitude following BCR cross-linking. At higher concentrations, IFN-tau enhanced IgA responses greater than twofold over the levels observed with IFN-alpha. Previous studies have shown that addition of IFN-gamma to BCR or pokeweed mitogen-activated bovine B cells stimulates IgG2 production. However, following CD40 stimulation alone, IFN-gamma was relatively ineffective at stimulating high-rate synthesis of any non-IgM isotype. Dual cross-linking via CD40 and the BCR resulted in decreased synthesis of IgM with a concomitant increase in IgA and similar levels of IgG2 production to those obtained via the BCR alone. We also assessed the effects of endogenous and exogenous TGF-beta on immunoglobulin synthesis by bovine B cells. Exogenous TGF-beta stimulates both IgG2 and IgA production following CD40 and BCR cross-linking in the presence of IL-2. Blocking endogenous TGF-beta did not inhibit the up-regulation of IgG2 or IgA by interferons.


Adhesion of Campylobacter jejuni and Mycobacterium avium onto polyethylene terephtalate (PET) used for bottled waters.
Adhesion of the bacteria Campylobacter jejuni and Mycobacterium avium onto polyethylene terephtalate (PET), a polymer widely used within the bottled water industry was measured in two different groundwater solutions. From this, it was found that whilst the percentage cell adhesion for a given strain did not change between groundwater types, substantial variation was obtained between the two bacterial species tested: M. avium (10-30% adhered cells) and C. jejuni (1-2%) and no major variations were measured as a function of groundwater composition for a given strain. To explain this, the interfacial electro-hydrodynamic properties of the bacteria were investigated by microelectrophoresis, with the resultant data analysed on the basis of electrokinetic theory for soft biocolloidal particles. The results obtained showed that M. avium carries a significant volume charge density and that its peripheral layer exhibits limited hydrodynamic flow permeation compared to that of C. jejuni. It was also demonstrated that steric hindrance to flow penetration and the degree of hydrophobicity within/of the outer bacterial interface are larger for M. avium cells. In line with this, the larger amount of M. avium cells deposited onto PET substrates as compared to that of C. jejuni can be explained by hydrophobic attraction and chemical binding between hydrophobic PET and outer soft surface layer of the bacteria. Hydrophobicity of PET was addressed by combining contact angle analyses and force spectroscopy using CH(3)-terminated AFM tip.


Transgender Health in Endocrinology: Current Status of Endocrinology Fellowship Programs and Practicing Clinicians.
The transgender population continues to face challenges in accessing appropriate health care. Adequate training of endocrinologists in this area is a priority. Assess the status of transgender health care education in US endocrinology fellowship training programs and assess knowledge and practice of transgender health among practicing US endocrinologists. Mayo Clinic and the Endocrine Society developed and administered a Web-based anonymous survey to 104 endocrinology fellowship program directors (PDs; members of the Association of Program Directors in Endocrinology, Diabetes and Metabolism) and 6992 US medical doctor members of Endocrine Society. There were 54 total responses from 104 PDs (51.9%). Thirty-five of these 54 programs (72.2%) provide teaching on transgender health topics; however, 93.8% respondents indicated that fellowship training in this area is important. Barriers to provision of education included lack of faculty interest or experience. The most desired strategies to increase transgender-specific content included online training modules for trainees and faculty. Of 411 practicing clinician responders, almost 80% have treated a transgender patient, but 80.6% have never received training on care of transgender patients. Clinicians were very or somewhat confident in terms of definitions (77.1%), taking a history (63.3%), and prescribing hormones (64.8%); however, low confidence was reported outside of the hormonal realm. The most requested methods of education included online training modules and presentation of transgender topics at meetings. Confidence and competence in transgender health needs to increase among endocrinologists. Strategies include the development of online training modules, expansion of formal transgender curricula in fellowship programs, and presentations at national and international meetings.


Conventional Therapies Do Not Prolong the Prognosis of Hepatocellular Carcinoma Patients with Extrahepatic Metastases under Receiving of Tyrosine Kinase Inhibitors.
Conventional therapies, including chemoembolization and radiation therapy, have been expected to prolong the prognosis of hepatocellular carcinoma (HCC) patients with extrahepatic metastases, which remains poor. However, little information is available on the efficacy of conventional therapies for such patients under tyrosine kinase inhibitor (TKI) treatment. We retrospectively investigated 127 HCC patients with extrahepatic metastases, who were divided into the non-TKI (conventional therapies) and TKI groups and further subdivided into the TKI alone and TKI plus conventional therapies groups. Conventional therapies included transcatheter arterial chemoembolization, cisplatin-based chemotherapy, radiation, surgery, and UFT, an oral chemotherapeutic agent. The median of the overall survival (OS) of the 127 patients with extrahepatic metastases was 7.0 months. Meanwhile, the median OS of the TKI and non-TKI groups was 12.1 and 4.1 months, respectively. Imitating TKI after diagnosing metastases promoted a favorable increase in OS. Among the TKI group, the median OS in the TKI alone group was 8.9 months. TKI plus conventional therapies promoted no improvement in OS after adjusting for the patients' background data. TKI promoted a better OS in HCC patients with extrahepatic metastases compared to conventional therapies. However, TKI plus conventional therapies promoted no improvement in the prognosis of such patients.


Indigenous Adolescents' Suicidal Behaviors and Risk Factors: Evidence from the National Youth Risk Behavior Survey.
The study sought to examine indigenous adolescents' suicidal behaviors and risk factors in a nationally representative sample and explore potential causes of disparities. The study analyzed the 1991-2013 Youth Risk Behavior Survey National Combined Datasets. Suicidal behavior outcomes included suicide consideration, planning, and attempts during the past 12 months. Logit regressions were used to estimate the effects of potential suicide risk factors on these suicidal behaviors. The results showed that a high percentage of indigenous adolescents exhibited suicidal behaviors (consideration: 24.6 %; planning: 20.7 %; attempts: 16.2 %). After adjusting for risk factors, indigenous adolescents were no more likely than other adolescents to consider or plan for suicide (consideration: OR 1.18, CI 0.96-1.45, p = 0.125; planning: OR 1.16, CI 0.95-1.42, p = 0.156); however, they remained significantly more likely to have made suicide attempts (OR 1.73, CI 1.32-2.26, p < 0.001). Disparities in adolescent suicidal behaviors could be explained by the heterogeneous prevalence of suicidal risk factors across different races/ethnicities.


Involvement of the serotonergic system in the hypoactive and antinociceptive effects of nicotine in mice.
Pretreatment with the 5-HT2 antagonist ketanserin and the 5-HT1A/2 antagonist spiperone did not reduce nicotine-induced hypomotility in mice, nor did MDL 7222, a selective 5-HT3 antagonist. In addition, 8-OH-DPAT and buspirone, 5-HT1A agonists, had no significant effects on nicotine-induced hypomotility. However, 8-OH-DPAT and buspirone did reduce the antinociceptive effects of nicotine in a dose-dependent manner. 8-OH-DPAT blockade of this nicotine effect was reversed by spiperone, a 5-HT1A/2 antagonist. Nicotine's ED50 was increased from 1.00 mg/kg (0.90-1.68) to 2.00 mg/kg (1.6-2.55) and 2.66 (1.7-3.51) by buspirone and 8-OH-DPAT, respectively. Ketanserin, spiperone and MDL 7222 had no significant effect on nicotine-induced antinociception. The present data suggest an important role of 5-HT1A receptors in the modulation of antinociceptive actions of nicotine.


Chemical structure and in vitro antitumor activity of rhamnolipids from Pseudomonas aeruginosa BN10.
A newly isolated indigenous strain BN10 identified as Pseudomonas aeruginosa was found to produce glycolipid (i.e., rhamnolipid-type) biosurfactants. Two representative rhamnolipidic fractions, RL-1 and RL-2, were separated on silica gel columns and their chemical structure was elucidated by a combination of nuclear magnetic resonance and mass spectroscopy. Subsequently, their cytotoxic effect on cancer cell lines HL-60, BV-173, SKW-3, and JMSU-1 was investigated. RL-1 was superior in terms of potency, causing 50 % inhibition of cellular viability at lower concentrations, as compared to RL-2. Furthermore, the results from fluorescent staining analysis demonstrated that RL-1 inhibited proliferation of BV-173 pre-B human leukemia cells by induction of apoptotic cell death. These findings suggest that RL-1 could be of potential for application in biomedicine as a new and promising therapeutic agent.


Novel highly-active Ag/Bi dual nanoparticles-decorated BiOBr photocatalyst for efficient degradation of ibuprofen.
The surface plasmon resonance (SPR) effect of noble nanometals can be utilized to effectively improve the catalytic performance of semiconductor photocatalysts. In this work, a novel composite photocatalyst of BiOBr microspheres simultaneously decorated by Ag and Bi dual nanoparticles (NPs) has been successfully synthesized by the hydrothermal method plus one-step reduction method. And the morphology, structure, chemical composition and photoelectrical properties of this composite photocatalyst (Ag/Bi-BiOBr) were further characterized. Due to the SPR effect of Ag and Bi dual NPs, Ag/Bi-BiOBr showed the high light absorption with narrow band gap, as well as fast charge separation via metal-semiconductor heterojunction so as to realize an efficient degradation of ibuprofen (IBP) under simulated solar irradiation. Through the further optimization of the loading amounts of Ag and Bi dual NPs, the excellent photocatalytic activity in the Ag/Bi-BiOBr has been achieved that 92.3% of IBP was removed within 60 min, which is among the best results reported so far for IBP degradation via photocatalysis.


