Interleukin 4 and interferon-gamma secretion by antigen and mitogen-stimulated mononuclear cells in the hyper-IgE syndrome: no TH-2 cytokine pattern.
Enhanced production of TH-2 cytokines plays a key role in increased IgE production in allergic diseases. Reports about the cytokine profile secreted by peripheral blood mononuclear cells of patients with hyper-IgE syndrome, however, are controversial, suggesting alternative causes for increased IgE production in this syndrome. We wished to determine whether mononuclear cells from patients with hyper-IgE syndrome have a pattern of interleukin-4 (IL-4) and interferon-gamma (IFN-gamma) production characteristic of a predominance of TH-2 cells and whether the cytokine production pattern is constant over time. IL-4 and IFN-gamma secretion by peripheral blood mononuclear cells stimulated with phytohemagglutinin and D. pteronyssinus was measured by ELISA in culture supernatants. Patients with the hyper-IgE syndrome were evaluated 3 times at 4-week intervals and compared with asthmatic patients and normal subjects. In PHA-stimulated cultures, patients with hyper-IgE syndrome had an IL-4 and IFN-gamma secretion similar to that of controls, while asthmatic patients had increased IL-4 and decreased IFN-gamma production. Cultures stimulated with D. pteronyssinus showed a variable pattern of secretion for both cytokines. In allergic diseases, increased serum IgE level is the result of a TH-2 pattern of cytokine production, with high IL-4 and decreased IFN-gamma protein secretion. The increased serum IgE concentration typical of the hyper-IgE syndrome is likely the result of a different immunoregulatory process.


On the exponential Diophantine equation related to powers of two consecutive terms of Lucas sequences.
Let r ≥ 1 be an integer and U : = ( U n ) n ≥ 0 be the Lucas sequence given by U 0 = 0 , U 1 = 1 , and U n + 2 = r U n + 1 + U n , for all n ≥ 0 . In this paper, we show that there are no positive integers r ≥ 3 , x ≠ 2 , n ≥ 1 such that U n x + U n + 1 x is a member of U .


Direct measurement of energetic electrons coupling to an imploding low-adiabat inertial confinement fusion capsule.
We have imaged hard x-ray (>100 keV) bremsstrahlung emission from energetic electrons slowing in a plastic ablator shell during indirectly driven implosions at the National Ignition Facility. We measure 570 J in electrons with E>100 keV impinging on the fusion capsule under ignition drive conditions. This translates into an acceptable increase in the adiabat α, defined as the ratio of total deuterium-tritium fuel pressure to Fermi pressure, of 3.5%. The hard x-ray observables are consistent with detailed radiative-hydrodynamics simulations, including the sourcing and transport of these high energy electrons.


Ultrastructural correlates of functional relationships between nigral dopaminergic or cortical afferent fibers and neuropeptide Y-containing neurons in the rat striatum.
This study examines the ultrastructural relationships established by the nigrostriatal dopaminergic and the corticostriatal afferent fibers with neuropeptide Y (NPY)-containing neurons in the rat striatum. By means of dual immunolabeling procedures using peroxidase conjugated F(ab) fragments and 125I-labeled protein A, direct appositions and morphologically defined synaptic contacts of the symmetrical type were visualized between tyrosine hydroxylase-labeled nerve terminals and NPY-labeled neurons. After deafferentation of the striatum from its cortical input direct appositions and asymmetrical synaptic contacts were evidenced between characteristic degenerative boutons and NPY-positive neurons in the striatum. These results suggest that striatal NPY interneurons undergo direct influence from both nigrostriatal dopaminergic and corticostriatal neuronal systems.


Toll-like receptors, inflammation and cancer.
Toll-like receptors (TLRs) play a crucial role in the host defense against invading microorganisms by recognizing pathogen-associated molecular patterns (PAMPs). The anti-cancer effects of a number of microbial components, that have been used as adjuvants for the immunotherapy of cancers, are mediated through TLR signaling. However, cancer immunotherapy is not always successful because of the immunosuppression associated with cancer progression. Recently, a number of endogenous molecules have been reported to be ligands of TLRs. It has been suggested that the release of these putative endogenous ligands of TLRs during cancer progression may cause chronic inflammation leading to the recruitment of myeloid suppressor cells and down-regulation of T-cell and natural killer (NK) cell receptor zeta (zeta) chain resulting in T and NK cell dysfunction. However, the reported putative endogenous TLR ligands may have been contaminated with PAMPs. Further studies are necessary to define the existence of endogenous TLR ligands and their potential contribution to the immunosuppression in cancer.


Risk of myocardial infarction in Parkinson's disease: A systematic review and meta-analysis.
Previous studies investigating cardiovascular disorders in patients with Parkinson's disease (PD) showed heterogeneous results regarding whether there is a higher or lower risk of myocardial infarction (MI) in these patients compared to the general population. Because of the inconsistency in findings, herein the aim was to perform a systematic review and meta-analysis to investigate the risk of MI in patients with PD. A comprehensive literature search was performed using four databases, PubMed, Web of Science, Scopus and Embase, in June 2022. Peer-reviewed observational studies comprising case-controls, cohort, cross-sectional and longitudinal studies that reported MI in the PD population were included. After the screening, 20 studies with a total of 80,441 patients with PD and 802,857 controls were included in our qualitative and quantitative synthesis. The pooled estimated odds ratio for MI in PD patients compared to controls was 0.80 (95% confidence interval [CI] 0.56-1.05) which indicates that there is no association. The pooled prevalence of MI was 5% (95% CI 3%-7%) with a range of 1%-20% amongst patients with PD. The men (6%, 95% CI 1%-13%) and women (6%, 95% CI 1%-14%, Q = 29.27, I2 = 98.50%, p < 0.001) had similar MI prevalence. This comprehensive systematic review and meta-analysis provide compelling evidence that PD is associated with a reduced risk of MI. Whilst the exact mechanism underlying this association remains to be fully elucidated, it is clear that certain risk factors for cardiac events appear to be less present in PD patients, which may serve as a protective factor. However, given the reports of increased risk for cerebrovascular events in PD patients, it is possible that the major risk factors for MI and cardiovascular accidents in this population differ. These findings have important implications for clinical management and further research in this area is warranted.


Enhanced ammonia content in compost leachate processed by black soldier fly larvae.
Black soldier fly (BSF) larvae (Hermetia illucens), feeding on leachate from decaying vegetable and food scrap waste, increase ammonia (NH (4) (+) ) concentration five- to sixfold relative to leachate unprocessed by larvae. NH (4) (+) in larva-processed leachate reached levels as high as ∼100 mM. Most of this NH (4) (+) appears to have come from organic nitrogen within the frass produced by the larvae as they fed on leachate. In nitrate-enriched solutions, BSF larvae also facilitate dissimilatory nitrate reduction to ammonia. The markedly higher concentration of NH (4) (+) recovered in leachates processed with BSF larvae and concomitant diversion of nutrients into insect biomass (itself a valuable feedstock) indicate that the use of BSF larvae in processing leachate of decaying organic waste could be advantageous in offsetting capital and environmental costs incurred in composting.


Gender Dysphoria and Anorexia Nervosa Symptoms in Two Adolescents.
The co-occurrence of gender dysphoria and anorexia nervosa has been described in the scientific literature. This paper presents two adolescents with gender dysphoria and pathological eating behaviors and questions with longitudinal observations the clinical meaning of anorexia nervosa symptoms (e.g., restricting eating behaviors and fear of gaining weight) in adolescents with gender dysphoria. Both received psychological evaluations at different times: at first admission to the gender dysphoria clinic (T0) and 6 months after starting treatment with gonadotropin-releasing analogues (GnRHa; T1). In both cases, treatment with GnRHa not only improved psychological functioning, but also resolved pathological eating behaviors. In fact, both adolescents reported quick restoring of healthy food habits with restricting eating behaviors as well as intensive exercise no longer needed after treatment with GnRHa. Therefore, pathological eating behaviors (e.g., food avoidance and weight loss) could be assessed as a dysfunctional coping strategy adopted to gain control over a body developing in an unwanted direction and to block irreversible physical pubertal changes. This psychopathological conceptualization of pathological eating behaviors in adolescents with gender dysphoria stresses the importance of providing, in selected cases, early medical intervention such as pubertal suppression with GnRHa. Mental health professionals should therefore perform a specific and detailed assessment on gender identity within the evaluation of apparent eating disorders in adolescents. Restrictive eating behaviors as well as the intense fear of gaining weight or of becoming fat may, in fact, be considered secondary to a gender dysphoria diagnosis instead of anorexia nervosa symptoms.


Erratum to "Organic zinc supplementation in early-lactation dairy cows and its effects on zinc content and distribution in milk and cheese" (JDS Commun. 2:110-113).
[This corrects the article DOI: 10.3168/jdsc.2020-0070.].


Intensity of in vitro incorporation of 3H-melatonin in the thyroid gland of rabbits with pineal gland hypofunction.
The structure and hormonal activity of the thyroid gland and its capacity to bind (3)H-melatonin were studied in young adult Chinchilla rabbits with pineal gland hypofunction induced by 2-month exposure to constant illumination. After 2 months of constant exposure to light, the experimental animals exhibited signs of the so-called "latent hypothyroidism" and more intense binding of (3)H-melatonin by the thyroid gland. This fact indicated intactness of its receptor system underlying the possibility of restoring activity of the thyroid gland under conditions of melatonin replacement therapy in hypothyroidism induced by chronic melatonin insufficiency.


Biofilms and effective porosity of hernia mesh: are they silent assassins?
The purpose of this paper is to communicate two new concepts with the potential to cause major morbidity in hernia repair, effective porosity and biofilm. These 2 concepts are interrelated and have the potential to result in mesh-related complications. Effective porosity is a term well described in the textile industry. It is best defined as the changes to pore morphology after implantation of mesh in situ. It is heavily dependent on mesh construct and repair technique and has the potential to impact hernia repair by reducing mesh tissue integration and promoting fibrosis. Bacterial biofilm is a well-described condition affecting prosthesis in breast and join replacement surgery with catastrophic consequences. There is a paucity of information on bacterial biofilm in mesh hernia repair. We speculate that bacterial biofilm has the potential to reduce the effective porosity of mesh, resulting in non-suppurative mesh-related complications as well as the potential for late suppurative infections. We describe the aetiology, pathogenesis, diagnosis, treatment and preventative measures to address bacterial biofilm in mesh hernia surgery. Hernia surgeons should be familiar with these two new concepts which have the potential to cause major morbidity in hernia repair and know how to address them. Ovid Medline and PubMed were searched for communications on "effective porosity" and "bacterial biofilm". There is a paucity of information in the literature of these conditions and their impact on outcomes following mesh hernia repair. We discuss the two concepts of effective porosity and biofilm and propose potential measures to reduce mesh-related complications. This includes choosing mesh with superior mesh construct and technical nuances in implanting mesh to improve effective porosity. Furthermore, measures to reduce bacterial biofilm and its consequences are suggested.


