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Nurses are giving increasing attention to independent nursing interventions. However, numerous conceptualizations of interventions have evolved and are being used. The purpose of this essay is to examine some of the existing definitions and classification systems for interventions and to provide a rationale for a common universal language for nursing interventions. Definitions and approaches used in five intervention classification systems are examined in relation to inclusion of assessment and evaluation activities, autonomy, level of conceptualization, and inclusiveness of intervention labels. Lack of a common intervention language can deter international collaboration, development of a scientific basis for practice, and reimbursement for nursing services. | Nursing Process |
INTRODUCTION: Optimal parameters of whole-body vibration (WBV), effective in increasing bone mass or preventing bone loss, are always being sought. We investigated effects of a 6-mo WBV program, consisting of brief daily vibratory sessions, on the bone mass and bone metabolic markers. METHODS: There were 10 male Wistar rats (3 mo old) that were subjected to the 6-mo WBV (frequency 50 Hz, acceleration 4.92 g, peak-to-peak displacement 2.5 mm) composed of 4 30-s bouts per day, performed 5 d per week. There were 10 not vibrated, age-matched rats that served as controls. RESULTS: After completion of the WBV program the concentrations of C-terminal telopeptide of type I collagen in the WBV treated animals were significantly lower in comparison to the controls. There were no effects of the WBV on areal bone mineral density, osteocalcin, and sRANKL levels. DISCUSSION: High-frequency high-magnitude WBV applied for 6 mo decreases bone resorption, but does not affect bone formation and bone mineral density. | Vibration |
BACKGROUND: Accurate hip joint center (HJC) determination is critical for preoperative planning, intraoperative execution, clinical outcomes after total hip arthroplasty, and commonly used classification systems in primary and revision hip replacement. However, current methods of preoperative HJC estimation are prone to subjectivity and human error. The purpose of the study was to leverage deep learning (DL) to develop a rapid and objective HJC estimation tool on anteroposterior (AP) pelvis radiographs. METHODS: Radiographs from 3,965 patients (7,930 hips) were included. A DL model workflow was created to detect bony landmarks and estimate HJC based on a pelvic height ratio method. The workflow was utilized to conduct a grid-search for optimal nonspecific, sex-specific, and patient-specific (using contralateral hip) pelvic height ratios on the training/validation cohort (6,344 hips). Algorithm performance was assessed on an independent testing cohort for HJC estimation comparison. RESULTS: The algorithm estimated HJC for the testing cohort at a rate of 0.65 seconds/hip based on features in AP radiographs alone. The model predicted HJC within 5 mm of error for 80% of hips using nonspecific ratios, which increased to 83% with sex-specific and 91% with patient-specific pelvic height ratio models. Mean error decreased utilizing the patient-specific model (3.09 +/- 1.69 mm, P < .001). CONCLUSION: Using DL, we developed nonspecific, sex-specific, and patient-specific models capable of estimating native HJC on AP pelvis radiographs. This tool may provide clinical value when considering preoperative component position in patients planned to undergo THA and in reducing the subjective variability in HJC estimation. LEVEL OF EVIDENCE: Diagnostic, level IV. | Hip Joint |
Epithelial sodium channels (ENaCs) are strongly expressed in the circumventricular organs (CVOs), and these structures may play an important role in sensing plasma sodium levels. Here, the potent ENaC blocker amiloride was injected intraperitoneally in rats and 2h later, the c-Fos activation pattern in the CVOs was studied. Amiloride elicited dose-related activation in the area postrema (AP) but only ~10% of the rats showed c-Fos activity in the organum vasculosum of the lamina terminalis (OVLT) and subfornical organ (SFO). Tyrosine hydroxylase-immunoreactive (catecholamine) AP neurons were activated, but tryptophan hydroxylase-immunoreactive (serotonin) neurons were unaffected. The AP projects to FoxP2-expressing neurons in the dorsolateral pons which include the pre-locus coeruleus nucleus and external lateral part of the parabrachial nucleus; both cell groups were c-Fos activated following systemic injections of amiloride. In contrast, another AP projection target--the aldosterone-sensitive neurons of the nucleus tractus solitarius which express the enzyme 11-beta-hydroxysteriod dehydrogenase type 2 (HSD2) were not activated. As shown here, plasma concentrations of amiloride used in these experiments were near or below the IC50 level for ENaCs. Amiloride did not induce changes in blood pressure, heart rate, or regional vascular resistance, so sensory feedback from the cardiovascular system was probably not a causal factor for the c-Fos activity seen in the CVOs. In summary, amiloride may have a dual effect on sodium homeostasis causing a loss of sodium via the kidney and inhibiting sodium appetite by activating the central satiety pathway arising from the AP. | Parabrachial Nucleus |
With less than a million neurons, the western honeybee Apis mellifera is capable of complex olfactory behaviors and provides an ideal model for investigating the neurophysiology of the olfactory circuit and the basis of olfactory perception and learning. Here, we review the most fundamental aspects of honeybee's olfaction: first, we discuss which odorants dominate its environment, and how bees use them to communicate and regulate colony homeostasis; then, we describe the neuroanatomy and the neurophysiology of the olfactory circuit; finally, we explore the cellular and molecular mechanisms leading to olfactory memory formation. The vastity of histological, neurophysiological, and behavioral data collected during the last century, together with new technological advancements, including genetic tools, confirm the honeybee as an attractive research model for understanding olfactory coding and learning. | Receptors, Odorant |
Objective: To retrospectively analyse the efficacy of surgerical comprehensive treatment for hypopharyngeal cancer. Methods: Four hundred and fifty-six cases of hypopharyngeal squamous cell carcinoma treated from Jan 2014 to Dec 2019 were analyzed retrospectively, including 432 males and 24 females, aged 37-82 years old. There were 328 cases of pyriform sinus carcinoma, 88 cases of posterior pharyngeal wall carcinoma, and 40 cases of postcricoid carcinoma. According to American Joint Committe on Cancer(AJCC) 2018 criteria, 420 cases were of stage âÂ
¢ or âÂ
£; 325 cases were of T3 or T4 stage. Treatment methods included surgery alone in 84 cases, preoperative planned radiotherapy plus surgery in 49 cases, surgery plus adjuvant radiotherapy or concurrent chemoradiotherapy in 314 cases, and inductive chemotherapy plus surgery and adjuvant radiotherapy in 9 cases. The primary tumor resection methods included transoral laser surgery in 5 cases, partial laryngopharyngectomy in 74 cases, of them 48 cases (64.9%) presented with supracricoid hemilaryngopharyngectomy, total laryngectomy with patial pharyngectomy in 90 cases, total laryngopharyngectomy or with cervical esophagectomy in 226 cases, and total laryngopharyngectomy with total esophagectomy in 61 cases. Among 456 cases, 226 cases received reconstruction surgery with free jejunum transplantation, 61 cases with gastric pull-up, and 32 cases with pectoralis myocutaneous flaps. All patients underwent retropharyngeal lymph node dissection, and high-definition gastroscopy was performed during admission and follow-up. SPSS 24.0 software was used to analyze the data. Results: The 3-year and 5-year overall survival rates were respectively 59.8%, and 49.5%. The 3-year and 5-year disease specific survival rates were respectively 69.0% and 58.8%. Total metastasis rate of retropharyngeal lymph nodes was 12.7%. A total of 132 patients (28.9%) suffered from simultaneous and metachronous multiple primary carcinoma of the hypopharynx. Multivariate Logistic regression analysis showed that T3-4 disease, cervical lymph node metastasis, retropharyngeal lymph node metastasis and postoperative adjuvant radiotherapy were independent factors affecting the prognosis of patients (all P<0.05). As of April 30, 2022, a total of 221 patients died during follow-up, of 109 (49.3%) with distant metastases, which were the main cause of death. Conclusions: The efficacy of comprehensive treatment for hypopharyngeal cancer can be improved by accurate preoperative evaluation, improved surgical resection, active retropharyngeal lymph node dissection and full process intervention of the second primary cancer. | Hypopharyngeal Neoplasms |
Nausea and dysautonomic crises severely limit function and quality of life for a large number of individuals with familial dysautonomia. We treated a small cohort of 15 patients with familial dysautonomia who suffered frequent dysautonomic crises with pregabalin. Nausea and overt crises markedly decreased in 13 (87%) of these patients and the overall assessments of benefit were extremely favorable, suggesting that pregabalin may be a potentially useful therapeutic agent for this disorder. | Dysautonomia, Familial |
BACKGROUND: Neck disorders are common, disabling, and costly. The effectiveness of manipulation and mobilisation remains unclear. OBJECTIVES: To assess whether manipulation and mobilisation, either alone or in combination with other treatments, relieve pain or improve function/disability, patient satisfaction, and global perceived effect in adults with mechanical neck disorders (MND). SEARCH STRATEGY: Computerised bibliographic databases including CENTRAL, MEDLINE, EMBASE, MANTIS, CINAHL, and ICL, were searched without language restrictions from their respective starting dates to March 2002. SELECTION CRITERIA: The studies had to be randomised (RCT) or quasi-randomised and investigate the use of manipulation or mobilisation as a treatment for mechanical neck disorders. DATA COLLECTION AND ANALYSIS: Two independent reviewers conducted citation identification, study selection, data abstraction, and methodological quality assessment. Using a random effects model, relative risk and standardised mean differences were calculated. The reasonableness of combining studies was assessed on clinical and statistical grounds. In the absence of heterogeneity, pooled effect measures were calculated. MAIN RESULTS: Of the 33 selected trials, 42% were high quality trials. Single sessions of manipulation or multiple sessions (3 to 11 weeks) of manipulation or mobilisation, or manipulation and mobilisation showed a nonsignificant benefit in pain relief when assessed against placebo, control groups or other treatments for acute/subacute/chronic MNDs with or without headache. There was strong evidence of benefit favouring multimodal care over a waiting list control for pain reduction [pooled SMD -0.85 (95% CI: -1.20 to -0.50)], improvement in function [pooled SMD -0.57 (95% CI: -0.94 to -0.21)] and global perceived effect [SMD -2.73 (95% CI: -3.30 to -2.16)] for subacute/chronic MND with or without headache. The common elements in this care strategy were mobilisation and/or manipulation plus exercise. There was moderate evidence of no difference in effect when multimodal care was compared to various other treatments. REVIEWER'S CONCLUSIONS: Multimodal care has short-term and long-term maintained benefits for subacute/chronic MND with or without headache. The common elements in this care strategy were mobilisation and/or manipulation plus exercise. The evidence did not favour manipulation and/or mobilisation done alone or in combination with various other physical medicine agents; when compared to one another, neither was superior. There was insufficient evidence available to draw conclusions for neck disorder with radicular findings. The added benefit of exercise needs to be further explored. Factorial design would help determine the active treatment agent(s) within a treatment mix. Phase II trials would help identify the most effective treatment characteristics and dosages. Greater attention to methodological quality is needed. | Manipulation, Orthopedic |
The most common causes of acute gastric outlet obstruction (GOO) are duodenal and type 3 gastric ulcers. However, mechanical or functional causes may also lead to this pathology. Acute GOO is characterized by delayed gastric emptying, anorexia, or nausea accompanied by vomiting. Herein we report a 56-year-old man diagnosed with GOO secondary to paraesophageal hiatal herniation of gastric antrum after laparoscopic fundoplication. Because of the rarity of this disease, common gastrointestinal complaints may mislead the emergency physician to diagnose a nonsurgical gastrointestinal disease if a detailed history and physical examinations are not obtained. | Gastric Outlet Obstruction |
Understanding the dynamics of biological invasions is crucial for managing numerous phenomena, from invasive species to tumors. While the Allee effect (where individuals in low-density populations suffer lowered fitness) is known to influence both the ecological and the evolutionary dynamics of an invasion, the possibility that an invader's susceptibility to the Allee effect might itself evolve has received little attention. Since invasion fronts are regions of perpetually low population density, selection should be expected to favor vanguard invaders that are resistant to Allee effects. This may not only cause invasions to accelerate over time but, by mitigating the Allee effects experienced by the vanguard, also make the invasion transition from a pushed wave, propelled by dispersal from behind the invasion front, to a pulled wave, driven instead by the invasion vanguard. To examine this possibility, we construct an individual-based model in which a trait that governs resistance to the Allee effect is allowed to evolve during an invasion. We find that vanguard invaders evolve resistance to the Allee effect, causing invasions to accelerate. This results in invasions transforming from pushed waves to pulled waves, an outcome with consequences for invasion speed, population genetic structure, and other emergent behaviors. These findings underscore the importance of accounting for evolution in invasion forecasts and suggest that evolution has the capacity to fundamentally alter invasion dynamics. | Introduced Species |
Promyelocytic leukemia (PML) protein is the core component of subnuclear structures called PML nuclear bodies that are known to play important roles in cell survival, DNA damage responses, and DNA repair. Fanconi anemia (FA) proteins are required for repairing interstrand DNA crosslinks (ICLs). Here we report a novel role of PML proteins, regulating the ICL repair pathway. We found that depletion of the PML protein led to the significant reduction of damage-induced FANCD2 mono-ubiquitination and FANCD2 foci formation. Consistently, the cells treated with siRNA against PML showed enhanced sensitivity to a crosslinking agent, mitomycin C. Further studies showed that depletion of PML reduced the protein expression of FANCA, FANCG, and FANCD2 via reduced transcriptional activity. Interestingly, we observed that damage-induced CHK1 phosphorylation was severely impaired in cells with depleted PML, and we demonstrated that CHK1 regulates FANCA, FANCG, and FANCD2 transcription. Finally, we showed that inhibition of CHK1 phosphorylation further sensitized cancer cells to mitomycin C. Taken together, these findings suggest that the PML is critical for damage-induced CHK1 phosphorylation, which is important for FA gene expression and for repairing ICLs." | Fanconi Anemia Complementation Group G Protein |