Restoration of respiratory muscle function following spinal cord injury. Review of electrical and magnetic stimulation techniques.
Respiratory complications are a leading cause of morbidity and mortality in patients with spinal cord injury. Several techniques, currently available or in development, have the capacity to restore respiratory muscle function allowing these patients to live more normal lives and hopefully reduce the incidence of respiratory complications. Bilateral phrenic nerve pacing, a clinically accepted technique to restore inspiratory muscle function, allows patients with ventilator dependent tetraplegia complete freedom from mechanical ventilation. Compared to mechanical ventilation, phrenic nerve pacing provides patients with increased mobility, improved speech, improved comfort level and reduction in health care costs. The results of clinical trials of laparoscopically placed intramuscular diaphragm electrodes suggest that diaphragm pacing can also be achieved without the need for a thoracotomy and associated long hospital stay, and without manipulation of the phrenic nerve which carries a risk of phrenic nerve injury. Other clinical trials are being performed to restore inspiratory intercostal function. In patients with only unilateral phrenic nerve function who are not candidates for phrenic nerve pacing, combined intercostal and unilateral diaphragm pacing appears to provide benefits similar to that of bilateral diaphragm pacing. Clinical trials are also underway to restore expiratory muscle function. Magnetic stimulation, surface stimulation and spinal cord stimulation of the expiratory muscles are promising techniques to restore an effective cough mechanism in this patient population. These techniques hold promise to reduce the incidence of respiratory tract infections, atelectasis and respiratory failure in patients with spinal cord injury and reduce the morbidity and mortality associated with these complications.


Administration of Oral Itraconazole Capsule with Whole Milk Shows Enhanced Efficacy As Supported by Scanning Electron Microscopy in a Child with Tinea Capitis Due to Microsporum canis.
Although diagnosis and treatment of tinea capitis in children are not difficult, treatment failures are still somewhat common. We report a case of pediatric tinea capitis cured using oral itraconazole administered with whole milk, after prior treatment failure when oral itraconazole was administered with water. This apparent enhanced efficacy in one individual was demonstrated using scanning electron microscopy.


Biochemical and physiologic consequences of carnitine palmityltransferase deficiency.
A patient with a long history of exercise-unduced pain developed myoglobinuria and respiratory failure following extensive exercise (football). Although muscle histochemistry was normal, tissue oxidation of 14C-labeled palmitate was decreased, and muscle carnitine palmityltransferase (CPT) activity was one-tenth of normal. During fasting, his creatine kinase (CK) rose from 127 mu/ml to 278 mu/ml and blood ketones failed to exhibit a normal rise. Triglycerides were normal, as was fatty-acid mobilization. Prolonged exercise resulted in an inordinately increased CK with only moderate elevations in lactate. Treatment with medium-chain triglycerides did not alter his symptoms or improve exercise performance. Pain on exercise is a common complaint, but the occurrence of myoglobinuria points to a defect of energy metabolism; Screening for defects of fat utilization may be accomplished by the prolonged-exercise test, invitro oxidation of 14C-labeled substrates, and prolonged fasting.


Cancer Chemoprevention with Korean Angelica: Active Compounds, Pharmacokinetics, and Human Translational Considerations.
Angelica gigas Nakai (AGN) is a major medicinal herb used in Korea and several other Asian countries. Traditionally, its dried root has been used to treat anemia, pain, infection and articular rheumatism, most often through boiling in water to prepare the dosage forms. AGN extract or AGN-containing herbal mixtures are sold in the US and globally as dietary supplements for pain killing, memory enhancement and post-menopausal symptom relief. Decursin (D) and its isomer decursinol angelate (DA) are the major chemicals in the alcoholic extracts of the root of AGN. The anti-cancer activity of AGN alcoholic extract has been established in a number of animal cancer models, including a transgenic model of prostate carcinogenesis. Cell culture structure-activity studies have uncovered distinct cellular and molecular effects of D and DA vs. their pyranocoumarin core decursinol (DOH) with respect to cancer cells and those associated with their microenvironment. Pharmacokinetic (PK) study by us and others in rodent models indicated that DOH is the major and rapid in vivo first-pass liver metabolite of D and DA. Cognizant of metabolic differences among rodents and humans, we carried out a first-in-human PK study of D/DA to inform the translational relevance of efficacy and mechanism studies with rodent models. The combined use of vigorous animal tests and human PK studies can provide stronger scientific rationale to inform design and execution of translational studies to move AGN toward evidence-based herbal medicine.


Obesity in young children and its relationship with diagnosis of asthma, vitamin D deficiency, iron deficiency, specific allergies and flat-footedness: A systematic review and meta-analysis.
There is evidence that a number of medical conditions and co-morbidities are associated with obesity in young children. This review explored whether there is evidence of associations with other conditions or co-morbidities. Observational studies of young children (mean age < 10 years) were identified using electronic searches of five databases (MEDLINE, Embase, CINAHL, AMED and SPORTDiscus). Of 27 028 studies screened, 41 (comprising 44 comparisons) met the inclusion criteria. These studies provided data on five distinct diseases/conditions: asthma (n = 16), vitamin D deficiency (n = 10), iron deficiency (n = 10), allergies (n = 4) and flat-footedness (n = 4). Thirty-two studies were appropriate for meta-analysis using random-effects models, and revealed obesity was significantly associated with having asthma (OR 1.5, 95% CI 1.3-1.7), vitamin D deficiency (OR 1.9, 95% CI 1.4-2.5) and iron deficiency (OR 2.1, 95% CI 1.4-3.2). Heterogeneity (I2 ) ranged from 57% to 61%. Narrative synthesis was conducted for all studies. There was no evidence of a consistent association between obesity in young children and eczema, dermatitis or rhinitis due to the low number of studies. However, there was an association with flat-footedness. These results have implications for health policy and practice and families. Further research leading to a greater understanding of the associations identified in this review is suggested.


Cost-effectively dissecting the genetic architecture of complex wool traits in rabbits by low-coverage sequencing.
Rabbit wool traits are important in fiber production and for model organism research on hair growth, but their genetic architecture remains obscure. In this study, we focused on wool characteristics in Angora rabbits, a breed well-known for the quality of its wool. Considering the cost to generate population-scale sequence data and the biased detection of variants using chip data, developing an effective genotyping strategy using low-coverage whole-genome sequencing (LCS) data is necessary to conduct genetic analyses. Different genotype imputation strategies (BaseVar + STITCH, Bcftools + Beagle4, and GATK + Beagle5), sequencing coverages (0.1X, 0.5X, 1.0X, 1.5X, and 2.0X), and sample sizes (100, 200, 300, 400, 500, and 600) were compared. Our results showed that using BaseVar + STITCH at a sequencing depth of 1.0X with a sample size larger than 300 resulted in the highest genotyping accuracy, with a genotype concordance higher than 98.8% and genotype accuracy higher than 0.97. We performed multivariate genome-wide association studies (GWAS), followed by conditional GWAS and estimation of the confidence intervals of quantitative trait loci (QTL) to investigate the genetic architecture of wool traits. Six QTL were detected, which explained 0.4 to 7.5% of the phenotypic variation. Gene-level mapping identified the fibroblast growth factor 10 (FGF10) gene as associated with fiber growth and diameter, which agrees with previous results from functional data analyses on the FGF gene family in other species, and is relevant for wool rabbit breeding. We suggest that LCS followed by imputation can be a cost-effective alternative to array and high-depth sequencing for assessing common variants. GWAS combined with LCS can identify new QTL and candidate genes that are associated with quantitative traits. This study provides a cost-effective and powerful method for investigating the genetic architecture of complex traits, which will be useful for genomic breeding applications.


Membrane transport and the antineoplastic action of nucleoside analogues.
This article summarizes recent studies characterizing nucleoside transport in mammalian cells and discusses evidence for a role of membrane transport in the pharmacologic action of nucleoside analogues. Some of these studies have also addressed the controversy concerning the multiplicity in transport routes. It seems clear that erythrocytes and, perhaps, some other mammalian cells possess a single, broadly specific system for transporting nucleosides. However, substantial evidence from valid studies discriminating between transport and intracellular metabolism suggests that at least some mammalian cells, including some tumor cells, possess more than a single system. Evidence now exists for a determining role of membrane transport of nucleoside analogues in their cytotoxicity and, in the case of one pyrimidine nucleoside (AraC), in therapeutic responsiveness in leukemic patients. There are also numerous examples of transport-related resistance to nucleoside analogues. Included in this article are the results of studies from the authors' laboratory pertaining to the therapeutic activity of the purine nucleoside, FAraA, in murine tumor models. These studies provide evidence for a determining role of both membrane transport and intracellular phosphorylation in the selective antitumor action of this agent against murine leukemia. Substantially increased transport inward of FAraA occurs at pharmacologically achievable concentrations of this agent in tumor cells as compared to drug-limiting, normal proliferative epithelium of the small intestine. The basis for this differential appears to be the kinetic duality of FAraA and adenosine transport inward found in tumor cells, but not in proliferative intestinal epithelial cells. Tumor cells have highly saturable (low influx Km) and poorly saturable (high influx Km) systems for adenosine transport, both of which are shared by FAraA. In contrast, proliferative epithelial cells have only a poorly saturable system for these substrates. If a similar kinetic duality of nucleoside transport is found in other tumor cells certain implications arise concerning the significance of the duality to neoplastic transformation.


The use of tranexamic acid in patients submitted to primary total hip arthroplasty: an evaluation of its impact in different administration protocols.
There is still no consensus as to the best form and dosages of use of tranexamic acid. The aim of this study was to evaluate the use of tranexamic acid in total hip arthroplasty, in order to reduce blood loss and decrease hemoglobin, taking into account different administration protocols. 42 patients submitted to total hip arthroplasty were divided into three groups. The study was prospective and randomized. Group 1 received a venous dose of tranexamic acid of 15 mg/kg, 20 min prior to bolus incision. Group 2 received an intravenous dose of 15 mg/kg bolus, 20 min before the incision, and an extra dose of 10 mg/kg by infusion pump during the duration of the surgical procedure. Patients in group 3 did not receive tranexamic acid, being the control group. Pre- and post-operative hemoglobin levels were measured and blood loss was measured 24 h after surgery using a Portovac drain. There was a significant reduction in the amount of bleeding through the Portovac drain and reduction in postoperative hemoglobin drop in patients who used tranexamic acid. There was neither significant difference in hemoglobin drop between groups 1 and 2, nor was there a need for hemotransfusion. Two patients in group 3 required blood transfusion. The findings demonstrated that the use of intravenous tranexamic acid in total hip arthroplasty reduced postoperative bleeding rates and significantly reduced serum hemoglobin without increasing thromboembolic effects. The bolus and bolus + infusion pump methods were shown to have a similar influence on hemoglobin and need for blood transfusion.