Effect of ascorbic acid on oxygen consumption, glycolysis and lipid metabolism of diabetic rat testis. Ascorbic acid and diabetes, I.
Alloxan diabetes caused a marked stimulation of endogenous oxygen uptake by rat testis tissues. However, the oxygen uptake in the presence of added glucose or pyruvate as substrate was significantly reduced. The ability of the testis tissues to utilize these substrates and to produce lactate was significantly inhibited in the diabetic animals. Alloxan diabetes also increased the levels of cholesterol, cholesterol esters, non-esterified fatty acids, triglycerides and phospholipids in rat testis tissues. Treatment of the diabetic rats with ascorbic acid caused more or less a normalization of all the parameters tested.


Donafenib in Progressive Locally Advanced or Metastatic Radioactive Iodine-Refractory Differentiated Thyroid Cancer: Results of a Randomized, Multicenter Phase II Trial.
Background: An unmet need for more effective and affordable kinase inhibitors remains in patients with progressive radioactive iodine-refractory differentiated thyroid cancer (RAIR-DTC) in China, where only sorafenib is approved for this indication. This study evaluated the 24-week objective response rate (ORR) to donafenib-a new, domestic multikinase inhibitor-in the treatment of locally advanced or metastatic RAIR-DTC in patients with measurable lesions. Two dose regimens (300 mg twice daily vs. 200 mg twice daily) were used to determine its optimal dosage and safety for further phase III studies. Methods: This study was a randomized, open-label, multicenter phase II trial. Thirty-five adult RAIR-DTC patients with at least one measurable targeted lesion according to RECIST 1.1 were enrolled from 12 centers in China and randomized to receive either 200 mg (17 patients) or 300 mg (18 patients) of donafenib orally twice daily for 24 weeks. The primary endpoint was ORR, and the secondary endpoints included progression-free survival (PFS) among others. Additionally, biochemical (serum thyroglobulin) and structural (total tumor diameter [TTD]) responses were assessed, change (ΔTTD) rates were calculated, and safety was evaluated. Results: The ORRs for the 200- and 300-mg arms were 12.5% and 13.33% (p = 1.000), respectively. The 300-mg arm had a nonsignificant, longer median PFS than the 200-mg arm (14.98 months vs. 9.44 months) (p = 0.351). There was a trend toward more tumor shrinkage in the 300-mg arm compared with the 200-mg arm (average ΔTTD rate -0.52 ± 0.71 vs. -0.04 ± 1.55 mm/month, p = 0.103). Most treatment-related adverse events (AEs) in both arms were grades 1-2. The most common grade 3 treatment-related AEs in both arms were palmar-plantar erythrodysesthesia and hypertension; the sum occurrence rates of these two AEs in the 200-mg and 300-mg arms were 11.43% and 22.86%, respectively. Conclusions: Donafenib was generally well tolerated. Both donafenib regimens demonstrated similar efficacy in terms of the ORR in locally advanced or metastatic RAIR-DTC. The results warrant further studies on donafenib as a new, feasible treatment option for RAIR-DTC patients. Clinical Trials.gov IDs: NCT02870569; CTR20160220.


Sex non-specific growth charts and potential clinical implications in the care of transgender youth.
The Centers for Disease Control and Prevention (CDC) and World Health Organization (WHO) created separate growth charts for girls and boys because growth patterns and rates differ between sexes. However, scenarios exist in which this dichotomizing "girls versus boys" approach may not be ideal, including the care of non-binary youth or transgender youth undergoing transitions consistent with their gender identity. There is therefore a need for growth charts that age smooth differences in pubertal timing between sexes to determine how youth are growing as "children" versus "girls or boys" (e.g., age- and sex-neutral, compared to age- and sex-specific, growth charts). Employing similar statistical techniques and datasets used to create the CDC 2000 growth charts, we developed age-adjusted, sex non-specific growth charts for height, weight, and body mass index (BMI), and z-score calculators for these parameters. Specifically, these were created using anthropometric data from five US cross-sectional studies including National Health Examination Surveys II-III and National Health and Nutrition Examination Surveys I-III. To illustrate contemporary clinical practice, we overlaid our charts on CDC 2000 girls and boys growth charts. 39,119 youth 2-20 years old (49.5% female; 66.7% non-Hispanic White; 21.7% non-Hispanic Black) were included in the development of our growth charts, reference ranges, and z-score calculators. Respective curves were largely superimposable through around 10 years of age after which, coinciding with pubertal onset timing, differences became more apparent. We conclude that age-adjusted, sex non-specific growth charts may be used in clinical situations such as transgender youth in which standard "girls versus boys" growth charts are not ideal. Until longitudinal auxological data are available in these populations, our growth charts may help to assess a transgender youth's growth trajectory and weight classification, and expectations surrounding these.


Isolation and characterization of phytotoxic compounds produced by Streptomyces sp. AMC 23 from red mangrove (Rhizophora mangle).
Natural products produced by microorganisms have been utilized as sources of new drugs possessing a wide range of agrochemical and pharmacological activities. During our research on Actinomycetes from Brazilian mangroves, the ethyl acetate extract of Streptomyces sp. AMC 23 isolated from the red mangrove (Rhizophora mangle) rhizosphere produced a highly active compound against the microalga Chlorella vulgaris, often used to assess the phytotoxic activity. As a result, the bioassay-guided fractionation led to the isolation of the mixture of the known compounds bafilomycin B1 and bafilomycin B2. The chemical structures of bafilomycin B1 and bafilomycin B2 were established based on their spectroscopic data by infrared (IR), mass spectrometry (MS), (1)H nuclear magnetic resonance (NMR), gradient-enhanced heteronuclear multiple quantum coherence (gHMQC), and gradient-enhanced heteronuclear multiple-bond connectivity (gHMBC) as well as comparison with reference data from the literature. Moreover, it was also possible to identify other bafilomycins using non-chromatographic-dependent techniques (Tandem mass spectrometry). Additionally, this is the first report on the phytotoxic activity of bafilomycin B1.


Modification of the 8th American Joint Committee on Cancer staging system for gallbladder carcinoma to improve prognostic precision.
The 8th edition of the American Joint Committee on Cancer (AJCC) staging system for gallbladder carcinoma (GBC) came into force since 2018. However, the prognostic precision of this staging system has not been properly assessed. This study aimed to evaluate the latest staging system and suggest modifications to improve its prognostic precision. Data of patients with GBC was included from the Surveillance, Epidemiology and End Results (SEER) database (2004-2015) and multicenter database (2010-2017). Baseline clinicopathologic characteristics were recorded including age, sex, race, grade, T category, N category, M category and stage. The Kaplan-Meier method was used to plot survival functions. The prediction power of the AJCC 8th edition and its modified version were evaluated using the concordance index (C-index). A total of 2779 GBC patients were included in the SEER database and 591 were collected from multicenter database. While no significant difference in survival of patients was observed between stages IVA and IVB using the 8th AJCC staging system (p > 0.05), the prognosis of stage IIIA showed a slightly better outcome than stage IIIB (p = 0.046) in the SEER database. In the multicenter database, there was no significant difference between stage IIIA and stage IIIB (p > 0.05). Similarly, no significant difference in the survival of patients between stages IIIA and IIIB was observed when M0 patients with at least 6 lymph nodes (LNs) were analyzed (p > 0.05) for both SEER and multicenter database. On the other hand, a modified staging system was able to stratify patients from stage IIIA, stage IIIB and stage IV (p < 0.001). For the SEER database, the C-indexes of 8th AJCC staging system and that of its modified version were 0.709 and 0.742, respectively. For the multicenter database, the C-index of 8th AJCC staging system and that of our modified version were 0.635 and 0.679, respectively. The modified 8th staging system proposed in this study can improve the prognostic precision of the 8th AJCC staging system for GBC. We therefore suggest including these modifications in the next update of AJCC staging system for GBC.


Aberrant dendritic cell function conditions Th2-cell polarization in allergic rhinitis.
Myeloid (m) and plasmacytoid (p) dendritic cells (DCs) regulate immune responses to allergens, whereas it remains unclear whether abnormal DC function characterizes patients with airway allergy and whether putative dysfunction exists only in target organs. To evaluate DC function from patients with allergic rhinitis (AR), we assessed nasal, cutaneous as well as blood DCs after in vivo and in vitro allergen challenge, respectively. DCs were immunostained in nasal and skin tissues, and cytokine expression was assessed by dual immunofluorescence. Cytokine production and regulation of cocultured peripheral CD4+ T cells were assayed by ELISA. In AR patients, local allergen challenge resulted in increases in pDC and mDC numbers at 8 h in the nasal mucosa and at 8-48 h in the skin. Defects in IL-10 and IFN-α were observed in both organs from AR. Blood mDCs from AR exhibited reduced IL-10 and IL-12 expression. The capacity of activated pDCs from AR to produce IFN-α and to trigger IL-10 by allogeneic CD4(+) T cells was diminished, whereas mDCs from these patients supported Th2- and Th17-cell differentiation. In allergic rhinitis, DCs are altered not only locally but also in the systemic circulation. mDCs and pDCs increased in airway and skin tissues exposed to the allergen and displayed reduced production of IL-10 and 'type 1 signals' (IL-12, IFN-α) both locally and in blood. Functional studies showed that this results in preferential Th2/Th17-cell polarization and impaired generation by blood DCs of IL-10+ T cells, linking systemic DC dysfunction and biased T-cell responses.


Antiepileptic drugs and vitamin D supplementation.
The incidence of biochemical signs of vitamin D deficiency and the effects of vitamin D supplementation were investigated in 83 children and 95 adults on chronic antiepileptic therapy and 40 mentally retarded controls living under comparable conditions. Low 25-hydroxyvitamin D and serum calcium, and elevated immunoreactive parathyroid hormone and alkaline phosphatase was a common finding in all groups, but in patients on antiepileptic drugs, signs of vitamin D deficiency were recorded more frequently. Supplementation of 125 microgram or 250 microgram vitamin D3 per week for 9 months normalized the laboratory findings in most patients; the effect of 37.5 microgram/week only slightly exceeded the influences of season observed in the controls and in epileptic patients without vitamin D. It is suggested that a dose between 37.5 and 125 microgram vitamin D3/week might be most suitable to avoid biochemical signs of vitamin D deficiency in children and adults on antiepileptic drugs.


