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The aim of the present study was to investigate character and temperament dimensions of personality in six men and 31 women (aged 20-57 yr) with severe dental anxiety, and to evaluate whether these dimensions were associated with the level of dental anxiety. The Dental Anxiety Scale (DAS) and the Temperament and Character Inventory (TCI) were used. High ratings in novelty seeking and female gender predicted high DAS scores. Compared with controls, the patients scored significantly higher on the temperament dimension, novelty seeking. For character dimensions, the patients scored lower on cooperativeness and higher on self-transcendence than controls. Our results indicated that patients with dental anxiety are neurotic extravert (i.e. novelty seekers who experience brief dissociative periods and magical thinking). Furthermore, the combination of the inherited temperament dimension novelty seeking and the social learned character dimension cooperativeness and self-transcendence seem to form a vulnerable personality to develop dental anxiety. | Manifest Anxiety Scale |
ALS-8112 is the parent molecule of ALS-8176, a first-in-class nucleoside analog prodrug effective in the clinic against respiratory syncytial virus (RSV) infection. The antiviral activity of ALS-8112 is mediated by its 5'-triphosphate metabolite (ALS-8112-TP, or 2'F-4'ClCH2-cytidine triphosphate) inhibiting the RNA polymerase activity of the RSV L-P protein complex through RNA chain termination. Four amino acid mutations in the RNA-dependent RNA polymerase (RdRp) domain of L (QUAD: M628L, A789V, L795I, and I796V) confer in vitro resistance to ALS-8112-TP by increasing its discrimination relative to natural CTP. In this study, we show that the QUAD mutations specifically recognize the ClCH2 group of ALS-8112-TP. Among the four mutations, A789V conferred the greatest resistance phenotype, which was consistent with its putative position in the active site of the RdRp domain. AZ-27, a non-nucleoside inhibitor of RSV, also inhibited the RdRp activity, with decreased inhibition potency in the presence of the Y1631H mutation. The QUAD mutations had no effect on the antiviral activity of AZ-27, and the Y1631H mutation did not significantly increase the discrimination of ALS-8112-TP. Combining ALS-8112 with AZ-27 in vitro resulted in significant synergistic inhibition of RSV replication. Overall, this is the first mechanistic study showing a lack of cross-resistance between mutations selected by different classes of RSV polymerase inhibitors acting in synergy, opening the door to future potential combination therapies targeting different regions of the L protein. | Cytidine Triphosphate |
Metabolic-associated fatty liver disease (MAFLD), formerly referred to as non-alcoholic fatty liver disease (NAFLD), is a common liver disease characterized by an abnormal buildup of fat in liver. This study aimed to investigate whether bioactive dipeptides mitigate high-fat and high-fructose corn syrup diet (HFFD)-induced MAFLD in C57BL/6J mice. Sixty male C57BL/6J mice were randomly divided into six groups. The naive group (untreated) was fed a standard chow diet and other groups were fed with HFFD along with vehicle and bioactive dipeptides treatment throughout experiment period. The control group received vehicle, YF10 and YF50 groups received Tyr-Phe, 10 and 50 mg/kg/day, FY10 and FY50 groups received Phe-Tyr, 10 and 50 mg/kg/day. At the end of experiment, body weight was recorded, and glucose homeostasis was assessed. Mice were sacrificed and blood samples were collected to measure biochemical parameters. Further, liver, visceral fat pads, and other organs were acutely dissected, weighed, and processed. Histopathological and immunohistochemical changes were analyzed. Long-term HFFD feeding resulted in elevated body weight gain, liver weight, visceral adiposity, liver injury, fasting hyperglycemia, hyperinsulinemia, and hyperlipidemia. It also increased severe hepatic steatosis, chronic low-grade inflammation, oxidative stress, mitochondrial dysfunction, and lipid peroxidation. However, bioactive dipeptides dose-dependently alleviated these complications which are associated with MAFLD by modulating adipokines secretion and antioxidant defense system via upregulation of Nrf2/HO-1 expressions. This study highlights potential of bioactive dipeptides as a promising approach for prevention and/or treatment of MAFLD induced by HFFD, providing novel insights into alternative therapeutic strategies. | High Fructose Corn Syrup |
Depolarizing 1-s pulses to 0 mV from a holding potential of -70 mV, induced whole-cell currents through Ca2+ channels (ICa) in patch-clamped cat adrenal medulla chromaffin cells. The dihydropyridine (DHP) furnidipine (3 microM) reduced the peak current by 47% and the late current by 80%. omega-Conotoxin GVIA (CgTx, 1 microM) reduced the peak ICa by 42% and the late ICa by 55%. Pulses (10 s duration) with 70 mM K+/2.5 mM Ca2+ solution (70 K+/2.5 Ca2+), applied to single fura-2-loaded cat chromaffin cells increased the cytosolic Ca2+ concentration ([Ca2+]i) from 0.1 to 2.21 microM; this increase was reduced by 43.7% by furnidipine and by 42.5% by CgTx. In the perfused cat adrenal gland, secretion evoked by 10-s pulses of 70 K+/2.5 Ca2+ was reduced by 25% by CgTx and by 96% by furnidipine. Similar results were obtained when secretion from superfused isolated cat adrenal chromaffin cells was studied and when using a tenfold lower [Ca2+]o. The results are compatible with the existence of DHP-sensitive (L-type) as well as CgTx-sensitive (N-type) voltage-dependent Ca2+ channels in cat chromaffin cells. It seems, however, that though extracellular Ca2+ entry through both channel types leads to similar increments of averaged [Ca2+]i, the control of catecholamine release is dominated only by Ca2+ entering through L-type Ca2+ channels. This supports the idea of a preferential segregation of L-type Ca2+ channels to localized hot spots" in the plasmalemma of chromaffin cells where exocytosis occurs." | Adrenal Medulla |
Activin, nodal, Vg1, and growth and differentiation factor 1 are members of the transforming growth factor beta superfamily and signal via the activin type II (ActRII/IIB) and type I (ALK4) serine/threonine kinase receptors. Unlike activins, however, signaling by nodal, Vg1, and growth and differentiation factor 1 requires a coreceptor from the epidermal growth factor-Cripto-FRL1-Cryptic protein family such as Cripto. Cripto has important roles during development and oncogenesis and binds nodal or related ligands and ALK4 to facilitate assembly of type I and type II receptor signaling complexes. Because Cripto mediates signaling via activin receptors and binds directly to ALK4, we tested whether transfection with Cripto would affect the ability of activin to signal and/or interact with its receptors. Here we show that Cripto can form a complex with activin and ActRII/IIB. We were unable to detect activin binding to Cripto in the absence of ActRII/IIB, indicating that unlike nodal, activin requires type II receptors to bind Cripto. If cotransfected with ActRII/IIB and ALK4, Cripto inhibited crosslinking of activin to ALK4 and the association of ALK4 with ActRII/IIB. In addition, Cripto blocked activin signaling when transfected into either HepG2 cells or 293T cells. We have also shown that under conditions in which Cripto facilitates nodal signaling, it antagonizes activin. Inhibition of activin signaling provides an additional example of a Cripto effect on the regulation of signaling by transforming growth factor-beta superfamily members. Because activin is a potent inhibitor of cell growth in multiple cell types, these results provide a mechanism that may partially explain the oncogenic action of Cripto. | Activin Receptors, Type I |
A controlled, double-blind comparison of naphalzoline hydrochloride 0.05%, antazoline phosphate 0.5%, a combination of both components and a placebo was performed on 51 ragweed sensitive patients presenting allergic conjunctivitis. Evaluation of response at various times after instillation of medication for lacrimation, conjunctival inflammation, pruritus, photophobia and pain showed naphazoline hydrochloride, antazoline phosphate and the combination product superior to placebo. The combination product was statistically significantly superior for conjunctival inflammation and photophobia. The need for post-challenge treatment with epinephrine hydrochloride was significantly less in those eyes treated with the combination product. demonstrating prophylactic efficacy. | Antazoline |
We have recently demonstrated that the keratin K3 gene, which is active in the suprabasal human corneal epithelium, is missing in the genome of the mouse. We show that a normal K3 gene exists in a wide variety of mammals while in rodents the gene is converted to a pseudogene with a very strong sequence drift. The availability of K5-/- mice provides a unique opportunity to investigate type-specific keratin function during corneal differentiation in the absence of both K5 and K3. Here, we report that the deletion of K5, which in wild-type mice forms a cytoskeleton with K12, does neither cause keratin aggregation nor cytolysis in the cornea. This is due to the induction of K4 in corneal epithelial cells, normally restricted to corneal stem stem cells residing in the limbus. Using a combination of antibodies and RT-PCR, we identified additional keratins expressed in the mouse cornea including K23 which was previously thought to be specific for pancreatic carcinomas. This reflects an unexpected complexity of keratin expression in the cornea. Our data suggest that in the absence of mechanical stress, corneal differentiation does not depend on distinct keratin pairs, supporting a concept of functional redundancy, at least for certain keratins. | Keratin-15 |
Perinatally, granulosa cells encase individual oocytes within the ovary to form primordial follicles. The initial stages of folliculogenesis are independent of gonadotropins and involve cell-autonomous and non-cell-autonomous factors. Although still poorly understood at a molecular level, successful follicle formation and initiation of follicle growth must involve genetic networks both in germ and in somatic cells. Mouse models offer useful windows into these essential processes. By investigating phenotypes of mouse lines lacking specific gene products, genetic hierarchies that regulate the initial stages of folliculogenesis are being elucidated. These investigations will provide insight into the regulation of mammalian fertility. | Gonads |
Health information technology can support the development of national learning health and care systems, which can be defined as health and care systems that continuously use data-enabled infrastructure to support policy and planning, public health, and personalisation of care. The COVID-19 pandemic has offered an opportunity to assess how well equipped the UK is to leverage health information technology and apply the principles of a national learning health and care system in response to a major public health shock. With the experience acquired during the pandemic, each country within the UK should now re-evaluate their digital health and care strategies. After leaving the EU, UK countries now need to decide to what extent they wish to engage with European efforts to promote interoperability between electronic health records. Major priorities for strengthening health information technology in the UK include achieving the optimal balance between top-down and bottom-up implementation, improving usability and interoperability, developing capacity for handling, processing, and analysing data, addressing privacy and security concerns, and encouraging digital inclusivity. Current and future opportunities include integrating electronic health records across health and care providers, investing in health data science research, generating real-world data, developing artificial intelligence and robotics, and facilitating public-private partnerships. Many ethical challenges and unintended consequences of implementation of health information technology exist. To address these, there is a need to develop regulatory frameworks for the development, management, and procurement of artificial intelligence and health information technology systems, create public-private partnerships, and ethically and safely apply artificial intelligence in the National Health Service. | Learning Health System |
INTRODUCTION: Air-rotor stripping (ARS) is a commonly used method to alleviate crowding in the permanent dentition. Its widespread acceptance, however, has been limited by the potential increase in caries risk of the abraded enamel surface. The aim of this study was to compare the susceptibility of ARS-treated enamel surfaces with intact surfaces in patients undergoing fixed orthodontic therapy. METHODS: Forty patients treated with ARS were examined clinically and radiographically for caries 1 to 6 years after interproximal enamel reduction. All patients were seen by their dentists for prophylaxis at 6-month intervals during active orthodontic treatment and were exposed to fluoridated water and toothpaste. Topical fluoride agents or sealants were not applied on the abraded surface after any ARS session. Caries incidence was compared between ARS-treated and unaltered surfaces within subjects. The decayed, missing, filled tooth (DMFT) and surface (DMFS) scores were used to evaluate the subjects' overall caries risk. RESULTS: Totals of 376 test and 376 control surfaces were examined. The number of interproximal lesions detected was found to be low with no statistically significant difference detected between the groups (test = 3; control = 6; P = .33]. The DMFT and DMFS scores increased significantly during the study period, indicating that these patients were clearly at risk of tooth decay (P <.001). CONCLUSIONS: The findings indicate that the risk of caries is not affected by ARS. Furthermore, our data show that the application of topical fluoride on the enamel surfaces immediately after ARS in patients exposed to fluoridated water and fluoride-containing toothpaste may not provide any additional benefit. | Air Abrasion, Dental |