Taxonomically relevant characteristics of a fastidiously Gram-positive, obligately endoparasitic prokaryote (strain S-1) that uses the phytoparasitic sting nematode Belonolaimus longicaudatus as its host are reviewed. 16S rDNA sequence similarity (> or = 93%) confirms its congeneric ranking with other Pasteuria species and strains from nematodes and cladocerans and corroborates morphological, morphometric and host range evidence suggesting a novel taxon. The 16S rDNA sequence of strain S-1 has greatest similarity (96%) to the 16S rDNA sequences of both Pasteuria penetrans from root-knot nematodes (Meloidogyne species) and the recently reported strain of Pasteuria isolated from the soybean cyst nematode Heterodera glycines. Because the obligately endoparasitic nature of prokaryotes in the genus Pasteuria prevents isolation of definitive type strains, strain S-1 is proposed as 'Candidatus Pasteuria usgae' sp. nov." | Gram-Positive Endospore-Forming Bacteria |
Hypohidrotic ectodermal dysplasia (HED) is a genetic disorder characterized by the absence or hypoplasia of hair, teeth, and eccrine sweat glands. The inheritance pattern of HED may be X-linked or autosomal (dominant or recessive). Mutations in the EDA 1 gene cause X-linked HED and mutations in either EDAR or EDARADD genes cause autosomal forms of HED. To search for a mutation in human EDA1 gene in a large Pakistani family demonstrating X-linked form of HED (XLHED), eight exons and splice junction sites of EDA1 gene were amplified by PCR from genomic DNA and sequenced directly in an ABI Prism 310 automated DNA sequencer. A novel four bases insertion mutation (913_914insTATA) was identified in exon 8 of the EDA 1 gene. This insertion introduces a reading frameshift leading to downstream premature termination codon in the same exon. In the present study a novel insertion mutation in EDA1 gene in a Pakistani family with XLHED has been reported. This extends our knowledge of mutations in EDA1 gene that define the pathogenic basis of HED." | Ectodermal Dysplasia 1, Anhidrotic |
The nematode Spirocerca lupi (S. lupi), a parasite of dogs and other carnivores, affects mainly the esophagus and the aorta leading to gastrointestinal, respiratory, and circulatory signs. Aberrant migration of the worm to unusual anatomical structures, especially the thoracic cavity, resulting in atypical clinical signs is being reported more frequently. Aberrant migration of S. lupi is reviewed, and two such cases (i.e., migration to the heart, causing an aortico-pulmonary window-like" opening, and to a subcutaneous abscess in the caudal thoracic region) are presented." | Spirurida Infections |
A new virus capable of replication on E. coli C was isolated from Penicillium chrysogenum. Six strains of P. chrysogenum differing in the cultural-morphological and biochemical properties and the titer of virus PBV5 were studied. The data provided a supposition that there were definite connections between the titer of virus PBV5 in the mycelium and the fungus ability for the antibiotic production. | Biureas |
Mandibuloacral dysplasia with type A lipodystrophy (MADA) is a rare genetic disorder inherited in an autosomal recessive fashion characterized by hypoplasia of the mandible and clavicles, acroosteolysis and lipodystrophy due to mutations in the LMNA or ZMPSTE24 genes. In the current study, we have investigated a consanguineous family clinically diagnosed with mandibuloacral dysplasia type A having an affected child for the LMNA gene alteration(s). Mother is now 15weeks pregnant, seeking advice on the health of her fetus. Peripheral blood was obtained from all family members after informed consent was achieved. Genomic DNA was isolated. The sequence of the LMNA gene, including all exons and intron boundaries was analyzed by PCR and Sanger sequencing. Chorionic villus was collected from the placenta to reveal the condition of the fetus. Molecular analysis ascertained a homozygous mutation c.1620G>A (p.M540I) in the proband and heterozygous alteration in the family. Genomic DNA isolated from the CVS was amplified using specific primers for identified deleterious mutation and analyzed by Sanger sequencing. Two pathogenic mutations c.1620G>A and c.1698C>T were identified in the fetus. Genetic counseling as well as justified rapid and sensitive genetic testing can provide reassurance for the families to prevent the high burden of genetic disorders. We have also applied several online tools including PolyPhen2, MUpro, SIFT, PoPMuSiC, Project HOPE and Mutation Taster to predict the impact of p.Met540Ile substitution as a hotspot region within LMNA. All tools showed reduction in the stability of the protein structure. We conclude that p.M540I mutation may causes disease in the homozygous state. | Acro-Osteolysis |
Human erythrocyte membranes are elastic and undergo a deformation under shear stress. The phenomenon has been analysed by recording the fluorescence anisotropy of labelled isolated membranes. A model has been developed which assumes an orientation correlation function of a molecular probe incorporated in an elongated membrane. This model has been successfully used to analyse quantitatively data obtained with (1-trimethylamino)-(1,6-diphenyl)-1,3,5-hexatriene (TMA-DPH) and 6-(9-anthroyloxy)-stearic acid (6-AS). In agreement with the model, the effect of the membrane deformation is opposite for these two probes, which corroborates the concept that the alteration of the fluorescence anisotropy reflects mainly the deformation of the membrane and not the rotational freedom of the molecular probe. | Diphenylhexatriene |
INTRODUCTION: Long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHADD) is a rare disease, inherited as autosomal-recessive trait, with variable clinical presentation including severe hypoglycaemia, cardiomyopathy, sudden infant death, progressive liver failure, 'Reye like' syndrome, neuromyopathy, muscle weakness and rhabdomyolysis. CASE REPORT: We report a 3 years old male patient admitted to our emergency department with vomiting, hypotonia and prostration, after a common respiratory infection. The presence of hypoketotic hypoglycaemia and elevated liver enzymes in the admission motivated a metabolic study. We found an abnormal low lactate/pyruvate ratio, decreased serum carnitine and dicarboxylic aciduria leading to the diagnosis of a fatty acid oxidation disorder (LCHADD). The molecular study of HADHA gene revealed homozygosity for the G1528C mutation in the patient DNA, and heterozygosity in both parents. CONCLUSIONS: The diagnosis of a fatty acid oxidation disorder must be considered in the presence of vomiting associated with excessive prostration specially if there is hypoketotic hypoglycaemia or familiar sudden infant death history. Physicians should be aware about these conditions and for the importance of measuring both glycaemia and ketone bodies during the evaluation of high risk situations." | Mitochondrial Trifunctional Protein, alpha Subunit |
Apelin is an endogenous peptide ligand for the G protein-coupled receptor APJ/AGTRL1/APLNR and is widely expressed throughout human body. In adult hearts Apelin-APJ/Apelin receptor axis is potently inotropic, vasodilatory, and pro-angiogenic and thereby contributes to maintaining homeostasis in normal and pathological hearts. Apelin-APJ/Apelin receptor is also involved in heart development including endoderm differentiation, heart morphogenesis, and coronary vascular formation. APJ/Apelin receptor had been originally identified as an orphan receptor for its sequence similarity to Angiotensin II type 1 receptor, and it was later deorphanized by identification of Apelin in 1998. Both Apelin and Angiotensin II are substrates for Angiotensin converting enzyme 2 (ACE2), which degrades the peptides and thus negatively regulates their agonistic activities. Elabela/Toddler, which shares little sequence homology with Apelin, has been recently identified as a second endogenous APJ ligand. Elabela plays crucial roles in heart development and disease conditions presumably at time points or at areas of the heart different from Apelin. Apelin and Elabela seem to constitute a spatiotemporal double ligand system to control APJ/Apelin receptor signaling in the heart. These expanding knowledges of Apelin systems would further encourage therapeutic applications of Apelin, Elabela, or their synthetic derivatives for cardiovascular diseases. | Apelin Receptors |
BACKGROUND: Endo-epicardial substrate ablation reduces ventricular tachycardia (VT) recurrences; however, not all patients in whom the epicardium is explored have a VT substrate. Contrast-enhanced magnetic resonance imaging (ceMRI) is used to characterize VT substrate after myocardial infarction. OBJECTIVE: The purpose of this study was to determine if epicardial VT substrate can be identified noninvasively by ceMRI-based endo-epicardial signal intensity (SI) mapping. METHODS: Myocardial infarction was induced in 31 pigs. Four or 16 weeks later, ceMRI was obtained, and the averaged subendocardial and subepicardial SIs were projected onto 3-dimensional endocardial and epicardial shells in which dense scar, heterogeneous tissue (HT), and normal tissue were differentiated. An HT channel was defined as a corridor of HT surrounded by dense scar and connected to normal tissue. A patchy" scar pattern was defined as the presence of at least 3 dense scar islets surrounded by HT forming >/=2 HT channels. Electrophysiologic study was performed after ceMRI. RESULTS: Thirty-three different sustained monomorphic VTs (291 +/- 49 ms) were induced in 25 pigs. Mid-diastolic electrograms were recorded in the endocardium (endocardial VT) in 17 and in the epicardium (epicardial VT) in 13. Epicardial SI mapping showed that scar area was similar in animals with and without epicardial VT (24 +/- 6 cm2 vs. 25 +/- 12 cm2), but HT covered a higher surface of the epicardial scar in animals with VT (76 +/- 6% vs. 61 +/- 10%, P = .03). A patchy scar pattern was observed in all animals with epicardial VT but only in 3 animals without VT (P < .001). CONCLUSION: CeMRI-based SI mapping allows identification of the epicardial VT substrate." | Epicardial Mapping |
Aleutian disease viral (ADV) antigen was prepared by fluorocarbon extraction of spleen, liver, and lymph nodes from mink experimentally infected ten days previously. Using a potent ADV antigen, antibody was detected by immunodiffusion (ID) and immunoelectroosmophoresis (IEOP). Utilizing these precipitin tests, antibody was detected in all the mink sera tested as early as seven days after experimental infection. Titer of antibody increased throughout the infection period. Titers of more than 100 were reached by 15 days post infection, titers of 1,000 at one month, and titers of more than 5,000 to 10,000 were achieved at two months post infection and thereafter. The immunodiffusion test gave similar or slightly lower titers than those detected by the IEOP. The IEOP test promises to be a most useful technique for the diagnosis of aleutian disease because it is simple, rapid and specific and is capable of detecting infection early in the course of the disease. It is suggested that this test should be utilized especially for the screening of animals purchased or imported as breeding stock onto ranches. | Aleutian Mink Disease |
Scallop eye lens Omega-crystallin is an inactive aldehyde dehydrogenase (ALDH1A9) related to cytoplasmic ALDH1A1 and mitochondrial ALDH2 that migrates by gel filtration chromatography as a homodimer. Because mammalian ALDH1A1 and ALDH2 are homotetramers, we investigated the native molecular mass of scallop Omega-crystallin by multi-angle laser light scattering. The results indicate that the scallop Omega-crystallin is a tetrameric, not a dimeric protein. Moreover, phylogenetic tree analysis shows that scallop Omega-crystallin clusters with the mitochondrial ALDH2 and ALDH1B1 rather than the cytoplasmic ALDH1A, yet it lacks the mitochondrial N-terminal leader sequence characteristic of the mitochondrial ALDHs. The mitochondrial grouping, enzymatic inactivity, and anomalous gel filtration behavior make scallop cytoplasmic Omega-crystallin an interesting protein for structural studies of evolutionary adaptations to become an enzyme-crystallin. | omega-Crystallins |
The use of growth factors for accelerated healing of sports injuries is restricted under the terms of the World Anti-Doping Agency (WADA) anti-doping code. Cheating athletes have used the black market as a source of performance-enhancing substances. Drugs that currently undergo clinical trials are frequently offered--despite the unknown health risks associated with the administration of unapproved pharmaceuticals. Recently, a new growth factor (referred to as fibroblast growth factor 1/FGF-1) with known effects on the repair and regeneration of damaged tissue was detected in an unlabelled black market product confiscated by the German customs. The identification of the protein was achieved by one- and two-dimensional polyacrylamide gel electrophoresis (SDS-PAGE and 2D-PAGE), different proteolytic digestions, immunological methods and nano-liquid chromatography high-resolution/high-accuracy Orbitrap mass spectrometry. The SDS-PAGE analysis revealed slight differences concerning the molecular weight of recombinant human and black market FGF-1. Using in-gel proteolysis, a truncation or modification located at the N-terminus of the protein was suggested. These findings demonstrate that drug candidates without clinical approval can be readily obtained from the black market, regardless of potential dangerous consequences for the consumer, which corroborates the necessity of proactive and preventive doping control approaches. In that regard, physiological concentrations of blood and urine specimens collected from healthy individuals were analyzed and were found to range below 28 pg/ml in urine, while there was no detectable FGF-1 in plasma. | Fibroblast Growth Factor 1 |
The lysis-lysogeny decision of bacteriophage lambda (lambda) is a paradigm for developmental genetic networks. There are three key features, which characterize the network. First, after infection of the host bacterium, a decision between lytic or lysogenic development is made that is dependent upon environmental signals and the number of infecting phages per cell. Second, the lysogenic prophage state is very stable. Third, the prophage enters lytic development in response to DNA-damaging agents. The CI and Cro regulators define the lysogenic and lytic states, respectively, as a bistable genetic switch. Whereas CI maintains a stable lysogenic state, recent studies indicate that Cro sets the lytic course not by directly blocking CI expression but indirectly by lowering levels of CII which activates cI transcription. We discuss how a relatively simple phage like lambda employs a complex genetic network in decision-making processes, providing a challenge for theoretical modeling. | Operon |