Age-dependent excretion of 3-hydroxy-3-methylglutaric acid (HMG) and ketone bodies in the urine of full-term and pre-term newborns.
Total ketone bodies and 3-hydroxy-3-methylglutaric acid (HMG) were determined in urines of full-term and pre-term newborns from the first day after birth to an age of 17. Significantly higher levels of the two catabolites were observed in the first two weeks of life of the pre-term newborns. A peak of excretion of both ketone bodies and HMG was found between the 7th and the 10th day after birth in both groups of newborns. After the 3rd month there is no significant difference between full-term and pre-term children as far as the excretion of the two analytes is concerned.


Correction of severe ptosis with a silicone implant suspensor: 22 years of experience.
Patients with severe ptosis caused by poor or absent function of the levator muscle but with good frontalis muscle excursion usually benefit from a frontalis sling procedure. This is currently carried out using organic or inorganic material to connect the upper eyelid to the frontalis muscle. The aim of this study was to evaluate retrospectively 112 patients who underwent frontalis sling procedures between 1989 and 2011 using a preformed silicone implant suspensor to correct severe ptosis. The results obtained using this technique were good or fair in 95.54 percent of the cases and poor in 4.46 percent of the cases. The authors discuss the results of the study and the cases in which the procedure should be indicated and highlight the advantages of the method. The availability of this low-cost sterile device, together with the fact that it is ready to use, requires less invasive surgery, saves time, and is sufficiently versatile to allow adjustments to be made at any time, makes the silicone eyelid sling an attractive choice for correcting ptosis. Therapeutic, IV.


Zinc- and oxidative property-dependent degradation of pro-caspase-1 and NLRP3 by ziram in mouse macrophages.
The NLRP3 inflammasome, composed of caspase-1, NLRP3 and ASC, plays a critical role in the clearance of microbial pathogens. Here, we found that the treatment of mouse macrophages with the zinc-containing dithiocarbamate ziram, a widely used fungicide in agriculture, caused a decrease in pro-caspase-1 and NLRP3 levels while not affecting ASC level. Ziram did not affect levels of pro-caspase-1 and NLRP3 mRNA, and no cleavage products of pro-caspase-1 including p10 subunit, which is an autocleavage product of pro-caspase-1, were detected, indicating that the decrease was associated with degradation of these proteins. The decrease was inhibited by SH-type antioxidants, N-acetyl cysteine, dithiothreitol and 2-mercaptoethanol, or a metal chelator EDTA but not by inhibitors of proteasome, lysosomes, autophagy and matrix metalloproteases. Thiram, a comparator for ziram that does not contain zinc, showed a weaker decrease in protein levels. Furthermore, the zinc-containing dithiocarbamate, zinc diethyldithiocarbamate, efficiently decreased the levels of pro-caspase-1 and NLRP3, whereas dithiocarbamates, dimethyldithiocarbamate and diethyldithiocarbamate without zinc, were less active. The organic zinc compound [3,4-toluenedithiolato(2-)]zinc hydrate did not induce a decrease in protein levels. Ziram also inhibited IL-1β production by macrophages in response to lipopolysaccharide and bacterial clearance during Salmonella infection of macrophage cells. These results indicate that ziram causes degradation of pro-caspase-1 and NLRP3 in a zinc- and oxidative property-dependent manner and suggest that exposure to ziram may compromise the clearance of microbial pathogens.


Long-term effects of hydralazine on ventilation and blood gas values in patients with chronic obstructive pulmonary disease and pulmonary hypertension.
Hydralazine has been shown to increase minute ventilation, alveolar ventilation, and arterial partial pressure of oxygen (PaO2) after short-term administration in patients with chronic obstructive pulmonary disease and pulmonary hypertension. The effects of orally administered hydralazine on ventilation and blood gas values were evaluated after six to 18 months of treatment in 10 male patients who had demonstrated an increase in minute ventilation after 24 hours of treatment. Hydralazine was administered at a dose of 200 mg per day during the initial 24 hours and in doses ranging from 40 mg per day to 200 mg per day during long-term therapy. Following 24 hours of treatment, a statistically significant increase in minute ventilation, alveolar ventilation, and PaO2, and reduction in arterial partial pressure of carbon dioxide (PaCO2) were seen both at rest and during exercise. After six to 18 months of hydralazine therapy, the increase in minute ventilation at rest persisted when compared with the pre-hydralazine value (15.3 +/- 1.3 liters/minute versus 13.1 +/- 1.1 liters/minute; p less than 0.05). The improvement in PaO2 at rest continued relative to the pre-hydralazine value (70.9 +/- 3.2 mm Hg versus 65.1 +/- 3.0 mm Hg, p less than 0.05) as did the PaO2 during exercise (60.3 +/- 3.5 mm Hg versus 53.3 +/- 2.0 mm Hg; p less than 0.05). The reduction in PaCO2 at rest persisted compared with the pre-hydralazine value (41.2 +/- 2.4 mm Hg versus 47.0 +/- 3.0 mm Hg; p less than 0.05) as did the PaCO2 during exercise (44.0 +/- 2.8 mm Hg versus 48.0 +/- 2.8 mm Hg; p less than 0.05). No significant changes in minute ventilation, PaO2, or PaCO2 were seen at rest or during exercise, when re-measured after six to 18 months in an age- and sex-matched control group of 10 patients who did not receive hydralazine. These results demonstrate that the short-term effects of hydralazine on ventilation and blood gas values persisted after six to 18 months of treatment in this sample of patients, some of whom received doses less than 200 mg per day.


Suppression of phrenic nerve activity as a potential predictor of imminent sudden unexpected death in epilepsy (SUDEP).
Sudden unexpected death in epilepsy (SUDEP) is a leading cause of death in patients with refractory epilepsy. Centrally-mediated respiratory dysfunction has been identified as one of the principal mechanisms responsible for SUDEP. Seizures generate a surge in adenosine release. Elevated adenosine levels suppress breathing. Insufficient metabolic clearance of a seizure-induced adenosine surge might be a precipitating factor in SUDEP. In order to deliver targeted therapies to prevent SUDEP, reliable biomarkers must be identified to enable prompt intervention. Because of the integral role of the phrenic nerve in breathing, we hypothesized that suppression of phrenic nerve activity could be utilized as predictive biomarker for imminent SUDEP. We used a rat model of kainic acid-induced seizures in combination with pharmacological suppression of metabolic adenosine clearance to trigger seizure-induced death in tracheostomized rats. Recordings of EEG, blood pressure, and phrenic nerve activity were made concomitant to the seizure. We found suppression of phrenic nerve burst frequency to 58.9% of baseline (p < 0.001, one-way ANOVA) which preceded seizure-induced death; importantly, irregularities of phrenic nerve activity were partly reversible by the adenosine receptor antagonist caffeine. Suppression of phrenic nerve activity may be a useful biomarker for imminent SUDEP. The ability to reliably detect the onset of SUDEP may be instrumental in the timely administration of potentially lifesaving interventions.


Ultrasonic effects on Dacus dorsalis.
Larvae of Dacus dorsalis (Hendel), the oriental fruit fly, were exposed to cw ultrasound at frequencies of 43, 123 and 447 kHz, with eggs also exposed to 43 and 447 kHz. Mortality as a function of ultrasonic intensity and duration of exposure was determined. At 43 kHz, no eggs or larvae were found to survive 0.5 W/cm2 or 0.2 W/cm2, respectively. Also at higher frequencies the larvae were more sensitive to ultrasound than were the eggs. A dramatic increase of lethal intensity with frequency suggests cavitation as the mechanism by which mortality is induced.


Soft tissue chondroma of the plantar foot in a 14-year-old boy: a case report.
Soft tissue chondroma is a rare benign tumor with a predilection for hands and feet. The incidence is only about 1.5% of all benign tumors and this neoplasm is rarely seen in the paediatric population. In this paper we report the case of a 14-year-old boy treated for a soft tissue chondroma located next to the left foot second metatarsal. A 14-year-old boy presented with a slowly growing plantar swelling of the left foot. The mass was solid, mobile, measuring 4 cm and located in soft tissues opposite of the left foot second metatarsal. Magnetic resonance imaging was performed and revealed a mass measuring 37 ∗ 27 mm with regular seams, on iso-signal T1 and hyposignal T2 without any skeletal connection. A marginal excision of the mass was performed and the postoperative time was uneventful. The clinical presentation of soft tissue chondroma is generally not specific which makes the diagnosis mostly challenging. Magnetic resonance imaging is the most performed paraclinical examination that allows a better analysis of the lesion. A surgical excision of the tumor is the treatment of choice. Soft tissue as a primary site of chondroma is a rarely reported localisation and this neoplasm should be kept in mind as a possible diagnosis face to any plantar mass in childhood.