Transposable elements (TEs) are various DNA fragments inserted throughout genomes, which are able to move or duplicate themselves. Recent advances in genomics have placed them back at the center of genome dynamics. One of the emerging observations, especially in plants, is the importance of interactions between TEs and genes to generate or to participate in relevant functions essential for development, adaptation and/or life cycle. A recent publication illustrates the influence of TEs epigenetic control on the expression of a neighboring gene crucial for reproduction. Different reports lately showed that a fundamental mechanism such as imprinting is likely to be closely linked to the dynamics of TEs epigenetic control. Here we discuss and bring together these and others recent findings, to underline that the cis-vicinity or the trans-relation between TEs and genes could bring unexpected but positive outcomes. | DNA Transposable Elements |
Mucoepidermoid carcinoma (MEC) is the most common malignant, locally-invasive tumour of the salivary glands, and accounts for approximately 35% of all malignancies of the major and minor salivary gland. Minor salivary glands are scattered in different areas of the oral cavity such as palate, retromolar area, floor of the mouth, buccal mucosa, lips and tongue. MECs of tongue base are not common. We present a rare case of MEC localised at the tongue base in a 42-year-old Caucasian woman and discuss the histopathological types, management and review the literature. Adequate intra-oral excision was the treatment of choice in this case and in low-grade MEC. Prognosis of MEC is a function of the histological grade, adequacy of excision and clinical staging. | Carcinoma, Mucoepidermoid |
OBJECTIVE: To study the outcome of military working dogs (MWDs) diagnosed with degenerative lumbosacral stenosis (DLS) after surgical intervention and to determine what prognostic indicators affected outcome. STUDY DESIGN: Retrospective study. ANIMALS: Twenty-nine MWDs with DLS. METHODS: The medical records of dogs diagnosed and surgically treated for DLS at the Department of Defense Military Working Dog Veterinary Service Hospital were reviewed. Retrieved data were signalment, clinical signs, survey radiograph results, and surgical findings. RESULTS: Breed and sex were not found to have prognostic significance. Increasing age at surgery correlated with a poor surgical outcome. Twelve dogs (41%) returned to normal function, 11 (38%) improved, and 6 (20%) never returned to active duty. The average age at surgery was 74 months, 93 months, and 112 months for normal, improved, and dogs not returning to duty, respectively. Significant clinical findings associated with a poor prognosis were related to increasing neurologic severity. The only significant radiographic finding indicating a poor prognosis was foraminal narrowing. Surgical findings with negative prognostic significance were hypertrophic articular facets and interarcuate ligament. Recurrence rates were 16.7% and 54.5% for normal and improved dogs, respectively. CONCLUSIONS: MWDs with DLS have a good prognosis with surgical decompression if they are young dogs with mild clinical signs at the time of diagnosis. As age and severity of clinical signs increase, the prognosis for successful outcome decreases. Recurrence may be seen in some dogs. CLINICAL RELEVANCE: Information provided by this study should help military veterinarians determine the prognosis for working dogs with DLS after surgical treatment. | Veterinary Service, Military |
Cryopreservation is the most promising option for the long-term germplasm conservation of recalcitrant-seeded species. However, the variable post-cryo success achieved with the excised zygotic explants traditionally used for cryopreservation has been a concern for some time. Differential drying rates amongst explants of different species, uneven drying amongst explants within a batch of seeds and uneven drying across tissues within individual embryos could be contributory factors to this variable success and these phenomena form the foci of the present study. Using zygotic explants from a range of recalcitrant-seeded species, which included sub-tropical dicotyledonous trees and sub-tropical monocotyledonous geophytes, the study showed that embryo morphology and anatomy are critical determinants of the drying characteristics of the different tissues composing the explant and hence, post-cryo survival. The results suggest that the rates of drying of explants to water contents (WCs) in the theoretically optimal range for successful cryopreservation are species-specific, and that more rapid drying rates may promote post-cryo survival. However, the large variation in WC amongst individual explants in bulk samples challenges the selection of the theoretically optimum WC for cryopreservation. As a consequence of differential drying rates across the different tissues composing explants, either lethal ice crystal damage or desiccation damage may sometimes be likely in tissues responsible for the onwards development of the embryo. Drying times for cryopreservation of such explants should, therefore, be selected on the basis of WC of segments containing root or shoot meristem, rather than embryo bulk WC. Drying intensity and duration also interact with explant morphology and embryo/axis size and anatomy to bring about - or preclude - post-cryo survival. | Castanospermum |
While molecular genetic abnormalities can tell us much about the pathogenesis of acute myeloid leukemia (AML), these molecular genetics do not always explain drug resistance or sensitivity, leaving room for other mechanisms of tumor pathogenesis outside of genetic events. The Beat AML 1.0 project was a multicenter project to sequence and functionally query AML samples against over 120 drugs. The results have helped form disease models on how mutations affect disease phenotype and drug sensitivity and have assisted in identifying gene signature profiles that may facilitate selecting the most effective treatment options. However, there are factors outside of genetic abnormalities that affect disease pathogenesis. For example, tumor-associated macrophages in the tumor microenvironment play a role in pathogenesis and represent therapeutic targets." | Gene Expression Regulation, Leukemic |
Intracellular recordings were made of neurons in the myenteric plexus of the guinea-pig distal ileum. Slow excitatory postsynaptic potentials (sEPSPs) were evoked by electrical stimulation of an interganglionic fibre tract. The effect of cholecystokinin (CCK) receptor antagonists on the sEPSPs was investigated in 11 neurons. Application of the CCK receptor antagonists L-364,718 and L-365,260 (each 250 nM) markedly attenuated the sEPSPs in five of 11 neurons. The amplitude of the sEPSP reduced from 15 +/- 3 to 7 +/- 2 mV and the change in membrane resistance during the sEPSP was reduced from 28 +/- 9 to 11 +/- 8 MS. In six of 11 neurons the CCK antagonists had no effect on the sEPSPs. The results provide evidence that neurally released CCK is involved in the mediation of sEPSPs in some enteric neurons. | Devazepide |
A new membrane-based strategy to purify oxidized coenzyme A ((CoAS)(2)) from adenosine triphosphate (ATP), adenosine diphosphate (ADP) and adenosine monophosphate (AMP) has been developed. Commercially available membranes were screened and studied (permeate flux and overall compounds retention) which allowed the identification of one efficient membrane (GK from Suez Water Technologies & Solutions). Different total compounds concentrations solutions were used in the system in order to find the following working conditions: 4 bars with a total compounds solution of 5.19 g L(-1). Applying these conditions to a dia-filtration set-up allowed us to reach 68% pure (CoAS)(2) in 4.8 diafiltration volumes (DV) and a 95% (CoAS)(2) purity can be predicted in 8.5 DV. A comparative study of green metrics-i.e. process mass index (PMI)-of the classic chromatography vs the membrane-based one demonstrated the great advantages of the latter in terms of sustainability. This strategy unlocks the access to the essential and central cofactor that is coenzyme A." | Heterocyclic Compounds, Fused-Ring |
In this article, I analyze the experience and consequences of grief among the Ayoreo from the Paraguayan Chaco through the study of mourning songs. As a methodological proposal, I suggest that the study of verbal art in conjunction with an ethnography of everyday domestic life can provide clues to understanding the experience of grief and its relation to expected behavior. This study shows that grief among the Ayoreo can be socially disruptive if not dealt with properly, as songs depict grieving Ayoreo as opposite to healthy people in terms of sociability and expected role fulfillment. | Grief |
The cysteinyl leukotrienes (leukotriene C4, D4 and E4) have potent biological actions which significantly contribute to the airway obstruction in asthma. Several of these effects are blocked by drugs known as CysLT1-receptor antagonists. However, there are actions of leukotrienes which are not sensitive to these antagonists, suggesting the presence of additional receptor subtypes. It was the aim of this Thesis to extend the knowledge about receptors for cysteinyl leukotrienes. Three different isolated smooth muscle preparations kept in organ baths under non-flow conditions were characterised with respect to responsiveness to cysteinyl leukotrienes and sensitivity to purported CysLT1-receptor antagonists. In addition, the study involved evaluation of a leukotriene E4 analogue, BAY u9773, suggested to inhibit responses which cannot be blocked by CysLT1-receptor antagonists. These responses have provisionally been considered to be mediated by CysLT2-receptors. In the guinea pig ileum, BAY u9773 but not the selective CysLT1 receptor antagonist ICI 198,615 inhibited the contractile response to leukotriene C4 in a fashion suggesting competitive antagonism. In sheep trachealis muscle, BAY u9773 antagonised contractions induced by leukotriene C4 and leukotriene D4 in a similar manner, whereas ICI 198,615 did not. The observations support that leukotriene C4 in guinea pig ileum, and leukotriene C4 as well as leukotriene D4 in sheep trachealis muscle, mediated contractions via activation of CysLT2-receptors. In guinea pig lung parenchyma, the effects of BAY u9773 and conventional cysteinyl leukotriene receptor antagonists (ICI 198,615, FPL 55,712) were more complex. First, BAY u9773 evoked a contraction, which could be inhibited by antagonists of CysLT1- and TP-receptors. This suggested that BAY u9773 acted as an agonist at these two receptors. Second, pretreatment with BAY u9773 inhibited a distinct but relatively small component of the contractile response to leukotriene C4 and D4. The effects of BAY u9773 and ICI 198,615 were similar in guinea pig lung parenchyma. The findings suggest that the receptor mediating the major part of the contractile response to exogenous cysteinyl leukotrienes in guinea pig lung parenchyma was different from the currently defined CysLT2-receptor. Furthermore, the data suggested that BAY u9773 was a partial agonist at cysteinyl leukotriene receptors, which presumably contributed to its profile of activity as a combined CysLT1- and CysLT2-receptor antagonist. In addition to contracting guinea pig lung parenchyma, leukotriene C4 and lipoxin A4 also evoked release of thromboxane A2. This release was sensitive to CysLT1-receptor antagonists and contributed to part of the contractile response. Finally, the investigations included a characterisation of the role of leukotrienes in antigen-induced contractions of lung parenchyma from actively sensitised guinea pigs. Combination of antihistamines with CysLT1-receptor antagonists or inhibitors of leukotriene biosynthesis blocked the major component of the antigen-induced contraction. The findings are similar to those observed in isolated human bronchi and support that this model may be used to investigate mediator mechanisms of relevance to asthma. | Leukotrienes |
The Toll-like receptor 4 is a key mediator of the innate immune response. Besides its main ligand, the Gram-negative bacterial lipopolysaccharides, other molecules such as heat-shock protein 60, oxidized low density lipoprotein and fibronectin can also bind to the receptor. Activation of the Toll-like receptor induces the production of proinflammatory cytokines. There is increasing evidence showing that the Toll-like receptor 4 plays a role not only in the immune reaction against infectious agents but also in chronic non-infectious inflammatory diseases, such as atherosclerosis, diabetes mellitus and inflammatory bowel disease. This review briefly summarizes recent knowledge on the Toll-like receptor 4, its common co-segregation polymorphisms and the impact of these polymorphisms on various human diseases. | Toll-Like Receptor 4 |
A most convenient model to study mechanisms of live organism response to chemical carcinogens is tumor induction in murine liver by aminoazodyes, in particular by ortho-aminoazotoluene (OAT). We studied both early and late stages of hepatocarcinogenesis on several lines of inbred mice differing in sensibility to OAT. By means of autoradiography, we examined proliferative activity of hepatocytes obtained from the liver of sensitive (A/He, DD, SWR) and resistant to OAT AKR, CC57Br, BALB/c lines of mice, which were injected carcinogen. The level of p53, p21Cip1, bax, mdm2, cyclin G, gadd45 genes expression in the liver of mice of different lines given OAT injection was studied by multiplex PCR method. Carcinogen caused a decrease of hepatocyte proliferative activity induced by partial hypatectomy (PHE), and an increase in p53, p21Cip, bax, mdm2, and cyclin G genes within mice of A/He, DD and SWR lines. Cell fusion experiments on hepatocytes obtained from regenerating murine liver sensitive to A/He line carcinogen and given long-time OAT administrations with resting and proliferating fibroblasts of NIH 3T3 mice revealed no obvious suppression of DNA synthesis in heterokaryons. Unlike, in fusion experiments on serum-stimulated fibroblasts with hepatocytes obtained from the liver of BALB/c line mice also given OAT suppression of DNA synthesis in stimulated fibroblasts in heterokaryons was observed 15 days following PHE. These results enable us to conclude that OAT administrations break negative endogenous mechanisms of hepatocyte proliferation control in the liver of mice sensitive to carcinogenes. | o-Aminoazotoluene |