Motives for competitive sports participation in masters track and field athletes: Impact of sociodemographic factors and competitive background.
Masters athletes due to their lifelong engagement in sport represent a unique group to study motivation for regular physical activity, but there is less scientific data on the sport motives in masters athletes. Therefore, the aim of this study was to evaluate the association of age, sex, education, nationality, competitive background and training amount with sport motives of masters track and field athletes. 811 (254 women) athletes aged 35-89 years participated in European Veterans Athletics Championships in the year of 2000. Sport motives were assessed with a questionnaire and categorized into1) well-being, 2) competitive and performance 3) health and fitness motives. Men considered health and fitness motives more important than women (p = 0.022). Over 65-year-old athletes considered health and fitness motives more important than the youngest, 35-49-year age group (p<0.001). Education was not associated with sport motives, while motives varied significantly among different nationalities. Athletes from Nordic Countries considered well-being motives more important than Southern Europeans (p<0.001) or Western Europeans (p<0.05). Athletes from Nordic Countries (p = 0.003), Eastern Europe (p<0.001) and Central Europe (p<0.001) found health and fitness motives more meaningful than athletes from the British Isles. Furthermore, athletes with competitive background before the age of 35 and training amount more than 7.5 h a week found competitive and performance motives more important than athletes without a competitive history (p = 0.002). These results suggest that age, sex, nationality and former athleticism are associated with sports motives among international level masters track and field athletes. It seems that while for masters athletes with competitive background performance motives dominate, for older adults, particularly for males, health and fitness motives are more important. In addition, when designing the exercise interventions for older adults, different sport motives across countries should be considered.


Dominance of flow-mediated constriction over flow-mediated dilatation in the rat carotid artery.
The shearing forces generated by flow generally evoke dilatation in systemic vessels but constriction in the cerebral circulation. The aim of this study was to determine the effects of flow on the conduit artery delivering blood to the brain in the rat, that is, the carotid artery. Carotid artery segments were mounted in a pressure myograph and pressurized to 100 mmHg. Changes in vessel diameter to flow (0.5-10 mL·min⁻¹ for 2-10 min) at constant pressure were then measured using a video dimension analyser. Following the induction of tone, the onset of flow evoked a transient dilatation followed by a powerful constriction that was sustained until the termination of flow. Endothelial denudation or treatment with indomethacin, N(G)-nitro-L-arginine methyl ester, or the combination of apamin and TRAM-34 showed that the initial flow-mediated dilatation arose from the combined actions of endothelium-derived NO and endothelium-derived hyperpolarizing factor (EDHF). The flow-mediated constriction, which increased in magnitude with increasing flow rate and duration of flow, was also endothelium dependent, but was unaffected by treatment with superoxide dismutase, BQ-123, indomethacin, HET0016 or carbenoxolone. Flow-mediated constriction therefore appeared not to involve superoxide anion, endothelin-1, a COX product, 20-HETE or gap-junctional communication. Although a weak, transient flow-mediated dilatation is observed in the rat carotid artery, the dominant response to flow is a powerful and sustained constriction. Whether this flow-mediated constriction in the carotid artery serves as an extracranial mechanism to regulate cerebral blood flow remains to be determined.


The cytotoxicity of volatile JP-8 jet fuel components in keratinocytes.
In vitro models are being used to evaluate the toxic and irritating effects of JP-8, a kerosene-based jet fuel. JP-8 components are volatile, which makes in vitro studies difficult to evaluate dose-response relationships due to changes in chemical dosimetry caused by evaporation from the exposure medium. An in vitro approach testing volatile chemical toxicity that we have recently developed was used to evaluate the toxicity of the JP-8 components m-xylene, 1-methylnaphthalene (1-MN), and n-nonane in keratinocytes. Partition coefficients were measured and used to estimate the chemical concentration in the keratinocytes. The EC50 for m-xylene and 1-MN decreased significantly (P < or = 0.05) at 1, 2, and 4h. For n-nonane, no significant decreases in the EC50 values were observed over time; marginal cytotoxicity of n-nonane in keratinocytes was observed at 1h. Within 4h, about 75-90% of each volatile chemical was observed to be lost from the exposure medium when tissues were exposed in unsealed 24-well plates. This decrease resulted in significantly higher medium chemical concentrations needed to obtain EC50 values when compared to tissues exposed in sealed vials. This study demonstrates that chemical evaporation during in vitro exposures can significantly affect toxicological endpoint measurements. Ultimately, relating target cell chemical concentration to cellular responses in vitro could be used in determining an equivalent external dose using a biologically-based mathematical model.


In situ injectable hyaluronic acid/gelatin hydrogel for hemorrhage control.
Tissue sealants are used for hemorrhage control which is imperative in many surgical procedures. It is a highly challenging task to obtain the ideal tissue sealant. Only a few commercially tissue sealants are available to be used for internal tissue or organ hemorrhage control. This study introduced two in situ injectable hydrogels for hemorrhage control: self-crosslinking gelatin (sc-G) hydrogel and hyaluronic acid/gelatin (HA/G) hydrogel. They were prepared on the tissue surface in situ and characterized by rheological analysis, stability, cytotoxicity, and bursting strength test. The hemostatic ability of the hydrogels was evaluated in a liver-bleeding rat model. The sc-G and HA/G hydrogels gelled around 90 s and 50 s, respectively. They were preferable for cell attachment and proliferation. The bursting strengths of both hydrogels exceeded that of fibrin glue. The hemostatic ability of HA/G hydrogel was better than that of sc-G hydrogel, and was same as that of fibrin glue. The HA/G hydrogel could be used as a tissue sealant for hemorrhage control in clinic.


Interactive effects of gestational diabetes mellitus and maximum level of total bile acid in maternal serum on adverse pregnancy outcomes in women with intrahepatic cholestasis of pregnancy.
To study the combined effect of gestational diabetes mellitus (GDM) and maximum level of maternal serum total bile acid (TBA) on the incidence of adverse pregnancy outcomes in women with intrahepatic cholestasis of pregnancy (ICP). This was an observational study with 724 women with ICP. Perinatal outcomes were compared by the presence of GDM. Logistic regression was used to assess the independent and multiplicative interactions of GDM and maximum maternal serum TBA on adverse pregnancy outcomes. Additive interactions were calculated using an Excel sheet developed by Andersson to calculate relative excess risks. The incidence of GDM in patients with ICP was 21.55%. Maternal age, pre-pregnancy weight, parity, and gravidity were positively correlated with GDM. Hypertensive disorders of pregnancy (HDP) and fetal distress rates were higher in the GDM vs. non-GDM group. There were no significant differences in biochemical outcomes (i.e., Triglyceride (TG), low density lipoprotein (LDL), alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bile acid (TBA)) between the two groups. In terms of adverse pregnancy outcomes, GDM was only associated with maximum TBA concentration for cesarean section. No additive or pairwise interactions were detected between GDM and maximum TBA concentration and HDP, PPH, preterm delivery, LGA, SGA, and cesarean section. GDM independently contributes to adverse pregnancy outcomes among women with ICP. However, the combined effects of GDM and maximum TBA concentration on adverse pregnancy outcomes do not appear to be multiplicative or additive.


Medical nomenclature and common conventions for trauma registries.
A trauma registry has been created containing lexicons of terms arranged to foster the adoption of standardized and extensible terminology for the nature and mode of injury. Identification of attribute sets for the nature-of-injury (body region:detailed part:type of injury) and for the mode-of-injury (mechanism:agent:activity:intent:setting) allows the assembly of a clear, concise, easily usable, nad extensible format for representing the appropriate level of detail for nomenclature or classification. This ability allows the use of a common list of terms that is adaptable for case records used in patient care as well as in trauma registry statistics. Several examples of reports using these attributes are shown.


[Erythrocyte phenotypes and frequency of ABO system genes in the Senegalese population].
The determination of ABO blood groups, sub-groups of A and genic frequencies in 4,083 Senegalese subjects show an important frequency of the gene O (0.7042), similar frequencies of the gene A and B. The frequencies of the genes A1 and A2 are respectively 0.1248 and 0.0223.


Benzoquinone- and Naphthoquinone-Bearing Polymers Synthesized by Ring-Opening Metathesis Polymerization as Cathode Materials for Lithium-Ion Batteries.
Organic electrode materials have attracted great interest for next-generation lithium-ion batteries owing to their merits of low cost, resource sustainability, and environmental friendliness. Dissolution in organic electrolyte is one of critical factors that limit their development, and constructing corresponding polymers is an effective way to prevent it. Herein, the synthesis of benzoquinone- and naphthoquinone-bearing polymers by ring-opening metathesis polymerization of monomers with an exo-type four-membered ring between polymerizable norbornene and redox-active quinone units is reported. They exhibit significantly reduced solubility and clearly enhanced electrochemical performance. In particular, a high capacity (189.7 mAh g-1 at 0.1 C, 1 C=216.1 mA g-1 ), stable cycling (75.6 % capacity retention after 500 cycles at 2 C), and good rate capability (retaining 80.4 % from 0.1 to 2 C) were obtained for the naphthoquinone-bearing polymer, which stand out among naphthoquinone-bearing polymer electrode materials. This work offers rational molecular design and a new polymerization strategy to construct high-performance polymer electrode materials.


Spontaneous occurrence of spike-wave discharges in five inbred strains of rats.
The number and the duration of the cortical registered spike-wave discharges were studied in four inbred strains of rats (G/Cpb, B/Cpb, BN/BiRij, ACI) and compared to those of the WAG/Rij strain. The latter strain is considered to be a model of absence epilepsy. Eight rats of each strain were recorded during a continuous period of 48 hours. An analysis of variance showed significant strain differences in both the number and the mean duration of spike-wave discharges. The value of both parameters increased in the following order: ACI less than BN/BiRij less than B/Cpb less than G/Cpb less than WAG/Rij, whereby the ACI strain was almost free of spike-wave discharges and the WAG/Rij strain showed a considerable number per hour. Since a clear strain difference between the five inbred strains emerged, the investigation of biological and genetic factors underlying these strain differences may provide useful information for absence epilepsy in humans.