Concentrations and leachability of chemical elements in estuarine sulfur-rich sediments, W. Finland.
Concentrations, distributions and mobility of chemical elements were investigated in reduced sulfur-rich estuarine sediments located in western Finland. The main objective was to determine the possible extent of metal leaching when dredged masses of these sulfur-rich sediments are dumped on the land and thus exposed to air. When dredged, the reduced sulfur in the sediments oxidises resulting in a lowering of pH, which in turn is expected to leach metals. The study area is an artificial lake claimed from the Botnian sea in 1962. In this lake, several mass-kills of fish have occurred, believed partly to be due to dredging. Two sediment samples (0-50 and 50-100 cm) were taken from 39 sampling points in the lake. These samples were leached in aqua regia (2:2:2 HNO3/HCl/H2O1) and analysed for Fe, Al, Mg, Ca, K, P, Na, Mn, Zn, Ba, V, Sr, Cr, Ni, Cu, Co, As, Pb, B, Mo and Cd with ICP-AES. Sulfur and organic carbon were analysed with Leco. In a controlled laboratory experiment, the sediments were allowed to oxidise for 1 year while moisturised with deionised water every month. The pH and conductivity were determined in the beginning of the experiment (reduced state) and in the end (oxidised state). In the supernatants in the oxidised states the amount of leached metals (Na, Al, Mn, Zn, Sr, Co, Ni, Cu, Cd, Cr, Pb, U, Li, Rb and As) were determined with ICP-MS. The sediments were found to contain low levels of toxic metals but, as expected, high concentrations of sulfur. In the experiment, pH was lowered (down to 3.0) and the conductivity increased in all samples due to oxidation and release of metal ions. The extent of leaching varied between 0.03% for As and 12.3% for Na. Critical pH values, at which high amounts of metals begin to leach, were obtained graphically. These values varied between 4.8 (Ni) and 3.3 (Cr). Not all elements were controlled by pH, e.g. Mn correlated well with its aqua regia leachable concentration. In a planned dredging operation in the area some 23,300 t (10,500 m3) (dry wt.) of sediments will be dredged. The amounts of metals likely to be leached, according to the results from this study, are as follows (kg): Al (1710), Mn (1230), Zn (59), Sr (39), Co (13), Ni (12), Cu (2) and less than 1 kg of Cd-Cr-As-Pb.


Proteomic and Immunological Identification of Diagnostic Antigens from Spirometra erinaceieuropaei Plerocercoid.
Human sparganosis is a food-borne parasitic disease caused by the plerocercoids of Spirometra species. Clinical diagnosis of sparganosis is crucial for effective treatment, thus it is important to identify sensitive and specific antigens of plerocercoids. The aim of the current study was to identify and characterize the immunogenic proteins of Spirometra erinaceieuropaei plerocercoids that were recognized by patient sera. Crude soluble extract of the plerocercoids were separated using 2-dimensional gel electrophoresis coupled with immunoblot and mass spectrometry analysis. Based on immunoblotting patterns and mass spectrometry results, 8 antigenic proteins were identified from the plerocercoid. Among the proteins, cysteine protease protein might be developed as an antigen for diagnosis of sparganosis.


The visual detection of threat: a cautionary tale.
The fear response hypothesis and the associated claim that humans have an evolutionary propensity to detect threats automatically in their immediate visual environment are critically appraised. This review focuses on reports of visual search experiments in which participants were tested with speeded oddball tasks in which the search displays contained photographic images of naturally occurring entities. In such tasks, participants have to judge whether all the images are from one category or whether the display contains a distinctive image. The evidence, which has been used to support the fear response hypothesis, is assessed against a series of concerns that relate to stimulus factors and stimulus selection. It is shown that when careful consideration is given to such methodological details, it becomes very difficult to defend the fear response hypothesis. It is concluded that, at present, the fear response hypothesis has no convincing empirical support, and it is urged that, in the future, researchers who wish to study visual threat detection take stimulus selection much more seriously.


An innovative index for separating the effects of temperature and precipitation on global vegetation change.
Temperature and precipitation changes are among the vital climatic driving forces of global vegetation change. However, the strategy to separate the relative contributions of these two critical climatic factors is still lacking. Here, we propose an index CRTP (contribution ratio of temperature and precipitation) to quantify their impacts on vegetation and then construct the CRTP classification prediction models based on climatic, geographic, and environmental factors using the Random Forest classifier. We find that precipitation predominates more than 70% of the significant vegetation change, mainly located in the low and middle latitudes during 2000-2021. Precipitation will remain the dominant climatic factor affecting global vegetation change in the coming six decades, whereas areas with temperature-dominated vegetation change will expand under higher radiative forcings. Hopefully, the promising index CRTP will be applied in the research about climatic attribution for regional vegetation degradation, monitoring drought-type conversion, and alarming the potential ecological risk.


Prehospital trauma care in Tehran: potential areas for improvement.
To evaluate the existing prehospital trauma care system in Tehran, Iran. This was a cross-sectional study in which all trauma-related dispatches of Tehran's emergency medical services (EMS) system were evaluated-during 18 randomly selected days from September 22,1997, to March 17,1998. Emergency medical technicians completed a checklist for all trauma cases, and the criteria for this performance evaluation were different partial time intervals in each dispatch and different procedures that had been done for the patients. The means of the "dispatch-beginning-to-scene-arrival interval" and "scene-arrival-to-scene-leaving interval" were 10 and 18 minutes, respectively (median: 10 minutes, range 0-55 minutes for the first; and median: 15 minutes, range 1-165 minutes for the second time interval). The mean of the "dispatch-beginning-to-hospital-arrival interval" was 45 minutes (median: 42 minutes, range: 5-170 minutes). Among advanced life support (ALS) procedures that include cardiac monitoring, intratracheal intubation, intravenous fluid therapy, nasogastric tube insertion, defibrillation, and tracheostomy, only intravenous fluid therapy had been administered for the patients. The patients, however, had received different kinds of basic life support (BLS) that include initial evaluation, bleeding control, oxygen administration, splinting, suction use, and cardiopulmonary resuscitation. The prolonged response, scene, and dispatch-beginning-to-hospital-arrival intervals compared with those for a developed EMS system indicate one potential area for improvement. Furthermore, significant differences in the field of prehospital care (conducting no ALS procedure) showed that ambulance equipment and training of EMS personnel are two other potential sites for improvement.


Freeze-drying of live virus vaccines: A review.
Freeze-drying is the preferred method for stabilizing live, attenuated virus vaccines. After decades of research on several aspects of the process like the stabilization and destabilization mechanisms of the live, attenuated viruses during freeze-drying, the optimal formulation components and process settings are still matter of research. The molecular complexity of live, attenuated viruses, the multiple destabilization pathways and the lack of analytical techniques allowing the measurement of physicochemical changes in the antigen's structure during and after freeze-drying mean that they form a particular lyophilization challenge. The purpose of this review is to overview the available information on the development of the freeze-drying process of live, attenuated virus vaccines, herewith focusing on the freezing and drying stresses the viruses can undergo during processing as well as on the mechanisms and strategies (formulation and process) that are used to stabilize them during freeze-drying.


Surgical resection following combination chemotherapy with oral S-1 and biweekly docetaxel in a patient with advanced gastric cancer and a prior coronary artery bypass graft with the right gastroepiploic artery: report of a case.
Cardiothoracic surgeons commonly use the internal thoracic artery (ITA) and the right gastroepiploic artery (RGEA) when performing a coronary artery bypass graft (CABG). Although the development of CABG surgery has enabled long-term survival in patients with coronary artery disease, malignant diseases are more common in older patients. We present the case of a 75-year-old man who had previously undergone CABG with the RGEA and had later developed advanced gastric cancer. We treated this patient with two courses of combination chemotherapy using S-1 and docetaxel as induction therapy, followed by successful tumor resection. Therefore, neoadjuvant chemotherapy was effective for preserving the CABG with the RGEA in a patient with advanced gastric cancer.


Population physiologically-based pharmacokinetic model incorporating lymphatic uptake for a subcutaneously administered pegylated peptide.
Physiologically-based pharmacokinetic (PBPK) models provide a rational mechanistic approach for predicting the time course of macromolecules in plasma. Population PBPK models for large molecules necessitate incorporation of lymphatic circulation to mechanistically account for biodistribution. Moreover, characterization of subcutaneous absorption requires consideration of the microvascular transit from the injection site to the systemic circulation. A PBPK model for a pegylated peptide conjugate, previously developed for primates, was modified to describe the lymphatic uptake in a population of humans by incorporation of interindividual variability in the lymphatic circulation and a unique lymphatic drainage compartment (LDC). The model was then used to simulate the time course of the drug in a population of humans and compared to the same drug administered to a group of human subjects participating in a first-in-human study. Organ, blood and lymph masses for the population were sampled from either normal or log-normal distributions. Blood flows were calculated for each organ based on mean organ perfusion per gram of organ tissue and lymphatic flow was set as a fixed fraction of blood flow. Interindividual variability in lymphatic volume was assumed to be similar to that of blood volume. The volume of the LDC was parameterzed as a fraction of the injection volume. Sensitivity analysis was performed to study uncertain parameters and distribution assumptions. The population generator was capable of simulating a virtual population incorporating the lymphatic circulation. Incorporation of a LDC resulted in similar line shape relative to the observed data and incorporation of anthropometric variability accounted for individual differences in the absorption and elimination phases across all dose cohorts. Line shape was sensitive to the inclusion of LDC while peak and elimination portions of the time course were influenced by the magnitude of variance assumed for blood volume and renal clearance, respectively. Lymphatic circulation can be incorporated into a population PBPK model assuming similar interindividual variability as observed for blood volume. Incorporation of an LDC, where the volume of this transit compartment is proportional to the SC injection volume may be an important mechanistic means of predicting the transit from the SC depot to the systemic circulation.


Facile synthesis of multifunctional silver nanoparticles using mangrove plant Excoecaria agallocha L. for its antibacterial, antioxidant and cytotoxic effects.
The current study describes a simple, rapid and eco-friendly method for the synthesis of silver nanoparticles (AgNPs) using Excoecaria agallocha (E. agallocha) leaf extract as stabilizer, bioreductant and capping agent. Synthesized AgNPs were characterized by UV-Visible spectroscopy (UV-Vis), X-ray diffraction (XRD), fourier transform infrared (FT-IR) spectroscopy, field emission scanning electron microscopy (FESEM) and energy dispersive X-ray spectroscopy (EDX). Generation of AgNPs was initially confirmed with the color change from yellow to dark brown which produces intense absorbance spectra at 440 nm in UV-Vis spectroscopy without any shifting of peaks. Further, XRD pattern confirms that the synthesized AgNPs was face centered cubic (fcc) crystalline in structure with an average size of 20 nm. On the other hand, FTIR spectrum reveals that the active metabolites like water soluble phenolic compounds, flavonoids, methylene groups, amides and carboxylate groups. These active biocompounds plays a vital role in the reduction of Ag+ into their nanoscale values, it also acts as a stabilizing and surface functionalization agent. FESEM micrographs of synthesized AgNPs shows spherical and hexagonal shaped well dispersed particles in the dimension ranging between 23 and 42 nm. EDAX confirms the presence of silver (Ag) as the major constituent element without any impurities; also substantiate the stability of generated AgNPs. The biomedical insights of nanoparticles (NPs) were assessed through radical scavenging and antibacterial properties. Additionally, synthesized AgNPs was also exhibits an excellent cytotoxic effect against human breast carcinoma cell lines (MCF-7). This study proves that synthesized AgNPs can be developed as a potential nano-drug formulation to combat pathogenic disease and also for the expansion of breast cancer therapy.