BACKGROUND: Scarpa fascia preservation has been proposed to minimize complications associated with conventional abdominoplasty, but its efficacy is unclear. The purpose of this article is to determine the influence of preserving scarpa fascia on reducing postabdominoplasty complications. METHODS: A comprehensive search of Medline Ovid, PubMed, Web of Science, and the Cochrane CENTRAL databases was conducted from the inception till June 2021. Eligible studies were prospective controlled studies investigating postoperative complications after scarpa fascia preservation following abdominoplasty. Stata 15.1 software was used for the meta-analysis. RESULTS: The meta-analysis included seven studies with 682 abdominoplasty patients. Abdominoplasty with scarpa fascia preservation could significantly reduce incidence of seroma (OR = - 1.34, 95% CI = - 2.09 - - 0.59, P < 0.05), length of hospital stay (SMD = - 1.65; 95% CI = - 3.50-0.20; P = 0.08), time to drain removal (SMD = - 3.64; 95% CI = - 5.76 - - 1.52; P < 0.05), and total drain output (SMD = - 401.60; 95% CI = - 593.75 - - 209.44; P < 0.05) compared with that of conventional abdominoplasty. However, it failed to achieve a statistically significant reduction in hematoma (OR=- 1.30, 95% CI = - 2.79-0.18, P = 0.08), infection (OR = - 1.03; 95% CI = - 2.17-0.12; P = 0.08), skin necrosis (OR = 0.63; 95% CI = - 1.20-2.45; P = 0.50), and wound dehiscence (OR = 0.28; 95% CI = - 0.28-0.83; P = 0.33). The seroma incidence rate was lower when a scalpel was utilized for dissection rather than electrocautery (3% (95% CI = 1-7%) versus 11% (95% CI = 5-18%)). CONCLUSIONS: Preservation of scarpa fascia during abdominoplasty might reduce the likelihood of postoperative seroma, length of hospital stay, time to drain removal, and total drain output. However, it did not significantly affect the incidence of hematoma, infection, skin necrosis, and wound dehiscence. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 . | Prospective Studies |
The composition of plant membrane lipids was investigated by reversed-phase high performance liquid chromatography mass spectrometry with accurate mass measurement. The data dependent methods for the analysis of monogalactosyldiacylglycerols (MGDGs) and digalactosyldiacylglycerols (DGDGs) have been developed. The optimised chromatographic systems were based on a 2.0 mm i.d. Nucleosil C18 column with methanol/water (MGDGs) or acetonitrile/methanol/water (DGDGs) gradients. The galactolipids were ionised by electrospray operated in the positive ion mode and identified based on their MS/MS spectra. High resolution spectra with accurate masses were found to be essential for correct interpretation of the MS data. The elution order of non-oxidised MGDGs and DGDGs followed the equivalent carbon numbers. The methods were applied for detailed characterisation of the MGDGs and DGDGs in the leaves of Arabidopsis thaliana and Melissa officinalis. | Galactolipids |
Although the benefit of extra-oral implants in the reconstruction of maxillofacial oncological defects is undisputable, some relevant issues need to be clarified. The purpose of this retrospective study was to evaluate the relationship between implants placed during ablation (DA-implants) and after ablation (AA-implants) of the tumor with respect to implant survival. In total, 103 implants were assessed: 44 nasal implants (17 patients) and 59 orbital implants (18 patients). All patients received their implant-retained maxillofacial epithesis between 1997 and 2010, with a mean follow-up of 35 months (range 8-156 months). The survival rate of DA-implants was 90.0% for the orbital region and 93.5% for the nasal region. The survival rate of the AA-implants for the orbital and the nasal region was 82.8% and 61.5%, respectively. This study shows a significant higher survival rate of extra-oral implants placed during ablative surgery compared to implants in a later stage (p=0.044), thereby stressing the importance of installing extra-oral implants during the ablative surgical session. | Orbital Implants |
Adenoviruses are medium size nonenveloped viruses with a trend of coevolution with their hosts. We surveyed South American fur seals (Arctocephalus australis) and Humboldt penguins (Spheniscus humboldti) for adenoviruses at two sites from 2009 to 2012. Despite the common pattern of host specificity, some of the adenoviruses in our study were present in samples from unexpected host species. We identified mastadenoviruses, aviadenoviruses, and siadenoviruses in A. australis from Peru and Chile and in S. humboldti from Peru. The El Nino Southern Oscillation (ENSO) significantly reduces the productivity of the Humboldt upwelling system, which can change trophic and other ecological interactions, facilitating exposure to new pathogens. One aviadenovirus was detected in both the penguins and the fur seals, an interclass distance. This finding occurred only during the 2009 ENSO and not in 2010 or 2012. Further studies of viral diversity in sites with high-density mixed species populations are necessary to better understand viral evolution and the effect of environmental change on viral evolution and host specificity. | Fur Seals |
PURPOSE: The purpose of this review was to examine the wheelchair accessibility in public buildings and discuss the role of professional in this practice area. METHOD: Of the 85 originally identified publications from a search of major electronic bibliographic databases, 12 studies relating to wheelchair accessibility in public buildings were selected. The compliance rates with wheelchair accessibility in different areas were summarised. RESULTS: No study reported 100% wheelchair accessibility despite the enforcement of existing laws and regulations. Parking had the lowest compliance rate among all facilities in terms of accessibility, while entrances had the highest. CONCLUSIONS: A global review is needed of both new and old buildings regarding wheelchair accessibility. Professional in this practice area has an important role to play in advocating wheelchair accessibility and assisting wheelchair users to participate fully in all areas of the community." | Facility Design and Construction |
L- and D-aspartic acids (L-Asp and D-Asp) are present in the majority of nervous systems. In phylogeny, significant levels have been reported in mollusc brains, particularly cephalopods. To examine the role of L- and D-Asp on a cephalopod receptor, we studied ligand gating of a squid glutamate receptor (SqGluR) expressed in HEK 239 (human embryonic kidney) cells. Under voltage clamp, application of L-glutamate (L-Glu; 1-30 mM), but not D-glutamate (D-Glu), or L- or D-Asp, evoked an inward current of 0.1 nA. L- or D-Asp (200 microM) applied with 20 mM L-Glu, slowed the time course of activation and inactivation of the L-Glu gated current (time constant increased from 1 s (L-Glu alone) to 3 s (D-Asp and L-Glu) and to 19 s (L-Asp and L-Glu)). Our results suggest that in molluscan systems, aspartic acid could act as a neuromodulator during glutamatergic transmission and could significantly alter synaptic integration by slowing glutamate receptor gating. | D-Aspartic Acid |
Education in laryngology has been a subject of interest at least since Louis Elsberg's address to the first meeting of the American Laryngological Association in 1879. Remarkable scientific, technological, and clinical advances during the 1980s and 1990s have elevated the standard of laryngological care. It is essential for training programs to promulgate these important advances through well-planned, comprehensive curricula. Such training should also foster an appreciation for the kinds of creative thought, interdisciplinary collaboration, and imaginative clinical practice that have been responsible for many of the recent dramatic advances in the field of laryngology. | Otolaryngology |
During the summer of 1849-50, a yellow fever epidemic hit the city of Rio de Janeeiro. In analyzing the epidemic's impact on local funeral customs, the article asked to what extent the subsequent high mortality rate was a catalyst that changed people's attitudes towards death and the deceased. The central hypothesis is that the epidemic was the final argument physicians needed to convince the imperial government and the population to implement these doctors' project, one which would medicalize death and standardize funeral customs. | Urban Health |
Since its discovery in 1982, numerous biological activities of interleukin-4 (IL-4) have been described. Like other cytokines, IL-4 is highly pleiotropic, both with respect to the number of different target cells that are responsive to it and with respect to the number of different biological responses it elicits. Interleukin-4 was initially described as a costimulant for the proliferation of B lymphocytes stimulated with anti-IgM antibody. Synonyms for this cytokine are B cell growth factor-1 (BCGF-1) and B cell stimulatory factor-1 (BSF-1). After cloning of both the murine and human IL-4, the use of recombinant IL-4 enabled detailed studies of its biological functions. Many cell types, mainly of hematological origin, express receptors for IL-4. Accordingly, effects of IL-4 have been described on B lymphocytes, T lymphocytes, NK cells, mononuclear phagocytes, mast cells, fibroblasts and hematopoietic progenitor cells. Currently, there are three major areas in which IL-4 appears to play an important role: 1) regulation of B cell growth and of antibody isotype expression. In this context, a possible role for IL-4 in allergic reactions is of special interest. 2) Stimulation of T cell growth and the generation of cytotoxic T lymphocytes. In addition to the suppressive effects on the induction of non HLA-restricted cellular cytotoxicity by natural killer- (NK) and lymphokine-activated killer (LAK) cells, this suggests a role for IL-4 in the regulation of cellular immune responses. 3) Regulation of the growth and differentiation of hematopoietic bone marrow stem cells. IL-4 itself does not induce proliferation of hematological progenitor cells but it can modulate the growth-factor dependent proliferation of these cells. In this review the biological functions of IL-4, reported until present, are discussed. | Interleukin-4 |
Different gamma radiation interaction parameters has been measured experimentally for the prepared diaspore-flyash concretes at 59.54, 662, 1173 and 1332 keV using narrow-beam transmission geometry and results are found to be in good agreement with theoretical values computed with a computer programme, WinXCom. The radiation exposure rate and absorbed dose rate for the gamma radiation with and without shielding of diaspore-flyash concretes have been determined using linear attenuation results. The results show that on average, there is reduction of 95%, 53% and 40% in dose rate for gamma sources (241)Am, (137)Cs and (60)Co, respectively with diaspore-flyash concretes as shielding material. Other health physics parameters namely equivalent dose, effective dose, gamma flux and energy fluence rate have also been determined. | Absorption, Physicochemical |
Male Club-winged Manakins, Machaeropterus deliciosus (Aves: Pipridae), produce a sustained tonal sound with specialized wing feathers. The fundamental frequency of the sound produced in nature is approximately 1500 Hz and is hypothesized to result from excitation of resonance in the feathers' hypertrophied shafts. We used laser Doppler vibrometry to determine the resonant properties of male Club-winged Manakin's wing feathers, as well as those of two unspecialized manakin species. The modified wing feathers exhibit a response peak near 1500 Hz, and unusually high Q-values (a measure of resonant tuning) for biological objects (Q up to 27). The unmodified wing feathers of the Club-winged Manakin do not exhibit strong resonant properties when measured in isolation. However, when measured still attached to the modified feathers (nine feathers held adjacent by an intact ligament), they resonate together as a unit near 1500 Hz, and the wing produces a second harmonic of similar or greater amplitude than the fundamental. The feathers of the control species also exhibit resonant peaks around 1500 Hz, but these are significantly weaker, the wing does not resonate as a unit and no harmonics are produced. These results lend critical support to the resonant stridulation hypothesis of sound production in M. deliciosus. | Feathers |
The effect of a hormone-like substance first reaching a receptor is of decisive importance in the unicellular (Tetrahymena) model system. The effect of the similar or dissimilar molecule after the first or second pretreatment depends to a great extent on pretreatment if it was carried out by a similar substance, but it does not depend on it if the agent used for pretreatment was different chemically. Receptor memory developing after hormonal imprinting can thus be disturbed by molecules of similar nature, but the effect of a different molecule--if it acts immediately after the imprinting--cannot be neglected, either. | Diiodotyrosine |