In the presence of transition metal ions and peroxides, polyphenols, well-known dietary antioxidants, can act as pro-oxidants. We investigated the effect of 13 polyphenols and their metabolites on oxidative degradation of deoxyribose by an (*)OH generating Fenton system (Fe(2+)-ethylenediaminetetraacetic acid (EDTA)-H(2)O(2)). The relationship between phenolics pro-oxidant/anti-oxidant effects and their molecular structure was analyzed using multivariate analysis with multiple linear regression and a backward stepwise technique. Four phenolics revealed a significant inhibitory effect on OH-induced deoxyribose degradation, ranging from 54.4% +/- 28.6% (3,4-dihydroxycinnamic acid) to 38.5% +/- 10.4% (catechin) (n = 6), correlating with the number of -OH substitutions (r = 0.58). Seven phenolics augmented the oxidative degradation of deoxyribose with the highest enhancement at 95.0% +/- 21.3% (quercetin) and 60.6% +/- 12.2% (phloridzin). The pro-oxidant effect correlated (p < 0.05) with the number of -OH groups (r = 0.59), and aliphatic substitutes (r = -0.22) and weakly correlated with the occurrence of a catechol structure within the compound molecule (r = 0.17). Selective dietary supplementation with phenolics exhibiting pro-oxidant activity may increase the possibility of systemic oxidative stress in patients treated with medications containing chelating properties or those with high plasma concentrations of H(2)O(2) and non-transferrin bound iron. | Deoxyribose |
There has been little emphasis placed on the excision of accessory bones of the foot. The authors present a review of the literature and a description of a surgical procedure for excision of the hallux interphalangeal joint sesamoid using minimal incision technique. A detailed analysis of the anatomy involved is also presented. A variety of other procedures for excision of this accessory bone are reviewed. | Hallux |
BACKGROUND: Misoprostol is a synthetic analog of prostaglandin-E1 and it is the most widely used drug for the medical management of incomplete abortion. Acute Coronary Syndrome (ACS) rarely occurs in perimenopausal women, in addition, its presentation is atypical, so the disease is not always recognized. CASE REPORT: We describe a case of 39-year-old woman with no major underlying cardiovascular risk factors, who developed an episode of ACS following the administration of two doses of misoprostol. After the discontinuation of misoprostol treatment, there was a complete resolution of patient's symptoms. The case draws attention to a rare side effect of a commonly used drug and alerts the clinicians to be cautious in those patients having baseline risk factors which make the patient more susceptible to such serious adverse drug effect. | Abortion, Incomplete |
Four xanthones were isolated from mycelia of Emericella variecolor, an endophytic fungus isolated from the leaves of Croton oblongifolius. Their structures were elucidated by spectroscopic analysis to be shamixanthone, 14-methoxytajixanthone-25-acetate, tajixanthone methanoate, and tajixanthone hydrate. All compounds were tested for cytotoxic activity against various human tumor cell lines including gastric carcinoma, colon carcinoma, breast carcinoma, human hepatocarcinoma, and lung carcinoma. The antitumor activities of these xanthones were compared with that of doxorubicin hydrochloride, a chemotherapeutic substance. All of them showed moderate activities and were selective against gastric carcinoma, colon carcinoma, and breast carcinoma. Only tajixanthone hydrate exhibited moderate activity against all cancer cell lines. Furthermore, under the test conditions it was found that 14-methoxytajixanthone-25-acetate and tajixanthone hydrate are almost as active as doxorubicin hydrochloride against gastric carcinoma (KATO3) and breast carcinoma (BT474). | Emericella |
The synthetic growth-promoting hormones trenbolone and melengestrol acetate have been detected in the environment near beef cattle feedlots and are reportedly transported via wind-borne particulate matter. Therefore, movement of synthetic hormones from beef cattle feedlots to water bodies via particulate matter is possible. Our objective was to evaluate potential effects of 17alpha-trenbolone (17alpha-TB), melengestrol acetate (MGA), and combinations of both on growth, development, and survival of Xenopus laevis larvae. On post-hatch day 2 (stage 33/34), X. laevis larvae were exposed to three nominal concentrations of 17alpha-TB (10, 100, and 500 ng/L), MGA (1, 10, and 100 ng/L), a combination of both (1/10, 10/100, and 100/500 ng/L MGA/17alpha-TB), frog embryo teratogenesis assay-Xenopus medium, or a solvent control. Significant increases in all X. laevis growth metrics were observed among larvae in the 1 ng/L MGA + 10 ng/L 17alpha-TB and 10 ng/L MGA + 100 ng/L 17alpha-TB treatments. Stage of development was increased among larvae in the 1 ng/L MGA + 10 ng/L 17alpha-TB treatment group and significantly decreased among those in the 500 ng/L 17alpha-TB treatment. Total body mass and snout-vent length of X. laevis larvae were significantly reduced in the 100 ng/L MGA and 100 ng/L MGA + 500 ng/L 17alpha-TB treatment groups. Larvae exposed to 500 ng/L 17alpha-TB had decreased total body mass, snout-vent length, and total length. In general, growth measurements decreased with increasing concentration of MGA, 17alpha-TB, or a combination of both. Survival among all treatments was not significantly different from controls. Amphibians exposed to MGA and 17alpha-TB in the environment may experience alterations in growth and development. | Melengestrol Acetate |
OBJECTIVE: The purpose of this systematic review was to evaluate the mandibular canal (MC) variations and their anatomical incidences using cone-beam computed tomography (CBCT). DESIGNS: Related articles on the anatomical variations of the MC using CBCT were searched through PubMed, Cochrane, and China National Knowledge Infrastructure (CNKI) to identify all relevant articles eligible for inclusion. Data extracted included incidences of the anatomical variations of the MC including the accessory mental foramen (AMF), retromolar foramen (RMF), mandibular lingual foramina (MLF), and the bifid mandibular canal (BMC). RESULTS: In total, 16 descriptive cross-sectional studies (one low quality and fifteen high quality) were included in the meta-analysis analyzing 8862 MC. The meta-analysis performed with a random-effects model showed that the incidence of AMF was 9.54% (95% CI 6.39-12.69%), the incidence of RMF was 23.64% (95% CI 14.44-32.84%). MLF was found in almost all adults studied, and the incidence of BMC was about 38.0%. CONCLUSIONS: The foramina and canals branched from the MC presented significant anatomical variations among individuals. CBCT-based study on the anatomical variations of the MC could provide guidance for clinical practice. | Mandibular Canal |
Bruceine D (BD) is an effective insecticidal compound found in the Chinese herb Brucea javanica (L.) Merr. BD inhibits the growth and metamorphosis of Plutella xylostella and Drosophila melanogaster; however, its target protein and the molecular mechanism of insecticidal activity remain unclear. In this study, proteins with high affinity for BD were screened using surface plasmon resonance and high-performance liquid chromatography coupled with matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry, revealing the ecdysone receptor (EcR) is the main target of BD. In vivo results showed that BD inhibited insect growth and metamorphosis through inhibition of the expression of 20E response genes. In vitro dual luciferase and enhanced green fluorescent protein (EGFP) fluorescence experiments indicated that BD suppressed the transcriptional activation activity of EcR by blocking the ecdysone response element (EcRE)-triggered transcriptional cascade, suggesting that BD inhibits the formation of the 20E-EcR-USP-EcRE complex. Moreover, molecular docking demonstrated that BD bound well to EcR. Elucidating the insecticidal mechanism of BD will be helpful in the development of green pesticides to control pests. | Cholestenones |
ABSTRACT Byssinosis and other respiratory symptoms and acute and chronic changes in FVC and FEV(1.0) were investigated in 77 workers in sisal spinning and 83 workers in sisal brushing departments in six Tanzanian sisal factories. Although the prevalence of byssinosis in spinning departments was found to be low (5.2%), it was very high in brushing departments (48.2%). Workers in brushing were exposed to sisal dust for a significantly longer period (11.77 +/- 7.3 years) compared to workers exposed to sisal in spinning (2.85 +/- 2.56 years). Although the number of smokers in brushing (42%) was similar to that in spinning (37%), smokers were more prone to byssinosis than were non- or ex-smokers after standardisation for duration of exposure. We were unable to measure dust levels in this study, but dust levels in spinning and brushing are cited from previous studies. These confirm our impression that the dust level in spinning is higher than that in an average cotton carding department and far higher in brushing than in spinning. Acute falls in FVC and FEV(1.0) were found during the work shift. The extent of the fall in FEV(1.0) correlated well with the severity of byssinosis; 75% of the workers with grade II byssinosis and 33% of those with grade (1/2) + I were found to have acute falls in FEV(1.0) greater than 0.2 litres. However some workers, 10% in spinning and 33% in brushing, who denied symptoms of byssinosis, were also found to have acute falls in FEV(1.0). Some workers had slight or severe chronic ventilatory impairment from dust (FEV(1.0) less than 80%, or less than 60% of the respective predicted values), and these workers were mostly from the brushing department. The prevalence of chronic cough and chronic bronchitis was found to be negligible in workers in the spinning and in the brushing departments: 9.6% had a chronic cough and 12% had chronic bronchitis. It is concluded that a high prevalence of byssinosis associated with chronic and acute changes in FVC and FEV(1.0) occurs in the brushing departments of sisal factories, and that this is related to lengthy exposure, high dust level and smoking. | Byssinosis |
Ectopia cordis is defined as a congenital malposition of the heart outside of the thoracic cavity. It is a rare condition, and complete ectopia cordis can be a fatal condition. Successful surgical reconstruction of this defect has been reported but is uncommon. The general approach to reconstructing the chest wall involves repositioning the heart and providing adequate coverage of the chest wall defect. We describe our experience with a patient who had complete thoracic ectopia cordis treated with staged chest wall reconstruction. The first stage involved temporary closure with synthetic material, and the second stage involved definitive reconstruction with autologous bone and cartilage grafts supported with plates. The patient has been active and without complaints since the second stage and is awaiting tracheal decannulation. There have been a few descriptions of how to approach chest wall reconstruction in patients with ectopia cordis. The 2 stage method described can be considered to repair the chest wall defect in complete thoracic ectopia cordis. | Ectopia Cordis |
TFIIH is a general transcription and repair factor implicated in RNA polymerase II transcription, nucleotide excision repair, and transcription-coupled repair. Genetic defects in TFIIH lead to three distinct inheritable diseases: xeroderma pigmentosa, Cockayne syndrome, and trichothiodystrophy, with xeroderma pigmentosa patients being highly susceptible to skin cancer. Earlier data revealed that the cyclin H subunit of TFIIH associates with U1 small nuclear RNA, a core-splicing component. In addition to its role in RNA processing U1 small nuclear RNA also regulates diverse stages of transcription by RNA polymerase II both in vivo and in vitro, including abortive initiation and re-initiation. Here we identify structural components of U1 and cyclin H implicated in the direct interaction and show how they affect function. Because of unique features of cyclin H we have developed a new methodology for mapping RNA interaction with the full-length cyclin H polypeptide based on electrospray ionization tandem mass spectrometry. We also demonstrate the importance of U1 stem-loops 1 and 2 for the interaction with cyclin H. Functional assays implicate the identified interaction with U1 in regulation of the activity of the cyclin H associated kinase CDK7." | Cyclin-Dependent Kinase-Activating Kinase |
Pancreatic cancer is one of the most aggressive human malignancies and is associated with a dismal prognosis, which can be contributed to its atypical symptoms, metastatic propensity, and significant chemoresistance. Emerging evidence shows that pancreatic cancer cell-derived exosomes (PEXs) play critical roles in tumorigenesis and tumor development, as they are involved in drug resistance, immune evasion and metabolic reprograming, and distant metastasis of pancreatic cancer. Their numerous differentially expressed and functional contents make PEXs promising screening tools and therapeutic targets, which require further exploration. In this review, we focus on the functions of PEX contents and their clinical implications in pancreatic cancer. | Exosomes |
A 39-nt DNA sequence, the interferon gamma (IFN-gamma) response region (GRR), is necessary for the IFN-gamma-induced transcription of the high-affinity Fc receptor for IgG (Fc gamma RI) and sufficient for the IFN-gamma-induced transcription of transfected plasmids. By using extracts from IFN-gamma-treated cells, three protein complexes will assemble in vitro on a 9-nt core region in the 3' domain of the GRR. The sequence of this core resembles the IFN-gamma-activated sequence (GAS) described for the GBP gene. Mutations in this GAS core region prevent complex assembly and result in the loss of IFN-gamma induction of reporter constructs containing the mutation. In addition to the GAS core region, a 5' region of the GRR is necessary for optimal IFN-gamma induction and for formation of one of the DNA-protein complexes. By antibody reactivity, we show that a 91-kDa protein, first identified as a component of ISGF3, the IFN-alpha-induced transcription complex, is present in at least two of the DNA-protein complexes. IFN-alpha can induce the formation of the faster-migrating 91-kDa protein-GAS complex but not the slower-migrating complex. Furthermore, IFN-alpha does not result in appreciable transcriptional activation of Fc gamma RI or constructs containing the GRR. Thus, these data demonstrate that the IFN-gamma-activated 91-kDa protein is required for IFN-gamma induction of Fc gamma RI and suggest that an additional complex may be required for optimal expression and specificity." | Interferon-Stimulated Gene Factor 3, gamma Subunit |
Activating transcription factor 3 (ATF3) is an early-induced gene involved in diverse cellular functions in response to various stresses including viral infection. Here we observed marked reduction of ATF3 by coxsackievirus B3 (CVB3) infection and investigated the regulation and functional role of ATF3 in HeLa cells for the understanding of biological significance of ATF3 downregulation. CVB3 infection markedly reduced ATF3 expression at mRNA and protein levels in parallel with p53 degradation, and preservation of p53 expression rescued CVB3 infection-induced ATF3 downregulation. ATF3 overexpression stimulated apoptotic cell death following CVB3 infection, accompanying with augmentation of CVB3 infection-induced eIF2alpha phosphorylation. However, ATF3 overexpression did not affect viral protein production but promoted virus progeny release. Taken together, our results suggest that ATF3 is under control of p53 in part and that the ATF3 downregulation via p53 degradation may contribute to effective viral production as a modulation mechanism of CVB3 infection-induced cell death." | Activating Transcription Factors |
We report a novel chromosomal translocation (X;5)(q13;q33) in a woman with no history of prior chemotherapy or radiotherapy, found to have essential thrombocythemia. Aberrations in chromosome 5, mostly deletions of 5q, have been described in essential thrombocythemia; however, a t(X;5) translocation has not been reported. | Chromosomes, Human, 4-5 |