Mitochondrial DNA quality control in the female germline requires a unique programmed mitophagy.
Mitochondria have their own DNA (mtDNA), which is susceptible to the accumulation of disease-causing mutations. To prevent deleterious mutations from being inherited, the female germline has evolved a conserved quality control mechanism that remains poorly understood. Here, through a large-scale screen, we uncover a unique programmed germline mitophagy (PGM) that is essential for mtDNA quality control. We find that PGM is developmentally triggered as germ cells enter meiosis by inhibition of the target of rapamycin complex 1 (TORC1). We identify a role for the RNA-binding protein Ataxin-2 (Atx2) in coordinating the timing of PGM with meiosis. We show that PGM requires the mitophagy receptor BNIP3, mitochondrial fission and translation factors, and members of the Atg1 complex, but not the mitophagy factors PINK1 and Parkin. Additionally, we report several factors that are critical for germline mtDNA quality control and show that pharmacological manipulation of one of these factors promotes mtDNA quality control.


The combined toxicity and mechanism of multi-walled carbon nanotubes and nano copper oxide toward freshwater algae: Tetradesmus obliquus.
Nanoparticles (NPs) are widely used for their special physical properties and released into the natural environment. When two types of NPs exist in the same environment, the presence of one type of NP may affect the properties of the other type of NP. This study investigated the toxic effects of multi-walled carbon nanotubes (MWCNTs) and copper oxide nanoparticles (CuO NPs) on Tetradesmus obliquus. Both NPs had toxic effects on algae, and the toxic effects of MWCNTs were significantly stronger than CuO NPs which the 96-hr median effective concentration to algae were 33.8 and 169.2 mg/L, respectively. Oxidative stress and cell membrane damage were the main reasons for the toxicity of NPs to algae, and they were concentration-dependent, and the existence of CuO NPs in some groups reduced cell membrane damage caused by MWCNTs which may because that CuO NPs formed heteroaggregation with MWCNTs, reducing the contact of nanoparticles with cell membranes, then reducing physical damage. Scanning electron microscopy (SEM) and transmission electron microscope (TEM) results indicated cell damage, the heteroaggregation of MWCNTs-CuO NPs and obvious nanoparticles internalization. In some groups, the presence of CuO NPs significantly reduced reactive oxygen species (ROS) level induced by MWCNTs. However, for the highest concentration group, the ROS level was much higher than that of the two NPs alone treatment groups, which might be related to the high concentration of MWCNTs promoting the internalization of CuO NPs. MWCNTs and CuO NPs affected and interacted with each other, causing more complex toxic effects on aquatic organisms.


Reduction in seed set upon exposure to high night temperature during flowering in maize.
High temperature reduces crop production; however, little is known about the effects of high night temperature (HNT) on the development of male and female reproductive organs, pollination, kernel formation and grain yield in maize (Zea mays L.). Therefore, a temperature-controlled experiment was carried out using heat-sensitive maize hybrid and including three temperature treatments of 32/22°C (day/night; control), 32/26°C and 32/30°C during 14 consecutive days encompassing the flowering stage. When exposed to 30°C night temperature, grain yield and kernel number reduced by 23.8 and 25.1%, respectively, compared with the control. The decrease in grain yield was mainly because of the lower kernel number rather than change in kernel weight under HNT exposure around flowering. No significant differences in grain yield and kernel number were found between 22 and 26°C night temperatures. HNT had no significant effects on the onset of flowering time and anthesis-silking interval but significantly reduced time period of pollen shedding duration and pollen viability, and increased leaf night respiration. Different from high daytime temperature, HNT had no lasting effects on daytime leaf photosynthesis, biomass production and assimilate transportation. From the perspective of source-flow-sink relationship, the unchanged source and flow capacities during daytime are supposed to alleviate the adverse effects on sink strength caused by HNT compared with daytime heat stress. These new findings commendably filled the knowledge gaps concerning heat stress in maize.


A healthy mind in a healthy body: Effects of arteriosclerosis and other risk factors on cognitive aging and dementia.
In this review we start from the assumption that, to fully understand cognitive aging, it is important to embrace a holistic view, integrating changes in bodily, brain, and cognitive functions. This broad view can help explain individual differences in aging trajectories and could ultimately enable prevention and remediation strategies. As the title of this review suggests, we claim that there are not only indirect but also direct effects of various organ systems on the brain, creating cascades of phenomena that strongly contribute to age-related cognitive decline. Here we focus primarily on the cerebrovascular system, because of its direct effects on brain health and close connections with the development and progression of Alzheimer's Disease and other types of dementia. We start by reviewing the main cognitive changes that are often observed in normally aging older adults, as well as the brain systems that support them. Second, we provide a brief overview of the cerebrovascular system and its known effects on brain anatomy and function, with a focus on aging. Third, we review genetic and lifestyle risk factors that may affect the cerebrovascular system and ultimately contribute to cognitive decline. Lastly, we discuss this evidence, review limitations, and point out avenues for additional research and clinical intervention.


Enumerating the preventive youth health care workforce: Size, composition and regional variation in the Netherlands.
The progress in workforce planning in preventive youth health care (YHC) is hampered by a lack of data on the current workforce. This study aimed to enumerate the Dutch YHC workforce. To understand regional variations in workforce capacity we compared these with the workforce capacity and the number of children and indicators of YHC need per region. A national survey was conducted using online questionnaires based on WHO essential public health operations among all YHC workers. Respondents (n=3220) were recruited through organisations involved in YHC (participation: 88%). The YHC workforce is multi-disciplinary, 62% had >10 years working experience within YHC and only small regional variations in composition existed. The number of children per YHC professional varied between regions (range 688-1007). All essential public health operations were provided and could be clustered in an operational or policy profile. The operational profile prevailed in all regions. Regional differences in the number of children per YHC professional were unrelated to the indicators of YHC need. The essential public health operations provided by the YHC workforce and the regional variations in children per YHC professional were not in line with indicators of YHC needs, indicating room for improvement of YHC workforce planning. The methodology applied in this study is probably relevant for use in other countries.


Unusual BK polyomavirus-associated urologic malignancies in renal transplant recipients: Report of two cases and review of the literature.
Renal transplant recipients are at increased risk of developing urologic malignancies, some of which are associated with prolonged BK virus infection. We report two cases of BK virus-associated carcinoma with variant morphological patterns (clear cell adenocarcinoma of the bladder and micropapillary urothelial carcinoma of the pelvicaliceal system) arising in the urinary tract of renal transplant recipients. In both cases, the diagnosis was initially established on cytologic specimens: on urine cytology in one patient and on fine needle aspiration of an inguinal lymph node in the other patient. The unusual cytologic features of both cases (multiple morphologies in one patient and micropapillary pattern in the other), co-occurrence of decoy cells in the urine of one patient and the occurrence of these tumors in renal transplant recipients raised the possibility of BK polyomavirus-associated malignancy and led to confirmatory SV40 immunostains that were positive. These cases expand the morphologic variants of BK virus-associated urologic malignancies diagnosed in solid organ transplant patients. While differentiating BK virus-infected cells from malignant cells in urine cytology specimens is a diagnostic challenge, greater awareness of their possible co-existence is vital, as this could be the only chance for an early diagnosis.


Understanding readmission after primary total hip and knee arthroplasty: who's at risk?
Readmission has been cited as an important quality measure in the Patient Protection and Affordable Care Act. We queried an electronic database for all patients who underwent Total Hip Arthroplasty or Total Knee Arthroplasty at our institution from 2006 to 2010 and identified those readmitted within 90 days of surgery, reviewed their demographic and clinical data, and performed a multivariable logistic regression analysis to determine significant risk factors. The overall 90-day readmission rate was 7.8%. The most common readmission diagnoses were related to infection and procedure-related complications. An increased likelihood of readmission was found with coronary artery disease, diabetes, increased LOS, underweight status, obese status, age (over 80 or under 50), and Medicare. Procedure-related complications and wound complications accounted for more readmissions than any single medical complication.


Identification from skeletal remains.
The remains of a suspected case of homicide, found to be almost totally skeletal on exhumation, was dug out from a pit in a tract of marshy land in the deep south or Sri Lanka. No clothing or other identifying articles were found with the remains. During exhumation a distinct odour of kerosene oil was observed. Examination revealed that the major part of the skeleton was present, including the skull and lower jaw. Examination of these enabled an opinion to be given on the stature, sex and age of the deceased. The head hair found at exhumation showed evidence of burning. Two groups of injuries were found in the bones. One group was consistent with injuries caused during life and showing the characters of healing and moulding. Although medical records were not available, it was possible to obtain a description of the injuries from the court records as a doctor had given evidence on injuries sustained by the deceased years previously. The other group comprised of injuries that would have caused or contributed to death, or were post-mortem injuries inflicted for purposes of disposal. This case illustrates that personal identification may be established from old healed skeletal injuries.


New insights on pathophysiology, clinical manifestations, diagnosis, and treatment of sickle cell nephropathy.
Sickle cell nephropathy is one of the main chronic complications of sickle cell disease (SCD), the most common of the hematological hereditary disorders. Several studies have been performed since the first description of SCD 100 years ago to investigate the mechanisms of kidney involvement in this disease. It has been demonstrated that both glomerular and tubular compartments can be damaged as a direct consequence of SCD, including renal function loss, concentration and acidification deficits, and glomerulopathies. This article highlights the aspects of sickle cell nephropathy pathophysiology and clinical manifestations and describes the most recent advances in the diagnosis and treatment of this disorder.