In vitro roots cultures of Typha latifolia and Scirpus americanus aquatic plants have the capacity to remove Pb (II), Mn (II), and Cr (III) from the culture medium. Both species remove Cr and Pb by an absorption process, while Mn is mainly adsorbed to the root surface. This chapter describes a protocol for the establishment of in vitro roots cultures (nontransformed) from T. latifolia and S. americanus, and the procedure for the uptake analysis of Pb (II), Mn (II), and Cr (III) by roots. | Typhaceae |
The first synthesis of kottamide E, a marine natural product containing a 5,6-dibromoindole linked via a (Z)-enamide to an unusual 1,2-dithiolane-containing amino acid, is reported. | Thioctic Acid |
Pentazocine, butorphanol, nalbuphine, and buprenorphine are mixed agonist-antagonist opioids that are effective analgesics, with less abuse potential than the agonists morphine, propoxyphene, and codeine. The dual properties of the agonist-antagonists are largely explained by their varying actions at the postulated three types (mu, chi, and sigma) of opioid receptors. The agonist-antagonists are classified as either morphine-like or nalorphine-like, based on their acute effects and withdrawal symptoms after chronic dosing. Buprenorphine is morphine-like, while the other drugs are nalorphine-like. These agents vary in the duration of analgesia, with pentazocine having a mean action of three hours and buprenorphine greater than six hours. The hemodynamic effects of nalbuphine and buprenorphine generally resemble those of morphine, while pentazocine and butorphanol increase cardiac workload, blood pressure, and pulmonary artery pressure. The agonist-antagonists have ceilings for respiratory depression, whereas the agonists produce dose-dependent depression. Agonist-antagonists generally produce less increase in biliary ductal pressure than does morphine. The major clinical limitations are that agonist-dependent patients may experience unpleasant subjective effects, when treated with the agonist-antagonists, and the nalorphine-like agents can produce psychotomimetic effects. More clinical experience is needed to rank the abuse potential within this group of opioids. The newer agents are being studied for oral use in acute and chronic pain." | Peripheral Nervous System Agents |
A 52-year-old gravida 1, para 1 woman with M- red cells experienced a delayed hemolytic transfusion reaction and exhibited an anti-M antibody following the infusion of four units of M+ red cells. Measurements of erythrocyte survival using 51Cr-labeled donor M+ and M- red cells and in vitro studies of monocyte-macrophage phagocytosis of sensitized reagent red cells implicate anti-M in the pathogenesis of hemolysis. | Chromium Radioisotopes |
The nasal septal cartilage plays an important role in the growth of midface and as a vertical strut preventing the collapse of the nasal bones. The repair of nasal cartilage defects remains a major challenge in reconstructive surgery. The tissue engineering strategy in the development of tissue has opened a new perspective to generate functional tissue for transplantation. Given the poor regenerative properties of cartilage and a limited amount of autologous cartilage availability, intense interest has evoked for tissue engineering approaches for cartilage development to provide better outcomes for patients who require nasal septal reconstruction. Despite numerous attempts to substitute the shapely hyaline cartilage in the nasal cartilages, many significant challenges remained unanswered. The aim of this research was to carry out a critical review of the literature on research work carried out on the development of septal cartilage using a tissue engineering approach, concerning different cell sources, scaffolds and growth factors, as well as its clinical pathway and trials have already been carried out. | Nasal Cartilages |
PURPOSE: To investigate the associated features and the surgical outcomes in eyes with microcystoid macular edema (MME) and cone bouquet abnormalities (CBA) undergoing epiretinal membrane peeling. METHODS: Retrospective study including patients who underwent pars plana vitrectomy for idiopathic epiretinal membrane. Factors associated with MME and CBA at baseline and their regression were identified with logistic regression models. Postoperative visual acuity was evaluated with linear mixed models from baseline to 12 months. Risk factors for new or worsened macular edema were explored with a Cox regression model. RESULTS: One hundred and eighty-seven eyes are included in this study; 30 eyes (16%) had MME and 53 eyes (28%) had CBA preoperatively. Microcystoid macular edema was associated with severe epiretinal membrane stage (odds ratio [95% confidence interval] = 3.6 [1.3-12.7], P = 0.02); CBA was inversely associated with ectopic inner foveal layer thickness (odds ratio [95% confidence interval] = 0.97 [0.97-0.99] for each 1- mu m EIFL increase, P = 0.006). Eyes with MME had worse visual acuity after epiretinal membrane peeling ( P = 0.01) and were at risk of macular edema worsening (hazard ratio [95% confidence interval] = 2.22 [1.01-5.16], P = 0.04). Older age was associated with MME persistence (odds ratio [95% confidence interval] = 2.46 [1.06-6.82] for each 10-year increase, P = 0.04). No significant associations were found for CBA. CONCLUSION: Although CBA had no prognostic consequences, MME was associated with suboptimal visual recovery and less efficient control of inflammation after surgery. Degeneration of Muller cells may have an alleged role, and further imaging and functional tests are warranted. | Epiretinal Membrane |
The aim of this study was to estimate the relative frequency of Fetishes in a large sample of individuals. Using the Internet as a data source, we examined 381 discussion groups. We estimate, very conservatively, that at least 5000 individuals were targeted. The relative frequency of each preference category was estimated considering (a) the number of groups devoted to the category, (b) the number of individuals participating in the groups and (c) the number of messages exchanged. The three measures agree both parametrically (Cronbach's alpha=0.91) and non-parametrically (Kendall's W=0.94, P<0.01). Preferences for body parts or features and for objects usually associated with the body were most common (33 and 30%, respectively), followed by preferences for other people's behavior (18%), own behavior (7%), social behavior (7%) and objects unrelated to the body (5%). Feet and objects associated with feet were the most common target of preferences. These findings provide the first large database in an area, where the knowledge is particularly scarce. | Fetishism, Psychiatric |
We report a case of a falsely elevated-bispectral index (BIS) during a general anaesthesia combining remifentanil TCI, desflurane and nitrous oxide for an isolated-limb chemotherapy. During surgery, BIS increased and stabilized around 70, with neither residual neuromuscular blockade nor clinical sign of awareness. These high BIS values were attributed to high-electromyographic activity and electric artefacts, such as extracorporeal-circulation machine and tourniquet. At the end of the surgery, the BIS returned to expected values around 50. The patient did not complain of intraoperative recall. This case reminds us that the BIS has some limits as being sensitive to EMG or environment artefacts that should be eliminated before deepening anesthesia. To do so, a decision algorithm is proposed that may be used for all situations of surprising high BIS, taking into account the level of neuromuscular blockade, clinical response to orders and the presence of devices likely to induce electrical or mechanical artefacts. | False Positive Reactions |
BACKGROUND: Urogenital tuberculosis is still a frequent presentation, and it constitutes a current public health problem in endemic areas. The clinical presentation of this form of the disease may be misleading. The pseudotumoral type of renal tuberculosis is extremely uncommon. CASE PRESENTATION: We present a case of a 52-year-old African woman who presented with urogenital tuberculosis in its pseudotumoral form. This case was initially diagnosed and managed as renal cancer. Histopathology confirmed the diagnosis of pseudotumoral renal tuberculosis. CONCLUSIONS: The pseudotumoral form of urinary tuberculosis can be difficult to diagnose. Only bacteriological or histological confirmation allows diagnosis for adequate treatment. | Tuberculosis, Renal |
We report a female stillborn with typical clinical, radiological, and anatomopathological features of Blomstrand chondrodysplasia. The main findings in this lethal osteochondrodysplasia are osteosclerosis and advanced skeletal maturation. Autosomal recessive inheritance has been proposed because of parental consanguinity of affected siblings in all reported cases, including this one. Histopathological study of the bones confirmed the advanced skeletal maturation radiological features. We also review this rare lethal osteochondrodysplasia. | Osteochondrodysplasias |
Developments in the treatment of sickle cell disease (SCD) have not kept pace with advances in understanding the pathophysiology of this haemoglobinopathy. Drugs undergoing preclinical and clinical assessment for the therapy of these globin gene disorders are discussed in this article. Beginning with investigational agents for treatment of SCD as a whole, the discussion proceeds to drugs being developed for specific manifestations or iatrogenic complications. Despite being licensed in the USA, the prototype antisickling agent, hydroxycarbamide, has not attained worldwide clinical use because of concerns about long-term toxicity. The less toxic decitabine, which (as with hydroxycarbamide) increases fetal haemoglobin level, cannot be administered orally; therefore, the search continues for effective and safe antisickling drugs that can be taken orally. The naturally occurring benzaldehyde 5-hydroxymethyl-2-furfural has shown promising antisickling properties in vitro, and when administered to transgenic sickle mice. These effects are surpassed by the new synthetic pyridyl derivatives of benzaldehyde. Studies in humans with SCD are required to assess the clinical efficacy of these benzaldehydes. Niprisan, another antisickling agent with significant clinical efficacy and an attractive safety profile, is undergoing further development. The prospects of antiadhesion therapy in SCD are demonstrated by a recombinant protein containing the Fc fragment of IgG fused to the natural ligand for selectins: the conjugate significantly inhibited blood vessel occlusion in transgenic sickle mice. Whereas the orally administrable iron-chelating agent deferasirox is likely to increasingly take the place of desferioxamine (which can only be given parenterally), effective treatment of priapism in SCD remains a distressing challenge. | Etilefrine |
Vitrification by using two-step exposures to combined cryoprotective agents (CPAs) has become one of the most common methods for oocyte cryopreservation. By quantitatively examining the status of oocytes during CPA additions and dilutions, we can analyze the degree of the associated osmotic damages. The osmotic responses of mouse MII oocyte in the presence of the combined CPAs (ethylene glycol, EG, and dimethyl sulfoxide, DMSO) were recorded and analyzed. A two-parameter model was used in the curve-fitting calculation to determine the values of hydraulic conductivity (L(p)) and permeability (P(s)) to the combined CPAs at 25 degrees C and 37 degrees C. The effects of exposure durations and the exposure temperatures on the cryopreservation in terms of frozen-thawed cell survival rates and subsequent development were examined in a series of cryopreservation experiments. Mouse MII oocytes were exposed to pretreatment solution (PTS) and vitrification solution (VS) at specific temperatures. The PTS used in our experiment was 10% EG and 10% DMSO dissolved in modified PBS (mPBS), and the VS was EDFS30 (15% EG, 15% DMSO, 3 x 10(-3) M Ficoll, and 0.35 M sucrose in mPBS).The accumulative osmotic damage (AOD) and intracellular CPA concentrations were calculated under the different cryopreservation conditions, and for the first time, the quantitative interactions between survival rates, subsequent development rates, and values of AOD were investigated. | Osmosis |
The events leading up to the discovery of genetically controlled polymorphic metabolism of xenobiotics and pharmaceutical chemicals are briefly summarised with the salient historical features being emphasised. Especial attention has been given to seminal works in the then emerging field.The evolving knowledge of such polymorphic metabolism and its role in the quest for personalised medicine and the individualisation of patient drug therapy are appraised. Opinion is offered as to whether or not the full potential has been exploited and if the practical application of this information may be regarded as a success or failure within the present clinical arena. | Inactivation, Metabolic |
Target of rapamycin (TOR), a conserved protein kinase and central controller of cell growth, functions in two structurally and functionally distinct complexes: TORC1 and TORC2. Dysregulation of mammalian TOR (mTOR) signaling is implicated in pathologies that include diabetes, cancer, and neurodegeneration. We resolved the architecture of human mTORC1 (mTOR with subunits Raptor and mLST8) bound to FK506 binding protein (FKBP)-rapamycin, by combining cryo-electron microscopy at 5.9 angstrom resolution with crystallographic studies of Chaetomium thermophilum Raptor at 4.3 angstrom resolution. The structure explains how FKBP-rapamycin and architectural elements of mTORC1 limit access to the recessed active site. Consistent with a role in substrate recognition and delivery, the conserved amino-terminal domain of Raptor is juxtaposed to the kinase active site." | mTOR Associated Protein, LST8 Homolog |