BACKGROUND: Loop diuretics help to manage the patients with edema associated with congestive heart failure, liver cirrhosis, and renal disease and hypertension. The patients taking loop diuretics may receive other medications to treat comorbidities leading to drug interactions. METHODS: The literature was searched in databases such as Medline/PMC/PubMed, Google Scholar, Cochrane Library, Science Direct, EMBASE, Web of science, Ebsco, Directory of open access journals (DOAJ) and reference lists were used to spot relevant articles using keywords Drug interactions, Pharmacodynamic interactions, Loop diuretics, Bumetanide, Ethacrynic acid, Furosemide, and Torsemide. RESULTS: Loop diuretics are associated with hypokalemia, ototoxicity and other adverse effects. The drugs affected by hypokalemia and having the potential of inducing ototoxicity could interact with loop diuretics pharmacodynamically. Loop diuretics can interact with drugs such as amphotericin B, digoxin, angiotensin-converting enzyme inhibitors (ACE inhibitors), antidiabetic drugs, antifungal agents, dobutamine, gossypoland sotalol due to diuretic associated hypokalemia. In addition, the risk of ototoxicity could be enhanced by the concomitant use of loop diuretics and cisplatin, aminoglycoside antibiotics or phosphodiesterase 5 (PDE 5) inhibitors. Loop diuretics may also interact pharmacodynamically with drugs like cephalosporins, ceritinib, levothyroxine, pixantrone, probenecid, lithium, nonsteroidal anti-inflammatory drugs (NSAIDs), sulfonylureas and herbal drugs. CONCLUSION: Clinicians, pharmacists and other health care providers should take responsibility for the safe use of medications. In addition, they are required to be aware of the drugs interacting with loop diuretics to prevent adverse drug interactions. | Furosemide |
Viruses, including the novel coronavirus SARS-CoV-2, redirect infected cell metabolism to their own purposes. After binding to its receptor angiotensin-converting enzyme 2 (ACE2) on the cell surface, the SARS-CoV-2 is taken up by receptor-mediated endocytosis ending in the acidic endolysosomal compartment. The virus hijacks the endosomal machinery leading to fusion of viral and endosomal membranes and release of the viral RNA into the cytosol. This mini-review specifically highlights the membrane lipid organization of the endosomal system focusing on the unconventional and late endosome/lysosome-specific phospholipid, bis(monoacylglycero)phosphate (BMP). BMP is enriched in alveolar macrophages of lung, one of the target tissue of SARS-CoV-2. This review details the BMP structure, its unsaturated fatty acid composition and fusogenic properties that are essential for the highly dynamic formation of the intraluminal vesicles inside the endosomes. Interestingly, BMP is necessary for infection and replication of enveloped RNA virus such as SARS-CoV-1 and Dengue virus. We also emphasize the role of BMP in lipid sorting and degradation, especially cholesterol transport in cooperation with Niemann Pick type C proteins (NPC 1 and 2) and with some oxysterol-binding protein (OSBP)-related proteins (ORPs) as well as in sphingolipid degradation. Interestingly, numerous virus infection required NPC1 as well as ORPs along the endocytic pathway. Furthermore, BMP content is increased during pathological endosomal lipid accumulation in various lysosomal storage disorders. This is particularly important knowing the high percentage of patients with metabolic disorders among the SARS-CoV-2 infected patients presenting severe forms of COVID-19. | Monoglycerides |
BACKGROUND: The rarity of esophageal achalasia has resulted in little being known about the characteristics of its three subtypes. The upper esophageal sphincter is considered one key factor to prevent aspiration pneumonia, a serious complication of esophageal achalasia. This study aimed to reveal the subtype characteristics of esophageal achalasia and how the upper esophageal sphincter functions and relates to other clinical parameters of the disease. METHODS: We retrospectively investigated the clinical records of patients diagnosed with esophageal achalasia. All participants underwent esophagogastroduodenoscopy and then, within 2 weeks, high-resolution manometry. Gastrointestinal symptoms were assessed using a previously validated self-reported questionnaire. RESULTS: A total of 110 patients with esophageal achalasia were enrolled: 50 with type I, 40 with type II, and 20 with type III. Mean age at diagnosis was 54.5, 50.4, and 66.1 years for types I, II, and III, respectively. Mean resting upper esophageal sphincter pressure was 28.0, 51.8, and 43.6 mmHg for patients with types I, II, and III, respectively (p < 0.01). Patients with type III esophageal achalasia more frequently reported stomachache than those with type I (p = 0.03). A negative correlation between resting upper esophageal sphincter pressure and age was observed in all subtypes. CONCLUSIONS: A negative correlation was confirmed between resting upper esophageal sphincter pressure and age in all subtypes of esophageal achalasia. Type III patients were older at diagnosis, type II patients showed higher upper esophageal sphincter pressure, and type I patients showed a lower upper esophageal sphincter pressure at the early life stage. | Esophageal Sphincter, Upper |
The EtOH extract of the roots of Paeonia veitchii afforded two new monoterpene glycosides paeonidanin I (1) and paeonidanin J (2), and a new dimeric monoterpene glycoside paeonidanin K (3). Their structures were elucidated on the basis of spectroscopic means and hydrolysis products. | Paeonia |
The purpose of this study was to assess the clinical and radiological patterns and outcome predictors of posterior reversible encephalopathy syndrome (PRES) in pediatric cancer patients. A retrospective study included patients who developed PRES during their treatment at the Children's Cancer Hospital Egypt. A total of 50 patients developed PRES. Leukemia and lymphoma were the commonest diagnoses (64%). Regarding the MRI findings, occipital affection was the most common (92%), followed by frontal and temporal lobes involvement in 32% and 22% respectively and advanced PRES was described in 8 patients. Of the whole patients, 80% had complete clinical resolution and 60% showed complete radiological resolution at 2 weeks' evaluation and 2 patients died out of PRES. Unfavorable outcome was associated with those who had motor dysfunction, status epilepticus at presentation, frontal lobe and thalamic affection and atypical PRES. PRES might present in atypical sites with poor outcome including death." | Posterior Leukoencephalopathy Syndrome |
BACKGROUND: Multiple endocrine neoplasia type 1 (MEN 1) syndrome is a rare, complex genetic disorder characterized by increased predisposition to tumorigenesis in multiple endocrine and non-endocrine tissues. Diagnosis and management of MEN 1 syndrome is challenging due to its vast heterogeneity in clinical presentation. CASE PRESENTATION: A 23-year-old female, previously diagnosed with Polycystic Ovarian Syndrome (PCOS) and pituitary microprolactinoma presented with drowsiness,confusion and profuse sweating developing over a period of one day. It was preceded by fluctuating, hallucinatory behavior for two weeks duration. There was recent increase in appetite with significant weight gain. There was no fever, seizures or symptoms suggestive of meningism. Her Body mass index(BMI) was 32 kg/m(2).She had signs of hyperandrogenism. Multiple cutaneous collagenomas were noted on anterior chest and abdominal wall. Her Glasgow Coma Scale was 9/15. Pupils were sluggishly reactive to light. Tendon reflexes were exaggerated with up going planter reflexes. Moderate hepatomegaly was present. Rest of the clinical examination was normal. Laboratory evaluation confirmed endogenous hyperinsulinaemic hypoglycaemia suggestive of an insulinoma. Hypercalcemia with elevated parathyroid hormone level suggested a parathyroid adenoma. Presence of insulinoma, primary hyperparathyroidism and pituitary microadenoma, in 3(rd) decade of life with characteristic cutaneous tumours was suggestive of a clinical diagnosis of MEN 1 syndrome. Recurrent, severe hypoglycaemia complicated with hypoglycaemic encephalopathy refractory to continuous, parenteral glucose supplementation and optimal pharmacotherapy complicated the clinical course. Insulinoma was localized with selective arterial calcium stimulation test. Distal pancreatectomy and four gland parathyroidectomy was performed leading to resolution of symptoms. CONCLUSIONS: Renal calculi or characteristic cutaneous lesions might be the only forewarning clinical manifestations of an undiagnosed MEN 1 syndrome impending a life-threatening presentation. Comprehensive management of MEN 1 syndrome requires multi-disciplinary approach with advanced imaging modalities, advanced surgical procedures and long-term follow up due to its heterogeneous presentation and the varying severity depending on the disease phenotype. | Insulinoma |
Ayahuasca is a hallucinogenic brew traditionally used by Northwestern Amazonian indigenous groups for therapeutic purposes. It is prepared by the decoction of Banisteriopsis caapi with the leaves of Psychotria viridis. Banisteriopsis caapi contains beta-carbolines that are inhibitors of monoamine oxidase and P. viris is rich in dimethyltryptamine, a 5-HT(1A/2A/2C) agonist. Acute ayahuasca administration produces moderate cardiovascular effects in healthy volunteers, but information regarding long-term use is lacking. This study investigated the effects of ayahuasca (2-4 mL/kg) in the rat aorta after acute and chronic (14 days) administration. Ayahuasca caused flattening and stretching of vascular smooth muscle cells and changes in the arrangement and distribution of collagen and elastic fibers. Chronic treatment with the higher dose significantly increased media thickness and the ratio of media thickness to lumen diameter. More research is needed on the cardiovascular function of long-term ayahuasca consumers. | Banisteriopsis |
4,6-Bis(2-hydroxyphenyl)-2-alkylpyrimidines with two anthryl or 9-ethylnylanthryl substituents at the positions para to the OH groups prefer a U-shaped conformation supported by two intramolecular OHâÂÂ
âÂÂ
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N hydrogen bonds in the solid state and in CDCl3 solution. The compound with a hexyl substituent on the pyrimidine group and two 9-ethynylanthryl arms at the hydroxyphenyl groups forms a 1:1 complex with 2,4,7-trinitrofluorenone. Its association constant K(a) was estimated to be 2100 M(-1) at 298 K, which is larger than those of other molecular tweezers (K(a) < 1000 M(-1)). DFT calculations suggested that the complex adopts a stable conformation supported by intramolecular hydrogen bonds among the OH groups and the pyrimidine ring as well as by intermolecular pi-pi interaction between the anthryl groups and 2,4,7-trinitrofluorenone. Addition of nBu4NF to a solution of the molecular tweezers or their complexes causes the cleavage of one or two OHâÂÂ
âÂÂ
âÂÂ
N hydrogen bonds, formation of new OâÂÂ
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HF hydrogen bonds, and changes in the molecular conformation. The resulting structure of the molecular tweezers contains nonparallel anthryl groups, which do not bind the guest molecule. Photochemical measurements on 4,6-bis(2-hydroxyphenyl)-2-methylpyrimidine with two anthryl substituents showed negligible luminescence (quantum yield varphi<0.01), owing to photoinduced electron transfer of the molecule with a U-shaped structure. However, the O-hexylated compound exhibits emission from the anthryl groups with varphi=0.39. | Fluorenes |
OBJECTIVE: Intracapsular tonsillotomy continues to gain acceptance as an alternative to traditional tonsillectomy. Despite large clinical studies, there is a lack of consensus as to which technique offers lower complication rates. This study seeks to analyze the available data and surmise the complication rates of partial tonsillectomy as compared with traditional tonsillectomy. Data Sources. MEDLINE was searched using multiple search terms. REVIEW METHODS: After the MEDLINE search, the following inclusion criteria were applied: English language, human subjects, and related to partial tonsillectomy. Multiple tonsillotomy techniques were included. The results of these studies were summated and the results analyzed. Subgroup analysis was then performed. RESULTS: Thirty-three studies met inclusion criteria. Tonsillotomy had a lower postoperative bleeding rate, lower postoperative dehydration rate requiring medical care, reduced days of analgesic use, and reduced days to return to normal diet compared with tonsillectomy. When separated into higher versus lower quality studies, the differences in bleeding and dehydration were negligible, while differences in return to diet and days of analgesic use persisted. Mean intraoperative blood loss was similar for both techniques. Insufficient data were available to assess tonsil regrowth rates. CONCLUSIONS: Tonsillotomy appears to be a safe technique that may offer some advantages over tonsillectomy in terms of postoperative morbidity, but differences in hemorrhage and dehydration were not evident in high-quality studies. Data regarding tonsil regrowth rates and efficacy in treating sleep-disordered breathing are not yet sufficient for formal analysis, which may preclude widespread acceptance of this technique. | Tonsillectomy |
The corticotropin-releasing factor (CRF) system plays a role in alcohol consumption, and its dysregulation can contribute to alcohol use disorder. This system includes four peptide ligands: CRF, urocortin (Ucn)1, Ucn2, and Ucn3. Historically, attention focused on CRF, however, Ucn1 also plays a critical role in excessive alcohol use. This review covers evidence for this contribution and contrasts the role of Ucn1 with CRF. While CRF can promote binge consumption, this regulation occurs through generalized mechanisms that are not specific for alcohol. In contrast, inhibition of Ucn1 action specifically blunts escalation of alcohol drinking. Lesions, genetic knockout, and RNA interference experiments indicate that the centrally projecting Edinger-Westphal nucleus is the neuroanatomical source of Ucn1 critical for alcohol drinking. We propose that the contributions of Ucn1 to excessive drinking likely occur through enhancing rewarding properties of alcohol and symptoms of alcohol withdrawal, whereas CRF drives dependence-induced drinking at later stages of alcohol use. The transition from occasional binge drinking to dependence intricately depends on CRF system plasticity and coordination of CRF and Ucn1. | Urocortins |
Rat interferon, alpha-interferon, interleukin-2 and recombinant interleukin-2 microinjected into the third cerebral ventricle produced in rats typical behavioural sedation and/or sleep and ECoG synchronization while beta-interferon produced no behavioural sleep and ECoG synchronization. A slight sedation was observed after highest dose of beta-interferon only. During sleep induced by these lymphokines a dose-dependent increase in total voltage power as well as in the 0.5-3, 4-7 and 12-16 Hz frequency bands was observed. Much lower doses were required to produce similar behavioural and ECoG spectrum power effects after microinfusion of interferons and interleukin-2 into the locus coeruleus. No significant behavioural and ECoG changes were obtained after microinfusion of the same doses of interferons and interleukin-2 into other areas of the brain (caudate nucleus, dorsal hippocampus, substantia nigra-pars compacta-, ventromedial hypothalamus). The behavioural and ECoG effects of alpha-interferon, rat interferon and interleukin-2 were blocked in animals pretreated with naloxone. These results are consistent with the hypothesis that the behavioural and ECoG effects of these lymphokines are mediated at locus coeruleus level via a stimulation of opiate receptors. | Lymphokines |