A live attenuated RHΔompdcΔuprt mutant of Toxoplasma gondii induces strong protective immunity against toxoplasmosis in mice and cats.
Toxoplasma gondii is an obligate intracellular apicomplexan parasite and is responsible for zoonotic toxoplasmosis. It is essential to develop an effective anti-T. gondii vaccine for the control of toxoplasmosis, and this study is to explore the immunoprotective effects of a live attenuated vaccine in mice and cats. First, the ompdc and uprt genes of T. gondii were deleted through the CRISPR-Cas9 system. Then, the intracellular proliferation and virulence of this mutant strain were evaluated. Subsequently, the immune responses induced by this mutant in mice and cats were detected, including antibody titers, cytokine levels, and subsets of T lymphocytes. Finally, the immunoprotective effects were evaluated by challenge with tachyzoites of different strains in mice or cysts of the ME49 strain in cats. Furthermore, to discover the effective immune element against toxoplasmosis, passive immunizations were carried out. GraphPad Prism software was used to conduct the log-rank (Mantel-Cox) test, Student's t test and one-way ANOVA. The RHΔompdcΔuprt were constructed by the CRISPR-Cas9 system. Compared with the wild-type strain, the mutant notably reduced proliferation (P < 0.05). In addition, the mutant exhibited virulence attenuation in both murine (BALB/c and BALB/c-nu) and cat models. Notably, limited pathological changes were found in tissues from RHΔompdcΔuprt-injected mice. Furthermore, compared with nonimmunized group, high levels of IgG (IgG1 and IgG2a) antibodies and cytokines (IFN-γ, IL-4, IL-10, IL-2 and IL-12) in mice were detected by the mutant (P < 0.05). Remarkably, all RHΔompdcΔuprt-vaccinated mice survived a lethal challenge with RHΔku80 and ME49 and WH6 strains. The immunized sera and splenocytes, especially CD8+ T cells, could significantly extend (P < 0.05) the survival time of mice challenged with the RHΔku80 strain compared with naïve mice. In addition, compared with nonimmunized cats, cats immunized with the mutant produced high levels of antibodies and cytokines (P < 0.05), and notably decreased the shedding numbers of oocysts in feces (95.3%). The avirulent RHΔompdcΔuprt strain can provide strong anti-T. gondii immune responses, and is a promising candidate for developing a safe and effective live attenuated vaccine.


Affective computing in virtual reality: emotion recognition from brain and heartbeat dynamics using wearable sensors.
Affective Computing has emerged as an important field of study that aims to develop systems that can automatically recognize emotions. Up to the present, elicitation has been carried out with non-immersive stimuli. This study, on the other hand, aims to develop an emotion recognition system for affective states evoked through Immersive Virtual Environments. Four alternative virtual rooms were designed to elicit four possible arousal-valence combinations, as described in each quadrant of the Circumplex Model of Affects. An experiment involving the recording of the electroencephalography (EEG) and electrocardiography (ECG) of sixty participants was carried out. A set of features was extracted from these signals using various state-of-the-art metrics that quantify brain and cardiovascular linear and nonlinear dynamics, which were input into a Support Vector Machine classifier to predict the subject's arousal and valence perception. The model's accuracy was 75.00% along the arousal dimension and 71.21% along the valence dimension. Our findings validate the use of Immersive Virtual Environments to elicit and automatically recognize different emotional states from neural and cardiac dynamics; this development could have novel applications in fields as diverse as Architecture, Health, Education and Videogames.


Reliability and validity of a satisfaction questionnaire on virtual education in the coronavirus disease 2019 pandemic era aimed at cardiology faculty members.
In the coronavirus disease 2019 pandemic era, clinical programs and mandatory hands-on activities have been supplanted by remote teaching to maintain the fundamental capabilities of medical training and to furnish medical students with quality education. Nonetheless, the satisfaction of faculty members with this training method in the current pandemic has yet to be assessed. The aim of this study was to design a Persian questionnaire with appropriate validity and reliability on cardiology professors' satisfaction level with virtual education. In this cross-sectional study, a questionnaire was devised drawing upon scientific sources and Iranian medical educators' expertise. Seventeen faculty members in various specialties evaluated the questionnaire concerning face and content validity. Content validity was assessed through the calculation of the content validity ratio (CVR) (values >0.62 were considered acceptable) and the content validity index (CVI) (values >0.79 were considered acceptable), construct validity was evaluated through principal component factor analysis by the Kaiser-Meyer-Olkin (KMO) statistic and Bartlett's sphericity test, internal reliability was measured through the calculation of Cronbach's alpha coefficient, and consistency was appraised through the use of test-retest reliability at two different time points. The questionnaire had a reliability rate of 95%, indicating high internal validity. Concerning test-retest reliability, the intraclass correlation coefficient was 0.96 (P < 0.001), demonstrating relatively good stability. The CVI was 0.81, and the CVR was 0.85. The KMO measure of sampling adequacy was 0.954, indicating the acceptability of the degree of common variance among the all items. This Persian questionnaire on virtual education aimed at cardiology faculty members in the current pandemic with its low question count and appropriate domains had high reliability and validity. By knowing the level of professors' satisfaction with the new method of education, it is possible to take steps to better provide specialized medical education to cardiology residents.


The effects of nesiritide on renal function and diuretic responsiveness in acutely decompensated heart failure patients with renal dysfunction.
Strategies to preserve renal function and enhance diuretic responsiveness during therapy for heart failure (HF) are needed. We hypothesized that brain natriuretic peptide (nesiritide) added to standard HF therapy would preserve renal function and enhance diuretic responsiveness. Patients with HF with underlying renal dysfunction who were admitted with volume overload were randomized to standard therapy with nesiritide (2 mug/kg bolus; 0.01 mug/kg/min for 48 hours) or without nesiritide. Patients requiring intravenous vasodilator or inotropic therapy for rapid symptom relief were ineligible. In all patients, diuretics were administered according to a standardized dosing algorithm. Patients (n = 72) had a mean creatinine level of 1.75 +/- 0.59 mg/dL. Patients receiving nesiritide had a lesser increase in creatinine (P = .048) and blood urea nitrogen (P = .02), but a greater reduction in blood pressure (P < .01). Nesiritide did not enhance diuretic responsiveness (P = .57) but increased 3'5' cyclic guanosine monophosphate and decreased endothelin more (P < .05 for both). There were no differences in the change in atrial natriuretic peptide, N-terminal pro-brain natriuretic peptide, plasma renin activity, angiotensin II, and aldosterone between groups. When used as adjuvant "renal protective" therapy in patients with HF with renal dysfunction, the recommended dose of nesiritide reduced blood pressure, did not seem to worsen renal function, and suppressed endothelin but did not enhance diuretic responsiveness or prevent activation of the renin-angiotensin-aldosterone system.


The influence of acetylsalicylic acid and paracetamol on menstrual blood loss in women with and without an intrauterine contraceptive device.
The influence of ASA and paracetamol on menstural blood loss and on some hematologic parameters was investigated in 23 women without an IUD and 10 women with an IUD. Neither in women with normal nor in women with small defects in the hemostatic mechanism were statistically significant increases in menstrual blood losses observed during treatment with ASA or paracetamol when compared to placebo. There was no linear correlation between bleeding time and basal menstrual blood loss or between the blood losses induced by ASA and paracetamol and the bleeding time.


Hypoxia inducible factor 1 alpha regulates matrigel-induced endovascular differentiation under normoxia in a human extravillous trophoblast cell line.
Extravillous trophoblast (EVT) cells mimic endothelial cells during angiogenesis, inducing remodeling of the spiral arteries that increases blood flow toward the intravillous space. We have previously shown that signals involving the vascular endothelial growth factor (VEGF) axis are essential for endovascular differentiation through integrin signaling from the extracellular matrix: This was accomplished with use of the human EVT cell line TCL1, which shows tube formation that specifically recalls morphological changes in endothelial cells. To investigate endovascular differentiation in EVT further, we investigated the role of hypoxia inducible factor (HIF)1A, a subunit of HIF1 transcription factor that regulates not only adaptive responses to hypoxia, but also many cellular functions under normoxia, which was up-regulated in DNA microarray analysis during matrigel-induced endovascular differentiation under normoxia. HIF1A induces VEGF and ITGAV/ITGB3 aggregation, actions known to be important for cellular survival and endovascular differentiation in EVT. Inhibition of HIF1A up-regulation using siRNA introduction or chemical inhibition suppressed hypoxia-responsive element transcriptional activity, VEGF induction, ITGAV/ITGB3 aggregation accompanied by the inhibition of tube formation in TCL1 cells. These results suggest that HIF1A has a crucial role in regulating EVT behavior including matrigel-induced endovascular differentiation under normoxia.


Intestinal fate of dietary zinc and copper: Postprandial net fluxes of these trace elements in portal vein of pigs.
In pig, the assessment of bioavailability of dietary trace minerals with classical approaches such as relative bioavailability estimates or digestive tract balances have often generated inconsistent responses. In the present study, net portal-drained-viscera fluxes were monitored after a meal to assess intestinal absorption of zinc (Zn) or copper (Cu) according to dietary sources and levels of these trace minerals. Twelve pigs were surgically equipped with portal and carotid catheters and a portal ultrasonic flow probe for 12-h postprandial measurements. In a cross-over design, pigs received boluses of inorganic (I) or organic (O) dietary Cu and Zn at adequate (A, 20 and 200mg, respectively) or high (H, 40 and 400mg, respectively) level just before a 0.8-kg meal (semi-purified diet). Whatever treatments, arterial Zn increased by 72% at 45min postprandial and gradually declined thereafter (P<0.01). Arterial Zn were greater by 11% after O than I (P=0.02) and by 19% after H than A (P<0.01) meals. Net portal-drained-viscera fluxes of Zn during the first 240min postprandial were greater by 44% after O than I (P=0.10) and by 51% after H than A (P=0.07) meals. For Cu, portal-drained-viscera fluxes of Cu up to 240min postprandial were greater (P=0.03) after A than H meals. Those results suggest that Zn is absorbed rapidly, likely in the upper digestive tract of pigs and, whatever dietary levels, more efficiently after O meals. It appears that H levels of both Zn and Cu interfered with intestinal absorption of Cu and/or stimulate post-absorption enterocyte sequestration of this mineral.