Osmotic pressure and ion movements in and out of the vitreous space after open-sky vitrectomy were studied in the in vivo eyecup of rabbits. The osmotic pressure of several hypo-osmotic solutions rose over a period of time by the penetration of ions from the surrounding tissue; increases in the concentration of sodium, chloride, potassium, and calcium were documented. Appearance and disappearance of ions were independent of the total osmolarity and depended on the concentration gradient for each ion. | Perfusion |
Epithelial cell polarity may be regulated by protein sorting in the Golgi and delivery to different membrane domains, a view from the inside looking out. But from the outside looking in, cell adhesion may be required first to establish sites for delivery, retention, and separation of membrane proteins, and delivery of presorted proteins from the Golgi subsequently reinforces and maintains different membrane domains. | Cell Polarity |
The eukaryotic linear motif (ELM http://elm.eu.org) resource is a hub for collecting, classifying and curating information about short linear motifs (SLiMs). For >10 years, this resource has provided the scientific community with a freely accessible guide to the biology and function of linear motifs. The current version of ELM contains approximately 200 different motif classes with over 2400 experimentally validated instances manually curated from >2000 scientific publications. Furthermore, detailed information about motif-mediated interactions has been annotated and made available in standard exchange formats. Where appropriate, links are provided to resources such as switches.elm.eu.org and KEGG pathways. | Protein Structural Elements |
Reducing the required frequence of drug dosing can improve the adherence of patients to chronic treatments. Hence, drugs with longer in vivo half-lives are highly desirable. One of the most promising approaches to extend the in vivo half-life of drugs is conjugation to human serum albumin (HSA). In this work, we describe the use of AlbuBinder 1, a small-molecule noncovalent HSA binder, to extend the in vivo half-life and pharmacology of small-molecule BMP1/TLL inhibitors in humanized mice (HSA KI/KI). A series of conjugates of AlbuBinder 1 with BMP1/TLL inhibitors were prepared. In particular, conjugate c showed good solubility and a half-life extension of >20-fold versus the parent molecule in the HSA KI/KI mice, reaching half-lives of >48 h with maintained maximal inhibition of plasma BMP1/TLL. The same conjugate showed a half-life of only 3 h in the wild-type mice, suggesting that the half-life extension was principally due to specific interactions with HSA. It is envisioned that conjugation to AlbuBinder 1 should be applicable to a wide range of small molecule or peptide drugs with short half-lives. In this context, AlbuBinders represent a viable alternative to existing half-life extension technologies." | Tolloid-Like Metalloproteinases |
In vitro methods are used as an alternative to the expensive and time-consuming official method in mice for the titration of tetanus antibodies. Numerous techniques have been developed and used for this purpose, but with mixed results. The difficulty is to get good correlation with in vivo units whatever the vaccinal status of the individual. Today, some of these serological techniques have been virtually abandoned in favor of others which are becoming widespread. RIA is still used, but only in laboratories which already have the necessary equipment and skill. It is gradually replaced by ELISA, a rather delicate technique which however has kept its promises and is amenable to further progress. Passive haemagglutination has been greatly improved by the use of turkey erythrocytes. With this modification, this technique becomes reliable and sensitive and is apparently able to give good results for a large number of sera in case of mass investigation as well as for a quick estimate of the protective level in an individual. | Immunologic Techniques |
We aimed to compare the reliability of aspiration via a nasogastric tube with ultrasound for assessment of residual gastric volume. Sixty-one adult patients who were mechanically ventilated and received continuous enteral feeding through a nasogastric tube for > 48 h were included. A first qualitative and quantitative ultrasound examination of the gastric antrum was followed by gastric suctioning, performed by an operator blinded to the result of the ultrasound examination. A second ultrasound examination was performed thereafter, followed by re-injection of the aspirated gastric contents (</= 250 ml) into the stomach. A third ultrasound assessment was then immediately performed. If the suctioned volume was >/= 250 ml, 250 mg erythromycin was infused over 30 min. A fourth ultrasound was performed 90 min after the third. Sixty (98%) patients had a qualitatively assessed full stomach at first ultrasound examination vs. 52 (85%) after gastric suctioning (p = 0.016). The calculated gastric volume significantly decreased after gastric suctioning, without a significant decrease in the number of patients with volume >/= 250 ml. Four of the nine patients with calculated gastric volume >/= 250 ml had vomiting within the last 24 h (p = 0.013). The antral cross-sectional area significantly decreased between the third and the fourth ultrasound examination (p = 0.015). Erythromycin infusion did not make a significant difference to gastric volume (n = 10). Our results demonstrate that gastric suctioning is not a reliable tool for monitoring residual gastric volume. Gastric ultrasound is a feasible and promising tool for gastric volume monitoring in clinical practice." | Respiratory Aspiration of Gastric Contents |
Guinea pigs and chinchillas, which have become increasingly popular pets, are today more commonly presented as adult and geriatric animals. Problems of older guinea pigs and chinchillas include those related to diet and management, infections whose symptoms are more common in older animals, and neoplasia. | Chinchilla |
The major characteristic lesion observed following spontaneous infection of sheep by the prototype lentivirus, maedi-visna virus (MVV), is a lymphocytic intestitial pneumonia. Similar lesions may be observed with variable frequency following infection of other species by pathogenic lentiviruses, for example in children infected by HIV-1. Further, lentivirus-induced lesions involving organs other than the lungs frequently involve a comparable cellular infiltration. The cellular composition of bronchoalveolar lavage specimens from naturally- or experimentally-infected sheep has been examined with a view to describing the pathological progression of lentivirus-induced lung lesions. The naturally-infected sheep presented advanced lesions typical of 'maedi', while the experimentally-infected newborn lambs permitted the study of early lesions which we refer to as 'pre-maedi'. In both cases there was a considerable infiltration of lymphocytes, predominantly CD8+ in maedi, but with nearly equal numbers of CD4+ cells in pre-maedi. A large proportion of the alveolar lymphocytes in spontaneous maedi, but not in experimentally-infected lambs, express high levels of MHC class II antigen, suggesting an activated phenotype. Activated macrophages, the chief target cells for MVV infection, are also present at this advanced stage of the disease suggesting the involvement of mediators such as IL-8 in the cellular interactions leading to the localization of particular lymphocyte sub-populations in the pulmonary parenchyma during lentiviral disease. | Retroviridae Infections |
During the routine impurity profile of lisinopril bulk drug by HPLC (high-performance liquid chromatography), a potential impurity was detected. Using multidimensional NMR (nuclear magnetic resonance) technique, the trace-level impurity was unambiguously identified to be 2-(-2-oxo-azocan-3-ylamino)-4-phenyl-butyric acid after isolation from lisinopril bulk drug by semi-preparative HPLC. Formation of the impurity was also discussed. To our knowledge, this is a novel impurity and not reported elsewhere. | Lisinopril |
The adaptor protein complex AP-1 mediates vesicular protein sorting between the trans Golgi network and endosomes. AP-1 recycles between membranes and the cytoplasm together with clathrin during transport vesicle formation and vesicle uncoating. AP-1 recycles independent of clathrin, indicating binding to unproductive membrane domains and premature termination of vesicle budding. Membrane recruitment requires ADP ribosylation factor-1-GTP, a transmembrane protein containing an AP-1-binding motif and phosphatidyl-inositol phosphate (PI-4-P). Little is known about the regulation of AP-1 membrane-cytoplasm recycling. We identified the N-terminal domain of micro1A-adaptin as being involved in the regulation of AP-1 membrane-cytoplasm recycling by constructing chimeras of micro1A and its homologue micro2. The AP-1* complex containing this mu2-micro1A chimera had slowed down recycling kinetics, resulting in missorting of mannose 6-phosphate receptors. The N-terminal domain is only accessible from the cytoplasmic AP-1 surface. None of the proteins known to influence AP-1 membrane recycling bound to this micro1A domain, indicating the regulation of AP-1 membrane-cytoplasm recycling by an yet unidentified cytoplasmic protein." | Adaptor Protein Complex mu Subunits |
A short cut review was carried out to determine if anitvenom reduces serum venom concentrations. Using the reported search, 69 papers were found, of which four presented the best evidence to answer the clinical question. The author, date, and country of publication, patient group studied, study type, relevant outcomes, results, and study weaknesses of these best papers are tabulated. A clinical bottom line is stated. | Scorpion Stings |
Some managers find awards of arbitrators arbitrary, capricious, and discriminatory", Donald A. Woolf believes, however, that a knowledge of decisional criteria used by arbitrators can help managers to understand how they reason. Among the criteria discussed are the de minimus rule, the major/minor test, promissory estoppel, parol evidence, contract language, past practice, "clean hands", and the punishment fitting the crime (equity). Such knowledge can also help managers avoid actions that are likely to lead to grievances in addition to planning a course of action to avoid grievances going to arbitration in the future." | Collective Bargaining |
UBA1 is the primary E1 ubiquitin-activating enzyme responsible for generation of activated ubiquitin required for ubiquitination, a process that regulates stability and function of numerous proteins. Decreased or insufficient ubiquitination can cause or drive aging and many diseases. Therefore, a small-molecule enhancing UBA1 activity could have broad therapeutic potential. Here we report that auranofin, a drug approved for the treatment of rheumatoid arthritis, is a potent UBA1 activity enhancer. Auranofin binds to the UBA1's ubiquitin fold domain and conjugates to Cys1039 residue. The binding enhances UBA1 interactions with at least 20 different E2 ubiquitin-conjugating enzymes, facilitating ubiquitin charging to E2 and increasing the activities of seven representative E3s in vitro. Auranofin promotes ubiquitination and degradation of misfolded ER proteins during ER-associated degradation in cells at low nanomolar concentrations. It also facilitates outer mitochondrial membrane-associated degradation. These findings suggest that auranofin can serve as a much-needed tool for UBA1 research and therapeutic exploration. | Ubiquitin-Activating Enzymes |
Methyl jasmonate (MeJA) is a plant hormone important for the mediation of signals for developmental processes and defence reactions in higher plants. The effects of MeJA and the signalling pathways on other photosynthetic organism groups are largely unknown, even though MeJA may have very important roles. Therefore the effects of MeJA in a red alga were studied. A medium-scale expression profiling approach to identify genes regulated by MeJA in the red seaweed Chondrus crispus is described here. The expression profiles were studied 0, 2, 4, 6, 12, and 24 h after the addition of MeJA to the seawater surrounding the algae. The changes in the transcriptome were monitored using cDNA microarrays with 1920 different cDNA representing 1295 unique genes. The responses of selected genes were verified with real-time PCR and the correlation between the two methods was generally satisfying. The study showed that 6% of genes studied showed a response to the addition of MeJA and the most dynamic response was seen after 6 h. Genes that showed up-regulation included several glutathione S-transferases, heat shock protein 20, a xenobiotic reductase, and phycocyanin lyase. Down-regulated transcripts included glucose kinase, phosphoglucose isomerase, and a ribosomal protein. A comparison between different functional groups showed an up-regulation of stress-related genes and a down-regulation of genes involved in energy conversion and general metabolism. It is concluded that MeJA, or a related compound, has a physiological role as a stress hormone in red algae. This study represents to our knowledge the first analysis of gene expression using cDNA microarrays in a red macroalga. | Chondrus |
Acceptance by target populations of new programs funded by government is a phenomenon which one should be able to explain with existing innovation theory. In a study of a newly formed group health practice, funded in part by OEO, it is found that a commonly used set of predictors has little utility in explaining individuals' adoption decisions or their levels of knowledge and attitudes regarding the program. Additional analysis suggests that the ways in which potential and actual clients reacted to certain components of the program "bundle" determined their decisions." | United States Office of Economic Opportunity |