Impact of renal insufficiency on angiographic, procedural, and in-hospital outcomes following percutaneous coronary intervention.
Patients with chronic renal insufficiency (RI) have higher in-hospital mortality and major adverse cardiac event (MACE) rates after percutaneous coronary intervention (PCI). The mechanisms of this adverse course are not well understood. It was hypothesized that this worse outcome may be caused by inadequate PCI results secondary to more complex coronary anatomy in patients with RI. Baseline, procedural, and outcome variables of all PCI cases at the University Health Network are entered prospectively in the PCI Registry. All PCI cases between April 1, 2000, and October 31, 2005, excluding patients in shock, who had preprocedural creatinine clearance (CrCl) measured were included in this study (n = 10,821 of 11,023 patients). Moderate RI (CrCl <60 ml/min) was evaluated as an independent predictor of procedural outcomes, death, and MACE (defined as death, myocardial infarction, abrupt closure, or coronary artery bypass grafting). Moderate RI (CrCl <60 ml/min) independently predicted the procedural outcomes of worse residual stenosis >20% (p = 0.03), number of undeliverable stents (p = 0.003), and smallest stent diameter (p <0.001). Worst residual stenosis >20% and any undeliverable stent were significantly associated with in-hospital MACEs (odds ratio [OR] 3.97, 95% confidence interval [CI] 3.0 to 5.3, p <0.001 and OR 1.89, 95% CI 1.2 to 2.9, p = 0.002) and mortality (OR 3.82, 95% CI 2.2 to 6.7, p <0.001 and OR 3.0, 95% CI 1.6 to 5.9, p = 0.002). These risks were independent of all other measured variables. In conclusion, moderate to severe RI was a strong predictor of worse procedural results during PCI, which, in turn, were independent predictors of in-hospital MACE and mortality and independent contributors to the higher risk of in-hospital adverse events observed after PCI in patients with RI.


Numerical interpretation of molecular surface field in dielectric modeling of solvation.
Continuum solvent models, particularly those based on the Poisson-Boltzmann equation (PBE), are widely used in the studies of biomolecular structures and functions. Existing PBE developments have been mainly focused on how to obtain more accurate and/or more efficient numerical potentials and energies. However to adopt the PBE models for molecular dynamics simulations, a difficulty is how to interpret dielectric boundary forces accurately and efficiently for robust dynamics simulations. This study documents the implementation and analysis of a range of standard fitting schemes, including both one-sided and two-sided methods with both first-order and second-order Taylor expansions, to calculate molecular surface electric fields to facilitate the numerical calculation of dielectric boundary forces. These efforts prompted us to develop an efficient approximated one-dimensional method, which is to fit the surface field one dimension at a time, for biomolecular applications without much compromise in accuracy. We also developed a surface-to-atom force partition scheme given a level set representation of analytical molecular surfaces to facilitate their applications to molecular simulations. Testing of these fitting methods in the dielectric boundary force calculations shows that the second-order methods, including the one-dimensional method, consistently perform among the best in the molecular test cases. Finally, the timing analysis shows the approximated one-dimensional method is far more efficient than standard second-order methods in the PBE force calculations. © 2017 Wiley Periodicals, Inc.


Enhanced fractional-order PIλDμ control for a forced circulation evaporator system via advanced disturbance observer.
Strong disturbances, time delays, and coupling effects complicate the control of evaporator systems. In this paper, to overcome these difficulties a three-stage controller design is given and as a first step a disturbance observer (DOB) is designed. Then, fractional order PIλDμ controllers (PIλDμ FOC) with inverted decoupling structure are realized. Finally, PIλDμ FOC is enhanced via DOB and applied to control of a considered forced circulation evaporator system. Controlling the evaporator system with the DOB-enhanced PIλDμ FOC is showed more accurate and precise control results when compared with the optimally tuned PID and fuzzy logic controller (FLC). The DOB-enhanced PIλDμ FOC method has remarkable superiority in disturbance rejection and the proposed control method is improved the tracking ability of the system for reference changes.


Women's preferences for antenatal care in Tanzania: a discrete choice experiment.
The stillbirth rate in Tanzania remains high. Greater engagement with antenatal care may help to reduce stillbirths. We investigated which characteristics of antenatal care clinics are preferred by pregnant women in Tanzania. We conducted an unlabelled discrete choice experiment (DCE) with think-aloud interviews. Participants were pregnant women, regardless of parity/gestation, from the Mwanza and Manyara regions of Tanzania. We asked participants to choose which of two hypothetical antenatal clinics they would rather attend. Clinics were described in terms of transport mode, cleanliness, comfort, visit content, and staff attitude. Each participant made 12 choices during the experiment, and a purposively selected sub-set simultaneously verbalised the rationale for their choices. We analysed DCE responses using a multinomial logit model adjusted for study region, and think-aloud data using the Framework approach. We recruited 251 participants split evenly between the 2 geographical regions. Staff attitude was the most important attribute in clinic choice and dominated the think-aloud narratives. Other significant attributes were mode of transport (walking was preferred) and content of clinic visit (preference was stronger with each additional element of care provided). Cleanliness of the clinic was not a significant attribute overall and the think-aloud exercise identified a willingness to trade-off cleanliness and comfort for respectful care. Women would prefer to attend a clinic with kind staff which they can access easily. This study suggests that exploration of barriers to providing respectful care, and enabling staff to deliver it, are important areas for future investment. The DCE shows us what average preferences are; antenatal care that is aligned with identified preferences should increase uptake and engagement versus care which does not acknowledge them.


Sleep in children with refractory epilepsy and epileptic encephalopathies: A systematic review of literature.
Children with epilepsy have more sleep disorders compared to healthy children. The bidirectional interaction between epilepsy and sleep is not completely understood. However, disruption of sleep architecture during childhood may have consequences for cognitive development. As children with drug-refractory epilepsy often have intellectual disability, sleep disruption could be an important contributing factor in severity of their cognitive impairment. To better understand these interactions, sleep architecture in children with drug-refractory epilepsy and epileptic encephalopathies should be investigated. In this review, we conducted a systematic literature search on this topic. Articles that investigated sleep macro- and/or microstructure by means of electroencephalogram/polysomnography were included, as well as articles that used validated questionnaires. Sixteen articles were reviewed, eight of which used polysomnography. Only 2 articles examined sleep in children with epileptic encephalopathies. Consistent findings on measures of sleep architecture were a reduction in REM percentage and an increase in sleep fragmentation when comparing drug-refractory patients with non-refractory and healthy subjects. The findings on slow wave sleep were less clear. Studies with questionnaires unambiguously confirmed subjectively more sleep problems in children with drug-refractory epilepsy. This is the first review of literature in this patient population. More good quality sleep studies in children with drug-refractory epilepsy are warranted. The use of wearables in the home setting together with automatic sleep staging could provide more insights.


Development and Validation of a Coronary Heart Disease Risk Prediction Model in Snorers with Hypertension: A Retrospective Observed Study.
To develop and validate a risk prediction model for coronary heart disease (CHD) in snorers with hypertension, including traditional and new risk factors. Twenty factors were evaluated in the records of 2810 snorers with hypertension. Training (70%) and validation (30%) sets were created by random allocation of data, and a new nomogram model was developed. The model's discrimination and calibration were measured by calculating the area under the receiver operating curve (AUC) and creating calibration charts. The performance of the nomogram model was compared with that of the Prediction for ASCVD Risk in China (China-PAR) and Framingham models by decision curve analysis. An optimal cutoff point for the risk score in the training set was computed to stratify patients. In the nomogram model, the AUCs for predicting CHD at 5, 7 and 9 years in the training set were 0.706 (95% confidence interval [CI] 0.649-0.763), 0.703 (95% CI 0.655-0.751) and 0.669 (95% CI 0.593-0.744), respectively. The respective AUCs were 0.682 (95% CI 0.607-0.758), 0.689 (95% CI 0.618-0.760) and 0.664 (95% CI 0.539-0.789) in the validation set. The calibration chart showed that the predicted events from the nomogram score were close to the observed events. Decision curve analysis indicated that the nomogram score was slightly better than the Prediction for ASCVD Risk in China (China-PAR) and Framingham models for predicting the risk of CHD in snorers with hypertension. A cutoff point was identified for being CHD-free (a nomogram score of ≤121), which could be helpful for the early identification of individuals at high-risk of CHD. The nomogram score predicts the risk probability of CHD in snorers with hypertension at 5, 7 and 9 years, and shows good capability in terms of discrimination and calibration. It may be a useful tool for identifying individuals at high risk of CHD.


Impact of Sequencing of Androgen Suppression and Radiation Therapy on Testosterone Recovery in Localized Prostate Cancer.
We performed a secondary analysis of a phase 3 randomized trial to determine the influence of sequencing of radiation therapy and androgen deprivation therapy (ADT) on posttreatment testosterone recovery and implications of testosterone recovery on subsequent relapse. Patients with localized prostate cancer with Gleason score ≤7, clinical stage T1b to T3a, and prostate-specific antigen <30 ng/mL were randomized to neoadjuvant and concurrent ADT for 6 months starting 4 months before prostate radiation therapy (NHT arm) or concurrent and adjuvant ADT for 6 months starting simultaneously with radiation therapy (CAHT arm). Full testosterone recovery (FTR) was defined as recovery of testosterone to >10.5 nmol/L in patients with baseline ≥10.5 nmol/L or to baseline level in patients with baseline <10.5 nmol/L. Restricted mean survival time (RMST) since ADT initiation to supracastrate testosterone level (>1.7 nmol/L), and to FTR was compared between the arms using a truncation time point of 36 months. The adjusted difference in RMST to supracastrate testosterone between the CAHT and NHT arm was 1.5 months (95% confidence interval [CI], 0.5-2.5; P = .005). No difference was noted in RMST to FTR between the arms (18.7 vs 18.5 months, adjusted difference: 0.5; 95% CI, -1.4 to 2.4; P = .61). There was no evidence of heterogeneity of treatment effect (interaction P = .76) on risk of relapse over subgroups stratified by testosterone recovery to supracastrate level at 15 months after start of ADT. Based on a multistate Markov model, no independent effect of time to FTR on risk of subsequent relapse was observed (adjusted hazard ratio: 1.02; 95% CI, 0.96-1.08). Patients should be counseled that an additional 12 months on average is needed for FTR to occur after treatment with prostate radiation therapy and 6 months of ADT. This is independent of the sequencing of ADT and radiation therapy. Furthermore, recovery of testosterone does not appear to affect the risk of subsequent relapse.


Intestinal antibody to Vibrio cholerae in immunised mice.
The immune response of the mouse to priming and booster doses of V. cholerae was studied to establish whether serum antibody could be used as a correlate of local immunity. Serum antibody titres following oral boosting of orally-primed animals were shown to reflect the state of local intestinal immunity. This was not the case when the same oral booster dose was given to parenterally-primed animals. These results were discussed in relation to the human endemic situation. The highest titres of intestinal protective antibodies were found following combination of the oral and parenteral routes of immunisation. Various killed or extracted preparations of V. cholerae were used as oral vaccines to test their ability to induce protective antibodies in the gut. Only Boivin antigen was capable of inducing as good an intestinal antibody response as would the living organism.