Plasmodium falciparum msp-1 and msp-2 genetic diversity and multiplicity of infection in isolates from Congolese patients in the Republic of Congo.
With limited up to date data from the Republic of Congo, the aim of this study was to investigate allelic polymorphism of merozoite surface protein-1 (msp-1) and merozoite surface protein-2 (msp-2). This will help assess the genetic diversity and multiplicity of Plasmodium falciparum infection (MOI), from uncomplicated malaria individuals living in Brazzaville. Between March and October 2021, a cross-sectional study was carried out at a health center in Madibou District located in the south of Brazzaville. Plasmodium infection was diagnosed in human blood by microscopy and the block 2 of P. falciparum msp-1 and block 3 of msp-2 genes were genotyped by nested PCR. Overall, 57 genotypes with fragment sizes ranging from 110 to 410 bp were recorded for msp-1, among which 25, 21, and 11 genotypes identified for K1, MAD20, and RO33 allelic families respectively. RO33 (34.3%) and MAD20 (34.3%) allelic families were more frequent compared to K1 (31.4%) although the difference was not statistically significant. Also, 47 msp-2 genotypes were identified, including 26 FC27 genotypes type, and 21 genotypes belonging to the 3D7 allelic family. FC27 was more frequent (52.3%) compared to 3D7 (47.7%). The prevalence of the polyclonal infection was 90.0% while the MOI was 2.90 ± 1.0. The MOI and polyclonal infection were not significantly associated with the parasitaemia and anaemia. This study reveals a high genetic diversity and the trend of increasing MOI of P. falciparum isolates from the south of Brazzaville, compared to the reports from the same setting before the COVID-19 pandemic.


Patient Risk Factors Associated With 30- and 90-Day Readmission After Cervical Discectomy: A Nationwide Readmission Database Study.
This is a retrospective cohort study. The aim of this study was to assess the patient-level risk factors associated with 30- and 90-day unplanned readmissions following elective anterior cervical decompression and fusion (ACDF) or cervical disk arthroplasty (CDA). For cervical disk pathology, both ACDF and CDA are increasingly performed nationwide. However, relatively little is known about the adverse complications and rates of readmission for ACDF and CDA. A retrospective cohort study was performed using the Nationwide Readmission Database from the years 2013 to 2015. All patients undergoing either CDA or ACDF were identified using the International Classification of Diseases, Ninth Revision, Clinical Modification coding system. Unique patient linkage numbers were used to follow patients and to identify 30- and 31-90-day readmission rates. Patients were grouped by no readmission (Non-R), readmission within 30 days (30-R), and readmission within 31-90 days (90-R). There were a total of 13,093 index admissions with 856 (6.5%) readmissions [30-R: n=532 (4.0%); 90-R: n=324 (2.5%)]. Both overall length of stay and total cost were greater in the 30-R cohort compared with 90-R and Non-R cohorts. The most prevalent 30- and 90-day complications seen among the readmitted cohorts were infection, genitourinary complication, and device complication. On multivariate regression analysis, age, Medicaid status, medium and large hospital bed size, deficiency anemia, and any complication during index admission were independently associated with increased 30-day readmission. Whereas age, large hospital bed size, coagulopathy, and any complication during the initial hospitalization were independently associated with increased 90-day readmission. Our nationwide study identifies the 30- and 90-day readmission rates and several patient-related risk factors associated with unplanned readmission after common anterior cervical spine procedures. Level III.


Initial observations on the effect of corticosterone and inbred antibody competency in chickens on population development of the northern fowl mite.
Roosters from a line artificially selected for high initial antibody response to sheep red blood cells were more resistant to development of populations of Ornitbonyssus sylviarum (Canestrini and Fanzago) than were birds selected for low antibody response. Oral administration of corticosterone to test chickens at doses ranging from 10 to 40 ppm did not affect mite development. The steroid regimen was shown to reduce lymphocyte and testes mass as well as total weight gain. Postmortem measurements were not different for the 2 inbred lines. Analysis of data indicated that antibody competency alone probably was not responsbile for the observed differences in mite populations.


A stable core-shell metal-organic framework@covalent organic framework composite as solid-phase extraction adsorbent for selective enrichment and determination of flavonoids.
Hydrophobization and stability is crucial for the practical application of most metal-organic frameworks (MOFs) in extraction technique. In this study, a stable core-shell MOF@COF composite (NH2-MIL-101(Fe)@TAPB-FPBA-COF) was successfully prepared by Schiff base reaction and applied to solid-phase extraction (SPE) of hydrophobic flavonoids. Notably, the TAPB-FPBA-COF shell acts as a hydrophobic "shield", which not only improves the hydrophobicity and stability of hydrophilic NH2-MIL-101(Fe), but also makes the extraction efficiency of flavonoids from MOF@COF composite significantly higher than that of pure NH2-MIL-101(Fe) and TAPB-FPBA-COF. In addition, a sensitive analytical method with excellent linearities (0.1-500 ng mL-1, R2 ≥ 0.9967), low limits of detection (0.02-0.04 ng mL-1 for water; 0.04-0.07 ng mL-1 for grape juice; 0.06-0.08 ng mL-1 for honey), good repeatability (intra-day/inter-day precision are 1.86-5.37%/1.82-7.79%, respectively) and only 5 mg of adsorbent per cartridge was established by optimizing the SPE process combined with high performance liquid chromatography with ultraviolet-visible detector (HPLC-UV). Meanwhile, selectivity study and comparative experiments with the commercial C18 adsorbent showed that the MOF@COF adsorbent exhibited satisfactory extraction efficiency for flavonoids due to multiple interactions such as hydrogen bonding, hydrophobic, and π-π interactions. Finally, the good recoveries in grape juice (84.5-102.5%) and honey (87.5-104.6%) samples further validated the applicability of the proposed method in complex samples.


Autonomic nerves in experimental allergic neuritis in the rat.
After experimental allergic neuritis (EAN) was induced in 16 male Lewis rats with bovine peripheral myelin and adjuvants, peripheral nerves were examined morphologically at intervals of 12-21 days post inoculation (dpi). Signs of motor involvement were present in ten rats and were first elicited 12 dpi. They ranged from tail droop to complete lower limb paralysis. Autonomic nervous system (ANS) involvement was studied by contrasting morphological findings in the cervical sympathetic nerves (CSN), which are poorly myelinated and vagal nerves (VN) which contain numerous myelinated fibers in the endoneurium. Edema, perivenular infiltrates, and demyelination appeared in the VN of seven of nine neurologically affected rats, while the CSN showed edema and infiltrates in only one rat. ELISA assays were negative for anti-galactocerebroside antibody, and electron microscopy failed to show abnormalities of Schwann cells.


Clinical results of ab interno trabeculotomy using the trabectome for open-angle glaucoma: the Mayo Clinic series in Rochester, Minnesota.
To determine outcomes of ab interno trabeculotomy for treatment of open-angle glaucoma (OAG). Retrospective interventional single-surgeon, single-center case series. Data were collected from 246 patients undergoing ab interno trabeculotomy between September 1, 2006, and December 1, 2010, with 3 months' follow-up or longer. Kaplan-Meier analysis was performed using Criteria A (postoperative intraocular pressure [IOP] ≤21 mm Hg or ≥20% reduction from preoperative IOP) and Criteria B (IOP ≤18 mm Hg and ≥20% reduction in IOP). Failure included increased glaucoma medications or subsequent surgery. Failure risk factors were identified using Cox proportional hazards ratio (HR). Of 88 cases of ab interno trabeculotomy-only and 158 cases of ab interno trabeculotomy with cataract extraction, the retention rate was 70% for 1 year and 62% for 2 years. Preoperative mean IOP was 21.6 ± 8.6 mm Hg; the number of glaucoma medications was 3.1 ± 1.1. At 24 months postoperatively, mean IOP was reduced 29% to 15.3 ± 4.6 mm Hg (P < 0.001) and the number of glaucoma medications was reduced 38% to 1.9 ± 1.3 (P < 0.001) with a success rate of 62% (95% CI, 56%-68%) using Criteria A and 22% (95% CI, 16%-29%) using Criteria B. Failure risk factors using Criteria A included primary OAG (HR 3.14, P < 0.01, 95% CI, 1.91-5.17) and past argon laser trabeculoplasty (HR 1.81, P < 0.01, 95% CI, 1.18-2.77). Using Criteria B, the HR for pseudoexfoliative glaucoma was 0.43 (P < 0.01, 95% CI 0.27-0.67). Of the cases, 66 (26.8%) required subsequent surgery on an average of 10 months (2 days to 3.2 years) after ab interno trabeculotomy. For criteria involving IOP ≤18 mm Hg, the 24-month survival of ab interno trabeculotomy is low. This surgery is appropriate for patients requiring a target IOP of 21 mm Hg or above.