Blood pressure was measured indirectly in 203 cats using an oscillometric technique in conjunction with a tail cuff. Systolic blood pressure was found to be log normally distributed across the population, while diastolic pressure was log log normally distributed. Blood pressure was found to rise with age (systolic, diastolic, mean arterial and pulse pressure were significantly higher in animals aged 11 years or over than in animals aged under 11 years) but this rise did not parallel an increase in plasma urea or creatinine. Cats with clinical renal disease did however have higher blood pressures than normal cats, as did cats with ocular change consistent with hypertensive retinopathy. | Oscillometry |
Leiomyosarcoma is a rare, aggressively malignant connective tissue tumor of mature adults, which arises from smooth muscle. It occurs most frequently in the uterus, bowel, vascular tissues, and less commonly in somatic soft tissue or bone. The tumor when it arises in soft tissue has distinctive histologic features which somewhat resemble malignant fibrous histiocytoma (otherwise known as myxofibrosarcoma). The Orthopaedic Oncology Service at our institution has treated 66 patients with these lesions and thus far, 1/2 of the patients have died of disease at a mean of 3 years after discovery. Factors that increase the death rate include size of the tumor, Musculoskeletal Tumor Society Stage of disease, and to a lesser extent particularly in the lower extremities, anatomic site. Radiation and chemotherapy had little direct effect on the outcome but patients treated with surgery and adjunctive agents seemed to live longer than their cohorts treated with surgery alone. The purpose of this study is a general review of the clinical and prognostic features of this cancer. | Leiomyosarcoma |
CREB-binding protein (CBP) and its homolog p300 possess histone acetyltransferase activity and function as key transcriptional co-activators in the regulation of gene expression that controls differentiation and development in animals. However, the role of CBP/p300-like genes in plants has not yet been elucidated. Here, we show that Arabidopsis CBP/p300-like genes promote flowering by affecting the expression of a major floral repressor FLOWERING LOCUS C (FLC). Although animal CBP and p300 generally function as co-activators, Arabidopsis CBP/p300-like proteins are required for the negative regulation of FLC. This CBP/p300-mediated FLC repression may involve reversible protein acetylation independent of histone modification within FLC chromatin." | p300-CBP Transcription Factors |
Allometric scaling relationships between body weight, bone length, and cross-sectional dimensions of the lower limb bones which measure structural strength and rigidity (area, second moments of area) are investigated in Homo, Gorilla, Pan, Pongo, and Macaca. Cross-sectional dimensions are slightly positively allometric and highly correlated with body weight; within-bone proportional differences are largely a result of differences in relative bone length to body weight. Orangutans show the greatest deviation from general scaling relationships between lower limb bone structural strength and weight, probably due to habitual upper limb suspension. Formulas for the prediction of weight from cross-sectional dimensions are presented. | Haplorhini |
Despite advances in understanding the metabolism of Pseudomonas putida KT2440, a promising bacterial host for producing valuable chemicals from plant-derived feedstocks, a strain capable of producing free fatty acid-derived chemicals has not been developed. Guided by functional genomics, we engineered P. putida to produce medium- and long-chain free fatty acids (FFAs) to titers of up to 670 mg/L. Additionally, by taking advantage of the varying substrate preferences of paralogous native fatty acyl-CoA ligases, we employed a strategy to control FFA chain length that resulted in a P. putida strain specialized in producing medium-chain FFAs. Finally, we demonstrate the production of oleochemicals in these strains by synthesizing medium-chain fatty acid methyl esters, compounds useful as biodiesel blending agents, in various media including sorghum hydrolysate at titers greater than 300 mg/L. This work paves the road to produce high-value oleochemicals and biofuels from cheap feedstocks, such as plant biomass, using this host. | Pseudomonas putida |
Several diseases can, at least in theory, be treated by the administration of an enzyme, the deficiency of which is the cause of the disease. Various attempts have been made to correct enzymatic deficiencies responsible for the clinical manifestation of diseases for which prevention cannot be achieved by modification of the diet or by supportive therapy with drugs. Except for treating certain digestive disorders, enzyme-replacement therapy has not yet found a broad application. In this review article a compilation is given of the problems and prospects of enzyme-replacement therapy in diseases caused by the deficiency of an enzyme. | Enzyme Therapy |
Hypothalamic neurons regulate body homeostasis by sensing and integrating changes in the levels of key hormones and primary nutrients (amino acids, glucose, and lipids). However, the molecular mechanisms that enable hypothalamic neurons to detect primary nutrients remain elusive. Here, we identified l-type amino acid transporter 1 (LAT1) in hypothalamic leptin receptor-expressing (LepR-expressing) neurons as being important for systemic energy and bone homeostasis. We observed LAT1-dependent amino acid uptake in the hypothalamus, which was compromised in a mouse model of obesity and diabetes. Mice lacking LAT1 (encoded by solute carrier transporter 7a5, Slc7a5) in LepR-expressing neurons exhibited obesity-related phenotypes and higher bone mass. Slc7a5 deficiency caused sympathetic dysfunction and leptin insensitivity in LepR-expressing neurons before obesity onset. Importantly, restoring Slc7a5 expression selectively in LepR-expressing ventromedial hypothalamus neurons rescued energy and bone homeostasis in mice deficient for Slc7a5 in LepR-expressing cells. Mechanistic target of rapamycin complex-1 (mTORC1) was found to be a crucial mediator of LAT1-dependent regulation of energy and bone homeostasis. These results suggest that the LAT1/mTORC1 axis in LepR-expressing neurons controls energy and bone homeostasis by fine-tuning sympathetic outflow, thus providing in vivo evidence of the implications of amino acid sensing by hypothalamic neurons in body homeostasis. | Amino Acid Transport System L |
One hundred cases of empyema thoracic have been reviewed. Aetiology of empyema was tubercular in 21 per cent cases and non-tubercular in 79 per cent cases. Gram negative organisms were cultured in 84.6% cases, whereas gram positive organisms were cultured only in 15.4% cases. It was observed that management of cases of empyema differed considerably with the presence or absence of BPF, thick or thin pus and size of empyema. It was concluded that all cases of simple empyema with thin pus and only those cases of simple empyema with thick pus where size of empyema is small should be managed by aspiration/s. Cases failed by above method, all cases of simple empyema with thick pus and with moderate to large size of empyema and all cases of empyema with BPF should be straightway managed by intercostal drainage tube connected to water seal. On the whole, cases of empyema with BPF were difficult to manage and needed major surgery in 45.8 per cent cases in comparison to only 2.9 per cent cases of simple empyema. | Empyema |
A comprehensive analysis of repeat rates has been obtained from an observational study of radiological practice in diagnostic X-ray departments throughout Wales. Interdepartmental and intradepartmental repeat rates are investigated for chest, abdomen, pelvis, sinus, lumbar spine, cervical spine and intravenous pyelographic examinations. The confounding effects upon observed repeat rates of trainee practitioners and automatic exposure control devices are also considered. The overall proportions of total film cost and patient exposure attributable to repeat radiographs are estimated to be 10% and 14% respectively. | Hospital Departments |
A point-of-service (POS) option is a type of plan offered by managed care organizations (MCOs), including health maintenance organizations (HMOs), that allows people who are willing to pay higher out-of-pocket costs to see out-of-plan providers. Mandating a point-of-service option essentially eliminates the use of closed-panel HMOs. This issue brief addresses only bills that mandate managed care plans to offer a point-of-service option." | Patient Freedom of Choice Laws |
Encainide is a class IC antiarrhythmic agent that has been under clinical investigation for the last decade. Laboratory and clinical studies have demonstrated it to be a potent suppressor of ventricular extrasystoles. It is effective in approximately one-half of patients with malignant ventricular arrhythmias. The preliminary experience in patients with supraventricular arrhythmias indicates that the drug is particularly effective in arrhythmias associated with an accessory pathway. Side effects most commonly include blurred vision, nausea, heart block, and proarrhythmic effects. The hemodynamic effect of oral encainide are insignificant in patients with well-preserved left ventricular function. Despite minimal myocardial depression in patients with left ventricular dysfunction, there is the potential for worsening of heart failure. Encainide has a short half-life of 3 hours, but has 2 active metabolites with longer half-lives. No clinically significant drug interaction has been demonstrated with encainide therapy. | Anti-Arrhythmia Agents |
OBJECTIVES: The aim was to identify, appraise, and synthesize the scientific evidence of the relationship between potential occupational sensitizing exposures and the development of asthma based on systematic reviews. METHODS: The study was conducted as an overview of systematic reviews. A systematic literature search was conducted for systematic reviews published up to 9 February 2020. Eligibility study criteria included persons in or above the working age, potential occupational sensitizing exposures, and outcomes defined as asthma. Potential occupational sensitizing exposures were divided into 23 main groups comprising both subgroups and specific exposures. Two reviewers independently selected studies, extracted study data, assessed study quality, and evaluated confidence in study results and level of evidence of the relationship between potential occupational sensitizing exposures and asthma. RESULTS: Twenty-seven systematic reviews were included covering 1242 studies and 486 potential occupational sensitizing exposures. Overall confidence in study results was rated high in three systematic reviews, moderate in seven reviews, and low in 17 reviews. Strong evidence for the main group of wood dusts and moderate evidence for main groups of mites and fish was found. For subgroups/specific exposures, strong evidence was found for toluene diisocyanates, Aspergillus, Cladosporium, Penicillium, and work tasks involving exposure to laboratory animals, whereas moderate evidence was found for 52 subgroups/specific exposures. CONCLUSIONS: This overview identified hundreds of potential occupational sensitizing exposures suspected to cause asthma and evaluated the level of evidence for each exposure. Strong evidence was found for wood dust in general and for toluene diisocyanates, Aspergillus, Cladosporium, Penicillium, and work tasks involving exposure to laboratory animals. | Toluene 2,4-Diisocyanate |
Terra firma-forme dermatosis (TFFD) is a benign and likely underdiagnosed disorder with relatively few reports in the literature. A 46-year-old woman presented to our clinic with a 3-year history of linear TFFD extending from the upper sacrum to the midline upper back. It initially was thought to be acanthosis nigricans or lichen simplex chronicus, and a topical steroid cream was applied without success. The lesion ultimately was removed by rubbing with isopropyl alcohol, which confirmed a diagnosis of TFFD. Due to its ability to mimic other skin diseases, TFFD should be considered when patients present with hyperkeratotic hyperpigmented lesions. | 2-Propanol |
In recent years, zebrafish (Danio rerio) has been used as a model vertebrate organism for studies of human disease, development, and genetics. This chapter describes detailed methods for the preparation of whole-mount meiotic oocytes and spermatocytes as well as cryostat sectioning of ovaries and testes for immunofluorescence microscopy studies of zebrafish. | Tissue Fixation |
The clinical criteria for the diagnosis of urticarial vasculitis lack accuracy, according to previous studies. The aim of the study was to assess the accuracy of a clinical and a clinical-dermoscopic model for the differential diagnosis of chronic spontaneous urticaria (CSU) and urticarial vasculitis (UV). Dermoscopic images of lesions with histopathologically confirmed diagnosis of CSU and UV were evaluated for the presence of selected criteria (purpuric patches/globules (PG) and red linear vessels). Clinical criteria of CSU and UV were also registered. Univariate and adjusted odds ratios were calculated. Multivariate regression analyses were conducted separately for clinical variables (clinical diagnostic model) and for both clinical and dermoscopic variables (clinical-dermoscopic diagnostic model). 108 patients with CSU and 27 patients with UV were included in the study. The clinical-dermoscopic model notably showed higher diagnostic sensitivity than the clinical approach (63% vs. 44%). Dermoscopic purpuric patches/globules (PG) was the variable that better discriminated UV, increasing by 19-fold the odds for this diagnosis. In conclusion, dermoscopy helps the clinical discrimination between CSU and UV. The visualization of dermoscopic PG may contribute to optimize decisions regarding biopsy in patients with urticarial rashes. | Dermoscopy |
BACKGROUND: Early surgical repair to restore nerve integrity has become the most commonly practiced method for managing facial nerve injury. However, the evidence for the efficacy of surgical repair for restoring the function of facial nerves remains deficient. This study evaluated the outcomes of surgical repair for facial nerve lesions. METHODS: This retrospective observational study recruited 28 patients with the diagnosis of facial nerve injury who consecutively underwent surgical repairs from September 2012 to May 2019. All related clinical data were retrospectively analyzed according to age, sex, location of the facial nerve lesion, size of the facial nerve defect, method of repair, facial electromyogram, and blink reflex. Facial function was then stratified with the House-Brackmann grading system pre-operation and 3, 9, 15, and 21 months after surgical repair. RESULTS: The 28 patients enrolled in this study included 17 male and 11 female patients with an average age of 34.3 +/- 17.4 years. Three methods were applied for the repair of an injured facial nerve, including great auricular nerve transplantation in 15 patients, sural nerve grafting in 7 patients, and hypoglossal to facial nerve anastomosis in 6 patients. Facial nerve function was significantly improved at 21 months after surgery compared with pre-operative function (P = 0.008). Following surgical repair, a correlation was found between the amplitude of motor unit potential (MUP) and facial nerve function (r = -6.078, P = 0.02). Moreover, the extent of functional restoration of the facial nerve at 21 months after surgery depended on the location of the facial nerve lesion; lesions at either the horizontal or vertical segment showed significant improvement(P = 0.008 and 0.005), while no functional restoration was found for lesions at the labyrinthine segment (P = 0.26). CONCLUSIONS: For surgical repair of facial nerve lesions, the sural nerve, great auricular nerve, and hypoglossal-facial nerve can be grafted effectively to store the function of a facial nerve, and MUP may provide an effective indicator for monitoring the recovery of the injured nerve. | Facial Nerve Injuries |