Repurposing the Hedgehog pathway inhibitor, BMS-833923, as a phosphatidylglycerol-selective membrane-disruptive colistin adjuvant against ESKAPE pathogens.
The rapid emergence and spread of multi-drug- or pan-drug-resistant bacterial pathogens, such as ESKAPE, pose a serious threat to global health. However, the development of novel antibiotics is hindered by difficulties in identifying new antibiotic targets and the rapid development of drug resistance. Drug repurposing is an effective alternative strategy for combating antibiotic resistance that both saves resources and extends the life of existing antibiotics in combination treatment regimens. Screening of a chemical compound library identified BMS-833923 (BMS), a smoothened antagonist that kills Gram-positive bacteria directly, and potentiates colistin to destroy various Gram-negative bacteria. BMS did not induce detectable antibiotic resistance in vitro, and showed effective activity against drug-resistant bacteria in vivo. Mechanistic studies revealed that BMS caused membrane disruption by targeting the membrane phospholipids phosphatidylglycerol and cardiolipin, promoting membrane dysfunction, metabolic disturbance, leakage of cellular components, and, ultimately, cell death. This study describes a potential strategy to enhance the efficacy of colistin and combat multi-drug-resistant ESKAPE pathogens.


Consistency of Cranial Shape Measures Obtained From Laser Surface and Computed Tomography Imaging.
Children with cranial shape abnormalities are often subjected to radiation from computed tomography (CT) for evaluation and clinical decision making. The STARscanner Laser Data Acquisition System (Orthomerica, Orlando, FL) may be a noninvasive alternate. The purpose of this study is to determine whether the STARscanner provides valid and accurate cranial measurements compared to CT. We performed an institutional review board-approved retrospective review of a prospectively maintained database of patients with metopic suture abnormalities from 2013 to 2016. Plastic surgery clinic in an institutional tertiary care center. Eight patients were included that presented with metopic suture abnormalities, age less than 1 year, and CT and STARscanner imaging within 30 days of one another. Cranial measurements were collected twice from 3 scan types: STARscanner, CT windowed for soft tissue, and CT windowed for bone. Measurements included: intracranial volume, height, base width, maximum antero-posterior length, maximum medio-lateral width, and oblique diameters. Nested analysis of variance were performed to determine the proportion of error attributable to: between-subject variance, scan type, and rater. Measurements from STARscanner and both CT scans windows were highly consistent, with less than 1% of total error attributable to scan type for all measures. Cranial shape measurements obtained from STARscanner images are highly consistent with those obtained from CT scans. The STARscanner has added benefits of speed of acquisition, minimal cost, and lack of radiation.


Crystalloid inclusions reminiscent of Hirano bodies in autolyzed peripheral nerve of normal wistar rats.
In a study of experimental autolysis of peripheral nerves of normal Wistar rats, crystalloid inclusions similar to Hirano bodies were observed. They occurred in the nuclei and cytoplasms of Schwann cells and in myelinated axons. They first developed after a 12-h autolysis and increased in number and size with time. Their fine structure, localization, and morphogenesis are discussed in relation to the autolysis of the cellular organelles.


The virtual-patient pilot: testing a new tool for undergraduate surgical education and assessment.
The virtual patient (VP) is a web-based tool that allows students to test their clinical decision-making skills using simulated patients. Three VP cases were developed using commercially available software to simulate common surgical scenarios. Surgical clerks volunteered to complete VP cases. Upon case completion, an individual performance score (IPS, 0-100) was generated and a 16-item survey was administered. Surgery shelf exam scores of clerks who completed VP cases were compared with a cohort of students who did not have exposure to VP cases. Descriptive statistics were performed to characterize survey results and mean IPS. Surgical clerks felt that the VP platform was simple to use, and both the content and images were well presented. They also felt that VPs enhanced learning and were helpful in understanding surgical concepts. Mean IPS at conclusion of the surgery clerkship was 69.2 (SD 26.5). Mean performance on the surgery shelf exam for the student cohort who had exposure to VPs was 86.5 (SD 7.4), whereas mean performance for the unexposed student cohort was 83.5 (SD 9). The VP platform represents a new educational tool that allows surgical clerks to direct case progression and receive feedback regarding clinical-management decisions. Its use as an assessment tool will require further validation.


Mechanisms of corticotropin action in rat adrenal cells. I. The effects of inhibitors of protein synthesis and of microfilament formation on corticosterone synthesis.
The contributions of protein synthesis and formation of microtubules and microfilaments to corticotropin-stimulated steroidogenesis in rat adrenal cell suspensions has been assessed by use of a series of inhibitors to each function. Five inhibitors of protein synthesis (cycloheximide, puromycin, blastocidin S, anisomycin, and trichodermin) each exhibited time-dependent inhibition of corticotropin-stimulated steroidogenesis. For the first 30 min, steroidogenesis was more extensively inhibited than protein synthesis, after which the effectiveness of the inhibitors diminished on steroidogenesis but not on protein synthesis. The reversal effect was not observed at high levels of inhibitors. One inhibitor of microfilament formation (cytochalasin B) and four inhibitors of microtubule formation (colchicine, podophyllotoxin, vinblastine sulfate and griseofulvin) inhibited steroidogenesis without inhibiting protein synthesis and without any reversal effect with prolonged incubation. The actions of all ten inhibitors were shown to be fully reversible. Cell superfusion of adrenal cells showed that the decay of steroidogenesis upon addition of all the protein synthesis inhibitors was similar to decay upon removal of corticotropin from the medium (t1/2 = 4--6 min). Recoveries from inhibition upon removal of the inhibitors were similar to each other and comparable to initial corticotropin stimulation of the cells (lag of 3--5 min, t1/2=7--9 min). Similar kinetics of inhibition and recovery were observed for vinblastine sulfate while a direct inhibition of cytochrome P-450scc by aminoglutethimide was complete within 1 min and was rapidly reversed. Injection of each inhibitor (all classes) into hypophysectomized rats inhibited the elevation of plasma corticosterone by corticotropin. The extent of cholesterol combination with cytochrome P-450scc in adrenal mitochondria isolated from these rats was also decreased by all of the inhibitors. Decreases in plasma corticosterone correlated directly with decreases in cholesterol combination with cytochrome P-450scc (r=0.94). It is concluded that protein synthesis and steroidogenesis must be intimately coupled probably due to the requirement of a labile protein for cholesterol transport to cytochrome P-450scc. An involvement of microtubules and microfilaments in this process is clearly indicated.


Depressive symptomatology among Mexican-American adults: an examination with the CES-D Scale.
The presence and persistence of specific depressive symptomatology among a large sample of Mexican-American adults (n = 3,084) were examined with the Center for Epidemiologic Studies Depression (CES-D) Scale. Compared to studies of Anglos, a substantially larger percentage reported persistent hopelessness about the future (29%), self-depreciation (21%), and lack of enjoyment out of life (14%). The prevalence of these symptoms was higher among those who had not adapted to mainstream American society and among older participants. Women were generally more distressed than men. Factor analyses of the items demonstrated a slightly different factor structure than previously obtained with Anglos. For both sexes and for those under age 30 and ages 30-59, the items "loneliness," "sadness," and "crying" loaded on a common factor. The tendency for these items to group together was stronger for those exhibiting a low or medium degree of cultural adaptation than for those exhibiting a high degree of adaptation. Discussion focuses on the cultural variation of response to items on the CES-D.


Predominantly cerebral manifestation in Urbach-Wiethe's syndrome (lipoid proteinosis cutis et mucosae): a clinical and pathomorphological study.
The neurological and psychiatric manifestations in a case of Urbach-Wiethe's disease are reported. The present case is characterized by the predominance of cerebral symptoms: ataxia, psychomotoric seizures, paranoic hallucinatory psychosis and attacks of rage. At autopsy, deposits of amyloid-like material in the walls of the brain vessels could be observed. This finding, together with the mucocutaneous alterations, confirmed the diagnosis of the rare disease know as "lipoid proteinosis cutis et mucosae".


Wharton's Jelly-Mesenchymal Stem Cell-Engineered Conduit for Pediatric Translation in Heart Defect.
The materials available for the right ventricular outflow tract (RVOT) reconstruction in patients with tetralogy of fallot (TOF)/pulmonary atresia come with the severe limitation of long-term degeneration and lack of growth potential, causing right ventricular dysfunction, aneurysm formation, and arrhythmias, thus necessitating several high-risk reoperations throughout patients' lives. In this study, we evaluated the capacity of mesenchymal stem cells (MSCs) derived from the Wharton's Jelly (WJ-MSCs), the gelatinous inner portion of the umbilical cord, to grow and recellularize an extracellular matrix (ECM) graft in our optimized xeno-free, good manufacturing practice-compliant culture system. WJ-MSCs were phenotypically and functionally characterized by flow cytometry and multilineage differentiation capacity, respectively. The typical MSC immunophenotype and functional characteristics were retained in our xeno-free culture system, as well as the capacity to grow and engraft onto a naturally occurring scaffold. WJ-MSCs, from both human and swine source, showed excellent capacity to recellularize ECM graft producing a living cell-seeded construct. In addition, we have provided an in vivo proof of concept of feasibility of the cellularized conduit, engineered with swine WJ-MSCs, to be used in a novel porcine model of main pulmonary artery reconstruction, where it showed good integration within the host tissue. Our study indicates that the addition of WJ-MSCs to the ECM scaffold can upgrade the material, converting it into a living tissue, with the potential to grow, repair, and remodel the RVOT. These results could potentially represent a paradigm shift in pediatric cardiac intervention toward new modalities for effective and personalized surgical restoration of pulmonary artery and RVOT function in TOF/pulmonary atresia patients. Impact Statement The materials available for pulmonary artery reconstruction in pediatric patients with Congenital Heart Defect come with the limitation of long-term degeneration and lack of growth, thus necessitating several reoperations. Here, we describe a novel approach combining perinatal stem cells and naturally occurring scaffold to create a living tissue engineered conduit that showed good growth potential in a pulmonary artery reconstruction porcine model. We envision this approach is of great interest and relevance in tissue engineering field applied to cardiovascular regenerative medicine, as it may open up new avenues for correction of congenital cardiac defects, with remarkable medical and social benefits.