Hot flushes during menopause are distressing for women and result in poor quality of life. Purpose of the current review was to evaluate the available treatment modalities that should be utilised for the management of hot flushes. Menopause refers to last menses of women life and can be declared after amenorrhea of 12 months. Vasomotor symptoms including hot flushes and night sweats are common after menopause, affecting almost 50 - 85% women older than 45 years. The mean increment in core body and skin temperature is 0.5 degrees C and 0.25 - 3 degrees C during a hot flush attack. Low level of estrogen during menopause and its association in triggering episodes of hot flushes, is still under debate. The most accepted hypothesis is a narrowing of the thermoneutral zone (TNZ) triggered by estrogen fluctuations. Although, hormone replacement therapy (HRT) remains the standard treatment for the alleviation of such symptoms, incidence of life threatening side effects restrained medical professionals from its use. Complications associated with the use of HRT can be avoided by appropriate evaluation of patients before initiating therapy. Several guidelines have also recommended HRT (estrogen and progesterone) to be safe for up to a period of seven years. Both hormonal and non-hormonal treatments are used for the management of hot flushes. Since hot flushes are the least appreciated and neglected complication of menopause, current review provides detailed information on its background, pathophysiology and management, and emphasises the need of its treatment. | Hot Flashes |
BACKGROUND: Inherited epidermolysis bullosa (EB) is a group of genodermatoses with considerable clinical and genetic heterogeneity. Clinical diagnosis of the EB subtypes is frequently imprecise and requires confirmation with genetic testing. There is still limited study using genetic testing to identify EB subtypes in Indonesia. This study aims to identify the pathogenic variants of inherited EB patients at the Department of Dermatology and Venereology, Universitas Padjadjaran-Dr Hasan Sadikin General Hospital in Bandung, West Java, Indonesia and to describe the correlation between the phenotype and genotype of our patients. METHODS: Twelve patients clinically diagnosed with EB were included in this study. Genetic testing was performed in collaboration with KK Women's and Children's Hospital, Singapore. RESULTS: Pathogenic variants were identified in the COL7A1 gene in seven patients, namely Dominant Dystrophic EB (DDEB) with mutation types c.5945G>T, c.6218G>A, Recessive Dystrophic EB (RDEB) c.2005C>T, c.6081dup, c.1268C>T, c.1784C>T which are all known mutations. Novel mutations were found in the COL7A1 gene in two patients namely DDEB c.6253G>T and RDEB c.6740C>T. Two EB Simplex (EBS) patients showed mutation KRT14 gene as c.356T>C, c.373C>T which are known mutation. In addition, a novel mutation in LAMA3 gene c.2649del was found in one Junctional EB (JEB) patient. CONCLUSION: The molecular diagnoses of 12 Indonesian EB patients were identified, of which three were novel pathogenic variants. Concordance between the initial clinical diagnosis and genetic testing was only 33%. This demonstrated the importance of early genetic testing for accurate diagnosis, prognostication, management and genetic counselling." | Epidermolysis Bullosa Dystrophica |
New gemini pyridinium amphiphiles having alkyl chain lengths of C10, C12, C14 , and C16 and appended with hydroxyl-substituted spacers have been synthesized, characterized, and investigated for their self-assembly as well as adsorption behavior by state-of-the-art techniques such as conductometry, tensiometry, isothermal titration calorimetry (ITC), and spectrofluorometry. Dynamic light scattering (DLS) and transmission electron microscopy (TEM) have provided excellent acumen with respect to the micellar size distribution of investigated dicationics in aqueous media. Furthermore, the interaction of these dicationics with plasmid DNA, at different charge ratios (N/P), has been studied by DLS, agarose gel electrophoresis, and ethidium bromide exclusion measurements. The cytotoxicity of these geminis has been evaluated by using an MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay on BV2 (microglial) and C6 glioma cell lines. It was found that the varying alkyl chain length, fashioned by ether linkage close to the headgroup, and the presence of a polar linker significantly altered the physicochemical properties of these new dicationics as compared to the properties of nonfunctionalized gemini surfactants. | Pyridinium Compounds |
This study aims to examine the association of adverse childhood experiences (ACE) with emotional and behavioral problems (EBP) among adolescents and the degree to which this association is stronger for more ACE. In addition, we assessed whether socioeconomic position (SEP) modifies the association of ACE with EBP. We obtained data from 341 adolescents aged 10-16 (mean age = 13.14 years; 44.0% boys), the baseline of a cohort study. We measured EBP with the strengths and difficulties questionnaire and socioeconomic position (SEP) with self-reported financial status. We used generalized linear models to analyze the association between ACE (0 vs. 1-2 vs. 3 and more) and EBP, and the modifying effect of SEP. Adolescents with 1-2 ACE (regression coefficient: 0.19; 95%-confidence interval (CI): 0.06-0.32) and with 3 ACE and over (0.35; 0.17-0.54) reported more overall problems compared with adolescents without ACE. Moreover, adolescents with 1-2 ACE (0.16; -0.01-0.32, and 0.16; 0.03-0.29) and with 3 and over ACE (0.33; 0.10-0.56, and 0.28; 0.09-0.47) reported more emotional problems and behavioral problems, respectively. The interactions of SEP with ACE were not significant. ACE are related to EBP among adolescents, with a clear dose-response association, and this association similarly holds for all SEP categories. | Problem Behavior |
Aberrations in the excitatory/inhibitory balance within the brain have been associated with both intellectual disability (ID) and schizophrenia (SZ). The bHLH-PAS transcription factors NPAS3 and NPAS4 have been implicated in controlling the excitatory/inhibitory balance, and targeted disruption of either gene in mice results in a phenotype resembling ID and SZ. However, there are few human variants in NPAS3 and none in NPAS4 that have been associated with schizophrenia or neurodevelopmental disorders. From a clinical exome sequencing database we identified three NPAS3 variants and four NPAS4 variants that could potentially disrupt protein function in individuals with either developmental delay or ID. The transcriptional activity of the variants when partnered with either ARNT or ARNT2 was assessed by reporter gene activity and it was found that variants which truncated the NPAS3/4 protein resulted in a complete loss of transcriptional activity. The ability of loss-of-function variants to heterodimerise with neuronally enriched partner protein ARNT2 was then determined by co-immunoprecipitation experiments. It was determined that the mechanism for the observed loss of function was the inability of the truncated NPAS3/4 protein to heterodimerise with ARNT2. This further establishes NPAS3 and NPAS4 as candidate neurodevelopmental disorder genes." | Aryl Hydrocarbon Receptor Nuclear Translocator |
Cyclophilin A (CyPA) or peptidylprolyl isomerase A (PPIA), an immunophilin with peptidyl-prolyl cis/trans isomerase (PPIase) activity, is an abundant cellular protein widely expressed across various cell types and tissues, including the kidney. Expression of CyPA in the kidney is relatively higher in proximal tubular epithelial cells than others along the nephron. Alterations in expression and secretion of CyPA play important roles in physiological processes and pathophysiology of several diseases affecting the kidney. Herein, we provide a brief overview of CyPA structural biology and present the current update on its theranostic roles in various kidney diseases, including diabetic nephropathy, acute kidney injury, chronic kidney disease, renal fibrosis, and nephrotoxicity associated with organ transplantation. Notably, the diagnostic/prognostic role for urinary CyPA in several of these kidney diseases is promising. Finally, future perspectives on the CyPA research, especially targeting CyPA for therapeutics, are discussed. A comprehensive understanding of the theranostic roles of CyPA in kidney diseases is expected to provide novel insights into the design of new therapeutic interventions and prevention strategies. | Peptidylprolyl Isomerase |
The next decade presents formidable challenges for hospitals and for American health care in general. Whatever emerges from the current health care reform debates, a fundamental shift is taking place toward outpatient and non-hospital site care. Carol M. McCarthy, J.D., Ph.D, AHA president, outlines the association's plans for the coming year. | American Hospital Association |
OBJECTIVES: The soluble bacterial pattern recognition receptor, sCD14 augments inflammatory responses in oral cavity. The aim of the study was to investigate whether patients with geographic tongue (GT) with and without fissured tongue (FT) have impaired inflammatory regulation, manifesting as increased levels of sCD14 in the saliva. MATERIAL AND METHODS: An enzyme-linked immunosorbent assay was used to measure the amount of sCD14 in whole and parotid saliva of patients diagnosed with GT (GT whole, n = 21; GT parotid, n = 23) and control subjects (GT whole, n = 25; GT parotid, n = 18). The levels of sCD14 were also evaluated according to our previous clinical assessment of GT based on the number of lesions detected on the tongue, as 'mild' (a single lesion), 'moderate' (2-5 lesions), or 'severe' (>/=6 lesions). Diagnosis of FT was established when multiple grooves or fissures were observed on the dorsal and lateral surfaces of the tongue. RESULTS: GT patients had significantly higher sCD14 levels in whole (p<.05) and parotid saliva (p<.001), compared with controls. GT patients with FT had significantly increased sCD14 levels only in parotid saliva. A gradual increase in sCD14 levels in parotid and unstimulated saliva was seen in GT patients with multiple tongue lesions compared with single lesions. CONCLUSIONS: GT patients had increased sCD14 in both parotid and unstimulated saliva. sCD14 seems to increase local inflammatory responses, which suggests its involvement in the pathophysiology of GT. | Tongue, Fissured |
Deacetoxy/deacetylcephalosporin C synthase (acDAOC/DACS) from Acremonium chrysogenum is a bifunctional enzyme that catalyzes both the ring-expansion of penicillin N to deacetoxycephalosporin C (DAOC) and the hydroxylation of the latter to deacetylcephalosporin C (DAC). Three residues N305, R307 and R308 located in close proximity to the C-terminus of acDAOC/DACS were each mutated to leucine. The N305L and R308L mutant acDAOC/DACSs showed significant improvement in their ability to convert penicillin analogs. R308 was identified for the first time as a critical residue for DAOC/DACS activity. Kinetic analyses of purified R308L enzyme indicated its improved catalytic efficiency is due to combined improvements of K(m) and k(cat). Comparative modeling of acDAOC/DACS supports the involvement of R308 in the formation of substrate-binding pocket. | Oxygenases |
Premature ovarian insufficiency (POI) affects 1% of women and is a leading cause of infertility. It is often considered to be a monogenic disorder, with pathogenic variants in ~100 genes described in the literature. We sought to systematically evaluate the penetrance of variants in these genes using exome sequence data in 104,733 women from the UK Biobank, 2,231 (1.14%) of whom reported at natural menopause under the age of 40 years. We found limited evidence to support any previously reported autosomal dominant effect. For nearly all heterozygous effects on previously reported POI genes, we ruled out even modest penetrance, with 99.9% (13,699 out of 13,708) of all protein-truncating variants found in reproductively healthy women. We found evidence of haploinsufficiency effects in several genes, including TWNK (1.54 years earlier menopause, P = 1.59 x 10(-6)) and SOHLH2 (3.48 years earlier menopause, P = 1.03 x 10(-4)). Collectively, our results suggest that, for the vast majority of women, POI is not caused by autosomal dominant variants either in genes previously reported or currently evaluated in clinical diagnostic panels. Our findings, plus previous studies, suggest that most POI cases are likely oligogenic or polygenic in nature, which has important implications for future clinical genetic studies, and genetic counseling for families affected by POI. | Primary Ovarian Insufficiency |
Malformations of cortical development (MCD) are important causes of chronic epilepsy in human beings. A blanket term, MCD encompasses many varied developmental disorders with diverse clinical manifestations in patients that neurologists, paediatricians, and learning disability psychiatrists will encounter. Advances in imaging and genetics have led to a significant increase in our understanding of MCD, which has in turn enriched our knowledge of human epileptogenesis and normal brain development and function. In this review, I discuss some of the most common or enlightening MCD: focal cortical dysplasia, periventricular heterotopia, polymicrogyria, band heterotopia and lissencephaly, dysembryoplastic neuroepithelial tumours, and microdysgenesis. Clinical and imaging features, genetic aetiologies, treatments, and the insights that have resulted from MCD study are covered. The burden of epilepsy due to MCD is significant and there is still much to learn about MCD. | Nervous System Malformations |