Dentinogenesis can be initiated secondarily as an intrinsic ability of the dental pulp to repair, or after interaction of pulp cells with specific exogenous inductive factors. In the present article the basic developmental aspects, highlighting the mechanism by which dentinogenesis is initiated during tooth development, are discussed. Furthermore, clinical and experimental observations concerning the events taking place during secondary initiation of dentine formation, as part of exposed or non-exposed pulp tissue repair, or as a result of dentine matrix or other chemical-pulp cell interactions, are reviewed. Discussion includes hypotheses relating to the crucial biological steps leading to expression of odontoblastic-like cell phenotype and secondary initiation of dentine histogenesis. | Dentinogenesis |
A number of compounds were isolated from the medicinal plant Aster tataricus including shionone, epifriedelinol, quercetin, kaempferol, scopoletin, emodin, aurantiamide acetate and 1,7-dihydroxy-6-methyl-anthraquinone. The compounds were compared with regard to their ability in inhibiting hemolysis of rat erythrocytes induced by 2'-2' azobis (2-amidinopropane) dihydrochloride, lipid peroxidation using the FeSO(4)-ascorbic acid system, and generation of superoxide radicals using a phenazine methosulfate-nicotinamide adenine dinucleotide system. The effects on the Fe-bleomycin-induced DNA damage reflected pro-oxidant activity. Quercetin and kaempferol were most potent in inhibiting hemolysis, lipid peroxidation and superoxide radical generation. Scopoletin and emodin were similar to quercetin and kaempferol in inhibiting superoxide radical generation and second to them in inhibiting lipid peroxidation. Aurantiamide acetate exhibited some inhibitory activity toward superoxide radical generation. 1,7-dihydroxy-6-methyl-anthraquinone exerted an inhibitory activity only on superoxide radical generation. Shionone and epifriedelinol did not display any antioxidant activity. Quercetin and kaempferol, but not the remaining compounds, exhibited some pro-oxidant activity. | Aster Plant |
The nanometer scale is a special place where all sciences meet and develop a particularly strong interdisciplinarity. While biology is a source of inspiration for nanoscientists, chemistry has a central role in turning inspirations and methods from biological systems to nanotechnological use. DNA is the biological molecule by which nanoscience and nanotechnology is mostly fascinated. Nature uses DNA not only as a repository of the genetic information, but also as a controller of the expression of the genes it contains. Thus, there are codes embedded in the DNA sequence that serve to control recognition processes on the atomic scale, such as the base pairing, and others that control processes taking place on the nanoscale. From the chemical point of view, DNA is the supramolecular building block with the highest informational content. Nanoscience has therefore the opportunity of using DNA molecules to increase the level of complexity and efficiency in self-assembling and self-directing processes. | Base Pairing |
Nanoparticles have potential applications in diagnostics, imaging, gene and drug delivery and other types of therapy. Iron oxide nanoparticles, gold nanoparticles and quantum dots have all generated substantial interest and their properties and applications have been thoroughly studied. Yet, metal-containing particles raise biodistribution and toxicity concerns because they can be quickly cleared from the blood by the reticuloendothelial system and can remain in organs, such as the liver and spleen, for prolonged periods of time. Design considerations, such as size, shape, surface coating and dosing, can be manipulated to prolong blood circulation and enhance treatment efficacy, but nonspecific distribution has thus far been unavoidable. Renal excretion of nanoparticles is possible and is size dependent, but the need to incorporate coatings to particles for increased circulation can hinder such excretion. Further long-term studies are needed because recent work has shown varying degrees of in vivo toxicity as well as varying levels of nanoparticle excretion over time. The interaction of these particles with immune cells and their effect on the innate and adaptive immune response also needs further characterization. Finally, more systematic in vitro approaches are needed to both guide in vivo work and better correlate nanoparticle properties to their biological effects. | Ferric Compounds |
OBJECTIVES: The present study was aimed to determine whether trefoil factor family (TFF) peptides which were generally considered to be resistant to proteolysis could be digested by gingipains, a major proteinases produced by Porphyromonas gingivalis. MATERIALS AND METHODS: Recombinant human TFF1, TFF2, and TFF3 peptides were used as substrates. Gingipains including arginine gingipain (RgpB) and lysine gingipain (Kgp) were used as enzymes. Trypsin was used as a control protease. Matrix-assisted laser desorption/ionization with time-of-flight / time-of-flight (MALDI-TOF/TOF) and liquid chromatography mass spectrometry (LC-MS) were used for analyzing peptide mass signals and amino acid sequences of digested TFF peptides. RESULTS: MALDI-TOF/TOF analyses demonstrated that Kgp, RgpB, and trypsin were able to cleave TFF1 and TFF2 peptides, resulting in different patterns of digested fragments. However, impurity in recombinant TFF3 peptide substrates affected the interpretations of enzymatic reaction by MALDI-TOF/TOF. LC-MS analyses demonstrated that identified fragments of TFF1, TFF2, and TFF3 from digestion by gingipains were similar to those by trypsin. CONCLUSIONS: Using MALDI-TOF/TOF and LC-MS, the present study provides new information that gingipains containing trypsin-like activities are able to digest TFF peptides. CLINICAL RELEVANCE: The proteolytic effects of gingipains on TFF peptides may be responsible for reduction of salivary TFF peptides in chronic periodontitis patients. Further investigations to determine the pathological effects of gingipains on TFF peptides in saliva and periodontal tissues of patients with chronic periodontitis would be of interest." | Gingipain Cysteine Endopeptidases |
The NH2-terminal amino acid sequences (initial 23 residues) of Friend murine leukemia virus gp71 and gp69 were determined and found to be different but highly related. Friend murine leukemia virus gp71 differed from Rauscher murine leukemia virus gp70 in only one position. Friend murine leukemia virus gp69 showed approximately 41% homology to these glycoproteins but lacked the glycosylation site (sequon) occurring at position 12 in Rauscher murine leukemia virus gp70. | Friend murine leukemia virus |
OBJECTIVE: To explore the potential of non-ionic surfactants as novel intranasal absorption enhancers. METHODS: Taking sumatriptan succinate (SMS) as a model drug, influence of different non-ionic surfactants, including laurate sucrose ester (SE), cremophor EL and poloxamer 188, on the intranasal absorption of SMS was investigated using an in situ nasal perfusion technique in rats. Ciliotoxicity of the non-ionic surfactants was evaluated using an in situ toad palate model. In vivo behavior of the selected formulations was studied in rats. RESULTS: All the non-ionic surfactants investigated increased the intranasal absorption of SMS remarkably but with varied extent and trend. Moreover, it was revealed that at the same concentration, laurate SE had better permeation-enhancing effect than that of cremophor EL and poloxamer 188. The ciliotoxicity results showed that all the non-ionic surfactants were regarded as safe at selected concentrations. Based on the in situ absorption data and ciliotoxicity results, the following three samples, 0.5% laurate SE, 0.1% cremophor EL and 0.5% poloxamer 188 were selected for in vivo absorption studies in rats. Among them, 0.5% laurate SE group presented the highest enhancing effect, followed by 0.1% cremophor EL and 0.5% poloxamer 188 group, with absolute bioavailability 29.99%, 22.64% and 20.90%, respectively. CONCLUSIONS: Laurate SE is a promising intranasal absorption enhancer. | Respiratory Tract Absorption |
INTRODUCTION: Recent evidences demonstrated that male factor alone is responsible for about 30% cases of infertility. Human follicle-stimulating hormone (hFSH) has been introduced to increase sperm concentration, spermatogonial population, or both natural or assisted pregnancy rates (PRs) in oligozoospermic subjects with normal concentrations of gonadotropins. METHODS: Fifty infertile men affected by idiopathic azoospermia were enrolled in this study, after undergoing medical history, physical and clinical examination, baseline semen parameters and hormonal plasma concentrations. Inclusion criteria were infertility for at least 2 years, idiopathic azoospermia, FSH <12 mIU/ml. Twenty-five patients were allocated to treatment with hFSH three times/week per 3 months (Fostimon), and 25 patients underwent just testicular sperm extraction (TESE) without medical treatment. All patients underwent, after 3 months, assisted reproduction techniques (ARTs) with TESE. The primary outcome was represented by the differences in the sperm retrieval rate (SRR) between groups, while the secondary outcomes were the differences in PR and fertilization rate (FR). RESULTS: We observed a PR of 15% (3/25) and 28% (7/25) in control and treated group, respectively. SRR after medical treatment and ART was 24% (6/25), while in the control group was 12.5% (2/25). The sperm in the ejaculate of five patients (20%) after medical treatment exhibited a mean concentration of 0.9 million/ml and a mean motility of 12%. The FR was significantly greater in the treatment group with respect to the control group, 30% and 20%, respectively. CONCLUSIONS: FSH treatment showed greater efficacy rather than control by increasing the rate of PR and FR in azoospermic patients who underwent TESE. | Urofollitropin |
We performed an experimental study of the influence on pacemakers (PM) of X-rays from the angiocardiography equipment. (1) We used one PM of DDD mode in this study. (2) The PM was irradiated under two exposure levels: one the standard dose and the other the maximum dose in the angiocardiography study situation. (3) We set the pacing lead wires to the bilateral atria and ventricles in Irnich's human body model. (4) We set two irradiation fields, one with a lead block on the PM and the other without the lead block. The result showed that when the PM was included in the irradiation field and the exposure level was of the maximum dose, the influence of irradiation on the PM was that of level 2 as classified by a research report by the Ministry of Internal Affairs and Communications. The absorbed dose of the PM was 93.4 mGy under these conditions. We confirmed that radiation dose does not affect a pacemaker with pacing lead wire. However, it acts on the generator of the PM owing to the direct photoelectric effect. When there were many dose rates (or total radiation dose), an obstacle occurred. | Angiocardiography |
In metazoa, cilia assembly is a cellular process that starts with centriole to basal body maturation, migration to the cell surface, and docking to the plasma membrane. Basal body docking involves the interaction of both the distal end of the basal body and the transition fibers/distal appendages, with the plasma membrane. Mutations in numerous genes involved in basal body docking and transition zone assembly are associated with the most severe ciliopathies, highlighting the importance of these events in cilium biogenesis. In this context, the ciliate Paramecium has been widely used as a model system to study basal body and cilia assembly. However, despite the evolutionary conservation of cilia assembly events across phyla, whether the same molecular players are functionally conserved, is not fully known. Here, we demonstrated that CEP90, FOPNL, and OFD1 are evolutionary conserved proteins crucial for ciliogenesis. Using ultrastructure expansion microscopy, we unveiled that these proteins localize at the distal end of both centrioles/basal bodies in Paramecium and mammalian cells. Moreover, we found that these proteins are recruited early during centriole duplication on the external surface of the procentriole. Functional analysis performed both in Paramecium and mammalian cells demonstrate the requirement of these proteins for distal appendage assembly and basal body docking. Finally, we show that mammalian centrioles require another component, Moonraker (MNR), to recruit OFD1, FOPNL, and CEP90, which will then recruit the distal appendage proteins CEP83, CEP89, and CEP164. Altogether, we propose that this OFD1, FOPNL, and CEP90 functional module is required to determine in mammalian cells the future position of distal appendage proteins. | Paramecium |
This paper provides a special flexible graphene film based capacitive wireless power transfer (FGCPT) system for powering biomedical sensors of smart wearable devices. The graphene conductive material is flexible, transparent, highly conductive, and impermeable to most gases and liquids. Generally, the coupling structure of capacitive wireless power transfer (CPT) system is consisted of metal plates. However, it is hard to use for the biomedical sensors as the low power density and big volume. The shape of graphene conductive material could be easily built and changed according to the application requirements. In this paper, the power supply of biomedical sensing system could be accomplished by a single graphene film which is acted as the receiver of FGCPT system. The 200 mW power level is achieved with the maximum 9 V output voltage. The theory and calculation are verified by the simulated and experimental results. | Electric Wiring |
While osajin and pomiferin are known for their anticancer, antibacterial and antidiabetic properties, scandenone and auriculasin have been proposed as anti-inflammatory and antinociceptive agents. Curiously, these two couples of molecules are, from a chemical point of view, structural isomers which can all be extracted from Maclura pomifera. Although previous works described, separately, the isolation in reasonable amounts of the sole osajin/pomiferin couple or of scandenone/auriculasin, we report the extraction and characterization using direct spectral and chromatographical comparison of the four compounds. 2D NMR allowed to unambiguously assign the correct structures to the isomers. The compounds were screened in silico against PDE5 and their interaction pattern with the protein was compared with that of icarisid II, a natural PDE5 inhibitor. | Benzopyrans |