Differential placental expression profile of human Growth Hormone/Chorionic Somatomammotropin genes in pregnancies with pre-eclampsia and gestational diabetes mellitus.
The human GH/CSH cluster consisting of one pituitary-expressed (GH1) and four placenta-expressed loci has been implicated in maternal metabolic adaptation to pregnancy, regulation of intrauterine and postnatal growth. We investigated how the mRNA expression profile of placental GH2, CSH1 and CSH2 genes and their alternative transcripts correlates with maternal pre-eclampsia (PE) and/or gestational diabetes mellitus (GD). The expression of studied genes in PE placentas (n=17) compared to controls (n=17) exhibited a trend for reduced transcript levels. The alternative transcripts retaining intron 4, GH2-2 and CSH1-2 showed significantly reduced expression in PE cases without growth restriction (P=0.007, P=0.008, respectively). In maternal GD (n=23), a tendency of differential expression was detected only for the GH2 gene and in pregnancies with large-for-gestational-age newborns. Our results, together with those reported by others, are consistent with a pleiotropic effect of placental hGH/CSH genes at the maternal-fetal interface relating to the regulation of fetal growth and the risk of affected maternal metabolism.


Outer membrane protein of OmpF contributes to swimming motility, biofilm formation, osmotic response as well as the transcription of maltose metabolic genes in Citrobacter werkmanii.
Bacterial outer membrane proteins (Omps) are essential for environmental sensing, stress responses, and substance transport. Our previous study discovered that OmpA contributes to planktonic growth, biocide resistance, biofilm formation, and swimming motility in Citrobacter werkmanii, whereas the molecular functions of OmpF in this strain are largely unknown. Thus, in this study, the ompF gene was firstly knocked out from the genome of C. werkmanii using a homologous recombination method, and its phenotypical alternations of ∆ompF were then thoroughly characterized using biochemical and molecular approaches with the parental wild type (WT) and complementary (∆ompF-com) strains. The results demonstrated that the swimming ability of ∆ompF on semi-solid plates was reduced compared to WT due to the down-regulation of flgC, flgH, fliK, and fliF. Meanwhile, ompF deletion reduces biofilm formation on both glass and polystyrene surfaces due to decreased cell aggregation. Furthermore, ompF inactivation induced different osmotic stress (carbon sources and metal ions) responses in its biofilms when compared to WT and ∆ompF-com. Finally, a total of 6 maltose metabolic genes of lamB, malE, malK, malG, malM, and malF were all up-regulated in ∆ompF. The gene knockout and HPLC results revealed that the MalEFGK2 cluster was primarily responsible for maltose transport in C. werkmanii. Furthermore, we discovered for the first time that the upstream promoter of OmpF and its transcription can be combined with and negatively regulated by MalT. Overall, OmpF plays a role in a variety of biochemical processes and molecular functions in C. werkmanii, and it may even act as a targeted site to inhibit biofilm formation.


Current evidence is insufficient to define an optimal threshold for intervention in isolated type II endoleak after endovascular aneurysm repair.
To report a systematic review and meta-regression of the association between the threshold for intervention in patients with isolated type II endoleak after endovascular aneurysm repair (EVAR) and the fate of the aneurysm sac. Medline, trial registries, conference proceedings, and article reference lists were searched to identify case series reporting sac outcomes following a specific treatment threshold for isolated type II endoleak. Articles were classified by the threshold for intervention as conservative, selective (intervention for >5-mm sac expansion or persistent type II endoleak >6 months), or aggressive (any type II endoleak or persistent for >3 months) and sac outcomes were extracted for review. Standard meta-regression to estimate the pooled odds ratios (OR), presented with the 95% confidence interval (CI), was performed to identify whether an aggressive, selective, or conservative threshold for intervention was associated with sac expansion or sac regression. Ten series were analyzed that reported the outcomes of isolated type II endoleak in 231 patients; of these, 56 patients were treated at an aggressive threshold, 104 at a selective threshold, and 71 at a conservative threshold. The majority (194/231, 84.0%) demonstrated either stable or shrinking sacs during follow-up. No ruptures occurred. Meta-regression demonstrated no evidence that any strategy, compared to using a conservative approach, reduced sac expansion (aggressive estimated OR 0.70, 95% CI 0.15 to 3.31, p = 0.60; selective estimated OR 1.72, 95% CI 0.49 to 6.00, p = 0.34) or improved sac regression (aggressive estimated OR 0.55, 95% CI 0.02 to 16.94, p = 0.69; selective estimated OR 5.54, 95% CI 0.39 to 79.21, p = 0.17). There is inadequate information to support any one threshold for intervention. The rarity of rupture and sac expansion confirms the predominantly benign nature of isolated type II endoleak. In the absence of statistical support for a uniform approach to this problem, patient and physician preference remain key. Prospective data are still needed to investigate whether an optimum management algorithm can be devised.


A comparison of two predator-prey models with Holling's type I functional response.
In this paper, we analyze a laissez-faire predator-prey model and a Leslie-type predator-prey model with type I functional responses. We study the stability of the equilibrium where the predator and prey coexist by both performing a linearized stability analysis and by constructing a Lyapunov function. For the Leslie-type model, we use a generalized Jacobian to determine how eigenvalues jump at the corner of the functional response. We show, numerically, that our two models can both possess two limit cycles that surround a stable equilibrium and that these cycles arise through global cyclic-fold bifurcations. The Leslie-type model may also exhibit super-critical and discontinuous Hopf bifurcations. We then present and analyze a new functional response, built around the arctangent, that smoothes the sharp corner in a type I functional response. For this new functional response, both models undergo Hopf, cyclic-fold, and Bautin bifurcations. We use our analyses to characterize predator-prey systems that may exhibit bistability.


Strain-dependent regulation of plasticity-related proteins in the mouse hippocampus.
Inbred mouse strains have different genetic backgrounds that can result in impairment of synaptic plasticity and memory. Strain-dependent performance in behavioral and cognitive tasks is well-documented. Hippocampal long-term potentiation (LTP), an activity-dependent enhancement of synaptic transmission that may underlie some forms of learning and memory has been shown to differ significantly between inbred mouse strains. However, an effect of strain on the expression of proteins, critically involved in synaptic plasticity, learning and memory has not been described yet. We have been addressing this question by determining expressional levels of a panel of proteins involved in neuronal information processing in hippocampus of five mouse strains by immunoblotting. Four inbred strains (FVB/N, C57Bl/6J, 129S2/Sv and Balb/c), commonly used for generating genetically modified mice and for conventional experiments in pharmacology and toxicology and one outbred strain (OF1) have been selected. A significant effect of strain was detected for total and phosphorylated calcium-calmodulin dependent kinase IIalpha (CaMKII, pCaMKII), phosphorylated mitogen-activated protein kinase (pMAPK), total and phosphorylated calcium-responsive element binding 1 (creb, pcreb), early-growth response protein 1 (egr 1), brain derived neurotrophic factor (BDNF), drebrin and postsynaptic density-95 (PSD-95). These results may indicate genetic determination of synaptic plasticity-related mechanisms relevant for the molecular events mediating hippocampal information processing and storage. Data presented herein highlight the importance of careful selection of the mouse strain for studies of synaptic plasticity.


Isolation and identification of mutants constitutive for aspartokinase III synthesis in Escherichia coli K 12.
We devised a procedure in order to isolate, in Escherichia coli, constitutive mutants for aspartokinase III synthesis, the first enzyme of the lysine regulon. It consists of the introduction of a limiting step in lysine biosynthesis, by the use of the partial suppression of a nonsense mutation. For the first time we could isolate many constitutive mutants. Their characteristics (cotransduction with the lysC structural gene; no effect on the synthesis of other enzymes of the regulon; cis-dominance) lead to classify these mutations as operator-type. The fact that no repressor mutations could be isolated is discussed.


Primary pleural melanoma. A first reported case and literature reivew.
Although metastatic pulmonary and pleural melanoma has previously been noted, primary pleural melanoma has not been reported. In addition, an extracutaneous response to Adriamycin chemotherapy for melanoma is documented. The patient demonstrated a continued objective response and remained in remission for 10 months. His death was not related to the tumor, and at autopsy there was no gross or microscopic evidence of other organ involvement or origin. Previously reported unusual primary sites associated with this tumor are reviewed, and the established criteria for determination of a primary site in the lung are reiterated. Possibilities of prior unrecognized presence of a primary site are discussed. After having reviewed pertinent literature regarding this intriguing case, we believe that all necessary criteria for proof of a first report have been met.


[Atypical epilepsy symptomatology as cause of a dementia like state in a mentally and physically retarded patient].
We report on a 50-year-old man with mental retardation and right-sided hemi-paresis. He seemed to be cured from epilepsy. In a short time a mental and physical deterioration developed which looked like a dementia, which was suggested by vascular risk factors. The EEG showed marked epileptic activity characterized by spikes appearing every 10 seconds over the left temporal lobe. After introduction of carbamazepine, a fast and long-term improvement of symptoms was noticed resulting in self sufficiency. The fast and marked effect of an antiepileptic drug being given to the patient with an non-typical reactivation of epilepsy in which the dementia-syndrome was caused by a transitory cognitive impairment due to sub-clinic electric seizures or non-convulsive status epilepticus.


Within-subjects vs between-subjects co-variation of prepulse-elicited reaction and the diminution of startle to the succeeding pulse stimulus in the prepulse inhibition paradigm.
Prepulse inhibition (PPI) refers to the diminution of the startle reflex to a sudden and intense acoustic stimulus (pulse) when this startle-eliciting pulse is preceded shortly by a weaker prepulse stimulus. PPI is widely used in evaluating the effects of psychomimetic and antipsychotic drugs on sensorimotor gating, but individual differences in PPI expression have received scant attention. We have previously shown that mice and rats exhibiting stronger motor response to the prepulse also exhibit more PPI. It remains unexplored, however, if this between-subjects correlation may be similarly observed across trials from a within-subjects perspective. Here, we mapped the prepulse-elicited response to the diminution of the startle response to the succeeding pulse stimulus, trial-by-trial, across nine prepulse-pulse definitions with varying prepulse and pulse intensities. The resulting within-subjects correlation independently obtained in 113 adult C57BL6 mice revealed that trials registering a stronger prepulse reaction also recorded a larger startle response to the pulse stimulus, indicative of weaker PPI, especially when higher-intensity prepulses were paired with low-intensity pulses. The within- and between-subjects analyses have apparently yielded two contrasting relationships between the direct motor response to the prepulse and the inhibition of subsequent startle reaction induced by the same prepulse. One interpretation is that the within-subjects correlation reflects state-dependent variation, whereas the between-subjects correlation stems from trait-dependent individual variation. Finally, whether our present findings may depend on the nature of the prepulse reaction is further discussed.