Di- and trichloroisocyanuric acids are widely used as water disinfection agents, but cyanuric acid accumulates with repeated additions and must be removed to maintain free hypochlorite for disinfection. This study describes the development of methods for using a cyanuric acid-degrading enzyme contained within nonliving cells that were encapsulated within a porous silica matrix. Initially, three different bacterial cyanuric acid hydrolases were compared: TrzD from Acidovorax citrulli strain 12227, AtzD from Pseudomonas sp. strain ADP, and CAH from Moorella thermoacetica ATCC 39073. Each enzyme was expressed recombinantly in Escherichia coli and tested for cyanuric acid hydrolase activity using freely suspended or encapsulated cell formats. Cyanuric acid hydrolase activities differed by only a 2-fold range when comparing across the different enzymes with a given format. A practical water filtration system is most likely to be used with nonviable cells, and all cells were rendered nonviable by heat treatment at 70 degrees C for 1 h. Only the CAH enzyme from the thermophile M. thermoacetica retained significant activity under those conditions, and so it was tested in a flowthrough system simulating a bioreactive pool filter. Starting with a cyanuric acid concentration of 10,000 muM, more than 70% of the cyanuric acid was degraded in 24 h, it was completely removed in 72 h, and a respike of 10,000 muM cyanuric acid a week later showed identical biodegradation kinetics. An experiment conducted with water obtained from municipal swimming pools showed the efficacy of the process, although cyanuric acid degradation rates decreased by 50% in the presence of 4.5 ppm hypochlorite. In total, these experiments demonstrated significant robustness of cyanuric acid hydrolase and the silica bead materials in remediation. | Moorella |
Proteolytic processing of the mouse hepatitis virus strain A59 (MHV-A59) replicase gene product, pp1a, results in polypeptides p28, p65, p50, and p240 in infected cells. Based on previously identified p28 and p65 cleavage sites, a p50 cleavage site was proposed to occur between Ala-1262 and Ala-1263. Results of mutagenesis and in vitro cleavage assays show that PLP-1 was able to cleave in trans when the proposed p50 cleavage sequence replaced the p28 cleavage sequence. Mutagenesis was also used to investigate cleavage between Gly-904 and Val-905, a cleavage site predicted to produce a precursor of p65, p72, that was detected in cells infected with MHV strain JHM, but not with MHV-A59. No cleavage could be detected using substrate that carried both the p65 site and the predicted p72 cleavage sequence. Thus, it appeared that PLP-1 could recognize the proposed p50 sequence but not the predicted p72 site under the in vitro conditions used. | Viral Papain-like Proteases |
Recent epidemiologic investigations of the relationship between residential radon gas exposure and lung cancer relied on contemporary radon gas measurements to estimate past radon gas exposures. Significant uncertainties in these exposure estimates can arise from year-to-year variation of indoor radon concentrations and subject mobility. Surface implanted 210Po has shown potential for improving retrospective radon gas exposure estimates. However, in previous studies, the ability of implanted 210Po activity to reconstruct cumulative radon gas exposure was not tested because glass was not available from homes with known radon-gas concentration histories. In this study, we tested the validity of the retrospective radon gas reconstruction using implanted 210Po surface activity by measuring glass surfaces from homes whose annual-average radon gas concentrations had been measured almost every year during two decades. Regression analysis showed a higher correlation between measured surface activity and cumulative radon gas exposure in these homes (R2>0.8) than was observed in homes where only contemporary radon gas measurements were available. The regression slope (0.57 ky m(-1)) was consistent with our earlier retrospective results. Surface activity measurements were as reliable for retrospective radon gas exposure reconstruction as yearlong gas measurements. Both methods produced estimates that were within 25% of the long-term average radon gas concentrations in a home. Surface measurements can be used for home screening tests because they can provide rapid, reliable estimates of past radon gas concentrations. Implanted 210Po measurements are also useful in retrospective epidemiologic studies that include participants who may have been exposed to highly variable radon concentrations in previously occupied or structurally modified homes. | Elements, Radioactive |
The presence of the cryptic species belonging to the Candida glabrata complex has not been studied in Argentina. We analyzed a collection of 117 clinical isolates of C. glabrata complex belonging to a National Culture Collection of Instituto Nacional de Microbiologia Dr. Carlos G. Malbran" from Argentina (40 isolates from blood samples, 18 from other normally sterile sites, 20 from vagina, 14 from urine, 7 from oral cavity, 3 from catheter, 1 from a stool sample and 14 isolates whose clinical origin was not recorded). The aims of this work were to determine the prevalence of the cryptic species Candida nivariensis and Candida bracarensis and to evaluate the susceptibility profile of isolates against nine antifungal drugs. Identification was carried out by using classical phenotypic tests, CHROMagar Candida, PCR and MALDI-TOF. The minimal inhibitory concentrations of amphotericin B, 5-fluorocytosine, fluconazole, itraconazole, voriconazole, ketoconazole, posaconazole, caspofungin and anidulafungin were determined according to the EDef 7.3 (EUCAST) reference document. Of the 117 isolates, 114 were identified as C. glabrata and three as C. nivariensis by using PCR and MALDI-TOF. There were no major differences between C. nivariensis and C. glabrata susceptibility profiles. No resistant strains were found to echinocandins. We have found that the percentage of C. nivariensis in our culture collection was 2.56. This is the first description of C. nivariensis in Argentina, and data obtained could contribute to the knowledge of the epidemiology of this cryptic species." | Candida glabrata |
Apg7p is a unique E1 enzyme which is essential for both the Apg12p- and Apg8p-modification systems, and plays indispensable roles in yeast autophagy. A cDNA encoding murine Apg7p homolog (mApg7p) was isolated from a mouse brain cDNA library. The predicted amino acid sequence of the clone shows a significant homology to human Apg7p and yeast Apg7p. Murine Apg12p as well as the three mammalian Apg8p homologs co-immunoprecipitate with mApg7p. Site-directed mutagenesis revealed that an active-site cysteine within mApg7p is Cys(567), indicating that mApg7p is an authentic E1 enzyme for murine Apg12p and mammalian Apg8p homologs. The mutagenesis study also revealed that Apg12p has a substrate preference for mApg7p over the three Apg8p homologs, suggesting that the Apg12p conjugation by Apg7p occurs preferentially in mammalian cells compared with the modification of the three Apg8p homologs. We also report here on the ubiquitous expression of human APG7 mRNA in human adult and fetal tissues and of rat Apg7p in adult tissues. | Autophagy-Related Protein 12 |
Intra-oral tests of a fruit bar, a muesli bar and jelly beans were performed to establish their cariogenic potential by means of enamel hardness changes. Little difference was found when the fruit finger and muesli bar were compared. Surprisingly, the jelly beans did not produce a greatly increased degree of softening when compared with the fruit fingers. Statistical significance was not reached in either of the experiments carried out. | Cariogenic Agents |
Epilepsy is defined as a chronic disorder that presents with recurrent episodes of unprovoked seizures. Epileptic seizures are caused by excessive excitation of cortical neurons. The condition has various etiologies and comorbidities. Here, we introduce the definition of epilepsy and classify it based on the newly proposed ILAE (International League Against Epilepsy) classification. In addition, we explain the process of diagnosing epilepsy and delineating the epileptic focus by presenting a case description. Transient functional alterations occur in an epileptic focus only during seizures. Thus, epileptologists are required to record a detailed history and examine its semiology to determine the epileptic focus based on knowledge in neuroscience and epileptology. | Clinical Reasoning |
Developed in the 1960s, the concept for vocational rehabilitation in the vocational retraining centres has proven its worth also in the face of the great challenges of the 80s. Not all of the partly profound changes which have taken place in the environs of vocational rehabilitation over the last few years had been positive ones. Before this background, it must therefore be asked how the standard attained by the vocational retraining centres is to be viewed and which route the vocational rehabilitation field is going to take in the 90s. The process of societal and technological change over recent years is likely to further accelerate in the 90s, with numerous implications for vocational education and disability policies. Even more so than in the past, this process will require adjustments to be made, but equally give rise to innovative efforts and developments. The demands to be faced by the facilities are therefore going to increase, and major re-structuring processes will have to take place also in the vocational retraining centres. | Rehabilitation Centers |
Cytochrome P450 1A (CYP1A) expression in fish is used as a biomarker of exposure to organic contaminants, such PAHs, PCBs and dioxins, in the aquatic environment. South American guppy fish Jenynsia multidentata were exposed to the prototypical aryl hydrocarbon receptor (AHR) agonist beta-naphthoflavone (BNF; 1muM) and the fins were biopsied to characterize different aspects of CYP1A induction. RTq-PCR was used to quantify CYP1A mRNA levels in fish tissues. CYP1A induction in the gill, liver and anal fin (gonopodium) occurred within the first hour of waterborne exposure to BNF and persisted throughout 2, 4, 8, 24, 48 and 96h compared to controls (DMSO vehicle; p<0.05). The organ-specific temporal pattern of induction was marked by mRNA levels consistently augment as duration of exposure increases and tend to a sustained induction from 24h to 96h for gill and liver ( approximately 15-fold and approximately 50-fold over control, respectively). In gonopodium, there was a maximum CYP1A mRNA level at 4h ( approximately 34-fold over control). Basal CYP1A mRNA levels and its induction following BNF exposure were not affected by administration of a chemical anesthetic (fish immersion in 100mgl(-1) MS-222 for 2-5min) in the gill, liver, gonopodium, dorsal or tail fin (p<0.05). In an ex vivo assay, in which small pieces of biopsied fins were exposed to BNF for 4h, high CYP1A induction was observed in the tail and gonopodium ( approximately 49-fold and approximately 69-fold, respectively) but not in the dorsal fin compared to controls. To our knowledge, this is the first study to show that a 1h waterborne exposure to an AHR agonist is sufficient to cause CYP1A induction in fish organs and fins. The present study added new information to the field regarding the use of MS-222 as an anesthetic on fish and the analysis of biopsied fins as an alternative non-lethalex vivo assay for evaluating the CYP1A biomarker in fish. This observation could be useful for planning fish toxicological bioassays and biomonitoring studies on the aquatic environments in South America. | beta-Naphthoflavone |
During neurotransmitter release, the neuronal SNARE proteins synaptobrevin/VAMP, syntaxin, and SNAP-25 form a four-helix bundle, the SNARE complex, that pulls the synaptic vesicle and plasma membranes together possibly causing membrane fusion. Complexin binds tightly to the SNARE complex and is essential for efficient Ca(2+)-evoked neurotransmitter release. A combined X-ray and TROSY-based NMR study now reveals the atomic structure of the complexin/SNARE complex. Complexin binds in an antiparallel alpha-helical conformation to the groove between the synaptobrevin and syntaxin helices. This interaction stabilizes the interface between these two helices, which bears the repulsive forces between the apposed membranes. These results suggest that complexin stabilizes the fully assembled SNARE complex as a key step that enables the exquisitely high speed of Ca(2+)-evoked neurotransmitter release. | Vesicular Transport Proteins |
Epuli (granulomas) are the most frequently observed gingival tumours. The etiopathogenesis of the hyperplasia is not yet clear, and classification inconsistent. Literature on the subject presents considerable discrepancies regarding the tumours origin. The factors determining their development, growth rate, and tendency to recur are still unknown although several options have been considered, i.e., type of injury or inflammatory process, hygiene, nutrition, alcohol, nicotine, pharmacotherapy, hormonal status, and immune efficiency. The opinions of authors of the literature on etiopathogenetic, the classification, the clinical images and the treatment of epulides are represented. | Gingival Diseases |
BACKGROUND: Muscovy duck parvovirus (MDPV) causes high mortality and morbidity in Muscovy ducks, with the pathogenesis of the virus still unknown in many respects. Specific MDPV detection is often rife with false positive results because of high identity at the genomic nucleotide level and antigenic similarity with goose parvovirus (GPV). The objective of this study was to develop a sensitive, highly specific, and repeatable TaqMan-based real-time PCR (qPCR) assay for facilitating the molecular detection of MDPV. RESULTS: The specific primers and probe were designed based on the conserved regions within MDPVs, but there was a variation in GPVs of the nonstructural (NS) genes after genetic comparison. After the optimization of qPCR conditions, the detection limit of this qPCR assay was 29.7 copies/mul. The assay was highly specific for the detection of MDPV, and no cross-reactivity was observed with other non-targeted duck-derived pathogens. Intra- and inter-assay variability was less than 2.21%, means a high degree of repeatability. The diagnostic applicability of the qPCR assay was proven that MDPV-positive can be found in cloacal swabs samples, Muscovy duck embryos and newly hatched Muscovy ducklings. CONCLUSIONS: Our data provided incidents that MDPV could be possible vertically transmitted from breeder Muscovy ducks to Muscovy ducklings. The developed qPCR assay in the study could be a reliable and specific tool for epidemiological surveillance and pathogenesis studies of MDPV. | Parvovirus |