CASE DESCRIPTION: An 8-year-old male Golden Retriever was evaluated because of an 8-week history of intermittent diarrhea with melena and hematochezia that were not responsive to medical treatment and resulted in severe anemia. CLINICAL FINDINGS: Exploratory celiotomy with intestinal and colonic biopsy revealed mild enterocolitis but did not result in diagnosis of the cause of melena and hematochezia. Endoscopy of the upper portion of the gastrointestinal tract and colonoscopy were performed. Multifocal areas of coalescing, tortuous mucosal blood vessels were observed in the cecum and all regions of the colon. A diagnosis of vascular ectasia (VE) was made on the basis of the endoscopic and histologic appearance of the lesions. TREATMENT AND OUTCOME: An ileorectal anastamosis was performed. Melena and hematochezia resolved within 3 days after surgery, and the anemia resolved within 6 weeks after surgery. Surgical resection of the cecum and colon and feeding of a highly digestible diet resulted in long-term (22 months) resolution of clinical signs. CLINICAL RELEVANCE: Initial exploratory celiotomy with intestinal and colonic biopsy failed to reveal the VE lesions responsible for the melena, hematochezia, and anemia. Endoscopic evaluation was necessary for detection of the colonic VE lesions. Surgical resection of the cecum and colon and feeding of a highly digestible diet may result in a favorable outcome in affected dogs." | Gastric Antral Vascular Ectasia |
Linker histones (LHs) bind to the DNA entry/exit points of nucleosomes and demonstrate preference for AT-rich DNA, although the recognized sequence patterns remain unknown. These patterns are expected to be more pronounced in metazoan nucleosomes with abundant LHs, compared to yeast nucleosomes with few LHs. To test this hypothesis, we compared the nucleosome core particle (NCP) sequences from chicken, Drosophila and yeast, extending them by the flanking sequences extracted from the genomes. We found that the known approximately 10-bp periodic oscillation of AT-rich elements goes beyond the ends of yeast nucleosomes, but is distorted in metazoan sequences where the 'out-of-phase' AT-peaks appear at the NCP ends. The observed difference is likely to be associated with sequence-specific LH binding. We therefore propose a new structural model for LH binding to metazoan nucleosomes, postulating that the highly conserved nonpolar 'wing' region of the LH globular domain (tetrapeptide GVGA) recognizes AT-rich fragments through hydrophobic interactions with the thymine methyl groups. These interactions lead to DNA bending at the NCP ends and formation of a 'stem-like' structure. The same mechanism accounts for the high affinity of LH to methylated DNA-a feature critical for stabilization of the higher-order structure of chromatin and for repression of transcription. | AT Rich Sequence |
The authors relate their experience of 61 rectal anesthesias with ketamine (10 mg/kg) and diazepam (0.25-0.5 mg/kg). Rectal anesthesia is well accepted by children who are afraid of percutaneous injection. When ketamine is used alone, they obtained only 76 p. cent good result. When diazepam is associated, good results arise to 95 p. cent. Diazepam added to ketamine allows surface surgery during 10 to 15 minutes. | Anesthesia, Rectal |
Cryptosporidiosis is a major cause of diarrhoeal illness among African children, and is associated with childhood mortality, malnutrition, cognitive development and growth retardation. Cryptosporidium hominis is the dominant pathogen in Africa, and genotyping at the glycoprotein 60 (gp60) gene has revealed a complex distribution of different subtypes across this continent. However, a comprehensive exploration of the metapopulation structure and evolution based on whole-genome data has yet to be performed. Here, we sequenced and analysed the genomes of 26 C. hominis isolates, representing different gp60 subtypes, collected at rural sites in Gabon, Ghana, Madagascar and Tanzania. Phylogenetic and cluster analyses based on single-nucleotide polymorphisms showed that isolates predominantly clustered by their country of origin, irrespective of their gp60 subtype. We found a significant isolation-by-distance signature that shows the importance of local transmission, but we also detected evidence of hybridization between isolates of different geographical regions. We identified 37 outlier genes with exceptionally high nucleotide diversity, and this group is significantly enriched for genes encoding extracellular proteins and signal peptides. Furthermore, these genes are found more often than expected in recombinant regions, and they show a distinct signature of positive or balancing selection. We conclude that: (1) the metapopulation structure of C. hominis can only be accurately captured by whole-genome analyses; (2) local anthroponotic transmission underpins the spread of this pathogen in Africa; (3) hybridization occurs between distinct geographical lineages; and (4) genetic introgression provides novel substrate for positive or balancing selection in genes involved in host-parasite coevolution. | Cryptosporidium |
Here I report the complete mitochondrial genome of the African palm civet, (Nandinia binotata) as sequenced from overlapping PCR products. The genome is 17,103 bp in length and contains the 37 genes found in a typical mammalian genome: 13 protein-coding genes, 22 transfer RNA genes and 2 ribosomal RNA genes. The control region of N. binotata includes both RS2 and RS3 tandem repeats. The overall base composition on the L-strand is A: 33.6%, C: 27.3%, G: 13.0%, and T: 26.1%. | Nandiniidae |
Spring systems, whether natural or engineered, are composed of compliant and rigid regions. Biological springs are often similar to monolithic structures that distribute compliance and rigidity across the whole system. For example, to confer different amounts of compliance in distinct regions within a single structure, biological systems typically vary regional morphology through thickening or elongation. Here, we analyze the monolithic spring in mantis shrimp (Stomatopoda) raptorial appendages to rapidly acquire or process prey. We quantified the shape of cross-sections of the merus segment of the raptorial appendage. We also examined specific regions of the merus that are hypothesized to either store elastic energy or provide structural support to permit energy storage in other regions of the system. We found that while all mantis shrimp contain thicker ventral bars in distal cross-sections, differences in thickness are more pronounced in high-impact smasher" mantis shrimp than in the slower-striking "spearer" mantis shrimp. We also found that spearer cross-sections are more circular while those of smashers are more eccentric with elongation along the dorso-ventral axis. The results suggest that the regional thickening of ventral bars provides structural support for resisting spring compression and also reduces flexural stiffness along the system's long axis. This multilevel morphological analysis offers a foundation for understanding the evolution and mechanics of monolithic systems in biology." | Extremities |
Protein splicing is a self-catalyzed process mediated by inteins. The observation that inteins occur only in microorganisms and that they often interrupt genes that play an essential role in nucleic acid metabolism makes them attractive as potential antibacterial targets. Because mycobacteria are the only intein-containing bacteria associated with human hosts, inteins would represent highly specific antimycobacterial targets. In Mycobacterium tuberculosis, two important proteins of DNA repair and replication, RecA and DnaB, respectively, are interrupted by inteins that must be excised by protein splicing before these proteins can function. This review describes the screening systems for the detection of mutations or inhibitors that interfere with proteins splicing that have been developed and published to date. In three of these experimental system, inteins have been inserted into proteins that are toxic under certain conditions. Protein splicing therefore leads to conditional growth inhibition or cell death and its inhibition can be monitored in terms of bacterial growth. A fourth assay for protein splicing and its inhibition is based on purified proteins and measures the formation of Green Fluorescent Protein or its inhibition. The advantages of inteins as antimycobacterial targets are discussed. | Protein Splicing |
In food, salt has several key roles including conservative and food perception. For this latter, it is well-known that the interaction of sodium with the food matrix modifies the consumer perception. It is then critical to characterize these interactions in various real foods. For this purpose, we exploited the information obtained on both single and double quantum (23) Na nuclear magnetic resonance (NMR) spectroscopies. All salted food samples studied showed strong interactions with the food matrix leading to quadrupolar interactions. However, for some of them, the single quantum analysis did not match the theoretical prediction. This was explained by the presence of another type of sodium population, which did not produce quadrupolar interactions. This finding is of critical importance to perform quantitative magnetic resonance imaging (MRI) and to understand the consumer salty taste perception. | Metals, Light |
Decoquinate is a quinolone coccidiostat introduced during 1967 as an in-feed prophylactic for broiler chickens. Despite early drug-resistance problems and its age, the drug is still used commercially worldwide. Decoquinate here serves as a valuable model in a field study that addresses the dynamics and economic impact of the development of coccidial resistance to potent synthetic anticoccidial drugs. The results of this unique, hitherto unpublished, study on the initial emergence of resistance of avian coccidia (Eimeria spp.) to a new drug in the field may be of strategic value in the continued use of decoquinate or the introduction of new drugs. The commercial performance of the first 3-5 crops of broilers to be medicated with decoquinate on each of six farms was monitored during 14 months in 1968-1969, supplemented by assessments of the species, population dynamics and decoquinate-resistance of coccidia isolated from each farm. During the rearing of each flock in a single shed on each farm, oocysts were counted in fresh faecal samples collected on three occasions, and the species were identified by their morphology if possible, supported if necessary by the biological characteristics of infections in chickens. E. acervulina was the most common species, followed by E. mitis, E. maxima, E. tenella and E. praecox. E. brunetti occurred rarely, and E. necatrix was not found. Decoquinate-resistance was evident in several species during the rearing of the first decoquinate-medicated crop on each farm, although clinical coccidiosis did not occur. It was concluded that inherently resistant mutants of E. acervulina, E. brunetti, E. maxima, E. tenella, and probably also E. mitis and E. praecox, were selected from field populations by 6 weeks during their first exposure to decoquinate. During up to four more subsequent crops, cycling of resistant parasites stimulated host immunity, which had no obvious adverse impact on commercial performance. There was no apparent seasonal effect. A hypothesis is proposed to explain the sudden and rapid emergence of quinolone-resistance in the coccidia, and why bird health was not thereby compromised in these circumstances. | Decoquinate |
Repression of transcription by the classical nuclear receptors (e.g. TR, RAR), the orphan nuclear receptors (e.g. Rev-erbAalpha/beta), Mxi-1 and Mad bHLH-zip proteins and the oncoproteins PLZF and LAZ3/BCL6 is mediated by the corepressors N-CoR and SMRT. The interaction of the corepressors with the components involved in chromatin remodelling, such as the recruiting proteins Sin3A/B and the histone deacteylases HDAc-1 and RPD3, has been analysed in detail. The N-CoR/Sin3/HDAc complexes have a key role in the regulation of cellular proliferation and differentiation. However, the interaction of these corepressors with the basal transcriptional machinery has remained obscure. In this study we demonstrated that the N-terminalrepression domains and the receptor interactiondomains (RID) of N-CoR and its splice variants, RIP13a and RIP13Delta1, directly interact with TAFII32 in vivo and in vitro . We show that interaction domain II within the N-CoR and RIP13a RID is required for the interaction with TAFII32. We also observed that N-CoR directly interacts with each of the basal factors, TFIIB and TAFII70, and can simultaneously interact with all three basal factors in a non-competitive manner. Furthermore, we provide evidence that suggests the RVR/Rev-erbbeta-corepressor complex also interacts with the general transcriptional machinery, and that the physicalassociation of TFIIB with N-CoR also occurs in the presence of Sin3B and HDAc-1. Interestingly, we observed that N-CoR expression ablated the functional interaction between TFIIB and TAFII32 that is critical to the initiation of transcription. In conclusion, this study demonstrates that the N-terminal repressor region and the C-terminal RIDs are part of the corepressor contact interface that mediates the interaction with the general transcription factors, and demonstrates that TAFs can also directly interact with corepressors to mediate signals from repressors to the basal machinery. We also suggest that N-CoR interacts with the central components of the transcriptional initiation process (TFIIB, TAFs) and locks them into a non-functional complex or conformation that is not conducive to transcription. | Transcription Factors, TFII |
Alcohol consumption is common in Western countries and has been increasing in older adults. Latest figures from Great Britain suggest 75% of those over 65 years drink, an increase from 71% 10 years ago. Chronic heavy intake is a well-established cause of brain atrophy and dementia, with a recent long-term prospective study from the USA reporting a doubling of the odds of later severe memory impairment in those with a history of an alcohol use disorder. Drinking of moderate amounts has been reported to be protective for brain health in a number of epidemiological studies, including some claims of possibly reducing dementia risk. Rigorous recent research has questioned this belief, with new evidence of harmful associations in moderate drinkers compared with abstainers. This has raised suspicion that reported protective effects of moderate drinking were due to confounding by socioeconomic class and intelligence. Clinicians should look out for cognitive impairment in heavy drinkers, considering that abstinence may induce a degree of clinical improvement. Discussions with patients regarding moderate drinking should be informed by recent research. Health benefits of moderate drinking at least for cognitive function are questionable, and if they exist are probably limited to one unit of alcohol daily with respect to other body systems. | Alcoholic Korsakoff Syndrome |
A study of 18 normal subjects was undertaken to evaluate the rapidity of gallbladder filling with Tc-99m IDA during fast, and the degree of emptying and incidence of refilling after intravenous infusion of either 20 or 40 ng/kg of octapeptide of cholecystokinin (CCK-8). During fast, the frequency of onset of gallbladder filling with Tc-99m IDA at 20, 30, 40, and 42 min was 68%, 84%, 95%, and 100%, respectively. Following CCK-8 infusion, the gallbladder mean ejection period of 11 +/- 4 (s.d.) min and ejection fraction of 40% +/- 23 were similar in subjects given either a 20 ng/kg or a 40 ng/kg dose. The frequency of onset of refilling at 20, 30, 40, and 50 min after CCK-8 was 33%, 63%, 71%, and 79%, respectively for the combined groups. At 50 min after CCK-8, all subjects given 20 ng/kg refilled, whereas only 63% of the 40-ng/kg group did so. There was no correlation between the degree of emptying (ejection fraction) and onset of refilling. We conclude that the frequency of post CCK-8 onset of gallbladder refilling, which reflects sphincter tone recovery, is widely variable, depending upon both the dose and the duration from the time of infusion of CCK-8 and should be taken into consideration if a pre-emptying procedure is adopted during hepatobiliary imaging with Tc-99m IDA agents. | Sphincter of Oddi |