Impact of reported NSAID "allergies" on opioid use disorder in back pain.
It is crucial to identify patients at highest risk for opioid use disorder (OUD) and to address challenges in reducing opioid use. Reported nonsteroidal anti-inflammatory drug (NSAID) allergies may predispose to use of stronger pain medications and potentially to OUD. We sought to investigate the clinical impact of reported NSAID allergy on OUD in patients with chronic back pain. We conducted a retrospective study of adults receiving care at a tertiary health care system from January 1, 2013, to December 31, 2018. Back pain and OUD were identified using administrative data algorithms. We used propensity score matching and logistic regression to estimate the impact of self-reported NSAID adverse drug reactions (ADRs) on risk of OUD, adjusting for other relevant clinical information. Of 47,114 patients with chronic back pain, 3,620 (7.7%) had a reported NSAID ADR. In an adjusted propensity score-matched analysis, patients with NSAID ADRs had higher odds (odds ratio, 1.34; 95% CI, 1.07-1.67) of developing OUD as compared with those without NSAID ADRs. Additional risk factors for OUD included younger age, male sex, Medicaid insurance, Medicare insurance, higher number of inpatient and outpatient visits in the previous year, and comorbid anxiety and depression. Patients with listed NSAID ADRs also had higher odds of a documented opioid prescription during the study period (odds ratio, 1.22; 95% CI, 1.11-1.34). Adults with chronic back pain and reported NSAID ADRs are at a higher risk of developing OUD and receiving opioid analgesics, even after accounting for comorbidities and health care utilization. Allergy evaluation is critical for potential delabeling of patients with reported NSAID allergies and chronic pain.


Resource partitioning by three species of hemipteran herbivores on the basis of host plant density.
Three hemipteran herbivores partition a common resource plant, Senecio smallii, on the basis of bud density and plant patch size. The monophagous herbivore, Neacoryphus bicrucis, is most abundant in larger patches where bud density is greatest. The oligophagous herbivore, Harmostes reflexulus, is most abundant in small patches of high bud density. The polyphagous species, Lygus pratensis, is most abundant in small patches where abundance is independent of bud density. The aggressive nature of the monophagous herbivore appears to mediate the responses of the other species.


Long-Term Outcome in a Phase II Study of Regional Hyperthermia Added to Preoperative Radiochemotherapy in Locally Advanced and Recurrent Rectal Adenocarcinomas.
Hyperthermia was added to standard preoperative chemoradiation for rectal adenocarcinomas in a phase II study. Patients with T3-4 N0-2 M0 rectal cancer or local recurrences were included. Radiation dose was 54 Gy combined with capecitabine 825 mg/m2 × 2 daily and once weekly oxaliplatin 55 mg/m2. Regional hyperthermia aimed at 41.5-42.5 °C for 60 min combined with oxaliplatin infusion. Radical surgery with total or extended TME technique, was scheduled at 6-8 weeks after radiation. From April 2003 to April 2008, a total of 49 eligible patients were recruited. Median number of hyperthermia sessions were 5.4. A total of 47 out of 49 patients (96%) had the scheduled surgery, which was clinically radical in 44 patients. Complete tumour regression occurred in 29.8% of the patients who also exhibited statistically significantly better RFS and CSS. Rate of local recurrence alone at 10 years was 9.1%, distant metastases alone occurred in 25.6%, including local recurrences 40.4%. RFS for all patients was 54.8% after 5 years and CSS was 73.5%. Patients with T50 temperatures in tumours above median 39.9 °C had better RFS, 66.7% vs. 31.3%, p = 0.047, indicating a role of hyperthermia. Toxicity was acceptable.


Characteristics of endothelin receptors in the central nervous system of spontaneously hypertensive rats.
The binding of [125I]sarafotoxin 6b (SRT 6b) and [125I]endothelin-1 (ET-1) to endothelin (ET) receptors of neuronal membranes prepared, from regions of the brain and spinal cord of 8 week-old, spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats was determined. Spontaneously hypertensive rats had significantly higher blood pressure as compared to WKY rats. Heart rate was similar in SHR and WKY rats. [125I]SRT 6b and [125I]ET-1 bound to the membranes of the cerebral cortex, hypothalamus, ventrolateral medulla, dorsomedial medulla and spinal cord at a single, high affinity site. The Kd and Bmax values of the binding of [125I]SRT 6b were found to be similar to binding of [125I]ET-1 in all the regions. The concentration-dependent inhibition of binding of [125I]ET-1 by unlabeled ET-1, in spinal cord membranes showed an IC50 value of 2.66 +/- 0.59 nM and a Ki value of 2.35 +/- 0.52 nM in WKY rats and an IC50 value of 2.82 +/- 0.76 nM and a Ki value of 2.43 +/- 0.70 nM in SHR rats. On the other hand, the concentration-dependent inhibition of the binding of [125I]SRT 6b by unlabeled ET-1, in spinal cord membranes showed an IC50 value of 10.31 +/- 1.82 pM and a Ki value of 8.44 +/- 1.41 pM in WKY rats, while SHR rats showed an IC50 value of 10.28 +/- 1.94 pM and a Ki value of 8.89 +/- 2.00 pM. The binding of [125I]SRT 6b and [125I]ET-1 in the cerebral cortex, dorsomedial medulla and spinal cord membranes was found to be similar in SHR and WKY rats.(ABSTRACT TRUNCATED AT 250 WORDS) [corrected]


Consumer Response to Tomato Pomace Powder as an Ingredient in Bread: Impact of Sensory Liking and Benefit Information on Purchase Intent.
This study evaluated consumer acceptance and purchase intent (PI) for bread formulated with dried tomato pomace powder (DTPP). DTPP was used to substitute 5 or 10% by weight for a 50/50 mix of white and whole-wheat flour used in a control bread. Consumers (n = 231) evaluated sensory attributes and PI on the breads, which were produced and presented as slices from a typical commercial sandwich loaf. Before answering PI questions, panelists were presented with information regarding the DTPP ingredient. Some received information on nutritional quality, some on sustainability impact, some both, some neither. This approach allowed the impacts of those messages on PI to be tested, along with impact of liking, price, and other factors. PI was analyzed using a fractional logistic model. Statistically significant differences were observed in several sensory attributes, some favoring the DTPP ingredient with overall liking very similar for the 5% DTPP and control bread samples. Price and overall liking were highly significant variables effecting PI. DTPP proved to be an excellent ingredient to replace a portion of wheat flours to improve nutritional value of bread products. PRACTICAL APPLICATION: This study shows that dried tomato pomace powder (DTPP) has potential application as an ingredient, since it improved nutritional content, appearance, and color appeal of wheat bread. Furthermore, food producers who are considering the use of byproducts in their product formulations should be encouraged by the finding that informed consumers were as willing to purchase the bread with the ingredient, as they were to purchase a typical comparable sandwich bread without it. Furthermore, both a nutrition message and a sustainability message can increase PI for the bread containing the byproduct relative to their PI toward the control bread.


Neuronal overexpression of hTDP-43 in Caenorhabditis elegans mimics the cellular pathology commonly observed in TDP-43 proteinopathies.
Inclusions consisting of transactive response DNA-binding protein 43 (TDP-43) are a characteristic feature of amyotrophic lateral sclerosis (ALS). Caenorhabditis elegans has been instrumental in studying the underlying mechanisms of TDP-43 pathology. Here, we extend the possibilities of previous studies by examining a C. elegans model expressing human wild-type TDP-43 ( hTDP-43 ) pan-neuronally. We show that disease-related (hyper)phosphorylation and cytosolic localisation of hTDP-43 are present in hTDP-43 worms and that these features can be enhanced by adjusting the environmental temperature.


Fasciola hepatica: identification of molecular markers for resistant and susceptible Pseudosuccinea columella snail hosts.
Protein electrophoresis, RAPD-PCR and nuclear rDNA ITS sequencing were performed to search for genetic differences between Pseudosuccinea columella snails susceptible and resistant to Fasciola hepatica infection. Of the 21 enzymatic loci analyzed in both populations, none of them exhibited neither within- or between-group variation. Such an absence of enzyme polymorphism support the hypothesis of selfing as the "prevalent" mating system for this hermaphroditic species. Conversely, the RAPD profiles displayed clear differences between susceptible and resistant isolates for 17 of the 26 primers tested while no within-group variation was detected. rDNA ITS sequence analysis from snails of each isolates showed only two bases that differed between groups accounting for a 0.17% of variation confirming that susceptible and resistant snails belong to the same species. This is the first time that a genetic variation using RAPD markers is demonstrated between susceptible and resistant lymnaeid snails vis-a-vis of F. hepatica infection in absence of experimental selection.


Zika NS2B is a crucial factor recruiting NS3 to the ER and activating its protease activity.
Zika virus (ZIKV) is an emergent flavivirus associated with severe neurological disorders. ZIKV NS3 protein is a viral protease that cleaves the ZIKV polyprotein precursor into individual viral proteins. In this study, we found that ZIKV NS3 by itself exhibited mitochondrial localization, which was quite different from its endoplasmic reticulum (ER) localization in ZIKV-infected cells. We screened viral proteins and identified NS2B as the bona fide recruiter of NS3 to the ER. The NS2B C-terminal tail interacted with NS3 protease domain to retain NS3 on the ER. β-Sheet motifs that formed between NS2B and the NS3 protease domain played important roles in their interaction, while mutation in the β-strand of NS2B attenuated NS2B-NS3 interaction and impaired the ability of NS3 protease to cleave the polyprotein precursor into multiple viral proteins. Consequently, NS2B mutations led to severe inhibition of ZIKV replication and production due to insufficient NS3 protease activity. In summary, our study reveals the critical role of NS2B in NS3 recruitment and protease function and provides mechanistic insight into ZIKV replication.


Total ankle replacement.
Total ankle replacement is emerging as a viable treatment for symptomatic ankle arthritis that has not responded to nonoperative treatment. Most modern implant designs involve the use of a three-component, mobile-bearing implant. Although the results of the different design approaches are encouraging in limited clinical series, there is still the need for careful, long-term analyses to estimate to what extent the current designs are mimicking the biomechanics of the ankle joint. More attention must be paid to more accurate implantation techniques that result in a well-balanced ligament and allow the ligaments to act together with the replaced surfaces in a most physiologic manner. To improve the stability of the bone-implant interface over time, specific efforts should be made to better understand the extrinsic and intrinsic forces of the ankle joint, including the forces that are created by the prosthesis itself.