Rapid progress is being made in elucidating the molecular mechanisms involved in invertebrate immunity. This search for molecules runs the risk of missing important phenomena. In vertebrates, acquired protection and pathogen-specific responses were demonstrated experimentally long before the mechanisms responsible were elucidated. Without analogous experiments, mechanism-driven work may not demonstrate the full richness of invertebrate immunity. | Immunologic Memory |
Biotransformation of betulonic acid (1) by Rhizopus arrhizus CGMCC 3.868 resulted in the production of 16 new (3, 5, 6, and 9-21) and five known compounds. Structures of the new compounds were established by analysis of spectroscopic data. Hydroxylation, acetylation, oxygenation, glycosylation, and addition reactions involved the C-20-C-29 double bond. Antineuroinflammatory activities of the obtained compounds in NO production were tested in lipopolysaccharides-induced BV-2 cells. Compared with the substrate betulonic acid, biotransformation products 3, 8, 9, 14, and 21 exhibited an improved inhibitory effect, with IC(50) values of 10.26, 11.09, 5.38, 1.55, and 4.69 muM, lower than that of the positive control, N(G)-monomethyl-l-arginine. | Rhizopus oryzae |
The metabolism of propionylpromazine in the horse was studied. Although propionylpromazine is not currently approved or recommended for use in horses, it has been used illegally to alter their performance. Propionylpromazine hydrochloride was administered intramuscularly at clinical and subclinical doses. Three metabolites were detected in urine. The major metabolite was identified as 2-(1-hydroxypropyl) promazine sulfoxide. The detection of this metabolite in routine drug testing has been described. | Promazine |
Acute lipodermatosclerosis (ALDS) is a painful counterpart of chronic lipodermatosclerosis (LDS) resulting from venous insufficiency. Severe pain is the leading symptom and many patients with ALDS are unable to tolerate compression therapy. We evaluated clinical efficacy of stanozolol (2 mg bid for 8 weeks) for the reduction of pain and dermal-thickness in 17 patients with ALDS. All patients had superficial venous insufficiency documented by duplex scans, and in all of them incompetent perforators were found under the area of ALDS. Mean pain scores prior to institution of stanozolol (7+/-2; range 4-10) lowered significantly at the end of the 8-week treatment (3+/-2; range 0-5, p<0.001). Dermal thickness was also significantly reduced (p<0.01) over the treatment period. Side effects were not noted. Stanozolol, given over 8 weeks, effectively and safely alleviates pain and reduces dermal thickness in patients with ALDS. | Stanozolol |
Spinal neural tube defects are a heterogeneous group of disorders, which remain relatively common, with a prevalence of 1-2 per 1000 live births despite advances in maternal antenatal care. They range from mild disorders with limited neurodevelopmental sequelae to extensive abnormalities with significant morbidity and mortality. The advent of in utero magnetic resonance imaging has enabled accurate anatomical characterization of an increasing number of abnormalities with increasing confidence. Recognition of the salient radiological features of these disorders and their relationship to the embryogenesis of the spinal cord and its coverings is now possible. This review describes the radiological appearances of these disorders with examples from Fetal Imaging Unit, University of Sheffield to illustrate the key anatomical and radiological features to aid the radiologist in their recognition. | Neural Tube Defects |
Mean lift coefficients have been calculated for hawkmoth flight at a range of speeds in order to investigate the aerodynamic significance of the kinematic variation which accompanies changes in forward velocity. The coefficients exceed the maximum steady-state value of 0.71 at all except the very fastest speeds, peaking at 2.0 or greater between 1 and 2 ms-1. Unsteady high-lift mechanisms are therefore most important during hovering and slow forward flight. In combination with the wingtip paths relative to the surrounding air, the calculated mean lift coefficients illustrate how the relative contributions of the two halfstrokes to the force balance change with increasing forward speed. Angle of incidence data for fast forward flight suggest that the sense of the circulation is not reversed between the down- and upstrokes, indicating a flight mode qualitatively different from that proposed for lower-speed flight in the hawkmoth and other insects. The mid-downstroke angle of incidence is constant at 30-40 degrees across the speed range. The relationship between power requirements and flight speed is explored; above 5 ms-1, further increases in forward velocity are likely to be constrained by available mechanical power, although problems with thrust generation and flight stability may also be involved. Hawkmoth wing and body morphology, and the differences between males and females, are evaluated in aerodynamic terms. Steady-state force measurements show that the hawkmoth body is amongst the most streamlined for any insect. | Manduca |
Breast cancer is one of the most common cancers worldwide, and the second most fatal cancer in women after lung cancer. Because there are instances of cancer resistance to existing therapies, studies focused on the identification of novel therapeutic drugs are very important. In this study, we identified a natural anticancer agent from Lantana camara, a flowering plant species of the genus Verbena. The extract obtained from the L. camara exhibited cell death properties in the human breast cancer cell line, MCF-7. We found that the apoptosis induced by treatment with the L. camara extract was regulated by the Bcl-2 family. Bid and Bax was increased and Bcl-2 was decreased by L. camara extract. L. camara extract modulated cleavage of caspase-8, and caspase-9, as well as poly (ADP-ribose) polymerase (PARP). Our results support the potential use of the L. camara extract as an anti-breast cancer drug. | Lantana |
The impact of long-term chronic cadmium stress (ChS, 0.1 microM Cd, 85 days) or short-term acute cadmium stress (AS, 10 microM Cd, 4 days) on Carlina acaulis (Asteraceae) metabolites was compared to identify specific traits. The content of Cd was higher under AS in all organs in comparison with ChS (130 vs. 16 microg.g(-1) DW, 7.9 vs. 3.2 microg.g(-1) DW, and 11.5 vs. 2.4 microg.g(-1) DW in roots, leaves, and trichomes, respectively) while shoot bioaccumulation factor under ChS (ca. 280) indicates efficient Cd accumulation. High content of Cd in the trichomes from the AS treatment may be an anatomical adaptation mechanism. ChS evoked an increase in root biomass (hormesis), while the impact on shoot biomass was not significant in any treatment. The amounts of ascorbic acid and sum of phytochelatins were higher in the shoots but organic (malic and citric) acids dominated in the roots of plants from the ChS treatment. Chlorogenic acid, but not ursolic and oleanolic acids, was elevated by ChS. These data indicate that both chelation and enhancement of antioxidative power contribute to protection of plants exposed to long-term (chronic) Cd presence with subsequent hormetic effect. | Phytochelatins |
OBJECTIVE: To study effect of acupuncture on pH values of acupoints and non-acupoints. METHODS: The pH values of acupoints and non-acupoints were determined with pH sense needles at the same time and separately in the goat. RESULTS: (1) The pH value of the acupoints and non-acupoints decreased when acupuncture was separately at acupoints and non-acupoints with the pH value of the acupoint decreased more significantly; (2) there was no significant difference in decreasing amplitudes of the pH values between the acupoint and non-acupoint when acupuncture was simultaneously given at acupoints and non-acupoints. CONCLUSION: Acupuncture can more significantly strengthen metabolism of acupoints; when acupuncture was simultaneously given at acupoints and non-acupoints, local metabolism is influenced each other. | Acupuncture Points |
Blood flow in normal skin and skin treated with ultraviolet light (UVL) has been determined by measuring the clearance of epicutaneously applied xenon 133 gas. Mean blood flow in UVL-irradiated skin was 25.7 ml/100 gm/min, which is about twice that found in normal skin (12.2 ml/100 gm/min). Orally administered indomethacin reduced by one third the increase in blood flow produced by UVL irradiation. | Blood Circulation |
Recent breakouts of several epidemics, such as flu pandemics, are serious threats to human health. The measures of protection against these epidemics are urgent issues in epidemiological studies. Prevention and quarantine are two major approaches against disease spreads. We here investigate the combined effects of these two measures of protection using the SIR model. We use site percolation for prevention and bond percolation for quarantine applying on a lattice model. We find a strong synergistic effect of prevention and quarantine under local interactions. A slight increase in protection measures is extremely effective in the initial disease spreads. Combination of the two measures is more effective than a single protection measure. Our results suggest that the protection policy against epidemics should account for both prevention and quarantine measures simultaneously. | Quarantine |
The economic aspects of morbidity with temporary incapacity for work are in close connection with the setbacks of the industrial unit, as a result of illness of their workers. On the basis of data taken from the Planning and Economic Department of the Success Plant and using the corresponding method for defining the waste of production, connected with temporary incapacity for work because of illness, which comes up to more than 2 million leva and at the same time payed compensations for 73,000 leva. This allows to establish the true balance between the expenditures of the plant for preventive measures, directed towards a decrease of the setback because of temporary invalidity and take decisions on behalf of the managers of the plant. | Sheltered Workshops |
Stress fractures are common painful conditions in athletes, usually associated to biomechanical overloads. Low risk stress fractures usually respond well to conservative treatments, but up to one third of the athletes may not respond, and evolve into high-risk stress fractures. Surgical stabilization may be the final treatment, but it is a highly invasive procedure with known complications. Shockwave treatments (ESWT), based upon the stimulation of bone turnover, osteoblast stimulation and neovascularization by mechanotransduction, have been successfully used to treat delayed unions and avascular necrosis. Since 1999 it has also been proposed in the treatment of stress fractures with excellent results and no complications. We have used focused shockwave treatments in professional athletes and military personnel with a high rate of recovery, return to competition and pain control. We present the current concepts of shockwave treatments for stress fractures, and recommend it as the primary standard of care in low risk patients with poor response to conventional treatments. | High-Energy Shock Waves |
Total CO2 (CO2+HCO3-) was measured in alkaline extracts of quickly frozen rat renal cortex. The mean concentration calculated for tissue water was 18.7 +/- SD 1.6 mEq/l (n = 10) when that measured in plasma water was 23.5 +/- 1.7. In other experiments (n = 6-10), the mean concentration in tissue water increased to 28.3 mEq/l after the animals were treated with benzolamide to inhibit carbonic anhydrase and to 38.1 mEq/l after they were infused with NaHCO3. On the other hand, the tissue concentration decreased to 14-15 mEq/l when they were hyperventilated or infused with HCl. Calculations based on published micropuncture data indicate that the usual intracellular concentration is 20-25 mEq/l or about twice that usually reported for skeletal muscle; and in contrast to muscle, the findings are suggestive of large variations in metabolic disorders. | Benzolamide |
A 96-well equilibrium dialysis block was designed and constructed that is compatible with most standard 96-well format laboratory supplies and instruments. The unique design of the dialysis apparatus allows one to dispense and aspirate from either or both the sample and dialysate sides from the top of the apparatus, which is not possible with systems currently on the market. This feature permits the investigator to analyze a large number of samples, time points, or replicates in the same experiment. The novel alignment of the dialysis membrane vertically in the well maximizes the surface-to-volume ratio, eliminates problems associated with trapped air pockets, and allows one to add or remove samples independently or all at once. Furthermore, the design of the apparatus allows both the sample and dialysate sides of the dialysis well to be accessible by robotic systems, so assays can be readily automated. Teflon construction is used to minimize nonspecific binding of test samples to the apparatus. The device is reusable, easily assembled, and can be shaken in controlled temperature environments to decrease the time required to reach equilibrium as well as facilitate dissolution of test compounds. Plasma protein binding values obtained for 10 diverse compounds using standard dialysis equipment and the 96-well dialysis block validates this method. | Dialysis |
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