Adenosine-angiotensin II interactions. Part II. The role of adenosine in regulating angiotensin II-induced changes in heart rate and aldosterone release.
The purpose of the present study was to determine whether endogenous adenosine (ADO) participates in angiotensin II (AII)-induced decreases in heart rate (HR) and regulates AII-induced aldosterone (ALDO) release. To test these hypotheses we investigated: 1) the effects of ADO and AII on base-line HR and ALDO levels; 2) the effects of ADO on AII-induced bradycardia and AII-induced increases in ALDO levels; 3) the effects of ADO receptor antagonists [caffeine and/or 1,3-dipropyl-8-p-sulfophenylxanthine (DPSPX)] on AII-induced bradycardia and AII-induced increases in ALDO levels; and 4) the effects of ADO receptor hypersensitivity on AII-induced bradycardia. In the latter experiments, the animals were rendered hypersensitive to the bradycardic effects of ADO by administering caffeine for 1 week then abruptly withdrawing caffeine 18 hr before the experiment, i.e., caffeine withdrawal. Intravenous infusions of either ADO or AII decreased base-line HR and ADO reduced the bradycardic response to AII. Intravenous infusions of DPSPX attenuated and caffeine withdrawal potentiated AII-induced bradycardia without modifying AII-induced increases in arterial blood pressure. AII increased and ADO did not alter base-line plasma ALDO levels; however, ADO attenuated by 50% AII-induced increases in ALDO levels. Neither DPSPX nor caffeine altered the ability of AII to increase plasma ALDO levels. These results indicate that although ADO has the potential to modulate AII-induced increases in plasma ALDO concentrations, endogenous ADO does not regulate the effects of AII on plasma ALDO levels under the conditions of these studies. However, endogenous ADO, in some way, contributes substantially to AII-induced bradycardia.


Perceptions of, and Obstacles to, SARS-CoV-2 Vaccination Among Adults in Lebanon: Cross-sectional Online Survey.
The COVID-19 pandemic is an additional burden on Lebanon's fragmented health care system and adds to its ongoing political, economic, and refugee crises. Vaccination is an important means of reducing the impact of the pandemic. Our study's aims were to (1) assess the prevalences of intention to vaccinate and vaccine hesitancy in Lebanon; (2) determine how vaccine hesitancy in Lebanon varies by sociodemographic, economic, and geographic characteristics; and (3) understand individuals' motivations for vaccinating as well as concerns and obstacles to vaccination. We performed a cross-sectional study from January 29, 2021, to March 11, 2021, using an online questionnaire of open- and closed-ended questions in Arabic via convenience "snowball" sampling to assess the perceptions of adults residing in Lebanon. Of the 1185 adults who participated in the survey, 46.1% (95% CI: 43.2%-49.0%) intended to receive the SARS-CoV-2 vaccine when available to them, 19.0% (95% CI 16.8%-21.4%) indicated they would not, and 34.0% (95% CI 31.3%-36.8%) were unsure (with an additional 0.9% skipping this question). The most common reasons for hesitancy were concerns about safety, limited testing, side effects, and efficacy. Top motivations for vaccinating were to protect oneself, protect one's family and the public, and end the pandemic. Despite financial hardships in Lebanon, barriers to vaccine access were not frequently described as concerns. Established health care facilities, rather than new temporary vaccination centers, were most frequently selected as preferred vaccination sites. Vaccine hesitancy appears to be high in Lebanon. Disseminating clear, consistent, evidence-based safety and efficacy information on vaccines may help reduce vaccine hesitancy, especially among the large proportion of adults who appear to be unsure about (rather than opposed to) vaccination.


In vitro fitness of SARS-CoV-2 variants as assessed by competition experiments followed by ddRT-PCR and whole genome sequencing.
To develop a new method for reliable and rapid determination of the fitness of SARS-CoV-2 variants of concern. Competition experiments between two SARS-CoV-2 variants were performed in cells of the upper (nasal human airway epithelium) and lower (Calu-3 cells) respiratory tracts followed by quantification of variant ratios by droplet digital reverse transcription (ddRT)-PCR. In competition experiments, the delta variant outcompeted the alpha variant in both cells of the upper and lower respiratory tracts. A 50/50% mixture of delta and omicron variants indicated a predominance of omicron in the upper respiratory tract whereas delta predominated in the lower respiratory tract. There was no evidence of recombination events between variants in competition as assessed by whole gene sequencing. Differential replication kinetics were shown between variants of concern which may explain, at least partly, the emergence and disease severity associated with new SARS-CoV-2 variants.


Unraveling a Unique Encounter of Fusobacterium nucleatum With Empyema: A Case Report and Review of Literature.
We report a case of Fusobacterium nucleatum (F. nucleatum) empyema in a 34-year-old male with no significant past medical history or obvious risk factors who presented with shortness of breath and chest pain. His imaging showed complicated parapneumonic effusion which grew F. nucleatum. He was started on piperacillin-tazobactam. The patient's clinical condition deteriorated despite initial therapeutic efforts, leading to escalated antibiotic therapy and further investigations. The patient's subsequent clinical course included pigtail catheter placement with drainage of fluid requiring tpa and dornase alpha, leading to significant improvement and eventual discharge on oral amoxicillin-clavulanic acid.


Methods for studying primary cilia in heart tissue after ischemia-reperfusion injury.
Cardiovascular diseases are the leading cause of death and disability worldwide. After heart injury triggered by myocardial ischemia or myocardial infarction, extensive zones of tissue are damaged and some of the tissue dies by necrosis and/or apoptosis. The loss of contractile mass activates a series of biochemical mechanisms that allow, through cardiac remodeling, the replacement of the dysfunctional heart tissue by fibrotic material. Our previous studies have shown that primary cilia, non-motile antenna-like structures at the cell surface required for the activation of specific signaling pathways, are present in cardiac fibroblasts and required for cardiac fibrosis induced by ischemia/reperfusion (I/R) in mice. I/R-induced myocardial fibrosis promotes the enrichment of ciliated cardiac fibroblasts where the myocardial injury occurs. Given discussions about the existence of cilia in specific cardiac cell types, as well as the functional relevance of studying cilia-dependent signaling in cardiac fibrosis after I/R, here we describe our methods to evaluate the presence and roles of primary cilia in cardiac fibrosis after I/R in mice.


The influence of age and depth of dentin on bonding.
The purpose of this study was to investigate what influence the two variables of dentin depth and age may have on the tensile bond strengths of three bonding systems. Dentin discs prepared from human molars were divided into young and old, superficial and deep surfaces. Three bonding systems, Scotchbond Multi-purpose (3M Dental Products), Superbond D-liner (Sun Medical Co.), and Liner Bond II (Kuraray Co.) were the materials tested for tensile bond strength. In addition, the structural variation of the resin-impregnated, or hybrid, layer was compared among the two variables and three bonding systems. Tensile bond strengths exceeding 10 MPa were obtained for all materials. After ANOVA, an effect on tensile bond strength could be attributed to dentin age or depth for only Superbond D-liner used on deep-young dentin as compared with old-superficial dentin. All other group comparisons failed to show any variation between dentin depth or age. However, specimens bonded to deeper dentin showed slightly lower strengths. SEM observations showed thicker resin-impregnated layers for Scotchbond MP and Superbond D-liner compared with Liner Bond II. Liner Bond II exhibited a thinner and more diffuse resin-impregnated layer, believed to be due to the different dentin conditioning method. Dentin age or depth may not show as great an influence on bond strengths with the newer type of bonding systems. The resin-impregnated layer quality, rather than thickness, is believed to be the most important factor for obtaining high tensile bond strengths.


Trauma and envenoming caused by stingrays and other fish in a fishing community in Pontal do Paranapanema, state of São Paulo, Brazil: epidemiology, clinical aspects, and therapeutic and preventive measures.
Accidents caused by fish are common in inland fishing communities in Brazil, being work-related injuries in the majority of cases. These populations have no information on the mechanisms of trauma or envenoming. Through a questionnaire administered to fishermen, we obtained clinical and epidemiological data on accidents in Rosana, Pontal do Paranapanema, State of São Paulo, Brazil. These data were analyzed and converted into an easily understood prevention and treatment program for the colony. Thirty-nine fishermen replied to the survey. All of the patients had been hurt by fish. Of those mentioned, the yellow catfish (Pimelodus maculatus) was the main fish species associated with injuries, but others also caused trauma to the fishermen. Six fishermen had been envenomed by stingrays. Pain and ulcers were the main symptoms and were described as intolerable. Approximately half of those injured were treated using traditional folk remedies. The fishermen suffered multiple accidents with catfish, which are venomous and cause intense pain, as well as trauma due to other fish, such as surubins, traíras, freshwater croakers, and piranhas. Approximately 16% of those interviewed presented with envenomation from stingrays. Our data and previous experience in the area led to the creation of a pamphlet with clear language that can effectively help fishermen in the region, an area in need of health services and disease prevention. This initiative also applies to the whole La Plata River basin, which has similar fauna.


Alpha synuclein is present in Lewy bodies in sporadic Parkinson's disease.
A missense mutation in the human alpha synuclein gene was recently identified in some cases of familial Parkinson's disease (FPD). We have developed an antibody that recognizes the C-terminal 12 amino acids of the human alpha synuclein protein and have demonstrated that alpha synuclein is an abundant component of the Lewy bodies found within the degenerating neurons of patients with Parkinson's disease (PD). The presence of alpha synuclein in Lewy bodies of sporadic PD patients suggests a central role for alpha synuclein in the pathogenesis of PD.


M1 linear ubiquitination of LKB1 inhibits vascular endothelial cell injury in atherosclerosis through activation of AMPK.
Endothelial cell injury is confirmed to be the initial step in the atherosclerosis (AS) process. Here, we tried to elucidate the role of liver kinase B1 (LKB1) and adenosine phosphate protein kinase (AMPK) in modulating vascular endothelial cells (VECs) in AS. High-fat feed (HFD)-induced AS rat models were prepared and treated with AMPK activator A-769662 alone or combined with chloroquine. An analysis of VEC injury, inflammation response, and autophagy followed it. The M1 linear ubiquitination of LKB1 was assessed by co-immunoprecipitation. The interaction between LKB1 and AMPK was analyzed. Primary aortic VECs were isolated and induced by LPS to verify the effects of LKB1 and AMPK on VEC injury in AS. Activation of AMPK reduced the VEC injury and inflammatory response of VECs and promoted autophagy caused by AS. LKB1 could regulate the activation of AMPK in AS. M1 linear ubiquitination enhanced LKB1 activity and increased AMPK activation to protect against VEC injury in AS, which was validated by in vitro experiments. Our current study highlighted that M1 linear ubiquitination of LKB1 may induce the activation of LKB1 to activate AMPK, which inhibited VEC injury in AS.