Comparative cross-over pharmacokinetic study on two types of postcoital contraceptive tablets containing levonorgestrel.
A pharmaceutical and pharmacokinetic study was carried out on levonorgestrel tablets from two different sources (Hungarian- and Chinese-made). Both preparations contained 0.75 mg levonorgestrel and had been shown to have similar contraceptive efficacy and side effects when used for postcoital contraception. Absorption and bioavailability of the Hungarian-made tablets were greater as evidenced by higher serum concentrations of levonorgestrel, a greater area under the concentration-time curve during the first 24 hours, and a more marked suppressive effect on SHBG levels. These differences most probably reflect differences in their pharmaceutical formulation, in particular the extent of tablet dissolution and the degree of micronisation of levonorgestrel.


Dissolution of two arsenic compounds by rabbit alveolar macrophages in vitro.
The ability of rabbit alveolar macrophages to dissolve two arsenic compounds, 74As-labeled lead arsenate and arsenic trisulfide, was studied in vitro. The solubilities in water of these two compounds are related differently to pH. The solubility of lead arsenate increases and that of arsenic trisulfide decreases with decreasing pH. The radiolabeled particles were incubated with and without macrophages for up to 3 days, whereafter the amount of 74As in soluble form and the amount in particle form and/or bound to macrophages were determined. The results strongly support the hypothesis that the dissolution of particles by macrophages is influenced by the acid milieu in the phagosomes. About 14% of the 74As-labeled lead arsenate particles incubated for 3 days with the macrophages was released into the culture medium, compared with about 2% of the particles incubated with the culture medium without macrophages. With the arsenic trisulfide particles, less soluble 74As was released into the medium in samples with macrophages than in samples without macrophages, although the solubility in all incubations was considerably greater than that for lead arsenate. The results indicate that dissolution in the phagosomes of the macrophages may be of great importance for the clearance of particles such as lead arsenate, which are more soluble at pH 4 than at pH 7.


[Restructuring of the efferent activity of the scratching generator due to cyclic shifting of the position of the hindlimb in the decerebrate immobilized cat].
The influence of the afferent inflow conditioned by passive cyclic movement of the ipsilateral hindlimb tip along a trajectory near to that of real scratching on the scratching generator activity was studied in decerebrated immobilized cat. This inflow caused significant rebuilding of the scratching generator efferent activity aimed to bring efferent activity into a definite phase correlation with the afferent inflow. Synchronization of fictitious scratching with passive moving occurred at the first movement cycle, the phase correlation between them being contrary to that of real scratching.


Bladder cancer and its mimics: a sonographic pictorial review with CT/MR and histologic correlation.
Bladder cancer is the most common cancer of the urinary system and often presents with hematuria. Despite its relatively high incidence, bladder cancer is often under-recognized sonographically. Moreover, even when bladder abnormalities are identified, numerous other entities may mimic the appearance of bladder cancer. Given the incidence and prevalence of bladder cancer, it is important to recognize its variable appearance sonographically and distinguish it from its common mimics. We review the sonographic appearance of bladder cancer and its mimics, providing correlative CT/MR imaging as well as pathology. We stress the importance and advantage of ultrasound as a dynamic imaging modality, with the ability to optimize distinguishing bladder cancer from similar-appearing entities.


Rhodopsin, Gq and phospholipase C activation in cephalopod photoreceptors.
We present characterization of the rhodopsin, Gq and phosphatidylinositol-specific phospholipase C (PLC) from the signal transduction pathway of cephalopod photoreceptors. Cephalopod rhodopsins are unique in possessing a C-terminal extension of proline-rich repeats, and they have a strong tendency to form ordered arrays. Two-dimensional arrays of a full-length and C-terminally-truncated cephalopod rhodopsin have been obtained. The C termini appear to cluster the rhodopsins into small groups. An AlF4(-)-activated Gq alpha subunit has been isolated and shown to activate a partially purified PLC beta. This 130 kDa PLC, isolated by absorption on heparin agarose, showed a specific activity of 195 nmol of phosphatidylinositol 4,5-bisphosphate hydrolysed per milligram of protein per minute in the presence of 1.6 microM free calcium.


Fluocinolone acetonide 0.19-mg implant for the treatment of noninfectious uveitis with involvement of the posterior segment: a real-world study.
To evaluate the effectiveness of 0.19-mg fluocinolone acetonide implant (FAi) for preventing inflammatory relapses in noninfectious uveitis with posterior segment involvement in standard clinical practice. Further, to assess the value of remission induction therapy with intraocular and periorbital administered high-dose corticosteroids before FAi. A retrospective cohort study in a tertiary referral center specialized in uveitis management. The primary study outcomes were the best-corrected visual acuity (BVCA) and central retinal thickness (CRT) within a 12-month observation period. The secondary outcomes were intraocular pressure (IOP) and intraocular inflammation. The main safety measures were IOP increase and cataract formation. In total, 76 eyes of 57 patients received FAi. Locally administered high-dose corticosteroids were applied in 68.4% of all eyes before FAi. BCVA remained stable within the 12-month observation period (63.21 vs. 62.95, difference 0.26 letters; 95% CI: - 6.31 to 6.84; p > 0.9). Significant CRT reduction upon FAi was sustained after 12 months (362.7 vs. 309.1 μm, difference 53.57 μm; 95% CI: 1.55 to 105.6; p = 0.04). Intraocular inflammation was reduced until 9 months of follow-up (0.82 vs. 0.3, difference 0.53; 95% CI: 0.11 to 0.95; p = 0.007). A mean IOP increase (13.68 vs. 15.6; difference - 1.92; 95% CI: - 3.85 to 0.004; p = 0.0507) and cataract development (20% of all phakic eyes) were noted. We observed similar levels of FAi effectiveness for the treatment of noninfectious uveitis in standard clinical practice compared to previous randomized clinical trials. Moreover, remission induction therapy before FAi can benefit patients with increased baseline uveitis activity.


Neuroinflammation, Diabetes and COVID-19: Perspectives Coming from Ca2+/cAMP Signalling.
A link between inflammatory diseases, e.g., epilepsy, dementia, diabetes, and COVID-19, has been established. For instance, observational studies involving several individuals reported that people with epilepsy show an enhanced incidence of manifesting dysfunctions related to cognition, e.g., dementia, while people with dementia have a higher incidence of manifesting epilepsy, thus an evident bidirectional relationship between epilepsy and dementia might occur. In addition, epilepsy commonly cooccurs in patients with diabetes, indicating an association between these two disorders. Intriguingly, some reports have also observed a poor prognosis of people with both diabetes and COVID-19. It is recognized that a dyshomeostasis of both Ca2+ and cAMP signalling pathways could be a molecular connection for these disorders. Therefore, clarifying this clinical relationship among epilepsy, dementia, diabetes, and COVID-19 may outcome in novel hypotheses for identifying the etiology of these disorders.


Defining an optimal control for RNAi experiments with adult Schistosoma mansoni.
In parasites such as Schistosoma mansoni, gene knockdown by RNA interference (RNAi) has become an indispensable tool for functional gene characterization. To distinguish target-specific RNAi effects versus off-target effects, controls are essential. To date, however, there is still no general agreement about suitable RNAi controls, which limits the comparability between studies. To address this point, we investigated three selected dsRNAs for their suitability as RNAi controls in experiments with adult S. mansoni in vitro. Two dsRNAs were of bacterial origin, the neomycin resistance gene (neoR) and the ampicillin resistance gene (ampR). The third one, the green fluorescent protein gene (gfp), originated from jellyfish. Following dsRNA application, we analyzed physiological parameters like pairing stability, motility, and egg production as well as morphological integrity. Furthermore, using RT-qPCR we evaluated the potential of the used dsRNAs to influence transcript patterns of off-target genes, which had been predicted by si-Fi (siRNA-Finder). At the physiological and morphological levels, we observed no obvious changes in the dsRNA treatment groups compared to an untreated control. However, we detected remarkable differences at the transcript level of gene expression. Amongst the three tested candidates, we suggest dsRNA of the E. coli ampR gene as the most suitable RNAi control.


Targeting endoplasmic reticulum stress, Nrf-2/HO-1, and NF-κB by myristicin and its role in attenuation of ulcerative colitis in rats.
Ulcerative colitis (UC) is characterized by the up-regulation of pro-inflammatory mediators, apoptotic signals, and oxidative stress that can lead to an increased risk of colorectal cancer. The present study aims to investigate the possible role of myristicin in modulating endoplasmic reticulum stress (ERS) and risk-associated conditions in acetic acid (AA)-induced UC. Adult male rats were treated with 150 mg/kg body weight of myristicin or mesalazine orally either as pre/post treatment or post-treatment only. The gene expression of glucose-related protein 78 (GRP78), CCAAT/enhancer-binding protein homologous protein (CHOP), and nuclear factor kappa B (NF-κB), percentage of DNA fragmentation, and serum levels of some oxidative and inflammatory markers were measured. The results indicated the potential upregulation of ERS, pro-apoptotic, lipid peroxidation, and pro-inflammatory cascades by induction of UC in rats. However, myristicin could effectively reverse the deteriorated effects of ulceration in colonic mucosa. It was mediated through downregulation of the ERS markers GRP78 and CHOP genes expression, reduction of NF-κB mRNA expression, DNA fragmentation, reduced lipid peroxidation, myeloperoxidase (MPO) activity and pro-inflammatory markers (Tumor necrosis factor-α (TNF-α), Interleukin-1β (IL-1β) and cyclo‑oxygenase (COX-2) activity). Accompanied by elevated levels of IL-10, colonic Nuclear erythroid factor (Nrf-2) and Heme oxygenase (HO-1) activity as well as blood antioxidant enzymes activity. Results of docking might confirm the biological results of our study. Myristicin could effectively modulate important stress, and inflammatory effectors and protect mucosal DNA from oxidative damage which can serve as a promising candidate for the treatment of ulcerative colitis.


"European Resuscitation Council 2015 burn 1st Aid recommendations-concerns and issues for first responders".
As the lead author of a recently published systematic review on hydrogel burn dressings in pre-hospital, I was alarmed to read the claim by the authors to the effect no one method of burn wound cooling was superior to any other; "There is no evidence to recommend a specific temperature or method of cooling". The reputation and prominence of the ERC within the circle of resuscitation councils now delving into 1st Aid recommendations leads to the conclusion that misguided recommendations may cause confusion amongst first responders, may falsely misdirect 1st Aid providers to unsupported practices or alternatively create a window of opportunity for marketers or sellers of alternative burn 1st Aid technologies to make unsupported claims in respect of comparable efficacy of their own product versus "traditional" methods.