Sepsis-induced myocardiopathy, characterized by innate immune cells infiltration and proinflammatory cytokines release, may lead to perfusion failure or even life-threatening cardiogenic shock. Macrophages-mediated inflammation has been shown to contribute to sepsis-induced myocardiopathy. In the current study, we introduced two photoactivated adenylyl cyclases (PACs), Beggiatoa sp. PAC (bPAC) and Beggiatoa sp. IS2 PAC (biPAC) into macrophages by transfection to detect the effects of light-induced regulation of macrophage pro-inflammatory response and LPS-induced sepsis-induced myocardiopathy. By this method, we uncovered that blue light-induced bPAC or biPAC activation considerably inhibited the production of pro-inflammatory cytokines IL-1 and TNF-alpha, both at mRNA and protein levels. Further, we assembled a GelMA-Macrophages-LED system, which consists of GelMA-a type of light crosslink hydrogel, gene modulated macrophages and wireless LED device, to allow light to regulate cardiac inflammation in situ with murine models of LPS-induced sepsis. Our results showed significant inhibition of leukocytes infiltration, especially macrophages and neutrophils, suppression of pro-inflammatory cytokines release, and alleviation of sepsis-induced cardiac dysfunction. Thus, our study may represent an emerging means to treat sepsis-induced myocardiopathy and other cardiovascular diseases by photo-activated regulating macrophage function. | Thiotrichaceae |
BACKGROUND: There are increasing numbers of surviving children who were born extremely preterm (EP; gestational age <28 weeks) or extremely low birth weight (ELBW; birth weight <1000 g). Our objective in this study was to compare the rates of motor impairment at 8 years of age between 3 cohorts of EP and/or ELBW and term-born children to establish if motor impairment rates are changing over time. METHODS: All children born EP and/or ELBW in the calendar years of 1991-1992, 1997, and 2005 in Victoria, Australia, were recruited at birth. Randomly selected normal birth weight (>2499 g) and term-born controls were matched for expected date of birth, sex, and sociodemographic status. At 8 years' corrected age, motor impairment was defined as cerebral palsy (CP) or a score less than the fifth centile on the Movement Assessment Battery for Children for the 1991-1992 and 1997 cohorts and less than or equal to the fifth centile on the Movement Assessment Battery for Children-Second Edition for the 2005 cohort. RESULTS: Motor impairment was more likely in children born EP and/or ELBW compared with children born at term for all epochs. There was a significant increase in motor impairment in EP and/or ELBW children over the 3 eras, from 23% in 1991-1992 and 26% in 1997 to 37% in 2005 (chi(2)(trend) = 10.2; P = .001). This was due to an increase in non-CP motor impairment (13% in 1991 to 1992; 15% in 1997; 26% in 2005; chi(2)(trend) = 12.5; P < .001), not CP (11% in 1991 to 1992; 11% in 1997; 12% in 2005). CONCLUSIONS: The rate of motor impairment in EP and/or ELBW children assessed at 8 years of age increased between eras, an increase caused by non-CP motor impairment. | Motor Skills Disorders |
OBJECTIVE: To evaluate a novel physiological approach for setting the tidal volume in mechanical ventilation according to inspiratory capacity, and to determine if it results in an appropriate mechanical and gas exchange measurements in healthy and critically ill dogs. METHODS: Twenty healthy animals were included in the study to assess the tidal volume expressed as a percentage of inspiratory capacity. For inspiratory capacity measurement, the mechanical ventilator was set as follows: pressure control mode with 35cmH2O of inspired pressure and zero end-expiratory pressure for 5 seconds. Subsequently, the animals were randomized into four groups and ventilated with a tidal volume corresponding to the different percentages of inspiratory capacity. Subsequently, ten critically ill dogs were studied. RESULTS: Healthy dogs ventilated with a tidal volume of 17% of the inspiratory capacity showed normal respiratory mechanics and presented expected PaCO2 values more frequently than the other groups. The respiratory system and transpulmonary driving pressure were significantly higher among the critically ill dogs but below 15 cmH2O in all cases. CONCLUSIONS: The tidal volume based on the inspiratory capacity of each animal has proven to be a useful and simple tool when setting ventilator parameters. A similar approach should also be evaluated in other species, including human beings, if we consider the potential limitations of tidal volume titration based on the calculated ideal body weight. | Inspiratory Capacity |
OBJECTIVE: To compare the intensity of posterior capsular opacification (PCO) between a 1-piece and a 3-piece microincision cataract surgery intraocular lens (MICS IOL) in a prospective randomised study. METHODS: 80 eyes of 40 patients with age-related cataract were enrolled in this study. Each patient received a 1-piece MICS IOL (AF-1 NY-60, Hoya, Tokyo, Japan) in one eye and a 3-piece MICS IOL (AF-1 iMICS Y-60H, Tokyo, Hoya) in the other eye. At the 1-year follow-up, the patients were examined at the slit lamp, visual acuity was determined and standardised high-resolution digital retroillumination images were taken for objective quantification of regeneratory PCO using an automated image analysis software (AQUA). RESULTS: The mean regeneratory PCO score (1-piece IOL: 0.2, 3-piece IOL 0.3, p=0.7) and the neodymium:yttrium-aluminium-garnet laser capsulotomy rate (two cases in 3-piece IOL group; p=0.5) were comparable low for both IOLs. Capsular folds occurred significantly more often in the 3-piece IOL group (p=0.02). CONCLUSIONS: Modification of the MICS IOL from a 3-piece to a 1-piece haptic design caused in short term no significant change in PCO amount. Compared with the 3-piece IOL, the 1-piece IOL led to significantly less capsular folds 1 year after surgery. | Capsule Opacification |
Cell and tissue culture studies suggest that the long-lasting (L-type) voltage-sensitive calcium channels (VSCC) play a role in the signaling cascade in bone cells after mechanical loading. We investigated whether the L-type VSCC mediates mechanically induced bone formation in vivo using two L-type VSCC antagonists verapamil and nifedipine. Female Sprague-Dawley rats were divided into five groups: control group (Veh), two verapamil-treated groups (20 mg/kg, Vera-L; 100 mg/kg, Vera-H), and two nifedipine-treated groups (20 mg/kg, Nife-L; 100 mg/kg, Nife-H). One bout of mechanical loading was applied to the right tibia 90 minutes after oral administration of verapamil or 30 minutes after oral administration of nifedipine. Mechanical loading increased mineralizing surface (MS/bone surface [BS]), mineral apposition rate (MAR), and bone formation rate (BFR/BS) on the endocortical surface in loaded tibias of control animals compared with nonloaded (left) tibias. Verapamil and nifedipine suppressed the load-induced increase in BFR/BS observed in vehicle-treated controls by 56-61% (p < 0.01) and 56-74% (p < 0.01), respectively. Yet, significant differences in MS/BS and BFR/BS between right and left limbs were found in verapamil- and nifedipine-treated animals, indicating that the treatments did not completely abolish load-induced bone formation. This study shows that blocking the L-type calcium channel in vivo substantially suppresses the mechanically induced increase in bone formation that normally would occur and suggests that the L-type calcium channel mediates mechanically induced bone adaptation in vivo. | Calcium Channels, L-Type |
As a byproduct of the increased use of high-resolution radiological imaging, the prevalence of incidental findings (IFs) has been increasing for years. The discovery of an incidental finding can allow early treatment of a potentially health-threatening disease and thus decisively change the course of the disease. However, many incidental findings are of low risk with little or no health impact, and yet their discovery often leads to a cascade of additional investigations. It is undisputed that incidental findings can have a direct impact on the life of the person and that not only psychosocial aspects such as worries and anxiety due to false-positive findings play a role, but that insurance, legal or professional problems can also occur under certain circumstances, which is why the correct handling of incidental findings and the accompanying ethical challenges that apply to them regularly give rise to discussions. General principles to consider when managing incidental findings are responsibility for the well-being of the patient/study participant and of society. In order to avoid overdiagnosis and overtreatment and to achieve high patient benefit, radiologists and clinicians must know how to properly deal with IFs. In recent years, various national and international societies have published important guidelines (white papers") on how to deal with the management of IFs. It is important that radiologists are fully aware of and follow these guidelines and are also available to referring physicians for further discussions and advice. The most important fact is that the well-being of the patient must always be at the center of all decisions." | Incidental Findings |
1-Polyoxyphenyl-3-(2,6-dioxyphenyl)propane-1,3-diones have been synthesized as intermediates for flavone synthesis by condensation of 2-(2,6-dioxybenzoyloxy)polyoxyacetophenone in the presence of phase transfer catalyst. The average yields of 1-polyoxyphenyl-3-phenylpropane-1,3- diones, 1-polyoxyphenyl-3-(2-benzyloxyphenyl)propane-1,3-diones and 1-polyoxy-3-(2,6-dibenzyloxyphenyl)propane-1,3-diones were 79%, 74% and 71%, respectively. The bulkiness of the benzyloxy groups or methoxy groups exerted steric hindrance and reduced the yield. Nevertheless, the yields were higher than the previously reported ones. | Methane |
Nine forms of cytochrome P-450 have been purified to electrophoretic homogeneity from human-liver microsomes. These include the enzymes involved in debrisoquine 4-hydroxylation, phenacetin O-deethylation and mephenytoin 4-hydroxylation, three reactions which are characterized by genetic polymorphism in humans. Evidence for the involvement of the above enzymes comes from reconstituted immunochemical inhibition studies with human-liver microsomes. These and other lines of evidence are consonant with the view that different forms of cytochrome P-450 are involved in the three reactions. The debrisoquine 4-hydroxylase has been studied most extensively in terms of its substrate specificity. In addition, an analogous rat enzyme shows some homology and serves as a useful model. The use of antibodies raised to the rat-liver enzyme in immuno-inhibition studies with human-liver microsomes provides a means of determining the extent to which this enzyme participates in other reactions. Translation of rat-liver mRNA in vitro yields the intact debrisoquine 4-hydroxylase; studies with human mRNA suggest a lower frequency than in rats. The basis for impaired catalytic activity in phenotypically poor human metabolizers appears to be an altered enzyme in all three cases, as opposed to a decreased level of a single enzyme. Using antibody screening of fusion proteins expressed in a cDNA library, it has been possible to isolate cDNA probes for all three of these cytochromes P-450 for use in screening individuals and ultimately determining the basis of these polymorphisms. | Mixed Function Oxygenases |
Systematic analyses of the interaction between liposomes and cells were examined. Liposomes were found to affect the growth of mouse NIH 3T3 cells depending upon their size, net charge, and cholesterol content. Among the charged compounds, stearylamine was the most inhibitory and showed complete inhibition of cell growth at 100 microM. The cholesterol-rich and small unilamellar vesicles were more suppressive compared to the cholesterol-poor and multilamellar ones, respectively. The binding assay of liposomes to the cells showed a positive correlation between liposome binding and the extent of growth inhibition. Suppression of liposome uptake by inhibitors of the cytoskeletal system and energy metabolism were suggestive of an endocytotic mechanism for the cellular uptake of liposomes. The growth inhibitory effect seemed secondary to the intracellular uptake of liposomes, and peroxidation of incorporated lipids would lead to cellular damage. Therefore, it is highly recommended that potential growth inhibitory effects associated with the particular composition and other properties of liposomes should be carefully assessed in any human studies, especially for long-term use. | Drug Carriers |
Blackleg disease causes yield losses in canola (Brassica napus L.). To identify resistance genes and genomic regions, genome-wide association studies (GWAS) of 585 diverse winter and spring canola accessions were performed using imputed whole-genome sequence (WGS) and transcriptome genotype-by-sequencing (GBSt). Blackleg disease phenotypes were collected across three years in six trials. GWAS were performed in several ways and their respective power was judged by the number of significant single nucleotide polymorphisms (SNP), the false discovery rate (FDR), and the percentage of SNP that validated in additional field trials in two subsequent years. WGS GWAS with 1,234,708 million SNP detected a larger number of significant SNP, achieved a lower FDR and a higher validation rate than GBSt with 64,072 SNP. A meta-analysis combining survival and average internal infection resulted in lower FDR but also lower validation rates. The meta-analysis GWAS identified 79 genomic regions (674 SNP) conferring potential resistance to L. maculans. While several GWAS signals localised in regions of known Rlm genes, fifty-three new potential resistance regions were detected. Seventeen regions had underlying genes with putative functions related to disease defence or stress response in Arabidopsis thaliana. This study provides insight into the genetic architecture and potential molecular mechanisms underlying canola L. maculans resistance. | Leptosphaeria |
To investigate the influence of androgens on secretory protein expression during the development of the guinea pig seminal vesicle epithelium, we examined the patterns of mRNA and protein accumulation during the first 2 wk after birth. Hybridization of total seminal vesicle RNA to cDNA probes revealed that the secretory protein genes were active as early as 5 days after birth. However, the accumulation of secretory proteins was barely detectable between Days 5 and 10, and could not be enhanced by treatment of neonatal animals with exogenous androgens. Secretory protein mRNA and protein levels both increased rapidly between Days 10 and 15. However, the 800-fold rise in protein levels between Days 5 and 15 greatly exceeded the magnitude of the increase in secretory protein mRNA that occurred during this interval. These data indicate that the rate of secretory protein accumulation in the guinea pig seminal vesicle is not determined strictly by the availability of secretory protein mRNA, and suggest that post-transcriptional mechanisms may contribute to the regulation of secretory protein accumulation in neonatal guinea pigs. | Seminal Vesicles |
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